Synthesis of N-[3′-(acetylthio)alkanoyl] and N-[3′-mercaptoalkanoyl]-4-α(s)-(phenylmethyl) pyroglutamic acids and prolines as potent ACE inhibitors

Abstract

Angiotensin converting enzyme (ACE) inhibitors have emerged as a revolution in antihypertensive therapy. Introduction of captopril, the first rationally designed ACE inhibitor, has encouraged researchers all over the world to design and synthesize target molecules controlling hypertension based on these lines. It has been observed that replacing proline part of captopril with 4-substituted prolines or 5-oxo-prolines led to significant enhancement in ACE inhibitory activity, and this observation prompted us to design and synthesize N-acyl 4-substituted pyroglutamates and prolinates with the objective of developing therapeutically better ACE inhibitors. Herein we describe an easy approach for N-acylation of 4-a(S)-(phenylmethyl) pyroglutamates with the aim of synthesizing N-[3 0 -(acetylthio)alkanoyl] and N-[3 0 -mercaptoalkanoyl]-4-a-(s)-(phenylmethyl) pyroglutamic acids and prolines as ACE inhibitors.