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

Autor: Ferguson FM; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02215, USA., Doctor ZM; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02215, USA., Ficarro SB; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Blais Proteomics Center, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA., Marto JA; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Blais Proteomics Center, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA; Department of Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA 02215, USA., Kim ND; Daegu-Gyeongbuk Medical Innovation Foundation, Republic of Korea., Sim T; Chemical Kinomics Research Center, Korea Institute of Science and Technology, Republic of Korea; KU-KIST Graduate School of Converging Science and Technology, Korea University, Republic of Korea., Gray NS; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA. Electronic address: nathanael_gray@dfci.harvard.edu.
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2019 Aug 01; Vol. 29 (15), pp. 1985-1993. Date of Electronic Publication: 2019 May 23.
DOI: 10.1016/j.bmcl.2019.05.024
Abstrakt: 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.
(Copyright © 2019 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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