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

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

doi:10.1016/j.bmcl.2011.12.090

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

Bioorg Med Chem Lett. 2012 Mar 1;22(5):2119-24. doi: 10.1016/j.bmcl.2011.12.090. Epub 2012 Jan 12.

Authors

Junwon Kim¹, Changmin Park, Taedong Ok, Wonyoung So, Mina Jo, Minjung Seo, Youngmi Kim, Jeong-Hun Sohn, Youngsam Park, Moon Kyeong Ju, Junghwan Kim, Sung-Jun Han, Tae-Hee Kim, Jonathan Cechetto, Jiyoun Nam, Peter Sommer, Zaesung No

Affiliation

¹ Medicinal Chemistry Group, Institut Pasteur Korea (IP-K), Sampyeong-dong 696, Bundang-gu, Seongnam-si, Gyeonggi-do 463-400, Republic of Korea.

PMID: 22305583
DOI: 10.1016/j.bmcl.2011.12.090

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-HIV Agents / chemistry*
Anti-HIV Agents / pharmacology*
Drug Design
HIV Infections / drug therapy
HIV-1 / drug effects*
Humans
Pyrimidinones / chemistry*
Pyrimidinones / pharmacology*
Stereoisomerism
Structure-Activity Relationship
Virus Replication / drug effects*

Substances

Anti-HIV Agents
Pyrimidinones