Patent ID: 6627634
Filing Date: 2003-09-30
Classification: A61P,C07D

Abstract:
A compound of formula (I): wherein: X is a nitrogen atom; Ra is a hydrogen atom or a C1-4-alkyl group; Rb is a phenyl, benzyl, or 1-phenylethyl group, wherein the phenyl nucleus in each case is substituted by the groups R1 to R3, wherein R1 and R2, which are identical or different, are each a hydrogen, fluorine, chlorine, bromine, or iodine atom, a C1-4-alkyl, hydroxy, C1-4-alkoxy, C3-6-cycloalkyl, C4-6-cycloalkoxy, C2-5-alkeny, or C2-5-alkynyl group, an aryl, aryloxy, arylmethyl, or arylmethoxy group, a C3-5-alkenyloxy or C3-5-alkynyloxy group, wherein the unsaturated moiety is not linked to the oxygen atom, a C1-4-alkylsulfenyl, C1-4-alkylsulfinyl, C1-4-alkylsulfonyl, C1-4-alkylsulfonyloxy, trifluoromethylsulfenyl, trifluoromethylsulfinyl, or trifluoromethylsulfonyl group, a methyl or methoxy group substituted by 1 to 3 fluorine atoms, an ethyl or ethoxy group substituted by 1 to 5 fluorine atoms, a cyano or nitro group or an amino group optionally substituted by one or two C1-4-alkyl groups, wherein the substituents are identical or different, or R1 together with R2, if they are bound to adjacent carbon atoms, are a â€”CH&boxH;CHâ€”CH&boxH;CHâ€”, â€”CH&boxH;CHâ€”NHâ€”, or â€”CH&boxH;Nâ€”NHâ€” group, and R3 is a hydrogen, fluorine, chlorine, or bromine atom, or a C1-4-alkyl, trifluoromethyl, or C1-4-alkoxy group; Rc is a hydrogen atom or a C1-4-alkyl group; Rd is a hydrogen atom, or a C1-6-alkoxy, C4-7-cycloalkoxy, or C3-7-cycloalkyl-C1-4-alkoxy group, a C2-6-alkoxy group substituted from position 2 by a hydroxy, C1-4-alkoxy, C4-7-cycloalkoxy, C3-7-cycloalkyl-C1-3-alkoxy, di-(C1-4-alkyl)-amino, pyrrolidino, piperidino, morpholino, piperazino, or 4-(C1-4-alkyl)piperazino group, wherein the cyclic imino groups thereof are optionally substituted by one or two C1-2-alkyl groups, or a tetrahydrofuran-3-yloxy, tetrahydropyran-3-yloxy, tetrahydropyran-4-yloxy, tetrahydrofuranylmethoxy, or tetrahydropyranylmethoxy group; A is a 1,1- or 1,2-vinylene group optionally substituted by a methyl or trifluoromethyl group or by two methyl groups, or a 1,3-butadien-1,4-ylene group optionally substituted by a methyl or trifluoromethyl group or by two methyl groups, or an ethynylene group; B is a C1-6-alkylene group wherein one or two hydrogen atoms are optionally replaced by fluorine atoms, or, if B is bound to a carbon atom of C, it is optionally a bond; and C is a pyrrolidino group wherein the two hydrogen atoms in the 2 position are replaced by D, a pyrrolidino group wherein the two hydrogen atoms in the 3 position are replaced by E, a piperidino or hexahydroazepino group wherein the two hydrogen atoms in the 2 position are replaced by D, a piperidino or hexahydroazepino group wherein the two hydrogen atoms in the 3 position or in the 4 position are replaced by E, a piperazino or 4-(C1-4-alkyl)piperazino group wherein the two