Scaffold hopping in the rational design of novel HIV-1 non-nucleoside reverse transcriptase inhibitors

Jeff A O'Meara; Araz Jakalian; Steven LaPlante; Pierre R Bonneau; René Coulombe; Anne-Marie Faucher; Ingrid Guse; Serge Landry; Jennifer Racine; Bruno Simoneau; Bounkham Thavonekham; Christiane Yoakim

doi:10.1016/j.bmcl.2007.03.097

Scaffold hopping in the rational design of novel HIV-1 non-nucleoside reverse transcriptase inhibitors

Bioorg Med Chem Lett. 2007 Jun 15;17(12):3362-6. doi: 10.1016/j.bmcl.2007.03.097. Epub 2007 Apr 5.

Authors

Jeff A O'Meara¹, Araz Jakalian, Steven LaPlante, Pierre R Bonneau, René Coulombe, Anne-Marie Faucher, Ingrid Guse, Serge Landry, Jennifer Racine, Bruno Simoneau, Bounkham Thavonekham, Christiane Yoakim

Affiliation

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

PMID: 17451954
DOI: 10.1016/j.bmcl.2007.03.097

Abstract

High-throughput screening hit 1 was identified as a potent, broad-spectrum, non-nucleoside reverse transcriptase inhibitor (NNRTI) of HIV-1 replication. Analysis of the bound conformation of analogs of this inhibitor via molecular modeling and NMR contributed to the design of novel tertiary amide, carbamate, and thiocarbamate based NNRTIs.

MeSH terms

Amides / chemistry
Anti-HIV Agents / chemical synthesis
Anti-HIV Agents / pharmacology*
Carbamates / chemistry
Drug Design
Drug Resistance, Viral
HIV Reverse Transcriptase / antagonists & inhibitors*
Humans
Inhibitory Concentration 50
Magnetic Resonance Spectroscopy
Models, Chemical
Reverse Transcriptase Inhibitors / chemical synthesis
Reverse Transcriptase Inhibitors / pharmacology*
Structure-Activity Relationship
Thiocarbamates / chemistry
Virus Replication / drug effects*

Substances

Amides
Anti-HIV Agents
Carbamates
Reverse Transcriptase Inhibitors
Thiocarbamates
HIV Reverse Transcriptase