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

详细信息    查看全文

• 作者：Hiroaki Ohno^a ; ^{hohno@pharm.kyoto-u.ac.jp" class="auth_mail" title="E-mail the corresponding author} ; Daiki Minamiguchi^a ; Shinya Nakamura^b ; Keito Shu^a ; Shiho Okazaki^a ; Maho Honda^a ; Ryosuke Misu^a ; Hirotomo Moriwaki^b ; Shinsuke Nakanishi^b ; Shinya Oishi^a ; Takayoshi Kinoshita^c ; Isao Nakanishi^b ; Nobutaka Fujii^a ; ^{nfujii@pharm.kyoto-u.ac.jp" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Protein kinase CK2 ; Kinase inhibitor ; Structure&ndash ; activity relationship ; Rational design
• 刊名：Bioorganic & Medicinal Chemistry
• 出版年：2016
• 出版时间：1 March 2016
• 年：2016
• 卷：24
• 期：5
• 页码：1136-1141
• 全文大小：1158 K

文摘

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) = 0.014–0.017 μM; IC₅₀ (CK2α′) = 0.0046–0.010 μM]. 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) = 0.014–0.016 μM; IC₅₀ (CK2α′) = 0.0088–0.014 μM] and led to antiproliferative activities [CC₅₀ (A549) = 1.5–3.3 μM] three to six times higher than those of the parent compound.