Design, Synthesis, and Biological Evaluation of New Potential Inhibitors of Monocarboxylate Transporters MCT1 Based on 1,5-Diarylpyrazoles

The article describes the synthesis of potential inhibitors of lactic acid transport proteins (MCT proteins). The key stage of the synthesis is the arylation of pyrazole by the Suzuki reaction. According to the synthetic scheme proposed in the work, a number of target derivatives containing aryl and heteroaryl substituents at position 5 of the pyrazole ring were obtained. The ability to block lactate transport into the cell was assessed for all the derivatives obtained. It was shown that the most promising compound is derivative 3a, containing a chloropyridine fragment at position 5 of pyrazole. Its activity at concentrations of 25 and 50 μM was comparable to the activity of the confirmed MCT1 inhibitor BAY-8002, which was used as a reference compound.