Discovery and characterization of novel, potent, non-peptide parathyroid hormone-1 receptor antagonists.

A 1,3,4-benzotriazepine was identified as a suitable lead in our effort toward obtaining a non-peptide parathyroid hormone-1 receptor (PTH 1 R) antagonist. A process of optimization afforded derivatives displaying nanomolar PTH 1 R affinity, a representative example of which behaved as a PTH 1 R antagonist in cell-based cyclic adenosine monophosphate (cAMP) assays, with selectivity over PTH 2 receptors.