- Design, synthesis and biological evaluation of novel 1, 3, 4-oxadiazole derivatives as potent neuraminidase inhibitors
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Neuraminidase (NA) is an important target in the development of anti-influenza virus drugs. Compounds containing 1,3, 4-oxadiazole heterocycles have good biological activity and have been proved to have wide applications in antibacterial and antiviral drugs. In this paper, a series of novel 1, 3, 4-oxadiazole neuraminidase inhibitors (6a-6l) were designed and synthesized and their inhibitory activities of NA was tested in vitro. The results displayed that compound 6d exerts the best inhibitory activity (IC50 = 0.027 μM), which was obviously lower than that of oseltamivir carboxylate (OSC) (IC50 = 0.082 μM). Molecular docking analysis showed that the 1, 3, 4-oxadiazole heterocycle plays crucial part in compound 6d, and it can interact with the key arginine triad (Arg118, Arg292 and Arg 371) at the NA S1 site. The good efficacy of 6d may also be attributed to the extension of the substituted aniline ring to the 150-cavitiy. The theoretical and experimental results may provide reference for development of new anti-influenza drugs.
- Ling Guo, Ling,Pang, Wan,Ping Cheng, Li,Yu, Wei
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supporting information
(2022/02/05)
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- Pleuromutilin derivative with 1, 3, 4-oxadiazole side chain and preparation and application thereof
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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.
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Paragraph 0055-0056; 0070; 0090; 0094; 0095; 0103
(2021/07/24)
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- Ultrasound-assisted, low-solvent and acid/base-free synthesis of 5-substituted 1,3,4-oxadiazole-2-thiols as potent antimicrobial and antioxidant agents
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Abstract: One of the goals of green chemistry is to use environmentally friendly solvents or remove and reduce the volume of harmful spent solvents. In this study, a novel process for the synthesis of 5-substituted 1,3,4-oxadiazole-2-thiol derivatives was proposed via ultrasound-assisted reaction of aryl hydrazides with CS2 (1:1 molar ratio) in some drops of DMF in the absence of basic or acidic catalysts. They were produced in good to excellent yields under easy workup and purification conditions. In order to prove the usefulness of the prepared compounds, their antioxidant, antibacterial, and antifungal potentials were screened by DPPH free radical scavenging, serial twofold microdilution and streak plate methods. Acceptable to significant inhibitory activities were observed with synthesized heterocycles. The results showed that 5-(4-fluorophenyl)-1,3,4-oxadiazole-2-thiol (3c) is an broad-spectrum antimicrobial agent. Many of them displayed remarkable antioxidant properties comparable to standard controls (ascorbic acid and α-tocopherol). Synthesized 1,3,4-oxadiazoles are also potent candidates to treat cancer, Parkinson, inflammatory, and diabetes diseases. Graphic Abstract: Eighteen 5-substituted 1,3,4-oxadiazole-2-thiol derivatives as potent antimicrobial and antioxidant agents were prepared via a new, efficient and green procedure.[Figure not available: see fulltext.].
- Yarmohammadi, Elahe,Beyzaei, Hamid,Aryan, Reza,Moradi, Ashraf
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p. 2367 - 2378
(2020/08/10)
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- Design, synthesis, in vitro and in vivo evaluation against MRSA and molecular docking studies of novel pleuromutilin derivatives bearing 1, 3, 4-oxadiazole linker
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A class of pleuromutilin derivatives containing 1, 3, 4-oxadiazole were designed and synthesized as potential antibacterial agents against Methicillin-resistant staphylococcus aureus (MRSA). The ultrasound-assisted reaction was proposed as a green chemistry method to synthesize 1, 3, 4-oxadiazole derivatives (intermediates 85–110). Among these pleuromutilin derivatives, compound 133 was found to be the strongest antibacterial derivative against MRSA (MIC = 0.125 μg/mL). Furthermore, the result of the time-kill curves displayed that compound 133 could inhibit the growth of MRSA in vitro quickly (- 4.36 log10 CFU/mL reduction). Then, compound 133 (- 1.82 log10 CFU/mL) displayed superior in vivo antibacterial efficacy than tiamulin (- 0.82 log10 CFU/mL) in reducing MRSA load in mice thigh model. Besides, compound 133 exhibited low cytotoxicity to RAW 264.7 cells. Molecular docking studies revealed that compound 133 was successfully localized in the binding pocket of 50S ribosomal subunit (ΔGb = -10.50 kcal/mol). The results indicated that these pleuromutilin derivatives containing 1, 3, 4-oxadiazole might be further developed into novel antibiotics against MRSA.
- Liu, Jie,Zhang, Guang-Yu,Zhang, Zhe,Li, Bo,Chai, Fei,Wang, Qi,Zhou, Zi-Dan,Xu, Ling-Ling,Wang, Shou-Kai,Jin, Zhen,Tang, You-Zhi
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- Antibacterial and Antiviral Activities of 1,3,4-Oxadiazole Thioether 4H-Chromen-4-one Derivatives
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Various 1,3,4-oxadiazole thioether 4H-chromen-4-one derivatives were conceived. The title compounds demonstrated striking inhibitory effects againstXac,Psa, andXoo. EC50data exhibited that A8 (19.7 μg/mL) had better antibacterial activity againstXoothan myricetin, BT, and TC. Simultaneously, the mechanism of action of A8 had been verified by SEM. The results of anti-tobacco mosaic virus indicated that A9 had the bestin vivoantiviral effect compared with ningnanmycin. From the data of MST, it could be seen that A9 (0.003 ± 0.001 μmol/L) exhibited a strong binding capacity, which was far superior to ningnanmycin (2.726 ± 1.301 μmol/L). This study shows that the 1,3,4-oxadiazole thioether 4H-chromen-4-one derivatives may become agricultural drugs with great potential.
