Patent ID: 7276484
Filing Date: 2007-10-02
Classification: C07K

Abstract:
1. A method of inhibiting deposition of Aβ peptide in a mammal comprising administering to a mammal in need thereof an effective amount of a compound of formula 1 wherein: A is wherein Aryl is mono or bicyclic and has from 5 to 10 ring atoms and may optionally include up to 3 heteroatoms chosen from N, O and S; each x is independently 0, 1 or 2; R is H, C each R and n is 1 or 2; wherein D is chosen from aryl having 5 to 6 atoms, optionally including up to 2 heteroatoms selected from the N, O, and S; fused aryl of 8 to 14 atoms optionally including up to 3 heteroatoms selected from the N, O, and S; mono or fused cycloalkyl having 5 to 12 carbon atoms; and mono or fused heterocycloalkyl having 5 to 12 carbon atoms including up to 3 heteroatoms selected from N, O, and S; biaryl, diaryl ether; diarylketone, and phenyl(C and wherein E is a divalent group chosen from carbonyl, sulfonyl, C and D may optionally be substituted with up to two groups chosen from OH, C iii) C 1 -C 6 alkanoyl; C 2 -C- 6 alkenoyl; and methylthioC 1 -C 5 alkanoyl, any of which may be substituted with up to two groups chosen from OH, C 1 -C 6 alkylacylamino, C 1 -C 6 alkylacyloxy; C 1 -C 6 alkyloxy; C 1 -C 6 alkylthioxy, amido (including primary, C 1 -C 6 alkyl secondary; C 1 -C 6 alkyl and phenyl tertiary, amino, C 1 -C 6 alkyl and phenyl amino, carbamyl (including C 1 -C 6 alkyl and phenyl amides and esters), carboxyl (including C 1 -C 6 alkyl and phenyl esters), carboxy(C 2 -C 5 )alkyloxy and N-heterocyclylacyl, C 1 -C 3 alkylsulfonyl, sulfonamide and C 1 -C 3 alkylsulfonamide; and iv) a divalent group of the formula: wherein each carbonyl of the divalent group bonds to the nitrogen to form a five membered ring and Ra is as defined above; B is selected from —OH; C 1 -C 6 alkyl or C 1 -C 6 alkyl amino, di(C 1 -C 6 alkyl)amino, C 1 -C 6 alkyloxy, N-heterocyclylic and each n′ is independently 0, 1 or 2; m is 0, 1, 2 or 3; and G is N or O; J is selected from the group consisting of aryl having a 5 to 6 membered ring optionally including up to 2 heteroatoms selected from the N, O, and S; fused aryl rings of 8 to 14 atoms optionally including up to 3 heteroatoms selected from N, O, and S, mono or fused ring cycloalkyl having 5 to 12 carbon atoms; and mono or fused ring heterocyclic having 5 to 12 carbon atoms including up to 3 heteroatoms chosen from the group consisting of N, O, and S; each K is chosen from OH, C 1 -C 3 alkyl; C 1 -C 6 alkylacylamino, C 1 -C 6 alkylacyloxy, C 1 -C 6 alkyloxy, C 1 -C 6 alkylthioxy, amido (including primary, C 1 -C 6 alkyl and phenyl secondary and tertiary), NH 2 , mono and di(C 1 -C 6 alkyl and phenyl) amino, carbamyl (including C 1 -C 6 alkyl and phenyl amides and esters), carboxyl (including C 1 -C 6 alkyl and phenyl esters) and carboxy(C 2 -C 5 )alkyloxy; R 1 is straight or branched chain C 1 -C 5 alkanyl or C 2 -C 5 alkenyl; R 2 is C 1-5 straight or branched chain alkanyl or alkenyl; methylthiomethyl; aryl or arylalkyl or heteroaryl or heteroarylalkyl wherein any of the above are optionally substituted with up to 2 of C 1-3 alkyl, trifluoromethyl or halogen, or a pharmaceutically acceptable salts and esters thereof.