Dihydropyrrolopyrazole transforming growth factor-β type I receptor kinase domain inhibitors: A novel benzimidazole series with selectivity versus transforming growth factor-β type II receptor kinase and mixed lineage kinase-7

Hong Yu Li, Yan Wang, Charles R. Heap, Chi Hsin R. King, Sreenivasa R. Mundla, Matthew Voss, David K. Clawson, Lei Yan, Robert M. Campbell, Bryan D. Anderson, Jill R. Wagner, Karen Britt, Ku X. Lu, William T. McMillen, Jonathan M. Yingling

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41 Scopus citations

Abstract

Novel dihydropyrrolopyrazole-substituted benzimidazoles were synthesized and evaluated in vitro as inhibitors of transforming growth factor-β type I receptor (TGF-β RI), TGF-β RII, and mixed lineage kinase-7 (MLK-7). These compounds were found to be potent TGF-β RI inhibitors and selective versus TGF-β RII and MLK-7 kinases. Benzimidazole derivative 8b was active in an in vivo target (TGF-β RI) inhibition assay.

Original languageEnglish (US)
Pages (from-to)2138-2142
Number of pages5
JournalJournal of Medicinal Chemistry
Volume49
Issue number6
DOIs
StatePublished - Mar 23 2006

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ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Cite this

Li, H. Y., Wang, Y., Heap, C. R., King, C. H. R., Mundla, S. R., Voss, M., Clawson, D. K., Yan, L., Campbell, R. M., Anderson, B. D., Wagner, J. R., Britt, K., Lu, K. X., McMillen, W. T., & Yingling, J. M. (2006). Dihydropyrrolopyrazole transforming growth factor-β type I receptor kinase domain inhibitors: A novel benzimidazole series with selectivity versus transforming growth factor-β type II receptor kinase and mixed lineage kinase-7. Journal of Medicinal Chemistry, 49(6), 2138-2142. https://doi.org/10.1021/jm058209g