RESUMO
Synthesis and structure-activity relationship of a series of 4-(2-aryl-cyclopropylamino)-quinoline-3-carbonitrile derivatives as EGFR inhibitors is described. Compounds 29 and 30 showed potent in vitro inhibitory activity in the enzymatic assay as well as in the functional cellular assay. They are moderately selective against other types of tyrosine kinases.
Assuntos
Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Receptores ErbB/antagonistas & inibidores , Nitrilas/química , Nitrilas/farmacologia , Quinolinas/química , Quinolinas/farmacologia , Inibidores Enzimáticos/síntese química , Nitrilas/síntese química , Quinolinas/síntese química , Relação Estrutura-AtividadeRESUMO
A structurally novel liver X receptor (LXR) agonist (1) was identified from internal compound collection utilizing the combination of structure-based virtual screening and high-throughput gene profiling. Compound 1 increased ABCA1 gene expression by eightfold and SREBP1c by threefold in differentiated THP-1 macrophage cell lines. Confirmation of its agonistic activity against LXR was obtained in the co-factor recruitment and reporter transactivation assays. Structure-activity relationship studies on compound 1 are described.