- Cao, Xiao,Liu, Fang,Liu, Liwei,Liu, Tingting,Peng, Feng,Wang, Qifan,Xie, Chengwei,Xue, Wei,Yang, Jinsong
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p. 11085 - 11094
(2021/10/01)
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- Development of Novel (+)-Nootkatone Thioethers Containing 1,3,4-Oxadiazole/Thiadiazole Moieties as Insecticide Candidates against Three Species of Insect Pests
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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.
- Cheng, Wanqing,Fan, Jiangping,Guo, Yong,Han, Meiyue,Ma, Nannan,Yan, Xiaoting,Yang, Ruige
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p. 15544 - 15553
(2022/01/03)
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- Synthesis, crystal structures, computational studies and α-amylase inhibition of three novel 1,3,4-oxadiazole derivatives
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Oxadiazoles have broad range of biological applications and have been investigated widely by the scientific community. In this study, we report the synthesis, X-ray diffraction, density functional theory (DFT) and α-amylase inhibition activities of three 1,3,4-oxadiazole derivatives (1–3). The compounds are synthesized in good yields (70–83%) and their structures are confirmed through different spectro-analytical techniques and single crystal X-ray diffraction. Density functional theory (DFT) calculations are performed to validate not only X-ray results, but also to investigate the dispersion of charges and reactivity through frontier molecular orbitals and molecular electrostatic potential (MEP) analyses. α-Amylase inhibition assay is performed in order to find out the enzyme inhibitory potential of the synthesized compounds (1–3). The low IC50 value (86.83 ± 0.23 μg/mL) of compound 2 reflects the potential α-amylase inhibitory activity of the compound as compared to others.
- Hamdani, Syeda Shamila,Khan, Bilal Ahmad,Ahmed, Muhammad Naeem,Hameed, Shahid,Akhter, Kulsoom,Ayub, Khurshid,Mahmood, Tariq
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- Rational Optimization and Action Mechanism of Novel Imidazole (or Imidazolium)-Labeled 1,3,4-Oxadiazole Thioethers as Promising Antibacterial Agents against Plant Bacterial Diseases
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The emergence and widespread occurrence of plant bacterial diseases that cause global production constraints have become major challenges to agriculture worldwide. To promote the discovery and development of new bactericides, imidazole-labeled 1,3,4-oxadiazole thioethers were first fabricated by integrating the crucially bioactive scaffolds of the imidazole motif and 1,3,4-oxadiazole skeleton in a single molecular architecture. Subsequently, a superior antibacterial compound A6 was gradually discovered possessing excellent competence against plant pathogens Xanthomonas oryzae pv oryzae and Xanthomonas axonopodis pv citri with EC50 values of 0.734 and 1.79 μg/mL, respectively. These values were better than those of commercial agents bismerthiazol (92.6 μg/mL) and thiodiazole copper (77.0 μg/mL). Further modifying the imidazole moiety into the imidazolium scaffold led to the discovery of an array of potent antibacterial compounds providing the corresponding minimum EC50 values of 0.295 and 0.607 μg/mL against the two strains. Moreover, a plausible action mechanism for attacking pathogens was proposed based on the concentration dependence of scanning electron microscopy, transmission electron microscopy, and fluorescence microscopy images. Given the simple molecular structures, easy synthetic procedure, and highly efficient bioactivity, imidazole (or imidazolium)-labeled 1,3,4-oxadiazole thioethers can be further explored and developed as promising indicators for the development of commercial drugs.
- Wang, Pei-Yi,Wang, Ming-Wei,Zeng, Dan,Xiang, Meng,Rao, Jia-Rui,Liu, Qing-Qing,Liu, Li-Wei,Wu, Zhi-Bing,Li, Zhong,Song, Bao-An,Yang, Song
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p. 3535 - 3545
(2019/03/26)
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- Synthesis and bioactivity of sulfide derivatives containing 1,3,4-oxadiazole and pyridine
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A series of novel sulfide derivatives containing 1,3,4-oxadiazole and pyridine were synthesized, characterized, and tested for their antibacterial activity against tobacco bacterial wilt and rice bacterial blight and for insecticidal activity toward diamondback moth. The results showed that some compounds had good insecticidal and bactericidal activity, e.g., the activities of compounds 6e and 6g–6j toward tobacco bacterial wilt were much better than those of commercial thiodiazole-copper, and some of the synthesized compounds possessed good insecticidal activity against Plutella xylostella. Compounds 6d, 6h, 6j, 6l, 6p, 6r, and 6p displayed over 93% activity at 500 mg L? 1.
- Yu, Gang,Chen, Shunhong,He, Feng,Luo, Dexia,Zhang, Yu,Wu, Jian
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p. 1075 - 1085
(2019/09/10)
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- Microwave assisted synthesis and evaluation of some substituted 1,3,4-oxadiazoles as free radical scavenger
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A series of 5-(4-substituted phenyl)-1,3,4-oxadiazoles (4a-h) were prepared from 4-substituted benzoic acid hydrazides (3a-h). Structures of the synthesized compounds were confirmed on the basis of IR, 13C NMR, Mass spectral methods and elemental analysis. The compounds were screened for antioxidant activities using hydrogen peroxide scavenging method comparing with ascorbic acid as standard antioxidant. The results reveal that the compounds possess significant free radical scavenging activities. It is recommended that these compounds might be used in future to generate derivatives for emerging free radical scavenger.
- Upadhyay, Prabhat Kumar,Mishra, Pradeep
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p. 661 - 666
(2020/07/02)
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- Design, Synthesis and Evaluation of Antitubercular Activity of Novel 1,2,4-Triazoles Against MDR Strain of Mycobacterium tuberculosis
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Emergence of various forms of resistant strains of Mycobacterium tuberculosis led to the exploration of drugs with novel mechanism of action. Recently econazole, an azole based antitubercular agent, attracted major attention for targeting mycobacterial cytochrome P450. In the present study, we designed novel 1,2,4-triazole derivatives based on econazole moiety and evaluated them for in vitro antitubercular activity against M. tuberculosis H37Rv and multi-drug resistant (MDR) strains of Mycobacterium.
