2. Academic Validation
  3. 2'-deoxy-2'-α-fluoro-2'-β-C-methyl 3',5'-cyclic phosphate nucleotide prodrug analogs as inhibitors of HCV NS5B polymerase: discovery of PSI-352938

2'-deoxy-2'-α-fluoro-2'-β-C-methyl 3',5'-cyclic phosphate nucleotide prodrug analogs as inhibitors of HCV NS5B polymerase: discovery of PSI-352938

  • Bioorg Med Chem Lett. 2010 Dec 15;20(24):7376-80. doi: 10.1016/j.bmcl.2010.10.035.
P Ganapati Reddy 1,  Donghui Bao,  Wonsuk Chang,  Byoung-Kwon Chun,  Jinfa Du,  Dhanapalan Nagarathnam,  Suguna Rachakonda,  Bruce S Ross,  Hai-Ren Zhang,  Shalini Bansal,  Christine L Espiritu,  Meg Keilman,  Angela M Lam,  Congrong Niu,  Holly Micolochick Steuer,  Phillip A Furman,  Michael J Otto,  Michael J Sofia
Affiliations

Affiliation

  • 1 Pharmasset, Inc., 303A College Road East, Princeton, NJ 08540, USA. pgreddy@pharmasset.com
PMID: 21050754 DOI: 10.1016/j.bmcl.2010.10.035
Abstract

A series of novel 2'-deoxy-2'-α-fluoro-2'-β-C-methyl 3',5'-cyclic phosphate nucleotide prodrug analogs were synthesized and evaluated for their in vitro anti-HCV activity and safety. These prodrugs demonstrated a 10-100-fold greater potency than the parent nucleoside in a cell-based replicon assay due to higher cellular triphosphate levels. Our structure-activity relationship (SAR) studies provided compounds that gave high levels of active triphosphate in rat liver when administered orally to rats. These studies ultimately led to the selection of the clinical development candidate 24a (PSI-352938).

Figures
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z