1-[3-(1H-tetrazol-1-yl)phenyl]-3-(pyridin-3-yl)prop-2-en-1-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-[3-(1H-tetrazol-1-yl)phenyl]-3-(pyridin-3-yl)prop-2-en-1-one
• 英文别名: 3-Pyridin-3-yl-1-[3-(tetrazol-1-yl)phenyl]prop-2-en-1-one；3-pyridin-3-yl-1-[3-(tetrazol-1-yl)phenyl]prop-2-en-1-one
• 化学式: C₁₅H₁₁N₅O
• 分子量: 277.285
• InChiKey: XRTBMPAXQLKWTF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  21
• 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：
  73.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3-吡啶甲醛 、 1-[3-(1H-四唑-1-基)苯基]-乙酮 在 potassium hydroxide 作用下， 以 甲醇 为溶剂， 反应 24.33h， 以59%的产率得到1-[3-(1H-tetrazol-1-yl)phenyl]-3-(pyridin-3-yl)prop-2-en-1-one
  参考文献：
  名称：

  Novel tetrazole-based selective COX-2 inhibitors: Design, synthesis, anti-inflammatory activity, evaluation of PGE2, TNF-α, IL-6 and histopathological study

  摘要：

  To search for effective and selective COX-2 inhibitors, four novel series of tetrazole derivatives were designed based on bioisosteric replacement of SO₂NH₂ in celecoxib with tetrazole ring incorporating different central moieties as chalcone (2a-f), isoxazole (3a-c) or pyrazole (4a-c & 5a-c). Target tetrazoles were synthesized and their structures were confirmed by spectroscopic techniques and elemental analyses. All target compounds were more selective for COX-2 isozyme than COX-1 when compared to standard drugs indomethacin and celecoxib. Compounds 3b, 3c, 4b, 4c, 5b and 5c exhibited potent in vitro COX-2 inhibitory activity (IC₅₀ = 0.039-0.065 μM). Trimethoxy derivatives 3c, 4c and 5c acquired superior COX-2 selectivity index values (SI = 297.67-317.95) and were 1.1 fold higher than celecoxib (SI = 282.22). The most active six compounds were evaluated for their in vivo anti-inflammatory activity and serum levels of PGE₂, TNF-α and IL-6 in addition to their ulcerogenic liability and histopathological profile. At a dose of 50 mg/Kg, compounds 3c and 5c showed better anti-inflammatory activity (% edema inhibition = 29.209-42.643) than celecoxib (% edema inhibition = 28.694-40.114) at different time intervals and were less ulcerogenic (UI = 0.123 and 0.11 in sequent) than celecoxib (UI = 0.167). Also, they displayed potent inhibitory effect on the production of PGE₂ (% inhibition = 81.042 and 82.724 in sequent) greater than celecoxib (% inhibition = 79.666). Compound 5c decreased rat serum concentrations of both TNF-α (% inhibition = 55.349) and IL-6 (% inhibition = 61.561) in a comparable or better activity to celecoxib as reference drug. Finally, docking poses of the most active compounds showed strong binding interactions and effective overall docking energy scores explaining their remarkable COX-2 inhibitory activity.

  DOI：

  10.1016/j.bioorg.2020.104308

文献信息

• Novel tetrazole-based selective COX-2 inhibitors: Design, synthesis, anti-inflammatory activity, evaluation of PGE2, TNF-α, IL-6 and histopathological study
  作者：Madlen B. Labib、Ahmed M. Fayez、EL-Shaymaa EL-Nahass、M. Awadallah、Peter A. Halim

  DOI：10.1016/j.bioorg.2020.104308

  日期：2020.11

  To search for effective and selective COX-2 inhibitors, four novel series of tetrazole derivatives were designed based on bioisosteric replacement of SO₂NH₂ in celecoxib with tetrazole ring incorporating different central moieties as chalcone (2a-f), isoxazole (3a-c) or pyrazole (4a-c & 5a-c). Target tetrazoles were synthesized and their structures were confirmed by spectroscopic techniques and elemental analyses. All target compounds were more selective for COX-2 isozyme than COX-1 when compared to standard drugs indomethacin and celecoxib. Compounds 3b, 3c, 4b, 4c, 5b and 5c exhibited potent in vitro COX-2 inhibitory activity (IC₅₀ = 0.039-0.065 μM). Trimethoxy derivatives 3c, 4c and 5c acquired superior COX-2 selectivity index values (SI = 297.67-317.95) and were 1.1 fold higher than celecoxib (SI = 282.22). The most active six compounds were evaluated for their in vivo anti-inflammatory activity and serum levels of PGE₂, TNF-α and IL-6 in addition to their ulcerogenic liability and histopathological profile. At a dose of 50 mg/Kg, compounds 3c and 5c showed better anti-inflammatory activity (% edema inhibition = 29.209-42.643) than celecoxib (% edema inhibition = 28.694-40.114) at different time intervals and were less ulcerogenic (UI = 0.123 and 0.11 in sequent) than celecoxib (UI = 0.167). Also, they displayed potent inhibitory effect on the production of PGE₂ (% inhibition = 81.042 and 82.724 in sequent) greater than celecoxib (% inhibition = 79.666). Compound 5c decreased rat serum concentrations of both TNF-α (% inhibition = 55.349) and IL-6 (% inhibition = 61.561) in a comparable or better activity to celecoxib as reference drug. Finally, docking poses of the most active compounds showed strong binding interactions and effective overall docking energy scores explaining their remarkable COX-2 inhibitory activity.