Patent ID: 6410577
Filing Date: 2002-06-25
Classification: A61P,C07D

Abstract:
A compound of formula (I): in whichR1, R1â€² are independently selected from H, F, Cl, Br, I, CF3, NO2, CN, COOH, COO(C1-C6)-alkyl, CONH2, CONH(C1-C6)-alkyl, CON[(C1-C6)-alkyl]2, (C1-C6)-alkyl, (C2-C6)-alkenyl, (C2-C6)-alkynyl, O-(C1-C6)-alkyl, wherein one or more of the hydrogens of the alkyl, alkenyl, or alkynyl radicals may be replaced by fluorine, or one hydrogen may be replaced by OH, OC(O)CH3, OC(O)H, Oâ€”CH2â€”Ph, NH2, NHâ€”COâ€”CH3 or N(COOCH2Ph)2; SO2â€”NH2, SO2NH(C1-C6)-alkyl, SO2N[(C1-C6)-alkyl]2, Sâ€”(C1-C6)-alkyl, Sâ€”(CH2)n-phenyl, SOâ€”(C1-C6)-alkyl, SOâ€”(CH2)n-phenyl, SO2â€”(C1-C6)-alkyl, SO2â€”(CH2)n-phenyl, wherein n is 0-6 and the phenyl radical may be substituted up to two times by F, Cl, Br, OH, CF3, NO2, CN, OCF3, Oâ€”(C1-C6)-alkyl, (C1-C6)-alkyl or NH2; NH2, NHâ€”(C1-C6)-alkyl, N[(C1-C6)-alkyl]2, NH(C1-C7)-acyl, phenyl, biphenylyl, Oâ€”(CH2)n-phenyl, where n is 0-6, 1- or 2-naphthyl, 2-, 3- or 4-pyridyl, 2- or 3-furanyl or 2- or 3-thienyl, wherein any of the phenyl, biphenyl, naphthyl, pyridyl, furanyl or thienyl rings may be optionally substituted one to 3 times by F, Cl, Br, I, OH, CF3, NO2, CN, OCF3, Oâ€”(C1-C6)-alkyl, (C1-C6)-alkyl, NH2, NH(C1-C6)-alkyl, N[(C1-C6)-alkyl]2, SO2â€”CH3, COOH, COOâ€”(C1-C6)-alkyl or CONH2; 1,2,3-triazol-5-yl, wherein the triazole ring may be substituted in the 1-, 2- or 3-position by methyl or benzyl; tetrazol-5-yl, where the tetrazole ring may be substituted in the 1 - or 2-position by methyl or benzyl; 1,3,4-oxadiazol-2-yl; 2-amino-1,3,4-oxadiazol-5-yl, wherein the amino function may be mono- or disubstituted by (C1-C6)-alkyl, â€”C(O)â€”(C1-C6)-alkyl, â€”C(O)â€”(cyclo-C3-C7)-alkyl, â€”C(O)-phenyl, â€”C(O)â€”NHâ€”(C1-C6)-alkyl, â€”C(O)â€”NHâ€”(cyclo-C3-C7)-alkyl, or â€”C(O)â€”NH-aryl, wherein aryl is phenyl, 2-, 3- or 4-pyridyl, 2- or 3-thienyl or 2- or 3-furanyl, â€”C(O)-morpholin-4-yl, â€”C(O)-piperidin-1-yl, â€”C(O)-piperazin-4-yl, â€”C(O)â€”1-methyl-, 1-benzyl-piperazin-4-yl, â€”SO2â€”(C1-C6)-alkyl or â€”SO2-phenyl, wherein the phenyl ring may be substituted up to two times by F, Cl, Br, CN, CF3, OH, OCF3, (C1-C6)-alkyl, Oâ€”(C1-C6)-alkyl, (CH2)n-phenyl, Oâ€”(CH2)n-phenyl, where n is 0-6, NH2, NH(C1-C6)-alkyl, N[(C1-C6)-alkyl]2, SO2â€”CH3, COOH, COOâ€”(C1-C6)-alkyl or CONH2; R2 is H, (C1-C6)-alkyl, (C3-C6)-cycloalkyl, (CH2)n-phenyl, (CH2)n-thienyl, (CH2)n-pyridyl, (CH2)n-furyl, C(O)â€”(C1-C6)-alkyl, C(O)â€”(C3-C6)-cycloalkyl, C(O)â€”(CH2)n-phenyl, C(O)â€”(CH2)n-thienyl, C(O)â€”(CH2)n-pyridyl