3690-47-9

Usage

InChI:InChI=1/C7H5N3OS/c12-7-10-9-6(11-7)5-3-1-2-4-8-5/h1-4H,(H,10,12)

Upstream product

• 1452-63-7 picolinic acid hydrazide 
• 75-15-0 carbon disulfide 
• 2524-52-9 ethyl-2-picolinate 
• 98-98-6 2-Picolinic acid 
• 2459-07-6 methyl pyridine-2-carboxylate 

Downstream Products

• 1355947-54-4 1,2,4,5-tetrakis[5-(2-pyridyl)-1,3,4-oxadiazol-2-ylthiomethyl]benzene 
• 81555-93-3 1-Phenyl-2-(5-pyridin-2-yl-[1,3,4]oxadiazol-2-ylsulfanyl)-ethanone 
• 129136-45-4 3-mercapto-4-benzyl-5-(pyridin-2-yl)-1,2,4-triazole 
• 197371-76-9 2-(5-Benzylsulfanyl-[1,3,4]oxadiazol-2-yl)-pyridine 
• 81556-09-4 6-Phenyl-3-pyridin-2-yl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine 
• 1391013-27-6 C₁₆H₁₃N₃O₃S 

Relevant academic research and scientific papers

Design, Synthesis, Herbicidal Activity, and Molecular Docking Study of 2-Thioether-5-(Thienyl/Pyridyl)-1,3,4-Oxadiazoles as Potent Transketolase Inhibitors

Transketolase (TK) has been regarded as a new target for the development of novel herbicides. In this study, a series of 2-thioether-5-(thienyl/pyridyl)-1,3,4-oxadiazoles were designed and synthesized based on TK as the new target. The preliminary bioassay results indicated that compounds 4l and 4m displayed the best herbicidal activities against Amaranthus retroflexus (AR) and Digitaria sanguinalis (DS), with the inhibition exceeding 90% at 100-200 mg/L in vitro. Moreover, they also displayed higher postemergence herbicidal activities (90% control) against AR and DS than all of the positive controls at 45-90 g [active ingredient (ai)]/ha in a greenhouse. Notably, compounds 4l and 4m showed a broad spectrum of weed control at 90 g ai/ha. More significantly, compound 4l exhibited good crop selectivity against maize at 90 g ai/ha. Both fluorescent binding experiments and molecular docking analyses indicated that compounds 4l and 4m exhibited strong TK inhibitory activities with superior binding affinities than the others. Preliminary mechanism studies suggested that they might exert their TK inhibitory effects by occupying the active cavity of At TK and forming more strong interactions with amino acids in the active site. Taken together, these results suggested that compound 4l was a potential herbicide candidate for weed control in maize fields targeting TK.

Design, synthesis, in vitro and in vivo evaluation against MRSA and molecular docking studies of novel pleuromutilin derivatives bearing 1, 3, 4-oxadiazole linker

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.

Pleuromutilin derivative with 1, 3, 4-oxadiazole side chain and preparation and application thereof

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.

Design, synthesis, and biological evaluation of new challenging thalidomide analogs as potential anticancer immunomodulatory agents

Thalidomide and its analogs are immunomodulatory drugs that inhibit the production of certain inflammatory mediators associated with cancer. In the present work, a new series of thalidomide analogs was designed and synthesized to obtain new effective antitumor immunomodulatory agents. The synthesized compounds were evaluated for their cytotoxic activities against a panel of four cancer cell lines (HepG-2, HCT-116, PC3 and MCF-7). Compounds 33h, 33i, 42f and 42h showed strong potencies against all tested cell lines with IC50 values ranging from 14.63 to 49.90 μM comparable to that of thalidomide (IC50 values ranging from 32.12 to 76.91 μM). The most active compounds were further evaluated for their in vitro immunomodulatory activities via estimation of human tumor necrosis factor alpha (TNF-α), human caspase-8 (CASP8), human vascular endothelial growth factor (VEGF), and nuclear factor kappa-B P65 (NF-κB P65) in HCT-116 cells. Thalidomide was used as a positive control. Compounds 33h and 42f showed a significant reduction in TNF-α. Furthermore, compounds 33i and 42f exhibited significant elevation in CASP8 levels. Compounds 33i and 42f inhibited VEGF. In addition, compound 42f showed significant decrease in levels of NF-κB p65. Moreover, apoptosis and cell cycle tests of the most active compound 42f, were performed. The results indicated that compound 42f significantly induce apoptosis in HCT-116 cells and arrest cell cycle at the G2/M phase.

