Kynostatin (KNI)-227 and -272, highly potent anti-HIV agents: conformationally constrained tripeptide inhibitors of HIV protease containing allophenylnorstatine.
Selective and potent HIV protease inhibitors containing allophenylnorstatine [Apns; (2S, 3S)-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. 1), 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.
Mimoto
T
T
Department of Medicinal Chemistry, Kyoto Pharmaceutical University, Japan.
Imai
J
J
Kisanuki
S
S
Enomoto
H
H
Hattori
N
N
Akaji
K
K
Kiso
Y
Y
D000998:Antiviral Agents / Q000494:pharmacology*; D017320:HIV Protease Inhibitors / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects*; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000494:pharmacology
D000998:Antiviral Agents; D017320:HIV Protease Inhibitors; D009842:Oligopeptides; C077823:kynostatin 227; C077822:kynostatin 272