评价含羟乙胺等排体的 HTLV-1 蛋白酶抑制剂的反式-顺式构象变化。

Evaluation of retro-inverso modifications of HTLV-1 protease inhibitors containing a hydroxyethylamine isoster.

机构信息

Department of Medicinal Chemistry, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kita-ku, Kyoto 603-8334, Japan.

出版信息

Bioorg Med Chem. 2010 Apr 1;18(7):2720-7. doi: 10.1016/j.bmc.2010.02.019. Epub 2010 Feb 18.

DOI:10.1016/j.bmc.2010.02.019

PMID:20226680

Abstract

Effects of retro-inverso (RI) modifications of HTLV-1 protease inhibitors containing a hydroxyethylamine isoster backbone were clarified. Construction of the isoster backbone was achieved by a stereoselective aldol reaction. Four diastereomers with different configurations at the isoster hydroxyl site and the scissile site substituent were synthesized. Inhibitory activities of the new inhibitors suggest that partially modified RI inhibitors would interact with HTLV-1 protease in the same manner as the parent hydroxyethylamine inhibitor.

摘要

阐明了含有羟乙基胺等排体骨架的 HTLV-1 蛋白酶抑制剂的反式-顺式（RI）修饰的效果。等排体骨架的构建是通过立体选择性的醛醇反应实现的。合成了在等排羟基部位和裂解部位取代基处具有不同构型的四个非对映异构体。新抑制剂的抑制活性表明，部分修饰的 RI 抑制剂将以与母体羟乙基胺抑制剂相同的方式与 HTLV-1 蛋白酶相互作用。