1,3,4-oxadiazole-a bioactive scaffold for treating major depression-associated cognitive dysfunction

Background:Alzheimer’s disease affects millions of people worldwide,and one of its major characteristics is the accumulation of extracellular Aβpeptides in the human brain,leading to neuronal death and resulting in memory deficits,disorientation,and inappropriate behaviour.Objective and Methodology:This review study aims to develop new molecular targets for major depression-associated cognitive dysfunction and determine the mechanisms of action of 1,3,4-oxadiazole-based drug candidates.It encourages scientists to develop and synthesize drugs with low side effects to treat Alzheimer’s disease.Furthermore,the drug has shown significant improvement in memory function among dementia patients,which is due to the increased production of acetylcholine in the brain.These derivatives show a high affinity to amyloid plaques,which are thought to cause cognitive damage in patients with Alzheimer’s disease.This review study emphasizes newly developed inhibitors of amyloid deposition using the enzymeα-secretase,which cleaves amyloid precursor protein into smaller fragments that are toxic to neurons.1,3,4-Oxadiazole compounds have demonstrated no significant toxicity to the central nervous system.The antioxidant properties of 1,3,4-oxadiazoles can reduce free radicals,which play an active role in cell damage and disease.Conclusion:This review aims to provide readers with an overview of the current state of knowledge about oxadiazole-related drugs,emphasizing their biological importance.Key aspects related to the discovery and development of these drug candidates are discussed in detail,including information on their structure,biological activity,chemistry,and pharmacological properties.In addition,different derivatives discovered for Alzheimer’s disease to enhance the therapeutic efficiency of oxadiazole drugs have been comprehensively discussed in this review.

Synthesis and optical properties of an alternating copolymer composed of MEHPV and 1,3,4-oxadiazole

A poly （ p-phenylenevinylene ） （ PPV ） alternating copolymer, poly [ （ 2, 5-diphenylene-1, 3, 4-oxadiazole ）-4-4＇ - vinylene-alt-2-methoxy-5-（ 2-ethylhexyloxy ）-1, 4-phenylenevinylene] （oxa-MEHPV）, is synthesized by Heck coupling reaction and characterized with UV-vis, Fourier transform infrared （ FT-IR ）, ^1H-NMR and photoluminescence （ PL ） spectroscopy, oxa-MEHPV possesses an outstanding thermal stability and shows excellent solubility in common organic solvents such as dichloromethane, chloroform, toluene, and tetrahydrofuran（THF）. The introduction of the electron-deficient 1, 3, 4-oxadiazole units into the MEH-PPV backbone also increases the electron affinities of the conjugated segment, which leads to the blue-shift of the maximum absorption wavelength and makes the polymer have a high optical band-gap energy, good electron-transporting stability and high PL quantum yield.

Improved Synthesis of Fructose-Derived 1, 3, 4-Oxadiazole as Novel Antitumor Agents

Aim To optimize the reaction condition for preparation of 3-spiro-1, 3, 4-oxadiazole substituted fructose and hydrolysis of its isopropylidenes stepwisely. Methods Cyclohexane was added to the reaction mixture every 8 h to remove acetic acid at 90 ℃. The isopropylidenes were hydrolyzed in 80% AcOH at 60 ℃ stepwisely in a reaction time- dependent manner. Results The yields of cyclization products 1b and 1c were improved from 53% and 51% to 74% and 79% respectively. The 1, 2-di-O-isopropylidene product 3 was obtained after 1 h and the total deprotected product 4 was obtained after 3 h in 80% AcOH at 60 ℃. Conclusion The yield of 1 is improved by cyclohexane-aided azeotropic removal of AcOH from the reaction mixture. Deprotection of 1 in 80% AcOH at 60 ℃ gives 3 or 4 after different time periods.

Synthesis and Crystal Structure of N-(2-(1,3,4-oxadiazol-2-yl)phenyl)-2,3-dimethylaniline

The title compound, N-（2-（1,3,4-oxadiazol-2-yl）phenyl）-2,3-dimethylaniline, was synthesized and studied by single-crystal X-ray diffraction method. The structure of the product was confirmed by IR, ^1H- and ^13C-NMR spectroscopy, elemental analysis and mass spectrometry. These experimental studies were supported by theoretical optimizations.

