BIOMAT Database Logo BIOMAT Database Logo

Discovery of thiapyran-pyrimidine derivatives as potential EGFR inhibitors. 2020

Zhen Xiao, and Cilong Chu, and Lingjia Zhou, and Zhihui Zhou, and Qian Zhang, and Feiyi Yang, and Zunhua Yang, and Pengwu Zheng, and Shan Xu, and Wufu Zhu
Jiangxi Provincial Key Laboratory of Drug Design and Evaluation, School of Pharmacy, Jiangxi Science & Technology Normal University, 605 Fenglin Road, Nanchang, Jiangxi 330013, China.

A series of novel thiapyran-pyrimidine derivatives (10a-10h, 11a-11g, 12a-12f, 13a-13f, 14a-14f) were synthesized and their antiproliferative activities were tested. Most of the target compounds showed good activity on one or more cancer cell lines but low activity on human normal cell LO2. The most promising compound 13a exhibited the similar IC50 values on A549 and H1975 cell lines to the lead drug Olmutinib, and exhibited excellent activity and selectivity on EGFRT790M/L858R in the kinase experiment. AO and Hoechst33258 staining indicated that 13a could effectively induce H1975 cells apoptosis. Cell cycle and apoptosis analysis suggested that 13a could block cancer cells in G2/M phase and induce into late apoptosis in a manner of concentration-dependent. The structure-activity relationship of 13a was analyzed to explore its mechanism. All the results showed that 13a was a promising EGFR inhibitor.

UI MeSH Term Description Entries
D011714 Pyrans Pyran
D011743 Pyrimidines A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (CYTOSINE; THYMINE; and URACIL) and form the basic structure of the barbiturates.
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004354 Drug Screening Assays, Antitumor Methods of investigating the effectiveness of anticancer cytotoxic drugs and biologic inhibitors. These include in vitro cell-kill models and cytostatic dye exclusion tests as well as in vivo measurement of tumor growth parameters in laboratory animals. Anticancer Drug Sensitivity Tests,Antitumor Drug Screens,Cancer Drug Tests,Drug Screening Tests, Tumor-Specific,Dye Exclusion Assays, Antitumor,Anti-Cancer Drug Screens,Antitumor Drug Screening Assays,Tumor-Specific Drug Screening Tests,Anti Cancer Drug Screens,Anti-Cancer Drug Screen,Antitumor Drug Screen,Cancer Drug Test,Drug Screen, Anti-Cancer,Drug Screen, Antitumor,Drug Screening Tests, Tumor Specific,Drug Screens, Anti-Cancer,Drug Screens, Antitumor,Drug Test, Cancer,Drug Tests, Cancer,Screen, Anti-Cancer Drug,Screen, Antitumor Drug,Screens, Anti-Cancer Drug,Screens, Antitumor Drug,Test, Cancer Drug,Tests, Cancer Drug,Tumor Specific Drug Screening Tests
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000970 Antineoplastic Agents Substances that inhibit or prevent the proliferation of NEOPLASMS. Anticancer Agent,Antineoplastic,Antineoplastic Agent,Antineoplastic Drug,Antitumor Agent,Antitumor Drug,Cancer Chemotherapy Agent,Cancer Chemotherapy Drug,Anticancer Agents,Antineoplastic Drugs,Antineoplastics,Antitumor Agents,Antitumor Drugs,Cancer Chemotherapy Agents,Cancer Chemotherapy Drugs,Chemotherapeutic Anticancer Agents,Chemotherapeutic Anticancer Drug,Agent, Anticancer,Agent, Antineoplastic,Agent, Antitumor,Agent, Cancer Chemotherapy,Agents, Anticancer,Agents, Antineoplastic,Agents, Antitumor,Agents, Cancer Chemotherapy,Agents, Chemotherapeutic Anticancer,Chemotherapy Agent, Cancer,Chemotherapy Agents, Cancer,Chemotherapy Drug, Cancer,Chemotherapy Drugs, Cancer,Drug, Antineoplastic,Drug, Antitumor,Drug, Cancer Chemotherapy,Drug, Chemotherapeutic Anticancer,Drugs, Antineoplastic,Drugs, Antitumor,Drugs, Cancer Chemotherapy
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D015394 Molecular Structure The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds. Structure, Molecular,Molecular Structures,Structures, Molecular
D045744 Cell Line, Tumor A cell line derived from cultured tumor cells. Tumor Cell Line,Cell Lines, Tumor,Line, Tumor Cell,Lines, Tumor Cell,Tumor Cell Lines
D047428 Protein Kinase Inhibitors Agents that inhibit PROTEIN KINASES. Protein Kinase Inhibitor,Inhibitor, Protein Kinase,Inhibitors, Protein Kinase,Kinase Inhibitor, Protein,Kinase Inhibitors, Protein

