Synthesis and structure–activity relationship of tetrahydropyrazolopyrimidine derivatives—A novel structural class of potent calcium-sensing receptor antagonists

A series of novel tetrahydropyrazolopyrimidine derivatives containing an adamantyl group were synthesized and evaluated as potential calcium-sensing receptor (CaSR) antagonists. After chemical modification of 9a, which was identified as a hit compound in a random screening of CaSR antagonist assay, 7,7-dimethyl derivative 16c was found to be the most active compound of this new series (IC50 = 10 nM). We report the synthesis of this series and their biological activities and structure–activity relationship.

Synthesis and structure–activity relationships of novel tetrahydropyrazolopyrimidine derivatives as calcium-sensing receptor antagonists are reported.Figure optionsDownload as PowerPoint slide