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【结 构 式】 
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【药物名称】 【化学名称】2(S)-Allyl-3(R)-[N-[1(S)-(1H-pyrrol-2-ylcarbonyl)-2-phenylethyl]carbamoyl]-5-methylhexanehydroxamic acid 【CA登记号】 【 分 子 式 】C24H31N3O4 【 分 子 量 】425.53237 |
【开发单位】Abbott (Originator) 【药理作用】Antiarthritic Drugs, Bone Diseases, Treatment of, METABOLIC DRUGS, TREATMENT OF MUSCULOSKELETAL & CONNECTIVE TISSUE DISEASES, Treatment of Osteoporosis, Matrix Metalloproteinase Inhibitors, TNF-alpha Production Inhibitors |
合成路线1
Condensation of N-(tert-butoxycarbonyl)phenylalanine methyl ester (I) with pyrrolyl magnesium bromide (generated from pyrrole (II) and MeMgBr) furnished ketone (III). The N-Boc group of (III) was deprotected with HCl in dioxan to yield aminoketone (IV), which was then condensed with the succinate building block (V) in DMF to afford succinamide (VI). Further deprotection of the tert-butyl ester of (VI) by treatment with trifluoroacetic acid provided carboxylic acid (VII), which was coupled with O-tert-butyldimethylsilyl hydroxylamine (VIII) in the presence of EDC and HOBt to yield, after desilylation, the target hydroxamic acid.
| 【1】 Sheppard, G.S.; Florjancic, A.S.; Giesler, J.R.; Xu, L.; Guo, Y.; Davidsen, S.K.; Marcotte, P.A.; Elmore, I.; Albert, D.H.; Terrance, J.M.; Bouska, J.J.; Goodfellow, C.L.; Morgan, D.W.; Summers, J.B.; Aryl ketones as novel replacements for the C-terminal amide bond of succinyl hydroxamate MMP inhibitors. Bioorg Med Chem Lett 1998, 8, 22, 3251. |
| 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) | 21673 | methyl (2S)-2-[(tert-butoxycarbonyl)amino]-3-phenylpropanoate | C15H21NO4 | 详情 | 详情 | |
| (II) | 21674 | 1H-pyrrole | 109-97-7 | C4H5N | 详情 | 详情 |
| (III) | 21675 | tert-butyl (1S)-1-benzyl-2-oxo-2-(1H-pyrrol-2-yl)ethylcarbamate | C18H22N2O3 | 详情 | 详情 | |
| (IV) | 21676 | (2S)-2-amino-3-phenyl-1-(1H-pyrrol-2-yl)-1-propanone hydrochloride | C13H15ClN2O | 详情 | 详情 | |
| (V) | 21641 | 1-(tert-butyl) 4-(2,3,4,5,6-pentafluorophenyl) (2S,3R)-2-allyl-3-isobutylbutanedioate | C21H25F5O4 | 详情 | 详情 | |
| (VI) | 21678 | tert-butyl (2S)-2-[(1R)-1-([[(1S)-1-benzyl-2-oxo-2-(1H-pyrrol-2-yl)ethyl]amino]carbonyl)-3-methylbutyl]-4-pentenoate | C28H38N2O4 | 详情 | 详情 | |
| (VII) | 21679 | (2S)-2-[(1R)-1-([[(1S)-1-benzyl-2-oxo-2-(1H-pyrrol-2-yl)ethyl]amino]carbonyl)-3-methylbutyl]-4-pentenoic acid | C24H30N2O4 | 详情 | 详情 | |
| (VIII) | 21644 | (Aminooxy)(tert-butyl)dimethylsilane; O-[tert-Butyl(dimethyl)silyl]hydroxylamine | 41879-39-4 | C6H17NOSi | 详情 | 详情 |