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【结 构 式】 
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【药物名称】Nabutan hyrochloride(former USAN), Nabitan hydrochloride(Prop INNM; USAN), SP-106, Abbott-4056, NIB, BPP 【化学名称】(±)-8-(3-Methyl-2-octyl)-1,3,4,5-tetrahydro-5,5-dimethyl-2-(2-propynyl)-2H-[1]benzopyrano[4,3-c]pyridin-10-yl 1-piperidinebutyrate hydrochloride 【CA登记号】49637-08-3, 66556-74-9 (free base) 【 分 子 式 】C35H53ClN2O3 【 分 子 量 】585.27726 |
【开发单位】Abbott (Originator), Sisa (Originator) 【药理作用】ANALGESIC AND ANESTHETIC DRUGS, Analgesic Drugs, Nausea and Vomiting, Treatment of, NEUROLOGIC DRUGS, Non-Opioid Analgesics |
合成路线1
Ethyl 4-bromobutyrate (I) is condensed with piperidine (II) in refluxing benzene to give ethyl 4-(1-piperidyl)butyrate (III), which is hydrolyzed with refluxing aqueous HCl to 4-(1-piperidyl)butyric acid (IV) . Finally, this acid is esterified with 5,5-dimethyl-8-(3-methyl-2-octyl)-10-hydroxy-2-(2-propynyl)-1,2,3,4-tetrahydro-5H[1]benzopyrano[3,4-d]pyridine (V) by means of dicyclohexylcarbodiimide (A) in methylene chloride.
| 【1】 Dren, A.T.; Ebert, D.M.; US 4025630 . |
| 【2】 Razdan, R.K.; et al.; Drugs derived from cannabinoids. 2. Basic esters of nitrogen and carboxylic analogs. J Med Chem 1976, 19, 4, 454-461. |
| 【3】 Castaner, J.; Paton, D.M.; Nabitan Hydrochloride. Drugs Fut 1980, 5, 9, 439. |
| 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) | 11263 | ethyl 4-bromobutanoate; Ethyl 4-bromobutyrate | 2969-81-5 | C6H11BrO2 | 详情 | 详情 |
| (II) | 10158 | Piperidine | 110-89-4 | C5H11N | 详情 | 详情 |
| (III) | 39196 | ethyl 4-(1-piperidinyl)butanoate | C11H21NO2 | 详情 | 详情 | |
| (IV) | 39197 | 4-(1-piperidinyl)butyric acid | C9H17NO2 | 详情 | 详情 | |
| (V) | 39198 | 8-(1,2-dimethylheptyl)-5,5-dimethyl-2-(2-propynyl)-1,3,4,5-tetrahydro-2H-chromeno[4,3-c]pyridin-10-ol | C26H37NO2 | 详情 | 详情 | |
| (VI) | 39199 | N,N'-dicyclohexylcarbodiimide | 538-75-0 | C13H22N2 | 详情 | 详情 |