Synthesis and activity of new aryl- and heteroaryl-substituted pyrazole inhibitors of the transforming growth factor-beta type I receptor kinase domain.

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Sawyer JS, Anderson BD, Beight DW, Campbell RM, Jones ML, Herron DK, Lampe JW, McCowan JR, McMillen WT, Mort N, Parsons S, Smith EC, Vieth M, Weir LC, Yan L, Zhang F, Yingling JM

Synthesis and activity of new aryl- and heteroaryl-substituted pyrazole inhibitors of the transforming growth factor-beta type I receptor kinase domain.

J Med Chem. 2003 Sep 11;46(19):3953-6.

PubMed ID

12954047 [ View in PubMed

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Abstract

Pyrazole-based inhibitors of the transforming growth factor-beta type I receptor kinase domain (TbetaR-I) are described. Examination of the SAR in both enzyme- and cell-based in vitro assays resulted in the emergence of two subseries featuring differing selectivity versus p38 MAP kinase. A common binding mode at the active site has been established by successful cocrystallization and X-ray analysis of potent inhibitors with the TbetaR-I receptor kinase domain.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
4-(3-Pyridin-2-Yl-1h-Pyrazol-4-Yl)Quinoline	TGF-beta receptor type-1	IC 50 (nM)	47	N/A	N/A	Details
4-(3-Pyridin-2-Yl-1h-Pyrazol-4-Yl)Quinoline	TGF-beta receptor type-1	IC 50 (nM)	51	N/A	N/A	Details
4-(3-Pyridin-2-Yl-1h-Pyrazol-4-Yl)Quinoline	TGF-beta receptor type-1	IC 50 (nM)	89	N/A	N/A	Details