Discovery of 2-Arylbenzoxazoles as Upregulators of Utrophin Production for the Treatment of Duchenne Muscular Dystrophy
- 4 April 2011
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 54 (9), 3241-3250
- https://doi.org/10.1021/jm200135z
Abstract
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.Keywords
This publication has 23 references indexed in Scilit:
- Approaching a New Age in Duchenne Muscular Dystrophy TreatmentNeurotherapeutics, 2008
- Biochemical and Structural Evaluation of Highly Selective 2-Arylbenzoxazole-Based Transthyretin Amyloidogenesis InhibitorsJournal of Medicinal Chemistry, 2007
- New therapies for Duchenne muscular dystrophy: challenges, prospects and clinical trialsTrends in Molecular Medicine, 2007
- Safety, Tolerability, and Pharmacokinetics of PTC124, a Nonaminoglycoside Nonsense Mutation Suppressor, Following Single‐ and Multiple‐Dose Administration to Healthy Male and Female Adult VolunteersThe Journal of Clinical Pharmacology, 2007
- Naturally occurring utrophin correlates with disease severity in Duchenne muscular dystrophyHuman Molecular Genetics, 2006
- Duchenne muscular dystrophy and dystrophin: pathogenesis and opportunities for treatmentEMBO Reports, 2004
- Expression of full-length utrophin prevents muscular dystrophy in mdx miceNature Medicine, 1998
- Utrophin: A Structural and Functional Comparison to DystrophinBrain Pathology, 1996
- Utrophin: A potential replacement for dystrophin?Neuromuscular Disorders, 1993
- Isolation of candidate cDNAs for portions of the Duchenne muscular dystrophy geneNature, 1986