作者
Thorsten Kirschberg,Sammy Metobo,Michael O. Clarke,Vangelis Aktoudianakis,Darius Babusis,Ona Barauskas,Gabriel Birkuš,Thomas Butler,Daniel Byun,Gregory T. Chin,Edward Doerffler,Thomas E. Edwards,Martijn Fenaux,Richard T. Lee,Willard Lew,Michael Mish,Eisuke Murakami,Yeojin Park,Neil Squires,Neeraj Tirunagari,Ting Wang,Mark Whitcomb,Jie Xu,Huiling Yang,Hong Ye,Lijun Zhang,T.C. Appleby,Joy Y. Feng,Adrian S. Ray,Aesop Cho,Choung U. Kim
摘要
A series of 2'-fluorinated C-nucleosides were prepared and tested for anti-HCV activity. Among them, the triphosphate of 2'-fluoro-2'-C-methyl adenosine C-nucleoside (15) was a potent and selective inhibitor of the NS5B polymerase and maintained activity against the S282T resistance mutant. A number of phosphoramidate prodrugs were then prepared and evaluated leading to the identification of the 1-aminocyclobutane-1-carboxylic acid isopropyl ester variant (53) with favorable pharmacokinetic properties including efficient liver delivery in animals.