Journal of Medicinal Chemistry 2006-03-23

Dihydropyrrolopyrazole transforming growth factor-beta type I receptor kinase domain inhibitors: a novel benzimidazole series with selectivity versus transforming growth factor-beta 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

Index: J. Med. Chem. 49 , 2138-2142, (2006)

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Abstract

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