title: Nonsteroidal 2,3-dihydroquinoline glucocorticoid receptor agonists with reduced PEPCK activation.
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.
authors.affiliation: Discovery Research, Ligand Pharmaceuticals, La Jolla, CA 92037, USA. andyrhudson@gmail.com
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Hudson
authors.forename: Robert I
authors.initials: RI
authors.lastname: Higuchi
authors.forename: Steven L
authors.initials: SL
authors.lastname: Roach
authors.forename: Lino J
authors.initials: LJ
authors.lastname: Valdez
authors.forename: Mark E
authors.initials: ME
authors.lastname: Adams
authors.forename: Angie
authors.initials: A
authors.lastname: Vassar
authors.forename: Deepa
authors.initials: D
authors.lastname: Rungta
authors.forename: Peter M
authors.initials: PM
authors.lastname: Syka
authors.forename: Dale E
authors.initials: DE
authors.lastname: Mais
authors.forename: Keith B
authors.initials: KB
authors.lastname: Marschke
authors.forename: Lin
authors.initials: L
authors.lastname: Zhi
mesh_terms: D002262:Carboxy-Lyases / Q000378:metabolism*; D004789:Enzyme Activation; D011804:Quinolines / Q000737:chemistry / Q000494:pharmacology*; D011965:Receptors, Glucocorticoid / Q000819:agonists*; D013329:Structure-Activity Relationship
chemical_list: D011804:Quinolines; D011965:Receptors, Glucocorticoid; D002262:Carboxy-Lyases