摘要
Human immunodeficiency virus(HIV)is the primary infectious agent of acquired immunodeficiency syndrome(AIDS),and non-nucleoside reverse transcriptase inhibitors(NNRTIs)are the cornerstone of HIV treatment.In the last 20 years,our medicinal chemistry group has made great strides in developing several distinct novel NNRTIs,including 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine(HEPT),thio-dihydro-alkoxy-benzyl-oxopyrimidine(S-DABO),diaryltriazine(DATA),diarylpyrimidine(DAPY)analogues,and their hybrid derivatives.Application of integrated modern medicinal strategies,including structure-based drug design,fragment-based optimization,scaffold/fragment hopping,molecular/fragment hybridization,and bioisosterism,led to the development of several highly potent analogues for further evaluations.In this paper,we review the development of NNRTIs in the last two decades using the above optimization strategies,including their structure-activity relationships,molecular modeling,and their binding modes with HIV-1 reverse transcriptase(RT).Future directions and perspectives on the design and associated challenges are also discussed.
基金
funded by grants from the National Natural Science Foundation of China(81872791 and 21372050)
the Young Elite Scientists Sponsorship Program by the China Association forScience and Technology(2017QNRC061)
National Key R&D Program of China(2017YFA0506000)
the Key Research and Development Program of Ningxia(2019BFG02017 and 2018BFH02001,China)
作者简介
Corresponding author:Fener Chen,E-mail address:rfchen@fudan.edu.cn
