The new era of 1,2,4-oxadiazoles

Abstract

The synthesis, the chemical and photochemical reactivity, and the use of 1,2,4-oxadiazoles in materials and as bioactive compounds have been reviewed. The material in this survey includes some historical background, general features, state-of-the-art applications together with a critical discussion about current limitations and suggestions for future developments.

1,2,4‐ and 1,3,4‐Oxadiazole Synthesis by Palladium‐Catalyzed Carbonylative Assembly of Aryl Bromides with Amidoximes or Hydrazides

“…A similar importance surrounds the 1,2,4-oxadiazole motif with examples of structures showing antiasthmatic, antidiabetic, anti-inflammatory and antiviral activity. [9] Ataluren (Scheme 1, a), a small molecule drug, is currently in late stage clinical trials as a therapy for Duchenne muscular dystrophy and cystic fibrosis. The mechanism of action is believed to arise from interaction with the ribosomes causing these to be less sensitive to premature stop codons that stem from a genetic mutation.…”

Diaminoglyoxime as a versatile reagent in the synthesis of bis(1,2,4-oxadiazoles), 1,2,4-oxadiazolyl-quinazolines and 1,2,4-oxadiazolyl-benzothiazinones

“…The derivatives of this oxadiazole have different biological activities such as antiinflammatory, antidiabetic [7], immunosuppressive [8], antimicrobial [9,10], Alzheimer's disease [11], genotoxic activity [12], peptide inhibitory [13], antihyperglycemic [14], anticancer [15][16][17], antitumor [18,19], and antitrypanosomal [20] activity. Furthermore, 1,2,4-oxadiazole derivatives are not only helpful for DNA interaction [21] and inhibiting bacterial infections [22], but also have applications in advanced materials discotic liquid crystals (DLCs) or film forming compounds [23,24]. In addition, the use of pyridyl-1,2,4-oxadiazoles [25] and bis(1,2,4-oxadiazole) [26] as ligands that chelate Ni(II), Cu(II), Zn(II) and Pd(II) has been reported [27].…”

Synthesis of Phidianidine B, a highly cytotoxic 1,2,4-oxadiazole marine metabolite

“…Although 1,2,4-oxadiazole derivatives are extremely rare also in terrestrial sources, there is a wide interest in the chemistry community towards the synthesis of compounds containing this system. [2][3][4][5][6] In fact, 1,2,4-oxadiazole is extensively utilized in the design of compounds with improved physicochemical properties and bioavailability being a bioisostere of esters and amides and a dipeptide mimetic. For these reasons it can be found in a number of biologically important synthetic molecules, such as muscarinic agonists, serotoninergic (5-HT3) antagonists, benzodiazepine receptor agonists, and dopamine ligands.…”