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【结 构 式】 
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【药物名称】SM-19712 【化学名称】N-(4-Chlorophenylsulfonyl)-N'-(4-cyano-3-methyl-1-phenylpyrazol-5-yl)urea sodium salt 【CA登记号】194542-56-8 【 分 子 式 】C18H13ClN5NaO3S 【 分 子 量 】437.84281 |
【开发单位】Sumitomo Pharmaceuticals (Originator) 【药理作用】CARDIOVASCULAR DRUGS, Hypertension, Treatment of, Renal Failure, Agents for, RENAL-UROLOGIC DRUGS, Treatment of Renal Diseases, Endothelin-Converting Enzyme Inhibitors |
合成路线1
The known 5-amino-4-cyano-1-phenylpyrazole (I) was coupled with 4-chlorobenzenesulfonyl isocyanate (II) to produce the sulfonyl urea (III). This compound was converted to the corresponding sodium salt by evaporation of its solution in aqueous NaOH.
| 【1】 Hasegawa, H.; et al.; Synthesis of endothelin converting enzyme inhibitors and their structure activity relationships. 21st Symp Med Chem (Nov 28 2001, Kyoto) 2001, Abst 1P-21. |
| 【2】 Matsushita, K.; Hasegawa, H.; Kuribayashi, Y.; Ohashi, N. (Sumitomo Pharmaceuticals Co., Ltd.); Sulfonylureidopyrazole derivs.. EP 0885890; JP 1998007658; WO 9730978 . |
| 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) | 49117 | 5-amino-3-methyl-1-phenyl-1H-pyrazole-4-carbonitrile | C11H10N4 | 详情 | 详情 | |
| (II) | 28973 | 4-chlorobenzenesulfonyl isocyanate | 5769-15-3 | C7H4ClNO3S | 详情 | 详情 |
| (III) | 49118 | 5-[([[(4-chlorophenyl)sulfonyl]amino]carbonyl)amino]-4-cyano-3-methyl-1-phenyl-1H-pyrazole | C18H14ClN5O3S | 详情 | 详情 |
合成路线2
The intermediate amino pyrazole (I) was prepared as follows. Acylation of malononitrile (IV) with acetyl chloride (V) in the presence of Et3N afforded (1-hydroxyethyliden)malononitrile (VI). Subsequent methylation of the hydroxyl group with dimethyl sulfate gave enol ether (VII). Alternatively, malononitrile (IV) was converted to the ethyl enol ether (VIII) by condensation with triethyl orthoacetate in the presence of Ac2O. Cyclization of either (VII) or (VIII) with phenylhydrazine (IX) furnished 5-amino-4-cyano-1-phenylpyrazole (I).
| 【1】 Hasegawa, H.; et al.; Synthesis of endothelin converting enzyme inhibitors and their structure activity relationships. 21st Symp Med Chem (Nov 28 2001, Kyoto) 2001, Abst 1P-21. |
| 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) | 49117 | 5-amino-3-methyl-1-phenyl-1H-pyrazole-4-carbonitrile | C11H10N4 | 详情 | 详情 | |
| (IV) | 11818 | Phenyl hydrazine; 1-Phenylhydrazine | 100-63-0 | C6H8N2 | 详情 | 详情 |
| (IV) | 12061 | Malononitrile | 109-77-3 | C3H2N2 | 详情 | 详情 |
| (V) | 19273 | acetyl chloride | 75-36-5 | C2H3ClO | 详情 | 详情 |
| (VI) | 56569 | 2-(1-hydroxyethylidene)malononitrile | C5H4N2O | 详情 | 详情 | |
| (VII) | 56570 | 2-(1-methoxyethylidene)malononitrile | C6H6N2O | 详情 | 详情 | |
| (VIII) | 56571 | 2-(1-ethoxyethylidene)malononitrile | C7H8N2O | 详情 | 详情 |