- Ganesh Kumar,Gautham Shenoy,Kar, Sidhartha Sankar,Shenoy, Vishnu,Bairy, Indira
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p. 907 - 917
(2018/02/07)
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- Synthesis and biological activities of cyclanone O-(2-(3-aryl-4- amino-4H-1,2,4-triazol-3-yl)thio)acetyl)oxime derivatives
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Twelve cyclanone O-(2-(3-aryl-4-amino-4H-1,2,4-triazol-3-yl)thio)acetyl)oxime derivatives were synthesized and their structures were confirmed by spectroscopy (IR, 1H NMR, 13C NMR, 19F NMR) and elemental analysis. Their antifungal and antibacterial activities were evaluated against six fungi (Gibberella zeae, Fusarium oxysporum, Clematis mandshurica, Phytophthora infestans, Paralepetopsis sasakii, Sclerotinia sclerotiorum) and two bacteria (Xanthomonas oryzae pv. oryzae (Xoo), Xanthomonas citri subsp. Citri (Xcc)). The results indicated that most of the title compounds exhibited good antibacterial activities. Among them, compounds 6d, 6g, 6h, and 6j showed better antibacterial activities against Xoo and Xcc than that of the commercial agent thiodiazole-copper.
- Chen, Meihang,Chen, Lijuan,Zhu, Xuesong,Wang, Xiaobin,Li, Qin,Zhang, Juping,Lu, Daowang,Xue, Wei
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p. 1259 - 1263
(2017/10/18)
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- Synthesis and Biological Activity of Anthranilic Diamide Derivatives Incorporating 1,3,4-oxadiazole or Nitrogen-containing Saturated Heterocyclic Moieties
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A series of novel anthranilic diamide derivatives incorporating 1,3,4-oxadiazole or nitrogen-containing saturated heterocyclic moieties were synthesized, characterized, and evaluated for bacteriostatic activity against three phytopathogenic bacteria Xanthomonas oryzae pv. Oryzae (Xoo), Xanthomonas axonopodis pv. Citri (Xac), Ralstonia solanacearum (R. solanacearum). The preliminary biological results indicated that most compounds exhibit bacteriostatic activity against three phytopathogenic bacteria. Among these compounds, compounds 6g, 6f, and 6i displayed better antibacterial activity. In the test with concentration of 200 μg/mL, antibacterial activity of compound 6i and 6j was 96%. In particular, the bacteriostatic activity displayed by compound 6h against Xoo is similar to the one displayed by commercial drug bismerthiazol.
- Zhou, Wen-Juan,Zhang, Li,Xiao, Wei,Chen, He-Ju,Wu, Wen-Neng,Ouyang, Gui-Ping
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p. 1423 - 1429
(2017/03/27)
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- Design, synthesis, biological evaluation, and 3D-QSAR analysis of podophyllotoxin–dioxazole combination as tubulin targeting anticancer agents
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The advancement of cancer-fighting drugs has never been a simple linear process. Those drug design professionals begin to find inspiration from the nature after failing to find the ideal products by creative drug design and high-throughput screening. To obtain new molecules for inhibiting tubulin, podophyllotoxin was adopted as the leading compound and 1,3,4-oxadiazole was brought in to the C-4 site of podophyllotoxin in this research. A series of seventeen podophyllotoxin-derived esters have been achieved and then evaluated their antitumor activities against four different cancer cell lines: A549, MCF-7, HepG2, and HeLa. Among all the compounds, compound 7c showed the best antiproliferating properties with IC50?=?2.54?±?0.82?μm against MCF-7 cancer cell line. It was obvious that the content of ROS grew significantly in MCF-7 in a way depending on the dosage. The time- and dose-dependent cell cycle assays revealed that compound 7c could apparently block cell cycle in the phase of G2/M along with the upregulation of cyclin A2 and CDK2 protein. According to further studies, confocal microscopy experiment has certified that compound 7c could restrain cancer from growing by blocking the polymerization of microtubule. Meanwhile, compound 7c could be ideally integrated with the colchicine site of tubulin. In future, it would be feasible to selectively design tubulin inhibitors with the help of 3D-QSAR. This means that it is hopeful to develop compound 7c as a potential agent against cancer due to its biological characteristics.
- Wang, Zi-Zhen,Sun, Wen-Xue,Wang, Xue,Zhang, Ya-Han,Qiu, Han-Yue,Qi, Jin-Liang,Pang, Yan-Jun,Lu, Gui-Hua,Wang, Xiao-Ming,Yu, Fu-Gen,Yang, Yong-Hua
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p. 236 - 243
(2017/07/13)
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- Containing 1, 3, 4 - oxadiazole of thio pentadiene ketone compound of preparation method and use thereof
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The invention discloses a preparation method and biological activity of a pentadiene ketone compound, containing 1,3,4-oxadiazole sulfo-ethyoxyl, with a function of preventing and treating a plant virus disease, namely a compound expressed in a general formula (I) and a preparation method of the compound. According to the method, by using substituted carboxylic acid, hydrazine hydrate, carbon disulfide, acetone, 4-substituted hydroxy benzaldehyde, substituted aromatic aldehyde, 1,2-dibromoethane and the like as raw materials, methanol, ethanol and N,N-dimethylformamide as solvents and potassium carbonate, sodium hydroxide and potassium hydroxide as catalysts, pentadiene ketone compound containing 1,3,4-oxadiazole sulfo-ethyoxyl is prepared through seven-step synthesis. The compounds I3, I4, I6, I11, I13, I14, I16 and I17 have good functions in cucumber mosaic virus, tobacco mosaic virus, southern rice black-streaked dwarf virus and the like. The formula is shown in the specification.
