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A series of benzo[d]imidazole analogues of thiabenzole were synthesized and their antiinflammatory activities toward NLRP3 (nucleotide-binding domain leucine-rich repeat containing protein familypyrin domain-containing 3also known as cryopyrin or NALP3) inflammasome were evaluated in vitro. Two lead compounds, TBZ-09 and TBZ-21, were identified by antiproduction of IL-1β. In the second round of biological evaluation, based on the lead, 34 more compounds were synthesized and their in vitro anti-inflammatory activities were investigated. Several compounds were identified as anti-inflammatory agents that can reduce IL-1β expression in a dosedependent manner. A preliminary structure-activity relationship is also summarized here.

Synthesis and Biological Evaluation of Novel Benzimidazole Derivatives and Analogs Targeting the NLRP3 Inflammasome