title: Triazolo[1,5-a]pyrimidines as novel CDK2 inhibitors: protein structure-guided design and SAR.
abstract: Crystallographic and modelling data, in conjunction with a medicinal chemistry template-hopping approach, led to the identification of a series of novel and potent inhibitors of human cyclin-dependent kinase 2 (CDK2), with selectivity over glycogen synthase kinase-3beta (GSK-3beta). One example had a CDK2 IC(50) of 120 nM and showed selectivity over GSK-3beta of 167-fold.
authors.affiliation: Vernalis (R&D) Ltd, Granta Park, Great Abington, Cambridge CB1 6GB, UK.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Richardson
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Williamson
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Parratt
authors.forename: Jenifer
authors.initials: J
authors.lastname: Borgognoni
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Cansfield
authors.forename: Pawel
authors.initials: P
authors.lastname: Dokurno
authors.forename: Geraint L
authors.initials: GL
authors.lastname: Francis
authors.forename: Rob
authors.initials: R
authors.lastname: Howes
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Moore
authors.forename: James B
authors.initials: JB
authors.lastname: Murray
authors.forename: Alan
authors.initials: A
authors.lastname: Robertson
authors.forename: Allan E
authors.initials: AE
authors.lastname: Surgenor
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Torrance
mesh_terms: D045744:Cell Line, Tumor; D051357:Cyclin-Dependent Kinase 2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000737:chemistry*
chemical_list: D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D014230:Triazoles; D051357:Cyclin-Dependent Kinase 2