4-nitro-3-phenylaminopyridine N-oxide | 19349-84-9

• 分子结构分类: 有机化合物 - 有机1,3-偶极化合物 - 烯丙基型1,3-偶极有机化合物
• 英文名称: 4-nitro-3-phenylaminopyridine N-oxide
• 英文别名: 3-phenylamino-4-nitropyridine N-oxide；3-Anilino-4-nitro-pyridin-N-oxid；3-Phenylamino-4-nitro-pyridin-N-oxyd；4-Nitro-3-anilino-pyridin-N-oxid；(4-nitro-1-oxy-pyridin-3-yl)-phenyl-amine；4-nitro-1-oxido-N-phenylpyridin-1-ium-3-amine
• CAS: 19349-84-9
• 化学式: C₁₁H₉N₃O₃
• 分子量: 231.211
• InChiKey: DOKXFGLYRTUOAE-UHFFFAOYSA-N

物化性质

• 熔点：
  180 °C (decomp)(Solv: ethyl acetate (141-78-6))
• 沸点：
  491.5±30.0 °C(Predicted)
• 密度：
  1.35±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  83.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-nitro-3-phenylaminopyridine N-oxide 在 铁粉 作用下， 以 水 、 溶剂黄146 为溶剂， 生成 4-amino-3-phenylaminopyridine
  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
• 作为产物：
  描述：

  3-溴-4-硝基吡啶-N-氧化物 、 苯胺 反应 5.0h， 以66%的产率得到4-nitro-3-phenylaminopyridine 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.
• Nucleophilic β-amination of pyridine nuclei
  作者：Nagatoshi Nishiwaki、Yutaka Nishida、Eiko Tominaga、Masahiro Ariga

  DOI：10.1016/j.tetlet.2007.04.102

  日期：2007.6

  3-Bromo-4-nitropyridine N-oxide behaves as a useful substrate for causing nucleophilic substitution at the P-position (3-position) with arnines to afford 3-aminopyridine derivatives. (c) 2007 Elsevier Ltd. All rights reserved.
• BECALSKI, A.;KACZMAREK, L.;NANTKA-NAMIRSKI, P., ACTA POL. PHARM., 1984, 41, N 6, 601-606
  作者：BECALSKI, A.、KACZMAREK, L.、NANTKA-NAMIRSKI, P.

  DOI：——

  日期：——
• 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.