hydrogen atoms in the 2 position or in the 3 position of the piperazino ring are replaced by D, a pyrrolidino or piperidino group wherein two vicinal hydrogen atoms are replaced by an â€”Oâ€”COâ€”CH2â€”, â€”CH2â€”Oâ€”COâ€”, â€”Oâ€”COâ€”CH2CH2â€”, â€”CH2â€”Oâ€”COâ€”CH2â€”, â€”CH2CH2â€”Oâ€”COâ€”, â€”Oâ€”COâ€”CH2â€”NR4â€”, or â€”Oâ€”COâ€”CH2â€”Oâ€” bridge optionally substituted by one or two C1-2-alkyl groups, wherein the heteroatoms of the bridge thereof are not bound at the 2 or 5 position of the pyrrolidine ring and are not bound at the 2 or 6 position of the piperidino ring, a piperazino or 4-(C1-4-alkyl)piperazino group wherein a hydrogen atom in the 2 position together with a hydrogen atom in the 3 position of the piperazino ring are replaced by a â€”CH2â€”Oâ€”COâ€”CH2â€” or â€”CH2CH2â€”Oâ€”COâ€” bridge optionally substituted by one or two C1-2-alkyl groups, a piperazino group wherein a hydrogen atom in the 3 position together with the hydrogen atom in the 4 position are replaced by a â€”COâ€”Oâ€”CH2CH2â€” or â€”CH2â€”Oâ€”COâ€”CH2â€” bridge optionally substituted by one or two C1-2-alkyl groups, wherein in each case the left-hand end of the bridge thereof is bound to the 3 position of the piperazino ring, a pyrrolidino, piperidino, or hexahydroazepino group substituted by R5, a pyrrolidino group substituted in the 3 position by a 2-oxomorpholino group, wherein the 2-oxomorpholino group is optionally substituted by one or two C1-2-alkyl groups, a piperidino or hexahydroazepino group substituted in the 3 or 4 position by a 2-oxomorpholino group, wherein the 2-oxomorpholino group is optionally substituted by one or two C1-2-alkyl groups, a 4-(C1-4-alkyl)piperazino or 4-(C1-4-alkyl)-homopiperazino group substituted at a cyclic carbon atom by R5, a piperazino or homopiperazino group substituted in the 4 position by R6, a pyrrolidino group substituted in the 3 position by a (R4NR6), R6O, R6S, R6SO, or R6SO2 group, a piperidino or hexahydroazepino group substituted in the 3 or 4 position by an (R4NR6), R6O, R6S, R6SO, or R6SO2 group, a pyrrolidino, piperidino, or hexahydroazepino group substituted by a R5â€”C1-4-alkyl, (R4NR6)â€”C1-4-alkyl, R6Oâ€”C1-4-alkyl, R6Sâ€”C1-4-alkyl, R6SOâ€”C1-4-alkyl, R6SO2â€”C1-4-alkyl, or R4NR6â€”CO group, a pyrrolidino group substituted in the 3 position by a R5â€”COâ€”NR4, R5â€”C1-4-alkylene-CONR4, (R4N6)â€”C1-4-alkylene-CONR4, R6Oâ€”C1-4-alkylene-CONR4, R6Sâ€”C1-4-alkylene-CONR4, R6SOâ€”C1-4-alkylene-CONR4, R6SO2â€”C1-4-alkylene-CONR4, 2-oxomorpholino-C1-4-alkylene-CONR4, R5â€”C1-4-alkylene-Y, or C2-4-alkyl-Y group, wherein the C2-4-alkyl moiety of the C2-4-alkyl-Y group is substituted from position 2 by a (R4NR6), R6O, R6S, R6SO, or R6SO2 group and the 2-oxomorpholino moiety is optionally substituted by one or two C1-2-alkyl groups, a piperidino or hexahydroazepino group substituted in the 3 or 4 position by a