Aminopyrimidinone cdc7 kinase inhibitors.
We have investigated the SAR of a series of pyrimidinone-containing Cdc7 kinase inhibitors. A wide range of amine substitutions give potent compounds with activities (K(i)) less than 1nM. Kinase selectivity is reasonable and cytotoxicity corresponds to inhibition of MCM2 phosphorylation.
Abbott Laboratories, 100 Abbott Park Rd., R47S AP10/307, Abbott Park, IL 60064-6101, USA. keith.w.woods@abbott.com
Keith W
KW
Woods
Chunqiu
C
Lai
Julie M
JM
Miyashiro
Yunsong
Y
Tong
Alan S
AS
Florjancic
Edward K
EK
Han
Niru
N
Soni
Yan
Y
Shi
Loren
L
Lasko
Joel D
JD
Leverson
Eric F
EF
Johnson
Alexander R
AR
Shoemaker
Thomas D
TD
Penning
D000588:Amines / Q000737:chemistry / Q000494:pharmacology; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D045744:Cell Line, Tumor; D006801:Humans; D064111:Minichromosome Maintenance Complex Component 2; D009687:Nuclear Proteins / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011744:Pyrimidinones / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000588:Amines; D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D047428:Protein Kinase Inhibitors; D011744:Pyrimidinones; C068619:CDC7 protein, human; D017346:Protein Serine-Threonine Kinases; C084859:MCM2 protein, human; D064111:Minichromosome Maintenance Complex Component 2