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【结 构 式】 
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【药物名称】 【化学名称】3-Methyl-2-[N-methyl-N-[4-(pyridin-4-yloxy)phenylsulfonyl]amino]benzohydroxamic acid 【CA登记号】 【 分 子 式 】C20H19N3O5S 【 分 子 量 】413.45553 |
【开发单位】Wyeth Pharmaceuticals (Originator) 【药理作用】Antiarthritic Drugs, TREATMENT OF MUSCULOSKELETAL & CONNECTIVE TISSUE DISEASES, MMP-13 (Collagenase 3) Inhibitors, MMP-9 (Gelatinase B) Inhibitors |
合成路线1
Acylation of methyl 3-methylanthranilate (I) with 4-(4-pyridyloxy)benzenesulfonyl chloride (II) gave sulfonamide (III). Subsequent N-alkylation of the sulfonamide function with iodomethane in the presence of NaH afforded the N-methyl sulfonamide (IV). Basic hydrolysis of the ester group of (IV) yielded carboxylic acid (V), which was further activated as the acid chloride (VI) upon treatment with oxalyl chloride. Finally, reaction of acid chloride (VI) with hydroxylamine yielded the corresponding hydroxamic acid.
| 【1】 Levin, J.I.; et al.; The discovery of anthranilic acid-based MMP inhibitors. Part 2: SAR of the 5-position P11 groups. Bioorg Med Chem Lett 2001, 11, 16, 2189. |
| 【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 . |
| 【3】 Nelson, F.C.; Venkatesan, A.M.; Levin, J.I.; Du, M.T.; Gu, Y.; Zask, A. (American Cyanamid Co.); The preparation and use of ortho-sulfonamido aryl hydroxamic acids as matrix metalloproteinase and TACE inhibitors. WO 9816503 . |
| 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) | 48424 | methyl 2-amino-3-methylbenzoate | C9H11NO2 | 详情 | 详情 | |
| (II) | 32887 | 4-(4-pyridinyloxy)benzenesulfonyl chloride | C11H8ClNO3S | 详情 | 详情 | |
| (III) | 51112 | methyl 3-methyl-2-([[4-(4-pyridinyloxy)phenyl]sulfonyl]amino)benzoate | C20H18N2O5S | 详情 | 详情 | |
| (IV) | 51113 | methyl 3-methyl-2-(methyl[[4-(4-pyridinyloxy)phenyl]sulfonyl]amino)benzoate | C21H20N2O5S | 详情 | 详情 | |
| (V) | 51114 | 3-methyl-2-(methyl[[4-(4-pyridinyloxy)phenyl]sulfonyl]amino)benzoic acid | C20H18N2O5S | 详情 | 详情 | |
| (VI) | 51115 | 3-methyl-2-(methyl[[4-(4-pyridinyloxy)phenyl]sulfonyl]amino)benzoyl chloride | C20H17ClN2O4S | 详情 | 详情 |