tert-butyl 3-{[6-(2-tert-butoxy-2-oxoethyl)-5-oxo-1-phenyl-5,6-dihydro-4H-[1,2,4]triazolo[4,3-a][1,5]benzodiazepin-4-yl]methyl}-1H-indazole-1-carboxylate | 1228935-05-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: tert-butyl 3-{[6-(2-tert-butoxy-2-oxoethyl)-5-oxo-1-phenyl-5,6-dihydro-4H-[1,2,4]triazolo[4,3-a][1,5]benzodiazepin-4-yl]methyl}-1H-indazole-1-carboxylate
• 英文别名: tert-butyl 3-[[6-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]-5-oxo-1-phenyl-4H-[1,2,4]triazolo[4,3-a][1,5]benzodiazepin-4-yl]methyl]indazole-1-carboxylate
• CAS: 1228935-05-4
• 化学式: C₃₅H₃₆N₆O₅
• 分子量: 620.708
• InChiKey: NMTQWHBATSQHOQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  46
• 可旋转键数：
  9
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  121
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  tert-butyl 3-{[6-(2-tert-butoxy-2-oxoethyl)-5-oxo-1-phenyl-5,6-dihydro-4H-[1,2,4]triazolo[4,3-a][1,5]benzodiazepin-4-yl]methyl}-1H-indazole-1-carboxylate 在 二氧化碳 、 三乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 2.0h， 生成 (4S)-4-(1H-indazol-3-ylmethyl)-6-{2-[2-(2-methoxyethyl)piperidin-1-yl]-2-oxoethyl}-1-phenyl-4H-[1,2,4]triazolo[4,3-a][1,5]benzodiazepin-5(6H)-one
  参考文献：
  名称：

  [EN] 1,2,4 TRIAZOLO [4, 3 -A] [1,5] BENZODIAZEPIN-5 (6H) -ONES AS AGONISTS OF THE CHOLECYSTOKININ-1 RECEPTOR (CCK-IR)
  [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)

  摘要：

  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。

  公开号：

  WO2010067233A1
• 作为产物：
  描述：

  1-phenyl-4H-<1,2,4>-triazolo<4,3-a><1,5>benzodiazepin-5(6H)-one 在 sodium hexamethyldisilazane 、 sodium t-butanolate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 tert-butyl 3-{[6-(2-tert-butoxy-2-oxoethyl)-5-oxo-1-phenyl-5,6-dihydro-4H-[1,2,4]triazolo[4,3-a][1,5]benzodiazepin-4-yl]methyl}-1H-indazole-1-carboxylate
  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

• [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。
• Discovery of new piperidine amide triazolobenzodiazepinones as intestinal-selective CCK1 receptor agonists
  作者：Kimberly O. Cameron、Elena E. Beretta、Yue Chen、Margaret Chu-Moyer、Dilinie Fernando、Hua Gao、Jeffrey Kohrt、Sophie Lavergne、Paul Da Silva Jardine、Angel Guzman-Perez、Christopher Hoth、David A. Perry、John R. Hadcock、Denise Gautreau、Michael Makowski、Sylvie Perez、Jana Polivkova、Lucy Rogers、Dennis O. Scott、Andrew G. Swick、Lucinda Thiede、Catherine E. Trebino、Richard V. Trilles、Julie Wilmowski、Yingxin Zhang

  DOI：10.1016/j.bmcl.2012.02.049

  日期：2012.4

  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.