Methyl 7-(3-(3-tert-butyl-1-p-tolyl-1h-pyrazol-5-yl)ureido)-1h-indole-2-carboxylate | 1415484-15-9

• 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: Methyl 7-(3-(3-tert-butyl-1-p-tolyl-1h-pyrazol-5-yl)ureido)-1h-indole-2-carboxylate
• 英文别名: methyl 7-[[5-tert-butyl-2-(4-methylphenyl)pyrazol-3-yl]carbamoylamino]-1H-indole-2-carboxylate
• CAS: 1415484-15-9
• 化学式: C₂₅H₂₇N₅O₃
• 分子量: 445.521
• InChiKey: WXXRKUKOZYLHRQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.39
• 重原子数：
  33.0
• 可旋转键数：
  4.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  101.04
• 氢给体数：
  3.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  Methyl 7-(3-(3-tert-butyl-1-p-tolyl-1h-pyrazol-5-yl)ureido)-1h-indole-2-carboxylate 在 甲醇 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 sodium hydroxide 作用下， 以 N-甲基吡咯烷酮 为溶剂， 反应 6.0h， 生成 1-[5-tert-butyl-2-(4-methylphenyl)pyrazol-3-yl]-3-[2-(2,7-diazaspiro[4.4]nonane-2-carbonyl)-1H-indol-7-yl]urea
  参考文献：
  名称：

  Identification of novel series of pyrazole and indole-urea based DFG-out PYK2 inhibitors

  摘要：

  Previous drug discovery efforts identified classical PYK2 kinase inhibitors such as 2 and 3 that possess selectivity for PYK2 over its intra-family isoform FAK. Efforts to identify more kinome-selective chemical matter that stabilize a DFG-out conformation of the enzyme are described herein. Two sub-series of PYK2 inhibitors, an indole carboxamide-urea and a pyrazole-urea have been identified and found to have different binding interactions with the hinge region of PYK2. These leads proved to be more selective than the original classical inhibitors. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.10.039
• 作为产物：
  描述：

  2,2,2-三氯乙基 3-叔丁基-1-(4-甲基苯基)-1H-吡唑-5-基氨基甲酸酯 、 甲基7-氨基-1H-吲哚-2-羧酸酯 在 N,N-二异丙基乙胺 作用下， 以 二甲基亚砜 为溶剂， 反应 12.0h， 以81%的产率得到Methyl 7-(3-(3-tert-butyl-1-p-tolyl-1h-pyrazol-5-yl)ureido)-1h-indole-2-carboxylate
  参考文献：
  名称：

  Identification of novel series of pyrazole and indole-urea based DFG-out PYK2 inhibitors

  摘要：

  Previous drug discovery efforts identified classical PYK2 kinase inhibitors such as 2 and 3 that possess selectivity for PYK2 over its intra-family isoform FAK. Efforts to identify more kinome-selective chemical matter that stabilize a DFG-out conformation of the enzyme are described herein. Two sub-series of PYK2 inhibitors, an indole carboxamide-urea and a pyrazole-urea have been identified and found to have different binding interactions with the hinge region of PYK2. These leads proved to be more selective than the original classical inhibitors. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.10.039