ArticleEuropean journal of medicinal chemistry2020
Design, synthesis, and electrophysiological evaluation of NS6740 derivatives: Exploration of the structure-activity relationship for alpha7 nicotinic acetylcholine receptor silent activation.
Article in European journal of medicinal chemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 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
9 citing papers in PubMed, 14 citations in OpenAlex.
- Recent Advances in the Discovery of Nicotinic Acetylcholine Receptor Allosteric Modulators.Molecules (Basel, Switzerland) · 2023Review
- Differential Activation and Desensitization States Promoted by NoncanonicalThe Journal of pharmacology and experimental therapeutics · 2022Article
- Pharmacological characterization of 5-iodo-A-85380, a β2-selective nicotinic receptor agonist, in mice.Journal of psychopharmacology (Oxford, England) · 2022Article
- Functional α7 nicotinic acetylcholine receptors in GABAergic neurons of the interpeduncular nucleus.Neuropharmacology · 2022Article
- AI-Driven Synthetic Route Design Incorporated with Retrosynthesis Knowledge.Journal of chemical information and modeling · 2022Article
- The Mechanisms Mediated by α7 Acetylcholine Nicotinic Receptors May Contribute to Peripheral Nerve Regeneration.Molecules (Basel, Switzerland) · 2021Article
- Homomeric and Heteromeric α7 Nicotinic Acetylcholine Receptors in Health and Some Central Nervous System Diseases.Membranes · 2021Review
- Stable desensitization of αEuropean journal of pharmacology · 2021Article
- Therapeutic Targeting ofPharmacological reviews · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
The α7 nicotinic acetylcholine receptor (nAChR) silent agonists, able to induce receptor desensitization and promote the α7 metabotropic function, are emerging as new promising therapeutic anti-inflammatory agents. Herein, we report the structure-activity relationship investigation of the archetypal silent agonist NS6740 (1,4-diazabicyclo[3.2.2]nonan-4-yl(5-(3-(trifluoromethyl)-phenyl)-furan-2-yl)methanone) (1) to elucidate the ligand-receptor interactions responsible for the α7 silent activation. In this study, NS6740 fragments 11-16 and analogs 17-32 were designed, synthesized, and assayed on human α7 nAChRs expressed in Xenopus laevis oocytes with two-electrode voltage clamping experiments. All together the structural portions of NS6740 were critical to engender its peculiar activity profile. The diazabicyclic nucleus was essential but not sufficient for inducing α7 silent activation. The central hydrogen-bond acceptor core and the aromatic moiety were crucial for promoting prolonged α7 receptor binding and sustained desensitization. Compounds 13 and 17 were efficacious partial agonists. Compounds 12, 21, 23-26, and 30 strongly desensitized α7 nAChR and therefore may be of interest for additional investigation of inflammation responses. We gained key structural information useful for further silent agonist development.
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.