94-08-6Relevant articles and documents
Synthesis, spectral analysis, antibacterial, antifungal, antioxidant and hemolytic activity studies of some new 2,5-disubstituted-1,3,4-oxadiazoles
Adole, Vishnu A.,Chobe, Santosh S.,Dhonnar, Sunil L.,Jagdale, Bapu S.,More, Rahul A.,Sadgir, Nutan V.
, (2022/01/04)
Series of 1,3,4-oxadiazole derivatives (5a–5g and 5h, 5i) were synthesized and characterized by FT-IR, 1H NMR, 13C NMR and HR-MS spectral analysis. All the target compounds were screened for their in vitro antibacterial activity against two Gram-negative bacterial strains namely Escherichia coli (MTCC 405) and Salmonella typhi (MTCC 3224) and two Gram-positive bacterial strains namely Bacillus subtilis (MTCC 1790) and Bacillus megaterium (MTCC 1684) and antifungal activity against Aspergillus niger (MTCC 282), Rhizopus oryzae (MTCC 262), Penicillium chrysogenum (MTCC 974), and Candida albicans (MTCC 183) fungal strains. The synthesized compounds exhibited significant antibacterial and antifungal potential. Three compounds (5e, 5f and 5g) have shown higher antibacterial activity with very low MIC values comparable to streptomycin. According to the SAR study, the antibacterial efficacy can be intensified by substituting fluoro and methyl substituents at the para position in acid hydrazide. The synthesized compounds were also screened for % radical scavenging activity by OH and DPPH assay and found to be good antioxidant agents. Besides, the hemolytic study revealed that the synthesized 1,3,4-oxadiazoles possessed negligible cytotoxicity compared with the standard.
Pleuromutilin derivative with 1, 3, 4-oxadiazole side chain and preparation and application thereof
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Paragraph 0055-0056; 0070; 0090; 0092; 0095; 0102, (2021/07/24)
The invention belongs to the field of medicinal chemistry, and particularly relates to a pleuromutilin derivative with a 1, 3, 4-oxadiazole side chain and preparation and application thereof The pleuromutilin derivative with the 1, 3, 4-oxadiazole side chain is a compound shown in a formula 2 or a pharmaceutically acceptable salt thereof, and a solvent compound, an enantiomer, a diastereoisomer and a tautomer of the compound shown in the formula 2 or the pharmaceutically acceptable salt thereof or a mixture of the solvent compound, the enantiomer, the diastereoisomer and the tautomer in any proportion, including a racemic mixture. The pleuromutilin derivative has good antibacterial activity, is especially suitable for being used as a novel antibacterial agent for systemic system infection of animals or human beings, and has good water solubility.
Oxazole ring-containing honokiol thioether derivative and preparation method and application thereof
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Paragraph 0042-0044, (2021/08/11)
The invention discloses an oxazole ring-containing honokiol thioether derivative, a preparation method thereof and application of the oxazole ring-containing honokiol thioether derivative as an alpha-glucosidase inhibitor, the chemical structure of the oxazole ring-containing honokiol thioether derivative is shown as a general formula (I), and R is selected from non-substituted or substituted phenyl. Compared with the prior art, the invention provides the novel honokiol thioether derivative containing the oxazole ring, and the honokiol thioether derivative containing the oxazole ring has good inhibitory activity on alpha-glucosidase, provides more possibilities for treating diabetes, and is expected to be used for preparing novel candidate drug molecules for treating diabetes. In addition, the preparation process is simple, the cost is low, and the yield is high.
