Search

5-Aryl-1H-pyrrole-2,3-diones reacted with amidoximes to give enamines containing a 1,2,4-oxadi-azole fragment that are potential precursors to novel 1H-pyrrole-2,3-diones. The described reaction is the first example of recyclization of 4-unsubstitued 5-aryl-1H-pyrrole-2,3-diones by the action of 1,4-binucleophiles. [ABSTRACT FROM AUTHOR]

The carbodiimide-mediated coupling of 4-cyanonicotinic acid with L-amino acid methyl esters takes place with the predominant formation of bicyclic compounds – methyl 2-(1-imino-3-oxo-1,3-dihydro-2H-pyrrolo[3,4-c]pyridin-2-yl)alkanoates, which are monoimino derivatives of 4-azaphthalimide. Under the action of hydroxylamine they undergo pyrrolidine cycle opening with the formation of pseudopeptides – coupling products of nicotinic acid with amino acid esters bearing an amidoxime function at position 4. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Petrochemical Universities / Shiyou Huagong Gaodeng Xuexiao Xuebao is the property of Journal Editorial Department Of Liaoning Shihua University and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The DNA photocleavage effect of halogenated O-carbamoyl derivatives of 4-MeO-benzamidoxime under UVB and UVA irradiation was studied in order to identify the nature, position, and number of halogens on the carbamoyl moiety that ensure photoactivity. F, Cl, and Br-phenyl carbamate esters (PCME) exhibited activity with the p-Cl-phenyl derivative to show excellent photocleavage against pBR322 plasmid DNA. m-Cl-PCME has diminished activity, whereas the presence of two halogen atoms reduced DNA photocleavage. The substitution on the benzamidoxime scaffold was irrelevant to the activity. The mechanism of action indicated function in the absence of oxygen, probably via radicals derived from the N-O bond homolysis of the carbamates and in air via hydroxyl radicals and partially singlet oxygen. The UVA-vis area of absorption of the nitro-benzamidoxime p-Cl-PCMEs allowed for the investigation of their potential efficacy as photopesticides under UVA irradiation against the whitefly Bemisia tabaci, a major pest of numerous crops. The m-nitro derivative exhibited a moderate specificity against the adult population. Nymphs were not affected. The compound was inactive in the dark. This result may allow for the development of lead compounds for the control of agricultural insect pests that can cause significant economic damage in crop production.

The DNA photocleavage effect of halogenated O-carbamoyl derivatives of 4-MeO-benzamidoxime under UVB and UVA irradiation was studied in order to identify the nature, position, and number of halogens on the carbamoyl moiety that ensure photoactivity. F, Cl, and Br-phenyl carbamate esters (PCME) exhibited activity with the p-Cl-phenyl derivative to show excellent photocleavage against pBR322 plasmid DNA. m-Cl-PCME has diminished activity, whereas the presence of two halogen atoms reduced DNA photocleavage. The substitution on the benzamidoxime scaffold was irrelevant to the activity. The mechanism of action indicated function in the absence of oxygen, probably via radicals derived from the N-O bond homolysis of the carbamates and in air via hydroxyl radicals and partially singlet oxygen. The UVA-vis area of absorption of the nitro-benzamidoxime p-Cl-PCMEs allowed for the investigation of their potential efficacy as photopesticides under UVA irradiation against the whitefly Bemisia tabaci, a major pest of numerous crops. The m-nitro derivative exhibited a moderate specificity against the adult population. Nymphs were not affected. The compound was inactive in the dark. This result may allow for the development of lead compounds for the control of agricultural insect pests that can cause significant economic damage in crop production. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

