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Synthesis and characterization of 2'-C-Me branched C-nucleosides as HCV polymerase inhibitors. 2012
Aesop Cho, and
Lijun Zhang, and
Jie Xu, and
Darius Babusis, and
Thomas Butler, and
Rick Lee, and
Oliver L Saunders, and
Ting Wang, and
Jay Parrish, and
Jason Perry, and
Joy Y Feng, and
Adrian S Ray, and
Choung U Kim
Gilead Sciences, 333 Lakeside Drive, Foster City, CA 94044, USA. acho@gilead.com
A series of 2'-C-methyl branched purine and pyrimidine C-nucleosides were prepared. Their anti-HCV activity and pharmacological properties were profiled, and compared with known 2'-C-Me N-nucleoside counterparts. In particular, 2'-C-Me 4-aza-7,9-dideazaadenosine C-nucleoside (2) was found to have potent and selective anti-HCV activity in vitro as well as a favorable pharmacokinetic profile and in vivo potential for enhanced potency over the corresponding N-nucleoside.
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