Discovery and structure–activity relationships of 2-benzylpyrrolidine-substituted aryloxypropanols as calcium-sensing receptor antagonists

Abstract A structure–activity relationship study of the amine portion of the calcilytic compound NPS-2143 resulted in the discovery of substituted 2-benzylpyrrolidines as replacements for the 1,1-dimethyl-2-naphthalen-2-yl-ethylamine. When compared to NPS-2143, a newly discovered compound, 3h , exhibited similar potency as a calcium-sensing receptor (CaR) antagonist and a superior human ether-a-go-go related gene (hERG) profile.