Related Publications

Zhen Xiao, and Cilong Chu, and Lingjia Zhou, and Zhihui Zhou, and Qian Zhang, and Feiyi Yang, and Zunhua Yang, and Pengwu Zheng, and Shan Xu, and Wufu Zhu
Discovery and optimization of tetrahydropyrido[4,3-d]pyrimidine derivatives as novel ATX and EGFR dual inhibitors.
May 2018, Bioorganic & medicinal chemistry,
Zhen Xiao, and Cilong Chu, and Lingjia Zhou, and Zhihui Zhou, and Qian Zhang, and Feiyi Yang, and Zunhua Yang, and Pengwu Zheng, and Shan Xu, and Wufu Zhu
Rational design-aided discovery of novel 1,2,4-oxadiazole derivatives as potential EGFR inhibitors.
September 2021, Bioorganic chemistry,
Zhen Xiao, and Cilong Chu, and Lingjia Zhou, and Zhihui Zhou, and Qian Zhang, and Feiyi Yang, and Zunhua Yang, and Pengwu Zheng, and Shan Xu, and Wufu Zhu
Discovery of 5-(methylthio)pyrimidine derivatives as L858R/T790M mutant selective epidermal growth factor receptor (EGFR) inhibitors.
June 2016, Bioorganic & medicinal chemistry,
Zhen Xiao, and Cilong Chu, and Lingjia Zhou, and Zhihui Zhou, and Qian Zhang, and Feiyi Yang, and Zunhua Yang, and Pengwu Zheng, and Shan Xu, and Wufu Zhu
Discovery of aminopyridine-containing spiro derivatives as EGFR mutations inhibitors.
December 2019, Journal of enzyme inhibition and medicinal chemistry,
Zhen Xiao, and Cilong Chu, and Lingjia Zhou, and Zhihui Zhou, and Qian Zhang, and Feiyi Yang, and Zunhua Yang, and Pengwu Zheng, and Shan Xu, and Wufu Zhu
Discovery of 2,4,6-trisubstitued pyrido[3,4-d]pyrimidine derivatives as new EGFR-TKIs.
March 2018, European journal of medicinal chemistry,
Zhen Xiao, and Cilong Chu, and Lingjia Zhou, and Zhihui Zhou, and Qian Zhang, and Feiyi Yang, and Zunhua Yang, and Pengwu Zheng, and Shan Xu, and Wufu Zhu
Discovery of [1,2,3]Triazolo[4,5-d]pyrimidine Derivatives as Novel LSD1 Inhibitors.
April 2017, ACS medicinal chemistry letters,
Zhen Xiao, and Cilong Chu, and Lingjia Zhou, and Zhihui Zhou, and Qian Zhang, and Feiyi Yang, and Zunhua Yang, and Pengwu Zheng, and Shan Xu, and Wufu Zhu
Discovery of 4,6-Disubstituted Pyrimidine Derivatives as Novel Dual VEGFR2/FGFR1 Inhibitors.
May 2021, Chemistry & biodiversity,
Zhen Xiao, and Cilong Chu, and Lingjia Zhou, and Zhihui Zhou, and Qian Zhang, and Feiyi Yang, and Zunhua Yang, and Pengwu Zheng, and Shan Xu, and Wufu Zhu
Discovery of anilino-furo[2,3-d]pyrimidine derivatives as dual inhibitors of EGFR/HER2 tyrosine kinase and their anticancer activity.
January 2018, European journal of medicinal chemistry,
Zhen Xiao, and Cilong Chu, and Lingjia Zhou, and Zhihui Zhou, and Qian Zhang, and Feiyi Yang, and Zunhua Yang, and Pengwu Zheng, and Shan Xu, and Wufu Zhu
Discovery of New Pyrrolo[2,3-d]pyrimidine Derivatives as Potential Multi-Targeted Kinase Inhibitors and Apoptosis Inducers.
September 2023, Pharmaceuticals (Basel, Switzerland),
Zhen Xiao, and Cilong Chu, and Lingjia Zhou, and Zhihui Zhou, and Qian Zhang, and Feiyi Yang, and Zunhua Yang, and Pengwu Zheng, and Shan Xu, and Wufu Zhu
Discovery of a series of novel phenylpiperazine derivatives as EGFR TK inhibitors.
September 2015, Scientific reports,
Copied contents to your clipboard!