ABSTRACT
Cholesteryl ester transfer protein is a plasma glycoprotein that transfers cholesterol ester between lipoprotein particles. Inhibition of this protein, in vitro and in vivo, produces an increase in plasma high density lipoprotein cholesterol (HDL-C). This communication will describe the SAR and synthesis of a series of substituted tetrahydroquinoxaline CETP inhibitors from early mu lead to advanced enantiomerically pure analogs.
Subject(s)
Chemistry, Pharmaceutical/methods , Cholesterol Ester Transfer Proteins/antagonists & inhibitors , Esters/chemistry , Quinoxalines/chemical synthesis , Quinoxalines/pharmacology , Tetrazoles/chemistry , Animals , Cholesterol, HDL/metabolism , Drug Design , Humans , Hydrogen-Ion Concentration , Inhibitory Concentration 50 , Molecular Conformation , Rats , Stereoisomerism , Structure-Activity RelationshipABSTRACT
Optically active (S)-alpha-amino acids are prepared in 54-95% ee (12 cases) by reaction of the Schiff base acetate of glycine tert-butyl ester with B-alkyl-9-BBN derivatives in the presence of the Cinchona alkaloid, cinchonidine, and base. The enantiomeric (R)-alpha-amino acids are available in 59-92% ee (3 cases) by using cinchonine as the chiral control element.
