Synthesis and biological evaluation of C-5 methyl substituted 4-arylthio and 4-aryloxy-3-Iodopyridin-2(1H)-one type anti-HIV agents.
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.
Guillemont
Jérôme
J
Medicinal Chemistry Department, TIBOTEC, Campus de Maigremont BP315, 27430 Val de Reuil, France. ,jguillem@its.jnj.com
Benjahad
Abdellah
A
Oumouch
Said
S
Decrane
Laurence
L
Palandjian
Patrice
P
Vernier
Daniel
D
Queguiner
Laurence
L
Andries
Koen
K
de Béthune
Marie-Pierre
MP
Hertogs
Kurt
K
Grierson
David S
DS
Nguyen
Chi Hung
CH
D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D006678:HIV / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors / Q000235:genetics; D006801:Humans; D020128:Inhibitory Concentration 50; D007469:Iodopyridones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D009154:Mutation; D054852:Small Molecule Libraries / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
D019380:Anti-HIV Agents; D007469:Iodopyridones; D054852:Small Molecule Libraries; D054303:HIV Reverse Transcriptase