Synthesis of a new homologous series of p-chlorophenyl alcohol amides, their anticonvulsant activity and their testing as potential GABAB receptor antagonists.
The anticonvulsant activity of a homologous series of p-chlorophenyl alcohol amides is described. The new compounds (+/-)-2-hydroxy-2-(4'-chlorophenyl)-butyramide (2), (+/-)-3- hydroxy-3-(4'-chlorophenyl)pentanamide (4) and (+/-)-4-hydroxy-4-(4'-chlorophenyl)-hexanamide (6), were prepared and tested for their anticonvulsant activity. Compounds 2, 4, and 6 exhibited significant activity in seizures provoked by pentylenetetrazol. Chlorine in the para position of the phenyl ring increased both their potency at the peak effect and the duration of their anticonvulsant activity. The anticonvulsant activities of (+/-)-3-hydroxy-3-phenylpentanamide (3) and compound 4 were antagonized by DL-baclofen. This, and the protecting activity of 3 in the genetic-absence-epilepsy rats of the Strasbourg model suggest that the phenyl alcohol amides could be GABAB receptor antagonists.
Meza-Toledo
S E
SE
Departamento de Bioquímica, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, México D.F. México.
Juárez-Carvajal
E
E
Carvajal-Sandoval
G
G
D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001418:Baclofen / Q000494:pharmacology; D003292:Convulsants / Q000633:toxicity; D058788:GABA-B Receptor Antagonists; D007274:Injections, Intraperitoneal; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D010433:Pentylenetetrazole / Q000633:toxicity; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control; D013329:Structure-Activity Relationship
C115219:2-hydroxy-2-(4'-chlorophenyl)butyramide; C115220:3-hydroxy-3-(4'-chlorophenyl)pentanamide; C115221:4-hydroxy-4-(4'-chlorophenyl)hexanamide; D000577:Amides; D000927:Anticonvulsants; D003292:Convulsants; D058788:GABA-B Receptor Antagonists; D001418:Baclofen; D010433:Pentylenetetrazole