New 1-arylindoles based serotonin 5-HT7 antagonists. Synthesis and binding evaluation studies
Charlène Sagnes1, Guy Fournet1, Grzegorz Satala2
1Institut de Chimie et Biochimie Moléculaires et Supramoléculaires, UMR CNRS 5246, Université de Lyon, Université Claude Bernard - Lyon 1, Bâtiment Curien, 43 Bd du 11 Novembre 1918, F-69622 Villeurbanne, France.
Abstract:
Based on 5-HT1A and 5-HT7 ligand MR25003 scaffold, a new series of 1-aryl indole analogues were prepared and evaluated against 5-HT7 receptors. Modulations of aryl moieties provided a large number of new indolic derivatives. Most of compounds tested have displayed 5-HT7 affinity in the nanomolar range. Among them, 1-(naphthyl)indole derivative 3p (Ki (5-HT7) = 4.5 nM) showed also a good selectivity over 5-HT1A, 5-HT2A and 5-HT6 receptors. This compound was pharmacology characterized as an antagonist.
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