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【结 构 式】 
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【药物名称】Dofequidar fumarate, MS-209 【化学名称】5-[3-[4-(2,2-Diphenylacetyl)piperazin-1-yl]-2-hydroxypropoxy]quinoline sesquifumarate 【CA登记号】153653-30-6 ((E)-2-butenedioate salt (1:1)), 153653-33-9 ((R)-isomer), 153653-31-7 ((S)-isomer), 129716-58-1 (free base) 【 分 子 式 】C34H35N3O7 【 分 子 量 】597.67395 |
【开发单位】Mitsui Pharmaceuticals (Originator), Nihon Schering (Originator), Schering AG (Originator) 【药理作用】Modulators of the Therapeutic Activity of Antineoplastic Agents, Multidrug Resistance Modulators, ONCOLYTIC DRUGS, P-Glycoprotein (MDR-1) Inhibitors |
合成路线1
N-(2,2-Diphenylacetyl)piperazine (IV) was prepared by acylation of N-formylpiperazine (II) with 2,2-diphenylacetyl chloride (I), followed by acid-promoted formyl deprotection of the resulting amide (III). Condensation of 5-hydroxyquinoline (VI) with epichlorohydrin (V) in the presence of potassium tert-butoxide in DMF at 90 C provided 5-(2,3-epoxypropoxy)quinoline (VII), which was subsequently coupled with acylpiperazine (IV) in boiling isopropanol to yield (VIII). This was finally treated with fumaric acid (IX) in MeOH to furnish the title sesquifumarate salt.
| 【1】 Suzuki, T.; et al.; Structure-activity relationship of newly synthesiz. J Med Chem 1997, 40, 13, 2047. |
| 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) | 23800 | Diphenylacetyl chloride; 2,2-diphenylacetyl chloride | 1871-76-7 | C14H11ClO | 详情 | 详情 |
| (II) | 23801 | 1-piperazinecarbaldehyde; N-Formylpiperazine | 7755-92-2 | C5H10N2O | 详情 | 详情 |
| (III) | 23802 | 4-(2,2-diphenylacetyl)-1-piperazinecarbaldehyde | C19H20N2O2 | 详情 | 详情 | |
| (IV) | 23803 | 2,2-diphenyl-1-(1-piperazinyl)-1-ethanone | C18H20N2O | 详情 | 详情 | |
| (V) | 10146 | Epichlorohydrin; 2-(Chloromethyl)oxirane | 106-89-8 | C3H5ClO | 详情 | 详情 |
| (VI) | 23805 | 5-quinolinol | 578-67-6 | C9H7NO | 详情 | 详情 |
| (VII) | 23806 | 5-(2-oxiranylmethoxy)quinoline; 2-oxiranylmethyl 5-quinolinyl ether | C12H11NO2 | 详情 | 详情 | |
| (VIII) | 23807 | 1-[4-[2-hydroxy-3-(5-quinolinyloxy)propyl]-1-piperazinyl]-2,2-diphenyl-1-ethanone | C30H31N3O3 | 详情 | 详情 | |
| (IX) | 23808 | Fumaric acid; (E)-2-butenedioic acid | 110-17-8 | C4H4O4 | 详情 | 详情 |