ANTIOXIDANT INFLAMMATION MODULATORS: TRITERPENOID OLEANOLIC ACID DERIVATIVES WITH SATURATION IN THE C-RING

摘要

Disclosed are oleanane derivative compounds of Formula (I) and methods for their preparation. Specific examples of compounds of Formula (I) include: (4aS,6aR,6bR,8aR,12aR,14aR,14bS)-methyl 11-cyano-2,2,6a,6b,9,9,12a-heptamethyl-10,14-dioxo-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,12a,12b,13,14,14a,14b-icosahydropicene-4a-carboxylate, (4aS,6aR,6bR,8aR,12aR,12bR,14aR,14bS)-11-cyano-2,2,6a,6b,9,9,12a-heptamethyl-10,14-dioxo-N-(2,2,2-trifluoroethyl)-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,12a,12b,13,14,14a,14b-icosahydropicene-4acarboxamide, and (4aR,6aR,6bS,8aS,12aR,12bR,15aR,15bR)-methyl 2-cyano-4,4,6a,6b,11,11,15b-heptamethyl-3,14-dioxo-4,4a,5,6,6a,6b,7,8,8a,9,10,11,12,12a,12b,13,14,15,15a,15b-icosahydro-3H-dinaphtho[1,2-b:2',1'-d]azepine-8a-carboxylate. Compounds of Formula (I) have antioxidant and anti-inflammatory properties and are useful to: treat cancer, treat or prevent a disease with an inflammatory component, treat or prevent a cardiovascular disease, treat or prevent a neurodegenerative disease, improve glomerular filtration rate or creatinine clearance, inhibit IFN-g-induced nitric oxide production in cells treat or prevent a disorder characterized by overexpression of COX-2 genes, or treat renal/kidney disease (RKD).