Synthesis and pharmacological evaluation of CNS activities of [1,2,3]triazolo[4,5-b][1,5]-, imidazolo[4,5-b][1,5]-, and pyrido[2,3-b][1,5]benzodiazepines. 10-Piperazinyl-4H-1,2,3-triazolo[4,5-b][1,5]benzodiazepines with neuroleptic activity.
The synthesis of [1,2,3]triazolo[4,5-b][1,5]-, imidazolo[4,5-b][1,5]-, and pyrido[2,3-b][1,5]benzodiazepines is described. The antidopaminergic and anticholinergic activities of the compounds have been examined by the respective in vitro [3H]spiperone and [3H]QNB receptor binding assay. The neuroleptic potential has been further evaluated in terms of their ability to produce hypothermia and catalepsy in mice and a conditioned avoidance response in rats. Only compounds from the triazolobenzodiazepine series show antipsychotic potential. The lack of activity in the imidazolo- and pyridobenzodiazepine series indicates that the basicity of the heteroarene moiety may be determinant for activity.
Chakrabarti
J K
JK
Lilly Research Centre Limited, Eli Lilly and Company, Windlesham, Surrey, England.
Hotten
T M
TM
Pullar
I A
IA
Steggles
D J
DJ
D000818:Animals; D014150:Antipsychotic Agents / Q000138:chemical synthesis*; D001362:Avoidance Learning / Q000187:drug effects*; D001569:Benzodiazepines / Q000138:chemical synthesis* / Q000494:pharmacology; D002490:Central Nervous System / Q000187:drug effects / Q000502:physiology; D007093:Imidazoles / Q000138:chemical synthesis / Q000494:pharmacology; D008297:Male; D015394:Molecular Structure; D009043:Motor Activity / Q000187:drug effects*; D010879:Piperazines / Q000138:chemical synthesis / Q000494:pharmacology; D011725:Pyridines / Q000138:chemical synthesis / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis / Q000494:pharmacology
D014150:Antipsychotic Agents; D007093:Imidazoles; D010879:Piperazines; D011725:Pyridines; D014230:Triazoles; D001569:Benzodiazepines