Discovery and structure-activity relationship of 2,6-disubstituted pyrazines, potent and selective inhibitors of protein kinase CK2.
Basic Information
ID: ALA2046363
Journal: Bioorg Med Chem Lett
Title: Discovery and structure-activity relationship of 2,6-disubstituted pyrazines, potent and selective inhibitors of protein kinase CK2.
Authors: Fuchi N, Iura Y, Kaneko H, Nitta A, Suyama K, Ueda H, Yamaguchi S, Nishimura K, Fujii S, Sekiya Y, Yamada M, Takahashi T.
Abstract: We report the discovery and structure-activity relationship of 2,6-disubstituted pyrazines, which are potent and selective CK2 inhibitors. Lead compound 1 was identified, and derivatives were prepared to develop potent inhibitory activity. As a result, we obtained compound 7, which was the smallest unit that retained potency. Then, introducing an aminoalkyl group at the 6-position of the indazole ring resulted in improved efficacy in both enzymatic and cell-based CK2 inhibition assays. Moreover, compound 13 showed selectivity against other kinases and in vivo efficacy in a rat nephritis model. These results show that 2,6-disubstituted pyrazines have potential as therapeutic agents for nephritis.
CiteXplore: 22633690
DOI: 10.1016/j.bmcl.2012.05.006
Patent ID: ┄