ArticleJournal of medicinal chemistry2011
Computationally-guided optimization of a docking hit to yield catechol diethers as potent anti-HIV agents.
Article in Journal of medicinal chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed.
- Structural biology of HIV-1 reverse transcriptase allosteric inhibitors for drug design.Acta pharmaceutica Sinica. B · 2026Review
- Mechanistic basis for a novel dual-function Gag-Pol dimerizer potentiating CARD8 inflammasome activation and clearance of HIV-infected cells.npj drug discovery · 2025Article
- Covalent and noncovalent strategies for targeting Lys102 in HIV-1 reverse transcriptase.European journal of medicinal chemistry · 2023Article
- Exploring novel HIV-1 reverse transcriptase inhibitors with drug-resistant mutants: A double mutant surprise.Protein science : a publication of the Protein Society · 2023Article
- The maximal and current accuracy of rigorous protein-ligand binding free energy calculations.Communications chemistry · 2023Article
- In Vitro and In Silico Antiviral Activity of Di-Halogenated Compounds Derived from L-Tyrosine against Human Immunodeficiency Virus 1 (HIV-1).Current issues in molecular biology · 2023Article
- Strategies in the Design and Development of Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs).Viruses · 2023Review
- Recent Advances in the Synthesis and Applications of m-Aryloxy Phenols.Molecules (Basel, Switzerland) · 2023Review
- Design, synthesis, and biological testing of biphenylmethyloxazole inhibitors targeting HIV-1 reverse transcriptase.Bioorganic & medicinal chemistry letters · 2023Article
- Structural Studies and Structure Activity Relationships for Novel Computationally Designed Non-nucleoside Inhibitors and Their Interactions With HIV-1 Reverse Transcriptase.Frontiers in molecular biosciences · 2022Article
- Towards design of drugs and delivery systems with the Martini coarse-grained model.QRB discovery · 2022Review
- The Fellowship of Privileged Scaffolds-One Structure to Inhibit Them All.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Covalent Inhibition of Wild-Type HIV-1 Reverse Transcriptase Using a Fluorosulfate Warhead.ACS medicinal chemistry letters · 2021Article
- Thermodynamics and Kinetics of Drug-Target Binding by Molecular Simulation.Chemical reviews · 2020Review
- Structure activity relationship towards design of cryptosporidium specific thymidylate synthase inhibitors.European journal of medicinal chemistry · 2019Article
- Molecular and cellular studies evaluating a potent 2-cyanoindolizine catechol diether NNRTI targeting wildtype and Y181C mutant HIV-1 reverse transcriptase.Bioorganic & medicinal chemistry letters · 2019Article
- An Overview of Molecular Modeling for Drug Discovery with Specific Illustrative Examples of Applications.Molecules (Basel, Switzerland) · 2019Review
- Aryl Substituted Benzimidazolones as Potent HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors.ACS medicinal chemistry letters · 2019Article
- Diaryl ethers with carboxymethoxyphenacyl motif as potent HIV-1 reverse transcriptase inhibitors with improved solubility.Journal of enzyme inhibition and medicinal chemistry · 2018Article
- Predicting Binding Free Energies in a Large Combinatorial Chemical Space Using Multisite λ Dynamics.The journal of physical chemistry letters · 2018Article
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
A 5-μM docking hit has been optimized to an extraordinarily potent (55 pM) non-nucleoside inhibitor of HIV reverse transcriptase. Use of free energy perturbation (FEP) calculations to predict relative free energies of binding aided the optimizations by identifying optimal substitution patterns for phenyl rings and a linker. The most potent resultant catechol diethers feature terminal uracil and cyanovinylphenyl groups. A halogen bond with Pro95 likely contributes to the extreme potency of compound 42. In addition, several examples are provided illustrating failures of attempted grafting of a substructure from a very active compound onto a seemingly related scaffold to improve its activity.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.