Synthesis and anti-inflammatory activity of N-(aza)arylcarboxamides derived from Trolox

Article abstract of DOI:10.1016/S0223-5234(98)80065-2

A series of 6-(aza)arylmethoxychroman-2-carboxamides 22-38, derived from Trolox or 6-hydroxy-2,5,7,8-tetra-methylchroman-2-carboxylic acid, was prepared using two strategies, i.e. phenol blockade was carried out before or after amidification. These compounds were evaluated against peripheral inflammation by a carrageenin-induced foot-pad edema test. A permanent blockade of the phenol function by arylmethoxy groupings, in particular by the quinolylmethoxy moiety, was generally detrimental to activity; only the 6-benzyloxy and quinolylmethoxy derivatives 22 and 31 exhibited significant inhibition (58.3 and 97.1%) after oral administration of 0.4 mrnol kg^-1. Among their 6-acetoxy or 6-hydroxy precursors 12-21. evaluated at 0.4 and 0.1 mmol kg^-1, the N-(4-pyridyl) chromancarboxamides 15 and 20 exerted the highest inhibitory activity. Their ID₅₀ were 14.7 ± 5.5 mg kg^-1 and 14.7 ± 4.5 mg kg^-1, respectively. Elsevier, Paris.