Preparation and biological evaluation of 1′-cyano-2′-C-methyl pyrimidine nucleosides as HCV NS5B polymerase inhibitors

Mish, Michael; Cho, Aesop; Kirschberg, Thorsten; Xu, Jie; Zonte, Catalin; Fenaux, Martijn; Park, Yeojin; Babusis, Darius; Feng, Joy Y.; Ray, Adrian S.; Kim, Choung U.

doi:10.1016/j.bmcl.2014.05.015

Cited by 12 publications

(2 citation statements)

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“…68,69 Butora et al 70 then demonstrated that the C-nucleoside scaffold could be tolerated for HCV inhibitory activity, as exemplified specifically for 9-deaza-and 7,9-dideaza-7-oxa-2′-C-methyladenosine (Figure 6). 71 The synthesis of the 1′-cyano-2′-C-methyl-Cnucleoside parent (20, 23) (Figure 6) of 2 was described by Mish et al 72 In fact, various derivatives of imidazotriazine and pyrrolotriazine C-nucleosides were described as potential new anti-HCV agents by Draffan et al, 73 and one, the 7-carboxamido derivative (21) (Figure 6) drew particular attention because of its extremely potent activity (EC 50 = 0.006 μM) against HCV. This (carbox)amido group could be involved in hydrogen bonding during base pairing.…”

Section: C-nucleoside Hcv Polymerase Inhibitormentioning

confidence: 99%

C-Nucleosides To Be Revisited

2015

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Two new C-nucleoside analogues, BCX4430, an imino-C-nucleoside, and GS-6620, a phosphoramidate derivative of 1'-cyano-2'-C-methyl-4-aza-7,9-dideazaadenosine C-nucleoside, have been recently described as effective against filovirus infections (Marburg) and hepatitis C virus (HCV), respectively. The first C-nucleoside analogues were described about half a century ago. The C-nucleoside pseudouridine is a natural component of RNA, and various other C-nucleoside analogues have been reported previously for their antiviral and/or anticancer potential, the most prominent being pyrazofurin, tiazofurin, and selenazofurin. In the meantime, showdomycin, formycin, and various triazole, pyrazine, pyridine, dihydroxyphenyl, thienopyrimidine, pyrazolotriazine, and porphyrin C-nucleoside analogues have been described. It would be worth revisiting these C-nucleosides and derivatives thereof, including their phosphoramidates, for their therapeutic potential in the treatment of virus infections and, where appropriate, cancer as well.

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Section: C-nucleoside Hcv Polymerase Inhibitormentioning

confidence: 99%

C-Nucleosides To Be Revisited

2015

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“…In view of those, in 2014 Mish et al [48] firstly reported the synthesis of 1'-cyano-2'-C-methyl pyrimidine nucleosides as HCV NS5B polymerase inhibitors with a moderate HCV polymerase enzyme inhibitory activity. In particular, compound 27 was a prominent inhibitor starting from 25 which was subjected to the reaction with 4-nitrophenolate 26 to provide monophosphoramidate prodrug 27 in 20% yield.…”

Section: (Scheme 4)mentioning

confidence: 99%