Du Youlong, Semghouli Anas, Wang Qian, Mei Haibo, Kiss Loránd, Baecker Daniel, Soloshonok Vadim A, Han Jianlin
Jiangsu Co-Innovation Center of Efficient Processing and Utilization of Forest Resources, College of Chemical Engineering, Nanjing Forestry University, Nanjing, China.
Institute of Organic Chemistry, Stereochemistry Research Group, HUN-REN Research Centre for Natural Sciences, Budapest, Hungary.
Arch Pharm (Weinheim). 2025 Jan;358(1):e2400890. doi: 10.1002/ardp.202400890.
Macrocycles or medium-sized rings offer diverse functionality and stereochemical complexity in a well-organized ring structure, allowing them to fulfill various biochemical functions, resulting in high affinity and selectivity for protein targets, while preserving sufficient bioavailability to reach intracellular compartments. These features have made macrocycles attractive candidates in organic synthesis and drug discovery. Since the 20th century, more than three-score macrocyclic drugs, including radiopharmaceuticals, have been approved by the US Food and Drug Administration (FDA) for treating bacterial and viral infections, cancer, obesity, immunosuppression, inflammatory, and neurological disorders, managing cardiovascular diseases, diabetes, and more. This review presents 17 FDA-approved macrocyclic drugs during the past 5 years, highlighting their importance and critical role in modern therapeutics, and the innovative synthetic approaches for the construction of these macrocycles.
大环化合物或中等大小的环在结构规整的环状结构中提供了多样的功能和立体化学复杂性，使其能够履行各种生化功能，从而对蛋白质靶点具有高亲和力和选择性，同时保持足够的生物利用度以到达细胞内区室。这些特性使大环化合物成为有机合成和药物发现中具有吸引力的候选物。自20世纪以来，包括放射性药物在内的六十多种大环药物已被美国食品药品监督管理局（FDA）批准用于治疗细菌和病毒感染、癌症、肥胖症、免疫抑制、炎症和神经系统疾病，管理心血管疾病、糖尿病等。本综述介绍了过去5年中17种FDA批准的大环药物，强调了它们在现代治疗中的重要性和关键作用，以及构建这些大环化合物的创新合成方法。
