Aminodiol HIV protease inhibitors. Synthesis and structure-activity relationships of P1/P1' compounds: correlation between lipophilicity and cytotoxicity.
Aminodiol HIV protease inhibitors. Synthesis and structure-activity relationships of P1/P1' compounds: correlation between lipophilicity and cytotoxicity.
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氨基二醇 HIV 蛋白酶抑制剂。
DOI：
10.1021/jm950717a
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发表时间：
1996
影响因子：
7.3
通讯作者：
J. Barrish
中科院分区：
文献类型：
--
作者：
Ping Chen;P. Cheng;Masud Alam;B. Beyer;G. Bisacchi;T. Dejneka;Adelaide J. Evans;J. Greytok;M. Hermsmeier;W. Humphreys;G. Jacobs;O. Kocy;P. Lin;Karen A. Lis;M. Marella;D. Ryono;A. Sheaffer;S. Spergel;Chong;J. Tino;G. Vite;R. Colonno;Robert B Zahler;J. Barrish
为了降低先导化合物1的细胞毒性，合成了一系列基于先导化合物1的新型HIV蛋白酶抑制剂。我们已经观察到这一系列抑制剂的亲脂性和细胞毒性之间的高度相关性。发现在1的P1'苯基的帕拉上的适当取代导致鉴定出具有显著降低的细胞毒性的等效（针对酶和在细胞培养物中）化合物（10 l、10 m、10 n和15 c）。
A series of novel aminodiol inhibitors of HIV protease based on the lead compound 1 with structural modifications at P1' were synthesized in order to reduce the cytotoxicity of 1. We have observed a high degree of correlation between the lipophilicity and cytotoxicity of this series of inhibitors. It was found that appropriate substitution at the para position of the P1' phenyl group of 1 resulted in the identification of equipotent (both against the enzyme and in cell culture) compounds (10l, 10m, 10n, and 15c) which possess significantly decreased cytotoxicity.