New Potential Biologically Active Compounds: Synthesis and Characterization of Urea and Thiourea Derivativpes Bearing 1,2,4-oxadiazole Ring

Abstract

Background: Urea, thiourea, and 1,2,4-oxadiazole compounds are of great interest due to their different activities such as anti-inflammatory, antiviral, analgesic, fungicidal, herbicidal, diuretic, antihelminthic and antitumor along with antimicrobial activities. Objective: In this work, we provide a new series of potential biologically active compounds containing both 1,2,4- oxadiazole and urea/thiourea moiety. Methods: First, 5-chloromethyl-3-aryl-1,2,4-oxadiazoles (3a-j) were synthesized from the reaction of different substituted amidoximes (2a-j) and chloroacetyl chloride in the presence of pyridine by conventional and microwave-assisted methods. In the conventional method, 1,2,4-oxadiazoles were obtained in two steps. Oacylamidoximes obtained in the first step at room temperature was heated in toluene for an average of one hour to obtain 1,2,4-oxadiazoles. The yields varied from 70 to 96 %. 1,2,4-oxadiazoles were obtained under microwave irradiation in a single step in a 90-98 % yield at 160 °C in five minutes. 5-aminomethyl-3-aryl-1,2,4-oxadiazoles (5a-j) were obtained by Gabriel amine synthesis in two step from corresponding 5-chloromethyl-3-aryl-1,2,4- oxadiazoles. Finally, twenty new urea (6a-j) and thiourea (7a-j) compounds bearing oxadiazole ring were synthesized by reacting 5-aminomethyl-3-aryl-1,2,4-oxadiazoles with phenyl isocyanate and isothiocyanate in tetrahydrofuran (THF) at room temperature with average yields (40-70 %). Results: An efficient and rapid method for the synthesis of 1,2,4-oxadiazoles from the reaction of amidoximes and acyl halides without using any coupling reagent under microwave irradiation has been developed, and twenty new urea/thiourea compounds bearing 1,2,4-oxadiazole ring have been synthesized and characterized. Conclusion: We have synthesized a new series of urea/thiourea derivatives bearing 1,2,4-oxadiazole ring. Also, a facile synthesis of 3,5-disubstituted 1,2,4-oxadiazoles from amidoximes and acyl chlorides under microwave irradiation was reported. The compounds were characterized using FTIR, 1H NMR, 13C NMR, and elemental analysis techniques

Synthesis, enzyme inhibition and molecular docking studies of novel 1,2,4-oxadiazole thioether derivatives

“…The reaction sequence for the synthesis of target compounds is shown in Scheme 1. Firstly, 5chloromethyl-1,2,4-oxadiazole compounds (1a-f) were synthesized by microwave-assisted reaction of amidoximes with chloroacetyl chloride using the method given in the literature [30]. iii.…”

“…The product was purified by column chromatography using ethyl acetate:hexane (1:3 or 1:1) eluent system [30].…”

Síntese, caracterização e avaliação antimicrobiana de 1,2,4-oxadiazóis derivados do ácido trans-3,4-(metilenodioxi)-cinâmico

“…Several biological functions, such as anticancer, (Maftei, et al, 2013;Kumar et al, 2011;Moniot et al, 2017), antiinflammatory (Bezerra et al, 2005;Gobec et al, 2015;Bora et al, 2014), anticonvulsant (Mohammadi-Khanaposhtani et al, 2016, antibacterial (Baral et al, 2019), antifungal (Sortino et al, 2008), antiviral (Chernyshov et al, 2022), antioxidant Gobec et al, 2015), analgesic (Farooqui et al, 2009), antiinsomnia (Brotschi et al, 2019), antiparasitic (Haugwitz et al, 1985), antidepressant, anti-edema, and anti-Alzheimer (Biernacki et al, 2020) activity have been attributed to compounds with the 1,2,4-oxadiazole ring. Additionally, 1,2,4-oxadiazoles exhibit pesticidal activity, such as insecticidal (Liu et al, 2017), antifungal (Yang et al, 2021), and herbicidal activity (Ölmez & Waseer, 2020).…”