Synthesis and Biological Evaluation of 5‐Arylpyrazoles as Potential MCT 1 Inhibitors Targeting Lactate Transport

Monocarboxylate transporter 1 (MCT1) represents an attractive therapeutic target as an important regulator of tumor metabolism. In this study, we developed a convenient synthetic approach to novel 5‐arylpyrazole derivatives as potential MCT1 inhibitors. Eleven new pyrazole derivatives ( 17a–k ) were prepared through a six‐step sequence in 5%–19% overall yields. Screening using 3‐bromopyruvate assays revealed that compound 17c, bearing a 3‐fluorophenyl substituent, significantly inhibited MCT1‐mediated transport at below its cytotoxic concentrations. The compound 17c induced dose‐ and time‐dependent accumulation of intracellular lactate in multiple cell lines, confirming its ability to interfere with MCT1‐driven metabolism. These results identify 5‐arylpyrazoles as a promising chemotype of MCT1 inhibitors, and highlight compound 17c as a potential lead for further optimizations in cancer metabolism‐targeted therapy.