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

Junwon Kim (1) , Changmin Park (1) , Taedong Ok (1) , Wonyoung So (1) , Mina Jo (1) , Minjung Seo (1) , Youngmi Kim (1) , Jeong-Hun Sohn (1) , Youngsam Park (1) , Moon Kyeong Ju (1) , Junghwan Kim (1) , Sung-Jun Han (1) , Tae-Hee Kim (1) , Jonathan Cechetto (1) , Jiyoun Nam (1) , Peter Sommer (1) , Zaesung No (1)

1 Institut Pasteur Korea - Institut Pasteur de Corée

3,4-Dihydropyrimidin-2(1H)-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.

Keywords: HIV; 4-Dihydropyrimidin-2(1H)-one; Biginelli reaction; Fractional crystallization; Enantiomers

Domains: Virology

Junwon Kim, Changmin Park, Taedong Ok, Wonyoung So, Mina Jo, et al.. Discovery of 3,4-dihydropyrimidin-2(1H)-ones with inhibitory activity against HIV-1 replication.. Bioorganic and Medicinal Chemistry Letters, 2012, 22 (5), pp.2119-24. ⟨10.1016/j.bmcl.2011.12.090⟩. ⟨pasteur-00683848⟩