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Paragraph 0113; 0114
(2017/07/31)
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- A containing methanesulfonyl fungus zuo and organic copper germicide compound composition and preparation
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The invention relates to a compound composition with methanesulphonyl myclobutanil and an organic copper bactericide and a preparation. The compound composition consists of methanesulphonyl myclobutanil and the organic copper bactericide, wherein the orga
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Paragraph 0028-0029
(2017/08/25)
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- A containing methanesulfonyl fungus zuo and plant growth regulator compound composition and preparation
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The invention provides a compound composition containing methanesulphonyl myclobutanil and a plant growth regulator and a preparation. The compound composition consists of the methanesulphonyl myclobutanil and the plant growth regulator, wherein the weigh
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Paragraph 0038; 0039
(2017/09/13)
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- A containing methanesulfonyl fungus zuo and new nicotinamide insecticide compound composition
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The invention discloses a compound composition and a preparation thereof. The compound composition consists of methanesulphonyl myclobutanil and a neonicotinoid insecticide, wherein the chemical name of the methanesulphonyl myclobutanil is 2-(p-fluorophen
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Paragraph 0008; 0018-0019
(2017/09/13)
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- Synthesis and biological evaluation of 1,2,4-triazole-3-thione and 1,3,4-oxadiazole-2-thione as antimycobacterial agents
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Resistance among dormant mycobacteria leading to multidrug-resistant and extremely drug-resistant tuberculosis is one of the major threats. Hence, a series of 1,2,4-triazole-3-thione and 1,3,4-oxadiazole-2-thione derivatives (4a–5c) have been synthesized and screened for their antitubercular activity against Mycobacterium tuberculosis H37Ra (H37Ra). The triazolethiones 4b and 4v showed high antitubercular activity (both MIC and IC50) against the dormant H37Ra by in vitro and ex vivo. They were shown to have more specificity toward mycobacteria than other Gram-negative and Gram-positive pathogenic bacteria. The cytotoxicity was almost insignificant up to 100?μg/ml against THP-1, A549, and PANC-1 human cancer cell lines, and solubility was high in aqueous solution, indicating the potential of developing these compounds further as novel therapeutics against tuberculosis infection.
- Sonawane, Amol D.,Rode, Navnath D.,Nawale, Laxman,Joshi, Rohini R.,Joshi, Ramesh A.,Likhite, Anjali P.,Sarkar, Dhiman
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p. 200 - 209
(2017/07/13)
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- Synthesis and biological evaluation of novel resveratrol-oxadiazole hybrid heterocycles as potential antiproliferative agents
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A novel class of resveratrol-oxadiazole hybrid compounds was synthesized to screen for their in vitro antiproliferative activity against three human cancer cell lines. All the compounds showed superior antiproliferative activity than the reference compound resveratrol. The most promising active compounds in this series were 1g, 2g, 1c, 2c, 2i and 1a (GI50 0.1 μM), endowed with excellent antiproliferative activity. Thus, we believe that resveratrol-oxadiazole hybrid compounds may possibly be used as a good leads for the development of new antiproliferative agents. Structures of newly synthesized compounds were confirmed by NMR and IR spectral data.
- Murty,Penthala, Raju,Polepalli, Sowjanya,Jain
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p. 627 - 643
(2016/03/08)
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- Rational design, synthesis and biological evaluation of 1,3,4-oxadiazole pyrimidine derivatives as novel pyruvate dehydrogenase complex E1 inhibitors
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On the basis of previous study on 2-methylpyrimidine-4-ylamine derivatives I, further synthetic optimization was done to find potent PDHc-E1 inhibitors with antibacterial activity. Three series of novel pyrimidine derivatives 6, 11 and 14 were designed and synthesized as potential Escherichia coli PDHc-E1 inhibitors by introducing 1,3,4-oxadiazole-thioether, 2,4-disubstituted-1,3-thiazole or 1,2,4-triazol-4-amine-thioether moiety into lead structure I, respectively. Most of 6, 11 and 14 exhibited good inhibitory activity against E. coli PHDc-E1 (IC50 0.97-19.21 μM) and obvious inhibitory activity against cyanobacteria (EC50 0.83-9.86 μM). Their inhibitory activities were much higher than that of lead structure I. 11 showed more potent inhibitory activity against both E. coli PDHc-E1 (IC50 50 50 = 0.97 μM) and cyanobacteria (EC50 = 0.83 μM). The possible interactions of the important residues of PDHc-E1 with title compounds were studied by molecular docking, site-directed mutagenesis, and enzymatic assays. The results indicated that 11d had more potent inhibitory activity than that of 14d or I due to its 1,3,4-oxadiazole moiety with more binding position and stronger interaction with Lsy392 and His106 at active site of E. coli PDHc-E1.
- He, Haifeng,Wang, Wei,Zhou, Yuan,Xia, Qin,Ren, Yanliang,Feng, Jiangtao,Peng, Hao,He, Hongwu,Feng, Lingling
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p. 1879 - 1888
(2016/04/05)
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- 1,2,4-TRIAZOLE, 1,3,4-OXADIAZOLE, AND 1,3,4-THIADIAZOLE DERIVATIVES AND THEIR ANTIMYCOBACTERIAL ACTIVITY
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Disclosed herein are novel five membered heterocyclic compounds of Formula (I) wherein, X is S or SO2; n is 0, 1; m is1 or 2; Y is N, O or S; R2 independently represents H or alkyl or halo selected from -CI, -F; or -CF3, or -OH or-NH2 or - NO2; and R1 independently represents H or C1 to C5 straight or branched chain alkyl, alkenyl, alkynyl or a group -(CH2)5Br or pyrrolidine or - NHR' wherein R' is H or isopropyl or (II) or (III) which selectively act against dormant pathogenic tuberculi bacilli and exhibit antiproliferative activities and for treatment of a disease or disorder associated with GroEL1/GroEL2 activity. The invention relates to a process for preparation of novel five membered heterocyclic compounds of Formula I and to pharmaceutical compositions thereof.
