| Literature DB >> 22542194 |
Mark L Boys1, Feng Bian, James B Kramer, Christopher L Chio, Xiao-Dan Ren, Huifen Chen, Stephen D Barrett, Karen E Sexton, Donna M Iula, Gary F Filzen, Maria N Nguyen, Paul Angell, Victoria L Downs, Zhi Wang, Neil Raheja, Edmund L Ellsworth, Stephen Fakhoury, Larry D Bratton, Paul R Keller, Richard Gowan, Elena M Drummond, Samarendra N Maiti, Mostofa A Hena, Leroy Lu, Patrick McConnell, John D Knafels, Venkataraman Thanabal, Fang Sun, Diane Alessi, Ann McCarthy, Erli Zhang, Barry C Finzel, Sneha Patel, Susan M Ciotti, Rone Eisma, N A Payne, Richard B Gilbertsen, Catherine R Kostlan, David J Pocalyko, Deepak S Lala.
Abstract
A series of 2-(1H-pyrazol-1-yl)pyridines are described as inhibitors of ALK5 (TGFβ receptor I kinase). Modeling compounds in the ALK5 kinase domain enabled some optimization of potency via substitutions on the pyrazole core. One of these compounds PF-03671148 gave a dose dependent reduction in TGFβ induced fibrotic gene expression in human fibroblasts. A similar reduction in fibrotic gene expression was observed when PF-03671148 was applied topically in a rat wound repair model. Thus these compounds have potential utility for the prevention of dermal scarring.Entities:
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Year: 2012 PMID： 22542194 DOI： 10.1016/j.bmcl.2012.04.013
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823