Oxadiazole Fragments Research Articles

Design, Synthesis, and Biological Evaluation of Eukaryotic Initiation Factor 2B (eIF2B) Activators.

The eukaryotic initiation factor 2B (eIF2B) is a key regulator in protein-regulated signaling pathways and is closely related to the function of the central nervous system. Modulating eIF2B could retard the process of neurodegenerative diseases, including Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and vanishing white matter disease (VWM) et al. Here, we designed and synthesized a series of novel eIF2B activators containing oxadiazole fragments. The activating effects of compounds on eIF2B were investigated through testing the inhibition of ATF4 expression. Of all the targeted compounds, compounds 21 and 29 exhibited potent inhibition on ATF4 expression with IC50 values of 32.43 nM and 47.71 nM, respectively, which were stronger than that of ISRIB (IC50=67.90 nM). ATF4 mRNA assay showed that these two compounds could restore ATF4 mRNA to normal levels in thapsigargin-stimulated HeLa cells. Protein Translation assay showed that both compounds were effective in restoring protein synthesis. Compound potency assay showed that both compounds had similar potency to ISRIB with EC50 values of 5.844 and 37.70 nM. Cytotoxicity assay revealed that compounds 21 and 29 had low toxicity and were worth further investigation.

Conversion of oxadiazolo[3,4-b]pyrazines to imidazo[4,5-b]pyrazines via a tandem reduction-cyclization sequence generates new mitochondrial uncouplers

We report new mitochondrial uncouplers derived from the conversion of [1,2,5]oxadiazolo[3,4-b]pyrazines to 1H-imidazo[4,5-b]pyrazines. The in situ Fe-mediated reduction of the oxadiazole fragment followed by cyclization gave access to imidazopyrazines in moderate to good yields. A selection of orthoesters also allowed functionalization on the 2-position of the imidazole ring. This method afforded a variety of imidazopyrazine derivatives with varying substitution on the 2, 5 and 6 positions. Our studies suggest that both a 2-trifluoromethyl group and N-methylation are crucial for mitochondrial uncoupling capacity.

Synthesis and characterization of a novel latent ring-opening metathesis polymerization catalyst

The synthesis and characterization of a novel latent ruthenium catalyst bearing a chelate ligand containing an oxadiazole fragment for the olefin metathesis are described. The main advantages of the utilization of this ligand are the straightforwardness of preparation, mild reaction conditions, and availability of the feedstock. Preliminary study of the catalytic activity of the Ru complex for metathesis reactions demonstrated its inactive nature for the ring-closing metathesis (RCM), but an excellent thermo-switchability for the ring-opening metathesis polymerization of norbornene.

Design, Synthesis and Insecticidal Activity of 3-(Ethylsulfonyl)-Pyridines Bearing Trifluoromethyl-Oxadiazole Fragment

Background: Oxadiazole fragment is one of the most prevalent structures in biochemicals, especially in the research of new pesticides. It is necessary to develop new insecticides with a different mode of action for the treatment of insecticide resistance problems. And, it is worth exploring the new active insecticidal lead structures with oxadiazole fragments. Methods: We used a “splicing up” method introducing the trifluoromethyl-oxadiazole moiety to 3- (ethylsulfonyl)-pyridine structure, and replaced the 6-position on the pyridine ring by different substituted amines. Then, a series of novel 3-(ethylsulfonyl)-pyridines containing trifluoromethyloxadiazole moiety were designed and synthesized. All these title compounds were confirmed by 1H NMR, 13C NMR and ESI-MS. Results: The primary insecticidal activity results indicated that some of them (A1-A7, A10, A13- A14) exhibited good mortality against Mythimna separate at 500 mg/L (80-100%), and compounds A13 and A14 have moderate insecticidal activity against M. separate at 250 mg/L (50-55%). Discussion: The bioassay results showed that the designed compounds did not achieve excellent insecticidal activity by introducing the potential oxadiazole fragment. Therefore, it seems that the special physicochemical properties of the oxadiazole fragment should be considered in fragment splicing-based design. Conclusion: According to the bioassay studies, the results revealed that compounds A13 and A14 may provide useful information for further designing of efficient insecticides.

