title: 1-Phenyl-8-azabicyclo[3.2.1]octane ethers: a novel series of neurokinin (NK1) antagonists.
abstract: 1-Phenyl-8-azabicyclo[3.2.1]octane ethers are NK(1) receptor antagonists. Substitution at the 6-exo-position led to high affinity NK(1) antagonists with a prolonged duration of action in vivo. Incorporation of an alpha-methyl substituent in the pendent benzyl ether side chain gave compounds with increased selectivity over the hERG channel.
authors.affiliation: Department of Medicinal Chemistry, Merck Sharp & Dohme Research Laboratories, The Neuroscience Research Centre, Terlings Park, Harlow, Essex CM20 2QR, UK. ian_huscroft@merck.com
authors.forename: Ian T
authors.initials: IT
authors.lastname: Huscroft
authors.forename: Emma J
authors.initials: EJ
authors.lastname: Carlson
authors.forename: Gary G
authors.initials: GG
authors.lastname: Chicchi
authors.forename: Marc M
authors.initials: MM
authors.lastname: Kurtz
authors.forename: Clare
authors.initials: C
authors.lastname: London
authors.forename: Piotr
authors.initials: P
authors.lastname: Raubo
authors.forename: Alan
authors.initials: A
authors.lastname: Wheeldon
authors.forename: Janusz J
authors.initials: JJ
authors.lastname: Kulagowski
mesh_terms: D000818:Animals; D001372:Aza Compounds / Q000494:pharmacology*; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D016466:CHO Cells; D006224:Cricetinae; D003500:Cyclization; D051638:Ether-A-Go-Go Potassium Channels / Q000187:drug effects; D006801:Humans; D064729:Neurokinin-1 Receptor Antagonists
chemical_list: D001372:Aza Compounds; D001643:Bridged Bicyclo Compounds; D051638:Ether-A-Go-Go Potassium Channels; C092509:KCNH6 protein, human; D064729:Neurokinin-1 Receptor Antagonists