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Paragraph 053
(2016/07/27)
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- Antiviral and Antibacterial Activities of N-(4-Substituted phenyl) Acetamide Derivatives Bearing 1,3,4-Oxadiazole Moiety
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In this paper, a series of N-(4-substituted phenyl) acetamide derivatives bearing 1,3,4-oxadiazole moiety were synthesised. Preliminary bioassays revealed that these compounds not only exhibited favourable antiviral activities toward tobacco mosaic virus (TMV) but also demonstrated sustained inhibition activities against plant pathogenic bacteria, including Xanthomonas oryzae pv. oryzae, Ralstonia solanacearum, and Xanthomonas axonopodis pv. citri. Among the derivatives, TC8and TC20exerted the strongest curative activities against TMV, with half-maximal effective concentration (EC50) values of 239.5 and 236.2 μg/mL, respectively, which were comparable to that of ningnanmycin (EC50=273.2 μg/mL). Given their simple synthesis, the target compounds can serve as alternative antiviral candidates.
- Chen, Ling,Wang, Peiyi,Li, Zhenxing,Zhou, Lei,Wu, Zhibing,Song, Baoan,Yang, Song
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p. 1236 - 1244
(2016/12/27)
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- A containing methanesulfonyl [...] desinsection sterilizing composition and preparation (by machine translation)
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This invention discloses a containing methanesulfonyl [...] desinsection sterilizing composition and its preparation, the pesticide and sterilizing composition containing methanesulfonyl [...] and insecticidal compound II, wherein the insecticidal compoun
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Paragraph 0021-0022
(2017/04/03)
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- A containing methanesulfonyl [...] and leaf die azoles compound composition and preparation
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The invention discloses a compound composition and a preparation thereof. The compound composition comprises two active ingredients, the first active ingredient is methylsulfonyl azole, and the second active ingredient is bismerthiazol, wherein the weight ratio of the first active ingredient to the second active ingredient is (20-1):(1-40); and the chemical name of methylsulfonyl azole is 2-(4-fluorophenyl)-5-methylsulfonyl-1,3,4-oxadiazole. The compound composition can be used for effectively preventing and controlling bacterial diseases, and has a remarkable synergetic effect relatively to a single agent, the using amount and application times of pesticide can be reduced, the drug resistance of pathogenic bacteria can be retarded, and the prevention and control effect can be improved. Methylsulfonyl azole and bismerthiazol have high safety, and can be used for better guaranteeing safe production of agriculture and protecting the ecological environment.
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Paragraph 0008; 0018; 0019
(2017/04/03)
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- A containing methanesulfonyl [...] and azoxystrobin compound composition and preparation
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The invention discloses a compound composition and a preparation thereof. The compound composition is prepared from methylsulfonyl azole and azoxystrobin, wherein the chemical name of methylsulfonyl azole is 2-(4-fluorophenyl)-5-methylsulfonyl-1,3,4-oxadi
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Paragraph 0018-0019
(2017/04/04)
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- A containing methanesulfonyl [...] and enemy sulphur sodium compound composition and preparation
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The invention provides a compound composition containing 2-(p-fluorophenyl)-5-methanesulfonyl-1,3,4-oxadiazole and leasn. The compound composition is composed of 2-(p-fluorophenyl)-5-methanesulfonyl-1,3,4-oxadiazole and leasn, wherein the weight ratio of
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Paragraph 0019; 0020
(2017/04/19)
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- A containing methanesulfonyl [...] compound composition and preparation
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The invention discloses a compound composition and a preparation. The compound composition contains two active components; the first active component is methanesulfonyl bacteria oxazole; the second active component is selected from any one of fosthiazate,
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Paragraph 0021; 0022
(2017/05/12)
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- A containing methanesulfonyl [...] and flutriafol fungicide compound composition and
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The invention provides a compound composition with a synergistic effect. The compound composition comprises active components, namely 2-(p-fluorophenyl)-5-methanesulfonyl-1,3,4-oxadiazole and flutriafol, wherein the weight ratio of 2-(p-fluorophenyl)-5-me
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Paragraph 0018; 0019
(2017/05/12)
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- A containing methanesulfonyl [...] and [...] amide compound composition and preparation
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The invention discloses a compound composition containing methanesulphonyl myclobutanil and thifluzamide and a preparation. The compound composition consists of the methanesulphonyl myclobutanil and the thifluzamide, wherein the chemical name of the metha
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Page/Page column 0018; 0019
(2018/02/04)
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- Synthesis and Biological Activity of Some Novel Aryl-Substituted 1,3,4-Oxadiazole Mannich Bases Containing Pyrimidine Rings
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A series of novel Mannich base derivatives (E1-E15) of 5-aryl-1,3,4-oxadiazole-2-thione with substituted pyrimidine were synthesized and characterized by elemental analysis, IR, 1H-NMR. The antifungal activities of these compounds were also originally studied. The results showed that most of the title compounds exhibited relatively good fungicidal activities. Especially compounds E8 and E13 showed better antifungal activity than comparison compound hymexazol. The relationship of structure and activity revealed that the presence of the methyl group at four and six positions of pyrimidine ring remarkably enhanced the antifungal activity of title compounds.
- Shen, Shengqiang,Sun, Xiaohong,Liu, Yuanfa,Chen, Bang,Jin, Ruyi,Ma, Haixia
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p. 1296 - 1301
(2015/10/06)
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- Ultrasound-assisted, one-pot, three-component synthesis and antibacterial activities of novel indole derivatives containing 1,3,4-oxadiazole and 1,2,4-triazole moieties
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Thirteen novel indole derivatives were efficiently synthesized through ultrasound irradiation by using 4-amino-5-(1H-indol-3-yl)-4H-[1,2,4]triazole-3-thiol (8) and 2-mercapto-5-substituted-1,3,4-oxadiazoles (5a-m). Compared with conventional and microwave methods, yields increased to 82-93%, and reaction times decreased to 15-35 min. The structures of these novel compounds were characterized by spectral data and elemental analysis. Two out of the synthesized compounds (10f and 10l) exhibited excellent activity against Staphylococcus aureus and Escherichia coli, and thus warrant further research.
