药物化学

Synthesis, Antiproliferative and Anti-inflammatory Activities of Novel Simplified Imatinib Analogues

Abstract

Thiago Stevanatto Sampaio, Lídia Moreira Lima, Renata da Silva Zardo, Cláudia Pessoa, Bruno Coêlho Cavalcanti, Rosane de Paula Castro, José Ricardo Sabino, Patrícia Dias Fernandes and Eliezer J Barreiro

We described the synthesis of carboxamide derivatives designed as novel simplified imatinib analogues and their antiproliferative and anti-inflammatory activities. Compound 2c showed a unique conformation determined by X-ray diffraction and by NMR 1H and displayed antiproliferative potency in the same magnitude order than the standard imatinib. Compounds 6-10 were prepared by structural modification in carboxamide 2c, and with exception of derivative 10, they were inactive as antiproliferative agent. However, these compounds showed same anti-inflammatory potency than imatinib, standing out carboxamide 9 that was six time more potent as TNF-α inhibitor production.