QUINOLONE COMPOUND

Abstract

The present invention provides a compound represented by the formula (I) wherein X is a hydrogen atom or a fluorine atom; R is a hydrogen atom or alkyl; R1 is (1) cyclopropyl optionally substituted by to 3 halogen atoms or (2) phenyl optionally substituted by 1 to 3 halogen atoms; R2 is alkyl, alkoxy, haloalkoxy, a halogen atom, cyano, etc.; and R3 is 7-oxo-7,8-dihydro-1,8-naphthyridinyl, 3-pyridyl, etc., or a salt thereof. The compound of the present invention has excellent antimicrobial activity against Clostridium difficile and is useful for the prevention or treatment of intestinal infection such as Clostridium difficile-associated diarrhea.

Description

TECHNICAL FIELD

The present invention relates to quinolone compounds and pharmaceutical use thereof.

BACKGROUND ART

Clostridium difficile infection is associated with consumption of antibiotics which disrupt the normal microbial flora of the gut, allowing Clostridium difficile to establish itself and produce disease. Currently, only vancomycin or metronidazole is recommended for treatment and many patients suffer from relapse on infection (Expert Opin. Ther. Patents (2010) 20(10), pp. 1389-1399).

EP2177214 A1 describes use of ozenoxacin for Clostridium difficile.

Some quinolone compounds useful as antibacterial agents are disclosed in JP1-319463 A, WO99/51588, WO99/03465, JP3-66301 B and WO99/07682.

SUMMARY OF INVENTION

The object of the present invention is to provide a novel quinolone compound which has excellent antimicrobial activity, particularly excellent antimicrobial activity against Clostridium difficile. Another object of the present invention is to provide a pharmaceutical composition containing said quinolone compound, which is useful for the prevention or treatment of various infectious diseases including antibiotics-associated diarrhea (AAD) such as Clostridium difficile-associated diarrhea (CDAD). A further object of the present invention is to provide a method for preventing or treating a bacterial infection including AAD such as CDAD, which comprises administering said quinolone compound to a human or an animal.

The present invention provides a quinolone compound, a pharmaceutical composition comprising said compound, use of said compound, and a method for preventing or treating a bacterial infection, as described in Items 1 to 27 below.

Item 1. A compound represented by the formula (I)

wherein
X is a hydrogen atom or a fluorine atom;
R is a hydrogen atom or alkyl;
R¹ is (1) cyclopropyl optionally substituted by 1 to 3 halogen atoms or (2) phenyl optionally substituted by 1 to 3 halogen atoms;
R² is a hydrogen atom; alkyl optionally substituted by 1 or 2 substituents selected from the group consisting of a halogen atom and hydroxyl; alkoxy; haloalkoxy; a halogen atom; cyano; cyclopropyl; nitro; amino; formyl; alkenyl or alkynyl; or
R¹ and R² are bonded to form a 5- or 6-membered ring optionally substituted by alkyl;

R³ is

• • (1) a fused heterocyclic group of the formula

wherein
represents a single bond or a double bond,

X¹ is C(R⁵) or N,

R⁴ is a hydrogen atom or alkyl, and
R⁵ is (a) a hydrogen atom,

• • (b) a halogen atom,
  • (c) cyano,
  • (d) nitro,
  • (e) hydroxy,
  • (f) alkyl optionally substituted by 1 to 3 halogen atoms,
  • (g) alkenyl or alkynyl,
  • (h) aryl, or
  • (i) alkoxy optionally substituted by 1 to 3 halogen atoms,
    when X¹ is C(R⁵), R⁴ and R⁵ are optionally bonded to form a 5- or 6-membered ring optionally substituted by oxo,
    said fused heterocyclic group is optionally substituted by 1 or 2 substituents selected from the group consisting of a halogen atom, cyano, nitro, hydroxy and alkyl,
  • (2) a group of the formula

wherein

X² is C(R⁸) or N, and

R⁶, R⁷ and R⁸ are each independently,

• • (a) a hydrogen atom,
  • (b) a halogen atom,
  • (c) cyano,
  • (d) nitro,
  • (e) amino,
  • (f) alkyl optionally substituted by 1 to 3 substituents selected from the group consisting of a halogen atom, alkoxy and amino,
  • (g) alkenyl,
  • (h) alkynyl,
  • (i) aryl,
  • (j) formyl or CH═N—OH,
  • (k) carboxy,
  • (l) carbamoyl,
  • (m) a 5- to 10-membered aromatic heterocyclic group optionally substituted by alkyl, or
  • (n) alkenyloxy,
  • (3) a group of the formula

wherein

X³ and X⁴ are N, or

X³ is N and X⁴ is CR″, wherein R″ is hydrogen atom, amino, hydroxy, alkyl optionally substituted by 1 to 3 substituents selected from the group consisting of alkoxy and dimethylamino or mercapto, or

X³ is CH and X⁴ is N,

R′ is a hydrogen atom or alkyl optionally substituted by 1 to 3 substituents selected from the group consisting of substituted hydroxyl and amino, and
R⁶ is as defined above,

• • (4) a group of the formula

wherein
represents a single bond or a double bond and R⁶ is as defined above,

• • (5) 3-pyridyl optionally substituted by 1 or 2 substituents selected from the group consisting of
    • (a) a halogen atom,
    • (b) cyano,
    • (c) nitro,
    • (d) hydroxy,
    • (e) amino,
    • (f) alkyl optionally substituted by 1 to 3 substituents selected from the group consisting of a halogen atom, alkylamino, dialkylamino and hydroxy,
    • (g) alkenyl, alkynyl
    • (h) aryl,
    • (i) cycloalkyl,
    • (j) alkoxy,
    • (k) alkylamino,
    • (l) dialkylamino,
    • (m) phenylamino optionally substituted by 1 to 3 halogen atoms,
    • (n) a cyclic amino group optionally substituted by alkoxycarbonyl,
    • (o) formyl,
    • (p) carbamoyl optionally substituted by alkyl optionally substituted by hydroxy, and
    • (q) a 5- to 10-membered aromatic heterocyclic group optionally substituted by alkyl,
  • (6) 4-pyridyl optionally substituted by a halogen atom,
  • (7) 5-pyrimidinyl optionally substituted by 1 or 2 substituents selected from the group consisting of amino, alkylamino, dialkylamino and carboxy,
  • (8) 2-indolyl, 3-indolyl, 5-indolyl, 6-indolyl, benzofuranyl, benzothiophenyl, benzoxazolyl or benzothiazolyl, each optionally substituted by 1 or 2 substituents selected from the group consisting of
    • (a) a halogen atom,
    • (b) cyano,
    • (c) nitro,
    • (d) hydroxy,
    • (e) alkyl optionally substituted by 1 to 3 substituents selected from the group consisting of amino, alkoxycarbonylamino, alkylamino and dialkylamino,
    • (f) alkoxy,
    • (g) formyl,
    • (h) carboxy, and
    • (j) amino optionally substituted by 1 or 2 substituents selected from the group consisting of
      • (i) alkoxycarbonyl,
      • (ii) alkylcarbonyl optionally substituted by a substituent selected from the group consisting of
        • (A) cycloalkyloxy optionally substituted by 1 to 3 alkyl,
        • (B) alkylamino,
        • (C) dialkylamino,
        • (D) a cyclic amino group optionally substituted by alkoxycarbonyl, and
        • (E) a halogen atom,
      • (iii) phenylcarbonyl optionally substituted by 1 to 3 substituents selected from the group consisting of alkyl and alkoxy,
      • (iv) cycloalkylcarbonyl,
      • (v) a 5- to 10-membered aromatic heterocyclylcarbonyl group optionally substituted by alkyl optionally substituted by 1 to 3 halogen atoms,
      • (vi) benzylcarbonyl optionally substituted by 1 to 3 substituents selected from the group consisting of a halogen atom and alkoxy,
      • (vii) arylsulfonyl optionally substituted by alkoxy,
      • (viii) cycloalkylalkylsulfonyl optionally substituted by 1 to 3 substituents selected from the group consisting of alkyl and oxo,
      • (ix) a 5- to 10-membered aromatic heterocyclylsulfonyl group optionally substituted by 1 to 3 alkyl, and
      • (x) —C(═N—CN)—SR⁹ wherein R⁹ is alkyl,
  • (9) a group of the formula

wherein
one of Y¹, Y², Y³ and Y⁴ is N or N⁺ (—O⁻), and the remaining three are each C(R²⁵), C(R²⁶) and C(R²⁷),

W is O, S, NH or N(R²³)

R²³ is a hydrogen atom or alkyl, and
R²⁴, R²⁵, R²⁶ and R²⁷ are each independently,

• • (a) a hydrogen atom,
  • (b) cyano, or
  • (c) nitro,
  • (10) a group of the formula

wherein
R²⁸ is a hydrogen atom or hydroxy, and
R²⁹ is a hydrogen atom or alkyl,

• • (11) a group of the formula

wherein

X⁵ is C(R¹¹) or N,

X⁶ is CH₂, C(═O), O, S, SO₂ or N(R¹²),

X⁷ is CH(R¹³), C(═O) or N(R¹⁴),

X⁸ is CH(R¹⁵) or C(═O),

R¹⁰, R¹² and R¹⁴ are each independently,

• • (a) a hydrogen atom or
  • (b) alkyl, and
    R¹¹, R¹³ and R¹⁵ are each independently,
  • (a) a hydrogen atom,
  • (b) a halogen atom,
  • (c) cyano,
  • (d) nitro,
  • (e) amino,
  • (f) alkylamino,
  • (g) dialkylamino,
  • (h) alkyl optionally substituted by hydroxy, or
  • (i) alkenyl,
    when X⁵ is C(R¹¹), R¹⁰ and R¹¹ are optionally bonded to form a 5- or 6-membered ring optionally substituted by alkyl or oxo, and
    when X⁶ is N(R¹²) and X⁷ is CH(R¹³), R¹² and R¹³ are optionally bonded to form a 5- or 6-membered ring,
    (12) a group of the formula

wherein R¹⁶ is

• • (a) a hydrogen atom,
  • (b) alkyl optionally substituted by 1 to 3 substituents selected from the group consisting of cyano, alkylamino and dialkylamino,
  • (c) alkenyl optionally substituted by carboxy,
  • (d) formyl,
  • (e) carboxy,
  • (f) carbamoyl,
  • (g) —C(R¹⁷)═N—OH wherein R¹⁷ is a hydrogen atom, cyano or hydroxy,
  • (h) a 5- to 10-membered aromatic heterocyclic group optionally substituted by alkyl, alkoxycarbonyl, carboxy or phenyl, or
  • (i) cyano,
  • (13) a group of the formula

wherein
R¹⁸ is a hydrogen atom or alkyl optionally substituted by 1 to 3 substituents selected from the group consisting of a halogen atom and phenyl,
n is 0 or 1,
R¹⁹, R²⁰ and R³³ are each independently,

• • (a) a hydrogen atom,
  • (b) a halogen atom,
  • (c) cyano,
  • (d) alkyl optionally substituted by 1 to 3 substituents selected from the group consisting of
    • (i) a halogen atom,
    • (ii) cyano,
    • (iii) hydroxy,
    • (iv) amino,
    • (v) alkylamino,
    • (vi) dialkylamino, and
    • (vii) a cyclic amino group optionally substituted by alkyl,
  • (e) alkoxy,
  • (f) amino optionally substituted by 1 or 2 substituents selected from the group consisting of
    • (i) alkylcarbonyl optionally substituted by a cyclic amino group,
    • (ii) alkylsulfonyl,
    • (iii) carbamoyl,
    • (iv) alkyl, cycloalkyl or cycloalkylalkyl, and
    • (v) 5- to 10-membered saturated heterocyclic group,
  • (g) carboxy,
  • (h) alkoxycarbonyl,
  • (i) carbamoyl optionally substituted by alkyl optionally substituted by amino, alkylamino, dialkylamino or alkoxycarbonylamino,
  • (j) formyl,
  • (k) a 5- to 10-membered aromatic heterocyclic group optionally substituted by alkyl,
  • (l) —CH═N—OR²¹ wherein R²¹ is a hydrogen atom or alkyl optionally substituted by alkylamino or dialkylamino,
  • (m) nitro,
  • (n) a 5- to 10-membered saturated heterocyclic group optionally substituted by amino,
  • (o) phenyl, or
  • (p) —NHC(SMe)=CHCN,
  • (14) a group of the formula

wherein
R³⁰ is (a) a hydrogen atom,

• • (b) a halogen atom,
  • (c) cyano,
  • (d) alkyl optionally substituted by 1 to 3 substituents selected from the group consisting of a halogen atom and hydroxy,
  • (e) alkenyl,
  • (f) alkynyl,
  • (g) alkoxy,
  • (h) formyl,
  • (i) —CH═N—OH, or
  • (j) carbamoyl,
  • (15) naphthyl or isochromenyl,
  • (16) quinolyl or isoquinolyl, or their oxide derivatives,
  • (17) a group of the formula

• • (18) a group of the formula

wherein

U is O or S, and

R³¹ is (a) a hydrogen atom,

• • (b) a halogen atom,
  • (c) alkyl optionally substituted by 1 to 3 halogen atoms,
  • (d) carboxy,
  • (e) nitro,
  • (f) cyano, or
  • (g) amino,
  • (19) a group of the formula

wherein
R³² is (a) a halogen atom,

• • (b) phenyl, or
  • (c) a group of the formula

• • (20) a group of the formula

wherein

R³⁴ and R³⁵ are each independently,

• • (a) a hydrogen atom, or
  • (b) aminoalkyl,
    or
    R³⁴ and R³⁵ are bonded to form a 6-membered ring optionally substituted by amino or oxo,
  • (21) a group of the formula

wherein R³⁶ is

• • (a) a hydrogen atom,
  • (b) a halogen atom,
  • (c) nitro, or
  • (d) thienyl, or
  • (22) a group of the formula

or a salt thereof.

Item 1A. The compound of item 1, wherein

X is a hydrogen atom or a fluorine atom;
R is a hydrogen atom or alkyl;
R¹ is (1) cyclopropyl optionally substituted by 1 to 3 halogen atoms or (2) phenyl optionally substituted by 1 to 3 halogen atoms;
R² is alkyl, alkoxy, haloalkoxy, a chlorine atom or cyano; or
R¹ and R² are bonded to form a 5- or 6-membered ring optionally substituted by alkyl; and

R³ is

• • (1) a fused heterocyclic group of the formula

wherein
represents a single bond or a double bond,

X¹ is 0 (R⁵) or N,

R⁴ is a hydrogen atom or alkyl, and
R⁵ is (a) a hydrogen atom,

• • (b) a halogen atom,
  • (c) cyano,
  • (d) nitro,
  • (e) hydroxy,
  • (f) alkyl optionally substituted by 1 to 3 halogen atoms,
  • (g) alkenyl or alkynyl,
  • (h) aryl, or
  • (i) alkoxy optionally substituted by 1 to 3 halogen atoms,
    when X¹ is C(R⁵), R⁴ and R⁵ are optionally bonded to form a 5- or 6-membered ring optionally substituted by oxo,
    said fused heterocyclic group is optionally substituted by 1 or 2 substituents selected from the group consisting of a halogen atom, cyano, nitro, hydroxy and alkyl,
  • (2) a group of the formula

wherein

X² is C(R⁸) or N, and

R⁶, R⁷ and R⁸ are each independently,

• • (a) a hydrogen atom,
  • (b) a halogen atom,
  • (c) cyano,
  • (d) nitro,
  • (e) amino,
  • (f) alkyl optionally substituted by 1 to 3 substituents selected from the group consisting of a halogen atom, alkoxy and amino,
  • (g) alkenyl,
  • (h) alkynyl,
  • (i) aryl,
  • (j) formyl or CH═N—OH,
  • (k) carboxy,
  • (l) carbamoyl, or
  • (m) a 5- to 10-membered aromatic heterocyclic group optionally substituted by alkyl,
  • (3) a group of the formula

wherein

X³ and X⁴ are N, or

X³ is N and X⁴ is CR″, wherein R″ is a hydrogen atom, amino, hydroxy, alkyl or mercapto, or

X³ is CH and X⁴ is N,

R′ is a hydrogen atom or alkyl optionally substituted by 1 to 3 substituents selected from the group consisting of substituted hydroxy and amino, and
R⁶ is as defined above,

• • (4) a group of the formula

wherein
represents a single bond or a double bond and R⁶ is as defined above,

• • (5) 3-pyridyl optionally substituted by 1 or 2 substituents selected from the group consisting of
    • (a) a halogen atom,
    • (b) cyano,
    • (c) nitro,
    • (d) hydroxy,
    • (e) amino,
    • (f) alkyl optionally substituted by 1 to 3 substituents selected from the group consisting of a halogen atom, alkylamino, dialkylamino and hydroxy,
    • (g) alkenyl or alkynyl,
    • (h) aryl,
    • (i) cycloalkyl,
    • (j) alkoxy,
    • (k) alkylamino,
    • (l) dialkylamino,
    • (m) phenylamino optionally substituted by 1 to 3 halogen atoms,
    • (n) a cyclic amino group optionally substituted by alkoxycarbonyl,
    • (o) formyl,
    • (p) carbamoyl optionally substituted by alkyl optionally substituted by hydroxy, and
    • (q) a 5- to 10-membered aromatic heterocyclic group optionally substituted by alkyl,
  • (6) 4-pyridyl optionally substituted by a halogen atom,
  • (7) 5-pyrimidinyl optionally substituted by 1 or 2 substituents selected from the group consisting of amino, alkylamino, dialkylamino and carboxy,
  • (8) 2-indolyl, 3-indolyl, 5-indolyl, 6-indolyl, benzofuranyl, benzothiophenyl, benzoxazolyl or benzothiazolyl, each optionally substituted by 1 or 2 substituents selected from the group consisting of
    • (a) a halogen atom,
    • (b) cyano,
    • (c) nitro,
    • (d) hydroxy,
    • (e) alkyl optionally substituted by 1 to 3 substituents selected from the group consisting of amino, alkoxycarbonylamino, alkylamino and dialkylamino,
    • (f) alkoxy,
    • (g) formyl,
    • (h) carboxy, and
    • (j) amino optionally substituted by 1 or 2 substituents selected from the group consisting of
      • (i) alkoxycarbonyl,
      • (ii) alkylcarbonyl optionally substituted by a substituent selected from the group consisting of
        • (A) cycloalkyloxy optionally substituted by 1 to 3 alkyl,
        • (B) alkylamino,
        • (C) dialkylamino,
        • (D) a cyclic amino group optionally substituted by alkoxycarbonyl, and
        • (E) a halogen atom,
      • (iii) phenylcarbonyl optionally substituted by 1 to 3 substituents selected from the group consisting of alkyl and alkoxy,
      • (iv) cycloalkylcarbonyl,
      • (v) a 5- to 10-membered aromatic heterocyclylcarbonyl group optionally substituted by alkyl optionally substituted by 1 to 3 halogen atoms,
      • (vi) benzylcarbonyl optionally substituted by 1 to 3 substituents selected from the group consisting of a halogen atom and alkoxy,
      • (vii) arylsulfonyl optionally substituted by alkoxy,
      • (viii) cycloalkylalkylsulfonyl optionally substituted by 1 to 3 substituents selected from the group consisting of alkyl and oxo,
      • (ix) a 5- to 10-membered aromatic heterocyclylsulfonyl group optionally substituted by 1 to 3 alkyl, and
      • (x) —C(═N—CN)—SR⁹ wherein R⁹ is alkyl,
  • (9) a group of the formula

wherein
one of Y¹, Y², Y³ and Y⁴ is N or N⁺ (—O⁻), and the remaining three are each C(R²⁵), C(R²⁶) and C(R²⁷),

W is O, S or N(R²⁸)

R²³ is a hydrogen atom or alkyl, and
R²⁴, R²⁵, R²⁶ and R²⁷ are each independently,

• • (a) a hydrogen atom,
  • (b) cyano, or
  • (c) nitro,
  • (10) a group of the formula

wherein
R²⁸ is a hydrogen atom or hydroxy, and
R²⁹ is a hydrogen atom or alkyl,

• • (11) a group of the formula

wherein

X⁵ is C(R¹¹) or N,

X⁶ is CH₂, C(═O), O, S, SO₂ or N(R¹²),

X⁷ is CH(R¹³), C(═O) or N(R¹⁴),

X⁸ is CH(R¹⁵) or C(═O),

R¹⁰, R¹² and R¹⁴ are each independently,

• • (a) a hydrogen atom or
  • (b) alkyl, and
    R¹¹, R¹³ and R¹⁵ are each independently,
  • (a) a hydrogen atom,
  • (b) a halogen atom,
  • (c) cyano,
  • (d) nitro,
  • (e) amino,
  • (f) alkylamino,
  • (g) dialkylamino,
  • (h) alkyl optionally substituted by hydroxy, or
  • (i) alkenyl,
    when X⁵ is C(R¹¹), R¹⁰ and R¹¹ are optionally bonded to form a 5- or 6-membered ring optionally substituted by alkyl or oxo, and
    when X⁶ is N(R¹²) and X⁷ is CH(R¹³), R¹² and R¹³ are optionally bonded to form a 5- or 6-membered ring,
  • (12) a group of the formula

wherein R¹⁶ is

• • (a) a hydrogen atom,
  • (b) alkyl optionally substituted by 1 to 3 substituents selected from the group consisting of cyano, alkylamino and dialkylamino,
  • (c) alkenyl optionally substituted by carboxy,
  • (d) formyl,
  • (e) carboxy,
  • (f) carbamoyl,
  • (g) —C(R¹⁷)═N—OH wherein R¹⁷ is a hydrogen atom, cyano or hydroxy,
  • (h) a 5- to 10-membered aromatic heterocyclic group optionally substituted by alkyl, alkoxycarbonyl, carboxy or phenyl, or
  • (i) cyano,
  • (13) a group of the formula

wherein
R¹⁸ is a hydrogen atom or alkyl optionally substituted by 1 to 3 substituents selected from the group consisting of a halogen atom and phenyl, and
R¹⁹ and R²⁰ are each independently,

• • (a) a hydrogen atom,
  • (b) a halogen atom,
  • (c) cyano,
  • (d) alkyl optionally substituted by 1 to 3 substituents selected from the group consisting of
    • (i) a halogen atom,
    • (ii) cyano,
    • (iii) hydroxy,
    • (iv) amino,
    • (v) alkylamino,
    • (vi) dialkylamino, and
    • (vii) a cyclic amino group optionally substituted by alkyl,
  • (e) alkoxy,
  • (f) amino optionally substituted by 1 or 2 substituents selected from the group consisting of
    • (i) alkylcarbonyl optionally substituted by a cyclic amino group,
    • (ii) alkylsulfonyl,
    • (iii) carbamoyl, and
    • (iv) alkyl or cycloalkyl,
  • (g) carboxy,
  • (h) alkoxycarbonyl,
  • (i) carbamoyl optionally substituted by alkyl optionally substituted by amino, alkylamino, dialkylamino or alkoxycarbonylamino,
  • (j) formyl,
  • (k) a 5- to 10-membered aromatic heterocyclic group optionally substituted by alkyl,
  • (l) —CH═N—OR²¹ wherein R²¹ is a hydrogen atom or alkyl optionally substituted by alkylamino or dialkylamino, or
  • (m) nitro,
  • (14) a group of the formula

wherein
R³⁰ is (a) a hydrogen atom,

• • (b) a halogen atom,
  • (c) cyano,
  • (d) alkyl optionally substituted by 1 to 3 substituents selected from the group consisting of a halogen atom and hydroxy,
  • (e) alkenyl,
  • (f) alkynyl,
  • (g) alkoxy,
  • (h) formyl, or
  • (i) —CH═N—OH,
  • (15) naphthyl or isochromenyl, or
  • (16) quinolyl or isoquinolyl, or oxide derivative thereof, or a salt thereof.

Item 2. The compound of item 1 or 1A, wherein X is a fluorine atom, or a salt thereof.

Item 3. The compound of item 1 or 1A, wherein R³ is a fused heterocyclic group of the formula

wherein , X¹ and R⁴ are as defined in item 1, and said fused heterocyclic group is optionally substituted by 1 or 2 substituents selected from the group consisting of a halogen atom, cyano, nitro, hydroxy and alkyl, or a salt thereof.

Item 4. The compound of item 1 or 1A, wherein R³ is a group of the formula

wherein X², R⁶ and R⁷ are as defined in item 1, or a salt thereof.

Item 5. The compound of item 1 or 1A, wherein R³ is a group of the formula

wherein X³, X⁴, R⁶ and R′ are as defined in item 1, or a salt thereof.

Item 6. The compound of item 1 or 1A, wherein R³ is a group of the formula

wherein and R⁶ are as defined in item 1, or a salt thereof.

Item 7. The compound of item 1 or 1A, wherein R³ is a group of the formula

wherein R²² is

• • (a) a halogen atom,
  • (b) cyano,
  • (c) nitro,
  • (d) alkyl optionally substituted by 1 to 3 substituents selected from the group consisting of a halogen atom, alkylamino, dialkylamino and hydroxy,
  • (e) alkenyl or alkynyl,
  • (f) aryl,
  • (g) cycloalkyl,
  • (h) alkoxy,
  • (i) formyl, or
  • (j) carbamoyl optionally substituted by alkyl optionally substituted by hydroxy,
    or a salt thereof.

Item 8. The compound of item 1 or 1A, wherein R³ is 5-pyrimidinyl substituted by 1 or 2 substituents selected from the group consisting of amino, alkylamino, dialkylamino and carboxy, or a salt thereof.

Item 9. The compound of item 1 or 1A, wherein R³ is 2-indolyl optionally substituted by 1 or 2 substituents selected from the group consisting of

• • (a) a halogen atom,
  • (b) cyano,
  • (c) nitro,
  • (d) hydroxy,
  • (e) alkyl optionally substituted by 1 to 3 substituents selected from the group consisting of amino, alkoxycarbonylamino, alkylamino and dialkylamino,
  • (f) alkoxy,
  • (g) formyl,
  • (h) carboxy, and
  • (j) amino optionally substituted by 1 or 2 substituents selected from the group consisting of
    • (i) alkoxycarbonyl,
    • (ii) alkylcarbonyl optionally substituted by a substituent selected from the group consisting of
      • (A) cycloalkyloxy optionally substituted by 1 to 3 alkyl,
      • (B) alkylamino,
      • (C) dialkylamino,
      • (D) a cyclic amino group optionally substituted by alkoxycarbonyl, and
      • (E) a halogen atom,
    • (iii) phenylcarbonyl optionally substituted by 1 to 3 substituents selected from the group consisting of alkyl and alkoxy,
    • (iv) cycloalkylcarbonyl,
    • (v) a 5- to 10-membered aromatic heterocyclylcarbonyl group optionally substituted by alkyl optionally substituted by 1 to 3 halogen atoms,
    • (vi) benzylcarbonyl optionally substituted by 1 to 3 substituents selected from the group consisting of a halogen atom and alkoxy,
    • (vii) arylsulfonyl optionally substituted by alkoxy,
    • (viii) cycloalkylalkylsulfonyl optionally substituted by 1 to 3 substituents selected from the group consisting of alkyl and oxo,
    • (ix) a 5- to 10-membered aromatic heterocyclylsulfonyl group optionally substituted by 1 to 3 alkyl, and
    • (x) —C(═N—CN)—SR⁹ wherein R⁹ is alkyl, or a salt thereof.

Item 10. The compound of item 1 or 1A, wherein R³ is a group of the formula

wherein Y¹, Y², Y³, Y⁴, W and R²⁴ are as defined in item 1, or a salt thereof.

Item 11. The compound of item 1 or 1A, wherein R³ is a group of the formula

wherein R²⁸ and R²⁹ are as defined in item 1, or a salt thereof.

Item 12. The compound of item 1 or 1A, wherein R³ is a group of the formula

wherein X⁵, X⁶, X⁷, X⁸ and R¹⁰ are as defined in item 1, or a salt thereof.

Item 13. The compound of item 1 or 1A, wherein R³ is a group of the formula

wherein R^16a is

• • (a) alkyl optionally substituted by 1 to 3 substituents selected from the group consisting of cyano, alkylamino and dialkylamino,
  • (b) alkenyl optionally substituted by carboxy,
  • (c) formyl,
  • (d) carboxy,
  • (e) carbamoyl,
  • (f) —C(R¹⁷)═N—OH wherein R¹⁷ is a hydrogen atom, cyano or hydroxy,
  • (g) a 5- to 10-membered aromatic heterocyclic group optionally substituted by alkyl, alkoxycarbonyl, carboxy or phenyl, or
  • (h) cyano,
    or a salt thereof.

Item 14. The compound of item 1 or 1A, wherein R³ is a group of the formula

wherein
R^18a is alkyl, and
R^19a is (a) a halogen atom,

• • (b) cyano,
  • (c) alkyl optionally substituted by 1 to 3 substituents selected from the group consisting of
    • (i) a halogen atom,
    • (ii) cyano,
    • (iii) hydroxy,
    • (iv) amino,
    • (v) alkylamino,
    • (vi) dialkylamino, and
    • (vii) a cyclic amino group optionally substituted by alkyl,
  • (d) alkoxy,
  • (e) amino optionally substituted by 1 or 2 substituents selected from the group consisting of
    • (i) alkylcarbonyl optionally substituted by a cyclic amino group,
    • (ii) alkylsulfonyl,
    • (iii) carbamoyl, and
    • (iv) alkyl or cycloalkyl,
  • (f) carboxy,
  • (g) alkoxycarbonyl,
  • (h) carbamoyl optionally substituted by alkyl optionally substituted by amino, alkylamino, dialkylamino or alkoxycarbonylamino,
  • (i) formyl,
  • (j) a 5- to 10-membered aromatic heterocyclic group optionally substituted by alkyl,
  • (k) —CH═N—OR²¹ wherein R²¹ is a hydrogen atom or alkyl optionally substituted by alkylamino or dialkylamino, or
  • (l) nitro,
    or a salt thereof.

Item 15. The compound of item 1 or 1A, wherein R³ is a group of the formula

wherein R³⁰ is as defined in item 1, or a salt thereof.

Item 16. The compound of item 1 or 1A, wherein R³ is naphthyl or isochromenyl, or a salt thereof.

Item 17. The compound of item 1 or 1A, wherein R³ is quinolyl or isoquinolyl, or oxide derivative thereof, or a salt thereof.

Item 18. The compound of item 1 or 1A, wherein R is a hydrogen atom, or a salt thereof.

Item 19. The compound of item 1 or 1A, wherein R¹ is cyclopropyl, 2-fluorocyclopropyl or 2,4-difluorophenyl, or a salt thereof.

Item 20. The compound of item 1 or 1A, wherein R² is methyl, methoxy or a chlorine atom, or a salt thereof.

Item 21. A pharmaceutical composition comprising a compound of item 1 or 1A or a salt thereof and a pharmaceutically acceptable carrier.

Item 22. An antimicrobial agent comprising a compound of item 1 or 1A or a salt thereof.

Item 23. A compound of item 1 or 1A or a salt thereof for use as a medicament.

Item 24. A compound of item 1 or 1A or a salt thereof for use as an antimicrobial agent.

Item 25. A compound of item 1 or 1A or a salt thereof for use in the prevention or treatment of a bacterial infection.

Item 26. Use of a compound of item 1 or 1A or a salt thereof for the manufacture of a medicament for preventing or treating a bacterial infection.

Item 27. A method for preventing or treating a bacterial infection which comprises administering an effective amount of a compound of item 1 or 1A or a salt thereof to a human or an animal.

The compound of the formula (I) or a salt thereof (hereinafter sometimes to be abbreviated as compound (I)) has excellent antibacterial activity against various gram positive and gram negative bacteria, and is useful for the prevention or treatment of various infectious diseases induced by various bacteria in human, other animals and fish and is also useful as an external antimicrobial or disinfectant agent for medical instruments or the like.

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1 is a graph showing the results of the animals administered with compound 2-18 in Experimental Example 2.

FIG. 2 is a graph showing the results of the animals administered with vancomycin in Experimental Example 2.

DETAILED DESCRIPTION OF THE INVENTION

Specific examples of groups in the formula (I) are as follows.

Examples of “halogen atom” include fluorine atom, chlorine atom, bromine atom, and iodine atom.

Examples of “alkyl” and “alkyl” moiety in “alkylamino”, “dialkylamino”, “alkylcarbonyl”, “cycloalkylalkylsulfonyl”, “cycloalkylalkyl”, “aminoalkyl” and “alkylsulfonyl” include straight or branched C_1-6 alkyl such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, 1-ethylpropyl, isopentyl, neopentyl, tert-pentyl, hexyl, 1,2,2-trimethylpropyl, 3,3-dimethylbutyl, 2-ethylbutyl, isohexyl, 3-methylpentyl, etc.

Examples of “alkenyl” include straight or branched C_2-6 alkenyl such as vinyl, 1-propenyl, 2-propenyl, 1-butenyl, 2-butenyl, 3-butenyl, 1-methyl-2-propenyl, 2-pentenyl, 2-hexenyl, etc.

Examples of “alkynyl” include straight or branched C_2-6 alkynyl such as ethynyl, 2-propynyl, 2-butynyl, 3-butynyl, 1-methyl-2-propynyl, 2-pentynyl, 2-hexynyl, etc.

Examples of “alkoxy” and “alkoxy” moiety in “haloalkoxy”, “alkoxycarbonyl” and “alkoxycarbonylamino” include straight or branched C_1-6 alkoxy such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentyloxy, isopentyloxy, neopentyloxy, tert-pentyloxy, hexyloxy, isohexyloxy, 3-methylpentyloxy, etc.

Examples of “haloalkoxy” include straight or branched C_1-6 alkoxy substituted by 1 to 3 halogen atoms. Examples thereof include fluoromethoxy, difluoromethoxy, trifluoromethoxy, chloromethoxy, dichloromethoxy, trichloromethoxy, bromomethoxy, dibromomethoxy, dichlorofluoromethoxy, 2,2,2-trifluoroethoxy, 2-chloroethoxy, 3,3,3-trifluoropropoxy, 2-chloropropoxy, 3-chloropropoxy, 3-bromopropoxy, 4,4,4-trifluorobutoxy, 2-chlorobutoxy, 4-chlorobutoxy, 4-bromobutoxy, 5,5,5-trifluoropentyloxy, 5-chloropentyloxy, 6,6,6-trifluorohexyloxy, 6-chlorohexyloxy, etc. Preferable examples thereof include difluoromethoxy.

Examples of “alkenyloxy” include straight or branched C_2-6 alkenyloxy such as vinyloxy, 1-propenyloxy, 2-propenyloxy, 1-butenyloxy, 2-butenyloxy, 3-butenyloxy, 1-methyl-2-propenyloxy, 2-pentenyloxy, 2-hexenyloxy, etc.

Examples of “aryl” and “aryl” moiety in “arylsulfonyl” include C_6-14 (preferably C_6-10) aryl such as phenyl, naphthyl (e.g., 1-naphthyl, 2-naphthyl), etc. Preferable examples thereof include phenyl.

Examples of “5- to 10-membered aromatic heterocyclic group” and “5- to 10-membered aromatic heterocyclyl” moiety in “5- to 10-membered aromatic heterocyclylcarbonyl group” and “5- to 10-membered aromatic heterocyclylsulfonyl group” include 5- to 10-membered (preferably 5- or 6-membered) aromatic heterocyclic group containing 1 to 4 (preferably 1 to 3, more preferably 1 or 2) heteroatoms selected from a nitrogen atom, an oxygen atom and a sulfur atom. Examples thereof include furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl (e.g., 1,2,3-triazolyl, 1,2,4-triazolyl), tetrazolyl, isoxazolyl, oxazolyl, furazanyl, isothiazolyl, thiazolyl, pyridyl (e.g., 2-pyridyl, 3-pyridyl, 4-pyridyl), pyridazinyl, pyrimidinyl, pyrazinyl, benzofuranyl, isobenzofuranyl, benzo[b]thiophenyl, benzo[c]thiophenyl, indolyl, isoindolyl, indolizinyl, indazolyl, benzimidazolyl, benzotriazolyl, benzoxazolyl, 1,2-benzisoxazolyl, benzothiazolyl, 1,2-benzisothiazolyl, purinyl, quinolyl, isoquinolyl, quinolizinyl, cinnolinyl, quinazolinyl, quinoxalinyl, phthalazinyl, naphthyridinyl, pteridinyl, etc. Preferable examples thereof include pyrrolyl, imidazolyl, oxazolyl, triazolyl (e.g., 1,2,3-triazolyl, 1,2,4-triazolyl), tetrazolyl, pyridyl (e.g., 2-pyridyl, 3-pyridyl, 4-pyridyl), benzimidazolyl, etc.

Examples of “alkylamino” include C_1-6 alkylamino such as methylamino, ethylamino, propylamino, isopropylamino, butylamino, isobutylamino, sec-butylamino, tert-butylamino, pentylamino, isopentylamino, neopentylamino, tert-pentylamino, hexylamino, etc.

Examples of “dialkylamino” include di(C_1-6 alkyl)amino such as dimethylamino, diethylamino, dipropylamino, diisopropylamino, dibutylamino, diisobutylamino, di(sec-butyl)amino, di(tert-butyl)amino, dipentylamino, di(tert-pentyl)amino, dihexylamino, ethylmethylamino, etc.

Examples of “aminoalkyl” include amino-C_1-6 alkyl such as aminomethyl, 2-aminoethyl, 3-aminopropyl, 4-aminobutyl, 5-aminopentyl, 6-aminohexyl, etc.

Examples of “cycloalkyl” and “cycloalkyl” moiety in “cycloalkyloxy”, “cycloalkylcarbonyl”, “cycloalkylalkyl” and “cycloalkylalkylsulfonyl” include C_3-8 cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, norbornanyl (e.g., 2-norbornanyl), etc.

Examples of “cycloalkylalkyl” include C_3-8 cycloalkyl-C_1-6 alkyl such as cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, cycloheptylmethyl, cyclooctylmethyl, norbornanylmethyl (e.g., norbornan-2-ylmethyl), etc.

Examples of “cyclic amino group” includes a 4- to 7-membered (preferably 5- or 6-membered) cyclic amino group containing one nitrogen atom and optionally further containing one heteroatom selected from a nitrogen atom, an oxygen atom and a sulfur atom. Examples thereof include 1-azetidinyl, 1-pyrrolidinyl, 1-imidazolidinyl, 1-pyrazolidinyl, piperidino, 1-piperazinyl, morpholino, thiomorpholino, 1-azepanyl, 1,4-oxazepan-4-yl, etc. Preferable examples thereof include 1-pyrrolidinyl, piperidino, 1-piperazinyl, morpholino, thiomorpholino, etc.

Examples of “alkoxycarbonyl” include C_1-6 alkoxy-carbonyl wherein the alkoxy moiety is C_1-6 alkoxy. Examples thereof include methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, sec-butoxycarbonyl, tert-butoxycarbonyl, pentyloxycarbonyl, hexyloxycarbonyl, etc.

Examples of “alkoxycarbonylamino” include C_1-6 alkoxy-carbonylamino wherein the alkoxy moiety is C_1-6 alkoxy. Examples thereof include methoxycarbonylamino, ethoxycarbonylamino, propoxycarbonylamino, isopropoxycarbonylamino, butoxycarbonylamino, isobutoxycarbonylamino, sec-butoxycarbonylamino, tert-butoxycarbonylamino, pentyloxycarbonylamino, hexyloxycarbonylamino, etc.

Examples of “alkylcarbonyl” include C_1-6 alkyl-carbonyl wherein the alkyl moiety is C_1-6 alkyl. Examples thereof include acetyl, ethylcarbonyl, propylcarbonyl, isopropylcarbonyl, butylcarbonyl, isobutylcarbonyl, sec-butylcarbonyl, tert-butylcarbonyl, pentylcarbonyl, hexylcarbonyl, etc.

Examples of “cycloalkyloxy” include C_3-8 cycloalkyloxy such as cyclopropyloxy, cyclobutyloxy, cyclopentyloxy, cyclohexyloxy, cycloheptyloxy, cyclooctyloxy, etc.

Examples of “cycloalkylcarbonyl” include C_3-8 cycloalkylcarbonyl such as cyclopropylcarbonyl, cyclobutylcarbonyl, cyclopentylcarbonyl, cyclohexylcarbonyl, cycloheptylcarbonyl, cyclooctylcarbonyl, etc.

Examples of “5- to 10-membered aromatic heterocyclylcarbonyl group” include a 5- to 10-membered (preferably 5- or 6-membered) aromatic heterocyclylcarbonyl group wherein the heterocyclyl moiety contains 1 to 4 (preferably 1 to 3, more preferably 1 or 2) heteroatoms selected from a nitrogen atom, an oxygen atom and a sulfur atom. Examples of the heterocyclyl moiety are same as the examples of the 5- to 10-membered aromatic heterocyclic group mentioned above. Preferable examples of “5- to 10-membered aromatic heterocyclylcarbonyl group” include pyridylcarbonyl (e.g., 2-pyridylcarbonyl, 3-pyridylcarbonyl, 4-pyridylcarbonyl).

Examples of “arylsulfonyl” include C_6-14 (preferably C_6-10) arylsulfonyl such as phenylsulfonyl, naphthylsulfonyl (e.g., 1-naphthylsulfonyl, 2-naphthylsulfonyl), etc. Preferable examples thereof include phenylsulfonyl.

Examples of “cycloalkylalkylsulfonyl” include C_3-8 cycloalkyl-C_1-6 alkylsulfonyl such as cyclopropylmethylsulfonyl, cyclobutylmethylsulfonyl, cyclopentylmethylsulfonyl, cyclohexylmethylsulfonyl, cycloheptylmethylsulfonyl, cyclooctylmethylsulfonyl, norbornanylmethylsulfonyl (e.g., norbornan-2-ylmethylsulfonyl), etc.

Examples of “5- to 10-membered aromatic heterocyclylsulfonyl group” include a 5- to 10-membered (preferably 5- or 6-membered) aromatic heterocyclylsulfonyl group wherein the heterocyclyl moiety contains 1 to 4 (preferably 1 to 3, more preferably 1 or 2) heteroatoms selected from a nitrogen atom, an oxygen atom and a sulfur atom. Examples of the heterocyclyl moiety are same as the examples of the 5- to 10-membered aromatic heterocyclic group mentioned above. Preferable examples of “5- to 10-membered aromatic heterocyclylsulfonyl group” include imidazolylsulfonyl.

Examples of “alkylsulfonyl” include C_1-6 alkylsulfonyl wherein the alkyl moiety is C_1-6 alkyl. Examples thereof include methylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, butylsulfonyl, isobutylsulfonyl, sec-butylsulfonyl, tert-butylsulfonyl, pentylsulfonyl, hexylsulfonyl, etc.

Examples of “cyclopropyl optionally substituted by 1 to 3 halogen atoms” include cyclopropyl optionally substituted by 1 fluorine atom such as cyclopropyl, 2-fluorocyclopropyl, etc.

Examples of “phenyl optionally substituted by 1 to 3 halogen atoms” include phenyl substituted by two fluorine atoms such as 2,4-difluorophenyl, etc.

Examples of “5- to 10-membered saturated heterocyclic group” include a 5- to 10-membered (preferably 5- or 6-membered) saturated heterocyclic group containing 1 to 4 (preferably 1 to 3, more preferably 1 or 2) heteroatoms selected from a nitrogen atom, an oxygen atom and a sulfur atom. Examples thereof include pyrrolidinyl, piperidyl, piperazinyl, morpholinyl, thiomorpholinyl, etc.

Examples of “6-membered ring optionally substituted by amino or oxo” formed by R³⁴ and R³⁵ include a 6-membered ring optionally containing one nitrogen atom, and said ring is optionally substituted by amino or oxo. Examples thereof include cyclohexene and dihydropyridine, each optionally substituted by amino or oxo.

Examples of “5- or 6-membered ring optionally substituted by alkyl” formed by R¹ and R² include a 5- or 6-membered (preferably 6-membered) ring containing one nitrogen atom and optionally further containing one oxygen atom, and said ring is optionally substituted by alkyl. Preferably, R¹ and R² are optionally bonded to form —O—CH₂—CH(CH₃)— wherein the oxygen atom is bonded to the phenyl ring of the quinolone ring as shown below.

Examples of “5- or 6-membered ring optionally substituted by oxo” formed by R⁴ and R⁵ include a 5- or 6-membered (preferably 6-membered) ring containing one nitrogen atom and optionally further containing one oxygen atom, and said ring is optionally substituted by oxo. Preferably, R⁴ and R⁵ are optionally bonded to form —CH₂—O—(C═O)— wherein the carbonyl is bonded to the phenyl ring of the quinolone ring as shown below.

Examples of “5- or 6-membered ring optionally substituted by alkyl or oxo” formed by R¹⁰ and R¹¹ include a 5- or 6-membered (preferably 5-membered) ring containing 2 or 3 nitrogen atoms, and said ring is optionally substituted by alkyl or oxo. Preferably, R¹⁰ and R¹¹ are optionally bonded to form —(C═O)—NH—, —C(R³¹)═N— or —N═N— wherein R³¹ is a hydrogen atom or alkyl, and the nitrogen atom is bonded to the phenyl ring of the fused ring, as shown below.

