1-Phenyl-8-azabicyclo[3.2.1]octane ethers: a novel series of neurokinin (NK1) antagonists.
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.
Huscroft
Ian T
IT
Department of Medicinal Chemistry, Merck Sharp & Dohme Research Laboratories, The Neuroscience Research Centre, Terlings Park, Harlow, Essex CM20 2QR, UK. ian_huscroft@merck.com
Carlson
Emma J
EJ
Chicchi
Gary G
GG
Kurtz
Marc M
MM
London
Clare
C
Raubo
Piotr
P
Wheeldon
Alan
A
Kulagowski
Janusz J
JJ
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
D001372:Aza Compounds; D001643:Bridged Bicyclo Compounds; D051638:Ether-A-Go-Go Potassium Channels; C092509:KCNH6 protein, human; D064729:Neurokinin-1 Receptor Antagonists