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.
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Matsumaru
authors.affiliation: School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Inai
authors.affiliation: School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
authors.forename: Kana
authors.initials: K
authors.lastname: Ishigami
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
authors.forename: Toshiki
authors.initials: T
authors.lastname: Iwamatsu
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Maita
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
authors.forename: Satoko
authors.initials: S
authors.lastname: Otsuguro
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Nomura
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Matsuda
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ichikawa
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Sakaitani
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Shuto
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan. Electronic address: maenaka@pharm.hokudai.ac.jp.
authors.forename: Katsumi
authors.initials: K
authors.lastname: Maenaka
authors.affiliation: School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan. Electronic address: kant@u-shizuoka-ken.ac.jp.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Kan
mesh_terms: D002384:Catalysis; D004353:Drug Evaluation, Preclinical; D000081410:Germinal Center Kinases; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D007211:Indoles / Q000737:chemistry; D020128:Inhibitory Concentration 50; D009536:Niacinamide / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D010165:Palladium / Q000737:chemistry; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship; D000072377:Syk Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: C477642:2-(7-(3,4-dimethoxyphenyl)imidazo(1,2-c)pyrimidin-5-ylamino)nicotinamide; D000081410:Germinal Center Kinases; D007093:Imidazoles; D007211:Indoles; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; C584266:imidazo(1,2-c)pyrimidine; D009536:Niacinamide; D010165:Palladium; C030374:indole; D000072377:Syk Kinase; D017346:Protein Serine-Threonine Kinases
keywords: BAY 61-3606; Gck; Imidazo[1,2-c]pyrimidine; Indole; Kinase inhibitor