- Shi, Zhichuan,Zhao, Zhigang,Huang, Meiwei,Fu, Xiaolin
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p. 1320 - 1327
(2015/12/11)
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- Antibacterial activities against rice bacterial leaf blight and tomato bacterial wilt of 2-mercapto-5-substituted-1,3,4-oxadiazole/thiadiazole derivatives
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In this study, a series of 2-mercapto-5-substituted-1,3,4-oxadiazole/thiadiazole derivatives were synthesized and evaluated for their antibacterial activities against rice bacterial leaf blight and tomato bacterial wilt caused by Xanthomonas oryzae pv. oryzae (Xoo) and Ralstonia solanacearum (R. solanacearum) via the turbidimeter test in vitro. Antibacterial bioassays indicated that most compounds demonstrated appreciable antibacterial bioactivities against Xoo and R. solanacearum. Among the title compounds, compound 4i demonstrated the best inhibitory effect against Xoo and R. solanacearum with half-maximal effective concentration (EC50) values of 14.69 and 15.14 μg/mL, respectively, which were even better than those of commercial agents Bismerthiazol and Thiodiazole Copper. In vivo antibacterial activities tests under greenhouse conditions revealed that the control efficiency of compound 4i against rice bacterial leaf blight and tobacco bacterial wilt were better than those of Bismerthiazol and Thiodiazole Copper. Meanwhile, field trials also indicated that compound 4i demonstrated appreciable control efficiency against rice bacterial leaf blight and tomato bacterial wilt.
- Li, Pei,Shi, Li,Gao, Man-Ni,Yang, Xia,Xue, Wei,Jin, Lin-Hong,Hu, De-Yu,Song, Bao-An
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supporting information
p. 481 - 484
(2015/02/18)
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- Synthesis, characterization and antimicrobial activities of mercaptoxadiazoles, mercaptotriazoles and their derivatives
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Five member heterocycles are famous for their universal activities. Starting with suitably substituted hydrazides 1,3,4-oxadiazole-2-thiones (1-5) and 1,2,4-triazolethionamines (6-11) were synthesized which were later on converted into Mannich products (13-22) and traizolothiadiazines (23-28) respectively. Structures were established by FTIR, hydrogen, carbon NMR, and mass spectrometric analysis. Compounds were evaluated for their antimicrobial studies. Compounds 13, 19 and 23 showed maximum inhibitions in opposition to the bacterial strains while compounds 7, 11, 13 and 27 showed utmost percentage inhibition aligned with the yeast cells.
- Mumtaz, Amara,Saeed, Aamer,Malik, Imran
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p. 852 - 857
(2015/01/30)
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- Synthesis and evaluation of novel azoles as potent antifungal agents
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Using a rational approach to the design of antifungal agents, a series of azole agents with 1,3,4-oxadiazole side chains were designed and synthesized. The results of preliminary in vitro antifungal tests with eight human pathogenic compounds showed that all of the title compounds exhibited excellent activities against all of the tested fungi except Aspergillus fumigatus. Compounds 11e and 11f were found to be the most effective, with a minimum inhibitory concentration of 0.0039 μg/mL, followed by voriconazole, which has a MIC of 0.0625 μg/mL. The 1,3,4-oxadiazole side chain is not the major contributor but plays a role in eliciting the observed antifungal activity.
- Li, Liangjing,Ding, Hao,Wang, Baogang,Yu, Shichong,Zou, Yan,Chai, Xiaoyun,Wu, Qiuye
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supporting information
p. 192 - 194
(2014/01/17)
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- Synthesis and evaluation of 2-(5-(aryl)-1,3,4-oxadiazol-2-ylthio)-N-(3- (trifluoromethyl)phenyl)acetamides and N-(4-chloro-3-fluorophenyl)-2-(5-(aryl)- 1,3,4-oxadiazol-2-ylthio)acetamides as antimicrobial agents
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A series of 2-mercapto-5-phenyl-1,3,4-oxadiazole derivatives have been condensed with different phenyl acetamide derivatives possessing fluorine atom at meta position; resulting in the formation of 2-(5-aryl-1,3,4-oxadiazol-2- ylthio)-N-(3-(trifluoromethyl)phenyl)acetamide (5a-j) and N-(4-chloro-3- fluorophenyl)-2-(5-aryl-1,3,4-oxadiazol-2-ylthio)acetamide (5k-t) derivatives. The antimicrobial properties of the synthesized entities (5a-t) measured as their MIC (Minimum Inhibitory Concentration) values were evaluated by using the broth dilution method against Gram-positive bacteria (S. aureus and E. faecalis), Gram-negative bacteria (E. coli and P. aeruginosa) and fungi (C. albicans and A. niger). The results of antimicrobial activities (in μg/ml) revealed the fact that the compounds 5a and g bearing a maximum number of fluorine atoms showed the highest potency among the synthesized compounds against the broad panel of bacterial and fungal strains. The presence of fluorine atom at the meta position in the phenyl ring of final derivatives (5a-t) brought about an enhancement of their antimicrobial properties to a notable extent.
- Parikh, Kalpesh,Joshi, Deepkumar
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p. 827 - 835
(2014/07/07)
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- Novel 1,3,4-oxadiazole thioether derivatives targeting thymidylate synthase as dual anticancer/antimicrobial agents
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A series of novel 1,3,4-oxadiazole thioether derivatives (compounds 9-44) were designed and synthesized as potential inhibitors of thymidylate synthase (TS) and as anticancer agents. The in vitro anticancer activities of these compounds were evaluated against three cancer cell lines by the MTT method. Among all the designed compounds, compound 18 bearing a nitro substituent exhibited more potent in vitro anticancer activities with IC50 values of 0.7 ± 0.2, 30.0 ± 1.2, 18.3 ± 1.4 μM, respectively, which was superior to the positive control. In the further study, it was identified as the most potent inhibitor against two kinds of TS protein (for human TS and Escherichia coli TS, IC50 values: 0.62 and 0.47 μM, respectively) in the TS inhibition assay in vitro and the most potent antibacterial agents with MIC (minimum inhibitory concentrations) of 1.56-3.13 μg/mL against the tested four bacterial strains. Molecular docking and 3D-QSAR study supported that compound 18 can be selected as dual antitumor/antibacterial candidate in the future study.
