Design, synthesis and antitumor activity of 5-trifluoromethylpyrimidine derivatives as EGFR inhibitors.

Zuo, Y; Li, R; Zhang, Y; Bao, G; Le, Y; Yan, L

Design, synthesis and antitumor activity of 5-trifluoromethylpyrimidine derivatives as EGFR inhibitors.

Zuo, Y Li, R Zhang, Y Bao, G

Le, Y Yan, L

Permalink

Publisher:: Taylor and Francis Group
Publication Type:: Journal Article
Citation:: Journal of Enzyme Inhibition and Medicinal Chemistry, 2022, 37, (1), pp. 2742-2754
Issue Date:: 2022-12

Open Access

Copyright Clearance Process

Recently Added
In Progress
Open Access

This item is open access.

Download Accepted versionAdobe PDF (2.86 MB)

View on publisher's site

View statistics

Full metadata record

Field	Value	Language
dc.contributor.author	Zuo, Y
dc.contributor.author	Li, R
dc.contributor.author	Zhang, Y
dc.contributor.author	Bao, G https://orcid.org/0000-0001-5103-5009
dc.contributor.author	Le, Y
dc.contributor.author	Yan, L
dc.date.accessioned	2022-11-17T03:20:16Z
dc.date.available	2022-11-17T03:20:16Z
dc.date.issued	2022-12
dc.identifier.citation	Journal of Enzyme Inhibition and Medicinal Chemistry, 2022, 37, (1), pp. 2742-2754
dc.identifier.issn	1475-6366
dc.identifier.issn	1475-6374
dc.identifier.uri	http://hdl.handle.net/10453/163547
dc.description.abstract	A new series of 5-trifluoromethylpyrimidine derivatives were designed and synthesised as EGFR inhibitors. Three tumour cells A549, MCF-7, PC-3 and EGFR kinase were employed to evaluate their biological activities. The results were shown that most of the target compounds existed excellent antitumor activities. In particular, the IC50 values of compound 9u (E)-3-((2-((4-(3-(3-fluorophenyl)acrylamido)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)amino)-N-methylthiophene-2-carboxamide against A549, MCF-7, PC-3 cells and EGFR kinase reached to 0.35 μM, 3.24 μM, 5.12 μM, and 0.091 μM, respectively. Additionally, further researches revealed that compound 9u could induce early apoptosis of A549 cells and arrest the cells in G2/M phase. Taken together, these findings indicated that compound 9u was potential for developing as antitumor reagent.
dc.format	Print
dc.language	eng
dc.publisher	Taylor and Francis Group
dc.relation.ispartof	Journal of Enzyme Inhibition and Medicinal Chemistry
dc.relation.isbasedon	10.1080/14756366.2022.2128797
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	0304 Medicinal and Biomolecular Chemistry, 0601 Biochemistry and Cell Biology
dc.subject.classification	Medicinal & Biomolecular Chemistry
dc.subject.mesh	Antineoplastic Agents
dc.subject.mesh	Apoptosis
dc.subject.mesh	Cell Proliferation
dc.subject.mesh	Dose-Response Relationship, Drug
dc.subject.mesh	Drug Design
dc.subject.mesh	Drug Screening Assays, Antitumor
dc.subject.mesh	ErbB Receptors
dc.subject.mesh	Molecular Structure
dc.subject.mesh	Protein Kinase Inhibitors
dc.subject.mesh	Structure-Activity Relationship
dc.subject.mesh	Antineoplastic Agents
dc.subject.mesh	Apoptosis
dc.subject.mesh	Cell Proliferation
dc.subject.mesh	Dose-Response Relationship, Drug
dc.subject.mesh	Drug Design
dc.subject.mesh	Drug Screening Assays, Antitumor
dc.subject.mesh	ErbB Receptors
dc.subject.mesh	Molecular Structure
dc.subject.mesh	Protein Kinase Inhibitors
dc.subject.mesh	Structure-Activity Relationship
dc.subject.mesh	Antineoplastic Agents
dc.subject.mesh	Protein Kinase Inhibitors
dc.subject.mesh	Drug Screening Assays, Antitumor
dc.subject.mesh	Apoptosis
dc.subject.mesh	Cell Proliferation
dc.subject.mesh	Molecular Structure
dc.subject.mesh	Structure-Activity Relationship
dc.subject.mesh	Dose-Response Relationship, Drug
dc.subject.mesh	Drug Design
dc.subject.mesh	ErbB Receptors
dc.title	Design, synthesis and antitumor activity of 5-trifluoromethylpyrimidine derivatives as EGFR inhibitors.
dc.type	Journal Article
utslib.citation.volume	37
utslib.location.activity	England
utslib.for	0304 Medicinal and Biomolecular Chemistry
utslib.for	0601 Biochemistry and Cell Biology
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Mathematical and Physical Sciences
utslib.copyright.status	open_access	*
pubs.consider-herdc	false
dc.date.updated	2022-11-17T03:20:11Z
pubs.issue	1
pubs.publication-status	Published
pubs.volume	37
utslib.citation.issue	1

Abstract:

A new series of 5-trifluoromethylpyrimidine derivatives were designed and synthesised as EGFR inhibitors. Three tumour cells A549, MCF-7, PC-3 and EGFR kinase were employed to evaluate their biological activities. The results were shown that most of the target compounds existed excellent antitumor activities. In particular, the IC50 values of compound 9u (E)-3-((2-((4-(3-(3-fluorophenyl)acrylamido)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)amino)-N-methylthiophene-2-carboxamide against A549, MCF-7, PC-3 cells and EGFR kinase reached to 0.35 μM, 3.24 μM, 5.12 μM, and 0.091 μM, respectively. Additionally, further researches revealed that compound 9u could induce early apoptosis of A549 cells and arrest the cells in G2/M phase. Taken together, these findings indicated that compound 9u was potential for developing as antitumor reagent.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/163547