Design, synthesis, and biological evaluation of novel disubstituted dibenzosuberones as highly potent and selective inhibitors of p38 mitogen activated protein kinase.

doi:10.1021/jm300327h

Paper

Design, synthesis, and biological evaluation of novel disubstituted dibenzosuberones as highly potent and selective inhibitors of p38 mitogen activated protein kinase.

Published Jun 15, 2012 · S. Koeberle, S. Fischer, D. Schollmeyer

Journal of medicinal chemistry

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33

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1

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Abstract

Synthesis, biological testing, structure-activity relationships (SARs), and selectivity of novel disubstituted dibenzosuberone derivatives as p38 MAP kinase inhibitors are described. Hydrophilic moieties were introduced at the 7-, 8-, and 9-position of the 2-phenylamino-dibenzosuberones, improving physicochemical properties as well as potency. Extremely potent inhibitors were obtained, with half-maximal inhibitory concentration (IC(50)) values in the low nM range in a whole blood assay measuring the inhibition of cytokine release. The high potency of the target compounds together with the outstanding selectivity of this novel class of compounds toward p38 mitogen activated protein (MAP) kinase as compared to other kinases indicate them to be most applicable as tools in pharmacological research and eventually they may foster a new generation of anti-inflammatory drugs.

In Vitro Study

Study Snapshot

Novel disubstituted dibenzosuberone derivatives show high potency and selective inhibition of p38 MAP kinase, potentially fostering a new generation of anti-inflammatory drugs.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

Design, synthesis, and biological evaluation of novel disubstituted dibenzosuberones as highly potent and selective inhibitors of p38 mitogen activated protein kinase.

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