4-(2,6-dichlorobenzoyl)-1H-pyrrole-2-carboxylic acid | 1096950-33-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-(2,6-dichlorobenzoyl)-1H-pyrrole-2-carboxylic acid
• CAS: 1096950-33-2
• 化学式: C₁₂H₇Cl₂NO₃
• mdl: MFCD11545663
• 分子量: 284.098
• InChiKey: ALEFSPISICVDFS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  70.2
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(2,6-dichlorobenzoyl)-1H-pyrrole-2-carboxylic acid 在 氯化亚砜 作用下， 以 N,N-二甲基乙酰胺 为溶剂， 生成
  参考文献：
  名称：

  The discovery and initial optimisation of pyrrole-2-carboxamides as inhibitors of p38α MAP kinase

  摘要：

  A novel pyrrole-2-carboxamide series of p38 alpha inhibitors, discovered through the application of virtual screening, is presented. Following evaluation of activity, selectivity and developability properties of commercially available analogues, a synthesis program enabled rapid assessment of the series' suitability for further lead optimisation studies. (c) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.05.011
• 作为产物：
  描述：

  2-吡咯甲酸甲酯 在 aluminum (III) chloride 、 lithium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 34.0h， 生成 4-(2,6-dichlorobenzoyl)-1H-pyrrole-2-carboxylic acid
  参考文献：
  名称：

  Identification of a novel orally bioavailable ERK5 inhibitor with selectivity over p38α and BRD4

  摘要：

  Extracellular regulated kinase 5 (ERK5) signalling has been implicated in driving a number of cellular phenotypes including endothelial cell angiogenesis and tumour cell motility. Novel ERK5 inhibitors were identified using high throughput screening, with a series of pyrrole-2-carboxamides substituted at the 4 position with an aroyl group being found to exhibit 1050 values in the micromolar range, but having no selectivity against p38 alpha MAP kinase. Truncation of the N-substituent marginally enhanced potency (similar to 3-fold) against ERK5, but importantly attenuated inhibition of p38 alpha. Systematic variation of the substituents on the aroyl group led to the selective inhibitor 4-(2-bromo-6-fluorobenzoy1)-N-(pyridin-3-yl)-1H-pyrrole-2-carboxamide (IC50 0.82 mu M for ERK5; IC50 > 120 mu M for p38 alpha). The crystal structure (PDB 5071) of this compound in complex with ERK5 has been solved. This compound was orally bioavailable and inhibited bFGF-driven Matrigel plug angiogenesis and tumour xenograft growth. The selective ERK5 inhibitor described herein provides a lead for further development into a tool compound for more extensive studies seeking to examine the role of ERK5 signalling in cancer and other diseases. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.05.057