9-bromo-6H-1,3,3a,6-tetraaza-benzo[e]azulen-5-one | 882517-94-4

• 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: 9-bromo-6H-1,3,3a,6-tetraaza-benzo[e]azulen-5-one
• 英文别名: 10-Bromo-5H-benzo[f][1,2,4]triazolo[1,5-d][1,4]diazepin-6(7H)-one；10-bromo-5,7-dihydro-[1,2,4]triazolo[1,5-d][1,4]benzodiazepin-6-one
• CAS: 882517-94-4
• 化学式: C₁₀H₇BrN₄O
• 分子量: 279.096
• InChiKey: RXDJEGWKDWSRHG-UHFFFAOYSA-N

物化性质

• 密度：
  1.95±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  16
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  59.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  9-bromo-6H-1,3,3a,6-tetraaza-benzo[e]azulen-5-one 在 N,N-二甲基对甲苯胺 、 三氯氧磷 作用下， 以 氯仿 为溶剂， 反应 22.0h， 生成
  参考文献：
  名称：

  Substituted imidazo[1,5-a][1,2,4]triazolo[1,5-d][1,4]benzodiazepine derivatives

  摘要：

  本发明涉及一种治疗从认知障碍、焦虑、阿尔茨海默病和精神分裂症中选择的疾病的方法，包括给予下列公式的取代咪唑[1,5-a][1,2,4]三唑[1,5-d][1,4]苯二氮䓬啉衍生物的治疗有效量：其中R1是卤素、较低烷基、较低炔基、环烷基、较低烷氧基、OCF3、—NHR、—NHC(O)R或—NHSO2R；R2是氢、甲基或芳基，未取代或由卤素和较低烷氧基中选择的一种或两种取代基取代；R3是氢、较低烷基、较低烯基、环烷基、较低烷氧基、—O(CH2)n+1—O-较低烷基、—(CH2)n-芳基，可由较低烷基或卤素取代，杂芳基、—NHR、—N(R)2，其中每个R可以相同也可以不同，—NHCH2C≡CH，或吡咯烷酮；R是氢、较低烷基、由卤素取代的较低烷基、杂芳基、—(CH2)nO-较低烷基、—NH-较低烷基、环烷基或芳基，n为0、1、2或3；以及其药学上可接受的酸盐。该发明还提供了公式I-A的新化合物和含有它们的药物组合物。最受欢迎的适应症是阿尔茨海默病。

  公开号：

  US20060079507A1
• 作为产物：
  描述：

  9-溴-[1,2,4]噻唑[1,5-c]喹唑啉-5(6H)-酮 、 氯乙酰氯 在 sodium hydroxide 作用下， 以 乙二醇 、 溶剂黄146 、 1,4-二氧六环 为溶剂， 以56%的产率得到9-bromo-6H-1,3,3a,6-tetraaza-benzo[e]azulen-5-one
  参考文献：
  名称：

  The discovery and unique pharmacological profile of RO4938581 and RO4882224 as potent and selective GABAA α5 inverse agonists for the treatment of cognitive dysfunction

  摘要：

  Lead optimisation of the imidazo[1,5-a][1,2,4]-triazolo[1,5-d][1,4] benzodiazepine class led to the identification of two clinical leads [RO4882224 (11) and RO4938581 (44)] functioning as novel potent and selective GABA(A) alpha 5 inverse agonists. The unique pharmacological profiles and optimal pharmacokinetic profiles resulted in in vivo activity in selected cognition models. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.08.053

文献信息

• Halogen substituted imidazol[1,5-A][1,2,4]triazolo[1,5-D][1,4]benzodiazepine derivatives
  申请人：Knust Henner

  公开号：US20060084801A1

  公开（公告）日：2006-04-20

  The invention relates to halogen substituted imidazo[1,5-a][1,2,4]triazolo[1,5-d][1,4]benzodiazepine derivatives of formula I wherein R 1 , R 2 , R 3 , R 4 and n are as defined in the specification and to pharmaceutically acceptable acid addition salts thereof. The compounds can be used as a cognitive enhancer or for the treatment of cognitive disorders, anxiety, Alzheimer's disease and schizophrenia.

  该发明涉及公式I中卤代咪唑[1,5-a][1,2,4]三唑[1,5-d][1,4]苯二氮平衍生物，其中R1、R2、R3、R4和n如规范中定义，并且其药学上可接受的酸盐。这些化合物可用作认知增强剂或用于治疗认知障碍、焦虑、阿尔茨海默病和精神分裂症。
• Substituted imidazol[1,5-A][1,2,4]triazolo[1,5-D][1,4]benzodiazepine derivatives
  申请人：Knust Henner

  公开号：US20060084642A1

  公开（公告）日：2006-04-20

  The present invention is concerned with substituted imidazo[1,5-a][1,2,4]triazolo[1,5-d][1,4]benzodiazepine derivatives of formula I wherein R 1 is hydrogen, halogen, lower alkyl, lower alkynyl, cycloalkyl, heterocycloalkyl, benzyl, cyano, lower alkoxy, OCF 3 , —NHR, —NHC(O)R or —NHSO 2 R; R 2 is lower alkyl substituted by halogen; R 3 is hydrogen, methyl or aryl; R is lower alkyl, cycloalkyl or aryl; and pharmaceutically acceptable acid addition salts thereof. Such compounds have a high affinity and selectivity for GABA A α5 receptor binding sites and might be useful as cognitive enhancer or for the treatment of cognitive disorders, anxiety, schizophrenia or Alzheimer's disease.

