Aryl aminopyrazole benzamides as oral non-steroidal selective glucocorticoid receptor agonists

Aryl aminopyrazole amides capped with N-alkylbenzamides 13–16 are selective glucocorticoid receptor agonists. 2,6-Disubstituted benzamides have prednisolone-like potency or better in vitro. Good oral exposure was demonstrated in the rat, with compounds with lower lipophilicity, for example N-hydroxyethyl benzamides (e.g., 16e).

Graphical abstractSAR leading to the oral selective non-steroidal GR agonist 16e is described.Figure optionsDownload full-size imageDownload as PowerPoint slide