title: Cyclin-dependent kinase 4 inhibitors as a treatment for cancer. Part 2: identification and optimisation of substituted 2,4-bis anilino pyrimidines.
abstract: Through chemical modification and X-ray crystallography we identified the 2,4-bis anilino pyrimidines as potent inhibitors of CDK4. Herein, we describe the optimisation of this series.
authors.affiliation: AstraZeneca, Alderley Park, Macclesfield, Cheshire SK10 4TG, UK.
authors.forename: Gloria A
authors.initials: GA
authors.lastname: Breault
authors.forename: Rebecca P A
authors.initials: RP
authors.lastname: Ellston
authors.forename: Stephen
authors.initials: S
authors.lastname: Green
authors.forename: S Russell
authors.initials: SR
authors.lastname: James
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Jewsbury
authors.forename: Catherine J
authors.initials: CJ
authors.lastname: Midgley
authors.forename: Richard A
authors.initials: RA
authors.lastname: Pauptit
authors.forename: Claire A
authors.initials: CA
authors.lastname: Minshull
authors.forename: Julie A
authors.initials: JA
authors.lastname: Tucker
authors.forename: J Elizabeth
authors.initials: JE
authors.lastname: Pease
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D001665:Binding Sites; D018360:Crystallography, X-Ray; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors*; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D011518:Proto-Oncogene Proteins; D011743:Pyrimidines / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D011518:Proto-Oncogene Proteins; D011743:Pyrimidines; D000255:Adenosine Triphosphate; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases