(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate

• 分子结构分类: 有机化合物 - 苯类化合物 - 二苯并环庚烯
• 英文名称: (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate
• 英文别名: (+/-)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate；5-methyl-10,11-di-hydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate；5-methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5,10-imine maleate；5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate；(+)-MK-801 hydrogen maleate；MK-801 hydrogen maleate；(+)-10,11-Dihydro-5-methyl-5H-dibenzo(a,d)cyclohepten-5,10-diyldiammonium maleate；(Z)-but-2-enedioic acid;1-methyl-16-azatetracyclo[7.6.1.02,7.010,15]hexadeca-2,4,6,10,12,14-hexaene
• 化学式: C₄H₄O₄*C₁₆H₁₅N
• 分子量: 337.375
• InChiKey: QLTXKCWMEZIHBJ-BTJKTKAUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.86
• 重原子数：
  25
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  86.6
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  5-二苯并环庚烯酮 在 N-溴代丁二酰亚胺(NBS) 、 palladium 10% on activated carbon 、 三氟化硼乙醚 、 氢气 、 magnesium 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 40.0h， 生成 (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate
  参考文献：
  名称：

  二唑西平的合成

  摘要：

  描述了一种简单的五步合成路线，以总产率的28％从二苯并顺丁烯二酮（2）开始，向二唑西平（1）合成。简便的路线是通过在回流中在MeCN中用NBS和氯胺-T进行二苯并双氢肾上腺素（2）的叠氮反应，氮杂环丁酮的氢解，氨基酮的格利雅甲基化，BF 3 ·OEt 2促进的氨基醇环化以及用Mg和Et 3 N的MeOH溶液。蒽骨架9也通过频哪醇到匹那康的分子内重排而合成。

  DOI：

  10.1016/j.tet.2012.03.007

文献信息

• Novel treatment for alzheimer's disease
  申请人：EPFL Ecole Polytechnique Fédérale de Lausanne

  公开号：EP2111858A1

  公开（公告）日：2009-10-28

  The present invention concerns a new pharmaceutical composition comprising an antagonist and a co-agonist of the N-methyl-D-aspartate-type glutamate receptor (NMDAR). The inventors found that the co-administration of these two compounds effectively inhibits production of amyloide-β peptide. In patient's suffering from Alzheimer's disease, these peptides are deposited in the extracellular matrix forming neuritic "plaques". Therefore, the present inventors identified a new possibility for prophylaxis and/or treatment of Alzheimer's disease by stopping the continued formation of neuropathological extracellular deposits.

  本发明涉及一种新的药物组合物，包括N-甲基-D-天门冬氨酸型谷氨酸受体（NMDAR）的拮抗剂和共激动剂。发明人发现这两种化合物的联合使用有效地抑制了淀粉样β肽的产生。在患有阿尔茨海默病的患者中，这些肽沉积在细胞外基质中形成神经突起“斑块”。因此，本发明人发现了一种新的预防和/或治疗阿尔茨海默病的可能性，即通过阻止神经病理性细胞外沉积物的持续形成。
• Histogranin peptide and their analgesic use
  申请人：——

  公开号：US20040006013A1

  公开（公告）日：2004-01-08

  The invention relates to linear and cyclic peptide and pseudopeptide compounds useful as analgesics, pharmaceutical compositions comprising such compounds, the use of the compounds and the compositions in the treatment of pain, and commercial packages containing such compounds and compositions.

  本发明涉及线性和环状肽和伪肽化合物，这些化合物可作为镇痛剂使用，包括这些化合物的制药组合物，以及这些化合物和组合物在治疗疼痛方面的应用，以及包含这些化合物和组合物的商业包装。
• Screen for glutamate reuptake inhibitors, stimulators, and modulators
  申请人：——

