Benzimidazoles as non-peptide luteinizing hormone-releasing hormone (LHRH) antagonists. Part 3: Discovery of 1-(1H-benzimidazol-5-yl)-3-tert-butylurea derivatives.

Abstract 1-(1 H -Benzimidazol-5-yl)-3- tert -butylurea derivatives have been identified as a novel class of non-peptide luteinizing hormone-releasing hormone (LHRH) antagonists. Herein, we disclose the synthesis and structure–activity relationships (SAR) of this class resulting in the identification of compound 12c , with dual functional activity on human and rat receptors (rat LHRH: IC 50  = 120 nM; human LHRH: IC 50  = 18 nM). These SAR studies suggest that 1-(1 H -benzimidazol-5-yl)-3- tert -butylurea is a new pharmacophore for small molecule LHRH antagonists.