ArticleACS medicinal chemistry letters2011
Synthesis of a novel suppressor of beta-cell apoptosis via diversity-oriented synthesis.
Article in ACS medicinal chemistry letters, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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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, 45 citations in OpenAlex.
- Diversity-oriented synthesis encoded by deoxyoligonucleotides.Nature communications · 2023Article
- Small-molecule discovery in the pancreatic beta cell.Current opinion in chemical biology · 2022Review
- Phenotypic Screening for Small Molecules that Protect β-Cells from Glucolipotoxicity.ACS chemical biology · 2022Article
- The Use of Informer Sets in Screening: Perspectives on an Efficient Strategy to Identify New Probes.SLAS discovery : advancing life sciences R & D · 2021Article
- Synthesis of Medium-Sized Heterocycles by Transition-Metal-Catalyzed Intramolecular Cyclization.Molecules (Basel, Switzerland) · 2020Review
- Synthesis of Benzannulated Medium-ring Lactams via a Tandem Oxidative Dearomatization-Ring Expansion Reaction.Chemistry (Weinheim an der Bergstrasse, Germany) · 2018Article
- Chemical probes and drug leads from advances in synthetic planning and methodology.Nature reviews. Drug discovery · 2018Review
- Recent Applications of Diversity-Oriented Synthesis Toward Novel, 3-Dimensional Fragment Collections.Frontiers in chemistry · 2018Review
- Identification of Highly Specific Diversity-Oriented Synthesis-Derived Inhibitors of Clostridium difficile.ACS infectious diseases · 2017Article
- Discovery, Synthesis, and Evaluation of 2,4-Diaminoquinazolines as a Novel Class of Pancreatic β-Cell-Protective Agents against Endoplasmic Reticulum (ER) Stress.Journal of medicinal chemistry · 2016Article
- Identification of 1,2,3-triazole derivatives that protect pancreatic β cells against endoplasmic reticulum stress-mediated dysfunction and death through the inhibition of C/EBP-homologous protein expression.Bioorganic & medicinal chemistry · 2016Article
- Kinase-Independent Small-Molecule Inhibition of JAK-STAT Signaling.Journal of the American Chemical Society · 2015Article
- Synthesis of oxazocenones via gold(I)-catalyzed 8-endo-dig hydroalkoxylation of alkynamides.Organic letters · 2015Article
- Modulators of hepatic lipoprotein metabolism identified in a search for small-molecule inducers of tribbles pseudokinase 1 expression.PloS one · 2015Article
- HDAC inhibitor-mediated beta-cell protection against cytokine-induced toxicity is STAT1 Tyr701 phosphorylation independent.Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2015Article
- Targeting the pancreatic β-cell to treat diabetes.Nature reviews. Drug discovery · 2014Review
- Diversity-oriented synthesis yields a new drug lead for treatment of chagas disease.ACS medicinal chemistry letters · 2014Article
- Small-molecule inhibition of inflammatory β-cell death.Diabetes, obesity & metabolism · 2013Review
- Discovery of small-molecule modulators of the Sonic Hedgehog pathway.Journal of the American Chemical Society · 2013Article
- Small-molecule inhibitors of cytokine-mediated STAT1 signal transduction in β-cells with improved aqueous solubility.Journal of medicinal chemistry · 2013Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
The synthesis of a stereochemically diverse library of medium-sized rings accessible via a 'build/couple/pair' strategy is described. Key aspects of the synthesis include S(N)Ar cycloetherification of a linear amine template to afford eight stereoisomeric 8-membered lactams and subsequent solid-phase diversification of these scaffolds to yield a 6488-membered library. Screening of this compound collection in a cell-based assay for the suppression of cytokine-induced beta-cell apoptosis resulted in the identification of a small-molecule suppressor capable of restoring glucose-stimulated insulin secretion in a rat beta-cell line. The presence of all stereoisomers in the screening collection enabled preliminary determination of the structural and stereochemical requirements for cellular activity, while efficient follow-up chemistry afforded BRD-0476 (probe ML187), which had an approximately three-fold increase in activity. These results demonstrate the utility of diversity-oriented synthesis to probe discovery using cell-based screening, and the importance of including stereochemical diversity in screening collections for the development of stereo/structure-activity relationships.
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.