A novel 3,4-dihydropyrimidin-2(1H)-one: HIV-1 replication inhibitors with improved metabolic stability.

Junwon Kim (1) , Taedong Ok (1) , Changmin Park (1) , Wonyoung So (1) , Mina Jo (1) , Youngmi Kim (1) , Minjung Seo (1) , Doohyun Lee (1) , Suyeon Jo (1) , Yoonae Ko (1) , Inhee Choi (1) , Youngsam Park (1) , Jaewan Yoon (1) , Moon Kyeong Ju (1) , Jiye Ahn (1) , Junghwan Kim (1) , Sung-Jun Han (1) , Tae-Hee Kim (1, 2) , Jonathan Cechetto (1) , Jiyoun Nam (1) , Michel Liuzzi (1) , Peter Sommer (1) , Zaesung No (1)

1 Institut Pasteur Korea - Institut Pasteur de Corée
2 Department of Biotechnology, College of Life Science and Biotechnology

Following the previous SAR of a novel dihydropyrimidinone scaffold as HIV-1 replication inhibitors a detailed study directed towards optimizing the metabolic stability of the ester functional group in the dihydropyrimidinone (DHPM) scaffold is described. Replacement of the ester moiety by thiazole ring significantly improved the metabolic stability while retaining antiviral activity against HIV-1 replication. These novel and potent DHPMs with bioisosteres could serve as advanced leads for further optimization.

Mots clés: HIV; Inhibitor; 4-Dihydropyrimidin-2(1H)-one; Biginelli reaction; Bioisostere

Domaines: Virologie

Junwon Kim, Taedong Ok, Changmin Park, Wonyoung So, Mina Jo, et al.. A novel 3,4-dihydropyrimidin-2(1H)-one: HIV-1 replication inhibitors with improved metabolic stability.. Bioorganic and Medicinal Chemistry Letters, 2012, 22 (7), pp.2522-6. ⟨10.1016/j.bmcl.2012.01.133⟩. ⟨pasteur-00683846⟩