Examples of “5- or 6-membered ring” formed by R¹² and R¹³ include a 5- or 6-membered (preferably 6-membered) ring containing one nitrogen atom. Preferably, R¹² and R¹² are optionally bonded to form —(CH₂)₄— as shown below.

X is a hydrogen atom or a fluorine atom, preferably, a fluorine atom.

R is a hydrogen atom or alkyl, preferably, a hydrogen atom.

R¹ is (1) cyclopropyl optionally substituted by 1 to 3 halogen atoms or (2) phenyl optionally substituted by 1 to 3 halogen atoms, preferably, cyclopropyl, 2-fluorocyclopropyl or 2,4-difluorophenyl.

R² is a hydrogen atom; alkyl optionally substituted by 1 or 2 substituents selected from the group consisting of a halogen atom and hydroxyl; alkoxy; haloalkoxy; a halogen atom; cyano; cyclopropyl; nitro; amino; formyl; alkenyl or alkynyl, preferably, alkyl, alkoxy, haloalkoxy, a chlorine atom or cyano, more preferably, C_1-6 alkyl, C_1-6 alkoxy, C_1-6 alkoxy substituted by 1 to 3 halogen atoms, a chlorine atom or cyano, still more preferably, methyl, methoxy or a chlorine atom.

Examples of a fused heterocyclic group of the formula (A) or (B) include a fused heterocyclic group of the formula

wherein X¹ and R⁴ are as defined above, and said fused heterocyclic group is optionally substituted by 1 or 2 substituents selected from the group consisting of a halogen atom, cyano, nitro, hydroxy and alkyl.

Preferable examples of a fused heterocyclic group of the formula (A) or (B) include a fused heterocyclic group of the formula

wherein R⁴ and R⁵ are as defined above, and said fused heterocyclic group is optionally substituted by 1 or 2 substituents selected from the group consisting of a halogen atom, cyano, nitro, hydroxy and alkyl.

Other preferable examples of a fused heterocyclic group of the formula (A) or (B) include a fused heterocyclic group of the formula

wherein X¹ and R⁴ are as defined above, and said fused heterocyclic group is optionally substituted by 1 or 2 substituents selected from the group consisting of a halogen atom, cyano, nitro, hydroxy and alkyl.

Examples of a group of the formula (C) include a group of the formula

wherein X², R⁶ and R⁷ are as defined above.

Preferable examples of a group of the formula (C) include a group of the formula

wherein R⁶, R⁷ and R⁸ are as defined above.

In the above formulas, R⁶, R⁷ and R⁸ are each independently,

• • (a) a hydrogen atom,
  • (b) a halogen atom,
  • (c) cyano,
  • (d) nitro,
  • (e) amino,
  • (f) alkyl optionally substituted by 1 to 3 substituents selected from the group consisting of a halogen atom and amino,
  • (g) alkenyl,
  • (h) alkynyl,
  • (i) aryl,
  • (j) formyl,
  • (k) carboxy,
  • (l) carbamoyl, or
  • (m) a 5- to 10-membered aromatic heterocyclic group (e.g., pyridyl, triazolyl) optionally substituted by alkyl.

Examples of a group of the formula (D) or (E) include a group of the formula

wherein R⁶ is as defined above. R⁶ is preferably a hydrogen atom, a halogen atom, nitro or amino.

Preferably, R³ is 3-pyridyl optionally substituted by 1 or 2 substituents selected from the group consisting of

• • (a) a halogen atom,
  • (b) cyano,
  • (c) nitro,
  • (d) hydroxy,
  • (e) amino,
  • (f) alkyl optionally substituted by 1 to 3 substituents selected from the group consisting of a halogen atom, alkylamino, dialkylamino and hydroxy,
  • (g) alkenyl,
  • (h) aryl,
  • (i) cycloalkyl,
  • (j) alkoxy,
  • (k) alkylamino,
  • (l) dialkylamino,
  • (m) phenylamino optionally substituted by 1 to 3 halogen atoms,
  • (n) a cyclic amino group (e.g., 1-piperazinyl, morpholino) optionally substituted by alkoxycarbonyl,
  • (o) formyl,
  • (p) carbamoyl, and
  • (q) a 5- to 10-membered aromatic heterocyclic group (e.g., triazolyl) optionally substituted by alkyl.

More preferably, R³ is a group of the formula

wherein R²² is

• • (a) a halogen atom,
  • (b) cyano,
  • (c) nitro,
  • (d) alkyl optionally substituted by 1 to 3 substituents selected from the group consisting of a halogen atom, alkylamino, dialkylamino and hydroxy,
  • (e) alkenyl,
  • (f) aryl,
  • (g) cycloalkyl,
  • (h) alkoxy,
  • (i) formyl, or
  • (j) carbamoyl.

Preferably, R²² is

• • (a) cyano,
  • (b) nitro,
  • (c) aryl,
  • (d) formyl, or
  • (e) carbamoyl.

Preferably, R³ is 5-pyrimidinyl substituted by 1 or 2 substituents selected from the group consisting of amino, alkylamino and dialkylamino.

Preferably, R³ is 2-indolyl, 3-indolyl, 5-indolyl or 6-indolyl, each optionally substituted by 1 or 2 substituents selected from the group consisting of (a) a halogen atom,

• • (b) cyano,
  • (c) nitro,
  • (d) hydroxy,
  • (e) alkyl optionally substituted by 1 to 3 substituents selected from the group consisting of amino, alkoxycarbonylamino, alkylamino and dialkylamino,
  • (f) alkoxy,
  • (g) formyl,
  • (h) carboxy, and
  • (j) amino optionally substituted by 1 or 2 substituents selected from the group consisting of
    • (i) alkoxycarbonyl,
    • (ii) alkylcarbonyl optionally substituted by a substituent selected from the group consisting of
      • (A) cycloalkyloxy optionally substituted by 1 to 3 alkyl,
      • (B) alkylamino,
      • (C) dialkylamino,
      • (D) a cyclic amino group (e.g., morpholino, 1-piperazinyl) optionally substituted by alkoxycarbonyl, and
      • (E) a halogen atom,
    • (iii) phenylcarbonyl optionally substituted by 1 to 3 substituents selected from the group consisting of alkyl and alkoxy,
    • (iv) cycloalkylcarbonyl,
    • (v) a 5- to 10-membered aromatic heterocyclylcarbonyl group (e.g., pyridylcarbonyl) optionally substituted by alkyl optionally substituted by 1 to 3 halogen atoms,
    • (vi) benzylcarbonyl optionally substituted by 1 to 3 substituents selected from the group consisting of a halogen atom and alkoxy,
    • (vii) arylsulfonyl optionally substituted by alkoxy,
    • (viii) cycloalkylalkylsulfonyl optionally substituted by 1 to 3 substituents selected from the group consisting of alkyl and oxo (e.g., camphorsulfonyl),
    • (ix) a 5- to 10-membered aromatic heterocyclylsulfonyl group (e.g., imidazolylsulfonyl) optionally substituted by 1 to 3 alkyl, and
    • (x) —C(═N—CN)—SR⁹ wherein R⁹ is alkyl.

More preferably, R³ is 2-indolyl optionally substituted by 1 or 2 substituents selected from the group consisting of

• • (a) a halogen atom,
  • (b) cyano,
  • (c) nitro,
  • (d) hydroxy,
  • (e) alkyl optionally substituted by 1 to 3 substituents selected from the group consisting of amino, alkoxycarbonylamino, alkylamino and dialkylamino,
  • (f) alkoxy,
  • (g) formyl,
  • (h) carboxy, and
  • (j) amino optionally substituted by 1 or 2 substituents selected from the group consisting of
    • (i) alkoxycarbonyl,
    • (ii) alkylcarbonyl optionally substituted by a substituent selected from the group consisting of
      • (A) cycloalkyloxy optionally substituted by 1 to 3 alkyl,
      • (B) alkylamino,
      • (C) dialkylamino,
      • (D) a cyclic amino group (e.g., morpholino, 1-piperazinyl) optionally substituted by alkoxycarbonyl, and
      • (E) a halogen atom,
    • (iii) phenylcarbonyl optionally substituted by 1 to 3 substituents selected from the group consisting of alkyl and alkoxy,
    • (iv) cycloalkylcarbonyl,
    • (v) a 5- to 10-membered aromatic heterocyclylcarbonyl group (e.g., pyridylcarbonyl) optionally substituted by alkyl optionally substituted by 1 to 3 halogen atoms,
    • (vi) benzylcarbonyl optionally substituted by 1 to 3 substituents selected from the group consisting of a halogen atom and alkoxy,
    • (vii) arylsulfonyl optionally substituted by alkoxy,
    • (viii) cycloalkylalkylsulfonyl optionally substituted by 1 to 3 substituents selected from the group consisting of alkyl and oxo (e.g., camphorsulfonyl),
    • (ix) a 5- to 10-membered aromatic heterocyclylsulfonyl group (e.g., imidazolylsulfonyl) optionally substituted by 1 to 3 alkyl, and
    • (x) —C(═N—CN)—SR⁹ wherein R⁹ is alkyl.

Examples of a group of the formula (F) or (G) include a group of the formula

wherein
R²³ is a hydrogen atom or alkyl, and
R²⁴, R²⁵, R²⁶ and R²⁷ are each independently,

• • (a) a hydrogen atom,
  • (b) cyano, or
  • (c) nitro.

Examples of a group of the formula (K) include a group of the formula

wherein X⁵, X⁶, X⁷, X⁸ and R¹⁰ are as defined above.

Preferable examples of a group of the formula (K) include a group of the formula

wherein R¹⁰, R¹¹, R¹², R¹³, R¹⁴ and R¹⁵ are as defined above.

When R¹⁰ and R¹¹ are bonded to form a 5- or 6-membered ring optionally substituted by alkyl or oxo, preferable examples of a group of the formula (K) include a group of the formula

wherein R³¹ is a hydrogen atom or alkyl.

When R¹² and R¹³ are bonded to form a 5- or 6-membered ring, preferable examples of a group of the formula (K) include a group of the formula

More preferable examples of a group of the formula (K) include a group of the formula

wherein R^10a is

• • (a) a hydrogen atom or
  • (b) alkyl, and
    R^11a, R^13a and R^15a are each independently,
  • (a) a hydrogen atom,
  • (b) a halogen atom,
  • (c) cyano,
  • (d) nitro,
  • (e) amino,
  • (f) alkylamino,
  • (g) dialkylamino,
  • (h) alkyl optionally substituted by hydroxy, or
  • (i) alkenyl,
    R^10a and R^11a are optionally bonded to form a 5- or 6-membered ring optionally substituted by alkyl or oxo,
    provided that R^10a, R^11a, R^13a, and R^15a are not simultaneously hydrogen atom.

Preferably, R³ is a group of the formula

wherein R¹⁶ is

• • (a) a hydrogen atom,
  • (b) alkyl optionally substituted by 1 to 3 substituents selected from the group consisting of cyano, alkylamino and dialkylamino,
  • (c) alkenyl optionally substituted by carboxy,
  • (d) formyl,
  • (e) carboxy,
  • (f) carbamoyl,
  • (g) —C(R¹⁷)═N—OH wherein R¹⁷ is a hydrogen atom, cyano or hydroxy, or
  • (h) a 5- to 10-membered aromatic heterocyclic group (e.g., tetrazolyl, pyrrolyl, oxazolyl, benzimidazolyl, triazolyl) optionally substituted by alkyl, alkoxycarbonyl, carboxy or phenyl.

More preferably, R³ is a group of the formula

wherein R^16a is

• • (a) alkyl optionally substituted by 1 to 3 substituents selected from the group consisting of cyano, alkylamino and dialkylamino,
  • (b) alkenyl optionally substituted by carboxy,
  • (c) formyl,
  • (d) carboxy,
  • (e) carbamoyl,
  • (f) —C(R¹⁷)═N—OH wherein R¹⁷ is a hydrogen atom, cyano or hydroxy, or
  • (g) a 5- to 10-membered aromatic heterocyclic group (e.g., tetrazolyl, pyrrolyl, oxazolyl, benzimidazolyl, triazolyl) optionally substituted by alkyl, alkoxycarbonyl, carboxy or phenyl.

Preferably, R³ is a group of the formula

wherein
R¹⁸ is alkyl optionally substituted by 1 to 3 substituents selected from the group consisting of a halogen atom and phenyl, and
R¹⁹ and R²⁰ are each independently,

• • (a) a hydrogen atom,
  • (b) a halogen atom,
  • (c) cyano,
  • (d) alkyl optionally substituted by 1 to 3 substituents selected from the group consisting of
    • (i) a halogen atom,
    • (ii) cyano,
    • (iii) hydroxy,
    • (iv) amino,
    • (v) alkylamino,
    • (vi) dialkylamino, and
    • (vii) a cyclic amino group (e.g., 1-piperazinyl) optionally substituted by alkyl,
  • (e) alkoxy,
  • (f) amino optionally substituted by 1 or 2 substituents selected from the group consisting of
    • (i) alkylcarbonyl optionally substituted by a cyclic amino group (e.g., morpholino),
    • (ii) alkylsulfonyl, and
    • (iii) carbamoyl,
  • (g) carboxy,
  • (h) alkoxycarbonyl,
  • (i) carbamoyl optionally substituted by alkyl optionally substituted by amino, alkylamino, dialkylamino or alkoxycarbonylamino,
  • (j) formyl,
  • (k) a 5- to 10-membered aromatic heterocyclic group (e.g., oxazolyl, benzimidazolyl), or
  • (l) —CH═N—OR²¹ wherein R²¹ is a hydrogen atom or alkyl optionally substituted by alkylamino or dialkylamino.

More preferably, R³ is a group of the formula

wherein
R^18a is alkyl, and
R^19a is (a) a halogen atom,

• • (b) cyano,
  • (c) alkyl optionally substituted by 1 to 3 substituents selected from the group consisting of
    • (i) a halogen atom,
    • (ii) cyano,
    • (iii) hydroxy,
    • (iv) amino,
    • (v) alkylamino,
    • (vi) dialkylamino, and
    • (vii) a cyclic amino group (e.g., 1-piperazinyl) optionally substituted by alkyl,
  • (d) alkoxy,
  • (e) amino optionally substituted by 1 or 2 substituents selected from the group consisting of
    • (i) alkylcarbonyl optionally substituted by a cyclic amino group (e.g., morpholino),
    • (ii) alkylsulfonyl, and
    • (iii) carbamoyl,
  • (f) carboxy,
  • (g) alkoxycarbonyl,
  • (h) carbamoyl optionally substituted by alkyl optionally substituted by amino, alkylamino, dialkylamino or alkoxycarbonylamino,
  • (i) formyl,
  • (j) a 5- to 10-membered aromatic heterocyclic group (e.g., oxazolyl, benzimidazolyl), or
  • (k) —CH═N—OR²¹ wherein R²¹ is a hydrogen atom or alkyl optionally substituted by alkylamino or dialkylamino.

Preferable examples of compound (I) are as described below.

[Compound I-1]

A compound of the formula (I) wherein

R is a hydrogen atom;

R¹ is cyclopropyl, 2-fluorocyclopropyl or 2,4-difluorophenyl;
R² is C_1-6 alkyl (e.g., methyl), C_1-6 alkoxy (e.g., methoxy) or a chlorine atom; or
R¹ and R² are optionally bonded to form —O—CH₂—CH(CH₃)— wherein the oxygen atom is bonded to the phenyl ring of the quinolone ring; and
R³ is a fused heterocyclic group of the formula

wherein

X¹ is C(R⁵) or N,

R⁴ is a hydrogen atom or C_1-6 alkyl, and
R⁵ is (a) a hydrogen atom,

• • (b) a halogen atom,
  • (c) cyano,
  • (d) nitro,
  • (e) hydroxy,
  • (f) C_1-6 alkyl optionally substituted by 1 to 3 halogen atoms,
  • (g) C_2-6 alkynyl,
  • (h) C_6-14 aryl, or
  • (i) C_1-6 alkoxy optionally substituted by 1 to 3 halogen atoms,
    when X¹ is C(R⁵), R⁴ and R⁵ are optionally bonded to form —CH₂—O—(C═O)— wherein the carbonyl is bonded to the phenyl ring of the quinolone ring,
    said fused heterocyclic group is optionally substituted by 1 or 2 substituents selected from the group consisting of a halogen atom, cyano, nitro, hydroxy and C_1-6 alkyl, or a salt thereof.

[Compound I-2]

A compound of the formula (I) wherein

R is a hydrogen atom;
R¹ is cyclopropyl, 2-fluorocyclopropyl or 2,4-difluorophenyl;
R² is C_1-6 alkyl (e.g., methyl), C_1-6 alkoxy (e.g., methoxy) or a chlorine atom; or
R¹ and R² are optionally bonded to form —O—CH₂—CH(CH₃)— wherein the oxygen atom is bonded to the phenyl ring of the quinolone ring; and
R³ is a group of the formula

wherein

X² is C(R⁸) or N, and

R⁶, R⁷ and R⁸ are each independently,

• • (a) a hydrogen atom,
  • (b) a halogen atom,
  • (c) cyano,
  • (d) nitro,
  • (e) amino,
  • (f) C_1-6 alkyl optionally substituted by 1 to 3 substituents selected from the group consisting of a halogen atom and amino,
  • (g) C_2-6 alkenyl,
  • (h) C_2-6 alkynyl,
  • (i) C_6-14 aryl,
  • (j) formyl,
  • (k) carboxy,
  • (l) carbamoyl, or
  • (m) a 5- to 10-membered aromatic heterocyclic group (e.g., pyridyl, triazolyl) optionally substituted by C_1-6 alkyl,
    or a salt thereof.

[Compound I-3]

A compound of the formula (I) wherein

R is a hydrogen atom;
R¹ is cyclopropyl, 2-fluorocyclopropyl or 2,4-difluorophenyl;
R² is C_1-6 alkyl (e.g., methyl), C_1-6 alkoxy (e.g., methoxy) or a chlorine atom; and
R³ is a group of the formula

wherein

X³ and X⁴ are N, or

X³ is N and X⁴ is CH, or

X³ is CH and X⁴ is N, and

R⁶ is a hydrogen atom, a halogen atom, nitro or amino,
or a salt thereof.

[Compound I-4]

A compound of the formula (I) wherein

R is a hydrogen atom;
R¹ is cyclopropyl, 2-fluorocyclopropyl or 2,4-difluorophenyl;
R² is C_1-6 alkyl (e.g., methyl), C_1-6 alkoxy (e.g., methoxy) or a chlorine atom; and
R³ is a group of the formula

or a salt thereof.

[Compound I-5]

A compound of the formula (I) wherein

R is a hydrogen atom;
R¹ is cyclopropyl, 2-fluorocyclopropyl or 2,4-difluorophenyl;
R² is C_1-6 alkyl (e.g., methyl), C_1-6 alkoxy (e.g., methoxy) or a chlorine atom; or
R¹ and R² are optionally bonded to form —O—CH₂—CH(CH₃)— wherein the oxygen atom is bonded to the phenyl ring of the quinolone ring; and
R³ is a group of the formula

wherein R²² is

• • (a) a halogen atom,
  • (b) cyano,
  • (c) nitro,
  • (d) C_1-6 alkyl optionally substituted by 1 to 3 substituents selected from the group consisting of a halogen atom, C_1-6 alkylamino, di(C_1-6 alkyl)amino and hydroxy,
  • (e) C_2-6 alkenyl,
  • (f) C_6-14 aryl,
  • (g) C_3-8 cycloalkyl,
  • (h) C_1-6 alkoxy,
  • (i) formyl, or
  • (j) carbamoyl,
    or a salt thereof.

[Compound I-6]

A compound of the formula (I) wherein

• • R is a hydrogen atom;
  • R¹ is cyclopropyl, 2-fluorocyclopropyl or 2,4-difluorophenyl;
  • R² is C_1-6 alkyl (e.g., methyl), C_1-6 alkoxy (e.g., methoxy) or a chlorine atom; or
  • R¹ and R² are optionally bonded to form —O—CH₂—CH(CH₃)— wherein the oxygen atom is bonded to the phenyl ring of the quinolone ring; and
  • R³ is a group of the formula

wherein R²² is

• • (a) cyano,
  • (b) nitro,
  • (c) C_6-14 aryl,
  • (d) formyl, or
  • (e) carbamoyl,
    or a salt thereof.

[Compound I-7]

A compound of the formula (I) wherein

R is a hydrogen atom;
R¹ is cyclopropyl, 2-fluorocyclopropyl or 2,4-difluorophenyl;
R² is C_1-6 alkyl (e.g., methyl), C_1-6 alkoxy (e.g., methoxy) or a chlorine atom; and
R³ is 5-pyrimidinyl substituted by 1 or 2 substituents selected from the group consisting of amino, C_1-6 alkylamino and di(C_1-6 alkyl)amino,
or a salt thereof.

[Compound I-8]

A compound of the formula (I) wherein

R is a hydrogen atom;
R¹ is cyclopropyl, 2-fluorocyclopropyl or 2,4-difluorophenyl;
R² is C_1-6 alkyl (e.g., methyl), C_1-6 alkoxy (e.g., methoxy) or a chlorine atom; and
R³ is 2-indolyl optionally substituted by 1 or 2 substituents selected from the group consisting of

• • (a) a halogen atom,
  • (b) cyano,
  • (c) nitro,
  • (d) hydroxy,
  • (e) C_1-6 alkyl optionally substituted by 1 to 3 substituents selected from the group consisting of amino, C_1-6 alkoxy-carbonylamino, C_1-6 alkylamino and di(C_1-6 alkyl)amino,
  • (f) C_1-6 alkoxy,
  • (g) formyl,
  • (h) carboxy, and
  • (j) amino optionally substituted by 1 or 2 substituents selected from the group consisting of
    • (i) C_1-6 alkoxy-carbonyl,
    • (ii) C_1-6 alkyl-carbonyl optionally substituted by a substituent selected from the group consisting of
      • (A) C_3-8 cycloalkyloxy optionally substituted by 1 to 3 C_1-6 alkyl,
      • (B) C_1-6 alkylamino,
      • (C) di(C_1-6 alkyl)amino,
      • (D) a cyclic amino group (e.g., morpholino, 1-piperazinyl) optionally substituted by C_1-6 alkoxy-carbonyl, and
      • (E) a halogen atom,
    • (iii) phenylcarbonyl optionally substituted by 1 to 3 substituents selected from the group consisting of C_1-6 alkyl and C_1-6 alkoxy,
    • (iv) C_3-8 cycloalkylcarbonyl,
    • (v) a 5- to 10-membered aromatic heterocyclylcarbonyl group (e.g., pyridylcarbonyl) optionally substituted by C_1-6 alkyl optionally substituted by 1 to 3 halogen atoms,
    • (vi) benzylcarbonyl optionally substituted by 1 to 3 substituents selected from the group consisting of a halogen atom and C_1-6 alkoxy,
    • (vii) C_6-14 arylsulfonyl optionally substituted by C_1-6 alkoxy,
    • (viii) C_3-8 cycloalkyl-C_1-6 alkylsulfonyl optionally substituted by 1 to 3 substituents selected from the group consisting of C_1-6 alkyl and oxo (e.g., camphorsulfonyl),
    • (ix) a 5- to 10-membered aromatic heterocyclylsulfonyl group (e.g., imidazolylsulfonyl) optionally substituted by 1 to 3 C_1-6 alkyl, and
    • (x) —C(═N—CN)—SR⁹ wherein R⁹ is C_1-6 alkyl,
      or a salt thereof.

[Compound I-9]

A compound of the formula (I) wherein

R is a hydrogen atom;
R¹ is cyclopropyl, 2-fluorocyclopropyl or 2,4-difluorophenyl;
R² is C_1-6 alkyl (e.g., methyl), C_1-6 alkoxy (e.g., methoxy) or a chlorine atom; and
R³ is a group of the formula

wherein
R²³ is a hydrogen atom or C_1-6 alkyl, and
R²⁴, R²⁵, R²⁶ and R²⁷ are each independently,

• • (a) a hydrogen atom,
  • (b) cyano, or
  • (c) nitro,
    or a salt thereof.

[Compound I-10]

A compound of the formula (I) wherein

R is a hydrogen atom;
R¹ is cyclopropyl, 2-fluorocyclopropyl or 2,4-difluorophenyl;
R² is C_1-6 alkyl (e.g., methyl), C_1-6 alkoxy (e.g., methoxy) or a chlorine atom; and
R³ is a group of the formula

wherein
R²⁸ is a hydrogen atom or hydroxy, and
R²⁹ is a hydrogen atom or alkyl,
or a salt thereof.

[Compound I-11]

A compound of the formula (I) wherein

R is a hydrogen atom;
R¹ is cyclopropyl, 2-fluorocyclopropyl or 2,4-difluorophenyl;
R² is C_1-6 alkyl (e.g., methyl), C_1-6 alkoxy (e.g., methoxy) or a chlorine atom; and
R³ is a group of the formula

wherein
R¹⁰, R¹² and R¹⁴ are each independently,

• • (a) a hydrogen atom or
  • (b) C_1-6 alkyl, and
    R¹¹, R¹³ and R¹⁵ are each independently,
  • (a) a hydrogen atom,
  • (b) a halogen atom,
  • (c) cyano,
  • (d) nitro,
  • (e) amino,
  • (f) C_1-6 alkylamino,
  • (g) di(C_1-6 alkyl)amino,
  • (h) C_1-6 alkyl optionally substituted by hydroxy, or
    • (i) C_2-6 alkenyl, or
      R¹⁰ and R^1l are optionally bonded to form —(C═O)—NH—, —C(R³¹)═N— or —N═N— wherein R³¹ is a hydrogen atom or C_1-6 alkyl, and the nitrogen atom is bonded to the phenyl ring of the fused ring,
      or
      R¹² and R¹³ are optionally bonded to form —(CH₂)₄—,
      or a salt thereof.

[Compound I-12]

A compound of the formula (I) wherein

R is a hydrogen atom;
R¹ is cyclopropyl, 2-fluorocyclopropyl or 2,4-difluorophenyl;
R² is C_1-6 alkyl (e.g., methyl), C_1-6 alkoxy (e.g., methoxy) or a chlorine atom; and
R³ is a group of the formula

wherein R^10a is

• • (a) a hydrogen atom or
  • (b) C_1-6 alkyl, and
    R^11a, R^13a and R^15a are each independently,
  • (a) a hydrogen atom,
  • (b) a halogen atom,
  • (c) cyano,
  • (d) nitro,
  • (e) amino,
  • (f) C_1-6 alkylamino,
  • (g) di(C_1-6 alkyl)amino,
  • (h) C_1-6 alkyl optionally substituted by hydroxy, or
  • (i) C_2-6 alkenyl, and
    provided that R^10a, R^11a, R^13a and R^15a are not simultaneously hydrogen atom,
    or a salt thereof.

[Compound I-13]

A compound of the formula (I) wherein

R is a hydrogen atom;
R¹ is cyclopropyl, 2-fluorocyclopropyl or 2,4-difluorophenyl;
R² is C_1-6 alkyl (e.g., methyl), C_1-6 alkoxy (e.g., methoxy) or a chlorine atom; and
R³ is a group of the formula

wherein R³¹ is a hydrogen atom or C_1-6 alkyl,
or a salt thereof.

[Compound I-14]

A compound of the formula (I) wherein

R is a hydrogen atom;
R¹ is cyclopropyl, 2-fluorocyclopropyl or 2,4-difluorophenyl;
R² is C_1-6 alkyl (e.g., methyl), C_1-6 alkoxy (e.g., methoxy) or a chlorine atom; and
R³ is a group of the formula

wherein R^16a is

• • (a) C_1-6 alkyl optionally substituted by 1 to 3 substituents selected from the group consisting of cyano, C_1-6 alkylamino and di(C_1-6 alkyl)amino,
  • (b) C_2-6 alkenyl optionally substituted by carboxy,
  • (c) formyl,
  • (d) carboxy,
  • (e) carbamoyl,
  • (f) —C(R¹⁷)═N—OH wherein R¹⁷ is a hydrogen atom, cyano or hydroxy, or
  • (g) a 5- to 10-membered aromatic heterocyclic group (e.g., tetrazolyl, pyrrolyl, oxazolyl, benzimidazolyl, triazolyl) optionally substituted by C_1-6 alkyl, C_1-6 alkoxy-carbonyl, carboxy or phenyl, or a salt thereof.

[Compound I-15]

A compound of the formula (I) wherein

R is a hydrogen atom;
R¹ is cyclopropyl, 2-fluorocyclopropyl or 2,4-difluorophenyl;
R² is C_1-6 alkyl (e.g., methyl), C_1-6 alkoxy (e.g., methoxy) or a chlorine atom; and
R³ is a group of the formula

wherein
R^18a is C_1-6 alkyl, and
R^19a is (a) a halogen atom,

• • (b) cyano,
  • (c) C_1-6 alkyl optionally substituted by 1 to 3 substituents selected from the group consisting of
    • (i) a halogen atom,
    • (ii) cyano,
    • (iii) hydroxy,
    • (iv) amino,
    • (v) C_1-6 alkylamino,
    • (vi) di(C_1-6 alkyl)amino, and
    • (vii) a cyclic amino group (e.g., 1-piperazinyl) optionally substituted by C_1-6 alkyl,
  • (d) C_1-6 alkoxy,
  • (e) amino optionally substituted by 1 or 2 substituents selected from the group consisting of
    • (i) C_1-6 alkyl-carbonyl optionally substituted by a cyclic amino group (e.g., morpholino),
    • (ii) C_1-6 alkylsulfonyl, and
    • (iii) carbamoyl,
  • (f) carboxy,
  • (g) C_1-6 alkoxy-carbonyl,
  • (h) carbamoyl optionally substituted by C_1-6 alkyl optionally substituted by amino, C_1-6 alkylamino, di(C_1-6 alkylamino or C_1-6 alkoxy-carbonylamino,
  • (i) formyl,
  • (j) a 5- to 10-membered aromatic heterocyclic group (e.g., oxazolyl, benzimidazolyl), or
  • (k) —CH═N—OR²¹ wherein R²¹ is a hydrogen atom or C_1-6 alkyl optionally substituted by C_1-6 alkylamino or di(C_1-6 alkyl)amino,
    or a salt thereof.

[Compound I-16]

A compound of the formula (I) wherein

R is a hydrogen atom;
R¹ is cyclopropyl, 2-fluorocyclopropyl or 2,4-difluorophenyl;
R² is C_1-6 alkyl (e.g., methyl), C_1-6 alkoxy (e.g., methoxy) or a chlorine atom; and
R³ is a group of the formula

wherein
R³⁰ is (a) a hydrogen atom,

• • (b) a halogen atom,
  • (c) cyano,
  • (d) C_1-6 alkyl optionally substituted by 1 to 3 substituents selected from the group consisting of a halogen atom and hydroxy,
  • (e) O_2-6 alkenyl,
  • (f) O_2-6 alkynyl,
  • (g) C_1-6 alkoxy,
  • (h) formyl, or
  • (i) —CH═N—OH,
    or a salt thereof.

Examples of salts of the compound of the formula (I) include pharmaceutically acceptable salts. Suitable pharmaceutically acceptable salts of the compound of the formula (I) are conventional non-toxic salts and include, for example, a salt with a base or an acid addition salt such as a salt with an inorganic base, for example, an alkali metal salt (e.g., sodium salt, potassium salt, etc.), an alkaline earth metal salt (e.g., calcium salt, magnesium salt, etc.), an ammonium salt; a salt with an organic base, for example, an organic amine salt (e.g., trimethylamine salt, triethylamine salt, pyridine salt, picoline salt, ethanolamine salt, triethanolamine salt, dicyclohexylamine salt, N,N′-dibenzylethylenediamine salt, etc.); an inorganic acid addition salt (e.g., hydrochloride, hydrobromide, sulfate, hydrogensulfate, phosphate, etc.); an organic carboxylic or sulfonic acid addition salt (e.g., formate, acetate, trifluoroacetate, maleate, tartrate, citrate, fumarate, methanesulfonate, benzenesulfonate, toluenesulfonate, etc.); and a salt with a basic or acidic amino acid (e.g., arginine, aspartic acid, glutamic acid, etc.).

Compound (I) can be produced, for example, by a method according to the following reaction schemes.

wherein X, R¹ and R² are as defined above, R³² is alkyl and R³³ is alkyl.

Step a

Compound (1) can be converted to acid halide by reacting compound (1) with a halogenating agent in the presence or absence of a solvent. The solvent includes aromatic hydrocarbons such as benzene, toluene and xylene; halogenated hydrocarbons such as dichloromethane, chloroform and carbon tetrachloride; ethers such as dioxane, tetrahydrofuran and diethyl ether; N,N-dimethylformamide (DMF); dimethyl sulfoxide (DMSO); and the like. The halogenating agent may be any conventional halogenating agents which can convert hydroxy in carboxy group into a halogen atom, and includes, for example, thionyl chloride, phosphorus oxychloride, phosphorus oxybromide, phosphorus pentachloride, phosphorus pentabromide, and the like. The amounts of compound (1) and the halogenating agent are not particularly limited, but, in case of using no solvent, the halogenating agent is usually used in a large excess amount, and in case of using a solvent, the halogenating agent is usually used in an amount of at least 1 mole, preferably 2 to 4 moles, per 1 mole of compound (1). The reaction temperature and the reaction period of time are not particularly limited, but the reaction is usually carried out at a temperature of from room temperature to about 100° C. for about 30 minutes to about 6 hours.

The obtained acid halide is reacted with magnesium salt of malonic acid monoalkyl ester to give compound (2). Magnesium salt of malonic acid monoalkyl ester can be prepared in situ from potassium salt of malonic acid monoalkyl ester such as potassium ethyl malonate in the presence of magnesium chloride and a basic compound such as triethylamine. The reaction can be carried out in a suitable solvent. The solvent used in the reaction may be any conventional solvents unless they give any undesirable effect on the reaction, and includes, for example, esters such as ethyl acetate; ethers such as diethyl ether, dioxane, tetrahydrofuran, monoglyme and diglyme; alcohols such as methanol, ethanol and isopropanol; aromatic hydrocarbons such as benzene, toluene and xylene; aliphatic hydrocarbons such as n-hexane, heptane, cyclohexane and ligroin; amines such as pyridine and N,N-dimethylaniline; halogenated hydrocarbons such as chloroform, dichloromethane and carbon tetrachloride; aprotic polar solvents such as DMF, DMSO and hexamethylphosphoric triamide (HMPA); and a mixture of these solvents. The reaction is usually carried out at a temperature of from about 0° C. to about 150° C., preferably from about 0° C. to about 120° C., for about 0.5 to about 20 hours. Potassium salt of malonic acid monoalkyl ester is usually used in an amount of at least 1 mole, preferably 1 to 2 moles, per 1 mole of compound (1). Magnesium chloride and the basic compound are usually used in an amount of at least 1 mole, preferably 1 to 2 moles, per 1 mole of compound (1).

Step b

Compound (3) can be prepared by reacting compound (2) with trialkyl orthoformate such as trimethyl orthoformate and triethyl orthoformate in acetic anhydride. The reaction is usually carried out at a temperature of from about 0° C. to about 200° C., preferably from about 0° C. to about 150° C., for about 0.5 to about 20 hours. Trialkyl orthoformate is usually used in an amount of at least 1 mole, preferably 1 to 10 moles, per 1 mole of compound (2).

Step c

Compound (4) can be prepared by reacting compound (3) with compound (6).

The reaction between compound (3) and compound (6) can be carried out in a suitable solvent. The solvent employed in the reaction may be any conventional solvents unless they give any undesirable effect on the reaction, and includes, for example, alcohols such as methanol, ethanol and propanol; ethers such as diethyl ether, dioxane, tetrahydrofuran, monoglyme and diglyme; aromatic hydrocarbons such as benzene, toluene and xylene; aliphatic hydrocarbons such as n-hexane, heptane, cyclohexane and ligroin; halogenated hydrocarbons such as chloroform, methylene chloride and carbon tetrachloride; aprotic polar solvents such as DMF, DMSO and HMPA; and the like. The reaction is usually carried out at a temperature of from about 0° C. to about 150° C., preferably from room temperature to about 100° C., for about 0.1 to about 15 hours. Compound (6) is usually used in an amount of at least 1 mole, preferably 1 to 2 moles, per 1 mole of compound (3).

Step d

Compound (5) can be prepared by cyclization of compound (4).

The cyclization of compound (4) can be carried out in a suitable solvent in the presence of a basic compound. The solvent employed in the reaction may be any conventional solvents unless they give any undesirable effect on the reaction, and includes, for example, ethers such as diethyl ether, dioxane, tetrahydrofuran, monoglyme and diglyme; aliphatic hydrocarbons such as n-hexane, heptane and ligroin; halogenated hydrocarbons such as chloroform, methylene chloride and carbon tetrachloride; aprotic polar solvents such as DMF, DMSO and HMPA; and the like. The basic compound employed in the reaction includes inorganic bases such as metallic sodium, metallic potassium, sodium hydride, sodium amide, sodium hydroxide, potassium hydroxide, sodium carbonate and potassium carbonate, metal alcoholates such as sodium methylate and sodium ethylate, organic bases such as 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), N-benzyltrimethylammonium hydroxide and tetrabutylammonium hydroxide, and the like. The reaction is usually carried out at a temperature of from about 0° C. to about 200° C., preferably from room temperature to about 150° C., for about 0.5 to about 15 hours. The basic compound is usually used in an amount of at least 1 mole, preferably 1 to 2 moles, per 1 mole of the compound (4).

wherein X, R¹, R², R³ and R³² are as defined above.

Step a

Compound (Ia) can be prepared by reacting compound (5) and compound (7) or compound (8) in an inert solvent or without using any solvents, in the presence or absence of a basic compound, in the presence of a palladium catalyst.

Examples of inert solvents include water; ethers such as dioxane, tetrahydrofuran, diethyl ether, 1,2-dimethoxyethane, diethylene glycol dimethyl ether and ethylene glycol dimethyl ether; aromatic hydrocarbons such as benzene, toluene and xylene; alcohols such as methanol, ethanol and isopropanol; ketones such as acetone and methyl ethyl ketone; and aprotic polar solvents such as DMF, DMSO, HMPA and acetonitrile. These inert solvents can be used singly or in combinations of two or more.

The palladium catalyst used in the reaction is not particularly limited, but include, for example, tetravalent palladium catalysts such as sodium hexachloropalladate(IV) tetrahydrate and potassium hexachloropalladate(IV); divalent palladium catalysts such as palladium(II) chloride, palladium(II) bromide, palladium(II) acetate, palladium(II) acetylacetonate, dichlorobis(benzonitrile)palladium(II), dichlorobis(acetonitrile)palladium(II), dichlorobis(triphenylphosphine)palladium(II), dichlorotetramine palladium(II), dichloro(cycloocta-1,5-diene)palladium(II), palladium(II) trifluoroacetate, and 1,1′-bis(diphenylphosphino)ferrocene dichloropalladium(II) dichloromethane complex (Pd(dppf)Cl₂.CH₂Cl₂); zerovalent palladium catalysts such as tris(dibenzylideneacetone)dipalladium(0), tris(dibenzylideneacetone)dipalladium(0) chloroform complex and tetrakis(triphenylphosphine)palladium(0), etc. These palladium catalysts are used singly or in combinations of two or more.

In the reaction, the amount of the palladium catalyst is not particularly limited, but is typically in the range from 0.000001 to 20 moles in terms of palladium relative to 1 mole of compound (5). The amount of the palladium catalyst is preferably in the range from 0.0001 to 5 moles in terms of palladium relative to 1 mole of compound (5).

This reaction advantageously proceeds in the presence of a suitable ligand. Examples of ligands of the palladium catalyst include, for example, 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (BINAP), tri-o-tolylphosphine, bis(diphenylphosphino)ferrocene, triphenylphosphine, tri-t-butylphosphine and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (Xantphos). These ligands are used singly or in combinations of two or more.

The proportion of the palladium catalyst and ligand is not particularly limited. The amount of the ligand is about 0.1 to about 100 moles per 1 mole of the palladium catalyst, and preferably about 0.5 to about 15 moles per 1 mole of the palladium catalyst.

Various known inorganic and organic bases can be used as basic compounds.

Inorganic bases include, for example, alkali metal hydroxides such as sodium hydroxide, potassium hydroxide, cesium hydroxide and lithium hydroxide; alkali metal carbonates such as sodium carbonate, potassium carbonate, cesium carbonate and lithium carbonate; alkali metal hydrogen carbonates such as lithium hydrogen carbonate, sodium hydrogen carbonate and potassium hydrogen carbonate; alkali metals such as sodium and potassium; phosphates such as sodium phosphate and potassium phosphate; amides such as sodium amide; and alkali metal hydrides such as sodium hydride and potassium hydride.

Organic bases include, for example, alkali metal lower alkoxides such as sodium methoxide, sodium ethoxide, sodium t-butoxide, potassium methoxide, potassium ethoxide and potassium t-butoxide, and amines such as triethylamine, tripropylamine, pyridine, quinoline, piperidine, imidazole, N-ethyldiisopropylamine, dimethylaminopyridine, trimethylamine, dimethylaniline, N-methylmorpholine, 1,5-diazabicyclo[4.3.0]non-5-ene (DBN), 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), 1,4-diazabicyclo[2.2.2]octane (DABCO), etc.

Such basic compounds can be used singly or in combinations of two or more. More preferable basic compounds used in the reaction include alkali metal carbonates such as sodium carbonate, potassium carbonate, cesium carbonate and lithium carbonate.

The basic compound is usually used in an amount of 0.5 to 10 moles per 1 mole of compound (5), and preferably 0.5 to 6 moles per 1 mole of compound (5).

Compound (7) or compound (8) is usually used in an amount of at least 1 mole per 1 mole of compound (5), and preferably about 1 to about 5 moles per 1 mole of compound (5).

The reaction can be conducted under normal pressure, under inert gas atmosphere including nitrogen, argon, etc., or under increased pressure.

The reaction proceeds usually from room temperature to about 200° C., and preferably from room temperature to about 150° C., and is usually completed in about 1 to about 30 hours. The reaction is also achieved by heating at about 100° C. to about 200° C. for about 5 minutes to about 1 hour using a microwave reactor.

Step b

Compound (Ib) can be prepared by hydrolysis of compound (Ia).

The hydrolysis of compound (Ia) can be carried out under the conditions of conventional hydrolysis, for example, in the presence of a basic compound such as sodium hydroxide, potassium hydroxide, barium hydroxide or potassium carbonate; a mineral acid such as sulfuric acid, hydrochloric acid or nitric acid; or an organic acid such as acetic acid or an aromatic sulfonic acid, in a solvent including water, alcohols such as methanol, ethanol and isopropanol; ketones such as acetone and methyl ethyl ketone; ethers such as dioxane and ethylene glycol diethyl ether; acetic acid; or a mixture thereof. The reaction is usually carried out at a temperature of from room temperature to about 200° C., preferably from room temperature to about 150° C., for about 0.1 to about 30 hours.

wherein R³ is as defined above, and Z is a bromine atom or an iodine atom.

Step a

Compound (7) can be prepared by reacting compound (9) with bis(pinacolato)diboron (10) in an inert solvent in the presence of a palladium catalyst and a basic compound.

Examples of inert solvents and palladium catalyst are same as those described in Step a in Reaction Scheme II.

The basic compound employed in the reaction includes potassium acetate, triethylamine, N-methylmorpholin, sodium carbonate, potassium carbonate, cesium carbonate, lithium carbonate, potassium phosphate and sodium hydrogen carbonate.

In the reaction, the amount of the palladium catalyst is not particularly limited, but is typically in the range from 0.000001 to 20 moles in terms of palladium relative to 1 mole of compound (9). The amount of the palladium catalyst is preferably in the range from 0.0001 to 5 moles in terms of palladium relative to 1 mole of compound (9).

The basic compound is usually used in an amount of 0.5 to 10 moles per 1 mole of compound (9), and preferably 0.5 to 6 moles per 1 mole of compound (9).

Bis(pinacolato)diboron (10) is usually used in an amount of at least 1 mole per 1 mole of compound (9), and preferably about 1 to about 5 moles per 1 mole of compound (9).

The reaction can be conducted under normal pressure, under inert gas atmosphere including nitrogen, argon, etc., or under increased pressure.

The reaction proceeds usually from room temperature to about 200° C., and preferably from room temperature to about 150° C., and is usually completed in about 1 to about 30 hours.

Step b

Compound (8) can be prepared by reacting compound (9) with trialkyl borate such as trimethyl borate, triethyl borate, tri(isopropyl) borate and tri(n-butyl) borate in an inert solvent in the presence of n-butyllithium or lithium diisopropylamide.

Examples of inert solvents are same as those described in Step a in Reaction Scheme II.

