1,2,4- and 1,3,4-Oxadiazoles as Scaffolds in the Development of Antiparasitic Agents

Abstract

In this review, we present the potential use of the heterocyclic oxadiazole rings in the design and synthesis of new drugs to treat parasitic infections. We intend to compare herein all the four isomeric forms of oxadiazole rings as well as discuss the differences and similarities between them. In addition, we discuss aspects on their reactivity that justify the great importance of both 1,2,4-and 1,3,4-oxadiazoles isomers when compared with their other two isomers. Although some oxadiazole isomers satisfy Hückel's rule, there are differences concerning their aromaticity, which have a great impact on the possible interactions of the oxadiazole ring with biological receptors. The set of works selected from the literature and discussed herein points out the oxadiazole core as an important and versatile scaffold in the development of new chemical entities potentially useful as antiparasitic drugs.

Solid‐Phase Synthesis of Substrate‐Based Dipeptides and Heterocyclic Pseudo‐dipeptides as Potential NO Synthase Inhibitors

“…Although the number of examples was too low to establish a reliable ranking between the various links, the present results suggested that 1,2,4‐oxadiazole and 1,2,4‐triazole rings could be as favorable as the peptide bond. As stated above, the observed variation in inhibitory potencies between compounds only differing by the heterocyclic link probably originated from the different aromatic, electrostatic, and hydrogen bonding properties of the three heterocycles …”

“…Although the three heterocyclic moieties are similar in size and shape and present the two substituents in very similar positions, they show variations in aromatic, electrostatic, and hydrogen bonding properties. This could lead to different binding modes with the target, and therefore to variation in inhibitory potencies between compounds only differing by the heterocyclic moiety …”

“…This could lead to different binding modes with the target, and therefore to variation in inhibitory potencies between compounds only differing by the heterocyclic moiety. [54,55] Forty-four 1,2,4-oxadiazole derivatives were synthesized and the specific synthetic steps of their preparation on standard resin and Synphase lanterns are shown in Scheme 3.…”

“…As stated above, the observed variation in inhibitory potencies between compounds only differing by the heterocyclic link probably originated from the different aromatic, electrostatic, and hydrogen bonding properties of the three heterocycles. [54,55]…”

Synthesis and Antibacterial Evaluation of 3,5-Diaryl-1,2,4-oxadiazole Derivatives

“…The oxadiazole nucleus presents four isomers ( Figure 1); however, one of them, the 1,2,3-oxadiazole isomer, is not of any practical use, as it is unstable and decomposes easily. 4 Although the 1,2,4-oxadiazole heterocycle was first synthesized in 1884, 5 it was only in the 1990s that this nucleus aroused interest within the scientific community. 6 The literature reports a diverse set of applications for the 1,2,4-oxadiazole core in medicinal chemistry, 7,8 such as antiasthmatic, 9 antidiabetic, 10 antitumoral, 11 anti-inflammatory, 12 antioxidant, 12 and antimicrobial.…”