title: Spirocyclic NK(1) antagonists II: [4.5]-spiroethers.
abstract: A series of novel spiroether-based neurokinin-1 (NK(1)) antagonists is described. The effect of modifications to the spiroether ring and aromatic substituents are discussed, leading to the identification of compounds with high affinity and excellent CNS penetration.
authors.affiliation: Department of Medicinal Chemistry, Merck Sharp & Dohme Research Laboratories, The Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex, UK. brian_williams@merck.com
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Williams
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Cascieri
authors.forename: Gary G
authors.initials: GG
authors.lastname: Chicchi
authors.forename: Timothy
authors.initials: T
authors.lastname: Harrison
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Owens
authors.forename: Simon N
authors.initials: SN
authors.lastname: Owen
authors.forename: Nadia M J
authors.initials: NM
authors.lastname: Rupniak
authors.forename: David F
authors.initials: DF
authors.lastname: Tattersall
authors.forename: Angela
authors.initials: A
authors.lastname: Williams
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Swain
mesh_terms: D000818:Animals; D000932:Antiemetics / Q000138:chemical synthesis / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D001667:Binding, Competitive / Q000187:drug effects; D016466:CHO Cells; D006224:Cricetinae; D004285:Dogs; D004987:Ethers / Q000138:chemical synthesis* / Q000494:pharmacology*; D005289:Ferrets; D005849:Gerbillinae; D006801:Humans; D064729:Neurokinin-1 Receptor Antagonists; D051381:Rats; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000494:pharmacology*
chemical_list: D000932:Antiemetics; D004987:Ethers; D064729:Neurokinin-1 Receptor Antagonists; D013141:Spiro Compounds