Viramidine
From Wikipedia, the free encyclopedia
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Viramidine
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| Systematic (IUPAC) name | |
| 1-[(2R,3R,4S,5S)- 3,4-dihydroxy-5- (hydroxymethyl)oxolan-2-yl]- 1,2,4-triazole-3-carboximidamide (also commonly 1-(β-D-Ribofuranosyl)- 1,2,4-triazole-3-carboximide) | |
| Identifiers | |
| CAS number | 119567-79-2 |
| ATC code | J05AB04 |
| PubChem | 451448 |
| DrugBank | none |
| Chemical data | |
| Formula | C8H13N5O4 |
| Mol. weight | 243.220 (279.681 for HCl salt) |
| Pharmacokinetic data | |
| Bioavailability | ? |
| Metabolism | Metabolized to 5'phosphates, de-riboside, and deriboside carboxylic acid |
| Half life | 12 days - Multiple Dose; 120-170 hours - Single Dose |
| Excretion | 10% fecal, remainder in urine (30% unchanged, remainder metabolites) |
| Therapeutic considerations | |
| Pregnancy cat. |
US: X; AU: X |
| Legal status |
In Phase III drug trials. |
| Routes | oral capsule |
Viramidine (ICN 3142) is an anti-viral 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. Viramidine 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.
Viramidine 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. PMID 16087250
Viramidine is being developed by Valeant Pharmaceuticals International, formerly Ribapharm, the company which first reported synthesis and testing of the drug in 1973.
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.
[edit] References
1. 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, 935–7. PMID 4355593
2. Barnard, D. (2002). Viramidine (Ribapharm). Current Opinion in Investigational Drugs 3, 1585–9. PMID 12476957
[edit] External links
| Antivirals (primarily J05A, also S01AD and D06BB) edit | ||||||||||||||||||||||
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