SAR and lead optimization of an HIV-1 Vif-APOBEC3G axis inhibitor

Idrees Mohammed, Maloy K. Parai, Xinpeng Jiang, Natalia Sharova, Gatikrushna Singh, Mario Stevenson, Tariq M. Rana

Research output: Contribution to journalArticle

20 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)465-469
Number of pages5
JournalACS Medicinal Chemistry Letters
Volume3
Issue number6
DOIs
StatePublished - May 14 2012

Keywords

  • HIV-1 Vif-APOBEC3G axis inhibition
  • pharmacological studies
  • RN-18
  • structure-activity relationship and optimization

ASJC Scopus subject areas

  • Organic Chemistry
  • Drug Discovery
  • Biochemistry

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  • Cite this

    Mohammed, I., Parai, M. K., Jiang, X., Sharova, N., Singh, G., Stevenson, M., & Rana, T. M. (2012). SAR and lead optimization of an HIV-1 Vif-APOBEC3G axis inhibitor. ACS Medicinal Chemistry Letters, 3(6), 465-469. https://doi.org/10.1021/ml300037k