Pyrrole analogues of the pyrrolidinone moiety of the potassium channel activator cromakalim as relaxants of guinea pig trachealis.

A series of C-4 pyrrole substituted benzopyrans and benzopyranols has been prepared, some members of which are potent relaxants of guinea pig trachealis in vitro. These compounds appear to act via potassium channel opening. It is envisaged that a pyrrole ring substituted with an electron-withdrawing group can function as a bioisostere of the pyrrolidinone of cromakalim. Two tetracyclic derivatives have been also prepared, one of which (18) appears to act as a potassium channel activator in a similar manner to cromakalim while the other (15), although a potent relaxant of guinea pig trachealis, has a profile which is inconsistent with this mechanism of action.