ArticleJournal of the American Chemical Society2011
Efficient discovery of potent anti-HIV agents targeting the Tyr181Cys variant of HIV reverse transcriptase.
Article in Journal of the American Chemical Society, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
25 citing papers in PubMed, 65 citations in OpenAlex.
- Synthesis of novel N1 functionalized diazepinone analoguesRSC advances · 2025Article
- Development of a Highly Potent Transthyretin Amyloidogenesis Inhibitor: Design, Synthesis, and Evaluation.Journal of medicinal chemistry · 2022Article
- 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
- Computational approach for binding prediction of SARS-CoV-2 with neutralizing antibodies.Computational and structural biotechnology journal · 2022Article
- The Fellowship of Privileged Scaffolds-One Structure to Inhibit Them All.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Structure activity relationship towards design of cryptosporidium specific thymidylate synthase inhibitors.European journal of medicinal chemistry · 2019Article
- Tryptoline-based benzothiazoles re-sensitize MRSA to β-lactam antibiotics.Bioorganic & medicinal chemistry · 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
- Covalent inhibitors for eradication of drug-resistant HIV-1 reverse transcriptase: From design to protein crystallography.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Computer-aided discovery of anti-HIV agents.Bioorganic & medicinal chemistry · 2016Article
- Article
- Evaluating thermodynamic integration performance of the new amber molecular dynamics package and assess potential halogen bonds of enoyl-ACP reductase (FabI) benzimidazole inhibitors.Journal of computational chemistry · 2016Article
- Molecular dynamics and Monte Carlo simulations for protein-ligand binding and inhibitor design.Biochimica et biophysica acta · 2015Article
- Design, synthesis, and protein crystallography of biaryltriazoles as potent tautomerase inhibitors of macrophage migration inhibitory factor.Journal of the American Chemical Society · 2015Article
- Enhanced Monte Carlo Sampling through Replica Exchange with Solute Tempering.Journal of chemical theory and computation · 2014Article
- Picomolar inhibitors of HIV reverse transcriptase featuring bicyclic replacement of a cyanovinylphenyl group.Journal of the American Chemical Society · 2013Article
- Extension into the entrance channel of HIV-1 reverse transcriptase--crystallography and enhanced solubility.Bioorganic & medicinal chemistry letters · 2013Article
- One Size Does Not Fit All: The Limits of Structure-Based Models in Drug Discovery.Journal of chemical theory and computation · 2013Article
- Accurate calculation of mutational effects on the thermodynamics of inhibitor binding to p38α MAP kinase: a combined computational and experimental study.Journal of chemical theory and computation · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Non-nucleoside reverse transcriptase inhibitors (NNRTIs) that interfere with the replication of human immunodeficiency virus (HIV) are being pursued with guidance from molecular modeling including free-energy perturbation (FEP) calculations for protein-inhibitor binding affinities. The previously reported pyrimidinylphenylamine 1 and its chloro analogue 2 are potent anti-HIV agents; they inhibit replication of wild-type HIV-1 in infected human T-cells with EC(50) values of 2 and 10 nM, respectively. However, they show no activity against viral strains containing the Tyr181Cys (Y181C) mutation in HIV-RT. Modeling indicates that the problem is likely associated with extensive interaction between the dimethylallyloxy substituent and Tyr181. As an alternative, a phenoxy group is computed to be oriented in a manner diminishing the contact with Tyr181. However, this replacement leads to a roughly 1000-fold loss of activity for 3 (2.5 μM). The present report details the efficient, computationally driven evolution of 3 to novel NNRTIs with sub-10 nM potency toward both wild-type HIV-1 and Y181C-containing variants. The critical contributors were FEP substituent scans for the phenoxy and pyrimidine rings and recognition of potential benefits of addition of a cyanovinyl group to the phenoxy ring.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.