Quantitative structure-activity relationships (QSAR): studies of inhibitors of tyrosine kinase

Eur J Pharm Sci. 2003 Sep;20(1):63-71. doi: 10.1016/s0928-0987(03)00170-2.

Abstract

A quantitative structure-activity relationship (QSAR) study of the 1-phenylbenzimidazoles as inhibitors of the platelet-derived growth factor receptor (PDGFR) was performed. Some new electronic parameters Q(o), Q(m) and Q(p) are suggested for characterizing the effect of substituents. Many other descriptors are also used which are selected by evolution algorithm (EA) using modified Cp as objective function proposed by the present authors. The descriptor Q(m) is shown to be an important variable to express effect of substituents. The variable selection shows that spatial descriptors are most important variables revealing important properties of the inhibitors. Electron-releasing substitutes at 5-position and the absence of bulky groups at 4,7-positions of the parent structure can enhance inhibitor activity. Principal component analysis is performed to classify this series of compounds.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzimidazoles / chemistry
  • Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Protein-Tyrosine Kinases / chemistry*
  • Protein-Tyrosine Kinases / classification
  • Quantitative Structure-Activity Relationship*
  • Receptors, Platelet-Derived Growth Factor / antagonists & inhibitors
  • Receptors, Platelet-Derived Growth Factor / chemistry
  • Regression Analysis

Substances

  • Benzimidazoles
  • Protein-Tyrosine Kinases
  • Receptors, Platelet-Derived Growth Factor