Synthesis and neuroleptic activity of 3-(1-substituted-4-piperidinyl)-1,2-benzisoxazoles.
The synthesis of a series of 3-(1-substituted-4-piperidinyl)-1,2-benzisoxazoles is described. The neuroleptic activity of the series was evaluated by utilizing the climbing mice assay and inhibition of [3H]spiroperidol binding. Structure-activity relationships were studied by variation of the substituent on the benzisoxazole ring with concomitant variation of four different 1-piperidinyl substituents. Maximum neuroleptic activity was realized when there was a 6-fluoro substituent on the benzisoxazole ring. The 1-piperidinyl substituent appeared less significant, although in most cases, the (1,3-dihydro-2-oxo-2H-benzimidazol-1-yl)propyl group imparted maximum potency. The most potent compound in both assays was 6-fluoro-3-[1-[3-(1,3-dihydro-2-oxo-2H-benzimidazol-1-yl) propyl]-4-piperidinyl]-1,2-benzisoxazole (11b).
Strupczewski
J T
JT
Allen
R C
RC
Gardner
B A
BA
Schmid
B L
BL
Stache
U
U
Glamkowski
E J
EJ
Jones
M C
MC
Ellis
D B
DB
Huger
F P
FP
Dunn
R W
RW
D000818:Animals; D014150:Antipsychotic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D003342:Corpus Striatum / Q000378:metabolism; D066298:In Vitro Techniques; D007555:Isoxazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D008297:Male; D051379:Mice; D009043:Motor Activity; D010080:Oxazoles / Q000138:chemical synthesis*; D010880:Piperidines / Q000138:chemical synthesis* / Q000494:pharmacology; D013134:Spiperone / Q000378:metabolism; D013329:Structure-Activity Relationship
D014150:Antipsychotic Agents; D007555:Isoxazoles; D010080:Oxazoles; D010880:Piperidines; D013134:Spiperone