7-(N-substituted)amino-2,3-polymethylene benzofurane derivatives with tracheal relaxant activity

A set of twelve 7-(N-substituted)amino-2,3-polymethylenebenzofuranes (1-12) together with three related compounds (13-15) was prepared. Ten selected compounds were tested for tracheal relaxant activity in vitro and two of them (6,7) were also subjected to a broad pharmacological screening. Five compounds (2,7,9,12,14) at the concentration of 30 micrograms/ml exhibited high tracheal relaxant activity (73-94% tone reduction) that was superior than that of theophylline at the same concentration. The 7-(N-trifluoromethylsulfonyl)amino-2,3-tetramethylenebenzofuran e (9) was highly active till the concentration of 1 microgram/ml giving a stronger tracheal relaxation than amrinone at 3 micrograms/ml. On the other hand the general screening did not show any other major activity. The benzofurane derivatives 1-13 were obtained through obvious steps from the corresponding 7-nitrobenzofuranes, which were prepared by a Fischer indole-like cyclization of O-[(2-nitro)phenyl] ketone oximes. In one case two peculiar side products were isolated.