Visible-Light-Promoted Metal-Free Synthesis of (Hetero)Aromatic Nitriles from C(sp3)?H Bonds**
Murugesan, Kathiravan,Donabauer, Karsten,K?nig, Burkhard
supporting information, p. 2439 - 2445 (2020/12/07)
The metal-free activation of C(sp3)?H bonds to value-added products is of paramount importance in organic synthesis. We report the use of the commercially available organic dye 2,4,6-triphenylpyrylium tetrafluoroborate (TPP) for the conversion of methylarenes to the corresponding aryl nitriles via a photocatalytic process. Applying this methodology, a variety of cyanobenzenes have been synthesized in good to excellent yield under metal- and cyanide-free conditions. We demonstrate the scope of the method with over 50 examples including late-stage functionalization of drug molecules (celecoxib) and complex structures such as l-menthol, amino acids, and cholesterol derivatives. Furthermore, the presented synthetic protocol is applicable for gram-scale reactions. In addition to methylarenes, selected examples for the cyanation of aldehydes, alcohols and oximes are demonstrated as well. Detailed mechanistic investigations have been carried out using time-resolved luminescence quenching studies, control experiments, and NMR spectroscopy as well as kinetic studies, all supporting the proposed catalytic cycle.
Design, Synthesis, and Study of the Insecticidal Activity of Novel Steroidal 1,3,4-Oxadiazoles
Bai, Hangyu,Jiang, Weiqi,Li, Qi,Li, Tian,Ma, Shichuang,Shi, Baojun,Wu, Wenjun
, p. 11572 - 11581 (2021/10/12)
A series of novel steroidal derivatives with a substituted 1,3,4-oxadiazole structure was designed and synthesized, and the target compounds were evaluated for their insecticidal activity against five aphid species. Most of the tested compounds exhibited potent insecticidal activity against Eriosoma lanigerum (Hausmann), Myzus persicae, and Aphis citricola. Compounds 20g and 24g displayed the highest activity against E. lanigerum, showing LC50 values of 27.6 and 30.4 μg/mL, respectively. Ultrastructural changes in the midgut cells of E. lanigerum were detected by transmission electron microscopy, indicating that these steroidal oxazole derivatives might exert their insecticidal activity by destroying the mitochondria and nuclear membranes in insect midgut cells. Furthermore, a field trial showed that compound 20g exhibited effects similar to those of the positive controls chlorpyrifos and thiamethoxam against E. lanigerum, reaching a control rate of 89.5% at a dose of 200 μg/mL after 21 days. We also investigated the hydrolysis and metabolism of the target compounds in E. lanigerum by assaying the activities of three insecticide-detoxifying enzymes. Compound 20g at 50 μg/mL exhibited inhibitory action on carboxylesterase similar to the known inhibitor triphenyl phosphate. The above results demonstrate the potential of these steroidal oxazole derivatives to be developed as novel pesticides.
Photophysical and Electrochemical Properties of Highly π-Conjugated Bipolar Carbazole-1,3,4-Oxadiazole-based D-π-A Type of Efficient Deep Blue Fluorescent Dye
Najare, Mahesh Sadashivappa,Patil, Mallikarjun Kalagouda,Tilakraj, Tarimakki Shankar,Yaseen, Mohammed,Nadaf, AfraQuasar A,Mantur, Shivaraj,Inamdar, Sanjeev Ramchandra,Khazi, Imtiyaz Ahmed M
, p. 1645 - 1664 (2021/08/16)
In this contribution, we have designed and synthesized a novel carbazole-1,3,4-oxadiazole based bipolar fluorophore (E)-2-(4-(4-(9H-carbazol-9-yl)styryl)phenyl)-5-(4-(tertbutyl) phenyl)-1,3,4-oxadiazole (CBZ-OXA-IV). Wittig reaction is utilised for the synthesis of the designed bipolar target compound CBZ-OXA-IV.1H NMR, 13C NMR, FT-IR and ESI–MS results confirmed the designed chemical structure of the fluorophore CBZ-OXA-IV. The photophysical properties have been investigated in detail using UV–Vis absorption, photoluminescence spectroscopy. Also, the photoluminescence studies on solid state samples (as thin films) were carried out. The CBZ-OXA-IV dye emits intense deep blue fluorescence with observed absorption and emission maxima occurring are at 353?nm and 470?nm, respectively. Fluorophore CBZ-OXA-IV has shown high Stokes shift of 7052?cm?1. The experimentally measured optical band gap (Egopt) value is found to be 3.01?eV and the fluorescence quantum yields (Φf) is 0.40. The intramolecular charge transfer property of CBZ-OXA-IV dye was examined by using photophysical properties such as absorption, emission in different solvents of different varying polarities. In addition, Density Functional Theory computations are studied in detail including the MEP surface plots and natural bond orbital analysis. The electrochemical properties have been investigated in detail by using cyclic voltammetry measurements. Thermal gravimetric analysis (TGA) and differential scanning calorimetry (DSC) measurement results display a high thermal stability with decomposition temperature (Td5%) 387?°C and a large glass transition temperature (Tg) of 98?°C. The obtained results demonstrated that the novel bipolar fluorophore CBZ-OXA-IV could play an important role in organic optoelectronics and possibly can be utilized as bipolar transport materials for electroluminescence applications in optoelectronic devices/OLEDs. Graphical abstract: [Figure not available: see fulltext.]
