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. Epub 2011 Apr 15.

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.

MeSH terms

  • Animals
  • Benzoxazoles / chemical synthesis*
  • Benzoxazoles / chemistry
  • Benzoxazoles / pharmacology
  • Cell Line
  • Mice
  • Muscular Dystrophy, Duchenne / drug therapy*
  • Naphthalenes
  • Structure-Activity Relationship
  • Up-Regulation
  • Utrophin / biosynthesis*
  • Utrophin / genetics

Substances

  • Benzoxazoles
  • Naphthalenes
  • Utrophin
  • ezutromid