The discovery of novel calcium sensing receptor negative allosteric modulators.

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.

• Authors: Gayatri Balan, Jonathan Bauman, Samit Bhattacharya, Mayda Castrodad, David R Healy, Michael Herr, Paul Humphries, Sandra Jennings, Amit S Kalgutkar, Brendon Kapinos, Vishal Khot, Kimberly Lazarra, Mei Li, Yan Li, Constantin Neagu, Robert Oliver, David W Piotrowski, David Price, Hong Qi, Holly A Simmons, James Southers, Liuqing Wei, Yan Zhang, Vishwas M Paralkar
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 19 Issue 12 Pg. 3328-32 (Jun 15 2009) ISSN: 1464-3405 [Electronic] England
• PMID: 19442519 (Publication Type: Journal Article)

Chemical References

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

Topics

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