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

Marc O. Anderson, Hong Yu, Cristina Penaranda, Betty A. Maddux, Ira D. Goldfine, Jack F. Youngren, R. Kiplin Guy

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


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-IR. 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 IC50 values better than 40 μM.

Original languageEnglish
Pages (from-to)784-790
Number of pages7
JournalJournal of Combinatorial Chemistry
Issue number5
StatePublished - Sep 2006

ASJC Scopus subject areas

  • General Chemistry


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