Discovery of 3,4-dihydropyrimidin-2(1H)-ones with inhibitory activity against HIV-1 replication.
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.
Medicinal Chemistry Group, Institut Pasteur Korea (IP-K), Sampyeong-dong 696, Bundang-gu, Seongnam-si, Gyeonggi-do 463-400, Republic of Korea.
Junwon
J
Kim
Changmin
C
Park
Taedong
T
Ok
Wonyoung
W
So
Mina
M
Jo
Minjung
M
Seo
Youngmi
Y
Kim
Jeong-Hun
JH
Sohn
Youngsam
Y
Park
Moon Kyeong
MK
Ju
Junghwan
J
Kim
Sung-Jun
SJ
Han
Tae-Hee
TH
Kim
Jonathan
J
Cechetto
Jiyoun
J
Nam
Peter
P
Sommer
Zaesung
Z
No
D019380:Anti-HIV Agents / Q000737:chemistry* / Q000494:pharmacology*; D015195:Drug Design; D015658:HIV Infections / Q000188:drug therapy; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D011744:Pyrimidinones / Q000737:chemistry* / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014779:Virus Replication / Q000187:drug effects*
D019380:Anti-HIV Agents; D011744:Pyrimidinones