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

doi:10.1016/j.bmcl.2017.03.055

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 journal › Article › peer-review

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 language	English
Pages (from-to)	2144-2147
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	27
Issue number	10
DOIs	https://doi.org/10.1016/j.bmcl.2017.03.055
Publication status	Published - 2017
Externally published	Yes

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

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10.1016/j.bmcl.2017.03.055

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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, 27(10), 2144-2147. https://doi.org/10.1016/j.bmcl.2017.03.055

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

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

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.",

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

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

note = "Funding Information: This research is (partially) supported by the Platform Project for Supporting in Drug Discovery and Life Science Research (Platform for Drug Discovery, Informatics, and Structural Life Science) from the Ministry of Education, Culture, Sports, Science (MEXT) and Japan Agency for Medical Research and development (AMED). Publisher Copyright: {\textcopyright} 2017 Elsevier Ltd",

year = "2017",

doi = "10.1016/j.bmcl.2017.03.055",

language = "English",

volume = "27",

pages = "2144--2147",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Elsevier Limited",

number = "10",

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TY - JOUR

T1 - Divergent synthesis of kinase inhibitor derivatives, leading to discovery of selective Gck inhibitors

AU - Matsumaru, Takanori

AU - Inai, Makoto

AU - Ishigami, Kana

AU - Iwamatsu, Toshiki

AU - Maita, Hiroshi

AU - Otsuguro, Satoko

AU - Nomura, Takao

AU - Matsuda, Akira

AU - Ichikawa, Satoshi

AU - Sakaitani, Masahiro

AU - Shuto, Satoshi

AU - Maenaka, Katsumi

AU - Kan, Toshiyuki

N1 - Funding Information: This research is (partially) supported by the Platform Project for Supporting in Drug Discovery and Life Science Research (Platform for Drug Discovery, Informatics, and Structural Life Science) from the Ministry of Education, Culture, Sports, Science (MEXT) and Japan Agency for Medical Research and development (AMED). Publisher Copyright: © 2017 Elsevier Ltd

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

KW - BAY 61-3606

KW - Gck

KW - Imidazo[1,2-c]pyrimidine

KW - Indole

KW - Kinase inhibitor

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U2 - 10.1016/j.bmcl.2017.03.055

DO - 10.1016/j.bmcl.2017.03.055

M3 - Article

C2 - 28385506

AN - SCOPUS:85017374783

SN - 0960-894X

VL - 27

SP - 2144

EP - 2147

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 10

ER -

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

Abstract

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ASJC Scopus subject areas

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