ArticleJournal of medicinal chemistry2017
Highly Potent and Selective New Diphenethylamines Interacting with the κ-Opioid Receptor: Synthesis, Pharmacology, and Structure-Activity Relationships.
Article in Journal of medicinal chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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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.
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Who cites it
22 citing papers in PubMed, 30 citations in OpenAlex.
- Development and Biological Characterization of Fluorescent Dynorphins for the Visualization of Kappa Opioid Receptors.Journal of medicinal chemistry · 2026Article
- Review
- Kappa opioid receptor control of motivated behavior revisited.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Review
- Limitations and potential of κOR biased agonists for pain and itch management.Neuropharmacology · 2024Review
- Discovery of Novel, Selective, and Nonbasic Agonists for the Kappa-Opioid Receptor Determined by Salvinorin A-Based Virtual Screening.Journal of medicinal chemistry · 2024Article
- Design and structural validation of peptide-drug conjugate ligands of the kappa-opioid receptor.Nature communications · 2023Article
- Development of a Selective Peptide κ-Opioid Receptor Antagonist by Late-Stage Functionalization with Cysteine Staples.Journal of medicinal chemistry · 2023Article
- Solving an Old Puzzle: Elucidation and Evaluation of the Binding Mode of Salvinorin A at the Kappa Opioid Receptor.Molecules (Basel, Switzerland) · 2023Article
- Opioid signaling and design of analgesics.Progress in molecular biology and translational science · 2023Review
- Design of κ-Opioid Receptor Agonists for the Development of Potential Treatments of Pain with Reduced Side Effects.Molecules (Basel, Switzerland) · 2023Review
- In Vitro, In Vivo and In Silico Characterization of a Novel Kappa-Opioid Receptor Antagonist.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Sex- and β-arrestin-dependent effects of kappa opioid receptor-mediated ethanol consumption.Pharmacology, biochemistry, and behavior · 2022Article
- An updated assessment of the translational promise of G-protein-biased kappa opioid receptor agonists to treat pain and other indications without debilitating adverse effects.Pharmacological research · 2022Review
- Kappa Opioid Receptor Ligands and Pharmacology: Diphenethylamines, a Class of Structurally Distinct, Selective Kappa Opioid Ligands.Handbook of experimental pharmacology · 2022Review
- Design of a Stable Cyclic Peptide Analgesic Derived from Sunflower Seeds that Targets the κ-Opioid Receptor for the Treatment of Chronic Abdominal Pain.Journal of medicinal chemistry · 2021Article
- The Role of the Kappa Opioid System in Comorbid Pain and Psychiatric Disorders: Function and Implications.Frontiers in neuroscience · 2021Review
- Development of Diphenethylamines as Selective Kappa Opioid Receptor Ligands and Their Pharmacological Activities.Molecules (Basel, Switzerland) · 2020Review
- Strategies for DevelopingThe Journal of pharmacology and experimental therapeutics · 2020Review
- Biased Opioid Ligands.Molecules (Basel, Switzerland) · 2020Review
- A Review of the Therapeutic Potential of Recently Developed G Protein-Biased Kappa Agonists.Frontiers in pharmacology · 2019Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
We previously reported on a series of small molecules targeting the κ-opioid (KOP) receptor featuring a diphenethylamine scaffold and showed the promise of these ligands as effective analgesics with reduced liability for adverse effects. This study expands the structure-activity relationships on our original series by presenting several modifications in the lead compounds 1 (HS665) and 2 (HS666). A library of new diphenethylamines was designed, synthesized, and pharmacologically evaluated. In comparison with 1 and 2, the KOP receptor affinity, selectivity, and agonist activity were modulated by introducing bulkier N-substituents, a 2-fluoro substitution, and additional hydroxyl groups at positions 3' and 4'. Several analogues showed subnanomolar affinity and excellent KOP receptor selectivity acting as full or partial agonists, and one as an antagonist. The new diphenethylamines displayed antinociceptive efficacies with increased potencies than U50,488, 1 and 2 in the writhing assay and without inducing motor dysfunction after sc administration in mice.
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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.