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.