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

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. (C) 2017 Elsevier Ltd. All rights reserved.

Journal

• Bioorganic & medicinal chemistry letters

  Bioorganic & medicinal chemistry letters 27 (10), 2144-2147, 2017-05-15

  Elsevier

Keywords

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

Details

• CRID: 1050564289014147968
• NII Article ID: 120006628669
• DOI: 10.1016/j.bmcl.2017.03.055
• HANDLE: 2115/74002
• ISSN: 0960894X
• Web Site: https://api.elsevier.com/content/article/PII:S0960894X17303062?httpAccept=text/xml
• Web Site: https://api.elsevier.com/content/article/PII:S0960894X17303062?httpAccept=text/plain
• Text Lang: en
• Article Type: journal article
• Data Source:
  • IRDB
  • Crossref
  • CiNii Articles
  • KAKEN