Laqv-requimte & Department of Chemistry, University of Aveiro, Aveiro, Portugal.
Expert Opin Drug Discov. 2022 Jun;17(6):603-618. doi: 10.1080/17460441.2022.2055544. Epub 2022 Mar 25.
Spirocyclic scaffolds are an exceptional tool in drug design, allowing fine-tuning of a molecule's conformational and physicochemical properties. As it expands and diversifies, so does the number of therapeutics that contain this core. Several spirocyclic drugs are already marketed, and considerably more have shown promising results.
This review addresses recent studies (2017-2021) on applying spirocyclic compounds to treat various diseases, mainly grouped within neurological, infectious, and metabolic diseases and cancer. An emphasis is given on the influence of the spiro-structure on activity and consequent structure-activity study. results and their significance in the future progression towards clinical trials are also presented.
Spirocyclic compounds present an exciting opportunity as an unexplored chemical space in medicinal chemistry. However, their development is hindered by their complexity and synthesis challenges. Furthermore, a clear preference is still seen for readily available spirocyclic compounds involving amine or amide bonds. Nevertheless, these are temporary as high-throughput synthesis, and computational techniques allow fast optimization studies. In our opinion, the field of spirocyclic chemistry will continue to thrive and contribute to drug development, improving activity and selectivity on emergent ailments, such as cancer, metabolic, infectious, and neurological diseases.
螺环骨架是药物设计中的一种特殊工具，可精细调整分子的构象和物理化学性质。随着它的扩展和多样化，包含这种核心的治疗药物的数量也在增加。有几种螺环药物已经上市，还有更多的药物显示出了有希望的结果。
本文综述了 2017 年至 2021 年期间应用螺环化合物治疗各种疾病的最新研究，主要集中在神经、传染和代谢疾病以及癌症领域。重点介绍了螺环结构对活性的影响以及由此产生的构效关系研究。还介绍了研究结果及其对未来临床试验进展的意义。
螺环化合物作为药物化学中一个尚未开发的化学空间，具有令人兴奋的机会。然而，它们的发展受到复杂性和合成挑战的阻碍。此外，人们仍然明显偏爱容易获得的涉及胺或酰胺键的螺环化合物。尽管如此，这只是暂时的，因为高通量合成和计算技术允许快速进行优化研究。在我们看来，螺环化学领域将继续蓬勃发展，为药物开发做出贡献，提高对新兴疾病（如癌症、代谢、传染病和神经疾病）的活性和选择性。
