5-氨基羰基-10,11-二氢-5H-二苯并(a,d)环庚烯-5,10-亚胺 | 124070-15-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 二苯并环庚烯
• 中文名称: 5-氨基羰基-10,11-二氢-5H-二苯并(a,d)环庚烯-5,10-亚胺
• 英文名称: ADCI
• 英文别名: 5-aminocarbonyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine；(+/-)-5-(aminocarbonyl)-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine；16-azatetracyclo[7.6.1.02,7.010,15]hexadeca-2,4,6,10,12,14-hexaene-1-carboxamide
• CAS: 124070-15-1
• 化学式: C₁₆H₁₄N₂O
• 分子量: 250.3
• InChiKey: IFLVGRRVGPXYON-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  55.1
• 氢给体数：
  2
• 氢受体数：
  2

制备方法与用途

ADCI 是一种非竞争性的 NMDA 受体拮抗剂，同时也是一种广谱的抗惊厥药物。

反应信息

• 作为反应物：
  描述：

  5-氨基羰基-10,11-二氢-5H-二苯并(a,d)环庚烯-5,10-亚胺 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 以92%的产率得到(+/-)-5-(aminomethyl)-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine
  参考文献：
  名称：

  Synthesis and structure-activity relationship of C5-substituted analogs of (.+-.)-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5, 10-imine [(.+-.)-desmethyl-MK801]: ligands for the NMDA receptor-coupled phencyclidine binding site

  摘要：

  A series of eight C5-substituted analogues of (+-)-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (1) have been prepared by the directed lithiation-alkylation (and acylation) of its (+-)-N-tert-butylformamidinyl derivative 2 followed by formamidine solvolysis. An additional 10 analogues were prepared by elaboration of the C5-ethyl ester derivative. Analogues possessing large (e.g. propyl and larger) lipophilic substituents displace [3H]-1-(1-thienylcyclohexyl)piperidine [( 3H]TCP) from the high-affinity phencyclidine (PCP) binding site in rat brain homogenates only at high concentrations (Ki greater than 1000 nM); however, the presence of a polar amino functionality (e.g. 2-aminoethyl) offsets this effect (Ki = 20 nM). Thus, the boundary condition for lipophilic substituents larger than ethyl appears to be polar in nature. Interaction of the 11 relatively small (MR less than 14) C5-substituted analogues of 1 with the high-affinity PCP binding site associated with the N-methyl-D-aspartate (NMDA) receptor is best described by the equation log (1/Ki) = -5.83F + 0.64 pi + 7.41 (r = 0.90).

  DOI：

  10.1021/jm00165a029
• 作为产物：
  描述：

  (+/-)-N-<(tert-butylimino)methyl>-10,11-dihydro-5H-dibenzocyclohepten-5,10-imine 在 六甲基磷酰三胺 、 硫酸 、 氰化钠 、 氨 、 仲丁基锂 作用下， 以 甲醇 、 乙醇 为溶剂， 反应 52.5h， 生成 5-氨基羰基-10,11-二氢-5H-二苯并(a,d)环庚烯-5,10-亚胺
  参考文献：
  名称：

  Synthesis and structure-activity relationship of C5-substituted analogs of (.+-.)-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5, 10-imine [(.+-.)-desmethyl-MK801]: ligands for the NMDA receptor-coupled phencyclidine binding site

  摘要：

  A series of eight C5-substituted analogues of (+-)-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (1) have been prepared by the directed lithiation-alkylation (and acylation) of its (+-)-N-tert-butylformamidinyl derivative 2 followed by formamidine solvolysis. An additional 10 analogues were prepared by elaboration of the C5-ethyl ester derivative. Analogues possessing large (e.g. propyl and larger) lipophilic substituents displace [3H]-1-(1-thienylcyclohexyl)piperidine [( 3H]TCP) from the high-affinity phencyclidine (PCP) binding site in rat brain homogenates only at high concentrations (Ki greater than 1000 nM); however, the presence of a polar amino functionality (e.g. 2-aminoethyl) offsets this effect (Ki = 20 nM). Thus, the boundary condition for lipophilic substituents larger than ethyl appears to be polar in nature. Interaction of the 11 relatively small (MR less than 14) C5-substituted analogues of 1 with the high-affinity PCP binding site associated with the N-methyl-D-aspartate (NMDA) receptor is best described by the equation log (1/Ki) = -5.83F + 0.64 pi + 7.41 (r = 0.90).

  DOI：

  10.1021/jm00165a029

文献信息

• TREATMENTS FOR ALZHEIMER'S RELATED DISEASES AND DISORDERS
  申请人：Alkermes, Inc.

  公开号：US20160243112A1

  公开（公告）日：2016-08-25

  The invention relates to a method for the treatment of neuropsychiatric behavioral symptoms in patients with Alzheimer's Disease wherein the symptoms are selected from the group consisting of anxiety, agitation, aggression, depression, hallucination, memory loss, confusion, repetition, sleep issues, sun downing, suspicion, delusions, and wandering, comprising the step of administering to the patient an effective amount of a compound of Formula I, IA, IB, Table 1, preferably Compound-1, or a pharmaceutically acceptable salt thereof.

