School of Chemistry , The University of Sydney , Sydney , NSW 2006 , Australia.
School of Chemistry and Molecular Biosciences , University of Queensland , Brisbane , QLD 4072 , Australia.
J Med Chem. 2019 Feb 14;62(3):1078-1095. doi: 10.1021/acs.jmedchem.8b00888. Epub 2018 Sep 6.
Cubane is a highly strained saturated hydrocarbon system that has historically been of interest in theoretical organic chemistry. More recently it has become a molecule of interest for biological applications due to its inherent stability and limited toxicity. Of greater significance is the ability to potentially functionalize cubane at each of its carbon atoms, providing complex biologically active molecules with unique spatial arrangements for probing active sites. These characteristics have led to an increased use of cubane in pharmaceutically relevant molecules. In this Perspective we describe synthetic methodology for accessing a range of functionalized cubanes and their applications in pharmaceuticals. We also provide some perspectives on challenges and future directions in the advancement of this field.
立方烷是一种高度应变的饱和烃体系,在理论有机化学中一直具有重要意义。最近,由于其固有稳定性和有限毒性,它已成为生物应用的一种分子。更重要的是,有可能在每个碳原子上对立方烷进行功能化,为具有独特空间排列的复杂生物活性分子提供探测活性部位的能力。这些特性导致立方烷在药物相关分子中的使用增加。在本观点中,我们描述了获得一系列功能化立方烷的合成方法及其在药物中的应用。我们还对该领域的挑战和未来方向提供了一些看法。