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【结 构 式】 
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【药物名称】Masnidipine hydrochloride, Lercanidipine hydrochloride, TJN-324, Rec-15/2375, Lercan, Cardiovasc, Lerzam, Zanidip, Lerdip, Lercadip, Zanedip 【化学名称】(±)-1,4-Dihydro-2,6-dimethyl-4-(3-nitrophenyl)pyridine-3,5-dicarboxylic acid 2-[N-(3,3-diphenylpropyl)-N-methylamino]-1,1-dimethylethyl methyl diester hydrochloride 【CA登记号】132866-11-6, 100427-26-7 (free base) 【 分 子 式 】C36H42ClN3O6 【 分 子 量 】648.20564 |
【开发单位】Recordati (Originator), Asta Medica (Licensee), Dainippon Pharmaceutical (Licensee), Forest (Licensee), Kwizda (Licensee), Napp (Licensee), Rotta (Licensee), Tsumura (Licensee), UCB (Licensee), Uriach (Licensee), Zambon (Licensee), LifeCycle Pharma (Formu 【药理作用】CARDIOVASCULAR DRUGS, Hypertension, Treatment of, Calcium Channel Blockers |
合成路线1
Two new related ways for the synthesis of lercanidipine have been reported: 1) The condensation of diketene (I) with the aminoalcohol (II) gives the corresponding acetoacetate ester (III), which is allowed to react with 3-nitrobenzaldehyde (IV) by means of HCl in chloroform yielding the expected benzylidene derivative (V). Finally, this compound is cyclized with methyl 3-aminocrotonate (VI) in refluxing isopropanol. 2) By esterification of 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid monomethyl ester (VIII) with alcohol (II) by means of SOCl2 in DMF/dichloromethane.
| 【1】 Catto, A.; Motta, G.; Pennini, R.; Testa, R.; Sironi, G.; Cerri, A.; Leonardi, A.; Asymmetric N-(3,3-diphenylpropyl)aminoalkyl esters of 4-aryl-2,6-dimethyl-1,4-dihydropyridine-3, 5-dicarboxylic acids with antihypertensive activity. Eur J Med Chem 1998, 33, 5, 399. |
| 【2】 Nardi, D.; Leonardi, A.; Graziani, G.; Bianchi, G. (Recordati Industria Chimica e Farmaceutica SpA); N-(3,3-diphenylpropyl)aminoethylesters of 1,4-dihydro-2,6-dimethylpyridine-3,5-dicarboxylic acid, compositions and use. EP 0153016; JP 60199874; US 4772621; US 4968832 . |
| 【3】 Bianchi, G.; Leonardi, A.; REC 15/2375. Drugs Fut 1987, 12, 12, 1113. |
| 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) | 11367 | 4-Methylene-2-oxetanone; Acetyl ketene | 674-82-8 | C4H4O2 | 详情 | 详情 |
| (II) | 17748 | 1-[(3,3-diphenylpropyl)(methyl)amino]-2-methyl-2-propanol | C20H27NO | 详情 | 详情 | |
| (III) | 17749 | 2-[(3,3-diphenylpropyl)(methyl)amino]-1,1-dimethylethyl 3-oxobutanoate | C24H31NO3 | 详情 | 详情 | |
| (IV) | 12646 | 3-Nitrobenzaldehyde | 99-61-6 | C7H5NO3 | 详情 | 详情 |
| (V) | 17751 | 2-[(3,3-diphenylpropyl)(methyl)amino]-1,1-dimethylethyl (Z)-2-acetyl-3-(3-nitrophenyl)-2-propenoate | C31H34N2O5 | 详情 | 详情 | |
| (VI) | 11372 | Methyl (E)-3-amino-2-butenoate; Methyl 3-aminocrotonate | C5H9NO2 | 详情 | 详情 | |
| (VII) | 13950 | 5-(Methoxycarbonyl)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydro-3-pyridinecarboxylic acid | C16H16N2O6 | 详情 | 详情 |