5-Functionalized indazoles as glucocorticoid receptor agonists.
An indazole based series of glucocorticoid receptor agonists is reported. The SAR exploration of this scaffold yielded compounds with nanomolar affinity for the glucocorticoid receptor with indications of selectivity for the preferred transrepression mechanism; in vivo efficacy was observed in the mouse LPS induced TNFalpha model for compound 28.
Bai
Mei
M
AMRI, Albany, NY 12212-5098, USA.
Carr
Grant
G
Deorazio
Russell J
RJ
Friedrich
Thomas D
TD
Dobritsa
Svetlana
S
Fitzpatrick
Kevin
K
Guzzo
Peter R
PR
Kitchen
Douglas B
DB
Lynch
Michael A
MA
Peace
Denise
D
Sajad
Mohammed
M
Usyatinsky
Alexander
A
Wolf
Mark A
MA
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D007191:Indazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D051379:Mice; D011965:Receptors, Glucocorticoid / Q000819:agonists* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D007191:Indazoles; D011965:Receptors, Glucocorticoid; D014409:Tumor Necrosis Factor-alpha