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【结 构 式】 
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【药物名称】HI-368 【化学名称】N-[3-Chloro-2-oxo-1(R)-[(2E,6E)-3,7,11-trimethyl-2,6,10-dodecatrienylsulfanylmethyl]propyl]acetamide 【CA登记号】253871-57-7 【 分 子 式 】C21H34ClNO2S 【 分 子 量 】400.02763 |
【开发单位】Parker Hughes Institute (Originator) 【药理作用】ONCOLYTIC DRUGS |
合成路线1
The alkylation of N-acetyl-L-cysteine (I) with farnesyl bromide (II) in methanolic ammonia provided the corresponding farnesyl thioether (III). After activation of the S-alkylated acid (III) as the mixed anhydride (IV) using isobutyl chloroformate and N-methylmorpholine, reaction with diazomethane yielded the diazomethyl ketone (V). This was then converted into the title chloromethyl ketone by treatment with HCl in ethyl acetate.
| 【1】 Narla, R.K.; Uckun, F.M.; Perrey, D.A.; Cysteine chloromethyl and diazomethyl ketone derivatives with potent anti-leukemic activity. Bioorg Med Chem Lett 2000, 10, 6, 547. |
| 【2】 Narla, R.K.; Uckun, F.M.; Perry, D.A. (Parker Hughes Institute); Alkyl ketones as potent anti-cancer agents. WO 0000469 . |
| 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) | 43592 | (2R)-2-(acetamido)-3-sulfanylpropionic acid | C5H9NO3S | 详情 | 详情 | |
| (II) | 27414 | (2E,6E)-1-bromo-3,7,11-trimethyl-2,6,10-dodecatriene | C15H25Br | 详情 | 详情 | |
| (III) | 44902 | (2R)-2-(acetamido)-3-[[(2E,6E)-3,7,11-trimethyl-2,6,10-dodecatrienyl]sulfanyl]propionic acid | 135304-07-3 | C20H33NO3S | 详情 | 详情 |
| (IV) | 44903 | C25H41NO5S | 详情 | 详情 | ||
| (V) | 44904 | C21H33N3O2S | 详情 | 详情 |
Extended Information