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【结 构 式】 
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【药物名称】 【化学名称】2(R)-[4-(5-Chloro-2-pyridinyl)-1-piperazinylsulfonamido]-N-hydroxy-3-methylbutyramide 【CA登记号】210913-38-5 【 分 子 式 】C14H22ClN5O4S 【 分 子 量 】391.87954 |
【开发单位】Agouron (Originator), Roche (Originator) 【药理作用】Antiarthritic Drugs, TREATMENT OF MUSCULOSKELETAL & CONNECTIVE TISSUE DISEASES, Matrix Metalloproteinase Inhibitors |
合成路线1
Treatment of D-valine methyl ester (I) with chlorosulfonic acid and then with phosphorus pentachloride produced valinesulfamoyl cloride (II). This was condensed with N-(5-chloro-2-pyridinyl)piperazine (III) to afford sulfamide (IV). Basic hydrolysis of the methyl ester of (IV) gave carboxylic acid (V), which was further converted to acid chloride (VI) using oxalyl chloride in the presence of DMF. Finally, the title hydroxamic acid was obtained by condensation with N,O-bis(trimethylsilyl)hydroxylamine, followed by desilylation with MeOH.
| 【1】 Castelhano, A.L.; Hendricks, R.T.; Melnick, M.J.; Campbell, J.A.; Walker, K.A.M.; Broka, C.A.; Chen, J.J. (Agouron Pharmaceuticals, Inc.; F. Hoffmann-La Roche AG); Sulfamide-metalloprotease inhibitors. DE 19802350; EP 0958287; US 5998412; WO 9832748 . |
| 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) | 16613 | methyl (2S)-2-amino-3-methylbutanoate | C6H13NO2 | 详情 | 详情 | |
| (II) | 25289 | methyl (2R)-2-[(chlorosulfonyl)amino]-3-methylbutanoate | C6H12ClNO4S | 详情 | 详情 | |
| (III) | 25290 | 1-(5-chloro-2-pyridinyl)piperazine | C9H12ClN3 | 详情 | 详情 | |
| (IV) | 25291 | methyl (2R)-2-([[4-(5-chloro-2-pyridinyl)-1-piperazinyl]sulfonyl]amino)-3-methylbutanoate | C15H23ClN4O4S | 详情 | 详情 | |
| (V) | 25292 | (2R)-2-([[4-(5-chloro-2-pyridinyl)-1-piperazinyl]sulfonyl]amino)-3-methylbutyric acid | C14H21ClN4O4S | 详情 | 详情 | |
| (VI) | 25293 | (2R)-2-([[4-(5-chloro-2-pyridinyl)-1-piperazinyl]sulfonyl]amino)-3-methylbutanoyl chloride | C14H20Cl2N4O3S | 详情 | 详情 |