PMID: 7540209Jun 9, 1995Paper

Design and synthesis of novel inhibitors of HIV-1 reverse transcriptase

Journal of Medicinal Chemistry
H Maruenda, F Johnson

Abstract

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)thymidine 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 microM), 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).

Citations

Nov 15, 2008·Chemical Communications : Chem Comm·Hanfeng DingCheng Ma
Nov 25, 2000·Nucleosides, Nucleotides & Nucleic Acids·M JokićD Katalenić
Jun 19, 2008·Bioorganic & Medicinal Chemistry·Betty C GalarretaHelena Maruenda
Apr 14, 2016·The Journal of Organic Chemistry·Andreia M P W da SilvaNilo Zanatta
Aug 12, 2014·European Journal of Medicinal Chemistry·Meng Li, Bao-Xiang Zhao
Mar 25, 2006·The Journal of Organic Chemistry·Alexey P IlynAlexandre V Ivachtchenko

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