Design and synthesis of 6-oxo-1,6-dihydropyridines as CDK5 inhibitors.
Cyclin-dependent kinase 5 (CDK5) is a serine-threonine protein kinase that plays a significant role in neuronal development. In association with p25, CDK5 abnormally phosphorylates a number of cellular targets involved in neurodegenerative disorders. Using active site homology and previous structure-activity relationships, a new series of potent CDK5 inhibitors was designed. This report describes the optimization of 6-oxo-1,6-dihydropyridines as CDK5 inhibitors.
Kaller
Matthew R
MR
Chemistry Research and Discovery, Amgen Inc, One Amgen Center Drive, Thousand Oaks, CA 91320, United States. mkaller@amgen.com
Zhong
Wenge
W
Henley
Charles
C
Magal
Ella
E
Nguyen
Thomas
T
Powers
David
D
Rzasa
Robert M
RM
Wang
Weiya
W
Xiong
Xiaoling
X
Norman
Mark H
MH
D051360:Cyclin-Dependent Kinase 5 / Q000037:antagonists & inhibitors*; D015195:Drug Design; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011728:Pyridones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D047428:Protein Kinase Inhibitors; D011728:Pyridones; D051360:Cyclin-Dependent Kinase 5