RESUMO
1-(1H-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: IC50=120 nM; human LHRH: IC50=18 nM). These SAR studies suggest that 1-(1H-benzimidazol-5-yl)-3-tert-butylurea is a new pharmacophore for small molecule LHRH antagonists.
Assuntos
Benzimidazóis/farmacologia , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Ureia/análogos & derivados , Animais , Benzimidazóis/síntese química , Humanos , Cinética , Modelos Moleculares , Estrutura Molecular , Ratos , Relação Estrutura-Atividade , Ureia/síntese química , Ureia/farmacologiaRESUMO
A new class of benzimidazole-5-sulfonamides has been identified as nonpeptide luteinizing hormone-releasing hormone (LHRH) antagonists. Initial structure-activity relationships are presented resulting in compounds 19 and 28 with submicromolar dual functional activity on human and rat receptors.
