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Synthesis of spiro[isobenzofuran-1(3H),4'-piperidines] as potential central nervous system agents. 4. Central nervous system depressants
- Source :
- Journal of medicinal chemistry. 21(11)
- Publication Year :
- 1978
-
Abstract
- The synthesis of 1'-[3-(4-fluorobenzyoyl)propyl]-3-phenylspiro[isobenzofuran-1(3H),4'-piperidine] (2a) and eight halo and methoxy analogues is described. The compounds were generally more potent per os than chlorpromazine in the Sidman avoidance paradigm in rats and less potent than haloperido. 1'-[3-(4-Fluorobenzoyl)propyl]-3-(4-fluorophenyl)spiro[isobenzofuran-1(3H),4'-piperidine] (2e) approached the per os potency of haloperidol in this test and was shown to be active in inhibiting monkey avoidance also. Compound 2e was much less active than haloperidol in antagonizing apomorphine-induced emesis in dogs, apomorphine-induced stereotypy in rats, and amphetamine-induced circling in lesioned rats. This lack of nonselective, dopamine-receptor blocking effects makes 2e attrative as a potential neuroleptic.
- Subjects :
- Male
Isobenzofuran
Apomorphine
Vomiting
Central nervous system
Pharmacology
Receptors, Dopamine
chemistry.chemical_compound
Structure-Activity Relationship
Dogs
Escape Reaction
Drug Discovery
medicine
Haloperidol
Avoidance Learning
Potency
Animals
Humans
Spiro Compounds
Chlorpromazine
Saimiri
Dose-Response Relationship, Drug
Chemistry
Central Nervous System Depressants
Haplorhini
Rats
Stereotypy (non-human)
Amphetamine
medicine.anatomical_structure
Molecular Medicine
Female
Piperidine
Stereotyped Behavior
medicine.drug
Antipsychotic Agents
Subjects
Details
- ISSN :
- 00222623
- Volume :
- 21
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- Journal of medicinal chemistry
- Accession number :
- edsair.doi.dedup.....248dc1ca87aad4a72509edca3a2c17a6