4-nitro-3-(2-chlorophenoxy)pyridine N-oxide | 73407-30-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-nitro-3-(2-chlorophenoxy)pyridine N-oxide
• 英文别名: 3-(o-chlorophenoxy)-4-nitropyridine N-oxide；3-(2-chlorophenoxy)-4-nitro-1-oxidopyridin-1-ium
• CAS: 73407-30-4
• 化学式: C₁₁H₇ClN₂O₄
• 分子量: 266.641
• InChiKey: DYCFWMFPOMJQLF-UHFFFAOYSA-N

物化性质

• 熔点：
  123-124 °C(Solv: methanol (67-56-1))
• 沸点：
  451.5±40.0 °C(Predicted)
• 密度：
  1.46±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  80.5
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-nitro-3-(2-chlorophenoxy)pyridine N-oxide 在 铁粉 、 溶剂黄146 作用下， 反应 12.0h， 生成 4-amino-3-(2-chlorophenoxy)pyridine
  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 、 邻氯苯酚 在 sodium hydroxide 作用下， 以 乙腈 为溶剂， 反应 12.0h， 以45%的产率得到4-nitro-3-(2-chlorophenoxy)pyridine 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
• 作为试剂：
  描述：

  3-氟-4-硝基-N-氧化吡啶 、 、 邻氯苯酚 、 potassium carbonate 在 乙腈 、 alumina 、 4-nitro-3-(2-chlorophenoxy)pyridine N-oxide 、 methanol diethyl ether 作用下， 以 丙酮 为溶剂， 反应 16.0h， 生成 4-nitro-3-(2-chlorophenoxy)pyridine N-oxide
  参考文献：
  名称：

  3-Aryloxy-substituted-aminopyridines and methods for their production

  摘要：

  本发明涉及3-芳氧基取代氨基吡啶及其盐，它们可用作药理学制剂，特别是认知活化剂。它们可以通过将氯代3-芳氧基吡啶与取代胺反应，将3-溴取代氨基吡啶与苯酚化合物的碱金属盐反应，或将3-芳氧基取代氨基吡啶N-氧化物脱氧制备。

  公开号：

  US04179563A1

文献信息

• US4179563A
  申请人：——

  公开号：US4179563A

  公开（公告）日：1979-12-18
• 3-Aryloxy-substituted-aminopyridines and methods for their production
  申请人：Warner-Lambert Company

  公开号：US04179563A1

  公开（公告）日：1979-12-18

  3-Aryloxy-substituted-aminopyridines and salts thereof, which are useful as pharmacological agents, especially cognition activators, are disclosed. They can be produced by reacting a chloro-3-aryloxypyridine with a substituted amine, 3-bromo-substituted-aminopyridine with an alkali metal salt of a phenol compound or by deoxygenation of a 3-aryloxy-substituted-aminopyridine N-oxide.

  本文披露了作为药理活性剂特别是认知活化剂有用的3-芳氧基取代氨基吡啶及其盐。它们可通过将氯-3-芳氧基吡啶与取代胺反应、3-溴取代氨基吡啶与酚化合物的碱金属盐反应，或者通过脱氧化3-芳氧基取代氨基吡啶N-氧化物来制备。
• 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.