1,2,3-triazoles as amide bioisosteres: Discovery of a new class of potent HIV-1 Vif antagonists

Idrees Mohammed, Indrasena Reddy Kummetha, Gatikrushna Singh, Natalia Sharova, Gianluigi Lichinchi, Jason Dang, Mario Stevenson, Tariq M. Rana

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

RN-18 based viral infectivity factor (Vif), Vif antagonists reduce viral infectivity by rescuing APOBEC3G (A3G) expression and enhancing A3G-dependent Vif degradation. Replacement of amide functionality in RN-18 (IC50 = 6 μM) by isosteric heterocycles resulted in the discovery of a 1,2,3-trizole, Id (IC50 = 1.2 μM). We identified several potent HIV-1 inhibitors from a Id based library including 5ax (IC50 = 0.01 μM), 5bx (0.2 μM), 2ey (0.4 μM), 5ey (0.6 μM), and 6bx (0.2 μ M).

Original languageEnglish (US)
Pages (from-to)7677-7682
Number of pages6
JournalJournal of Medicinal Chemistry
Volume59
Issue number16
DOIs
StatePublished - Aug 25 2016

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Triazoles
Amides
Inhibitory Concentration 50
HIV-1
Libraries

ASJC Scopus subject areas

  • Medicine(all)
  • Molecular Medicine
  • Drug Discovery

Cite this

Mohammed, I., Kummetha, I. R., Singh, G., Sharova, N., Lichinchi, G., Dang, J., ... Rana, T. M. (2016). 1,2,3-triazoles as amide bioisosteres: Discovery of a new class of potent HIV-1 Vif antagonists. Journal of Medicinal Chemistry, 59(16), 7677-7682. https://doi.org/10.1021/acs.jmedchem.6b00247

1,2,3-triazoles as amide bioisosteres : Discovery of a new class of potent HIV-1 Vif antagonists. / Mohammed, Idrees; Kummetha, Indrasena Reddy; Singh, Gatikrushna; Sharova, Natalia; Lichinchi, Gianluigi; Dang, Jason; Stevenson, Mario; Rana, Tariq M.

In: Journal of Medicinal Chemistry, Vol. 59, No. 16, 25.08.2016, p. 7677-7682.

Research output: Contribution to journalArticle

Mohammed, I, Kummetha, IR, Singh, G, Sharova, N, Lichinchi, G, Dang, J, Stevenson, M & Rana, TM 2016, '1,2,3-triazoles as amide bioisosteres: Discovery of a new class of potent HIV-1 Vif antagonists', Journal of Medicinal Chemistry, vol. 59, no. 16, pp. 7677-7682. https://doi.org/10.1021/acs.jmedchem.6b00247
Mohammed, Idrees ; Kummetha, Indrasena Reddy ; Singh, Gatikrushna ; Sharova, Natalia ; Lichinchi, Gianluigi ; Dang, Jason ; Stevenson, Mario ; Rana, Tariq M. / 1,2,3-triazoles as amide bioisosteres : Discovery of a new class of potent HIV-1 Vif antagonists. In: Journal of Medicinal Chemistry. 2016 ; Vol. 59, No. 16. pp. 7677-7682.
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