4-Ethoxycarbonyl-5,6-dihydro-1,2,3-triazolo[1,5-a]benzo[1,5]diazepin-6(7H)-one | 130137-35-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 三唑并二氮卓类
• 英文名称: 4-Ethoxycarbonyl-5,6-dihydro-1,2,3-triazolo[1,5-a]benzo[1,5]diazepin-6(7H)-one
• 英文别名: Ethyl 5-oxo-4,6-dihydrotriazolo[1,5-a][1,5]benzodiazepine-3-carboxylate
• CAS: 130137-35-8
• 化学式: C₁₃H₁₂N₄O₃
• 分子量: 272.263
• InChiKey: VFVISTHXNAFMRL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  86.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-Ethoxycarbonyl-5,6-dihydro-1,2,3-triazolo[1,5-a]benzo[1,5]diazepin-6(7H)-one 在 锂硼氢 、 氢溴酸 作用下， 以 四氢呋喃 、 溶剂黄146 为溶剂， 反应 60.0h， 生成 3-(Bromomethyl)-4,6-dihydrotriazolo[1,5-a][1,5]benzodiazepin-5-one
  参考文献：
  名称：

  [EN] BENZODIAZEPINE DERIVATIVES, COMPOSITIONS, AND METHODS FOR TREATING COGNITIVE IMPAIRMENT
  [FR] DÉRIVÉS DE BENZODIAZÉPINE, COMPOSITIONS ET PROCÉDÉS DE TRAITEMENT DE LA DÉFICIENCE COGNITIVE

  摘要：

  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、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中所述的α5-含GABAA受体激动剂（例如，α5-含GABAA受体正向变构调节剂）的使用。

  公开号：

  WO2015095783A1
• 作为产物：
  描述：

  1,3-丙酮二羧酸二乙酯 在 palladium on activated charcoal 、 对甲苯磺酸 乙醇 、 氢气 、 sodium 作用下， 以 乙醇 、 xylene 为溶剂， 反应 15.0h， 生成 4-Ethoxycarbonyl-5,6-dihydro-1,2,3-triazolo[1,5-a]benzo[1,5]diazepin-6(7H)-one
  参考文献：
  名称：

  1,2,3-Triazolo[1,5-a]quinolines, -[1,7]naphthyridines, and -benzo[1,5]diazepines by the Action of Diethyl 1,3-Acetonedicarboxylate Anion onortho-Substituted Aryl Azides

  摘要：

  所述化合物是通过二乙基1,3-酮二酸酯阴离子与邻位取代的芳香胺叠氮化物反应制备的。该阴离子是通过使用适当的醇中的钠烷氧基或通过离子交换树脂 [Amberlite IRA-400(OH)] 形成的。

  DOI：

  10.1055/s-1990-26970

文献信息

• [EN] BENZODIAZEPINE DERIVATIVES, COMPOSITIONS, AND METHODS FOR TREATING COGNITIVE IMPAIRMENT<br/>[FR] DÉRIVÉS DE BENZODIAZÉPINE, COMPOSITIONS ET MÉTHODES DE TRAITEMENT DE LA DÉFICIENCE COGNITIVE
  申请人：MEKONNEN BELEW

  公开号：WO2016205739A1

  公开（公告）日：2016-12-22

  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 GABAA receptor agonist (e.g., a α5-containing GABAA 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.

  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，包括但不限于具有或有风险患上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、雷特综合症、强迫行为和物质成瘾。
• 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）。
• [EN] BENZODIAZEPINE DERIVATIVES, COMPOSITIONS, AND METHODS FOR TREATING COGNITIVE IMPAIRMENT<br/>[FR] DÉRIVÉS DE BENZODIAZÉPINE, COMPOSITIONS ET PROCÉDÉS DE TRAITEMENT DE LA DÉFICIENCE COGNITIVE
  申请人：AGENEBIO INC

  公开号：WO2015095783A1

  公开（公告）日：2015-06-25

  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 a5- containing GABAA receptor agonist (e.g., a α5 -containing GABAA 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.

  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、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中所述的α5-含GABAA受体激动剂（例如，α5-含GABAA受体正向变构调节剂）的使用。
• Benzodiazepine derivatives, compositions, and methods for treating cognitive impairment
  申请人：AGENEBIO, INC.

  公开号：US10329301B2

  公开（公告）日：2019-06-25

  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 GABAA receptor agonist (e.g., a α5-containing GABAA 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.

  本发明涉及苯并二氮杂卓衍生物、包含治疗有效量的这些苯并二氮杂卓衍生物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。特别是，它涉及使用含 α5 的 GABAA 受体激动剂（如本文所述的含α5的GABAA受体正性异位调节剂）用于治疗有需要或有风险的受试者与中枢神经系统（CNS）疾病相关的认知障碍，包括但不限于有年龄相关认知障碍、轻度认知障碍（MCI）、失忆性MCI（aMCI）、年龄相关记忆障碍（AAMI）的受试者或有此类风险的受试者、与年龄相关的认知功能减退 (ARCD)、痴呆、阿尔茨海默病 (AD)、前驱 AD、创伤后应激障碍 (PTSD)、精神分裂症、双相情感障碍、肌萎缩性脊髓侧索硬化症 (ALS)、与癌症治疗相关的认知功能障碍、精神发育迟滞、帕金森病 (PD)、自闭症谱系障碍、脆性 X 障碍、雷特综合征、强迫行为和药物成瘾。
• 1,2,3-Triazolo[1,5-a][1,4]- and 1,2,3-triazolo[1,5-a][1,5]benzodiazepine derivatives: synthesis and benzodiazepine receptor binding
  作者：Lucia Bertelli、Giuliana Biagi、Irene Giorgi、Oreste Livi、Clementina Manera、Valerio Scartoni、Claudia Martini、Gino Giannaccini、Letizia Trincavelli、Pier Luigi Barili

  DOI：10.1016/s0014-827x(98)00025-1

  日期：1998.4

  This paper reports the synthesis of new 1,2,3-triazolo[1,4]benzodiazepine and 1,2,3-triazolo[1,5]benzodiazepine derivatives and their evaluation toward benzodiazepine receptors, Receptor affinity gradually and remarkably increases by moving the nitrogen atom of the central ring from position 3 through 4 to position 5, to give the most effective compound 6a (K-i = 150 nM). N-methylation of the diazepine ring (7a) lowers receptorial binding. Introduction of a chlorine atom on the benzene ring doubles the K-i value (6b) which remains unaltered by the N-methylation (7b). (C) 1998 Elsevier Science S.A. All rights reserved.