Carboxyboronates: powerful building blocks for chemical synthesis

能够合成新的化学实体对推动药物发现工作至关重要。我们发现了羧酸硼酸盐（CBA），这是一种分子，其特征是两种广泛使用的官能团——羧酸盐和硼酸盐——的新组合，直到现在还没有化学合成。CBA将作为一种新的药物发现平台技术，为生成新的小分子候选药物提供独特的合成可能性。这是因为硼的官能团在交叉偶联反应中得到了广泛的应用。除了提供广泛适用的硼基合成手柄外，从CBA衍生的含硼分子（bcm）是一类更大的小分子，称为靶向共价抑制剂（tci）的一部分。tci在现代药物发现中经历了复兴，在包括癌症、细菌感染和真菌感染在内的多种疾病领域显示出效用。我们的技术克服了这些挑战，使治疗剂的组装基于碳硼键的合成效用。此外，该技术还提供了一种生成大量强效和细胞渗透性bcm的方法，包括含羧酸的bcm，如CBA，这将成为药物发现领域的颠覆性平台。

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.