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Structural investigation of 3,5‐disubstituted isoxazoles by 1 H‐nuclear magnetic resonance
Author(s) -
Sechi Mario,
Sannia Luciano,
Orecchioni Maria,
Carta Fabrizio,
Paglietti Giuseppe,
Neamati Nouri
Publication year - 2003
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.5570400621
Subject(s) - isoxazole , pharmacophore , chemistry , integrase , combinatorial chemistry , stereochemistry , biochemistry , gene
HIV‐1 integrase (IN) is a very promising and validated target for the development of therapeutic agents against AIDS. In an effort to design and synthesize biological isosteric analogs of β‐diketoacid‐containing inhibitors of IN, we prepared a series of substituted isoxazole carboxylic acids. Several of these compounds inhibited catalytic activities of purified IN at micromolar concentration range. With an aim to prepare a large number of analogues based on the isoxazole pharmacophore we focused our study on a series of 3,5‐disubstituted isoxazole isomers. For a rapid structural analysis we discovered a convenient 1 H‐nmr method for distinguishing between isomeric structures based on their H‐4 assignments. This “finger print” approach to isomer identification will be useful in combinatorial chemistry settings where a mixture can be further derivatized.