4-Amino-1,2,4-triazole-3-thione-derived Schiff bases as metallo-β-lactamase inhibitors

Resistance to β-lactam antibiotics in Gram-negatives producing metallo-β-lactamases (MBLs) represents a major medical threat and there is an extremely urgent need to develop clinically useful inhibitors. We previously reported the original binding mode of 5-substituted-4-amino/H-1,2,4-triazole-3-thione compounds in the catalytic site of an MBL. Moreover, we showed that, although moderately potent, they represented a promising basis for the development of broad-spectrum MBL inhibitors. Here, we synthesized and characterized a large number of 4-amino-1,2,4-triazole-3-thione-derived Schiff bases. Compared to the previous series, the presence of an aryl moiety at position 4 afforded an average 10-fold increase in potency. Among 90 synthetic compounds, more than half inhibited at least one of the six tested MBLs (L1, VIM-4, VIM-2, NDM-1, IMP-1, CphA) with Ki values in the μM to sub-μM range. Several were broad-spectrum inhibitors, also inhibiting the most clinically relevant VIM-2 and NDM-1. Active compounds generally contained halogenated, bicyclic aryl or phenolic moieties at position 5, and one substituent among o-benzoic, 2,4-dihydroxyphenyl, p-benzyloxyphenyl or 3-(m-benzoyl)-phenyl at position 4. The crystallographic structure of VIM-2 in complex with an inhibitor showed the expected binding between the triazole-thione moiety and the dinuclear centre and also revealed a network of interactions involving Phe61, Tyr67, Trp87 and the conserved Asn233. Microbiological analysis suggested that the potentiation activity of the compounds was limited by poor outer membrane penetration or efflux. This was supported by the ability of one compound to restore the susceptibility of an NDM-1-producing E. coli clinical strain toward several β-lactams in the presence only of a sub-inhibitory concentration of colistin, a permeabilizing agent. Finally, some compounds were tested against the structurally similar di-zinc human glyoxalase II and found weaker inhibitors of the latter enzyme, thus showing a promising selectivity towards MBLs.

The synthesis and structure of pyridine-oxadiazole iridium complexes and catalytic applications: Non-coordinating-anion-tuned selective C–N bond formation

Several novel pyridine-oxadiazole iridium complexes were synthesized and characterized through X-ray crystallography. The designed iridium complexes revealed surprisingly high catalytic activity in C–N bondformation of amides and benzyl alcohols with the assistance of non-coordinating anions. In an attempt to achieve borrowing hydrogen reactions of amides with benzyl alcohols, N,N'-(phenylmethylene)dibenzamide products were unexpectedly isolated under non-coordinating anion conditions, whereas N-benzylbenzamide products were achieved in the absence of non-coordinating anions. The mechanism explorations excluded the possibility of “silver effect” (silver-assisted or bimetallic catalysis) and revealed that the reactivity of iridium catalyst was varied by non-coordinating anions. This work provided a convenient and useful methodology that allowed the iridium complex to be a chemoselective catalyst and demonstrated the first example of non-coordinating-anion-tuned selective C–N bond formation

Antioxidant and tyrosinase docking studies of heterocyclic sulfide derivatives containing a thymol moiety

