title: Inhibitors of the tyrosine kinase EphB4. Part 4: Discovery and optimization of a benzylic alcohol series.
abstract: Optimization of our bis-anilino-pyrimidine series of EphB4 kinase inhibitors led to the discovery of compound 12 which incorporates a key m-hydroxymethylene group on the C4 aniline. 12 displays a good kinase selectivity profile, good physical properties and pharmacokinetic parameters, suggesting it is a suitable candidate to investigate the therapeutic potential of EphB4 kinase inhibitors.
authors: AstraZeneca, Centre de Recherches, Z.I. la Pompelle, BP1050, 51689 Reims, Cedex 2, France.
authors: Bernard
authors: B
authors: Barlaam
authors: Richard
authors: R
authors: Ducray
authors: Christine
authors: C
authors: Lambert-van der Brempt
authors: Patrick
authors: P
authors: Plé
authors: Catherine
authors: C
authors: Bardelle
authors: Nigel
authors: N
authors: Brooks
authors: Tanya
authors: T
authors: Coleman
authors: Darren
authors: D
authors: Cross
authors: Jason G
authors: JG
authors: Kettle
authors: Jon
authors: J
authors: Read
mesh_terms: D000284:Administration, Oral; D000814:Aniline Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D000818:Animals; D019905:Benzyl Alcohol / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D001665:Binding Sites; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D004353:Drug Evaluation, Preclinical; D051379:Mice; D008819:Mice, Nude; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D036224:Receptor, EphB4 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000814:Aniline Compounds; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D036224:Receptor, EphB4; D019905:Benzyl Alcohol