2-ethyl-N-[1-(hydroxyacetyl)piperidin-4-yl]-7-methyl-4-oxo-5-(2,2,2-trifluoroethoxy)-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidine-6-carboxamide | 1269118-55-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶并嘧啶类
• 英文名称: 2-ethyl-N-[1-(hydroxyacetyl)piperidin-4-yl]-7-methyl-4-oxo-5-(2,2,2-trifluoroethoxy)-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidine-6-carboxamide
• 英文别名: 2-ethyl-N-[1-(2-hydroxyacetyl)piperidin-4-yl]-7-methyl-4-oxo-5-(2,2,2-trifluoroethoxy)-3H-pyrrolo[2,3-d]pyrimidine-6-carboxamide
• CAS: 1269118-55-9
• 化学式: C₁₉H₂₄F₃N₅O₅
• 分子量: 459.425
• InChiKey: VJLZIYPJHZVQFH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  125
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  2-ethyl-N-[1-(hydroxyacetyl)piperidin-4-yl]-7-methyl-4-oxo-5-(2,2,2-trifluoroethoxy)-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidine-6-carboxamide 、 2-溴-4'-氟苯乙酮 在 potassium carbonate 作用下， 以 乙二醇二甲醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 以41%的产率得到2-ethyl-3-[2-(4-fluorophenyl)-2-oxoethyl]-N-[1-(hydroxyacetyl)piperidin-4-yl]-7-methyl-4-oxo-5-(2,2,2-trifluoroethoxy)-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidine-6-carboxamide
  参考文献：
  名称：

  FUSED HETEROCYCLIC RING DERIVATIVE AND USE THEREOF

  摘要：

  公开号：

  EP2471793B1
• 作为产物：
  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 、 1-羟基苯并三唑 、 溶剂黄146 、 三乙胺 、 sodium hydroxide 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 11.25h， 生成 2-ethyl-N-[1-(hydroxyacetyl)piperidin-4-yl]-7-methyl-4-oxo-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

文献信息

• US8614208B2
  申请人：——

  公开号：US8614208B2

  公开（公告）日：2013-12-24