Abstract:
:We report the design, synthesis, and structure-activity relationship (SAR) of a series of novel pyrido[2,3-d]pyrimidin-7-one compounds as potent Abl kinase inhibitors. We evaluate their specificity profile against a panel of human recombinant kinases, as well as their biological profile toward a panel of well-characterized cancer cell lines. Our study reveals that substitutions in the 3- and 4-positions of the phenylamino moiety lead to improved potency and improved selectivity both in target-based and cell-based assays. Altogether, our results provide an insight into the SAR of pyrido[2,3-d]pyrimidin-7-ones for the development of drug candidates with improved potency and selectivity for the targeted treatment of CML.
journal_name
Bioorg Med Chem Lettjournal_title
Bioorganic & medicinal chemistry lettersauthors
Antczak C,Veach DR,Ramirez CN,Minchenko MA,Shum D,Calder PA,Frattini MG,Clarkson B,Djaballah Hdoi
10.1016/j.bmcl.2009.10.085subject
Has Abstractpub_date
2009-12-15 00:00:00pages
6872-6issue
24eissn
0960-894Xissn
1464-3405pii
S0960-894X(09)01496-6journal_volume
19pub_type
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