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BMS-200475, a novel carbocyclic 2′-deoxyguanosine analog with potent and selective anti-hepatitis B virus activity in vitro

✍ Scribed by G.S. Bisacchi; S.T. Chao; C. Bachard; J.P. Daris; S. Innaimo; G.A. Jacobs; O. Kocy; P. Lapointe; A. Martel; Z. Merchant; W.A. Slusarchyk; J.E. Sundeen; M.G. Young; R. Colonno; R. Zahler

Publisher
Elsevier Science
Year
1997
Tongue
English
Weight
297 KB
Volume
7
Category
Article
ISSN
0960-894X

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✦ Synopsis

BMS-200475

, a novel carbocyclic analog of 2'-deoxyguanosine, is a potent inhibitor of hepatitis B virus in vitro (EDs0 = 3 nM) with relatively low cytotoxicity (CC50 = 21-120 pNI). A practical 10-step asymmetric synthesis was developed affording BMS-200475 in 18% overall chemical yield and >99% optical purity. The enantiomer of BMS-200475 as well as the adenine, thymine, and iodouracil analogs are much less active.

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## Anti -hepatitis C virus (HCV) drug development has been challenged by a lack of experience with inhibitors inclusive of in vitro, animal model, and clinical study. This manuscript outlines activity and correlation across such a spectrum of models and into clinical trials with a novel selective