2'-Deoxy-2'-fluorocytidine

2'-Deoxy-2'-fluorocytidine
Legal status
Legal status	US: Investigational New Drug;
Identifiers
	IUPAC name 4-amino-1-[(2R,3R,4R,5R)-3-fluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one;
CAS Number	10212-20-1;
PubChem CID	101507;
ChemSpider	91721;
UNII	LCY080JPY9;
ChEBI	CHEBI:230019;
ChEMBL	ChEMBL374528;
CompTox Dashboard (EPA)	DTXSID20907103 ;
Chemical and physical data
Formula	C9H12FN3O4
Molar mass	245.210 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES C1=CN(C(=O)N=C1N)[C@H]2[C@@H]([C@@H]([C@H](O2)CO)O)F;
	InChI InChI=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; Key: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.^[1]^[2]^[3]^[4]^[5]^[6]^[7]^[8]^[9]^[10]

References

^ Doerr IL, Fox JJ (May 1967). "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. doi:10.1021/jo01280a035. PMID 6041430.
^ Wohlrab F, Jamieson AT, Hay J, Mengel R, Guschlbauer W (March 1985). "The effect of 2'-fluoro-2'-deoxycytidine on herpes virus growth". Biochimica et Biophysica Acta. 824 (3): 233–242. doi:10.1016/0167-4781(85)90053-3. PMID 2982405.
^ Bajramovic JJ, Volmer R, Syan S, Pochet S, Gonzalez-Dunia D (April 2004). "2'-fluoro-2'-deoxycytidine inhibits Borna disease virus replication and spread". Antimicrobial Agents and Chemotherapy. 48 (4): 1422–1425. doi:10.1128/AAC.48.4.1422-1425.2004. PMC 375289. PMID 15047559.
^ Kumaki Y, Day CW, Smee DF, Morrey JD, Barnard DL (November 2011). "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. doi:10.1016/j.antiviral.2011.09.001. PMC 3216401. PMID 21925541.
^ Welch SR, Guerrero LW, Chakrabarti AK, McMullan LK, Flint M, Bluemling GR, et al. (December 2016). "Lassa and Ebola virus inhibitors identified using minigenome and recombinant virus reporter systems". Antiviral Research. 136: 9–18. doi:10.1016/j.antiviral.2016.10.007. PMID 27771389.
^ Welch SR, Scholte FE, Flint M, Chatterjee P, Nichol ST, Bergeron É, et al. (November 2017). "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. doi:10.1016/j.antiviral.2017.10.008. PMC 8191813. PMID 29024765.
^ Smee DF, Jung KH, Westover J, Gowen BB (December 2018). "2'-Fluoro-2'-deoxycytidine is a broad-spectrum inhibitor of bunyaviruses in vitro and in phleboviral disease mouse models". Antiviral Research. 160: 48–54. doi:10.1016/j.antiviral.2018.10.013. PMID 30339848.
^ Yu P, Wang Y, Li Y, Li Y, Miao Z, Peppelenbosch MP, et al. (November 2020). "2'-Fluoro-2'-deoxycytidine inhibits murine norovirus replication and synergizes MPA, ribavirin and T705". Archives of Virology. 165 (11): 2605–2613. doi:10.1007/s00705-020-04759-4. PMC 7414258. PMID 32770483.
^ Dai S, Deng F, Wang H, Ning Y (June 2021). "Crimean-Congo Hemorrhagic Fever Virus: Current Advances and Future Prospects of Antiviral Strategies". Viruses. 13 (7): 1195. doi:10.3390/v13071195. PMC 8310003. PMID 34206476.
^ Hawman DW, Feldmann H (July 2023). "Crimean-Congo haemorrhagic fever virus". Nature Reviews. Microbiology. 21 (7): 463–477. doi:10.1038/s41579-023-00871-9. PMC 10013989. PMID 36918725.

[1] Doerr IL, Fox JJ (May 1967). "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. doi:10.1021/jo01280a035. PMID 6041430.

[2] Wohlrab F, Jamieson AT, Hay J, Mengel R, Guschlbauer W (March 1985). "The effect of 2'-fluoro-2'-deoxycytidine on herpes virus growth". Biochimica et Biophysica Acta. 824 (3): 233–242. doi:10.1016/0167-4781(85)90053-3. PMID 2982405.

[3] Bajramovic JJ, Volmer R, Syan S, Pochet S, Gonzalez-Dunia D (April 2004). "2'-fluoro-2'-deoxycytidine inhibits Borna disease virus replication and spread". Antimicrobial Agents and Chemotherapy. 48 (4): 1422–1425. doi:10.1128/AAC.48.4.1422-1425.2004. PMC 375289. PMID 15047559.

[4] Kumaki Y, Day CW, Smee DF, Morrey JD, Barnard DL (November 2011). "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. doi:10.1016/j.antiviral.2011.09.001. PMC 3216401. PMID 21925541.

[5] Welch SR, Guerrero LW, Chakrabarti AK, McMullan LK, Flint M, Bluemling GR, et al. (December 2016). "Lassa and Ebola virus inhibitors identified using minigenome and recombinant virus reporter systems". Antiviral Research. 136: 9–18. doi:10.1016/j.antiviral.2016.10.007. PMID 27771389.

[6] Welch SR, Scholte FE, Flint M, Chatterjee P, Nichol ST, Bergeron É, et al. (November 2017). "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. doi:10.1016/j.antiviral.2017.10.008. PMC 8191813. PMID 29024765.

[7] Smee DF, Jung KH, Westover J, Gowen BB (December 2018). "2'-Fluoro-2'-deoxycytidine is a broad-spectrum inhibitor of bunyaviruses in vitro and in phleboviral disease mouse models". Antiviral Research. 160: 48–54. doi:10.1016/j.antiviral.2018.10.013. PMID 30339848.

[8] Yu P, Wang Y, Li Y, Li Y, Miao Z, Peppelenbosch MP, et al. (November 2020). "2'-Fluoro-2'-deoxycytidine inhibits murine norovirus replication and synergizes MPA, ribavirin and T705". Archives of Virology. 165 (11): 2605–2613. doi:10.1007/s00705-020-04759-4. PMC 7414258. PMID 32770483.

[9] Dai S, Deng F, Wang H, Ning Y (June 2021). "Crimean-Congo Hemorrhagic Fever Virus: Current Advances and Future Prospects of Antiviral Strategies". Viruses. 13 (7): 1195. doi:10.3390/v13071195. PMC 8310003. PMID 34206476.

[10] Hawman DW, Feldmann H (July 2023). "Crimean-Congo haemorrhagic fever virus". Nature Reviews. Microbiology. 21 (7): 463–477. doi:10.1038/s41579-023-00871-9. PMC 10013989. PMID 36918725.

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