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

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

  • Bioorg Med Chem. 2016 Mar 1;24(5):1136-41. doi: 10.1016/j.bmc.2016.01.043.
Hiroaki Ohno 1,  Daiki Minamiguchi 2,  Shinya Nakamura 3,  Keito Shu 2,  Shiho Okazaki 2,  Maho Honda 2,  Ryosuke Misu 2,  Hirotomo Moriwaki 3,  Shinsuke Nakanishi 3,  Shinya Oishi 2,  Takayoshi Kinoshita 4,  Isao Nakanishi 3,  Nobutaka Fujii 5
Affiliations

Affiliations

  • 1 Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan. Electronic address: hohno@pharm.kyoto-u.ac.jp.
  • 2 Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
  • 3 Faculty of Pharmacy, Department of Pharmaceutical Sciences, Kinki University, 3-4-1 Kowakae, Higashi-Osaka, Osaka 577-8502, Japan.
  • 4 Graduate School of Science, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, Japan.
  • 5 Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan. Electronic address: nfujii@pharm.kyoto-u.ac.jp.
PMID: 26850376 DOI: 10.1016/j.bmc.2016.01.043
Abstract

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.

Keywords

Kinase inhibitor; Protein kinase CK2; Rational design; Structure–activity relationship.

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