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

Bioorg Med Chem Lett. 2010 Nov 15;20(22):6764-72. doi: 10.1016/j.bmcl.2010.08.131. Epub 2010 Sep 24.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / chemistry
  • Cyclin-Dependent Kinase 2 / antagonists & inhibitors*
  • Models, Molecular
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology*
  • Pyrazoles / chemistry*
  • Quantitative Structure-Activity Relationship
  • Quinazolines / chemistry
  • Quinazolines / pharmacology*
  • Structure-Activity Relationship

Substances

  • Amides
  • Protein Kinase Inhibitors
  • Pyrazoles
  • Quinazolines
  • Cyclin-Dependent Kinase 2