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Rapid generation of a high quality lead for transforming growth factor-beta (TGF-beta) type I receptor (ALK5).

Journal of medicinal chemistry (2009-09-10)
Frederick W Goldberg, Richard A Ward, Steven J Powell, Judit E Debreczeni, Richard A Norman, Nicola J Roberts, Allan P Dishington, Helen J Gingell, Kate F Wickson, Andrew L Roberts
RÉSUMÉ

A novel class of 4-pyridinoxy-2-anilinopyridine-based TGF-beta type I receptor (also known as activin-like kinase 5 or ALK5) inhibitors is reported. The binding mode of this scaffold was successfully predicted by analyzing possible docked binding modes of literature inhibitors and novel synthetic ideas. Compounds such as 19 are potent ALK5 inhibitors with good physicochemical and pharmacokinetic properties and thus represent high quality leads for further optimization.

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AZ12799734, ≥98% (HPLC)