R5â€”COâ€”NR4, R5â€”C1-4-alkylene-CONR4, (R4NR6)â€”C1-4-alkylene-CONR4, R6Oâ€”C1-4-alkylene-CONR4, R6Sâ€”C1-4-alkylene-CONR4, R6SOâ€”C1-4-alkylene-CONR4, R6SO2â€”C1-4-alkylene-CONR4, 2-oxomorpholino-C1-4-alkylene-CONR4, R5â€”C1-4-alkylene-Y, or C2-4-alkyl-Y group, wherein the 2-oxomorpholino moiety is optionally substituted by one or two C1-2-alkyl groups and the C2-4-alkyl moiety of the C2-4-alkyl-Y group is substituted from position 2 by a (R4NR6), R6O, R6S, R6SO, or R6SO2 group, a 4-(C1-4-alkyl)piperazino or 4-(C1-4-alkyl)-homopiperazino group substituted at a cyclic carbon atom by an R5â€”C1-4-alkyl, (R4NR6)â€”C1-4-alkyl, R6â€”Oâ€”C1-4-alkyl, R6Sâ€”C1-4-alkyl R6SOâ€”C1-4-alkyl, R6SO2â€”C1-4-alkyl, or R4NR6â€”CO group, a piperazino or homopiperazino group substituted in the 4 position by an R5â€”C1-4-alkyl, R5â€”CO, R5â€”C1-4-alkylene-CO, (R4NR6)â€”C1-4-alkylene-CO, R6Oâ€”C1-4-alkylene-CO, R6Sâ€”C1-4-alkylene-CO, R6SOâ€”C1-4-alkylene-CO, or R6SO2â€”C1-4-alkylene-CO group, a piperazino or homopiperazino group substituted in the 4 position by a C2-4-alkyl group, wherein the C2-4-alkyl group is substituted from position 2 by an (R4NR6), R6O, R6S, R6SO, or R6SO2 group, a pyrrolidino, piperidino, or hexahydroazepino group substituted by a 2-oxomorpholino-C1-4-alkyl group, wherein the 2-oxomorpholino moiety is optionally substituted by one or two C1-2-alkyl groups, a pyrrolidino group substituted in the 3 position by a C2-4-alkyl-Y group, wherein the C2-4-alkyl moiety of the C2-4-alkyl-Y group is substituted from position 2 by a 2-oxomorpholino group optionally substituted by one or two C1-2-alkyl groups, a piperidino or hexahydroazepino group substituted in the 3 or 4 position by a C2-4-alkyl-Y group wherein the C2-4-alkyl moiety of the C2-4-alkyl-Y group is substituted from position 2 by a 2-oxomorpholino group optionally substituted by one or two C1-2-alkyl groups, a 4-(C1-4-alkyl)piperazino or 4-(C1-4-alkyl)-homopiperazino group substituted at a cyclic carbon atom by a 2-oxomorpholino-C1-4-alkyl group, wherein the 2-oxomorpholino moiety is optionally substituted by one or two C1-2-alkyl groups, a piperazino or homopiperazino group substituted in the 4 position by a 2-oxomorpholino-C1-4-alkylene-CO group, wherein the 2-oxomorpholino moiety is optionally substituted by one or two C1-2-alkyl groups, a piperazino or homopiperazino group substituted in the 4 position by a C2-4-alkyl group, wherein the C2-4-alkyl moiety is substituted from position 2 by a 2-oxomorpholino group optionally substituted by one or two C1-2-alkyl groups, a pyrrolidinyl or piperidinyl group substituted in the 1 position by R6, by an R5â€”C1-4-alkyl, R5â€”CO, R5â€”C1-4-alkylene-CO, (R4NR6)â€”C1-4-alkylene-CO, R6Oâ€”C1-4-alkylene-CO, R6Sâ€”C1-4-alkylene-CO, R6SOâ€”C1-4-alkylene-CO, R6SO2â€”C1-4-alkylene-CO, or 2-oxomorpholino-C1-4-alkylene-CO group, wherein the 2-oxomorpholino moiety is optionally substituted by one or two C1-2-alkyl groups, a pyrrolidinyl or piperidinyl group