MALONAMIDE DERIVATIVES BLOCKING THE ACTIVITY OF GAMA-SECRETASE

摘要

The invention relates to malonamide derivatives of formula (I), wherein: R<1> is one of the following groups (Formulae a), b), c), d)); R<2 >is lower alkyl, lower alkinyl, -(CH2)n-O-lower alkyl, -(CH2)n-S-lower alkyl, -(CH2)n-CN, -(CR'R")n-CF3, -(CR'R")n-CHF2, -(CR'R")n-CH2F, -(CH2)n-C(O)O-lower alkyl, -(CH2)n-halogen, or is -(CH2)n-cycloalkyl, optionally substituted by one or more substituents, selected from the group consisting of phenyl, halogen or CF3; R',R" are independently from n and from each other hydrogen, lower alkyl, lower alkoxy, halogen or hydroxy; R<3>, R<4> are independently from each other hydrogen, lower alkyl, lower alkoxy, phenyl or halogen; R<5 >is hydrogen, lower alkyl, -(CH2)n-CF3 or -(CH2)n-cycloalkyl; R<6> is hydrogen or halogen; R<7> is hydrogen or lower alkyl; R<8> is hydrogen, lower alkyl, lower alkinyl, -(CH2)n-CF3,-(CH2)n-cycloalkyl or -(CH2)n-phenyl, optionally substituted by halogen; R<9> is hydrogen, lower alkyl, -C(O)H, -C(O)-lower alkyl, -C(O)-CF3,-C(O)-CH2F,-C(O)-CHF2,-C(O)-cycloalkyl,-C(O)-(CH2)n-O-lower alkyl,-C(O)O-(CH2)n-cycloalkyl, -C(O)-phenyl, optionally substituted by one or more substituents selected from the group consisting of halogen or -C(O)O-lower alkyl, or is -S(O)2-lower alkyl, -S(O)2-CF3,-(CH2)n-cycloalkyl or is -(CH2)n-phenyl, optionally substituted by halogen; n is 0, 1, 2, 3 or 4; and to pharmaceutically suitable acid addition salts, optically pure enantiomers, racemates or diastereomeric mixture thereof. These compounds may be used for the treatment of Alzheimer's disease.