Discovery of quinolines as selective glucocorticoid receptor agonists.
The dissociated glucocorticoid receptor (GR) agonist ZK 216348 is rendered GR-selective over other nuclear hormone receptors through replacing the methylbenzoxazine with a quinoline moiety. Compounds were shown to be efficacious in cell assays with respect to inflammation endpoints, along with reduced activity in a transactivation assay, hinting at an improved therapeutic window over corticosteroids.
Jaroch
Stefan
S
Medicinal Chemistry Berlin, Lead Generation & Optimization, Bayer Schering Pharma AG, Berlin D-13342, Germany. stefan.jaroch@bayerhealthcare.com
Berger
Markus
M
Huwe
Christoph
C
Krolikiewicz
Konrad
K
Rehwinkel
Hartmut
H
Schäcke
Heike
H
Schmees
Norbert
N
Skuballa
Werner
W
D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D002460:Cell Line; D004353:Drug Evaluation, Preclinical; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011965:Receptors, Glucocorticoid / Q000819:agonists* / Q000378:metabolism; D015533:Transcriptional Activation
D000893:Anti-Inflammatory Agents; D011804:Quinolines; D011965:Receptors, Glucocorticoid