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.}",

year = "2006",

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doi = "10.1021/jm058209g",

language = "English (US)",

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AU - Wang, Yan

AU - Heap, Charles R.

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AU - Mundla, Sreenivasa R.

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.

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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