Synthesis and structure activity relationships of a series of 4-amino-1H-pyrazoles as covalent inhibitors of CDK14

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:29

Article

Ferguson, Fleur M.^1,2  Doctor, Zainab M.^1,2  Ficarro, Scott B.^1,3,4  Marto, Jarrod A.^1,3,4,5  Kim, Nam Doo⁶  Sim, Taebo^7,8  Gray, Nathanael S.¹ 

[1] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA

[2] Harvard Med Sch, Dept Biol Chem & Mol Pharmacol, Boston, MA 02215 USA

[3] Dana Farber Canc Inst, Blais Prote Ctr, Boston, MA 02215 USA

[4] Harvard Med Sch, Dept Pathol, Brigham & Womens Hosp, Boston, MA 02215 USA

[5] Dana Farber Canc Inst, Dept Oncol Pathol, Boston, MA 02215 USA

[6] Daegu Gyeongbuk Med Innovat Fdn, Daegu, South Korea

[7] Korea Inst Sci & Technol, Chem Kin Res Ctr, Seoul, South Korea

[8] Korea Univ, KU KIST Grad Sch Converging Sci & Technol, Seoul, South Korea

关键词: Covalent kinase inhibitor;    CDK14;    TAIRE kinase;    CDK15;    CDK16;    CDK17;    CDK18;    CDK inhibitor;    Mitosis;    Cell cycle;   

DOI  :  10.1016/j.bmcl.2019.05.024

来源: Elsevier

【 摘 要 】

The TAIRE family of kinases are an understudied branch of the CDK kinase family, that have been implicated in a number of cancers. This manuscript describes the design, synthesis and SAR of covalent CDK14 inhibitors, culminating in identification of FMF-04-159-2, a potent, covalent CDK14 inhibitor with a TAIRE kinase biased selectivity profile.

【 授权许可】

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