Synthesis and biological evaluation of C-5 methyl substituted 4-arylthio and 4-aryloxy-3-Iodopyridin-2(1H)-one type anti-HIV agents

  • J Med Chem. 2009 Dec 10;52(23):7473-87. doi: 10.1021/jm900802y.
Jérôme Guillemont  1 ,  Abdellah Benjahad ,  Said Oumouch ,  Laurence Decrane ,  Patrice Palandjian ,  Daniel Vernier ,  Laurence Queguiner ,  Koen Andries ,  Marie-Pierre de Béthune ,  Kurt Hertogs ,  David S Grierson ,  Chi Hung Nguyen
Affiliations
  • 1. Medicinal Chemistry Department, TIBOTEC, Campus de Maigremont BP315, 27430 Val de Reuil, France. ,[email protected]
PMID: 19645483 DOI: 10.1021/jm900802y
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.