Nonsteroidal 2,3-dihydroquinoline glucocorticoid receptor agonists with reduced PEPCK activation

  • Bioorg Med Chem Lett. 2011 Mar 15;21(6):1654-7. doi: 10.1016/j.bmcl.2011.01.104.
Andrew R Hudson  1 ,  Robert I Higuchi ,  Steven L Roach ,  Lino J Valdez ,  Mark E Adams ,  Angie Vassar ,  Deepa Rungta ,  Peter M Syka ,  Dale E Mais ,  Keith B Marschke ,  Lin Zhi
Affiliations
  • 1. Discovery Research, Ligand Pharmaceuticals, La Jolla, CA 92037, USA. [email protected]
PMID: 21324689 DOI: 10.1016/j.bmcl.2011.01.104
Abstract

Continuing studies based on dihydroquinoline Glucocorticoid Receptor agonists lead to the discovery of a series of C4-oxime analogs. Representative compounds exhibited potent transrepression activity with minimal transactivation of phosphoenolpyruvate caboxykinase (PEPCK), a key protein in the gluconeogenesis pathway. These compounds represent promising leads in identifying GR agonists with high anti-inflammatory activity and attenuated potential for glucose elevation.