22706-15-6

Upstream product

• 2231-57-4 Thiocarbohydrazide 
• 69-72-7 salicylic acid 
• 75-15-0 carbon disulfide 
• 936-02-7 2-Hydroxybenzoylhydrazine 
• 29638-33-3 5‐(2‐hydroxyphenyl)‐1,3,4‐oxadiazole‐2(3H)‐thione 
• 119-36-8 methyl salicylate 
• 118-61-6 2-hydroxy-benzoic acid ethyl ester 
• 1251851-79-2 C₈H₇N₂O₃S^(1-)*K⁽¹⁺⁾ 

Downstream Products

• 139267-99-5 4-<5-(4-p-Chlorophenyl)-2-furfurylidene>amino-3-mercapto-5-o-hydroxyphenyl-1,2,4-triazole 
• 139268-17-0 6-<5-(4-Chlorophenyl)-2-furyl>-3-o-hydroxyphenyl-1,2,4-triazolo<3,4-b>-1,3,4-thiadiazole 
• 139268-05-6 6-<5-(4-Nitrophenyl)-2-furyl>-3-o-hydroxyphenyl-1,2,4-triazolo<3,4-b>-1,3,4-thiadiazole 
• 139267-93-9 4-<5-(4-p-Bromophenyl)-2-furfurylidene>amino-3-mercapto-5-o-hydroxyphenyl-1,2,4-triazole 
• 250727-08-3 3-mercapto-6-(p-methoxyphenyl)-s-triazolo[4,3-d]-1,3,4,2-benzoxadiazaphosphopine-6-sulphide 
• 250727-19-6 4-amino-3-benzylthio-5-(o-hydroxyphenyl)-1,2,4-triazole 
• 250727-21-0 4-amino-3[(N-phenyl)carboxamidomethylthio]-5-(o-hydroxyphenyl)-s-triazole 
• 936259-74-4 1,3-di-[4-amino-5(2'-hydroxyphenyl)-1,2,4-triazol-3-yl]mercapto propane 

Relevant academic research and scientific papers

Accelerated synthesis of novel 1,2,4-triazolo[3,4-b][1,3,4]-thiadiazepines under microwave irradiation

A convenient and efficient one step, base catalyzed synthesis of 3,5-disubstituted-4-amino-1,2,4-triazoles by condensation of thiol and hydrazide is presented. An environmentally benign and economic synthesis for the title compounds is described from readily accessible substituted 4-amino-5-mercapto-1,2,4-triazoles and substituted chalcones on basic alumina that are accelerated by exposure to microwave irradiation.{A figure is presented}.

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.

1,2,4-Triazole-3-thione Compounds as Inhibitors of Dizinc Metallo-β-lactamases

Metallo-β-lactamases (MBLs) cause resistance of Gram-negative bacteria to β-lactam antibiotics and are of serious concern, because they can inactivate the last-resort carbapenems and because MBL inhibitors of clinical value are still lacking. We previously identified the original binding mode of 4-amino-2,4-dihydro-5-(2-methylphenyl)-3H-1,2,4-triazole-3-thione (compound IIIA) within the dizinc active site of the L1 MBL. Herein we present the crystallographic structure of a complex of L1 with the corresponding non-amino compound IIIB (1,2-dihydro-5-(2-methylphenyl)-3H-1,2,4-triazole-3-thione). Unexpectedly, the binding mode of IIIB was similar but reverse to that of IIIA. The 3 D structures suggested that the triazole–thione scaffold was suitable to bind to the catalytic site of dizinc metalloenzymes. On the basis of these results, we synthesized 54 analogues of IIIA or IIIB. Nineteen showed IC50 values in the micromolar range toward at least one of five representative MBLs (i.e., L1, VIM-4, VIM-2, NDM-1, and IMP-1). Five of these exhibited a significant inhibition of at least four enzymes, including NDM-1, VIM-2, and IMP-1. Active compounds mainly featured either halogen or bulky bicyclic aryl substituents. Finally, some compounds were also tested on several microbial dinuclear zinc-dependent hydrolases belonging to the MBL-fold superfamily (i.e., endonucleases and glyoxalase II) to explore their activity toward structurally similar but functionally distinct enzymes. Whereas the bacterial tRNases were not inhibited, the best IC50 values toward plasmodial glyoxalase II were in the 10 μm range.

Facile synthesis of new 10-substituted-5H-naphtho[1,2-e][1,2,4]triazolo[3,4-b][1,3,4]thiadiazin-5-ones

The reaction of 2-bromo-1,4-naphthoquinone with 4-amino-5-aryl-4H-1,2,4-triazole-3-thiols in ethanol at 50 °C gave the corresponding 2-[(4-amino-5-aryl-4H-1,2,4-triazol-3-yl)thio]naphthalene-1,4-diones. Their treatment with EtOH/HCl under reflux conditions produced 10-substituted-5H-naphtho[1,2-e][1,2,4]triazolo[3,4-b][1,3,4]thiadiazin-5-ones through intramolecular cyclization.

