Trifluoromethyl-containing 3-alkoxymethyl- and 3-aryloxymethyl-2-pyridinones are potent inhibitors of HIV-1 non-nucleoside reverse transcriptase.
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.
Corbett
J W
JW
DuPont Pharmaceuticals Company, Experimental Station, Wilmington, DE 19880-0500, USA. jeffrey.w.corbett@am.pnu.com
Kresge
K J
KJ
Pan
S
S
Cordova
B C
BC
Klabe
R M
RM
Rodgers
J D
JD
Erickson-Viitanen
S K
SK
D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D020650:Combinatorial Chemistry Techniques; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D005461:Fluorine / Q000737:chemistry; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors* / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics; D020128:Inhibitory Concentration 50; D009154:Mutation; D011728:Pyridones / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D019380:Anti-HIV Agents; D004791:Enzyme Inhibitors; D011728:Pyridones; D005461:Fluorine; D054303:HIV Reverse Transcriptase