Design, synthesis, and fungicidal activity of novel 1,3,4-oxadiazole derivatives

Employing the intermediate derivatization method（IDM）, twenty novel 1,3,4-oxadiazole derivatives containing arylpyrazoloxyl moiety were designed and synthesized. The structures of the title compounds were identified by1 H NMR,13 C NMR, MS and elemental analyses, compound 4 was further identified by single-crystal X-ray diffraction. Antifungal activities against rice sheath blight（RSB） and sorghum anthracnose（SA） were evaluated by the mycelium linear growth rate method. Compounds 4, 16 and 20 displayed significant activities against RSB（EC50= 0.88 mg/L, 0.91 mg/L and 0.85 mg/L, respectively）,higher than the reference tebuconazole; While compound 3 exhibited higher activity against SA（EC50= 1.03 mg/L）, equal to commercial pyraclostrobin（EC50= 1.06 mg/L）. The study showed that compound 20 is a promising fungicide for further development.

Synthesis and bioactivities of novel 2-(thioether/sulfone)-5-pyrazolyl-1,3,4-oxadiazole derivatives

By introducing the pyrazole moiety into the 5-position of 1,3,4-oxadiazole,a series of novel 2-（thioether/sulfone）-5-pyrazolyl-l,3,4-oxadiazole derivatives were synthesized.Preliminary bioassays suggested that target compounds exhibited appreciable activity against pathogenic bacteria Xanthomonas oryzae pv.oryzae（Xoo） and five phytopathogenic fungi in vitro.Among them,the half-maximal effective concentration（EC_（50）） values of 6c,7a,7b and 7c against Xoo were within 16.6 μg/mL and 65.7 μg/mL,which were better than those of commercial agricultural antibacterial bismerthiazol（92.6 μg/mL） and thiodiazole copper（121.8 μg/mL）.While compounds 7a,7b,and 7c exerted comprehensive antifungal activity toward five plant fungi,which were comparable with that of hymexazol.The results demonstrated that this kind of compounds can be further studied and developed as promising antifungal and antibacterial agents.

SYNTHESIS OF DERIVATIVES OF 3-β-D-XYLOPYRANOSYL-1,2,4-OXADIAZOLES

The synthesis of derivatives of 3-β-D-xylopyranosyl-1,2,4-oxadiazoles is accomplished by condensing protected β-D-xylopyranosyl amidoxime with acid anhydrides or various substituted benzoyl chlorides in good yield.The structures of now derivatives were identified by spectra and elemental analysis. The stability of 1,2,4-oxadiazole ring and mechanism of cyclization were. investigated.

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 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.

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.

1,3,4-Oxadiazole as an emerging telomerase inhibitor-a promising anticancer motif

Currently,cancer is the most rapidly growing life-threatening disease after cardiovascular in the world,posing a major threat to human life.Telomerase promotes tumorigenesis and development in most cancers and dyskerin plays a crucial role in telomere maintenance.Cancer molecules are being developed continuously as a result of continuous research.A series of novel anticancer agents have been developed using telomerase inhibitors with improved specificity and pharmacokinetics.As medicinal chemistry advances,heterocyclic-based drugs find increasing applications,including anticancer agents.These properties have led to the development of five-membered aromatic rings of oxadiazoles.In order to enhance their anticancer activity,oxadiazole scaffolds can be modified.In this review,we discuss the functions and mechanism of action of the telomerase enzyme.The paper also summarizes the interaction between 1,3,4-oxadiazole inhibitors and telomerase enzymes.

QSAR and Pharmacophore Studies of Thiazolidine-4-carboxylic Acid Derivatives as Novel Influenza Neuraminidase Inhibitors Using HQSAR, Topomer CoMFA and CoMSIA

In order to understand the chemical-biological interactions governing their activities toward neuraminidase （NA）, QSAR models of 28 thiazolidine-4-carboxylic acid derivatives with inhibitory influenza A virus were developed. The obtained HQSAR （hologram quantitative structure activity relationship）, Topomer CoMFA and CoMSIA （comparative molecular similarity indices analysis） models were robust and had good exterior predictive capabilities. Moreover, QSAR modeling results elucidated that hydrogen bonds highly contributed to the inhibitory activity, then electrostatic and hydrophobic factors. Squared multiple correlation coefficients （R2） of HQSAR, Topomer CoMFA and CoMSIA models were 0.994, 0.978 and 0.996, respectively. Squared cross-validated correlation coefficients （Q2） of HQSAR, Topomer CoMFA and CoMSIA models were in turn 0.951, 919 and 0.820. Furthermore, squared multiple correlation coefficients for the test set （R2test） of HQSAR, CoMFA and CoMSIA models were 0.879, 0.912 and 0.953, respectively. Squared cross-validated correlation coefficients for the test set （Q2ext） of HQSAR, Topomer CoMFA and CoMSIA models were 0.867, 0.884 and 0.899, correspondingly.

