ArticleJournal of the American Chemical Society2008
Optimization of azoles as anti-human immunodeficiency virus agents guided by free-energy calculations.
Article in Journal of the American Chemical Society, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
What it found
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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.
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Who cites it
31 citing papers in PubMed, 94 citations in OpenAlex.
- Design, synthesis, and biological testing of biphenylmethyloxazole inhibitors targeting HIV-1 reverse transcriptase.Bioorganic & medicinal chemistry letters · 2023Article
- Synthesis of 2-Imino-1,3,4-oxadiazolines from Acylhydrazides and Isothiocyanates via Aerobic Oxidation and a DMAP-Mediated Annulation Sequence.ACS omega · 2022Article
- Enhancing Side Chain Rotamer Sampling Using Nonequilibrium Candidate Monte Carlo.Journal of chemical theory and computation · 2019Article
- Impact of domain knowledge on blinded predictions of binding energies by alchemical free energy calculations.Journal of computer-aided molecular design · 2018Article
- Computer-aided discovery of anti-HIV agents.Bioorganic & medicinal chemistry · 2016Article
- Discovery, characterization, and lead optimization of 7-azaindole non-nucleoside HIV-1 reverse transcriptase inhibitors.Bioorganic & medicinal chemistry letters · 2016Article
- Obese diet-induced mouse models of nonalcoholic steatohepatitis-tracking disease by liver biopsy.World journal of hepatology · 2016Article
- Computational drug design strategies applied to the modelling of human immunodeficiency virus-1 reverse transcriptase inhibitors.Memorias do Instituto Oswaldo Cruz · 2015Review
- Molecular dynamics and Monte Carlo simulations for protein-ligand binding and inhibitor design.Biochimica et biophysica acta · 2015Article
- Enhanced Monte Carlo Sampling through Replica Exchange with Solute Tempering.Journal of chemical theory and computation · 2014Article
- 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
- Optimization of benzyloxazoles as non-nucleoside inhibitors of HIV-1 reverse transcriptase to enhance Y181C potency.Bioorganic & medicinal chemistry letters · 2013Article
- Entropy-enthalpy compensation: role and ramifications in biomolecular ligand recognition and design.Annual review of biophysics · 2013Review
- Structural characterization and computer-aided optimization of a small-molecule inhibitor of the Arp2/3 complex, a key regulator of the actin cytoskeleton.ChemMedChem · 2012Article
- Article
- Identification of HIV inhibitors guided by free energy perturbation calculations.Current pharmaceutical design · 2012Review
- Article
- The future of molecular dynamics simulations in drug discovery.Journal of computer-aided molecular design · 2012Article
- Computationally-guided optimization of a docking hit to yield catechol diethers as potent anti-HIV agents.Journal of medicinal chemistry · 2011Article
- Molecular dynamics simulations and drug discovery.BMC biology · 2011Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Efficient optimization of an inactive 2-anilinyl-5-benzyloxadiazole core has been guided by free energy perturbation (FEP) calculations to provide potent non-nucleoside inhibitors of human immunodeficiency virus (HIV) reverse transcriptase (NNRTIs). An FEP "chlorine scan" was performed to identify the most promising sites for substitution of aryl hydrogens. This yielded NNRTIs 8 and 10 with activities (EC50) of 820 and 310 nM for protection of human T-cells from infection by wild-type HIV-1. FEP calculations for additional substituent modifications and change of the core heterocycle readily led to oxazoles 28 and 29, which were confirmed as highly potent anti-HIV agents with activities in the 10-20 nM range. The designed compounds were also monitored for possession of desirable pharmacological properties by use of additional computational tools. Overall, the trends predicted by the FEP calculations were well borne out by the assay results. FEP-guided lead optimization is confirmed as a valuable tool for molecular design including drug discovery; chlorine scans are particularly attractive since they are both straightforward to perform and highly informative.
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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.