title: Design, synthesis and SAR of thienopyridines as potent CHK1 inhibitors.
abstract: A novel series of CHK1 inhibitors based on thienopyridine template has been designed and synthesized. These inhibitors maintain critical hydrogen bonding with the hinge and conserved water in the ATP binding site. Several compounds show single digit nanomolar CHK1 activities. Compound 70 shows excellent enzymatic activity of 1 nM.
authors.affiliation: Department of Chemistry, Merck Research Laboratories, Cambridge, MA 02141, USA. lianyun.zhao@merck.com
authors.forename: Lianyun
authors.initials: L
authors.lastname: Zhao
authors.forename: Yingxin
authors.initials: Y
authors.lastname: Zhang
authors.forename: Chaoyang
authors.initials: C
authors.lastname: Dai
authors.forename: Timothy
authors.initials: T
authors.lastname: Guzi
authors.forename: Derek
authors.initials: D
authors.lastname: Wiswell
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Seghezzi
authors.forename: David
authors.initials: D
authors.lastname: Parry
authors.forename: Thierry
authors.initials: T
authors.lastname: Fischmann
authors.forename: M Arshad
authors.initials: MA
authors.lastname: Siddiqui
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry; D001665:Binding Sites; D000071877:Checkpoint Kinase 1; D018360:Crystallography, X-Ray; D015195:Drug Design; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011494:Protein Kinases / Q000737:chemistry* / Q000378:metabolism; D011724:Pyridazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D058924:Thienopyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013876:Thiophenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D047428:Protein Kinase Inhibitors; D011724:Pyridazines; D058924:Thienopyridines; D013876:Thiophenes; D000255:Adenosine Triphosphate; D011494:Protein Kinases; D000071877:Checkpoint Kinase 1