BIOMAT Database Logo BIOMAT Database Logo

Pyrimidine-based pyrazoles as cyclin-dependent kinase 2 inhibitors: Design, synthesis, and biological evaluation. 2018

Mayur K Vekariya, and Rajesh H Vekariya, and Pathik S Brahmkshatriya, and Nisha K Shah
Department of Chemistry, Gujarat University, Ahmedabad, India.

A series of new pyrimidine-pyrazole hybrid molecules were designed as inhibitors of cyclin-dependent kinase 2. Designed compounds were docked using Glide and the compounds showing good score values and encouraging interactions with the residues were selected for synthesis. They were then evaluated using CDK2-CyclinA2 enzyme inhibition by a luminescent ADP detection assay. We show that of the 26 compounds synthesized and evaluated, at least 5 compounds were found to be highly potent (IC50  < 20 nm); which can be further optimized to have selectivity over other kinase isoforms.

UI MeSH Term Description Entries
D011720 Pyrazoles Azoles of two nitrogens at the 1,2 positions, next to each other, in contrast with IMIDAZOLES in which they are at the 1,3 positions.
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.
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D001665 Binding Sites The parts of a macromolecule that directly participate in its specific combination with another molecule. Combining Site,Binding Site,Combining Sites,Site, Binding,Site, Combining,Sites, Binding,Sites, Combining
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
D017434 Protein Structure, Tertiary The level of protein structure in which combinations of secondary protein structures (ALPHA HELICES; BETA SHEETS; loop regions, and AMINO ACID MOTIFS) pack together to form folded shapes. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Tertiary Protein Structure,Protein Structures, Tertiary,Tertiary Protein Structures
D047428 Protein Kinase Inhibitors Agents that inhibit PROTEIN KINASES. Protein Kinase Inhibitor,Inhibitor, Protein Kinase,Inhibitors, Protein Kinase,Kinase Inhibitor, Protein,Kinase Inhibitors, Protein
D051357 Cyclin-Dependent Kinase 2 A key regulator of CELL CYCLE progression. It partners with CYCLIN E to regulate entry into S PHASE and also interacts with CYCLIN A to phosphorylate RETINOBLASTOMA PROTEIN. Its activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P27 and CYCLIN-DEPENDENT KINASE INHIBITOR P21. Cdk2 Protein Kinase,CDK2 Protein,Cdc2-Related Protein Kinase,p33cdk2 Kinase,Cdc2 Related Protein Kinase,Cyclin Dependent Kinase 2
D062105 Molecular Docking Simulation A computer simulation technique that is used to model the interaction between two molecules. Typically the docking simulation measures the interactions of a small molecule or ligand with a part of a larger molecule such as a protein. Molecular Docking,Molecular Docking Simulations,Molecular Docking Analysis,Analysis, Molecular Docking,Docking Analysis, Molecular,Docking Simulation, Molecular,Docking, Molecular,Molecular Docking Analyses,Molecular Dockings,Simulation, Molecular Docking

Related Publications

Mayur K Vekariya, and Rajesh H Vekariya, and Pathik S Brahmkshatriya, and Nisha K Shah
Design, synthesis and biological evaluation of pyrimidine-based derivatives as VEGFR-2 tyrosine kinase inhibitors.
August 2018, Bioorganic chemistry,
Mayur K Vekariya, and Rajesh H Vekariya, and Pathik S Brahmkshatriya, and Nisha K Shah
Development of in silico models for pyrazoles and pyrimidine derivatives as cyclin-dependent kinase 2 inhibitors.
September 2011, Journal of molecular graphics & modelling,
Mayur K Vekariya, and Rajesh H Vekariya, and Pathik S Brahmkshatriya, and Nisha K Shah
3-Hydroxychromones as cyclin-dependent kinase inhibitors: synthesis and biological evaluation.
March 2007, Bioorganic & medicinal chemistry letters,
Mayur K Vekariya, and Rajesh H Vekariya, and Pathik S Brahmkshatriya, and Nisha K Shah
Synthesis and biological evaluation of 3,5-diaminoindazoles as cyclin-dependent kinase inhibitors.
April 2008, Bioorganic & medicinal chemistry letters,
Mayur K Vekariya, and Rajesh H Vekariya, and Pathik S Brahmkshatriya, and Nisha K Shah
Design, synthesis, and biological evaluation of indolin-2-one derivatives as novel cyclin-dependent protein kinase 8 (CDK8) inhibitors.
March 2023, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie,
Mayur K Vekariya, and Rajesh H Vekariya, and Pathik S Brahmkshatriya, and Nisha K Shah
3-Acyl-2,6-diaminopyridines as cyclin-dependent kinase inhibitors: synthesis and biological evaluation.
May 2005, Bioorganic & medicinal chemistry letters,
Mayur K Vekariya, and Rajesh H Vekariya, and Pathik S Brahmkshatriya, and Nisha K Shah
Design, synthesis and biological evaluation of pyrazolo[3,4-d]pyrimidine-based protein kinase D inhibitors.
November 2020, European journal of medicinal chemistry,
Mayur K Vekariya, and Rajesh H Vekariya, and Pathik S Brahmkshatriya, and Nisha K Shah
Design, synthesis and biological evaluation of novel 2-phenyl pyrimidine derivatives as potent Bruton's tyrosine kinase (BTK) inhibitors.
February 2019, MedChemComm,
Mayur K Vekariya, and Rajesh H Vekariya, and Pathik S Brahmkshatriya, and Nisha K Shah
Design, synthesis and biological evaluation of 4-arylamino-pyrimidine derivatives as focal adhesion kinase inhibitors.
November 2023, Bioorganic chemistry,
Mayur K Vekariya, and Rajesh H Vekariya, and Pathik S Brahmkshatriya, and Nisha K Shah
Design, synthesis, and biological evaluation of pyrimidine derivatives as potential inhibitors of human calcium/calmodulin-dependent protein kinase IV.
May 2017, Chemical biology & drug design,
Copied contents to your clipboard!