Discovery of a novel class of triazolones as checkpoint kinase inhibitors--hit to lead exploration.
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.
Oza
Vibha
V
AstraZeneca R&D Boston, 35 Gatehouse Drive, Waltham, MA 02451, USA. Vibha.Oza@astrazeneca.com
Ashwell
Susan
S
Brassil
Patrick
P
Breed
Jason
J
Deng
Chun
C
Ezhuthachan
Jay
J
Haye
Heather
H
Horn
Candice
C
Janetka
James
J
Lyne
Paul
P
Newcombe
Nicholas
N
Otterbien
Ludo
L
Pass
Martin
M
Read
Jon
J
Roswell
Sian
S
Su
Mei
M
Toader
Dorin
D
Yu
Dingwei
D
Yu
Yan
Y
Valentine
Anna
A
Webborn
Peter
P
White
Ann
A
Zabludoff
Sonya
S
Zheng
Xiaolan
X
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*
D047428:Protein Kinase Inhibitors; D014230:Triazoles; D011494:Protein Kinases; D000071877:Checkpoint Kinase 1