3-(Arylsulfonyl)-1-(azacyclyl)-1H-indoles are 5-HT(6) receptor modulators.

ABSTRACT

Novel 3-(arylsulfonyl)-1-(azacyclyl)-1H-indoles 6 were synthesized as potential 5-HT(6) receptor ligands, based on constraining a basic side chain as either a piperidine or a pyrrolidine. Many of these compounds had good 5-HT(6) binding affinity with K(i) values <10nM. Depending on substitution, both agonists (e.g., 6o EC(50)=60nM, E(max)=70%) and antagonists (6y IC(50)=17 nM, I(max)=86%) were identified in a 5-HT(6) adenylyl cyclase assay.