Patent number: 7183288
Abstract: This invention concerns a compound of formula a N-oxide, a pharmaceutically acceptable addition salt, a quaternary amine and a stereochemically isomeric form thereof, wherein ring A represents a 6-membered heterocycle; R1 is hydrogen; aryl; formyl; C1-6alkylcarbonyl; optionally substituted C1-6alkyl; C1-6alkyloxycarbonyl; optionally substituted C1-6alkyloxyC1-6alkylcarbonyl; X is a direct bond or a linker atom or group; Z is O or S; R2 is hydrogen, C1-10alkyl, C2-10alkenyl, C2-10alkynyl, a carbocycle or a heterocycle, each of said groups may optionally be substituted; R3 is hydrogen; hydroxy; halo; optionally substituted C1-6alkyl or C2-6alkenyl or C2-6alkynyl; C1-6alkyloxy; C1-6alkylthio; C1-6alkyloxycarbonyl; C1-6alkylcarbonyloxy; carboxyl; cyano; nitro; amino; mono- or di(C1-6alkyl)amino; polyhaloC1-6alkyl; polyhaloC1-6alkyloxy; polyhaloC1-6alkylthio; R21; R21—C1-6alkyl; R21—O—; R21—S—; R21—C(?O)—; R21—S(?O)p—; R7—S(?O)p—; R7—S(?O)p—NH—; R21—S(?O)p—NH—; R7—C(?O)—; —NHC(?O)H; —C(?O)NHNH2; R7—C(?O)—NH—;
Type:
Grant
Filed:
October 29, 2002
Date of Patent:
February 27, 2007
Inventors:
Eddy Jean Edgard Freyne, Peter Jacobus Johannes Antonius Buijnsters, Marc Willems, Werner Constant Johan Embrechts, Jean Fernand Armand Lacrampe, Herwig Josephus Margareta Janssen, legal representative, Paul Peter Maria Janssen, legal representative, Graziella Maria Constantina Janssen, legal representative, Jasmine Josée Werner Janssen, legal representative, Maroussia Godelieve Frank Janssen, legal representative, Theodora Joanna Francisca Arts, Paulus Joannes Lewi, Jan Heeres, Marc René de Jonge, Lucien Maria Henricus Koymans, Frederik Frans Desiré Daeyaert, Michael Joseph Kukla, Hugo Alfons Gabriel Geerts, Rony Maria Nuydens, Marc Hubert Mercken, Donald William Ludovici, Paul Adriaan Jan Janssen, deceased
Patent number: 6951857
Abstract: The present invention is concerned with the use of compounds of formula the N-oxides, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein p represents 0, 1, 2 or 3; q represents 0, 1, 2, 3 or 4; R1 represents hydrogen, C1-6alkyl, mono- or di(C1-6alkyl)aminoC1-6alkyloxy, mercapto, C1-6alkylthio, C3-7cycloalkyl, aryl or C1-6alkyl substituted with mono- or di(C1-6alkyl)amino, C1-6alkyloxy, aryl or Het; R2 represents cyano or a radical of formula —C(?X)—Y—R5; wherein X represents O or S; Y represents O, S, NR6 or a direct bond; R5 represents hydrogen; C3-7cycloalkyl; aryl or optionally substituted C1-6alkyl; and where Y is a direct bond, R5 may also be halo or Het; R3 and R4 each independently represents halo, haloC1-6alkyl, C1-6alkyl, hydroxy, C1-6alkyloxy, C1-6alkylcarbonyloxy, mercapto, C1-6alkylthio, C1-6alkylsulfonyl, C1-6alkylsulfinyl, haloC1-6alkylsulfonyl, aryl, cyano, nitro, amino, mono- and di(C1-6alkyl)amino or (C1-6alkylcarbonyl)amino; aryl repre
Type:
Grant
Filed:
May 9, 2003
Date of Patent:
October 4, 2005
Inventors:
Eddy Jean Edgard Freyne, Gustaaf Maria Boeckx, Jean Pierre Frans Van Wauwe, Gaston Stanislas Marcella Diels
Patent number: 6894046
