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【结 构 式】 
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【药物名称】PD-157667 【化学名称】2-(4,4-Diphenylbutyl)-6-(perhydroazepin-1-yl)-1,2,3,4-tetrahydroisoquinolin-5-ol 【CA登记号】 【 分 子 式 】C32H40N2O 【 分 子 量 】468.6884 |
【开发单位】Neurex (Originator), Pfizer (Originator) 【药理作用】ANALGESIC AND ANESTHETIC DRUGS, Analgesic Drugs, Cerebrovascular Diseases, Treatment of, NEUROLOGIC DRUGS, Non-Opioid Analgesics, Stroke, Treatment of, Calcium Channel Blockers, Potassium Channel Blockers, Sodium Channel Blockers |
合成路线1
Alkylation of 5-hydroxyisoquinoline (I) with bromide (II) in DMF at 80 C afforded isoquinolinium salt (III). This was reduced to tetrahydroisoquinoline (IV) by catalytic hydrogenation in the presence of Pd/C. Finally, Mannich reaction with formaldehyde and perhydroazepine (V) in THF-water at r.t. provided the target compound.
| 【1】 Yuen, P.; Schelkun, R.M.; Szoke, B.; Tarczy-Hornoch K.; Synthesis and structure-activity relationship of substituted 1,2,3,4-tetrahydroisoquinolines as N-type calcium channel blockers. Bioorg Med Chem Lett 1998, 8, 18, 2415. |
| 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) | 18668 | 5-isoquinolinol | 2439-04-5 | C9H7NO | 详情 | 详情 |
| (II) | 18669 | 1-(4-bromo-1-phenylbutyl)benzene | C16H17Br | 详情 | 详情 | |
| (III) | 18670 | 2-(4,4-diphenylbutyl)-5-hydroxyisoquinolinium bromide | C25H24BrNO | 详情 | 详情 | |
| (IV) | 18671 | 2-(4,4-diphenylbutyl)-1,2,3,4-tetrahydro-5-isoquinolinol | C25H27NO | 详情 | 详情 | |
| (V) | 18672 | azepane | 111-49-9 | C6H13N | 详情 | 详情 |