Benzisoxazole- and benzisothiazole-3-carboxamides as potential atypical antipsychotic agents.
A series of benzisoxazole- and benzisothiazole-3-carboxamides has been prepared and tested for potential antipsychotic activity. In general, the compounds showed an affinity for dopamine D2 and serotonin 5HT2A and 5HT1A receptors. Several members of this series have demonstrated activity in animal models predictive of potential antipsychotic activity. In addition, compounds 18, 19, 22, 27, 28, 43, and 44 have also shown a potential for reduced EPS liability as suggested by the ratio of activity seen in mesolimbic-mediated vs nigrostriatal-mediated behavioral assays.
Hrib
N J
NJ
Neuroscience Strategic Business Unit, Hoechst-Roussel Pharmaceuticals, Inc., Somerville, New Jersey 08876.
Jurcak
J G
JG
Burgher
K L
KL
Conway
P G
PG
Hartman
H B
HB
Kerman
L L
LL
Roehr
J E
JE
Woods
A T
AT
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001058:Apomorphine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D007555:Isoxazoles / Q000494:pharmacology*; D008297:Male; D051379:Mice; D051381:Rats; D017208:Rats, Wistar; D013239:Stereotyped Behavior / Q000187:drug effects; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000494:pharmacology*
D014150:Antipsychotic Agents; D007555:Isoxazoles; D013844:Thiazoles; D001058:Apomorphine