Novel non-steroidal/non-anilide type androgen antagonists: discovery of 4-substituted pyrrole-2-carboxamides as a new scaffold for androgen receptor ligands

We designed and synthesized novel pyrrole-2-carboxamide derivatives as androgen antagonists. Compounds 10 and 13 bearing benzylamine or aniline at the 4-position of the pyrrole ring showed moderate androgen antagonistic activity, and inhibited the androgen-dependent growth of Shionogi carcinoma cells (SC-3). Study of the structure–activity relationships of compound 13 led to a potent androgen antagonist 36, which has higher affinity than flutamide (4) for androgen nuclear receptor (AR). Thus, pyrrole-2-carboxamide is a new scaffold for developing AR antagonists.

Novel pyrrole-2-carboxamide derivatives were designed and synthesized as androgen antagonists. Compound 1 is more active androgen antagonist than flutamide.Figure optionsDownload as PowerPoint slide