Article ID Journal Published Year Pages File Type
1365516 Bioorganic & Medicinal Chemistry Letters 2007 7 Pages PDF
Abstract

We describe the design, synthesis and structure–activity relationship studies in optimizing a series of benzotriazine compounds as potent inhibitors of both Abl and Abl-T315I enzymes. The design includes targeting of an acid functional residue on the αC-helix that is available only upon kinase activation. This designed interaction provides an advantage in overcoming the challenges arising from the T315I mutation of Abl and transforms poor (ca. 10 μM) inhibitors into those with low nM potency.

Graphical abstractWe describe the design, synthesis and structure–activity relationship studies in optimizing a series of benzotriazine compounds as potent inhibitors of both Abl and Abl-T315I enzymes.Figure optionsDownload full-size imageDownload as PowerPoint slide

Related Topics
Physical Sciences and Engineering Chemistry Organic Chemistry
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