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【结 构 式】 
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【药物名称】Carteolol hydrochloride, OPC-1085, Abbott-43326, Arteolol, Mikelan, Carteol, Teoptic, Arteoptic, Ocupress, Cartrol 【化学名称】5-[3-(1,1-Dimethylethylamino)-2-hydroxypropoxy]-3,4-dihydro-2H-quinolinone hydrochloride 【CA登记号】51781-21-6, 51781-06-7 (free base) 【 分 子 式 】C16H25ClN2O3 【 分 子 量 】328.84225 |
【开发单位】Otsuka (Not Determined), Chauvin (Licensee), Lacer (Licensee), Novartis (Licensee) 【药理作用】Angina pectoris, Treatment of, Antiarrhythmic Drugs, Antiglaucoma Agents, CARDIOVASCULAR DRUGS, Hypertension, Treatment of, OCULAR MEDICATIONS, Ophthalmic Drugs, Treatment of Disorders of the Coronary Arteries and Atherosclerosis, beta-Adrenoceptor Antagonists |
合成路线1
The reaction of cyclohexane-1,3-dione (I) with ammonia gives 3-amino-2-cyclohexen-1-one (II), which is cyclized with acrylic acid (III) by heating at 140 C yielding 1,2,3,4,5,6,7,8-octahydroquinoline-2,5-dione (IV). The dehydrogenation of (IV) by means of Pd/C in refluxing decaline affords 5-hydroxy-1,2,3,4-tetrahydroquinolin-2-one (V), which is condensed with epichlorohydrin (VI) by means of NaOMe or NaOH in methanol giving 5-(2,3-epoxypropoxy)-1,2,3,4-tetrahydroquinolin-2-one (VII). Finally, this compound is treated with tert-butylamine in methanol.
| 【1】 Castaner, J.; Sungurbey, K.; Carteolol. Drugs Fut 1977, 2, 5, 288. |
| 【2】 Shono, T.; et al.; A new practical synthesis of 5-hydroxy-3,4-dihydrocarbostyril and 5-hydroxycarbostyril. J Org Chem 1981, 46, 3719. |
| 【3】 Von Winkler, W.; Chemical and analytical data for the pharmaceutically active substance carteolol hydrochloride. Arzneim-Forsch Drug Res 1983, 33, 2a, 279. |
| 【4】 Mori, H.; Tamura, Y,.; Tominaga, M.; Yoshiaki, S.; Nakagawa, K.; Murakami, N. (Otsuka Pharmaceutical Co., Ltd.); 3,4-Dihydrocarbostyril derivs., their preparation, and pharmaceutical compsns. thereof. DE 2302027; GB 1424571 . |
| 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) | 11244 | 1,3-Cyclohexanedione | 504-02-9 | C6H8O2 | 详情 | 详情 |
| (II) | 31475 | 3-amino-2-cyclohexen-1-one | 5220-49-5 | C6H9NO | 详情 | 详情 |
| (III) | 19139 | acrylic acid | 79-10-7 | C3H4O2 | 详情 | 详情 |
| (IV) | 31476 | 4,6,7,8-tetrahydro-2,5(1H,3H)-quinolinedione | C9H11NO2 | 详情 | 详情 | |
| (V) | 31477 | 5-hydroxy-3,4-dihydro-2(1H)-quinolinone | C9H9NO2 | 详情 | 详情 | |
| (VI) | 29648 | 2-oxiranylmethanol | 556-52-5 | C3H6O2 | 详情 | 详情 |
| (VII) | 31478 | 5-(2-oxiranylmethoxy)-3,4-dihydro-2(1H)-quinolinone | C12H13NO3 | 详情 | 详情 | |
| (VIII) | 17895 | 2-Amino-2-methylpropane; tert-butylamine; 2-methyl-2-propanamine | 75-64-9 | C4H11N | 详情 | 详情 |