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【结 构 式】 
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【药物名称】Neramexane hydrochloride, MRZ-2/279, MRZ-2/579 【化学名称】1,3,3,5,5-Pentamethylcyclohexylamine hydrochloride 【CA登记号】209185-99-9 【 分 子 式 】C11H24ClN 【 分 子 量 】205.77363 |
【开发单位】Merz (Originator), Forest (Licensee) 【药理作用】Alzheimer's Dementia, Treatment of , Antiparkinsonian Drugs, Cerebrovascular Diseases, Treatment of, Cognition Disorders, Treatment of, Extrapyramidal Disorders, Treatment of, NEUROLOGIC DRUGS, Stroke, Treatment of, Treatment of Alcohol Dependency, TREATMENT OF POISONING, DRUG ABUSE & DEPENDENCY, Treatment of Substance Dependency, NMDA Antagonists |
合成路线1
Addition of methylmagnesium iodide to 3,3,5,5-tetramethylcyclohexanone (I) produced the tertiary alcohol (II). Subsequent treatment of alcohol (II) with hydrazoic acid in the presence of TiCl4 gave azide (III). This was then reduced with LiAlH4 to the corresponding amine, which was isolated as the hydrochloride salt.
| 【1】 Jirgensons, A.; et al.; Synthesis and structure-affinity relationships of 1,3,5-alkylsubstituted cyclohexylamines binding at NMDA receptor PCP site. Eur J Med Chem 2000, 35, 6, 555. |
| 【2】 Kalvinsh, I.; Gold, M.; Parsons, C.G.R.; Jirgensons, A.; Klauss, V. (Merz Pharmaceuticals GmbH); 1-Amino-alkylcyclohexane NMDA receptor antagonists. JP 2002511873; WO 9901416 . |
合成路线2
In an alternative method, the Ritter reaction of alcohol (II) with chloroacetonitrile in the presence of H2SO4 yielded the chloroacetamide (IV). This was then hydrolyzed to the desired amine by treatment with thiourea in HOAc-EtOH.
| 【1】 Jirgensons, A.; et al.; A practical synthesis of tert-alkylamines via the Ritter reaction with chloroacetonitrile. Synthesis (Stuttgart) 2000, 12, 1709. |