RESUMO
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.
Assuntos
Fármacos Anti-HIV/síntese química , Fármacos Anti-HIV/farmacologia , HIV/efeitos dos fármacos , Iodopiridonas/síntese química , Iodopiridonas/farmacologia , Fármacos Anti-HIV/química , Linhagem Celular , HIV/enzimologia , HIV/genética , Transcriptase Reversa do HIV/antagonistas & inibidores , Transcriptase Reversa do HIV/genética , Humanos , Concentração Inibidora 50 , Iodopiridonas/química , Mutação , Bibliotecas de Moléculas Pequenas/síntese química , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/farmacologiaRESUMO
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.