RESUMO
Background: Quinazoline-based compounds have been proved effective in the treatment of cancers for years. Materials & methods: The structural features of several inhibitors of EGFR were integrated and quinazolines with a benzazepine moiety at the 4-position were constructed. Results: Most of the compounds exhibited excellent antitumor activities. Compound 33e showed excellent antitumor activities against the four tested cell lines (IC50: 1.06-3.55 µM). The enzymatic, signaling pathways and apoptosis assay of 33e were subsequently carried out to study the action of the mechanism. Conclusion: Compound 33e with a benzazepine moiety at the 4-position can be screened in this study and provides useful information for the design of EGFR-T790M inhibitors, which deserve additional research.
Assuntos
Antineoplásicos/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Quinazolinas/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/metabolismo , Humanos , Modelos Moleculares , Estrutura Molecular , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Quinazolinas/síntese química , Quinazolinas/químicaRESUMO
A one-pot, three-component [3 + 3] benzannulation reaction of α,ß-unsaturated carbonyl compounds, bromoallylic sulfones, and sodium sulfinates had been developed. A series of multisubstituted arylsulfones were prepared with moderate to good yields. This method has the advantages of good step-economy, broad substrate scope and operational simplicity.
RESUMO
A series of meta-amido bromophenol derivatives were designed and synthesized. The compounds were found to potently inhibit the growth of Mycobacterium tuberculosis H37Ra. They also exhibited moderate inhibitory activity against Mycobacterium tuberculosis H37Rv and multidrug-resistant strains. The compounds did not show inhibitory activity against normal Gram-positive and Gram-negative bacteria. Moderate cytotoxicities and good metabolic stability were observed for the selected compounds. The results demonstrated meta-amido bromophenols as a new class of antitubercular agents with good potentials.
Assuntos
Antituberculosos/química , Fenóis/química , Desenho de Fármacos , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Mycobacterium tuberculosis/efeitos dos fármacos , Fenóis/farmacologia , Relação Estrutura-AtividadeRESUMO
A base-mediated [3 + 3] benzannulation strategy for the conversion of 1,3-bis(sulfonyl)propenes and ß,γ-unsaturated α-ketoesters to diaryl sulfones has been developed. This method provides facile, metal-free and efficient access to highly substituted diaryl sulfones in good to excellent yields. In addition, the sulfonyl group could be easily removed or converted to other functional groups via an organostannane intermediate.