Star-Shaped Compounds with Oxadiazole Fragments. III. Informativity of Molecular Parameters Developed for Columnar Mesomorphism Prediction of Star-Shaped Compounds Towards Polycatenar Molecules

Star-Shaped Compounds with Oxadiazole Fragments. III. Informativity of Molecular Parameters Developed for Columnar Mesomorphism Prediction of Star-Shaped Compounds Towards Polycatenar Molecules

Synthesis and Properties of Sulfonated Copolymers of Oxadiazole, Dioxophenoxathiine, and Diphenyl Oxide

Sulfonated copolymers of 1,3,4-oxadiazole, diphenyl oxide, and 10,10-dioxophenoxathiine are obtained for use as polymer superabsorbents. The one-pot synthesis of the copolymers is carried out in an oleum medium, with the starting reagents being 4,4'-oxydibenzoic acid and hydrazine sulfate. As a result, the copolymers are obtained with the same proportion of the oxadiazole fragment in the chain but different ratio of fragments containing sulfonic acid groups: diphenyl oxide fragments with two sulfonic acid groups and dioxophenoxathiine fragments with one sulfonic acid group and one sulfonyl group. The copolymers are capable of a 100-fold swelling in an aqueous medium and dissolving to a limited extent upon the addition of polar aprotic cosolvents or with an increase in pH. The ratio of sulfonic acid and sulfonyl groups in the composition of the copolymer influences its swelling in water and the viscoelasticity of hydrogels that are in the mesophase state in case of a high content of the copolymer.

Star-Shaped Compounds with Oxadiazole Fragments. I. Influence of Molecular Structure Variation of Azo-Diphthalic Acids Derivatives on their Mesomorphism According to Prognosis Data

Star-Shaped Compounds with Oxadiazole Fragments. I. Influence of Molecular Structure Variation of Azo-Diphthalic Acids Derivatives on their Mesomorphism According to Prognosis Data

Star-shaped discotic compounds with tetrazole and oxadiazole fragments

ABSTRACTTwo series of star-shaped discotic compounds (A and B) were studied to establish the relationship between their molecular structure and mesogenity. Series A included 19 three-arm compounds with known mesomorphism. Series B consisted of 132 new compounds with unknown mesomorphism: pyromellitic and cyanuric acid derivatives, 5,5′-azo-bis-isophthalic and 4,4′-azodiphthalic acids and triphenylene derivatives. The columnar mesomorphism prediction data for both series were obtained using the original program СМР ChemCard. The prediction data for series A are in good agreement with the experimental results and the reliability of the prediction was estimated to be 89.5%. The same method was applied for series B. The prediction results were approved by the synthesis of individual representatives of series B. A good correlation of the prediction with the experimental data was revealed.

Combined Pharmacophore and Molecular Docking-based In silico Study of Some Pyrrolyl 1,3,4-oxadiazole benzothioate Derivatives

Purpose: The purpose of the research was to synthesise novel pyrrole derivatives as antitubercular agents. Methodology: A series of various 5-(4-(1H-pyrrol-1-yl)phenyl)-1,3,4-oxadiazol-2-yl substituted benzothioate derivatives (5a-s) were synthesized. The newly synthesized compounds were characterized on the basis of IR, NMR and Mass spectra. The newly synthesized final compounds were evaluated for their in vitro antitubercular activity. Pharmacophore hypothesis and Surflex-Docking studies were carried out to understand the structure activity relationship. Findings: Preliminary results indicated that most of the compounds demonstrated moderate to good antitubercular activity. The effect of the nature of the substituent on the phenyl group; the effect of the hydrogen bond acceptors and the effect of the oxadiazole fragment on InhA and activities against Mycobacterium tuberculosis were assessed. The software generated results was in satisfactory agreement with the evaluated biological activity. Conclusion: These results can be exploited to develop potential leads and structure based drug design of novel InhA inhibitors.

