一类新型的HIV-1蛋白酶抑制剂，其在模拟过渡态的支架中含有叔醇。
A new class of HIV-1 protease inhibitors containing a tertiary alcohol in the transition-state mimicking scaffold.
作者信息
Ekegren Jenny K, Unge Torsten, Safa Mayada Zreik, Wallberg Hans, Samuelsson Bertil, Hallberg Anders
机构信息
Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry, BMC, Uppsala University, Box 574, SE-751 23 Uppsala, Sweden.
出版信息
J Med Chem. 2005 Dec 15;48(25):8098-102. doi: 10.1021/jm050790t.
Novel HIV-1 protease inhibitors encompassing a tertiary alcohol as part of the transition-state mimicking unit have been synthesized. Variation of the P1'-P3' residues and alteration of the tertiary alcohol absolute stereochemistry afforded 10 inhibitors. High potencies for the compounds with (S)-configuration at the carbon carrying the tertiary hydroxyl group were achieved with Ki values down to 2.4 nM. X-ray crystallographic data for a representative compound in complex with HIV-1 protease are presented.
已合成了包含叔醇作为过渡态模拟单元一部分的新型HIV-1蛋白酶抑制剂。对P1'-P3'残基进行变化并改变叔醇的绝对立体化学，得到了10种抑制剂。在携带叔羟基的碳上具有(S)-构型的化合物具有高效能，Ki值低至2.4 nM。给出了一种代表性化合物与HIV-1蛋白酶复合物的X射线晶体学数据。
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