Synthesis of reversible PAD4 inhibitors via copper-catalyzed C-H arylation of benzimidazole

• 来源期刊: 中国科学:化学（英文版）
• 年，卷（期）: 2019,（5）
• 页码范围: 592-596
• 页数: 5页
• 语种: 英文

摘要

PAD4 is a promising epigenetic drug target for various cancers and immune diseases.In this work,we applied a Cu-catalyzed C-H arylation reaction of N-heteroarene to the synthesis of complex non-covalent PAD4 inhibitors bearing a bi-heteroaryl pharmacophore.This strategy allowed us to access various analogs of C2-aryl substituted benzimidazoles from a common benzimidazole core and easily accessible aryl iodides.Preliminary SAR studies revealed the indole motif of GSK-484 is critical to its activity,Replacing the N-cyclopropylmethyl group to N-benzyl group on the indole ring of GSK-484 resulted in more than 5-fold increase in cell killing efficacy against 4T1 cell line.