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

Research output: Contribution to journalArticle

40 Citations (Scopus)

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
Externally publishedYes

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Growth Factor Receptors
Transforming Growth Factors
Phosphotransferases
Benzimidazoles
Assays
Derivatives
benzimidazole

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

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

In: Journal of Medicinal Chemistry, Vol. 49, No. 6, 23.03.2006, p. 2138-2142.

Research output: Contribution to journalArticle

Li, HY, Wang, Y, Heap, CR, King, CHR, Mundla, SR, Voss, M, Clawson, DK, Yan, L, Campbell, RM, Anderson, BD, Wagner, JR, Britt, K, Lu, KX, McMillen, WT & Yingling, JM 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, vol. 49, no. 6, pp. 2138-2142. https://doi.org/10.1021/jm058209g
Li, Hong Yu ; Wang, Yan ; Heap, Charles R. ; King, Chi Hsin R ; Mundla, Sreenivasa R. ; Voss, Matthew ; Clawson, David K. ; Yan, Lei ; Campbell, Robert M. ; Anderson, Bryan D. ; Wagner, Jill R. ; Britt, Karen ; Lu, Ku X. ; McMillen, William T. ; Yingling, Jonathan M. / 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. In: Journal of Medicinal Chemistry. 2006 ; Vol. 49, No. 6. pp. 2138-2142.
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AU - Wang, Yan

AU - Heap, Charles R.

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AU - Voss, Matthew

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AU - Campbell, Robert M.

AU - Anderson, Bryan D.

AU - Wagner, Jill R.

AU - Britt, Karen

AU - Lu, Ku X.

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