Design, synthesis and biological evaluation of novel (E)-α-benzylsulfonyl chalcone derivatives as potential BRAF inhibitors

Add time:07/11/2019    Source:sciencedirect.com

Activating mutations in the BRAF serine/threonine kinase are found in more than 70% of human melanomas, >90% of which are BRAFV600E. It provides new therapeutic opportunities in malignant melanoma. In silico and in vitro screening of our compound collection has identified Hit 2 as BRAFV600E inhibitor. Based on its structure, a series of novel (E)-α-benzylsulfonyl chalcone derivatives (13–40) were designed and synthesized. Compound 38 exhibited the most potent inhibitory activity with an IC50 value of 0.17 μM for BRAFV600E and GI50 value of 0.52 μM for mutant BRAF-dependent cells. The results of cell based pERK activity and cellular selectivity suggested that those compounds could selectively inhibit proliferation of mutant BRAF-dependent melanoma cell line through inhibition of oncogenic BRAF.

We also recommend Trading Suppliers and Manufacturers of 2-(benzylsulfonyl)-5-chloropyrimidine (cas 79685-43-1). Pls Click Website Link as below: cas 79685-43-1 suppliers

Prev:Straightforward Bienaymé and copper catalyzed N-arylation sequence to access diverse 5H-pyrido[2′,1′:2,3]imidazo[4,5-b]indoles and analogues
Next:Synthesis of 5,6-dihydro-2H-thiins and 2,3-dihydro-1,4-oxathiins based on 1-benzylsulfonyl-1,1-dihydropolyfluoroalkan-2-ones)