title: 1H NMR study of the conformation and absolute stereochemistry of two spirocyclic NK-1 antagonists.
abstract: 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.
authors.affiliation: The Neuroscience Research Centre, Merck Sharp and Dohme Research Laboratories, Terlings Park, Eastwick Road, Harlow, Essex CM20 2QR, UK.
authors.forename: Richard H
authors.initials: RH
authors.lastname: Herbert
authors.forename: Ute
authors.initials: U
authors.lastname: Gerhard
authors.forename: Russell J
authors.initials: RJ
authors.lastname: Mortishire-Smith
authors.forename: Steven R
authors.initials: SR
authors.lastname: Thomas
authors.forename: Gregory
authors.initials: G
authors.lastname: Hollingworth
mesh_terms: 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
chemical_list: D064729:Neurokinin-1 Receptor Antagonists; D011522:Protons; D013141:Spiro Compounds