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【结 构 式】 
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【药物名称】 【化学名称】N-[1(S)-Benzyl-3-[2-[5-(3-cyanophenyl)-2-thienylsulfonamido]ethylamino]-2,3-dioxopropyl]-2,6-dichlorobenzamide 【CA登记号】 【 分 子 式 】C30H24Cl2N4O5S2 【 分 子 量 】655.58358 |
【开发单位】Cephalon (Originator) 【药理作用】Cerebrovascular Diseases, Treatment of, Ischemic Stroke, Treatment of, NEUROLOGIC DRUGS, Stroke, Treatment of, Calpain Inhibitors |
合成路线1
Ethylenediamine (I) was selectively monoprotected as the N-Boc derivative (II) and then coupled with sulfonyl chloride (III), yielding sulfonamide (IV). After deprotection of the Boc group of (IV) with HCl in dioxan, the resulting amine (V) was condensed with hydroxyacid (VI) by means of BOP reagent to give amide (VII). Acid deprotection of the Boc group of (VII), followed by condensation with 2,6-dichlorobenzoyl chloride (IX), provided (X). Finally, the hydroxyl group of (X) was oxidized to the title ketone employing the Dess-Martin periodinane reagent in CH2Cl2.
| 【1】 Ator, M.A.; Mallamo, J.P.; Chatterjee, S.; Tao, M.; Wells, G.; Dunn, D.; Bihovsky, R.; Siman, R.; Gu, Z.-Q; P2-Achiral, P'-extended alpha-ketoamide inhibitors of calpain I. Bioorg Med Chem Lett 1999, 9, 16, 2371. |
| 【2】 Wells, G.J.; Mallamo, J.P.; Chatterjee, S.; Bihovsky, R. (Cephalon, Inc.); Peptidyl-containing alpha-ketoamide cysteine and serine protease inhibitors. US 6150378 . |
| 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) | 14574 | 3-methoxy-3-oxo-2-(2-thienylmethyl)propionic acid | C9H10O4S | 详情 | 详情 | |
| (II) | 13241 | N-Boc-ethylenediamine;tert-butyl (2-aminoethyl)carbamate；tert-butyl 2-aminoethylcarbamate; tert-Butyl n-(2-aminoethyl)carbamate | 57260-73-8 | C7H16N2O2 | 详情 | 详情 |
| (III) | 43065 | 5-(3-cyanophenyl)-2-thiophenesulfonyl chloride | C11H6ClNO2S2 | 详情 | 详情 | |
| (IV) | 43066 | tert-butyl 2-([[5-(3-cyanophenyl)-2-thienyl]sulfonyl]amino)ethylcarbamate | C18H21N3O4S2 | 详情 | 详情 | |
| (V) | 43067 | N-(2-aminoethyl)-5-(3-cyanophenyl)-2-thiophenesulfonamide | C13H13N3O2S2 | 详情 | 详情 | |
| (VI) | 43071 | (3S)-3-[(tert-butoxycarbonyl)amino]-2-hydroxy-4-phenylbutyric acid | C15H21NO5 | 详情 | 详情 | |
| (VII) | 43068 | tert-butyl (1S)-1-benzyl-3-[[2-([[5-(3-cyanophenyl)-2-thienyl]sulfonyl]amino)ethyl]amino]-2-hydroxy-3-oxopropylcarbamate | C28H32N4O6S2 | 详情 | 详情 | |
| (VIII) | 43069 | (3S)-3-amino-N-[2-([[5-(3-cyanophenyl)-2-thienyl]sulfonyl]amino)ethyl]-2-hydroxy-4-phenylbutanamide | C23H24N4O4S2 | 详情 | 详情 | |
| (IX) | 25087 | 2,6-dichlorobenzoyl chloride | 4659-45-4 | C7H3Cl3O | 详情 | 详情 |
| (X) | 43070 | N-((1S)-1-benzyl-3-[[2-([[5-(3-cyanophenyl)-2-thienyl]sulfonyl]amino)ethyl]amino]-2-hydroxy-3-oxopropyl)-2,6-dichlorobenzamide | C30H26Cl2N4O5S2 | 详情 | 详情 |