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 NK1 receptor antagonists. Substitution at the 6-exo-position led to high affinity NK1 antagonists with a prolonged duration of action in vivo. Incorporation of an α-methyl substituent in the pendent benzyl ether side chain gave compounds with increased selectivity over the hERG channel.

Graphical abstract1-Phenyl-8-azabicyclo[3.2.1]octane ethers are NK1 receptor antagonists. Substitution at the 6-exo-position leads to high affinity NK1 antagonists with a prolonged duration of action in vivo. Incorporation of an α-methyl substituent in the pendent benzyl ether side chain gave compounds with increased selectivity over the hERG channel.Figure optionsDownload full-size imageDownload as PowerPoint slide