Substituted amino acid ester derivatives useful for inhibiting beta-amyloid peptide release and/or synthesis

摘要

A substituted amino acid ester derivative of formula (I) or a pharmaceutically acceptable salt thereof is used to inhibiting b-amyloid peptide release and/or its synthesis in a cell or is used to prevent the onset of Alzheimer's disease in a patient at risk of developing Alzheimer's disease wherein: R1 is optionally substituted alkyl, alkenyl, or alkynyl or is cycloalkyl, cycloalkenyl, aryl, heteroaryl or heterocyclic; R2 is hydrogen, optionally substituted alkyl, alkenyl or alkynyl or is cycloalkyl, aryl, heteroaryl or heterocyclic; each R3 is independently hydrogen or methyl or R3 together with R4 can be fused to form a cyclic structure of from 3 to 8 atoms which is optionally fused with an aryl or heteroaryl group; each R4 is independently hydrogen, optionally substituted alkyl, alkenyl, or alkynyl, or is aryl, cycloalkyl, cycloalkenyl, heteroaryl or heterocyclic; each R5 is hydrogen or methyl or together with R4 forms a cycloalkyl group of from 3 to 6 carbon atoms; X is -C(O)Y, -C(S)Y or -CR6R6Y'; Y is optionally substituted alkyl provided that the substitution does not include a-haloalkyl, a-diazoalkyl, a-OC(O)alkyl or a-OC(O)aryl or is cycloalkyl, optionally substituted alkoxy or thioalkoxy, hydroxy, aryl, heteroaryl, heterocyclic, NR'R", -NHSO2-R8, -NR9NR10R10 or NR9[C(O)O]zR10; each R6 is independently hydrogen, optionally substituted alkyl, cycloalkyl, aryl, heteroaryl or heterocyclic; Y' is hydroxyl, amino, thiol, optionally substituted alkoxy or thioalkoxy, -OC(O)R7, -S-SR7, -S-SC(O)R7; R7 is optionally substituted alkyl, cycloalkyl, aryl, heteroaryl or heterocyclic; X' is hydrogen, hydroxy, or fluoro; X" is hydrogen, hydroxy or fluoro, or X' and X" together form an oxo group; Z is a bond covalently linking R to -CX'Xn-, oxygen or sulphur; n is 1 or 2; z is 0 or 1 and R', R", R8, R9, R10 are as defined in the specification limited by the provisos listed in the specification.