|
|||||
|
|
Discovery of a series of 2-(1H-pyrazol-1-yl)pyridines as ALK5 inhibitors with potential utility in the prevention of dermal scarring |
|
| Authors: | Boys Mark L Bian Feng Kramer James B Chio Christopher L Ren Xiao-Dan Chen Huifen Barrett Stephen D Sexton Karen E Iula Donna M Filzen Gary F Nguyen Maria N Angell Paul Downs Victoria L Wang Zhi Raheja Neil Ellsworth Edmund L Fakhoury Stephen Bratton Larry D Keller Paul R Gowan Richard Drummond Elena M Maiti Samarendra N Hena Mostofa A Lu Leroy McConnell Patrick Knafels John D Thanabal Venkataraman Sun Fang Alessi Diane McCarthy Ann Zhang Erli Finzel Barry C Patel Sneha Ciotti Susan M Eisma Rone Payne N A Gilbertsen Richard B Kostlan Catherine R Pocalyko David J Lala Deepak S |
| Affiliation: | Pfizer Global Research and Development, Ann Arbor Laboratories, Ann Arbor, MI 48105, USA. mark.boys@arraybiopharma.com |
| 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. |
| Keywords: | |
| 本文献已被 ScienceDirect PubMed 等数据库收录！ | |