An improved synthesis of 3,5-disubstituted-1,2,4-oxadiazoles with a sulfonamide fragment is proposed. Our previously developed synthesis of the target 1,2,4-oxadiazoles, which involves reaction in the superbasic NaOH/DMSO medium, has a number of disadvantages. The improved synthesis involves the reaction of amidoximes with carboxylic acid esters in a t-BuON/DMAA medium. The reaction proceeds at room temperature for 8– 18 h. The advantages of the proposed method consist in the broader temperature range of the reaction (due to the change of solvent from DMSO to DMAA), as well as the absence of side hydrolysis processes, which is important for moisture sensitive substrates. The potential of the method was demonstrated by the synthesis of 9 novel 1,2,4-oxadiazole derivatives containing various substituents in the 3 position (R = 2-ClPh, 3-C2H5C(O)NH-Ph, i-Pr, Ph, thiophene, 4-Me-thiophene, 4-OMe-Ph, Py, 2-tolyl) and at the 5-position of the 1,2,4-oxadiazole ring (R = 4-SO2NH2-Ph, 2-OMe-4-SO2NH2-phenyl). The 3,5-disubstituted-1,2,4-oxadiazole derivatives synthesized in good yields (35–89%) are of interest for medicinal chemistry as potential drugs for the treatment of neurodegenerative diseases (such as Parkinson's syndrome and Alzheimer's disease) by inhibiting monoamine oxidase B. The synthesized compounds can be useful as antiglaucoma and anticancer agents, because they inhibit carbonic anhydrase I, II, IX, and XII isoforms. The structure and purity of the novel heterocyclic derivatives were confirmed by 1H and 13C NMR spectroscopy and mass spectrometry. Biological ac testing of the synthesized compounds on cell and animal glaucoma models is planned. [ABSTRACT FROM AUTHOR]

We have developed a simple and convenient method for the synthesis of 3-aryl- and 3-hetaryl-1,2,4-oxadiazin-5-ones bearing an easily functionalizable (methoxycarbonyl)methyl group at position 6 via the reaction of aryl or hetaryl amidoximes with maleates or fumarates. The conditions for this reaction were optimized. Different products can be synthesized selectively in good yields depending on the base used and the ratio of reactants: substituted (1,2,4-oxadiazin-6-yl)acetic acids, corresponding methyl esters, or hybrid 3-(aryl)-6-((3-(aryl)-1,2,4-oxadiazol-5-yl)methyl)-4H-1,2,4-oxadiazin-5(6H)-ones. The reaction is tolerant to substituents' electronic and steric effects in amidoximes. As a result, a series of 2-(5-oxo-3-(p-tolyl)-5,6-dihydro-4H-1,2,4-oxadiazin-6-yl)acetic acids, their methyl esters, and 1,2,4-oxadiazoles based on them were prepared and characterized by HRMS, 1H, and 13C NMR spectroscopy. The structures of three of them were elucidated with X-ray diffraction. [ABSTRACT FROM AUTHOR]

Condensation of amidoximes 1 with isatoic anhydrides 2 or esters 3 in NaOH/DMSO medium afforded to substituted 1,2,4‐oxadiazolyl anilines. The compounds synthesized can exhibit luminescence, the presence and efficiency of which depends on the position of the amino group in these aminophenyl 1,2,4‐oxadiazol derivatives. The best luminophores are 2‐(ortho‐aminophenyl) 1,2,4‐oxadiazoles. More than 20 examples of the new organic luminophores were synthesized and studied. The effect of the luminophore structure on the emission band and on the quantum yield indicates that a luminescent scaffold has been obtained. [ABSTRACT FROM AUTHOR]

A one-pot method was developed for the preparation of 3,5-disubstituted 1,2,4-oxadiazoles containing an alkenyl fragment, which entails the preparation of O-acylamidoximes and their subsequent cyclization using N,N′-dimethylacetamide as a solvent. The proposed method allows to significantly reduce the overall synthesis time by carrying out all steps sequentially in a single reactor, avoiding the step of isolation of the intermediate O-acylamidoxime, leading to the production of 5-alkenyl-1,2,4-oxadiazoles in high yields. [ABSTRACT FROM AUTHOR]

