title: Synthesis of 3,5-Disubstituted Isoxazoles Containing Privileged Substructures with a Diverse Display of Polar Surface Area.
abstract: 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.
authors.affiliation: Department of Chemistry, CRI Center for Chemical Proteomics, Seoul National University , Seoul 08826, Korea.
authors.forename: Mingi
authors.initials: M
authors.lastname: Kim
authors.affiliation: Department of Chemistry, CRI Center for Chemical Proteomics, Seoul National University , Seoul 08826, Korea.
authors.forename: Yoon Soo
authors.initials: YS
authors.lastname: Hwang
authors.affiliation: Department of Chemistry, CRI Center for Chemical Proteomics, Seoul National University , Seoul 08826, Korea.
authors.forename: Wansang
authors.identifier: 0000-0002-5262-9543
authors.initials: W
authors.lastname: Cho
authors.affiliation: 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.
authors.forename: Seung Bum
authors.identifier: 0000-0003-1753-1433
authors.initials: SB
authors.lastname: Park
mesh_terms: D000480:Alkynes / Q000138:chemical synthesis / Q000737:chemistry; D020650:Combinatorial Chemistry Techniques; D061565:Cycloaddition Reaction; D054879:Halogenation; D007555:Isoxazoles / Q000138:chemical synthesis* / Q000737:chemistry; D009570:Nitriles / Q000138:chemical synthesis / Q000737:chemistry; D010087:Oxides / Q000138:chemical synthesis / Q000737:chemistry; D054852:Small Molecule Libraries / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D000480:Alkynes; D007555:Isoxazoles; D009570:Nitriles; D010087:Oxides; D054852:Small Molecule Libraries
keywords: 1,3-diopolar cycloaddition; 3,5-disubstituted isoxazoles; nitrile oxide; polar surface area; privileged substructure