Synthesis and Activity of 2-Methyl-3-aminopropiophenones as Centrally Acting Muscle Relaxants.

Summary Some novel 2-methyl-3-aminopropiophenones were synthesized and their centrally acting muscle relaxant activities were evaluated for an inhibitory effect on the flexor reflex in rats. The structure-activity relationships are discussed. In this series, 2-methyl-3-pyrrolidino-1-(4-trifluoromethylphenyl)-propan-1-one ( 28 ) showed significant centrally acting muscle relaxant activity. In addition, the activities of each enantiomer ( 28 -( S ) and ( R ) were studied along with their acute toxicities. Compound 28 -( R ) was found to exhibit more potent activity and weaker acute toxicity than 28 -( S ). Accordingly, compound 28 -( R ) (NK433) is under development as a novel centrally acting muscle relaxant.