2'-Deoxy-2'-fluorocytidine

vanc 6 4-amino-1-[(2R,3R,4R,5R)-3-fluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one 2'-Deoxy-2'-fluorocytidine.svg skin-invert-image Investigational New Drug 10212-20-1 101507 LCY080JPY9 91721 230019 374528 9 12 1 3 4 C1=CN(C(=O)N=C1N)[C@H]2[C@@H]([C@@H]([C@H](O2)CO)O)F 1S/C9H12FN3O4/c10-6-7(15)4(3-14)17-8(6)13-2-1-5(11)12-9(13)16/h1-2,4,6-8,14-15H,3H2,(H2,11,12,16)/t4-,6-,7-,8-/m1/s1 NVZFZMCNALTPBY-XVFCMESISA-N 2'-Deoxy-2'-fluorocytidine is a nucleoside derivative developed in the 1960s, which has antiviral properties against many different kinds of viral diseases. It is closely related to several other antiviral drugs such as azvudine and lumicitabine, as well as the anti-cancer drug gemcitabine. 2'-Deoxy-2'-fluorocytidine has never been developed for medical use due to its comparatively harsh side effect profile, despite its broad spectrum antiviral properties, but has attracted renewed attention in recent years as a potential treatment for Crimean–Congo hemorrhagic fever (CCHF), a tick-borne hemorrhagic fever from the bunyavirus family. CCHF is highly lethal with a case fatality rate upwards of 30%, and no vaccine is currently available though some are in development. Some existing drugs such as ribavirin and favipiravir show activity against CCHF, but neither is very effective and there are no approved treatments for human use. There is therefore a pressing need for improved treatments for CCHF, and 2'-deoxy-2'-fluorocytidine was one of the most effective agents identified in vitro and in animal studies. It is currently in pre-clinical development with a view to potential human clinical trials. Doerr IL, Fox JJ Nucleosides. XXXIX. 2'-deoxy-2'-fluorocytidine, 1-beta-D-arabinofuranosyl-2-amino-1,4(2H)-4-iminopyrimidine, and related derivatives The Journal of Organic Chemistry 32 5 1462–1471 May 1967 6041430 10.1021/jo01280a035 Wohlrab F, Jamieson AT, Hay J, Mengel R, Guschlbauer W The effect of 2'-fluoro-2'-deoxycytidine on herpes virus growth Biochimica et Biophysica Acta 824 3 233–242 March 1985 2982405 10.1016/0167-4781(85)90053-3 Bajramovic JJ, Volmer R, Syan S, Pochet S, Gonzalez-Dunia D 2'-fluoro-2'-deoxycytidine inhibits Borna disease virus replication and spread Antimicrobial Agents and Chemotherapy 48 4 1422–1425 April 2004 15047559 375289 10.1128/AAC.48.4.1422-1425.2004 Kumaki Y, Day CW, Smee DF, Morrey JD, Barnard DL In vitro and in vivo efficacy of fluorodeoxycytidine analogs against highly pathogenic avian influenza H5N1, seasonal, and pandemic H1N1 virus infections Antiviral Research 92 2 329–340 November 2011 21925541 3216401 10.1016/j.antiviral.2011.09.001 Welch SR, Guerrero LW, Chakrabarti AK, McMullan LK, Flint M, Bluemling GR, Painter GR, Nichol ST, Spiropoulou CF, Albariño CG Lassa and Ebola virus inhibitors identified using minigenome and recombinant virus reporter systems Antiviral Research 136 9–18 December 2016 27771389 10.1016/j.antiviral.2016.10.007 1397092 Welch SR, Scholte FE, Flint M, Chatterjee P, Nichol ST, Bergeron É, Spiropoulou CF Identification of 2'-deoxy-2'-fluorocytidine as a potent inhibitor of Crimean-Congo hemorrhagic fever virus replication using a recombinant fluorescent reporter virus Antiviral Research 147 91–99 November 2017 29024765 8191813 10.1016/j.antiviral.2017.10.008 Smee DF, Jung KH, Westover J, Gowen BB 2'-Fluoro-2'-deoxycytidine is a broad-spectrum inhibitor of bunyaviruses in vitro and in phleboviral disease mouse models Antiviral Research 160 48–54 December 2018 30339848 10.1016/j.antiviral.2018.10.013 Yu P, Wang Y, Li Y, Li Y, Miao Z, Peppelenbosch MP, Pan Q 2'-Fluoro-2'-deoxycytidine inhibits murine norovirus replication and synergizes MPA, ribavirin and T705 Archives of Virology 165 11 2605–2613 November 2020 32770483 7414258 10.1007/s00705-020-04759-4 Dai S, Deng F, Wang H, Ning Y Crimean-Congo Hemorrhagic Fever Virus: Current Advances and Future Prospects of Antiviral Strategies Viruses 13 7 June 2021 1195 34206476 8310003 10.3390/v13071195 free Hawman DW, Feldmann H Crimean-Congo haemorrhagic fever virus Nature Reviews. Microbiology 21 7 463–477 July 2023 36918725 10013989 10.1038/s41579-023-00871-9 References Category:Anti–RNA virus drugs Category:Antiviral drugs Category:Tetrahydrofurans Category:Pyrimidines Category:Diols Category:Ureas Category:Amines