RESUMO
The C797S mutation is one of the major factors behind resistance to the third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors. Herein, we describe the discovery of the 2,4-diaminonicotinamide derivative 5j, which shows potent inhibitory activity against EGFR del19/T790M/C797S and L858R/T790M/C797S. We also report the structure-activity relationship of the 2,4-diaminonicotinamide derivatives and the co-crystal structure of 5j and EGFR del19/T790M/C797S.
Assuntos
Receptores ErbB , Neoplasias Pulmonares , Niacinamida , Humanos , Resistencia a Medicamentos Antineoplásicos , Receptores ErbB/efeitos dos fármacos , Receptores ErbB/genética , Neoplasias Pulmonares/genética , Mutação , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/química , Relação Estrutura-Atividade , /farmacologia , Niacinamida/análogos & derivados , Niacinamida/químicaRESUMO
A concise synthesis of litseaones A and B, which were isolated from the stem barks of Litsea rubescens and L. pedunculata, is described in this study. Litseaone A was synthesized in just three steps from a known phloroglucinol derivative. The direct conversion of litseaone A into litseaone B was also achieved.
