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

doi:10.1016/j.bmcl.2019.05.024

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 journal › Article › peer-review

3 Citations (Scopus)

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 language	English
Pages (from-to)	1985-1993
Number of pages	9
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	29
Issue number	15
DOIs	https://doi.org/10.1016/j.bmcl.2019.05.024
Publication status	Published - 2019 Aug 1

Bibliographical note

Publisher Copyright:
© 2019 Elsevier Ltd

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.bmcl.2019.05.024

Cite this

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

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.",

keywords = "CDK inhibitor, CDK14, CDK15, CDK16, CDK17, CDK18, Cell cycle, Covalent kinase inhibitor, Mitosis, TAIRE kinase",

author = "Ferguson, {Fleur M.} and Doctor, {Zainab M.} and Ficarro, {Scott B.} and Marto, {Jarrod A.} and Kim, {Nam Doo} and Taebo Sim and Gray, {Nathanael S.}",

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day = "1",

doi = "10.1016/j.bmcl.2019.05.024",

language = "English",

volume = "29",

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journal = "Bioorganic and Medicinal Chemistry Letters",

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T1 - Synthesis and structure activity relationships of a series of 4-amino-1H-pyrazoles as covalent inhibitors of CDK14

AU - Ferguson, Fleur M.

AU - Doctor, Zainab M.

AU - Ficarro, Scott B.

AU - Marto, Jarrod A.

AU - Kim, Nam Doo

AU - Sim, Taebo

AU - Gray, Nathanael S.

PY - 2019/8/1

Y1 - 2019/8/1

N2 - 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.

AB - 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.

KW - CDK inhibitor

KW - CDK14

KW - CDK15

KW - CDK16

KW - CDK17

KW - CDK18

KW - Cell cycle

KW - Covalent kinase inhibitor

KW - Mitosis

KW - TAIRE kinase

UR - http://www.scopus.com/inward/record.url?scp=85066508646&partnerID=8YFLogxK

U2 - 10.1016/j.bmcl.2019.05.024

DO - 10.1016/j.bmcl.2019.05.024

M3 - Article

C2 - 31175010

AN - SCOPUS:85066508646

SN - 0960-894X

VL - 29

SP - 1985

EP - 1993

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 15

ER -

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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