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【结 构 式】 
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【药物名称】WAY-170523 【化学名称】N-[2-[4-[N-Benzyl-N-[2-(N-hydroxycarbamoyl)-4,6-dimethylphenyl]sulfamoyl]phenoxy]ethyl]-1-benzofuran-2-carboxamide 【CA登记号】 【 分 子 式 】C33H31N3O7S 【 分 子 量 】613.69492 |
【开发单位】Wyeth Pharmaceuticals (Originator) 【药理作用】ONCOLYTIC DRUGS, Angiogenesis Inhibitors, MMP-13 (Collagenase 3) Inhibitors |
合成路线1
Condensation of 4-fluorobenzenesulfonyl chloride (I) with anthranilic acid derivative (II) by means of pyridine yields sulfonamide derivative (III), which is then N-alkylated by reaction with benzyl bromide (IV) by means of NaH in DMF to furnish compound (V). Saponification of the methyl ester group of (V) by treatment with NaOH in refluxing MeOH affords carboxylic acid (VI) (1), which is then converted into compound (X) by condensation with hydroxy derivative (IX) by means of NaH in DMF. (In turn, compound (IX) can be obtained by coupling of 2-benzofurancarboxylic acid (VII) with ethanolamine (VIII) by means of HOBt/EDC and NMM in DMF. Finally, the target product is obtained by derivatization of the carboxylic acid moiety of (X) with hydroxylamine hydrochloride by means of HOBt/EDC and Et3N in DMF.
| 【2】 Gu, Y.; Nelson, F.C.; Zask, A.; Du, M.T.; Levin, J.I.; Venkatesan, M. (American Cyanamid Co.); Preparation and use of orthosulfonamido aryl hydroxamic acids as matrix metalloproteinase and TACE inhibitors. US 5929097 . |
| 【1】 Levin, J.I.; Nilakantan, R.; Mobilio, D.; Chen, J.M.; Nelson, F.C.; Powers, R.; Moy, F.J.; Zask, A.; Structure-based design of a novel, potent, and selective inhibitor for MMP-13 utilizing NMR spectroscopy and computer-aided molecular design. J Am Chem Soc 2000, 122, 40, 9648. |
| 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) | 12292 | 4-Fluorobenzenesulfonyl chloride | 349-88-2 | C6H4ClFO2S | 详情 | 详情 |
| (II) | 47141 | methyl 2-amino-3,5-dimethylbenzoate | C10H13NO2 | 详情 | 详情 | |
| (III) | 47142 | methyl 2-[[(4-fluorophenyl)sulfonyl]amino]-3,5-dimethylbenzoate | C16H16FNO4S | 详情 | 详情 | |
| (IV) | 12912 | 1-(Bromomethyl)benzene; Alpha-bromotoluene | 100-39-0 | C7H7Br | 详情 | 详情 |
| (V) | 47143 | methyl 2-[benzyl[(4-fluorophenyl)sulfonyl]amino]-3,5-dimethylbenzoate | C23H22FNO4S | 详情 | 详情 | |
| (VI) | 47144 | 2-[benzyl[(4-fluorophenyl)sulfonyl]amino]-3,5-dimethylbenzoic acid | C22H20FNO4S | 详情 | 详情 | |
| (VII) | 38339 | Benzofuran-2-carboxylic acid; 1-benzofuran-2-carboxylic acid | 496-41-3 | C9H6O3 | 详情 | 详情 |
| (VIII) | 10259 | Ethanol amine;Ethanolamine;2-Aminoethanol; 2-Amino-1-ethanol；2-Aminoethyl alcohol | 141-43-5 | C2H7NO | 详情 | 详情 |
| (IX) | 47145 | N-(2-hydroxyethyl)-1-benzofuran-2-carboxamide | C11H11NO3 | 详情 | 详情 | |
| (X) | 47146 | 2-[[(4-[2-[(1-benzofuran-2-ylcarbonyl)amino]ethoxy]phenyl)sulfonyl](benzyl)amino]-3,5-dimethylbenzoic acid | C33H30N2O7S | 详情 | 详情 |