Design and synthesis of N-methylpyrimidone derivatives as HIV-1 integrase inhibitors

Abstract

A series of novel β-diketo derivatives which combined the virtues of dihydroxypyrimidine carboxamide derived from the evolution of DKA and polyhydroxylated aromatics moieties, were designed and synthesized as potential HIV-1 integrase (IN) inhibitors and evaluated their inhibition to the strand transfer process of HIV-1 integrase and anti-HIV-1 activity. The result indicates that 3,4,5-trihydroxylated aromatic derivatives exhibit good inhibition to HIV-1 integrase, but dihydroxylated aromatic derivatives appear little inhibition to HIV-1 integrase. In addition, the preliminary structure–activity relationship (SAR) of these new derivatives was rationalized by docking studies.