substituted in the 1 position by a C2-4-alkyl group, wherein the C2-4-alkyl moiety is substituted from position 2 by an (R4NR6), R6O, R6S, R6SO, R6SO2, or 2-oxomorpholino group, wherein the 2-oxomorpholino moiety is optionally substituted by one or two C1-2-alkyl groups, a pyrrolidin-3-yl-NR4, piperidin-3-yl-NR4, or piperidin-4-yl-NR4 group substituted in each case at the cyclic nitrogen atom by R6, by an R5â€”C1-4-alkyl, R5â€”CO, R5â€”C1-4-alkylene-CO, (R4NR6)â€”C1-4-alkylene-CO, R6Oâ€”C1-4-alkylene-CO, R6Sâ€”C1-4-alkylene-CO, R6SOâ€”C1-4-alkylene-CO, R6SO2â€”C1-4-alkylene-CO, or 2-oxomorpholino-C1-4-alkylene-CO group, wherein the 2-oxomorpholino moiety is optionally substituted by one or two C1-2-alkyl groups, a pyrrolidin-3-yl-NR4, piperidin-3-yl-NR4, or piperidin-4-yl-NR4 group substituted in each case at the cyclic nitrogen atom by a C2-4-alkyl group, wherein the C2-4-alkyl moiety is substituted from position 2 by an (R4NR6), R6O, R6S, R6SO, R6SO2, or 2-oxomorpholino group, wherein the 2-oxomorpholino moiety is optionally substituted by one or two C1-2-alkyl groups, a R5â€”C1-4-alkylene-NP4 group, or a C2-4-alkyl-NR4-group, wherein the C2-4-alkyl moiety is substituted from position 2 by an (R4NR6), R6O, R6S, R6SO, R6SO2, or 2-oxomorpholino group, wherein the 2-oxomorpholino moiety is optionally substituted by one or two C1-2-alkyl groups, wherein: D is a â€”CH2â€”Oâ€”COâ€”CH2â€”, â€”CH2CH2â€”Oâ€”COâ€”, â€”CH2â€”Oâ€”COâ€”CH2CH2â€”, â€”CH2CH2â€”Oâ€”COâ€”CH2â€”, or â€”CH2CH2CH2â€”Oâ€”COâ€” bridge optionally substituted by one or two C1-2-alkyl groups; E is an â€”Oâ€”COâ€”CH2CH2â€”, â€”CH2â€”Oâ€”COâ€”CH2â€”, â€”CH2CH2â€”Oâ€”COâ€”, â€”Oâ€”COâ€”CH2CH2CH2â€”, â€”CH2â€”Oâ€”COâ€”CH2CH2â€”, â€”CH2CH2â€”Oâ€”COâ€”CH2â€”, â€”CH2CH2CH2â€”Oâ€”COâ€”, â€”Oâ€”COâ€”CH2â€”NR4â€”CH2â€”, â€”CH2â€”Oâ€”COâ€”CH2â€”NR4â€”, â€”Oâ€”COâ€”CH2â€”Oâ€”CH2â€”, or â€”CH2â€”Oâ€”COâ€”CH2â€”Oâ€” bridge optionally substituted by one or two C1-2-alkyl groups; R4 is a hydrogen atom or a C1-4-alkyl group; R5 is a 2-oxotetrahydrofuranyl, 2-oxotetrahydropyranyl, 2-oxo-1,4-dioxanyl, or 2-oxo-4-(C1-4-alkyl)-morpholinyl group optionally substituted by one or two C1-2-alkyl groups; and R6 is a 2-oxotetrahydrofuran-3-yl, 2-oxotetrahydrofuran-4-yl, 2-oxotetrahydropyran-3-yl, 2-oxotetrahydropyran-4-yl, or 2-oxotetrahydropyran-5-yl group optionally substituted by one or two C1-2-alkyl groups, and Y is an oxygen or sulfur atom, or an imino, N-(C1-4-alkyl)-imino, sulfinyl, or sulfonyl group, and wherein the aryl moieties are phenyl groups which are each optionally mono- or disubstituted by Râ€², wherein the substituents are identical or different, and Râ€² is a fluorine, chlorine, bromine, or iodine atom, or a C1-2-alkyl, trifluoromethyl, or C1-2-alkoxy group, or two groups Râ€², if they are bound to adjacent carbon atoms, are together a C3-4-alkylene, methylenedioxy, or 1,3-butadien-1,4-ylene group, or a tautomer, stereoisomer, or salt thereof.