Identification of novel inhibitors of the transforming growth factor β1 (TGF-β1) type 1 receptor (ALK5)

…, R Lehr, A Mathur, BA Olson, J Weinstock…

Index: Callahan, James F.; Burgess, Joelle L.; Fornwald, James A.; Gaster, Laramie M.; Harling, John D.; Harrington, Frank P.; Heer, Jag; Kwon, Chet; Lehr, Ruth; Mathur; Olson, Barbara A.; Weinstock, Joseph; Laping, Nicholas J. Journal of Medicinal Chemistry, 2002 , vol. 45, # 5 p. 999 - 1001

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Citation Number: 278

Abstract

Screening of our internal compound collection for inhibitors of the transforming growth factor β1 (TGF-β1) type I receptor (ALK5) identified several hits. Optimization of the dihydropyrroloimidazole hit 2 by introduction of a 2-pyridine and 3, 4-methylenedioxyphenyl group gave 7, a selective ALK5 inhibitor. With this information, optimization of the triarylimidazole hit 8 gave the selective inhibitor 14, which inhibits TGF-β1-induced ...