BIOMAT Database Logo BIOMAT Database Logo

Design, synthesis, and biological evaluation of thieno[2,3-d]pyrimidine derivatives as novel dual c-Met and VEGFR-2 kinase inhibitors. 2017

Jieming Li, and Weijie Gu, and Xinzhou Bi, and Huilan Li, and Chen Liao, and Chunxia Liu, and Wenlong Huang, and Hai Qian
Center of Drug Discovery, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China.

Both c-Met and VEGFR-2 are important targets for cancer therapies. Here we report a series of potent dual c-Met and VEGFR-2 inhibitors bearing thieno[2,3-d]pyrimidine scaffold. The cell proliferation assay in vitro demonstrated that most target compounds had inhibition potency both on c-Met and VEGFR-2 with IC50 values in nanomolar range, especially compound 12j and 12m. Based on the further enzyme assay in vitro, compound 12j was considered as the most potent one, the IC50 values of which were 25 nM and 48 nM for c-Met and VEGFR-2, respectively. Following that, we docked the compound 12j with the proteins c-Met and VEGFR-2, and interpreted the SAR of these analogues. All the results indicate that 12j is a dual inhibitors of c-Met and VEGFR-2 that holds promising potential.

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
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.
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
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
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
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
D015195 Drug Design The molecular designing of drugs for specific purposes (such as DNA-binding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include PHARMACOKINETICS, dosage analysis, or drug administration analysis. Computer-Aided Drug Design,Computerized Drug Design,Drug Modeling,Pharmaceutical Design,Computer Aided Drug Design,Computer-Aided Drug Designs,Computerized Drug Designs,Design, Pharmaceutical,Drug Design, Computer-Aided,Drug Design, Computerized,Drug Designs,Drug Modelings,Pharmaceutical Designs
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
D049109 Cell Proliferation All of the processes involved in increasing CELL NUMBER including CELL DIVISION. Cell Growth in Number,Cellular Proliferation,Cell Multiplication,Cell Number Growth,Growth, Cell Number,Multiplication, Cell,Number Growth, Cell,Proliferation, Cell,Proliferation, Cellular
D019859 Proto-Oncogene Proteins c-met Cell surface protein-tyrosine kinase receptors for HEPATOCYTE GROWTH FACTOR. They consist of an extracellular alpha chain which is disulfide-linked to the transmembrane beta chain. The cytoplasmic portion contains the catalytic domain and sites critical for the regulation of kinase activity. Mutations in the c-met proto-oncogene are associated with papillary renal carcinoma and other neoplasia. HGF Receptor,Hepatocyte Growth Factor Receptor,c-met Proteins,met Proto-Oncogene Proteins,MET Proto-Oncogene, Receptor Tyrosine Kinase,MET Receptor Tyrosine Kinase,Receptor, HGF,Receptor, Hepatocyte Growth Factor,Receptor, Scatter Factor,Scatter Factor Receptor,c-Met Receptor Tyrosine Kinase,MET Proto Oncogene, Receptor Tyrosine Kinase,Proto Oncogene Proteins c met,Proto-Oncogene Proteins, met,c Met Receptor Tyrosine Kinase,c met Proteins,met Proto Oncogene Proteins

Related Publications

Jieming Li, and Weijie Gu, and Xinzhou Bi, and Huilan Li, and Chen Liao, and Chunxia Liu, and Wenlong Huang, and Hai Qian
Design, synthesis, and biological evaluation of pyrido[2,3-d]pyrimidine and thieno[2,3-d]pyrimidine derivatives as novel EGFRL858R/T790M inhibitors.
December 2023, Journal of enzyme inhibition and medicinal chemistry,
Jieming Li, and Weijie Gu, and Xinzhou Bi, and Huilan Li, and Chen Liao, and Chunxia Liu, and Wenlong Huang, and Hai Qian
Design, Synthesis, and Biological Evaluation of [1,2,4]triazolo[4,3-a] Pyrazine Derivatives as Novel Dual c-Met/VEGFR-2 Inhibitors.
January 2022, Frontiers in chemistry,
Jieming Li, and Weijie Gu, and Xinzhou Bi, and Huilan Li, and Chen Liao, and Chunxia Liu, and Wenlong Huang, and Hai Qian
Design, synthesis and biological evaluation of pyrimidine-based derivatives as VEGFR-2 tyrosine kinase inhibitors.
August 2018, Bioorganic chemistry,
Jieming Li, and Weijie Gu, and Xinzhou Bi, and Huilan Li, and Chen Liao, and Chunxia Liu, and Wenlong Huang, and Hai Qian
Discovery of novel c-Met kinase inhibitors bearing a thieno[2,3-d]pyrimidine or furo[2,3-d]pyrimidine scaffold.
July 2011, Bioorganic & medicinal chemistry,
Jieming Li, and Weijie Gu, and Xinzhou Bi, and Huilan Li, and Chen Liao, and Chunxia Liu, and Wenlong Huang, and Hai Qian
Discovery of thieno[2,3-d]pyrimidine-based derivatives as potent VEGFR-2 kinase inhibitors and anti-cancer agents.
July 2021, Bioorganic chemistry,
Jieming Li, and Weijie Gu, and Xinzhou Bi, and Huilan Li, and Chen Liao, and Chunxia Liu, and Wenlong Huang, and Hai Qian
Design, Synthesis, and Biological Evaluation of 2-Substituted Aniline Pyrimidine Derivatives as Potent Dual Mer/c-Met Inhibitors.
January 2024, Molecules (Basel, Switzerland),
Jieming Li, and Weijie Gu, and Xinzhou Bi, and Huilan Li, and Chen Liao, and Chunxia Liu, and Wenlong Huang, and Hai Qian
Design, synthesis and anticancer evaluation of thieno[2,3-d]pyrimidine derivatives as dual EGFR/HER2 inhibitors and apoptosis inducers.
July 2019, Bioorganic chemistry,
Jieming Li, and Weijie Gu, and Xinzhou Bi, and Huilan Li, and Chen Liao, and Chunxia Liu, and Wenlong Huang, and Hai Qian
Design, synthesis, biological evaluation and molecular modeling of novel 1H-pyrazolo[3,4-d]pyrimidine derivatives as BRAFV600E and VEGFR-2 dual inhibitors.
July 2018, European journal of medicinal chemistry,
Jieming Li, and Weijie Gu, and Xinzhou Bi, and Huilan Li, and Chen Liao, and Chunxia Liu, and Wenlong Huang, and Hai Qian
Pyrrolo[2,3-d]pyrimidine derivatives as inhibitors of RET: Design, synthesis and biological evaluation.
November 2020, European journal of medicinal chemistry,
Jieming Li, and Weijie Gu, and Xinzhou Bi, and Huilan Li, and Chen Liao, and Chunxia Liu, and Wenlong Huang, and Hai Qian
Design, synthesis and evaluation of thieno[3,2-d]pyrimidine derivatives as novel potent CDK7 inhibitors.
May 2024, Bioorganic chemistry,
Copied contents to your clipboard!