The design and synthesis of 5- and 6-isoxazolylbenzimidazoles as selective inhibitors of the BET bromodomains.
Hay D., Fedorov O., Filippakopoulos P., Martin S., Philpott M., Picaud S., Hewings DS., Uttakar S., Heightman TD., Conway SJ., Knapp S., Brennan PE.
Simple 1-substituted 5- and 6-isoxazolyl-benzimidazoles have been shown to be potent inhibitors of the BET bromodomains with selectivity over the related bromodomain of CBP. The reported inhibitors were prepared from simple starting materials in two steps followed by separation of the regioisomers or regioselectively in three steps.