6-chloro-10-fluoro-5H-<1,2,4>triazolo<1,5-d><1,4>benzodiazepine | 147004-96-4

• 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: 6-chloro-10-fluoro-5H-<1,2,4>triazolo<1,5-d><1,4>benzodiazepine
• 英文别名: 5-chloro-9-fluoro-4H-1,3,3a,6-tetraaza-benzo[e]azulene；6-chloro-10-fluoro-5H-[1,2,4]triazolo[1,5-d][1,4]benzodiazepine
• CAS: 147004-96-4
• 化学式: C₁₀H₆ClFN₄
• 分子量: 236.636
• InChiKey: UQJVSIACLXDAIF-UHFFFAOYSA-N

物化性质

• 沸点：
  462.6±55.0 °C(predicted)
• 密度：
  1.62±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 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：
  43.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-chloro-10-fluoro-5H-<1,2,4>triazolo<1,5-d><1,4>benzodiazepine 在 sodium hydroxide 、 potassium tert-butylate 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 2.0h， 生成 3-fluoro-9H-imidazo<1,5-a><1,2,4>triazolo<1,5-d><1,4>benzodiazepine-10-carboxylic acid
  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：

  2-氨基-5-氟苯甲酰胺 在 吡啶 、 盐酸 、 一水合肼 、 N,N-二甲基对甲苯胺 、 三氯氧磷 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醚 、 氯仿 为溶剂， 反应 82.08h， 生成 6-chloro-10-fluoro-5H-<1,2,4>triazolo<1,5-d><1,4>benzodiazepine
  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

• Substituted imidazo[1,5-A][1,2,4]triazolo[1,5-D][1,4]benzodiazepine derivatives
  申请人：Buettelmann Bernd

  公开号：US20060128691A1

  公开（公告）日：2006-06-15

  The present invention is concerned with substituted imidazo[1,5-a][1,2,4]triazolo[1,5-d][1,4]benzodiazepine derivatives of the formula I wherein R 1 is hydrogen, halogen, lower alkyl, lower alkyl substituted by halogen, lower alkoxy, lower alkoxy substituted by halogen, nitro, cycloalkyl, —O(CH 2 ) m O(CH 2 ) m OH or —C≡C—R′; R 2 is hydrogen or methyl; R 3 is lower alkyl, lower alkyl substituted by halogen, lower alkenyl, lower alkenyl substituted by halogen, lower alkynyl, —(CH 2 ) n -cycloalkyl, —(CR′R″) m —CH 3 , phenyl that is unsubstituted or substituted by halogen, pyridinyl or thienyl each of which is unsubstituted or substituted by lower alkyl, —(CH 2 ) n —NH-cycloalkyl, lower alkenyl-cycloalkyl, lower alkynyl-(CR′R″) m OH, or lower alkynyl-phenyl wherein the phenyl ring is unsubstituited or substituted by halogen, CF 3 , lower alkyl or lower alkoxy; R′ is hydrogen or lower alkyl; R″ is hydrogen, hydroxy or lower alkyl; n is 0, 1 or 2; m is 1, 2 or 3 ; and o is 1 or 2; and pharmaceutically acceptable acid addition salts thereof. This class of compounds have high affinity and selectivity for GABA A α 5 receptor binding sites. Thus, the invention also relates to methods of enhancing cognition and treating cognitive disorders like Alzheimer's disease.

  本发明涉及公式I的取代咪唑[1,5-a][1,2,4]三唑[1,5-d][1,4]苯二氮杂环己烷衍生物，其中R1为氢、卤素、较低烷基、被卤素取代的较低烷基、较低烷氧基、被卤素取代的较低烷氧基、硝基、环烷基、—O(CH2)mO(CH2)mOH或—C≡C—R′；R2为氢或甲基；R3为较低烷基、被卤素取代的较低烷基、较低烯基、被卤素取代的较低烯基、较低炔基、—(CH2)n-环烷基、—(CR′R″)m—CH3、苯基（未取代或被卤素取代）、吡啶基或噻吩基，每种基未取代或被较低烷基取代、—(CH2)n—NH-环烷基、较低烯基-环烷基、较低炔基-(CR′R″)mOH或较低炔基-苯基，其中苯环未取代或被卤素、CF3、较低烷基或较低烷氧基取代；R′为氢或较低烷基；R″为氢、羟基或较低烷基；n为0、1或2；m为1、2或3；o为1或2；及其药学上可接受的酸盐。这类化合物对GABA A α5受体结合位点具有高亲和力和选择性。因此，该发明还涉及增强认知和治疗像阿尔茨海默病这样的认知障碍的方法。
• Substitued imidazo [1,5-A][1,2,4]triazolo[1,5-D][1,4]benzodiazepine derivatives
  申请人：Hoffman-La Roche Inc.