Synthesis of phenol-class azo derivatives of 4-aminosalicylic acid

To explore the better prodrug of 4-aminosalicylic acid（4-ASA）with higher activity and less side effects against the inflammatory bowel disease.4-ASA,after a succession of synthesis process,was conjugated with various carder molecules to get seven azo derivatives of 4-ASA.All compounds were characterized by FT-IR,^1H NMR,^13C NMR spectras in detail.New derivatives of 4-ASA were definituded.

Synthesis of azo derivatives of 4-aminosalicylic acid

For searching a better 4-aminosalicylic acid derivative with higher activity and less side effects against the inflammatory bowel disease, 4-aminosalicylic acid (4-ASA) was protected by benzyloxycarbonyl and acetyl, respectively. The resultant was hydrogenized to remove protective group of amino group, then the product was reacted with NaNO2 to give diazonium salt, which was conjugated with salicylic acid, hydroxybenzene, N-salicyloyl glycine acid to get azo derivatives of 4-ASA. The azo derivatives were hydrolyzed under the alkaline condition to get the target products. All compounds were characterized by FT-IR, (1)H NMR, (13)C NMR spectra in details. New derivatives of 4-ASA were characterized. The synthetic route was reasonable and feasible.

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.

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.

Inhibition of Na^+,K^+-ATPase in Housefly (Musca domestica L.) by Terpinen-4-ol and Its Ester Derivatives

To reveal the insecticidal mechanism of terpinen-4-ol, the activity of Na＋,K＋-ATPase in insects tested were determined in vivo and in vitro. The results showed that terpinen-4-ol and its ester derivatives had strong contact activity to housefly and the contact toxicities of its derivatives except Z3 were all superior or equivalent to terpinen-4-ol. All the 7 compounds had strong inhibition towards activity of Na＋,K＋-ATPase. With poisoning symptom exacerbating, the inhibition rates were gradually increased. In vitro, the IC50 of terpinen-4-ol, Z1, Z2, Z4, Z5, and Z6 was 155.89, 197.98, 96.02, 121.36, 124.85, and 153.74 μg mL% respectively. There was well correlation between the LDs0 of terpinen-4-ol derivatives to housefly and the IC50 of terpinen-4-ol derivatives to Na＋,K＋-ATPase in housefly. In conclusion, Na＋,K＋-ATPase was likely the target of terpinen-4-ol against insects.

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.

Synthesis of thiourea derivatives as CCR4 antagonists

A series of thiourea derivatives have been synthesized. Their structures were confirmed by MS and 1H NMR. Several compounds showed potent activities as antagonists of CCR4 receptor.

Quantum Chemical Studies on the Corrosion Inhibition of Mild Steel by Piperidin-4-One Derivatives in 1 M H₃PO₄

The corrosion inhibition properties of 2,6-diphenylpiperidin-4-one (DPP) (1A) and 2,6-diphenyldihydro-2H-thiopyran-4(3H)-one (DPDT) (1B) for mild steel in 1 M phosphoric acid were studied using weight loss, potentiodynamic polarization and electrochemical impedance spectroscopic techniques. The effect of temperature on the corrosion behavior of mild steel has been examined in the temperature range 303 - 328 K. The inhibition efficiency increases with increasing inhibitor concentration but decreases with increasing temperature. Potentiodynamic polarization studies indicated the mixed nature of inhibitors. The adsorption of the inhibitors on mild steel surface obeyed the Langmuir adsorption isotherms. The density functional theory (DFT) at the B3LYP/6- 31G (d) basis set level was performed on 1A and 1B to investigate the correlation between molecular structure and the corresponding inhibition efficiency (%). The quantum chemical parameters such as EHOMO, ELUMO, the energy gap (E), hardness (η), softness (S), dipole moment (μ), electron affinity (A), ionization potential (I), the absolute electronegativity (χ), the fraction of electron transferred (N), electrophilicity index (ω), the back-donation (EBack-donation) and Mulliken population analysis have been calculated.

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.

Use of Ultrasound and Microwave Irradiation for Clean and Efficient Synthesis of 3,3’-(Arylmethylene)bis (2-hydroxynaphthalene-1,4-dione) Derivatives

Nine 3,3’-(arylmethylene)bis(2-hydroxynaphthalene-1,4-dione) derivatives were synthesized through the reaction between 2-hydroxy-1,4-naphthalen-1,4-dione and different aromatic alde-hydes in water applying ultrasonic irradiation for 5 min at room temperature and microwave irradiation for 15 min at 70°;C. Two of the nine derivatives, compounds 3-e and 3-i, obtained from 3-bromo-hydroxybenzaldehyde and 5-methylfuran-2-carbaldehyde, respectively, are previously unpublished. The structures of all compounds were established on the basis of their spectral data and mass analysis. The attractive features of this synthesis protocol include mild conditions, high atom-economy and excellent yields with the elimination of water as the only by-product.

STUDIES ON THE SYNTHESIS AND BIOLOGICAL ACTIVITY OF 1-ARYLOXYACETYL-4-AROYLTHIOSEMICARBAZIDE DERIVATIVES

A series of new 1-aryloxyacetyl-4-aroylthiosemicarbazides were synthesized by means of solid-liguid phase transfer catalysis. The promoting effects of these new compounds on wheat growth were observed.