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.
Subject(s)
Aza Compounds/pharmacology , Bridged Bicyclo Compounds/pharmacology , Neurokinin-1 Receptor Antagonists , Animals , CHO Cells , Cricetinae , Cyclization , Ether-A-Go-Go Potassium Channels/drug effects , HumansABSTRACT
A novel series of 5-HT(7) receptor ligands has been identified and evaluated, providing compounds showing a broad spectrum of functional activities and good selectivity over selected receptors and ion channels.
Subject(s)
Receptors, Serotonin/chemistry , Receptors, Serotonin/metabolism , Sulfones/chemistry , Sulfones/metabolism , Alkylation , Amination , Cyclization , Ligands , Molecular Structure , Structure-Activity Relationship , Sulfones/chemical synthesisABSTRACT
A series of sarcosine based indandione hGlyT1 inhibitors has been developed. Optimization of substitution around the indandione and sarcosine moieties has led to highly potent inhibitors at hGlyT1, which show selectivity over a number of other receptors.
