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【结 构 式】 
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【药物名称】 【化学名称】4-[5-(5,5,8,8-Tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)isoxazol-3-yl]benzoic acid 【CA登记号】 【 分 子 式 】C24H25NO3 【 分 子 量 】375.47175 |
【开发单位】Università degli Studi di Bologna (Originator), Università degli Studi di Palermo (Originator), Università di Ferrara (Originator), University of Oklahoma Health Sci. Cent. (Originator) 【药理作用】ONCOLYTIC DRUGS, Apoptosis Inducers, Drugs Acting on Retinoid Receptors |
合成路线1
Wittig reaction of aldehyde (I) with methylene triphenylphosphorane produced olefin (II). Oxime (IV) was prepared from methyl 4-formylbenzoate (III) by treatment with hydroxylamine. The nitrile oxide generated from imine (IV) by chlorination, followed by elimination under basic conditions, underwent a [3+2] regioselective cycloaddition with alkene (II) to produce isoxazoline (V). Oxidation of the isoxazoline ring of (V) to the corresponding isoxazole derivative (VI) was accomplished by treatment with N-bromosuccinimide. Finally, ester hydrolysis with LiOH furnished the title carboxylic acid.
| 【1】 Simoni, D.; et al.; Heterocycle-containing retinoids. Discovery of a novel isoxazole arotinoid possessing potent apoptotic activity in multidrug and drug-induced apoptosis-resistant cells. J Med Chem 2001, 44, 14, 2308. |
| 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) | 50713 | 5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthalenecarbaldehyde | C15H20O | 详情 | 详情 | |
| (II) | 50714 | 1,1,4,4-tetramethyl-6-vinyl-1,2,3,4-tetrahydronaphthalene | C16H22 | 详情 | 详情 | |
| (III) | 10170 | methyl 4-formylbenzoate | 1571-08-0 | C9H8O3 | 详情 | 详情 |
| (IV) | 19219 | methyl 4-[(hydroxyimino)methyl]benzoate | C9H9NO3 | 详情 | 详情 | |
| (V) | 50715 | methyl 4-[5-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthalenyl)-4,5-dihydro-3-isoxazolyl]benzoate | C25H29NO3 | 详情 | 详情 | |
| (VI) | 50716 | methyl 4-[5-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthalenyl)-3-isoxazolyl]benzoate | C25H27NO3 | 详情 | 详情 |