3D-QSAR and docking studies on pyrazolo[4,3-h]qinazoline-3-carboxamides as cyclin-dependent kinase 2 (CDK2) inhibitors. 2010

Ping Lan, and Wan-Na Chen, and Gao-Keng Xiao, and Ping-Hua Sun, and Wei-Min Chen
Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou 510632, PR China.

3D-QSAR and docking studies were performed on a series of pyrazolo[4,3-h]quinazoline-3-carboxamides as CDK2/CyA inhibitors. The CoMFA and CoMSIA models using 54 molecules in the training set, gave r(cv)(2) values of 0.644 and 0.507, r(2) values of 0.959 and 0.951, respectively. 3D contour maps generated from the two models were applied to identify features important for the activity and better understand the interaction between the inhibitors and the receptor. Molecular docking was employed to explore the binding mode between these compounds and the receptor, as well as help understanding the structure-activity relationship revealed by CoMFA and CoMSIA. The results provide a useful guideline for the rational design of novel CDKs inhibitors.

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
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.
D011799 Quinazolines A group of aromatic heterocyclic compounds that contain a bicyclic structure with two fused six-membered aromatic rings, a benzene ring and a pyrimidine ring. Quinazoline
D000577 Amides Organic compounds containing the -CO-NH2 radical. Amides are derived from acids by replacement of -OH by -NH2 or from ammonia by the replacement of H by an acyl group. (From Grant & Hackh's Chemical Dictionary, 5th ed) Amide
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
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
D021281 Quantitative Structure-Activity Relationship A quantitative prediction of the biological, ecotoxicological or pharmaceutical activity of a molecule. It is based upon structure and activity information gathered from a series of similar compounds. Structure Activity Relationship, Quantitative,3D-QSAR,QSAR,QSPR Modeling,Quantitative Structure Property Relationship,3D QSAR,3D-QSARs,Modeling, QSPR,Quantitative Structure Activity Relationship,Quantitative Structure-Activity Relationships,Relationship, Quantitative Structure-Activity,Relationships, Quantitative Structure-Activity,Structure-Activity Relationship, Quantitative,Structure-Activity Relationships, Quantitative

Related Publications

Ping Lan, and Wan-Na Chen, and Gao-Keng Xiao, and Ping-Hua Sun, and Wei-Min Chen
March 2010, Journal of medicinal chemistry,
Ping Lan, and Wan-Na Chen, and Gao-Keng Xiao, and Ping-Hua Sun, and Wei-Min Chen
September 2010, International journal of molecular sciences,
Ping Lan, and Wan-Na Chen, and Gao-Keng Xiao, and Ping-Hua Sun, and Wei-Min Chen
January 2007, Medicinal chemistry (Shariqah (United Arab Emirates)),
Ping Lan, and Wan-Na Chen, and Gao-Keng Xiao, and Ping-Hua Sun, and Wei-Min Chen
November 2006, European journal of medicinal chemistry,
Ping Lan, and Wan-Na Chen, and Gao-Keng Xiao, and Ping-Hua Sun, and Wei-Min Chen
May 2023, Current medicinal chemistry,
Ping Lan, and Wan-Na Chen, and Gao-Keng Xiao, and Ping-Hua Sun, and Wei-Min Chen
September 2003, Bioorganic & medicinal chemistry letters,
Ping Lan, and Wan-Na Chen, and Gao-Keng Xiao, and Ping-Hua Sun, and Wei-Min Chen
May 2011, Journal of molecular modeling,
Ping Lan, and Wan-Na Chen, and Gao-Keng Xiao, and Ping-Hua Sun, and Wei-Min Chen
September 2018, Bioorganic chemistry,
Ping Lan, and Wan-Na Chen, and Gao-Keng Xiao, and Ping-Hua Sun, and Wei-Min Chen
November 2000, Journal of medicinal chemistry,
Ping Lan, and Wan-Na Chen, and Gao-Keng Xiao, and Ping-Hua Sun, and Wei-Min Chen
July 2008, Medicinal chemistry (Shariqah (United Arab Emirates)),
Copied contents to your clipboard!