The trialkyl borate is usually used in an amount of at least 1 mole per 1 mole of compound (9), and preferably about 1 to about 5 moles per 1 mole of compound (9).

n-Butyllithium or lithium diisopropylamide is usually used in an amount of at least 1 mole per 1 mole of compound (9), and preferably about 1 to about 5 moles per 1 mole of compound (9).

The reaction is usually carried out at a temperature of from about −70° C. to about 0° C. for about 0.1 to about 15 hours.

Compound (I) of the present invention can easily be converted into a salt thereof by treating with a pharmaceutically acceptable acid or base. The acid includes inorganic acids such as hydrochloric acid, sulfuric acid, phosphoric acid and hydrobromic acid and organic acids such as oxalic acid, maleic acid, fumaric acid, malic acid, tartaric acid, citric acid, benzoic acid, lactic acid, methanesulfonic acid and propionic acid. The base includes sodium hydroxide, potassium hydroxide, calcium hydroxide, sodium carbonate, potassium hydrogen carbonate, and the like.

The compound thus obtained can easily be isolated and purified by conventional methods, such as, for example, extraction with solvents, dilution method, recrystallization, column chromatography and preparative thin layer chromatography.

Compound (I) shows an excellent antimicrobial activity against mycoplasma, Pseudomonas aeruginosa, anaerobic bacteria, resistant cells against various antimicrobials, clinically isolated bacteria, and gram negative and gram positive bacteria such as Clostridium difficile, Enterococcus faecalis and Staphylococcus pyogenes and hence is useful as an antimicrobial agent for the treatment of diseases induced by these microorganisms. Compound (I) also shows low toxicity and less side effects and is characteristic in good absorbability and in sustained activity.

Since compound (I) shows an excellent antimicrobial activity against Clostridium difficile, it is useful for the prevention or treatment of intestinal infections including antibiotics-associated diarrhea (AAD) such as Clostridium difficile-associated diarrhea (CDAD).

The compounds of the present invention are usually used in the form of a usual pharmaceutical preparation. The pharmaceutical preparation can be prepared in admixture with conventional pharmaceutically acceptable diluents or carriers, such as fillers, bulking agents, binding agents, wetting agents, disintegrators, surfactants and lubricating agents. The pharmaceutical preparation includes various preparations suitable for treatment of the diseases, for example, tablets, pills, powders, solutions, suspensions, emulsions, granules, capsules, suppositories, injections such as solutions and suspensions, and the like. In the preparation of tablets, there may be used any conventional carriers, for example, excipients such as lactose, white sugar, sodium chloride, glucose, urea, starches, calcium carbonate, kaolin, crystalline cellulose and silicate, binding agents such as water, ethanol, propanol, simple syrup, glucose solution, starch solution, gelatin solution, carboxymethyl cellulose, shellac, methyl cellulose, potassium phosphate and polyvinylpyrrolidone, disintegrators such as dry starch, sodium alginate, agar powder, laminaran powder, sodium hydrogen carbonate, calcium carbonate, polyoxyethylene sorbitan fatty acid esters, sodium lauryl sulfate, stearic monoglyceride, starches and lactose, disintegration inhibitors such as white sugar, stearin, cacao butter and hydrogenated oils, absorption promoters such as quaternary ammonium salts and sodium lauryl sulfate, wetting agents such as glycerin and starches, adsorbents such as starches, lactose, kaolin, bentonite and colloidal silicates, lubricants such as purified talc, stearates, boric acid powder and polyethylene glycol, and the like. The tablets may also be coated with conventional coating agents, for example, may be in the form of a sugar coated tablet, a gelatin-coated tablets, an enteric coating tablet, a film coating tablet, or a double or multiple layers tablet. In the preparation of pills, there may be used conventional carriers, including excipients such as glucose, lactose, starches, cacao butter, hydrogenated vegetable oils, kaolin and talc, binding agents such as gum arabic powder, tragacanth powder, gelatin and ethanol, disintegrators such as laminaran and agar, and the like. In the preparation of suppositories, there may be used conventional carriers, such as, for example, polyethylene glycol, cacao butter, higher alcohols, higher alcohol esters, gelatin and semi-synthesized glycerides. In the preparation of injections, the solutions, emulsions or suspensions of the compounds are sterilized and are preferably made isotonic with the body liquid. These solutions, emulsions and suspensions are prepared by admixing the active compound with a conventional diluent, such as water, aqueous lactic acid solution, ethyl alcohol, propylene glycol, ethoxylated isostearyl alcohol, polyoxylated isostearyl alcohol or polyoxyethylene sorbitan fatty acid esters. The preparations may also be incorporated with sodium chloride, glucose or glycerin in an amount sufficient to make them isotonic with the body liquid. The preparations may also be incorporated with conventional solubilizers, buffering agents, anesthetizing agents, and further, with coloring agents, preservatives, perfumes, flavors, sweetening agents, and other medicaments. The preparations in the form of a paste, cream or gel may be prepared by using as a diluent such as white petrolatum, paraffin, glycerin, cellulose derivatives, polyethylene glycol, silicone, bentonite, or the like. When the compound of the active ingredient precipitates in the injection, an acid such as, for example, methanesulfonic acid, propionic acid, hydrochloric acid, succinic acid or lactic acid may be added to the injection as required to preserve the injection in a stable solution.

Compound (I) may be contained in any amount in the preparations, and are usually contained in an amount of from 1% to 70% by weight based on the whole weight of the preparations.

The pharmaceutical preparations of the present invention can be administered in any methods. Suitable method for administration may be selected in accordance with the preparation form, age and sex of patients, severity of the diseases, and the like. For instance, tablets, pills, solutions, suspensions, emulsions, granules and capsules are administered in oral route. In case of injection, it is administered intravenously in a single form or together with an auxiliary liquid such as glucose or amino solution. The injections may also be administered in intramuscular, intracutaneous, subcutaneous, or intraperitoneal route. Suppositories are administered in intrarectal route.

The dosage of the pharmaceutical preparations of the present invention may vary according to administration methods, age and sex of patients, severity of the diseases, and the like, usually in the range of about 0.1 to about 100 mg, more preferably in the range of about 0.1 to about 50 mg, of compound (I) per 1 kg body weight of the patient per day. The preparation is usually administered by dividing into 2 to 4 times per day.

The present invention is illustrated by the following Examples, Experimental Examples and Preparation Examples. It is to be understood that the present invention is not limited to these Examples, Experimental Examples or Preparation Examples and various changes and modifications can be made without departing from the scope and spirit of the present invention.

EXAMPLES

In our work, Suzuki coupling was employed as key reaction to construct our final products. For the coupling, the corresponding iodo-intermediates could be prepared through well-known methods that were wildly used to synthesis of quinolones before (General Scheme I).

Example 1

Synthesis of Intermediate 5a (R²=Me)

1.1. Compound 2: A mixture of compound 1 (2 g, 6.71 mmol) and thionyl chloride (9.8 mL) was refluxed for 3 hr, and then concentrated to give acid chloride. To the residue was added dry EtOAc (10 mL) and then the mixture was concentrated.

A mixture of potassium ethyl malonate (1.6 g, 9.40 mmol) and MgCl₂ (1.91 g, 20.13 mmol) in dry EtOAc was stirred for 30 min below 50° C. To the mixture was added Et₃N (2.83 mL, 20.13 mmol) below 50° C. Then, the mixture was refluxed for 1 hr. To the mixture was added dropwise a solution of the acid chloride in dry EtOAc (10 mL) at 50-70° C. and then the mixture was refluxed for 1.5 hr. Water (30 mL) and 5 N HCl (30 mL) were added to the reaction mixture under ice-cooling. The EtOAc solution was washed with water, dried and concentrated to give compound 2 as a yellow oil, which was used in the next step without purification.

1.2. Compound 3: A mixture of compound 2 (11 g, 29.88 mmol), triethyl orthoformate (7.47 mL, 44.82 mmol) and acetic anhydride (6.77 mL, 71.72 mmol) was heated at 150° C. for 1 hr, and then concentrated to give compound 3, which was used in the next step without purification.

1.3. Compound 4: To compound 3 (obtained above) were added EtOH (50 mL) and cyclopropylamine (2.48 mL, 35.86 mmol). The mixture was stirred for 30 min and concentrated to give compound 4, which was used in the next step without purification.

1.4. Intermediate 5a: Compound 4 (obtained above) was dissolved in dry DMSO (100 mL). K₂CO₃ (16.52 g, 119.53 mmol) was added to the solution. The reaction mixture was stirred at 100° C. for 1 hr. When TLC (EtOAc/dipropyl ether=1/1) indicated the reaction was completed, the mixture was cooled to room temperature, poured into water, and extracted with EtOAc. The organic layer was washed with brine, dried and concentrated to give a yellow solid which was recrystallized from EtOAc. Intermediate 5a was obtained as a white solid in 75% overall yield. ¹H NMR (400 MHz, DMSO) δ 8.60 (s, 1H), 7.70 (d, J=7.8 Hz, 1H), 4.29-4.14 (m, 3H), 2.96 (s, 3H), 1.28 (t, J=7.1 Hz, 3H), 1.14 (q, J=7.0 Hz, 2H), 0.87-0.76 (m, 2H).

The following compounds were synthesized according to General Scheme I.

Example 2

Intermediate 5b (R²═OMe): ¹H NMR (400 MHz, DMSO) δ 8.51 (s, 1H), 7.69 (d, J=7.7 Hz, 1H), 4.23 (dd, J=14.0, 6.9 Hz, 2H), 4.03 (s, 1H), 3.80 (s, 3H), 1.28 (t, J=7.0 Hz, 3H), 1.09 (d, J=6.2 Hz, 2H), 0.97 (m, 2H).

Example 3

Intermediate 5c (R²═Cl): ¹H NMR (400 MHz, DMSO) δ 8.61 (s, 1H), 7.81 (d, J=7.6 Hz, 1H), 4.23 (m, 3H), 1.28 (t, J=7.1 Hz, 3H), 1.21-1.08 (dd, J=7.1, 2.2 Hz, 2H), 0.99-0.92 (m, 2H).

Example 4

Intermediate 5d: ¹H NMR (400 MHz, CDCl₃) δ 8.59-8.51 (d, J=3.1 Hz, 1H), 8.03-7.92 (d, J=7.5 Hz, 1H), 4.98-4.73 (dddd, J=62.9, 6.3, 4.9, 3.4 Hz, 1H), 4.44-4.34 (q, J=7.1 Hz, 2H), 3.91-3.83 (dt, J=8.6, 5.4 Hz, 1H), 2.95-2.88 (s, 3H), 1.59-1.48 (m, 1H), 1.45-1.38 (t, J=7.1 Hz, 3H), 1.35-1.18 (m, 1H).

Example 5

Intermediate 5e: ¹H NMR (400 MHz, CDCl₃) δ 8.51-8.43 (d, J=2.0 Hz, 1H), 7.94-7.86 (d, J=7.6 Hz, 1H), 4.90-4.65 (dddd, J=62.7, 6.0, 5.1, 3.3 Hz, 1H), 4.37-4.28 (q, J=7.1 Hz, 2H), 3.80-3.76 (s, 3H), 3.75-3.69 (dt, J=8.7, 5.5 Hz, 1H), 1.61-1.47 (m, 2H), 1.46-1.30 (m, 4H).

Example 6

Intermediate 5f: ¹H NMR (400 MHz, DMSO) δ 8.65 (s, 1H), 7.48 (d, J=8.16 Hz, 1H), 4.79 (q, J=6.65 Hz, 1H), 4.62 (dd, J=1.82, 11.36 Hz, 1H), 4.44 (dd, J=2.20, 11.36 Hz, 1H), 4.23 (qd, J=2.95, 7.09 Hz, 2H), 1.40 (d, J=6.65 Hz, 3H), 1.28 (t, J=7.09 Hz, 3H).

Reaction reagents and conditions: a. Pd(dppf)Cl₂.CH₂Cl₂ (5% mol), KOAc, dioxane, 80° C.; b. nBuLi (or LDA), B(OiPr)₃, THF

General Scheme II outlined the preparation of required boronic acids and boronates. They are readily prepared through general methods.

Example 7

Synthesis of Boronic Acid 7

Reaction reagents and conditions: a. 1) NaH, THF, r.t.; 2) nBuLi, B(OiPr)₃, −70° C. to 0° C.

7.1 Boronic acid 7: To a solution of compound 6 (10 g, 44.44 mmol) in dry tetrahydrofuran (350 mL) was added sodium hydride (2 g, 66.66 mmol, 80% dispersion) at 0° C. After the mixture was stirred at room temperature for 30 min, the mixture was cooled below −60° C. in a dry ice/acetone bath, and n-butyllithium (70 mL, 112 mmol, 1.6 M in hexane) was added over 30 min. The mixture was kept stirring for another 30 min, then triisopropyl borate (40 mL, 177 mmol) was added dropwise. The reaction mixture was stirred for 10 min, and then warmed to 0° C. slowly in an ice bath. HCl (5 N) was added to the mixture to adjust pH=3-4, and the mixture was stirred for 20 min. Aq. NaOH was added to the mixture to adjust pH=10. After filtration, the organic layer was separated. The aqueous layer was extracted with a mixture of ethyl acetate/THF (4/1; 2×120 mL) and EtOAc (100 mL). The aqueous layer was adjusted to pH=5-6 with HCl. The precipitate thus formed was collected by filtration and dried to give boronic acid 7 (3.5 g, 41%) as a white solid.

Example 8

Synthesis of Boronate 10

8.1 Compound 9: 2-Aminonicotinonitrile 8 (100 g, 0.839 mol) was dissolved in HOAc (800 mL). To the solution was added Na₂CO₃ (88.97 g, 0.839 mol). Then, Br₂ (46.4 mL, 0.923 mol) was added dropwise. The reaction mixture was stirred at room temperature for 50 min. To the mixture was added water (600 mL). The mixture was cooled to about 5° C. The precipitate thus formed was collected by filtration and dried to give compound 9 (207 g, 96%).

8.2 Boronate 10: Compound 9 (50 g, 0.224 mol), bis(pinacolato)diboron (85.6 g, 0.337 mol), KOAc (44.1 g, 0.449 mol) and Pd(dppf)Cl₂.CH₂Cl₂ (2.77 g, 3.4 mmol) were charged into a flask. Dioxane (400 mL) was added. The reaction mixture was stirred at 100° C. for 2 hr under Ar. When LC-MS indicated that the reaction was completed, the mixture was cooled to room temperature. The mixture was filtered through diatomite, concentrated, diluted with a mixture of ethyl acetate and hexane in 3/1 ratio (1000 mL), filtered through silica gel (300-400 mesh), concentrated, crystallized and dried to give boronate 10 (32 g, 66%) as a white solid.

Example 9

Synthesis of Boronate 13

9.1 Compound 12: 3-Chloropyridin-2-amine (100 g, 0.778 mol) was dissolved in acetic acid (1200 mL). To the solution was added Na₂CO₃ (82.4 g, 0.778 mol). Then, Br₂ (39.1 mL, 0.856 mmol) was added dropwise. After addition, the reaction mixture was stirred at room temperature for 30 min. To the mixture was added water (800 mL). The mixture was cooled to about 5° C. The resulting solid was collected by filtration and dried to give compound 12 (147 g, 91%) as a white solid.

9.2 Boronate 13: Compound 12 (4 g, 17.2 mmol), bis(pinacolato)diboron (4.79 g, 18.8 mmol), KOAc (3.37 g, 34.2 mmol) and Pd(dppf)Cl₂.CH₂Cl₂ (0.210 g, 0.25 mmol) were charged into a flask. Dioxane (80 mL) was added. The mixture was stirred at 85° C. for 2 hr under Ar. When LC-MS indicated that the reaction was completed, the mixture was cooled to room temperature. The mixture was filtered through diatomite and concentrated. The residue was diluted with ethyl acetate and hexane (3/1, 100 mL), filtered through silica gel (300-400 mesh), concentrated and crystallized by n-hexane to give boronate 13 (3.4 g, 78%) as a white solid.

Reaction reagents and conditions: a. Pd(dppf)Cl₂.CH₂Cl₂(5% mol), K₂CO₃, dioxane, 80° C.; b. NaOH, EtOH

Example 10

Synthesis of Compound 1-2

10.1 Compound 16: Intermediate 5a (30 g, 65 mmol), boronic acid 7 (17 g, 71.6 mmol) and K₂CO₃ (27, 195 mmol) were charged into a flask. Dioxane (600 mL) and water (60 mL) were added. The solution was deoxygenated with N₂ for 15 min. Pd(dppf)Cl₂.CH₂Cl₂ (2.8 g, 3.24 mmol) was added to the mixture. The reaction mixture was stirred at 85° C. overnight. When the reaction was completed, the reaction mixture was cooled to room temperature. The precipitate was filtered, dissolved in water, filtered, triturated with EtOH, filtered and dried to give compound 16 (16 g, 57%) as an off-white solid. The obtained compound was pure enough for use.

The organic filtrate was concentrated. To the residue were added water, dichloromethane and EtOAc. The precipitate thus formed was collected by filtration and dissolved in HCl (5 N). After filtration to remove Pd residue, the filtrate was basified with aq. NaOH (pH=7-8). The precipitate was collected by filtration and dried to give compound 16 (3 g, 11%) as an off-white solid.

10.2 Compound 1-2: Compound 16 (33 g, 76.1 mmol) was suspended in EtOH (300 mL). Aq. NaOH (4 N, 100 mL) was added to the suspension, and the mixture was stirred at 60° C. for 2 hr. 200 mL of EtOH was evaporated under reduced pressure. To the residue was added HCl (5 N) to adjust pH=4. The resulting precipitate was filtered, triturated with EtOH, filtered and dried to give compound 1-2 (30 g, 97%) as an off-white solid. m.p. >300° C. ¹H NMR (400 MHz, DMSO) δ 14.64 (s, 1H), 12.39 (s, 1H), 8.92 (s, 1H), 8.58 (s, 1H), 8.28 (s, 1H), 8.01 (m, 2H), 6.67 (d, J=9.4 Hz, 1H), 4.42 (s, 1H), 2.68 (s, 3H), 1.27 (d, J=6.4 Hz, 2H), 1.12-1.03 (m, 2H). ¹³C NMR (101 MHz, DMSO) δ 176.92, 165.25, 162.85, 158.16, 155.72, 152.71, 150.92, 149.62, 139.29, 138.79, 137.62, 133.70, 133.52, 131.80, 127.47, 127.38, 123.75, 123.42, 113.89, 108.05, 107.81, 107.29, 41.29, 20.64, 20.62, 10.62. HPLC-MS m/z 406 (MH⁺). Anal. Calcd for C₂₂H₁₆FN₃O₄: C, 65.18; H, 3.98; N, 10.37. Found: C, 63.50; H, 4.00; N, 9.91.

Example 11

Synthesis of Compound 2-18

11.1 Compound 17: Boronate 10 (14 g, 56.1 mmol), intermediate 5a (20 g, 46.7 mmol), Cs₂CO₃ (15.22 g, 46.7 mmol) and Pd(dppf)Cl₂.CH₂Cl₂ (0.98 g, 1.2 mmol) were charged into a flask. Dioxane (500 mL) and water (5 mL) were added. The mixture was stirred at 110° C. overnight under Ar. The mixture was cooled to room temperature. The mixture was filtered, and the solid was washed with dioxane and ethyl acetate. The solid was dissolved in hot CH₂Cl₂ (1200 mL), and the solution was filtered through diatomite. The operation was repeated twice. The organic layers were combined and concentrated. To the residue was added ethyl acetate (200 mL). The solid was collected by filtration, washed with ethyl acetate (60 mL) and dried to give compound 17 (17.6 g, 90%) as a white solid.

11.2 Compound 2-18: Compound 17 (43 g, 0.101 mol) was dissolved in THF and EtOH (1/1, 500 mL). To the solution was added NaOH (60 mL, 4 N). The mixture was stirred at room temperature for 2 hr. HCl (63 mL, 4 N) was added to acidify the mixture (pH=3-4). The solid was collected by filtration, washed with EtOH (100 mL) and dried to give compound 2-18 (35.7 g, 99%) as a white solid. m.p. >300° C. ¹H NMR (400 MHz, DMSO) δ 14.65 (s, 1H), 8.89 (s, 1H), 8.32-8.23 (m, 1H), 8.08 (d, J=2.09 Hz, 1H), 7.94 (d, J=8.87 Hz, 1H), 7.28 (s, 2H), 4.40 (tt, J=3.74, 7.17 Hz, 1H), 2.67 (s, 3H), 1.31-1.19 (m, 2H), 1.10-0.99 (m, 2H). ¹³C NMR (101 MHz, DMSO) δ 176.95, 176.92, 165.32, 159.60, 158.29, 155.86, 154.07, 152.67, 143.59, 139.32, 133.39, 133.22, 131.73, 127.13, 127.05, 116.93, 116.52, 107.96, 107.71, 107.27, 89.15, 41.32, 20.64, 20.62, 10.65. HPLC-MS m/z 379 (MH³⁰). Anal. Calcd for C₂₀H₁₅FN₄O₃: C, 63.49; H, 4.00; N, 14.81. Found: C, 62.04; H, 4.20; N, 13.97.

Example 12

Synthesis of Compound 3-11

12.1 Compound 18: Boronate 13 (20 g, 75.4 mmol), intermediate 5a (24.1 g, 58.03 mmol), Cs₂CO₃ (26.5 g, 81.2 mmol) and Pd(dppf)Cl₂.CH₂Cl₂ (1.42 g, 1.7 mmol) were charged into a flask. Dioxane (400 mL) and water (4 mL) were added. The mixture was stirred at 100° C. overnight under Ar. The mixture was cooled to room temperature. The mixture was filtered, and the solid was washed with dioxane and ethyl acetate. The solid was dissolved in hot CH₂Cl₂ (1200 mL), and the solution was filtered through diatomite. The operation was repeated twice. The organic layers were combined and concentrated. To the residue was added ethyl acetate (200 mL). The solid was collected by filtration, washed with ethyl acetate (60 mL) and dried to give compound 18 (21 g, 85%) as a white solid.

12.2 Compound 19: Compound 18 (39 g, 91.91 mmol) was dissolved in THF and EtOH (1/1, 600 mL). To the mixture was added NaOH (4 N, 60 mL). The mixture was stirred at room temperature for 2 hr. HCl (4 N, 62 mL) was added to acidify the solution (pH=3-4). The solid was collected by filtration, washed with EtOH (100 mL) and dried to give compound 19 (34 g, 98%) as a white solid.

12.3 Compound 3-11: Chloroacetaldehyde (40% in water, 80 mL) was added to a solution of compound 19 (34 g, 91.9 mmol) in EtOH (600 mL). The mixture was refluxed for 3 hr. When LC-MS indicated that the reaction was completed, the mixture was cooled to 5° C. and filtered. The solid was dried to give compound 3-11 (21 g). The mother liquid was basified (pH=7-8) with aq. NaOH. The precipitate was collected by filtration, washed with EtOH and dried to give compound 3-11 (11.5 g) as a white solid. In total, 32.5 g of compound 3-11 was obtained in 93% yield. m.p.: 307-311° C. ¹H NMR (400 MHz, DMSO) δ 14.53 (s, 1H), 8.98-8.84 (m, 2H), 8.28 (d, J=1.16 Hz, 1H), 7.98 (d, J=8.83 Hz, 1H), 7.90 (d, J=0.89 Hz, 1H), 7.77 (s, 1H), 4.43 (tt, J=3.70, 7.10 Hz, 1H), 3.50-3.36 (m, 1H), 2.72 (s, 3H), 1.26 (d, J=6.80 Hz, 2H), 1.07 (d, J=18.24 Hz, 2H). ¹³C NMR (101 MHz, DMSO) δ 176.91, 176.88, 165.23, 158.22, 155.77, 152.84, 139.98, 139.17, 139.16, 132.44, 132.15, 131.98, 131.54, 127.86, 127.78, 127.38, 120.72, 118.97, 116.37, 108.15, 107.91, 107.37, 41.38, 20.54, 20.52, 10.72. HPLC-MS: m/z 412 (MH⁺). Anal. Calcd for C₂₁H₁₅ClFN₃O₃: C, 61.25; H, 3.67; N, 10.20. Found: C, 58.59; H, 3.86; N, 9.76.

Compounds listed in the following Tables were synthesized according to General Scheme III.

TABLE 1
Com-
pound					MS
No.	R3 =	R2 =	R1 =	NMR	(MH+)	HPLC
1-1		OMe	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.63 (s, 1H), 12.41 (s, 1H), 8.82 (s, 1H), 8.69 (s, 1H), 8.38 (s, 1H), 8.05 (d, J = 9.6 Hz, 1H), 7.99 (d, J = 9.1 Hz, 1H), 6.66 (dd, J = 9.5, 1.6 Hz, 1H), 4.24 (s, 1H), 3.42 (s, 3H), 1.19	422	98%
				(d, J = 7.2 Hz, 4H).
1-2		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.64 (s, 1H), 12.39 (s, 1H), 8.92 (s, 1H), 8.58 (s, 1H), 8.28 (s, 1H), 8.01 (m, 2H), 6.67 (d, J = 9.4 Hz, 1H), 4.42 (s, 1H), 2.68 (s, 3H), 1.27 (d, J = 6.4 Hz, 2H), 1.12-1.03 (m, 2H).	406	98%
1-3		OMe		1H NMR (400 MHz, DMSO) δ 14.49 (s, 1H), 12.41 (s, 1H), 8.85 (d, J = 1.3 Hz, 1H), 8.67 (s, 1H), 8.36 (s, 1H), 8.05 (d, J = 9.6 Hz, 1H), 8.00 (d, J = 9.1 Hz, 1H), 6.77- 6.54 (m, 1H), 5.24-4.97 (m, 1H), 4.29-4.10 (m, 1H), 3.44	440	98%
				(s, 3H), 1.89-1.59 (m, 2H).
1-4		Me		1H NMR (400 MHz, DMSO) δ 14.50 (s, 1H), 12.39 (s, 1H), 8.90 (d, J = 3.0 Hz, 1H), 8.58 (s, 1H), 8.27 (s, 1H), 8.02 (m, 2H), 6.74-6.61 (m, 1H), 5.17 (dd, J = 64.3, 3.1 Hz, 1H), 4.39 (m, 1H), 2.60 (s, 3H), 1.84-1.50 (m, 2H).	424	98%
1-5		Cl	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.22 (s, 1H), 12.42 (s, 1H), 8.94 (s, 1H), 8.61 (d, J = 2.0 Hz, 1H), 8.31 (d, J = 2.0 Hz, 1H), 8.20 (d, J = 8.5 Hz, 1H), 8.03 (d, J = 9.6 Hz, 1H), 6.67 (d, J = 9.5 Hz, 1H), 4.51-4.34 (m, 1H), 1.29-1.19 (m,	426	98%
				2H), 1.17-1.05 (m, 2H).
1-7		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.65 (s, 1H), 11.27 (s, 1H), 8.91 (s, 1H), 8.04 (d, J = 9.5 Hz, 1H), 7.98 (d, J = 8.8 Hz, 1H), 7.78 (s, 2H), 6.69 (d, J = 9.5 Hz, 1H), 4.49-4.30 (m, 1H), 2.65 (s, 3H), 1.25 (d, J = 6.7 Hz, 2H), 1.08 (s, 2H).	439	98%
1-8		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.66 (s, 1H), 11.99 (s, 1H), 8.91 (s, 1H), 8.03 (d, J = 9.1 Hz, 1H), 7.98 (d, J = 8.8 Hz, 1H), 7.60 (s, 1H), 7.57 (d, J = 11.5 Hz, 1H), 6.66 (d, J = 9.6 Hz, 1H), 4.51- 4.29 (m, 1H), 1.25 (d, J = 6.3 Hz, 2H), 1.15-0.94 (m, 2H).	423	98%
1-9		OMe	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.64 (s, 1H), 11.30 (s, 1H), 8.82 (s, 1H), 8.15-8.03 (m, 1H), 8.00- 7.93 (d, J = 9.1 Hz, 1H), 7.93- 7.80 (d, J = 12.9 Hz, 2H), 6.79- 6.51 (d, J = 9.4 Hz, 1H), 4.28- 4.15 (m, 1H), 3.51-3.38 (s, 3H), 1.31-1.09 (m, 4H).	455	93%
1-10		OMe	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.69-14.59 (s, 1H), 12.08-11.94 (s, 1H), 8.90-8.74 (s, 1H), 8.13- 8.01 (d, J = 1.8 Hz, 1H), 7.99- 7.91 (d, J = 9.1 Hz, 1H), 7.77- 7.71 (s, 1H), 7.68-7.59 (d, J = 11.6 Hz, 1H), 6.71-6.62 (d, J = 9.6 Hz, 1H), 4.30-4.17 (ddd, J = 11.2, 7.5, 4.7 Hz, 1H), 3.47-	439	95%
				3.39 (s, 3H), 1.22-1.11 (m, 4H).
1-11		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.68 (s, 1H), 9.92 (s, 1H), 8.91 (s, 1H), 8.09 (d, J = 9.6 Hz, 1H), 7.99 (d, J = 8.8 Hz, 1H), 7.81 (s, 1H), 7.62-7.53 (m, 4H), 7.52- 7.47 (m, 1H), 7.46 (s, 1H), 6.65 (d, J = 9.5 Hz, 1H), 4.65-4.23 (m, 1H), 2.70 (s, 3H), 1.24 (d, J = 7.0 Hz, 2H), 1.07 (s, 2H).	481	98%
1-12		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.68 (s, 1H), 12.23 (s, 1H), 8.92 (s, 1H), 8.10 (d, J = 9.5 Hz, 1H), 8.00 (d, J = 8.7 Hz, 1H), 7.87 (s, 1H), 7.70 (s, 1H), 6.70 (d, J = 9.3 Hz, 1H), 4.43 (s, 1H), 2.64 (s, 3H), 1.23 (s, 2H), 1.07 (d, J = 12.5 Hz, 2H).	489	98%
1-13		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.66 (s, 1H), 10.55 (s, 1H), 8.91 (s, 1H), 8.04 (d, J = 9.5 Hz, 1H), 7.99 (d, J = 8.7 Hz, 1H), 7.84 (s, 1H), 7.74 (s, 1H), 6.68 (d, J = 9.4 Hz, 1H), 4.75 (s, 1H), 4.40 (m, 1H), 2.64 (s, 3H), 1.25 (d, J = 6.9 Hz, 2H), 1.08 (s, 2H).	429	90%
1-14		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.70 (s, 1H), 11.06 (s, 1H), 8.91 (s, 1H), 8.05-7.87 (m, 2H), 7.31 (s, 1H), 7.16 (s, 1H), 6.60 (d, J = 9.5 Hz, 1H), 4.40 (dd, J = 7.0, 3.4 Hz, 1H), 3.94 (s, 3H), 2.65 (s, 3H), 1.25 (d, J = 7.1 Hz, 2H), 1.08 (s, 2H).	435	90%
1-15		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.65 (s, 1H), 10.97 (s, 1H), 8.92 (s, 1H), 8.28-8.06 (m, 2H), 8.01 (d, J = 8.8 Hz, 1H), 7.95 (s, 1H), 6.74 (d, J = 8.5 Hz, 1H), 4.49- 4.33 (m, 1H), 2.64 (s, 3H), 1.25 (d, J = 6.8 Hz, 2H), 1.10 (s, 2H).	473	90%
1-16		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.72 (s, 1H), 11.95 (s, 1H), 8.91 (s, 1H), 7.99 (d, J = 7.9 Hz, 2H), 7.76 (s, 1H), 7.54 (d, J = 8.4 Hz, 1H), 7.47 (d, J = 8.4 Hz, 1H), 6.59 (d, J = 9.5 Hz, 1H), 4.40 (s, 1H), 2.63 (s, 3H), 1.25 (d, J = 6.1 Hz,	405	98%
				2H), 1.07 (s, 2H).
1-17		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.66 (s, 1H), 10.76 (s, 1H), 8.92 (s, 1H), 8.03 (d, J = 9.7 Hz, 1H), 7.99 (d, J = 8.8 Hz, 1H), 7.93 (s, 1H), 7.83 (s, 1H), 6.68 (d, J = 9.4 Hz, 1H), 2.65 (s, 3H), 1.25 (m, 2H), 1.07 (m, 2H).	482; 484	96%
1-18		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.63 (s, 1H), 11.86 (s, 1H), 8.92 (s, 1H), 8.16 (m, 3H), 8.00 (d, J = 8.7 Hz, 1H), 6.80 (s, 1H), 4.42 (s, 1H), 2.65 (s, 3H), 1.26 (m, 2H), 1.09 (m, 2H).	430	96%
1-19		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.69 (s, 1H), 11.10 (s, 1H), 8.90 (s, 1H), 7.97 (t, J = 9.04 Hz, 2H), 7.58 (s, 1H), 7.39 (s, 1H), 6.59 (d, J = 9.48 Hz, 1H), 4.39 (dt, J = 3.29, 6.75 Hz, 1H), 3.36 (s, 3H), 2.63 (s, 3H), 1.25 (d, J = 6.45 Hz, 2H), 1.06 (s, 2H).	419	96%
1-20		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.64 (s, 1H), 8.93 (s, 1H), 8.21 (s, 1H), 8.18 (s, 1H), 8.15 (d, J = 9.7 Hz, 1H), 8.02 (d, J = 8.9 Hz, 1H), 6.81 (d, J = 9.7 Hz, 1H), 6.24 (s, 2H), 4.41 (m, 2H), 2.65 (s, 4H), 1.25 (m, 2H), 1.10 (m, 2H).	461	90%
1-21		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.75 (s, 1H), 12.18 (s, 1H), 8.91 (s, 1H), 8.14 (s, 1H), 7.96 (d, J = 8.8 Hz, 1H), 7.78 (d, J = 7.7 Hz, 1H), 7.60 (d, J = 7.8 Hz, 1H), 7.41 (d, J = 7.9 Hz, 1H), 7.28 (d, J = 7.4 Hz, 1H), 4.43 (s, 1H), 2.71	405	98%
				(s, 3H), 1.24 (s, 2H), 1.05 (s, 2H).
1-22		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.75 (s, 1H), 8.91 (s, 1H), 8.16 (s, 1H), 7.96 (d, J = 8.2 Hz, 1H), 7.90 (s, 1H), 7.85 (d, J = 7.3 Hz, 1H), 7.66 (d, J = 8.5 Hz, 1H), 7.38 (d, J = 6.7 Hz, 1H), 4.42 (s, 1H), 3.74 (s, 3H), 2.69 (s, 3H), 1.23 (s, 2H), 1.05 (s, 2H).	419	95%
1-23		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.72 (s, 1H), 12.04 (s, 1H), 8.93 (s, 1H), 8.04 (d, J = 8.2 Hz, 1H), 7.68 (t, J = 7.5 Hz, 1H), 7.48 (d, J = 8.1 Hz, 1H), 7.35 (d, J = 9.7 Hz, 1H), 7.17 (d, J = 7.1 Hz, 1H), 6.49 (d, J = 9.7 Hz, 1H), 4.39 (s, 1H), 2.50 (s, 3H), 1.16 (m, 4H).	405	96%
1-24		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.82 (s, 1H), 10.88 (s, 1H), 8.95 (s, 1H), 8.20-7.94 (m, 2H), 7.86 (d, J = 30.6 Hz, 1H), 7.44 (d, J = 7.5 Hz, 1H), 7.36 (s, 1H), 6.57 (s, 1H), 4.41 (s, 1H), 2.67 (s, 3H), 1.47-0.92 (m, 4H).	405	90%
1-25		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.66 (s, 1H), 12.12 (s, 1H), 8.94 (s, 1H), 8.06 (d, J = 8.5 Hz, 1H), 7.58 (s, 1H), 7.45 (d, J = 7.0 Hz, 1H), 7.13 (s, 1H), 7.02 (d, J = 8.0 Hz, 1H), 6.65 (s, 1H), 4.40 (m, 1H), 2.62 (s, 3H), 1.28-1.04 (m, 4H).	405	90%
1-26		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.70 (s, 1H), 11.88 (s, 1H), 8.92 (s, 1H), 8.01 (d, J = 8.8 Hz, 2H), 7.86 (d, J = 7.8 Hz, 1H), 7.29 (s, 1H), 7.22 (d, J = 7.6 Hz, 1H), 6.60 (d, J = 9.6 Hz, 1H), 4.40 (s, 1H),	405	94%
				2.62 (s, 3H), 1.24 (d, J = 5.6 Hz,
				2H), 1.07 (s, 2H).
1-27		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.80 (s, 1H), 11.57 (s, 1H), 11.48 (s, 1H), 8.97 (s, 1H), 8.04 (d, J = 8.5 Hz, 1H), 7.82 (s, 1H), 7.60 (d, J = 8.1 Hz, 1H), 7.49 (d, J = 8.2 Hz, 1H), 5.86 (s, 1H), 4.45 (s, 1H), 2.68 (s, 3H), 1.30 (d, J = 5.7 Hz, 2H), 1.13 (s, 2H).	421	98%
1-28		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.75 (s, 1H), 10.73 (s, 1H), 8.90 (s, 1H), 7.97 (d, J = 8.4 Hz, 1H), 7.89 (s, 1H), 7.43 (s, 1H), 7.28 (d, J = 7.6 Hz, 1H), 4.40 (s, 1H), 2.62 (s, 3H), 1.24 (s, 2H), 1.06 (s, 2H).	466	96%
1-29		OMe	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.69 (s, 1H), 11.96 (s, 1H), 8.81 (s, 1H), 8.01 (d, J = 9.6 Hz, 1H), 7.95 (d, J = 9.1 Hz, 1H), 7.87 (s, 1H), 7.68 (d, J = 8.6 Hz, 1H), 7.49 (d, J = 8.6 Hz, 1H), 6.57 (dd, J = 9.5, 1.7 Hz, 1H), 4.32-4.10 (m,	421	98%
				1H), 3.38 (s, 3H), 1.18 (m, 4H).
1-30		Cl	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.41 (s, 1H), 11.96 (s, 1H), 8.91 (s, 1H), 8.20 (d, J = 8.8 Hz, 1H), 7.95 (d, J = 9.1 Hz, 1H), 7.80 (s, 1H), 7.68 (d, J = 8.6 Hz, 1H), 7.49 (d, J = 8.6 Hz, 1H), 6.62 (dd, J = 9.5, 1.7 Hz, 1H), 4.32-4.10 (m,	425	96%
				1H), 1.30 (m, 2H), 1.18 (m, 2H).
1-31		OMe	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.67 (s, 1H), 11.89 (s, 1H), 8.82 (s, 1H), 8.17-7.90 (m, 2H), 7.85 (d, J = 8.0 Hz, 1H), 7.48 (s, 1H), 7.35 (d, J = 7.9 Hz, 1H), 6.60 (d, J = 11.2 Hz, 1H), 4.28-	421	90%
				4.14 (m, 1H), 3.41 (s, 4H), 1.18
				(m, 4H).
1-32		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.69 (s, 1H), 11.78 (s, 1H), 8.91 (s, 1H), 7.98 (d, J = 8.77 Hz, 1H), 7.72 (s, 1H), 7.54 (s, 1H), 7.50-7.44 (m, 1H), 6.48 (s, 1H), 2.63 (s, 3H), 2.44 (s, 3H), 1.28-1.21 (m, 2H), 1.12-1.02 (m, 2H).	419	96%
1-33		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.62 (s, 1H), 13.15 (s, 1H), 8.92 (s, 1H), 8.87 (s, 1H), 8.77 (d, J = 1.74 Hz, 1H), 8.38 (d, J = 1.97 Hz, 1H), 8.02 (d, J = 8.86 Hz, 1H), 4.42 (tt, J = 3.74, 7.15 Hz, 1H), 2.66 (s, 3H), 1.25 (q, J =	431	96%
				6.85 Hz, 2H), 1.08 (s, 2H).
1-34		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 9.11 (s, 1H), 8.92 (s, 1H), 8.31 (d, J = 8.86 Hz, 1H), 8.16 (d, J = 8.54 Hz, 1H), 8.03 (d, J = 8.91 Hz, 1H), 6.51 (s, 1H), 4.44 (tt, J = 3.64, 7.02 Hz, 2H), 2.69 (s, 3H), 2.51 (s, 3H), 1.24 (d, J = 6.83 Hz, 2H), 1.10 (s, 2H).	420	95%
1-35		OMe	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.75-14.55 (m, 1H), 9.83-9.67 (d, J = 3.2 Hz, 1H), 8.89-8.73 (s, 1H), 7.96-7.86 (d, J = 9.1 Hz, 1H), 7.58-7.47 (s, 1H), 7.42- 7.34 (s, 1H), 4.30-4.14 (tt, J = 7.3, 4.5 Hz, 1H), 3.52-3.39 (s, 3H), 3.11-2.95 (t, J = 7.5 Hz, 2H), 2.62-2.56 (dd, J = 8.5, 6.3	457	99%
				Hz, 2H), 1.21-1.12 (m, 4H).
1-36		OMe	Cyclopropyl	1H NMR (400 MHz, CDCl3) δ 14.52-14.39 (s, 1H), 8.87-8.82 (s, 1H), 8.01-7.92 (m, 1H), 7.75- 7.69 (s, 1H), 7.39-7.34 (t, J = 1.7 Hz, 1H), 7.21-7.18 (s, 1H), 6.79-6.69 (dd, J = 17.3, 11.0 Hz, 1H), 5.70-5.62 (d, J = 17.3 Hz, 1H), 5.54-5.44 (d, J = 11.0 Hz, 1H), 4.09-3.99 (d, J = 3.7 Hz,	449	85%
				1H), 3.45-3.36 (s, 3H), 3.03-2.95
				(dd, J = 8.5, 6.5 Hz, 2H), 2.68-
				2.59 (dd, J = 8.7, 6.5 Hz, 2H),
				1.26-1.21 (dd, J = 5.2, 1.8 Hz,
				2H), 1.11-1.03 (dt, J = 4.0, 1.9
				Hz, 2H).
1-37		OMe	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.73-14.60 (s, 1H), 10.38- 10.26 (s, 1H), 8.84-8.76 (s, 1H), 7.96-7.88 (d, J = 9.1 Hz, 1H), 7.36-7.28 (d, J = 11.2 Hz, 1H), 7.25-7.19 (s, 1H), 4.29-4.18 (ddd, J = 11.3, 7.3, 4.4 Hz, 1H), 3.47-3.43 (s, 3H), 3.07-2.99 (t, J = 7.4 Hz, 2H), 2.60-2.53	441	85%
				(dd, J = 8.5, 6.5 Hz, 2H), 1.21-
				1.08 (d, J = 5.3 Hz, 4H).
1-38		OMe	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.70 (s, 1H), 9.62 (s, 1H), 8.79 (s, 1H), 7.89 (d, J = 9.2 Hz, 1H), 7.20 (d, J = 8.5 Hz, 2H), 4.39- 4.16 (m, 1H), 3.42 (s, 3H), 3.03- 2.88 (m, 2H), 2.54 (m, 5H), 1.16 (m, 4H).	436	99%
1-39		OMe	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 15.13-14.27 (m, 1H), 10.76- 10.64 (s, 5H), 8.98-8.88 (s, 1H), 8.19-8.14 (d, J = 2.2 Hz, 1H), 8.00-7.94 (d, J = 8.7 Hz, 1H), 7.75-7.70 (d, J = 2.1 Hz, 1H), 4.49-4.32 (tt, J = 7.3, 3.8 Hz,	408	90%
				1H), 3.03-2.95 (m, 2H), 2.69-
				2.64 (s, 3H), 2.62-2.56 (t, J =
				7.5 Hz, 2H), 1.28-1.22 (m,
				2H), 1.09-1.03 (m, 2H).
1-40		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.60 (s, 1H), 12.01 (s, 1H), 8.92 (s, 1H), 8.53 (s, 1H), 8.08-7.98 (m, 2H), 7.72 (s, 1H), 6.85 (d, J = 9.75 Hz, 1H), 4.41 (s, 1H), 3.34 (s, 1H), 2.65 (s, 3H), 2.54 (s, 3H), 1.24 (d, J = 6.54 Hz,	406	96%
				2H), 1.09 (s, 2H).
1-41		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.85-14.51 (s, 1H), 9.00-8.91 (m, 2H), 8.60-8.53 (s, 1H), 8.18-8.09 (t, J = 8.4 Hz, 2H), 8.09-8.02 (m, 1H), 7.95-7.84 (s, 1H), 7.79-7.68 (s, 1H), 4.51-4.31 (s, 1H), 2.79-2.61	389	100%
				(s, 3H), 1.36-1.20 (d, J = 6.9
				Hz, 2H), 1.16-1.04 (s, 2H).
1-42		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 15.01-14.88 (d, J =2.6 Hz, 1H), 8.95-8.82 (d, J = 2.5 Hz, 1H), 8.05-7.94 (d, J = 6.7 Hz, 1H), 7.89-7.77 (d, J = 9.4 Hz, 1H), 7.62-7.40 (m, 3H), 6.33-6.21	392	100%
				(s, 1H), 5.59-5.49 (s, 2H), 4.48-
				4.35 (s, 1H), 2.86-2.76 (s, 3H),
				1.30-1.15 (d, J = 7.0 Hz, 2H),
				1.00-0.88 (s, 2H).
1-43		Me	Cyclopropyl	1H NMR (400 MHz, MeOD) δ 9.05-8.91 (s, 1H), 8.87-8.77 (s, 1H), 8.43-8.36 (s, 1H), 8.14-8.06 (d, J = 7.3 Hz, 1H), 8.02-7.88 (d, J = 21.7 Hz, 2H), 7.74-7.62 (d, J = 8.7 Hz, 1H), 7.59-7.51 (s, 1H), 4.35-4.15 (s, 1H), 2.73-	389	97%
				2.53 (m, 3H), 1.05-0.93 (s, 2H),
				0.85-0.71 (d, J = 8.0 Hz, 2H).
1-44		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.72-14.59 (s, 1H), 9.01-8.91 (s, 1H), 8.88-8.80 (s, 1H), 8.66- 8.56 (d, J = 8.6 Hz, 1H), 8.25- 8.16 (d, J = 8.0 Hz, 1H), 8.14- 8.09 (s, 1H), 8.08-8.01 (d, J = 8.6 Hz, 1H), 7.95-7.89 (d, J = 8.7 Hz, 1H), 7.88-7.79 (d, J = 7.7 Hz, 1H), 4.51-4.35 (s, 1H),	405	97.5%
				2.75-2.67 (s, 3H), 1.30-1.19
				(d, J = 6.8 Hz, 2H), 1.16-1.07
				(s, 2H).
1-45		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.85-14.58 (s, 1H), 9.00-8.88 (s, 1H), 8.19-8.07 (d, J = 8.3 Hz, 1H), 8.07-7.94 (m, 4H), 7.68- 7.58 (d, J = 6.0 Hz, 2H), 7.57- 7.48 (d, J = 8.2 Hz, 1H), 4.49-	388	98%
				4.33 (s, 1H), 2.72-2.59 (s, 3H),
				1.33-1.19 (d, J = 7.4 Hz, 2H),
				1.16-1.00 (s, 2H).
1-46		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 9.69-9.59 (s, 1H), 9.01-8.92 (d, J = 2.5 Hz, 1H), 8.69-8.58 (d, J = 2.4 Hz, 1H), 8.47-8.34 (d, J = 7.6 Hz, 1H), 8.14-8.04 (d, J = 8.1 Hz, 1H), 7.95-7.80 (t, J = 8.7 Hz, 2H), 7.57-7.46 (d, J = 7.9 Hz, 1H), 4.48-4.34 (s, 1H), 2.52-2.50 (s, 3H), 1.29-	389	98%
				1.01 (m, 4H).
1-47		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.96-14.46 (s, 1H), 12.04-11.50 (s, 1H), 8.98-8.89 (s, 1H), 8.34- 8.17 (d, J = 12.3 Hz, 1H), 8.17- 8.01 (m, 2H), 7.97-7.90 (d, J = 8.1 Hz, 1H), 4.48-4.36 (dd, J = 7.3, 4.1 Hz, 1H), 2.66-2.56 (s, 3H), 1.31-1.17 (d, J = 7.1 Hz, 2H), 1.15-1.03 (s, 2H).	422	99%
1-48		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 9.19-9.11 (s, 1H), 8.98-8.92 (s, 1H), 8.45-8.39 (s, 1H), 8.13-8.00 (dd, J = 16.7, 8.4 Hz, 2H), 7.80- 7.69 (t, J = 7.7 Hz, 1H), 7.66- 7.55 (t, J = 7.7 Hz, 1H), 7.38- 7.29 (d, J = 8.3 Hz, 1H), 4.47- 4.34 (s, 1H), 2.65-2.54 (s, 3H), 1.28-1.07 (m, 4H).	405	98%
1-49		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.69-14.45 (s, 1H), 10.31- 10.19 (s, 1H), 9.06-8.94 (d, J = 3.6 Hz, 2H), 8.73-8.62 (d, J = 8.2 Hz, 1H), 8.61-8.43 (m, 2H), 8.32-8.21 (t, J = 7.5 Hz, 1H), 8.21-8.11 (m, 2H), 7.83-7.71 (d, J = 8.3 Hz, 1H), 4.67-4.52 (s, 3H), 4.50-	404	100%
				4.39 (d, J = 7.6 Hz, 1H), 2.52-
				2.50 (m, 3H), 1.32-1.03 (m, 4H).
1-50		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.72-14.45 (s, 1H), 9.88-9.78 (s, 1H), 9.58-9.48 (s, 1H), 9.02- 8.92 (s, 1H), 8.70-8.60 (d, J = 9.0 Hz, 1H), 8.59-8.51 (d, J = 8.2 Hz, 1H), 8.46-8.36 (t, J = 7.9 Hz, 1H), 8.24-8.06 (t, J = 9.7 Hz, 2H), 4.78-4.67 (s, 2H), 4.53-	404	98%
				4.40 (s, 1H), 2.82-2.71 (s, 3H),
				1.37-1.18 (d, J = 6.4 Hz, 2H),
				1.16-1.07 (m, 2H).
1-51		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 9.10-9.01 (d, J = 4.0 Hz, 1H), 8.98-8.91 (d, J = 2.6 Hz, 1H), 8.30-8.19 (d, J = 8.4 Hz, 1H), 8.14-8.07 (s, 1H), 8.05-7.97 (t, J = 7.7 Hz, 1H), 7.96-7.89 (d, J = 8.4 Hz, 1H), 7.78-7.68 (d, J = 6.8 Hz, 1H), 7.65-7.57 (m, 1H), 4.45-4.33 (s, 1H), 2.48-	389	93.6%
				2.40 (d, J = 2.8 Hz, 3H), 1.28-
				1.03 (m, 4H).
1-52		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.78-14.66 (s, 1H), 9.06-8.97 (s, 1H), 8.96-8.88 (s, 1H), 8.54- 8.46 (d, J = 8.1 Hz, 1H), 8.26- 8.14 (d, J = 8.3 Hz, 1H), 8.14- 8.06 (s, 1H), 8.06-7.98 (d, J =	389	100%
				8.6 Hz, 1H), 7.74-7.58 (d, J =
				8.3 Hz, 2H), 4.51-4.29 (s, 1H),
				2.73-2.60 (s, 3H), 1.29-1.18 (d,
				J = 7.0 Hz, 2H), 1.15-1.07 (s, 2H).
1-53		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 8.96-8.88 (d, J = 2.4 Hz, 1H), 8.85- 8.78 (s, 1H), 8.57-8.47 (d, J = 8.2 Hz, 1H), 8.25-8.13 (d, J = 8.3 Hz, 1H), 8.03-7.95 (d, J = 8.3 Hz, 1H), 7.86-7.77 (m, 2H), 7.69-7.54 (d, J = 8.7 Hz, 1H), 4.44-4.31 (s, 1H), 2.48-2.42 (s, 3H), 1.29-1.16 (d, J = 7.6 Hz, 2H), 1.15-1.02 (s, 2H).	389	98%
1-54		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 9.17-9.09 (s, 1H), 9.01-8.91 (d, J = 2.7 Hz, 1H), 8.26-8.17 (d, J = 8.5 Hz, 1H), 8.15-8.06 (d, J = 8.5 Hz, 1H), 7.94-7.84 (s, 1H), 2.48-2.42 (m, 2H), 7.72- 7.59 (d, J = 9.2 Hz, 2H), 7.56- 7.45 (d, J = 8.3 Hz, 1H), 4.45- 4.35 (s, 1H), 2.52-2.45 (s, 3H),	389	98%
				1.29-1.03 (dd, J = 16.6, 7.5 Hz,
				4H).
1-55		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 15.08-14.78 (s, 1H), 8.95-8.83 (s, 2H), 8.48-8.37 (d, J = 6.0 Hz, 1H), 8.33-8.19 (d, J = 8.2 Hz, 1H), 8.14-8.02 (d, J = 8.5 Hz, 1H), 7.94-7.76 (m, 2H), 7.68- 7.59 (d, J = 7.1 Hz, 1H), 7.58- 7.49 (t, J = 7.2 Hz, 1H), 4.47- 4.34 (s, 1H), 2.73-2.56 (s, 3H),	405	95%
				1.31-0.99 (m, 4H).
1-56		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 9.00-8.91 (s, 1H), 8.85-8.75 (d, J = 6.1 Hz, 1H), 8.73-8.64 (d, J = 8.6 Hz, 1H), 8.13-8.05 (d, J = 8.4 Hz, 1H), 7.97-7.86 (d, J = 8.1 Hz, 1H), 7.80-7.71 (s, 1H), 7.65-7.58 (d, J = 5.8 Hz, 1H), 7.57-7.48 (d, J = 8.4 Hz, 1H), 4.46-4.35 (s, 1H), 2.57-2.52 (s, 3H), 1.28- 1.04 (m, 4H).	405	96%
1-57		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.95-14.35 (m, 1H), 9.01-8.90 (t, J = 2.0 Hz, 1H), 8.80-8.63 (m, 2H), 8.13-8.06 (m, 1H), 8.04- 7.95 (t, J = 7.8 Hz, 1H), 7.84-7.75 (d, J = 6.5 Hz, 1H), 7.52-7.41 (ddd, J = 10.0, 5.1, 2.5 Hz, 1H), 7.38-7.29 (d, J = 8.4 Hz, 1H), 4.46-4.32 (d, J = 6.9 Hz, 1H), 2.49-2.44 (s, 3H), 1.29-0.99 (m, 4H).	405	93.3%
1-58		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 8.98-8.89 (s, 1H), 8.73-8.64 (d, J = 6.6 Hz, 1H), 8.58-8.52 (s, 1H), 8.35-8.26 (d, J = 8.2 Hz, 1H), 8.12-7.99 (t, J = 10.7 Hz, 2H), 7.83-7.75 (d, J = 8.3 Hz, 1H), 7.65-7.53 (s, 1H), 4.46-4.36	405	96.2%
				(s, 1H), 2.65-2.59 (s, 3H), 1.29-
				1.19 (d, J = 7.8 Hz, 2H), 1.14-
				1.07 (s, 2H).
1-59		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 8.96-8.87 (s, 1H), 8.75-8.64 (d, J = 7.2 Hz, 2H), 8.28-8.19 (s, 1H), 8.10-7.99 (d, J = 8.5 Hz, 2H), 7.90-7.80 (d, J = 9.0 Hz, 1H), 7.63-7.52 (s, 1H), 4.48- 4.34 (s, 1H), 2.65-2.57 (s, 3H), 1.30-1.18 (d, J = 7.1 Hz, 2H), 1.14-1.02 (s, 2H).	405	99%
1-60		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 9.77-9.61 (s, 1H), 9.00-8.90 (d, J = 3.1 Hz, 1H), 8.75-8.62 (d, J = 5.8 Hz, 1H), 8.57-8.42 (d, J = 8.2 Hz, 1H), 8.31-8.21 (s, 1H), 8.22- 8.13 (d, J = 5.3 Hz, 1H), 8.11-	389	93.6%
				8.01 (d, J = 8.7 Hz, 1H), 7.94-
				7.81 (d, J = 8.4 Hz, 1H), 4.49-
				4.34 (s, 1H), 2.68-2.59 (s, 3H),
				1.34-1.18 (d, J = 7.6 Hz, 2H),
				1.15-1.00 (s, 2H).
1-61		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 9.19-9.10 (s, 1H), 9.03-8.95 (s, 1H), 8.37-8.27 (d, J = 6.9 Hz, 1H), 8.18-8.05 (m, 4H), 7.81-7.73 (d, J = 8.4 Hz, 1H), 4.52-4.42 (t, J = 5.2 Hz, 1H), 2.74-2.65 (s, 3H), 1.36-1.27 (d, J = 7.1 Hz,	405	1005
				2H), 1.19-1.10 (s, 2H).
1-62		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.82-14.70 (s, 1H), 11.54-11.41 (s, 1H), 9.03-8.93 (s, 1H), 8.44- 8.33 (d, J = 8.2 Hz, 1H), 8.14- 8.01 (d, J = 8.0 Hz, 1H), 7.84- 7.75 (s, 1H), 7.58-7.51 (d, J = 7.6 Hz, 1H), 7.39-7.26 (s, 1H), 6.76-6.64 (d, J = 6.6 Hz, 1H), 4.52-4.40 (s, 1H), 2.70-2.61	405	100%
				(s, 3H), 1.37-1.22 (d, J = 6.8
				Hz, 2H), 1.19-1.04 (s, 2H).
1-63		1H NMR (400 MHz, DMSO) δ 15.18 (s, 1H), 12.31 (s, 1H), 9.09 (s, 1H), 8.82 (d, J = 2.0 Hz, 1H), 8.45 (d, J = 1.7 Hz, 1H), 8.03 (t, J = 9.3 Hz, 2H), 7.76 (d, J = 8.4 Hz, 1H), 6.63 (d, J = 9.4 Hz, 1H), 5.00 (d, J = 6.7 Hz, 1H), 4.58 (d, J = 10.8 Hz, 1H), 4.45 (d, J = 10.0 Hz, 1H), 2.54 (s, 1H), 1.52 (d, J = 6.7 Hz, 3H).	390	98%
1-64		1H NMR (400 MHz, DMSO) δ 14.96 (s, 1H), 12.35 (s, 1H), 9.10 (s, 1H), 8.68 (s, 1H), 8.34 (s, 1H), 8.01 (d, J = 9.53 Hz, 1H), 7.79 (d, J = 9.70 Hz, 1H), 6.64 (d, J = 9.45 Hz, 1H), 5.01 (d, J = 6.68 Hz, 1H), 4.60-4.54 (m, 1H), 4.46 (d, J = 9.78 Hz, 1H), 1.49 (d, J = 6.71 Hz, 3H).	408	96%
1-65		1H NMR (400 MHz, DMSO) δ 9.27 (s, 1H), 8.95 (s, 1H), 8.87 (d, J = 15.4 Hz, 1H), 8.41-8.22 (m, 3H), 8.01 (t, J = 7.3 Hz, 1H), 7.85 (t, J = 7.3 Hz, 1H), 7.73 (d, J = 8.2 Hz, 1H), 4.45 (m, 1H), 2.77 (s, 3H), 1.31 (d, J = 6.2 Hz, 2H), 1.11 (s, 2H).	371	97%

