4-(4-(4-chloro-6-(4-methoxyphenylamino)-1,3,5-triazin-2-ylamino)phenyl)morpholin-3-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 恶嗪烷类
• 英文名称: 4-(4-(4-chloro-6-(4-methoxyphenylamino)-1,3,5-triazin-2-ylamino)phenyl)morpholin-3-one
• 英文别名: 4-[4-[[4-Chloro-6-(4-methoxyanilino)-1,3,5-triazin-2-yl]amino]phenyl]morpholin-3-one；4-[4-[[4-chloro-6-(4-methoxyanilino)-1,3,5-triazin-2-yl]amino]phenyl]morpholin-3-one
• 化学式: C₂₀H₁₉ClN₆O₃
• 分子量: 426.862
• InChiKey: HMLAPCMRJADLSK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  102
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  甲氧苯胺 以 丙酮 、 乙腈 为溶剂， 反应 5.0h， 生成 4-(4-(4-chloro-6-(4-methoxyphenylamino)-1,3,5-triazin-2-ylamino)phenyl)morpholin-3-one
  参考文献：
  名称：

  Tailoring the Substitution Pattern on 1,3,5-Triazine for Targeting Cyclooxygenase-2: Discovery and Structure–Activity Relationship of Triazine–4-Aminophenylmorpholin-3-one Hybrids that Reverse Algesia and Inflammation in Swiss Albino Mice

  摘要：

  Here, we report analgesic and anti-inflammatory activity of a series of compounds obtained by appending 4-aminophenylmorpholin-3-one and acyclic, cyclic, or hetero-cyclic moieties on 1,3,5-triazine. The structures of compounds 4b and 6b are optimized for the best inhibition of COX-2 with IC50 values of 0.06 and 0.08 mu M, respectively, and selectivity over COX-1 of 166 and >125, respectively. At the dose of 5 mg kg(-1), these compounds significantly reduced acetic acid induced writhings, and their ED50 values were found to be 2.2 and 1.9 mg kg(-1), respectively. Besides the cell-based and animal-based experiments showing the modes of action of these compounds targeting COX-2, the interaction behavior of 4b with COX-2 was also characterized, with physicochemical experiments including ITC, NMR, UV-vis, and molecular-modeling studies. Characteristically, these compounds interact with R120, Y355, and W385, the residues responsible for holding the substrate and mediating the process of electron transfer during the metabolic phase of the enzyme.

  DOI：

  10.1021/acs.jmedchem.8b00922

文献信息

• Tailoring the Substitution Pattern on 1,3,5-Triazine for Targeting Cyclooxygenase-2: Discovery and Structure–Activity Relationship of Triazine–4-Aminophenylmorpholin-3-one Hybrids that Reverse Algesia and Inflammation in Swiss Albino Mice
  作者：Palwinder Singh、Sukhmeet Kaur、Priya Kumari、Baljit Kaur、Manpreet Kaur、Gurjit Singh、Rajbir Bhatti、Manpreet Bhatti

  DOI：10.1021/acs.jmedchem.8b00922

  日期：2018.9.13

  Here, we report analgesic and anti-inflammatory activity of a series of compounds obtained by appending 4-aminophenylmorpholin-3-one and acyclic, cyclic, or hetero-cyclic moieties on 1,3,5-triazine. The structures of compounds 4b and 6b are optimized for the best inhibition of COX-2 with IC50 values of 0.06 and 0.08 mu M, respectively, and selectivity over COX-1 of 166 and >125, respectively. At the dose of 5 mg kg(-1), these compounds significantly reduced acetic acid induced writhings, and their ED50 values were found to be 2.2 and 1.9 mg kg(-1), respectively. Besides the cell-based and animal-based experiments showing the modes of action of these compounds targeting COX-2, the interaction behavior of 4b with COX-2 was also characterized, with physicochemical experiments including ITC, NMR, UV-vis, and molecular-modeling studies. Characteristically, these compounds interact with R120, Y355, and W385, the residues responsible for holding the substrate and mediating the process of electron transfer during the metabolic phase of the enzyme.