Deacylcortivazol-like pyrazole regioisomers reveal a more accommodating expanded binding pocket for the glucocorticoid receptor.

ABSTRACT: Glucocorticoids (GCs) are widely used, potent anti-inflammatory and chemotherapeutic drugs. They work by binding to the glucocorticoid receptor (GR), a ligand-activated transcription factor, inducing translocation to the nucleus and regulation of genes that influence a variety of cellular activities. Despite being effective for a broad number of conditions, GC use is limited by severe side effects. To identify ligands that are more selective, we synthesized pairs of regioisomers in the pyrazole ring that probe the expanded binding pocket of GR opened by deacylcortivazol (DAC). Using an Ullmann-type reaction, a deacylcortivazol-like (DAC-like) backbone was modified with five pendant groups at the 1'- and 2'-positions of the pyrazole ring, yielding 9 ligands. Most of the compounds were cytot

SUBMITTER: Zimmerman JAO 

PROVIDER: S-EPMC8127617 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature