We designed and synthesized the molecular framework of 3,5-disubstituted isoxazoles containing privileged substructures with various substituents which uniquely display polar surface area in a diverse manner. A library of 3,5-disubstituted isoxazoles were systematically prepared via 1,3-dipolar cycloaddition of alkynes with nitrile oxides prepared by two complementary synthetic routes; method A utilized a halogenating agent with a base and method B utilized a hypervalent iodine reagent. Through the biological evaluation of corresponding isoxazoles via three independent phenotypic assays, the different pattern of biological activities was shown according to the type of privileged substructure and substituent. These results demonstrated the significance of molecular design via introducing privileged substructures and various substituents to make a diverse arrangement of polar surface area within a similar 3-dimensional molecular framework.

中文翻译：

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含有特权子结构的3,5-二取代异恶唑的合成，极性表面的显示多样。

我们设计并合成了3,5-二取代异恶唑的分子骨架，其中包含具有各种取代基的特权子结构，这些取代基以多种方式唯一显示极性表面积。通过炔烃的1，3-偶极环加成与通过两种互补的合成途径制备的腈氧化物，系统地制备了3，5-二取代的异恶唑的文库。方法A使用带有碱的卤化剂，方法B使用高价碘试剂。通过三个独立的表型分析法对相应的异恶唑进行生物学评估，根据特权亚结构和取代基的类型显示了不同的生物学活性模式。