RESUMO
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.
Assuntos
Química Farmacêutica/métodos , Proteínas de Transferência de Ésteres de Colesterol/antagonistas & inibidores , Ésteres/química , Quinoxalinas/síntese química , Quinoxalinas/farmacologia , Tetrazóis/química , Animais , HDL-Colesterol/metabolismo , Desenho de Fármacos , Humanos , Concentração de Íons de Hidrogênio , Concentração Inibidora 50 , Conformação Molecular , Ratos , Estereoisomerismo , Relação Estrutura-AtividadeRESUMO
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.
