title: 4,4-Disubstituted cyclohexylamine NK(1) receptor antagonists I.
abstract: A series of novel 4,4-disubstituted cyclohexylamine based NK(1) antagonists is described. The effect of changes to the C(1)-C(4) relative stereochemistry on the cyclohexane ring and replacements for the flexible linker are discussed, leading to the identification of compounds with high affinity and good in vivo duration of action.
authors.affiliation: Department of Medicinal Chemistry, Merck Sharp & Dohme Research Laboratories, The Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex CM20 2QR, UK. jason_elliot@merck.com
authors.forename: Jason M
authors.initials: JM
authors.lastname: Elliott
authors.forename: Jose L
authors.initials: JL
authors.lastname: Castro
authors.forename: Gary G
authors.initials: GG
authors.lastname: Chicchi
authors.forename: Laura C
authors.initials: LC
authors.lastname: Cooper
authors.forename: Kevin
authors.initials: K
authors.lastname: Dinnell
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Hollingworth
authors.forename: Mark P
authors.initials: MP
authors.lastname: Ridgill
authors.forename: Wayne
authors.initials: W
authors.lastname: Rycroft
authors.forename: Marc M
authors.initials: MM
authors.lastname: Kurtz
authors.forename: Duncan E
authors.initials: DE
authors.lastname: Shaw
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Swain
authors.forename: Kwei-Lan
authors.initials: KL
authors.lastname: Tsao
authors.forename: Lihu
authors.initials: L
authors.lastname: Yang
mesh_terms: D000818:Animals; D001665:Binding Sites; D016466:CHO Cells; D002490:Central Nervous System / Q000187:drug effects / Q000378:metabolism; D006224:Cricetinae; D003514:Cyclohexylamines / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D005849:Gerbillinae; D020128:Inhibitory Concentration 50; D008968:Molecular Conformation; D064729:Neurokinin-1 Receptor Antagonists; D011869:Radioligand Assay; D018040:Receptors, Neurokinin-1 / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D003514:Cyclohexylamines; D064729:Neurokinin-1 Receptor Antagonists; D018040:Receptors, Neurokinin-1