| Literature DB >> 21353545 |
Joydev K Laha1, Xuemei Zhang, Lixin Qiao, Min Liu, Snigdha Chatterjee, Shaughnessy Robinson, Kenneth S Kosik, Gregory D Cuny.
Abstract
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.Entities:
Mesh：
Substances：
Year: 2011 PMID： 21353545 PMCID： PMC3062192 DOI： 10.1016/j.bmcl.2011.01.140
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823