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

doi:10.1021/jm058209g

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 journal › Article › peer-review

49 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 language	English (US)
Pages (from-to)	2138-2142
Number of pages	5
Journal	Journal of Medicinal Chemistry
Volume	49
Issue number	6
DOIs	https://doi.org/10.1021/jm058209g
State	Published - Mar 23 2006
Externally published	Yes

ASJC Scopus subject areas

Molecular Medicine
Drug Discovery

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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

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

Research output: Contribution to journal › Article › peer-review

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 HY, Wang Y, Heap CR, King CHR, Mundla SR, Voss M et al. 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. 2006 Mar 23;49(6):2138-2142. doi: 10.1021/jm058209g

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title = "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",

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.",

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

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doi = "10.1021/jm058209g",

language = "English (US)",

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AU - Mundla, Sreenivasa R.

AU - Voss, Matthew

AU - Clawson, David K.

AU - Yan, Lei

AU - Campbell, Robert M.

AU - Anderson, Bryan D.

AU - Wagner, Jill R.

AU - Britt, Karen

AU - Lu, Ku X.

AU - McMillen, William T.

AU - Yingling, Jonathan M.

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AB - 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.

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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

Abstract

ASJC Scopus subject areas

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