TABLE 2
Com-
pound					MS
No.	R3 =	R2 =	R1 =	NMR	(MH+)	HPLC
2-1		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 8.28 (s, 1H), 7.98 (s, 1H), 7.80 (s, 1H), 7.33 (d, J = 8.90 Hz, 1H), 7.16 (d, J = 9.30 Hz, 1H), 3.66 (d, J = 3.58 Hz, 1H), 1.96 (s, 3H), 0.58 (d, J = 5.78 Hz, 2H), 0.37 (d, J = 1.61 Hz, 2H).	357	94%
2-2		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 8.93 (s, 1H), 8.48 (d, J = 2.77 Hz, 1H), 8.13 (s, 1H), 8.01 (d, J = 8.72 Hz, 1H), 7.61 (s, 1H), 4.50-4.30 (m, 1H), 3.49 (d, J = 5.30 Hz, 5H), 3.36- 3.29 (m, 5H), 2.66 (d, J = 15.95 Hz, 3H), 1.43 (s, 9H), 1.28-1.21 (m,2H), 1.08 (s, 2H).	523	98%
2-3		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 8.92 (s, 1H), 8.79 (d, J = 5.61 Hz, 2H), 8.01 (d, J = 8.93 Hz, 1H), 7.50 (d, J = 5.50 Hz, 2H), 4.40 (s, 1H), 2.61 (s, 3H), 1.24 (d, J = 5.97 Hz, 2H), 1.07 (s, 2H).	339	98%
2-4		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 9.00 (s, 2H), 8.92 (s, 1H), 8.49 (d, J = 2.73 Hz, 1H), 8.12 (s, 1H), 7.98 (t, J = 11.57 Hz, 1H), 7.56 (s, 1H), 4.44-4.34 (m, 1H), 3.64 (s, 5H), 3.26 (s, 4H), 2.62 (s, 3H), 1.23 (d, J = 6.27 Hz, 2H), 1.07 (s, 2H).	423	95%
2-5		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 8.93 (s, 1H), 8.71 (t, J = 26.47 Hz, 1H), 8.04 (d, J = 8.68 Hz, 2H), 7.61 (d, J = 45.28 Hz, 1H), 4.44- 4.38 (m, 1H), 2.55 (s, 2H), 2.34 (d, J = 9.33 Hz, 3H), 1.23 (s, 2H), 1.06 (dd, J = 4.45, 8.57 Hz, 2H).	353	95%
2-6		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.55 (s, 1H), 8.92 (s, 1H), 8.83 (t, J = 8.69 Hz, 1H), 8.65 (dt, J = 8.70, 17.42 Hz, 1H), 8.05 (d, J = 8.87 Hz, 1H), 7.73-7.52 (m, 1H), 4.41 (tt, J = 3.77, 7.16 Hz, 1H), 2.64 (s, 3H), 1.31-1.16 (m, 2H), 1.10-0.97 (m, 2H).	357	98%
2-7		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 8.93 (s, 1H), 8.85-8.61 (m, 2H), 8.03 (d, J = 6.60 Hz, 1H), 7.96 (s, 2H), 7.69 (dd, J = 5.19, 7.64 Hz, 1H), 4.41 (ddd, J = 3.87, 7.26, 10.97 Hz, 2H), 2.75-2.72 (m, 5H), 1.33-1.20 (m, 3H), 1.13-1.03 (m, 2H).	339	98%
2-8		Me	Cyclopropyl	1H NMR (400 MHz, MeOD) δ 8.79 (s, 1H), 7.92-7.71 (m, 2H), 7.55 (t, J = 17.62 Hz, 1H), 6.84 (t, J = 36.31 Hz, 1H), 4.16-4.04 (m, 1H), 3.02 (s, 5H), 1.09-1.01 (m, 2H), 0.81 (q, J = 7.23 Hz, 2H).	355	98%
2-9		Me	Cyclopropyl	1H NMR (400 MHz, MeOD) δ 8.06 (t, J = 38.62 Hz, 2H), 7.68 (dd, J = 8.35, 33.76 Hz, 2H), 7.47 (d, J = 8.87 Hz, 1H), 7.13- 6.77 (m, 2H), 4.33 (s, 1H), 3.97 (d, J = 7.85 Hz, 3H), 2.20-1.90 (m, 2H), 1.35-1.22 (m, 1H), 1.05 (s, 1H).	369	98%
2-10		Me	Cyclopropyl	1H NMR (400 MHz, MeOD) δ 9.06 (s, 1H), 8.33 (s, 1H), 8.01 (d, J = 9.18 Hz, 1H), 7.67 (t, J = 24.14 Hz, 2H), 7.17 (s, 1H), 4.37 (s, 1H), 3.94 (s, 3H), 2.66 (s, 3H), 1.32 (d, J = 6.60 Hz, 2H), 1.07 (s, 2H).	369	98%
2-11		Me	Cyclopropyl	1H NMR (400 MHz, MeOD) δ 9.05 (s, 1H), 8.29 (s, 2H), 8.09 (d, J = 7.83 Hz, 1H), 7.94 (d, J = 23.80 Hz, 2H), 7.39-7.20 (m, 2H), 7.09 (s, 1H), 4.36 (s, 1H), 2.77 (s, 3H), 1.30 (s, 2H), 1.09 (s, 2H).	466	98%
2-12		Me	Cyclopropyl	1H NMR (400 MHz, MeOD) δ 9.02 (s, 1H), 8.40 (d, J = 92.33 Hz, 2H), 8.16-8.03 (m, 2H), 7.98-7.80 (m, 1H), 7.75-7.50 (m, 2H), 4.34 (s, 1H), 3.82 (d, J = 24.28 Hz, 4H), 3.45 (s, 4H), 2.70 (d, J = 23.16 Hz, 3H), 1.27 (dd, J = 11.61, 24.61 Hz, 3H), 1.09 (s, 2H).	424	98%
2-13		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.68 (s, 1H), 8.91 (s, 1H), 8.69 (s, 1H), 7.97 (d, J = 8.46 Hz, 1H), 7.79 (s, 1H), 7.63 (s, 1H), 4.40 (s, 1H), 3.82 (d, J = 6.95 Hz, 2H), 3.21 (s, 2H), 2.63 (d, J = 43.98 Hz, 3H), 1.22 (d, J = 5.36 Hz, 2H), 1.05 (s, 2H).	380	97%
2-14		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.69 (s, 2H), 8.91 (s, 1H), 8.49 (s, 2H), 8.24 (s, 2H), 7.98 (d, J = 8.62 Hz, 1H), 4.41 (s, 1H), 2.65 (d, J = 31.48 Hz, 3H), 1.24 (d, J = 6.48 Hz, 2H), 1.07 (s, 2H).	399	99%
2-15		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.67 (s, 1H), 8.91 (s, 1H), 8.13 (d, J = 25.11 Hz, 1H), 8.07 (s, 1H), 7.95 (dd, J = 8.95, 25.35 Hz, 2H), 7.06 (d, J = 8.71 Hz, 1H), 4.41 (s, 1H), 2.65 (d, J = 25.72 Hz, 3H), 1.22 (d, J = 5.45 Hz, 2H), 1.05 (s, 2H).	354	99%
2-16		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 8.91 (s, 1H), 8.74 (s, 1H), 8.54 (t, J = 24.30 Hz, 2H), 7.99 (d, J = 8.68 Hz, 1H), 4.41 (s, 1H), 3.10 (d, J = 17.91 Hz, 3H), 2.70 (s, 3H), 1.25 (d, J = 5.66 Hz, 2H), 1.07 (s, 2H).	413	99%
2-17		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.63 (s, 1H), 9.79 (s, 2H), 8.92 (s, 1H), 8.61 (s, 1H), 8.01 (d, J = 13.11 Hz, 2H), 4.67 (d, J = 32.94 Hz, 4H), 4.40 (s, 1H), 2.62 (s, 3H), 1.23 (s, 3H), 1.07 (s, 2H).	380	97%
2-18		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.65 (s, 1H), 8.89 (s, 1H), 8.27 (s, 1H), 8.07 (t, J = 6.62 Hz, 1H), 7.94 (d, J = 8.87 Hz, 1H), 7.28 (s, 2H), 4.40 (tt, J = 3.75, 7.16 Hz, 1H), 3.31 (s, 1H), 2.67 (s, 3H), 1.31-1.19 (m, 2H), 1.10-1.00 (m, 2H).	379	99%
2-19		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 9.28 (s, 1H), 8.93 (s, 1H), 8.70 (s, 1H), 8.36 (s, 1H), 8.03 (d, J = 8.65 Hz, 1H), 4.41 (s, 2H), 2.65 (s, 3H), 2.44 (s, 3H), 1.25 (d, J = 6.79 Hz, 2H), 1.10 (s, 2H).	420	97%
2-20		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 8.91 (s, 1H), 8.19 (d, J = 11.25 Hz, 3H), 7.99 (d, J = 8.83 Hz, 1H), 7.62 (s, 1H), 4.41 (s, 2H), 2.69 (s, 3H), 1.25 (d, J = 5.80 Hz, 2H), 1.05 (s, 2H).	397	99%
2-21		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.72 (s, 1H), 8.89 (s, 1H), 8.11-7.87 (m, 2H), 7.74 (s, 1H), 6.71 (s, 2H), 4.39 (s, 1H), 2.63 (d, J = 29.40 Hz, 3H), 1.20 (t, J = 25.86 Hz, 2H), 0.99 (d, J = 41.43 Hz, 2H).	388	98%
2-22		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.71 (s, 1H), 8.90 (s, 1H), 8.26 (s, 1H), 7.95 (d, J = 8.81 Hz, 1H), 7.86 (s, 1H), 6.89 (s, 2H), 4.39 (s, 1H), 2.66 (s, 3H), 1.24 (d, J = 5.61 Hz, 2H), 1.06 (s, 2H).	422	98%
2-23		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.71 (s, 1H), 8.98 (s, 1H), 8.13-8.02 (m, 2H), 7.92 (d, J = 14.79 Hz, 3H), 4.47 (s, 1H), 2.71 (d, J = 23.60 Hz, 3H), 2.31 (s, 3H), 1.29 (d, J = 5.54 Hz, 2H), 1.15 (d, J = 22.69 Hz, 2H).	368	99%
2-24		OMe	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.67 (s, 1H), 8.79 (s, 1H), 8.11 (s, 1H), 7.90 (s, 1H), 7.82 (s, 1H), 6.73 (s, 2H), 4.22 (s, 1H), 3.46 (s, 3H), 3.31 (s, 2H), 1.16 (s, 4H).	404	98%
2-25		OMe	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.66 (s, 1H), 8.80 (s, 1H), 8.39 (s, 1H), 8.13-7.81 (m, 2H), 6.91 (s, 2H), 4.23 (s, 1H), 3.31 (s, 3H), 1.17 (d, J = 6.99 Hz, 3H).	438	99%
2-26		OMe	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.74 (d, J = 61.68 Hz, 1H), 8.76 (d, J = 28.90 Hz, 1H), 8.39 (s, 1H), 7.97 (s, 1H), 7.92 (d, J = 9.13 Hz, 1H), 4.23 (s, 1H), 3.46 (s, 3H), 1.17 (d, J = 7.13 Hz, 4H).	395	98%
2-27		Me	Cyclopropyl	1H NMR (400 MHz, DMSO), 8.89 (s, 1H), 7.95-7.93 (m, 2H), 7.83 (s, 1H), 7.60-6.57 (d, 1H), 4.39 (s, 1H), 2.63 (d, J = 29.40 Hz, 3H), 1.20 (t, J = 25.86 Hz, 2H), 0.99 (d, J = 41.43 Hz, 2H).	372	98%
2-28		OMe	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 9.95 (s, 1H), 8.94-8.66 (m, 1H), 8.49-8.39 (m, 1H), 8.26 (d, J = 1.30 Hz, 1H), 7.91 (dd, J = 19.79, 31.75 Hz, 2H), 4.27-4.17 (m, 1H), 3.50-3.42 (m, 3H), 1.17 (dt, J = 7.59, 17.65 Hz, 3H).	398	98%
2-29		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 9.95 (s, 1H), 8.92 (d, J = 13.25 Hz, 1H), 8.32 (d, J = 1.05 Hz, 1H), 8.17 (d, J = 1.69 Hz, 1H), 8.00 (t, J = 18.18 Hz, 1H), 7.83 (d, J = 33.09 Hz, 1H), 4.40 (dt, J = 3.59, 10.71 Hz, 1H), 2.68 (d, J = 12.78 Hz, 3H), 1.25 (q, J = 6.89 Hz, 2H), 1.14-0.93 (m, 2H).	382	98%
2-30		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.64 (s, 2H), 8.90 (s, 1H), 7.97 (d, J = 8.81 Hz, 1H), 7.64 (d, J = 1.21 Hz, 1H), 7.34 (s, 1H), 4.40 (td, J = 3.75, 7.19 Hz, 1H), 3.90 (s, 3H), 2.78-2.61 (m, 3H), 1.23 (q, J = 7.19 Hz, 2H), 1.16-0.97 (m, 2H).	384	95%
2-31		Me		1H NMR (400 MHz, DMSO) δ 14.64 (s, 2H), 8.90 (s, 1H), 7.97 (d, J = 8.81 Hz, 1H), 7.64 (d, J = 1.21 Hz, 1H), 7.34 (s, 1H), 4.40 (td, J = 3.75, 7.19 Hz, 1H), 3.90 (s, 3H), 2.78-2.61 (m, 3H), 1.23 (q, J = 7.19 Hz, 2H), 1.16-0.97 (m, 2H).	406	99%
2-32		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.62 (s, 1H), 8.90 (s, 1H), 7.99 (d, J = 1.60 Hz, 1H), 7.95 (t, J = 10.20 Hz, 1H), 7.70-7.53 (m, 1H), 4.39 (td, J = 3.61, 7.03 Hz, 1H), 2.62 (d, J = 19.25 Hz, 3H), 1.84 (ddd, J = 5.42, 8.33, 13.56 Hz, 1H), 1.21 (t, J = 6.56 Hz, 1H), 1.05 (d, J =	394	98%
				8.64 Hz, 1H), 1.03-0.96 (m, 2H), 0.78-
				0.65 (m, 2H).
2-33		Me		1H NMR (400 MHz, DMSO) δ 8.88 (d, J = 3.01 Hz, 1H), 8.18 (s, 1H), 8.13 (s, 1H), 8.09 (s, 1H), 7.99 (d, J = 8.77 Hz, 1H), 7.54 (s, 1H), 5.29-5.01 (m, 1H), 4.50-4.31 (m, 1H), 2.71-2.57 (m, 2H), 1.76 (ddd, J = 9.04, 15.14, 17.62 Hz, 1H), 1.53 (d, J = 26.94 Hz, 1H).	415	98%
2-34		Cl	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 8.92 (s, 1H), 8.11 (d, J = 8.56 Hz, 1H), 8.02 (d, J = 0.96 Hz, 1H), 7.81 (d, J = 1.67 Hz, 1H), 4.44-4.39 (m, 2H), 1.32-1.17 (m, 2H), 1.17-1.04 (m, 2H).	408	94%
2-35		OMe	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 8.80 (s, 1H), 7.99 (s, 1H), 7.92 (d, J = 9.3 Hz, 1H), 7.69 (d, J = 12.0 Hz, 1H), 4.29-4.14 (m, 1H), 3.47 (s, 3H), 1.24-1.04 (m, 4H).	387	99%
2-36		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.67 (s, 1H), 8.92 (s, 1H), 8.37 (s, 1H), 8.30 (d, J = 2.3 Hz, 1H), 8.11-7.88 (m, 3H), 7.51 (s, 1H), 4.55-4.30 (m, 3H), 3.20 (m, 2H), 2.68 (s, 3H), 1.25 (d, J = 6.4 Hz, 2H), 1.08 (d, J = 7.0 Hz, 2H).	441	98%
2-37		OMe		1H NMR (400 MHz, DMSO) δ 14.52 (s, 1H), 8.82 (d, J = 1.51 Hz, 1H), 8.38 (s, 1H), 8.11 (s, 1H), 7.94 (d, J = 9.20 Hz, 1H), 7.36 (s, 2H), 5.10 (ddd, J = 5.42, 8.45, 64.07 Hz, 1H), 4.24- 4.12 (m, 1H), 1.86-1.55 (m, 2H).	413	98%
2-38		OMe		1H NMR (400 MHz, DMSO) δ 14.55 (s, 1H), 8.82 (d, J = 1.46 Hz, 1H), 8.15 (d, J = 36.97 Hz, 1H), 7.92 (d, J = 9.24 Hz, 1H), 7.80 (s, 1H), 6.75 (s, 2H), 5.10 (ddd, J = 5.43, 8.45, 64.08 Hz, 1H), 4.29-4.12 (m, 1H), 1.93-1.53 (m, 2H).	422	98%
2-39		Me		1H NMR (400 MHz, DMSO) δ 14.39 (s, 1H), 8.80 (s, 1H), 8.16-8.08 (m, 2H), 7.98-7.86 (m, 2H), 7.69-7.59 (m, 1H), 7.37 (dd, J = 5.20, 11.82 Hz, 1H), 7.26 (s, 2H), 1.67 (s, 3H).	451	99%
2-40		Me	Cyclopropyl	1H NMR (400 MHz, CDCl3) δ 14.60- 14.29 (s, 1H), 8.96-8.89 (s, 1H), 8.05- 7.96 (m, 2H), 7.48-7.40 (m, 4H), 7.40- 7.33 (dt, J = 8.5, 2.8 Hz, 1H), 7.33-7.29 (s, 1H), 4.88-4.75 (s, 2H), 4.17-3.98 (s, 1H), 2.73-2.62 (s, 3H), 1.28-1.20 (m, 2H), 1.02-0.93 (s, 2H).	430	99%
2-41		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.83-14.68 (s, 1H), 8.99-8.81 (s, 1H), 7.96-7.89 (d, J = 8.9 Hz, 1H), 7.88-7.81 (s, 1H), 7.36-7.20 (s, 1H), 6.19-6.08 (s, 2H), 4.47-4.31 (s, 1H), 2.75-2.60 (s, 3H), 1.36-1.10 (m, 6H), 1.10- 0.94 (t, J = 3.1 Hz, 2H).	382	93%
2-42		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.83- 14.67 (s, 3H), 8.97-8.85 (s, 3H), 8.00- 7.85 (m, 6H), 7.72-7.60 (t, J = 1.7 Hz, 3H), 6.97-6.81 (dd, J = 17.3, 11.0 Hz, 3H), 6.45-6.27 (s, 6H), 5.85-5.70 (m, 4H), 5.44-5.26 (dd, J = 11.0, 1.2 Hz, 3H), 4.47- 4.33 (s, 1H), 2.76-2.60 (s, 9H), 1.30-	380	99%
				1.18 (m, 6H), 1.12-0.98 (m, 5H), 1.32-
				1.20 (m, 7H).
2-43		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 8.95-8.90 (s, 1H), 8.36-8.31 (m, 1H), 8.13-8.07 (d, J = 2.0 Hz, 1H), 8.02-7.97 (d, J = 8.8 Hz, 1H), 4.49-4.36 (m, 3H), 2.90-2.79 (s, 5H), 2.76-2.67 (s, 3H), 1.33-1.20 (q, J = 6.9 Hz, 2H), 1.10-0.98 (m, 2H).	397	98%
2-44		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 8.93-8.91 (s, 1H), 8.24-8.20 (m, 1H), 8.01-7.96 (d, J = 8.8 Hz, 1H), 7.93-7.87 (t, J = 2.8 Hz, 1H), 4.49-4.38 (tt, J = 7.2, 3.9 Hz, 1H), 4.24-4.14 (t, J = 5.5 Hz, 2H), 2.85-2.77 (s, 6H), 1.29-1.20 (m, 2H), 1.09-0.98 (m, 2H).	411	97%
2-45		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 8.94-8.89 (s, 1H), 8.15-8.09 (d, J = 2.1 Hz, 1H), 8.02-7.96 (d, J = 8.9 Hz, 1H), 7.92-7.88 (s, 1H), 4.46- 4.37 (m, 1H), 4.57-4.46 (s, 2H), 2.71-2.65 (s, 3H), 1.25-1.18 (d, J = 6.7 Hz, 2H), 1.10- 0.98 (m, 2H).	384	90%
2-46		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.71 (s, 1H), 8.89 (s, 1H), 8.35 (s, 2H), 7.94 (d, J = 8.67 Hz, 1H), 7.09 (s, 2H), 4.39 (s, 1H), 2.70 (s, 3H), 1.24 (d, J = 5.31 Hz, 2H), 1.03 (s, 2H).	354	99%
2-47		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.72 (s, 1H), 8.89 (s, 1H), 8.41 (s, 2H), 7.95 (d, J = 8.41 Hz, 1H), 7.60 (d, J = 28.12 Hz, 1H), 4.40 (s, 1H), 2.88 (s, 3H), 2.70 (s, 3H), 1.25 (d, J = 5.56 Hz, 2H), 1.03 (s, 2H).	369	99%
2-48		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.73 (s, 1H), 8.89 (s, 1H), 8.39 (s, 2H), 7.95 (d, J = 8.73 Hz, 1H), 7.64 (s, 1H), 4.39 (s, 1H), 2.70 (s, 3H), 2.53 (d, J = 9.32 Hz, 3H), 1.24 (d, J = 6.11 Hz, 2H), 1.17 (t, J = 6.98 Hz, 2H), 1.03 (s, 2H).	383	97%
2-49		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.72 (s, 2H), 8.90 (s, 1H), 8.48 (s, 2H), 7.96 (d, J = 8.59 Hz, 1H), 4.39 (s, 1H), 3.24 (d, J = 22.01 Hz, 6H), 2.70 (s, 3H), 1.25 (d, J = 6.03 Hz, 2H), 1.04 (d, J = 7.73 Hz, 2H).	383	98%
2-50		Cl	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 8.92 (s, 1H), 8.35 (s, 2H), 8.13 (d, J = 8.6 Hz, 1H), 7.15 (s, 2H), 4.41 (m, 3.8 Hz, 1H), 1.37-1.17 (m, 2H), 1.18-1.02 (m, 2H).	375	99%
2-51		Me		1H NMR (400 MHz, DMSO) δ 8.87 (d, J = 3.2 Hz, 1H), 8.35 (d, J = 1.0 Hz, 2H), 7.97 (d, J = 8.9 Hz, 1H), 7.08 (s, 2H), 5.33-4.97 (m, 2H), 4.37 (m, 1H), 2.65 (s, 3H), 1.89-1.41 (m, 2H).	373	99%
2-52		MeO		1H NMR (400 MHz, DMSO) δ 14.54 (s, 1H), 8.82 (d, J = 1.2 Hz, 1H), 8.44 (s, 2H), 7.93 (d, J = 9.2 Hz, 1H), 7.10 (s, 2H), 5.09 (m, 1H), 4.37-3.96 (m, 1H), 3.50 (s, 3H), 1.98-1.52 (m, 2H).	389	98%
2-53		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.65 (s, 1H), 8.91 (d, J = 4.9 Hz, 1H), 8.76 (s, 2H), 8.15- 7.85 (m, 1H), 4.63-4.29 (m, 1H), 2.50 (s, 3H), 1.29-1.15 (m, 2H), 1.06 (d, J = 7.0 Hz, 2H).	384	99%
2-54		MeO	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 8.86 (s, 1H), 8.52 (s, 2H), 8.00 (d, J = 9.2 Hz, 1H), 7.18 (s, 2H), 4.29 (m, 1H), 3.55 (s, 3H), 1.27-1.11 (m, 4H).	371	99%
2-55		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.67 (s, 1H), 8.79 (s, 1H), 8.19 (s, 1H), 7.90 (d, J = 9.3 Hz, 1H), 7.81 (s, 1H), 6.91 (t, J = 5.6 Hz, 1H), 4.29-4.11 (m, 1H), 3.53-3.41 (m, 5H), 1.26- 1.06 (m, 7H).	432	98%
2-56		1H NMR (400 MHz, DMSO) δ 9.06 (s, 1H), 8.38 (s, 1H), 8.13 (d, J = 1.75 Hz, 1H), 7.72 (d, J = 9.80 Hz, 1H), 7.29 (s, 2H), 5.06-4.90 (m, 1H), 4.58 (d, J = 10.62 Hz, 1H), 4.44 (d, J = 9.71 Hz, 1H), 1.48 (d, J = 6.75 Hz, 3H).	381	95%
2-57		1H NMR (400 MHz, DMSO) δ 14.95 (s, 1H), 8.91 (s, 1H), 8.37-8.33 (d, J = 2.5 Hz, 1H), 8.24-8.19 (d, J = 8.3 Hz, 1H), 8.14-8.10 (d, J = 2.5 Hz, 1H), 7.58- 7.51 (d, J = 8.3 Hz, 1H), 7.22 (s, 2H), 4.42-4.36 (tt, J =7.1, 3.7 Hz, 1H), 2.71 (s, 3H), 1.30-1.25 (m, 2H), 1.05-0.94 (m, 2H).	361	95%
2-58		1H NMR (400 MHz, DMSO) δ 14.95 (s, 1H), 8.89 (s, 1H), 8.32 (d, J = 3.5 Hz, 1H), 8.21 (d, J = 8.2 Hz, 1H), 8.06 (s, 1H), 7.79 (s, 1H), 7.53 (d, J = 8.2 Hz, 1H), 6.61 (s, 2H), 4.39 (s, 1H), 2.72 (s, 3H), 1.27 (d, J = 6.1 Hz, 2H), 1.03 (s, 2H).	370	99%
2-59		1H NMR (400 MHz, DMSO) δ 15.00 (s, 1H), 9.06 (s, 1H), 8.17 (s, 1H), 7.80 (s, 1H), 7.72 (d, J = 9.8 Hz, 1H), 6.86 (t, J = 5.7 Hz, 1H), 4.98 (d, J = 6.7 Hz, 1H), 4.57 (d, J = 10.2 Hz, 1H), 4.48-4.32 (m, 1H), 3.55-3.37 (m, 2H), 1.48 (d, J = 6.8 Hz, 2H), 1.17 (t, J = 7.1 Hz, 2H).	418	98%
2-60		1H NMR (400 MHz, DMSO) δ 14.55 (s, 1H), 8.82 (d, J = 1.6 Hz, 1H), 8.18 (s, 1H), 7.92 (d, J = 9.3 Hz, 1H), 7.80 (s, 1H), 6.92 (t, J = 5.7 Hz, 1H), 5.10 (ddd, J = 64.1, 8.4, 5.4 Hz, 1H), 4.32- 4.06 (m, 1H), 3.58-3.37 (m, 5H), 1.93-1.51 (m, 2H), 1.19 (t, J = 7.1 Hz, 3H).	450	98%