Abstract: The present invention is concerned with the compounds of formula the N-oxides, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein p is 0 to 4; X is O, S, NR5 or a direct bond; Y is O, S, NR5 or S(O)2; R1 independently is C1-6alkyl, halo, polyhaloC1-6alkyl, hydroxy, mercapto, C1-6alkyloxy, C1-6alkylthio, C1-6alkylcarbonyloxy, aryl, cyano, nitro, Het3, R6, NR7R8 or substituted C1-4alkyl; R2 is Het1, C3-7cycloalkyl or optionally substituted C1-6alkyl and if X is O, S or NR5, then R2 may also represent aminocarbonyl, aminothiocarbonyl, C1-4alkylcarbonyl, C1-4alkylthiocarbonyl, arylcarbonyl, arylthiocarbonyl, Het1carbonyl or Het1thiocarbonyl; R3 and R4 independently are hydrogen, C1-6alkyl or C3-7cycloalkyl; R3 and R4 form a C2-6alkanediyl; R5 is hydrogen or C1-4alkyl; R6 is a sulfonyl or sulfinyl derivative; R7 and R8 are independently hydrogen, optionally substituted C1-4alkyl, aryl, a carbonyl containing moiety, C3-7cycloalkyl, —Y—C1-4alkanediyl-C(?O)—O—R
Type:
Grant
Filed:
March 19, 2001
Date of Patent:
May 17, 2005
Assignee:
Janssen Pharmaceutica N.V.
Inventors:
Eddy Jean Edgard Freyne, Jean Fernand Armand Lacrampe, Frederik Dirk Deroose, Marc Gaston Venet
Patent number: 6867207
Abstract: The present invention is concerned with the compounds of formula the N-oxides, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, p and q are 0, 1, 2, 3 or 4 and q is also 5; X is O, S, NR3 or a direct bond; R1 is hydrogen, hydroxy, halo, optionally substituted amino, optionally substituted C1-6alkyl, C1-6alkyloxy, C3-7cycloalkyl or aryl; R2 is aryl, Het1, C3-7cycloalkyl, optionally substituted C1-6alkyl; and if X is O, S or NR3, then R2 may also be a carbonyl or thiocarbonyl linked substituent; R3 is hydrogen or C1-4alkyl; R4 and R5 independently are optionally substituted C1-6alkyl, halo, hydroxy, mercapto, C1-6alkyloxy, C1-6akylthio, C1-6alkylcarbonyloxy, aryl, cyano, nitro, Het3, R6 or NR7R8; R6 is substituted sulfonyl or sulfinyl; R7 and R8 are hydrogen, optionally substituted C1-4alkyl, aryl, a carbonyl or thiocarbonyl linked substituent, C3-7cycloalkyl, Het3 and R6; R9 and R10 are each independently selected from hydrogen, optionally substituted C1-4alky
Type:
Grant
Filed:
June 26, 2001
Date of Patent:
March 15, 2005
Assignee:
Janssen Pharmaceutica N.V.
Inventors:
Jean Fernand Armand Lacrampe, Eddy Jean Edgard Freyne, Marc Gaston Venet, Gustaaf Maria Boeckx
Patent number: 6803364
Abstract: The present invention is concerned with the compounds of formula (I), a N-oxide, a pharmaceutically acceptable addition salt, a quaternary amine or a stereochemically isomeric form thereof, wherein p is 0 to 4; q is 0 to 5; X is O, S, NR3 or a direct bond; or —X—R2 is CN; R1 is H, OH, halo, NH2, mono- or di(C1-4alkyl)NH2, C1-6alkyl, C1-6alkylO, C3-7cycloalkyl, aryl, arylC1-6alkyl, NH2C1-4akyl, mono- or di(C1-4alkyl)NH2C1-4akyl or mono- or di(C1-4alkyl)NH2C1-4alkylNH2; R2 is aryl, Het1, optionally substituted C3-7cycloalkyl, optionally substituted C1-6alkyl; R3 is H or C1-4alkyl; R4 and R5 are —C(═O)—Z—R14, C1-6alkyl, halo, polyhaloC1-6alkyl, OH, mercapto, C1-6alkylO, C1-6alkylthio, C1-6alkylC(═O)O, aryl, cyano, nitro, Het3, R6, NR7R8 or C1-4alkyl substituted with —C(═O)—Z—R14, Het3, R6 or NR7R8; Z is O, S, NH, —CH2O or —CH2—S—; R14 is H, C1-20acyl, optionally substituted C1-20alkyl, optionally substituted C3-20alkenyl, C3-2
Type:
Grant
Filed:
August 29, 2001
Date of Patent:
October 12, 2004
Assignee:
Janssen Pharmaceutica N.V.
