Taribavirin

Taribavirin

Systematic (IUPAC) name
1-[(2R,3R,4S,5R)- 3,4-dihydroxy-5- (hydroxymethyl)oxolan-2-yl]- 1,2,4-triazole-3-carboximidamide
Clinical data
Pregnancy category	X
Routes of administration	Oral capsule
Legal status	In Phase III drug trials
Pharmacokinetic data
Bioavailability	9%
Metabolism	Metabolized to 5'phosphates, de-riboside, and deriboside carboxylic acid
Biological half-life	12 days - Multiple Dose; 120-170 hours - Single Dose
Excretion	10% fecal, remainder in urine (30% unchanged, remainder metabolites)
Identifiers
CAS Number	119567-79-2
ATC code	J05AB04 (WHO)
PubChem	CID 451448
DrugBank	none
ChemSpider	397669
UNII	R3B1994K2E
NIAID ChemDB	000198
Synonyms	1-(β-D-Ribofuranosyl)- 1,2,4-triazole-3-carboximide
Chemical data
Formula	C8H13N5O4
Molar mass	243.220 g/mol (279.681 g/mol for HCl salt)
SMILES n1c(nn(c1)[C@@H]2O[C@@H]([C@@H](O)[C@H]2O)CO)C(=[N@H])N
InChI InChI=1S/C8H13N5O4/c9-6(10)7-11-2-13(12-7)8-5(16)4(15)3(1-14)17-8/h2-5,8,14-16H,1H2,(H3,9,10)/t3-,4-,5-,8-/m1/s1 Key:NHKZSTHOYNWEEZ-AFCXAGJDSA-N
(what is this?)  (verify)

Taribavirin (rINN; also known as viramidine, codenamed ICN 3142) is an antiviral drug in Phase III human trials, but not yet approved for pharmaceutical use. It is a prodrug of ribavirin, active against a number of DNA and RNA viruses. Taribavirin has better liver-targeting than ribavirin, and has a shorter life in the body due to less penetration and storage in red blood cells. It is expected eventually to be the drug of choice for viral hepatitis syndromes in which ribavirin is active. These include hepatitis C and perhaps also hepatitis B and yellow fever.

Uses

Taribavirin is as active against influenza as ribavirin in animal models, with slightly less toxicity, so it may also eventually replace ribavirin as an anti-influenza agent.

History

Taribavirin was first reported in 1973 by J.T.Witkowski et al.,^[1] then working at ICN Pharmaceuticals, in an attempt to find a more active derivative of ribavirin. Taribavirin is being developed by Valeant Pharmaceuticals International. Valeant is testing the drug as a treatment for chronic hepatitis C.

Pharmacology

Note on formulas: The carboxamidine group of this molecule is somewhat basic, and therefore this drug is also known and administered as the hydrochloride salt (with a corresponding .HCl chemical formula and different ChemID / PubChem number). At physiologic pH, the positive charge on the molecule from partial protonation of the carboximide group contributes to the relative slowness with which the drug crosses cell membranes (such as in red blood cells) until it has been metabolized into ribavirin. In the liver, however, the transformation from carboxamidine to carboxamide happens on first-pass metabolism and contributes to the higher levels of ribavirin found in liver cells and bile when viramidine is administered.

Notes

1. "Synthesis and antiviral activity of 1,2,4-triazole-3-thiocarboxamide and 1,2,4-triazole-3-carboxamidine ribonucleosides". J. Med. Chem. 16 (8): 935–7. August 1973. doi:10.1021/jm00266a014. PMID 4355593.

References

1. Barnard, D (2002). "Viramidine (Ribapharm)". Current Opinion in Investigational Drugs 3 (11): 1585–9. PMID 12476957.
2. Gish, Robert G. (January 2006). "Treating HCV with ribavirin analogues and ribavirin-like molecules". Journal of Antimicrobial Chemotherapy 57 (1): 8–13. doi:10.1093/jac/dki405. PMID 16293677.
3. Lin, Chin-Chung; Kenneth Luu; David Lourenco; Li-Tain Yeh (2003). "Pharmacokinetics and Metabolism of 14CViramidine in Rats and Cynomolgus Monkeys". Antimicrob Agents Chemother 47 (8): 1458–2463. doi:10.1128/aac.47.8.2458-2463.2003. PMC 166067. PMID 12878505.
4. Sidwell, RW; Bailey KW; Wong MH; Barnard DL; Smee DF (October 2005). "In vitro and in vivo influenza virus-inhibitory effects of viramidine". Antiviral Research 68 (1): 8–13. doi:10.1016/j.antiviral.2005.06.003. PMID 16087250.
5. Witkowski, J. T.; Robins, R. K.; Khare, G. P.; et al. (1973). "Synthesis and antiviral activity of 1,2,4-triazole-3-thiocarboxamide and 1,2,4-triazole-3-carboxamidine ribonucleosides". Journal of Medicinal Chemistry 16 (8): 935–7. doi:10.1021/jm00266a014. PMID 4355593.