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.
Subject(s)
Indoles/chemistry , Indoles/pharmacology , Receptors, Serotonin/metabolism , Serotonin Antagonists/chemistry , Serotonin Antagonists/pharmacology , Animals , HEK293 Cells , Humans , Indoles/chemical synthesis , Ligands , Naphthalenes/chemical synthesis , Naphthalenes/chemistry , Naphthalenes/pharmacology , Rats , Receptor, Serotonin, 5-HT1A/metabolism , Serotonin/metabolism , Serotonin Antagonists/chemical synthesis , Structure-Activity RelationshipABSTRACT
Aliphatic thiolates were efficiently converted into the corresponding sulfenates by smooth oxidation with trans-(+/-)-2-tert-butyl-3-phenyloxaziridine at room temperature (five examples). Subsequent electrophilic quench with benzyl bromide led to sulfoxides (S-alkylation) in good to moderate yields. Application of the protocol to an aromatic substrate was also successful. This work represents the first valuable example of the use of this poorly active oxidizing agent in synthetic organic chemistry without the need for activating conditions.
