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

Abstract 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, 1 H NMR, 13 C 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 μmol/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.