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【结 构 式】 
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【药物名称】Pranidipine, OPC-13340, Acalas 【化学名称】2,6-Dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid 3-methyl 5-[3-phenyl-2(E)-propenyl] diester 【CA登记号】99522-79-9, 102106-08-1 ((Z)-isomer) 【 分 子 式 】C25H24N2O6 【 分 子 量 】448.47983 |
【开发单位】Otsuka (Originator) 【药理作用】Angina pectoris, Treatment of, CARDIOVASCULAR DRUGS, Hypertension, Treatment of, Treatment of Disorders of the Coronary Arteries and Atherosclerosis, Calcium Channel Blockers |
合成路线1
This compound can be obtained by three different ways: 1) The reaction of 3-nitrobenzaldehyde (I) with methyl acetoacetate (II) by means of m-toluidine in methanol gives methyl 2-(3-nitrobenzylidene)acetoacetate (III), which is then cyclized with 3-aminocrotonic acid 3-phenyl-2(E)-propenyl ester (IV) in refluxing isopropanol. 2) By cyclization of methyl 3-aminocrotonate (V) with aldehyde (I) and acetoacetic acid 3-phenyl-2(E)-propenyl ester (VI) in refluxing isopropanol. 3) By esterification of 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid monomethyl ester (VII) with 3-phenyl-2(E)-propenyl alcohol (VIII), by means of dicyclohexylcarbodiimide (DCC) in pyridine.
| 【1】 Nishitani, S.; Minamikawa, J.; Kano, M.; Otsubo, J.; Manabe, Y. (Otsuka Pharmaceutical Co., Ltd.); Process for preparing novel dihydropyridine derivs. EP 0173126 . |
| 【2】 Tamada, S.; Ei, K.; Teramoto, S.; Tanaka, T.; Nakagawa, T. (Otsuka Pharmaceutical Co., Ltd.); Dihydropyridine derivs. JP 1986140567 . |
| 【3】 Tamada, S.; Nagami, K.; Teramoto, S.; Tanaka, T.; Nakagawa, K. (Otsuka Pharmaceutical Co., Ltd.); Novel dihydropyridine derivs. and process for preparing the same. EP 0145434; ES 8604516; ES 8701726; ES 8701727; JP 1985120861; JP 1989151557; US 5034395; US 5137889 . |
| 【4】 Prous, J.; Castaner, J.; OPC-13340. Drugs Fut 1991, 16, 2, 119. |
| 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) | 12646 | 3-Nitrobenzaldehyde | 99-61-6 | C7H5NO3 | 详情 | 详情 |
| (II) | 11791 | methyl 3-oxobutanoate; Methyl acetoacetate | 105-45-3 | C5H8O3 | 详情 | 详情 |
| (III) | 12276 | methyl (Z)-2-acetyl-3-(3-nitrophenyl)-2-propenoate | C12H11NO5 | 详情 | 详情 | |
| (IV) | 13947 | (E)-3-phenyl-2-propenyl (E)-3-amino-2-butenoate | C13H15NO2 | 详情 | 详情 | |
| (V) | 11372 | Methyl (E)-3-amino-2-butenoate; Methyl 3-aminocrotonate | C5H9NO2 | 详情 | 详情 | |
| (VI) | 13949 | (E)-3-phenyl-2-propenyl 3-oxobutanoate | C13H14O3 | 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 | |
| (VIII) | 13951 | (E)-3-Phenyl-2-propen-1-ol | 104-54-1 | C9H10O | 详情 | 详情 |