Synthesis and structure–activity relationships of thieno[2,3-b]pyrroles as antagonists of the GnRH receptor

A new class of small-molecule GnRH antagonists, the thieno[2,3-b]pyrroles, was designed. Herein, the synthesis and structure–activity relationships are described. Substitution at the C4 position was investigated; during this study, it was observed that introducing piperazines and piperidines improved the physical properties of the compounds while retaining good in vitro potency. This exploration led to the discovery of amidopiperidines with improved pharmacokinetic properties.

Graphical abstractThe synthesis and structure–activity relationships (SAR) of GnRH receptor antagonists based on thieno[2,3-b]pyrrole scaffold are described. Introduction of a piperidine moiety at C4 position led to compounds combining good in vitro potency and improved pharmacokinetics.Figure optionsDownload full-size imageDownload as PowerPoint slide