ArticleProceedings of the National Academy of Sciences of the United States of America2011
Diversity through phosphine catalysis identifies octahydro-1,6-naphthyridin-4-ones as activators of endothelium-driven immunity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 43 citations in OpenAlex.
- Synthesis and Anticancer Properties of Functionalized 1,6-Naphthyridines.Topics in current chemistry (Cham) · 2021Review
- Asymmetric Synthesis of a 5,6,7,8-Tetrahydro-1,6-naphthyridine Scaffold Leading to Potent Retinoid-Related Orphan Receptor γt Inverse Agonist TAK-828F.The Journal of organic chemistry · 2020Article
- Discussion Addendum for: Phosphine-Catalyzed [4 + 2] Annulation: Synthesis of Ethyl 6-Phenyl-1-tosyl-1,2,5,6-tetrahydropyridine-3-carboxylate.Organic syntheses; an annual publication of satisfactory methods for the preparation of organic chemicals · 2019Article
- Phosphine Organocatalysis.Chemical reviews · 2018Review
- Chemical probes and drug leads from advances in synthetic planning and methodology.Nature reviews. Drug discovery · 2018Review
- Phosphine-catalyzed [5+1] annulation of δ-sulfonamido-substituted enones withChemical science · 2018Article
- Jagged1 Instructs Macrophage Differentiation in Leprosy.PLoS pathogens · 2016Article
- Nucleophilic Chiral Phosphines: Powerful and Versatile Catalysts for Asymmetric Annulations.Aldrichimica acta · 2016Article
- Mitochondrial Ca(2+) uptake by the voltage-dependent anion channel 2 regulates cardiac rhythmicity.eLife · 2015Article
- Phosphine catalysis of allenes with electrophiles.Chemical Society reviews · 2014Review
- Advances in nucleophilic phosphine catalysis of alkenes, allenes, alkynes, and MBHADs.Chemical communications (Cambridge, England) · 2013Article
- Endothelial cells in the eyes of an immunologist.Cancer immunology, immunotherapy : CII · 2012Review
- Phosphine-catalyzed intramolecular γ-umpolung addition of α-aminoalkylallenic esters: facile synthesis of 3-carbethoxy-2-alkyl-3-pyrrolines.Chemical communications (Cambridge, England) · 2012Article
- Enantioselective total synthesis of (+)-ibophyllidine via an asymmetric phosphine-catalyzed [3 + 2] annulation.Chemical science · 2012Article
- Phosphine-initiated general base catalysis: facile access to benzannulated 1,3-diheteroatom five-membered rings via double-Michael reactions of allenes.Organic letters · 2011Article
- Phosphine-catalyzed [4+2] annulations of 2-alkylallenoates and olefins: synthesis of multisubstituted cyclohexenes.Chemistry, an Asian journal · 2011Article
- Diversity-oriented synthesis based on the DPPP-catalyzed mixed double-Michael reactions of electron-deficient acetylenes and β-amino alcohols.Molecules (Basel, Switzerland) · 2011Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The endothelium plays a critical role in promoting inflammation in cardiovascular disease and other chronic inflammatory conditions, and many small-molecule screens have sought to identify agents that prevent endothelial cell activation. Conversely, an augmented immune response can be protective against microbial pathogens and in cancer immunotherapy. Yet, small-molecule screens to identify agents that induce endothelial cell activation have not been reported. In this regard, a bioassay was developed that identifies activated endothelium by its capacity to trigger macrophage inflammatory protein 1 beta from primary monocytes. Subsequently, a 642-compound library of 39 distinctive scaffolds generated by a diversity-oriented synthesis based on the nucleophilic phosphine catalysis was screened for small molecules that activated the endothelium. Among the active compounds identified, the major classes were synthesized through the sequence of phosphine-catalyzed annulation, Tebbe reaction, Diels-Alder reaction, and in some cases, hydrolysis. Ninety-six analogs of one particular class of compounds, octahydro-1,6-naphthyridin-4-ones, were efficiently prepared by a solid-phase split-and-pool technique and by solution phase analog synthesis. Structure-function analysis combined with transcriptional profiling of active and inactive octahydro-1,6-naphthyridin-4-one analogs identified inflammatory gene networks induced exclusively by the active compound. The identification of a family of chemical probes that augment innate immunity through endothelial cell activation provides a framework for understanding gene networks involved in endothelial inflammation as well as the development of novel endothelium-driven immunotherapeutic agents.
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