Phenyl heterocycles as cox-2 inhibitors

Abstract

The invention encompasses the novel compound of Formula I useful in the treatment of cyclooxygenase-2 mediated diseases. ##STR1## The invention also encompasses certain pharmaceutical compositions for treatment of cyclooxygenase-2 mediated diseases comprising compounds of Formula I.

Claims

1. A process of making a compound of formula XXXIII ##STR216## wherein R.sup.1 is selected from the group consisting of

(a) S(O).sub.2 CH.sub.3,

(b) S(O).sub.2 NH.sub.2,

(c) S(O).sub.2 NHC(O)CF.sub.3,

(d) S(O)(NH)CH.sub.3,

(e) S(O)(NH)NH.sub.2,

(f) S(O)(NH)NHC(O)CF.sub.3,

(g) P(O)(CH.sub.3)OH, and

(h) P(O)(CH.sub.3)NH.sub.2,

R.sup.2 is selected from the group consisting of

(a) mono-, di- or tri-substituted phenyl wherein the substituent is selected from the group consisting of

(1) hydrogen,

(2) halo,

(3) C.sub.1-6 alkoxy,

(4) C.sub.1-6 alkylthio,

(5) CN,

(6) CF.sub.3,

(7) C.sub.1-6 alkyl,

(8) N.sub.3,

(9) --CO.sub.2 --C.sub.1-4 alkyl,

(10) --C(R.sup.5)(R.sup.6)--OH,

(11) --C(R.sup.5)(R.sup.6)--O--C.sub.1-4 alkyl, and

(12) --C.sub.1-6 alkyl-CO.sub.2 --R.sup.5;

(b) mono-, di- or tri-substituted heteroaryl wherein the heteroaryl is a monocyclic aromatic ring of 5 atoms, said ring having one hetero atom which is S, O, or N, and optionally 1, 2, or 3 additionally N atoms, or

the heteroaryl is a monocyclic ring of 6 atoms, said ring having one hetero atom which is N, and optionally 1, 2, or 3 additional N atoms; said substituents are selected from the group consisting of

(1) hydrogen,

(2) halo, including fluoro, chloro, bromo and iodo,

(3) C.sub.1-6 alkyl,

(4) C.sub.1-6 alkoxy,

(5) C.sub.1-6 alkylthio,

(6) CN,

(7) CF.sub.3,

(8) N.sub.3,

(9) --C(R.sup.5)(R.sup.6)--OH, and

(10) --C(R.sup.5)(R.sup.6)--O--C.sub.1-4 alkyl;

R.sup.5 and R.sup.6 are each independently selected from the group consisting of

(a) hydrogen,

(b) C.sub.1-6 alkyl,

R.sup.5 and R.sup.6 together with the carbon to which they are attached form a saturated monocyclic carbon ring of 3, 4, 5, 6 or 7 atoms,

2. Process of claim 1 wherein the base is triethylamine.

3. A process of claim 1 wherein the compound of formula XXXII and the substituted aryl acetic acid are reacted in acetonitrile.

4. A process of claim 1 wherein

R.sup.1 is selected from the group consisting of

(a) S(O).sub.2 CH.sub.3, and

(b) S(O).sub.2 NH.sub.2.

6. A process of claim 5 wherein the base is triethylamine.

7. A process of claim 5 wherein phenyl acetic acid and 2-bromo-1-(4-methylsulfonylphenyl)ethanone are reacted in acetonitrile.