• Novel benzoxazole/carboximidamide hybrids were prepared. • Another 1,3-benzoxazole/3-aryl-1,2,4-oxadiazole hybrid series was designed. • Intramolecular cyclization conditions of carboximidamides was optimized. • Exhibited antibacterial activity against B. subtilis, S. aureus , and K. pneumoniae. Two series of 1,3-benzoxazole/carboximidamides 5a-i and 1,3-benzoxazole/3-aryl-1,2,4-oxadiazoles 6a-i were prepared from the reactions of (1,3-benzoxazol-2-ylthio)acetic acid (2) with the corresponding arylamidoximes 4a-i using excess N,N' -carbonyldiimidazole (CDI). The antibacterial studies revealed that hybrid 5a demonstrated exceptional activity against the Gram-positive bacteria Bacillus subtilis and Staphylococcus aureus , with inhibition zones measuring 34 mm and 36 mm, respectively. Moreover, hybrid 5a proved strong antibacterial activity against the against Gram-negative Klebsiella pneumoniae with inhibition zone equal to 32 mm. on the other hand, hybrid 5a displayed moderate activity against Gram-negative Escherichia coli , resulting in a 15 mm inhibition zone. Hybrid 6e (with 4-methoxyphenyl) was the most potent hybrid against B. subtilis, S. aureus and K. pneumoniae with inhibition zones equal to 32, 36 and 34 mm, respectively, followed by hybrids 6b (with 4-chlorophenyl) with inhibition zones equal to 31, 34 and 35 mm, respectively. Moreover, hybrid 5a exhibited strong antibacterial activity against B. subtilis, S. aureus and K. pneumoniae with minimum inhibitory concentration (MIC) values of 1.97, 0.97 and 3.90 μM, respectively, while hybrid 6b showed strong antibacterial activity with MIC values of 7.81, 3.90 and 3.90 μM, respectively, and hybrid 6e demonstrated antibacterial activity with MIC values of 3.90, 0.97 and 1.95 μM, respectively. [ABSTRACT FROM AUTHOR]

A preparative procedure has been developed for the synthesis of a series of new medicinally relevant 3-aryl-5-(aryloxymethyl)-1,2,4-oxadiazoles in 46–66% yields by alkylation of substituted phenols with 3-aryl-5-(chloromethyl)-1,2,4-oxadiazoles in the system K2CO3/KI/DMF. Poorly studied 3-R-4H-1,2,4-oxadiazin-5(6H)-ones were synthesized by a new method based on the reaction of methyl chloroacetate with amidoximes in the superbasic system t-BuONa/DMSO. The synthesized compounds at concentrations of up to 250 μg/mL showed no antibacterial activity against sensitive strains of Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Pseudomonas fluorescens, which supposedly suggests their low toxicity for human intestinal and mucous microflora. [ABSTRACT FROM AUTHOR]

A protocol has been devised for the synthesis of 3-substituted 5-amino-1,2,4-thiadiazoles utilizing isothiocyanates, amidoximes and water as an eco-friendly solvent. The strategy involves consecutive C−N and S−N bonds formation in a one-pot reaction under catalyst-free conditions. Operational simplicity, low cost, broad substrate scope and readily available starting materials are the main features of this protocol. [ABSTRACT FROM AUTHOR]

We have developed a simple and convenient method for the synthesis of 3-aryl- and 3-hetaryl-1,2,4-oxadiazin-5-ones bearing an easily functionalizable (methoxycarbonyl)methyl group at position 6 via the reaction of aryl or hetaryl amidoximes with maleates or fumarates. The conditions for this reaction were optimized. Different products can be synthesized selectively in good yields depending on the base used and the ratio of reactants: substituted (1,2,4-oxadiazin-6-yl)acetic acids, corresponding methyl esters, or hybrid 3-(aryl)-6-((3-(aryl)-1,2,4-oxadiazol-5-yl)methyl)-4H-1,2,4-oxadiazin-5(6H)-ones. The reaction is tolerant to substituents’ electronic and steric effects in amidoximes. As a result, a series of 2-(5-oxo-3-(p-tolyl)-5,6-dihydro-4H-1,2,4-oxadiazin-6-yl)acetic acids, their methyl esters, and 1,2,4-oxadiazoles based on them were prepared and characterized by HRMS, 1H, and 13C NMR spectroscopy. The structures of three of them were elucidated with X-ray diffraction.

Among poly(ADP‐ribose) polymerases (PARPs), PARP‐1 has emerged as a target in cancer therapy. The present work was aimed to design and synthesize O‐alkylaryl amidoximes as a new antiproliferative agents. The target compounds were designed through the study of molecular docking against the PARP‐1 and synthesized from commercially available starting materials in good yields under mild conditions and easy to perform reactions. The synthesized compounds exhibited in vitro antineoplastic activity (0.32–27.8 mM) against MCF‐7 and Caco‐2 cells, and one of them exhibited selective toxicity when tested against VERO cells. These compounds can be considered good candidates for the next stages in the development of new antiproliferative drugs. [ABSTRACT FROM AUTHOR]

