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【结 构 式】 
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【药物名称】Viramidine hydrochloride, Ribamidine hydrochloride, ICN-3142(hydrochloride), AVS-000206, AVS-206, Viramidine 【化学名称】1-beta-D-Ribofuranosyl-1,2,4-triazole-3-carboxamidine hydrochloride 【CA登记号】40372-00-7, 119567-79-2 (free base) 【 分 子 式 】C8H14ClN5O4 【 分 子 量 】279.68488 |
【开发单位】Ribapharm (Originator) 【药理作用】Anti-Hepatitis C Virus Drugs, Anti-Hepatitis Virus Drugs, ANTIINFECTIVE THERAPY, Antiviral Drugs, Inosine 5'-Monophosphate Dehydrogenase (IMPDH) Inhibitors |
合成路线1
This compound has been obtained by several related ways: The acylation of Ribavirin (1-(beta-D-ribofuranosyl)-1,2,4-triazole-3-carboxamide) (I) with Ac2O gives the triacetate (II), which is anhydrized by means of POCl3 and TEA in chloroform to yield the carbonitrile (III). The reaction of (III) with NaOMe in methanol affords the methyl carboximidate (IV), which is finally treated with NH4Cl and NH3 in methanol to provide the target carboxamidine. Alternatively, the intermediate carbonitrile (III) can be treated with NH4Cl and NH3 in methanol at 85 C in a steel bomb to give the target carboxamidine. Finally, the condensation of 1,2,3,5-tetra-O-acetyl-beta-D-ribofuranose (V) with 1,2,4-triazole-3-carbonitrile (VI) by means of bis-(4-nitrophenyl)phosphate (BNPP) at 150 C also gives the intermediate triacetyl carbonitrile derivative (III).
| 【1】 Laguna, N; Robins, R.K.; Witkowski, J.T. (ICN Pharmaceuticals, Inc.); 1,2,4-Triazole nucleosides. DE 2220246; US 3798209 . |
| 【2】 Robins, R.K.; Kini, G.D.; Synthesis and anti-leukemic activity of alkyl-1-(beta-ribofuranosyl)[1,2,4]triazole-3-carboximidates. US 4925930 . |
| 【3】 Ramasamy, K.; Hong, Z.; Tam, R.; Lau, J. (ICN Pharmaceuticals, Inc.); Nucleoside analogs with carboxamidine modified monocyclic base. WO 0160379 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 48598 | 1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-1H-1,2,4-triazole-3-carboxamide | C8H12N4O5 | 详情 | 详情 | |
| (II) | 48599 | (2R,3R,4R,5R)-4-(acetoxy)-2-[(acetoxy)methyl]-5-[3-(aminocarbonyl)-1H-1,2,4-triazol-1-yl]tetrahydro-3-furanyl acetate | C14H18N4O8 | 详情 | 详情 | |
| (III) | 48600 | (2R,3R,4R,5R)-4-(acetoxy)-2-[(acetoxy)methyl]-5-(3-cyano-1H-1,2,4-triazol-1-yl)tetrahydro-3-furanyl acetate | C14H16N4O7 | 详情 | 详情 | |
| (IV) | 48601 | methyl 1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-1H-1,2,4-triazole-3-carboximidoate | C9H14N4O5 | 详情 | 详情 | |
| (V) | 33835 | (2R,3R,4R,5S)-4,5-bis(acetoxy)-2-[(acetoxy)methyl]tetrahydro-3-furanyl acetate | 13035-61-5 | C13H18O9 | 详情 | 详情 |
| (VI) | 48602 | 1H-1,2,4-triazole-3-carbonitrile | C3H2N4 | 详情 | 详情 |