4-(2-bromo-6-fluorobenzoyl)-N-(pyridin-3-yl)-1H-pyrrole-2-carboxamide

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-(2-bromo-6-fluorobenzoyl)-N-(pyridin-3-yl)-1H-pyrrole-2-carboxamide
• 英文别名: Erk5-IN-2；4-(2-bromo-6-fluorobenzoyl)-N-pyridin-3-yl-1H-pyrrole-2-carboxamide
• 化学式: C₁₇H₁₁BrFN₃O₂
• 分子量: 388.196
• InChiKey: ATKCERYALDNMPL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  74.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-吡咯甲酸甲酯 在 aluminum (III) chloride 、 lithium hydroxide 、 三氯化磷 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 34.08h， 生成 4-(2-bromo-6-fluorobenzoyl)-N-(pyridin-3-yl)-1H-pyrrole-2-carboxamide
  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

文献信息

• [EN] PYRROLCARBOXAMIDE DERIVATIVES FOR THE INHBITION OF ERK5<br/>[FR] DÉRIVÉS DE PYRROLCARBOXAMIDE POUR L'INHIBITION DE L'ERK5
  申请人：CANCER REC TECH LTD

  公开号：WO2016042341A1

  公开（公告）日：2016-03-24

  The invention provides compounds of formula (I) or a tautomer, stereoisomer, N-oxide, pharmaceutically acceptable salt or solvate thereof. The compounds are useful for the prophylaxis or treatment of a disease state or condition mediated by ERK5, in particular cancers.

  这项发明提供了式(I)的化合物或其互变异构体、立体异构体、N-氧化物、药用可接受的盐或溶剂。这些化合物对于预防或治疗由ERK5介导的疾病状态或病况，特别是癌症，具有用处。
• Pyrrolcarboxamide derivatives for the inhibition of ERK5
  申请人：CANCER RESEARCH TECHNOLOGY LIMITED

  公开号：US10344017B2

  公开（公告）日：2019-07-09

  The invention provides compounds of formula (I) or a tautomer, stereoisomer, N-oxide, pharmaceutically acceptable salt or solvate thereof. The compounds are useful for the prophylaxis or treatment of a disease state or condition mediated by ERK5, in particular cancers.

  本发明提供了式 (I) 的化合物 或其同系物、立体异构体、N-氧化物、药学上可接受的盐或溶液。这些化合物可用于预防或治疗由 ERK5 介导的疾病状态或病症，尤其是癌症。
• PYRROLCARBOXAMIDE DERIVATIVES FOR THE INHBITION OF ERK5
  申请人：Cancer Research Technology Ltd

  公开号：EP3194390A1

  公开（公告）日：2017-07-26
• PYRROLCARBOXAMIDE DERIVATIVES FOR THE INHIBITION OF ERK5
  申请人：CANCER RESEARCH TECHNOLOGY LIMITED

  公开号：US20180170911A1

  公开（公告）日：2018-06-21

  The invention provides compounds of formula (I) or a tautomer, stereoisomer, N-oxide, pharmaceutically acceptable salt or solvate thereof. The compounds are useful for the prophylaxis or treatment of a disease state or condition mediated by ERK5, in particular cancers.