Comparative molecular field analysis(CoMFA)and comparative molecular similarity index analysis(CoMSIA)were used to establish 3D-QSAR models of 33 reported quinolinone BRD4 inhibitors,and the relationship between their chemical structure and biological activity was studied.Seven quinolinone BRD4 inhibitors were designed by computer-aided drug design(CADD).The results showed that the established CoMFA(q2 = 0.926,r2 = 0.997,r2pred = 0.744)and CoMSIA(q2 = 0.939,r2 = 0.991,r2pred = 0.786)models had good predictive ability.Seven new quinolone BRD4 inhibitors designed based on these models had high activity,and their ADMET properties and drug-likeness were evaluated.The above results are helpful for the modification and development of more effective quinolone BRD4 inhibitors.
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