Using m icrowave and ultrasound to synthesis of substituted bis-acyl hydrazone derivatives
Mohammed, Salim J.,Sheat, Attallah M.,A.abood, Salih,Yahya, Omar M.
, p. 6423 - 6427 (2021/11/01)
In this paper, some new bis-acyl hydrazone derivatives (4a-f) were prepared through the reaction of carboxylic acid hydrazides with 1,4-diacetylbenzene using classical methods, microwave and ultrasound irradiation methods. These compounds are obtained through a series of reactions where some carboxylic acids react with ethanol first in the presence of concentrated sulfuric acid to give the corresponding esters (2a-f), which when treatment with aqueous hydrazine give carboxylic acid hydrazides (3a-f).thus, The results proved that the use of microwave and ultrasound techniques is much better than the classical methods, as it gave a higher yield, shorter reaction time, and the absence of the use of solvents. All newly synthesized compounds were confirmed by IR, (1H & 13C) NMR spectral analysis and the corresponding reactions were monitored by TLC using the reported eluent.
Design and synthesis of pyrimidine-5-carbonitrile hybrids as COX-2 inhibitors: Anti-inflammatory activity, ulcerogenic liability, histopathological and docking studies
Alfayomy, Abdallah M.,Abdel-Aziz, Salah A.,Marzouk, Adel A.,Shaykoon, Montaser Sh. A.,Narumi, Atsushi,Konno, Hiroyuki,Abou-Seri, Sahar M.,Ragab, Fatma A.F.
, (2021/01/04)
Two new series of 1,3,4-oxadiazole and coumarin derivatives based on pyrimidine-5-carbonitrile scaffold have been synthesized and evaluated for their COX-1/COX-2 inhibitory activity. Compounds 10c, 10e, 10h-j, 14e-f, 14i and 16 were found to be the most potent and selective inhibitors of COX-2 (IC50 0.041–0.081 μM, SI 139.74–321.95). Eight compounds were further investigated for their in vivo anti-inflammatory activity. The most active derivatives 10c, 10j and 14e displayed superior in vivo anti-inflammatory activity (% edema inhibition 39.3–48.3, 1 h; 58.4–60.5, 2 h; 70.8–83.2, 3 h; 78.9–89.5, 4 h) to the reference drug celecoxib (% edema inhibition 38.0, 1 h; 48.8, 2 h; 58.4, 3 h; 65.4, 4 h). These derivatives were also tested for their ulcerogenic liability, compound 10j showed better safety profile with reference to celecoxib while 10c and 14e exhibited mild lesions. Molecular docking studies of 10c, 10j, and 14e in the COX-2 active site revealed similar orientation and binding interactions as selective COX-2 inhibitors with a higher liability to access the selectivity side pocket.
