Wu Xiongyu, Ohrngren Per, Ekegren Jenny K, Unge Johan, Unge Torsten, Wallberg Hans, Samuelsson Bertil, Hallberg Anders, Larhed Mats
Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry, BMC, Uppsala University, Box 574, SE-751 23 Uppsala, Sweden.
J Med Chem. 2008 Feb 28;51(4):1053-7. doi: 10.1021/jm070680h. Epub 2008 Jan 24.
A new generation of HIV-1 protease inhibitors encompassing a tertiary-alcohol-based transition-state mimic has been developed. By elongation of the core structure of recently reported inhibitors with two carbon atoms and by varying the P1' group of the compounds, efficient inhibitors were obtained with Ki down to 2.3 nM and EC50 down to 0.17 microM. Two inhibitor-enzyme X-ray structures are reported.
已开发出新一代包含基于叔醇的过渡态模拟物的HIV-1蛋白酶抑制剂。通过将最近报道的抑制剂的核心结构延长两个碳原子并改变化合物的P1'基团，获得了高效抑制剂，其Ki低至2.3 nM，EC50低至0.17 microM。报道了两种抑制剂-酶的X射线结构。