TABLE 3
Com-
pound					MS
No.	R3 =	R2 =	R1 =	NMR	(MH+)	HPLC
3-1		Me	Cyclo- propyl	1H NMR (400 MHz, DMSO) δ 14.59 (s, 1H), 9.08 (s, 1H), 8.94 (s, 1H), 8.33 (d, J = 1.3 Hz, 1H), 8.16 (d, J = 1.7 Hz, 1H), 8.06 (t, J = 8.5 Hz, 2H), 7.85 (d, J = 9.4 Hz, 1H), 4.49-4.38 (m, 1H), 2.70 (s, 3H), 1.25 (d, J = 6.6 Hz, 2H), 1.09 (s, 2H).	376	98%
3-2		Me	Cyclo- propyl	1H NMR (400 MHz, DMSO) δ 14.63 (s, 1H), 9.38 (s, 1H), 8.91 (d, J = 25.3 Hz, 1H), 8.79 (s, 1H), 8.13 (s, 1H), 8.06 (d, J = 8.8 Hz, 1H), 8.01 (s, 1H), 4.44 (s, 1H), 2.75 (s, 3H), 1.25 (s, 2H), 1.09 (s, 2H).	379	95%
3-3		Me	Cyclo- propyl	1H NMR (400 MHz, DMSO) δ 14.70 (s, 1H), 9.41 (s, 1H), 9.00 (s, 1H), 8.80 (s, 1H), 8.36 (s, 1H), 8.17 (s, 1H), 8.07 (s, 2H), 7.86 (s, 1H), 7.61 (s, 1H), 4.49 (s, 1H), 2.79 (s, 3H), 1.31 (s, 3H), 1.17 (s, 2H).	456	96%
3-4		Me	Cyclo- propyl	1H NMR (400 MHz, DMSO) δ 14.57 (d, J = 5.1 Hz, 1H), 9.05 (d, J = 6.5 Hz, 1H), 8.94 (s, 1H), 8.44 (s, 1H), 8.23 (s, 1H), 8.11 (s, 1H), 8.05 (d, J = 8.8 Hz, 1H), 7.54 (d, J = 6.4 Hz, 1H), 4.43 (s, 1H), 2.68 (s, 3H), 1.24 (d, J = 5.0 Hz, 2H), 1.11 (s, 2H).	378	97%
3-5		OMe	Cyclo- propyl	1H NMR (400 MHz, DMSO) δ 14.64 (s, 1H), 9.13 (d, J = 6.3 Hz, 1H), 8.90 (s, 1H), 8.53 (s, 1H), 8.31 (d, J = 11.7 Hz, 2H), 8.09 (d, J = 9.1 Hz, 1H), 7.72 (d, J = 5.8 Hz, 1H), 4.30 (s, 1H), 3.57 (s, 3H), 1.25 (s, 4H).	394	95%
3-6		Me	Cyclo- propyl	1H NMR (400 MHz, DMSO) δ 9.30 (s, 1H), 8.93 (s, 1H), 8.64 (s, 1H), 8.04 (t, J = 9.2 Hz, 2H), 7.75 (d, J = 9.2 Hz, 1H), 4.42 (s, 1H), 2.69 (s, 3H), 1.24 (s, 2H), 1.09 (s, 2H).	379	97%
3-7		OMe	Cyclo- propyl	1H NMR (400 MHz, DMSO) δ 14.61 (s, 1H), 9.33 (s, 1H), 8.83 (s, 1H), 8.64 (s, 1H), 8.06 (d, J = 9.2 Hz, 1H), 8.01 (d, J = 9.1 Hz, 1H), 7.86 (d, J = 9.3 Hz, 1H), 4.24 (s, 1H), 3.48 (s, 3H), 1.19 (d, J = 5.2 Hz, 4H).	395	98%
3-8		Me	Cyclo- propyl	1H NMR (400 MHz, DMSO) δ 14.60 (s, 1H), 9.11 (s, 1H), 8.93 (s, 1H), 8.22 (d, J = 1.2 Hz, 1H), 8.17 (s, 1H), 8.03 (d, J = 8.9 Hz, 1H), 7.84 (d, J = 1.1 Hz, 1H), 4.43 (tt, J = 7.1, 3.7 Hz, 1H), 2.70 (s, 3H), 1.26 (d, J = 6.8 Hz, 2H), 1.09 (s, 2H).	379	98%
3-9		Me	Cyclo- propyl	1H NMR (400 MHz, DMSO) δ 14.60 (s, 1H), 9.07 (s, 1H), 8.93 (s, 1H), 8.22 (s, 1H), 8.02 (d, J = 8.9 Hz, 1H), 7.81 (s, 1H), 7.80 (s, 1H), 4.49-4.37 (m, 1H), 2.70 (d, J = 21.5 Hz, 3H), 1.27 (t, J = 9.8 Hz, 2H), 1.14-1.05 (m, 2H).	446	97%
3-10		Me	Cyclo- propyl	1H NMR (400 MHz, DMSO) δ 14.62 (s, 1H), 8.94 (s,2H), 8.35 (s, 1H), 8.23 (s, 1H), 8.05 (d, J = 8.7 Hz, 1H), 7.75 (s, 1H), 4.43 (s, 1H), 2.69 (s, 3H), 2.66 (s, 3H), 1.24 (s, 2H), 1.08 (s, 2H).	392	98%
3-11		Me	Cyclo- propyl	1H NMR (400 MHz, DMSO) δ 14.61 (s, 1H), 8.92 (s, 1H), 8.79 (d, J =1.2 Hz, 1H), 8.16 (d, J = 1.1 Hz, 1H), 8.01 (d, J = 8.8 Hz, 1H), 7.76 (d, J = 1.1 Hz, 1H), 7.58 (s, 1H), 4.42 (tt, J = 7.2, 3.8 Hz, 1H), 2.70 (d, J = 20.2 Hz, 3H), 1.26 (d, J = 6.9 Hz, 2H), 1.15-1.03 (m, 2H).	412	99%
3-12		Me	Cyclo- propyl	1H NMR (400 MHz, DMSO) δ 9.40 (s, 1H), 8.94 (s, 1H), 8.88 (s, 1H), 8.18 (d, J = 9.3 Hz, 1H), 8.05 (d, J = 8.8 Hz, 1H), 7.89 (d, J = 9.3 Hz, 1H), 4.43 (s, 1H), 2.69 (s, 3H), 1.24 (d, J = 6.1 Hz, 2H), 1.12 (s, 2H).	423	96%
3-13		OMe	Cyclo- propyl	1H NMR (400 MHz, DMSO) δ 14.60 (s, 1H), 8.90 (s, 1H), 8.83 (s, 1H), 8.22 (d, J = 1.0 Hz, 1H), 7.98 (d, J = 9.2 Hz, 1H), 7.75 (d, J = 1.0 Hz, 1H), 7.66 (s, 1H), 4.29-4.18 (m, 1H), 3.51 (d, J = 13.2 Hz, 3H), 1.25-1.14 (m, 4H).	428	100%
3-14		OMe	Cyclo- propyl	1H NMR (400 MHz, DMSO) δ 14.59 (s, 1H), 9.19 (s, 1H), 8.83 (s, 1H), 8.28 (s, 1H), 8.01 (d, J = 9.2 Hz, 1H), 7.92 (s, 1H), 7.81 (s, 1H), 4.25 (dt, J = 11.0, 5.7 Hz, 1H), 3.50 (d, J = 12.8 Hz, 3H), 1.19 (m, 4H).	462	98%
3-15		Me	Cyclo- propyl	1H NMR (400 MHz, DMSO) δ 9.61 (s, 1H), 8.93 (s, 1H), 8.51 (s, 1H), 8.13 (s, 1H), 8.04 (d, J = 8.8 Hz, 1H), 7.97 (d, J = 9.2 Hz, 1H), 7.62 (d,J = 9.2 Hz, 1H), 7.55 (s, 1H), 4.42 (s, 1H), 2.69 (s, 3H), 1.24 (s, 2H), 1.10 (s, 2H).	421	98%
3-16		Me	Cyclo- propyl	1H NMR (44 MHz, DMSO) δ 14.87-13.95 (m, 2H), 9.60 (s, 1H), 8.94 (s, 1H), 8.44 (s, 1H), 8.05 (t, J = 9.5 Hz, 2H), 7.71 (d, J = 9.4 Hz, 1H), 4.46-4.39 (m, 1H), 2.71 (m, 3H), 2.46 (s, 3H), 1.25 (d, J = 6.3 Hz, 2H), 1.11 (s, 2H).	459	98%
3-17		Cl	Cyclo- propyl	1H NMR (400 MHz, DMSO) δ 14.44-13.91 (m, 1H), 9.16 (s, 1H), 8.95 (s, 1H), 8.37 (s, 1H), 8.23 (d, J = 8.6 Hz, 1H), 8.08 (s, 1H), 7.81 (s, 1H), 4.43 (m, 1H), 1.23 (m, 2H), 1.16 (s, 2H).	398	98%
3-18		Me	Cyclo- propyl	1H NMR (400 MHz, DMSO) δ 14.62 (s, 1H), 8.92 (s, 1H), 8.68 (s, 1H), 8.19 (d, J = 2.9 Hz, 1H), 8.01 (d, J = 8.8 Hz, 1H), 7.73 (d, J = 1.0 Hz, 1H), 7.32 (d, J= 11.7 Hz, 1H), 4.42 (m, 1H), 2.72 (s, 3H), 1.25 (d, 2H), 1.12-1.04 (m, 2H).	396	98%
3-19		Me	Cyclo- propyl	1H NMR (400 MHz, DMSO) δ 9.29 (s, 1H), 8.94 (s, 1H), 8.54 (s, 1H), 8.36 (s, 1H), 8.05 (d,J = 8.9 Hz, 1H), 8.00 (s, 1H), 4.49-4.38 (m, 1H), 2.74 (s, 3H), 1.25 (d, J = 6.9 Hz, 2H), 1.11 (s, 2H).	423	98%
3-20		Cl	Cyclo- propyl	1H NMR (400 MHz, DMSO) δ 8.95 (s, 1H), 8.88 (t, J = 4.2 Hz, 1H), 8.22 (t, J = 2.4 Hz, 1H), 8.20 (d, J = 8.5 Hz, 1H), 7.82 (s, 1H), 7.68 (s, 1H), 4.48-4.36 (m, 1H), 1.26-1.19 (m, 2H), 1.14 (m, 2H).	432	98%
3-21		Me	Cyclo- propyl	1H NMR (400 Mhz, DMSO) δ 14.60 (s, 1H), 9.32 (d, J = 1.2 Hz, 1H), 8.93 (s, 1H), 8.71 (s, 1H), 8.06 (s, 1H), 8.02 (d, J = 8.8 Hz, 1H), 4.43 (tt, J = 7.0, 3.6 Hz, 1H), 2.70 (d, J = 17.8 Hz, 3H), 1.30-1.20 (m, 2H), 1.15-1.05 (m, 2H).	413	98%
3-22		Me	Cyclo- propyl	1H NMR (400 MHz, DMSO) δ 14.57 (s, 1H), 9.22 (s, 1H), 8.93 (s, 1H), 8.71 (s, 1H), 8.02 (d, J = 8.8 Hz), 1H), 7.85 (d, J = 10.8 Hz, 1H), 4.47-4.37 (m, 1H), 2.72 (s, 3H), 1.29-1.22 (m, 2H), 1.10 (s, 2H).	397	99%
3-23		OMe	Cyclo- propyl	1H NMR (400 MHz, DMSO) δ 14.57 (s, 1H), 9.26 (s, 1H), 8.84 (s, 1H), 8.72 (s, 1H), 8.01 (d, J = 9.1 Hz, 1H), 7.92 (d, J = 10.9 Hz, 1H), 4.28-4.18 (m, 1H), 3.51 (s, 3H), 1.20 (d, J = 5.5 Hz, 4H).	413	95%
3-24		OMe		1H NMR (400 MHz, DMSO) δ 14.47 (s, 1H), 8.89 (t, J = 1.3 Hz, 1H), 8.86 (d, J = 1.8 Hz, 1H), 8.23 (d, J = 1.3 Hz, 1H), 8.00 (d, J = 9.1 Hz, 1H), 7.75 (d, J = 1.2 Hz, 1H), 7.63 (t, J = 1.3 Hz, 1H), 5.31-4.93 (dtd, J = 64.0, 5.5, 3.3 Hz, 1H), 4.26-4.12 (dt, J = 8.9, 5.4 Hz, 1H), 3.54 (s, 3H), 1.93-1.49 (m, 2H).	446	98%
3-25		Me		1H NMR (400 MHz, CDCl3) δ 14.07 (s, 1H), 8.55 (s, 1H), 8.14 (d, J = 8.4 Hz, 1H), 8.00 (d, J = 17.0 Hz, 1H), 7.66 (dd, J = 11.6, 4.8 Hz, 2H), 7.49 (d, J = 4.4 Hz, 1H), 7.13-7.03 (m, 2H), 7.01 (d, J = 0.8 Hz, 1H), 5.22 (s, 1H), 1.72 (s, 3H).	484	98%
3-26		Me	Cyclo- propyl	1H NMR (400 MHz, DMSO) δ 14.64 (s, 1H), 9.09 (s, 1H), 8.93 (s, 1H), 8.58 (s, 1H), 8.02 (d, J = 8.8 Hz, 1H), 7.54 (s, 1H), 4.46-4.36 (m, 1H), 2.70 (s, 3H), 2.64 (s, 3H), 1.25 (d, J = 6.2 Hz, 2H), 1.09 (s, 2H).	393	98%
3-27		Me		1H NMR (400 MHz, DMSO) δ 14.48 (s, 1H), 8.90 (d, J = 3.0 Hz, 1H), 8.78 (s, 1H), 8.16 (s, 1H), 8.03 (d, J = 8.8 Hz, 1H), 7.75 (s, 1H), 7.57 (s, 1H), 5.16 (d, J = 64.5 Hz, 1H), 4.44-4.33 (m, 1H), 2.65 (s, 3H), 1.83-1.68 (m, 1H), 1.62 (m, 1H).	430	98%
3-28		Me	Cyclo- propyl	1H NMR (400 MHz, DMSO) δ 14.59 (s, 1H), 9.63 (s, 1H), 8.94 (s, 1H), 8.81 (s, 1H), 8.30 (s, 1H), 8.04 (d, J = 8.9 Hz, 1H), 4.50-4.37 (m, 1H), 2.73 (s, 3H), 1.24 (t, J = 9.6 Hz, 2H), 1.12 (s, 2H).	447	98%
3-29		Me	Cyclo- propyl	1H NMR (400 MHz, DMSO) δ 9.33 (s, 1H), 8.94 (s, 1H), 8.74 (s, 1H), 8.63 (s, 2H), 8.05 (d, J = 8.8 Hz, 1H), 7.84 (s, 1H), 4.51 (s, 2H), 4.46-4.36 (m, 1H), 2.71 (s, 3H), 1.26 (d, J = 6.8 Hz, 2H), 1.09 (s, 2H).	408	95%
3-30		OMe	Cyclo- propyl	1H NMR (400 MHz, DMSO) δ 14.58 (s, 1H), 9.37 (s, 1H), 8.84 (s, 1H), 8.72 (s, 1H), 8.13 (s, 1H), 8.00 (d, J = 9.0 Hz, 1H), 4.29-4.18 (m, 1H), 3.51 (s, 3H), 1.20 (d, J = 5.4 Hz, 4H).	429	96%
3-31		Me	Cyclo- propyl	1H NMR (400 MHz, DMSO) δ 9.43 (s, 1H), 8.99 (s, 1H), 8.89 (s, 1H), 8.14-8.01 (m, 2H), 7.54 (d, J = 9.8 Hz, 1H), 4.49 (s, 2H), 2.77 (s, 3H), 1.30 (s, 2H), 1.14 (s, 2H).	379	88%
3-32		OMe	Cyclo- propyl	1H NMR (400 MHz, DMSO) δ 9.42 (s, 1H), 8.92 (s, 1H), 8.83 (s, 1H), 8.00 (s, 2H), 7.57 (d, J = 9.3 Hz, 1H), 4.23 (s, 1H), 3.51 (s, 3H), 1.18 (s, 4H).	395	95%
3-33		Me	Cyclo- propyl	1H NMR (400 MHz, DMSO) δ 8.98 (s, 1H), 8.74 (s, 1H), 8.48 (s, 1H), 8.23 (s, 1H), 8.04 (d, J = 8.9 Hz, 1H), 4.39 (s, 2H), 2.64 (s, 3H), 1.29 (s, 2H), 1.07 (s, 2H).	379	99%
3-34		Me	Cyclo- propyl	1H NMR (400 MHz, DMSO) δ 15.02-14.73 (m, 1H), 9.01 (s, 1H), 8.10 (s, 3H), 7.54 (s, 1H), 4.51 (s, 1H), 1.33 (s, 2H), 1.18 (s, 2H).	379	95%
3-35		Me	Cyclo- propyl	1H NMR (400 MHz, DMSO) δ 14.68 (s, 1H), 14.19 (s, 1H), 8.93 (s, 1H), 8.53 (s, 1H), 8.44 (s, 1H), 8.40 (s, 1H), 8.01 (d, J = 8.5 Hz, 1H), 4.42 (s, 1H), 2.64 (s, 3H), 1.22 (m, 2H), 1.12 (m, 2H).	423	98%
3-36		Me	Cyclo- propyl	1H NMR (400 MHz, DMSO) δ 12.87 (s, 1H), 8.97 (s, 1H), 8.10 (s, 1H), 8.01 (d, J = 8.7 Hz, 1H), 7.02 (s, 1H), 6.48 (s, 1H), 4.46 (s, 1H), 2.70 (s, 2H), 1.30 (s, 2H), 1.12 (s, 2H).	393	98%
3-37		Me	Cyclo- propyl	1H NMR (400 MHz, DMSO) δ 14.83 (s, 1H), 13.45 (b, 1H), 8.98 (s, 1H), 8.26 (s, 1H), 8.04 (d, J = 8.6 Hz, 1H), 7.90 (s, 1H), 7.78 (d, J = 8.5 Hz, 1H), 7.42 (d, J = 8.4 Hz, 1H), 4.46 (s, 1H), 2.68 (s, 3H), 1.31 (d, J = 5.7 Hz, 2H), 1.14 (s, 2H).	378	92%
3-38		Me	Cyclo- propyl	1H NMR (400 MHz, DMSO) δ 14.69 (s, 1H), 13.83 (s, 1H), 8.91 (s, 1H), 8.31 (s, 1H), 7.98 (d, J = 8.8 Hz, 1H), 7.83 (s, 1H), 7.53 (s, 1H), 4.46-4.34 (m, 1H), 2.63 (s, 3H), 1.25 (d, J = 6.9 Hz, 2H), 1.09 (s, 2H).	412	98%
3-39		OMe	Cyclo- propyl	1H NMR (400 MHz, DMSO) δ 14.74 (s, 1H), 14.27 (s, 1H), 8.90 (s, 1H), 8.62 (d, J = 10.6 Hz, 3H), 8.07 (d, J = 9.1 Hz, 1H), 4.31 (s, 1H), 3.44 (s, 3H), 1.26 (s, 4H).	439	95%
3-40		Me	Cyclo- propyl	1H NMR (400 MHz, DMSO) δ 14.77 (s, 1H), 13.23 (s, 1H), 8.91 (s, 1H), 8.49 (s, 1H), 7.98 (d, J = 8.3 Hz, 1H), 7.79 (d, J = 8.0 Hz, 1H), 7.67 (s, 1H), 7.25 (d, J = 7.9 Hz, 1H), 4.40 (s, 1H), 2.61 (s, 2H), 1.25 (s, 2H), 1.09 (s, 2H).	378	98%
3-41		Me	Cyclo- propyl	1H NMR (400 MHz, DMSO) δ 14.72 (s, 1H), 9.52 (s, 1H), 8.92 (s, 1H), 8.30 (s, 1H), 8.27 (d, J = 8.4 Hz, 1H), 8.01 (d, J = 8.8 Hz, 1H), 7.58 (d, J = 8.1 Hz, 1H), 4.40 (s, 1H), 2.62 (s, 3H), 1.25 (d, J = 5.9 Hz, 2H), 1.08 (s, 2H).	395	95%
3-42		Me	Cyclo- propyl	1H NMR (400 MHz, DMSO) δ 14.77 (s, 1H), 11.96 (s, 1H), 8.92 (s, 1H), 8.24 (s, 1H), 8.06 (s, 1H), 7.99 (d, J = 8.7 Hz, 1H), 7.61 (s, 1H), 6.57 (s, 1H), 4.41 (s, 1H), 2.64 (s, 3H), 1.26 (d, J = 6.1 Hz, 2H), 1.09 (s, 2H).	378	98%
3-43		Me	Cyclo- propyl	1H NMR (400 MHz, DMSO) δ 14.76-14.48 (s, 1H), 8.97-8.90 (d, J = 2.7 Hz, 2H), 8.63-8.55 (s, 1H), 8.07-7.97 (t, J = 9.2 Hz, 2H), 7.69-7.58 (m, 1H), 4.48-4.39 (s, 2H), 2.73-2.65 (s, 3H), 1.27-1.20 (m, 2H), 1.14-1.06 (s, 2H).	403	95%
3-44		Me	Cyclo- propyl	1H NMR (400 MHz, DMSO) δ 10.02-9.98 (s, 1H), 9.48-9.43 (s, 1H), 8.95-8.90 (s, 1H), 8.67-8.62 (s, 1H), 8.12-8.07 (d, J = 9.2 Hz, 1H), 8.07-8.01 (d, J = 8.9 Hz, 1H), 7.82-7.75 (dd, J = 9.4, 1.7 Hz, 1H), 4.48-4.36 (s, 1H), 2.72-2.67 (s, 3H), 1.25-1.21 (t, J = 3.8 Hz, 2H), 1.14-1.06 (m, 2H).	406	90%
3-45		Me	Cyclo- propyl	1H NMR (400 MHz, DMSO) δ 9.93 (s, 1H), 8.83 (s, 1H), 8.40 (s, 1H), 8.09-8.05 (dd, J = 9.2, 1.0 Hz, 1H), 8.05-8.00 (d, J = 8.7 Hz, 1H), 7.81-7.72 (dd, J = 9.3, 1.7 Hz, 1H), 5.35-5.16 (s, 1H), 4.53-4.33 (m, 1H), 2.75-2.64 (s, 3H), 1.28-1.20 (d, J = 6.2 Hz, 2H), 1.15-1.03 (d, J = 3.8 Hz, 2H).	402	98%
3-46		Me	Cyclo- propyl	1H NMR (400 MHz, DMSO) δ 14.70-14.56 (s, 1H), 9.23-9.15 (m, 1H), 8.99-8.89 (s, 1H), 8.72-8.65 (s, 1H), 8.08-7.99 (d, J = 8.8 Hz, 1H), 7.84-7.77 (s, 1H), 7.16-7.04 (m, 1H), 6.93-6.82 (m, 1H), 5.82-5.69 (dd, J = 11.2, 1.6 Hz, 1H), 4.49-4.36 (t, J = 3.5 Hz, 1H), 2.75-2.68 (s, 3H), 1.33-1.19 (t, J = 6.5 Hz, 2H), 1.16-1.03 (s, 2H).	405	97%
3-47		Me	Cyclo- propyl	1H NMR (400 MHz, DMSO) δ 14.76-14.48 (s, 1H), 8.96-8.91 (s, 4H), 8.86-8.79 (s, 4H), 8.64-8.56 (d, J = 2.3 Hz, 4H), 8.06-7.99 (d, J = 8.8 Hz, 4H), 7.86-7.79 (d, J = 9.4 Hz, 4H), 7.52-7.43 (s, 3H), 4.48-4.37 (s, 1H), 2.74-2.67 (s, 12H), 1.29-1.20 (d, J = 6.8 Hz, 9H), 1.11-1.01 (t, J = 3.0 Hz, 6H).	422	96%
3-48		Me	Cyclo- propyl	1H NMR (400 MHz, DMSO) δ 14.76-14.48 (s, 1H), 8.95-8.89 (s, 1H), 8.84-8.78 (s, 1H), 8.63-8.58 (s, 1H), 8.05-8.00 (d, J = 8.8 Hz, 1H), 7.90-7.84 (d, J = 9.4 Hz, 1H), 7.53-7.45 (d, J = 9.3 Hz, 1H), 4.47-4.40 (s, 1H), 2.73-2.68 (s, 3H), 1.27-1.21 (d, J = 6.6 Hz, 2H), 1.12-1.02 (s, 2H).	446	90%
3-49		Me	Cyclo- propyl	1H NMR (400 MHz, DMSO) δ 8.93 (s, 1H), 8.66 (s, 1H), 8.06-7.99 (d, J = 8.7 Hz, 1H), 7.99-7.95 (s, 1H), 7.94-7.88 (d, J = 9.3 Hz, 1H), 7.55-7.47 (dd, J = 9.3, 1.6 Hz, 1H), 4.52-4.32 (m, 1H), 2.77-2.61 (s, 3H), 1.33-1.17 (d, J = 6.6 Hz, 2H), 1.19-1.05 (t, J = 3.3 Hz, 2H).	412	98%
3-50		Me	Cyclo- propyl	1H NMR (400 MHz, DMSO) δ 8.93 (s, 1H), 8.60 (s, 1H), 8.06-8.00 (d, J = 8.7 Hz, 1H), 8.00-7.96 (s, 1H), 7.92-7.86 (d, J = 9.3 Hz, 1H), 7.56-7.48 (d, J = 9.4 Hz, 1H), 4.55-4.26 (m, 1H), 2.81-2.60 (s, 3H), 1.37-1.21 (d, J = 6.5 Hz, 2H), 1.15-1.05 (m, 2H).	456, 458	97%
3-51		Me	Cyclo- propyl	1H NMR (400 MHz, DMSO) δ 14.71-14.62 (s, 1H), 8.96-8.88 (s, 1H), 8.83-8.75 (s, 1H), 8.25-8.16 (d, J = 7.5 Hz, 2H), 8.15-8.07 (s, 1H), 8.07-7.97 (d, J = 8.8 Hz, 1H), 7.77-7.71 (s, 1H), 7.57-7.42 (m, 4H), 4.50-4.33 (s, 1H), 2.82-2.71 (s, 3H), 1.31-1.22 (d, J = 6.7 Hz, 2H), 1.15-1.04 (s, 2H).	454	99%
3-52		Me	Cyclo- propyl	1H NMR (400 MHz, DMSO) δ 14.71-14.60 (s, 1H), 8.95-8.88 (s, 1H), 8.73-8.65 (s, 1H), 8.10-7.96 (m, 2H), 7.74-7.68 (s, 1H), 7.40-7.32 (s, 1H), 7.11-7.02 (m, 1H), 6.96-6.83 (m, 1H), 5.70-5.60 (dd, J = 11.2, 2.0 Hz, 1H), 4.47-4.38 (t, J = 3.5 Hz, 1H), 2.78-2.69 (s, 3H), 1.31-1.20 (d, J = 6.9 Hz, 2H), 1.14-1.01 (s, 2H).	405	93%
3-53		Me	Cyclo- propyl	1H NMR (400 MHz, DMSO) δ 14.71-14.60 (s, 1H), 8.95-8.88 (s, 1H), 8.73-8.65 (s, 1H), 8.10-7.96 (m, 2H), 7.74-7.68 (s, 1H), 7.40-7.32 (s, 1H), 7.11-7.02 (m, 1H), 6.96-6.83 (m, 1H), 5.70-5.60 (dd, J = 11.2, 2.0 Hz, 1H), 4.47-4.38 (t, J = 3.5 Hz, 1H), 2.78-2.69 (s, 3H), 1.31-1.20 (d, J = 6.9 Hz, 2H), 1.14-1.01 (s, 2H).	403	95%
3-54		Me	Cyclo- propyl	1H NMR (400 MHz, DMSO) δ 14.76-14.39 (s, 1H), 9.20-9.07 (d, J = 7.0 Hz, 1H), 8.95-8.90 (s, 1H), 8.67-8.60 (s, 1H), 8.08-8.00 (m, 2H), 7.32-7.24 (m, 1H), 4.47-4.36 (s, 1H), 2.75-2.61 (s, 3H), 1.30-1.19 (m, 2H), 1.15-1.03 (q, J = 3.8, 3.1 Hz, 2H).	379	98%
3-55		Me	Cyclo- propyl	1H NMR (400 MHz, DMSO) δ 14.76-14.36 (s, 1H), 9.68-9.65 (d, J = 1.5 Hz, 1H), 8.95-8.92 (s, 1H), 8.84-8.81 (s, 1H), 8.63-8.59 (d, J = 1.5 Hz, 1H), 8.06-8.01 (d, J = 8.8 Hz, 1H), 4.46-4.39 (s, 1H), 2.76-2.69 (s, 3H), 1.30-1.20 (m, 2H), 1.14-1.05 (s, 2H).	404	98%
3-56		OMe		1H NMR (400 MHz, DMSO) δ 14.73-14.06 (s, 1H), 9.21-9.18 (m, 1H), 8.87-8.83 (d, J = 1.86 Hz, 1H), 8.32-8.27 (d, J = 1.33 Hz, 1H), 8.20-8.16 (s, 1H), 8.04-7.97 (d, J = 9.06 Hz, 1H), 7.87-7.80 (d, J = 1.20 Hz, 1H), 5.31-4.87 (m, 1H), 4.32-4.12 (m, 1H), 3.67-3.47 (s, 3H), 1.95-1.56 (m, 2H).	437	98%
3-57		OMe	Cyclo- propyl	1H NMR (400 MHz, DMSO) δ 14.61 (s, 1H), 8.83 (s, 1H), 8.77 (s, 1H), 8.23 (d, J = 2.1 Hz, 1H), 7.99 (d, J = 9.2 Hz, 1H), 7.73 (d, J = 1.0 Hz, 1H), 7.40 (d, J = 11.8 Hz, 1H), 4.46-4.08 (m, 1H), 3.51 (d, J = 10.5 Hz, 3H), 1.19 (d, J = 6.9 Hz, 4H).	412	90%
3-58		Me	Cyclo- propyl	1H NMR (400 MHz, DMSO) δ 14.83-14.57 (s, 1H), 9.83-9.48 (s, 2H), 9.01-8.84 (d, J = 2.6 Hz, 1H), 8.05-7.90 (dd, J = 8.5, 2.7 Hz, 1H), 7.65-7.57 (d, J = 7.5 Hz, 1H), 7.51-7.46 (s, 1H), 7.45-7.36 (d, J = 7.7 Hz, 1H), 4.72-4.50 (s, 4H), 4.47-4.28 (d, J = 6.8 Hz, 1H), 2.64-2.53 (d, J = 2.7 Hz, 3H), 1.31-1.14 (d, J = 6.1 Hz, 2H), 1.14-0.96 (s, 2H).	379	95%
3-59		Me	Cyclo- propyl	1H NMR (400 MHz, DMSO) δ 8.95-8.83 (d, J = 2.4 Hz, 1H), 7.98-7.86 (d, J = 8.8 Hz, 1H), 7.25-7.15 (s, 1H), 7.14-7.01 (d, J = 7.9 Hz, 1H), 6.97-6.81 (d, J = 7.9 Hz, 1H), 3.65-3.50 (m, 2H), 4.45-4.29 (dp, J = 9.2, 4.7, 3.9 Hz, 1H), 3.16-2.99 (t, J = 8.4 Hz, 2H), 2.65-2.56 (s, 3H), 1.28-1.16 (d, J = 6.6 Hz, 3H), 1.12-0.97 (m, 2H).	379	99%
3-60		Me	Cyclo- propyl	1H NMR (400 MHz, DMSO) δ 15.01-14.39 (m, 1H), 12.95-12.53 (s, 2H), 9.03-8.82 (t, J = 1.9 Hz, 1H), 8.73-8.47 (s, 2H), 8.10-7.90 (d, J = 8.4 Hz, 1H), 7.62-7.44 (m, 1H), 4.51-4.23 (m, 1H), 7.44-7.31 (s, 1H), 7.31-7.11 (d, J = 8.6 Hz, 1H), 2.65-2.55 (s, 3H), 1.30-1.16 (m, 2H), 1.16-0.96 (s, 2H).	393	90%
3-61		Me	Cyclo- propyl	1H NMR (400 MHz, MeOD) δ 9.17-9.06 (d, J = 2.8 Hz, 1H), 8.30-8.15 (m, 1H), 7.94-7.80 (m, 2H), 7.65-7.49 (dt, J = 7.5, 3.3 Hz, 2H), 4.47-4.32 (d, J = 6.9 Hz, 1H), 2.96-2.81 (d, J = 2.8 Hz, 3H), 1.43-1.27 (dd, J = 10.8, 4.5 Hz, 2H), 1.21-1.05 (s, 2H).	378	100%
3-62		Me	Cyclo- propyl	1H NMR (400 MHz, DMSO) δ 14.63-14.42 (s, 1H), 8.99-8.89 (s, 1H), 8.33-8.25 (d, J = 7.8 Hz, 1H), 8.25-8.18 (d, J = 8.0 Hz, 1H), 8.14-8.05 (d, J = 8.7 Hz, 1H), 7.71-7.56 (dt, J = 22.8, 7.4 Hz, 2H), 4.51-4.31 (s, 1H), 2.85-2.70 (s, 3H), 1.30-1.20 (d, J = 7.0 Hz, 2H), 1.13-0.97 (s, 2H).	395	100%
3-63		Me	Cyclo- propyl	1H NMR (400 MHz, DMSO) δ 15.01-14.28 (s, 2H), 9.04-8.82 (t, J = 2.3 Hz, 1H), 8.05-7.98 (d, J = 8.3 Hz, 1H), 7.98-7.92 (dd, J = 10.5, 2.5 Hz, 1H), 7.90-7.83 (s, 1H), 7.56-7.47 (d, J = 8.2 Hz, 1H), 4.46-4.34 (t, J = 6.3 Hz, 1H), 2.87-2.78 (t, J = 2.1 Hz, 3H), 2.64-2.55 (s, 3H), 1.29-1.16 (m, 2H), 1.16-1.03 (s, 1H).	392	100%
3-64		Me	Cyclo- propyl	1H NMR (400 MHz, DMSO) δ 15.01-14.28 (s, 2H), 9.04-8.82 (t, J = 2.3 Hz, 1H), 8.05-7.98 (d, J = 8.3 Hz, 1H), 7.98-7.92 (dd, J = 10.5, 2.5 Hz, 1H), 7.90-7.83 (s, 1H), 7.56-7.47 (d, J = 8.2 Hz, 1H), 4.46-4.34 (t, J = 6.3 Hz, 1H), 2.87-2.78 (t, J = 2.1 Hz, 3H), 2.64-2.55 (m, 6H), 1.29-1.16 (m, 2H), 1.16-1.03 (s, 2H).	421	100%
3-65		Me	Cyclo- propyl	1H NMR (400 MHz, DMSO) δ 15.05-14.35 (m, 1H), 10.46-9.91 (m, 1H), 9.02-8.80 (s, 1H), 8.80-8.47 (d, J = 15.2 Hz, 1H), 8.12-7.64 (m, 3H), 7.44-7.25 (dd, J = 23.7, 8.0 Hz, 1H), 4.84-4.63 (d, J = 8.8 Hz, 2H), 4.49-4.32 (s, 1H), 3.01-2.77 (d, J = 17.9 Hz, 6H), 1.37-1.13 (d, J = 6.9 Hz, 2H), 1.17-0.86 (s, 2H).	449	96%
3-66		Me	Cyclo- propyl	1H NMR (400 MHz, DMSO) δ 14.97-14.24 (s, 2H), 9.14-8.97 (m, 2H), 8.98-8.88 (s, 2H), 8.07-7.89 (dd, J = 24.1, 8.9 Hz, 6H), 7.86-7.79 (s, 1H), 7.52-7.37 (t, J = 9.6 Hz, 3H), 4.57-4.31 (t, J = 6.8 Hz, 5H), 2.66-2.55 (s, 7H), 1.60-1.40 (m, 7H), 1.30-1.16 (m, 2H), 1.16-0.98 (s, 2H).	406	97%
3-67		Me	Cyclo- propyl	1H NMR (400 MHz, DMSO) δ 14.97-14.24 (s, 2H), 9.14-8.97 (m, 2H), 8.98-8.88 (s, 2H), 8.07-7.89 (dd, J = 24.1, 8.9 Hz, 6H), 7.86-7.79 (s, 1H), 7.52-7.37 (t, J = 9.6 Hz, 3H), 4.57-4.31 (t, J = 6.8 Hz, 5H), 2.66-2.55 (s, 3H), 1.60-1.40 (m, 7H), 1.30-1.16 (m, 2H), 1.16-0.98 (s, 2H).	392	100%
3-68		Me	Cyclo- propyl	1H NMR (400 MHz, DMSO) δ 8.95-8.91 (s, 1H), 8.65-8.59 (s, 1H), 8.31-8.25(s, 1H), 8.23-8.17 (s, 1H), 8.05-7.98 (m, 1H), 4.48-4.35 (s, 1H), 2.68-2.61 (s, 3H), 1.30-1.22 (s, 2H), 1.16-1.06 (s, 2H).	423	97%
3-69		Me	Cyclo- propyl	1H NMR (400 MHz, DMSO) δ 14.96-14.48 (m, 1H), 10.94-10.65 (d, J = 25.6 Hz, 2H), 9.01-8.77 (m, 1H), 8.05-7.81 (d, J = 8.6 Hz, 1H), 7.18-7.00 (d, J = 7.8 Hz, 1H), 7.00-6.78 (m, 2H), 4.47-4.25 (td, J = 6.9, 3.6 Hz, 1H), 2.67-2.54 (s, 3H), 1.27-1.10 (d, J = 6.3 Hz, 2H), 1.14-0.88 (s, 2H).	394	94%
3-70		Me	Cyclo- propyl	1H NMR (400 MHz, DMSO) δ 15.02-14.18 (s, 1H), 9.00-8.67 (m, 2H), 8.12-7.68 (m, 3H), 7.49-7.25 (dd, J = 16.6, 8.2 Hz, 1H), 5.04-4.75 (m, 1H), 4.62-4.23 (m, 9H), 3.77-3.55 (m, 2H), 3.57-3.23 (d, J = 7.0 Hz, 1H), 2.70-2.53 (s, 3H), 1.37-1.15 (t, J = 8.0 Hz, 2H), 1.15-0.84 (td, J = 16.0, 7.8 Hz, 9H).	494	90%
3-71		Me	Cyclo- propyl	1H NMR (400 MHz, DMSO) δ 14.45-14.13 (s, 1H), 11.09-10.85 (s, 1H), 8.73-8.58 (d, J = 2.7 Hz, 1H), 7.85-7.61 (m, 2H), 7.31-7.15 (m, 1H), 7.07-6.83 (m, 2H), 4.27-4.07 (s, 1H), 3.82-3.71 (d, J = 2.5 Hz, 3H), 1.27-1.08 (m, 2H), 1.08-0.86 (s, 2H).	408	93%
3-72		OMe	Cyclo- propyl	1H NMR (400 MHz, DMSO) δ 15.07-14.72 (s, 1H), 9.21-8.97 (s, 1H), 8.95-8.73 (m, 1H), 8.41-8.14 (m, 1H), 8.12-7.95 (s, 1H), 3.40-3.18 (m, 4H), 7.95-7.79 (d, J = 8.6 Hz, 1H), 7.79-7.60 (dd, J = 8.5, 3.9 Hz, 2H), 4.34-4.10 (d, J = 6.3 Hz, 1.30-1.02 (s, 4H).	376	95%
3-73		Me	Cyclo- propyl	1H NMR (400 MHz, DMSO) δ 14.85-14.61 (s, 1H), 10.68-10.51 (s, 1H), 9.04-8.78 (m, 1H), 8.01-7.81 (m, 1H), 7.36-7.11 (m, 2H), 7.11-6.87 (dd, J = 7.8, 2.7 Hz, 1H), 4.47-4.29 (s, 1H), 3.72-3.47 (s, 2H), 1.27-1.08 (m, 2H), 1.08-0.86 (s, 2H).	393	97%
3-74		Me	Cyclo- propyl	1H NMR (400 MHz, DMSO) δ 14.85-14.61 (s, 1H), 10.68-10.51 (s, 1H), 9.04-8.78 (m, 1H), 8.01-7.81 (m, 1H), 7.36-7.11 (m, 2H), 7.11-6.87 (dd, J = 7.8, 2.7 Hz, 1H), 4.47-4.29 (s, 1H), 3.72-3.47 (s, 2H), 2.66-2.57 (d, J = 2.7 Hz, 3H), 2.55-2.45 (d, J = 3.4 Hz, 4H).	424	97%
3-75		OMe	Cyclo- propyl	1H NMR (400 MHz, DMSO) δ 14.80-14.62 (m, 1H), 8.38-8.18 (m, 1H), 8.03-7.83 (m, 1H), 8.96-8.82 (m, 1H), 7.77-7.59 (m, 1H), 7.37-7.22 (m, 1H), 4.48-4.29 (m, 1H), 3.24-3.08 (m, 2H), 3.94-3.70 (m, 2H), 1.32-1.12 (m, 2H), 1.12-0.86 (m, 2H).	394	100%
3-76		Me	Cyclo- propyl	1H NMR (400 MHz, DMSO) δ 15.11-14.26 (d, J = 53.0 Hz, 1H), 10.22-9.45 (m, 1H), 9.01-8.84 (m, 1H), 8.77-8.58 (s, 1H), 8.09-7.92 (d, J = 8.5 Hz, 1H), 7.88-7.68 (s, 1H), 7.51-7.33 (s, 1H), 4.84-4.58 (s, 2H), 4.53-4.25 (s, 1H), 2.96-2.72 (s, 6H), 2.72-2.56 (s, 3H), 1.34-1.17 (d, J = 6.5 Hz, 2H), 1.17-0.93 (d, J = 10.1 Hz, 2H).	435	94%
3-77		Me	Cyclo- propyl	1H NMR (400 MHz, DMSO) δ 14.87-14.59 (s, 1H), 12.20-12.00 (s, 1H), 9.01-8.79 (s, 1H), 8.09-7.83 (d, J = 8.6 Hz, 1H), 7.74-7.59 (s, 1H), 7.39-7.20 (m, 2H), 4.48-4.31 (s, 1H), 2.72-2.56 (s, 3H), 1.36-1.12 (d, J = 6.9 Hz, 2H), 1.12-0.79 (s, 2H).	411	98%
3-78		Me	Cyclo- propyl	1H NMR (400 MHz, DMSO) δ 14.85-14.61 (s, 1H), 10.68-10.51 (s, 1H), 9.04-8.78 (m, 1H), 8.01-7.81 (m, 1H), 7.36-7.11 (m, 2H), 7.11-6.87 (dd, J = 7.8, 2.7 Hz, 1H), 4.47-4.29 (s, 1H), 3.72-3.47 (s, 2H), 1.27-1.08 (m, 2H), 1.08-0.86 (s, 2H).	393	95%
3-79		Me	Cyclo- propyl	1H NMR (400 MHz, DMSO) δ 14.82-14.60 (s, 1H), 11.50-11.28 (s, 1H), 8.99-8.81 (s, 1H), 8.09-7.90 (m, 2H), 7.66-7.53 (d, J = 1.1 Hz, 1H), 6.91-6.78 (s, 1H), 6.17-5.99 (d, J = 15.7 Hz, 1H), 5.38-5.23 (d, J = 9.0 Hz, 1H), 4.48-4.31 (dd, J = 8.4, 4.4 Hz, 1H), 3.61-3.41 (s, 1H), 2.71-2.56 (s, 3H), 1.32-1.16 (s, 2H), 1.14-0.97 (s, 2H).	421	97%
3-80		MeO	Cyclo- propyl	1H NMR (400 MHz, DMSO) δ 14.82-14.60 (s, 1H), 11.50-11.28 (s, 1H), 8.99-8.81 (s, 1H), 8.09-7.90 (m, 2H), 7.66-7.53 (d, J = 1.1 Hz, 1H), 6.91-6.78 (s, 1H), 6.17-5.99 (d, J = 15.7 Hz, 1H), 5.38-5.23 (d, J = 9.0 Hz, 1H), 4.48-4.31 (dd, J = 8.4, 4.4 Hz, 1H), 3.61-3.41 (s, 1H), 2.71-2.56 (s, 3H), 1.14-0.97 (s, 4H).	437	90%
3-81		Me	Cyclo- propyl	1H NMR (400 MHz, DMSO) δ 14.85-14.61 (s, 1H), 10.95-10.69 (s, 1H), 9.06-8.79 (s, 2H), 8.05-7.90 (d, J = 8.7 Hz, 1H), 7.28-7.09 (s, 1H), 6.85-6.63 (s, 1H), 4.46-4.29 (tt, J = 7.4, 4.0 Hz, 1H), 2.72-2.54 (s, 3H), 1.32-1.14 (d, J = 5.8 Hz, 2H), 1.14-0.97 (d, J = 3.8 Hz, 2H).	394	94%
3-82		OMe	Cyclo- propyl	1H NMR (400 MHz, DMSO) δ 14.89-14.50 (s, 2H), 11.09-10.63 (s, 1H), 9.21-8.97 (s, 1H), 8.97-8.73 (s, 1H), 8.07-7.85 (m, 1H), 3.48-3.31 (m, 5H), 7.42-7.26 (m, 1H), 7.04-6.87 (m, 1H), 4.31-4.13 (p, J = 5.6 Hz, 1H), 2.72-2.54 (s, 3H), 1.27-1.01 (d, J = 5.6 H, 4H).	410	98%
3-83		OMe	Cyclo- propyl	1H NMR (400 MHz, DMSO) δ 15.05-14.39 (s, 1H), 13.02-12.32 (s, 1H), 8.97-8.77 (s, 1H), 8.47-8.20 (s, 1H), 7.85-7.39 (m, 2H), 7.33-6.98 (d, J = 8.0 Hz, 1H), 4.47-4.23 (s, 1H), 2.74-2.52 (s, 3H), 1.34-1.13 (m, 2H), 1.13-0.71 (s, 2H).	428	100%
3-84		Me	Cyclo- propyl	1H NMR (400 MHz, DMSO) δ 14.75 (d, J = 8.7 Hz, 1H), 8.91 (s, 1H), 8.13 (s, 1H), 7.99 (t, J = 11.1 Hz, 1H), 7.78 (t, J = 13.2 Hz, 1H), 7.72 (s, 1H), 7.33 (d, J = 8.5 Hz, 1H), 7.07 (s, 1H), 4.40 (m, 1H), 2.61 (s, 3H), 1.24 (d, J = 5.7 Hz, 2H), 1.08 (s, 2H).	378	98%
3-85		Me	Cyclo- propyl	1H NMR (400 MHz, DMSO) δ 14.70 (s, 1H), 8.90 (s, 1H), 8.21 (d, J = 8.0 Hz, 1H), 7.98 (d, J = 8.1 Hz, 1H), 7.94 (s, 1H), 7.90 (s, 1H), 7.56 (s, 1H), 7.38 (d, J = 7.9 Hz, 1H), 4.38 (s, 1H), 2.65 (s, 3H), 1.17 (m, 2H), 1.06 (m, 2H).	394	98%
3-86		1H NMR (400 MHz, DMSO) δ 15.38-14.22 (s, 1H), 9.14-9.08 (s, 1H), 9.00-8.94 (s, 1H), 8.32-8.24 (s, 1H), 7.93-7.90 (s, 1H), 7.90-7.86 (s, 1H), 7.83-7.76 (d, J = 9.72 Hz, 1H), 5.07-4.96 (d, J = 6.74 Hz, 1H), 4.65-4.56 (d, J = 11.26 Hz, 1H), 4.53-4.43 (d, J = 9.86 Hz, 1H), 1.54-1.46 (d, J = 6.76 Hz, 3H).	414	99%
3-87		1H NMR (400 MHz, DMSO) δ 14.87 (s, 1H), 8.93 (s, 1H), 8.77 (s, 1H), 8.27 (d, J = 8.2 Hz, 1H), 8.15 (s, 1H), 7.73 (d, J = 0.9 Hz, 1H), 7.63 (m, 2H), 4.46-4.36 (m, 1H), 2.76 (s, 3H), 1.29 (d, J = 6.5 Hz, 2H), 1.08 (t, J = 7.4 Hz, 2H).	394	99%

