(5-amino-4-(3-bromobenzoyl)-3-(2,4-dichlorophenyl)-1H-pyrrol-2-yl)(phenyl)methanone

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (5-amino-4-(3-bromobenzoyl)-3-(2,4-dichlorophenyl)-1H-pyrrol-2-yl)(phenyl)methanone
• 英文别名: [5-amino-4-(3-bromobenzoyl)-3-(2,4-dichlorophenyl)-1H-pyrrol-2-yl]-phenylmethanone
• 化学式: C₂₄H₁₅BrCl₂N₂O₂
• 分子量: 514.205
• InChiKey: OEIFBOMMVLNNCM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.5
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  76
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  3-溴苯酰乙腈 、 2,4-二氯苯甲醛 、 N-(2-氧代-2-苯基乙基)甲磺酰胺 在 potassium carbonate 作用下， 以 乙醇 为溶剂， 以25%的产率得到(5-amino-4-(3-bromobenzoyl)-3-(2,4-dichlorophenyl)-1H-pyrrol-2-yl)(phenyl)methanone
  参考文献：
  名称：

  Photoactivation provides a mechanistic explanation for pan-assay interference behaviour of 2-aminopyrroles in lipoxygenase inhibition

  摘要：

  Human 15-lipoxygenase-1 (h-15-LOX-1) is a promising drug target in inflammation and cancer. In this study substitution-oriented screening (SOS) has been used to identify compounds with a 2-aminopyrrole scaffold as inhibitors for h-15-LOX-1. The observed structure activity relationships (SAR) proved to be relatively flat. IC50's for the most potent inhibitor of the series did not surpass 6.3 mu M and the enzyme kinetics demonstrated uncompetitive inhibition. Based on this, we hypothesized that the investigated 2-aminopyrroles are pan assay interference compounds (PAINS) with photoactivation via a radical mechanism. Our results demonstrated clear photoactivation of h-15-LOX-1 inhibition under UV and visible light. In addition, the investigated 2-aminopyrroles decreased viability of cultured human hepatocarcinoma cells HCC-1.2 in a dose-dependent manner with LD50 ranging from 0.55 +/- 0.15 mu M (21B10) to 2.75 +/- 0.91 mu M (22). Taken together, this indicates that photoactivation can play an important role in the biological activity of compounds with a 2-amino-pyrrole scaffold as investigated here. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.07.047

文献信息

• Photoactivation provides a mechanistic explanation for pan-assay interference behaviour of 2-aminopyrroles in lipoxygenase inhibition
  作者：Hao Guo、Nikolaos Eleftheriadis、Nataliya Rohr-Udilova、Alexander Dömling、Frank J. Dekker

  DOI：10.1016/j.ejmech.2017.07.047

  日期：2017.10

  Human 15-lipoxygenase-1 (h-15-LOX-1) is a promising drug target in inflammation and cancer. In this study substitution-oriented screening (SOS) has been used to identify compounds with a 2-aminopyrrole scaffold as inhibitors for h-15-LOX-1. The observed structure activity relationships (SAR) proved to be relatively flat. IC50's for the most potent inhibitor of the series did not surpass 6.3 mu M and the enzyme kinetics demonstrated uncompetitive inhibition. Based on this, we hypothesized that the investigated 2-aminopyrroles are pan assay interference compounds (PAINS) with photoactivation via a radical mechanism. Our results demonstrated clear photoactivation of h-15-LOX-1 inhibition under UV and visible light. In addition, the investigated 2-aminopyrroles decreased viability of cultured human hepatocarcinoma cells HCC-1.2 in a dose-dependent manner with LD50 ranging from 0.55 +/- 0.15 mu M (21B10) to 2.75 +/- 0.91 mu M (22). Taken together, this indicates that photoactivation can play an important role in the biological activity of compounds with a 2-amino-pyrrole scaffold as investigated here. (C) 2017 Elsevier Masson SAS. All rights reserved.