  公开号：US20020115688A1

  公开（公告）日：2002-08-22

  Disclosed is a method for identifying compounds that bind to or modulate a glutamate transporter. The disclosed method is useful for identifying compounds that can inhibit, stimulate, or modulate the activity of the glutamate transporter and thus affect glutamate reuptake. The method is a screening technique where compounds known to bind to glutamate receptors (for example, glutamate receptor ligands, including many agonists, and antagonists) are bound to a glutamate transporter and compounds are screened to identify those that can alter the binding of the glutamate receptor-binding compounds. Compounds shown to alter the binding of the receptor compounds from glutamate transporters in the disclosed assay can have a variety of effects on glutamate transporter activity including activation or inhibition. These compounds are expected to affect or interfere with glutamate reuptake by the glutamate transporter and thus can be used to modulate, stimulate, or inhibit glutamate reuptake. Such compounds are useful to treat various neurological diseases and conditions involving glutamate transporter and glutamate receptor activation. One of the compounds is (2S,4R)-4-methylglutamate or [ 3 H]-(2S,4R)-4-methylglutamate. For example, excess extracellular glutamate is a cause of excessive activation of glutamate receptors. Stimulating glutamate reuptake by glutamate transporters can ameliorate excessive activation of glutamate receptors by reducing the extracellular glutamate concentration. Prodrug forms of transporter compounds are preferred for use as drugs.

  本文揭示了一种识别结合或调节谷氨酸转运体的化合物的方法。揭示的方法用于识别可以抑制、刺激或调节谷氨酸转运体活性的化合物，从而影响谷氨酸的再摄取。该方法是一种筛选技术，其中已知与谷氨酸受体结合的化合物（例如，谷氨酸受体配体，包括许多激动剂和拮抗剂）与谷氨酸转运体结合，并筛选化合物以识别可以改变谷氨酸受体结合化合物的结合的化合物。在揭示的测定中，被证明可以改变受体化合物从谷氨酸转运体中结合的化合物可以对谷氨酸转运体活性产生各种效应，包括激活或抑制。这些化合物预计会影响或干扰谷氨酸转运体的谷氨酸再摄取，从而可以用于调节、刺激或抑制谷氨酸再摄取。这些化合物对于治疗涉及谷氨酸转运体和谷氨酸受体激活的各种神经疾病和病症非常有用。其中一种化合物是（2S，4R）-4-甲基谷氨酸或[3H] -（2S，4R）-4-甲基谷氨酸。例如，过多的细胞外谷氨酸是谷氨酸受体过度激活的原因。通过刺激谷氨酸转运体的谷氨酸再摄取，可以通过降低细胞外谷氨酸浓度来缓解谷氨酸受体的过度激活。药物使用时，转运体化合物的前药形式更受欢迎。
• 3, 4-DIHYDRO-2-NAPHTHAMIDE DERIVATIVES AS SELECTIVE DOPAMINE D3 LIGANDS
  申请人：Sokoloff Pierre

  公开号：US20090124630A1

  公开（公告）日：2009-05-14

  The invention relates to 3,4-dihydro-2-naphthamide derivatives of formula (I), pharmaceutical compositions containing them and their therapeutic applications as partial agonists or antagonists of the dopamine D3 receptor for the treatment of neuropsychological disorders.

  本发明涉及式(I)的3,4-二氢-2-萘酰胺衍生物，含有它们的药物组合物以及它们作为多巴胺D3受体的部分激动剂或拮抗剂的治疗应用于神经心理障碍的治疗。
• Process for the preparation of 5-methyl-10,11-dihydro-5H-dibenzo(a,d)-cyclohepten-5,10-imine and its salts
  申请人：Merck & Co., Inc.

  公开号：EP0091071A1

  公开（公告）日：1983-10-12

  (+)-5-Methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclo- hepten-5,10-imine, and its pharmaceutically acceptable salts is useful as an anxiolytic, antidepressant, anticonvulsant, muscle relaxant and in the treatment of mixed anxiety-depression, minimal brain dysfunction and extrapyramidal disorders such as Parkinson's disease. The racemate of the compound is produced by a four-step synthetic process in about 65% yield from 5H-dibenzo[a,d]cyclohepten-5-one.

  (+)-5-甲基-10,11-二氢-5H-二苯并[a,d]-环庚烯-5,10-亚胺及其药学上可接受的盐类可用作抗焦虑剂、抗抑郁剂、抗惊厥剂、肌肉松弛剂，并可用于治疗混合焦虑-抑郁症、最小脑功能障碍和锥体外系疾病，如帕金森病。 该化合物的外消旋体是由 5H-二苯并[a,d]环庚烯-5-酮通过四步合成工艺制得的，收率约为 65%。