1028527-85-6Relevant academic research and scientific papers
Discovery of indazole ethers as novel, potent, non-steroidal glucocorticoid receptor modulators
Hemmerling, Martin,Edman, Karl,Lepist?, Matti,Eriksson, Anders,Ivanova, Svetlana,Dahmén, Jan,Rehwinkel, Hartmut,Berger, Markus,Hendrickx, Ramon,Dearman, Matthew,Jensen, Tina Jellesmark,Wissler, Lisa,Hansson, Thomas
, p. 5741 - 5748 (2016/11/28)
A structure-based design approach led to the identification of a novel class of indazole ether based, non-steroidal glucocorticoid receptor (GR) modulators. Several examples were identified that displayed cell potency in the picomolar range, inhibiting LPS-induced TNF-α release by primary peripheral blood mononuclear cells (PBMCs). Additionally, an improved steroid hormone receptor binding selectivity profile, compared to classical steroidal GR agonists, was demonstrated. The indazole ether core tolerated a broad range of substituents allowing for modulation of the physiochemical parameters. A small sub-set of indazole ethers, with pharmacokinetic properties suitable for oral administration, was investigated in a rat antigen-induced joint inflammation model and demonstrated excellent anti-inflammatory efficacy.
