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【结 构 式】 
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【药物名称】Laniquidar, R-101933 【化学名称】11-[1-[2-[4-(2-Quinolylmethoxy)phenyl]ethyl]piperidin-4-ylidene]-6,11-dihydro-5H-imidazo[2,1-b][3]benzazepine-3-carboxylic acid methyl ester 【CA登记号】197509-46-9, 278798-78-0 (error in cn), 221619-66-5 (fumarate) 【 分 子 式 】C37H36N4O3 【 分 子 量 】584.72447 |
【开发单位】Janssen (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
Condensation of 4-hydroxyphenylethanol (I) with 2-(chloromethyl)quinoline (II) in ethanolic KOH provided ether (III). The free hydroxyl group of (III) was then converted to the corresponding mesylate (IV) by treatment with methanesulfonyl chloride and Et3N. Alkylation of 11-(4-piperidinylidene)-6,11-dihydro-5H-imidazo[2,1-b][3]benzazepine-3-methanol (V) with mesylate (IV) in the presence of NaHCO3 gave adduct (VI). The primary alcohol of (VI) was oxidized to aldehyde (VII) using MnO2 in CH2Cl2. Finally, aldehyde (VII) was further oxidized to the title methyl ester by means of MnO2 in the presence of sodium cyanate in HOAc-MeOH.
| 【1】 Janssens, F.E.; Leenaerts, J.E.; Sommen, F.M.; Surleraux, D.L.N.G. (Janssen Pharmaceutica NV); Fused imidazole derivs. as multidrug resistance modulators. EP 0888352; JP 2000505477; US 6218381; WO 9734897 . |
| 【2】 Snoeck, H.J.M. (Janssen Pharmaceutica NV); Fused imidazole derivs. for improving oral bioavailability of pharmaceutical agents. WO 9913871 . |
| 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) | 47355 | 4-(2-hydroxyethyl)phenol | 501-94-0 | C8H10O2 | 详情 | 详情 |
| (II) | 13162 | 2-(Chloromethyl)quinoline; alpha-Chloroquinaldine | 4377-41-7 | C10H8ClN | 详情 | 详情 |
| (III) | 47356 | 2-[4-(2-quinolinylmethoxy)phenyl]-1-ethanol | C18H17NO2 | 详情 | 详情 | |
| (IV) | 47357 | 4-(2-quinolinylmethoxy)phenethyl methanesulfonate | C19H19NO4S | 详情 | 详情 | |
| (V) | 47358 | [11-(4-piperidinylidene)-6,11-dihydro-5H-imidazo[2,1-b][3]benzazepin-3-yl]methanol | C18H21N3O | 详情 | 详情 | |
| (VI) | 47359 | (11-[1-[4-(2-quinolinylmethoxy)phenethyl]-4-piperidinylidene]-6,11-dihydro-5H-imidazo[2,1-b][3]benzazepin-3-yl)methanol | C36H36N4O2 | 详情 | 详情 | |
| (VII) | 47360 | 11-[1-[4-(2-quinolinylmethoxy)phenethyl]-4-piperidinylidene]-6,11-dihydro-5H-imidazo[2,1-b][3]benzazepine-3-carbaldehyde | C36H34N4O2 | 详情 | 详情 |