An efficient one-pot method was developed for the synthesis of 2-(1,2,4-oxadiazol-5-yl)anilines via the reaction of amidoximes with isatoic anhydrides in a NaOH–DMSO medium at ambient temperature. The method allows to obtain structurally diverse substituted anilines bearing the 1,2,4-oxadiazole motif in moderate to excellent yields without the utilization of protective groups. The reaction scope includes aryl, hetaryl, and cycloalkyl amidoxime and isatoic anhydrides with different substituents in the aromatic ring as well as at the amide N atom. Structures of two anilines were studied by single crystal X-ray diffraction method and intramolecular hydrogen bonding between N atom of oxadiazole moiety and NH2 group was revealed. [ABSTRACT FROM AUTHOR]

A one-pot method for the synthesis of biphenylcarboxylic acids containing 1,2,4-oxadiazole ring in the NaOH–DMSO system was developed. The results of in vitro experiments showed that the synthesized compounds exhibit antibacterial activity against susceptible strains of E. coli and S. aureus. [ABSTRACT FROM AUTHOR]

The novel push–pull alkene, the 2-(nitro-nitrosomethylene)-pyrrolidine with numerous aliphatic or aromatic amines as nucleophiles afforded amidoximes. Various substituted oxadiazaborole and oxadiazole derivatives were prepared starting from these amidoximes, widening the synthetic applicability of the push–pull alkenes. Acylation of the amidoximes was also examined. The mechanism of the amidoxime formation was investigated by computational methods. [ABSTRACT FROM AUTHOR]

According to WHO, dengue virus is classed among major threats for future pandemics and remains at large an unmet medical need as there are currently no relevant antiviral drugs whereas vaccine developments have met with safety concerns, mostly due to secondary infections caused by antibody-dependant-enhancement in cross infections among the four dengue serotypes. This adds extra complexity in dengue antiviral research and has impeded the progress in this field. Following through our previous effort which born the allosteric, dual-mode inhibitor SP-471P (a carbazole derivative, EC 50 1.1 μM, CC 50 100 μM) we performed further optimisation while preserving the two arylamidoxime arms and the bromoaryl domain present in SP-471P. Examination of the relative positions of these functionalities within this three-point pharmacophore ultimately led us to an indolazepinone scaffold and our lead compound SP-1769B. SP-1769B is among the most cell-efficacious against all serotypes (DENV2/3 EC 50 100 nM, DENV1/4 EC 50 0.95–1.25 μM) and safest (CC 50 > 100 μM) anti-dengue compounds in the literature that also completely inhibits a secondary ADE-driven infection. [Display omitted] • Scaffold morphing on our previous hit led to a novel, pan-serotype, potent and safe DENV inhibitor. • Compounds were cross-examined in plaque reduction and dose-dependent inhibition cell assays. • Exemplified the importance of the relative spatial arrangement of three domain pharmacophore. • The synthesis of all compounds was optimised and performed to gram-scale reactions. [ABSTRACT FROM AUTHOR]

A molecular I2‐promoted one‐pot synthesis of 2‐aryl benzoxazoles has been developed by using amidoximes rather than the limited 2‐aminophenols or 2‐haloamides as substrates. The amidoxime substrates provided unique and efficient strategies for converting readily available aniline and benzaldehyde precursors into valuable chemicals. This transformation proceeded smoothly under transition‐metal‐free conditions through a sequential oxidative cyclization and ring contraction, and provided a potential route for introducing certain groups at any site of the scaffold. [ABSTRACT FROM AUTHOR]

A convenient reaction between arylamidoximes and functionalized Erlenmeyer azlactones in MeCN at 80 °C is described. This method leads to the formation of novel (Z)-N-[2-aryl-1-(3-aryl-1,2,4-oxadiazol-5-yl)vinyl]benzamide derivatives in moderate to good yields. The structure of target compounds was confirmed by X-ray diffraction study. [ABSTRACT FROM AUTHOR]

A unique example of the one‐pot trans‐diastereoselective reaction of meso‐tricyclic anhydrides is reported. The process involves anhydride ring opening by an amidoxime and the sequential cis‐ to trans‐ epimerization/cyclodehydration of the O‐acylamidoxime intermediate. The resulted 1,2,4‐oxadiazole/norborna(e)ne hybrids are obtained in moderate to good yields and > 95 % diastereomeric excess without any additional purifications. These compounds are interesting not only for drug discovery but for other chemistry‐related fields due to the presence of two easily modifiable moieties. [ABSTRACT FROM AUTHOR]

