title: Design and synthesis of quinolin-2(1H)-one derivatives as potent CDK5 inhibitors.
abstract: Cyclin-dependent kinase 5 (CDK5) is a serine/threonine protein kinase and its deregulation is implicated in a number of neurodegenerative disorders such as Alzheimer's disease, amyotrophic lateral sclerosis, and ischemic stroke. Using active site homology modeling between CDK5 and CDK2, we explored several different chemical series of potent CDK5 inhibitors. In this report, we describe the design, synthesis, and CDK5 inhibitory activities of quinolin-2(1H)-one derivatives.
authors: Chemistry Research and Discovery, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, USA.
authors: Wenge
authors: W
authors: Zhong
authors: Hu
authors: H
authors: Liu
authors: Matthew R
authors: MR
authors: Kaller
authors: Charles
authors: C
authors: Henley
authors: Ella
authors: E
authors: Magal
authors: Thomas
authors: T
authors: Nguyen
authors: Timothy D
authors: TD
authors: Osslund
authors: David
authors: D
authors: Powers
authors: Robert M
authors: RM
authors: Rzasa
authors: Hui-Ling
authors: HL
authors: Wang
authors: Weiya
authors: W
authors: Wang
authors: Xiaoling
authors: X
authors: Xiong
authors: Jiandong
authors: J
authors: Zhang
authors: Mark H
authors: MH
authors: Norman
mesh_terms: D001665:Binding Sites; D051357:Cyclin-Dependent Kinase 2 / Q000737:chemistry; D051360:Cyclin-Dependent Kinase 5 / Q000037:antagonists & inhibitors* / Q000737:chemistry; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D007202:Indicators and Reagents; D008958:Models, Molecular; D011485:Protein Binding; D011804:Quinolines / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D011804:Quinolines; D051360:Cyclin-Dependent Kinase 5; D051357:Cyclin-Dependent Kinase 2