Macrocycles Are Great Cycles: Applications, Opportunities, and Challenges of Synthetic Macrocycles in Drug Discovery
Macrocycles Are Great Cycles: Applications, Opportunities, and Challenges of Synthetic Macrocycles in Drug Discovery
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DOI：
10.1021/jm1012374
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发表时间：
2011-04-14
影响因子：
7.3
通讯作者：
Peterson, Mark L.
中科院分区：
文献类型：
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作者：
Marsault, Eric;Peterson, Mark L.
大环化合物占据了化学空间的独特部分。在过去十年中，它们的化学多样性在生物信息学和合成方法学进步的支持下显著扩大。因此，这种结构类型现在已经成功地在大多数生物靶标类别上进行了测试。本文的目标是透视与合成大环化合物在药物发现中相关的当前应用、机遇和挑战。1历史上，大环药物候选物主要来自两个来源。第一种是天然产品，提供了独特的药物，如红霉素、雷帕霉素、万古霉素、环孢菌素和埃博霉素。优秀的评论致力于这门课，以及它如何激发了进一步的合成和药物化学工作;因此，它将不在这里。1 r3从分子进化的角度来看，大环天然产物的药物化学通常涉及直接用作治疗剂或通过半合成使天然产物支架功能化。它与过去20年大环天然产物全合成的重大进展相平行
Macrocycles occupy a unique segment of chemical space. In the past decade, their chemical diversity expanded significantly, supported by advances in bioinformatics and synthetic methodology. As a consequence, this structural type has now been successfully tested on most biological target classes. The goal of this article is to put into perspective the current applications, opportunities, and challenges associated with synthetic macrocycles in drug discovery. 1Historically, macrocyclic drug candidates have originated primarily from two sources. The first, natural products, provided unique drugs such as erythromycin, rapamycin, vancomycin, cyclosporin, and epothilone. Excellent reviews are dedicated to this class and how it inspired further synthetic and medicinal chemistry efforts; thus, it will not be covered here. 1r3 From a molecular evolution standpoint, the medicinal chemistry of macrocyclic natural products usually involved direct use as a therapeutic agent or functionalization of the natural product scaffold by hemisynthesis. It parallels significant advances in the total synthesis of macrocyclic natural products during the past 2