Kim Mingi, Hwang Yoon Soo, Cho Wansang, Park Seung Bum
Department of Chemistry, CRI Center for Chemical Proteomics, Seoul National University , Seoul 08826, Korea.
WCU Department of Biophysics and Chemical Biology, Seoul National University , Seoul 08826, Korea.
ACS Comb Sci. 2017 Jun 12;19(6):407-413. doi: 10.1021/acscombsci.7b00032. Epub 2017 Mar 23.
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.
我们设计并合成了含有具有各种取代基的特权子结构的3,5-二取代异恶唑分子框架，这些取代基以不同方式独特地展现出极性表面积。通过两种互补合成路线制备的腈氧化物与炔烃进行1,3-偶极环加成反应，系统地制备了一系列3,5-二取代异恶唑；方法A使用卤化剂和碱，方法B使用高价碘试剂。通过三种独立的表型分析对相应异恶唑进行生物学评估，结果表明，根据特权子结构和取代基的类型，生物活性模式不同。这些结果证明了通过引入特权子结构和各种取代基进行分子设计的重要性，以便在相似的三维分子框架内实现极性表面积的多样化排列。
