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

Abstract

A series of pyrazole derivatives containing an aryl or heteroaryl substituent on C⁵ were synthesized according to the proposed scheme which involves Suzuki arylation of pyrazole as the key stage. The synthesized compounds were evaluated as inhibitors of monocarboxylate transporter (MCT) proteins. Compound 3a with a chloropyridine substituent on C⁵ of the pyrazole ring was found to be the most promising inhibitor of lactate transport into cells. Its activity at concentrations of 25 and 50 μM was comparable with the activity of the approved MCT1 inhibitor BAY-8002 used as reference.