ethyl 4-chloro-2-ethyl-7-methyl-5-(2,2,2-trifluoroethoxy)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylate | 1269118-49-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并嘧啶类
• 英文名称: ethyl 4-chloro-2-ethyl-7-methyl-5-(2,2,2-trifluoroethoxy)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylate
• 英文别名: Ethyl 4-chloro-2-ethyl-7-methyl-5-(2,2,2-trifluoroethoxy)pyrrolo[2,3-d]pyrimidine-6-carboxylate；ethyl 4-chloro-2-ethyl-7-methyl-5-(2,2,2-trifluoroethoxy)pyrrolo[2,3-d]pyrimidine-6-carboxylate
• CAS: 1269118-49-1
• 化学式: C₁₄H₁₅ClF₃N₃O₃
• 分子量: 365.74
• InChiKey: NMTUWDBNXAMXGU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  66.2
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  ethyl 4-chloro-2-ethyl-7-methyl-5-(2,2,2-trifluoroethoxy)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylate 在 水 、 sodium acetate 、 potassium carbonate 、 1-羟基苯并三唑 、 溶剂黄146 、 三乙胺 、 sodium hydroxide 作用下， 以 乙二醇二甲醚 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 49.75h， 生成 2-ethyl-N-[1-(hydroxyacetyl)piperidin-4-yl]-7-methyl-4-oxo-3-(2-oxo-2-phenylethyl)-5-(2,2,2-trifluoroethoxy)-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidine-6-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：

  在 sodium ethanolate 、 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 25.25h， 生成 ethyl 4-chloro-2-ethyl-7-methyl-5-(2,2,2-trifluoroethoxy)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylate
  参考文献：
  名称：

  FUSED HETEROCYCLIC RING DERIVATIVE AND USE THEREOF

  摘要：

  公开号：

  EP2471793B1

文献信息

• US8614208B2
  申请人：——

  公开号：US8614208B2

  公开（公告）日：2013-12-24
• FUSED HETEROCYCLIC RING DERIVATIVE AND USE THEREOF
  申请人：Takeda Pharmaceutical Company Limited

  公开号：EP2471793B1

  公开（公告）日：2016-10-05
• Synthesis and evaluation of hedgehog signaling inhibitor with novel core system
  作者：Tomohiro Ohashi、Yuta Tanaka、Zenyu Shiokawa、Hiroshi Banno、Toshio Tanaka、Sachio Shibata、Yoshihiko Satoh、Hiroko Yamakawa、Yukiko Yamamoto、Harumi Hattori、Shigeru Kondo、Maki Miyamoto、Hideaki Tojo、Atsuo Baba、Satoshi Sasaki

  DOI：10.1016/j.bmc.2015.05.036

  日期：2015.8

  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.