Novel 1-aminoethyl-3-arylsulfonyl-1H-pyrrolo[2,3-b]pyridines are potent 5-HT6 agonists

A series of 1-aminoethyl-3-arylsulfonyl-1H-pyrrolo[2,3-b]pyridines 10a–z was prepared as novel 5-HT6 ligands. The best compounds were high affinity, full agonists at 5-HT6 receptors. Several agonists demonstrated good selectivity over other serotonergic and dopaminergic receptors. Acute administration of selective agonist 10e significantly increased extracellular GABA concentrations in rat frontal cortex. This compound also reduced adjunctive drinking behavior in the rat schedule-induced polydipsia assay, possibly predictive of efficacy in obsessive compulsive disorder and other anxiety related disorders.

1-Aminoethyl-3-arylsulfonyl-1H-pyrrolo[2,3-b]pyridines (10) are potent 5-HT6 agonists.Figure optionsDownload as PowerPoint slide