Discovery of 2-arylbenzoxazoles as upregulators of utrophin production for the treatment of Duchenne muscular dystrophy

  • J Med Chem. 2011 May 12;54(9):3241-50. doi: 10.1021/jm200135z.
Daniel R Chancellor  1 ,  Kay E Davies ,  Olivier De Moor ,  Colin R Dorgan ,  Peter D Johnson ,  Adam G Lambert ,  Daniel Lawrence ,  Cristina Lecci ,  Carole Maillol ,  Penny J Middleton ,  Gary Nugent ,  Séverine D Poignant ,  Allyson C Potter ,  Paul D Price ,  Richard J Pye ,  Richard Storer ,  Jonathon M Tinsley ,  Renate van Well ,  Richard Vickers ,  Julia Vile ,  Fraser J Wilkes ,  Francis X Wilson ,  Stephen P Wren ,  Graham M Wynne
Affiliations
  • 1. Summit plc , 91 Milton Park, Abingdon, Oxfordshire, OX14 4RY, United Kingdom.
PMID: 21456623 DOI: 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.

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