The transient receptor potential cation channel 5 (TRPC5) has been previously shown to affect podocyte survival in the kidney. As such, inhibitors of TRPC5 are interesting candidates for the treatment of chronic kidney disease (CKD). Herein, we report the synthesis and biological characterization of a series of N-heterocyclic-1-benzyl-1H-benzo[d]imidazole-2-amines as selective TRPC5 inhibitors. Work reported here evaluates the benzimidazole scaffold and substituents resulting in the discovery of AC1903, a TRPC5 inhibitor that is active in multiple animal models of CKD.

中文翻译：

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设计，合成和表征新型N-杂环-1-苄基-1H-苯并[d]咪唑-2-胺作为选择性TRPC5抑制剂，从而鉴定了选择性化合物AC1903。

先前已显示出瞬时受体电位阳离子通道5（TRPC5）影响肾脏足细胞的存活。因此，TRPC5抑制剂是治疗慢性肾脏疾病（CKD）的有趣候选药物。在这里，我们报告了一系列的N-杂环-1-苄基-1H-苯并[d]咪唑-2-胺作为选择性TRPC5抑制剂的合成和生物学特性。此处报道的工作评估了苯并咪唑支架和取代基，从而发现了AC1903，这是一种在多种CKD动物模型中均具有活性的TRPC5抑制剂。