1H NMR study of the conformation and absolute stereochemistry of two spirocyclic NK-1 antagonists.
The binding affinities at the human NK-1 receptor of two spirocyclic compounds were found to be similar despite being epimeric at a key stereocentre. This unexpected result prompted a thorough investigation of the solution conformations of the two compounds. This revealed that a conformational switch in the tetrahydrofuran ring enabled the C-3-aryl group to be equatorial in both cases, leading to a similar juxtaposition of the aryl rings.
Herbert
Richard H
RH
The Neuroscience Research Centre, Merck Sharp and Dohme Research Laboratories, Terlings Park, Eastwick Road, Harlow, Essex CM20 2QR, UK.
Gerhard
Ute
U
Mortishire-Smith
Russell J
RJ
Thomas
Steven R
SR
Hollingworth
Gregory
G
D018360:Crystallography, X-Ray; D009682:Magnetic Resonance Spectroscopy / Q000379:methods* / Q000592:standards; D008958:Models, Molecular; D008968:Molecular Conformation; D064729:Neurokinin-1 Receptor Antagonists; D011522:Protons; D013141:Spiro Compounds / Q000737:chemistry* / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D064729:Neurokinin-1 Receptor Antagonists; D011522:Protons; D013141:Spiro Compounds