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

被引：284
作者：
Callahan, JF
Burgess, JL
Fornwald, JA
Gaster, LM
Harling, JD
Harrington, FP
Heer, J
Kwon, C
Lehr, R
Mathur, A
Olson, BA
Weinstock, J
Laping, NJ
机构：
[1] GlaxoSmithKline Pharmaceut, Dept Med Chem, Collegeville, PA 19426 USA
[2] GlaxoSmithKline Pharmaceut, Dept Med Chem, King Of Prussia, PA 19406 USA
[3] GlaxoSmithKline Pharmaceut, Dept Renal Pharmacol, King Of Prussia, PA 19406 USA
[4] GlaxoSmithKline Pharmaceut, Dept Prot Biochem, King Of Prussia, PA 19406 USA
[5] GlaxoSmithKline Pharmaceut, Dept Gene Express Sci, King Of Prussia, PA 19406 USA
[6] Dept Med Chem, Harlow CM19 5AD, Essex, England
来源：
JOURNAL OF MEDICINAL CHEMISTRY | 2002年 / 45卷 / 05期
关键词：
D O I：
10.1021/jm010493y
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
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.
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页码：999 / 1001
页数：3
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