(E)-4-(3-benzoyl-1H-pyrrol-1-yl)-2-nitrobenzaldoxime | 1594782-18-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (E)-4-(3-benzoyl-1H-pyrrol-1-yl)-2-nitrobenzaldoxime
• 英文别名: [1-[4-[(E)-hydroxyiminomethyl]-3-nitrophenyl]pyrrol-3-yl]-phenylmethanone
• CAS: 1594782-18-9
• 化学式: C₁₈H₁₃N₃O₄
• 分子量: 335.319
• InChiKey: QSRCHKWRYFMICX-YBFXNURJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  25
• 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：
  100
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-(3-benzoyl-1H-pyrrol-1-yl)-2-nitrobenzaldehyde 在 盐酸羟胺 、 sodium acetate 作用下， 以 乙醇 为溶剂， 反应 4.0h， 以47%的产率得到(E)-4-(3-benzoyl-1H-pyrrol-1-yl)-2-nitrobenzaldoxime
  参考文献：
  名称：

  Decreasing acidity in a series of aldose reductase inhibitors: 2-Fluoro-4-(1H-pyrrol-1-yl)phenol as a scaffold for improved membrane permeation

  摘要：

  Targeting long-term diabetic complications, as well as inflammatory pathologies, aldose reductase inhibitors (ARIs) have been gaining attention over the years. In the present work, in order to address the poor membrane permeation of previously reported ARIs, derivatives of N-phenylpyrrole, bearing groups with putative pK(a) >= 7.4, were synthesized and evaluated for aldose reductase inhibitory activity. The 2-fluorophenol group proved the most promising moiety, and further modifications were explored. The most active compound (31), identified as a submicromolar inhibitor (IC50 = 0.443 mu M), was also selective against the homologous enzyme aldehyde reductase. Cross-docking revealed that 31 displays a peculiar interaction network that may be responsible for high affinity. Physicochemical profiling of 31 showed a pK(a) of 7.64, rendering it less than 50% ionized in the physiological pH range, with potentially favorable membrane permeation. The latter was supported from the successful inhibition of sorbitol formation in rat lenses and the ability to permeate rat jejunum. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.02.016

文献信息

• Decreasing acidity in a series of aldose reductase inhibitors: 2-Fluoro-4-(1H-pyrrol-1-yl)phenol as a scaffold for improved membrane permeation
  作者：Maria Chatzopoulou、Alexandros Patsilinakos、Theodosia Vallianatou、Marta Soltesova Prnova、Simon Žakelj、Rino Ragno、Milan Stefek、Albin Kristl、Anna Tsantili-Kakoulidou、Vassilis J. Demopoulos

  DOI：10.1016/j.bmc.2014.02.016

  日期：2014.4

  Targeting long-term diabetic complications, as well as inflammatory pathologies, aldose reductase inhibitors (ARIs) have been gaining attention over the years. In the present work, in order to address the poor membrane permeation of previously reported ARIs, derivatives of N-phenylpyrrole, bearing groups with putative pK(a) >= 7.4, were synthesized and evaluated for aldose reductase inhibitory activity. The 2-fluorophenol group proved the most promising moiety, and further modifications were explored. The most active compound (31), identified as a submicromolar inhibitor (IC50 = 0.443 mu M), was also selective against the homologous enzyme aldehyde reductase. Cross-docking revealed that 31 displays a peculiar interaction network that may be responsible for high affinity. Physicochemical profiling of 31 showed a pK(a) of 7.64, rendering it less than 50% ionized in the physiological pH range, with potentially favorable membrane permeation. The latter was supported from the successful inhibition of sorbitol formation in rat lenses and the ability to permeate rat jejunum. (C) 2014 Elsevier Ltd. All rights reserved.