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.