Synthesis and evaluation of pyrido-thieno-pyrimidines as potent and selective Cdc7 kinase inhibitors.
Cdc7 kinase plays a critical role in the regulation of DNA replication in eukaryotic cells and has been proposed as a target for cancer therapy. We have identified a class of Cdc7/Dbf4 inhibitors with a pyrido-thieno-pyrimidine core structure. Synthesis of a focused pyrido-thieno-pyrimidine library yielded potent and selective Cdc7 inhibitors with antiproliferative activity against cancer cells in vitro. Their synthesis and SAR data are presented herein.
Zhao
Chunlin
C
Discovery Chemistry, Research Center, Roche, Nutley, NJ 07110, USA. chunlin.zhao@roche.com
Tovar
Christian
C
Yin
Xuefeng
X
Xu
Qui
Q
Todorov
Ivan T
IT
Vassilev
Lyubomir T
LT
Chen
Li
L
D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors*; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D018797:Cell Cycle Proteins; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; C068619:CDC7 protein, human; D017346:Protein Serine-Threonine Kinases