Plasmodium falciparum is responsible for most of the cases of malaria and its resistance to established antimalarial drugs is a major issue. Thus, new chemotherapies are needed to fight the emerging multi-drug resistance of P. falciparum malaria, like choline analogues targeting plasmodial phospholipidic metabolism. Here we describe the synthesis of amidoxime derivatives as prodrug candidates of reverse-benzamidines and hybrid compounds able to mimic choline, as well as the design of a new series of asymmetrical bis-cationic compounds. Bioconversion studies were conducted on amidoximes in asymmetrical series and showed that amidoxime prodrug strategy could be applied on C -alkylamidine moieties, like benzamidines and that N -substituents did not alter the bioconversion of amidoximes. The antimalarial activity of the three series of compounds was evaluated in vitro against P. falciparum and in vivo against P. vinckei petteri in mice. [ABSTRACT FROM AUTHOR]

3,5-Disubstituted 1,2,4-oxadiazoles were synthesized by the reaction of amidoximes with carboxylic acids or their esters under high-pressure conditions (10 kbar). The reaction proceeds without the use of other reagents or catalysts. Both aliphatic and aromatic carboxylic acids undergo this reaction. The obtained 1,2,4-oxadiazoles possess high fungicidal activity. [ABSTRACT FROM AUTHOR]

An efficient construction of imidazole ring by a Cs2CO3-promoted annulation of amidoximes with terminal alkynes in DMSO has been developed. This protocol provides a simple synthetic route with high atom-utilization for the synthesis of 2,4-disubstituted imidazoles in good yields under transition-metal-free and ligand-free conditions. Internal alkynes can also undergo the annulation to give 2,4,5-trisubstituted imidazoles.

Reactions of N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide with SeO 2 or thiourea afford complex materials containing elements of the reactants and diselenide or disulfide bridges, respectively. These materials were tested as agents for Uvi extraction from liquid media in the range of pH 6–9 including technological and sea water. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • A series of aromatic and aliphatic mono-amidoximes and bis-amidoximes were synthesized. • Amidoximes were tested for their NO release ability on rat liver microsomes and human vascular cells. • Amidoximes are cytocompatible with human vascular smooth muscle cells. • Mono-amidoximes 2a and 2b exhibit high NO release. • Bis-amidoxime 2d releases the same amount of NO than 2a and 2b at a twice lower concentration. Abstract Four compounds bearing amidoxime functions were synthetized: (1) 2a,b bearing an aromatic amidoxime function, (2) 2c bearing an aliphatic amidoxime function, and (3) 2d bearing aromatic and aliphatic amidoximes functions. The ability of these compounds to release NO was evaluated in vitro using the oxidative metabolism of cytochrome P450 from rat liver microsomes. Results obtained demonstrate that all amidoximes were able to release NO with a highest amount of NO produced by the 2a aromatic amidoxime. Moreover, all amidoximes exhibit cytocompatibility with human aorta smooth muscle cells. Using intracellular S -nitrosothiol formation as a marker of NO bioavailability, compounds 2a–c were demonstrated to deliver a higher amount of NO in the intracellular environment than the reference. Considering that the concentration of the bis-amidoxime 2d was two times lower that than of 2a and 2b , we can assume that 2d is the most potent molecule among the tested compounds for NO release. [ABSTRACT FROM AUTHOR]

A one‐pot synthesis of 1,2,4‐oxadiazoles has been achieved from the corresponding amidoximes and carboxylic acids or from nitriles, hydroxylamine and carboxylic acids, employing the OH activation property of the Vilsmeier reagent. The precursor O‐acylamidoxime could be derived in situ which underwent an intramolecular cyclization in the presence of Vilsmeier reagent to afford 1,2,4‐oxadiazole. The products were simply obtained in good to excellent yields under mild condition and compatible with a range of functional groups. Utilization of easy workup and purification of products make it very interesting. A one‐pot synthesis of 1,2,4‐oxadiazoles has been achieved from the corresponding amidoximes and carboxylic acids or from nitriles, hydroxylamine and carboxylic acids, employing the OH activation property of the Vilsmeier reagent. The products were simply obtained in good to excellent yields under mild condition and compatible with a range of functional groups. Utilization of easy workup and purification of products make it very interesting. [ABSTRACT FROM AUTHOR]

