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

Zhengwei Guo, Lai Shi, Bo Wang, Gang He, Yanming Wang, Gong Chen

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


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 C 2 -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.

Original languageEnglish (US)
Pages (from-to)592-596
Number of pages5
JournalScience China Chemistry
Issue number5
StatePublished - May 1 2019

All Science Journal Classification (ASJC) codes

  • General Chemistry


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