[4-(1H-indol-3-ylmethyl)-5-oxo-1-phenyl-4,5-dihydro-2,3,6,10b-tetraaza-benzo[e]azulen-6-yl]-acetic acid | 870615-45-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: [4-(1H-indol-3-ylmethyl)-5-oxo-1-phenyl-4,5-dihydro-2,3,6,10b-tetraaza-benzo[e]azulen-6-yl]-acetic acid
• 英文别名: 2-[4-(1H-indol-3-ylmethyl)-5-oxo-1-phenyl-4H-[1,2,4]triazolo[4,3-a][1,5]benzodiazepin-6-yl]acetic acid
• CAS: 870615-45-5
• 化学式: C₂₇H₂₁N₅O₃
• 分子量: 463.495
• InChiKey: JAQNYRPFQSQCQT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  35
• 可旋转键数：
  5
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  104
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  [4-(1H-indol-3-ylmethyl)-5-oxo-1-phenyl-4,5-dihydro-2,3,6,10b-tetraaza-benzo[e]azulen-6-yl]-acetic acid 、 3-苄基吡咯烷 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基乙酰胺 为溶剂， 生成 6-[2-(3-benzylpyrrolidin-1-yl)-2-oxoethyl]-4-(1H-indol-3-ylmethyl)-1-phenyl-4H-[1,2,4]triazolo[3,4-d][1,5]benzodiazepin-5-one
  参考文献：
  名称：

  Discovery of new piperidine amide triazolobenzodiazepinones as intestinal-selective CCK1 receptor agonists

  摘要：

  New cholecystokinin-1 receptor (CCK1R) agonist 'triggers' were identified using iterative library synthesis. Structural activity relationship studies led to the discovery of compound 10e, a potent CCK1R agonist that demonstrated robust weight loss in a diet-induced obese rat model with very low systemic exposure. Pharmacokinetic data suggest that efficacy is primarily driven through activation of CCK1R's located within the intestinal wall. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.02.049
• 作为产物：
  描述：

  [4-(1H-indol-3-ylmethylene)-5-oxo-1-phenyl-4,5-dihydro-2,3,6,10b-tetraaza-benzo[e]azulen-6-yl]-acetic acid tert-butyl ester 在 盐酸 、 palladium on activated charcoal 、 氢气 、 甲酸铵 作用下， 以 1,4-二氧六环 、 乙醇 为溶剂， 生成 [4-(1H-indol-3-ylmethyl)-5-oxo-1-phenyl-4,5-dihydro-2,3,6,10b-tetraaza-benzo[e]azulen-6-yl]-acetic acid
  参考文献：
  名称：

  Discovery of new piperidine amide triazolobenzodiazepinones as intestinal-selective CCK1 receptor agonists

  摘要：

  New cholecystokinin-1 receptor (CCK1R) agonist 'triggers' were identified using iterative library synthesis. Structural activity relationship studies led to the discovery of compound 10e, a potent CCK1R agonist that demonstrated robust weight loss in a diet-induced obese rat model with very low systemic exposure. Pharmacokinetic data suggest that efficacy is primarily driven through activation of CCK1R's located within the intestinal wall. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.02.049

文献信息

• Tetraazabenzo[e]azulene derivatives and analogs thereof
  申请人：Elliott L. Richard

  公开号：US20050267100A1

  公开（公告）日：2005-12-01

  This invention relates to CCK-A agonists of Formula (I) wherein R 1 -R 4 , A, B, X, D, E and G are as defined in the specificiation, as well as, among other things, pharmaceutical compositions containing the compounds and methods of use of the compounds and compositions. The compounds are useful in treating obesity.

  这项发明涉及公式（I）中的CCK-A激动剂， 其中R1-R4，A，B，X，D，E和G如规范中所定义，以及包含这些化合物的药物组合物和这些化合物和组合物的使用方法。这些化合物在治疗肥胖症方面是有用的。
• [EN] 1,2,4 TRIAZOLO [4, 3 -A] [1,5] BENZODIAZEPIN-5 (6H) -ONES AS AGONISTS OF THE CHOLECYSTOKININ-1 RECEPTOR (CCK-IR)<br/>[FR] 1,2,4 TRIAZOLO[4,3-A][1,5] BENZODIAZÉPIN-5(6H)-ONES UTILISÉES COMME AGONISTES DU RÉCEPTEUR DE LA CHOLÉCYSTOKININE-1 (CCK-1R)
  申请人：PFIZER

  公开号：WO2010067233A1

  公开（公告）日：2010-06-17

  This invention relates to CCK-1 R agonists of Formula (I) wherein R1-R5 and X are as defined in the specificiation, as well as pharmaceutical compositions containing the compounds and methods of use of the compounds and compositions. The compounds are useful in treating obesity, type 2 diabetes and associated diseases.

  这项发明涉及到式（I）中的CCK-1 R激动剂，其中R1-R5和X如规范中所定义，以及含有这些化合物的药物组合物和这些化合物和组合物的使用方法。这些化合物在治疗肥胖症、2型糖尿病及相关疾病方面是有用的。
• TETRAAZABENZO[E]AZULENE DERIVATIVES AND ANALOGS THEREOF
  申请人：Elliott L. Richard

  公开号：US20070265193A1

  公开（公告）日：2007-11-15

  This invention relates to CCK-A agonists of Formula (I) wherein R 1 -R 4 , A, B, X, D, E and G are as defined in the specification, as well as, among other things, pharmaceutical compositions containing the compounds and methods of use of the compounds and compositions. The compounds are useful in treating diabetes.

  本发明涉及式(I)的CCK-A激动剂，其中R1-R4，A，B，X，D，E和G如规范中所定义，以及包含该化合物的药物组合物和使用该化合物和组合物的方法，该化合物在治疗糖尿病方面有用。
• TETRAAZABENZO(E)AZULENE DERIVATIVES AND ANALOGS THEREOF
  申请人：Pfizer Products Inc.

  公开号：EP1753766A1

  公开（公告）日：2007-02-21
• US7265104B2
  申请人：——

  公开号：US7265104B2

  公开（公告）日：2007-09-04