ethyl 6-ethyl-1-methyl-3-(2,2,2-trifluoroethoxy)-5-{[(trifluoromethyl)sulfonyl]oxy}-1H-pyrrolo [3,2-b]pyridine-2-carboxylate | 1269028-94-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并吡啶类
• 英文名称: ethyl 6-ethyl-1-methyl-3-(2,2,2-trifluoroethoxy)-5-{[(trifluoromethyl)sulfonyl]oxy}-1H-pyrrolo [3,2-b]pyridine-2-carboxylate
• 英文别名: Ethyl 6-ethyl-1-methyl-3-(2,2,2-trifluoroethoxy)-5-(trifluoromethylsulfonyloxy)pyrrolo[3,2-b]pyridine-2-carboxylate；ethyl 6-ethyl-1-methyl-3-(2,2,2-trifluoroethoxy)-5-(trifluoromethylsulfonyloxy)pyrrolo[3,2-b]pyridine-2-carboxylate
• CAS: 1269028-94-5
• 化学式: C₁₆H₁₆F₆N₂O₆S
• 分子量: 478.369
• InChiKey: LHDQNEITAMKJTP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  31
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  105
• 氢给体数：
  0
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  ethyl 6-ethyl-1-methyl-3-(2,2,2-trifluoroethoxy)-5-{[(trifluoromethyl)sulfonyl]oxy}-1H-pyrrolo [3,2-b]pyridine-2-carboxylate 在 吡啶 、 盐酸 、 tris-(dibenzylideneacetone)dipalladium(0) 、 水 、 caesium carbonate 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 26.0h， 生成 6-ethyl-1-methyl-5-[(phenylcarbonyl)amino]-3-(2,2,2-trifluoroethoxy)-1H-pyrrolo[3,2-b]pyridine-2-carboxylic acid
  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：

  5-Ethylpyridin-2-carbonsaeureethylester 在 吡啶 、 盐酸 、 tris-(dibenzylideneacetone)dipalladium(0) 、 N-溴代丁二酰亚胺(NBS) 、 m-chloroperoxybenzoic acid 、 palladium 10% on activated carbon 、 水 、 氢气 、 sodium ethanolate 、 caesium carbonate 、 N,N-二异丙基乙胺 、 silver carbonate 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 、 三氟乙酸酐 作用下， 以 四氢呋喃 、 乙醇 、 N,N-二甲基甲酰胺 、 甲苯 、 乙腈 、 叔丁醇 为溶剂， 反应 125.0h， 生成 ethyl 6-ethyl-1-methyl-3-(2,2,2-trifluoroethoxy)-5-{[(trifluoromethyl)sulfonyl]oxy}-1H-pyrrolo [3,2-b]pyridine-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
• 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.