Structural investigation of 3,5‐disubstituted isoxazoles by 1H‐nuclear magnetic resonance
- 1 November 2003
- journal article
- research article
- Published by Wiley in Journal of Heterocyclic Chemistry
- Vol. 40 (6) , 1097-1102
- https://doi.org/10.1002/jhet.5570400621
Abstract
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 1H‐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.Keywords
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