Carboxyboronates: powerful building blocks for chemical synthesis

能够合成新的化学实体是推动药物发现努力的关键。我们已经发现了羧基硼酸酯(CBA)，这是一种具有两个广泛使用的官能团-羧酸盐和硼酸盐-的新颖组合的分子，到目前为止还没有得到化学合成。CBA将作为一种新型药物发现平台技术，通过为产生新型小分子候选药物提供独特的合成可能性。这是因为硼官能团在交叉偶联反应中发现了广泛的用途。除了提供一种广泛适用的基于硼的合成手柄外，从CBA衍生的含硼分子(BCM)还是一大类被称为靶向共价抑制剂(TCI)的小分子的一部分。TCI正在经历现代药物发现的复兴，在包括癌症、细菌感染和真菌感染在内的多个疾病领域显示出有效性。我们的技术克服了这些挑战，使人们能够获得其组装基于碳-硼键的合成效用的治疗剂。此外，这项技术提供了一种产生大量有效和细胞透过性BCMS的方法，包括CBA等含有羧酸盐的BCMS，它有望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.