Discovery of 3,4-dihydropyrimidin-2(1H)-ones with inhibitory activity against HIV-1 replication.

Abstract 3,4-Dihydropyrimidin-2(1 H )-ones (DHPMs) were selected and derivatized through a HIV-1 replication assay based on GFP reporter cells. Compounds 14 , 25 , 31 , and 36 exhibited significant inhibition of HIV-1 replication with a good safety profile. Chiral separation of each enantiomer by fractional crystallization showed that only the S enantiomer retained anti-HIV activity. Compound ( S )- 40 , a novel and potent DHPM analog, could serve as an advanced lead for further development and the determination of the mechanism of action.