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【结 构 式】 
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【药物名称】 【化学名称】2(R)-(Methylamino)-3-(4-phenoxyphenylsulfonyl)propionohydroxamic acid 【CA登记号】310464-35-8 (enantiomer) 【 分 子 式 】C16H18N2O5S 【 分 子 量 】350.39626 |
【开发单位】Pfizer (Originator) 【药理作用】Antiarthritic Drugs, TREATMENT OF MUSCULOSKELETAL & CONNECTIVE TISSUE DISEASES, MMP-13 (Collagenase 3) Inhibitors |
合成路线1
The reaction of N-(benzyloxycarbonyl)-L-serine methyl ester (I) with Ts-Cl gives the corresponding tosylate (II), which is condensed with 4-phenoxythiophenol (III) to yield the thioether (IV). The oxidation of (IV) with Oxone affords the sulfone (V), which is N-deprotected with H2 over Pd/C to provide compound (VI) with a free amino group. The methylation of (VI) with methyl iodide gives the N-methyl derivative (VII), which is finally treated with hydroxylamine to afford the target hydroxamic acid.
| 【1】 Bedell, L.; Becker, D.P.; Barta, T.E.; et al.; alpha-Amino-beta-sulphone hydroxamates as potent MMP-13 inhibitors that spare MMP-1. Bioorg Med Chem Lett 2001, 11, 20, 2719. |
| 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) | 51660 | methyl (2S)-2-[[(benzyloxy)carbonyl]amino]-3-hydroxypropanoate | C12H15NO5 | 详情 | 详情 | |
| (II) | 51655 | methyl (2S)-2-[[(benzyloxy)carbonyl]amino]-3-[[(4-methylphenyl)sulfonyl]oxy]propanoate | C19H21NO7S | 详情 | 详情 | |
| (III) | 26254 | 4-phenoxybenzenethiol; 4-phenoxyphenylhydrosulfide | C12H10OS | 详情 | 详情 | |
| (IV) | 51656 | methyl (2R)-2-[[(benzyloxy)carbonyl]amino]-3-[(4-phenoxyphenyl)sulfanyl]propanoate | C24H23NO5S | 详情 | 详情 | |
| (V) | 51657 | methyl (2R)-2-[[(benzyloxy)carbonyl]amino]-3-[(4-phenoxyphenyl)sulfonyl]propanoate | C24H23NO7S | 详情 | 详情 | |
| (VI) | 51658 | methyl (2R)-2-amino-3-[(4-phenoxyphenyl)sulfonyl]propanoate | C16H17NO5S | 详情 | 详情 | |
| (VII) | 51659 | methyl (2R)-2-(methylamino)-3-[(4-phenoxyphenyl)sulfonyl]propanoate | C17H19NO5S | 详情 | 详情 |