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Updated: Jun 12, 2026

Rapid Screening of HIV Reverse Transcriptase and Integrase Inhibitors
Published on: April 9, 2014
Pharmacophore and structure-activity relationships of integrase inhibition within a dual inhibitor scaffold of HIV
Zhengqiang Wang1, Jing Tang, Christine E Salomon
1Center for Drug Design, Academic Health Center, University of Minnesota, Minneapolis, MN 55455, USA. wangx472@umn.edu
Abstract:
Rational design of dually active inhibitors against human immunodeficiency virus (HIV) reverse transcriptase (RT) and integrase (IN) has proved viable with 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) type of non-nucleoside RT inhibitors (NNRTIs). To establish the pharmacophore and study the structure-activity relationships (SAR) of integrase inhibition within a previously disclosed RT/IN dual inhibitor scaffold, new analogues featuring substitution at different sites of the HEPT ring were designed and synthesized. These studies have revealed an IN inhibition pharmacophore that is merged with the known RT pharmacophore through a shared C-6 benzyl group. Further SAR also demonstrated that optimal IN inhibition within our dual inhibitor scaffold requires a regiospecific (N-1) diketoacid (DKA)-carrying pendant with a certain length.
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