Synthesis and antiviral property of allophenylnorstatine-based HIV protease inhibitors incorporating D-cysteine derivatives as P2/P3 moieties

  • Bioorg Med Chem Lett. 2007 Aug 1;17(15):4213-7. doi: 10.1016/j.bmcl.2007.05.039.
Ei'ichi Ami  1 ,  Koichiro Nakahara ,  Akihiko Sato ,  Jeffrey-Tri Nguyen ,  Koushi Hidaka ,  Yoshio Hamada ,  Shingo Nakatani ,  Tooru Kimura ,  Yoshio Hayashi ,  Yoshiaki Kiso
Affiliations
  • 1. Department of Medicinal Chemistry, Center for Frontier Research in Medicinal Science and 21st Century COE Program, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto 607-8412, Japan.
PMID: 17537628 DOI: 10.1016/j.bmcl.2007.05.039
Abstract

We designed several HIV Protease Inhibitors with various d-cysteine derivatives as P(2)/P(3) moieties based on the structure of clinical drug candidate, KNI-764. Herein, we report their synthesis, HIV Protease inhibitory activity, HIV IIIB cell inhibitory activity, cellular toxicity, and inhibitory activity against drug-resistant HIV strains. KNI-1931 showed distinct selectivity against HIV proteases and high potency against drug-resistant strains, surpassing those of Ritonavir and Nelfinavir.