Preparation of 3-spirocyclic indolin-2-ones as ligands for the ORL-1 receptor

A novel series of indolin-2-ones having a spirocyclic piperidine ring at the 3-position was synthesized and found to bind with high affinity to the ORL-1 receptor. Structure–activity relationships at the piperidine nitrogen were investigated. Substitution on the phenyl ring and nitrogen atom of the indolin-2-one core generated several selective high-affinity ligands that were antagonists of the ORL-1 receptor.

Synthesis and SAR of a series of indolin-2-ones provided compounds with high affinity for the ORL-1 receptor.Figure optionsDownload as PowerPoint slide