Synthesis and Affinities for Dopamine (D2) and 5-Hydroxytryptamine (5-HT2A Receptors of 1-(Benzoylpropyl)-4-(1-oxocycloalkyl-2-ethyl)- piperazines as Cyclic Butyrophenone Derivatives
| Autor: | Isabel Loza, Angeles Honrubia, Christian F. Masaguer, María L. de Ceballos, Jose Cid, Tomas G-Ferreiro, J. A. Fontenla, Jesus Negreira, J. M. Calleja, E. Ravina, Javier Fueyo, Helena Tristan, Elizabeth Rosa |
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| Rok vydání: | 1996 |
| Předmět: |
Male
Stereochemistry Butyrophenone Dopamine Agents Aorta Thoracic In Vitro Techniques Chemical synthesis Muscle Smooth Vascular Piperazines Rats Sprague-Dawley chemistry.chemical_compound Serotonin Agents Dopamine Dopamine receptor D2 Drug Discovery Haloperidol medicine Animals Receptor Receptors Dopamine D2 5-HT2 receptor General Chemistry General Medicine Butyrophenones Rats chemistry Receptors Serotonin Antipsychotic Agents medicine.drug |
| Zdroj: | Chemical and Pharmaceutical Bulletin. 44:534-541 |
| ISSN: | 1347-5223 0009-2363 |
| Popis: | Starting from benzo- or thienocycloalkaneacetic acids, we have prepared a series of 1-(3-p-fluorobenzoylpropyl)-4-(1-oxo-benzo- or thienocycloalkyl-2-ethyl)piperazines 8a-e containing both semirigid and linear butyrophenones pharmacophores. The affinities of these compounds for dopamine (D2) and 5-hydroxytryptamine (5-HT2A) receptors were evaluated in vitro in receptor-binding assays and in functional experiments. The ratios of pKi's for 5-HT2A/D2 receptors may be useful for rapid screening of new compounds and assessing potential induction of extrapyramidal symptoms; ratio values > or = 1.12 (Meltzer's ratio) are predictive of an atypical antipsychotic profile. The new molecules had a ratio in the range of 0.96-1.11 while haloperidol showed a ratio of 0.93. The 2-piperazinoethyl thiotetralone derivative 8d (QF 0506B) with a ratio of 1.11 was the most active compound. |
| Databáze: | OpenAIRE |
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