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【结 构 式】 
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【药物名称】Naltrexone hydrochloride, PTI-901, EN-1639A, Vivitrex, Naltrel(Slow Release), Celupan, Antaxone, ReVia(treatment of alcoholism), Nemexin, Nalorex, Trexan 【化学名称】(-)-17-(Cyclopropylmethyl)-4,5alpha-epoxy-3,14-dihydroxymorphinan-6-one hydrochloride 【CA登记号】16676-29-2, 16590-41-3 (free base) 【 分 子 式 】C20H24ClNO4 【 分 子 量 】377.87158 |
【开发单位】Bristol-Myers Squibb (Originator), DrugAbuse Sciences (Licensee), Lacer (Licensee), Roche (Licensee), Zambon (Licensee), Alkermes (Formulation), Pain Therapeutics (Formulation) 【药理作用】ANALGESIC AND ANESTHETIC DRUGS, Analgesic Drugs, Opioid Analgesics, Treatment of Alcohol Dependency, Treatment of Opioid Dependency, TREATMENT OF POISONING, DRUG ABUSE & DEPENDENCY, Treatment of Substance Dependency, Opioid Antagonists |
合成路线1
Compound can be prepared in two different ways both starting from 14-hydroxydihydronormorphinone (I): 1) By reaction of (I) with cyclopropylmethyl bromide (C) in DMF at 70 C. 2) Product (I) is ketalized with ethylene glycol (A) by means of p-toluenesulfonic acid giving the cyclic ketal (II), m.p. 311-3 C; this in turn, is treated with cyclopropyl carbonyl chloride (B) in a mixture of methylene chloride and triethylamine yielding the N,O-dicyclopropylcarbonyl derivative (III), mp 219-20 C. Compound (III) is reduced with LiAlH4, in refluxing THF yielding the ethylene ketal of naltrexone (IV), m.p. 221-2 C, which is finally hydrolyzed with aqueous HCl at 100 C.
| 【1】 Blumberg, H.; et al.; 14-Hydroxydihydronormorphinone derivatives. US 3332950 . |
| 【2】 Blumberg, H.; et al.; Verfahren zur Herstellung von N-substituierten 14-Hydroxydidronormorphinen. CH 493522; DE 1670616; DE 1795707; GB 1119270 . |
| 【3】 Derives de 14-hydroxydihydronormorphinones. FR 6358M . |
| 【4】 Castaner, J.; Roberts, P.J.; Naltrexone. Drugs Fut 1977, 2, 1, 45. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (A) | 11295 | Polyethylene glycol;1,2-Ethanediol;Monoethylene glycol; Ethylene glycol | 107-21-1 | C2H6O2 | 详情 | 详情 |
| (B) | 14061 | Cyclopropanecarbonyl chloride; Cyclopropanecarboxylic acid chloride | 4023-34-1 | C4H5ClO | 详情 | 详情 |
| (I) | 33610 | (1S,5R,13R,17R)-10,17-dihydroxy-12-oxa-4-azapentacyclo[9.6.1.0(1,13).0(5,17).0(7,18)]octadeca-7(18),8,10-trien-14-one | C16H17NO4 | 详情 | 详情 | |
| (II) | 33611 | C18H21NO5 | 详情 | 详情 | ||
| (III) | 33612 | C26H29NO7 | 详情 | 详情 | ||
| (IV) | 33613 | C22H27NO5 | 详情 | 详情 | ||
| (C) | 22277 | Cyclopropyl bromide; 1-(Bromomethyl)cyclopropane | 7051-34-5 | C4H7Br | 详情 | 详情 |