BIOMAT Database Logo BIOMAT Database Logo

Synthesis and evaluation of biological and antitumor activities of 5,7-dimethyl- oxazolo[5,4-d]pyrimidine-4,6(5H,7H)-dione derivatives as novel inhibitors of FGFR1. 2015

Faqing Ye, and Yuewu Wang, and Siyun Nian, and Yu Wang, and Di Chen, and Shufang Yu, and Sicen Wang
a School of Pharmacy, Health Science Center Xi'an Jiaotong University , Xi'an , China and.

A series of 5,7-dimethyl-oxazolo[5,4-d]pyrimidine-4,6(5H,7H)-dione derivatives, N5a-5l, was designed, synthesized and evaluated for their FGFR1-inhibition ability as well as cytotoxicity against three cancer cell lines (H460, B16F10 and A549) in vitro. Several compounds displayed good-to-excellent potency against these cancer cell lines compared to SU5402. Structure-activity relationship analyses indicated that compounds with a rigid structure and more heteroatoms at the side chain of the parent ring were more effective than those without these substitutions. The compound N5g (37.4% FGFR1 inhibition at 1.0 μM) was identified to have the most potent antitumor activities, with IC50 values of 5.472, 4.260 and 5.837 μM against H460, B16F10 and A549 cell lines, respectively. Together, our results suggest that 5,7-dimethyl-oxazolo[5,4-d]pyrimidine-4,6(5H,7H)-dione derivatives may serve as potential agents for the treatment of FGFR1-mediated cancers.

UI MeSH Term Description Entries
D008958 Models, Molecular Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures. Molecular Models,Model, Molecular,Molecular Model
D010080 Oxazoles Five-membered heterocyclic ring structures containing an oxygen in the 1-position and a nitrogen in the 3-position, in distinction from ISOXAZOLES where they are at the 1,2 positions. Oxazole,1,3-Oxazolium-5-Oxides,Munchnones,1,3 Oxazolium 5 Oxides
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

Related Publications

Faqing Ye, and Yuewu Wang, and Siyun Nian, and Yu Wang, and Di Chen, and Shufang Yu, and Sicen Wang
Cis-8,9-Dihydroisoxazol(5,4-d)pyrimidine-4,6(5H,7H)-diones.
September 1972, The Journal of organic chemistry,
Faqing Ye, and Yuewu Wang, and Siyun Nian, and Yu Wang, and Di Chen, and Shufang Yu, and Sicen Wang
Synthesis and Biological Activity of New 7-Amino-oxazolo[5,4-d]Pyrimidine Derivatives.
August 2020, Molecules (Basel, Switzerland),
Faqing Ye, and Yuewu Wang, and Siyun Nian, and Yu Wang, and Di Chen, and Shufang Yu, and Sicen Wang
Synthesis and biological evaluation of novel oxazolo[5,4-d]pyrimidines as potent VEGFR-2 inhibitors.
April 2015, Chemistry & biodiversity,
Faqing Ye, and Yuewu Wang, and Siyun Nian, and Yu Wang, and Di Chen, and Shufang Yu, and Sicen Wang
Design, synthesis and evaluation of the anti-breast cancer activity of 1,3-oxazolo[4,5-d]pyrimidine and 1,3-oxazolo[5,4-d]pyrimidine derivatives.
April 2023, RSC medicinal chemistry,
Faqing Ye, and Yuewu Wang, and Siyun Nian, and Yu Wang, and Di Chen, and Shufang Yu, and Sicen Wang
Synthesis and biological evaluation of selected 7H-pyrrolo[2,3-d]pyrimidine derivatives as novel CDK9/CyclinT and Haspin inhibitors.
November 2021, Chemico-biological interactions,
Faqing Ye, and Yuewu Wang, and Siyun Nian, and Yu Wang, and Di Chen, and Shufang Yu, and Sicen Wang
Discovery of 4,6-Disubstituted Pyrimidine Derivatives as Novel Dual VEGFR2/FGFR1 Inhibitors.
May 2021, Chemistry & biodiversity,
Faqing Ye, and Yuewu Wang, and Siyun Nian, and Yu Wang, and Di Chen, and Shufang Yu, and Sicen Wang
Design, synthesis and biological evaluation of novel 7H-pyrrolo[2,3-d]pyrimidine derivatives as potential FAK inhibitors and anticancer agents.
December 2019, European journal of medicinal chemistry,
Faqing Ye, and Yuewu Wang, and Siyun Nian, and Yu Wang, and Di Chen, and Shufang Yu, and Sicen Wang
Diarylureas and Diarylamides with Oxazolo[5,4-d]pyrimidine Scaffold as Angiogenesis Inhibitors.
September 2016, Chemistry & biodiversity,
Faqing Ye, and Yuewu Wang, and Siyun Nian, and Yu Wang, and Di Chen, and Shufang Yu, and Sicen Wang
Synthesis and biological evaluation of pyrido[2,3-d]pyrimidine-2,4-dione derivatives as eEF-2K inhibitors.
September 2014, Bioorganic & medicinal chemistry,
Faqing Ye, and Yuewu Wang, and Siyun Nian, and Yu Wang, and Di Chen, and Shufang Yu, and Sicen Wang
Design and Synthesis of Novel Thiazolo[5,4-d]pyrimidine Derivatives as Potential Angiogenesis Inhibitors.
August 2019, Chemistry & biodiversity,
Copied contents to your clipboard!