title: Synthesis and evaluation of pyrido-thieno-pyrimidines as potent and selective Cdc7 kinase inhibitors.
abstract: 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.
authors.affiliation: Discovery Chemistry, Research Center, Roche, Nutley, NJ 07110, USA. chunlin.zhao@roche.com
authors.forename: Chunlin
authors.initials: C
authors.lastname: Zhao
authors.forename: Christian
authors.initials: C
authors.lastname: Tovar
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Yin
authors.forename: Qui
authors.initials: Q
authors.lastname: Xu
authors.forename: Ivan T
authors.initials: IT
authors.lastname: Todorov
authors.forename: Lyubomir T
authors.initials: LT
authors.lastname: Vassilev
authors.forename: Li
authors.initials: L
authors.lastname: Chen
mesh_terms: 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
chemical_list: D018797:Cell Cycle Proteins; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; C068619:CDC7 protein, human; D017346:Protein Serine-Threonine Kinases