Novel 1,2,3-thiadiazole derivatives as HIV-1 NNRTIs with improved potency: Synthesis and preliminary SAR studies

  • Bioorg Med Chem. 2009 Aug 15;17(16):5920-7. doi: 10.1016/j.bmc.2009.07.004.
Peng Zhan  1 ,  Xinyong Liu ,  Zhenyu Li ,  Zengjun Fang ,  Zhong Li ,  Defeng Wang ,  Christophe Pannecouque ,  Erik De Clercq
Affiliations
  • 1. Institute of Medicinal Chemistry, Shandong University, Jinan, PR China.
PMID: 19620009 DOI: 10.1016/j.bmc.2009.07.004
Abstract

A novel synthetic route and anti-HIV activity evaluation of a new series of 2-(4-(2,4-dibromophenyl)-1,2,3-thiadiazol-5-ylthio)acetamide (TTA) derivatives are described. Bioactivity assay indicated that most of the title compounds showed good activities against HIV-1. In particular, compound 7c displayed the most potent anti-HIV-1 activity (EC(50)=36.4nM), inhibiting HIV-1 replication in MT-4 cells more effectively than NVP (by sevenfold) and DLV (by eightfold). The preliminary structure-activity relationships (SAR) of the newly synthesized congeners are discussed, and molecular modeling of compound 7c in complex with HIV-1 RT is described, allowing rationalization of some SAR conclusions.

Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-116469
    ZP7
    Anti-HIV-1 Agent
    target: HIV
    Research Areas: Infection