A series of isothiazole carboxamidine compounds were synthesized and discovered as novel and selective inhibitors for Chk2. They are not active against the related Chk1 kinase. The structure-activity relationship studies were performed on the scaffold, and enzymatic kinetic analysis showed they are simple ATP competitive inhibitors with K(i) values as low as 11 nM for Chk2. Computer modeling studies were employed to comprehend the mechanism of action and SAR of these compounds.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1016/j.bmcl.2006.09.067 | DOI Listing |
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!