- Du, Qian-Ru,Li, Dong-Dong,Pi, Ya-Zhou,Li, Jing-Ran,Sun, Jian,Fang, Fei,Zhong, Wei-Qing,Gong, Hai-Bin,Zhu, Hai-Liang
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p. 2286 - 2297
(2013/05/09)
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- Synthesis of piperazinyl benzothiazole/benzoxazole derivatives coupled with 1,3,4-oxadiazole-2-thiol: Novel hybrid heterocycles as anticancer agents
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The synthesis of a series of substituted 2-(piperazin-1-yl)benzothiazole/ benzoxazole coupled with 1,3,4-oxadiazole-2-thiol pharmacophore (8a-t) is described using a three carbon spacer (Jones and Helm, Drugs 69:1903-1910, 2009). The structures of the compounds were confirmed by NMR and mass spectral data. All the synthesized compounds have been evaluated for their cytotoxicity towards five human cancer cell lines of different origins, viz. MCF-7 (Breast), HeLa (Cervical), HepG2 (Liver), A431 (Skin) and A549 (Lung), and IC50 values were determined. Among the compounds tested, 8j and 8t displayed maximum cytotoxic activity. A431 was the most sensitive cell line against the compounds studied, followed by MCF7, A549, HepG2 and HeLa.
- Murty,Ramalingeswara Rao,Katiki, Mohana Rao,Nath, Lekshmi R.,Anto, Ruby John
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p. 4980 - 4991
(2013/09/23)
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- Design, synthesis and biological evaluation of novel arylidine- malononitrile derivatives as non-carboxylic inhibitors of protein tyrosine phosphatase 1B
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In this study, we describe the design, synthesis, biological evaluation and molecular modelling studies of novel non-carboxylic arylidine malononitrile-based molecules as Protein Tyrosine Phosphatase 1B (PTP1B) inhibitors. The synthesized derivatives were evaluated in vitro for glucose reuptake using L6 muscle cell lines and enzymatic assay against PTP1B. The biological activity results showed that the 2-methoxy substituted (14b) compound exhibited significant activity in both the assays. The unsubstituted compound (14a) also possessed comparable activity on glucose reuptake in L6 muscle cell lines and better inhibitory activity on PTP1B enzyme assays. Docking analysis was performed on the most potent compound of the series to understand the nature of interactions governing the binding of the designed molecule with the PTP1B enzyme.
- Deora, Girdhar Singh,Karthikeyan, Chandrabose,Moorthy, N. S. Hari Narayana,Rathore, Vandana,Rawat, Arun K.,Tamrakar, Akhilesh K.,Srivastava,Trivedi, Piyush
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p. 5344 - 5348
(2013/12/04)
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- Synthesis, antibacterial activities, and 3d-qsar of sulfone derivatives containing 1, 3, 4-oxadiazole moiety
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A series of sulfone derivatives containing 1, 3, 4-oxadiazole moiety were prepared and evaluated for their antibacterial activities by the turbidimeter test. Most compounds inhibited growth of Ralstonia solanacearum (R. solanacearum) from tomato and tobacco bacterial wilt with high potency, among which compounds 5a and 5b exhibited the most potent inhibition against R. solanacearum from tomato and tobacco bacterial wilts with EC50 values of 19.77 and 8.29 μg/mL, respectively. Our results also demonstrated that 5a, 5b, and a number of other compounds were more potent than commercial bactericides Kocide 3000 and Thiodiazole Copper, which inhibited R. solanacearum from tomato bacterial wilt with EC50 values of 93.59 and 99.80 μg/mL and tobacco bacterial wilt with EC50 values of 45.91 and 216.70 μg/mL, respectively. The structure-activity relationship (SAR) of compounds was studied using three-dimensional quantitative structure-activity relationship (3D-QSAR) models created by comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA) based on compound bioactivities against tomato and tobacco bacterial wilts. The 3D-QSAR models effectively predicted the correlation between inhibitory activity and steric-electrostatic properties of compounds.
- Li, Pei,Yin, Juan,Xu, Weiming,Wu, Jian,He, Ming,Hu, Deyu,Yang, Song,Song, Baoan
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p. 546 - 556
(2013/11/06)
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- Synthesis, molecular modeling and biological evaluation of 2-(benzylthio)-5-aryloxadiazole derivatives as anti-tumor agents
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A series of 2-(benzylthio)-5-aryloxadiazole derivatives have been designed and synthesized, and their biological activities are also evaluated for EGFR inhibitory activity. Fourteen compounds among the twenty compounds are reported for the first time. Their chemical structures are characterized by 1H NMR, MS, and elemental analysis. Anti-proliferative and EGFR inhibition assay results have demonstrated that compound 3e shows the most potent biological activity (IC50 = 1.09 μM for MCF-7 and IC50 = 1.51 μM for EGFR). Docking simulation has been performed to position compound 3e into the EGFR active site to determine the probable binding model, with an estimated binding free energy value of -10.7 kcal/mol. Compound 3e with potent inhibitory activity in tumor growth inhibition may be a promising anti-tumor leading compound for the further research.
