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

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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.

作者简介

I. Fonareva

Nizhny Novgorod State University

Faculty of Chemistry Nizhny Novgorod, Russia

E. Kolesnikova

Nizhny Novgorod State University

Faculty of Chemistry Nizhny Novgorod, Russia

E. Mitroshina

Nizhny Novgorod State University, Institute of Biology and Biomedicine

Nizhny Novgorod, Russia

E. Marasanova

Nizhny Novgorod State University, Institute of Biology and Biomedicine

Nizhny Novgorod, Russia

M. Vedunova

Nizhny Novgorod State University, Institute of Biology and Biomedicine

Nizhny Novgorod, Russia

A. Fedorov

Nizhny Novgorod State University

Email: afedorovNN@yandex.ru
Faculty of Chemistry Nizhny Novgorod, Russia

E. Shchegravina

Nizhny Novgorod State University

Email: sc.katarina@yandex.ru
Faculty of Chemistry Nizhny Novgorod, Russia

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