SAR and Lead Optimization of an HIV-1 Vif-APOBEC3G Axis Inhibitor

  • ACS Med Chem Lett. 2012 Jun 14;3(6):465-469. doi: 10.1021/ml300037k.
Idrees Mohammed  1 ,  Maloy K Parai  1 ,  Xinpeng Jiang  1 ,  Natalia Sharova  2 ,  Gatikrushna Singh  1 ,  Mario Stevenson  2 ,  Tariq M Rana  1
Affiliations
  • 1. Program for RNA Biology, Sanford-Burnham Medical Research Institute, La Jolla, California 92037 (USA).
  • 2. Division of Infectious Diseases, Miller School of Medicine, University of Miami, Miami, FL 33136 (USA).
PMID: 24533175 DOI: 10.1021/ml300037k
Abstract

We describe structure-activity relationship and optimization studies of RN-18, an HIV-1 Vif-APOBEC3G axis inhibitor. Targeted modifications of RN-18 ring-C, ring-B, ring-A, bridge A-B, and bridge B-C were performed to identify the crucial structural features, which generated new inhibitors with similar (4g and 4i) and improved (5, 8b, and 11) activities. Two potent water-soluble RN-18 analogues, 17 and 19, are also disclosed, and we describe the results of pharmacological studies with compound 19. The findings described here will be useful in the development of more potent Vif inhibitors and in the design of probes to identify the target protein of RN-18 and its analogues.

Keywords
HIV-1 Vif-APOBEC3G axis inhibition; RN-18; pharmacological studies; structure-activity relationship and optimization.
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-102014
    RN-18
    98.75%, HIV-1 Vif Inhibitor
    target: HIV
    Research Areas: Infection