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

doi:10.1021/acs.jmedchem.6b00247

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 journal › Article › peer-review

197 Scopus citations

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 language	English (US)
Pages (from-to)	7677-7682
Number of pages	6
Journal	Journal of medicinal chemistry
Volume	59
Issue number	16
DOIs	https://doi.org/10.1021/acs.jmedchem.6b00247
State	Published - Aug 25 2016
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2016 American Chemical Society.

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This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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http://europepmc.org/articles/pmc5534211

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

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).",

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doi = "10.1021/acs.jmedchem.6b00247",

language = "English (US)",

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T2 - Discovery of a new class of potent HIV-1 Vif antagonists

AU - Mohammed, Idrees

AU - Kummetha, Indrasena Reddy

AU - Singh, Gatikrushna

AU - Sharova, Natalia

AU - Lichinchi, Gianluigi

AU - Dang, Jason

AU - Stevenson, Mario

AU - Rana, Tariq M.

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Y1 - 2016/8/25

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AB - 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).

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

Abstract

Bibliographical note

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