3-iodo-4-phenoxypyridinones (IOPY's), a new family of highly potent non-nucleoside inhibitors of HIV-1 reverse transcriptase.
Building upon the potent anti-HIV-1 activities observed for the 3-dimethylamino-4-benzylpyridinone 2, and the corresponding 4-aryloxypyridinone analogue 3, a concise and efficient route to the 3-iodo-4-aryloxypyridinones 14a-c (IOPY's) was developed. This involved reaction of the 4-hydroxy substituted pyridinone 10 with the requisite dichloroiodobenzene reagent 11. IOPY compound 14c is active at IC(50)=1-45 nM against wild type HIV-1 and a panel of six major simple/double HIV mutant strains.
Benjahad
Abdellah
A
UMR 176 CNRS-Institut Curie, Laboratoire de Pharmacochimie, Section de Recherche, Batiment 110, Centre Universitaire, 91405 Orsay, France. abdellah.benjahad@curie.u-psud.fr
Guillemont
Jérôme
J
Andries
Koen
K
Nguyen
Chi Hung
CH
Grierson
David S
DS
D015497:HIV-1 / Q000187:drug effects*; D008958:Models, Molecular; D008968:Molecular Conformation; D011728:Pyridones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D011728:Pyridones; D018894:Reverse Transcriptase Inhibitors