A one-pot ambient-temperature procedure for the synthesis of 3,5-disubstituted-1,2,4-oxadiazoles from amidoximes and carboxylic acids under superbase-promoted conditions is reported. [ABSTRACT FROM AUTHOR]

In continuation to our previous findings on amidoximes' antiparasitic activities, a new series of 23 original derivatives was designed and obtained by convergent synthesis. First, new terminal alkenes were synthesized by cross-coupling reaction. Then, cyclization was performed between terminal alkenes and β-ketosulfones using manganese(III) acetate reactivity. Twenty-three amidoximes were tested for their in vitro activity against Leishmania amazonensis promastigotes and their toxicity on murine macrophages. Seven of the tested compounds exhibited an antileishmanial activity at lower than 10 μM with moderate to low toxicity. Six of these molecules showed activity at lower than 10 μM against promastigotes and toxicity at higher than 50 μM were selected and evaluated for their activity against intracellular Leishmania amazonensis amastigotes. Modulating chemical substituents in position 2 of dihydrofuran highly influenced their antileishmanial activities. The introduction of a methyl or trifluoromethyl group on the benzene ring of the benzyl group had a positive influence on activity without significantly increasing toxicity ( 52, 59, 60 ). [ABSTRACT FROM AUTHOR]

Abstract: The tautomerism of the aliphatic MeC(NH2)═NOH and the aromatic PhC(NH2)═NOH amidoximes in protic (H2O, MeOH) and aprotic (Me2CO, Me2SO, and CHCl3) solvents was studied by density functional theory calculations at the M06‐2X/6‐311+G(d,p) level of theory. In both types of solutions, these species exist in 3 tautomeric forms, viz, (Z)‐ or (E)‐amidoximes, and (Z)‐aminonitrone. The (Z)‐form is the dominant, and energy gap between the (Z)‐ and (E)‐tautomers of the amidoximes slightly depends on the nature of a solvent and significantly higher than that for other oxime species. For the amidoximes, the zwitterionic (Z)‐aminonitrone form is stabilized by protic solvents. The oxime‐nitrone energy gap is reduced by electron‐donor substituents at the oxime moiety at different types of oxime species. [ABSTRACT FROM AUTHOR]

This review summarizes and discusses seven significant classes of strategies for designing highly efficient UES adsorbents towards one or more desired directions (including high affinity, high selectivity, fast kinetics, and high environmental suitability), with an aim of boosting the U(VI) extraction capacity in natural seawater. [Display omitted] • Strategies for designing highly efficient UES adsorbents are comprehensively reviewed. • The coordination chemistry behind UES is important. • Enhancing ligand-binding specificity towards U(VI) by incorporating preorganizations or stereochemical constraints. • Exerting thermodynamic or kinetic driving forces during the adsorption process. • Nature-inspired solutions by mimicking biological mechanisms and processes in a cost-effective way. Mining uranium from seawater using highly efficient adsorbents has been redeemed as one of the most urgent demands for sustainable nuclear power. However, it remains a formidable task to achieve sufficient extraction capacities for practical applications given the trace concentration of uranium (∼3.3 ppb), the competition from massive coexisting ions, and the extreme complexity of marine environment. This review briefly introduces the coordination chemistry behind uranium extraction from seawater (UES). Subsequently, we summarize and discuss existing strategies for designing highly efficient UES adsorbents toward one or more desired directions (such as high affinity, high selectivity, fast kinetics, and excellent antifouling property) to boost the uptake capacity in natural seawater. They mainly include adsorption through optimization of ligands, bifunctional synergy, bioinspired and biomimetic, molecular imprinting, electrically driven and photo-driven strategies, and antimicrobial and antifouling strategies. Finally, four critical perspectives regarding the design strategies of UES adsorbents are highlighted. The goal of this review is to assist researchers in this field in designing promising adsorbents for practical UES. [ABSTRACT FROM AUTHOR]

[Display omitted] New (E)-5-[2-(5-nitrofuran-2-yl)vinyl]-1,2,4-oxadiazoles and 5-(5-nitrofuran-2-yl)-1,2,4-oxadiazoles were synthesized via the base-promoted condensation of nitrofuran-containing acyl chlorides with amidoximes. Testing these compounds against Gram-negative E. coli , Gram-positive B. subtilis and S. aureus as well as M. tuberculosis HRv37 strain revealed three compounds being selectively antimycobacterial. None of these compounds displayed any cytotoxicity towards human pancreatic epithelioid carcinoma cell line, PANC-1. [ABSTRACT FROM AUTHOR]

