Divergent synthesis of kinase inhibitor derivatives, leading to discovery of selective Gck inhibitors

Takanori Matsumaru, Makoto Inai, Kana Ishigami, Toshiki Iwamatsu, Hiroshi Maita, Satoko Otsuguro, Takao Nomura, Akira Matsuda, Satoshi Ichikawa, Masahiro Sakaitani, Satoshi Shuto, Katsumi Maenaka, Toshiyuki Kan

Research output: Contribution to journalArticle

Abstract

We accomplished divergent synthesis of potent kinase inhibitor BAY 61-3606 (1) and 27 derivatives via conjugation of imidazo[1,2-c]pyrimidine and indole ring compounds with aromatic (including pyridine) derivatives by means of palladium-catalyzed cross-coupling reaction. Spleen tyrosine kinase (Syk) and germinal center kinase (Gck, MAP4K2) inhibition assays showed that some of the synthesized compounds were selective Gck inhibitors.

Original languageEnglish
Pages (from-to)2144-2147
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume27
Issue number10
DOIs
Publication statusPublished - 2017
Externally publishedYes

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Cross Reactions
Palladium
Phosphotransferases
Derivatives
Protein-Tyrosine Kinases
Assays
imidazo(1,2-c)pyrimidine
Syk Kinase
pyridine
indole
2-(7-(3,4-dimethoxyphenyl)imidazo(1,2-c)pyrimidin-5-ylamino)nicotinamide
germinal center kinases

Keywords

  • BAY 61-3606
  • Gck
  • Imidazo[1,2-c]pyrimidine
  • Indole
  • Kinase inhibitor

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

Divergent synthesis of kinase inhibitor derivatives, leading to discovery of selective Gck inhibitors. / Matsumaru, Takanori; Inai, Makoto; Ishigami, Kana; Iwamatsu, Toshiki; Maita, Hiroshi; Otsuguro, Satoko; Nomura, Takao; Matsuda, Akira; Ichikawa, Satoshi; Sakaitani, Masahiro; Shuto, Satoshi; Maenaka, Katsumi; Kan, Toshiyuki.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 27, No. 10, 2017, p. 2144-2147.

Research output: Contribution to journalArticle

Matsumaru, T, Inai, M, Ishigami, K, Iwamatsu, T, Maita, H, Otsuguro, S, Nomura, T, Matsuda, A, Ichikawa, S, Sakaitani, M, Shuto, S, Maenaka, K & Kan, T 2017, 'Divergent synthesis of kinase inhibitor derivatives, leading to discovery of selective Gck inhibitors', Bioorganic and Medicinal Chemistry Letters, vol. 27, no. 10, pp. 2144-2147. https://doi.org/10.1016/j.bmcl.2017.03.055
Matsumaru, Takanori ; Inai, Makoto ; Ishigami, Kana ; Iwamatsu, Toshiki ; Maita, Hiroshi ; Otsuguro, Satoko ; Nomura, Takao ; Matsuda, Akira ; Ichikawa, Satoshi ; Sakaitani, Masahiro ; Shuto, Satoshi ; Maenaka, Katsumi ; Kan, Toshiyuki. / Divergent synthesis of kinase inhibitor derivatives, leading to discovery of selective Gck inhibitors. In: Bioorganic and Medicinal Chemistry Letters. 2017 ; Vol. 27, No. 10. pp. 2144-2147.
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