Editing Ribavirin (section)

==Derivatives==
Ribavirin is possibly best viewed as a ribosyl purine analogue with an incomplete purine 6-membered ring. This structural resemblance historically prompted replacement of the 2' nitrogen of the triazole with a carbon (which becomes the 5' carbon in an [[imidazole]]), in an attempt to partly "fill out" the second ring--- but to no great effect. Such 5' imidazole [[riboside]] derivatives show antiviral activity with 5' hydrogen or halide, but the larger the substituent, the smaller the activity, and all proved less active than ribavirin.<ref>{{cite book | veditors=Smith RA, Kirkpatrick W | year=1980 | chapter=Ribavirin: structure and antiviral activity relationships | title=Ribavirin: A Broad Spectrum Antiviral Agent | pages=1–21 | publisher=Academic Press | location=New York }}</ref> Note that two natural products were already known with this imidazole [[riboside]] structure: substitution at the 5' carbon with OH results in [[pyrazofurin]], an antibiotic with antiviral properties but unacceptable toxicity, and replacement with an amino group results in the natural purine synthetic precursor 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside ([[Acadesine|AICAR]]), which has only modest antiviral properties.{{citation needed|date=November 2022}}

===Taribavirin===
{{main|Taribavirin}}
The most successful ribavirin derivative to date is the 3-carboxamidine derivative of the parent 3-carboxamide, first reported in 1973 by J. T. Witkowski et al.,<ref>{{cite journal | vauthors = Witkowski JT, Robins RK, Khare GP, Sidwell RW | title = Synthesis and antiviral activity of 1,2,4-triazole-3-thiocarboxamide and 1,2,4-triazole-3-carboxamidine ribonucleosides | journal = Journal of Medicinal Chemistry | volume = 16 | issue = 8 | pages = 935–937 | date = August 1973 | pmid = 4355593 | doi = 10.1021/jm00266a014 }}</ref> and now called [[taribavirin]] (former names "viramidine" and "ribamidine"). This drug shows a similar spectrum of antiviral activity to ribavirin, which is not surprising as it is now known to be a pro-drug for ribavirin. Taribavirin, however, has useful properties of less erythrocyte-trapping and better liver-targeting than ribavirin. The first property is due to taribavirin's basic amidine group which inhibits drug entry into RBCs, and the second property is probably due to increased concentration of the enzymes which convert amidine to amide in liver tissue.<ref>{{cite journal | vauthors = Sidwell RW, Bailey KW, Wong MH, Barnard DL, Smee DF | title = In vitro and in vivo influenza virus-inhibitory effects of viramidine | journal = Antiviral Research | volume = 68 | issue = 1 | pages = 10–17 | date = October 2005 | pmid = 16087250 | doi = 10.1016/j.antiviral.2005.06.003 }}</ref> Taribavirin completed [[Clinical trial#Phase III|phase III]] human trials in 2012.<ref>{{cite report |author=U.S. National Library of Medicine |date=2012-06-22 |title=Study of Viramidine to Ribavirin in Patients With Chronic Hepatitis C Who Are Treatment Naive (VISER2) |url=https://clinicaltrials.gov/ct2/show/NCT00093093 |publisher=National Institutes of Health |access-date=2021-03-25}}</ref>

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