Stereoselective anticonvulsant activity of the enantiomers of (+/-)-2-hydroxy-2-phenylbutyramide.
The enantiomers of the anticonvulsant DL-2-hydroxy-2-phenylbutyramide (1) were prepared by resolving the (-)-quinine and (+)-1-phenylethylamine salts of the acids. The optically active acids were then esterified and reacted with ammonia to give (+)-1 and (-)-1. Optical purity of the amides was greater than 99.9% enantiomeric excess by chiral HPLC. Examination of the infrared spectra of the enantiomers and the racemate of 1 in chloroform solution showed identical spectra, but the spectrum of the racemate in a KBr disc was somewhat different from those of the pure enantiomers. Pharmacologically, 1 and its enantiomers have a similar significant anticonvulsant activity at peak drug effect against pentylenetetrazol seizures, but a variation in time between the enantiomers was found with the anticonvulsant activity. In the rotarod ataxia test (-)-1-possessed the lowest neurotoxicity.
Meza-Toledo
S E
SE
Departamento de Bioquímica, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Mexico D. F., Mexico.
Ortega-González
C
C
Juárez-Carvajal
E
E
Carvajal-Sandoval
G
G
D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D002851:Chromatography, High Pressure Liquid; D008297:Male; D051379:Mice; D010433:Pentylenetetrazole; D010654:Phenylbutyrates / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D004856:Postural Balance / Q000187:drug effects; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism
D000927:Anticonvulsants; D010654:Phenylbutyrates; C068956:2-hydroxy-2-phenylbutyramide; D010433:Pentylenetetrazole