A novel diketo phosphonic acid that exhibits specific, strand-transfer inhibition of HIV integrase and anti-HIV activity.
We have synthesized novel phosphonic acid analogues of beta-diketo acids. Interestingly, the phosphonic acid isostere, 2, of our anti-HIV compound, 1, was an inhibitor of only the strand transfer step, in stark contrast to 1. Compound 2 had lower anti-HIV activity than 1, but was more active and less toxic than the phosphonic acid analogue of L-708906. These isosteric compounds represent the first examples of beta-diketo phosphonic acids of structural, synthetic, and antiviral interest.
Chi
Guochen
G
The Center for Drug Discovery and the Department of Pharmaceutical and Biomedical Sciences, University of Georgia, Athens, GA 30602, USA.
Nair
Vasu
V
Semenova
Elena
E
Pommier
Yves
Y
D000090:Acetoacetates / Q000494:pharmacology; D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002460:Cell Line; D015658:HIV Infections / Q000188:drug therapy; D019428:HIV Integrase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D007659:Ketones; D063065:Organophosphonates / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000090:Acetoacetates; D019380:Anti-HIV Agents; D019428:HIV Integrase Inhibitors; D007659:Ketones; C403887:L 708906; D063065:Organophosphonates