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 journalArticle

Abstract

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
Volume62
Issue number5
DOIs
StatePublished - May 1 2019

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Copper
Bearings (structural)
Cells
Benzimidazoles
Iodides
Pharmaceutical Preparations
indole
benzimidazole

All Science Journal Classification (ASJC) codes

  • Chemistry(all)

Cite this

Guo, Zhengwei ; Shi, Lai ; Wang, Bo ; He, Gang ; Wang, Yanming ; Chen, Gong. / Synthesis of reversible PAD4 inhibitors via copper-catalyzed C−H arylation of benzimidazole. In: Science China Chemistry. 2019 ; Vol. 62, No. 5. pp. 592-596.
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Synthesis of reversible PAD4 inhibitors via copper-catalyzed C−H arylation of benzimidazole. / Guo, Zhengwei; Shi, Lai; Wang, Bo; He, Gang; Wang, Yanming; Chen, Gong.

In: Science China Chemistry, Vol. 62, No. 5, 01.05.2019, p. 592-596.

Research output: Contribution to journalArticle

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AU - Shi, Lai

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AU - Chen, Gong

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