  公开号：US07432256B2

  公开（公告）日：2008-10-07

  The present invention is concerned with substituted imidazo[1,5-a][1,2,4]triazolo[1,5-d][1,4]benzodiazepine derivatives of the formula I wherein R1 is hydrogen, halogen, lower alkyl, lower alkyl substituted by halogen, lower alkoxy, lower alkoxy substituted by halogen, nitro, cycloalkyl, —O(CH2)mO(CH2)mOH or —C≡C—R′; R2 is hydrogen or methyl; R3 is lower alkyl, lower alkyl substituted by halogen, lower alkenyl, lower alkenyl substituted by halogen, lower alkynyl, —(CH2)n-cycloalkyl, —(CR′R″)m—CH3, phenyl that is unsubstituted or substituted by halogen, pyridinyl or thienyl each of which is unsubstituted or substituted by lower alkyl, —(CH2)n—NH-cycloalkyl, lower alkenyl-cycloalkyl, lower alkynyl-(CR′R″)mOH, or lower alkynyl-phenyl wherein the phenyl ring is unsubstituited or substituted by halogen, CF3, lower alkyl or lower alkoxy; R′ is hydrogen or lower alkyl; R″ is hydrogen, hydroxy or lower alkyl; n is 0, 1 or 2; m is 1, 2 or 3; and o is 1 or 2; and pharmaceutically acceptable acid addition salts thereof. This class of compounds have high affinity and selectivity for GABA A α5 receptor binding sites. Thus, the invention also relates to methods of enhancing cognition and treating cognitive disorders like 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是氢、卤素、较低烷基、较低烷基卤素取代、较低烷氧基、较低烷氧基卤素取代、硝基、环烷基、—O(CH2)mO(CH2)mOH或—C≡C—R′; R2是氢或甲基; R3是较低烷基、较低烷基卤素取代、较低烯基、较低烯基卤素取代、较低炔基、—(CH2)n-环烷基、—(CR′R″)m—CH3、苯基，未取代或卤素取代、吡啶基或噻吩基，未取代或较低烷基取代、—(CH2)n—NH-环烷基、较低烯基-环烷基、较低炔基-(CR′R″)mOH或较低炔基-苯基，其中苯环为未取代或卤素、CF3、较低烷基或较低烷氧基取代; R′是氢或较低烷基; R″是氢、羟基或较低烷基; n为0、1或2; m为1、2或3; o为1或2;以及其药学上可接受的酸盐。这类化合物对GABA A α5受体结合位点具有高亲和力和选择性。因此，本发明还涉及增强认知和治疗认知障碍如阿尔茨海默病的方法。
• Tetracyclische Imidazodiazepine
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP0519307A2

  公开（公告）日：1992-12-23

  Die neuen Imidazodiazepin-Derivate der allgemeinen Formel worin A zusammen mit den beiden mit a und β bezeichneten Kohlenstoffatomen eine der Gruppen

  通式中的新咪唑二氮杂卓衍生物，其中 A 与指定为 a 和 β 的两个碳原子形成基团之一
• TETRACYCLIC IMIDAZO-BENZODIAZEPINES AS GABA RECEPTORS MODULATORS
  申请人：F. Hoffmann-Roche AG

  公开号：EP1828194A1

  公开（公告）日：2007-09-05
• US7432256B2
  申请人：——

  公开号：US7432256B2

  公开（公告）日：2008-10-07