Patent ID: 6451816
Filing Date: 2002-09-17
Classification: A61K,C07D,C07F

Abstract:
A method of inhibiting tumor cell growth in a human or animal body comprising administering an effective amount of a pharmaceutical composition, wherein the pharmaceutical composition includes a compound of general formula (I) and pharmaceutically acceptable salts of formula (I) whereinR1 is selected from the group consisting of hydrogen, halogen, cyano, C1-C6-alkyl, C3-C6-alkenyl, C3-C6-alkinyl, trifluoromethyl, C3-C8-cycloalkyl, C1-C6-hydroxyalkyl, hydroxy, C1-C6-alkoxy, C3-C6-alkenyloxy, C3-C6-alkinyloxy, benzyloxy, C1-C7-alkanoyloxy, C2-C7-alkoxycarbonyloxy, C1-C6-alkylthio, C3-C6-alkenylthio, C3-C6-alkinylthio, C3-C8-cycloalkyloxy, C3-C8-cycloalkylthio, C2-C7-alkoxycarbonyl, aminocarbonyl, C2-C7-alkylaminocarbonyl, C3-C13-dialkylaminocarbonyl, carboxy, phenyl, phenoxy, phenylthio, NR5R6, and bridged R1R2 wherein R5 is selected from the group consisting of hydrogen, C1-C6-alkyl, C3-C6-alkenyl and C3-C6-alkinyl, R6 is selected from the group consisting of hydrogen, C1-C6-alkyl, C3-C6-alkenyl and C3-C6-alkinyl, R2 is selected from the group consisting of hydrogen, halogen, cyano, C1-C6-alkyl, trifluoromethyl, hydroxy, C1-C6-alkoxy, benzyloxy, C1-C7-alkanoyloxy, and bridged R1R2; wherein bridged R1R2 is where R1R2 are adjacent and form a bridge which is selected from the group consisting of â€”(CH2)4â€” and â€”(CH&boxH;CH)2â€” and â€”CH2Oâ€”CR7R8â€”Oâ€”, wherein R7 is selected from the group consisting of hydrogen and C1-C6-alkyl and R8 is selected from the group consisting of hydrogen and C1-C6-alkyl, R3 is selected from the group consisting of hydrogen, halogen, C1-C6-alkyl, trifluoromethyl and C1-C6-hydroxyalkyl; R4 is selected from the group consisting of hydrogen, C1-C6-alkyl, C3-C6-alkenyl, C3-C6-alkinyl, C3-C6-cycloalkyl, hydroxy, C1-C6-alkoxy and benzyloxy; k is 0 or 1, A is selected from the group consisting of C1-C6-alkylene, a substituted C1-C6-alkylene which is substituted once to three-fold by C1-C3-alkyl, hydroxy, C1-C3-alkoxy, fluorine or phenyl, a 1,2-cyclopropylene and an isosterically substituted C2-C6-alkylene, which has a methylene unit which is isosterically replaced by O, S, NR9, CO, SO or SO2, wherein the isosteric replacement, with the exception of &boxH;CO, is not adjacent to the amide group, and wherein R9 is selected from the group consisting of hydrogen, C1-C6-alkyl, C3-C6-alkenyl, C3-C6-alkinyl, C1-C6-acyl and C1-C6-alkylsulfonyl, D is selected from C1-C10-alkylene, a substituted C1-C10-alkylene which is substituted once or twice by C1-C6-alkyl, hydroxy, or C1-C6-alkoxy, a C2-C10-alkenylene, a substituted C2-C10-alkenylene which is substituted once or twice by C1-C6-alkyl, hydroxy, C1-C6-alkoxy, an E double bonded C2-C10-alkenylene which has a double bond to ring E, an E double bonded substituted C2-C10-alkenylene which has a double bond to ring E, a C3-C10-alkinylene, a substituted C3-C10-alkinylene which is substituted once or twice by C1-C6-alkyl, hydroxy, or C1-C6-alkoxy, and an isosterically replaced C1-C10-alkylene, C2-C10-alkenylene or C3-C10-alkinylene, having an isosterically replaced group having one to three methylene units which are each isosterically replaced by O, S, NR10, CO, SO or SO2, wherein R10 has the same meaning as R9, but is selected independently therefrom, E is R11 is selected from the group consisting of hydrogen, C1-C6-alkyl, hydroxy, hydroxymethyl, carboxy and C2-C7-alkoxycarbonyl, and R12 is selected from the group consisting of hydrogen, C1-C6-alkyl and an oxo group adjacent to the nitrogen atom, or R11 and R12 together form a C1-C3-alkylene bridge under formation of a bi-cyclic ring system, G is selected from the group consisting of hydrogen, G1, G2, G3, G4 and G5, wherein G1 is â€”(CH2)râ€”(CR14R15)sâ€”R13 â€ƒwherein r is an integer from 1 to 3 or 0, s is 0 or 1, R13 is selected from the group consisting of hydrogen, C1-C6-alkyl, C3-C6-alkenyl, C3-C6-alkinyl, C3-C8-cycloalkyl, benzyl, phenyl, anellated bi- and tricyclic aromatic or partially hydrogenated carbocyclic ring systems with 8 to 16 ring atoms and at least one aromatic ring, wherein the linkage occurs either over an aromatic or a hydrogenated ring and either directly or over a methylene group, R14 has the same meaning as R13, but is selected independently thereof, R15 is selected from the group consisting of hydrogen, hydroxy, methyl, benzyl, phenyl, anellated bi- and tricyclic aromatic or partially hydrogenated carbocyclic ring systems with 8 to 16 ring atoms and at least one aromatic ring, wherein the linkage occurs either over an aromatic or a hydrogenated ring and either directly or over a methylene group, G2 is selected from the group consisting of â€ƒwherein the substituents R13 and R15 have the above meaning, G3 is â€”SO2â€”(CH2)rR13 and G4 is â€ƒwherein Ar1 is selected from the group consisting of phenyl, and naphthyl, Ar2 is selected from the group consisting of phenyl, and naphthyl, and G5 is â€”COR16 â€ƒwherein R16 is selected from the group consisting of trifluoromethyl, C1-C6-alkoxy, C3-C6-alkenyloxy, and benzyloxy, and wherein aromatic rings in the substituents R1, R2, R4, R13, R14, R15, R16, Ar1 and Ar2 are substituted and unsubstituted, the substituted rings in R1, R2, R4, R13, R14, R15, R16, Ar1 and Ar2 having substitutents which are independently selected from halogen, cyano, C1-C6-alkyl, trifluoromethyl, C3-C8-cycloalkyl, phenyl, benzyl, hydroxy, C1-C6-alkoxy, benzyloxy, phenoxy, mercapto, C1-C6-alkylthio, carboxy, C1-C6-alkoxycarbonyl, benzyloxycarbonyl, nitro, amino, mono-C1-C6-alkylamino, di-(C1-C6-alkyl)-amino, and substituted C1-C6 alkoxy which is entirely or partially substituted by fluorine, wherein two adjacent groups on the aromatic ring may form an additional ring over a methylenedioxy bridge.