Patent ID: 6436943
Filing Date: 2002-08-20
Classification: A61P,C07D

Abstract:
A method of treating a hepatitis B infection in a mammal, comprising administering an effective amount of a dihydropyrimidine of the general formula (I)or its mesomeric form (Ia) in whichR1 is phenyl, furyl, thienyl, triazolyl, pyridyl, cycloalkyl having from 3 to 6 carbon atoms or is a radical of the formula where the abovementioned ring systems are optionally mono- or polysubstituted, identically or differently, by substituents chosen from the group consisting of halogen, trifluoromethyl, nitro, cyano, trifluoromethoxy, carboxyl, hydroxyl, (C1-C6)-alkoxy, (C1-C6)-alkoxycarbonyl and (C1-C6)-alkyl which in turn can be substituted by aryl having from 6 to 10 carbon atoms or halogen, and/or the above ring systems are optionally substituted by groups of the formulae â€”Sâ€”R6, NR7R8, COâ€”NR9R10, SO2â€”CF3, and â€”Aâ€”CH2â€”R11, wherein R6 is phenyl, which is optionally substituted by halogen, R7, R8, R9, and R10 are identical or different and are hydrogen, phenyl, hydroxy-substituted phenyl, hydroxyl, (C1-C6)-acyl or (C1-C6)-alkyl, which for its part may be substituted by hydroxyl, (C1-C6)-alkoxycarbonyl, phenyl or hydroxy-substituted phenyl, A is a radical O, S, SO or SO2, R11 is phenyl, which is optionally mono- or polysubstituted, identically or differently, by substituents chosen form the group consisting of halogen, nitro, trifluoromethyl, (C1-C6)-alkyl and (C1-C6)-alkoxy, R2 is a radical of the formula â€”XR12 or â€”NR13R14, wherein x is a bond or oxygen R12 is hydrogen, straight-chain or branched (C1-C6)-alkoxycarbonyl or a straight-chain, branched or cyclic, saturated or unsaturated (C1-C8)-hydrocarbon radical, which optionally contains one or two identical or different hetero chain members from the group consisting of O, CO, NH, â€”NHâ€”(C1-C4)-alkyl, â€”Nâ€”((C1-C4)-alkyl)2, S and SO2, and which is optionally substituted by halogen, nitro, cyano, hydroxyl, aryl having from 6 to 10 carbon atoms or aralkyl having from 6 to 10 carbon atoms, heteroaryl or a group of the formula â€”NR15R16, wherein R15 and R16 are identical or different and are hydrogen, benzyl or (C1-C6)-alkyl, R13 and R14 are identical or different and are hydrogen, (C1-C6)-alkyl or cycloalkyl having from 3 to 6 carbon atoms, R3 is hydrogen, amino or is a radical of the formula is formyl, cyano, hydroxy-substituted (C1-C6)-alkylthio, trifluoromethyl or pyridyl, or is a straight-chain, branched or cyclic, saturated or unsaturated hydrocarbon radical having up to 8 carbon atoms, which is optionally mono- or polysubstituted, identically or differently, by aryloxy having from 6 to 10 carbon atoms, azido, halogen, cyano, hydroxyl, carboxyl, (C1-C6)-alkoxycarbonyl, (C1-C6)-alkylthio or (C1-C6)-alkoxy, which for its part can be substituted by azido or amino, and/or is substituted by triazolyl, which for its part can be substituted up to 3 times by (C1-C6)-alkoxycarbonyl, and/or can be substituted by groups of the formula â€”OSO2-H3, or (CO)aâ€”NR17R18, wherein a is a number 0 or 1, R17 and R18 are identical or different and are hydrogen or aryl, aralkyl having from 6 to 10 carbon atoms, or are (C1-C6)-alkyl, which is optionally substituted by (C1-C6)-alkoxycarbonyl, amino, hydroxyl, phenyl or benzyl, where phenyl or benzyl are optionally mono- or polysubstituted identically or differently, by hydroxyl, carboxyl, (C1-C6)-alkyl or (C1-C6)-alkoxy, or (C1-C6)-alkyl is optionally substituted by groups of the formula NHâ€”COâ€”CH3 or NHâ€”COâ€”CF3, or R17 and R18 together with the nitrogen atom form a morpholine, piperidinyl or pyrrolidinyl ring, or R3 is phenyl, which is optionally substituted by methoxy, or R2 and R3 together form a radical of the formula R4 is hydrogen, (C1-C4)-alkyl, (C2-4)-alkenyl, benzoyl or is acyl having from 2 to 6 carbon atoms, R4 is hydrogen, methyl, benzoyl or is (C2-C6)-acyl, R5 is pyridyl, pyrimidyl or pyrazinyl, or a salt thereof to a mammal in need of such treatment.