Makino Shingo
Pharmaceutical Research Laboratories, Ajinomoto Co. Inc., 1-1, Suzuki-cho, Kawasaki-ku, Kawasaki-shi, Kanagawa-ken, 210-0801, Japan.
Mini Rev Med Chem. 2006 Jun;6(6):625-32. doi: 10.2174/138955706777435760.
Solid-phase organic synthesis of heterocyclic compounds on solid-support has been a focus of recent investigations because of the potential applicability of these compounds toward a variety of drug targets. Among the various heterocycles, we have been especially interested in quinazoline-2,4-diones because of the wide range of their bioactivities. Therefore, in this article we review methods for the solid-phase synthesis of quinazoline-2,4-diones and their analogues. Since all of these heterocycles can be speedily derivatized from resin-bound primary amines, incorporating the amines at the 3N-position of quinazoline-2,4-diones or corresponding positions of its analogues, it becomes possible to efficiently compare the bioactivities of these quinazoline-2,4-diones and their analogues. Various methods of solid-phase synthesis described herein should be practical and useful tools for the medicinal chemist in supporting drug discovery initiatives.
由于杂环化合物对多种药物靶点具有潜在适用性，因此在固体载体上进行杂环化合物的固相有机合成一直是近期研究的重点。在各种杂环中，我们对喹唑啉 - 2,4 - 二酮特别感兴趣，因为它们具有广泛的生物活性。因此，在本文中，我们综述了喹唑啉 - 2,4 - 二酮及其类似物的固相合成方法。由于所有这些杂环都可以从树脂结合的伯胺快速衍生而来，将胺引入喹唑啉 - 2,4 - 二酮的3N位或其类似物的相应位置，就有可能有效地比较这些喹唑啉 - 2,4 - 二酮及其类似物的生物活性。本文所述的各种固相合成方法对于药物化学家支持药物发现计划应是实用且有用的工具。
