Synthesis of 1,2,4-oxadiazoles (a review)

Methods used for the synthesis of 3,5-substituted 1,2,4-oxadiazoles are reviewed. The syntheses are based mostly on the use of primary amidoximes and acylating agents as the initial reactants. The pathway to another large group of 1,2,4-oxadiazoles proceeding from a broad spectrum of reactants is via their reactions of 1,3-dipolar cycloaddition, in particular, with primary amidoximes. __________ Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 39, No. 10, pp. 32–40, October, 2005.     

Inhibition of α-Amylase and α-Glucosidase by New β-Aminopropionamidoxime Derivatives

Pharmaceutical Chemistry Journal - New antidiabetic agents are being sought because of the global problem with diabetes. Amidoxime derivatives are known to have antidiabetic activity....     

Synthesis and antituberculosis activity of O-aroyl-β-(4-phenylpiperazin-1-yl)propioamidoximes

The search for new tuberculostatics is an important task for medicinal chemistry. A series of new O-aroyl-β-(4-phenylpiperazin-1-yl)propioamidoximes were synthesized and tested in vitro for antituberculosis activity. The synthesis of the target substances consists of 3 – 4 steps. In the first step, β-(4-phenylpiperazin1-yl)propionitrile was obtained in 79% yield; the second step yields β-(4-phenylpiperazin-1-yl)propioamidoxime in 75% yield. Subsequent aroylation of this amidoxime by substituted benzoic acid chlorides in the presence of Et₃N leads to the target O-aroyl-β-(4-phenylpiperazin-1-yl)propioamidoximes in 61 – 93% yields. Hydrochlorides of the O-aroylated products were obtained in 72 – 94% yields by the action of ethereal HCl on solutions of the bases. PMR spectra of hydrochlorides of the O-aroylated products show evidence of slow inversion of the heterocycle at the β-position and coordination of HCl at the N1 atom of the 4-phenylpiperazine fragment. Some bases and hydrochlorides of O-aroyl-β-(4-phenylpiperazin-1-yl)propioamidoximes exhibited interesting antituberculosis properties when tested in vitro on sensitive, resistant, and multi-drug resistant strains of M. tuberculosis.     

Local anesthetic activity of new amidoxime derivatives

Three series of amidoxime derivatives including nitrous derivatives of α-chloro-α-isonitrosoacetone and hydrochlorides of O-aroyl-β-aminopropioamidoximes and 3-[β-(piperidin-1-yl)]ethyl-5-aryl-1,2,4-oxadiazoles were tested for conduction, infiltration, and terminal anesthesia. There are four interesting “hit” compounds, i.e., the hydrochloride of O-m-chlorophenyl-β-(benzimidazol-1-yl)propioamidoxime (VII), the hydrochloride of O-p-nitrophenyl-β-(benzimidazol-1-yl)propioamidoxime (VIII), 3-[β-(piperidin-1-yl)]ethyl-5-p-tolyl-1,2,4-oxadiazole (IX), and 3-[β-(piperidin-1-yl)]ethyl-5-m-chlorophenyl-1,2,4-oxadiazole (X), which exhibit higher activity than the reference drugs (trimecaine, lidocaine, novocaine, kazcaine). As a whole, all tested compounds were active in conduction and infiltration anesthesia (at the level of the reference drugs) and did not show activity in terminal anesthesia. Compounds VII – X are of interest for further testing under condition and infiltration anesthesia conditions.