Department of Pathology, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210000, China.
Molecules. 2022 Apr 29;27(9):2837. doi: 10.3390/molecules27092837.
The profound pharmacological properties of macrocyclic compounds have led to their development as drugs. In conformationally pre-organized ring structures, the multiple functions and stereochemical complexity provided by the macrocycle result in high affinity and selectivity of protein targets while maintaining sufficient bioavailability to reach intracellular locations. Therefore, the construction of macrocycles is an ideal choice to solve the problem of "undruggable" targets. Inspection of 68 macrocyclic drugs on the market showed that 10 of them were used to treat cancer, but this structural class still has been poorly explored within drug discovery. This perspective considers the macrocyclic compounds used for anti-tumor with different targets, their advantages and disadvantages, and the various synthetic methods of them.
大环化合物具有深刻的药理学性质，因此被开发为药物。在构象预组织的环结构中，大环提供的多种功能和立体化学复杂性导致与蛋白质靶标的高亲和力和选择性，同时保持足够的生物利用度以到达细胞内位置。因此，大环的构建是解决“不可成药”靶标的理想选择。对市场上的 68 种大环药物的检查表明，其中 10 种用于治疗癌症，但该结构类别在药物发现中仍未得到充分探索。本观点考虑了用于治疗不同靶点的抗肿瘤大环化合物，及其优缺点，以及它们的各种合成方法。
