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【结 构 式】 
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【药物名称】 【化学名称】[6-Methoxy-2-(4-methoxyphenyl)benzo[b]thien-3-yl](3,4,5-trimethoxyphenyl)methanone 【CA登记号】 【 分 子 式 】C26H24O6S 【 分 子 量 】464.54158 |
【开发单位】Lilly (Originator), Baylor University (Codevelopment), National Cancer Institute (Codevelopment) 【药理作用】Antiallergy/Antiasthmatic Drugs, Asthma Therapy, RESPIRATORY DRUGS, Antimitotic Drugs, Lipoxygenase Inhibitors, Microtubule-Stabilizing Agents, Thromboxane Synthase Inhibitors |
合成路线1
Alkylation of 3-methoxybenzenethiol (I) with 4'-methoxyphenacyl bromide (II) afforded sulfide (III). Cyclization of (III) with concomitant rearrangement in the presence of polyphosphoric acid produced a mixture of regioisomers (IV) and (V) that were separated by their different solubility in acetone. Then, Friedel-Crafts acylation of the desired insoluble isomer (IV) with 3,4,5-trimethoxybenzoyl chloride (VI) in the presence of AlCl3 provided the title ketone, which was separated from some demethylated byproduct by means of silica gel chromatography.
| 【1】 Lee, B.; et al.; Hepatocyte gene therapy in a large animal: A neonatal bovine model of citrullinemia. Proc Natl Acad Sci USA 1999, 96, 7, 3981. |
| 【2】 Jones, C.D.; et al.; Antiestrogens. 2. Structure-activity studies in a series of 3-aroyl-2-arylbenzo[b]thiophene derivatives leading to [6-hydroxy-2-(4-hydroxyphenyl)benzo[b]thien-3-yl] [4-[2-(1-piperidinyl)ethoxy]-phenyl]methanone hydrochloride (LY156758), a remarkably effec. J Med Chem 1984, 27, 8, 1057. |
| 【3】 Carlson, D.G.; Cullinan, G.J.; Fahey, K.J.; Jackson, W.T.; Roehm, N.W.; Spaethe, S.M. (Eli Lilly and Company); Novel benzothiophene cpds. and methods. EP 0732331; JP 1999501932; WO 9628156 . |
| 【4】 Pinney, K.G. (Baylor University); Anti-mitotic agents which inhibit tubulin polymerization. US 5886025 . |
| 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) | 25756 | 3-methoxybenzenethiol | 15570-12-4 | C7H8OS | 详情 | 详情 |
| (II) | 21991 | 2-Methoxyphenacyl bromide; 2-bromo-1-(4-methoxyphenyl)-1-ethanone | 2632-13-5 | C9H9BrO2 | 详情 | 详情 |
| (III) | 25757 | 1-(4-methoxyphenyl)-2-[(3-methoxyphenyl)sulfanyl]-1-ethanone | C16H16O3S | 详情 | 详情 | |
| (IV) | 10121 | 4-(6-Methoxy-1-benzothiophen-2-yl)phenyl methyl ether; 6-Methoxy-2-(4-methoxyphenyl)-1-benzothiophene | 63675-74-1 | C16H14O2S | 详情 | 详情 |
| (V) | 25758 | 4-(4-methoxy-1-benzothiophen-2-yl)phenyl methyl ether | C16H14O2S | 详情 | 详情 | |
| (VI) | 13571 | 3,4,5Ttrimethoxybenzoyl chloride | 4521-61-3 | C10H11ClO4 | 详情 | 详情 |