Structure-activity relationship study of 4-(thiazol-5-yl)benzoic acid derivatives as potent protein kinase CK2 inhibitors

Two classes of modified analogs of 4-(thiazol-5-yl)benzoic acid-type CK2 inhibitors were designed. The azabenzene analogs, pyridine-and pyridazine-carboxylic acid derivatives, showed potent protein kinase CK2 inhibitory activities [IC50 (CK2 alpha) = 0.014-0.017 mu M; IC50 (CK2 alpha') = 0.0046-0.010 mu M]. Introduction of a 2-halo- or 2-methoxy-benzyloxy group at the 3-position of the benzoic acid moiety maintained the potent CK2 inhibitory activities [IC50 (CK2 alpha) = 0.014-0.016 mu M; IC50 (CK2 alpha') = 0.0088-0.014 mu M] and led to antiproliferative activities [CC50 (A549) = 1.5-3.3 mu M] three to six times higher than those of the parent compound. (C) 2016 Elsevier Ltd. All rights reserved.