Cilibrizzi Agostino, Abbate Vincenzo, Chen Yu-Lin, Ma Yongmin, Zhou Tao, Hider Robert C
Institute of Pharmaceutical Science , King's College London , Stamford Street , London SE1 9NH , United Kingdom.
King's Forensics, School of Population Health & Environmental Sciences , King's College London , Franklin-Wilkins Building, 150 Stamford Street , London SE1 9NH , United Kingdom.
Chem Rev. 2018 Aug 22;118(16):7657-7701. doi: 10.1021/acs.chemrev.8b00254. Epub 2018 Jul 23.
Hydroxypyridinones (HOPOs) form outstanding building blocks for the development of a variety of agents in the field of metal chelation. The pyridinone ring is easily synthesized and readily converted into tetradentate, hexadentate, and octadentate chelators. There is considerable potential for the control of the stereochemistry of the resulting metal complex and hence the properties of these multidentate molecules. Their ability to rapidly bind hard metals in aqueous media has facilitated the development of efficient applications in both biological and medical contexts. In this Review, an in-depth analysis of the synthetic methodologies for HOPO-based ligands is presented, as well as the many aspects to achieve optimal biological activity. Recent advances and current challenges for the future application of HOPO structures are outlined. The present flourishing development of drug candidates and diagnostic agents based on this chemical scaffold opens access to many new applications in analytical, environmental, and clinical science.
羟基吡啶酮（HOPOs）是金属螯合领域中开发各种试剂的出色构建单元。吡啶酮环易于合成，并且很容易转化为四齿、六齿和八齿螯合剂。控制所得金属配合物的立体化学以及这些多齿分子的性质具有相当大的潜力。它们在水性介质中快速结合硬金属的能力促进了在生物和医学领域的高效应用的发展。在本综述中，对基于HOPO的配体的合成方法进行了深入分析，以及实现最佳生物活性的许多方面。概述了HOPO结构未来应用的最新进展和当前挑战。基于这种化学支架的候选药物和诊断试剂目前的蓬勃发展为分析、环境和临床科学中的许多新应用开辟了道路。
