Use of combinatorial and multiple parallel synthesis methodologies for the development of anti-infective natural products
Use of combinatorial and multiple parallel synthesis methodologies for the development of anti-infective natural products
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DOI：
10.1351/pac199971040559
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发表时间：
1999-04-01
影响因子：
1.8
通讯作者：
Shibata, M
中科院分区：
文献类型：
--
作者：
Fecik, RA;Frank, KE;Shibata, M
在短得惊人的时间内，用于合成小药物样分子的组合和多重平行合成方法改变了药物化学的实践，现在已得到普遍应用。为了药理学评估的目的，现在可以生产和快速测试大量聚焦和非聚焦的化学物质阵列。能够每周进行数万次分析的快速生物分析为新化学实体的快速生成提供了动力。适应这些目的的新化学策略被许多研究文章所代表。然而，这项工作的主要重点是完全集中在合成物质上。虽然天然产物可以被认为是自然界的组合文库，并继续提供许多重要的治疗物质，但在组合化学文献的大部分中，它们的代表性不足。的确，有些人认为，面对这些新方法，天然产品已经过时了。本文通过证明组合和天然产物方法不是对立的，而是可以互补的，从代表寻找对细菌，真菌和病毒病原体具有活性的新型化疗药物的有利位置解决了这个问题。
In an astonishingly short time, combinatorial and multiple parallel synthetic methodologies for the synthesis of small drug-like molecules have transformed the practice of medicinal chemistry and are now in general use. Large focused and unfocused arrays of chemicals can now be produced and tested rapidly for the purpose of pharmacological evaluation. Rapid biological assays capable of performing tens of thousands of assays per week provide a driving force for the rapid generation of new chemical entities. Novel chemical strategies adapted to these purposes are represented by numerous research articles. The primary emphasis of much of this work has, however, been focused upon wholly synthetic substances. Whereas natural products can be considered to be nature's combinatorial libraries and continue to provide many important therapeutic substances, they are under represented for the most part in the literature of combinatorial chemistry. Indeed, there are those who believe that natural products are archaic in the face of these new methods. This paper addresses this question from the vantage point of representing the search for novel chemotherapeutic agents active against bacterial, fungal and viral pathogens by demonstrating that combinatorial and natural products methodologies are not antithetical but can be complimentary.