ethyl 8-methyl-5,6-dihydro-6-oxo-4H-imidazo<1,5-a>benzodiazepine-3-carboxylate | 147005-26-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯二氮卓类
• 英文名称: ethyl 8-methyl-5,6-dihydro-6-oxo-4H-imidazo<1,5-a>benzodiazepine-3-carboxylate
• 英文别名: 8-Methyl-6-oxo-5,6-dihydro-4H-2,5,10b-triaza-benzo[e]azulene-3-carboxylic acid ethyl ester；ethyl 5,6-dihydro-8-methyl-6-oxo-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate；Ethyl 8-methyl-6-oxo-4,5-dihydroimidazo[1,5-a][1,4]benzodiazepine-3-carboxylate
• CAS: 147005-26-3
• 化学式: C₁₅H₁₅N₃O₃
• 分子量: 285.302
• InChiKey: VMCLHHXSXIJYAP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  73.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 8-methyl-5,6-dihydro-6-oxo-4H-imidazo<1,5-a>benzodiazepine-3-carboxylate 在 劳森试剂 、 吡啶 、 ammonium hydroxide 、 sodium hydroxide 、 溶剂黄146 、 N,N'-羰基二咪唑 作用下， 以 乙醇 为溶剂， 反应 205.0h， 生成
  参考文献：
  名称：

  New Tetracyclic Derivatives of Imidazo[1,5-a][1,4]benzodiazepines and of Imidazo[1,5-a]-thieno[3,2-f][1,4]-diazepines

  摘要：

  The synthesis of new tetracyclic 1,4-diazepine derivatives is described. In these compounds, an additional five-membered heterocycle is fused on the known tricyclic ring systems imidazo[1,5-a][1,4]benzodiazepine and imidazo[1,5-a]thieno[3,2-f][1,4]diazepine. Many of these new compounds display a very high affinity to the benzodiazepine receptor in mammals.

  DOI：

  10.3987/com-94-s(b)61
• 作为产物：
  描述：

  8-氟-5,6-二氢-6-氧代-4H-咪唑并[1,5-a][1,4]苯并二氮杂卓-3-羧酸乙酯 在 劳森试剂 、 吡啶 、 一水合肼 作用下， 以 四氢呋喃 为溶剂， 反应 140.0h， 生成 ethyl 8-methyl-5,6-dihydro-6-oxo-4H-imidazo<1,5-a>benzodiazepine-3-carboxylate
  参考文献：
  名称：

  New Tetracyclic Derivatives of Imidazo[1,5-a][1,4]benzodiazepines and of Imidazo[1,5-a]-thieno[3,2-f][1,4]-diazepines

  摘要：

  The synthesis of new tetracyclic 1,4-diazepine derivatives is described. In these compounds, an additional five-membered heterocycle is fused on the known tricyclic ring systems imidazo[1,5-a][1,4]benzodiazepine and imidazo[1,5-a]thieno[3,2-f][1,4]diazepine. Many of these new compounds display a very high affinity to the benzodiazepine receptor in mammals.

  DOI：

  10.3987/com-94-s(b)61

文献信息

• Imidazodiazepine derivatives
  申请人：Hoffmann-La Roche Inc.

  公开号：US05387585A1

  公开（公告）日：1995-02-07

  The novel imidazodiazepine derivatives of the formula: ##STR1## wherein the substituents are as described in the specification, can be used for the control or prevention of epileptic seizures, anxiety, tension and excitation states, sleep disorders, schizophrenic symptoms, hepatic encephalopathy and senile dementia, as well as, in the partial or complete antagonization of undesired side-effects of substances acting on benzodiazepine receptors after over-dosage or after their use in intensive medicine and in anesthesia.

  翻译结果如下： 所述的咪唑二氮䓬衍生物的公式为：##STR1##，其中取代基如说明书中所述，可用于控制或预防癫痫发作、焦虑、紧张和兴奋状态、睡眠障碍、精神分裂症症状、肝性脑病和老年痴呆症，以及部分或完全拮抗在过量使用或在其在重症医学和麻醉中使用后作用于苯二氮䓬受体的物质的副作用。
• BENZODIAZEPINE DERIVATIVES, COMPOSITIONS, AND METHODS FOR TREATING COGNITIVE IMPAIRMENT
  申请人：AgeneBio, Inc.

