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【结 构 式】 
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【药物名称】K-777, CRA-3316, APC-3316, K-11777 【化学名称】N-(4-Methylpiperazin-1-ylcarbonyl)-L-phenylalanine 1(S)-(2-phenylethyl)-3-(phenylsulfonyl) -2(E)-propenyl amide 【CA登记号】233277-99-1 【 分 子 式 】C32H38N4O4S 【 分 子 量 】574.74806 |
【开发单位】Celera (Originator), Institute for OneWorld Health (Licensee), National Institutes of Health (Codevelopment) 【药理作用】ANTIINFECTIVE THERAPY, Antitrypanosomals, Treatment of Protozoal Diseases, Cysteine Protease Inhibitors |
合成路线1
Phosphonylation of the lithium anion of phenyl methyl sulfone (I) with diethyl chlorophosphate afforded the sulfonyl phosphonate (II). This was condensed with N-Boc-L-homophenylalaninal (III) under Wadsworth-Emmons conditions to furnish the vinyl sulfone (IV). After acidic Boc group cleavage, the resultant amine (V) was coupled with the N-carbamoyl phenylalanine (VI), via the corresponding mixed anhydride with isobutyl chloroformate, to afford the target amide.
| 【1】 Palmer, J.T.; Rasnick, D.; Klaus, J.L. (Celera Genomics); Irreversible cysteine protease inhibitors containing vinyl groups conjugated to electron withdrawing groups. US 6287840 . |
| 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) | 23622 | methyl phenyl sulfone; methyl(dioxo)phenyl-lambda(6)-sulfane | 3112-85-4 | C7H8O2S | 详情 | 详情 |
| (II) | 23624 | diethyl (phenylsulfonyl)methylphosphonate | C11H17O5PS | 详情 | 详情 | |
| (III) | 23621 | tert-butyl (1S)-1-formyl-3-phenylpropylcarbamate | C15H21NO3 | 详情 | 详情 | |
| (IV) | 23625 | tert-butyl (1S,2E)-1-phenethyl-3-(phenylsulfonyl)-2-propenylcarbamate | C22H27NO4S | 详情 | 详情 | |
| (V) | 23626 | (1S,2E)-1-phenethyl-3-(phenylsulfonyl)-2-propenylamine; (E,3S)-5-phenyl-1-(phenylsulfonyl)-1-penten-3-amine | C17H19NO2S | 详情 | 详情 | |
| (VI) | 56040 | (2S)-2-{[(4-methyl-1-piperazinyl)carbonyl]amino}-3-phenylpropanoic acid | C15H21N3O3 | 详情 | 详情 |