tert-Butyl 3-{5-chloro-1-[3-(trifluoromethyl)phenyl]-1H-indol-2-yl}-3-oxopropanoate | 934615-62-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: tert-Butyl 3-{5-chloro-1-[3-(trifluoromethyl)phenyl]-1H-indol-2-yl}-3-oxopropanoate
• 英文别名: Tert-butyl 3-{5-chloro-1-[3-(trifluoromethyl)phenyl]-1h-indol-2-yl}-3-oxopropanoate；tert-butyl 3-[5-chloro-1-[3-(trifluoromethyl)phenyl]indol-2-yl]-3-oxopropanoate
• CAS: 934615-62-0
• 化学式: C₂₂H₁₉ClF₃NO₃
• 分子量: 437.846
• InChiKey: DGDMTNKSYKMRGI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  48.3
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  tert-Butyl 3-{5-chloro-1-[3-(trifluoromethyl)phenyl]-1H-indol-2-yl}-3-oxopropanoate 在 sodium hydride 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 1-{5-Chloro-1-[3-(trifluoromethyl)phenyl]-1H-indol-2-yl}-3-cyclopropylpropan-1-one
  参考文献：
  名称：

  Discovery of N-Aryl-2-acylindole human glucagon receptor antagonists

  摘要：

  A novel class of N-aryl-2-acylindole human glucagon receptor (hGCGR) antagonists is reported. These compounds demonstrate good pharmacokinetic profiles in multiple preclinical species. One compound from this series, indole 33, is orally active in a transgenic murine pharmacodynamic model. Furthermore, a 1 mg/kg oral dose of indole 33 lowers ambient glucose levels in an ob/ob/hGCGR transgenic murine diabetes model. This compound was deemed suitable for preclinical safety studies and was found to be well tolerated in an 8-day experimental rodent tolerability study. The combination of preclinical efficacy and safety observed with compound 33 highlights the potential of this class as a treatment for type 2 diabetes. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.09.105
• 作为产物：
  描述：

  Ethyl 5-chloro-1-[3-(trifluoromethyl)phenyl]-1H-indole-2-carboxylate 在 lithium hexamethyldisilazane 、 水 、 碳酸氢钠 作用下， 以 四氢呋喃 为溶剂， 反应 2.5h， 生成 tert-Butyl 3-{5-chloro-1-[3-(trifluoromethyl)phenyl]-1H-indol-2-yl}-3-oxopropanoate
  参考文献：
  名称：

  Acyl indoles, compositions containing such compounds and methods of use

  摘要：

  本发明涉及替代吲哚类化合物，含有这种化合物的组合物，以及治疗方法。这些化合物是胰高血糖素受体拮抗剂，因此可用于治疗、预防或延缓2型糖尿病及相关疾病的发生。

  公开号：

  US20070088071A1

文献信息

• Discovery of N-Aryl-2-acylindole human glucagon receptor antagonists
  作者：Christopher Sinz、Amy Bittner、Ed Brady、Mari Candelore、Qing Dallas-Yang、Victor Ding、Guoqiang Jiang、Zhen Lin、Sajjad Qureshi、Gino Salituro、Richard Saperstein、Jackie Shang、Deborah Szalkowski、Laurie Tota、Stella Vincent、Michael Wright、Shiyao Xu、Xiaodong Yang、Bei Zhang、James Tata、Ronald Kim、Emma R. Parmee

  DOI：10.1016/j.bmcl.2011.09.105

  日期：2011.12

  A novel class of N-aryl-2-acylindole human glucagon receptor (hGCGR) antagonists is reported. These compounds demonstrate good pharmacokinetic profiles in multiple preclinical species. One compound from this series, indole 33, is orally active in a transgenic murine pharmacodynamic model. Furthermore, a 1 mg/kg oral dose of indole 33 lowers ambient glucose levels in an ob/ob/hGCGR transgenic murine diabetes model. This compound was deemed suitable for preclinical safety studies and was found to be well tolerated in an 8-day experimental rodent tolerability study. The combination of preclinical efficacy and safety observed with compound 33 highlights the potential of this class as a treatment for type 2 diabetes. (C) 2011 Elsevier Ltd. All rights reserved.
• Acyl indoles, compositions containing such compounds and methods of use
  申请人：Kim M. Ronald

  公开号：US20070088071A1

  公开（公告）日：2007-04-19

  The present invention relates to substituted indoles, compositions containing such compounds and methods of treatment The compounds are glucagon receptor antagonists and thus are useful for treating, preventing or delaying the onset of type 2 diabetes mellitus and related conditions.

  本发明涉及替代吲哚类化合物，含有这种化合物的组合物，以及治疗方法。这些化合物是胰高血糖素受体拮抗剂，因此可用于治疗、预防或延缓2型糖尿病及相关疾病的发生。