Synthesis and Microbiological Evaluation of New 2- and 2,3-Diphenoxysubstituted Naphthalene-1,4-diones with 5-Oxopyrrolidine Moieties

New 3-substituted 1-(3-hydroxyphenyl)-5-oxopyrrolidine derivatives containing hydrazone, azole, diazole, oxadiazole fragments, as well as 2-phenoxy- and 2,3-diphenoxy-1,4-naphthoquinone derivatives were synthesized. The structure of all compounds has been confirmed by NMR, IR, mass spectra, and elemental analysis data. Methyl 1-{3-[(3-chloro-1,4-dioxo-1,4-dihydro-2-naphthalenyl)oxy]phenyl}-5-oxo-3-pyrrolidinecarboxylate demonstrated potential antibacterial and antifungal activities as determined by diffusion and serial dilution methods, while N'-[(4-bromophenyl)methylidene]-1-{3-[(3-chloro-1,4-dioxo-1,4-dihydro-2-naphthalenyl)oxy]phenyl}-5-oxo-3-pyrrolidinecarbohydrazide and 2-{3-[4-(1,2,3-oxadiazol-5-yl)-2-oxo-1-pyrrolidinyl]phenoxy}-3-{3-[4-(1,3,4-oxadiazol-2-yl)-2-oxo-1-pyrrolidinyl]phenoxy}naphthoquinone showed antifungal activity against Candida tenuis and Aspergillus niger at low concentrations, as determined by the serial dilution method. The substitution of the methoxy fragment by N-containing substituents in monophenoxy substituted naphthoquinones was found to decrease their activity against Mycobacterium luteum. Besides, introduction of the second phenoxy substituted fragment increased the antifungal activity against Candida tenuis and Aspergillus niger at lower concentrations.

Bipolar Heteroleptic Green Iridium Dendrimers Containing Oligocarbazole and Oxadiazole Dendrons for Bright and Efficient Nondoped Electrophosphorescent Devices

Bipolar heteroleptic green light-emitting iridium (Ir) dendrimers G(OXD) and G(DOXD) have been designed and synthesized under mild conditions in high yields, in which the first C^N and second O^O ligands are functionalized with oligocarbazole- and oxadiazole-based dendrons, respectively. To avoid affecting the optical properties of the emissive iridium core, all the functional moieties are attached to the ligands through a flexible spacer. Compared with the unipolar dendrimer G(acac), dendrimers G(OXD) and G(DOXD) exhibit the close emission maxima of 511-512 nm and photoluminescence quantum yield of 0.39-0.40 in a solution of toluene. Moreover, on going from G(acac) to G(OXD) and G(DOXD), we have found that the introduction of oxadiazole fragments decreases the lowest unoccupied molecular orbital (LUMO) energy levels to facilitate the electron injection and electron transporting, while their highest occupied molecular orbital (HOMO) energy levels remain unchanged. This means that, we can individually tune the HOMO and LUMO energy levels based on the heteroleptic structure to ensure the relative independence between the hole and electron in the emitting layer (EML), which is a favorable feature for bipolar optoelectronic materials. As a result, a bilayer nondoped electrophosphorescent device with G(DOXD) as the EML gives a maximum luminous efficiency of 25.5 cd A(-1) (η(ext): 7.4%) and a brightness of 33,880 cd m(-2). In comparison to G(acac) (17.2 cd A(-1), 17,680 cd m(-2)), both the efficiency and brightness are improved by about 1.5 and 2 times, respectively. These state-of-the-art performances indicate the potential of these bipolar heteroleptic iridium dendrimers as solution-processible emitting materials for nondoped device applications.

Asymmetric Rhodium-Catalyzed Addition of Arylboronic Acids to Alkenylheteroarenes

In this paper the authors report the first catalytic enantioselective addition of arylboronic acids and alkenyl N-methyliminodiacetic acid (MIDA) boronate to β-substituted alkenyl­heteroarenes. Various types of substrates were employed, containing π-deficient quinoline, quin­oxaline, pyrimidine moieties as well as π-excessive oxazole and oxadiazole fragments; the products were obtained in 56-91% yields and with 89-98% ee. Introduction of the alkenyl moiety could be ­accomplished via alkenyl MIDA boronates. Microwave irradiation could be replaced by thermal heating.