Synthesis and Photoluminescence of a Novel Iridium Complex (BuPhOXD)_2Ir(acac) with Unit of 1, 3, 4-Oxadiazole

A novel cyclometalated iridium complex with 1, 3, 4-oxadiazole moiety was synthesizedand characterized. Its UV and photoluminescent properties were studied. The strong UVabsorption intensity around 462 nm attributed to spin-forbidden triplet metal–ligand charge transferband and photoluminescence at 518 nm were observed. This indicated that achieved iridiumcomplex could be used as an efficient electrophosphorescent material.

Synthesis,Crystal Structure and Biological Activity of 2-(Anthracen-9-yl)-5-p-tolyl-1,3,4-oxadiazole

A novel compound,2-（anthracen-9-yl）-5-p-tolyl-1,3,4-oxadiazole（C23H16N2O）,has been synthesized by the condensation of 4-methylbenzohydrazide and anthracene-9-carbaldehyde in an ethanol solution with chloramine-T.The compound was characterized by 1H-NMR,13C-NMR,MS and single-crystal X-ray diffraction.The crystal belongs to the triclinic system,space group P with a = 7.7817（4）,b = 8.8544（5）,c = 12.4726（8） ,β = 92.8520（10）°,Z = 2,V = 826.58（8） 3,Dc = 1.352 g/cm3,Mr = 336.38,λ（MoKα） = 0.71073 ,μ = 0.084 mm-1,F（000） = 352,R = 0.0381 and wR = 0.1099.The dihedral angle between anthracene skeleton and phenyl ring is 64.19°.A total of 6354 unique reflections were collected,of which 3172 with I 〉 2σ（I） were observed.X-ray analysis indicated an offset face-to-face π-π stacking interaction between anthracene skeletons and an offset face-to-face π-π stacking interaction between phenyl ring planes.The novel compound molecules are connected through the offset face-to-face π-π stacking interactions to generate a three-dimensional network.The preliminary bioassay results showed that the novel compound exhibited significant insect growth inhibitory activity against Spodoptera litura Fabricius larvae.

Synthesis and Fungicidal Activities of 2-Alkylthio-5-(3,4,5-tribenzyloxyphenyl)-1,3,4-oxadiazoles

Abstract： Ten novel 2-alkylthio-5-（3, 4, 5-tribenzyloxyphenyl）-1, 3, 4-oxadiazole derivatives （5a-j） were synthesized from methyl 3, 4, 5-trihydroxybenzoate by ethedfication, hydrazidation, cyclization and thioetherification reactions. The structures of 5a-j were confirmed by 1HNMR, MS spectra and elemental analysis. The results indicated that most of the compounds 5 exhibited good fungicidal activities. The activity of 5h is higher than 90% against Fusarium oxysporum and Botrytis cinereapers in 50 mg/L.

Syntheses, Crystal Structures, and Biological Activities of Two 5-Pyrimidinyl-1,2,4-oxadiazoles

Two 5-pyrimidinyl-1,2,4-oxadiazoles were synthesized through two different routes and their structures were characterized by single-crystal X-ray diffraction, NMR and MS. Compound 3, 5-（2-chloro-4-methyl-6-phenylpyrimidin-5-yl）-3-phenyl-1,2,4-oxadiazole, crystallizes in orthorhombic, space group Pbca with a = 19.1575（11）, b = 8.2115（5）, c = 21.2035（12）A, V = 3335.6（3）A3 and Z = 4. Compound 6, 5-（2,6-dichloropyrimidin-4-yl）-3-phenyl-1,2,4-oxadiazole, crystallizes in monoclinic space group Pn with a = 8.4275（13）, b = 5.4088（8）, c = 13.493（2）A, β = 99.768（3）°, V = 4658.6（6）A3 and Z = 8. Preliminary bioassay indicated that the two title compounds had good herbicidal activities.

Solvent-free synthesis of some new 2-(3,5-dimethoxy-4-methylphenyl)-5-aryl-1,3,4-oxadiazoles

An expeditious microwave-accelerated one-step synthesis of some new 2-（3,5-dimethoxy-4-methylphenyl）-5-aryl-1,3,4- oxadiazoles by reaction of 3,5-dimethoxy-4-methyl hydrazide with different carboxylic acids in presence of thionyl chloride under neat conditions,has been achieved.

