5-chloromethyl-9-fluoro-1,2,4-triazolo<4,3-c>quinazoline | 147004-00-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 5-chloromethyl-9-fluoro-1,2,4-triazolo<4,3-c>quinazoline
• 英文别名: 5-(chloromethyl)-9-fluoro-1,2,4-triazolo[4,3-c]quinazoline；5-(Chloromethyl)-9-fluoro-[1,2,4]triazolo[4,3-c]quinazoline
• CAS: 147004-00-0
• 化学式: C₁₀H₆ClFN₄
• 分子量: 236.636
• InChiKey: GWAURELTCSFLPZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  16
• 可旋转键数：
  1
• 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：

  5-chloromethyl-9-fluoro-1,2,4-triazolo<4,3-c>quinazoline 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：

  Imidazodiazepine derivatives

  摘要：

  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。

  公开号：

  US05387585A1
• 作为产物：
  描述：

  2-氨基-5-氟苯甲酰胺 在 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 、 氯仿 为溶剂， 反应 50.0h， 生成 5-chloromethyl-9-fluoro-1,2,4-triazolo<4,3-c>quinazoline
  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。
• 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。
• Substituted imidazo[1,5-a][1,2,4]triazolo[1,5-d][1,4]benzodiazepine derivatives
  申请人：Knust Henner

  公开号：US20060079507A1

  公开（公告）日：2006-04-13

  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 R 1 is halogen, lower alkyl, lower alkynyl, cycloalkyl, lower alkoxy, OCF 3 , —NHR, —NHC(O)R or —NHSO 2 R; R 2 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; R 3 is hydrogen, lower alkyl, lower alkenyl, cycloalkyl, lower alkoxy, —O(CH 2 ) n+1 —O-lower alkyl, —(CH 2 ) 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, —NHCH 2 C≡CH, or pyrrolidin-1-one; R is hydrogen, lower alkyl, lower alkyl substituted by halogen, heteroaryl, —(CH 2 ) n O-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。
• 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。