DESIGN AND SYNTHESIS OF NOVEL INHIBITORS OF HIV-1 REVERSE-TRANSCRIPTASE

被引：44

作者：

MARUENDA, H ^{[1
]}

JOHNSON, F ^{[1
]}

机构：

[1] SUNY STONY BROOK,DEPT CHEM,STONY BROOK,NY 11794

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1995年 / 38卷 / 12期

关键词：

D O I：

10.1021/jm00012a014

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A variety of N1-substituted pyrimido[5,4-f]benzo[1,4]thiazepines, 5, designed as conformationally constrained analogs of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine HEPT (1), were synthesized and evaluated for their inhibition of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT). The preparation of these compounds was carried out based on a Mannich-type cyclization of 6-[(2-aminophenyl)thio]uracils followed by alkylation at N1 by a one-pot Vorbruggen reaction. The pyrimidobenzothiazepines were developed to give molecules with IC50 values in the micromolar range, as exemplified by [[(2-ethoxyethyl)oxy]methyl]-pyrimido[5,4-f]benzo[1,4]thiazepine, 25, (IC50 = 0.64 mu M), the most active compound of this series. The structural and electronic features of this novel class of HIV-1 RT inhibitors are presented and compared with those of HEPT (1), TIBO (2), and nevirapine (3).

引用

页码：2145 / 2151

页数：7

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