The discovery of novel calcium sensing receptor negative allosteric modulators

Bioorg Med Chem Lett. 2009 Jun 15;19(12):3328-32. doi: 10.1016/j.bmcl.2009.04.044. Epub 2009 Apr 18.

Abstract

The design and profile of a series of zwitterionic calcium sensing receptor negative allosteric modulators is described. Evaluation of key analogues using a rat model demonstrate a robust response, significantly improved potency over ronacaleret and have the potential as an oral, anabolic treatment for osteoporosis.

MeSH terms

  • Administration, Oral
  • Allosteric Regulation / drug effects*
  • Anabolic Agents
  • Animals
  • Cell Line
  • Cyclopropanes / chemistry*
  • Cyclopropanes / pharmacokinetics
  • Cyclopropanes / pharmacology
  • Drug Discovery
  • Humans
  • Indans / chemistry*
  • Indans / pharmacokinetics
  • Indans / pharmacology
  • Microsomes, Liver
  • Osteoporosis / drug therapy
  • Phenylpropionates / chemistry*
  • Phenylpropionates / pharmacokinetics
  • Phenylpropionates / pharmacology
  • Rats
  • Receptors, Calcium-Sensing / antagonists & inhibitors*

Substances

  • Anabolic Agents
  • Cyclopropanes
  • Indans
  • Phenylpropionates
  • Receptors, Calcium-Sensing
  • cyclopropanecarboxylic acid
  • ronacaleret