Varela Marina T, Dias Gleiston G, de Oliveira Luiz Fernando N, de Oliveira Ramon G, Aguiar Francielle D, Nogueira João Pedro, Cruz Luiza R, Dias Luiz C
Universidade Estadual de Campinas (UNICAMP), Instituto de Química, Rua Monteiro Lobato 270, 13083-862, Campinas, Brazil.
Universidade Estadual de Campinas (UNICAMP), Instituto de Química, Rua Monteiro Lobato 270, 13083-862, Campinas, Brazil; Drugs for Neglected Diseases Initiative, Rua São José, 70, 20010-020, Rio de Janeiro, Brazil.
Eur J Med Chem. 2025 Apr 5;287:117368. doi: 10.1016/j.ejmech.2025.117368. Epub 2025 Feb 5.
The occurrence of spirocyclic motifs in clinical candidates and approved drugs is on the rise. This is related to the improvement of drug-like properties that can be achieved by introducing this sp-rich system into bioactive compounds. Given the increasing number of synthetic methodologies and building blocks available, spirocycles are becoming widely accessible to medicinal chemists. From restricting conformation to induce a better fit with the target, to modulation of physicochemical and pharmacokinetic properties, spirocycles are being used to address several challenges in drug discovery. This review covers general aspects of the chemistry of spirocycles, highlighting some key strategies for their preparation. As reported in publications over the past five years, we demonstrate that, beyond the exploration of structure-activity relationships (SAR) in medicinal chemistry, the use of spirocycles is an attractive approach for enhancing properties such as potency, selectivity, physicochemistry, and pharmacokinetics.
临床候选药物和已批准药物中螺环基序的出现呈上升趋势。这与通过将这种富含螺环的体系引入生物活性化合物而实现的类药性质的改善有关。鉴于可用的合成方法和构建模块数量不断增加，螺环化合物正越来越容易被药物化学家所获取。从限制构象以诱导与靶点更好的契合，到调节物理化学和药代动力学性质，螺环化合物正被用于应对药物发现中的若干挑战。本综述涵盖螺环化合物化学的一般方面，重点介绍了其制备的一些关键策略。正如过去五年出版物中所报道的，我们证明，除了在药物化学中探索构效关系（SAR）之外，使用螺环化合物是增强诸如效力、选择性、物理化学性质和药代动力学等性质的一种有吸引力的方法。
