Design of novel quinazoline derivatives and related analogues as potent and selective ALK5 inhibitors.

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Gellibert F, Fouchet MH, Nguyen VL, Wang R, Krysa G, de Gouville AC, Huet S, Dodic N

Design of novel quinazoline derivatives and related analogues as potent and selective ALK5 inhibitors.

Bioorg Med Chem Lett. 2009 Apr 15;19(8):2277-81. doi: 10.1016/j.bmcl.2009.02.087. Epub 2009 Feb 26.

PubMed ID

19285388 [ View in PubMed

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Abstract

Starting from quinazoline 3a, we designed potent and selective ALK5 inhibitors over p38MAP kinase from a rational drug design approach based on co-crystal structures in the human ALK5 kinase domain. The quinazoline 3d exhibited also in vivo activity in an acute rat model of DMN-induced liver fibrosis when administered orally at 5mg/kg (bid).

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
2-(6-methylpyridin-2-yl)-N-pyridin-4-ylquinazolin-4-amine	TGF-beta receptor type-1	IC 50 (nM)	25	N/A	N/A	Details
2-(6-methylpyridin-2-yl)-N-pyridin-4-ylquinazolin-4-amine	TGF-beta receptor type-1	IC 50 (nM)	95	N/A	N/A	Details
N-1H-indazol-5-yl-2-(6-methylpyridin-2-yl)quinazolin-4-amine	TGF-beta receptor type-1	IC 50 (nM)	25	N/A	N/A	Details
N-1H-indazol-5-yl-2-(6-methylpyridin-2-yl)quinazolin-4-amine	TGF-beta receptor type-1	IC 50 (nM)	90	N/A	N/A	Details