- Liu, Kai,Lu, Xiang,Zhang, Hong-Jia,Sun, Juan,Zhu, Hai-Liang
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experimental part
p. 473 - 478
(2012/03/13)
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- Inhibition of tobacco bacterial wilt with sulfone derivatives containing an 1,3,4-oxadiazole moiety
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A series of new sulfone compounds containing the 1,3,4-oxadiazole moiety were designed and synthesized. Their structures were identified by 1H and 13C nuclear magnetic resonance and elemental analyses. Antibacterial bioassays indicated that most compounds exhibited promising in vitro antibacterial bioactivities against tobacco bacterial wilt at 200 μg/mL. The relationship between structure and antibacterial activity was also discussed. Among the title compounds, 5′c, 5′h, 5′i, and 5′j could inhibit mycelia growth of Ralstonia solanacearum in vitro by approximately 50% (EC50) at 39.8, 60.3, 47.9, and 32.1 μg/mL, respectively. Among them, compound 5′j was identified as the most promising candidate due to its stronger effect than that of Kocide 3000 [Cu(OH)2] within the same concentration range. Field trials demonstrated that the control effect of compound 5′j against tobacco bacterial wilt was better than that of the commercial bactericide Saisentong. For the first time, the present work demonstrated that sulfone derivatives containing 1,3,4-oxadiazole can be used to develop potential bactericides for plants.
- Xu, Wei-Ming,Han, Fei-Fei,He, Ming,Hu, De-Yu,He, Jiang,Yang, Song,Song, Bao-An
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scheme or table
p. 1036 - 1041
(2012/06/04)
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- Discovery of potent and selective inhibitors of human reticulocyte 15-lipoxygenase-1
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There are a variety of lipoxygenases in the human body (hLO), each having a distinct role in cellular biology. Human reticulocyte 15-lipoxygenase-1 (15-hLO-1), which catalyzes the dioxygenation of 1,4-cis,cis-pentadiene- containing polyunsaturated fatty acids, is implicated in a number of diseases including cancer, atherosclerosis, and neurodegenerative conditions. Despite the potential therapeutic relevance of this target, few inhibitors have been reported that are both potent and selective. To this end, we have employed a quantitative high-throughput (qHTS) screen against ~74000 small molecules in search of reticulocyte 15-hLO-1 selective inhibitors. This screen led to the discovery of a novel chemotype for 15-hLO-1 inhibition, which displays nM potency and is >7500-fold selective against the related isozymes, 5-hLO, platelet 12-hLO, epithelial 15-hLO-2, ovine cyclooxygenase-1, and human cyclooxygenase-2. In addition, kinetic experiments were performed which indicate that this class of inhibitor is tight binding, reversible, and appears not to reduce the active-site ferric ion.
- Rai, Ganesha,Kenyon, Victor,Jadhav, Ajit,Schultz, Lena,Armstrong, Michelle,Jameson, J. Brian,Hoobler, Eric,Leister, William,Simeonov, Anton,Holman, Theodore R.,Maloney, David J.
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experimental part
p. 7392 - 7404
(2011/01/12)
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- Synthesis, biological evaluation, and molecular docking studies of 2-chloropyridine derivatives possessing 1,3,4-oxadiazole moiety as potential antitumor agents
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A series of new 2-chloropyridine derivatives possessing 1,3,4-oxadiazole moiety were synthesized. Antiproliferative assay results indicated that compounds 6o and 6u exhibited the most potent activity against gastric cancer cell SGC-7901, which was more potent than the positive control. Especially, compound 6o exhibited significant telomerase inhibitory activity (IC 50 = 2.3 ± 0.07 μM), which was comparable to the positive control ethidium bromide. Docking simulation was performed to position compound 6o into the active site of telomerase (3DU6) to determine the probable binding model.
- Zheng, Qing-Zhong,Zhang, Xiao-Min,Xu, Ying,Cheng, Kui,Jiao, Qing-Cai,Zhu, Hai-Liang
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scheme or table
p. 7836 - 7841
(2011/01/13)
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- Stereoselective synthesis and fungicidal activities of (E)-α- (methoxyimino)-benzeneacetate derivatives containing 1,3,4-oxadiazole ring
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Fifteen novel (E)-α-(methoxyimino)-benzeneacetate derivatives, the analogues of strobilurins, which contain two pharmacophoric substructures of (E)-methyl methoxyiminoacetate moiety and 1,3,4-oxadiazole ring were stereoselectively synthesized. It was first found that the coupling reaction could give stereoselectively the key intermediate (E) and (Z)-methyl 2-(hydroxyimino)-2-o-tolylacetate 2 with a ratio of 14:1. The preliminary bioassays indicated that all the compounds 1 showed potent fungicidal activity against Rhizoctonia solani, Botrytis cinereapers, Gibberella zeae, Physalospora piricola and Bipolaris mayclis, and all of the tested compounds 1a-1o had more potent fungicidal activities against R. solani than Kresoxim-methyl.
- Li, Yan,Liu, Jie,Zhang, Hongquan,Yang, Xiangping,Liu, Zhaojie
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p. 2278 - 2282
(2007/10/03)
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- Novel inhibitors of cell adhesion molecule expression
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2-Alkylsulfinyl-1,3,4-oxadiazoles have been identified as novel inhibitors of cell adhesion molecule expression on endothelial cells. These compounds have been shown to inhibit the up-regulation of ELAM-1 and VCAM-1 on activated human umbilical vein endothelial cells (HUVECs) as measured by ELISA.
- Dodd, Dharmpal S.,Shen, Zhongqi,Nishi, Takao,Graber, Norma,Bealls, Dawson,Fong, Miranda,Ebert, Tracy
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p. 2693 - 2698
(2007/10/03)
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- Synthesis and a UV and IR spectral study of some 2-aryl-Δ2-1,3,4-oxadiazoline-5-thiones
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Twenty four 2-aryl-Δ2-1,3,4-oxadiazoline-5-thione derivatives 2 were synthesized and their uv and ir spectra were studied. Correlation between σ-Hammett constants of aryl substituents and the differences in absorption maxima (Δν = ν1-ν2 in kK) of the electronic spectra of the deprotonated species were also evaluated. A new method for the synthesis of the 2-(amino)aryl derivatives 2v,w,x is also reported.
- Charistos,Vagenas,Tzavellas,Tsoleridis,Rodios
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p. 1593 - 1598
(2007/10/02)
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