  本发明涉及公式I的取代咪唑[1,5-a][1,2,4]三唑并[1,5-d][1,4]苯二氮平衍生物，其中R1为氢、卤素、较低烷基、较低炔基、环烷基、杂环烷基、苄基、氰基、较低烷氧基、OCF3、—NHR、—NHC(O)R或—NHSO2R；R2为卤素取代的较低烷基；R3为氢、甲基或芳基；R为较低烷基、环烷基或芳基；以及其药学上可接受的酸盐。这些化合物对GABA A α5受体结合位点具有高亲和力和选择性，并可能用作认知增强剂或用于治疗认知障碍、焦虑、精神分裂症或阿尔茨海默病。
• SUBSTITUTED IMIDAZO[1,5-A][1,2,4]TRIAZOLO[1,5-D][1,4]BENZODIAZEPINE DERIVATIVES
  申请人：Knust Henner

  公开号：US20100075954A1

  公开（公告）日：2010-03-25

  The present invention is concerned with a method of treating Alzheimer's disease by administering a therapeutically effective amount of a substituted imidazo[1,5-a][1,2,4]triazolo[1,5-d][1,4]benzodiazepine of formula I wherein R 1 , R 2 , and R 3 are as defined herein, and their pharmaceutically acceptable acid addition salts. The invention also provides novel compounds of formula I-A and pharmaceutical compositions containing them.

  本发明涉及通过给予公式I中的取代咪唑[1,5-a] [1,2,4]三唑并[1,5-d] [1,4]苯二氮平的治疗有效量以治疗阿尔茨海默病的方法，其中R1，R2和R3如本文所定义，并且它们的药学上可接受的酸加盐。该发明还提供了公式I-A的新化合物和包含它们的药物组合物。
• Substituted imidazo[1,5-A][1,2,4]triazolo[1,5-D][1,4]benzodiazepine derivatives
  申请人：Hoffmann-La Roche Inc.

  公开号：US08293730B2

  公开（公告）日：2012-10-23

  The present invention is concerned with a method of treating Alzheimer's disease by administering a therapeutically effective amount of a substituted imidazo[1,5-a][1,2,4]triazolo[1,5-d][1,4]benzodiazepine of formula I wherein R1, R2, and R3 are as defined herein, and their pharmaceutically acceptable acid addition salts. The invention also provides novel compounds of formula I-A and pharmaceutical compositions containing them.

  本发明涉及一种通过给予公式I中的取代咪唑[1,5-a][1,2,4]三唑并[1,5-d][1,4]苯二氮平的治疗有效量来治疗阿尔茨海默病的方法，其中R1，R2和R3如本文所定义，并且它们的药学上可接受的酸加盐。本发明还提供了公式I-A的新化合物和含有它们的药物组合物。
• Substituted imidazo [1,5-a][1,2,4]triazolo[1,5-d][1,4]benzodiazepine derivatives
  申请人：Hoffmann-La Roche Inc.

  公开号：US07671048B2

  公开（公告）日：2010-03-02

  The present invention is concerned with a method of treating a disease selected from the group consisting of cognitive disorders, anxiety, Alzheimer's disease, and schizophrenia comprising administering a therapeutically effective amount of a substituted imidazo[1,5-a][1,2,4]triazolo[1,5-d][1,4]benzodiazepine derivatives of the following formula wherein R1 is halogen, lower alkyl, lower alkynyl, cycloalkyl, lower alkoxy, OCF3, —NHR, —NHC(O)R or —NHSO2R; R2 is hydrogen, methyl or aryl which is unsubstituted or substituted by one or two substituents selected from the group consisting of halogen and lower alkoxy; R3 is hydrogen, lower alkyl, lower alkenyl, cycloalkyl, lower alkoxy, —O(CH2)n+1—O-lower alkyl, —(CH2)n-aryl which is optionally substituted by lower alkyl or halogen, heteroaryl, —NHR, —N(R)2, wherein each R can be the same or different, —NHCH2C≡CH, or pyrrolidin-1-one; R is hydrogen, lower alkyl, lower alkyl substituted by halogen, heteroaryl, —(CH2)nO-lower alkyl, —NH-lower alkyl, cycloalkyl or aryl, and n is 0, 1, 2 or 3; and with their pharmaceutically acceptable acid addition salts. The invention also provides novel compounds of formula I-A and pharmaceutical compositions containing them. The most preferred indication is Alzheimer's disease.

  本发明涉及一种治疗认知障碍、焦虑、阿尔茨海默病和精神分裂症等疾病的方法，包括给予以下公式的取代咪唑[1,5-a][1,2,4]三唑并[1,5-d][1,4]苯二氮平衍生物的治疗有效量，其中R1是卤素、较低烷基、较低炔基、环烷基、较低烷氧基、OCF3、—NHR、—NHC(O)R或—NHSO2R;R2是氢、甲基或芳基，未经取代或经过一种或两种卤素和较低烷氧基的取代;R3是氢、较低烷基、较低烯基、环烷基、较低烷氧基、—O(CH2)n+1—O-较低烷基、—( )n-芳基，其可选择由较低烷基或卤素取代，杂环芳基、—NHR、—N(R)2，其中每个R可以相同或不同，—NH C≡CH或吡咯烷-1-酮;R为氢、较低烷基、经卤素取代的较低烷基、杂环芳基、—( )nO-较低烷基、—NH-较低烷基、环烷基或芳基，n为0、1、2或3;以及其药学上可接受的酸盐。本发明还提供了公式I-A的新化合物和含有它们的制药组合物。最优选的适应症是阿尔茨海默病。