Synthesis, Crystal Structure and Theoretical Calculations of N-Benzyl-1-(5-(3-chlorophenyl)-1,3,4-oxadiazol-2-yl)cyclopentanamine

N-benzyl-1-（5-（3-chlorophenyl）-1,3,4-oxadiazol-2-yl）cyclopentanamine was synthesized via one-pot reaction of appropriate benzylamine, cyclopentanone,（N-isocyanimino）triphenylphosphorane and m-chlorobenzoic acid. The quantum theoretical calculations for crystal structure were performed by density functional theory（DFT/B3LYP/6-311＋G＊）. From the optimized structure, geometric parameters were obtained and experimental measurements were compared with the calculated data. Frontier molecular orbitals（FMOs）, total density of states（DOS）, molecular electrostatic potential（MEP）, molecular properties, natural charges, NMR parameters and NBO analysis for the product were investigated by theoretical calculations.

Syntheses and Crystal Structures of Two New Complexes Generated from 2-（（Pyridin-3-ylmethyl）thio）-5-（6-quinolinyl）-1,3,4-oxadiazole and Ag~Ⅰ Salts

Two new Ag~Ⅰ-complexes have been synthesized based on the semi-rigid ligand 2-（（pyridin-3-ylmethyl）thio）-5-（6-quinolinyl）-1,3,4-oxadiazole（L）,obtained by the condensation reaction of 5-（6-quinolinyl）-1,3,4-oxadiazole-2-thiol and 3-chloromethyl pyridine hydrochloride. Crystallization of L with Ag OTf and Ag PF_6 in a CH_2Cl_2/MeO H mixed solvent system at room temperature affords a novel supramolecular [Ag_2L_2（CF_3SO_3）_2]（I） and a coordination polymer [Ag L（PF_6）]_n（Ⅱ）,respectively. Two complexes were characterized by TGA,X-ray powder and single-crystal diffraction.

One-pot synthesis,antibacterial and antifungal activities of novel 2,5-disubstituted-1,3,4-oxadiazoles

A series of novel 2,5-disubstituted-1,3,4-oxadiazoles have been synthesized from long-chain alkanoic and alkenoic acids. The structures of these compounds have been elucidated by elemental and spectral （IR, ^1H NMR, ^13C NMR, MS） analysis. Furthermore, compounds were screened for in vitro antibacterial activity against the representative panel of two Gram-positive and two Gram- negative bacteria. All the synthesized compounds were also tested for their inhibitory action against five strains of fungus. The various compounds show potent inhibitory action against test organisms. 2007 Abdul Rauf. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.

A mild and facile method for one pot synthesis of 2,5-di-substituted 1,3,4-oxadiazoles at room temperature

2,5-Di-substituted 1,3,4-oxadiazoles 3a-n have been synthesized as a one pot procedure from the reaction of acid hydrazide 1, acyl halides 2 and phosphorus pentoxide in acetonitrile at room temperature. High yield, short reaction time （10-15 min）, mild condition, and easy work-up are advantages of this methodology.

Structure and Biological Activities of Novel Triazole Compounds Containing 1,3,4-Oxadiazole Ring

Eighteen novel triazole compounds containing 1,3,4-oxadiazole groups were synthesized from 2-（1H-1,2,4-triazol-1-yl）acetohydrazide and carbon disulfide by several step reactions. The target compounds were characterized by elemental analysis, 1H NMR, 13C NMR, IR, MS, and X-ray crystallography. The results of preliminary biological tests show that all the compounds exhibit certain fungicidal activities.

An expeditious and one-pot synthesis of unsymmetrical 2,5-disubstituted-1,3,4-oxadiazoles under microwave irradiation and solvent-free conditions

A one-pot synthesis of some unsymmetrical 2,5-disubstituted-1,3,4-oxadiazoles via cyclocondensation of benzoylhydrazines with orthoesters under solvent-free and microwave conditions are described here. The reaction is efficiently catalyzed by silica- supported sulfuric acid as it provided the title compounds in high yields and relatively short times. The catalyst is reusable and can be applied several times without considerable decrease in the yields and rates of the reactions.

