title: Synthesis and neuroleptic activity of 3-(1-substituted-4-piperidinyl)-1,2-benzisoxazoles.
abstract: 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).
authors.forename: J T
authors.initials: JT
authors.lastname: Strupczewski
authors.forename: R C
authors.initials: RC
authors.lastname: Allen
authors.forename: B A
authors.initials: BA
authors.lastname: Gardner
authors.forename: B L
authors.initials: BL
authors.lastname: Schmid
authors.forename: U
authors.initials: U
authors.lastname: Stache
authors.forename: E J
authors.initials: EJ
authors.lastname: Glamkowski
authors.forename: M C
authors.initials: MC
authors.lastname: Jones
authors.forename: D B
authors.initials: DB
authors.lastname: Ellis
authors.forename: F P
authors.initials: FP
authors.lastname: Huger
authors.forename: R W
authors.initials: RW
authors.lastname: Dunn
mesh_terms: 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
chemical_list: D014150:Antipsychotic Agents; D007555:Isoxazoles; D010080:Oxazoles; D010880:Piperidines; D013134:Spiperone