  本发明涉及一种用于治疗阿尔茨海默病患者的神经精神行为症状的方法，其中所述症状选自焦虑、激动、攻击性、抑郁、幻觉、记忆丧失、混乱、重复、睡眠问题、日落综合征、怀疑、妄想和漫游的组，包括向患者施用有效量的公式I、IA、IB、表1中的化合物，优选化合物-1或其药用可接受的盐。
• Compounds for the Treatment of Neurological Disorders
  申请人：Kamalesh Babu Ruppa Poornachary

  公开号：US20120302543A1

  公开（公告）日：2012-11-29

  Provided are compounds, pharmaceutical compositions and methods of treatment or prophylaxis of certain neurologic disorders, including disorders related to NMDA receptor activation, neuropsychiatric disorders, neurodegenerative disorders and other neurologic diseases, disorders and related conditions. The compounds are of the Formulas I and Ia-Ij as described herein.

  本发明提供了化合物、制药组合物及其治疗或预防某些神经系统疾病的方法，包括与NMDA受体激活相关的疾病、神经精神障碍、神经退行性疾病和其他神经系统疾病、障碍和相关病况。所述化合物为本文中所述的I和Ia-Ij式。
• New use of glutamate antagonists for the treatment of cancer
  申请人：Ikonomidou, Hrissanthi

  公开号：EP1002535A1

  公开（公告）日：2000-05-24

  New therapies can be devised based upon a demonstration of the role of glutamate in the pathogenesis of cancer. Inhibitors of the interaction of glutamate with the AMPA, kainate, or NMDA receptor complexes are likely to be useful in treating cancer and can be formulated as pharmaceutical compositions. They can be identified by appropriate screens.

  根据谷氨酸在癌症发病机制中的作用，可以设计出新的疗法。谷氨酸与 AMPA、kainate 或 NMDA 受体复合物相互作用的抑制剂可能有助于治疗癌症，并可配制成药物组合物。它们可以通过适当的筛选来确定。
• Method of treating lower urinary tract disorders
  申请人：Dynogen Pharmaceuticals, Inc.

  公开号：EP1795196A2

  公开（公告）日：2007-06-13

  The invention relates to the treatment of at least one symptom of a lower urinary tract disorder in a subject in need of treatment wherein the symptom is selected from the group consisting of urinary frequency, urinary urgency, urinary urge incontinence, nocturia and enuresis, and wherein to a subject in need of treatment a therapeutically effective amount of a compound that has 5-HT3 receptor antagonist activity and NorAdrenaline Reuptake Inhibitor (NARI) activity is to be administered. The invention further relates to the treatment of at least one symptom of a lower urinary tract disorder in a subject in need of treatment wherein the symptom is selected from the group consisting of urinary frequency, urinary urgency, urinary urge incontinence, nocturia and enuresis, comprising coadministering to said subject a first amount of a 5HT3 antagonist and a second amount of a NARI, wherein the first and second amounts together comprise a therapeutically effective amount or are each present in a therapeutically effective amount.

  本发明涉及需要治疗的受试者至少一种下尿路疾病症状的治疗，其中该症状选自由尿频、尿急、尿失禁、夜尿和遗尿组成的组，并且对需要治疗的受试者施用治疗有效量的具有5-HT3受体拮抗剂活性和去甲肾上腺素再摄取抑制剂（NARI）活性的化合物。本发明进一步涉及对需要治疗的受试者的至少一种下尿路疾病症状的治疗，其中该症状选自由尿频、尿急、尿失禁、夜尿和遗尿组成的组，包括向所述受试者联合施用第一量的5-HT3受体拮抗剂和第二量的NARI，其中第一量和第二量共同组成治疗有效量或各自以治疗有效量存在。
• Conjugates of glutamate and NMDA receptor channel blockers without excito-toxic effects
  申请人：Tschollar,, Werner

  公开号：EP1903028A1

  公开（公告）日：2008-03-26

  Methods for delivering therapeutic amounts of glutamate to the CNS while simultaneously protecting against its excito-toxic effects are provided. By administering a blood-brain barrier-permeable Conjugate Compound, which comprises glutamate linked to an N-methyl-D-aspartate receptor antagonist, glutamate is released within the CNS for beneficial effect without causing excito-toxicity. Examples of such Conjugate Compounds are provided and their cognition-enhancing effect without engendering excito-toxicity in both normal and cognition-impaired animals is demonstrated.

  本研究提供了向中枢神经系统输送治疗量谷氨酸的方法，同时防止其兴奋毒性效应。通过施用可透过血脑屏障的共轭化合物（其中包括与 N-甲基-D-天冬氨酸受体拮抗剂相连的谷氨酸），谷氨酸可在中枢神经系统内释放，从而产生有益效果，同时不会导致兴奋毒性。本文提供了此类共轭化合物的实例，并证明了它们在正常动物和认知障碍动物中的认知增强效果，而不会产生兴奋毒性。