Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10595618 | Bioorganic & Medicinal Chemistry Letters | 2009 | 5 Pages |
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.
Related Topics
Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Christophe Antczak, Darren R. Veach, Christina N. Ramirez, Maria A. Minchenko, David Shum, Paul A. Calder, Mark G. Frattini, Bayard Clarkson, Hakim Djaballah,