Fourteen heterocyclic sulfide derivatives (4–17) containing a thymol moiety and oxadiazole, thiadiazole, triazole, oxazole, thiazole, imidazole, pyridine or purine heterocycles were synthesized in three steps. The cupric, Cu(II), ion reducing antioxidant capacity of the compounds was examined, and molecular docking studies were performed to determine whether the sulfur, thymol or heterocyclic moieties interact with the Cu ions in tyrosinase, a type-3 copper enzyme. Using the CUPRAC assay, eight compounds (5–8, 10, 15–17) showed equal or better Cu (II) reducing capacity than trolox at neutral pH, with trolox equivalent antioxidant capacity (TEAC) coefficients ranging between 1.00 and 1.48. The compounds containing a thiadiazole moiety were most effective, with the methyl thiadiazole derivative (8) having the highest Cu(II) reducing capacity. Molecular docking studies of the sulfide derivatives with tyrosinase revealed that there were no direct interactions between the sulfur atom and the active site copper ions. However, the compounds displayed two different binding interactions with the histidine-Cu catalytic center. For compounds 4–13, the thymol portion was embedded in the active site cavity, while for compounds 14–17 the heterocyclic portion of the molecule approached the cavity.

Synthesis of novel indole derivatives containing double 1,3,4-oxadiazole moiety as efficient bactericides against phytopathogenic bacterium Xanthomonas oryzae

Abstract: A series of novel indole derivatives containing double 1,3,4-oxadiazole moiety was designed, synthesized and evaluated for their antibacterial activities in vitro. These compounds were fully characterized by 1H NMR, 13C NMR, and HRMS. Bioassay results indicated that most of title compounds exhibited excellent antibacterial activities against rice bacterial pathogen Xanthomonas oryzae (Xoo). For example, compounds 7d, 7h, 7i, 7j, 7k, 7l and 7m had the half-maximal effective concentration (EC50) values of 52.31, 54.12, 40.65, 38.80, 51.13, 52.75 and 50.66?μg/mL, respectively, which was better than that of commercial product bismerthiazol (BMT) (85.18?μg/mL). The experimental results proved that indole derivatives bearing double 1,3,4-oxadiazole unit are promising candidates for the development of new agricultural bactericides against pathogenic bacterium Xoo. Graphical abstract: [Figure not available: see fulltext.].

Antifungal benzo[b]thiophene 1,1-dioxide IMPDH inhibitors exhibit pan-assay interference (PAINS) profiles

Fungi cause serious life-threatening infections in immunocompromised individuals and current treatments are now complicated by toxicity issues and the emergence of drug resistant strains. Consequently, there is a need for development of new antifungal drugs. Inosine monophosphate dehydrogenase (IMPDH), a key component of the de novo purine biosynthetic pathway, is essential for growth and virulence of fungi and is a potential drug target. In this study, a high-throughput screen of 114,000 drug-like compounds against Cryptococcus neoformans IMPDH was performed. We identified three 3-((5-substituted)-1,3,4-oxadiazol-2-yl)thio benzo[b]thiophene 1,1-dioxides that inhibited Cryptococcus IMPDH and also possessed whole cell antifungal activity. Analogs were synthesized to explore the SAR of these hits. Modification of the fifth substituent on the 1,3,4-oxadiazole ring yielded compounds with nanomolar in vitro activity, but with associated cytotoxicity. In contrast, two analogs generated by substituting the 1,3,4-oxadiazole ring with imidazole and 1,2,4-triazole gave reduced IMPDH inhibition in vitro, but were not cytotoxic. During enzyme kinetic studies in the presence of DTT, nucleophilic attack of a free thiol occurred with the benzo[b]thiophene 1,1-dioxide. Two representative compounds with substitution at the 5 position of the 1,3,4-oxadiazole ring, showed mixed inhibition in the absence of DTT. Incubation of these compounds with Cryptococcus IMPDH followed by mass spectrometry analysis showed non-specific and covalent binding with IMPDH at multiple cysteine residues. These results support recent reports that the benzo[b]thiophene 1,1-dioxides moiety as PAINS (pan-assay interference compounds) contributor.

Synthesis and Biological Activity of Anthranilic Diamide Derivatives Incorporating 1,3,4-oxadiazole or Nitrogen-containing Saturated Heterocyclic Moieties

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.