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【结 构 式】 
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【药物名称】SJA-6017 【化学名称】4-Fluorophenylsulfonyl-L-valyl-L-leucinal 【CA登记号】190274-53-4 【 分 子 式 】C17H25FN2O4S 【 分 子 量 】372.4622 |
【开发单位】Pfizer (Originator), Senju (Originator) 【药理作用】Anticataract Agents, Cerebrovascular Diseases, Treatment of, Ischemic Stroke, Treatment of, NEUROLOGIC DRUGS, OCULAR MEDICATIONS, Ophthalmic Drugs, Stroke, Treatment of, Cathepsin B Inhibitors, Cathepsin L Inhibitors, m-Calpain (Calpain-2) Inhibitors, mu-Calpain (Calpain-1) Inhibitors |
合成路线1
The condensation of L-valine (I) with 4-fluorobenzenesulfonyl chloride (II) by means of NaOH in THF/water gives N-(4-fluorobenzenesulfonyl)-L-valine (III), which is esterified with N-hydroxysuccinimide (IV) by means of EDC in dichloromethane to yield the activated ester (V). The condensation of (V) with L-leucinol (VI) by means of TEA in dichloromethane affords the N-(4-fluorobenzenesulfonyl)-L-valyl-L-leucinol (VII), which is finally oxidized with the SO3/Pyridine complex in DMSO/dichloromethane to provide the target leucinal derivative.
| 【1】 Fukiage, C.; et al.; SJA6017, a newly synthesized peptide aldehyde inhibitor of calpain: amelioration of cataract in cultured rat lenses. Biochim Biophys Acta 1997, 1361, 3, 304. |
| 【2】 Fukiage, C.; Azuma, M.; Inoue, J.; Nakamura, M.; Yoshida, Y. (Senju Pharmaceuticals Co., Ltd.); Angiogenesis inhibitor. EP 0771565; EP 0927716; EP 0928786; JP 1998147564; JP 1998147566; JP 2001233847; US 6057290; US 6214800 . |
| 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) | 37828 | L-2-Amino-3-methylbutyric acid; L-2-Aminoisovaleric acid; 2-Aminoisovaleric acid; L-2-Amino-3-methylbutyric acid; L-alpha-Aminoisovaleric acid; L-valine; (S)-(+)-Valine; (S)-alpha-Aminoisovaleric acid | 72-18-4 | C5H11NO2 | 详情 | 详情 |
| (II) | 12292 | 4-Fluorobenzenesulfonyl chloride | 349-88-2 | C6H4ClFO2S | 详情 | 详情 |
| (III) | 57911 | (2S)-2-{[(4-fluorophenyl)sulfonyl]amino}-3-methylbutanoic acid | C11H14FNO4S | 详情 | 详情 | |
| (IV) | 10264 | 1-Hydroxydihydro-1H-pyrrole-2,5-dione; N-Hydroxysuccinimide; 1-Hydroxy-2,5-pyrrolidinedione | 6066-82-6 | C4H5NO3 | 详情 | 详情 |
| (V) | 57912 | N-((1S)-1-{[(2,5-dioxo-1-pyrrolidinyl)oxy]carbonyl}-2-methylpropyl)-4-fluorobenzenesulfonamide | C15H17FN2O6S | 详情 | 详情 | |
| (VI) | 18171 | L-(+)-leucinol; (S)-2-amino-4-methyl-1-pentanol; (2S)-2-amino-4-methyl-1-pentanol | 7533-40-6 | C6H15NO | 详情 | 详情 |
| (VII) | 57913 | (2S)-2-{[(4-fluorophenyl)sulfonyl]amino}-N-[(1S)-1-(hydroxymethyl)-3-methylbutyl]-3-methylbutanamide | C17H27FN2O4S | 详情 | 详情 |