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【结 构 式】 
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【药物名称】AP-2238 【化学名称】3-[4-(N-Benzyl-N-methylaminomethyl)phenyl]-6,7-dimethoxy-2H-1-benzopyran-2-one 【CA登记号】553681-56-4 【 分 子 式 】C26H25NO4 【 分 子 量 】415.49345 |
【开发单位】Università degli Studi di Bologna (Originator) 【药理作用】Alzheimer's Dementia, Treatment of , Cognition Disorders, Treatment of, NEUROLOGIC DRUGS, Acetylcholinesterase Inhibitors, Antiamyloidogenic Agents |
合成路线1
Partial demethylation of 2,4,5-trimethoxybenzaldehyde (I) with BCl3 gives 2-hydroxy-4,5-dimethoxybenzaldehyde (II), which is condensed with the sodium salt of p-tolylacetic acid (III) in boiling acetic anhydride to afford the coumarin derivative (IV). Benzylic halogenation of (IV) with N-bromosuccinimide in the presence of a catalytic amount of benzoyl peroxide yields bromide (V), which is finally condensed with N-methyl benzylamine (VI) to afford the desired compound.
| 【1】 Piazzi, L.; Rampa, A.; Bisi, A.; Gobbi, S.; Belluti, F.; Cavalli, A.; Bartolini, M..; Andrisano, V.; Valenti, P.; Recanatini, M.; 3-(4-{[Benzyl(methyl)amino]methyl}phenyl)-6,7-dimethoxy-2H-2-chromenone (AP2238) inhibits both acetylcholinesterase and acetylcholinesterase-induced beta-amyloid aggregation: A dual function lead for Alzheimer's disease therapy. J Med Chem 2003, 46, 12, 2279. |
| 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) | 64839 | 2,4,5-trimethoxybenzaldehyde | C10H12O4 | 详情 | 详情 | |
| (II) | 64840 | 2-hydroxy-4,5-dimethoxybenzaldehyde | C9H10O4 | 详情 | 详情 | |
| (III) | 64841 | sodium 2-(4-methylphenyl)acetate | C9H9NaO2 | 详情 | 详情 | |
| (IV) | 64842 | 6,7-dimethoxy-3-(4-methylphenyl)-2H-chromen-2-one | C18H16O4 | 详情 | 详情 | |
| (V) | 64843 | 3-[4-(bromomethyl)phenyl]-6,7-dimethoxy-2H-chromen-2-one | C18H15BrO4 | 详情 | 详情 | |
| (VI) | 11969 | N-Methyl(phenyl)methanamine; N-Benzyl-N-methylamine; N-Methylbenzylamine | 103-67-3 | C8H11N | 详情 | 详情 |