614763-00-7Relevant articles and documents
Potent Anti-Inflammatory, Arylpyrazole-Based Glucocorticoid Receptor Agonists That Do Not Impair Insulin Secretion
Burke, Susan J.,Campagna, Shawn R.,Collier, J. Jason,Dunlap, Lee E.,Fisch, Alexander R.,Kennedy, Brandon J.,Kirkland, Justin K.,Lato, Ashley M.,Prevatte, Carson W.,Smith, Russell T.,Vogiatzis, Konstantinos D.
, p. 1568 - 1577 (2021/10/04)
Glucocorticoids (GCs) are widely used in medicine for their role in the treatment of autoimmune-mediated conditions, certain cancers, and organ transplantation. The transcriptional activities GCs elicit include transrepression, postulated to be responsible for the anti-inflammatory activity, and transactivation, proposed to underlie the undesirable side effects associated with long-term use. A GC analogue that could elicit only transrepression and beneficial transactivation properties would be of great medicinal value and is highly sought after. In this study, a series of 1-(4-substituted phenyl)pyrazole-based GC analogues were synthesized, biologically screened, and evaluated for SARs leading to the desired activity. Activity observed in compounds bearing an electron deficient arylpyrazole moiety showed promise toward a dissociated steroid, displaying transrepression while having limited transactivation activity. In addition, compounds 11aa and 11ab were found to have anti-inflammatory efficacy comparable to that of dexamethasone at 10 nM, with minimal transactivation activity and no reduction of insulin secretion in cultured rat 832/13 beta cells.
Design and evaluation of novel nonsteroidal dissociating glucocorticoid receptor ligands
Shah, Nilesh,Scanlan, Thomas S.
, p. 5199 - 5203 (2007/10/03)
A novel class of phenylpyrazole fused Wieland-Miescher ketone derivatives are high affinity, receptor specific, selective modulators of glucocorticoid receptor (GR) function.
