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. Epub 2011 Jan 27.

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.

MeSH terms

  • Carboxy-Lyases / metabolism*
  • Enzyme Activation
  • Quinolines / chemistry
  • Quinolines / pharmacology*
  • Receptors, Glucocorticoid / agonists*
  • Structure-Activity Relationship

Substances

  • Quinolines
  • Receptors, Glucocorticoid
  • Carboxy-Lyases