2,4-Dihydro-3H-1,2,4-triazol-3-ones as anticonvulsant agents.
A series of 5-aryl-2,4-dihydro-3H-1,2,4-triazol-3-ones was evaluated for anticonvulsant activity. In general the members of this series were prepared by the alkaline cyclization of 1-aroyl-4-alkylsemicarbazides. The resulting 2-unsubstituted 3H-1,2,4-triazol-3-ones were then alkylated, yielding 2,4-dialkyl-3H-1,2,4-triazol-3-ones. Approximately one-third of the compounds examined exhibited activity against both maximal electroshock- and pentylenetetrazole-induced seizures in mice. Receptor-binding studies suggest that this activity was not a consequence of activity at either benzodiazepine or NMDA-type glutamate receptors. From this series, compound 45 was selected for further evaluation where it was also found to be active against 3-mercaptopropionic acid, bicuculline, and quinolinic acid induced seizures in mice. In addition, 45 also protected gerbils from hippocampal neuronal degeneration produced by either hypoxia or intrastriatal quinolinic acid injection.
Kane
J M
JM
Merrell Dow Research Institute, Cincinnati, Ohio 45215.
Baron
B M
BM
Dudley
M W
MW
Sorensen
S M
SM
Staeger
M A
MA
Miller
F P
FP
D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000737:chemistry; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D005849:Gerbillinae; D006624:Hippocampus / Q000187:drug effects; D000860:Hypoxia; D008297:Male; D051379:Mice; D009474:Neurons / Q000187:drug effects; D010622:Phencyclidine / Q000633:toxicity; D011963:Receptors, GABA-A / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D014230:Triazoles / Q000138:chemical synthesis / Q000494:pharmacology*
D000927:Anticonvulsants; D011963:Receptors, GABA-A; D016194:Receptors, N-Methyl-D-Aspartate; D014230:Triazoles; D010622:Phencyclidine