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【结 构 式】 
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【药物名称】Vesnarinone, OPC-8212, Arkin, Arkin-Z 【化学名称】1-(1,2,3,4-Tetrahydro-2-oxo-6-quinolyl)-4-veratroylpiperazine 【CA登记号】81840-15-5 【 分 子 式 】C22H25N3O4 【 分 子 量 】395.46225 |
【开发单位】Otsuka (Originator), Johns Hopkins University (Not Determined) 【药理作用】CARDIOVASCULAR DRUGS, Heart Failure Therapy, Leukemia Therapy, Oncolytic Drugs, Apoptosis Inducers, CDKN1A Expression Enhancers |
合成路线1
OPC-8212 is obtained through the piperazine ring formation method from bis(beta-bromoethyl)amine hydrobromide and 6-amino-3,4-dihydro-2(1H)-quinolinone (V) to give (VI). (V) is synthesized using the ring closure reaction of p-acetylamino-beta-ethoxyacryloanilide (II). p-Acetylaminoaniline (I) is converted to (II) by treatment with beta-ethoxyacryloyl chloride and afterwards cyclized in the presence of sulfuric acid to give 6-acetylamino-2-(1H)-quinolinone (III). Hydrogenation of (III) over 10% palladium on charcoal gives 6-acetylamino-3,4-dihydro-2(1H)-quinolinone (IV). Hydrolysis of (IV) gives 6-amino-3,4-dihydro-2(1H)-quinolinone (V). OPC-8212 is obtained by adding 3,4-dimethoxybenzyl chloride (VII) to (VI).
| 【1】 Nakagawa, K.; Osumi, T.; Shimizu, T.; Niimi, K.; Physicochemical properties and stabilities of a new positive inotropic agent, OPC 8212. Arzneim-Forsch Drug Res 1984, 34, 3A, 334-341. |
| 【2】 Yo, E.; Ogawa, H.; Yamashita, S.; Tominaga, M.; Nakagawa, K.; Yabuuchi, Y.; Studies on positive inotropic agents. I. Synthesis of 3,4-dihydro-6-[4-(3,4-dimethoxybenzoyl)-1-piperazinyl]-2(1H)-quinolinone and related compounds. Chem Pharm Bull 1984, 32, 6, 2100. |
| 【3】 Mannhold, R.; OPC-8212. Drugs Fut 1985, 10, 1, 28. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (A) | 20616 | (E)-3-ethoxy-2-propenoyl chloride | 99471-66-6 | C5H7ClO2 | 详情 | 详情 |
| (B) | 29020 | 2-bromo-N-(2-bromoethyl)-1-ethanamine | C4H9Br2N | 详情 | 详情 | |
| (I) | 29016 | N-(4-aminophenyl)acetamide | 122-80-5 | C8H10N2O | 详情 | 详情 |
| (II) | 29017 | (E)-N-[4-(acetamido)phenyl]-3-ethoxy-2-propenamide | C13H16N2O3 | 详情 | 详情 | |
| (III) | 29018 | N-(2-oxo-1,2-dihydro-6-quinolinyl)acetamide | C11H10N2O2 | 详情 | 详情 | |
| (IV) | 29019 | N-(2-oxo-1,2,3,4-tetrahydro-6-quinolinyl)acetamide | C11H12N2O2 | 详情 | 详情 | |
| (V) | 29022 | 6-amino-3,4-dihydro-2(1H)-quinolinone | C9H10N2O | 详情 | 详情 | |
| (VI) | 29021 | 6-(1-piperazinyl)-3,4-dihydro-2(1H)-quinolinone | C13H17N3O | 详情 | 详情 | |
| (VII) | 13438 | 3,4-Dimethoxybenzoyl chloride | 3535-37-3 | C9H9ClO3 | 详情 | 详情 |