Parallel solution- and solid-Phase synthesis of spirohydantoin derivatives as neurokinin-1 receptor ligands

The combination of the 3,5-bis(trifluoromethyl)phenyl group with a spirohydantoin motive as a central scaffold was the basis for the design of a combinatorial library targeted towards the neurokinin-1 receptor. A solution- and solid-phase procedure is described and binding affinities of representative compounds presented. The generation of a compound library consisting of spirohydantoin as a privileged GPCR scaffold and the 3,5-bis(trifluoromethyl)phenyl motive as a neurokinin-1 specific needle is described. A series of nanomolar actives are disclosed.