or C(O)â€”(CH2)n-furyl, wherein n is 0-5 and in which any of phenyl, thienyl, pyridyl or furyl may be optionally substituted up to two times by Cl, F, CN, CF3, (C1-C3)-alkyl, OH or Oâ€”(C1-C6)-alkyl; R3 is H, (C1-C6)-alkyl, F, Cl, Br, CN, N3, Oâ€”(C1-C6)-alkyl, (CH2)n-phenyl, (CH2)n-thienyl, (CH2)n-pyridyl, (CH2)n-furyl, where n is 0-5 and in which any of phenyl, thienyl, pyridyl or furyl may be optionally substituted up to two times by Cl, F, CN, CF3, (C1-C3)-alkyl, OH or Oâ€”(C1-C6)-alkyl, (C2-C6)-alkynyl, (C2-C6)-alkenyl, OC(O)CH3, (CH2)nâ€”C(O)O(C1-C6)-alkyl, (CH2)nâ€”C(O)OH, (CH2)nâ€”C(O)NH2, (CH2)nâ€”C(O)NHCH3 or (CH2)nâ€”C(O)N(CH3)2, where n is 0-3; R4 is (C1-C8)-alkyl, (C3-C7)-cycloalkyl, (C2-C6)-alkenyl, (C2-C6)-alkynyl, (C4-C7)-cycloalkenyl, wherein one or more of the hydrogens of the alkyl radicals may be replaced by fluorine or one hydrogen may be replaced by OH, OC(O)CH3, OC(O)H, Oâ€”CH2â€”Ph or Oâ€”(C1-C4)-alkyl; is (CH2)n-pyrrolidin-1-yl, (CH2)n-piperidin-1-yl, (CH2)n-morpholin-4-yl, (CH2)n-piperazin-1-yl, (CH2)n-N-4-methylpiperazin-1-yl, (CH2)nâ€”N-4-benzylpiperazin-1-yl, (CH2)n-phthalimidoyl, where n is 1-6; (CH2)n-aryl or (CH2)n-heteroaryl, where n is 0-6 and aryl is phenyl, biphenylyl or 1 - or 2-naphthyl and heteroaryl is 2-, 3- or 4-pyridyl, 2- or 3-thienyl, 2- or 3-furyl, 2-, 4- or 5-thiazolyl, 2-, 4- or 5-oxazolyl, l-pyrazolyl, 3- or 5-isoxazolyl, 2- or 3-pyrrolyl, 2- or 3-pyridazinyl, 2-, 4- or 5-pyrimidinyl, 2-pyrazinyl, 2-(1,3,5-triazinyl), 2- or 5-benzimidazolyl, 2-benzothiazolyl, 1,2,4-triazol-3-yl, 1,2,4-triazol-5-yl, tetrazol-5-yl, indol-3-yl, indol-5-yl or N-methylimidazol-2-, -4- or -5-yl, wherein the aryl radical or the heteroaryl radical may be optionally substituted up to two times by F, Cl, Br, OH, CF3, NO2, CN, OCF3, Oâ€”(C1-C6)-alkyl, Sâ€”(C1-C6)-alkyl, SOâ€”(C1-C6)-alkyl, (CH2)nâ€”SO2â€”(C1-C6)-alkyl, (CH2)nâ€”SO2â€”NH2, (CH2)nâ€”SO2â€”N(&boxH;CHâ€”N(CH3)2), wherein n is 0-6, (C1-C6)-alkyl, (C3-C6)-cycloalkyl, COOH, COO(C1-C6)-alkyl, COO(C3-C6)-cycloalkyl, CONH2, CONH(C1-C6)-alkyl, CON[(C1-C6)-alkyl]2, CONH(C3-C6)-cycloalkyl, NH2, NHâ€”COâ€”(C1-C6)-alkyl, NHâ€”CO-phenyl, NHâ€”SO2-(C1-C6)-alkyl, NHâ€”SO2-phenyl, wherein the phenyl ring may be substituted up to two times by F, Cl, CN, OH, (C1-C6)-alkyl, Oâ€”(C1-C6)-alkyl, CF3, COOH, COO(C1-C6)-alkyl or CONH2; pyrrolidin-1-yl, morpholin-1-yl, piperidin-1-yl, piperazin-1-yl, 4-methylpiperazin-1-yl, (CH2)n-phenyl, Oâ€”(CH2)n-phenyl, Sâ€”(CH2)n-phenyl