Carboxyboronates: powerful building blocks for chemical synthesis

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Enabling the synthesis of novel chemical entities is critical to fueling drug discovery efforts. We have discovered carboxyboronate (CBA), a molecule that features a novel combination of two widely used functional groups-carboxylate and boronate-that has eluded chemical synthesis until now. CBA will serve as a novel drug discovery platform technology by enabling unique synthetic possibilities for the generation of novel small molecule drug candidates. This is because boron functionality has found widespread utility in cross-coupling reactions. In addition to offering a broadly applicable boron-based synthetic handle, boron-containing molecules (BCMs) derived from CBA are part of a larger class of small molecules called targeted covalent inhibitors (TCIs). TCIs have been experiencing a renaissance in modern drug discovery, having shown utility in multiple disease areas including cancer, bacterial infections, and fungal infections. Our technology overcomes these challenges to enable access to therapeutic agents whose assembly is based on the synthetic utility of the carbon-boron bond. In addition, this technology offers a way to generate large collections of potent and cell permeable BCMs, including carboxylate-containing BCMs such as CBA, which is poised to become a disruptive platform in the field of drug discovery.