Privileged structures have been widely used as effective templates for drug discovery. While benzo-1,4-diazepine constitutes the first historical example of such a structure, the 1,3 analogue is just as rich in terms of applications in medicinal chemistry. The 1,3-diazepine moiety is present in numerous biological active compounds including natural products, and is used to design compounds displaying a large range of biological activities. It is present in the clinically used anticancer compound pentostatin, in several recent FDA approved β-lactamase inhibitors (e.g., avibactam) and also in coformycin, a natural product known as a ring-expanded purine analogue displaying antiviral and anticancer activities. Several other 1,3-diazepine containing compounds have entered into clinical trials. This heterocyclic structure has been and is still widely used in medicinal chemistry to design enzyme inhibitors, GPCR ligands, and so forth. This review endeavours to highlight the main use of the 1,3-diazepine scaffold and its derivatives, and their applications in medicinal chemistry, drug design, and therapy. We will focus more particularly on the development of enzyme inhibitors incorporating this scaffold, with a strong emphasis on the molecular interactions involved in the inhibition mechanism.

中文翻译：

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1,3-二氮杂：药物化学中的特殊支架

特权结构已被广泛用作药物发现的有效模板。虽然苯并 1,4-二氮杂是这种结构的第一个历史例子，但 1,3 类似物在药物化学中的应用也同样丰富。1,3-二氮杂部分存在于包括天然产物在内的众多生物活性化合物中，用于设计具有多种生物活性的化合物。它存在于临床使用的抗癌化合物喷司他丁、最近 FDA 批准的几种 β-内酰胺酶抑制剂（例如阿维巴坦）中，也存在于共甲霉素中，这种天然产物被称为环扩展嘌呤类似物，具有抗病毒和抗癌活性。其他几种含有 1,3-二氮杂卓的化合物已进入临床试验。这种杂环结构已经并且仍然广泛用于药物化学以设计酶抑制剂、GPCR 配体等。本综述致力于重点介绍 1,3-二氮卓支架及其衍生物的主要用途，以及它们在药物化学、药物设计和治疗中的应用。我们将更专注于开发包含这种支架的酶抑制剂，重点强调抑制机制中涉及的分子相互作用。