A facile and practical protocol has been developed for the synthesis of 3,5-disubstituted 1,2,4-oxadiazoles and 1,4,2-oxathiazoles through oxidative cyclization of amidoximes and thiohydroximic acids, respectively at room temperature. Use of mild reaction conditions, inexpensive reagents, broad substrate scope and good to excellent yield of the products are the salient features of this protocol. [ABSTRACT FROM AUTHOR]

The first one-pot room-temperature protocol for the synthesis of 3,5-disubstituted-1,2,4-oxadiazoles via the condensation between amidoximes and carboxylic acid esters in superbase medium MOH/DMSO is reported. A broad spectrum of alkyl, aryl and hetaryl amidoximes and esters was examined. This reaction route provides convenient access to 1,2,4-oxadiazoles, which is highly desirable because in the light of this privileged scaffold is recognized as an important core in the design of novel therapeutic agents and high-tech materials. [ABSTRACT FROM AUTHOR]

A facile three step synthesis of a group of N1,N5-bis[4-(5-alkyl-1,2,4-oxadiazol-3-yl)phenyl]glutaramides, N1,N5-bis[4-(1,2,4-oxadiazol-3-yl)phenyl]glutaramide and N1,N5-bis[4-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)phenyl]glutaramide is described. These products are designed to function as masked bis-amidine prodrugs of a promising N1,N5-bis[4-(N'-(carbamimidoyl)phenyl]glutaramide antifungal lead.

Graphical abstract Highlights • A synthetic approach to 3-(5-amino-1,2,4-triazole)-1,2,4-oxadiazole is provided. • Trichloromethyl group offers possibility for facile further transformation. • Title compound can be considered as suitable building block for energetic materials. Abstract Nitrogen-rich heterocycles are increasingly used in energetic chemistry with the aim to achieve superior performance of the new energetic materials. Combining such building blocks into biheterocycles increases energy output while at the same time retains low sensitivity. Herein, we report the synthesis and characterization of a compound containing a 5-amino-1,2,4-triazole moiety connected with a 1,2,4-oxadiazole ring. The trichloromethyl group attached to the oxadiazole ring offers an attractive point for further transformations into potentially energetic compounds. [ABSTRACT FROM AUTHOR]

Arylhydrazonomalononitriles 1a,b react with phenylhydrazine to yield amidrazones 2a,b that cyclize to give 2-aryl-5-phenylhydrazono-2,5-dihydro-[1,2,4]-triazine-6-carbonitriles 5a,b upon reaction with dimethylformamide dimethylacetal (DMFDMA). Refluxing 5a,b in glacial acetic acid resulted in the formation of the pyrazolo-1,2,4-triazines 6a,b. Compounds 6a,b were also formed upon treatment of 3-amino-4-phenylhydrazono-1-phenyl-2-pyrazolin-5-ones 7a,b with DMFDMA. Reacting these triazinyl arylhydrazononitriles 5a,b with hydroxylamine hydrochloride in ethanolic sodium acetate afforded amidrazones 8a,b that are readily cyclized in refluxing dimethylformamide into [1,2,4]triazino[1,2,3]triazines 10a,b.

The synthesis of 14-(aryl)-14H-naphto[2,1-b]pyrano[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine-2-yl) acetamidoximes2a–ehas been accomplished by reaction of 2-acetonitrile derivatives1a–ewith hydroxylamine. Cyclocondensation reaction of precursors2a–ewith some elctrophilic species such as ethylorthoformate, acetic anhydride, and methyl-acetoacetate provided the new oxadiazole derivatives3a–e,4a–e, and5a–e, respectively. On the other hand, the reaction of precursors2a–ewith 2-chloropropanoyl chloride afforded the new acetimidamides6a–ewhich evolve under reflux of toluene to the new oxadiazoles7a–e. The synthetic compounds were screened for their anti-xanthine oxidase, anti-soybean lipoxygenase, and cytotoxic activities. Moderate to weak xanthine oxidase and soybean lipoxygenase inhibitions were obtained but significant cytotoxic activities were noted. The most cytotoxic activities were recorded mainly (i)5awas the most active (IC50 = 4.0 μM) and selective against MCF-7 and (ii)2awas cytotoxic against the four cell lines with selectivity for MCF-7 and OVCAR-3 (IC50 = 17 and 12 μM, respectively) while2eis highly selective against OVCAR-3 (IC50 = 10 μM). [ABSTRACT FROM PUBLISHER]