Inventors:
Eddy Jean Edgard Freyne, Frederik Dirk Deroose, Jean Fernand Armand Lacrampe, Werner Constant Johan Embrechts, Jerome Michel Claude Fortin
Patent number: 6743792
Abstract: The present invention is concerned with the use of compounds of formula
the N-oxides, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein p represents 0, 1, 2 or 3; q represents 0, 1, 2, 3 or 4; R1 represents hydrogen, C1-6alkyl, mono- or di(C1-6alkyl)aminoC1-6alkyloxy, mercapto, C1-6alkylthio, C3-7cycloalkyl, aryl or C1-6alkyl substituted with mono- or di(C1-6alkyl)-amino, C1-6alkyloxy, aryl or Het; R2 represents cyano or a radical of formula —C(═X)—Y—R5; wherein X represents O or S; Y represents O, S, NR6 or a direct bond; R5 represents hydrogen; C3-7cycloalkyl; aryl or optionally substituted C1-6alkyl; and where Y is a direct bond, R5 may also be halo or Het; R3 and R4 each independently represents halo, haloC1-6alkyl, C1-6alkyl, hydroxy, C1-6alkyloxy, C1-6alkylcarbonyloxy, mercapto, C1-6alkylthio, C1-6alkylsulfonyl, C1-6alkylsulfinyl, haloC1-6alkylsulfonyl, aryl, cyano, nitro, amino, mono- and di(C1-6alkyl)amino o
Type:
Grant
Filed:
May 14, 2001
Date of Patent:
June 1, 2004
Assignee:
Janssen Pharmaceutica N.V.
Inventors:
Eddy Jean Edgard Freyne, Gustaaf Maria Boeckx, Jean Pierre Frans Van Wauwe, Gaston Stanislas Marcella Diels
Patent number: 6583141
Abstract: The present invention is concerned with the compounds of formula
wherein m, n and p are each independently 0 or 1 and q is 0, 1, 2, 3, 4 or 5; —A1═A2—A3═A4— is a pyridinylidene, pyridazinylidene, pyrimidinylidene, pyrazinylidene or phenylidene; B represents an amide, ketone or oxadiazole; D represents Ar or Het; Q represents a covalent direct bond or a ketone, —N—, —O—, —CR5R6—, amide ethenyl, imine, sulfonyl, sulfinyl, 3-oxobutenyl, pyrazole, isoxazole or thiazole; L represents Ar or Het; R1 represents hydrogen, halo, hydroxy, C(2-6)alkenyl, C(2-6)alkynyl, C(3-6)cycloalkyl, C(3-6)cycloalkenyl, cyano, guanidine, nitro, NR17R18, an optionally substituted C(1-6)alkyl or C(1-6)alkyloxy; R2 and R3 each independently represent hydrogen, halo, C(1-6)alkyloxy or an optionally substituted C(1-6)alkyl; R5 and R6 each independently represent hydrogen, hydroxy, halo, an optionally substituted C(1-6)alkyl, C(2-6)alkenyl, C(2-6)alkynyl, C(3-
Type:
Grant
Filed:
April 6, 2001
Date of Patent:
June 24, 2003
Assignee:
Janssen Pharmaceutica, N.V.
