1,2,4-Oxadiazole Derivatives to Power Up Your Research

For the first time the ring system of 1,2,4-oxadiazole[1] was assembled as early as some 130 years ago. However, this class of heterocycles had not been given noticeable attention until the 1990s. Recent reports highlighting the use of the 1,2,4-oxadiazole derivatives as peptidomimetics [2], namely, as a stable isostere of ester and amide functionalities [3] and as inhibitors in several biological systems[4], reflect the remarkable revival of interest in this structural unit.

This increasing involvement of the 1,2,4-oxadiazoles in drug discovery has already resulted in the first 1,2,4-oxadiazole-based drug candidate - ataluren⁴ (compound 1 inFig. 1) that is currently in the latestage clinical development. Seven more 1,2,4-oxadiazole-based drug candidates are at the investigational stage.[5] Also, there are reports on the fungicidal activity of 1,2,4-oxadiazole derivatives (e.g., compound 2 in Fig 1) [6]. Moreover, a recent discovery of the first 1,2,4-oxadiazole-containing naturally occurring alkaloids, phidianidines A and B[7] (compound 3 in Fig. 1), isolated from some marine organisms is expected to stimulate further synthetic and biological studies of the title compounds. In addition to biomedical applications, the 1,2,4-oxadiazoles are used as building blocks in organic synthesis[8] and materials science.^1c For example, they were employed as subunits to create liquid crystals(compound 4 in Fig. 1)[9], luminescent materials, and ionic liquids.

Figure 1. Examples of biologically active and materials related to 1,2,4-oxadiazole-containing compounds

A representative set of functionalized 1,2,4-oxadiazoles available from Life Chemicals is listed below. Please, contact us at marketing@lifechemicals.com to obtain the full list of the title structures.

References

1. For reviews of 1,2,4-oxadiazoles, see (a) Hemming, K. J. Chem. Res., Synop. 2001, 209. (b) Kayukova, L. A. Pharm. Chem. J. 2005, 39, 539. (c) Pace, A.; Pierro, P. Org. Biomol. Chem. 2009, 7, 4337. (d) Hemming, K. in Comprehensive Heterocyclic Chemistry, 3rd edition, eds. A.R. Katritzky, C.A. Ramsden, E.F.V. Scriven, and R. J.K. Taylor Pergamon, Oxford, 2008. Vol. 5, p. 243. (e) Yogesh, M.; Senthilkumar, G. P. World J. Pharm. Res. 2019, 8, 1406-1428.
2. Hamzé, A.; Hernandez, J.-F.; Fulcrand, P.; Martinez, J. J. Org. Chem. 2003, 68, 7316.
3. Patani, G. A.; LaVoie, E. J. Chem. Rev. 1996, 96, 3147.
4. Boström, J.; Hogner, A.; Llinàs, Wellner, E.; Plowright, A.T. J. Med. Chem. 2012, 55, 1817.
5. Information retrieved from the open database at www.drugbank.ca; accessed in April 2019.
6. Filho, R.A.W.N.; da Silva, C.A.; da Silva, C.S.B.; Brustein, V.P. et al. Chem. Pharm. Bull. 2009, 57, 819.
7. Carbone, M.; Li, Y.; Irace, C.; Mollo, E.; Guo, Y.-W.; Gavagnin, M. et al. Org. Lett. 2011, 13, 2516.
8. Piccionello, A.P.; Pace, A.; Buscemi, S. Org. Lett. 2011, 13, 4749.
9. Parra, M.; Hidalgo, P.; Elgueta, E.Y. Liq. Cryst. 2008, 35, 823.