title: Parallel solution- and solid-phase synthesis of spiropyrrolo-pyrroles as novel neurokinin receptor ligands.
abstract: The combination of a 3,5-bis(trifluoromethyl)phenyl needle with the spiropyrrolo-pyrrole motive as a privileged GPCR scaffold was the basis for designing a focused combinatorial library targeted towards the neurokinin-1 receptor. A solution- and solid-phase method is described and binding affinities of representative compounds are presented.
authors.affiliation: F. Hoffmann-La Roche AG, Pharma Research, CH-4070, Basel, Switzerland. konrad.bleicher@roche.com
authors.forename: Konrad H
authors.initials: KH
authors.lastname: Bleicher
authors.forename: Yves
authors.initials: Y
authors.lastname: Wüthrich
authors.forename: Geo
authors.initials: G
authors.lastname: Adam
authors.forename: Torsten
authors.initials: T
authors.lastname: Hoffmann
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Sleight
mesh_terms: D020650:Combinatorial Chemistry Techniques; D019204:GTP-Binding Proteins / Q000378:metabolism; D007202:Indicators and Reagents; D008024:Ligands; D011758:Pyrroles / Q000138:chemical synthesis* / Q000494:pharmacology*; D018040:Receptors, Neurokinin-1 / Q000187:drug effects / Q000378:metabolism*; D018041:Receptors, Neurokinin-2 / Q000187:drug effects / Q000378:metabolism*; D018042:Receptors, Neurokinin-3 / Q000187:drug effects / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D007202:Indicators and Reagents; D008024:Ligands; D011758:Pyrroles; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; D018042:Receptors, Neurokinin-3; D019204:GTP-Binding Proteins