Isoxazole derivatives as centrally acting muscle relaxants. III. Synthesis and activity of conformationally restricted analogs.

Abstract

Conformationally restricted analogs of muscle-relaxant 3-amino-2-methyl-N- (3-phenyl-5-isoxazolyl) propanamides (1) and 5- (3-aminopropylamino) -3-phenylisoxazoles (2) were prepared, and their muscle-relaxant and other pharmacological activities were tested and compared with those of the corresponding acyclic derivatives. 7- (3-Diethylamino-2-methylpropanoyl) -3-phenyl-4, 5, 6, 7-tetrahydroisoxazolo [5, 4-b] pyridine (8) exhibited muscle-relaxant and anticonvulsant activities comparable with those of corresponding acyclic derivatives, i.e. 3-diethylamino-2-methyl-N- (3-phenyl-5-isoxazolyl) propanamides (1e-g), but other types of compounds showed decreased activities. The preferred conformation of the present isoxazole derivatives for muscle-relaxant activity is discussed.7-Benzyl-6-methyl-3-phenyl-4-pyrrolidino-4, 5, 6, 7-tetrahydroisoxazolo [5, 4-b] pyridine (3d) showed moderate central nervous system-depressant activity.