TABLE 4
Com-
pound			MS
No.	R3 =	NMR	(MH+)	HPLC
4-1		1H NMR (400 MHz, DMSO) δ 14.49 (s, 1H), 11.38 (s, 1H), 8.70 (s, 1H), 7.78 (d, J = 9.1 Hz, 1H), 7.42 (d, J = 7.9 Hz, 1H), 7.26 (d, J = 8.1 Hz, 1H), 7.00-6.92 (m, 1H), 6.86 (t, J = 7.5 Hz, 1H), 6.51 (s, 1H), 4.24-4.16 (m, 1H), 2.56 (s, 3H), 1.03 (dd, J = 12.0, 4.6 Hz, 2H), 0.86 (d, J = 7.4 Hz, 2H).	377	95%
4-2		1H NMR (400 MHz, DMSO) δ 14.70 (s, 1H), 11.59 (s, 1H), 8.92 (s, 1H), 8.00 (d, J = 9.1 Hz, 1H), 7.64 (d, J = 7.5 Hz, 1H), 7.48 (d, J = 8.0 Hz, 1H), 7.19 (t, J = 7.5 Hz, 1H), 7.08 (t, J = 7.3 Hz, 1H), 6.73 (s, 1H), 4.42 (s, 1H), 2.78 (s, 3H), 1.27 (d, J = 6.1 Hz, 2H), 1.07 (s, 2H).	377	100%
4-3		1H NMR (400 MHz, DMSO) δ 14.66 (s, 1H), 8.93 (s, 1H), 8.05 (d, J = 8.6 Hz, 1H), 7.65 (d, J = 7.7 Hz, 1H), 7.57 (d, J = 8.0 Hz, 1H), 7.30-7.24 (m, 1H), 7.14 (t, J = 7.3 Hz, 1H), 6.68 (s, 1H), 4.41 (s, 1H), 3.58 (s, 3H), 2.65 (s, 3H), 1.24 (s, 4H).	391	98%
4-4		1H NMR (400 MHz, DMSO) δ 14.82 (s, 1H), 11.36 (s, 1H), 8.90 (s, 1H), 7.95 (d, J = 7.8 Hz, 1H), 7.57 (s, 3H), 7.46 (s, 1H), 7.07 (d, J = 8.5 Hz, 1H), 6.53 (s, 1H), 4.39 (s, 1H), 2.62 (s, 3H), 1.24 (s, 2H), 1.09 (d, J = 18.8 Hz, 2H).	377	87%
4-5		1H NMR (400 MHz, DMSO) δ 14.71 (s, 1H), 11.55 (s, 1H), 8.92 (s, 1H), 8.00 (d, J = 9.0 Hz, 1H), 7.30 (d, J = 8.4 Hz, 1H), 7.09 (t, J = 7.4 Hz, 1H), 6.87 (d, J = 6.9 Hz, 1H), 6.75 (s, 1H), 4.42 (s, 1H), 2.79 (s, 3H), 2.09 (s, 3H), 1.28 (d, J = 6.0 Hz, 2H), 1.07 (s, 2H).	391	90%
4-6		1H NMR (400 MHz, DMSO) δ 14.71 (s, 1H), 11.43 (s, 1H), 8.91 (s, 1H), 7.99 (d, J = 8.7 Hz, 1H), 7.37 (d, J = 8.6 Hz,1H), 7.13 (s, 1H), 6.84 (d, J = 8.7 Hz, 1H), 6.63 (s, 1H), 4.41 (s, 1H), 3.78 (s, 4H), 2.77 (s, 3H), 1.26 (d, J = 5.7 Hz, 2H), 1.07 (s, 2H).	407	92.3%
4-9		1H NMR (400 MHz, DMSO) δ 14.65 (s, 1H), 12.23 (d, J = 30.1 Hz, 1H), 8.93 (s, 1H), 8.20 (d, J = 11.8 Hz, 1H), 7.65 (s, 1H), 7.53 (s, 2H), 6.87 (d, J = 26.1 Hz, 1H), 4.38 (d, J = 31.7 Hz, 1H), 2.74 (d, J = 19.6 Hz, 3H), 1.24 (d, J = 8.9 Hz, 2H), 1.07 (s, 2H).	402	92.8%
4-10		1H NMR (400 MHz, DMSO) δ 14.67 (s, 1H), 11.70 (s, 1H), 8.92 (s, 1H), 8.00 (d, J = 8.9 Hz, 1H), 7.52-7.44 (m, 1H), 7.41 (d, J = 9.8 Hz, 1H), 7.04 (t, J = 9.3 Hz, 1H), 6.72 (s, 1H), 4.42 (s, 1H), 2.77 (s, 3H), 1.26 (d, J = 6.4 Hz, 2H), 1.07 (s, 2H).	395	89.7%
4-11		1H NMR (400 MHz, DMSO) δ 14.68 (s, 1H), 11.98 (s, 1H), 8.93 (s, 1H), 8.02 (d, J = 9.1 Hz, 1H), 7.47 (d, J = 7.3 Hz, 1H), 7.19 (q, J = 7.8 Hz, 2H), 6.76 (s, 1H), 4.42 (s, 1H), 2.78 (s, 3H), 1.27 (d, J = 6.2 Hz, 2H), 1.08 (s, 2H).	411	97%
4-12		1H NMR (400 MHz, DMSO) δ 14.64 (s, 1H), 12.30 (s, 1H), 8.93 (s, 1H), 8.04 (d, J = 8.3 Hz, 1H), 7.86 (d, J = 6.8 Hz, 1H), 7.64 (s, 1H), 7.36 (s, 1H), 6.91 (s, 1H), 4.43 (s, 1H), 2.78 (s, 3H), 1.28 (s, 2H), 1.09 (s, 2H).	402	99%
4-13		1H NMR (400 MHz, DMSO) δ 14.66 (s, 1H), 11.93 (s, 1H), 8.92 (s, 1H), 8.01 (d, J = 9.1 Hz, 1H), 7.33 (d, J = 8.3 Hz, 1H), 7.17 (d, J = 6.5 Hz, 1H), 6.87 (t, J = 8.9 Hz, 1H), 6.80 (s, 1H), 4.42 (s, 1H), 2.78 (s, 3H), 1.27 (d, J = 6.4 Hz, 2H), 1.07 (s, 2H).	395	87%
4-14		1H NMR (400 MHz, DMSO) δ 14.70 (s, 1H), 11.43 (s, 1H), 8.92 (s, 1H), 8.00 (d, J = 8.8 Hz, 1H), 7.46 (s, 1H), 6.98 (s, 2H), 6.67 (s, 1H), 4.42 (s, 1H), 2.77 (s, 3H), 1.26 (d, J = 6.3 Hz, 2H), 1.09 (s, 2H).	391	92.7%
4-15		1H NMR (400 MHz, DMSO) δ 11.07 (s, 1H), 9.02 (s, 1H), 8.04 (s, 1H),7 .55 (s, 2H), 7.29 (s, 1H), 6.96 (s, 1H), 6.67 (s, 1H), 2.85 (s, 3H), 2.47 (s, 3H), 1.34 (s, 2H), 1.09 (s, 2H).	391	99%
4-16		1H NMR (400 MHz, DMSO) δ 14.64 (s, 1H), 12.41 (s, 1H), 8.93 (s, 1H), 8.69 (s, 1H), 8.07 (d, J = 13.8 Hz, 2H), 7.67 (s, 1H), 7.05 (s, 1H), 4.42 (s, 1H), 2.78 (s, 3H),1.26 (s, 2H), 1.08 (s, 2H).	422	100%
4-17		1H NMR (400 MHz, DMSO) δ 14.70 (s, 1H), 11.70 (s, 1H), 8.92 (s, 1H), 8.00 (d, J = 9.0 Hz, 1H), 7.65 (s, 1H), 7.24 (d, J = 10.1 Hz, 1H), 6.96 (t, J = 9.1 Hz, 1H), 6.76 (s, 1H), 4.42 (s, 1H), 2.77 (s, 3H), 1.26 (d, J = 5.7 Hz, 2H), 1.07 (s, 2H).	395	88%
4-18		1H NMR (400 MHz, DMSO) δ 14.68 (s, 1H), 12.08 (s, 1H), 8.92 (s, 1H), 8.01 (d, J = 8.9 Hz, 1H), 7.47 (d, J = 6.4 Hz, 1H), 7.04 (d, J = 9.3 Hz, 2H), 6.79 (s, 1H), 4.42 (s, 1H), 2.76 (s, 3H), 1.26 (d, J = 6.2 Hz, 2H), 1.08 (s, 2H).	395	89.1%
4-19		1H NMR (400 MHz, DMSO) δ 14.65 (s, 1H), 12.66 (s, 1H), 11.98 (s, 1H), 8.93 (s, 1H), 8.12 (s, 1H), 8.03 (d, J = 8.8 Hz, 1H), 7.70 (q, J = 8.2 Hz, 2H), 6.83 (s, 1H), 4.43 (s, 1H), 2.78 (s, 3H), 1.27 (d, J = 6.2 Hz, 2H), 1.08 (s, 2H).	421	100%
4-20		1H NMR (400 MHz, DMSO) δ 14.68 (s, 1H), 11.78 (s, 1H), 8.92 (s, 1H), 8.01 (d, J = 9.0 Hz, 1H), 7.66 (d, J = 8.6 Hz, 1H), 7.51 (s, 1H), 7.10 (d, J = 8.4 Hz, 1H), 6.77 (s, 1H), 4.42 (s, 1H), 2.77 (s, 3H), 1.26 (d, J = 6.1 Hz, 2H), 1.07 (s, 2H).	411	90%
4-21		1H NMR (400 MHz, DMSO) δ 14.49 (s, 1H), 12.71 (s, 1H), 8.92 (s, 1H), 8.15 (s, 1H), 8.04 (d, J = 9.4 Hz, 2H), 7.43 (s, 1H), 7.29 (s, 1H), 4.42 (s, 1H), 2.79 (s, 3H), 1.27 (s, 2H), 1.08 (s, 2H).	422	97%
4-22		1H NMR (400 MHz, MeOD) δ 8.98 (s, 1H), 7.93 (d, J = 9.1 Hz, 1H), 7.55 (d, J = 12.6 Hz, 2H), 7.47 (s, 1H), 7.34 (d, J = 8.1 Hz, 1H), 6.77 (s, 1H), 6.57 (d, J = 7.9 Hz, 1H), 6.51 (s, 1H), 4.29 (s, 1H), 2.78 (s, 3H), 1.38-1.24 (m, 2H), 1.20 (s, 2H).	393	90%
4-23		1H NMR (400 MHz, DMSO) δ 14.68 (s, 1H), 11.82 (s, 1H), 8.92 (s, 1H), 8.01 (d, J = 8.5 Hz, 1H), 7.70 (s, 1H), 7.50 (d, J = 8.3 Hz, 1H), 7.19 (d, J = 9.4 Hz, 1H), 6.73 (s, 1H), 4.42 (s, 1H), 2.76 (s, 3H), 1.26 (d, J = 6.1 Hz, 2H), 1.07 (s, 2H).	411	90%
4-24		1H NMR (400 MHz, DMSO) δ 14.63 (s, 1H), 11.61 (s, 1H), 8.95 (d, J = 9.5 Hz, 1H), 8.41 (s, 1H), 7.99 (s, 1H), 7.67 (d, J = 9.1 Hz, 1H), 6.52 (s, 1H), 4.43 (s, 1H), 2.78 (s, 3H), 1.25 (s, 2H), 1.08 (s, 2H).	422	90%
4-25		1H NMR (400 MHz, DMSO) δ 14.82 (s, 1H), 11.31 (s, 1H), 8.91 (s, 1H), 7.97 (d, J = 8.4 Hz, 1H), 7.71 (d, J = 7.8 Hz, 1H), 7.48 (s, 1H), 7.41 (s, 1H), 6.99 (d, J = 7.9 Hz, 1H), 6.53 (s, 1H), 4.40 (s, 1H), 2.63 (s, 3H), 1.24 (s, 2H), 1.08 (s, 2H).	377	100%
4-26		1H NMR (400 MHz, DMSO) δ 14.70 (s, 1H), 12.37 (s, 1H), 8.93 (s, 1H), 8.19 (t, J = 9.0 Hz, 2H), 8.01 (d, J = 8.0 Hz, 1H), 7.34 (s, 1H), 7.00 (s, 1H), 4.43 (s, 1H), 2.75 (s, 3H), 1.24 (s, 2H), 1.11 (s, 2H).	422	99%
4-27		1H NMR (400 MHz, DMSO) δ 14.73 (s, 1H), 11.45 (s, 1H), 9.17 (s, 1H), 8.92 (s, 1H), 7.99 (d, J = 8.6 Hz, 1H), 7.77 (s, 1H), 7.35 (d, J = 8.5 Hz, 1H), 7.24 (s, 1H), 6.64 (s, 1H), 4.42 (s, 1H), 2.77 (s, 2H), 1.46 (d, J = 29.9 Hz, 9H), 1.25 (s, 2H), 1.06 (s, 2H).	492	100%
4-28		1H NMR (400 MHz, DMSO) δ 14.67 (s, 1H), 11.94 (s, 1H), 9.97 (s, 2H), 8.93 (s, 1H), 8.02 (d, J = 8.7 Hz, 1H), 7.65 (s, 1H), 7.60 (d, J = 8.6 Hz, 1H), 7.19-7.13 (m, 1H), 6.84 (s, 1H), 4.42 (s, 2H), 2.76 (s, 3H), 1.14-1.00 (m, 4H).	392	94%
4-29		1H NMR (400 MHz, DMSO) δ 14.67 (s, 1H), 11.94 (s, 1H), 9.97 (s, 2H), 8.93 (s, 1H), 8.02 (d, J = 8.7 Hz, 1H), 7.65 (s, 1H), 7.60 (d, J = 8.6 Hz, 1H), 7.19-7.13 (m, 1H), 6.84 (s, 1H), 4.42 (s, 2H), 2.76 (s, 3H), 1.14-1.00 (m, 4H).	391	100%
4-30		1H NMR (400 MHz, DMSO) δ 14.73 (s, 1H), 11.38 (s, 1H), 9.33 (s, 1H), 8.91 (s, 1H), 7.98 (d, J = 9.1 Hz, 1H), 7.81 (s, 1H), 7.48 (d, J = 8.3 Hz, 1H), 7.09 (d, J = 8.7 Hz, 1H), 6.64 (s, 1H), 4.42 (s, 1H), 2.78 (s, 3H), 1.51 (s, 10H), 1.25 (d, J = 8.9 Hz, 2H), 1.08 (dd, J = 14.0, 6.3 Hz, 2H).	492	97%
4-31		1H NMR (400 MHz, DMSO) δ 14.31 (s, 1H), 11.68 (s, 1H), 8.94 (s, 1H), 8.17 (d, J = 8.7 Hz, 1H), 7.66 (d, J = 7.8 Hz, 1H), 7.49 (d, J = 8.1 Hz, 1H), 7.21 (t, J = 7.5 Hz, 1H), 7.08 (t, J = 7.4 Hz, 1H), 6.80 (s, 1H), 4.44 (s, 1H), 1.25 (d, J = 6.4 Hz, 2H), 1.12 (s, 2H).	397	100%
4-32		1H NMR (400 MHz, DMSO) δ 14.72 (s, 1H), 11.74 (s, 1H), 9.35 (s, 2H), 8.92 (s, 1H), 8.00 (d, J = 9.0 Hz, 1H), 7.66 (d, J = 8.5 Hz, 1H), 7.34 (s, 1H), 6.94 (d, J = 8.3 Hz, 1H), 6.76 (s, 1H), 4.42 (s, 1H), 2.78 (s, 3H), 1.27 (d, J = 5.6 Hz, 3H), 1.06 (s, 2H).	392	97%
4-33		1H NMR (400 MHz, DMSO) δ 14.73 (s, 1H), 11.56 (s, 1H), 9.17 (s, 1H), 8.93 (s, 1H), 8.00 (d, J = 7.7 Hz, 1H), 7.46 (s, 2H), 7.12 (d, J = 20.9 Hz, 2H), 5.18-4.56 (m, 1H), 4.44 (s, 1H), 2.80 (s, 3H), 1.24 (s, 2H), 1.07 (s, 2H).	492	91%
4-34		1H NMR (400 MHz, DMSO) δ 14.70 (s, 1H), 11.77 (s, 1H), 8.93 (s, 1H), 8.01 (d, J = 8.4 Hz, 1H), 7.23-7.03 (m, 2H), 6.88 (s, 1H), 6.76 (d, J = 6.4 Hz, 1H), 4.43 (m, 1H), 2.77 (s, 3H), 1.24 (d, J = 6.6 Hz, 2H), 1.12 (s, 2H).	392	99%
4-35		1H NMR (400 MHz, DMSO) δ 14.28 (s, 1H), 11.79 (s, 1H), 8.94 (s, 1H), 8.17 (d, J = 8.8 Hz, 1H), 7.56-7.38 (m, 2H), 7.06 (t, J = 8.8 Hz, 1H), 6.79 (s, 1H), 4.44 (s, 1H), 1.24 (d, J = 6.6 Hz, 2H), 1.12 (s, 2H).	415	91%
4-36		1H NMR (400 MHz, DMSO) δ 14.28 (s, 1H), 12.16 (s, 1H), 8.95 (s, 1H), 8.18 (d, J = 8.0 Hz, 1H), 7.49 (d, J = 4.2 Hz, 1H), 7.05 (d, J = 8.5 Hz, 2H), 6.85 (s, 1H), 4.43 (s, 1H), 1.24 (s, 2H), 1.13 (s, 2H).	415	95%
4-37		1H NMR (400 MHz, DMSO) δ 14.26 (s, 1H), 12.07 (s, 1H), 8.95 (s, 1H), 8.19 (d, J = 8.5 Hz, 1H), 7.49 (d, J = 7.6 Hz, 1H), 7.29-7.07 (m, 2H), 6.81 (s, 1H), 4.44 (s, 1H), 1.25 (s, 2H), 1.13 (s, 2H).	431	95%
4-38		1H NMR (400 MHz, DMSO) δ 14.28 (s, 1H), 12.04 (s, 1H), 8.95 (s, 1H), 8.19 (d, J = 8.7 Hz, 1H), 7.34 (d, J = 8.0 Hz, 1H), 7.20 (s, 1H), 6.93-6.81 (m, 2H), 4.44 (s, 1H), 1.24 (s, 2H), 1.13 (s, 2H).	415	87%
4-39		1H NMR (400 MHz, DMSO) δ 14.71 (s, 1H), 11.66 (s, 1H), 10.06 (s, 1H), 8.92 (s, 1H), 8.02 (s, 3H), 7.46 (s, 1H), 7.31 (s, 1H), 7.19 (s, 1H), 7.06 (s, 1H), 6.90 (s, 1H), 4.42 (s, 1H), 3.85 (s, 3H), 2.79 (s, 3H), 1.26 (s, 2H), 1.07 (s, 2H).	526	95.6%
4-40		1H NMR (400 MHz, DMSO) δ 14.71 (s, 1H), 11.62 (s, 1H), 10.05 (s, 1H), 8.93 (s, 1H), 7.99 (d, J = 9.2 Hz, 1H), 7.70 (d, J = 7.5 Hz, 2H), 7.28-6.87 (m, 6H), 4.42 (s, 1H), 3.75 (s, 3H), 2.68 (s, 3H), 1.25 (d, J = 9.3 Hz, 2H), 1.05 (d, J = 18.8 Hz, 2H).	562	96%
4-41		1H NMR (400 MHz, DMSO) δ 14.73 (s, 1H), 11.66 (s, 1H), 9.62 (s, 1H), 8.93 (s, 1H), 8.02 (d, J = 8.7 Hz, 1H), 7.72 (s, 1H), 7.21 (s, 1H), 7.12 (s, 1H), 7.04 (s, 1H), 4.44 (s, 1H), 3.05 (s, 1H), 2.82 (d, J = 25.3 Hz, 3H), 1.12 (d, J = 24.4 Hz, 10H).	462	87%
4-42		1H NMR (400 MHz, DMSO) δ 11.87 (s, 1H), 9.18 (s, 1H), 8.08-7.63 (m, 2H), 7.48 (s, 2H), 7.20 (s, 2H), 6.95 (s, 2H), 4.54 (s, 1H), 4.24 (s, 2H), 2.81 (s, 3H), 1.29 (s, 2H), 1.06 (s, 2H).	406	97%
4-43		1H NMR (400 MHz, DMSO) δ 14.78 (s, 1H), 11.70 (s, 1H), 8.98 (s, 1H), 8.06 (d, J = 9.0 Hz, 1H), 7.49 (s, 1H), 7.43 (d, J = 7.4 Hz, 1H), 7.20 (s, 1H), 7.00 (d, J = 6.8 Hz, 1H), 6.91 (s, 1H), 4.49 (s, 3H), 2.84 (s, 3H), 1.46 (s, 9H), 1.30 (s, 2H), 1.13 (s, 2H).	506	98%
4-44		1H NMR (400 MHz, DMSO) δ 14.76 (s, 1H), 12.92 (s, 1H), 8.92 (s, 1H), 8.79 (s, 1H), 8.07 (s, 1H), 7.99 (d, J = 8.6 Hz, 1H), 7.77 (d, J = 8.3 Hz, 1H), 7.37 (d, J = 8.0 Hz, 1H), 4.40 (s, 1H), 2.62 (s, 3H), 1.25 (d, J = 5.7 Hz, 2H), 1.10 (s, 2H).	422	100%
4-45		1H NMR (400 MHz, DMSO) δ 11.65 (s, 1H), 9.57 (s, 1H), 8.82 (s, 1H), 7.93 (d, J = 8.3 Hz, 1H), 7.71 (d, J = 5.5 Hz, 1H), 7.19 (s, 1H), 7.09 (s, 1H), 7.00 (s, 1H), 4.32 (s, 1H), 2.72 (d, J = 18.9 Hz, 3H), 1.89-1.77 (m, 5H), 1.65 (s, 1H), 1.45 (d, J = 10.5 Hz, 2H), 1.35-1.16 (m, 6H), 0.97 (s, 2H).	502	89%
4-46		1H NMR (400 MHz, DMSO) δ 14.69 (s, 1H), 11.94 (s, 1H), 9.39 (s, 1H), 8.92 (s, 1H), 8.00 (d, J = 7.8 Hz, 1H), 7.72 (s, 1H), 7.28 (s, 1H), 7.15 (s, 1H), 6.81 (s, 1H), 4.43 (s, 1H), 4.27-4.13 (m, 2H), 2.79 (s, 3H), 2.33 (s, 1H), 2.17 (s, 1H), 1.59 (d, J = 14.2 Hz, 2H), 1.26 (s, 5H), 1.07 (s, 2H), 0.85 (dd, J = 54.3, 14.6 Hz, 14H).	588	86.3%
4-47		1 H NMR (400 MHz, DMSO) δ 14.73 (s, 1H), 11.74 (s, 1H), 10.60 (s, 1H), 9.30 (s, 1H), 8.92 (s, 1H), 8.61 (d, J = 7.6 Hz, 1H), 8.11 (d, J = 7.9 Hz, 1H), 8.01 (d, J = 8.8 Hz, 1H), 7.59 (d, J = 6.7 Hz, 1H), 7.37 (d, J = 7.8 Hz, 1H), 7.24 (d, J = 8.0 Hz, 1H), 6.97 (s, 1H), 4.43 (s, 1H), 2.79 (s, 3H), 1.25 (s, 2H), 1.07 (s, 2H).	565	96%
4-48		1H NMR (400 MHz, DMSO) δ 14.70 (s, 1H), 11.74 (s, 1H), 9.76 (s, 1H), 8.93 (s, 1H), 8.01 (d, J = 8.7 Hz, 1H), 7.29 (d, J = 6.6 Hz, 1H), 7.23-7.01 (m, 3H), 4.43 (s, 1H), 3.49 (d, J = 14.6 Hz, 1H), 3.06 (d, J = 14.8 Hz, 1H), 2.37 (dd, J = 27.4, 15.5 Hz, 2H), 2.04 (s, 1H), 1.91 (d, J = 17.7 Hz, 2H), 1.51 (d, J = 11.3 Hz, 1H), 1.41 (d, J = 10.3 Hz, 1H), 1.25 (s, 2H), 1.09 (d, J = 11.8 Hz, 3H), 0.98 (s, 2H), 0.77 (d, J = 22.2 Hz, 3H).	606	88%
4-49		1H NMR (400 MHz, DMSO) δ 14.69 (s, 1H), 11.58 (s, 1H), 10.29 (s, 1H), 8.91 (s, 1H), 8.40 (s, 1H), 8.05 (dd, J = 15.6, 8.6 Hz, 2H), 7.97 (s, 2H), 7.83 (d, J = 8.2 Hz, 1H), 7.72-7.56 (m, 2H), 7.18 (d, J = 8.0 Hz, 1H), 7.04 (t, J = 8.0 Hz, 1H), 6.98 (d, J = 7.5 Hz, 1H), 6.81 (s, 1H), 4.35 (s, 1H), 2.54 (s, 3H), 1.23 (s, 2H), 1.04 (s, 2H).	582	100%
4-50		1H NMR (400 MHz, DMSO) δ 14.72 (s, 1H), 11.68 (s, 1H), 10.26 (s, 1H), 8.92 (s, 1H), 8.00 (s, 1H), 7.74 (s, 1H), 7.29 (s, 1H), 7.19 (s, 1H), 7.03 (s, 1H), 6.93 (s, 2H), 4.43 (s, 1H), 2.79 (s, 3H), 2.31 (s, 6H), 2.10 (s, 3H), 1.24 (s, 2H), 1.07 (s, 2H).	538	90%
4-51		1H NMR (400 MHz, DMSO) δ 14.73 (s, 1H), 11.62 (s, 1H), 10.08 (s, 1H), 8.93 (s, 1H), 8.00 (d, J = 7.6 Hz, 1H), 7.76 (d, J = 8.6 Hz, 2H), 7.18 (d, J = 7.7 Hz, 2H), 7.02 (d, J = 18.7 Hz, 2H), 4.44 (s, 1H), 3.63 (s, 3H), 2.76 (s, 3H), 1.24 (s, 2H), 1.08 (s, 2H).	536	99%
4-52		1H NMR (400 MHz, DMSO) δ 14.72 (s, 1H), 11.68 (s, 1H), 9.29 (s, 1H), 8.93 (s, 1H), 8.81 (s, 1H), 8.31 (s, 1H), 8.03 (d, J = 8.9 Hz, 1H), 7.15 (s, 2H), 7.02 (dd, J = 24.0, 8.3 Hz, 2H), 6.94 (s, 1H), 4.44 (s, 1H), 3.91 (s, 3H), 2.80 (s, 3H), 1.25 (d, J = 15.5 Hz, 2H), 1.08 (s, 2H).	575	96%
4-53		1H NMR (400 MHz, DMSO) δ 14.71 (s, 1H), 11.72 (s, 1H), 10.04 (s, 1H), 8.94 (s, 1H), 8.02 (d, J = 10.3 Hz, 1H), 7.71 (d, J = 7.0 Hz, 1H), 7.24 (s, 1H), 7.15 (d, J = 7.3 Hz, 1H), 7.04 (s, 1H), 4.44 (s, 1H), 3.98 (s, 2H), 3.76 (s, 2H), 3.43 (s, 2H), 3.07 (d, J = 24.3 Hz, 4H), 2.78 (s, 3H), 2.69 (d, J = 10.9 Hz, 1H), 1.26 (s, 2H), 1.08 (s, 2H).	533	99%
4-54		1H NMR (400 MHz, DMSO) δ 14.71 (s, 1H), 11.72 (s, 1H), 10.03 (s, 1H), 8.94 (s, 1H), 8.02 (d, J = 8.9 Hz, 1H), 7.70 (s, 1H), 7.24 (s, 1H), 7.14 (s, 1H), 7.03 (s, 1H), 5.33 (s, 1H), 4.43 (s, 1H), 4.03 (s, 2H), 3.03 (s, 4H), 2.78 (s, 3H), 2.00 (d, J = 7.6 Hz, 2H), 1.24 (s, 9H), 1.08 (s, 2H), 0.85 (s, 2H).	632	96%
4-55		1H NMR (400 MHz, DMSO) δ 14.71 (s, 1H), 11.72 (s, 1H), 10.04 (s, 1H), 9.57 (s, 1H), 8.94 (s, 1H), 8.02 (d, J = 8.9 Hz, 1H), 7.71 (d, J = 7.8 Hz, 1H), 7.26 (d, J = 7.6 Hz, 1H), 7.15 (d, J = 9.1 Hz, 1H), 7.03 (d, J = 9.6 Hz, 1H), 4.44 (s, 1H), 2.99 (s, 1H), 2.82 (s, 3H), 2.78 (s, 2H), 2.54 (s, 2H), 1.26 (s, 2H), 1.08 (s, 2H).	491	91%
4-56		1H NMR (400 MHz, DMSO) δ 14.71 (s, 1H), 11.87 (s, 1H), 10.45 (s, 1H), 8.93 (s, 1H), 8.02 (d, J = 8.8 Hz, 1H), 7.47 (d, J = 7.2 Hz, 1H), 7.23 (s, 1H), 7.07 (d, J = 7.9 Hz, 1H), 6.68 (s, 1H), 4.42 (s, 1H), 2.78 (s, 3H), 2.68 (s, 3H), 1.26 (s, 2H), 1.08 (s, 2H).	490	96%
4-57		1H NMR (400 MHz, DMSO) δ 14.78 (s, 1H), 11.75 (s, 1H), 9.64 (s, 1H), 8.92 (s, 1H), 7.99 (d, J = 8.7 Hz, 1H), 7.83 (s, 1H), 7.70 (s, 1H), 7.63 (d, J = 7.8 Hz, 1H), 7.18 (d, J = 8.6 Hz, 1H), 4.48 (s, 2H), 4.40 (s, 1H), 2.72 (d, J = 27.2 Hz, 7H), 2.62 (s, 3H), 1.25 (s, 2H), 1.08 (s, 2H).	M- (Me)2N 389	100%
4-58		1H NMR (400 MHz, DMSO) δ 14.79 (s, 1H), 9.84 (s, 1H), 8.92 (s, 1H), 7.97 (d, J = 8.2 Hz, 1H), 7.77 (d, J = 8.7 Hz, 1H), 7.62 (s, 1H), 7.56 (s, 1H), 7.20 (d, J = 8.0 Hz, 1H), 6.63 (s, 1H), 4.64 (s, 2H), 4.39 (s, 1H), 3.57 (s, 2H), 2.88 (s, 6H), 2.65 (d, J = 22.8 Hz, 3H), 1.24 (s, 2H), 1.08 (s, 2H).	448	100%
4-59		1H NMR (400 MHz, DMSO) δ 14.76 (s, 1H), 11.62 (s, 1H), 9.68 (s, 1H), 8.92 (s, 1H), 7.99 (s, 1H), 6.95 (s, 2H), 6.77 (s, 1H), 6.46 (s, 1H), 4.43 (s, 1H), 2.80 (s, 3H), 1.27 (s, 2H), 1.07 (s, 4H).	393	99%
4-60		1H NMR (400 MHz, DMSO) δ 14.77 (s, 1H), 11.29 (s, 1H), 8.91 (s, 1H), 7.97 (d, J = 9.0 Hz, 1H), 7.13 (s, 1H), 6.97 (s, 1H), 6.61 (s, 1H), 4.42 (s, 1H), 3.80 (d, J = 13.7 Hz, 7H), 2.78 (s, 3H), 1.26 (s, 2H), 1.06 (s, 2H).	437	99%
4-61		1H NMR (400 MHz, DMSO) δ 14.74 (s, 1H), 11.29 (s, 1H), 8.91 (s, 1H), 8.81 (s, 1H), 7.98 (d, J = 9.1 Hz, 1H), 7.27 (d, J = 8.8 Hz, 1H), 6.93 (s, 1H), 6.71 (d, J = 8.4 Hz, 1H), 6.53 (s, 1H), 4.41 (s, 2H), 2.77 (s, 3H), 1.25 (s, 2H), 1.06 (s, 2H).	393	98%
4-62		1H NMR (400 MHz, DMSO) δ 14.75 (s, 1H), 11.50 (s, 1H), 9.79 (s, 1H), 8.91 (s, 1H), 7.97 (d, J = 8.7 Hz, 1H), 7.07 (d, J = 6.7 Hz, 1H), 6.86 (s, 1H), 6.60 (s, 2H), 4.41 (s, 1H), 2.76 (s, 3H), 1.23 (s, 2H), 1.08 (s, 2H).	393	100%
4-63		1H NMR (400 MHz, DMSO) δ 12.18 (s, 1H), 10.24 (s, 1H), 8.93 (s, 1H), 8.04 (d, J = 8.8 Hz, 1H), 7.87 (d, J = 8.8 Hz, 2H), 7.78 (d, J = 7.0 Hz, 1H), 7.46 (d, J = 7.3 Hz, 2H), 7.35 (s, 1H), 4.43 (s, 1H), 2.77 (s, 3H), 1.27 (s, 2H), 1.09 (s, 2H).	405	85%
4-64		1H NMR (400 MHz, DMSO) δ 14.55 (s, 1H), 13.88 (s, 1H), 8.94 (s, 1H), 8.10 (d, J = 8.4 Hz, 1H), 8.01 (dd, J = 14.5, 7.6 Hz, 2H), 7.62 (s, 1H), 4.44 (s, 1H), 2.71 (s, 3H), 1.24 (s, 2H), 1.08 (s, 2H).	447	89%
4-65		1H NMR (400 MHz, DMSO) δ 14.44 (s, 1H), 11.53 (s, 1H), 8.84 (s, 1H), 8.16 (d, J = 9.1 Hz, 1H), 7.95 (d, J = 7.2 Hz, 1H), 7.69 (d, J = 9.7 Hz, 1H), 7.58 (t, J = 10.6 Hz, 1H), 7.42 (d, J = 7.4 Hz, 2H), 7.16 (t, J = 7.5 Hz, 1H), 7.04 (t, J = 7.4 Hz, 1H), 6.62 (s, 1H), 5.77 (s, 1H), 1.77 (d, J = 17.9 Hz, 3H).	449	94.06%
4-66		1H NMR (400 MHz, DMSO) δ 14.79 (s, 1H), 11.42 (s, 1H), 8.70 (s, 1H), 8.04 (d, J = 8.2 Hz, 1H), 7.57 (d, J = 8.2 Hz, 1H), 7.42 (d, J = 8.0 Hz, 1H), 7.25 (s, 1H), 6.96 (d, J = 8.1 Hz, 1H), 6.86 (d, J = 7.7 Hz, 1H), 6.61 (s, 1H), 4.23 (s, 1H), 2.70 (s, 3H), 1.06 (s, 2H), 0.81 (s, 2H).	359	91.2%
4-67		1H NMR (400 MHz, DMSO) δ 11.76 (s, 1H), 8.71 (s, 1H), 8.16 (d, J = 4.8 Hz, 1H), 7.81 (d, J = 8.8 Hz, 1H), 7.36 (s, 1H), 5.94 (dd, J = 3.4, 1.8 Hz, 1H), 5.10 (s, 1H), 4.22-4.08 (m, 1H), 2.33 (s, 3H), 1.09-0.88 (m, 4H).	378	97%
4-68		1H NMR (400 MHz, DMSO) δ 12.33 (s, 1H), 8.92 (s, 1H), 8.35 (d, J = 4.4 Hz, 1H), 7.99 (d, J = 8.8 Hz, 1H), 7.87 (s, 1H), 7.77 (d, J = 7.8 Hz, 1H), 7.21 (dd, J = 7.7, 4.0 Hz, 1H), 4.47-4.34 (m, 2H), 2.69 (s, 3H), 1.28 (d, J = 6.6 Hz, 2H), 1.10 (s, 2H).	378	98%
4-69		1H NMR (400 MHz, DMSO) δ 8.94 (s, 1H), 8.39 (t, J = 3.1 Hz, 1H), 8.08 (t, J = 9.0 Hz, 2H), 7.22 (dd, J = 8.1, 4.1 Hz, 1H), 6.74 (d, J = 2.9 Hz, 1H), 4.48-4.36 (m, 1H), 2.67 (s, 3H), 1.26 (d, J = 7.0 Hz, 4H), 1.09 (s, 4H).	392	98%
4-70		1H NMR (400 MHz, DMSO) δ 8.94 (s, 1H), 8.39 (t, J = 3.1 Hz, 1H), 8.07 (t, J = 9.0 Hz, 1H), 7.21 (dt, J = 7.7, 3.7 Hz, 1H), 6.74 (d, J = 2.9 Hz, 1H), 4.50-4.32 (m, 1H), 2.67 (s, 3H), 1.33-1.19 (d, J = 7.0 Hz, 2H), 1.09 (s, 2H).	392	96%
4-71		1H NMR (400 MHz, DMSO) δ 14.73 (s, 1H), 11.96 (s, 1H), 8.92 (s, 1H), 8.24 (s, 1H), 8.06 (s, 1H), 8.00 (d, J = 8.7 Hz, 1H), 7.61 (t, J = 2.8 Hz, 1H), 6.57 (s, 1H), 4.59-4.15 (dm, 1H), 2.64 (s, 3H), 1.26 (d, J = 6.8 Hz, 2H), 1.09 (m ,2H).	378	98%
4-72		1H NMR (400 MHz, DMSO) δ 14.67 (s, 1H), 13.15 (s, 1H), 8.93 (s, 1H), 8.27 (d, J = 6.1 Hz, 1H), 8.01 (d, J = 8.8 Hz, 1H), 7.78 (d, J = 7.9 Hz, 1H), 7.19 (t, J = 7.1 Hz, 1H), 6.88 (s, 1H), 4.49-4.33 (m, 1H), 2.77 (s, 3H), 1.39-1.21 (d, J = 7.0 Hz, 2H), 1.15-1.01 (m, 2H).	394	98%
4-73		1H NMR (400 MHz, DMSO) δ 14.63 (s, 1H), 12.94 (s, 1H), 8.93 (s, 1H), 8.72 (s, 1H), 8.65 (s, 1H), 8.04 (d, J = 8.7 Hz, 1H), 6.93 (s, 1H), 4.53-4.29 (m, 1H), 2.77 (s, 3H), 1.32-1.19 (m, 3H), 1.17-0.95 (m, 2H).	403	92%
4-74		1H NMR (400 MHz, DMSO) δ 14.65 (s, 1H), 13.00 (s, 1H), 8.94 (s, 1H), 8.53 (s, 7H), 8.04 (d, J = 8 Hz, 1H), 7.69 (dd, J = 4.4, 2.4 Hz, 1H), 7.01 (s, 6H), 4.58-4.31 (m, 1H), 2.78 (s, 3H), 1.27 (d, J = 6.6 Hz, 15H), 1.18-1.01 (m, 16H).	403	92%
4-75		1H NMR (400 MHz, DMSO) δ 14.57 (s, 1H), 13.95 (s, 1H), 8.94 (s, 1H), 8.58 (s, 2H), 8.09 (d, J = 8.7 Hz, 1H), 7.60-7.51 (m, 1H), 4.53-4.33 (m, 1H), 2.73 (s, 3H), 1.35-1.17 (m, 2H), 1.15-1.01 (m, 2H).	423	86%
4-76		1H NMR (400 MHz, DMSO) δ 13.25 (s, 1H), 8.99 (s, 1H), 8.36 (d, J = 5.9 Hz, 1H), 8.07 (d, J = 8.7 Hz, 1H), 7.95 (s, 1H), 7.52 (d, J = 8.0 Hz, 1H), 7.28 (t, J = 6.8 Hz, 1H), 4.54-4.44 (m, 1H), 2.76 (s, 3H), 1.34 (d, J = 6.8 Hz, 2H), 1.26-1.06 (m, 2H).	394	98%
4-77		1H NMR (400 MHz, DMSO) δ 12.56 (s, 1H), 8.93 (s, 1H), 8.38 (t, J = 3.6 Hz, 1H), 8.20 (d, J = 7.4 Hz, 1H), 8.02 (d, J = 9.1 Hz, 1H), 7.26 (dd, J = 8.0, 4.1 Hz, 1H), 6.83 (s, 1H), 4.57-4.33 (m, 1H), 2.78 (s, 3H), 1.35-1.19 (d, J = 6.9 Hz, 2H), 1.15-1.01 (s, 2H).	378	98%
4-78		1H NMR (400 MHz, DMSO) δ 14.65 (s, 1H), 12.47 (s, 1H), 11.98 (s, 1H), 8.91 (s, 1H), 7.95 (m, 2H), 6.76 (s, 1H), 4.51-4.36 (m, 1H), 2.78 (s, 3H), 1.26 (d, J = 6.9 Hz, 2H), 1.17-1.01 (m, 2H).	395	95%
4-79		1H NMR (400 MHz, DMSO) δ 14.57 (s, 1H), 13.19 (d, J = 8.5 Hz, 1H), 9.29 (d, J = 2.9 Hz, 1H), 9.02 (d, J = 2.4 Hz, 1H), 8.94 (s, 1H), 8.05 (d, J = 8.8 Hz, 1H), 7.06 (s, 1H), 4.49-4.35 (m, 1H), 2.77 (s, 3H), 1.26 (d, J = 7.2 Hz, 2H), 1.13-0.99 (s, 2H).	379	98%
4-80		1H NMR (400 MHz, DMSO) δ 15.167 (s, 1H), 14.59 (s, 1H), 13.80 (s, 1H), 9.32 (s, 1H), 8.96 (d, J = 2.3 Hz, 1H), 8.40 (d, J = 6.1 Hz, 1H), 8.25 (d, J = 6.0 Hz, 1H), 8.10 (d, J = 8.4 Hz, 1H), 7.27 (s, 1H), 4.51-4.39 (m, 1H), 2.76 (m, 3H), 1.29-1.17 (d, J = 7.0 Hz, 2H), 1.17-0.97 (m, 2H).	378	85%
4-81		1H NMR (400 MHz, DMSO) δ 14.56 (s, 1H), 13.05 (s, 1H), 8.95 (s, 1H), 8.68 (s, 1H), 8.08 (d, J = 9.1 Hz, 1H), 7.62 (s, 1H), 7.12 (s, 1H), 4.51-4.36 (m, 1H), 2.76 (s, 3H), 1.33-1.19 (d, J = 7.1 Hz, 2H), 1.13-1.05 (s, 2H).	378	85%
4-82		1H NMR (400 MHz, DMSO) δ 14.88 (s, 1H), 14.57 (s, 1H), 13.46 (s, 1H), 9.41 (s, 1H), 8.96 (s, 1H), 8.52 (d, J = 6.5 Hz, 1H), 8.21-7.93 (m, 2H), 7.38 (s, 1H), 4.53-4.29 (m, 1H), 2.77 (s, 3H), 1.35-1.17 (d, J = 6.7 Hz, 2H), 1.19-1.03 (s, 2H).	378	98%
4-83			421	90%
4-84			421	98%
4-85			482	93%
4-86		1H NMR (400 MHz, DMSO) δ 14.60 (s, 1H), 10.06 (s, 1H), 8.81 (s, 1H), 7.88 (d, J = 8.5 Hz, 1H), 7.21 (s, 1H), 7.05 (d, J = 8.1 Hz, 1H), 6.80 (d, J = 8.1 Hz, 1H), 4.36 (m, 1H), 3.08 (s, 2H), 1.06 (m, 4H).	392	95%
4-87		1H NMR (400 MHz, DMSO) δ 14.57 (s, 1H), 8.91 (s, 1H), 8.03 (d, J = 9.3 Hz, 1H), 7.80 (d, J = 7.7 Hz, 1H), 7.73 (d, J = 8.3 Hz, 1H), 7.56-7.22 (m, 3H), 4.57-4.32 (m, 1H), 2.84 (s, 3H), 1.27 (m, 2H), 1.06 (m, 2H).	378	98%
4-88		1H NMR (400 MHz, DMSO) δ 14.50 (s, 1H), 13.22 (s, 1H), 8.84 (s, 1H), 8.10-7.80 (m, 2H), 7.74-7.58 (s, 1H), 7.49 (s, 1H), 4.38 (m, 1H), 2.78 (s, 3H), 1.30-1.12 (m, 2H), 1.00 (m, 2H).	422	98%
4-89		1H NMR (400 MHz, DMSO) δ 14.56 (s, 1H), 8.93 (s, 1H), 8.02 (d, J = 9.2 Hz, 1H), 7.76 (dd, J = 8.8, 3.5 Hz, 1H), 7.61 (d, J = 8.6 Hz, 1H), 7.41 (s, 1H), 7.28 (t, J = 9.3 Hz, 1H), 4.43 (m, 1H), 2.82 (s, 3H), 1.26 (d, J = 6.4 Hz, 3H), 1.05 (s, 2H).	396	98%
4-90		1H NMR (400 MHz, DMSO) δ 8.88 (s, 1H), 7.95 (d, J = 8.9 Hz, 1H), 7.76 (s, 1H), 7.61 (d, J = 8.9 Hz, 1H), 7.36 (s, 1H), 7.20 (t, J = 9.0 Hz, 1H), 4.35 (m, 1H), 2.76 (s, 3H), 1.30-1.09 (m, 3H), 0.96 (s, 2H).	396	98%
4-91		1H NMR (400 MHz, DMSO) δ 14.57 (s, 1H), 8.86 (s, 1H), 7.96 (m, 3H), 7.59 (s, 1H), 7.41 (d, J = 5.1 Hz, 2H), 4.35 (m, 1H), 2.72 (s, 3H), 1.17 (m, 2H), 1.00 (m, 2H).	394	96%
4-92		1H NMR (400 MHz, DMSO) δ 14.65 (s, 1H), 8.86 (s, 1H), 8.08 (d, J = 7.6 Hz, 1H), 7.97 (m, 2H), 7.36 (m, 3H), 4.32 (m, 1H), 2.57 (s, 3H), 1.03 (m, 4H).	394	98%
4-93		1H NMR (400 MHz, DMSO) δ 14.51 (s, 1H), 8.92 (s, 1H), 8.32 (d, J = 8.1 Hz, 1H), 8.28 (d, J = 8.0 Hz, 1H), 8.05 (t, J = 13.1 Hz, 1H), 7.90 (s, 1H), 7.70 (t, J = 8.2 Hz, 1H), 4.45 (m, 1H), 2.86 (s, 3H), 1.26 (t, J = 11.6 Hz, 2H), 1.10 (d, J = 21.6 Hz, 2H).	423	98%
4-94		1H NMR (400 MHz, DMSO) δ 14.46 (s, 1H), 8.69 (s, 1H), 8.14 (s, 1H), 7.75 (d, J = 9.2 Hz, 1H), 7.52 (dd, J = 8.8, 3.5 Hz, 1H), 7.20-7.11 (m, 3H), 4.43 (s, 1H), 2.64 (s, 3H), 1.26 (d, J = 6.4 Hz, 3H), 1.05 (s, 2H).	378	98%
4-95		1H NMR (400 MHz, DMSO) δ 14.55 (s, 1H), 8.94 (s, 1H), 8.05 (d, J = 9.3 Hz, 1H), 7.64 (d, J = 2.9 Hz, 1H), 7.54 (s, 1H), 7.36 (d, J = 6.6 Hz, 2H), 4.44 (m ,1H), 2.85 (s, 3H), 1.34-1.19 (m, 2H), 1.06 (s, 2H).	396	96%
4-96		1H NMR (400 MHz, DMSO) δ 8.91 (s, 1H), 8.38 (s, 1H), 8.04 (d, J = 9.2 Hz, 1H), 7.96 (d, J = 8.4 Hz, 1H), 7.88 (d, J = 8.5 Hz, 1H), 7.55 (s, 1H), 4.44 (m, 1H), 2.83 (s, 3H), 1.35-1.18 (m, 2H), 1.06 (m, 2H).	403	98%
4-97		1H NMR (400 MHz, DMSO) δ 14.56 (s, 1H), 8.94 (s, 1H), 8.04 (d, J = 9.1 Hz, 1H), 7.95-7.77 (m, 2H), 7.53-7.33 (m, 2H), 4.45 (m, 1H), 2.83 (s, 3H), 1.27 (d, J = 6.3 Hz, 2H), 1.05 (s, 2H).	462	98%
4-98		1H NMR (400 MHz, DMSO) δ 14.61 (s, 1H), 8.86 (s, 1H), 7.95 (d, J = 9.0 Hz, 1H), 7.43 (s, 1H), 7.03 (t, J = 8.1 Hz, 1H), 6.77 (d, J = 7.4 Hz, 1H), 6.39 (d, J = 7.1 Hz, 1H), 4.38 (m, 1H), 2.77 (s, 3H), 1.19 (m, 2H), 0.98 (m, 1H).	393	96%

