Inhibitors of the tyrosine kinase EphB4. Part 1: Structure-based design and optimization of a series of 2,4-bis-anilinopyrimidines

Catherine Bardelle; Darren Cross; Sara Davenport; Jason G Kettle; Eun Jung Ko; Andrew G Leach; Andrew Mortlock; Jon Read; Nicola J Roberts; Peter Robins; Emma J Williams

doi:10.1016/j.bmcl.2008.04.015

Inhibitors of the tyrosine kinase EphB4. Part 1: Structure-based design and optimization of a series of 2,4-bis-anilinopyrimidines

Bioorg Med Chem Lett. 2008 May 1;18(9):2776-80. doi: 10.1016/j.bmcl.2008.04.015. Epub 2008 Apr 10.

Authors

Catherine Bardelle¹, Darren Cross, Sara Davenport, Jason G Kettle, Eun Jung Ko, Andrew G Leach, Andrew Mortlock, Jon Read, Nicola J Roberts, Peter Robins, Emma J Williams

Affiliation

¹ AstraZeneca, Mereside, Alderley Park, Macclesfield, Cheshire SK10 4TG, UK.

PMID: 18434142
DOI: 10.1016/j.bmcl.2008.04.015

Abstract

A series of bis-anilinopyrimidines have been identified as potent inhibitors of the tyrosine kinase EphB4. Structural information from two alternative series identified from screening efforts was combined to identify the initial leads.

MeSH terms

Aniline Compounds / chemical synthesis
Aniline Compounds / pharmacology*
Drug Design*
Hydrogen Bonding
Isomerism
Models, Chemical
Protein Kinase Inhibitors / chemical synthesis
Protein Kinase Inhibitors / pharmacology*
Pyrimidines / chemical synthesis
Pyrimidines / pharmacology*
Receptor, EphB4 / antagonists & inhibitors*
Structure-Activity Relationship

Substances

Aniline Compounds
Protein Kinase Inhibitors
Pyrimidines
Receptor, EphB4