Room Temperature Synthesis of Bioactive 1,2,4-Oxadiazoles

Abstract

1,2,4-Oxadiazole is an essential motif in drug discovery represented in many experimental, investigational, and marketed drugs. This review covers synthetic methods that allow the conversion of different types of organic compounds into 1,2,4-oxadiazole at ambient temperature and the practical application of the latter approaches for the preparation of pharmaceutically important molecules. The discussed methods are divided into three groups. The first combines two-stage protocols requiring the preliminary preparation of O-acylamidoximes followed by cyclization under the action of organic bases. The advantages of this route are its swiftness, high efficiency of the cyclization process, and uncomplicated work--up. However, it requires the preparation and isolation of O-acylamidoximes as a separate preliminary step. The second route is a one-pot synthesis of 1,2,4-oxadiazoles directly from amidoximes and various carboxyl derivatives or aldehydes in aprotic bipolar solvents (primarily DMSO) in the presence of inorganic bases. This recently proposed pathway proved to be highly efficient in the field of medicinal chemistry. The third group of methods consists of diverse oxidative cyclizations, and these reactions have found modest application in drug design thus far. It is noteworthy that the reviewed methods allow for obtaining 1,2,4-oxadiazoles with thermosensitive functions and expand the prospects of using the oxadiazole core as an amide- or ester-like linker in the design of bioactive compounds.

Design, synthesis, and biological evaluation of multiple F-18 S1PR1 radiotracers in rodent and nonhuman primate

“…Because the 1,2,4-oxadiazole core is a key factor for S1PR1 potency, 41 we focused on modifying both the lipophilic terminal and the hydrophilic head region of CS1P1 and TZ4877 . First, as shown in Fig.…”

“…We designed and synthesized a series of new fluorine-containing S1PR1 ligands based on three potent S1PR1 ligands, CS1P1, TZ4877, and TZ82112 with IC 50 values of 2.1, 14.0, and 8.7 nM, respectively. 24,30 Because the 1,2,4-oxadiazole core is a key factor for S1PR1 potency, 41 we focused on modifying both the lipophilic terminal and the hydrophilic head region of CS1P1 and TZ4877. First, as shown in Fig.…”

Benzocaine-N-acylindoline conjugates: synthesis and antiviral activity against Coxsackievirus B3

“…This scaffold consists of two key structural elements: sulfonamide and phthalimide moieties. Since we were interested in the medicinal application of sulfonamides [26][27][28][29] and azaheterocycles [30][31][32][33][34][35], an attempt of continued exploration of this scaffold was made by our group and compound 2 with improved inhibitory action was discovered (Fig. 1) [36].…”

Bioactive Oxadiazoles 3.0

“…The research fields explored in this Special Issue include the discovery of new compounds with various biological activities such as: antibacterial 1,2,4-oxadiazole derivatives [ 14 ], antiplasmodial 1,2,5-oxadiazoles [ 15 ], 1,2,4-oxadiazole derivatives as nematicides [ 16 ] and 1,3,4-oxadiazoles with anticancer activity [ 17 ]. Moreover, the synthetic accessibility of bioactive 1,2,4-oxadiazoles at room temperature, was reviewed [ 18 ]. These researches are just some examples of the fascinating and expanding field of oxadiazoles’ chemistry, that represent an emerging field with growing potential.…”