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【结 构 式】 
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【药物名称】PGE-5747401 【化学名称】N1-Benzyl-N3-hydroxy-4-(4-methoxyphenylsulfonyl)-N1-methylpiperazine-1,3(R)-dicarboxamide 【CA登记号】204140-21-6 (undefined isomer) 【 分 子 式 】C21H26N4O6S 【 分 子 量 】462.52857 |
【开发单位】Procter & Gamble (Originator) 【药理作用】Antiarthritic Drugs, TREATMENT OF MUSCULOSKELETAL & CONNECTIVE TISSUE DISEASES, Collagenase Inhibitors, Matrix Metalloproteinase Inhibitors, MMP-2 (Gelatinase A) Inhibitors, MMP-7 (Matrilysin) Inhibitors, MMP-9 (Gelatinase B) Inhibitors, Stromelysin Inhibitors |
合成路线1
The selective protection of piperazine-2-carboxylic acid (I) with tert-butoxycarbonyl anhydride gives the carbamate (II), which is sulfonated with 4-methoxybenzenesulfonyl chloride (II) and triethylamine yielding the sulfonamide (IV). The esterification and simultaneous deprotection of (IV) with SOCl2 and methanol affords the methyl ester (V), which is treated with phosgene and N-benzyl-N-methylamine (VI) to afford the cyclic urea derivative (VII). Finally, this compound is treated with KOH and hydroxylamine in methanol to provide the target hydroxamic acid.
| 【1】 De, B.; Natchus, M.G.; Pikul, S.; Almstead, N.G.; Matthews, R.S.; Taiwo, Y.O.; Cheng, M. (The Procter & Gamble Co.); 1,4-Heterocyclic metalloprotease inhibitors. EP 0923563; EP 0925287; WO 9808825; WO 9808827 . |
| 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) | 25933 | 2-piperazinecarboxylic acid; Piperazine-2-carboxylic acid | C5H10N2O2 | 详情 | 详情 | |
| (II) | 25934 | 4-(tert-butoxycarbonyl)-2-piperazinecarboxylic acid | C10H18N2O4 | 详情 | 详情 | |
| (III) | 15719 | 4-methoxybenzenesulfonyl chloride | 98-68-0 | C7H7ClO3S | 详情 | 详情 |
| (IV) | 25935 | 4-(tert-butoxycarbonyl)-1-[(4-methoxyphenyl)sulfonyl]-2-piperazinecarboxylic acid | C17H24N2O7S | 详情 | 详情 | |
| (V) | 25936 | methyl 1-[(4-methoxyphenyl)sulfonyl]-2-piperazinecarboxylate | C13H18N2O5S | 详情 | 详情 | |
| (VI) | 11969 | N-Methyl(phenyl)methanamine; N-Benzyl-N-methylamine; N-Methylbenzylamine | 103-67-3 | C8H11N | 详情 | 详情 |
| (VII) | 25937 | methyl 4-[[benzyl(methyl)amino]carbonyl]-1-[(4-methoxyphenyl)sulfonyl]-2-piperazinecarboxylate | C22H27N3O6S | 详情 | 详情 |