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【结 构 式】 
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【药物名称】TBC-11241 【化学名称】3-[N-(4-Chloro-3-methylisoxazol-5-yl)sulfamoyl]-N-(6-cyano-1,3-benzodioxol-5-yl)thiophene-2-carboxamide 【CA登记号】184036-18-8 【 分 子 式 】C17H11ClN4O6S2 【 分 子 量 】466.88142 |
【开发单位】Encysive Pharmaceuticals (Originator) 【药理作用】Renal Failure, Agents for, RENAL-UROLOGIC DRUGS, Treatment of Renal Diseases, Endothelin ETA Receptor Antagonists |
合成路线1
5-Amino-3-methylisoxazole (I) was chlorinated with N-chlorosuccinimide (NCS) in chloroform to afford 5-amino-4-chloro-3-methylisoxazole (II) (1). Condensation of this isoxazole (II) with 3-(chlorosulfonyl)thiophene-2-carboxylic acid methyl ester (III) was effected in the presence of sodium hydride in THF to give sulfonamide (IV), which was then hydrolyzed to the acid (V) on treatment with methanolic sodium hydroxide. This acid (V) was activated by reaction with carbonyldiimidazole (CDI) in DMF, and the resulting solution of acylimidazole was then cannulated into a cooled mixture of 2-amino-4,5-(methylenedioxy)benzonitrile (VI) and sodium hydride in DMF to yield the title amide.
| 【1】 Wu, C.; et al.; Structure-activity relationships of N2-aryl-3-(isoxazolylsulfamoyl)-2-thiophenecarboxamides as selective endothelin receptor-A antagonists. J Med Chem 1997, 40, 11, 1682. |
| 【2】 Chan, M.F.; Raju, B.G.; Kois, A.; Verner, E.J.; Wu, C.; Castillo, R.S.; Yalamoori, V.; Balaji, V.N. (Texas Biotechnology Corp.); Thienyl-, furyl-, pyrrolyl- and biphenylsulfonamides and derivs. thereof that modulate the activity of endothelin. EP 0819125; JP 1999507015; WO 9631492 . |
| 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) | 17834 | 3-methyl-5-isoxazolylamine; 3-methyl-5-isoxazolamine; 5-Amino-3-methylisoxazole | 14678-02-5 | C4H6N2O | 详情 | 详情 |
| (II) | 17835 | 4-chloro-3-methyl-5-isoxazolamine; 4-chloro-3-methyl-5-isoxazolylamine | C4H5ClN2O | 详情 | 详情 | |
| (III) | 17836 | Methyl 3-(chlorosulfonyl)-2-thiophenecarboxylate; Methyl-3-chlorosulfonylthiophene-2-carboxylate | C6H5ClO4S2 | 详情 | 详情 | |
| (IV) | 17837 | methyl 3-[[(4-chloro-3-methyl-5-isoxazolyl)amino]sulfonyl]-2-thiophenecarboxylate | C10H9ClN2O5S2 | 详情 | 详情 | |
| (V) | 17838 | 3-[[(4-chloro-3-methyl-5-isoxazolyl)amino]sulfonyl]-2-thiophenecarboxylic acid | C9H7ClN2O5S2 | 详情 | 详情 | |
| (VI) | 17839 | 6-amino-1,3-benzodioxole-5-carbonitrile | C8H6N2O2 | 详情 | 详情 |