N-((1-(2-chlorophenyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(1H-indol-3-yl)-2-oxoacetamide | 1456936-31-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: N-((1-(2-chlorophenyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(1H-indol-3-yl)-2-oxoacetamide
• 英文别名: N-[[1-(2-chlorophenyl)triazol-4-yl]methyl]-2-(1H-indol-3-yl)-2-oxoacetamide
• CAS: 1456936-31-4
• 化学式: C₁₉H₁₄ClN₅O₂
• 分子量: 379.805
• InChiKey: BROCFJBHUJPFGH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  92.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  吲哚-3-乙醛酰氯 在 copper(l) iodide 、 五甲基二乙烯三胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 6.0h， 生成 N-((1-(2-chlorophenyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(1H-indol-3-yl)-2-oxoacetamide
  参考文献：
  名称：

  One-pot three-component synthesis of indole-3-glyoxyl derivatives and indole-3-glyoxyl triazoles

  摘要：

  A general and efficient reaction of indole with oxalyl chloride and nucleophiles providing indole-3-glyoxyl derivatives has been developed in mild conditions. In the same fashion, the other reaction involved the addition of organic azides leading to the synthesis of indole-3-glyoxyl-1,2,3-triazoles, which proceeds smoothly generating the products in moderate to high yields. (c) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2013.08.064

文献信息

• 1,2,3-triazole tethered Indole-3-glyoxamide derivatives as multiple inhibitors of 5-LOX, COX-2 & tubulin: Their anti-proliferative & anti-inflammatory activity
  作者：Fatima Naaz、M.C. Preeti Pallavi、Syed Shafi、Naveen Mulakayala、M. Shahar Yar、H.M. Sampath Kumar

  DOI：10.1016/j.bioorg.2018.07.029

  日期：2018.12

  To evaluate the role of COX-2 and 5-LOX as dual inhibitors in controlling the cancer cell proliferation, a set of two series having 42 compounds of 1, 2, 3-Tethered Indole-3-glyoxamide derivatives were synthesized by employing click chemistry approach and were also evaluated for their in vitro cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX) inhibitory activities with in vivo anti-inflammatory and in vitro anti-proliferative potencies. Among the compounds tested, compounds 11q and 13s displayed excellent inhibition of COX-2 (IC50 0.12 mu M) with good COX-2 selectivity index (COX-2/COX-1) of 0.058 and 0.046 respectively. Compounds 11q and 13s also demonstrated comparable 5-LOX inhibitory activity with IC50 7.73 and 7.43 mu M respectively to that of standard Norhihydroguaiaretic acid (NDGA: IC50 7.31 mu M). Among all the selected cell lines, prostate cancer cell line DU145 was found to be susceptible to this class of compounds. Among all the tested compounds, compounds 11g, 11i, 11k, 11q, 13r, 13s and 13u demonstrated excellent to moderate anti-proliferative activity with IC50s ranging between 6.29 and 18.53 mu M. Compounds 11q and 11g demonstrated better anti-proliferative activities against DU145 cancer cell line with IC50 values 8.17 and 8.69 mu M respectively when compared to the standard drug etoposide (VP16; IC50 9.80 mu M). Compounds 11g, 11k, 11q, 13s and 13u showed good dual COX-2/5-LOX inhibitory potentials with excellent anti-proliferative activity. Results from carrageenan-induced hind paw edema demonstrated that compounds 11b, 11l, 11q and 13q exhibited significant anti-inflammatory activity with 69-77% inhibition at 3 h, 75-82% inhibition at 5 h when compared to the standard drug indomethacin (66.6% at 3 h and 77.94% at 5 h). Ulcerogenic study revealed that compounds 11q and 13q did not cause any gastric ulceration. In vitro tubulin assay resuted that compound 11q interfered with microtubulin dynamic and act as tubulin polymerization inhibitor. In silico molecular docking studies demonstrated that compounds 11q and 13s are occupying the colchicines binding site of tubulin polymer and 11q illustrated very good binding affinities towards COX-2 and 5-LOX.