Novel and potent transforming growth factor beta type I receptor kinase domain inhibitor:: 7-amino 4-(2-pyridin-2-yl-5,6-dihydro-4H-pyrrolol[1,2-b]pyrazol-3-yl)-quinolines

A novel series of 7-amino 4-(2-pyridin-2-yl-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl)-quinolines was synthesized and their TbetaR-1 inhibitory, p38 MAPK inhibitory, and TbetaR-1-dependent cellular activity were evaluated. Compound 5a was found to be a highly potent in the enzyme assay and TbetaR-1-dependent cellular assays. In addition, dimer (4g), with a urea linker, shows a similar enzyme and cellular activity despite a bulky substitution. (C) 2004 Elsevier Ltd. All rights reserved.