3,5-dimethyl-4-(4-(trifluoromethyl)-1H-pyrazol-1-yl)benzenamine | 1393125-32-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 3,5-dimethyl-4-(4-(trifluoromethyl)-1H-pyrazol-1-yl)benzenamine
• 英文别名: 3,5-Dimethyl-4-[4-(trifluoromethyl)pyrazol-1-yl]aniline
• CAS: 1393125-32-0
• 化学式: C₁₂H₁₂F₃N₃
• 分子量: 255.243
• InChiKey: AUUICGZUQIZHKI-UHFFFAOYSA-N

物化性质

• 沸点：
  355.4±42.0 °C(Predicted)
• 密度：
  1.31±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  43.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3,5-dimethyl-4-(4-(trifluoromethyl)-1H-pyrazol-1-yl)benzenamine 在 癸硼烷 、 水 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 生成
  参考文献：
  名称：

  The design and synthesis of a potent glucagon receptor antagonist with favorable physicochemical and pharmacokinetic properties as a candidate for the treatment of type 2 diabetes mellitus

  摘要：

  A novel and potent small molecule glucagon receptor antagonist for the treatment of diabetes mellitus is reported. This candidate, (S)-3-[4-(1-{3,5-dimethyl-4-[4-(trifluoromethyl)-1H-pyrazol-1-yl]phenoxy}butyl)benzamido]propanoic acid, has lower molecular weight and lipophilicity than historical glucagon receptor antagonists, resulting in excellent selectivity in broad-panel screening, lower cytotoxicity, and excellent overall in vivo safety in early pre-clinical testing. Additionally, it displays low in vivo clearance and excellent oral bioavailability in both rats and dogs. In a rat glucagon challenge model, it was shown to reduce the glucagon-elicited glucose excursion in a dose-dependent manner and at a concentration consistent with its rat in vitro potency. Its properties make it an excellent candidate for further investigation. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.03.014
• 作为产物：
  描述：

  在 palladium 10% on activated carbon 、 甲酸铵 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 生成 3,5-dimethyl-4-(4-(trifluoromethyl)-1H-pyrazol-1-yl)benzenamine
  参考文献：
  名称：

  The design and synthesis of a potent glucagon receptor antagonist with favorable physicochemical and pharmacokinetic properties as a candidate for the treatment of type 2 diabetes mellitus

  摘要：

  A novel and potent small molecule glucagon receptor antagonist for the treatment of diabetes mellitus is reported. This candidate, (S)-3-[4-(1-{3,5-dimethyl-4-[4-(trifluoromethyl)-1H-pyrazol-1-yl]phenoxy}butyl)benzamido]propanoic acid, has lower molecular weight and lipophilicity than historical glucagon receptor antagonists, resulting in excellent selectivity in broad-panel screening, lower cytotoxicity, and excellent overall in vivo safety in early pre-clinical testing. Additionally, it displays low in vivo clearance and excellent oral bioavailability in both rats and dogs. In a rat glucagon challenge model, it was shown to reduce the glucagon-elicited glucose excursion in a dose-dependent manner and at a concentration consistent with its rat in vitro potency. Its properties make it an excellent candidate for further investigation. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.03.014

文献信息

• GLUCAGON RECEPTOR MODULATORS
  申请人：Aspnes Gary Erik

  公开号：US20120202834A1

  公开（公告）日：2012-08-09

  The present invention provides a compound of Formula (I) or a pharmaceutically acceptable salt thereof wherein R 1 , R 2 , R 3 , A 1 , A 2 , A 3 , A 4 , L, B 1 , B 2 , B 3 and B 4 are as defined herein. The compounds of Formula I have been found to act as glucagon antagonists or inverse agonists. Consequently, the compounds of Formula I and the pharmaceutical compositions thereof are useful for the treatment of diseases, disorders, or conditions mediated by glucagon.

  本发明提供了一种式（I）的化合物或其药学上可接受的盐，其中R1、R2、R3、A1、A2、A3、A4、L、B1、B2、B3和B4如本文所定义。已发现式I的化合物可作为葡萄糖胰高血糖素拮抗剂或逆向激动剂。因此，式I的化合物及其药物组成物对于治疗由葡萄糖胰高血糖素介导的疾病、紊乱或症状是有用的。
• GLUCAGON RECEPTOR MODULATOR
  申请人：Pfizer Inc.

  公开号：EP2673260B1

  公开（公告）日：2016-08-17
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