NSAID derivatives of omega-3 polyunsaturated acids as gamma secretase modulators

Compounds of Formula (I)

• wherein:
• R is joined from the methylene moiety formed by reduction of the carboxylic acid of one of the following polyunsaturated fatty acids (PUFAs):
• cis,cis,cis-7,10,13-hexadecatrienoic acid (HTA),
• cis,cis,cis-9,12,15-octadecatrienoic acid (ALA),
• cis,cis,cis,cis-6,9,12,15-octadecatetraenoic acid (SDA),
• cis,cis,cis-11,14,17-eicosatrienoic acid (ETE),
• cis,cis,cis,cis-8,11,14,17-eicosatetraenoic acid (ETA);
• cis,cis,cis,cis,cis-5,8,11,14,17-eicosapentanenoic acid (EPA),
• cis,cis,cis,cis,cis-6,9,12,15,18-heneicosapentaenoic acid (HPA),
• cis,cis,cis,cis,cis-7,10,13,16,19-docosapentaenoic acid (DPA),
• cis,cis,cis,cis,cis,cis-4,7,10,13,16,19-docosahexaenoic acid (DHA),
• cis,cis,cis,cis,cis-9,12,15,18,21-tetracosapentaeonic acid (TPA) or
• cis,cis,cis,cis,cis,cis-6,9,12,15,18,21-tetracosahexaeonic acid (THA);
• and
• R1 is H;
• R2 is C1-C6 straight chain or branched alkyls;
• C3-C6 cycloalkyl;
• C3-C6 fluorocycloalkyl;
• C2-C6 alkenyl;
• C2-C6-alkynyl;
• C6-C10 aryl unsubstituted or substituted with C1-C6 straight chain or branched alkyls:
• C1-C6 alkoxyl;
• 1,3-dioxolanyl;
• cyano, halo, nitro, trihaloalkyl, acyl, or acylamino;
• alkylaryl unsubstituted or substituted with straight chain or branched alkyl;
• C1-C6 alkoxyl;
• 1,3-dioxolanyl;
• cyano, halo, trihaloalkyl, dialkylamino;
• or alkyldiaryls, or
• R1 and R2 are tethered together to form a 3- to 7-membered alicyclic ring, and
• the compound of Formula (I) can be a stereoisomer of either R or S configuration;
• or its pharmaceutically-acceptable salts.