A combinatorial scaffold approach toward kinase-directed heterocycle libraries

J Am Chem Soc. 2002 Feb 27;124(8):1594-6. doi: 10.1021/ja0170302.


A novel strategy for efficient synthesis of various substituted heterocycles as kinase-directed combinatorial libraries is described. The general scheme involves capture of various dichloroheterocycles onto solid support and further elaborations by aromatic substitution with amines at elevated temperature or by anilines, boronic acids, and phenols via palladium-catalyzed cross-coupling reactions, thus the scaffold itself is transformed into a diversity element within the combinatorial scheme. Libraries consisting of discrete and highly diverse heterocyclic small molecules constructed with these chemistries are currently being evaluated in a variety of cell and protein-based assays.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Combinatorial Chemistry Techniques / methods
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology*
  • Heterocyclic Compounds / chemical synthesis*
  • Heterocyclic Compounds / pharmacology*
  • Phosphotransferases / antagonists & inhibitors*
  • Structure-Activity Relationship


  • Enzyme Inhibitors
  • Heterocyclic Compounds
  • Phosphotransferases