Discovery of novel benzylidene-1,3-thiazolidine-2,4-diones as potent and selective inhibitors of the PIM-1, PIM-2, and PIM-3 protein kinases.
Novel substituted benzylidene-1,3-thiazolidine-2,4-diones (TZDs) have been identified as potent and highly selective inhibitors of the PIM kinases. The synthesis and SAR of these compounds are described, along with X-ray crystallographic, anti-proliferative, and selectivity data.
Oncology iMed Sciences Group, AstraZeneca R&D Boston, 35 Gatehouse Drive, Waltham, MA 02451, USA.
Les A
LA
Dakin
Michael H
MH
Block
Huawei
H
Chen
Erin
E
Code
James E
JE
Dowling
Xiaomei
X
Feng
Andrew D
AD
Ferguson
Isabelle
I
Green
Alexander W
AW
Hird
Tina
T
Howard
Erika K
EK
Keeton
Michelle L
ML
Lamb
Paul D
PD
Lyne
Hannah
H
Pollard
Jon
J
Read
Allan J
AJ
Wu
Tao
T
Zhang
Xiaolan
X
Zheng
D000818:Animals; D001597:Benzylidene Compounds / Q000737:chemistry* / Q000494:pharmacology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D055808:Drug Discovery; D006801:Humans; D008958:Models, Molecular; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors*; D051381:Rats; D013329:Structure-Activity Relationship; D045162:Thiazolidinediones / Q000737:chemistry* / Q000494:pharmacology
D001597:Benzylidene Compounds; D047428:Protein Kinase Inhibitors; D011518:Proto-Oncogene Proteins; D045162:Thiazolidinediones; D017346:Protein Serine-Threonine Kinases