Optimization of (arylpiperazinylbutyl)oxindoles exhibiting selective 5-HT₇ receptor antagonist activity
| Autor: | Balázs, Volk, István, Gacsályi, Katalin, Pallagi, László, Poszávácz, Ildikó, Gyönös, Eva, Szabó, Tibor, Bakó, Michael, Spedding, Gyula, Simig, Gábor, Szénási |
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| Rok vydání: | 2011 |
| Předmět: |
Male
Binding Sites Indoles Brain CHO Cells In Vitro Techniques Ligands Antidepressive Agents Piperazines Rats Mice Radioligand Assay Structure-Activity Relationship Cricetulus Anti-Anxiety Agents Cricetinae Receptors Adrenergic alpha-1 Receptors Serotonin Receptor Serotonin 5-HT1A Microsomes Liver Animals Tissue Distribution Serotonin Antagonists |
| Zdroj: | Journal of medicinal chemistry. 54(19) |
| ISSN: | 1520-4804 |
| Popis: | A series of (arylpiperazinylbutyl)oxindoles as highly potent 5-HT(7) receptor antagonists has been studied for their selectivity toward the 5-HT(1A) receptor and α(1)-adrenoceptor. Several derivatives exhibited high 5-HT(7)/5-HT(1A) selectivity, and the key structural factors for reducing undesired α(1)-adrenergic receptor binding have also been identified. Rapid metabolism, a common problem within this family of compounds, could be circumvented with appropriate substitution patterns on the oxindole carbocycle. Contrary to expectations, none of the compounds produced an antidepressant-like action in the forced swimming test in mice despite sufficiently high brain concentrations. On the other hand, certain analogues showed significant anxiolytic activity in two different animal models: the Vogel conflict drinking test in rats and the light-dark test in mice. |
| Databáze: | OpenAIRE |
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