| Literature DB >> 11855979 |
James F Callahan1, Joelle L Burgess, James A Fornwald, Laramie M Gaster, John D Harling, Frank P Harrington, Jag Heer, Chet Kwon, Ruth Lehr, A Mathur, Barbara A Olson, Joseph Weinstock, Nicholas J Laping.
Abstract
Screening of our internal compound collection for inhibitors of the transforming growth factor beta1 (TGF-beta1) 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-beta1-induced fibronectin mRNA formation while displaying no measurable cytotoxicity in the 48 h XTT assay.Entities:
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Year: 2002 PMID： 11855979 DOI： 10.1021/jm010493y
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446