Novel anxiolytic agents derived from alpha-amino-alpha-phenyl-o-tolyl-4H-triazoles and -imidazoles.
Several new alpha-amino-alpha-phenyl-o-tolytriazoles and -imidazoles have been prepared in one step by means of a novel reductive rearrangement of the corresponding benzodiazepines with hydrazine hydrate. These new triazoles were found to have moderate sedative and muscle relaxing activity in mice (i.e., these compounds depressed the traction and dish reflexes at higher doses than did diazepam) but were very potent antagonists of the clonic convulsions induced in mice by the administration of pentylenetetrazole. Furthermore, they antagonized the lethality induced by thiosemicarbazide. While these new compounds were very active in mice, most were inactive in rats. These results are discussed with reference to the metabolism of compound 13.
D000818:Animals; D014151:Anti-Anxiety Agents / Q000138:chemical synthesis* / Q000378:metabolism; D000927:Anticonvulsants / Q000138:chemical synthesis / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D003461:Crystallography; D006993:Hypnotics and Sedatives / Q000138:chemical synthesis / Q000378:metabolism; D007093:Imidazoles / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D008958:Models, Molecular; D008968:Molecular Conformation; D009126:Muscle Relaxation / Q000187:drug effects; D009538:Nicotine / Q000037:antagonists & inhibitors; D010433:Pentylenetetrazole / Q000037:antagonists & inhibitors; D051381:Rats; D012640:Seizures / Q000517:prevention & control; D012663:Semicarbazides / Q000037:antagonists & inhibitors; D014230:Triazoles / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology
D014151:Anti-Anxiety Agents; D000927:Anticonvulsants; D006993:Hypnotics and Sedatives; D007093:Imidazoles; D012663:Semicarbazides; D014230:Triazoles; D009538:Nicotine; D010433:Pentylenetetrazole