Structure-activity Relationship Study of 2,4-diaminothiazoles As Cdk5/p25 Kinase Inhibitors

Overview

Journal Bioorg Med Chem Lett

Specialty Biochemistry

Date 2011 Mar 1

PMID 21353545

Citations 8

Authors

Joydev K Laha

Xuemei Zhang

Lixin Qiao

Min Liu

Snigdha Chatterjee

Shaughnessy Robinson

Kenneth S Kosik

Gregory D Cuny

Affiliations

Soon will be listed here.

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.

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