Ami Ei'ichi, Nakahara Koichiro, Sato Akihiko, Nguyen Jeffrey-Tri, Hidaka Koushi, Hamada Yoshio, Nakatani Shingo, Kimura Tooru, Hayashi Yoshio, Kiso Yoshiaki
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.
Bioorg Med Chem Lett. 2007 Aug 1;17(15):4213-7. doi: 10.1016/j.bmcl.2007.05.039. Epub 2007 May 17.
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.
我们基于临床候选药物KNI-764的结构，设计了几种以不同的d-半胱氨酸衍生物作为P(2)/P(3)部分的HIV蛋白酶抑制剂。在此，我们报告它们的合成、HIV蛋白酶抑制活性、HIV IIIB细胞抑制活性、细胞毒性以及对耐药HIV毒株的抑制活性。KNI-1931对HIV蛋白酶表现出明显的选择性，对耐药毒株具有高效力，超过了利托那韦和奈非那韦。