Development of Novel (+)-Nootkatone Thioethers Containing 1,3,4-Oxadiazole/Thiadiazole Moieties as Insecticide Candidates against Three Species of Insect Pests
Cheng, Wanqing,Fan, Jiangping,Guo, Yong,Han, Meiyue,Ma, Nannan,Yan, Xiaoting,Yang, Ruige
, p. 15544 - 15553 (2022/01/03)
To improve the insecticidal activity of (+)-nootkatone, a series of 42 (+)-nootkatone thioethers containing 1,3,4-oxadiazole/thiadiazole moieties were prepared to evaluate their insecticidal activities against Mythimna separata Walker, Myzus persicae Sulzer, and Plutella xylostella Linnaeus. Insecticidal evaluation revealed that most of the title derivatives exhibited more potent insecticidal activities than the precursor (+)-nootkatone after the introduction of 1,3,4-oxadiazole/thiadiazole on (+)-nootkatone. Among all of the (+)-nootkatone derivatives, compound 8c (1 mg/mL) exhibited the best growth inhibitory (GI) activity against M. separata with a final corrected mortality rate (CMR) of 71.4%, which was 1.54- and 1.43-fold that of (+)-nootkatone and toosendanin, respectively; 8c also displayed the most potent aphicidal activity against M. persicae with an LD50 value of 0.030 μg/larvae, which was closer to that of the commercial insecticidal etoxazole (0.026 μg/larvae); and 8s showed the best larvicidal activity against P. xylostella with an LC50 value of 0.27 mg/mL, which was 3.37-fold that of toosendanin and slightly higher than that of etoxazole (0.28 mg/mL). Furthermore, the control efficacy of 8s against P. xylostella in the pot experiments under greenhouse conditions was better than that of etoxazole. Structure-activity relationships (SARs) revealed that in most cases, the introduction of 1,3,4-oxadiazole/thiadiazole containing halophenyl groups at the C-13 position of (+)-nootkatone could obtain more active derivatives against M. separata, M. persicae, and P. xylostella than those containing other groups. In addition, toxicity assays indicated that these (+)-nootkatone derivatives had good selectivity to insects over nontarget organisms (normal mammalian NRK-52E cells and C. idella and N. denticulata fries) with relatively low toxicity. Therefore, the above results indicate that these (+)-nootkatone derivatives could be further explored as new lead compounds for the development of potential eco-friendly pesticides.
Unravelling the anticancer potency of 1,2,4-triazole-N-arylamide hybrids through inhibition of STAT3: synthesis and in silico mechanistic studies
Turky, Abdallah,Bayoumi, Ashraf H.,Sherbiny, Farag F.,El-Adl, Khaled,Abulkhair, Hamada S.
, p. 403 - 420 (2020/08/25)
Abstract: The discovery of potent STAT3 inhibitors has gained noteworthy impetus in the last decade. In line with this trend, considering the proven biological importance of 1,2,4-triazoles, herein, we are reporting the design, synthesis, pharmacokinetic profiles, and in vitro anticancer activity of novel C3-linked 1,2,4-triazole-N-arylamide hybrids and their in silico proposed mechanism of action via inhibition of STAT3. The 1,2,4-triazole scaffold was selected as a privilege ring system that is embedded in core structures of a variety of anticancer drugs which are either in clinical use or still under clinical trials. The designed 1,2,4-triazole derivatives were synthesized by linking the triazole-thione moiety through amide hydrophilic linkers with diverse lipophilic fragments. In silico study to predict cytotoxicity of the new hybrids against different kinds of human cancer cell lines as well as the non-tumor cells was conducted. The multidrug-resistant human breast adenocarcinoma cells (MDA-MB-231) was found most susceptible to the cytotoxic effect of synthesized compounds and hence were selected to evaluate the in vitro anticancer activity. Four of the designed derivatives showed promising cytotoxicity effects against selected cancer cells, among which compound 12 showed the highest potency (IC50 = 3.61?μM), followed by 21 which displayed IC50 value of 3.93?μM. Also, compounds 14 and 23 revealed equipotent activity with the reference cytotoxic agent doxorubicin. To reinforce these observations, the obtained data of in vitro cytotoxicity have been validated in terms of ligand–protein interaction and new compounds were analyzed for ADMET properties to evaluate their potential to build up as good drug candidates. This study led us to identify two novel C3-linked 1,2,4-triazole-N-arylamide hybrids of interesting antiproliferative potentials as probable lead inhibitors of STAT3 with promising pharmacokinetic profiles. Graphic abstract: [Figure not available: see fulltext.]
