Trifluoromethyl-containing 3-alkoxymethyl- and 3-aryloxymethyl-2-pyridinones are potent inhibitors of HIV-1 non-nucleoside reverse transcriptase

J W Corbett; K J Kresge; S Pan; B C Cordova; R M Klabe; J D Rodgers; S K Erickson-Viitanen

doi:10.1016/s0960-894x(00)00662-4

Trifluoromethyl-containing 3-alkoxymethyl- and 3-aryloxymethyl-2-pyridinones are potent inhibitors of HIV-1 non-nucleoside reverse transcriptase

Bioorg Med Chem Lett. 2001 Feb 12;11(3):309-12. doi: 10.1016/s0960-894x(00)00662-4.

Authors

J W Corbett¹, K J Kresge, S Pan, B C Cordova, R M Klabe, J D Rodgers, S K Erickson-Viitanen

Affiliation

¹ DuPont Pharmaceuticals Company, Experimental Station, Wilmington, DE 19880-0500, USA. [email protected]

PMID: 11212098
DOI: 10.1016/s0960-894x(00)00662-4

Abstract

3-Alkoxymethyl- and 3-aryloxymethyl-2-pyridinones were synthesized and evaluated for activity as non-nucleoside reverse transcriptase inhibitors (NNRTIs) of HIV-1. It was found that several compounds were potent inhibitors of HIV-1 with the most potent compound 24 exhibiting an IC90 = 32 nM. Compound 24 also possessed a potent resistance profile as demonstrated by submicromolar IC90s against several clinically meaningful mutant virus strains.

MeSH terms

Anti-HIV Agents / chemical synthesis*
Anti-HIV Agents / pharmacology
Combinatorial Chemistry Techniques
Cytopathogenic Effect, Viral / drug effects
Enzyme Inhibitors / chemical synthesis
Enzyme Inhibitors / pharmacology
Fluorine / chemistry
HIV Reverse Transcriptase / antagonists & inhibitors*
HIV Reverse Transcriptase / genetics
HIV-1 / drug effects
HIV-1 / genetics
Inhibitory Concentration 50
Mutation
Pyridones / chemical synthesis
Pyridones / pharmacology*
Structure-Activity Relationship

Substances

Anti-HIV Agents
Enzyme Inhibitors
Pyridones
Fluorine
HIV Reverse Transcriptase