A general, facile, and efficient method is presented for the synthesis of 3-substituted 1,2,4-oxadiazoles from amidoximes and triethyl orthoformate. The procedure employs an iron(III) chloride/L-proline catalytic system and the 3-substituted 1,2,4-oxadiazole products are obtained in moderate to good yields. [ABSTRACT FROM AUTHOR]

An efficient synthesis of pyrazine-based amidoximes bearing amino acid residues is reported. Esterification of amidoximes with further microwave-assisted cyclization into α-amino acid-derived 1,2,4-oxadiazoles has been developed. Conformational analysis of the obtained pseudopeptides by NMR and FTIR spectroscopy revealed intramolecular interactions due to the influence of a pyrazine ring and prolyl amide bond isomerization. The content of trans / cis conformers depending on the substitution at the pyrazine moiety for Pro-containing derivatives has been estimated. [ABSTRACT FROM AUTHOR]

A FeCl 3 ·6H 2 O-mediated reaction of [60]fullerene with amidoximes for the preparation of fulleroimidazolines has been presented. This reaction shows a wide substrate scope, and the products obtained from alkyl-substituted amidoximes are first disclosed. In addition, a possible mechanism is proposed. [ABSTRACT FROM AUTHOR]

An efficient and simple synthesis of 3-aryl-5-(dialkoxymethyl)-1,2,4-oxadiazoles is described. The in situ prepared amidoximes from the reaction between nitriles and hydroxylamine are condensed with alkyl 2,2-dialkoxyacetates under solvent-free conditions to produce the title compounds in excellent yields. [ABSTRACT FROM AUTHOR]

Although the versatile chemistry of conventional oximes has been extensively reviewed over the years in both the organic chemistry literature and the coordination chemistry literature, amidoximes, RC(NH 2 ) NOH, have so far received substantially less attention. Taking into account the increased publication activity on the subject, we systematically review the data on the routes for preparation of amidoxime complexes, the coordination patterns of ligands, and the classification of metal-involving reactions of amidoxime species. This survey includes a comparison of the coordination chemistry and metal-involving reactions of amidoximes with those of conventional ketoximes and aldoximes. [ABSTRACT FROM AUTHOR]

Amino acid derived amide bond bioisosteric peptidomimetics, such as 1,2,4‐oxadiazoles are generally prepared by two‐step processes as demonstrated well in the literature. There have been no reports on the synthesis of 1,2,4‐oxadiazoles from heteroaroyl peptides in a single step to date. In our work, 1,2,4‐oxadiazole peptidomimetics were synthesized efficiently via one‐pot cyclodehydration of O‐acyl amidoximes engendered in situ, from heteroaroyl monopeptides and aryl or benzyl amidoximes with up to 93% yield. The process utilized DCC as the activating agent and did not considerably affect the conversion with the variation of amidoximes or monopeptides. Hence, the process could be useful in the design and synthesis of novel 1,2,4‐oxadiazole peptidomimetic based therapeutics. A convenient N,N′‐dicyclohexylcarbodiimide mediated successive O‐acylation of benzo/benzyl amidoximes with heteroaroyl monopeptides followed by a cyclodehydration reaction leading to 1,2,4‐oxadiazole peptidomimetics was developed in one‐pot fashion in good yields. [ABSTRACT FROM AUTHOR]

Oxadiazoles are heterocyclic compounds with a variety of application in many pharmaceuticals and agrochemical products. We report herein the convenient synthesis of 4-[(3-aryl-1,2,4-oxadiazol-5-yl)methoxy]-coumarins ( 4a- f), 6-[(3-aryl-1,2,4-oxadiazol-5-yl)methoxy]-4-methylcoumarins ( 7a- f) and 7-[(3-aryl-1,2,4-oxadiazol-5-yl)methoxy]-4-phenylcoumarins ( 10a- f) in high yields by one-pot condensation reaction of esters with amidoximes. The structures of the synthesized compounds were established on the basis of IR, NMR and mass spectrometry. The antibacterial and antifungal activities of synthesized compounds were evaluated. Graphical Abstract: [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]