N-(2-(5-methoxy-1H-indol-3-yl)ethyl)-2-(3-(4-methoxyphenyl)-4,5-dihydroisoxazol-5-yl)acetamide | 1352954-49-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: N-(2-(5-methoxy-1H-indol-3-yl)ethyl)-2-(3-(4-methoxyphenyl)-4,5-dihydroisoxazol-5-yl)acetamide
• 英文别名: N-[2-(5-methoxy-1H-indol-3-yl)ethyl]-2-[3-(4-methoxyphenyl)-4,5-dihydro-1,2-oxazol-5-yl]acetamide
• CAS: 1352954-49-4
• 化学式: C₂₃H₂₅N₃O₄
• 分子量: 407.469
• InChiKey: XGGVZCGUKMLSLV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  30
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  84.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  对甲氧基苯甲醛肟 在 N-氯代丁二酰亚胺 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 53.0h， 生成 N-(2-(5-methoxy-1H-indol-3-yl)ethyl)-2-(3-(4-methoxyphenyl)-4,5-dihydroisoxazol-5-yl)acetamide
  参考文献：
  名称：

  Synthesis and bio-evaluation of human macrophage migration inhibitory factor inhibitor to develop anti-inflammatory agent

  摘要：

  Macrophage migration inhibitory factor (MIF), a pro-inflammatory cytokine, is involved in the development of an array of inflammatory disorders including rheumatoid arthritis, inflammatory bowel disease, psoriasis, multiple sclerosis and sepsis. The synthesis of MIF-inhibitor is a rationale approach to develop novel anti-inflammatory agent to treat multitude of inflammatory diseases. In this work, we have synthesized and evaluated MIF-inhibitory activity of a series of small molecules containing isoxazoline skeleton. Mode of binding of this inhibitor to human MIF (huMIF) was determined by docking studies. The synthesized molecules inhibit tautomerase activity of huMIF. The anti-inflammatory activity of the most active inhibitor, 4-((3-(4-hydroxy-3-methoxyphenyl)-4, 5-dihydroisoxazol-5-yl) methoxy) benzaldehyde (4b) was evaluated against huMIF-induced inflammation in a cellular model (RAW 264.7 cell). Compound 4b significantly inhibits huMIF-mediated NF-kappa B translocation to the nucleus, up-regulation of inducible nitric oxide synthase and nitric oxide production in RAW 264.7 cell which are the markers for inflammation. The compound 4b is not cytotoxic as evident from cell viability assay. Hence, the compound 4b has potential to be a novel anti-inflammatory agent. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.10.056

文献信息

• Synthesis and bio-evaluation of human macrophage migration inhibitory factor inhibitor to develop anti-inflammatory agent
  作者：Athar Alam、Chinmay Pal、Manish Goyal、Milan Kumar Kundu、Rahul Kumar、Mohd Shameel Iqbal、Sumanta Dey、Samik Bindu、Souvik Sarkar、Uttam Pal、Nakul C. Maiti、Susanta Adhikari、Uday Bandyopadhyay

  DOI：10.1016/j.bmc.2011.10.056

  日期：2011.12

  Macrophage migration inhibitory factor (MIF), a pro-inflammatory cytokine, is involved in the development of an array of inflammatory disorders including rheumatoid arthritis, inflammatory bowel disease, psoriasis, multiple sclerosis and sepsis. The synthesis of MIF-inhibitor is a rationale approach to develop novel anti-inflammatory agent to treat multitude of inflammatory diseases. In this work, we have synthesized and evaluated MIF-inhibitory activity of a series of small molecules containing isoxazoline skeleton. Mode of binding of this inhibitor to human MIF (huMIF) was determined by docking studies. The synthesized molecules inhibit tautomerase activity of huMIF. The anti-inflammatory activity of the most active inhibitor, 4-((3-(4-hydroxy-3-methoxyphenyl)-4, 5-dihydroisoxazol-5-yl) methoxy) benzaldehyde (4b) was evaluated against huMIF-induced inflammation in a cellular model (RAW 264.7 cell). Compound 4b significantly inhibits huMIF-mediated NF-kappa B translocation to the nucleus, up-regulation of inducible nitric oxide synthase and nitric oxide production in RAW 264.7 cell which are the markers for inflammation. The compound 4b is not cytotoxic as evident from cell viability assay. Hence, the compound 4b has potential to be a novel anti-inflammatory agent. (C) 2011 Elsevier Ltd. All rights reserved.