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【结 构 式】 
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【药物名称】 【化学名称】2-[N-[4-(4-Chlorophenoxy)phenylsulfonyl]-N-methylamino]-3-(4-methylpiperazin-1-ylmethyl)benzohydroxamic acid 【CA登记号】 【 分 子 式 】C26H29ClN4O5S 【 分 子 量 】545.06183 |
【开发单位】Amgen (Originator), 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 anthranilate (I) with 4-(4-chlorophenoxy)phenylsulfonyl chloride (II) provided the sulfonamide (III). Subsequent alkylation of the sulfonamide N of (III) with iodomethane yielded the N-methyl derivative (IV). Selective ester hydrolysis of (IV) with NaOH afforded the carboxylic acid (V). This was finally converted to the target hydroxamic acid via activation with oxalyl chloride, followed by treatment with hydroxylamine.
| 【1】 Du, M.T.; Chen, J.M.; Levin, J.I.; et al.; The discovery of anthranilic acid-based MMP inhibitors: Part 3: Incorporation of basic amines. Bioorg Med Chem Lett 2001, 11, 22, 2975. |
| 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) | 53016 | methyl 2-amino-3-[(4-methyl-1-piperazinyl)methyl]benzoate | n/a | C14H21N3O2 | 详情 | 详情 |
| (II) | 39896 | 4-(4-chlorophenoxy)benzenesulfonyl chloride | C12H8Cl2O3S | 详情 | 详情 | |
| (III) | 53017 | methyl 2-({[4-(4-chlorophenoxy)phenyl]sulfonyl}amino)-3-[(4-methyl-1-piperazinyl)methyl]benzoate | n/a | C26H28ClN3O5S | 详情 | 详情 |
| (IV) | 53018 | methyl 2-[{[4-(4-chlorophenoxy)phenyl]sulfonyl}(methyl)amino]-3-[(4-methyl-1-piperazinyl)methyl]benzoate | n/a | C27H30ClN3O5S | 详情 | 详情 |
| (V) | 53019 | 2-[{[4-(4-chlorophenoxy)phenyl]sulfonyl}(methyl)amino]-3-[(4-methyl-1-piperazinyl)methyl]benzoic acid | n/a | C26H28ClN3O5S | 详情 | 详情 |