1. Synthesis and biological evaluation of C-5 methyl substituted 4-arylthio and 4-aryloxy-3-Iodopyridin-2(1H)-one type anti-HIV agents.
- Author
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Guillemont J, Benjahad A, Oumouch S, Decrane L, Palandjian P, Vernier D, Queguiner L, Andries K, de Béthune MP, Hertogs K, Grierson DS, and Nguyen CH
- Subjects
- Anti-HIV Agents chemistry, Cell Line, HIV enzymology, HIV genetics, HIV Reverse Transcriptase antagonists & inhibitors, HIV Reverse Transcriptase genetics, Humans, Inhibitory Concentration 50, Iodopyridones chemistry, Mutation, Small Molecule Libraries chemical synthesis, Small Molecule Libraries chemistry, Small Molecule Libraries pharmacology, Anti-HIV Agents chemical synthesis, Anti-HIV Agents pharmacology, HIV drug effects, Iodopyridones chemical synthesis, Iodopyridones pharmacology
- Abstract
A series of C-5 methyl substituted 4-arylthio- and 4-aryloxy-3-iodopyridin-2(1H)-ones has been synthesized as new pyridinone analogues for their evaluation as anti-HIV inhibitors. The optimization at the 5-position was developed through an efficient use of the key intermediates 5-ethoxycarbonyl- and 5-cyano-pyridin-2(1H)-ones (14 and 15). Biological studies revealed that several compounds show potent HIV-1 reverse transcriptase inhibitory properties, for example, compounds 93 and 99 are active at 0.6-50 nM against wild type HIV-1 and a panel of major simple/double HIV mutant strains.
- Published
- 2009
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