Taribavirin

Taribavirin

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Ball-and-stick model of the taribavirin molecule
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
Legal status	In Phase III drug trials
Routes of administration	Oral capsule
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 N
ATC code	J05AB04 (WHO)
PubChem	CID: 451448
DrugBank	none N
ChemSpider	397669 Y
UNII	R3B1994K2E Y
NIAID ChemDB	000198
Synonyms	1-(β-D-Ribofuranosyl)- 1,2,4-triazole-3-carboximide
Chemical data
Formula	C8H13N5O4
Molecular 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 Y Key:NHKZSTHOYNWEEZ-AFCXAGJDSA-N Y
NY (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., 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.