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Issue 5, 2020
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Discovery, SAR study and ADME properties of methyl 4-amino-3-cyano-1-(2-benzyloxyphenyl)-1H-pyrazole-5-carboxylate as an HIV-1 replication inhibitor

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Abstract

Inspired by the antiviral activity of known pyrazole-based HIV inhibitors, we screened our in-house library of pyrazole-based compounds to evaluate their in cellulo activity against HIV-1 replication. Two hits with very similar structures appeared from single and multiple-round infection assays to be non-toxic and active in a dose-dependent manner. Chemical expansion of their series allowed an in-depth and consistent structure–activity-relationship study (SAR) to be built. Further ADME evaluation led to the selection of 4-amino-3-cyano-1-(2-benzyloxyphenyl)-1H-pyrazole-5-carboxylate with an advantageous pharmacokinetic profile. Finally, examination of its mode of action revealed that this compound does not belong to the three main classes of anti-HIV drugs, a feature of prime interest in the context of viral resistance.

Graphical abstract: Discovery, SAR study and ADME properties of methyl 4-amino-3-cyano-1-(2-benzyloxyphenyl)-1H-pyrazole-5-carboxylate as an HIV-1 replication inhibitor

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Supplementary files

Article information


Submitted
23 Jan 2020
Accepted
14 Mar 2020
First published
27 Apr 2020

RSC Med. Chem., 2020,11, 577-582
Article type
Research Article

Discovery, SAR study and ADME properties of methyl 4-amino-3-cyano-1-(2-benzyloxyphenyl)-1H-pyrazole-5-carboxylate as an HIV-1 replication inhibitor

J. Fichez, C. Soulie, L. Le Corre, S. Sayon, S. Priet, K. Alvarez, O. Delelis, P. Gizzi, G. Prestat, C. Gravier-Pelletier, A. Marcelin, V. Calvez and P. Busca, RSC Med. Chem., 2020, 11, 577
DOI: 10.1039/D0MD00025F

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