Synthesis of spiro[isobenzofuran-1(3H),4'-piperidines] as potential central nervous system agents. 4. Central nervous system depressants
| Autor: | R C, Allen, V J, Bauer, R W, Kosley, A R, McFadden, G M, Shutske, M L, Cornfeldt, S, Fielding, H M, Geyer, J C, Wilker |
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| Rok vydání: | 1978 |
| Předmět: |
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 |
| Zdroj: | Journal of medicinal chemistry. 21(11) |
| ISSN: | 0022-2623 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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