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【结 构 式】 
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【药物名称】alpha-Difluoromethylornithine hydrochloride, Eflornithine hydrochloride, MDL-71782A, RMI-71782, DFMO, Vaniqa, Ornidyl 【化学名称】2-Difluoromethyl-DL-ornithine monohydrochloride monohydrate 【CA登记号】96020-91-6, 67037-37-0 (free base, anhydrous) 【 分 子 式 】C6H15ClF2N2O3 【 分 子 量 】236.64785 |
【开发单位】Aventis Pharma (Originator), Bristol-Myers Squibb (Licensee), Gillette (Licensee), Ilex Oncology (Licensee), National Cancer Institute (Codevelopment), World Health Organization (Codevelopment) 【药理作用】Adenomatous Polyposis Therapy, ANTIINFECTIVE THERAPY, Antitrypanosomals, Bladder Cancer Therapy , Colorectal Cancer Therapy, DERMATOLOGIC DRUGS, Esophageal Diseases, Treatment of, Excessive Facial Hair in Women, Treatment of, GASTROINTESTINAL DRUGS, Oncolytic Drugs, Prostate Cancer Therapy, Solid Tumors Therapy, Treatment of Protozoal Diseases, Ornithine Decarboxylase Inhibitors |
合成路线1
By reaction of N2,N5-dibenzylidinolysine methly ester (I), with chlorodifluoromethane (II) in the presence of lithium diisopropylamide, followed by acid hydrolysis of the ester. Isolated as the monohydrochloride salt, monohydrate.
| 【1】 Metcalf, B.W.; et al.; Catalytic irreversible inhibition of mammalial ornithine decarboxylase (E.C.4.1.1.17) by substrate and product analogues. J Am Chem Soc 1978, 100, 2551-53. |
| 【2】 Schijvenaars, M.; Franke, B.; Mariman, E.C.M.; Steegers-Theunissen, R.; Willemen, J.; Groenen, P.; Klootwijk, R.; Hol, F.; D,L-alpha-Difluoromethyl ornithine-RMI 71782. Product data sheet, Centre de recherche Merrell, Strasbourg Cedex 2002, Abst 1027. |
| 【3】 Castaner, J.; Blancafort, P.; Serradell, M.N.; D,L-alpha-Difluoromethyl ornithine. Drugs Fut 1981, 6, 3, 142. |
合成路线2
The optical resolution of 2,5-diamino-2-(difluoromethyl)pentanoic acid is performed as follows: The cyclization of its corresponding methyl ester (I) by means of sodium methoxide in methanol gives the racemic piperidone (II), which is submitted to optical resolution with (-)-binaphthylphosphoric acid yielding after crystallization and acidification with HCl the (+) and (-) piperidones (III) and (IV). Finally, both compounds are treated with refluxing 6N HCl to afford the target enantiomers.
| 【1】 Jung, M.; Bey, P. (Aventis Pharma SA); 2-(Difluoromethyl)-2,5-diaminopentanoic acid. US 4413141 . |
| 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) | 40918 | methyl 2,5-diamino-2-(difluoromethyl)pentanoate | C7H14F2N2O2 | 详情 | 详情 | |
| (II) | 40919 | 3-amino-3-(difluoromethyl)-2-piperidinone | C6H10F2N2O | 详情 | 详情 | |
| (III) | 40920 | (3R)-3-amino-3-(difluoromethyl)-2-piperidinone | C6H10F2N2O | 详情 | 详情 | |
| (IV) | 40921 | (3S)-3-amino-3-(difluoromethyl)-2-piperidinone | C6H10F2N2O | 详情 | 详情 |