New orally effective 3-(2-nitro)phenylpropanamide analgesic derivatives: Synthesis and antinociceptive evaluation

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• 作者：Marc Since ; Thomas Freret ; Gerald Nee ; Thierry Terme ; Patrice Vanelle ; Michel Boulouard
• 关键词：6-Nitrophenylpropanamide ; TDAE ; Analgesic ; Peripheral antinociceptive activity ; Writhing test ; Hot-plate test
• 刊名：European Journal of Medicinal Chemistry
• 出版年：November, 2013
• 年：2013
• 卷：69
• 期：Complete
• 页码：728-734
• 全文大小：459 K

文摘

A series of substituted 6-nitrophenylpropanamide derivatives (1-20) were synthesized using either the TDAE strategy or classical organic reactions. All these compounds were characterized by fusion point, ¹H NMR, ¹³C NMR, elemental analysis or mass spectrometry data. Because of their structural analogy with recently published compounds possessing antinociceptive properties, our derivatives were screened for peripheral analgesic activities on acetic acid-induced writhing in mice. Compound 13 showed the best result at 100聽渭mol/kg ip (50% inhibition vs 59% for aspirin). This antinociceptive activity was maintained after oral administration (40% inhibition vs 31.6% for aspirin). Both hot-plate and actimetry-based tests were non-significant suggesting the analgesic activity of 13 linked to a peripheral mechanism.