1-[(5-甲基-3-吡啶基)甲基]哌嗪 | 182354-90-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 中文名称: 1-[(5-甲基-3-吡啶基)甲基]哌嗪
• 中文别名: D-脯氨酸,3-羟基-,乙基酯,(3S)-rel-
• 英文名称: 1-[(5-Methylpyridin-3-YL)methyl]piperazine
• CAS: 182354-90-1
• 化学式: C₁₁H₁₇N₃
• 分子量: 191.276
• InChiKey: OBCVMHQQPMNEBP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  28.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-chloro-1-(4-chlorobenzyl)-1H-indole-2-carboxylic acid 、 1-[(5-甲基-3-吡啶基)甲基]哌嗪 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.25h， 以72%的产率得到(5-chloro-1-(4-chlorobenzyl)-1H-indol-2-yl)(4-((5-methylpyridin-3-yl)methyl)piperazin-1-yl) methanone
  参考文献：
  名称：

  Design, synthesis, biological evaluation and docking study of novel indole-2-amide as anti-inflammatory agents with dual inhibition of COX and 5-LOX

  摘要：

  In this work, a series of novel indole-2-amide compounds were designed, synthesized, characterized and the anti-inflammatory activity in vivo were evaluated. Compounds 8a, 10b, 12h, and 121 exhibited marked anti-inflammatory activity in 2,4-Dinitrofluorobenzenethe (DNFB) - induced mice auricle edema model. Further, compounds 8a, 10b and 12h exhibited potential in vitro COX-2 inhibitory activity (IC50 = 21.86, 233 and 23.21 nM, respectively), while the reference drug celecoxib was 11.20 nM. The most promising compound 10b was exhibited the highest selectivity for COX-2 (selectivity index (COX-1/COX-2) = 17.45) and moderate 5-LOX inhibitory activity (IC50 = 66 nM), which comparable to positive controlled zileuton (IC50 = 38.91 nM). In addition, the test results showed compounds 10b and 12h no significant cytotoxic activity on normal cells (RAW264.7). Further, at the active sites of the COX-1, COX-2 co crystals, 3b and 41 showed higher binding forces in the molecular docking study, which consistent with the results of in vitro experiments. These results demonstrated that these compounds had dual inhibitory activity of COX/5-LOX, providing clues for further searching for safer and more effective anti-inflammatory drugs. (C) 2019 Published by Elsevier Masson SAS.

  DOI：

  10.1016/j.ejmech.2019.07.004

文献信息

• [EN] ORGANIC COMPOUNDS<br/>[FR] COMPOSÉS ORGANIQUES
  申请人：NOVARTIS AG

  公开号：WO2009087212A2

  公开（公告）日：2009-07-16

  Compounds of formula (I) in free or salt or solvate form, are useful for treating inflammatory or obstructive airways, pulmonary hypertension, pulmonary fibrosis, liver fibrosis, muscle diseases and systemic skeletal disorders. Pharmaceutical compositions that contain the compounds and processes for preparing the compounds are also described.
• Design, synthesis, biological evaluation and docking study of novel indole-2-amide as anti-inflammatory agents with dual inhibition of COX and 5-LOX
  作者：Yuanzheng Huang、Bin Zhang、Jiaming Li、Huicai Liu、Yanchun Zhang、Zhang Yang、Wandong Liu

  DOI：10.1016/j.ejmech.2019.07.004

  日期：2019.10

  In this work, a series of novel indole-2-amide compounds were designed, synthesized, characterized and the anti-inflammatory activity in vivo were evaluated. Compounds 8a, 10b, 12h, and 121 exhibited marked anti-inflammatory activity in 2,4-Dinitrofluorobenzenethe (DNFB) - induced mice auricle edema model. Further, compounds 8a, 10b and 12h exhibited potential in vitro COX-2 inhibitory activity (IC50 = 21.86, 233 and 23.21 nM, respectively), while the reference drug celecoxib was 11.20 nM. The most promising compound 10b was exhibited the highest selectivity for COX-2 (selectivity index (COX-1/COX-2) = 17.45) and moderate 5-LOX inhibitory activity (IC50 = 66 nM), which comparable to positive controlled zileuton (IC50 = 38.91 nM). In addition, the test results showed compounds 10b and 12h no significant cytotoxic activity on normal cells (RAW264.7). Further, at the active sites of the COX-1, COX-2 co crystals, 3b and 41 showed higher binding forces in the molecular docking study, which consistent with the results of in vitro experiments. These results demonstrated that these compounds had dual inhibitory activity of COX/5-LOX, providing clues for further searching for safer and more effective anti-inflammatory drugs. (C) 2019 Published by Elsevier Masson SAS.