Patent ID: 6506782
Filing Date: 2003-01-14
Classification: A61K

Abstract:
A method for inhibiting &bgr;-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 &bgr;-amyloid peptide wherein said compounds are represented by formula I: where:R1 is selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, substituted alkyl, substituted alkenyl, substituted alkynyl, substituted cycloalkyl, substituted cycloalkenyl, aryl, heteroaryl and heterocyclic; Z is selected from the group consisting of: (a) a group having the formula â€”CXâ€²Xâ€³C(O)â€” where Xâ€² is hydrogen, hydroxy or fluoro; Xâ€³ is hydrogen, hydroxy or fluoro, or Xâ€² and Xâ€³ together form an oxo group; (b) a group having the formula â€”Tâ€”CXâ€²Xâ€³C(O)â€” where T is selected from the group consisting of oxygen, sulfur and â€”NR3 where R3 is hydrogen, acyl, alkyl, aryl or heteroaryl group; Xâ€² is hydrogen or fluoro, Xâ€³ is hydrogen, hydroxy or fluoro, or Xâ€² and Xâ€³ together form an oxo group; and (c) a group having the formula â€”CXâ€²Xâ€³â€”Tâ€”C(O)â€” where T is selected from the group consisting of oxygen, sulfur and â€”NR3 where R3 is hydrogen, acyl, alkyl, aryl or heteroaryl group; Xâ€² is hydrogen or fluoro, Xâ€³ is hydrogen, hydroxy or fluoro, or Xâ€² and Xâ€³ together form an oxo group; R2 is selected from the group consisting of alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, aryl, heteroaryl and heterocyclic; R6 is selected from the group consisting of alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, aryl, heteroaryl and heterocyclic; m is an integer equal to 0 or 1; p is an integer equal to 0 or 1; R5 is selected from the group consisting of alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, aryl, heteroaryl and heterocyclic; A, together with â€”C&boxH;Nâ€”, forms a heterocyclic group which is optionally fused to form a bi- or multi-fused ring system with one or more ring structures selected from the group consisting of cycloalkyl, cycloalkenyl, heterocyclic, aryl and heteroaryl group which, in turn, each of such ring structures is optionally substituted with 1 to 4 substituents selected from the group consisting of hydroxyl, halo, alkoxy, substituted alkoxy, thioalkoxy, substituted thioalkoxy, nitro, cyano, carboxyl, carboxyl esters, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, heteroaryl, heterocyclic, â€”NHC(O)R10, â€”NHSO2R10, â€”C(O)NH2, â€”C(O)NHR10, â€”C(O)NR10R10, â€”S(O)R10, â€”S(O)2R10, â€”S(O)2NHR10 and â€”S(O)2NR10R10 where each R10 is independently selected from the group consisting of alkyl, substituted alkyl, or aryl, amino, N-alkylamino, N,N-dialkylamino, N-substituted alkylamino, N,N-disubstituted alkylamino, N-alkenylamino, N,N-dialkenylamino, N-substituted alkenylamino, N,N-disubstituted alkenylamino, N-cycloalkylamino, N,N-dicycloalkylamino, N-substituted cycloalkylamino, N,N-disubstituted cycloalkylamino, N-arylamino, N,N-diarylamino, N-heteroarylamino, N,N-diheteroarylamino, N-heterocyclic amino, N,N-diheterocyclic amino and mixed N,N-amino groups comprising a first and second substituent on said amino group which substituents are selected from the group consisting of alkyl, substituted alkyl, alkenyl, substituted alkenyl, cycloalkyl, substituted cycloalkyl, aryl, heteroaryl, and heterocyclic provided that said first and second substituents are not the same.