Thiotetrazole alkynylacetanilides as potent and bioavailable non-nucleoside inhibitors of the HIV-1 wild type and K103N/Y181C double mutant reverse transcriptases

Alexandre Gagnon; Ma'an H Amad; Pierre R Bonneau; René Coulombe; Patrick L DeRoy; Louise Doyon; Jianmin Duan; Michel Garneau; Ingrid Guse; Araz Jakalian; Eric Jolicoeur; Serge Landry; Eric Malenfant; Bruno Simoneau; Christiane Yoakim

doi:10.1016/j.bmcl.2007.06.012

Thiotetrazole alkynylacetanilides as potent and bioavailable non-nucleoside inhibitors of the HIV-1 wild type and K103N/Y181C double mutant reverse transcriptases

Bioorg Med Chem Lett. 2007 Aug 15;17(16):4437-41. doi: 10.1016/j.bmcl.2007.06.012. Epub 2007 Jun 8.

Authors

Alexandre Gagnon¹, Ma'an H Amad, Pierre R Bonneau, René Coulombe, Patrick L DeRoy, Louise Doyon, Jianmin Duan, Michel Garneau, Ingrid Guse, Araz Jakalian, Eric Jolicoeur, Serge Landry, Eric Malenfant, Bruno Simoneau, Christiane Yoakim

Affiliation

¹ Boehringer Ingelheim (Canada) Ltd., Research and Development, 2100 Cunard Street, Laval, Que., Canada, H7S 2G5. [email protected]

PMID: 17583503
DOI: 10.1016/j.bmcl.2007.06.012

Abstract

A series of aryl thiotetrazolylacetanilides were synthesized and found to be potent inhibitors of the HIV-1 wild type and K103N/Y181C double mutant reverse transcriptases. The incorporation of an alkynyl fragment on the aniline provided inhibitors with excellent cellular activity and extensive SAR led to the identification of one inhibitor having good oral bioavailability in rats.

MeSH terms

Acetanilides / chemistry
Acetanilides / pharmacology*
Animals
Antiviral Agents / chemistry*
Antiviral Agents / pharmacology*
Biological Availability
HIV Reverse Transcriptase / genetics*
HIV-1 / drug effects*
HIV-1 / genetics*
Models, Molecular
Molecular Structure
Mutation
Rats
Reverse Transcriptase Inhibitors / chemistry
Reverse Transcriptase Inhibitors / pharmacology
Structure-Activity Relationship

Substances

Acetanilides
Antiviral Agents
Reverse Transcriptase Inhibitors
HIV Reverse Transcriptase