5-chloro-N-(2-hydroxyethyl)thiophene-2-carboxamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩类
• 英文名称: 5-chloro-N-(2-hydroxyethyl)thiophene-2-carboxamide
• 英文别名: 5-Chloro-N-(2-hydroxyethyl)-2-thiophenecarboxamide
• 化学式: C₇H₈ClNO₂S
• mdl: MFCD12177893
• 分子量: 205.665
• InChiKey: LNWYUJRYDSJJBL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  12
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.285
• 拓扑面积：
  77.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-chloro-N-(2-hydroxyethyl)thiophene-2-carboxamide 在 四丁基溴化铵 、 sodium hydroxide 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 7.5h， 生成 5-chloro-N-(2-(4-chloro-6-(4-(3-oxomorpholino)phenylamino)-1,3,5-triazin-2-yloxy)ethyl)thiophene-2-carboxamide
  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
• 作为产物：
  描述：

  2-氯噻吩-5-甲酸 、 C.I.酸性橙108 在 氯甲酸乙酯 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 1.25h， 以67%的产率得到5-chloro-N-(2-hydroxyethyl)thiophene-2-carboxamide
  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