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【结 构 式】 
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【药物名称】 【化学名称】12-Amino-9-methyl-6,7,10,11-tetrahydro-7(S),11(S)-methanocycloocta[b]quinoline 【CA登记号】189500-02-5, 189500-04-7 (as hydrochloride), 189500-03-6 (enantiomer), 189499-35-2 (racemate), 189499-36-3 (racemic; HCl) 【 分 子 式 】C17H18N2 【 分 子 量 】250.34641 |
【开发单位】Medichem (Originator) 【药理作用】Cognition Disorders, Treatment of, NEUROLOGIC DRUGS, Acetylcholinesterase Inhibitors |
合成路线1
Condensation of diketone (I) with the organocerium reagent derived from methylmagnesium bromide and CeCl3 afforded the oxaadamantanol (II), which was further converted to mesylate (III) upon reaction with methanesulfonyl chloride and Et3N. Subsequent fragmentation of (III) by treatment with silica gel in CH2Cl2 produced bicyclic enone (IV). This was condensed with 2-aminobenzonitrile (V) in the presence of AlCl3 in refluxing 1,2-dichloroethane to furnish the target tetracyclic derivative. Resolution was then achieved by chiral MPLC.
| 【1】 Awasthi, S.; Singhal, S.S.; Tetrahedron Asymmetry 1998, 9, 5, 835-849. |
| 【2】 Tetrahedron 1996, 51, 16, 5867-80. |
| 【3】 Muñoz-Torrero, D.; Gorbig, D.M.; Simon, M.; Contreras, J.; Camps, P.; Vivas, N.M.; Badia, A.; Banos, J.E.; Synthesis and evaluation of tacrine-huperzine A hybrids as acetylcholinesterase inhibitors of potential interest for the treatment of Alzheimer's disease. Bioorg Med Chem 1998, 6, 4, 427-440. |
| 【4】 El Achad, R.; Görbig, D.M.; Camps, P.; et al.; Synthesis, in vitro pharmacology, and molecular modeling of very potent tacrine - Huperzine A hybrids as acetylcholinesterase inhibitors of potential interest for the treatment of Alzheimer's disease. J Med Chem 1999, 42, 17, 3227. |
| 【5】 Contreras Lascorz, J.; El Achab, R.; Camps Garcia, P.; Baños Diez, J.E.; Muñoz-Torrero Lopez-Ibarra, D.; Badia Sancho, A.; Morral Cardoner, J.; Simon Fornell, M.; Görbig Romeu, M.; Vivas, N.M. (Medichem SA); Polycyclic aminopyridine cpds. which are acetylcholinesterase inhibitors, process for preparing them and their use. EP 0796849; ES 2100129; US 5965569; WO 9713754 . |
| 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) | 37697 | bicyclo[3.3.1]nonane-3,7-dione | C9H12O2 | 详情 | 详情 | |
| (II) | 37698 | 3-ethyl-2-oxatricyclo[3.3.1.1(3,7)]decan-1-ol | C11H18O2 | 详情 | 详情 | |
| (III) | 37699 | 3-ethyl-2-oxatricyclo[3.3.1.1(3,7)]dec-1-yl methanesulfonate | C12H20O4S | 详情 | 详情 | |
| (IV) | 37700 | 7-ethylbicyclo[3.3.1]non-6-en-3-one | C11H16O | 详情 | 详情 | |
| (V) | 19493 | 2-aminobenzonitrile | 1885-29-6 | C7H6N2 | 详情 | 详情 |