Discovery of 2-Arylbenzoxazoles as Upregulators of Utrophin Production for the Treatment of Duchenne Muscular Dystrophy

A series of novel 2-arylbenzoxazoles that upregulate the production of utrophin in murine H2K cells, as assessed using a luciferase reporter linked assay, have been identified. This compound class appears to hold considerable promise as a potential treatment for Duchenne muscular dystrophy. Followin...

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Bibliographic Details
Published in:Journal of medicinal chemistry 2011-05, Vol.54 (9), p.3241-3250
Main Authors: Chancellor, Daniel R, Davies, Kay E, De Moor, Olivier, Dorgan, Colin R, Johnson, Peter D, Lambert, Adam G, Lawrence, Daniel, Lecci, Cristina, Maillol, Carole, Middleton, Penny J, Nugent, Gary, Poignant, Séverine D, Potter, Allyson C, Price, Paul D, Pye, Richard J, Storer, Richard, Tinsley, Jonathon M, van Well, Renate, Vickers, Richard, Vile, Julia, Wilkes, Fraser J, Wilson, Francis X, Wren, Stephen P, Wynne, Graham M
Format: Article
Language:English
Subjects:
Animals
Benzoxazoles - chemical synthesis
Benzoxazoles - chemistry
Benzoxazoles - pharmacology
Cell Line
Mice
Muscular Dystrophy, Duchenne - drug therapy
Structure-Activity Relationship
Up-Regulation
Utrophin - biosynthesis
Utrophin - genetics
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Summary:A series of novel 2-arylbenzoxazoles that upregulate the production of utrophin in murine H2K cells, as assessed using a luciferase reporter linked assay, have been identified. This compound class appears to hold considerable promise as a potential treatment for Duchenne muscular dystrophy. Following the delineation of structure–activity relationships in the series, a number of potent upregulators were identified, and preliminary ADME evaluation is described. These studies have resulted in the identification of 1, a compound that has been progressed to clinical trials.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm200135z