title: Discovery of a novel class of triazolones as checkpoint kinase inhibitors--hit to lead exploration.
abstract: Checkpoint Kinase-1 (Chk1, CHK1, CHEK1) is a Ser/Thr protein kinase that mediates cellular responses to DNA-damage. A novel class of Chk1 inhibitors, triazoloquinolones/triazolones (TZ's) was identified by high throughput screening. The optimization of these hits to provide a lead series is described.
authors.affiliation: AstraZeneca R&D Boston, 35 Gatehouse Drive, Waltham, MA 02451, USA. Vibha.Oza@astrazeneca.com
authors.forename: Vibha
authors.initials: V
authors.lastname: Oza
authors.forename: Susan
authors.initials: S
authors.lastname: Ashwell
authors.forename: Patrick
authors.initials: P
authors.lastname: Brassil
authors.forename: Jason
authors.initials: J
authors.lastname: Breed
authors.forename: Chun
authors.initials: C
authors.lastname: Deng
authors.forename: Jay
authors.initials: J
authors.lastname: Ezhuthachan
authors.forename: Heather
authors.initials: H
authors.lastname: Haye
authors.forename: Candice
authors.initials: C
authors.lastname: Horn
authors.forename: James
authors.initials: J
authors.lastname: Janetka
authors.forename: Paul
authors.initials: P
authors.lastname: Lyne
authors.forename: Nicholas
authors.initials: N
authors.lastname: Newcombe
authors.forename: Ludo
authors.initials: L
authors.lastname: Otterbien
authors.forename: Martin
authors.initials: M
authors.lastname: Pass
authors.forename: Jon
authors.initials: J
authors.lastname: Read
authors.forename: Sian
authors.initials: S
authors.lastname: Roswell
authors.forename: Mei
authors.initials: M
authors.lastname: Su
authors.forename: Dorin
authors.initials: D
authors.lastname: Toader
authors.forename: Dingwei
authors.initials: D
authors.lastname: Yu
authors.forename: Yan
authors.initials: Y
authors.lastname: Yu
authors.forename: Anna
authors.initials: A
authors.lastname: Valentine
authors.forename: Peter
authors.initials: P
authors.lastname: Webborn
authors.forename: Ann
authors.initials: A
authors.lastname: White
authors.forename: Sonya
authors.initials: S
authors.lastname: Zabludoff
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Zheng
mesh_terms: D000071877:Checkpoint Kinase 1; D018360:Crystallography, X-Ray; D055808:Drug Discovery; D008958:Models, Molecular; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D011494:Protein Kinases / Q000187:drug effects*; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D047428:Protein Kinase Inhibitors; D014230:Triazoles; D011494:Protein Kinases; D000071877:Checkpoint Kinase 1