TABLE 5
Com-
pound					MS
No.	R3 =	R2 =	R1 =	NMR	(MH+)	HPLC
5-1		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.72 (s, 1H), 10.91 (s, 1H), 8.89 (s, 1H), 7.94 (d, J = 8.60 Hz, 1H), 7.13-6.90 (m, 3H), 4.67 (s, 2H), 4.38 (s, 1H), 2.62 (s, 3H), 1.23 (d, J = 5.80 Hz, 2H), 1.04 (s, 2H).	409	97%
5-2		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.71 (s, 1H), 10.78 (s, 1H), 8.90 (s, 1H), 7.95 (d, J = 8.72 Hz, 1H), 7.41 (s, 1H), 7.22 (d, J = 8.03 Hz, 1H), 7.13 (d, J = 8.17 Hz, 1H), 4.38 (s, 1H), 3.57 (s, 2H), 2.62 (s, 3H), 1.24 (d, J = 6.14 Hz, 2H), 1.05 (s, 2H).	425	98%
5-3		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.70 (s, 1H), 10.64 (s, 1H), 8.98 (s, 1H), 8.05 (d, J = 8.72 Hz, 1H), 7.90 (s, 1H), 7.62 (s, 1H), 4.92 (s, 2H), 4.46 (s, 1H), 2.71 (s, 3H), 1.30 (s, 3H), 1.15 (s, 2H).	454	97%
5-4		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.66 (s, 1H), 11.39 (s, 1H), 8.90 (s, 1H), 7.96 (d, J = 8.72 Hz, 1H), 7.57 (s, 1H), 7.43 (s, 1H), 4.75 (s, 2H), 4.39 (s, 1H), 2.62 (s, 3H), 1.23 (d, J = 5.26 Hz, 2H), 1.06 (s, 2H).	434	98%
5-5		OMe	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.72 (s, 1H), 10.94 (s, 1H), 8.80 (s, 1H), 7.90 (s, 1H), 7.11 (d, J = 26.18 Hz, 2H), 4.67 (s, 2H), 1.15 (s, 4H).	425	98%
5-6		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.75 (s, 1H), 10.87 (s, 1H), 8.90 (s, 1H), 7.96 (d, J = 8.58 Hz, 1H), 7.14 (d, J = 8.35 Hz, 1H), 6.97 (d, J = 8.15 Hz, 1H), 6.89 (s, 1H), 4.69 (s, 2H), 4.39 (s, 1H), 2.62 (s, 3H), 1.23 (s, 2H), 1.04 (s, 2H).	409	98%
5-9		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.74 (s, 1H), 10.28 (s, 1H), 8.90 (s, 1H), 7.94 (d, J = 8.20 Hz, 1H), 7.23 (s, 1H), 7.17 (s, 1H), 7.03 (s, 1H), 4.38 (s, 2H), 2.97 (s, 2H), 2.63 (s, 2H), 1.23 (s, 2H), 1.04 (s, 2H).	407	85%
5-10		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.71 (s, 1H), 11.47 (s, 1H), 11.39 (s, 1H), 8.91 (s, 1H), 7.98 (d, J = 8.50 Hz, 1H), 7.89 (s, 1H), 7.70 (d, J = 8.10 Hz, 1H), 7.35 (d, J = 8.11 Hz, 1H), 4.40 (s, 1H), 3.49 (d, J = 87.04 Hz, 2H), 2.62 (s, 3H), 1.23 (s, 2H), 1.08 (s, 3H).	422	98%
5-11		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.67 (s, 1H), 11.96 (s, 1H), 11.63 (s, 1H), 8.92 (s, 1H), 8.69 (s, 1H), 8.34 (s, 1H), 8.00 (d, J = 8.65 Hz, 1H), 4.41 (s, 1H), 2.61 (d, J = 29.62 Hz, 3H), 1.24 (d, J = 5.11 Hz, 2H), 1.09 (s, 2H).	423	99%
5-12		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.73 (s, 1H), 12.44-11.74 (m, 2H), 8.91 (s, 1H), 7.98 (d, J = 8.01 Hz, 1H), 7.53-7.03 (m, 3H), 4.39 (s, 1H), 2.61 (s, 3H), 1.20 (d, J = 26.27 Hz, 3H), 1.05 (s, 2H).	422	96%
5-13		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.83 (s, 1H), 8.88 (s, 1H), 7.90 (s, 2H), 6.70 (s, 3H), 4.27 (d, J = 77.51 Hz, 4H), 2.60 (d, J = 25.07 Hz, 3H), 1.23 (s, 2H), 1.02 (s, 2H).	395	98%
5-14		OMe	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.78 (s, 1H), 8.76 (s, 1H), 7.83 (d, J = 9.18 Hz, 1H), 6.92-6.81 (m, 2H), 6.70 (d, J = 7.26 Hz, 1H), 6.19 (d, J = 22.26 Hz, 1H), 4.16 (s, 4H), 3.39 (s, 3H), 2.50 (s, 7H).	411	96%
5-15		8-N	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.55 (s, 1H), 8.61 (s, 1H), 8.19 (d, J = 11.38 Hz, 1H), 7.55 (d, J = 8.31 Hz, 1H), 7.47 (s, 1H), 6.68 (s, 1H), 6.54 (d, J = 8.26 Hz, 1H), 4.00 (s, 2H), 3.73 (s, 1H), 1.15-0.91 (m, 5H).	382	94%
5-16		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.90 (s, 1H), 8.94 (s, 1H), 7.94 (d, J = 9.06 Hz, 1H), 6.95 (d, J = 8.81 Hz, 2H), 6.63 (d, J = 7.73 Hz, 1H), 6.14 (s, 1H), 4.43 (s, 1H), 3.31 (s, 2H), 2.79 (s, 2H), 2.70 (s, 3H), 1.90 (s, 2H), 1.30 (s, 2H), 1.08 (s, 2H).	393	94%
5-17		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.71 (s, 1H), 8.89 (s, 1H), 8.60 (s, 1H), 7.94 (d, J = 8.81 Hz, 1H), 7.67 (s, 1H), 7.10 (s, 1H), 4.38 (s, 1H), 4.27 (s, 2H), 3.63 (s, 2H), 2.66 (s, 3H), 1.24 (d, J = 5.67 Hz, 2H), 1.07 (s, 2H).	440	97%
5-18		Me	Cyclopropyl	1HNMR (400 MHz, DMSO) δ 10.19 (s, 1H), 8.89 (s, 1H), 7.91 (d, J = 8.74 Hz, 1H), 6.33 (s, 1H), 6.24 (s, 1H), 4.57 (s, 2H), 4.38 (s, 2H), 2.64 (s, 3H), 1.23 (d, J = 5.42 Hz, 3H), 1.03 (s, 2H).	424	97%
5-19		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 8.88 (s, 1H), 7.91 (s, 1H), 6.29 (s, 1H), 6.18 (s, 1H), 4.37 (s, 2H), 4.18 (s, 3H), 3.10 (s, 2H), 2.65 (d, J = 16.81 Hz, 6H), 1.23 (s, 3H), 1.03 (s, 2H).	424	97%
5-20		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 8.97 (s, 1H), 8.01 (d, J = 9.26 Hz, 1H), 7.85-7.65 (m, 2H), 7.64-7.40 (m, 1H), 7.36 (s, 1H), 4.46 (s, 1H), 4.32 (s, 3H), 3.63 (s, 3H), 2.74 (s, 3H), 1.30 (d, J = 5.75 Hz, 2H), 1.11 (s, 2H).	396	98%
5-21		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.72 (s, 1H), 8.85 (d, J = 23.76 Hz, 1H), 7.87 (t, J = 19.93 Hz, 1H), 7.17 (s, 1H), 6.99 (d, J = 9.29 Hz, 2H), 4.37 (s, 1H), 4.20 (s, 2H), 3.59 (s, 1H), 3.44 (s, 2H), 2.63 (s, 3H), 1.24 (s, 2H), 1.07 (d, J = 23.80 Hz, 2H).	420	95%
5-22		OMe	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.67 (s, 1H), 8.78 (s, 1H), 7.87 (d, J = 9.24 Hz, 1H), 7.26 (d, J = 10.63 Hz, 1H), 7.11 (s, 1H), 7.04 (s, 1H), 4.20 (s, 3H), 2.00 (dd, J = 7.56, 15.22 Hz, 1H), 1.21 (d, J = 14.05 Hz, 4H).	436	98%
5-24		OMe	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 8.77 (s, 1H), 7.87 (d, J = 9.25 Hz, 1H), 7.75 (s, 1H), 7.20 (s, 1H), 7.14 (s, 1H), 4.17 (s, 3H), 3.47 (s, 3H), 1.32-1.05 (m, 8H).	412	96%
5-25		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.82 (s, 1H), 10.92 (s, 1H), 10.86 (s, 1H), 8.96 (s, 1H), 7.98 (t, J = 12.31 Hz, 1H), 7.15 (d, J = 7.60 Hz, 1H), 7.00 (d, J = 8.89 Hz, 2H), 4.44 (s, 1H), 2.67 (s, 3H), 1.28 (s, 2H), 1.12 (s, 2H).	394	98%
5-26		OMe	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.63 (s, 1H), 10.94 (s, 1H), 10.87 (s, 1H), 8.86 (s, 1H), 7.97 (d, J = 8.82 Hz, 1H), 7.17 (d, J = 7.41 Hz, 3H), 4.29 (s, 1H), 1.23 (s, 4H).	410	98%
5-27		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 8.95 (s, 1H), 7.96 (d, J = 8.75 Hz, 1H), 6.96 (d, J = 10.17 Hz, 1H), 6.92 (d, J = 8.04 Hz, 1H), 6.72 (d, J = 7.83 Hz, 1H), 4.44 (s, 1H), 3.63 (s, 2H), 3.09 (s, 2H), 2.70 (s, 3H), 1.30 (d, J = 5.29 Hz, 2H), 1.10 (s, 2H).	411	98%
5-28		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.74 (s, 1H), 8.89 (s, 1H), 7.94 (d, J = 8.48 Hz, 1H), 7.53 (s, 1H), 7.44 (s, 1H), 7.33 (d, J = 8.57 Hz, 1H), 6.94 (d, J = 8.45 Hz, 1H), 4.39 (s, 1H), 3.80 (s, 2H), 3.48 (s, 2H), 2.64 (s, 3H), 1.23 (s, 2H), 1.06 (s, 2H).	443	98%
5-29		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.67 (s, 1H), 10.84 (s, 1H), 8.83 (s, 1H), 7.86 (d, J = 8.65 Hz, 1H), 6.52 (s, 2H), 4.38 (s, 2H), 4.31 (s, 1H), 3.89 (s, 2H), 2.54 (s, 3H), 1.16 (s, 2H), 1.00 (s, 2H).	436	98%
5-30		OMe	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.71 (s, 1H), 10.91 (s, 1H), 8.79 (s, 1H), 7.88 (d, J = 9.15 Hz, 1H), 6.75 (d, J = 14.51 Hz, 2H), 4.45 (t, J = 4.51 Hz, 2H), 4.27-4.16 (m, 1H), 3.96 (t, J = 4.53 Hz, 2H), 1.17 (d, J = 7.20 Hz, 4H).	452	99%
5-31		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 8.94 (s, 1H), 7.95 (d, J = 8.62 Hz, 1H), 6.79 (dd, J = 7.23, 14.68 Hz, 3H), 4.43 (s, 1H), 4.23 (d, J = 10.57 Hz, 1H), 4.06 (d, J = 10.42 Hz, 1H), 3.60-3.41 (m, 3H), 2.70 (s, 3H), 1.30 (d, J = 5.98 Hz, 2H), 1.09 (s, 2H).	425	99%
5-32		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 8.95 (s, 1H), 7.98 (d, J = 8.04 Hz, 1H), 7.09 (s, 1H), 6.96 (s, 2H), 4.44 (s, 1H), 4.15 (s, 2H), 3.29 (s, 3H), 2.69 (s, 3H), 2.02 (s, 2H), 1.30 (s, 2H), 1.10 (s, 2H).	409	99%
5-33		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 8.76 (s, 1H), 7.77 (d, J = 8.81 Hz, 1H), 6.59 (s, 3H), 4.25 (s, 1H), 4.04 (s, 2H), 3.27 (d, J = 11.94 Hz, 1H), 2.96-2.79 (m, 1H), 2.52 (s, 3H), 1.18 (t, J = 8.54 Hz, 3H), 1.12 (d, J = 5.48 Hz, 2H), 0.91 (s, 2H).	409	98%
5-34		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 8.71 (s, 1H), 7.72 (d, J = 8.62 Hz, 1H), 6.54 (s, 3H), 4.20 (s, 2H), 4.03 (d, J = 10.38 Hz, 2H), 3.52 (t, J = 8.97 Hz, 1H), 3.31 (s, 1H), 2.46 (s, 3H), 1.07 (d, J = 5.70 Hz, 2H), 0.96 (d, J = 4.88 Hz, 3H), 0.86 (s, 2H).	409	98%
5-35		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 10.57 (s, 1H), 8.89 (s, 1H), 7.93 (d, J = 8.73 Hz, 1H), 7.48 (d, J = 52.24 Hz, 1H), 6.96 (d, J = 7.83 Hz, 1H), 6.80 (s, 1H), 6.74 (d, J = 7.83 Hz, 1H), 4.38 (s, 1H), 3.76 (d, J = 12.76 Hz, 1H), 2.63 (s, 3H), 2.07 (s, 1H), 1.85 (s, 1H), 1.66 (s, 1H), 1.58-1.37 (m, 3H), 1.23 (d, J = 6.52 Hz, 2H), 1.06 (s, 2H).	462	98%
5-36		Cl	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 10.92 (s, 1H), 10.70 (s, 1H), 8.92 (s, 1H), 8.09 (d, J = 8.43 Hz, 1H), 7.82 (s, 1H), 7.04 (d, J = 22.18 Hz, 1H), 6.64 (d, J = 10.90 Hz, 2H), 4.52-4.28 (m, 3H), 4.01-3.82 (m, 2H), 1.20 (t, J = 10.03 Hz, 2H), 1.12 (d, J = 3.28 Hz, 2H).	456	97%
5-37		8-Me		1H NMR (400 MHz, DMSO) δ 8.85 (d, J = 3.12 Hz, 1H), 7.90 (d, J = 8.88 Hz, 1H), 6.71 (d, J = 5.48 Hz, 3H), 5.23 (d, J = 3.10 Hz, 1H), 5.07 (d, J = 2.78 Hz, 1H), 4.42-4.27 (m, 1H), 4.22-4.12 (m, 2H), 2.55 (s, 3H), 1.74 (ddd, J = 8.97, 14.93, 17.91 Hz, 1H), 1.62-1.45 (m, 1H).	413	98%
5-38		8-Me		1H NMR (400 MHz, DMSO) δ 14.44 (d, J = 137.56 Hz, 2H), 10.82 (d, J = 68.59 Hz, 1H), 8.85 (t, J = 9.38 Hz, 1H), 7.93 (t, J = 10.51 Hz, 1H), 6.56 (t, J = 40.40 Hz, 2H), 4.44 (d, J = 4.54 Hz, 3H), 4.39-4.29 (m, 1H), 4.04-3.90 (m, 3H), 2.54 (s, 3H), 1.64 (m, 2H).	454	98%
5-39		Cl	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 8.92 (s, 1H), 8.10 (d, J = 8.56 Hz, 1H), 7.69 (s, 1H), 7.18 (s, 1H), 4.41 (s, 2H), 4.23-4.19 (m, 3H), 3.51 (s, 2H), 1.22 (d, J = 6.34 Hz, 2H), 1.11 (s, 2H).	416	98%
5-40		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.67 (s, 1H), 8.91 (s, 1H), 7.97 (d, J = 8.68 Hz, 1H), 7.35 (s, 1H), 6.99 (s, 1H), 4.68 (d, J = 4.53 Hz, 2H), 4.58 (d, J = 4.64 Hz, 2H), 4.40 (dd, J = 3.32, 6.77 Hz, 1H), 2.61 (s, 3H), 1.24 (d, J = 6.14 Hz, 2H), 1.10 (s, 2H).	434	98%
5-41		8- OMe		1H NMR (400 MHz, DMSO) δ 14.59 (s, 1H), 10.91 (s, 1H), 8.82 (s, 1H), 7.89 (d, J = 9.04 Hz, 1H), 6.74 (d, J = 14.28 Hz, 2H), 5.08 (d, J = 64.31 Hz, 1H), 4.45 (s, 2H), 4.19 (s, 1H), 3.96 (s, 2H), 1.80 (d, J = 26.47 Hz, 1H), 1.65 (dd, J = 7.14, 16.55 Hz, 1H).	470	98%
5-42		8- OMe		1H NMR (400 MHz, DMSO) δ 8.80 (s, 1H), 7.86 (d, J = 9.34 Hz, 1H), 6.87 (d, J = 8.16 Hz, 1H), 6.84 (s, 1H), 6.70 (d, J = 8.14 Hz, 1H), 5.18-4.96 (m, 1H), 4.17 (s, 3H), 3.36 (s, 2H), 1.84-1.58 (m, 2H).	429	98%
5-43		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.75-14.70 (s, 1H), 8.80-8.76 (s, 1H), 7.89-7.83 (d, J = 9.4 Hz, 1H), 6.92-6.86 (d, J = 11.4 Hz, 1H), 6.77-6.73 (s, 1H), 6.16-6.10 (s, 1H), 4.27-4.15 (s, 3H), 3.47-3.41 (s, 3H), 3.40-3.34 (q, J = 3.6 Hz, 2H), 1.20-1.09 (dd, J = 14.4, 5.5 Hz, 4H).	429	90%
5-44		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.77-14.65 (s, 1H), 8.80-8.76 (s, 1H), 7.89-7.83 (d, J = 9.3 Hz, 1H), 7.09-7.03 (t, J = 1.6 Hz, 1H), 6.90-6.84 (t, J = 1.6 Hz, 1H), 6.19-6.10 (s, 1H), 4.26-4.15 (m, 3H), 3.48-3.39 (s, 5H), 1.20-1.09 (ddd, J = 10.6, 5.5, 3.0 Hz, 4H).	445	100%
5-45		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 8.80-8.74 (s, 1H), 7.88-7.80 (d, J = 9.3 Hz, 1H), 6.81-6.71 (dd, J = 17.1, 2.1 Hz, 2H), 4.28-4.18 (tt, J = 7.2, 4.3 Hz, 1H), 4.18-4.12 (t, J = 4.2 Hz, 2H), 3.44-3.35 (m, 5H), 2.16-2.10 (s, 3H), 1.20-1.08 (m, 4H).	425	100%
5-46		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 8.79-8.75 (s, 1H), 7.87-7.81 (d, J = 9.3 Hz, 1H), 6.55-6.49 (s, 1H), 6.43-6.39 (s, 1H), 4.27-4.18 (s, 1H), 4.16-4.10 (t, J = 4.3 Hz, 2H), 3.33-3.5 (s, 2H), 2.57-2.52 (s, 3H), 1.20-1.09 (m, 4H).	426	96%
5-47		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.83-14.56 (s, 1H), 8.81-8.77 (s, 1H),8.66-8.59 (m, 1H), 7.95-7.89 (d, J = 9.3 Hz, 1H), 7.89-7.84 (t, J = 1.7 Hz, 1H), 7.24-7.19 (s, 1H), 4.30-4.18 (m, 3H), 3.67-3.60 (q, J = 3.8 Hz, 2H), 3.52-3.44 (s, 3H), 1.20-1.12 (td, J = 6.5, 5.8, 2.7 Hz, 4H).	456	100%
5-48		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 15.22-14.17 (m, 1H), 8.97-8.90 (s, 1H), 8.84-8.80 (s, 1H), 7.97-7.90 (d, J = 9.0 Hz, 1H), 7.51-7.47 (s, 1H), 7.07-7.02 (s, 1H), 4.69-4.57 (s, 4H), 4.28-4.18 (p, J = 5.7 Hz, 1H), 3.42-3.35 (s, 3H), 1.21-1.12 (d, J = 5.6 Hz, 4H).	436	100%
5-49		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.70-14.66 (s, 1H), 8.84-8.80 (s, 1H), 7.97-7.92 (d, J = 9.0 Hz, 1H), 7.78-7.74 (s, 1H), 7.08-7.04 (s, 1H), 5.00-4.94 (t, J = 4.9 Hz, 2H), 4.82-4.74 (t, J = 4.8 Hz, 2H), 4.27-4.18 (p, J = 5.7 Hz, 1H), 3.43-3.38 (s, 3H), 1.21-1.13 (d, J = 5.6 Hz, 4H).	437	85%
5-50		OMe	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.72 (s, 1H), 8.94 (s, 1H), 7.87 (d, J = 9.4 Hz, 1H), 6.89 (d, J = 11.4 Hz, 1H), 6.75 (s, 1H), 6.13 (s, 1H), 4.21 (m, 3H), 3.40 (s, 3H), 1.31-0.94 (m, 4H).	429	90%
5-51		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.72 (s, 1H), 8.88 (s, 1H), 7.91 (d, J = 8.8 Hz, 1H), 6.91 (s, 1H), 6.72 (s, 1H), 6.07 (s, 1H), 4.48-4.30 (m, 1H), 4.20 (m, 2H), 3.43 (m, 2H), 2.70-2.56 (m, 3H), 1.24 (d, J = 4.0 Hz, 2H), 1.04 (s, 2H).	429	98%
5-52		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.5 (b, 1H), 8.91 (s, 1H), 8.86 (s, 1H), 7.97 (d, J = 8.8 Hz, 1H), 7.34 (s, 1H), 6.90 (s, 1H), 4.63 (s, 4H), 4.39 (mz, 1H), 2.61 (s, 3H), 1.24 (d, J = 4.6 Hz, 2H), 1.09 (s, 2H).	420	98%
5-53		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.73 (s, 1H), 8.88 (s, 1H), 7.90 (d, J = 8.8 Hz, 1H), 7.22 (s, 1H), 6.76 (s, 1H), 4.44-4.28 (m, 1H), 4.15 (m, 2H), 3.43 (m, 2H), 2.65 (s, 3H), 1.24 (s, 2H), 1.04 (s, 2H).	521	97%
5-54		Me	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 14.73 (s, 1H), 8.89 (s, 1H), 7.91 (d, J = 7.8 Hz, 1H), 6.75 (d, J = 11.3 Hz, 1H), 6.59 (s, 1H), 4.37 (m, 1H), 4.22 (s, 2H), 3.39 (s, 2H), 2.65 (s, 3H), 1.22 (m, 2H), 1.00 (m, 2H).	413	97%
5-55		Cl	Cyclopropyl	1H NMR (400 MHz, DMSO) δ 8.90 (s, 1H), 8.05 (d, J = 8.6 Hz, 1H), 6.91-6.49 (m, 3H), 4.46-4.36 (m, 1H), 4.16 (m, 2H), 3.49 (m, 2H), 2.67 (s, 3H), 1.19 (t, J = 15.1 Hz, 2H), 1.09 (s, 2H).	415	98%
5-56		1H NMR (400 MHz, DMSO) δ 8.77 (s, 1H), 8.15 (d, J = 7.00 Hz, 1H), 7.24-7.02 (m, 2H), 6.78 (d, J = 8.23 Hz, 1H), 4.28-4.13 (m, 2H), 4.05-3.86 (m, 1H), 3.49-3.34 (m, 2H), 2.90 (d, J = 2.66 Hz, 3H), 1.44-1.32 (m, 2H), 1.28-1.17 (m, 2H).	395	98%
5-57		1H NMR (400 MHz, DMSO) δ 15.13 (s, 1H), 8.84 (s, 1H), 8.16 (d, J = 8.2 Hz, 1H), 7.71 (s, 1H), 7.20-7.06 (m, 2H), 6.73 (t, J = 16.6 Hz, 1H), 4.30 (m, 1H), 4.22-4.17 (m, 2H), 3.68 (s, 2H), 3.44 (s, 3H), 1.43-0.95 (m, 4H).	393	98%

TABLE 6
Compound				MS
No.	R3 =	R2 =	NMR	(MH+)	HPLC
6-1		Me	1H NMR (400 MHz, MeOD) δ 7.92 (s, 1H), 7.35 (m, 2H), 6.96 (s, 1H), 6.80 (m, 2H), 4.30-4.19 (m, 1H), 3.75 (s, 3H), 2.59 (s, 3H), 0.96 (m, 2H), 0.79 (m, 2H).	368	98%
6-2		Me	1H NMR (400 MHz, DMSO) δ 14.75 (s, 1H), 8.89 (s, 1H), 7.92 (d, J = 8.6 Hz, 1H), 7.50 (t, J = 7.7 Hz, 1H), 7.24 (dd, J = 15.3, 7.9 Hz, 2H), 7.14 (d, J = 7.4 Hz, 1H), 4.38 (m, 1H), 3.76 (s, 3H), 2.55 (s, 3H), 1.41-1.15 (m, 2H), 1.12-0.96 (m, 2H).	482	90%
6-3		Me	1H NMR (400 MHz, DMSO) δ 14.80 (s, 1H), 8.95 (s, 1H), 8.00 (d, J = 8.8 Hz, 1H), 7.57 (d, J = 7.2 Hz, 2H), 7.49 (t, J = 7.3 Hz, 2H), 7.45-7.36 (m, 3H), 7.26 (d, J = 8.6 Hz, 2H), 5.25 (s, 2H), 4.54-4.32 (m, 1H), 2.67 (s, 3H), 1.30 (d, J = 6.2 Hz, 2H), 1.11 (s, 2H).	444	99%
6-4		Me	1H NMR (400 MHz, DMSO) δ 14.76 (s, 1H), 8.90 (s, 1H), 7.94 (d, J = 8.5 Hz, 1H), 7.35 (d, J = 8.0 Hz, 2H), 7.12 (d, J = 8.2 Hz, 2H), 4.38 (s, 1H), 3.84 (s, 3H), 2.61 (s, 3H), 1.23 (d, J = 6.2 Hz, 2H), 1.05 (s, 2H).	368	96%
6-5		Me	1H NMR (400 MHz, DMSO) δ 14.63 (s, 1H), 8.88 (s, 1H), 7.92 (d, J = 8.9 Hz, 1H), 7.31 (d, J = 8.4 Hz, 2H), 7.08 (d, J = 8.7 Hz, 2H), 4.71 (dt, J = 12.0, 6.0 Hz, 1H), 4.38 (m, 1H), 2.58 (d, J = 26.0 Hz, 3H), 1.32 (d, J = 6.0 Hz, 6H), 1.23 (q, J = 6.9 Hz, 2H), 1.02 (s, 2H).	396	99%
6-6		Me	1H NMR (400 MHz, DMSO) δ 14.68 (s, 1H), 8.91 (s, 1H), 7.98 (d, J = 8.8 Hz, 1H), 7.58 (s, 4H), 4.52-4.24 (m, 1H), 2.60 (s, 3H), 1.23 (q, J = 7.0 Hz, 2H), 1.15-1.01 (m, 2H).	422	99%
6-7		Me	1H NMR (400 MHz, DMSO) δ 14.66 (s, 1H), 8.91 (s, 1H), 7.99 (d, J = 8.8 Hz, 1H), 7.72 (t, J = 7.9 Hz, 1H), 7.54 (d, J = 8.3 Hz, 1H), 7.52-7.44 (m, 2H), 4.52-4.20 (m, 1H), 2.60 (s, 3H), 1.23 (d, J = 6.8 Hz, 2H), 1.08 (s, 2H).	422	99%
6-8		Me	1H NMR (400 MHz, DMSO) δ 14.48 (s, 1H), 8.76 (s, 1H), 7.86 (d, J = 8.7 Hz, 1H), 7.60-7.52 (m, 1H), 7.45 (ddd, J = 10.9, 9.8, 4.6 Hz, 3H), 4.25 (dt, J = 10.7, 3.6 Hz, 1H), 2.43 (s, 3H), 1.06 (dq, J = 9.4, 7.1 Hz, 2H), 0.99-0.71 (m, 3H).	422	99%
6-9		Me	1H NMR (400 MHz, DMSO) δ 14.64 (s, 1H), 8.83 (s, 1H), 7.87 (d, J = 8.7 Hz, 1H), 6.61 (s, 2H), 4.33 (m, 1H), 3.74 (s, 6H), 3.68 (s, 3H), 2.57 (s, 3H), 1.18 (d, J = 6.4 Hz, 2H), 1.01 (s, 2H).	428	95%
6-10		Me	1H NMR (400 MHz, DMSO) δ 14.80 (s, 1H), 8.88 (s, 1H), 7.90 (d, J = 8.6 Hz, 1H), 7.17 (d, J = 8.3 Hz, 1H), 6.76 (d, J = 2.2 Hz, 1H), 6.70 (dd, J = 8.4, 2.3 Hz, 1H), 4.47-4.28 (m, 1H), 3.85 (s, 3H), 3.75 (s, 3H), 2.55 (s, 3H), 1.21 (dd, J = 6.7, 4.5 Hz, 2H), 1.02 (dd, J = 10.3, 4.5 Hz, 2H).	398	96%
6-11		Me	1H NMR (400 MHz, DMSO) δ 14.70 (s, 1H), 8.80 (s, 1H), 7.86 (d, J = 8.1 Hz, 1H), 7.32 (m, 2H), 7.16 (d, J = 7.2 Hz, 1H), 4.25 (s, 1H), 3.92 (s, 3H), 2.57 (s, 3H), 1.41-1.10 (m, 2H), 0.89 (m, 2H).	386	96%
6-12		Me	1H NMR (400 MHz, DMSO) δ 14.74 (s, 1H), 8.90 (s, 1H), 7.93 (d, J = 8.8 Hz, 1H), 7.13 (d, J = 8.3 Hz, 1H), 6.97 (s, 1H), 6.93 (dd, J = 8.2, 1.7 Hz, 1H), 4.39 (tt, J = 7.1, 3.8 Hz, 1H), 3.84 (s, 3H), 3.79 (s, 3H), 2.63 (s, 3H), 1.24 (d, J = 6.8 Hz, 2H), 1.07 (s, 2H).	398	99%
6-13		Me	1H NMR (400 MHz, DMSO) δ 14.70 (s, 1H), 8.90 (s, 1H), 7.94 (d, J = 8.7 Hz, 1H), 7.54 (s, 1H), 7.35 (dd, J = 18.3, 8.3 Hz, 2H), 4.39 (m, 1H), 3.95 (s, 3H), 2.62 (s, 3H), 1.23 (d, J = 5.8 Hz, 2H), 1.06 (s, 2H).	402	99%
6-14		Me	1H NMR (400 MHz, DMSO) δ 14.69 (s, 1H), 8.91 (s, 1H), 7.97 (d, J = 8.6 Hz, 1H), 7.72 (d, J = 8.6 Hz, 1H), 7.67 (s, 1H), 7.47 (d, J = 8.6 Hz, 1H), 4.40 (m, 1H), 3.99 (s, 3H), 2.61 (s, 3H), 1.24 (d, J = 5.6 Hz, 2H), 1.08 (s, 2H).	436	99%
6-15		Me	1H NMR (400 MHz, DMSO) δ 14.76 (s, 1H), 8.89 (s, 1H), 7.93 (d, J = 8.5 Hz, 1H), 7.20 (d, J = 12.7 Hz, 2H), 7.11 (d, J = 8.0 Hz, 1H), 4.38 (m, 1H), 3.87 (s, 3H), 2.64 (s, 3H), 2.23 (s, 3H), 1.23 (m, 2H), 1.07 (m, 2H).	382	99%
6-16		Me	1NMR (400 MHz, DMSO) δ 14.78 (s, 1H), 8.88 (s, 1H), 7.91 (d, J = 8.6 Hz, 1H), 6.95 (d, J = 7.4 Hz, 1H), 6.62 (s, 1H), 6.52 (d, J = 6.8 Hz, 1H), 4.94 (s, 2H), 4.39 (s, 1H), 3.84 (s, 3H), 2.63 (s, 3H), 1.23 (s, 2H), 1.03 (s, 2H).	383	95%
6-17		Me	1H NMR (400 MHz, DMSO) δ 14.66 (s, 1H), 10.16 (s, 1H), 8.91 (s, 1H), 7.96 (d, J = 8.9 Hz, 2H), 7.26 (dd, J = 28.6, 8.1 Hz, 2H), 4.39 (m, 1H), 4.24 (m, 2H), 3.86 (m, 4H), 3.33 (m, 4H), 2.63 (s, 3H), 1.22 (d, J = 6.1 Hz, 2H), 1.05 (s, 2H).	510	90%
6-18		Me	1H NMR (400 MHz, DMSO) δ 14.73 (s, 1H), 9.12 (s, 1H), 8.90 (s, 1H), 7.95 (d, J = 9.0 Hz, 1H), 7.29 (s, 1H), 7.26 (s, 2H), 4.39 (m, 1H), 3.92 (s, 3H), 3.01 (s, 3H), 2.62 (s, 3H), 1.35-1.15 (m, 2H), 1.06 (m, 2H).	461	98%
6-19		Me	1H NMR (400 MHz, DMSO) δ 14.76 (s, 1H), 8.89 (s, 1H), 8.14 (d, J = 14.8 Hz, 2H), 7.94 (d, J = 8.9 Hz, 1H), 7.14 (d, J = 8.3 Hz, 1H), 6.90 (d, J = 7.9 Hz, 1H), 6.28 (s, 2H), 4.39 (s, 1H), 3.93 (s, 3H), 2.65 (s, 3H), 1.19 (m, 2H), 1.04 (m, 2H).	426	98%
6-20		Me	1H NMR (400 MHz, DMSO) δ 14.73 (s, 1H), 8.91 (s, 1H), 7.97 (d, J = 8.7 Hz, 1H), 7.56 (d, J = 6.9 Hz, 2H), 7.31 (d, J = 8.5 Hz, 1H), 4.39 (m, 1H), 3.91 (s, 3H), 2.62 (s, 3H), 1.52 (s, 9H), 1.24 (m, 2H), 1.07 (m, 2H).	468	98%
6-21		Me	1H NMR (400 MHz, DMSO) δ 14.80 (s, 1H), 12.93 (s, 1H), 8.97 (s, 1H), 8.02 (d, J = 8.8 Hz, 1H), 7.70 (s, 1H), 7.62 (d, J = 8.8 Hz, 1H), 7.38 (d, J = 0.8 Hz, 1H), 4.39 (m, 1H), 3.67 (s, 3H), 2.62 (s, 3H), 1.52 (s, 9H), 1.30 (m, 2H), 1.13 (m, 2H).	412	98%
6-22		Me	1H NMR (400 MHz, DMSO) δ 14.72 (s, 1H), 8.92 (s, 1H), 8.52 (s, 1H), 7.97 (d, J = 8.3 Hz, 1H), 7.81 (s, 3H), 7.57 (d, J = 7.9 Hz, 1H), 7.36 (d, J = 8.4 Hz, 1H), 4.39 (s, 1H), 3.96 (d, J = 24.7 Hz, 3H), 3.54 (s, 2H), 2.99 (s, 2H), 2.69-2.54 (m, 3H), 1.23 (d, J = 5.3 Hz, 2H), 1.07 (s, 2H).	454	95%
6-24		Me	1H NMR (400 MHz, DMSO) δ 14.72 (s, 1H), 9.40 (s, 1H), 8.92 (s, 1H), 8.60 (s, 1H), 7.99 (s, 1H), 7.81 (s, 1H), 7.57 (s, 1H), 7.38 (s, 1H), 4.40 (s, 1H), 4.00 (s, 3H), 3.66 (s, 2H), 3.28 (s, 2H), 2.85 (s, 6H), 2.61 (s, 3H), 1.24 (s, 2H), 1.07 (s, 2H).	482	99%
6-25		Me	1H NMR (400 MHz, DMSO) δ 14.73 (s, 1H), 8.91 (s, 1H), 8.37 (s, 1H), 7.96 (d, J = 8.3 Hz, 1H), 7.75 (s, 1H), 7.53 (d, J = 8.2 Hz, 1H), 7.33 (d, J = 8.4 Hz, 1H), 6.95 (s, 1H), 4.40 (s, 1H), 3.98 (s, 3H), 3.33 (d, J = 5.1 Hz, 2H), 3.13 (d, J = 5.4 Hz, 2H), 2.61 (s, 3H), 1.36 (s, 9H), 1.24 (d, J = 4.4 Hz, 2H), 1.07 (s, 2H).	554	95%
6-26		Me	1H NMR (400 MHz, DMSO) δ 14.72 (s, 1H), 10.43 (s, 1H), 8.91 (s, 1H), 7.97 (d, J = 8.7 Hz, 1H), 7.74 (d, J = 8.8 Hz, 1H), 7.70 (s, 1H), 7.45 (d, J = 8.6 Hz, 1H), 4.39 (m, 1H), 4.02 (s, 3H), 2.61 (s, 3H), 1.23 (m, 2H), 1.07 (m, 2H).	396	98%
6-27		Me	1H NMR (400 MHz, DMSO) δ 14.65 (s, 1H), 8.91 (s, 1H), 8.47 (s, 1H), 7.97 (d, J = 8.7 Hz, 1H), 7.71 (s, 1H), 7.66 (s, 1H), 7.44 (d, J = 8.7 Hz, 1H), 7.38 (d, J = 8.6 Hz, 1H), 4.40 (m, 1H), 4.05 (s, 3H), 2.65 (s, 3H), 1.25 (d, J = 6.7 Hz, 2H), 1.08 (s, 2H).	435	90%
6-28		Me	1H NMR (400 MHz, DMSO) δ 14.71 (s, 1H), 8.90 (s, 1H), 7.96 (d, J = 8.4 Hz, 1H), 7.40 (d, J = 11.8 Hz, 2H), 7.26 (d, J = 8.0 Hz, 1H), 4.39 (s, 1H), 3.94 (s, 5H), 2.62 (s, 3H), 1.23 (s, 2H), 1.06 (s, 2H).	407	95%
6-29		Me	1H NMR (400 MHz, DMSO) δ 14.68 (s, 1H), 10.43 (s, 1H), 8.91 (s, 1H), 7.97 (d, J = 8.8 Hz, 1H), 7.86-7.62 (m, 2H), 7.44 (d, J = 8.5 Hz, 1H), 4.39 (s, 1H), 4.02 (s, 2H), 2.64 (s, 3H), 1.23 (s, 2H), 1.07 (s, 2H).	396	95%
6-30		Me	1H NMR (400 MHz, DMSO) δ 14.66 (s, 2H), 8.93 (s, 1H), 8.33 (s, 1H), 8.02 (d, J = 8.6 Hz, 1H), 7.80 (s, 2H), 7.71 (d, J = 8.5 Hz, 1H), 7.56 (d, J = 8.4 Hz, 1H), 7.46 (s, 2H), 4.42 (s, 1H), 4.17 (s, 3H), 2.66 (s, 3H), 1.35-1.15 (m, 2H), 1.09 (s, 2H).	484	85%
6-31		Me	1H NMR (400 MHz, DMSO) δ 14.74 (s, 1H), 11.37 (s, 1H), 8.90 (s, 1H), 8.35 (s, 1H), 7.96 (d, J = 8.1 Hz, 1H), 7.64 (s, 1H), 7.43 (d, J = 8.1 Hz, 1H), 7.27 (d, J = 8.5 Hz, 1H), 4.39 (s, 1H), 3.92 (s, 3H), 2.63 (s, 3H), 1.23 (d, J = 5.2 Hz, 2H), 1.06 (s, 2H).	411	95%
6-32		Me	1H NMR (400 MHz, DMSO) δ 14.75 (s, 1H), 8.91 (s, 1H), 7.97 (d, J = 8.7 Hz, 1H), 7.78 (s, 2H), 7.70 (s, 1H), 7.54 (d, J = 8.2 Hz, 1H), 7.33 (d, J = 8.4 Hz, 1H), 4.40 (s, 1H), 3.98 (s, 3H), 2.61 (s, 3H), 1.23 (s, 2H), 1.07 (s, 2H).	411	94%
6-33		Me	1H NMR (400 MHz, DMSO) δ 14.73 (s, 1H), 8.92 (s, 1H), 7.96 (d, J = 8.6 Hz, 1H), 7.37 (s, 2H), 7.23 (d, J = 7.3 Hz, 1H), 4.39 (m, 1H), 3.89 (s, 3H), 3.74 (m, 4H), 3.07 (s, 4H), 2.76 (s, 3H), 2.62 (s, 3H), 1.24 (s, 2H), 1.06 (s, 2H).	480	96%
6-34		Me	1H NMR (400 MHz, DMSO) δ 14.73 (s, 1H), 8.92 (s, 1H), 8.87 (s, 1H), 7.97 (d, J = 8.1 Hz, 1H), 7.48 (s, 2H), 7.29 (d, J = 8.7 Hz, 1H), 4.40 (m, 1H), 4.18 (s, 2H), 3.94 (s, 3H), 2.63 (s, 3H), 2.55 (s, 3H), 1.24 (s, 2H), 1.05 (s, 2H).	411	86%
6-35		Me	1H NMR (400 MHz, DMSO) δ 14.69 (s, 1H), 8.91 (s, 1H), 7.97 (d, J = 8.6 Hz, 1H), 7.91 (s, 1H), 7.75 (d, J = 8.1 Hz, 1H), 7.44 (d, J = 8.1 Hz, 1H), 4.39 (s, 1H), 4.02 (s, 3H), 2.61 (s, 3H), 1.23 (s, 2H), 1.07 (s, 2H).	393	95%
6-36		Me	1H NMR (400 MHz, DMSO) δ 14.78 (s, 1H), 8.90 (s, 1H), 7.95 (d, J = 8.7 Hz, 1H), 7.37 (s, 1H), 7.26 (d, J = 8.0 Hz, 1H), 7.13 (d, J = 8.3 Hz, 1H), 5.18 (s, 1H), 4.57 (s, 2H), 4.39 (s, 1H), 3.87 (s, 3H), 2.62 (s, 3H), 1.23 (s, 2H), 1.05 (s, 2H).	398	95%
6-37		Me	1H NMR (400 MHz, DMSO) δ 14.71 (s, 1H), 9.63 (s, 1H), 8.92 (s, 1H), 8.51 (s, 1H), 7.98 (d, J = 8.5 Hz, 1H), 7.67 (s, 1H), 7.52 (d, J = 8.3 Hz, 1H), 7.32 (d, J = 8.5 Hz, 1H), 4.43 (m, 3H), 3.94 (s, 3H), 3.43 (s, 2H), 2.80 (d, J = 24.7 Hz, 6H), 2.62 (s, 3H), 1.23 (s, 2H), 1.07 (s, 2H).	482	95%
6-38		Me	1H NMR (400 MHz, DMSO) δ 14.74 (s, 1H), 8.90 (s, 1H), 7.93 (d, J = 9.2 Hz, 1H), 7.10 (d, J = 8.0 Hz, 1H), 7.02 (s, 1H), 6.86 (d, J = 8.0 Hz, 1H), 6.13 (s, 2H), 4.38 (m, 1H), 2.62 (s, 3H), 1.23 (m, 2H), 1.05 (m, 2H).	382	98%
6-39		Me	1H NMR (400 MHz, DMSO) δ 14.67 (s, 1H), 10.11 (s, 1H), 8.91 (s, 1H), 7.97 (d, J = 8.7 Hz, 1H), 7.33 (d, J = 1.6 Hz, 1H), 7.29 (d, J = 1.6 Hz, 1H), 6.45-6.21 (s, 2H), 4.41-4.30 (m, 1H), 2.74-2.56 (s, 3H), 1.33-1.17 (d, J = 6.6 Hz, 2H), 1.12-0.96 (t, J = 3.1 Hz, 2H).	410	98%
6-40		Me	1H NMR (400 MHz, DMSO) δ 14.69 (s, 1H), 11.53 (s, 1H), 8.90 (s, 1H), 8.16 (s, 1H), 7.95 (d, J = 8.7 Hz, 1H), 7.08 (d, J = 1.7 Hz, 1H), 7.02 (d, J = 1.7 Hz, 1H), 6.21 (s, 2H), 4.48-4.16 (m, 1H), 2.64 (s, 3H), 1.35-1.21 (d, J = 6.8 Hz, 2H), 1.12-1.01 (m, 2H).	425	98%
6-41		Me	1H NMR (400 MHz, DMSO) δ 14.64 (s, 1H), 8.90 (s, 1H), 7.96 (d, J = 8.8 Hz, 1H), 7.36 (d, J = 1.6 Hz, 1H), 7.4 (d, J = 1.6 Hz, 1H), 6.36 (s, 2H), 4.52-4.26 (m, 1H), 2.63 (s, 3H), 1.35-1.15 (d, J = 6.6 Hz, 2H), 1.10-0.99 (m, 2H).	407	98%
6-42		Me	1H NMR (400 MHz, DMSO) δ 14.68 (s, 1H), 8.89 (s, 1H), 794 (d, J = 8.7 Hz, 1H), 7.06 (d, J = 1.5 Hz, 1H), 6.95 (d, J = 1.5 Hz, 1H), 6.22 (s, 2H), 4.57-4.46 (s, 1H), 4.42-4.30 (m, 1H), 2.63 (s, 3H), 1.33-1.15 (d, J = 6.2 Hz, 2H), 1.12-0.90 (m, 1H).	406	95%
6-43		OMe	1H NMR (400 MHz, DMSO) δ 14.70 (s, 1H), 8.80 (s, 1H), 7.90 (d, J = 9.1 Hz, 1H), 7.06 (s, 1H), 7.01 (s, 1H), 6.13 (s, 2H), 5.31 (t, J = 5.6 Hz, 1H), 4.54 (d, J = 5.6 Hz, 2H), 4.34-4.12 (mz, 1H), 3.44 (s, 3H), 1.33-0.99 (m, 4H).	428	97%
6-44		Me	1H NMR (400 MHz, DMSO) δ 14.69 (s, 1H), 8.89 (s, 1H), 7.93 (d, J = 8.7 Hz, 1H), 6.97 (s, 1H), 6.93 (s, 1H), 6.73 (dd, J = 17.7, 11.3 Hz, 1H), 6.20 (s, 2H), 6.00 (d, J = 17.6 Hz, 1H), 5.49 (d, J = 11.5 Hz, 1H), 4.53-4.25 (m, 1H), 2.75-2.57 (s, 3H), 1.32-1.17 (d, J = 6.7 Hz, 2H), 1.11-0.89 (s, 2H).	408	95%
6-45		OMe	1H NMR (400 MHz, DMSO) δ 14.66 (s, 1H), 8.80 (s, 1H), 7.90 (d, J = 9.1 Hz, 1H), 7.17 (s, 1H), 7.09 (s, 1H), 6.23 (s, 2H), 4.49 (s, 1H), 4.34-4.14 (m, 1H), 3.47-3.42 (s, 3H), 1.31-0.96 (m, 4H).	422	98%
6-46		OMe	1H NMR (400 MHz, DMSO) δ 14.62 (s, 1H), 8.81 (s, 1H), 7.93 (d, J = 9.1 Hz, 1H), 7.45 (s, 1H), 7.44 (s, 1H), 6.36 (s, 2H), 4.39-4.04 (m, 1H), 3.46 (s, 3H), 1.26-1.06 (m, 4H).	423	98%
6-47		OMe	1H NMR (400 MHz, DMSO) δ 14.65 (s, 1H), 8.80 (s, 1H), 7.92 (d, J = 9.1 Hz, 1H), 7.30 (s, 1H), 7.19 (s, 11H), 7.17 (t, J = 56 Hz, 1H), 6.27 (s, 2H), 4.33-4.17 (m, 1H), 3.45 (s, 3H), 1.29-0.97 (m, 4H).	448	92%
6-48		OMe	1H NMR (400 MHz, DMSO) δ 14.67 (s, 1H), 8.80 (s, 1H), 7.93 (d, J = 9.1 Hz, 1H), 7.77 (s, 1H), 7.42 (t, J = 1.4 Hz, 1H), 7.28 (t, J = 1.3 Hz, 1H), 7.25 (s, 1H), 6.27 (s, 2H), 4.33-4.13 (m, 1H), 3.449 (s, 3H), 1.37-0.87 (m, 4H).	441	98%
6-49		OMe	1H NMR (400 MHz, DMSO) δ 14.66 (s, 1H), 10.12 (d, J = 1.2 Hz, 1H), 8.81 (s, 1H), 7.93 (d, J = 9.5 Hz, 1H), 7.44 (s, 1H), 7.42 (s, 1H), 6.35 (s, 2H), 4.33-4.17 (m, 1H), 3.46 (s, 3H), 1.32-0.97 (m, 4H).	426	98%
6-50		OMe	1H NMR (400 MHz, DMSO) δ 14.68 (s, 1H), 8.80 (s, 1H), 7.89 (d, J = 9.1 Hz, 1H), 6.83-6.80 (t, J = 1.3 Hz, 1H), 6.80-6.76 (t, J = 1.2 Hz, 1H), 6.11 (s, 2H), 4.34-4.12 (m, 1H), 3.86 (s, 3H), 3.31 (s, 3H), 1.26-1.02 (m, 4H).	428	98%
6-51		OMe	1H NMR (400 MHz, DMSO) δ 14.70-14.61 (s, 1H), 8.84-8.78 (s, 1H), 7.96-7.88 (d, J = 9.0 Hz, 1H), 7.14 (s, 1H), 7.13 (s, 1H), 6.33-6.22 (s, 2H), 4.26-4.18 (m, 1H), 3.47 (s, 3H), 1.20-1.11 (m, 4H).	432	95%
6-52		OMe	1H NMR (400 MHz, DMSO) δ 14.67 (s, 1H), 8.80 (s, 1H), 7.92 (d, J = 9.1 Hz, 1H), 7.77 (s, 1H), 7.42 (s, 1H), 7.28 (s, 1H), 7.25 (s, 1H), 6.27 (s, 2H), 4.22 (m, 1H), 3.44 (s, 3H), 1.17 (m, 4H).	441	85%
6-53		1H NMR (400 MHz, DMSO) δ 14.49 (s, 1H), 8.83 (s, 1H), 7.94 (d, J = 8.0 Hz, 1H), 7.42 (s, 1H), 6.36 (s, 2H), 5.10 (m, 1H), 4.18 (m, 1H), 3.47 (s, 3H), 1.82-1.63 (m, 4H).	441	98%
6-54		1H NMR (400 MHz, DMSO) δ 14.50 (s, 1H), 11.55 (s, 1H), 8.83 (s, 1H), 8.16 (s, 1H), 7.92 (d, J = 8.0 Hz, 1H), 7.27 (s, 1H), 7.10 (s, 1H), 6.22 (s, 1H), 5.10 (m, 1H), 4.18 (m, 1H), 3.47 (s, 3H), 1.82-1.63 (m, 4H).	459	95%
6-55		1H NMR (400 MHz, DMSO) δ 14.47 (s, 1H), 8.82 (s, 1H), 8.10 (d, J = 8.7 Hz, 1H), 8.00-7.87 (m, 1H), 7.66 (t, J = 9.4 Hz, 1H), 7.37 (t, J = 8.3 Hz, 1H), 7.21 (d, J = 8.0 Hz, 2H), 7.06 (d, J = 8.1 Hz, 2H), 3.81 (s, 3H).	440	99%
6-56		1H NMR (400 MHz, DMSO) δ 15.44-15.10 (s, 1H), 9.12-8.99 (t, J = 1.7 Hz, 1H), 8.03- 7.92 (dt, J = 8.4, 1.8 Hz, 1H), 7.67-7.56 (dd, J = 8.6, 2.5 Hz, 3H), 7.16-6.98 (m, 2H), 5.03-4.89 (d, J = 7.3 Hz, 1H), 4.60-4.47 (d, J = 11.4 Hz, 1H), 4.44-4.33 (d, J = 11.5 Hz, 1H), 3.86-3.75 (t, J = 1.7 Hz, 3H), 1.53-1.42 (d, J = 6.3 Hz, 3H).	352	99%

