SYNTHESIS AND ANTIINFLAMMATORY ACTIVITY OF N-(AZA)ARYLCARBOXAMIDES DERIVED FROM TROLOX(R)

A series of 6-(aza) arylmethoxychroman-2-carboxamides 22-38, derived f rom Trolox(R) or 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic aci d, was prepared using two strategies, i.e. phenol blockade was carried out before or after amidification. These compounds were evaluated aga inst peripheral inflammation by a carrageenin-induced foot-pad edema t est. A permanent blockade of the phenol function by arylmethoxy groupi ngs, in particular by the quinolylmethoxy moiety, was generally detrim ental to activity; only the 6-benzyloxy and quinolylmethoxy derivative s 22 and 31 exhibited significant inhibition (58.3 and 97.1%) after or al administration of 0.4 mmol kg(-1). Among their 6-acetoxy or 6-hydro xy precursors 12-21, evaluated at 0.4 and 0.1 mmol kg(-1), the N-(4-py ridyl) chromancarboxamides 15 and 20 exerted the highest inhibitory ac tivity. Their ID50 were 14.7 +/- 5.5 mg kg(-1) and 14.7 +/- 4.5 mg kg( -1), respectively. (C) Elsevier, Paris.