1-[[[5-(substituted phenyl)-2-oxazolyl]methylene]amino]-2,4- imidazolidinediones, a new class of skeletal muscle relaxants.

A series of 1-[[[5-(substituted phenyl)-2-oxazolyl]methylene]amino]- 2,4-imidazolidinediones (6a-t) was synthesized, and the compounds were evaluated for direct skeletal muscle inhibition in the pithed rat gastrocnemius muscle preparation. The correctness of structural assignment of the new series was verified by alternate, unequivocal synthesis of one representative structure (6f). The phenyloxazoles 6d, 6g, 6j, 6k, and 6l exhibited significant skeletal muscle relaxant activity when administered intravenously and orally. The skeletal muscle relaxant effect of these five compounds is similar to that of other direct-acting skeletal muscle relaxants. The oxazole moiety proved to be an acceptable isosteric replacement for furan, as the biological activity in the oxazole series was retained. The synthesis of this new class of compounds is described, and pharmacologic evaluation data are presented. A discussion of structure-activity relationships is also presented.