|
【结 构 式】 
|
【药物名称】Labedipinedilol A 【化学名称】4-[4-[2-Hydroxy-3-[2-(2-methoxyphenoxy)ethylamino]propoxy]-3-methoxyphenyl]-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid dimethyl ester 【CA登记号】257284-30-3 【 分 子 式 】C30H38N2O9 【 分 子 量 】570.64536 |
【开发单位】Kaohsiung Medical College (Originator) 【药理作用】CARDIOVASCULAR DRUGS, Hypertension, Treatment of, alpha-Adrenoceptor Antagonists, beta-Adrenoceptor Antagonists, Calcium Channel Blockers |
合成路线1
Guaiacol (I) was alkylated by means of boiling dibromoethane (II) to produce the bromoethyl ether (III). From this, the intermediate amine (VI) was prepared by Gabriel synthesis, via condensation with potassium phthalimide (IV) in hot DMF, followed by hydrazinolysis of the resultant N-substituted phthalimide (V).
| 【1】 Lin, T.-H.; Chen, I.-J.; Guaiacoxypropanolamines with alpha/beta-adrenergic blocking activity. EP 1108710; WO 0005209 . |
| 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) | 13182 | Guaiacol; 2-Methoxyphenol | 90-05-1 | C7H8O2 | 详情 | 详情 |
| (II) | 10252 | 1,2-Dibromoethane; Ethylene dibromide | 106-93-4 | C2H4Br2 | 详情 | 详情 |
| (III) | 51402 | 2-(2-Bromoethoxy)methoxybenzene; 1-Bromo-2-(2-methoxyphenoxy)ethane | 4463-59-6 | C9H11BrO2 | 详情 | 详情 |
| (IV) | 27890 | Potassium phthalimide | 1074-82-4 | C8H4KNO2 | 详情 | 详情 |
| (V) | 59617 | 2-[2-(2-methoxyphenoxy)ethyl]-1H-isoindole-1,3(2H)-dione | C17H15NO4 | 详情 | 详情 | |
| (VI) | 31105 | 2-(2-methoxyphenoxy)ethylamine; 2-(2-methoxyphenoxy)-1-ethanamine | 1836-62-0 | C9H13NO2 | 详情 | 详情 |
合成路线2
The condensation of vanillin (VII) with epichlorohydrin (VIII) in ethanolic NaOH produced the glycidyl ether (IX). Epoxide ring opening in (IX) by means of amine (VI) in EtOH furnished amino alcohol (X). The title dihydropyridine derivative was then obtained by reaction between aldehyde (X), methyl acetoacetate (XI), and ammonia under Hantzsch condensation conditions.
| 【1】 Liang, J.-C.; Chen, I.-J.; Tsai, C.-H.; Liou, S.-F.; Wang, C.-S.; Yeh, J.-L.; The new generation dihydropyridine type calcium blockers, bearing 4-phenyl oxypropanolamine, display alpha-/beta-adrenoceptor antagonist and long-acting antihypertensive activities. Bioorg Med Chem 2002, 10, 3, 719. |
| 【2】 Lin, T.-H.; Chen, I.-J.; Guaiacoxypropanolamines with alpha/beta-adrenergic blocking activity. EP 1108710; WO 0005209 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VI) | 31105 | 2-(2-methoxyphenoxy)ethylamine; 2-(2-methoxyphenoxy)-1-ethanamine | 1836-62-0 | C9H13NO2 | 详情 | 详情 |
| (VII) | 22701 | 4-hydroxy-3-methoxybenzaldehyde | 121-33-5 | C8H8O3 | 详情 | 详情 |
| (VIII) | 10146 | Epichlorohydrin; 2-(Chloromethyl)oxirane | 106-89-8 | C3H5ClO | 详情 | 详情 |
| (IX) | 59599 | 3-methoxy-4-(2-oxiranylmethoxy)benzaldehyde | C11H12O4 | 详情 | 详情 | |
| (X) | 59618 | 4-(2-hydroxy-3-{[2-(2-methoxyphenoxy)ethyl]amino}propoxy)-3-methoxybenzaldehyde | C20H25NO6 | 详情 | 详情 | |
| (XI) | 11791 | methyl 3-oxobutanoate; Methyl acetoacetate | 105-45-3 | C5H8O3 | 详情 | 详情 |