3D-QSAR and docking studies on pyrazolo[4,3-h]qinazoline-3-carboxamides as cyclin-dependent kinase 2 (CDK2) inhibitors.
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.
Lan
Ping
P
Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou 510632, PR China.
Chen
Wan-Na
WN
Xiao
Gao-Keng
GK
Sun
Ping-Hua
PH
Chen
Wei-Min
WM
D000577:Amides / Q000737:chemistry; D051357:Cyclin-Dependent Kinase 2 / Q000037:antagonists & inhibitors*; D008958:Models, Molecular; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D011720:Pyrazoles / Q000737:chemistry*; D021281:Quantitative Structure-Activity Relationship; D011799:Quinazolines / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000577:Amides; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011799:Quinazolines; D051357:Cyclin-Dependent Kinase 2