Eric M. Gordon

RATIONAL DESIGN OF POTENT CARBOXYLIC ACID BASED BISUBSTRATE INHIBITORS OF RAS FARNESYL PROTEIN TRANSFERASE

Abstract Bisubstrate analog inhibitors in which a substrate mimetic tripeptide is attached to a homologated farnesyl carboxylic acid were synthesized and evaluated for in vitro inhibition versus ras farnesyl protein transferase (FPT). Our results demonstrate that such bisubstrate analogs are potent inhibitors of FPT.

PHENOL BASED TRIPEPTIDE INHIBITORS OF RAS FARNESYL PROTEIN TRANSFERASE

Abstract Preparation and activity of phenol tripeptides, a new class of inhibitors of ras farnesyl protein transferase (FPT), is described. Based on the inhibitory potency of meta-phenol 11 (I50 = 29 uM) and the ortho-benzyl ether analog 7 (I50 = 63 uM), regioisomeric hybrid analogs 18 and 25 were designed and evaluated as partial bisubstrate analog inhibitors of FPT (18, I50 = 157 uM; 25, I50 = 137 uM).

Diastereoselective oxidation of sulfides to sulfoxides. Synthesis of novel C-6 sulfoxy tetrahydromevinic acids

Abstract The synthesis and diastereoselective oxidation of novel tetrahydromevinic acid lactone sulfides to sulfoxides is described.

C-2 desmethyl seco-mevinic acids. Monocyclic HMG-CoA reductase inbibitors

Abstract An efficient preparation of C-2 desmethyl seco-mevinic acid 2a from 2-cyclohexen-1-one (10 step, 24.7% overall yield) is described. Comparison of the activity of analogs 2a,b with other recently reported seco-mevinic acid based HMG-CoA reductase inhibitors suggests that all four substituents around the cyclohexyl ring are required for good biological activity.