|
【结 构 式】 
|
【药物名称】Nifekalant hydrochloride, MS-551, Shinbit 【化学名称】6-[2-[N-(2-Hydroxyethyl)-3-(4-nitrophenyl)propylamino]ethylamino]-1,3-dimethyl-2,4(1H,3H)-pyrimidinedione hydrochloride 【CA登记号】130656-51-8, 130636-43-0 (free base) 【 分 子 式 】C19H28ClN5O5 【 分 子 量 】441.91851 |
【开发单位】Mitsui Pharmaceuticals (Originator), Mitsui Chemicals (Bulk Supplier) 【药理作用】Antiarrhythmic Drugs, CARDIOVASCULAR DRUGS, Potassium Channel Blockers |
合成路线1
By condensation of N-(2-hydroxyethyl)-N-[3-(4-nitrophenyl)propyl]amine (I) with 1,3-dimethyl-6-[2-(p-toluenesulfonyloxy)ethylamino]pyrimidine-2,4(1H,3H)-dione (II) by means of NaOH in hot ethanol or methanol. The starting materials are obtained as follows: 1) The esterification of 3-(4-nitrophenyl)propanol (III) with p-toluenesulfonyl chloride (IV) by means of pyridine in chloroform gives the corresponding p-toluenesulfonate (V), which is then condensed with ethanolamine (VI) by heating at 100 C to afford amine (I). 2) The condensation of ethanolamine (VI) with 6-chloro-1,3-dimethylpyrimidine-2,4(1H,3H)-dione (VII) by heating at 90 C, or by means of triethylamine in refluxing isopropanol, gives 6-(2-hydroxyethylamino)-1,3-dimethylpyrimidine-2,4(1H,3H)-dione (VIII), which is then esterified with p-toluenesulfonyl chloride (IV) as before yielding pyrimidine (II).
| 【1】 Katakami, T.; Yokoyama, T.; Miyamoto, M.; Mori, H.; Kawauchi, N.; Nobori, T.; Sannohe, K.; Kamiya, J.; Ishii, M.; Yoshihara, K. (Mitsui Chemicals, Inc.); Pyrimidinedione deriv. cpds., method of producing the same and antiarrhythmic agents containing the same. AU 8943869; EP 0369627; JP 1991112948; JP 1991173873; US 5008267 . |
| 【2】 Kaiho, T.; Mori, H.; Miyamoto, M.; Nobori, T.; Yokoyama, T.; Kawauchi, N.; Katakami, T.; San-nohe, K.; Synthesis and pharmacological studies of N-substituted 6-[(2-aminoethyl)amino]-1,3-dimethyl-2,4(1H,3H) pyrimidinediones, novel class III antiarrhythmic agents. J Med Chem 1992, 35, 18, 3325-30. |
| 【3】 Castaner, J.; Prous, J.; MS-551. Drugs Fut 1993, 18, 3, 226. |
| 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) | 13972 | 2-[[3-(4-Nitrophenyl)propyl]amino]-1-ethanol | C11H16N2O3 | 详情 | 详情 | |
| (II) | 13973 | 2-[(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-4-pyrimidinyl)amino]ethyl 4-methylbenzenesulfonate | C15H19N3O5S | 详情 | 详情 | |
| (III) | 13974 | 3-(4-Nitrophenyl)-1-propanol | C9H11NO3 | 详情 | 详情 | |
| (IV) | 13975 | p-Toluenesulfonyl chloride;p-tosyl chloride;Toluene-4-sulfonyl chloride;4-Toluene sulfochloride;tosyl chloride; 4-Methylbenzenesulfonyl chloride | 98-59-9 | C7H7ClO2S | 详情 | 详情 |
| (V) | 13976 | 3-(4-nitrophenyl)propyl 4-methylbenzenesulfonate | C16H17NO5S | 详情 | 详情 | |
| (VI) | 10259 | Ethanol amine;Ethanolamine;2-Aminoethanol; 2-Amino-1-ethanol；2-Aminoethyl alcohol | 141-43-5 | C2H7NO | 详情 | 详情 |
| (VII) | 13978 | 6-Chloro-1,3-dimethyluracil; 6-Chloro-1,3-dimethyl-2,4(1H,3H)-pyrimidinedione | 6972-27-6 | C6H7ClN2O2 | 详情 | 详情 |
| (VIII) | 13979 | 6-[(2-Hydroxyethyl)amino]-1,3-dimethyl-2,4(1H,3H)-pyrimidinedione | C8H13N3O3 | 详情 | 详情 |