Inventors:
Eddy Jean Edgard Freyne, José Ignacio Andrés-Gil, Frederik Dirk Deroose, Davy Petrus Franciscus Maria Petit, Maria Encarnacion Matesanz-Ballesteros, Rosa Maria Alvarez Escobar
Patent number: 6498158
Abstract: The present invention is concerned with the compounds of formula
the N-oxides, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein p is 0 to 3; q is 0 to 4; —A—B— represents —(CH2)r—, —(CH2)t—O—, —(CH2)t—S(═O)u— or —(CH2)t—NR3—; r is 2 to 4; t is 1 to 3; u is 0 to 2; X1 is O, S, NR3 or a direct bond; R1 and R4 are C1-6alkyl, halo, polyhaloC1-6alkyl, hydroxy, mercapto, C1-6alkyloxy, C1-6alkylthio, C1-6alkylcarbonyloxy, aryl, cyano, nitro, Het3, R6, NR7R8 or substituted C1-4alkyl; R2 is aryl, Het1, C3-7cycloalkyl, cyano, optionally substituted C1-6alkyl, —C(═Q)—X2—R15; R3 is hydrogen or C1-4alkyl; R15 is hydrogen, optionally substituted C1-6alkyl, C3-7cycloalkyl, aryl; where X2 is a direct bond, R15 may also be halo or Het1; where X2 is NR5, R15 may also be hydroxy; where X2 is C(═O)—NH—NH or NH—NH—C(&bo
Type:
Grant
Filed:
May 22, 2001
Date of Patent:
December 24, 2002
Assignee:
Janssen Pharmaceutica N.V.
Inventors:
Jean Fernand Armand Lacrampe, Yannick Ligny, Eddy Jean Edgard Freyne, Frederik Dirk Deroose
Patent number: 6469001
Abstract: The present invention is concerned with the compounds of formula
the N-oxides, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein p is 0 to 3; q is 0 to 5; —A—B— is —(CH2)r—, —(CH2)t—O—, —(CH2)t—S(═O)u— or —(CH2)t—NR3—; r is 2 to 4; t is 1 to 3; u is 0 to 2; X1 is O, S, NR3 or a direct bond; R1 and R4 are C1-6alkyl, halo, polyhaloC1-6alkyl, hydroxy, mercapto, C1-6alkyloxy, C1-6alkylthio, C1-6alkylcarbonyloxy, aryl, cyano, nitro, Het3, R6, NR7R8 or C1-4alkyl substituted with Het3, R6 or NR7R8; R2 represents aryl, Het1, C3-7cycloalkyl, cyano, C1-6alkyl, —C(═Q)—X2—R15 or C1-6alkyl substituted with one or two substituents selected from hydroxy, cyano, amino, mono- or di(C1-4alkyl)amino, C1-6alkyloxy, C1-6alkylsulfonyloxy, C1-6alkyloxycarbonyl, C3-7cycloalkyl, aryl, aryloxy, arylthio, Het1, Het1 oxy, Het1 thio and —C(═Q)&md
Type:
Grant
Filed:
May 22, 2001
Date of Patent:
October 22, 2002
Inventors:
Eddy Jean Edgard Freyne, Frederik Dirk Deroose, Davy Petrus Franciscus Maria Petit, Jean Fernand Armand Lacrampe
Patent number: 6358961
Abstract: This invention concerns compounds of formula
the pharmaceutically acceptable acid addition salts and the stereochemically isomeric forms thereof, wherein the dotted line represents an optional bond; X is oxygen or sulfur; R1 and R2 each independently are hydrogen, hydroxy, halo, cyano, C1-6alkyl, trihalomethyl, trihalomethoxy, C2-6alkenyl, C1-6alkyloxy, hydroxyC1-6alkyloxy, C1-6alkyloxyC1-6alkyloxy, C1-6alkyloxycarbonyl, aminoC1-6alkyloxy, mono- or di(C1-6alkyl)aminoC1-6alkyloxy, Ar1, Ar1C1-6alkyl, Ar1oxy, Ar1C1-6alkyloxy; or when on adjacent positions R1 and R2 taken together may form a bivalent radical; R3 and R4 each independently are hydrogen, halo, cyano, C1-6alkyl, C1-6alkyloxy, Ar1oxy, C1-6alkylthio, di(C1-6alkyl)amino, trihalomethyl, trihalomethoxy; R5 is hydrogen, halo, cyano, optionally substituted C1-6alkyl, C1-6alkyloxycarbonyl or Ar1; or a radical of formula —OR10, —SR10, —NR11R12; R6 is an optionally substituted imidazolyl moiety; R7 is hydrogen or C1-6alkyl p
Type:
Grant
Filed:
October 13, 2000
Date of Patent:
March 19, 2002
Assignee:
Jannsen-Cilag S.A.
Inventors:
Patrick René Angibaud, Marc Gaston Venet, Eddy Jean Edgard Freyne