New Benzocycloalkylpiperazines, Potent and Selective 5-HT1A Receptor Ligands
| Autor: | Elisabeth Laurent, Philippe Maillet, Raymond Dokhan, Akram Talab, Roland Ollivier, Youssef El Ahmad, and Gilles Tran, Jean François Teste |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
Magnetic Resonance Spectroscopy
medicine.drug_class Stereochemistry Molecular Conformation Carboxamide Binding Competitive Chemical synthesis Piperazines Receptors Dopamine Structure-Activity Relationship chemistry.chemical_compound Drug Discovery Cyclic AMP medicine Animals Rats Wistar Receptor Behavior Animal Molecular Structure Bicyclic molecule Ligand Colforsin Stereoisomerism Combinatorial chemistry Rats Receptors Adrenergic Serotonin Receptor Agonists Electrophysiology Enzyme Activation Kinetics Piperazine chemistry Receptors Serotonin Molecular Medicine Enantiomer Selectivity Receptors Serotonin 5-HT1 Adenylyl Cyclases Protein Binding |
| Zdroj: | Journal of Medicinal Chemistry. 40:952-960 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm950759z |
| Popis: | A series of 1-(benzocycloalkyl)-4-(benzamidolkyl)piperazine derivatives was prepared in order to obtain compounds with a high affinity and selectivity for 5-HT1A receptors. The modifications of aromatic substituents, the length of the alkyl chain, and the size of the ring were explored. Most of N-(1,2,3,4-tetrahydronaphthyl)-N'-(benzamidoethyl)piperazines (32-37) were bound to 5-HT1A receptors in a nanomolar range and presented a high degree of selectivity. After resolution, levorotatory enantiomers showed affinity and selectivity higher than those of dextrorotory ones for 5-HT1A sites. The agonist type activity of selected derivatives was also confirmed in vitro on the inhibition of the activation of adenylate cyclase induced by forskolin and, in vivo, on the induction of the lower lip retraction in rats. |
| Databáze: | OpenAIRE |
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