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【结 构 式】 
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【药物名称】SMP-300 【化学名称】N-(11-Chloro-8-oxo-5,6,7,8-tetrahydro-4H-azocino[3,2,1-hi]indol-2-ylcarbonyl)guanidine methanesulfonate hydrate 【CA登记号】194869-85-7 (anhydrous) 【 分 子 式 】C16H21ClN4O6S 【 分 子 量 】432.88597 |
【开发单位】Sumitomo Pharmaceuticals (Originator) 【药理作用】Angina pectoris, Treatment of, CARDIOVASCULAR DRUGS, Treatment of Disorders of the Coronary Arteries and Atherosclerosis, Na+/H+ Exchange (NHE) Inhibitors |
合成路线1
Alkylation of ethyl 4-chloroindole-2-carboxylate (I) with ethyl 5-bromovalerate (II) in the presence of NaH in DMF afforded diester (III). Regioselective hydrolysis of the aliphatic ester group employing sulfuric acid and acetic acid at 75 C produced the mono-carboxylic acid (IV). The intramolecular cyclization of acid (IV) by means of phosphoric acid and phosphorus pentoxide furnished the tricyclic system (V). The ethyl ester group of (V) was then treated with guanidine (VI) to yield the target acyl guanidine derivative, which was finally converted to the title methanesulfonate salt.
| 【1】 Kitano, M.; Ohashi, N. (Sumitomo Pharmaceuticals Co., Ltd.); Substd. guanidine derivs., process for production thereof, and pharmaceutical uses thereof. EP 0787728; JP 1998237073; US 5834454; US 5977100; US 6271251 . |
| 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) | 47754 | ethyl 4-chloro-1H-indole-2-carboxylate | C11H10ClNO2 | 详情 | 详情 | |
| (II) | 37151 | ethyl 5-bromopentanoate | 14660-52-7 | C7H13BrO2 | 详情 | 详情 |
| (III) | 47755 | ethyl 4-chloro-1-(5-ethoxy-5-oxopentyl)-1H-indole-2-carboxylate | C18H22ClNO4 | 详情 | 详情 | |
| (IV) | 47756 | 5-[4-chloro-2-(ethoxycarbonyl)-1H-indol-1-yl]pentanoic acid | C16H18ClNO4 | 详情 | 详情 | |
| (V) | 47757 | ethyl 11-chloro-8-oxo-5,6,7,8-tetrahydro-4H-azocino[3,2,1-hi]indole-2-carboxylate | C16H16ClNO3 | 详情 | 详情 | |
| (VI) | 14790 | Guanidine | 113-00-8 | CH5N3 | 详情 | 详情 |