Efficient synthesis and antimicrobial activity of some novel S-β-d-glucosides of 5-aryl-1,2,4-triazole-3-thiones derivatives

A series of 3-S-β-d-glucosides-4-arylideneamino-5-aryl-1,2,4-triazoles were rationally designed and synthesized according to the principle of superposition of bioactive substructures by the combination of 1,2,4-triazole, Schiff base and glucosides. The structures of the target compounds have been characterized by 1H NMR, 13C NMR, IR, MS and HRMS. All the newly synthesized compounds have been evaluated for their antimicrobial activities in vitro against Staphylococcus aureus (ATCC 6538), Escherichia coli (ATCC 8099) as well as Monilia albican (ATCC 10231). The bioactive assay showed that most of the tested compounds displayed variable inhibitory effects on the growth of the Gram-positive bacterial strain (Staphylococcus aureus), Gram-negative bacterial strains (Escherichia coli) and fungal strains (Monilia albican). All the target compounds exhibited better antifungal activity than antibacterial activity. Especially, compounds 6b, 6c, 6f, 6j, 6k and 6l showed excellent activity against fungus Monilia albican with MIC values of 16 μg/mL.

Studies on fused heterocyclic 3,6-disubstituted-1,2, 4-triazolo-1,3,4- thiadiazoles: Synthesis and biological evaluation

In this study, a series of 3,6-disubstituted-1,2, 4-triazolo-[3,4-b]-1,3,4- thiadiazoles (5a-t) were synthesized by condensing 4-amino-3-mercapto-(4H)-1,2, 4-triazoles (4a-c) with different aromatic or aroyl acids through one-pot reaction. The compounds were evaluated for their anti-inflammatory, analgesic, ulcerogenic, and lipid peroxidation actions. Some of the newly synthesized compounds showed very good anti-inflammatory activity with low GI toxicity and reduced lipid peroxidation. These compounds also showed interesting profile of analgesic activity in acetic acid-induced writhing test. The findings of the study indicate that the synthesized compounds have superior GI safety profile along with reduction in lipid peroxidation as compared to that of the standard. Springer Science+Business Media, LLC 2010.

Combinatorial approach: Identification of potential antifungals from triazole minilibraries

Employing basic principles of solution phase combinatorial chemistry, a solution phase combinatorial synthesis and screening of mini libraries of 1,2,4-triazole derivatives has been carried out. 6 x 6 indexed mini libraries were synthesized comprising of 36 compounds. The libraries were analyzed by liquid chromatography - mass spectrometry - mass spectrometry (LC - MS - MS) analysis. All the synthesized mini libraries were screened for antifungal activity and by deconvolution methodology leads for every fungi used for study were identified. The leads were synthesized individually and screened for activity. The antifungal activity of individually synthesized leads was improved as anticipated, in comparison with that of any of the mini libraries. Springer Science+Business Media, LLC 2010.

Synthesis and evaluation of 4-amino-5-phenyl-4H-[1,2,4]-triazole-3-thiol derivatives as antimicrobial agents

A series of novel 1,2,4-triazole derivatives have been synthesized by condensing the methyl benzoate and methyl salicylate with various substituents; their structures were established on the basis of elemental analysis, Fourier transform infrared spectroscopy (FTIR), 1H nuclear magnetic resonance (NMR), and mass spectral data. All title compounds were subjected to in vitro antibacterial and antifungal screening against four different bacterial and fungal strains. Preliminary results indicate that some of them exhibit promising activities and deserve further consideration as potential antimicrobials. Birkhaeuser Boston 2009.

Synthesis and structure of novel 1,2,4-triazole derivatives containing the 2,4-dinitrophenylthio group

Some novel 1,2,4-triazole derivatives containing the 2,4-dinitrophenylthio group have been synthesised in high yields by means of the reactions of 3-substituted-4-amino -1H-1,2,4-triazole-5(4H)-thiones or (S-3-aryl-4- (benzylideneamino)-1H-l,2,4-triazole-5(4H)-thiones with 1-chloro-2,4- dinitrobenzene. The (S-3-aryl-4-(benzylideneamino)-1H-1,2,4-triazole-5(4H)- thiones were prepared by the reaction of 4-amino-3-aryl-2H-1,2,4-triazole-3(4H)- thiones and diverse aromatic aldehydes. The 2, 4-dinitrophenyl group linked to the S atom, not to the N atom, was confirmed by the crystal structures. The structures of all the compounds were determined by elemental analysis, IR, MS, 1H NMR and 13C NMR.

Synthesis and anti-inflammatory activity of 4-substituted-2,5-disubstituted indolyl azetidine-3-yl/thiazolidin-1-yl-substituted triazoles

A new series of 4-[2′-(substituted phenyl)-5′-methoxy indolyl azetidine-l-yl/thiazolin-1-yl-3-(substituted phenyl)-5-mercapto-l,2,4-triazoles were designed, synthesized and tested for anti-inflammatory and analgesic activities. All compounds were screened in vitro for anti-inflammatory activity against carrageenan induced rat paw oedema and tested for their analgesic activity against phenyl quinone induced pain syndrome in mice at a dose of 50 mg/kg p.o. All the compounds of this series have been analyzed and confirmed by elemental (C, H, N) and spectral methods, i.e. I.R., 1HNMR, 13C NMR and mass spectrometry data.