3-(4-Piperidinyl)indoles and 3-(4-piperidinyl)pyrrolo-[2,3-b]pyridines as ligands for the ORL-1 receptor

A novel series of indoles and 1H-pyrrolo[2,3-b]pyridines having a piperidine ring at the 3-position were synthesized and found to bind with high affinity to the ORL-1 receptor. Structure–activity relationships at the piperidine nitrogen were investigated in each series. Substitution on the phenyl ring and nitrogen atom of the indole and 1H-pyrrolo[2,3-b]pyridine cores generated several selective high-affinity ligands that were agonists of the ORL-1 receptor.

Graphical abstractThe synthesis and biological evaluation of a series of 3-(4-piperidinyl)indoles and 3-(4-piperidinyl)pyrrolo[2,3-b]pyridines afforded compounds with high ORL-1 affinity.Figure optionsDownload full-size imageDownload as PowerPoint slide