Polyhalogenobenzimidazoles: Synthesis and their inhibitory activity against casein kinases

A series of novel polyhalogenated benzimidazoles have been prepared by exhaustive bromination of a variety of 2-substituted benzimidazoles. The efficacy of both new compounds and a number of their previously described cognates as inhibitors of casein kinases CK1, CK2 and G-CK was investigated. The type of N-1 alkyl substituent as well as introduction of a polyfluoroalkyl moiety at position 2 did not markedly influence the inhibitory efficacy toward CK2 of the respective 4,5,6,7-tetra-bromobenzimidazole derivatives which conversely were almost ineffective toward CK1 and G-CK. However, 4,5,6,7-tetra-bromobenzimidazoles substituted at position 2 with either chlorine, bromine or sulfur atom, while manifesting a still considerable inhibitory activity against CK2 (IC50 in the 0.49-0.93 muM range) proved to be potentially powerful inhibitors also against CK1 (IC50 in the 18.4-2.2 muM range). (C) 2003 Elsevier Ltd. All rights reserved.