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  • Chemistry  (1)
  • Fibrosis, Heart Failure, Remodeling  (1)
  • 1
    ISSN: 0075-4617
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Description / Table of Contents: Diels-Alder Reactions of o-Benzoquinones with Fulveneso-Benzoquinone (1a) and alkyl-substituted o-benzoquinones 1b-d react with fulvenes 2a-d in a stereoselective and regiospecific cycloaddition to give endo-dicarbonyl compounds 3a-o and 4a, b. Photodecarbonylation and dehydrogenation of these adducts yields benzofulvenes 6, which could be synthesized from indanones 8 by an independent route.
    Notes: o-Benzochinon (1a) und alkylsubstituierte o-Benzochinone 1b-d reagieren mit Fulvenen 2a-d in einer stereoselektiv und regiospezifisch verlaufenden Cycloaddition unter Bildung von endo-Dicarbonylverbindungen 3a-o und 4a, b. Aus diesen sind durch Photodecarbonylierung und Dehydrierung Benzofulvene 6 zugänglich, die auch auf unabhängigem Wege aus Indanonen 8 dargestellt wurden.
    Additional Material: 12 Tab.
    Type of Medium: Electronic Resource
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  • 2
    Publication Date: 2018-03-09
    Description: Mineralocorticoid receptor antagonists (MRAs) reduce morbidity and mortality in chronic heart failure. Novel nonsteroidal MRAs are currently developed and need to be pharmacologically characterized in comparison to classical steroidal MRAs. A mouse model of cardiac fibrosis induced by short-term isoproterenol injection was used to compare the nonsteroidal MRA finerenone and the steroidal MRA eplerenone in equi-efficient systemic MR blocking dosages. Molecular mechanisms were studied in MR-expressing H9C2/MR+ cardiomyocytes and in MR transcriptional cofactor binding assays. Both MRAs significantly inhibited an isoproterenol-mediated increase of left ventricular mass. Isoproterenol-induced cardiac fibrosis and macrophage invasion were potently blocked by finerenone, whereas eplerenone had no significant effect. Speckle tracking echocardiography revealed a significant improvement of global longitudinal peak strain by finerenone, an effect less prominent with eplerenone. Antifibrotic actions of finerenone were accompanied by a significant inhibition of profibrotic cardiac TNX (tenascin-X) expression, a regulation absent with eplerenone. Finally, we show a higher potency/efficacy and inverse agonism of finerenone versus eplerenone in MR transcriptional cofactor binding assays indicating differential MR cofactor modulation by steroidal and nonsteroidal MRAs. This study demonstrates that the nonsteroidal MRA finerenone potently prevents cardiac fibrosis and improves strain parameters in mice. Cardiac antifibrotic actions of finerenone may result from the inhibition of profibrotic TNX gene expression mediated by differential MR cofactor binding. Selective MR cofactor modulation provides a molecular basis for distinct (pre)-clinical actions of nonsteroidal and steroidal MRAs.
    Keywords: Fibrosis, Heart Failure, Remodeling
    Print ISSN: 0194-911X
    Topics: Medicine
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