A series of novel isochromanone based urotensin II receptor agonists have been synthesized and evaluated for their activity using a functional cell based assay (R-SAT). Several potent and efficacious derivatives were identified, with 3-(3,4-dichlorophenyl)-6,7-dimethyl-3-(2-dimethylaminoethyl)isochroman-1-one being the most potent compound showing an EC₅₀-value of 51 nM, thereby being the most potent compound so far within the isochromanone series. In addition, two other heterocyclic systems (isochromanes and tetrahydroisoquinolinones) were investigated and these derivatives were found to be both potent and efficacious. The activity of the isochromane derivatives implies that the carbonyl group of the isochromanone is not necessary for activity. Furthermore it was found that the geometry of the heterocycles was more important for receptor interaction than the composition of the heteroatoms present.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bmc.2010.04.041 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Induction of Isochromanones by Co-Cultivation of the Marine Fungus sp. and the Phytopathogen .
Int J Mol Sci
January 2022
GEOMAR Centre for Marine Biotechnology (GEOMAR-Biotech), Research Unit Marine Natural Product Chemistry, GEOMAR Helmholtz Centre for Ocean Research Kiel, Am Kiel-Kanal 44, 24106 Kiel, Germany.
Microbial co-cultivation is a promising approach for the activation of biosynthetic gene clusters (BGCs) that remain transcriptionally silent under artificial culture conditions. As part of our project aiming at the discovery of marine-derived fungal agrochemicals, we previously used four phytopathogens as model competitors in the co-cultivation of 21 marine fungal strains. Based on comparative untargeted metabolomics analyses and anti-phytopathogenic activities of the co-cultures, we selected the co-culture of marine sp.
View Article and Find Full Text PDFSynthesis of 5 H-Dibenzo[ c, g]chromen-5-ones via FeCl-Mediated Tandem C-O Bond Cleavage/6π Electrocyclization/Oxidative Aromatization.
Org Lett
September 2018
Department of Chemistry , Zhejiang Sci-Tech University, Hangzhou , Zhejiang 310018 , P. R. China.
A novel and expedient method for transformation of readily available 1-isochromanones bearing a diaryl allenic moiety at the C4-position to functionalized 5 H-dibenzo[ c, g]chromen-5-ones under mild conditions is developed. This strategy is based on the dual abilities of iron(III) chloride to promote selective C-O bond cleavage/6π electrocyclization and an oxidative aromatization sequence.
View Article and Find Full Text PDFStereoselective Synthesis of Isochromanones by an Asymmetric Ortho-Lithiation Strategy: Synthetic Access to the Isochromanone Core of the Ajudazols.
J Org Chem
March 2016
Kekulé-Institut für Organische Chemie und Biochemie, Universität Bonn, Gerhard-Domagk-Straße 1, 53121 Bonn, Germany.
Full details on the design, development, and application of a highly stereoselective strategy for the synthesis of isochromanones are reported. The method is based on an asymmetric ortho lithiation with aldehyde electrophiles and utilizes the chiral memory of a preoriented atropisomeric amide axis for stereocontrol. For direct transformation of sterically hindered amides to isochromanones, efficient and mild one-pot protocols involving either O-alkylation or acidic microwave activation were developed.
View Article and Find Full Text PDFFull stereochemical determination of ajudazols A and B by bioinformatics gene cluster analysis and total synthesis of ajudazol B by an asymmetric ortholithiation strategy.
J Am Chem Soc
November 2012
Institut für Organische Chemie, Ruprecht-Karls Universität Heidelberg, Im Neuenheimer Feld 270, 69120 Heidelberg, Germany.
The stereochemical determination of the potent respiratory chain inhibitors ajudazols A and B and the total synthesis of ajudazol B are reported. Configurational assignment was exclusively based on biosynthetic gene cluster analysis of both ketoreductase domains for hydroxyl-bearing stereocenters and one of the first predictive enoylreductase alignments for methyl-bearing stereocenters. The expedient total synthesis resulting in unambiguous proof of the predicted stereochemistry involves a short stereoselective approach to the challenging isochromanone stereotriad by an innovative asymmetric ortholithiation strategy, a modular oxazole formation, and a late-stage Z,Z-selective Suzuki coupling.
View Article and Find Full Text PDFOptimization of isochromanone based urotensin II receptor agonists.
Bioorg Med Chem
July 2010
Department of Chemistry, Medicinal Chemistry, University of Gothenburg, SE-412 96 Göteborg, Sweden.
A series of novel isochromanone based urotensin II receptor agonists have been synthesized and evaluated for their activity using a functional cell based assay (R-SAT). Several potent and efficacious derivatives were identified, with 3-(3,4-dichlorophenyl)-6,7-dimethyl-3-(2-dimethylaminoethyl)isochroman-1-one being the most potent compound showing an EC₅₀-value of 51 nM, thereby being the most potent compound so far within the isochromanone series. In addition, two other heterocyclic systems (isochromanes and tetrahydroisoquinolinones) were investigated and these derivatives were found to be both potent and efficacious.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!