Derivatives of Pyrazine-2-carboxamide and Their Activity as Tyrosine Kinases Inhibitors
Widiastuti Agustina Eko Setyowati, Yana Maolana Syah, Ihsanawati, Anita Alni

1. Department of Chemistry, Faculty of Mathematics and Natural Sciences, Institute of Technology Bandung, Indonesia
2. Study Program of Chemistry Education, Faculty of Teacher Training and Education, Sebelas Maret University, Indonesia

Abstract

Three pyrazine-2-carboxamide derivatives, i.e. 3-amino-N-butylpyrazine-2-carboxamide (1), 3-amino-N-isobutylpyrazine-2-carboxamide (2), and 3-amino-N-(4-methylbenzyl)pyrazine-2-carboxamide (3) have been successfully synthesized from 3-aminopyrazine-2-carboxylic acid. The molecular structures of these compounds were determined based on 1D NMR (1H and 13C), 2D NMR (HMBC and HSQC) and MS spectroscopic data. The three compounds together with the three pyrazine-2-carboxamide derivatives previously reported, i.e. 3-amino-N-phenylpyrazine-2-carboxylic acid (4), 3-hydroxy-6-nitropyrazine-2-carboxamide (5) and 6-fluoro-3-hydroxypyrazine-2-carboxamide (6) were evaluated as inhibitors against eight tyrosine kinases, including AXL1, EPHA1 TRKA, FAK, ITK, JAK3, PYK2, and SYK. The assay was done by the bioluminescence method using a single-dose profile protocol. The results showed that pyrazine 4 has inhibitory activity against AXL1 and TRKA of 41% and 34%, respectively, while pyrazine 3 has inhibitory activity against AXL1 with the inhibitory activity of 21%. Pyrazine-2-carboxamide derivatives containing aromatic chains in the amide group have higher inhibitory activity so they can be lead compounds as tyrosine kinase inhibitors.

Keywords: pyrazine derivatives, inhibitor, tyrosine kinase

Topic: Organic Chemistry