Boron has unique and valuable properties as a building block in the design and creation of new, small molecule pharmaceuticals.  Due to its vacant P-orbital, boron-containing compounds are capable of forming high affinity, selective and reversible complexes with sugars and amino acids that contain a Lewis base donor.  This mechanism provides a unique opportunity to generate drug molecules of high potency and high ligand efficiency. Furthermore, boron moieties can bind to target proteins through noncovalent interactions.We have prepared a series of small molecule templates with a boron atom incorporated into a fused aromatic or heteroaromatic ring scaffold.  These boron scaffolds, exemplified by benzoxaboroles, have led to the discovery of potent and selective inhibitors of a diverse set of enzyme systems by interacting with target proteins in multitude of binding modes.  SAR, X-ray crystallography and kinetic studies have shed light on the nature of the interaction mechanisms, rationalizing the high potency and specificity, as well as the lack of general toxicity observed for our boron compounds.In this presentation,  we will show specific examples of the types of interactions for enzymes, including aminoacyl-tRNA synthase, phospodiesterase, beta-lactamase, and kinase. We will also share our experience and understanding on benzoxaboroles in the area of chemistry, metabolic stability, metabolism and safety profile.

Benzoxaboroles as high affinity, selective, and safe drug molecules

246th National Meeting (2013)

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