Pharmacokinetic evaluation,molecular docking and in vitro biological evaluation of 1,3,4-oxadiazole derivatives as potent antioxidants and STAT3 inhibitors

1, 3, 4-Oxadiazole derivatives(4 a–5 f) were previously synthesized to investigate their anticancer properties.However, studies relating to their antioxidant potential and signal transducer and activator of transcription(STAT) inhibition have not been performed. We investigated previously synthesized 1, 3, 4-oxadiazole derivatives(4 a–5 f) for various radical scavenging properties using several in vitro antioxidant assays and also for direct inhibition of STAT3 through molecular docking. The data obtained from various antioxidant assays such as 2, 2,-diphenyl-1-picrylhydrazyl radical(DPPH), nitric oxide, hydrogen peroxide, and superoxide anion radical revealed that among all the derivatives, compound 5 e displayed high antioxidant activities than the standard antioxidant L-ascorbic acid. Additionally, the total reduction assay and antioxidant capacity assay further confirmed the antioxidant potential of compound 5 e. Furthermore, the molecular docking studies performed for all derivatives along with the standard inhibitor STX-0119 showed that binding energy released in direct binding with the SH2 domain of STAT3 was the highest for compound 5 e(-9.91 kcal/mol).Through virtual screening, compound 5 e was found to exhibit optimum competency in inhibiting STAT3 activity. Compound 5 e decreased the activation of STAT3 as observed with Western blot. In brief, compound5 e was identified as a potent antioxidant agent and STAT3 inhibitor and effective agent for cancer treatment.

Preparation of 3-Aryl-5-phenylselenomethyl 1, 2, 4-Oxadiazole and their Further Deselenenylation Reaction

A mild Porco’s two-step, one-pot condensation reaction for the preparation of 3-aryl- 5-phenylselenomethyl 1, 2, 4-oxadiazole through phenylseleno acetic acid and benzamidoxime was reported. And further deselenenylation of 3-aryl-5-phenylselenomethyl 1, 2, 4-oxadiazole was studied.

The Reductive Addition Reaction of Substituted 2-Chloromethyl-1,3,4-oxadiazole to Aldehydes and Ketones Promoted by Samarium Diiodide

1-（β-Hydroxyalkyl）-l,3,4-oxadiazole derivatives were synthesized via reductive addition reactions of 2-chloromethyl-l,3,4-oxadiazole with carbonyl compounds under mild conditions promoted by SmI2.

Synthesis and Characterization of Mesomorphic Behaviour of New Mesogenic Compounds Incorporating Cholesteryl Ester Moiety Connected to 1,3,4-Oxadiazole

The synthesis and characterization of new series of liquid crystals containing cholesteryl moiety connected via an ester linkage to 1,3,4-oxadiazole are reported. The molecular structures of the intermediates and target compounds were confirmed by elemental analyses and FT-IR, ^1H NMR and mass spectrometry. The mesomorphic behaviors were investigated by polarizing optical microscopy （POM） attached with hot stage and differential scanning calorimetry （DSC）. Enantiotropic smectic 1, smectic A, blue phase and cholesteric mesophases are exhibited by the newly synthesized compounds.

Synthesis and Screening of New 5-Substituted-1,3,4-oxadiazole-2-thioglycosides as Potent Anticancer Agents

A series of newly 1,3,4-oxadiazole-2-thioglycoside derivatives were synthesized. The key step of this protocol is the coupling between 5-herteroaryl-1,3,4-oxadiazole-2-thione and activated sugars (cyclic or acyclic sugar analogues) in the presence of basic medium. Among of the synthesized compounds, compounds 7, 10, 11 and 13 were screened for them in vitro anticancer activity against four human cancer cells. MCF-7 (Breast), HEPG2 (Liver), HCT116 (Colon) and HEP2 (Larynx) carcinoma cell lines with IC50 values ranging from 2.08 - 8.72 μg/well. Compounds 11 and 13 were highly specific and potent for four cell lines (MCF-7, HCT116, HEPG2 and HEP2).