ethyl 6-ethyl-1-methyl-5-[(phenylcarbonyl)amino]-3-(2,2,2-trifluoroethoxy)-1H-indole-2-carboxylate | 1269027-77-1

• 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: ethyl 6-ethyl-1-methyl-5-[(phenylcarbonyl)amino]-3-(2,2,2-trifluoroethoxy)-1H-indole-2-carboxylate
• 英文别名: Ethyl 5-benzamido-6-ethyl-1-methyl-3-(2,2,2-trifluoroethoxy)indole-2-carboxylate
• CAS: 1269027-77-1
• 化学式: C₂₃H₂₃F₃N₂O₄
• 分子量: 448.442
• InChiKey: ZMVJPLZBJOBQJK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  32
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  69.6
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  ethyl 6-ethyl-1-methyl-5-[(phenylcarbonyl)amino]-3-(2,2,2-trifluoroethoxy)-1H-indole-2-carboxylate 在 水 、 1-羟基苯并三唑 、 三乙胺 、 sodium hydroxide 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.75h， 生成 6-ethyl-N-[1-(hydroxyacetyl)piperidin-4-yl]-1-methyl-5-[(phenylcarbonyl)amino]-3-(2,2,2-trifluoroethoxy)-1H-indole-2-carboxamide
  参考文献：
  名称：

  Synthesis and evaluation of hedgehog signaling inhibitor with novel core system

  摘要：

  As we previously reported, N-methylpyrrolo[3,2-c] pyridine derivatives 1 (TAK-441) was discovered as a clinical candidate of hedgehog (Hh) signaling inhibitor by modification of the upper part. We next focused on modification of the lower part including core skeletons to discover new Hh signaling inhibitors with novel core rings. Efforts to find novel chemotypes by using X-ray single crystal structure analysis led to some potent Hh signaling inhibitors (2c, 2d, 2e, 2f) with novel core ring systems, which had benzamide moiety at the 5-position as a key component for potent activity. The suppression of Gli1 expression with these new Hh signaling inhibitors were weaker than that of compound 1 (TAK-441) because of low pharmacokinetic property. We recognized again TAK-441 is a good compound as clinical candidate with good structural and pharmacokinetic advantages. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.05.036
• 作为产物：
  描述：

  ethyl 2-chloro-4-ethyl-5-nitrobenzoate 在 吡啶 、 palladium 10% on activated carbon 、 氢气 、 caesium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 25.5h， 生成 ethyl 6-ethyl-1-methyl-5-[(phenylcarbonyl)amino]-3-(2,2,2-trifluoroethoxy)-1H-indole-2-carboxylate
  参考文献：
  名称：

  Synthesis and evaluation of hedgehog signaling inhibitor with novel core system

  摘要：

  As we previously reported, N-methylpyrrolo[3,2-c] pyridine derivatives 1 (TAK-441) was discovered as a clinical candidate of hedgehog (Hh) signaling inhibitor by modification of the upper part. We next focused on modification of the lower part including core skeletons to discover new Hh signaling inhibitors with novel core rings. Efforts to find novel chemotypes by using X-ray single crystal structure analysis led to some potent Hh signaling inhibitors (2c, 2d, 2e, 2f) with novel core ring systems, which had benzamide moiety at the 5-position as a key component for potent activity. The suppression of Gli1 expression with these new Hh signaling inhibitors were weaker than that of compound 1 (TAK-441) because of low pharmacokinetic property. We recognized again TAK-441 is a good compound as clinical candidate with good structural and pharmacokinetic advantages. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.05.036

文献信息

• FUSED HETEROCYCLIC RING DERIVATIVE AND USE THEREOF
  申请人：Takeda Pharmaceutical Company Limited

  公开号：EP2471789B9

  公开（公告）日：2015-03-25
• US8486965B2
  申请人：——

  公开号：US8486965B2

  公开（公告）日：2013-07-16