Discovery of 2-arylbenzoxazoles as upregulators of utrophin production for the treatment of Duchenne muscular dystrophy.
Chancellor DR., Davies KE., De Moor O., Dorgan CR., Johnson PD., Lambert AG., Lawrence D., Lecci C., Maillol C., Middleton PJ., Nugent G., Poignant SD., Potter AC., Price PD., Pye RJ., Storer R., Tinsley JM., van Well R., Vickers R., Vile J., Wilkes FJ., Wilson FX., Wren SP., Wynne GM.
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.