Two series of sulfur-containing diarylbenzopyrimidines are designed by the fragment combination of a thioacetamide with our previous disclosed DABP 3 and further oxidation.The best compound 6 e with a sulfonyl scaffol...Two series of sulfur-containing diarylbenzopyrimidines are designed by the fragment combination of a thioacetamide with our previous disclosed DABP 3 and further oxidation.The best compound 6 e with a sulfonyl scaffold displayed EC(50)values of 0.0356μmol/L against WT and 0.0228μmol/L against HIV K103 N mutant strain.More pronounced,it had a lower cytotoxicity(CC(50)=99.6μmol/L),higher selectivity index(SIWT=2799,SIK103 N=4375)and better calculated logarithm of the octanol-water partition coefficient(cLogP)than the lead compound 3.Molecular docking and dynamics provided the binding modes of these compounds with reve rse transcriptase,explaining their activity.Collectively,the new compounds could be candidates for anti-HIV drug discovery.展开更多
基金financially supported by the National Natural Science Foundation of China(No.21372050)National Key R&D Program of China(No.2017YFA0506000)the Young Elite Scientists Sponsorship Program by the China Association for Science and Technology(No.2017QNRC061)。
文摘Two series of sulfur-containing diarylbenzopyrimidines are designed by the fragment combination of a thioacetamide with our previous disclosed DABP 3 and further oxidation.The best compound 6 e with a sulfonyl scaffold displayed EC(50)values of 0.0356μmol/L against WT and 0.0228μmol/L against HIV K103 N mutant strain.More pronounced,it had a lower cytotoxicity(CC(50)=99.6μmol/L),higher selectivity index(SIWT=2799,SIK103 N=4375)and better calculated logarithm of the octanol-water partition coefficient(cLogP)than the lead compound 3.Molecular docking and dynamics provided the binding modes of these compounds with reve rse transcriptase,explaining their activity.Collectively,the new compounds could be candidates for anti-HIV drug discovery.
