Development of non-nucleoside reverse transcriptase inhibitors (NNRTIs): our past twenty years
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...
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2020-06-01
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| Series: | Acta Pharmaceutica Sinica B |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211383519312183 |
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doaj-11873e32bb014d808e0b599333f5b12f2020-11-25T03:51:59ZengElsevierActa Pharmaceutica Sinica B2211-38352020-06-01106961978Development of non-nucleoside reverse transcriptase inhibitors (NNRTIs): our past twenty yearsChunlin Zhuang0Christophe Pannecouque1Erik De Clercq2Fener Chen3Engineering Center of Catalysis and Synthesis for Chiral Molecules, Department of Chemistry, Fudan University, Shanghai 200433, China; Shanghai Engineering Center of Industrial Asymmetric Catalysis for Chiral Drugs, Shanghai 200433, ChinaRega Institute for Medical Research, KU Leuven, Leuven B-3000, BelgiumRega Institute for Medical Research, KU Leuven, Leuven B-3000, BelgiumEngineering Center of Catalysis and Synthesis for Chiral Molecules, Department of Chemistry, Fudan University, Shanghai 200433, China; Shanghai Engineering Center of Industrial Asymmetric Catalysis for Chiral Drugs, Shanghai 200433, China; Institute of Pharmaceutical Science and Technology, Zhejiang University of Technology, Hangzhou 310014, China; Corresponding author.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.http://www.sciencedirect.com/science/article/pii/S2211383519312183HIV-1NNRTIsHENTsS-DABOsDATAsDAPYs |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Chunlin Zhuang Christophe Pannecouque Erik De Clercq Fener Chen |
| spellingShingle |
Chunlin Zhuang Christophe Pannecouque Erik De Clercq Fener Chen Development of non-nucleoside reverse transcriptase inhibitors (NNRTIs): our past twenty years Acta Pharmaceutica Sinica B HIV-1 NNRTIs HENTs S-DABOs DATAs DAPYs |
| author_facet |
Chunlin Zhuang Christophe Pannecouque Erik De Clercq Fener Chen |
| author_sort |
Chunlin Zhuang |
| title |
Development of non-nucleoside reverse transcriptase inhibitors (NNRTIs): our past twenty years |
| title_short |
Development of non-nucleoside reverse transcriptase inhibitors (NNRTIs): our past twenty years |
| title_full |
Development of non-nucleoside reverse transcriptase inhibitors (NNRTIs): our past twenty years |
| title_fullStr |
Development of non-nucleoside reverse transcriptase inhibitors (NNRTIs): our past twenty years |
| title_full_unstemmed |
Development of non-nucleoside reverse transcriptase inhibitors (NNRTIs): our past twenty years |
| title_sort |
development of non-nucleoside reverse transcriptase inhibitors (nnrtis): our past twenty years |
| publisher |
Elsevier |
| series |
Acta Pharmaceutica Sinica B |
| issn |
2211-3835 |
| publishDate |
2020-06-01 |
| description |
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. |
| topic |
HIV-1 NNRTIs HENTs S-DABOs DATAs DAPYs |
| url |
http://www.sciencedirect.com/science/article/pii/S2211383519312183 |
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