Journal ArticleDOI
Structural Modifications of DAPY Analogues with Potent Anti‐HIV‐1 Activity
Xiao-Qing Feng,Yong-Hong Liang,Zhaosen Zeng,Fen-Er Chen,Jan Balzarini,Christophe Pannecouque,Erik De Clercq +6 more
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A novel series of diarylpyrimidine analogues (DAPYs) featuring a naphthyl moiety at the C4 position were designed, with all compounds exhibiting strong activity against wild‐type HIV‐1.Abstract:
A novel series of diarylpyrimidine analogues (DAPYs) featuring a naphthyl moiety at the C4 position were designed, with all compounds exhibiting strong activity against wild-type HIV-1.A novel series of diarylpyrimidine analogues (DAPYs) featuring a naphthyl moiety at the C4 position were synthesized and evaluated for their in vitro activity against HIV in MT-4 cells. All compounds exhibited strong activity against wild-type HIV-1. The most active compound showed activity against wild-type HIV-1 with an EC(50) value of 2.35 nM and against the double mutant strain (K103N+Y181C) with an EC(50) value of 6.6 microM, with a selectivity index greater than 60 000 against wild-type HIV-1. Additionally, some compounds also showed activity against HIV-2 (EC(50)=5.82 microM).read more
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HIV-1 NNRTIs: structural diversity, pharmacophore similarity, and implications for drug design.
TL;DR: This review covers two decades of research and development for various NN RTI families based on their chemical scaffolds, and describes the structural similarity of NNRTIs.
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Synthetic approaches to the 2011 new drugs.
TL;DR: This review covers the synthesis of 26 NCEs that were launched in the world in 2011 and provides insights into molecular recognition and also serves as leads for designing future new drugs.
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Development of non-nucleoside reverse transcriptase inhibitors (NNRTIs): our past twenty years.
TL;DR: This paper reviews 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).
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Design, synthesis, anti-HIV evaluation and molecular modeling of piperidine-linked amino-triazine derivatives as potent non-nucleoside reverse transcriptase inhibitors
Xuwang Chen,Peng Zhan,Xin Liu,Ziheng Cheng,Caicai Meng,Siyuan Shao,Christophe Pannecouque,Erik De Clercq,Xinyong Liu +8 more
TL;DR: A novel series of piperidine-linked amino-triazine derivatives were designed, synthesized and evaluated for in vitro anti-HIV activity as non-nucleoside reverse transcriptase inhibitors and preliminary structure-activity relationship and molecular modeling of these new analogs were detailed in this manuscript.
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Fluorine-containing drugs approved by the FDA in 2021
Jing Liang He,Ziyi Li,Gagan Dhawan,Wei Zhang,Alexander E. Sorochinsky,Gregory Butler,Vadim A. Soloshonok,Jianlin Han +7 more
TL;DR: In this article , the authors presented a review of nine fluorine-containing drugs that have been approved by the US Food and Drug Administration (FDA) in 2021, which feature aromatic fluorine, trifluoromethyl and chlorodifluoro groups.
References
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Rapid and automated tetrazolium-based colorimetric assay for the detection of anti-HIV compounds
Rudi Pauwels,Jan Balzarini,Masanori Baba,Robert Snoeck,Dominique Schols,Piet Herdewijn,Jan Desmyter,Erik De Clercq +7 more
TL;DR: A rapid, sensitive and automated assay procedure was developed for the in vitro evaluation of anti-HIV agents, which significantly reduced labor time as compared to the trypan blue exclusion method, and permits the evaluation of large numbers of compounds for their anti-hIV activity.
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Automated docking of flexible ligands: applications of AutoDock.
TL;DR: AutoDock is a suite of C programs used to predict the bound conformations of a small, flexible ligand to a macromolecular target of known structure and the enhancements included in the current release are described.
Journal ArticleDOI
Roles of Conformational and Positional Adaptability in Structure-Based Design of TMC125-R165335 (Etravirine) and Related Non-nucleoside Reverse Transcriptase Inhibitors That Are Highly Potent and Effective against Wild-Type and Drug-Resistant HIV-1 Variants
Kalyan Das,Arthur D. Clark,Paul J. Lewi,Jan Heeres,Marc René De Jonge,Lucien Maria Henricus Koymans,H. Maarten Vinkers,Frederik Frans Desire Daeyaert,Donald William Ludovici,Michael J. Kukla,Bart De Corte,Robert W. Kavash,Chih Y. Ho,Hong Ye,Mark A. Lichtenstein,Koen Andries,Rudi Pauwels,Marie Pierre de Béthune,Paul L. Boyer,Patrick K. Clark,Stephen H. Hughes,Paul A. J. Janssen,Eddy Arnold +22 more
TL;DR: Structural studies showed that this inhibitor and other diarylpyrimidine (DAPY) analogues can adapt to changes in the NNRTI-binding pocket in several ways, and adaptations appear to be critical for potency against wild-type and a wide range of drug-resistant mutant HIV-1 RTs.
Journal ArticleDOI
The design of drugs for HIV and HCV
TL;DR: Considering the drug targets in the different stages of the life cycle of these two viruses, aspects of the history, medicinal chemistry and mechanisms of action of approved and investigational drugs for HIV and HCV are presented and general lessons learned from anti-HIV-drug design are highlighted.
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Tetrazolium-based colorimetric assay for the detection of HIV replication inhibitors: revisited 20 years later
TL;DR: The long-standing and intensive use of the MTT method has taught users of the limitations and the unexpected advantages of the MT-4/MTT assay, and this method can be extended to antiviral testing of compounds against other cyto-destructive viruses.
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