or SO2â€”(CH2)n-phenyl, wherein n is 0-3; (CH2)nâ€”Aâ€”R8, wherein n is 1-6; A is O, NH, Nâ€”(C1-C6)-alkyl, NCHO, N(COâ€”CH3), S, SO or SO2; R8 is (C1-C8)-alkyl, (C3-C8)-cycloalkyl, wherein one or more hydrogens of the alkyl radicals may be replaced by fluorine or one hydrogen may be replaced by OH, OC(O)CH3, OC(O)H, Oâ€”CH2â€”Ph or Oâ€”(C1-C4)-alkyl; is (CH2)m-aryl, wherein m is 0-6 and aryl is phenyl, thienyl or pyridyl and the aryl moiety may be optionally substituted up to two times by F, Cl, Br, OH, CF3, NO2, CN, OCF3, Oâ€”(C1-C6)-alkyl, Sâ€”(C1-C6)-alkyl, SOâ€”(C1-C6)-alkyl, (CH2)nâ€”SO2â€”(C1-C6)-alkyl, (CH2)nâ€”SO2â€”NH2, (CH2)nâ€”SO2â€”N(&boxH;CHâ€”N(CH3)2), (CH2)nâ€”SO2â€”NH(C1-C8)-alkyl, (CH2)nâ€”SO2â€”N[(C1-C8)-alkyl]2, (CH2)nâ€”SO2â€”NH(C3-C8)-cycloalkyl, (CH2)nâ€”SO2â€”N[(C3-C8)-cycloalkyl2], where n is 0-6, (C1-C6)-alkyl, (C3-C6)-cycloalkyl, COOH, COO(C1-C6)-alkyl, COO(C3-C6)-cycloalkyl, CONH2, CONH(C1-C6)-alkyl, CON[(C1-C6)-alkyl]2, CONH(C3-C6)-cycloalkyl, NH2, NH(C1-C6)-alkyl, N[(C1-C6)-alkyl]2, NHâ€”COâ€”(C1-C6)-alkyl, NHâ€”CO-phenyl, NHâ€”SO2-phenyl, where the phenyl ring may be optionally substituted up to two times by F, Cl, CN, OH, (C1-C6)-alkyl, Oâ€”(C1-C6)-alkyl, CF3, COOH, COO(C1-C6)-alkyl or CONH2; NHâ€”SO2â€”(C1-C8)-alkyl, N(C1-C6)-alkyl-SO2â€”(C1-C8)-alkyl, pyrrolidin-1-yl, morpholin-1-yl, piperidin-1-yl, piperazin-1-yl, 4-methylpiperazin-1-yl, (CH2)p-phenyl, Oâ€”(CH2)p-phenyl, Sâ€”(CH2)p-phenyl or SO2â€”(CH2)p-phenyl, wherein p is 0-3; R5 is H; R6 is Cl, Br, OH, Oâ€”(C1-C6)-alkyl, Oâ€”(CH2)n-aryl, Oâ€”(CH2)n-heteroaryl wherein n is 0-6 and aryl is phenyl and heteroaryl is 2-, 3- or 4-pyridyl or 2- or 3-thienyl; Oâ€”C(O)â€”H, Oâ€”C(O)â€”(C1-C6)-alkyl, Oâ€”C(O)â€”(C3-C8)-cycloalkyl, Oâ€”C(O)-aryl, Oâ€”C(O)-heteroaryl, wherein aryl is phenyl and heteroaryl is pyridyl, thienyl or furanyl; O-alpha- or -beta-glucuronic acid, SH, Sâ€”(C1-C6)-alkyl, Sâ€”(CH2)n-phenyl, wherein n is 0-6, Sâ€”C(O)â€”(C1-C6)-alkyl, Sâ€”C(O)â€”(C3-C8)-cycloalkyl, Sâ€”C(O)-phenyl; SOâ€”(C1-C6)-alkyl, SOâ€”(CH2)n-phenyl, wherein n is 0-6, SO2â€”(C1-C6)-alkyl, SO2â€”(CH2)n-phenyl, wherein n is 0-6, NH2, NHâ€”(C1-C6)-alkyl, NHâ€”(C3-C7)-cycloalkyl, N[(C1-C6)-alkyl]2, morpholin-4-yl, pyrrolidin-1-yl, piperidin-1-yl, piperazin-1-yl, 1-methylpiperazin-4-yl, 1-benzylpiperazin-4-yl, NH-phenyl, NHâ€”CH2-phenyl, NHâ€”C(O)â€”(C1-C6)-alkyl or NHâ€”C(O)-phenyl; or and their physiologically acceptable salts and physiologically functional derivatives.