Concise syntheses and HCV NS5B polymerase inhibition of (2′R)-3 and (2′S)-2′-ethynyluridine-10 and related nucleosides. Issue 23 (1st December 2017)

• Record Type: Journal Article
• Authors: Bennett, Frank; Buevich, Alexei V.; Huang, Hsueh-Cheng; Girijavallabhan, Vinay; Kerekes, Angela D.; Huang, Yuhua; Malikzay, Asra; Smith, Elizabeth; Ferrari, Eric; Senior, Mary; Osterman, Rebecca; Wang, Lingyan; Wang, Jun; Pu, Haiyan; Truong, Quang T.; Tawa, Paul; Bogen, Stephane L.; Davies, Ian W.; Weber, Ann E.
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 27:Issue 23(2017)
• Page Start: 5349
• Page End: 5352
• Publication Date: 2017-12-01
• Subjects: Nucleoside -- Hepatitis -- Cancer; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2017.06.064
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: (2′ R )-Ethynyl uridine3, and its (2′ S )-diastereomer10, are synthesised in a divergent fashion from the inexpensive parent nucleoside. Both nucleoside analogues are obtained from a total of 5 simple synthetic steps and 3 trivial column chromatography purifications. To evaluate their effectiveness against HCV NS5B polymerase, the nucleosides were converted to their respective 5′-O-triphosphates. Subsequently, this lead to the discovery of the 2′-β-ethynyl18 and -propynyl20 nucleotides having significantly improved potency over Sofosbuvir triphosphate24 .