Patent ID: 6818632
Filing Date: 2004-11-16
Classification: A61P,C07D,C07F

Abstract:
A compound of the formula (I): wherein one of Y, Z, A, and D is nitrogen and the others are carbon; X is CH, CCF3, C(C1-C12 aliphatic); R1 is selected from the group consisting of: hydrogen, C1-12 aliphatic, thiol, hydroxy, hydroxy-C1-12 aliphatic, Aryl, Aryl-C1-12 aliphatic, R9-Aryl-C1-12 aliphatic, Cyc, Cyc-C1-6 aliphatic, Het, Het-C1-12aliphatic, C1-12alkoxy, Aryloxy, amino, C1-12 aliphatic amino, di-C1-12 aliphatic amino, di-C1-12 aliphatic aminocarbonyl, di-C1-12 aliphatic aminosulfonyl, C1-12 alkoxycarbonyl, fluoro, bromo, iodo, cyano, sulfonamide, or nitro, where R9, Aryl, Cyc and Het are as defined below; R2 is selected from the group consisting of: hydrogen, C1-12 aliphatic, N-hydroxyimino-C1-12 aliphatic, C1-12 alkoxy, hydroxy-C1-12 aliphatic, C1-12 alkoxycarbonyl, carboxyl C1-12 aliphatic, Aryl, R9-Aryl-oxycarbonyl, R9-oxycarbonyl-Aryl, Het, aminocarbonyl, C1-12 aliphatic-aminocarbonyl, Aryl-C1-12 aliphatic-aminocarbonyl, R9-Aryl-C1-12 aliphatic-aminocarbonyl, Het-C1-12 aliphatic-aminocarbonyl, hydroxy-C1-12 aliphatic-aminocarbonyl, C1-12-alkoxy-C1-12 aliphatic-aminocarbonyl, C1-12 alkoxy-C1-12 aliphatic-amino, di-C1-12 aliphatic amino, di-C1-12 aliphatic aminocarbonyl, di-C1-12 aliphatic aminosulfonyl, halogen, hydroxy, C1-12 aliphatic-sulfonyl, aminosulfonyl, and C1-12 aliphatic-aminosulfonyl, where R9, Aryl and Het are as defined below; R1 and R2 are optionally joined to form a fused ring selected from the group as defined for Het below, and said fused ring is optionally substituted by a substituent selected from the group consisting of: C1-12 aliphatic, halogen, nitro, cyano, C1-12 alkoxy, amino, hydroxyl, (R10, R11)-amino, and oxo; R3 is selected from the group consisting of: hydrogen, C1-12 aliphatic, hydroxy, hydroxy aliphatic, di-C1-12 aliphatic amino, di-C1-12 aliphatic aminocarbonyl, di-C1-12 aliphatic aminosulfonyl, C1-12 alkoxy, Aryl, Aryloxy, hydroxy-Aryl, Het, hydroxy-Het, Het-oxy, or halogen, where Aryl and Het are as defined below; R2 and R3 are optionally joined to form a fused ring selected from the group as defined for Het below, and said fused ring is optionally substituted by C1-12 aliphatic or C1-12 aliphatic-carbonyl; with the provisa that R1, R2, and R3 cannot simultaneously be hydrogen; R4, R5 and R6 may be the same or different and are independently selected from the group consisting of: hydrogen, C1-12 aliphatic, thiol, C1-12 aliphatic-thia, di(trifluormethyl)hydroxymethyl, carboxamide, mono-C1-12 aliphatic aminocarbonyl, hydroxy, hydroxy-C1-12 aliphatic, Aryl, Aryl-C1-12 aliphatic, R9-Aryl-C1-12 aliphatic, Lye, Cyc-C1-12 aliphatic, Het, Het-C1-12 aliphatic, C1-12 alkoxy, Aryloxy, Het-oxy, amino, (R10,R11)-amino-C1-12 aliphatic aminocarbonyl, (R10,R11)-amino-C1-12 aliphatic alkoxycarbonyl, (R10,R11)-amino-C1-12 aliphatic aminocarbonylamino, (R10,R11)-amino-C1-6 aliphatic alkoxycarbonylamino, (R10,R11-amino-C1-6 aliphaticsulfonyl, Het-C1-6 aliphatic aminocarbonyl, Het-C1-6 aliphatic aminocarbonylamino, Het-C1-6 alkoxycarbonylamino, Het-C1-6 aliphatic carbonyl, Het-C1-6 alkoxycarbonyl, C1-6 aliphaticsulfonyl-C1-6 aliphatic aminoalkyl, C1-6 aliphaticsulfonyl-C1-6 aliphatic aminoalkyl-Het-, C1-6 alkoxycarbonyl, C1-6 aliphatic carbonylamino, (C1-6 aliphatic carbonyl)(C1-6 aliphatic)amino, (R10,R11-amino-C1-6 aliphatic carbonylamino, [(R10,R11)-amino-C1-6 aliphatic carbonyl][C1-6 aliphatic]amino, (R10,R11-amino-C1-6 aliphatic sulfonylamino, [(R10,R11-amino-C1-6 aliphaticsulfonyl][C1-6 aliphatic]amino, halogen, cyano, diethoxyphosphorylmethyl, nitro, trifluromethyl, and trifluoromethoxy, where R9, R10, R11, Aryl, Cyc and Het are as defined below; R7 and R8 may be the same or different and are independently selected from the group consisting of: hydrogen, halogen, C1-12 alkoxy, hydroxy, C1-3-aliphatic, and C1-3 aliphatic; with the proviso that R4, R5, R6, R7, and R8 cannot simultaneously be hydrogen; wherein R7 may additionally be optionally fused to R5 so as to form a fused benzo ring from the R5 to the R7 positions; R9 is selected from the group consisting of: C1-12 aliphatic, hydroxy, C1-12 alkoxy and halogen; R10 and R11 may be the same or different and are independently selected from the group consisting of: hydrogen, C1-6 aliphatic and Het; Aryl is selected from the group consisting of: phenyl, naphthyl, phenanthryl and anthracenyl; Cyc is selected from the group consisting of: cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl, and optionally has one or more degrees of unsaturation; Het is a saturated or unsaturated heteroatom ring system selected from the group consisting of: benzimidazole, dihydrothiophene, dioxin, dioxane, dioxolane, dithiane, dithiazine, dithiazole, dithiolane, furan, imidazole, isoquinoline, morpholine, oxazole, oxadiazole, oxathiazole, oxathiazolidine, oxazine, oxadiazine, piperazine, piperidine, pyran, pyrazine, pyrazole, pyridine, pyrimidine, pyrrale, pyrrolidine, quinoline, tetrahydrofuran, tetrazine, thiadiazine, thiadiazole, thiatriazole, thiazine, thiazole, thiomorpholine, thiophene, thiopyran, triazine and triazole, where any of said heterocyclic rings may be optionally substituted by a substituent selected from the group consisting of: C1-12 aliphatic, hydroxy, C1-12 alkoxy, (R10,R11)-amino, (R10,R11)-amino-C1-12 aliphatic, (R10,R11)-amino-C1-12 aliphatic amino, oxo and dioxo; and salts, solvates, and prodrugs thereof in either crystalline or amorphous form.