TABLE 7
Compound				MS
No.	R16 =	R2 =	NMR	(MH+)	HPLC
7-1	H	Me	1H NMR (400 MHz, DMSO) δ	344	100%
			14.74 (s, 1H), 8.90 (s, 1H), 7.95 (d, J = 9.3 Hz, 1H),
			7.80 (s, 2H), 7.27 (s, 1H), 4.39 (s, 1H), 2.68 (s, 3H), 1.23
			(s, 3H), 1.03 (s, 2H).
7-2		Me	1H NMR (400 MHz, DMSO) δ 14.69 (s, 1H), 9.37 (s, 2H), 8.91 (s, 1H), 7.96 (d, J = 8.9 Hz, 1H), 7.87 (s, 1H), 7.51 (s, 1H), 4.43 (s, 3H), 3.00 (d, J = 6.2 Hz, 2H), 2.71 (s, 3H), 1.24 (d, J = 6.4 Hz, 5H), 1.03 (s, 2H).	401	95%
7-3		Me	1H NMR (400 MHz, DMSO) δ 14.70 (s, 1H), 13.87 (s, 1H), 8.91 (s, 1H), 7.98 (d, J = 8.1 Hz, 2H), 7.60 (s, 1H), 4.41 (s, 1H), 2.70 (s, 3H), 1.23 (s, 2H), 1.06 (s, 2H).	412	100%
7-4	CH2CN	Me	1H NMR (400 MHz, DMSO) δ	383	97%
			14.75 (s, 1H), 8.90 (s, 1H), 7.95 (d, J = 8.8 Hz, 1H),
			7.76 (s, 1H), 7.22 (s, 1H). 5.76 (s, 2H), 4.40 (m, 1H), 2.69
			(s, 3H), 1.23 (m, 2H), 1.04 (s, 2H).
7-5	CHO	Me	1H NMR (400 MHz, DMSO) δ	372	98%
			14.67 (s, 1H), 10.03 (s, 1H), 8.92 (s, 1H), 8.39 (s, 1H), 8.23
			(s, 1H), 7.99 (d, J = 9.1 Hz, 1H), 4.42 (s, 1H), 2.71
			(s, 3H), 1.24 (d, J = 6.4 Hz, 2H), 1.05 (s, 2H).
7-6		Me	1H NMR (400 MHz, DMSO) δ 14.70 (s, 1H), 11.34 (d, J = 16.3 Hz, 1H), 8.90 (s, 1H), 8.40 (s, 1H), 7.96 (d, J = 8.6 Hz, 1H), 7.78 (s, 1H), 7.42 (d, J = 14.9 Hz, 1H), 4.40 (s, 1H), 2.71 (s, 3H), 1.24 (d, J = 5.8 Hz, 2H), 1.04 (s, 2H).	387	96%
7-7		Me	1H NMR (400 MHz, DMSO) δ 13.57-13.17 (m, 1H), 11.49 (s, 1H), 9.30 (s, 1H), 8.77 (s, 1H), 8.09 (s, 1H), 7.90 (d, J = 9.3 Hz, 1H), 7.83 (s, 1H), 4.33 (s, 1H), 2.66 (s, 3H), 1.22 (d, J = 7.5 Hz, 2H), 0.97 (s, 2H).	403	100%
7-8	CONH2	Me	11H NMR (400 MHz, DMSO) δ	387	100%
			14.70 (s, 1H), 8.91 (s, 1H), 8.12 (s, 1H), 7.98 (m, 2H), 7.89 (s,
			1H), 7.57 (s, 1H), 4.41 (s, 1H), 2.71 (s, 3H), 1.25 (d, J = 5.7
			Hz, 2H), 1.03 (s, 2H).
7-9	CO2H	Me	1H NMR (400 MHz, DMSO) δ	388	100%
			14.69 (s, 1H), 13.34 (s, 1H), 8.91 (s, 1H), 8.12 (s, 1H), 7.96
			(d, J = 8.7 Hz, 1H), 7.86 (s, 1H), 4.40 (s, 1H), 2.69
			(s, 3H), 1.24 (d, J = 6.2 Hz, 2H), 1.05 (s, 2H).
7-10		Me	1H NMR (400 MHz, DMSO) δ 14.68 (s, 1H), 12.49 (s, 1H), 8.87 (s, 1H), 7.96 (d, J = 11.9 Hz, 2H), 7.81 (d, J = 15.8 Hz, 1H), 7.69 (s, 1H), 6.30 (d, J = 15.7 Hz, 1H), 4.40 (s, 1H), 2.71 (s, 3H), 1.24 (d, J = 6.4 Hz, 2H), 1.04 (s, 2H).	414	95%
7-11		Me	1H NMR (400 MHz, DMSO) δ 14.69 (s, 1H), 8.92 (s, 1H), 8.13 (s, 1H), 8.00 (d, J = 8.7 Hz, 1H), 7.91 (s, 1H), 4.42 (s, 1H), 2.74 (s, 3H), 1.24 (s, 2H), 1.06 (s, 2H).	412	100%
7-12		Me	1H NMR (400 MHz, DMSO) δ 14.75 (s, 1H), 11.75 (s, 1H), 8.90 (s, 1H), 7.97 (s, 1H), 7.58 (s, 1H), 7.46 (s, 1H), 7.26 (s, 1H) , 7.13 (s, 1H), 7.00 (s, 2H), 4.41 (s, 1H), 4.17 (d, J = 6.9 Hz, 2H), 2.75 (s, 3H), 1.99 (s, 2H), 1.23 (s, 3H), 1.04 (s, 2H), 0.85 (s, 2H).	481	100%
7-13		Me	1H NMR (400 MHz, DMSO) δ 14.70 (s, 1H), 8.91 (s, 1H), 8.49 (s, 1H), 7.97 (d, J = 8.7 Hz, 1H), 7.91 (s, 1H), 7.64 (s, 2H), 4.41 (s, 1H), 2.73 (s, 3H), 1.25 (d, J = 6.5 Hz, 2H), 1.05 (s, 2H).	411	95%
7-14		Me	1H NMR (400 MHz, DMSO) δ 14.90-14.46 (m, 1H), 8.93 (s, 1H), 8.05 (s, 1H), 8.02 (d, J = 8.4 Hz, 2H), 7.63 (s, 2H), 7.28 (s, 2H), 4.44 (s, 1H), 2.78 (s, 3H), 1.27 (d, J = 6.4 Hz, 2H), 1.07 (s, 2H).	460	100%
7-15		Me	1H NMR (400 MHz, DMSO) δ 8.92 (s, 1H), 8.07 (d, J = 6.7 Hz, 2H), 7.99 (d, J = 8.8 Hz, 1H), 7.91 (s, 1H), 7.79 (s, 1H), 7.54 (s, 3H), 4.42 (s, 1H), 2.76 (s, 3H), 1.26 (d, J = 6.0 Hz, 3H), 1.07 (m, 2H).	487	95%
7-16		Me	1H NMR (400 MHz, DMSO) δ 14.68 (b, 1H), 13.75 (s, 1H), 8.90 (s, 1H), 7.96 (d, J = 8.9 Hz, 1H), 7.77 (s, 1H), 7.61 (s, 1H), 4.47-4.32 (m, 1H), 2.73 (s, 3H), 2.41 (s, 3H), 1.25 (t, J = 6.3 Hz, 2H), 1.07 (s, 2H).	425	98%
7-17	CN	OMe	1H NMR (400 MHz, DMSO) δ	385	98%
			14.63 (s, 1H), 8.80 (s, 1H), 8.42 (s, 1H), 7.28 (s, 1H), 7.96 (d,
			J = 9.2 Hz, 1H), 4.47-4.32 (m, 1H), 3.47 (s, 3H), 1.23-1.15
			(m, 4H).
7-18		OMe	1H NMR (400 MHz, DMSO) δ 8.57 (s, 1H), 7.72 (s, 2H), 7.58 (s, 1H), 7.43 (d, J = 9.7 Hz, 1H), 4.13 (m, 1H), 3.27 (s, 3H), 2.20 (s, 3H), 1.05-0.81 (m, 4H).	441	98%
7-19		Cl	1H NMR (400 MHz, DMSO) δ 8.93 (s, 1H), 8.13 (d, J = 8.0 Hz, 1H), 7.86 (s, 1H), 7.67 (s, 1H), 4.13 (m, 1H), 2.40 (s, 3H), 1.24-1.12 (m, 4H).	445	85%

TABLE 8-1
Compound
No.	R19 =	R2 =	MS (MH+)
8-1	H	Me	352.36
8-2	3-NH2	Me	337.34
8-3	4-F	Me	355.33
8-4	4-CO2H	Me	381.35
8-5	2-NH2	Me	352.36
8-6	3-Me	Me	351.37
8-7	4-Me	Me	351.37
8-8	2,3-Dimethyl	Me	365.4
8-9	2-Cl	Me	371.79
8-10	4-Cl	Me	371.79
8-11	3-CO2H	Me	381.35
8-12	3-CF3	Me	405.34
8-13	3,4-Dichloro	Me	406.23
8-14	3-F	Me	355.33
8-15	4-tBu	Me	393.45
8-16	4-MeO	Cyclopropyl	393.41
8-17	4-Ph	Me	413.44
8-18	4-NO2	Me	382.34
8-19	3,4-Dichloro	MeO	404.24
8-20	4-MeO	Me	365.38
8-21	3,4-Dimethyl	Me	365.4
8-22	4-CF3	Me	405.34
8-24	3-CONH2	Me	380.37
8-25	4-NH2	Me	352.36
8-26	4-OH	Me	353.34
8-27	4-OMe	F	353.34
8-28	4-OMe	NO2	398.34
8-29	4-OMe	Cl	387.79
8-30	4-OMe	NH2	368.36
8-31	4-OMe	Br	432.24
8-32	4-OMe	H	353.34
8-33	4-OMe	CN	378.35
8-34	4-OMe	CH2F	385.36
8-35	4-OMe	MeO	383.37
8-36	4-OMe	CH2Br	446.27
8-37	4-OMe	CH2OH	383.37
8-38	4-OMe	CHF2	403.35
8-39	4-Amino-3-hydroxy	Me	368.36
8-40	4-OMe	CHO	381.35
8-41	4-OMe	C≡CH	377.37
8-42	4-OMe	Et	381.4
8-43	4-OMe	CH═CH2	379.38
8-44	3,4-Diamino	Me	367.37
8-45	4-Amino-3-nitro	Me	397.36
8-46	4-Methylamino-3-nitro	Me	411.38
8-47	3-Dimethylamino	Me	380.41
8-48	2,4-Dinitro-3-dimethylamino	Me	470.41
8-49	4-Nitro-3-dimethylamino	Me	425.41
8-50	2-Nitro-3-dimethylamino	Me	425.41
8-51	4-Dimethylamino-3-nitro	Me	425.41
8-52	4-Ethylamino-3-nitro	Me	425.41
8-53	4-Dimethylamino	Me	380.41
8-54	3-Formyl-4-nitro	Me	410.35
8-55	4-Amino-3-nitro	Me	413.36
8-56	3-Fluoro-4-nitro	Me	400.33

TABLE 8-2
Compound			MS
No.	R3 =	R2 =	(MH+)
8-57		Me	451.45
8-58		Me	465.47
8-59		Me	480.49
8-60		Me	495.48
8-61		Me	508.54
8-62		Me	452.44
8-63		Me	466.46
8-64		Me	467.45
8-65		Me	411.38
8-66		Me	415.35
8-67		Me	425.41
8-68		Me	429.37
8-69		Me	426.35
8-70		Me	454.45
8-71		Me	449.39
8-72		Me	454.45
8-73		Me	463.42
8-74		Me	447.46
8-75		Me	406.45
8-76		Me	421.46
8-77		Me	418.42

TABLE 9
Compound
No.	R3 =	R2 =	MS (MH+)
9-1		Me	407.19
9-2		Me	404.39
9-3		Me	394.35
9-4		Me	397.4
9-5		Me	392.38
9-6		Me	326.32
9-7		Me	326.32
9-8		Me	394.4
9-9		Me	380.41
9-10		Me	395.43
9-11		Me	355.36
9-12		Me	393.37
9-13		Me	327.31
9-14		Me	406.2
9-15		Me	409.43
9-16		Me	372.3
9-17		Me	328.34
9-18		Me	397.44
9-19		Me	354.33
9-20		Me	354.33
9-21		Me	422.33
9-22		Me	342.36
9-24		Me	411.47

Experimental Example 1

In Vitro Antibacterial Activity

All compounds were dissolved in dimethyl sulfoxide (DMSO, Merck, purity >99.9%) to achieve final 1 mg/ml desired concentrations.

MICs (minimum inhibitory concentrations) were determined by the broth microdilution technique with 96-well microdilution plates. The antimicrobials were tested using the following MIC ranges: 0.008 to 8 μg/ml. The plates were filled with 100 μl of reinforced clostridial medium (Oxoid; Unipath Ltd., Basingstoke, United Kingdom) per well containing the final antibiotic concentrations. The plates were thawed and preincubated for 3 hours in an anaerobic chamber (Thermal, USA) containing an atmosphere of 80% N₂, 15% CO₂, and 5% H₂. The bacterial inocula were prepared by suspending growth from 48 hours cultures in reinforced clostridial medium. The final inoculum was approximately 1.0×10^5-6 CFU/well. The plates were incubated for 48 hours at 37° C. in the anaerobic chamber. The MIC was defined as the lowest antibiotic concentration that inhibited visible growth. Ciprofloxacin, vancomycin and metronidazole were used as a positive control. The results are shown in Table 10.

TABLE 10
MIC of example compounds against C. difficile (μg/mL)
Compound	C. difficile	C. difficile	C. difficile	C. difficile
No.	ATCC43255	ATCC700057	ATCC70092	IQCC23903
2-18	0.016-0.063	0.016-0.063	≦0.008-0.063	0.032-0.063
2-46	0.032-0.125	0.032-0.25	0.063-0.25	0.125-0.25
5-14	0.125-0.25	0.125-0.5	0.125-0.25	0.125-0.5
2-49	0.063-0.25	0.063-0.25	0.063-0.5	0.063-0.25
3-11	≦0.008-0.032	0.016-0.032	≦0.008-0.032	≦0.008-0.063
2-31	≦0.008-0.032	0.016-0.032	0.016-0.032	0.016-0.063
1-2	0.032-0.125	0.032-0.125	0.032-0.125	0.063-0.25
3-21	0.016-0.032	0.016-0.063	0.016-0.063	0.032-0.063
2-38	0.016-0.032	0.016-0.032	0.032-0.063	0.016-0.032
3-30	0.032-0.063	0.063-0.125	0.063-0.125	0.063-0.25

Experimental Example 2

In Vivo Antibacterial Efficacy

In vivo efficacy was evaluated in a hamster intestinal infection treatment model. Male Golden Syrian hamsters were purchased from Charles River Laboratories (Kingston, N.Y., USA) and were about 6 weeks of age, with weights ranging from 80 to 100 g at the start of the study. The animals were housed individually in filtered polycarbonate shoe-box style cages equipped with water bottles, and Harlan Teklab Global Diet 2016 was available ad libitum via food hoppers. The hamsters were pre-treated with clindamycin (1 mg/kg, p.o.) and vancomycin (50 mg/kg, p.o.), formulated in arabic gum, at Day 0. At Day 7, each hamster was inoculated via oral gavage with 0.5 mL of a suspension of C. difficile ATCC 43255 (10⁵ CFU/body, p.o.). To prepare this inoculum, C. difficile was grown in GAM agar (Japan) for 5 days at 37° C., and the bacteria were harvested by centrifugation, rinsed twice with arabic gum, resuspended in arabic gum and the exact bacteria density was determined using the dilution plate count method. Oral dosing of compounds, pulverized and formulated in arabic gum was commenced the following day (Day 8). Treatments were administered once a day for 5 consecutive days at specified doses (10, 2, and 0.4 mg/kg), with five hamsters per group. Controls were included an uninfected group and an infected but untreated group, and vancomycin was used as positive control. The hamsters were observed daily to record clinical signs (duration, time of onset, time of recovery or death), and animals in a lethargic, clearly moribund state were euthanized. A necropsy was performed on animals that were either found dead or were euthanized at the end of the study (37 days). The results are shown in FIG. 1 and FIG. 2.

Preparation Example 1

An injection preparation is prepared from the following components.

Components                    Amount
Compound 1-2                  200 mg
Glucose                       250 mg
Distilled water for injection q.s.
Total                         5 ml

Compound 1-2 and glucose are dissolved in distilled water for injection, and the solution is added to a 5 ml ampoule, which is purged with nitrogen gas and then subjected to sterilization at 121° C. for 15 minutes to give an injection preparation.

Preparation Example 2

Film coated tablets are prepared from the following components.

Components                   Amount
Compound 2-18                100 g
Avicel(registered trademark) 40 g
Corn starch                  30 g
Magnesium stearate           2 g
TC-5(registered trademark)   10 g
Polyethylene glycol 6000     3 g
Castor oil                   40 g
Ethanol                      40 g

Compound 2-18, Avicel (registered trademark of microcrystalline cellulose, manufactured by Asahi Kasei Corporation, Japan), corn starch and magnesium stearate are mixed and kneaded, and the mixture is tabletted using a conventional pounder (R 10 mm) for sugar coating (manufactured by Kikusui Seisakusho Ltd., Japan). The tablets thus obtained are coated with a film coating agent consisting of TC-5 (registered trademark of hydroxypropyl methylcellulose, manufactured by Shin-Etsu Chemical Co., Ltd., Japan), polyethylene glycol 6000, castor oil and ethanol to give film coated tablets.

Preparation Example 3

An ointment is prepared from the following components.

Components       Amount
Compound 3-11    2 g
Purified lanolin 5 g
Bleached beeswax 5 g
White petrolatum 88 g
Total            100 g

Bleached beeswax is made liquid by heating, and thereto are added compound 3-11, purified lanolin and white petrolatum, and the mixture is heated until it becomes liquid. The mixture is stirred until it is solidified to give an ointment.

Claims

1. A compound represented by the formula (I) wherein X is a hydrogen atom or a fluorine atom; R is a hydrogen atom or alkyl; R1 is (1) cyclopropyl optionally substituted by 1 to 3 halogen atoms or (2) phenyl optionally substituted by 1 to 3 halogen atoms; R2 is a hydrogen atom; alkyl optionally substituted by 1 or 2 substituents selected from the group consisting of a halogen atom and hydroxyl; alkoxy; haloalkoxy; a halogen atom; cyano; cyclopropyl; nitro; amino; formyl; alkenyl or alkynyl; or R1 and R2 are bonded to form a 5- or 6-membered ring optionally substituted by alkyl; R3 is wherein represents a single bond or a double bond, X1 is C(R5) or N, R4 is a hydrogen atom or alkyl, and R5 is (a) a hydrogen atom, when X1 is C(R5), R4 and R5 are optionally bonded to form a 5or 6-membered ring optionally substituted by oxo, said fused heterocyclic group is optionally substituted by 1 or 2 substituents selected from the group consisting of a halogen atom, cyano, nitro, hydroxy and alkyl, wherein X2 is C(R8) or N, and R6, R7 and R8 are each independently, wherein X3 and X4 are N, or X3 is N and X4 is CR″, wherein R″ is hydrogen atom, amino, hydroxy, alkyl optionally substituted by 1 to 3 substituents selected from the group consisting of alkoxy and dimethylamino or mercapto, or X3 is CH and X4 is N, R′ is a hydrogen atom or alkyl optionally substituted by 1 to 3 substituents selected from the group consisting of substituted hydroxyl and amino, and R6 is as defined above, wherein represents a single bond or a double bond and R6 is as defined above, wherein one of Y1, Y2, Y3 and Y4 is N or N+ (—O−), and the remaining three are each C(R25), C(R26) and C(R27), W is O, S, NH or N(R23) R23 is a hydrogen atom or alkyl, and R24, R25, R26 and R27 are each independently, wherein R28 is a hydrogen atom or hydroxy, and R29 is a hydrogen atom or alkyl, wherein X5 is C(R11) or N, X6 is CH2, C(═O), O, S, SO2 or N(R12), X7 is CH(R13), C(═O) or N(R14), X8 is CH(R15) or C(═O), R10, R12 and R14 are each independently, R11, R13 and R15 are each independently, when X5 is C(R11), R10 and R11 are optionally bonded to form a 5- or 6-membered ring optionally substituted by alkyl or oxo, and when X6 is N(R12) and X7 is CH(R13), R12 and R13 are optionally bonded to form a 5- or 6-membered ring, wherein R16 is wherein R18 is a hydrogen atom or alkyl optionally substituted by 1 to 3 substituents selected from the group consisting of a halogen atom and phenyl, n is 0 or 1, R19, R20 and R33 are each independently, wherein R30 is (a) a hydrogen atom, wherein U is O or S, and R31 is (a) a hydrogen atom, wherein R32 is (a) a halogen atom, wherein R34 and R35 are each independently, or R34 and R35 are bonded to form a 6-membered ring optionally substituted by amino or oxo, wherein R36 is or a salt thereof.

(1) a fused heterocyclic group of the formula

(b) a halogen atom,

(c) cyano,

(d) nitro,

(e) hydroxy,

(f) alkyl optionally substituted by 1 to 3 halogen atoms,

(g) alkenyl or alkynyl,

(h) aryl, or

(i) alkoxy optionally substituted by 1 to 3 halogen atoms,

(2) a group of the formula

(a) a hydrogen atom,

(b) a halogen atom,

(c) cyano,

(d) nitro,

(e) amino,

(f) alkyl optionally substituted by 1 to 3 substituents selected from the group consisting of a halogen atom, alkoxy and amino,

(g) alkenyl,

(h) alkynyl,

(i) aryl,

(j) formyl or CH═N—OH,

(k) carboxy,

(l) carbamoyl,

(m) a 5- to 10-membered aromatic heterocyclic group optionally substituted by alkyl, or

(n) alkenyloxy,

(3) a group of the formula

(4) a group of the formula

(5) 3-pyridyl optionally substituted by 1 or 2 substituents selected from the group consisting of (a) a halogen atom, (b) cyano, (c) nitro, (d) hydroxy, (e) amino, (f) alkyl optionally substituted by 1 to 3 substituents selected from the group consisting of a halogen atom, alkylamino, dialkylamino and hydroxy, (g) alkenyl, alkynyl (h) aryl, (i) cycloalkyl, (j) alkoxy, (k) alkylamino, (l) dialkylamino, (m) phenylamino optionally substituted by 1 to 3 halogen atoms, (n) a cyclic amino group optionally substituted by alkoxycarbonyl, (o) formyl, (p) carbamoyl optionally substituted by alkyl optionally substituted by hydroxy, and (q) a 5- to 10-membered aromatic heterocyclic group optionally substituted by alkyl,

(6) 4-pyridyl optionally substituted by a halogen atom,

(7) 5-pyrimidinyl optionally substituted by 1 or 2 substituents selected from the group consisting of amino, alkylamino, dialkylamino and carboxy,

(8) 2-indolyl, 3-indolyl, 5-indolyl, 6-indolyl, benzofuranyl, benzothiophenyl, benzoxazolyl or benzothiazolyl, each optionally substituted by 1 or 2 substituents selected from the group consisting of (a) a halogen atom, (b) cyano, (c) nitro, (d) hydroxy, (e) alkyl optionally substituted by 1 to 3 substituents selected from the group consisting of amino, alkoxycarbonylamino, alkylamino and dialkylamino, (f) alkoxy, (g) formyl, (h) carboxy, and (j) amino optionally substituted by 1 or 2 substituents selected from the group consisting of (i) alkoxycarbonyl, (ii) alkylcarbonyl optionally substituted by a substituent selected from the group consisting of (A) cycloalkyloxy optionally substituted by 1 to 3 alkyl, (B) alkylamino, (C) dialkylamino, (D) a cyclic amino group optionally substituted by alkoxycarbonyl, and (E) a halogen atom, (iii) phenylcarbonyl optionally substituted by 1 to 3 substituents selected from the group consisting of alkyl and alkoxy, (iv) cycloalkylcarbonyl, (v) a 5- to 10-membered aromatic heterocyclylcarbonyl group optionally substituted by alkyl optionally substituted by 1 to 3 halogen atoms, (vi) benzylcarbonyl optionally substituted by 1 to 3 substituents selected from the group consisting of a halogen atom and alkoxy, (vii) arylsulfonyl optionally substituted by alkoxy, (viii) cycloalkylalkylsulfonyl optionally substituted by 1 to 3 substituents selected from the group consisting of alkyl and oxo, (ix) a 5- to 10-membered aromatic heterocyclylsulfonyl group optionally substituted by 1 to 3 alkyl, and (x) —C(═N—CN)—SR9 wherein R9 is alkyl,

(9) a group of the formula

(a) a hydrogen atom,

(b) cyano, or

(c) nitro,

(10) a group of the formula

(11) a group of the formula

(a) a hydrogen atom or

(b) alkyl, and

(a) a hydrogen atom,

(b) a halogen atom,

(c) cyano,

(d) nitro,

(e) amino,

(f) alkylamino,

(g) dialkylamino,

(h) alkyl optionally substituted by hydroxy, or

(i) alkenyl,

(12) a group of the formula

(a) a hydrogen atom,

(b) alkyl optionally substituted by 1 to 3 substituents selected from the group consisting of cyano, alkylamino and dialkylamino,

(c) alkenyl optionally substituted by carboxy,

(d) formyl,

(e) carboxy,

(f) carbamoyl,

(g) —C(R17)═N—OH wherein R17 is a hydrogen atom, cyano or hydroxy,

(h) a 5- to 10-membered aromatic heterocyclic group optionally substituted by alkyl, alkoxycarbonyl, carboxy or phenyl, or

(i) cyano,

(13) a group of the formula

(a) a hydrogen atom,

(b) a halogen atom,

(c) cyano,

(d) alkyl optionally substituted by 1 to 3 substituents selected from the group consisting of (i) a halogen atom, (ii) cyano, (iii) hydroxy, (iv) amino, (v) alkylamino, (vi) dialkylamino, and (vii) a cyclic amino group optionally substituted by alkyl,

(e) alkoxy,

(f) amino optionally substituted by 1 or 2 substituents selected from the group consisting of (i) alkylcarbonyl optionally substituted by a cyclic amino group, (ii) alkylsulfonyl, (iii) carbamoyl, (iv) alkyl, cycloalkyl or cycloalkylalkyl, and (v) 5- to 10-membered saturated heterocyclic group,

(g) carboxy,

(h) alkoxycarbonyl,

(i) carbamoyl optionally substituted by alkyl optionally substituted by amino, alkylamino, dialkylamino or alkoxycarbonylamino,

(j) formyl,

(k) a 5- to 10-membered aromatic heterocyclic group optionally substituted by alkyl,

(l) —CH═N—OR21 wherein R21 is a hydrogen atom or alkyl optionally substituted by alkylamino or dialkylamino,

(m) nitro,

(n) a 5- to 10-membered saturated heterocyclic group optionally substituted by amino,

(o) phenyl, or

(p) —NHC(SMe)=CHCN,

(14) a group of the formula

(b) a halogen atom,

(c) cyano,

(d) alkyl optionally substituted by 1 to 3 substituents selected from the group consisting of a halogen atom and hydroxy,

(e) alkenyl,

(f) alkynyl,

(g) alkoxy,

(h) formyl,

(i) —CH═N—OH, or

(j) carbamoyl,

(15) naphthyl or isochromenyl,

(16) quinolyl or isoquinolyl, or their oxide derivatives,

(17) a group of the formula

(18) a group of the formula

(b) a halogen atom,

(c) alkyl optionally substituted by 1 to 3 halogen atoms,

(d) carboxy,

(e) nitro,

(f) cyano, or

(g) amino,

(19) a group of the formula

(b) phenyl, or

(c) a group of the formula

(20) a group of the formula

(a) a hydrogen atom, or

(b) aminoalkyl,

(21) a group of the formula

(a) a hydrogen atom,

(b) a halogen atom,

(c) nitro, or

(d) thienyl, or

(22) a group of the formula

2. The compound of claim 1, wherein X is a fluorine atom, or a salt thereof.

3. The compound of claim 1, wherein R3 is a fused heterocyclic group of the formula wherein, X1 and R4 are as defined in claim 1, and said fused heterocyclic group is optionally substituted by 1 or 2 substituents selected from the group consisting of a halogen atom, cyano, nitro, hydroxy and alkyl, or a salt thereof.

4. The compound of claim 1, wherein R3 is a group of the formula wherein X2, R6 and R7 are as defined in claim 1, or a salt thereof.

5. The compound of claim 1, wherein R3 is a group of the formula wherein X3, X4, R6 and R′ are as defined in claim 1, or a salt thereof.

6. The compound of claim 1, wherein R3 is a group of the formula wherein and R6 are as defined in claim 1, or a salt thereof.

7. The compound of claim 1, wherein R3 is a group of the formula wherein R22 is or a salt thereof.

(a) a halogen atom,

(b) cyano,

(c) nitro,

(d) alkyl optionally substituted by 1 to 3 substituents selected from the group consisting of a halogen atom, alkylamino, dialkylamino and hydroxy,

(e) alkenyl, alkynyl,

(f) aryl,

(g) cycloalkyl,

(h) alkoxy,

(i) formyl, or

(j) carbamoyl optionally substituted by alkyl optionally substituted by hydroxyl,

8. The compound of claim 1, wherein R3 is 5-pyrimidinyl substituted by 1 or 2 substituents selected from the group consisting of amino, alkylamino, dialkylamino and carboxy, or a salt thereof.

9. The compound of claim 1, wherein R3 is 2-indolyl optionally substituted by 1 or 2 substituents selected from the group consisting of or a salt thereof.

(a) a halogen atom,

(b) cyano,

(c) nitro,

(d) hydroxy,

(e) alkyl optionally substituted by 1 to 3 substituents selected from the group consisting of amino, alkoxycarbonylamino, alkylamino and dialkylamino,

(f) alkoxy,

(g) formyl,

(h) carboxy, or

(j) amino optionally substituted by 1 or 2 substituents selected from the group consisting of (i) alkoxycarbonyl, (ii) alkylcarbonyl optionally substituted by a substituent selected from the group consisting of (A) cycloalkyloxy optionally substituted by 1 to 3 alkyl, (B) alkylamino, (C) dialkylamino, (D) a cyclic amino group optionally substituted by alkoxycarbonyl, and (E) a halogen atom, (iii) phenylcarbonyl optionally substituted by 1 to 3 substituents selected from the group consisting of alkyl and alkoxy, (iv) cycloalkylcarbonyl, (v) a 5- to 10-membered aromatic heterocyclylcarbonyl group optionally substituted by alkyl optionally substituted by 1 to 3 halogen atoms, (vi) benzylcarbonyl optionally substituted by 1 to 3 substituents selected from the group consisting of a halogen atom and alkoxy, (vii) arylsulfonyl optionally substituted by alkoxy, (viii) cycloalkylalkylsulfonyl optionally substituted by 1 to 3 substituents selected from the group consisting of alkyl and oxo, (ix) a 5- to 10-membered aromatic heterocyclylsulfonyl group optionally substituted by 1 to 3 alkyl, and (x) —C(═N—CN)—SR9 wherein R9 is alkyl,

10. The compound of claim 1, wherein R3 is a group of the formula wherein Y1, Y2, Y3, Y4, W and R24 are as defined in claim 1, or a salt thereof.

11. The compound of claim 1, wherein R3 is a group of the formula wherein R28 and R29 are as defined in claim 1, or a salt thereof.

12. The compound of claim 1, wherein R3 is a group of the formula wherein X5, X6, X7, X8 and R10 are as defined in claim 1, or a salt thereof.

13. The compound of claim 1, wherein R3 is a group of the formula wherein R16a is or a salt thereof.

(a) alkyl optionally substituted by 1 to 3 substituents selected from the group consisting of cyano, alkylamino and dialkylamino,

(b) alkenyl optionally substituted by carboxy,

(c) formyl,

(d) carboxy,

(e) carbamoyl,

(f) —C(R17)═N—OH wherein R17 is a hydrogen atom, cyano or hydroxy,

(g) a 5- to 10-membered aromatic heterocyclic group optionally substituted by alkyl, alkoxycarbonyl, carboxy or phenyl, or

(h) cyano,

14. The compound of claim 1, wherein R3 is a group of the formula wherein R18a is alkyl, and R19a is (a) a halogen atom, or a salt thereof.

(b) cyano,

(c) alkyl optionally substituted by 1 to 3 substituents selected from the group consisting of (i) a halogen atom, (ii) cyano, (iii) hydroxy, (iv) amino, (v) alkylamino, (vi) dialkylamino, and (vii) a cyclic amino group optionally substituted by alkyl,

(d) alkoxy,

(e) amino optionally substituted by 1 or 2 substituents selected from the group consisting of (i) alkylcarbonyl optionally substituted by a cyclic amino group, (ii) alkylsulfonyl, (iii) carbamoyl, and (iv) alkyl or cycloalkyl,

(f) carboxy,

(g) alkoxycarbonyl,

(h) carbamoyl optionally substituted by alkyl optionally substituted by amino, alkylamino, dialkylamino or alkoxycarbonylamino,

(i) formyl,

(j) a 5- to 10-membered aromatic heterocyclic group optionally substituted by alkyl,

(k) —CH═N—OR21 wherein R21 is a hydrogen atom or alkyl optionally substituted by alkylamino or dialkylamino, or

(l) nitro,

15. The compound of claim 1, wherein R3 is a group of the formula wherein R30 is as defined in claim 1, or a salt thereof.

16. The compound of claim 1, wherein R3 is naphthyl or isochromenyl, or a salt thereof.

17. The compound of claim 1, wherein R3 is quinolyl or isoquinolyl, or their oxide derivatives, or a salt thereof.

18. The compound of claim 1, wherein R is a hydrogen atom, or a salt thereof.

19. The compound of claim 1, wherein R1 is cyclopropyl, 2-fluorocyclopropyl or 2,4-difluorophenyl, or a salt thereof.

20. The compound of claim 1, wherein R2 is methyl, methoxy or a chlorine atom, or a salt thereof.

21. A pharmaceutical composition comprising a compound of claim 1 or a salt thereof and a pharmaceutically acceptable carrier.

22. An antimicrobial agent comprising a compound of claim 1 or a salt thereof.

23. A compound of claim 1 or a salt thereof for use as a medicament.

24. A compound of claim 1 or a salt thereof for use as an antimicrobial agent.

25. A compound of claim 1 or a salt thereof for use in the prevention or treatment of a bacterial infection.

26. Use of a compound of claim 1 or a salt thereof for the manufacture of a medicament for preventing or treating a bacterial infection.

27. A method for preventing or treating a bacterial infection which comprises administering an effective amount of a compound of claim 1 or a salt thereof to a human or an animal.