The discovery of an orally efficacious positive allosteric modulator of the calcium sensing receptor containing a dibenzylamine core

Paul E Harrington; David J St Jean Jr; Jeffrey Clarine; Thomas S Coulter; Michael Croghan; Adam Davenport; James Davis; Chiara Ghiron; Jonathan Hutchinson; Michael G Kelly; Fred Lott; Jenny Ying-Lin Lu; David Martin; Sean Morony; Steve F Poon; Elena Portero-Larragueta; Jeff D Reagan; Kelly A Regal; Andrew Tasker; Minghan Wang; Yuhua Yang; Guomin Yao; Qingping Zeng; Charles Henley 3rd; Christopher Fotsch

doi:10.1016/j.bmcl.2010.07.060

The discovery of an orally efficacious positive allosteric modulator of the calcium sensing receptor containing a dibenzylamine core

Bioorg Med Chem Lett. 2010 Sep 15;20(18):5544-7. doi: 10.1016/j.bmcl.2010.07.060. Epub 2010 Aug 12.

Affiliation

¹ Chemistry Research and Discovery, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, USA. pharring@amgen.com

PMID: 20708930
DOI: 10.1016/j.bmcl.2010.07.060

Abstract

The discovery of a series of novel and orally efficacious type II calcimimetics, developed from the lead compound 1, is described herein. Compound 22 suppressed plasma PTH levels relative to vehicle when dosed orally in a rat pharmacodynamic model.

MeSH terms

Administration, Oral
Animals
Benzylamines / administration & dosage
Benzylamines / chemistry*
Benzylamines / pharmacokinetics
Benzylamines / pharmacology*
Male
Parathyroid Hormone / antagonists & inhibitors*
Parathyroid Hormone / blood*
Rats
Rats, Sprague-Dawley
Receptors, Calcium-Sensing / metabolism*
Structure-Activity Relationship

Substances

Benzylamines
Parathyroid Hormone
Receptors, Calcium-Sensing
dibenzylamine