3-substituted-1,2-benzisoxazoles: novel antipsychotic agents.
A series of 3-substituted-6-fluoro-1,2-benzisoxazoles (II) was synthesized and evaluated for potential antipsychotic activity. Many of the compounds displayed potent antipsychotic-like activity in the apomorphine induced climbing in mice (CMA) or spiroperidol binding assays, and compound 42 (HRP 392, 1-[3-(6-fluoro-1,2-benzisoxazol-3-yl)propyl]-4-(2-methoxyphenyl) piperazine) was selected for more detailed antipsychotic evaluation in a battery of preclinical assays. The results of these studies suggests that 42 is a potential antipsychotic drug with less propensity for EPS than some standard neuroleptics in monkeys. The compound was advanced for toxicological evaluation.
Chemical Research Department, Hoechst-Roussel Pharmaceuticals Inc., Somerville, New Jersey 08876.
L
L
Davis
R C
RC
Effland
J T
JT
Klein
R W
RW
Dunn
H M
HM
Geyer
W W
WW
Petko
D000818:Animals; D014150:Antipsychotic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D001058:Apomorphine / Q000037:antagonists & inhibitors; D001522:Behavior, Animal / Q000187:drug effects; D007555:Isoxazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D051379:Mice; D010879:Piperazines / Q000138:chemical synthesis / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012453:Saimiri; D013329:Structure-Activity Relationship
D014150:Antipsychotic Agents; C076732:HRP 392; D007555:Isoxazoles; D010879:Piperazines; D001058:Apomorphine