Patent ID: 6096782
Filing Date: 2000-08-01
Classification: A61K,C07C,C07D

Abstract:
A method for inhibiting .beta.-amyloid peptide release and/or its synthesis in a cell which method comprises administering to such a cell an amount of a compound or a mixture of compounds effective in inhibiting the cellular release and/or synthesis of .beta.-amyloid peptide wherein said compounds are represented by formula I: ##STR9## wherein: R.sup.1 is selected from the group consisting of(a) phenyl,(b) a substituted phenyl group of formula II: ##STR10## wherein R.sup.c is selected from the group consisting of acyl, alkyl, alkoxy, alkylalkoxy, azido, cyano, halo, hydrogen, nitro, trihalomethyl, thioalkoxy, and wherein R.sup.b and R.sup.c are fused to form a heteroaryl or heterocyclic ring with the phenyl ring,R.sup.b and R.sup.b' are independently selected from the group consisting of hydrogen, halo, nitro, cyano, trihalomethyl, alkoxy, and thioalkoxy with the proviso that when R.sup.c is hydrogen, then R.sup.b and R.sup.b' are either both hydrogen or both substituents other than hydrogen,(c) 2-naphthyl,(d) 2-naphthyl substituted at the 4, 5, 6, 7 and/or 8 positions with 1 to 5 substituents selected from the group consisting of alkyl, alkoxy, halo, cyano, nitro, trihalomethyl, thioalkoxy, aryl, and heteroaryl,(e) heteroaryl, and(f) substituted heteroaryl containing 1 to 3 substituents selected from the group consisting of alkyl, alkoxy, aryl, aryloxy, cyano, halo, nitro, heteroaryl, thioalkoxy and thioaryloxy provided that said substituents are not ortho to the heteroaryl attachment to the --NH group;R.sup.2 is selected from the group consisting of hydrogen, alkyl of from 1 to 4 carbon atoms, alkylalkoxy of from 1 to 4 carbon atoms, alkylthioalkoxy of from 1 to 4 carbon atoms, aryl, heteroaryl, substituted aryl and substituted heteroaryl provided that the substituents are not ortho to the attachment of the aryl or heteroaryl atom to the carbon atom;R.sup.3 is selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, heteroaryl, substituted alkyl, substituted alkenyl, substituted alkynyl, and heterocyclic;X is --C(O)Y where Y is selected from the group consisting of(a) alkyl,(b) substituted alkyl with the proviso that the substitution on said substituted alkyl does not include .alpha.-haloalkyl, .alpha.-diazoalkyl or .alpha.-OC(O)alkyl groups,(c) alkoxy or thioalkoxy,(d) substituted alkoxy or substituted thioalkoxy,(e) hydroxy,(f) aryl,(g) heteroaryl,(h) heterocyclic,(i) --NR'R"" where R' and R"" are independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, cycloalkyl, aryl, heteroaryl, heterocyclic, and where R' and R"" are joined to form a cyclic group having from 2 to 8 carbon atoms optionally containing 1 to 2 additional heteroatoms selected from the group consisting of oxygen, sulfur and nitrogen and optionally substituted with one or more alkyl or alkoxy groups, andwhen R.sup.3 contains at least 3 carbon atoms, X can also be --CR.sup.4 R.sup.4 Y' where each R.sup.4 is independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, heteroaryl and heterocyclic and Y' is selected from the group consisting of hydroxyl, amino, thiol, --OC(O)R.sup.5, --SSR.sup.5, --SSC(O)R.sup.5 where R.sup.5 is selected from the group consisting of alkyl, substituted alkyl, cycloalkyl, aryl, heteroaryl and heterocyclic,and with the proviso that when R.sup.1 is 3,4-dichlorophenyl, R.sup.2 is methyl, and R.sup.3 is benzyl derived from D-phenylalanine, then X is not --C(O)OCH.sub.3.