877218-66-1Relevant academic research and scientific papers
Structure-activity relationship study of 2,4-diaminothiazoles as Cdk5/p25 kinase inhibitors
Laha, Joydev K.,Zhang, Xuemei,Qiao, Lixin,Liu, Min,Chatterjee, Snigdha,Robinson, Shaughnessy,Kosik, Kenneth S.,Cuny, Gregory D.
supporting information; experimental part, p. 2098 - 2101 (2011/04/24)
Cdk5/p25 has emerged as a principle therapeutic target for numerous acute and chronic neurodegenerative diseases, including Alzheimer's disease. A structure-activity relationship study of 2,4-diaminothiazole inhibitors revealed that increased Cdk5/p25 inhibitory activity could be accomplished by incorporating pyridines on the 2-amino group and addition of substituents to the 2- or 3-position of the phenyl ketone moiety. Interpretation of the SAR results for many of the analogs was aided through in silico docking with Cdk5/p25 and calculating protein hydrations sites using WaterMap. Finally, improved in vitro mouse microsomal stability was also achieved.
