title: Synthesis and pharmacological evaluation of a series of 4-piperazinylpyrazolo[3,4-b]- and -[4,3-b][1,5]benzodiazepines as potential anxiolytics.
abstract: 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.
authors.affiliation: Lilly Research Centre Limited, Eli Lilly and Company, Windlesham, Surrey, England.
authors.forename: J K
authors.initials: JK
authors.lastname: Chakrabarti
authors.forename: T M
authors.initials: TM
authors.lastname: Hotten
authors.forename: I A
authors.initials: IA
authors.lastname: Pullar
authors.forename: N C
authors.initials: NC
authors.lastname: Type
mesh_terms: 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
chemical_list: D014151:Anti-Anxiety Agents; D001381:Azepines; D010879:Piperazines; D011720:Pyrazoles; D011950:Receptors, Cholinergic; D011954:Receptors, Dopamine; D011976:Receptors, Muscarinic