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【结 构 式】 
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【药物名称】Clamikalant sodium, HMR-1098 【化学名称】5-Chloro-2-methoxy-N-[2-[4-methoxy-3-(3-methylthioureidosulfonyl)phenyl]ethyl]benzamide sodium salt 【CA登记号】261717-22-0, 158751-64-5 (free acid) 【 分 子 式 】C19H21ClN3NaO5S2 【 分 子 量 】493.96712 |
【开发单位】Aventis Pharma (Originator) 【药理作用】Antiarrhythmic Drugs, CARDIOVASCULAR DRUGS, K(ATP) Channel Blockers |
合成路线1
Condensation of 2-(4-methoxyphenyl)ethylamine (I) with either 5-chloro-2-methoxybenzoic acid (II) by means of CDI and TEA or 5-chloro-2-methoxybenzoyl chloride (III) by means of pyridine and DMAP gives the corresponding benzamide (IV), which by treatment with chlorosulfonic acid yields the sulfonyl chloride (V). Reaction of compound (V) with aqueous ammonia in acetone affords the expected sulfonamide (VI), which is finally treated with methyl isothiocyanate (VII) by means of either KOtBu or NaH in DMF.
| 【3】 Englert, H.; Mania, D.; Hartung, J.; Gögelein, H.; Kaiser, J.; Linz, W.; Wettlaufer, D. (Aventis Pharma Deutschland GmbH); Substd. benzenesulfonylureas and -thioureas, process for their preparation and their use as pharmaceuticals. CA 2116165; EP 0612724; JP 1995304728; US 5574069; US 5698596; US 5776980 . |
| 【1】 Martin, L.; Mealy, N.M.; Castaner, J.; Clamikalant sodium. Drugs Fut 2001, 26, 10, 951. |
| 【2】 Gerlach, U.; Scheidler, S.; Mania, D.; Heitsch, H.; Goegelein, H.; Hartung, J.; Englert, H.C.; Cardioselective KATP channel blockers derived from a new series of m-anisamidoethylbenzenesulfonylthioureas. J Med Chem 2001, 44, 7, 1085. |
| 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) | 48701 | 1-(p-Methoxyphenyl)ethylamine; 1-Amino-2-(4-methoxyphenyl)ethane; 2-(4-Methoxyphenyl)ethylamine; 4-(2-Aminoethyl)anisole; 4-Methoxybenzeneethanamine; 4-Methoxyphenethylamine; 4-Methoxyphenylethylamine; p-Methoxy phenethylamine; p-Methoxy phenylethylamine | 55-81-2 | C9H13NO | 详情 | 详情 |
| (II) | 48702 | 5-Chloro-2-methoxybenzoic acid; 5-Chloro-o-anisic acid | 3438-16-2 | C8H7ClO3 | 详情 | 详情 |
| (III) | 44240 | 5-chloro-2-methoxybenzoyl chloride | C8H6Cl2O2 | 详情 | 详情 | |
| (IV) | 48703 | 5-chloro-2-methoxy-N-(4-methoxyphenethyl)benzamide | C17H18ClNO3 | 详情 | 详情 | |
| (V) | 48704 | 5-[2-[(5-chloro-2-methoxybenzoyl)amino]ethyl]-2-methoxybenzenesulfonyl chloride | C17H17Cl2NO5S | 详情 | 详情 | |
| (VI) | 48705 | N-[3-(aminosulfonyl)-4-methoxyphenethyl]-5-chloro-2-methoxybenzamide | C17H19ClN2O5S | 详情 | 详情 | |
| (VII) | 12092 | Methyl isothiocyanate; MITC; (Methylimino)(thioxo)methane | 556-61-6 | C2H3NS | 详情 | 详情 |