N'-methyl-4-nitro-N'-phenyl-3-pyridinamine N-oxide | 833455-42-8

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: N'-methyl-4-nitro-N'-phenyl-3-pyridinamine N-oxide
• 英文别名: 3-Pyridinamine, N-methyl-4-nitro-N-phenyl-, 1-oxide；N-methyl-4-nitro-1-oxido-N-phenylpyridin-1-ium-3-amine
• CAS: 833455-42-8
• 化学式: C₁₂H₁₁N₃O₃
• 分子量: 245.238
• InChiKey: HSMQISKLWUWLID-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  74.5
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N'-methyl-4-nitro-N'-phenyl-3-pyridinamine N-oxide 在 铁粉 、 溶剂黄146 作用下， 生成 4-amino-N'-methyl-N'-phenyl-3-pyridinamine
  参考文献：
  名称：

  Design, Synthesis, and Pharmacological Evaluation of Pyridinic Analogues of Nimesulide as Cyclooxygenase-2 Selective Inhibitors

  摘要：

  In this study, we report the synthesis and pharmacological evaluation of original pyridinic sulfonamides related to nimesulide, a cyclooxygenase-2 (COX-2) preferential inhibitor widely used as an anti-inflammatory agent. These original pyridinic derivatives were synthesized in three steps starting from the condensation of 3-bromo-4-nitropyridine N-oxide with appropriately substituted phenols, thiophenols, or anilines followed by a reduction of the nitro moiety into the corresponding aminopyridine, which was finally condensed with alkane- or trifluoromethanesulfonyl chloride to obtain the corresponding sulfonamides. The pK(a) determinations demonstrated that the major ionic form present in solution at physiological pH depends on the nature of the sulfonamide moiety subsituent. Indeed, alkanesulfonamides were mainly present as zwitterionic molecules while trifluoromethanesulfonamides, more acidic derivatives, were mainly present as anionic molecules. The in vitro pharmacological evaluation of the synthesized compounds against COX-1 and COX-2 was performed in a human whole blood model. Results obtained demonstrated that most of alkanesulfonamide derivatives displayed a COX-2 preferential inhibition with selectivity ratio values (IC50(COX-1)/IC50(COX-2)) up to 7.92 (celecoxib displaying a ratio value of 7.46 in the same test). On the other hand, trifluoromethanesulfonamide derivatives displayed weaker selectivity ratios although they exhibited IC50 values against COX-2 up to 0.09 muM (celecoxib IC50 against COX-2: 0.35 muM). Finally, in vivo evaluation of selected compounds showed that they exhibited anti-inflammatory properties similar to that of nimesulide when tested in a carrageenan-induced rat paw oedema model.

  DOI：

  10.1021/jm049480l
• 作为产物：
  描述：

  3-溴-4-硝基吡啶-N-氧化物 、 N-甲基苯胺 反应 24.0h， 以58%的产率得到N'-methyl-4-nitro-N'-phenyl-3-pyridinamine N-oxide
  参考文献：
  名称：

  Design, Synthesis, and Pharmacological Evaluation of Pyridinic Analogues of Nimesulide as Cyclooxygenase-2 Selective Inhibitors

  摘要：

  In this study, we report the synthesis and pharmacological evaluation of original pyridinic sulfonamides related to nimesulide, a cyclooxygenase-2 (COX-2) preferential inhibitor widely used as an anti-inflammatory agent. These original pyridinic derivatives were synthesized in three steps starting from the condensation of 3-bromo-4-nitropyridine N-oxide with appropriately substituted phenols, thiophenols, or anilines followed by a reduction of the nitro moiety into the corresponding aminopyridine, which was finally condensed with alkane- or trifluoromethanesulfonyl chloride to obtain the corresponding sulfonamides. The pK(a) determinations demonstrated that the major ionic form present in solution at physiological pH depends on the nature of the sulfonamide moiety subsituent. Indeed, alkanesulfonamides were mainly present as zwitterionic molecules while trifluoromethanesulfonamides, more acidic derivatives, were mainly present as anionic molecules. The in vitro pharmacological evaluation of the synthesized compounds against COX-1 and COX-2 was performed in a human whole blood model. Results obtained demonstrated that most of alkanesulfonamide derivatives displayed a COX-2 preferential inhibition with selectivity ratio values (IC50(COX-1)/IC50(COX-2)) up to 7.92 (celecoxib displaying a ratio value of 7.46 in the same test). On the other hand, trifluoromethanesulfonamide derivatives displayed weaker selectivity ratios although they exhibited IC50 values against COX-2 up to 0.09 muM (celecoxib IC50 against COX-2: 0.35 muM). Finally, in vivo evaluation of selected compounds showed that they exhibited anti-inflammatory properties similar to that of nimesulide when tested in a carrageenan-induced rat paw oedema model.

  DOI：

  10.1021/jm049480l

文献信息

• Design, Synthesis, and Pharmacological Evaluation of Pyridinic Analogues of Nimesulide as Cyclooxygenase-2 Selective Inhibitors
  作者：Fabien Julémont、Xavier de Leval、Catherine Michaux、Jean-François Renard、Jean-Yves Winum、Jean-Louis Montero、Jacques Damas、Jean-Michel Dogné、Bernard Pirotte

  DOI：10.1021/jm049480l

  日期：2004.12.1

  In this study, we report the synthesis and pharmacological evaluation of original pyridinic sulfonamides related to nimesulide, a cyclooxygenase-2 (COX-2) preferential inhibitor widely used as an anti-inflammatory agent. These original pyridinic derivatives were synthesized in three steps starting from the condensation of 3-bromo-4-nitropyridine N-oxide with appropriately substituted phenols, thiophenols, or anilines followed by a reduction of the nitro moiety into the corresponding aminopyridine, which was finally condensed with alkane- or trifluoromethanesulfonyl chloride to obtain the corresponding sulfonamides. The pK(a) determinations demonstrated that the major ionic form present in solution at physiological pH depends on the nature of the sulfonamide moiety subsituent. Indeed, alkanesulfonamides were mainly present as zwitterionic molecules while trifluoromethanesulfonamides, more acidic derivatives, were mainly present as anionic molecules. The in vitro pharmacological evaluation of the synthesized compounds against COX-1 and COX-2 was performed in a human whole blood model. Results obtained demonstrated that most of alkanesulfonamide derivatives displayed a COX-2 preferential inhibition with selectivity ratio values (IC50(COX-1)/IC50(COX-2)) up to 7.92 (celecoxib displaying a ratio value of 7.46 in the same test). On the other hand, trifluoromethanesulfonamide derivatives displayed weaker selectivity ratios although they exhibited IC50 values against COX-2 up to 0.09 muM (celecoxib IC50 against COX-2: 0.35 muM). Finally, in vivo evaluation of selected compounds showed that they exhibited anti-inflammatory properties similar to that of nimesulide when tested in a carrageenan-induced rat paw oedema model.