Patent ID: 6387935
Filing Date: 2002-05-14
Classification: A61K,A61P,C07D

Abstract:
A compound of formula I: wherein:Y is selected from the group consisting of a direct bond, â€”CH2â€”, and â€”CH2â€”CH2â€”; X is selected from the group consisting of CH2, CH(CH3), CH(C2H5), CH(C3H7), and CH(C6H5); R1, R1â€² are independently selected from the group consisting of 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, Oâ€”(C1-C6)-alkyl, wherein one or more of the hydrogens in the alkyl moieties may be optionally replaced by fluorine, or a hydrogen may be optionally replaced by OH, OC(O)CH3, OC(O)H, Oâ€”CH2â€”Ph, NH2, NHâ€”COâ€”CH3 or N(COOCH2Ph)2, â€ƒSO2â€”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, where n is 0-6 and wherein the phenyl radical is optionally substituted in up to two positions by F, Cl, Br, OH, CF3, NO2, CN, OCF3, Oâ€”(C1C6)-alkyl, (C1-C6)-alkyl, or NH2; â€ƒNH2, NHâ€”(C1-C6)-alkyl, N((C1-C6)-alkyl)2, NH(C1-C7)-acyl, phenyl, biphenyl, Oâ€”(CH2)n-phenyl, where n is 0-6, 1- or 2-naphthyl, 2-, 3- or 4-pyridyl, 2-or 3-furanyl, 2- or 3-thienyl, wherein the phenyl, biphenyl, naphthyl, pyridyl, furanyl or thienyl rings may be independently optionally substituted up to 3 times by F, Cl, Br, I, OH, CF3, NO2, CN, OCF3, Oâ€”(C1-C6)-alkyl, (C1-6)-alkyl, NH2, NH(C1-C6)-alkyl, N((C1-C6)-alkyl)2, SO2â€”CH3, COOH, COOâ€”(C1-C6)-alkyl, or CONH2; â€ƒ1,2,3-triazol-5-yl, wherein the triazole ring may be optionally substituted in the 1-, 2- or 3-position by methyl or benzyl; and â€ƒtetrazol-5-yl, wherein the tetrazole ring may be optionally substituted in the 1- or 2-position by methyl or benzyl; R2 is selected from the group consisting of H, (C1-6)-alkyl, (C3-C6)-cycloalkyl, (CH2)nâ€²-phenyl, (CH2)nâ€²-thienyl, (CH2)nâ€²-pyridyl, (CH2)nâ€²-furyl, C(O)â€”(C1-C6)-alkyl, C(O)â€”(C3-C6)-cycloalkyl, C(O)â€”(CH2)nâ€²-phenyl, C(O)â€”(CH2)nâ€²-thienyl, C(O)â€”(CH2)nâ€²-pyridyl and C(O)â€”(CH2)nâ€²-furyl, where nâ€² is 0-5, wherein the phenyl, thienyl, pyridyl, or furyl ring may be optionally substituted up to two times by Cl, F, CN, CF3, (C1-C3)-alkyl, OH or Oâ€”(C1-C6)-alkyl; R3 is selected from the group consisting of H, (C1-C6)-alkyl, F, CN, N3, Oâ€”(C1-C6)-alkyl, (CH2)nâ€²-phenyl, (CH2)nâ€²-thienyl, (CH2)nâ€²-pyridyl and (CH2)nâ€²-furyl, where nâ€² is 0-5, wherein the phenyl, thienyl, pyridyl, or furyl ring 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, C(O)OCH3, C(O)OCH2CH3, C(O)OH, C(O)NH2, C(O)NHCH3, C(O)N(CH3)2, or OC(O)CH3; R4 is selected from the group consisting of (C8-C6)-cycloalkyl, wherein one or more hydrogens of the alkyl moiety may be optionally replaced by fluorine, or a hydrogen may be optionally replaced by OH, OC(O)CH3, OC(O)H, Oâ€”CH2â€”Ph or Oâ€”(C1-C4)-alkyl; â€ƒ(CH2)nâ€³â€”Aâ€”R8, where nâ€³ is 1-6, except for when (CH2)nâ€³â€”Aâ€”R8 is â€”CH2â€”Oâ€”CH2-phenyl, then the phenyl moiety is unsubstituted; and â€ƒ(CH2)râ€”Bâ€”R9, where r is 1-6; A is selected from the group consisting of O, S, SO and SO2; B is selected from the group consisting of NH, Nâ€”(C1-6)-alkyl, NCHO and N(COâ€”CH3); R8 is selected from the group consisting of (C5-C24)-alkyl, (C3-C10)-cycloalkyl, wherein one or more hydrogens of the alkyl radical may be optionally replaced by fluorine, or a hydrogen may be optionally replaced by OH, OC(O)CH3, OC(O)H, Oâ€”CH2â€”Ph or Oâ€”(C1-C4)-alkyl; and â€ƒ(CH2)m-aryl, where m is 0-6 and aryl is selected from the group consisting of phenyl, naphthyl, biphenyl, thienyl and pyridyl; wherein 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, SO2â€”(C1-C6)-alkyl, SO2â€”NH2, SO2â€”NH(C1-C8-alkyl), SO2â€”N(C1-C8-alkyl)2, SO2â€”NH(C3-C8-cycloalkyl), SO2â€”N(C3-C8-cycloalkyl)2, (CH2)mâ€², â€”SO2â€”NH2, (CH2)mâ€”SO2â€”NHâ€”(C1-C6)-alkyl, (CH2)mâ€²â€”SO2â€”N((C1-C6)-alkyl)2, where mâ€² is 1-6, SO2â€”N(&boxH;CHâ€”N(CH3)2), (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€”COâ€”phenyl, NHâ€”SO2â€”(C1-C8-alkyl), N(C1-C6-alkyl)â€”SO2â€”(C1-C8-alkyl), NHâ€”SO2-phenyl, wherein 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, â€ƒpyrrolidin-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, where p is 0-3; R9 is (CH2)m-aryl, where m is 0-6 and aryl is selected from the group consisting of phenyl, naphthyl, biphenyl, thienyl and pyridyl; wherein 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€”(C1-6)-alkyl, SOâ€”(C1-C6)-alkyl, SO2â€”(C1-C6)-alkyl, SO2â€”NH2, SO2â€”NH(C1-C8-alkyl), SO2â€”N(C1C8-alkyl)2, SO2â€”NH(C3-C8-cycloalkyl), SO2â€”N(C3-C8-cycloalkyl)2, (CH2)mâ€²â€”SO2â€”NH2, (CH2)mâ€”SO2â€”NHâ€”(C1-C6)-alkyl, (CH2)mâ€²â€”SO2â€”N((C1-C6)-alkyl)2, where mâ€² is 1-6, SO2â€”N(&boxH;CHâ€”N(CH3)2), (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€”COâ€”phenyl, NHâ€”SO2â€”(C1-C8-alkyl), N(C1-C6-alkyl)â€”SO2â€”(C1-C8-alkyl), NHâ€”SO2-phenyl, wherein 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, â€ƒpyrrolidin-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, where p is 0-3; and a physiologically acceptable salt thereof.