SynBioC Research Group, Department of Sustainable Organic Chemistry and Technology, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, B-9000 Ghent, Belgium.
Bioorg Med Chem. 2013 Jul 1;21(13):3643-7. doi: 10.1016/j.bmc.2013.04.033. Epub 2013 Apr 23.
The concept of pharmacophore hybridization is attracting an increasing interest from medicinal chemists. Whereas the main motivation for the application of this methodology relates to the pharmacological advantages associated with hybrid molecules, molecular hybridization can also deliver a synthetic advantage through selective chemical modification of the more reactive entity within hybrid systems. Moreover, if both features are combined, new hybrid structures result displaying both a biological and a synthetic benefit, and elaboration of this methodology might culminate in structural diversity and chemical novelty. In this perspective, a new approach based on hybrid structures combining a biologically interesting yet rather chemically reactive nucleus with a privileged heterocyclic scaffold is discussed by means of β-lactam-purine chimeras useful in antiviral research and aziridine-(iso)quinoline hybrids for antimalarial purposes.
药物杂化体的概念正引起越来越多的药物化学家的兴趣。虽然这种方法应用的主要动机与杂合分子相关的药理优势有关，但分子杂化也可以通过选择性地修饰杂合体系中更具反应性的实体来提供合成优势。此外，如果同时结合这两个特征，新的杂合结构将显示出生物学和合成优势，并且这种方法的阐述可能会导致结构多样性和化学新颖性。从这个角度来看，本文通过讨论用于抗病毒研究的β-内酰胺-嘌呤嵌合体和用于抗疟疾的氮丙啶-(异)喹啉杂合体，讨论了一种基于结合具有生物学意义但化学活性较高的核与优势杂环支架的杂合结构的新方法。
