Synthesis and antidopaminergic activity of some 3-(aminomethyl)tetralones as analogues of butyrophenone
| Autor: | J. M. Calleja, E. Castro, L. Cortizo, J. A. Fontenla, M. L. De Ceballos, Francisco Orallo, Enrique Raviña, Lourdes Santana |
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| Rok vydání: | 1991 |
| Předmět: |
Male
Chemical Phenomena Stereochemistry Butyrophenone Catalepsy Receptors Dopamine Mice Structure-Activity Relationship chemistry.chemical_compound Drug Discovery medicine Haloperidol Tetralone Animals Structure–activity relationship Bicyclic molecule Muscle Smooth Rats Inbred Strains Biological activity medicine.disease Butyrophenones Rats Chemistry chemistry Dopamine Antagonists Molecular Medicine Stereotyped Behavior Antipsychotic Agents Muscle Contraction medicine.drug Tetralones |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname |
| Popis: | Starting from β-benzoylpropionic acid we synthesized 3-(aminomethyl)tetralones in which the amino substituent was 4-(N-piperazinyl)-p-fluorobutyrophenone (14), 4-benzoylpiperidine (15), 4-hydroxy-4-phenylpiperidine (16) or 4-(o-methoxyphenyl)piperazine (17). The possible dopamine antagonist activity of these compounds was investigated in both >in vitro> and >in vivo> experiments. These compounds potently inhibited [3H]spiperone binding to D2 striatal receptors and moderately inhibited [3H]SCH-23390 binding to D1 striatal receptors (Kis in the nanomolar and micromolar ranges, respectively). Apomorphine-induced stereotypies and amphetamine group toxicity were antagonized, to different extents, by the compounds under study, with a potency similar to that of haloperidol. Interestingly, no catalepsy was observed after administration of the new compounds (2-8 mg/kg). The most active compounds >in vivo> 14 and 15 possessed two butyrophenone pharmacophores. However, the tetralone moiety appeared not critical for their antidopaminergic activity, since all target compounds were less active than haloperidol. These studies provide a pharmacological basis for future research on these new compounds devoid of cataleptogenic activity. © 1991 American Chemical Society. |
| Databáze: | OpenAIRE |
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