title: Structure-guided design of pyrazolo[1,5-a]pyrimidines as inhibitors of human cyclin-dependent kinase 2.
abstract: The protein structure guided design of a series of pyrazolo[1,5-a]pyrimidines with high potency for human cyclin-dependent kinase 2 (CDK2) is described. Some examples were shown to inhibit the growth of human colon tumour cells, were equipotent for CDK1 and were selective against GSK-3beta and other kinases.
authors.affiliation: Vernalis (R&D) Ltd, Granta Park, Great Abington, Cambridge CB1 6GB, United Kingdom. d.williamson@vernalis.com
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Williamson
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Parratt
authors.forename: Justin F
authors.initials: JF
authors.lastname: Bower
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Moore
authors.forename: Christine M
authors.initials: CM
authors.lastname: Richardson
authors.forename: Pawel
authors.initials: P
authors.lastname: Dokurno
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Cansfield
authors.forename: Geraint L
authors.initials: GL
authors.lastname: Francis
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Hebdon
authors.forename: Rob
authors.initials: R
authors.lastname: Howes
authors.forename: Philip S
authors.initials: PS
authors.lastname: Jackson
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Lockie
authors.forename: James B
authors.initials: JB
authors.lastname: Murray
authors.forename: Claire L
authors.initials: CL
authors.lastname: Nunns
authors.forename: Jenifer
authors.initials: J
authors.lastname: Powles
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: D016203:CDC2 Protein Kinase / Q000037:antagonists & inhibitors; D042846:CDC2-CDC28 Kinases / Q000037:antagonists & inhibitors*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D051357:Cyclin-Dependent Kinase 2; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D011743:Pyrimidines / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D011743:Pyrimidines; D016203:CDC2 Protein Kinase; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2