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

Bioorg Med Chem. 2010 Dec 15;18(24):8501-11. doi: 10.1016/j.bmc.2010.10.035. Epub 2010 Oct 20.

Abstract

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 (IC(50)=10nM). We report the synthesis of this series and their biological activities and structure-activity relationship.

MeSH terms

  • Adamantane / analogs & derivatives
  • Adamantane / pharmacokinetics
  • Adamantane / pharmacology
  • Animals
  • Inhibitory Concentration 50
  • Pyrimidines / administration & dosage
  • Pyrimidines / chemical synthesis*
  • Pyrimidines / pharmacokinetics
  • Rats
  • Receptors, Calcium-Sensing / antagonists & inhibitors*
  • Structure-Activity Relationship

Substances

  • Pyrimidines
  • Receptors, Calcium-Sensing
  • Adamantane