RESUMEN
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.
Asunto(s)
Química Farmacéutica/métodos , Proteínas de Transferencia de Ésteres de Colesterol/antagonistas & inhibidores , Ésteres/química , Quinoxalinas/síntesis química , Quinoxalinas/farmacología , Tetrazoles/química , Animales , HDL-Colesterol/metabolismo , Diseño de Fármacos , Humanos , Concentración de Iones de Hidrógeno , Concentración 50 Inhibidora , Conformación Molecular , Ratas , Estereoisomerismo , Relación Estructura-ActividadRESUMEN
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.