  公开号：US20180170941A1

  公开（公告）日：2018-06-21

  This invention relates to benzodiazepine derivatives, compositions comprising therapeutically effective amounts of those benzodiazepine derivatives and methods of using those derivatives or compositions in treating cognitive impairment associated with central nervous system (CNS) disorders. In particular, it relates to the use of a α5-containing GABA A receptor agonist (e.g., a α5-containing GABA A receptor positive allosteric modulator) as described herein in treating cognitive impairment associated with central nervous system (CNS) disorders in a subject in need or at risk thereof, including, without limitation, subjects having or at risk for age-related cognitive impairment, Mild Cognitive Impairment (MCI), amnestic MCI (aMCI), Age-Associated Memory Impairment (AAMI), Age Related Cognitive Decline (ARCD), dementia, Alzheimer's Disease(AD), prodromal AD, post traumatic stress disorder (PTSD), schizophrenia, bipolar disorder, amyotrophic lateral sclerosis (ALS), cancer-therapy-related cognitive impairment, mental retardation, Parkinson's disease (PD), autism spectrum disorders, fragile X disorder, Rett syndrome, compulsive behavior, and substance addiction. It also relates to the use of a α5-containing GABA A receptor agonist (e.g., a α5-containing GABA A receptor positive allosteric modulator) as described herein in treating brain cancers (including brain tumors, e.g., medulloblastomas), and cognitive impairment associated therewith.

  这项发明涉及苯二氮卓啉衍生物，包括含有这些苯二氮卓啉衍生物的治疗有效量的组合物，以及使用这些衍生物或组合物治疗与中枢神经系统（CNS）疾病相关的认知障碍的方法。具体而言，它涉及在需要或有风险的受试者中治疗与中枢神经系统（CNS）疾病相关的认知障碍，包括但不限于患有或有风险患有与年龄相关的认知障碍、轻度认知障碍（MCI）、遗忘性MCI（aMCI）、年龄相关记忆障碍（AAMI）、年龄相关认知衰退（ARCD）、痴呆症、阿尔茨海默病（AD）、前驱期AD、创伤后应激障碍（PTSD）、精神分裂症、躁郁症、肌萎缩侧索硬化（ALS）、癌症治疗相关认知障碍、智力障碍、帕金森病（PD）、自闭症谱系障碍、脆性X综合症、瑞特综合症、强迫行为和物质成瘾。它还涉及在治疗与之相关的脑癌（包括脑肿瘤，例如髓母细胞瘤）和认知障碍的情况下，如本文所述使用α5含有的GABAA受体激动剂（例如，α5含有的GABAA受体正向变构调节剂）。
• Discovery of the imidazo[1,5-a][1,2,4]-triazolo[1,5-d][1,4]benzodiazepine scaffold as a novel, potent and selective GABAA α5 inverse agonist series
  作者：Guido Achermann、Theresa M. Ballard、Francesca Blasco、Pierre-Emmanuel Broutin、Bernd Büttelmann、Holger Fischer、Martin Graf、Maria-Clemencia Hernandez、Peter Hilty、Frédéric Knoflach、Andreas Koblet、Henner Knust、Anke Kurt、James R. Martin、Raffaello Masciadri、Richard H.P. Porter、Heinz Stadler、Andrew W. Thomas、Gerhard Trube、Jürgen Wichmann

  DOI：10.1016/j.bmcl.2009.07.153

  日期：2009.10

  Through iterative design cycles we have discovered a number of novel new classes where the imidazo[1,5-a][1,2,4]-triazolo[1,5-d][1,4]benzodiazepine was deemed the most promising GABAA α5 inverse agonist class with potential for cognitive enhancement. This class combines a modest subtype binding selectivity with inverse agonism and has the most favourable molecular properties for further lead optimisation

  通过迭代设计周期，我们发现了许多新颖的新类，其中咪唑并[1,5- a ] [1,2,4]-三唑并[1,5- d ] [1,4]苯并二氮杂被认为是最有前途的GABA一个α5反相激动剂类的认知提高的潜力。此类具有适度的亚型结合选择性和反向激动作用，并具有最有利的分子特性，可进一步优化针对中枢神经系统（CNS）的药物。
• Substituted imidazo [1,5-a] [1,2,4] triazolo [4,3-d] [1,4] benzodiazepine derivatives
  申请人：——

  公开号：US20020103371A1

  公开（公告）日：2002-08-01

  The present invention is a compound of formula 1 The compound and derivatives or pharmaceutically acceptable salts thereof of the invention have a good affinity and selectivity to the GABA A &agr;5 receptor and are useful for the treatment of diseases related to this receptor.

  本发明是一种化合物，化学式为1。该发明的化合物及其衍生物或药学上可接受的盐具有良好的亲和力和选择性，对GABA A &agr;5受体具有作用，并可用于治疗与该受体相关的疾病。
• BENZODIAZEPINE DERIVATIVES AS GABA A RECEPTOR MODULATORS
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP1337535A2

  公开（公告）日：2003-08-27