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.
Subject(s)
Anti-HIV Agents/chemical synthesis , Anti-HIV Agents/pharmacology , HIV/drug effects , Iodopyridones/chemical synthesis , Iodopyridones/pharmacology , 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/pharmacologyABSTRACT
The synthesis and biological evaluation of 4-(aminomethyl)-6-(1,1-dimethylethyl)-2-iodo-3-pyridinol dihydrochloride (7b) are described. Compound 7b proved to be highly active as a saluretic diuretic in both rats and dogs.
