Synthesis and anti-hepatitis C virus (HCV) activity of 3'-C-substituted-methyl pyrimidine and purine nucleosides.
On the basis of potent anti-hepatitis C virus (HCV) activity of 2'-C-hydroxymethyladenosine, 3'-C-substituted-methyl-ribofuranosyl pyrimidine and purine nucleosides were designed and synthesized from D-xylose. Among compounds tested, all adenine analogues, 4a, 4d, and 4g showed significant anti-HCV activity in a replicon-based cell assay irrespective of the substituent (Y=OH, N₃, or F) at the 3'-C-substituted methyl position, among which 4g (Y=N₃) was the most potent, but it is also cytotoxic. This study guarantees the 3'-C-substituted-methyl nucleoside serves as a new template for the development of new anti-HCV agents.
Choi
Won Jun
WJ
Department of Bioinspired Science, Ewha Womans University, 11-1 Seodaemun-gu, Daehyun-dong, Seoul 120-750, Republic of Korea.
Kim
Yu Min
YM
Kim
Hea Ok
HO
Lee
Hyuk Woo
HW
Kim
Dong-Eun
DE
Park
Kwang-su
KS
Chong
Youhoon
Y
Jeong
Lak Shin
LS
D000241:Adenosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D016174:Hepacivirus / Q000187:drug effects*; D011684:Purine Nucleosides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011741:Pyrimidine Nucleosides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects
C559340:(3beta-C-fluoromethyl-beta-D-ribofuranosyl)-N6-methyladenine; C559339:(3betaC-fluoromethyl-beta-D-ribofuranosyl)adenine; D000998:Antiviral Agents; D011684:Purine Nucleosides; D011741:Pyrimidine Nucleosides; D000241:Adenosine