Optimization of azoles as anti-human immunodeficiency virus agents guided by free-energy calculations

…, CM Bailey, RA Domaoal, KS Anderson…

文献索引：Barreiro, Gabriela; Kim, Joseph T.; Guimaraes, Cristiano R. W.; Bailey, Christopher M.; Domaoal, Robert A.; Wang, Ligong; Anderson, Karen S.; Jorgensen, William L. Journal of Medicinal Chemistry, 2007 , vol. 50, # 22 p. 5324 - 5329

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被引用次数: 70

摘要

Efficient optimization of an inactive 2-anilinyl-5-benzyloxadiazole core has been guided by free energy perturbation (FEP) calculations to provide potent non-nucleoside inhibitors of human immunodeficiency virus (HIV) reverse transcriptase (NNRTIs). An FEP “chlorine scan” was performed to identify the most promising sites for substitution of aryl hydrogens. This yielded NNRTIs 8 and 10 with activities (EC50) of 820 and 310 nM for protection of ...