Parallel solution- and solid-phase synthesis of spiropyrrolo-pyrroles as novel neurokinin receptor ligands.
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.
Bleicher
Konrad H
KH
F. Hoffmann-La Roche AG, Pharma Research, CH-4070, Basel, Switzerland. konrad.bleicher@roche.com
Wüthrich
Yves
Y
Adam
Geo
G
Hoffmann
Torsten
T
Sleight
Andrew J
AJ
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
D007202:Indicators and Reagents; D008024:Ligands; D011758:Pyrroles; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; D018042:Receptors, Neurokinin-3; D019204:GTP-Binding Proteins