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.
Structural Investigation of 3,5-Disubstituted Isoxazoles by1H-Nuclear Magnetic Resonance / Sechi, Mario; Sannia, Luciano; Orecchioni, Maria; Carta, Fabrizio; Paglietti, Giuseppe; Neamati, Nouri. - In: JOURNAL OF HETEROCYCLIC CHEMISTRY. - ISSN 0022-152X. - ELETTRONICO. - 40:(2003), pp. 1097-1102. [10.1002/jhet.5570400621]
Structural Investigation of 3,5-Disubstituted Isoxazoles by1H-Nuclear Magnetic Resonance
Carta, FabrizioMembro del Collaboration Group
;
2003
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.File | Dimensione | Formato | |
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