Synthesis of 3,5-Disubstituted Isoxazoles Containing Privileged Substructures with a Diverse Display of Polar Surface Area

被引:17
作者
Kim, Mingi [1 ]
Hwang, Yoon Soo [1 ]
Cho, Wansang [1 ]
Park, Seung Bum [1 ,2 ]
机构
[1] Seoul Natl Univ, Dept Chem, CRI Ctr Chem Prote, Seoul 08826, South Korea
[2] Seoul Natl Univ, WCU Dept Biophys & Chem Biol, Seoul 08826, South Korea
基金
新加坡国家研究基金会;
关键词
3,5-disubstituted isoxazoles; privileged substructure; polar surface area; 1,3-diopolar cycloaddition; nitrile oxide; NITRILE OXIDES; DISCOVERY; CYCLOADDITION; ALKENES; POTENT;
D O I
10.1021/acscombsci.7b00032
中图分类号
O69 [应用化学];
学科分类号
081704 ;
摘要
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.
引用
收藏
页码:407 / 413
页数:7
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