Malonamide derivatives as gamma secretase inhibitors

Details Malonamide derivatives as gamma secretase inhibitors Malonamide derivatives as gamma secretase inhibitors

C - Chemistry, Metallurgy

07

D

C07D 223/18 (2006.01) A61K 31/55 (2006.01) A61P 25/28 (2006.01)

Patent

CA 2645756

The invention relates to malonamide derivatives of Formula (I) wherein A1 is -CHR- or -C(O)-; A2 is -C(O)- and R2/R3 are independently from each other hydrogen, lower alkyl, halogen, hydroxy or lower alkoxy; or A2 is -O-C(O)- and R2/R3 are independently from each other hydrogen or lower alkyl; R is hydrogen or lower alkyl substituted by halogen; R1 is hydrogen, lower alkyl or -(CH2)n-aryl, optionally substituted by halogen; R4 is lower alkyl substituted by halogen n is 0, 1 or 2; and to pharmaceutically suitable acid addition salts, optically pure enantiomers, racemates or diastereomeric mixtures thereof for the treatment of Alzheimer's disease.

L'invention concerne des dérivés de malonamide de formule (I) dans laquelle A1 est -CHR- ou -C(O)-; A2 est -C(O)- et R2/R3 sont chacun indépendamment de l'autre un hydrogène, un alkyle inférieur, un halogène, un hydroxy ou un alcoxy inférieur; ou bien A2 est -O-C(O)- et R2/R3 sont chacun indépendamment de l'autre un hydrogène ou un alkyle inférieur; R est un hydrogène ou un alkyle inférieur substitué par un halogène; R1 est un hydrogène, un alkyle inférieur ou un -(CH2)n-aryle, éventuellement substitué par un halogène; R4 est un alkyle inférieur substitué par un halogène; n est 0, 1 ou 2; et des sels d'addition avec un acide appropriés du point de vue pharmaceutique, des énantiomères optiquement purs, des racémates ou des mélanges de diastéréoisomères de ceux-ci pour le traitement de la maladie d'Alzheimer.

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