2-Aminoimidazoles inhibitors of TGF-beta receptor 1.

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Bonafoux D, Chuaqui C, Boriack-Sjodin PA, Fitch C, Hankins G, Josiah S, Black C, Hetu G, Ling L, Lee WC

2-Aminoimidazoles inhibitors of TGF-beta receptor 1.

Bioorg Med Chem Lett. 2009 Feb 1;19(3):912-6. doi: 10.1016/j.bmcl.2008.11.119. Epub 2008 Dec 11.

PubMed ID

19135364 [ View in PubMed

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Abstract

The 4-(5-fluoro-6-methyl-pyridin-2-yl)-5-quinoxalin-6-yl-1H-imidazol-2-ylamine 3 is a potent and selective inhibitor of TGF-betaR1. Substitution of the amino group of 3 typically led to a slight decrease in the affinity for the receptor and in TGF-beta-inducted PAI-luciferase reporter activity. However, 2-acetamidoimidazoles were identified as attractive candidates for further optimization as a result of their significant activity combined to their superior pharmacokinetic profile.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
N-[4-(5-fluoro-6-methylpyridin-2-yl)-5-quinoxalin-6-yl-1H-imidazol-2-yl]acetamide	TGF-beta receptor type-1	EC 50 (nM)	180	N/A	N/A	Details
N-[4-(5-fluoro-6-methylpyridin-2-yl)-5-quinoxalin-6-yl-1H-imidazol-2-yl]acetamide	TGF-beta receptor type-1	Ki (nM)	7.1	N/A	N/A	Details