Download MendeleyInhibitors 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, C.L., Olivier, A., Read, J.(2010) Bioorg Med Chem Lett 20: 6242
- PubMed: 20850301
- DOI: https://doi.org/10.1016/j.bmcl.2010.08.100
- Primary Citation of Related Structures:
2X9F - PubMed Abstract:
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.
Organizational Affiliation:
AstraZeneca, Mereside, Alderley Park, Macclesfield SK10 4TG, UK.
