N-[3-(3-bromophenylamino)-4-pyridinyl]trifluoromethanesulfonamide | 1189641-70-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-[3-(3-bromophenylamino)-4-pyridinyl]trifluoromethanesulfonamide
• 英文别名: N-[3-(3-bromophenylamino)pyridin-4-yl]trifluoromethanesulfonamide；N-[3-(3-bromoanilino)pyridin-4-yl]-1,1,1-trifluoromethanesulfonamide
• CAS: 1189641-70-0
• 化学式: C₁₂H₉BrF₃N₃O₂S
• 分子量: 396.188
• InChiKey: WYMPMNZWERFHGE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  79.5
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  N-[3-(3-bromophenylamino)-4-pyridinyl]trifluoromethanesulfonamide 、 copper(l) cyanide 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 以47%的产率得到N-[3-(3-cyanophenylamino)pyridin-4-yl]trifluoromethanesulfonamide
  参考文献：
  名称：

  N-(3-Arylaminopyridin-4-yl)alkanesulfonamides as pyridine analogs of nimesulide: Cyclooxygenases inhibition, anti-inflammatory studies and insight on metabolism

  摘要：

  Nimesulide, a COX-2 preferential inhibitor with a favorable gastric and cardiovascular safety profile, was responsible for some cases of acute liver failure attributed to the nitrobenzene ring. A series of analogs of nimesulide resulting from isosteric replacement of the nitrobenzene ring by the pyridine nucleus, was synthesized and their ability to inhibit both cyclooxygenases (COXs) isoforms was evaluated in vitro using a human whole blood model. Compounds 19c, 23b and 23c displayed an important inhibitory activity associated to a COX-2/COX-1 selectivity ratio similar to or higher than that of celecoxib. The anti-inflammatory activity and the ability of several compounds to decrease leukocyte infiltration were further evaluated in vivo in a model of a X carrageenan-induced pleurisy. Plasma assays were performed on blood samples collected from rats and allowed us to identify the 4-position of the phenyl ring as a major metabolism site explaining the occasionally observed lack of correlation between in vitro and in vivo results. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.12.033
• 作为产物：
  描述：

  三氟甲烷磺酰氯 、 4-amino-3-(3-bromophenylamino)pyridine 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 以69%的产率得到N-[3-(3-bromophenylamino)-4-pyridinyl]trifluoromethanesulfonamide
  参考文献：
  名称：

  Pyridine Analogues of Nimesulide: Design, Synthesis, and in Vitro and in Vivo Pharmacological Evaluation as Promising Cyclooxygenase 1 and 2 Inhibitors

  摘要：

  Nonsteroidal anti-inflammatory drugs (NSAIDs) represent one of the most prescribed medications, although the chronic use of such pharmacological agents is commonly associated with numerous side effects. The demonstration that the use of COX-2 selective or preferential inhibitors is associated with a better tolerability opened new horizons in the search of safer drugs for the management of inflammation. In the present study, we report the synthesis and the pharmacological evaluation of pyridine analogues of nimesulide, a COX-2 preferential inhibitor. The cyclooxygenases (COXs) inhibitory activities were evaluated in vitro using a human whole blood model. According to the in vitro results, a selection of compounds exhibiting moderate to high COX-2/COX-1 selectivity ratio (from weak COX-2 preferential inhibitors to compounds displaying a celecoxib-like selectivity profile) were further evaluated in vivo in a model of A carrageenan-induced pleurisy in rats. Some of the selected compounds displayed similar or improved anti-inflammatory properties when compared to nimesulide and celecoxib.

  DOI：

  10.1021/jm900702b

文献信息

• Pyridine Analogues of Nimesulide: Design, Synthesis, and in Vitro and in Vivo Pharmacological Evaluation as Promising Cyclooxygenase 1 and 2 Inhibitors
  作者：Jean-François Renard、Deniz Arslan、Nancy Garbacki、Bernard Pirotte、Xavier de Leval

  DOI：10.1021/jm900702b

  日期：2009.10.8

  Nonsteroidal anti-inflammatory drugs (NSAIDs) represent one of the most prescribed medications, although the chronic use of such pharmacological agents is commonly associated with numerous side effects. The demonstration that the use of COX-2 selective or preferential inhibitors is associated with a better tolerability opened new horizons in the search of safer drugs for the management of inflammation. In the present study, we report the synthesis and the pharmacological evaluation of pyridine analogues of nimesulide, a COX-2 preferential inhibitor. The cyclooxygenases (COXs) inhibitory activities were evaluated in vitro using a human whole blood model. According to the in vitro results, a selection of compounds exhibiting moderate to high COX-2/COX-1 selectivity ratio (from weak COX-2 preferential inhibitors to compounds displaying a celecoxib-like selectivity profile) were further evaluated in vivo in a model of A carrageenan-induced pleurisy in rats. Some of the selected compounds displayed similar or improved anti-inflammatory properties when compared to nimesulide and celecoxib.
• N-(3-Arylaminopyridin-4-yl)alkanesulfonamides as pyridine analogs of nimesulide: Cyclooxygenases inhibition, anti-inflammatory studies and insight on metabolism
  作者：Jean-François Renard、Frédéric Lecomte、Philippe Hubert、Xavier de Leval、Bernard Pirotte

  DOI：10.1016/j.ejmech.2013.12.033

  日期：2014.3

  Nimesulide, a COX-2 preferential inhibitor with a favorable gastric and cardiovascular safety profile, was responsible for some cases of acute liver failure attributed to the nitrobenzene ring. A series of analogs of nimesulide resulting from isosteric replacement of the nitrobenzene ring by the pyridine nucleus, was synthesized and their ability to inhibit both cyclooxygenases (COXs) isoforms was evaluated in vitro using a human whole blood model. Compounds 19c, 23b and 23c displayed an important inhibitory activity associated to a COX-2/COX-1 selectivity ratio similar to or higher than that of celecoxib. The anti-inflammatory activity and the ability of several compounds to decrease leukocyte infiltration were further evaluated in vivo in a model of a X carrageenan-induced pleurisy. Plasma assays were performed on blood samples collected from rats and allowed us to identify the 4-position of the phenyl ring as a major metabolism site explaining the occasionally observed lack of correlation between in vitro and in vivo results. (C) 2014 Elsevier Masson SAS. All rights reserved.