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【结 构 式】 
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【药物名称】Estramustine phosphate sodium, Ro-21-8837/001, Estracyt, Emcyt 【化学名称】(17beta)-Estra-1,3,5(10)-triene-3,17-diol 3-[bis(2-chloroethyl)carbamate] 17-(dihydrogen phosphate) disodium salt 【CA登记号】52205-73-9, 2998-57-4 (free acid) 【 分 子 式 】C23H30Cl2NNa2O6P 【 分 子 量 】564.35805 |
【开发单位】Roche (Originator), Nippon Shinyaku (Not Determined), Leo (Licensee), Lundbeck (Licensee), Pfizer (Licensee) 【药理作用】Oncolytic Drugs, Prostate Cancer Therapy, DNA Alkylating Drugs |
合成路线1
Estradiol 3-N-bis(2-chloroethyl)carbamate (IV) was prepared by treatment of estradiol (I) with either the carbamoyl chloride (II) or the carbamoyl bromide (III) in the presence of various bases such as triethylamine and DMAP or DBU. Phosphorylation of (IV) with phosphorus oxychloride and pyridine, followed by aqueous hydrolysis, produced the 17-O-phosphate ester (V). This was converted to the corresponding disodium salt by treatment with sodium methoxide.
| 【1】 Stamvik, A.R.; Kristensson, S.K. (Leo Pharma AB); A selective acylation process. EP 0138153 . |
| 【2】 Ohwaki, K.; Niino, H.; Method for selective acylation of estradiol. EP 0614909 . |
| 【3】 Ohwaki, K.; Niino, H.; norose, S.; Method for purification of estramustin phosphate or salt thereof. EP 0612760 . |
| 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) | 34210 | (8R,9S,13S,14S,17S)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthrene-3,17-diol | 50-28-2 | C18H24O2 | 详情 | 详情 |
| (II) | 56313 | N,N-Bis(2-chloroethyl)carbamoyl chloride; Bis(2-chloroethyl)carbamoyl chloride | 2998-56-3 | C5H8Cl3NO | 详情 | 详情 |
| (III) | 56314 | 1-[(bromocarbonyl)(2-chloroethyl)amino]-2-chloroethane | C5H8BrCl2NO | 详情 | 详情 | |
| (IV) | 56315 | (8R,9S,13S,14S,17S)-17-hydroxy-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-3-yl bis(2-chloroethyl)carbamate | C23H31Cl2NO3 | 详情 | 详情 | |
| (V) | 56316 | (8R,9S,13S,14S,17S)-13-methyl-17-(phosphonooxy)-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-3-yl bis(2-chloroethyl)carbamate | C23H32Cl2NO6P | 详情 | 详情 |