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

Fleur M. Ferguson, Zainab M. Doctor, Scott B. Ficarro, Jarrod A. Marto, Nam Doo Kim, Taebo Sim, Nathanael S. Gray

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)1985-1993
Number of pages9
JournalBioorganic and Medicinal Chemistry Letters
Volume29
Issue number15
DOIs
Publication statusPublished - 2019 Aug 1

Fingerprint

Pyrazoles
Structure-Activity Relationship
Phosphotransferases
Neoplasms

Keywords

  • CDK inhibitor
  • CDK14
  • CDK15
  • CDK16
  • CDK17
  • CDK18
  • Cell cycle
  • Covalent kinase inhibitor
  • Mitosis
  • TAIRE kinase

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

Synthesis and structure activity relationships of a series of 4-amino-1H-pyrazoles as covalent inhibitors of CDK14. / Ferguson, Fleur M.; Doctor, Zainab M.; Ficarro, Scott B.; Marto, Jarrod A.; Kim, Nam Doo; Sim, Taebo; Gray, Nathanael S.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 29, No. 15, 01.08.2019, p. 1985-1993.

Research output: Contribution to journalArticle

Ferguson, Fleur M. ; Doctor, Zainab M. ; Ficarro, Scott B. ; Marto, Jarrod A. ; Kim, Nam Doo ; Sim, Taebo ; Gray, Nathanael S. / Synthesis and structure activity relationships of a series of 4-amino-1H-pyrazoles as covalent inhibitors of CDK14. In: Bioorganic and Medicinal Chemistry Letters. 2019 ; Vol. 29, No. 15. pp. 1985-1993.
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