Kynostatin (kni)-227 And -272, Highly Potent Anti-hiv Agents: Conformationally Constrained Tripeptide Inhibitors of Hiv Protease Containing Allophenylnorstatine1'2)

Abstract

Selective and potent HIV protease inhibitors containing allophenylnorstatine [Apns; (25, 35)-3-amino-2-hydroxy-4-phenylbutyric acid] as a transition-state mimic were designed and synthesized. Among them, conformationally constrained tripeptide derivatives, kynostatin (KNI)-227 and -272 (Fig.l), exhibited highly potent antiviral activities against a wide spectrum of HIV isolates. Ready availability due to the simple synthetic procedure and the excellent antiviral properties indicate that KNI-227 and KNI-272 are promising candidates as selective anti-AIDS drugs. © 1992, The Pharmaceutical Society of Japan. All rights reserved.