4-(2,6-difluorobenzoyl)-1H-pyrrole-2-carboxylic acid

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-(2,6-difluorobenzoyl)-1H-pyrrole-2-carboxylic acid
• 化学式: C₁₂H₇F₂NO₃
• mdl: MFCD11545652
• 分子量: 251.189
• InChiKey: WEFTWJFPDFSXFK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 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：
  5

反应信息

• 作为反应物：
  描述：

  4-氨基吡啶 、 4-(2,6-difluorobenzoyl)-1H-pyrrole-2-carboxylic acid 在 N,N'-羰基二咪唑 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 生成 4-(2,6-difluorobenzoyl)-N-(pyridin-4-yl)-1H-pyrrole-2-carboxamide
  参考文献：
  名称：

  [EN] PYRROLCARBOXAMIDE DERIVATIVES FOR THE INHBITION OF ERK5
  [FR] DÉRIVÉS DE PYRROLCARBOXAMIDE POUR L'INHIBITION DE L'ERK5

  摘要：

  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。

  公开号：

  WO2016042341A1
• 作为产物：
  描述：

  2-吡咯甲酸甲酯 在 aluminum (III) chloride 、 水 、 lithium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 38.5h， 生成 4-(2,6-difluorobenzoyl)-1H-pyrrole-2-carboxylic acid
  参考文献：
  名称：

  [EN] PYRROLCARBOXAMIDE DERIVATIVES FOR THE INHBITION OF ERK5
  [FR] DÉRIVÉS DE PYRROLCARBOXAMIDE POUR L'INHIBITION DE L'ERK5

  摘要：

  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。

  公开号：

  WO2016042341A1

文献信息

• [EN] P38 KINASE INHIBITING AGENTS<br/>[FR] AGENTS INHIBITEURS DE LA P38 KINASE
  申请人：MERCK SHARP & DOHME

  公开号：WO2010129208A1

  公开（公告）日：2010-11-11

  Compounds described by the chemical formula (I) or pharmaceutically acceptable salts thereof: Formula (I); are inhibitors of p38 and are useful in the treatment of inflammation such as in the treatment of asthma, COPD, ARDS, rheumatoid arthritis, rheumatoid spondylitis, osteoarthritis, gouty arthritis and other arthritic conditions; inflamed joints, eczema, psoriasis or other inflammatory skin conditions such as sunburn; inflammatory eye conditions including conjunctivitis; pyresis, pain and other conditions associated with inflammation.

  化学式(I)描述的化合物或其药用可接受的盐：化学式(I)；是p38的抑制剂，对于治疗炎症如哮喘、慢性阻塞性肺病（COPD）、急性呼吸窘迫综合征（ARDS）、类风湿关节炎、类风湿脊柱炎、骨关节炎、痛风性关节炎和其他关节炎症状；炎症性关节、湿疹、牛皮癣或其他炎症性皮肤病如晒伤；包括结膜炎在内的炎症性眼部疾病；发热、疼痛和其他与炎症相关的症状中有用。
• P38 KINASE INHIBITING AGENTS
  申请人：Sahoo Soumya P.

  公开号：US20090325953A1

  公开（公告）日：2009-12-31

  Compounds described by the chemical formula (I) or pharmaceutically acceptable salts thereof: are inhibitors of p38 and are useful in the treatment of inflammation such as in the treatment of asthma, COPD, ARDS, rheumatoid arthritis, rheumatoid spondylitis, osteoarthritis, gouty arthritis and other arthritic conditions; inflamed joints, eczema, psoriasis or other inflammatory skin conditions such as sunburn; inflammatory eye conditions including conjunctivitis; pyresis, pain and other conditions associated with inflammation.

  化学式（I）或其药学上可接受的盐所描述的化合物：它们是p38的抑制剂，可用于治疗炎症，如哮喘、COPD、ARDS、类风湿关节炎、类风湿脊柱炎、骨关节炎、痛风性关节炎和其他关节炎症状；发炎的关节、湿疹、牛皮癣或其他炎症性皮肤状况，如晒伤；炎症性眼部状况，包括结膜炎；发热、疼痛和其他与炎症有关的状况。
• PYRROLO [2,3-C] PYRIDINE DERIVATIVES AS P38 KINEASE INHIBITING AGENTS
  申请人：Sahoo Soumya P.

  公开号：US20110105430A1

  公开（公告）日：2011-05-05

  Compounds described by the chemical formula (I) or pharmaceutically acceptable salts thereof: (A) are inhibitors N of p38 and are useful in the treatment of inflammation such as in the treatment of asthma, rheumatoid arthritis, rheumatoid spondylitis, osteoarthritis, gouty arthritis and other arthritic conditions; inflamed joints, eczema, psoriasis or other inflammatory skin conditions such as sunburn; inflammatory eye conditions including conjunctivitis; pyresis, pain and other conditions associated with inflammation.

  化学式（I）描述的化合物或其药学上可接受的盐：（A）是p38的抑制剂，可用于治疗炎症，例如哮喘、类风湿性关节炎、类风湿性脊柱炎、骨关节炎、痛风性关节炎和其他关节炎症状；炎症关节、湿疹、牛皮癣或其他炎症性皮肤病，如晒伤；炎症性眼部疾病，包括结膜炎；与炎症相关的发热、疼痛和其他症状。
• 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。
• Identification of a novel orally bioavailable ERK5 inhibitor with selectivity over p38α and BRD4
  作者：Stephanie M. Myers、Duncan C. Miller、Lauren Molyneux、Mercedes Arasta、Ruth H. Bawn、Timothy J. Blackburn、Simon J. Cook、Noel Edwards、Jane A. Endicott、Bernard T. Golding、Roger J. Griffin、Tim Hammonds、Ian R. Hardcastle、Suzannah J. Harnor、Amy B. Heptinstall、Pamela A. Lochhead、Mathew P. Martin、Nick C. Martin、David R. Newell、Paul J. Owen、Leon C. Pang、Tristan Reuillon、Laurent J.M. Rigoreau、Huw D. Thomas、Julie A. Tucker、Lan-Zhen Wang、Ai-Ching Wong、Martin E.M. Noble、Stephen R. Wedge、Celine Cano

  DOI：10.1016/j.ejmech.2019.05.057

  日期：2019.9

  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.