Synthesis and pharmacological evaluation of a series of 4-piperazinylpyrazolo[3,4-b]- and -[4,3-b][1,5]benzodiazepines as potential anxiolytics.
The synthesis and pharmacological evaluation of a series of pyrazolo[b][1,5]benzodiazepines are described. Some of the 4-piperazinyl-2,10-dihydropyrazolo[3,4-b][1,5]benzodiazepine derivatives demonstrated potent anxiolytic activity in the three-part operant anticonflict test in rats. Compounds 21 and 30 were more active than the clinically effective anxiolytic chlordiazepoxide in releasing conflict-suppressed behavior. This study shows a dissociation of the anxiolytic and antidopaminergic activities found in the thieno- and dibenzodiazepine derivatives flumezapine and clozapine, respectively. Examples of the three other dihydropyrazolo[b][1,5]benzodiazepine ring systems are described and evaluated for comparison and were found to be less active.
Chakrabarti
J K
JK
Lilly Research Centre Limited, Eli Lilly and Company, Windlesham, Surrey, England.
Hotten
T M
TM
Pullar
I A
IA
Type
N C
NC
D000818:Animals; D014151:Anti-Anxiety Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D001381:Azepines / Q000138:chemical synthesis / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D002375:Catalepsy / Q000139:chemically induced; D055598:Chemical Phenomena; D002621:Chemistry; D008297:Male; D051379:Mice; D010879:Piperazines / Q000138:chemical synthesis / Q000494:pharmacology*; D011720:Pyrazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011950:Receptors, Cholinergic / Q000187:drug effects; D011954:Receptors, Dopamine / Q000187:drug effects; D011976:Receptors, Muscarinic / Q000187:drug effects
D014151:Anti-Anxiety Agents; D001381:Azepines; D010879:Piperazines; D011720:Pyrazoles; D011950:Receptors, Cholinergic; D011954:Receptors, Dopamine; D011976:Receptors, Muscarinic