|2x9f, resolution 1.75Å ()|
|Related:||2bba, 2vwu, 2vx0, 2vwv, 2vwz, 2vwy, 2vww, 2vx1, 2vwx|
EPHB4 KINASE DOMAIN INHIBITOR COMPLEX
Starting from the initial bis-anilinopyrimidine 1, good potency against EphB4 was retained when benzodioxole at C-4 was replaced by an indazole. The key interactions of the indazole with the protein were characterised by crystallographic studies. Further optimisation led to compound 20, a potent inhibitor of the EphB4 and Src kinases with good pharmacokinetics in various preclinical species and high fraction unbound in plasma. Compound 20 may be used as a tool for evaluating the potential of EphB4 kinase inhibitors in vivo.
Inhibitors of the tyrosine kinase EphB4. Part 3: Identification of non-benzodioxole-based kinase inhibitors., Bardelle C, Barlaam B, Brooks N, Coleman T, Cross D, Ducray R, Green I, Brempt CL, Olivier A, Read J, Bioorg Med Chem Lett. 2010 Sep 15. PMID:20850301
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.