Parallel synthesis of diarylureas and their evaluation as inhibitors of insulin-like growth factor receptor

J Comb Chem. 2006 Sep-Oct;8(5):784-90. doi: 10.1021/cc050136z.


Diarylurea (DAU) compounds, particularly species composed of a heteroaryl ring system conjugated through a urea linkage to a substituted arene, were previously identified by the screening of a diverse chemical library to be active against the insulin growth factor receptor (IGF-1R). DAU compounds 4{a,b} were synthesized in parallel by the coupling of aryl amines 2{a} with aryl isocyanates 3{b}. Preparative RP-HPLC purification was found necessary to remove an impurity 5{b}, the symmetric urea resulting from the hydrolytic degradation of aryl isocyanates. Two libraries of DAU compounds were prepared to perform preliminary optimization of the two-ring systems for inhibitory activity against IGF-1R. In the first library, we explored a series of heteroaryl ring systems and found the 4-aminoquinaldine ring system to be optimal among those evaluated. The second library fixed the 4-aminoquinaldine ring system and we evaluated a series of substituted arenes conjugated to it. Overall, eight compounds based on the 4-aminoquinaldine heteroaryl system were found to have moderate activity against IGF-1R with IC(50) values better than 40 microM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CHO Cells
  • Combinatorial Chemistry Techniques*
  • Cricetinae
  • Cricetulus
  • Humans
  • Protein Kinase Inhibitors / chemical synthesis
  • Protein Kinase Inhibitors / chemistry*
  • Protein Kinase Inhibitors / pharmacology
  • Receptor, IGF Type 1 / antagonists & inhibitors*
  • Urea / chemistry*


  • Protein Kinase Inhibitors
  • Urea
  • Receptor, IGF Type 1