A series of 4-(imidazo[1,2-a]pyridin-3-yl)-pyrimidine derivatives are claimed as inhibitors of c-KIT and as potential treatments for cancer. Their chemical preparation and biological evaluation against imatinib-resistant tumor cells have been described. Several claimed molecules have excellent IC50 values in the nanomolar range. Several molecules were also selective against a wide panel of kinases. Few specific inhibitors have been found to have promising oral bioavailability and acceptable to excellent values regarding the inhibition of hERG channel. This class represents a new platform for developing new anticancer treatment against a wide range of c-KIT mutations and secondary mutations that may arise in gastrointestinal stromal tumor patients.
Keywords: 4-(imidazo[1,2-a]pyridin-3-yl)-pyrimidine; V654A mutation; anticancer; c-KIT; gastrointestinal stromal tumor; imatinib.