title: Imidazoles: SAR and development of a potent class of cyclin-dependent kinase inhibitors.
abstract: An imidazole series of cyclin-dependent kinase (CDK) inhibitors has been developed. Protein inhibitor structure determination has provided an understanding of the emerging structure activity trends for the imidazole series. The introduction of a methyl sulfone at the aniline terminus led to a more orally bioavailable CDK inhibitor that was progressed into clinical development.
authors.affiliation: AstraZeneca, Alderley Park, Macclesfield, Cheshire SK10 4TG, UK.
authors.forename: Malcolm
authors.initials: M
authors.lastname: Anderson
authors.forename: David M
authors.initials: DM
authors.lastname: Andrews
authors.forename: Andy J
authors.initials: AJ
authors.lastname: Barker
authors.forename: Claire A
authors.initials: CA
authors.lastname: Brassington
authors.forename: Jason
authors.initials: J
authors.lastname: Breed
authors.forename: Kate F
authors.initials: KF
authors.lastname: Byth
authors.forename: Janet D
authors.initials: JD
authors.lastname: Culshaw
authors.forename: M Raymond V
authors.initials: MR
authors.lastname: Finlay
authors.forename: Eric
authors.initials: E
authors.lastname: Fisher
authors.forename: Helen H J
authors.initials: HH
authors.lastname: McMiken
authors.forename: Clive P
authors.initials: CP
authors.lastname: Green
authors.forename: Dave W
authors.initials: DW
authors.lastname: Heaton
authors.forename: Ian A
authors.initials: IA
authors.lastname: Nash
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Newcombe
authors.forename: Sandra E
authors.initials: SE
authors.lastname: Oakes
authors.forename: Richard A
authors.initials: RA
authors.lastname: Pauptit
authors.forename: Andrew
authors.initials: A
authors.lastname: Roberts
authors.forename: Judith J
authors.initials: JJ
authors.lastname: Stanway
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Thomas
authors.forename: Julie A
authors.initials: JA
authors.lastname: Tucker
authors.forename: Mike
authors.initials: M
authors.lastname: Walker
authors.forename: Hazel M
authors.initials: HM
authors.lastname: Weir
mesh_terms: D000814:Aniline Compounds / Q000737:chemistry; D000818:Animals; D018797:Cell Cycle Proteins / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods; D018360:Crystallography, X-Ray / Q000379:methods; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors*; D015195:Drug Design; D006801:Humans; D006860:Hydrogen Bonding; D007093:Imidazoles / Q000737:chemistry*; D020128:Inhibitory Concentration 50; D051379:Mice; D008956:Models, Chemical; D008968:Molecular Conformation; D013329:Structure-Activity Relationship
chemical_list: D000814:Aniline Compounds; D018797:Cell Cycle Proteins; D007093:Imidazoles; D018844:Cyclin-Dependent Kinases; C023650:aniline