Synthesis, photoluminescent and electroluminescent properties of a novel europium(III) complex involving both hole- and electron-transporting functional groups

A novel europium(III) complex involving a carbazole fragment as hole-transporting group and an oxadiazole fragment as electron-transporting group was synthesized and used as red light-emitting material in organic light-emitting diodes (OLEDs). The complex is amorphous, and exhibits high glass transition temperature ( T g = 157 °C) and high thermal stability with a 5% weight loss temperature of 367 °C. Two devices, device 1: ITO/NPB (40 nm)/Eu(III) complex (30 nm)/Alq 3 (30 nm)/LiF (1 nm)/Al (100 nm) and device 2: ITO/NPB (40 nm)/3% Eu(III) complex: CBP (30 nm)/BCP (10 nm)/Alq 3 (30 nm)/LiF (1 nm)/Al (100 nm), were fabricated, where NPB is N, N′-di(naphthalene-1-yl)- N, N′-diphenyl-benzidine, Alq 3 is tris(8-hydroxyquinoline) Al(III), CBP is 4,4′-bis(carbazole-9-yl)-biphenyl, and BCP is 2,9-dimethyl-4,7-diphenyl-1,10-phenanthroline, respectively. In contrast with device 1, owing to less self-quenching and better charge confinement, device 2 shows improved performances: the maximum luminance of device 2 was dramatically increased from 199 to 1845 cd/m 2, the maximum current efficiency was increased from 0.69 to 2.62 cd/A, the turn-on voltage was decreased from 9.5 to 5.5 V, and higher color purity was attained.

The host materials containing carbazole and oxadiazole fragment for red triplet emitter in organic light-emitting diodes

Abstract Three new oxadiazole substituted carbazole derivatives 9-{4-[5-(4-tert-butylphenyl)-[1,3,4] oxadiazol-2-yl]-benzyl}-9H-carbazole (t-CmOxa), 9-[4-5-phenyl-[1,3,4]oxadiazol-2-yl-benzyl]-9H-carbazole (p-CmOxa) and 9-[4-5-biphenyl-[1,3,4]oxadiazol-2-yl-benzyl]-9H-carbazole (d-CmOxa) were successfully synthesized and characterized by spectroscopy (NMR, UV–vis, mass spectrum and photoluminescence) and cyclic voltammetry measurements. Employing t-CmOxa as a host and Ir(DBQ)2(acac) (DBQ = dibenzo[f,h]quinoxaline, acac = acetylacetonate) as the dopant emitter, OLEDs with structures of ITO/NPB(30 nm)/Ir(DBQ)2(acac): t-CmOxa (30 nm, x%)/Alq3(30 nm)/Mg0.9:Ag0.1 were fabricated without using BCP as the hole blocking layer. Red emission was obtained with CIE coordinates (x = 0.66, and y = 0.34) at 5 V and a very high external electroluminescent (EL) quantum efficiency of 9.5 ± 0.1%, and an energy conversion efficiency of 9.9 ± 0.1 lm/W were achieved for the device when the doping concentration x is equal to 4%.

The oxadiazole as a structural fragment in liquid crystals

This paper examines in some detail the effect of introducing the oxadiazole fragment into the molecular core of liquid crystals on their physico-chemical properties. The results of this study are compared with those obtained for other molecular fragments, and are rationalized in terms of existing theories.

Features of radiolysis of poly-[2,5-(4′,4″-diphenylenephthalide)-1,3,4-oxadiazole

A study was made of the behaviour of cardo poly-[2,5-(4′,4″-diphenylenephthalide)-1,3,4-oxadiazole] by the action of γ-radiation in air and in vacuo. It was shown that during irradiation the polymer undergoes breakdown in both cases, the rate of breakdown conversions being higher in the presence of atmospheric oxygen. Chemical transformations taking place in poly-1,3,4-oxadiazole during irradiation in vacuo represent a reaction complex and are accompanied by the breakdown of the heterocycle of the main chain and the lactone ring of the phthalide group. Decomposition of the oxadiazole fragment takes place more extensively. The main trend of the breakdown of poly-1,3,4-oxadiazole samples irradiated in vacuo is related to the type of decomposition of the oxadiazole ring, accompanied by the elimination of oxygen, which takes part in the subsequent reactions with the polymer.