4-(噻唑-5-基)苯甲酸衍生物作为高效蛋白激酶CK2抑制剂的构效关系研究
Structure-activity relationship study of 4-(thiazol-5-yl)benzoic acid derivatives as potent protein kinase CK2 inhibitors.
作者信息
Ohno Hiroaki, Minamiguchi Daiki, Nakamura Shinya, Shu Keito, Okazaki Shiho, Honda Maho, Misu Ryosuke, Moriwaki Hirotomo, Nakanishi Shinsuke, Oishi Shinya, Kinoshita Takayoshi, Nakanishi Isao, Fujii Nobutaka
机构信息
Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
出版信息
Bioorg Med Chem. 2016 Mar 1;24(5):1136-41. doi: 10.1016/j.bmc.2016.01.043. Epub 2016 Jan 22.
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 (CK2α)=0.014-0.017μM; IC50 (CK2α')=0.0046-0.010μM]. 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 (CK2α)=0.014-0.016μM; IC50 (CK2α')=0.0088-0.014μM] and led to antiproliferative activities [CC50 (A549)=1.5-3.3μM] three to six times higher than those of the parent compound.
设计了两类4-(噻唑-5-基)苯甲酸型CK2抑制剂的修饰类似物。氮杂苯类似物，即吡啶和哒嗪羧酸衍生物，表现出强大的蛋白激酶CK2抑制活性[IC50(CK2α)=0.014 - 0.017μM；IC50(CK2α')=0.0046 - 0.010μM]。在苯甲酸部分的3位引入2-卤代或2-甲氧基苄氧基基团，保持了强大的CK2抑制活性[IC50(CK2α)=0.014 - 0.016μM；IC50(CK2α')=0.0088 - 0.014μM]，并导致抗增殖活性[CC50(A549)=1.5 - 3.3μM]比母体化合物高3至6倍。
Zotero 插件