87239-96-1

Usage

Uses

Used in Pharmaceutical Industry:
4-AMINO-5-(3-BROMOPHENYL)-4H-1,2,4-TRIAZOLE-3-THIOL is used as a pharmaceutical compound for its potential antibacterial, antifungal, and antitumor properties. Its diverse biological activities contribute to the development of new drugs targeting a range of diseases and conditions.
Used in Agrochemical Industry:
In the agrochemical sector, 4-AMINO-5-(3-BROMOPHENYL)-4H-1,2,4-TRIAZOLE-3-THIOL is utilized as an active ingredient in pesticides and fungicides, leveraging its antimicrobial properties to protect crops from various pathogens.
Used in Organic Chemistry:
4-AMINO-5-(3-BROMOPHENYL)-4H-1,2,4-TRIAZOLE-3-THIOL serves as a building block in organic chemistry, facilitating the synthesis of a variety of pharmaceutical compounds and other organic molecules.
Used in Chemical Sensors:
4-AMINO-5-(3-BROMOPHENYL)-4H-1,2,4-TRIAZOLE-3-THIOL has been studied for its potential role in chemical sensors, where its unique structure and properties can be employed to detect specific chemical species or changes in the environment.
Used in Coordination Chemistry:
4-AMINO-5-(3-BROMOPHENYL)-4H-1,2,4-TRIAZOLE-3-THIOL also finds application as a ligand for metal complexes in coordination chemistry, where it can influence the properties and reactivity of the resulting metal-organic compounds.

InChI:InChI=1/C8H7BrN4S/c9-6-3-1-2-5(4-6)7-11-12-8(14)13(7)10/h1-4H,10H2,(H,12,14)

Upstream product

• 618-89-3 methyl 3-bromobenzoate 
• 2231-57-4 Thiocarbohydrazide 
• 75-15-0 carbon disulfide 
• 39115-96-3 3-bromo-benzoic acid hydrazide 
• 585-76-2 m-bromobenzoic acid 
• 203268-69-3 5-(3-Bromo-phenyl)-3H-[1,3,4]oxadiazole-2-thione 
• 24398-88-7 ethyl 3-bromobenzoate 
• 87239-93-8 C₈H₆BrN₂OS₂^(1-)*K⁽¹⁺⁾ 
• 1711-09-7 3-bromobenzoyl chloride 

Downstream Products

• 113486-73-0 6-Amino-3-(3-bromophenyl)-s-triazolo<3,4-b><1,3,4>thiadiazole 
• 1427500-98-8 3-(3-bromophenyl)-6-(furan-3-yl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole 
• 947921-72-4 3-(3-bromophenyl)-6-(pyridin-2-yl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole 
• 874466-73-6 3-(3-bromophenyl)-6-(pyridin-4-yl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole 
• 1427468-57-2 3-(3-bromophenyl)-6-(3,5-difluoropyridin-2-yl)[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole 
• 947064-13-3 3-(3-bromophenyl)-6-(thiophen-2-yl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole 
• 1427468-60-7 3-(3-bromophenyl)-6-(thiophen-2-ylmethyl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole 
• 111827-98-6 C₁₇H₁₄Br₂N₈S₂ 
• 111828-16-1 [4-Amino-5-(3-bromo-phenyl)-4H-[1,2,4]triazol-3-ylsulfanyl]-acetic acid hydrazide 
• 1085387-60-5 C₂₃H₁₈Br₂N₈S₂ 
• 1119751-46-0 1,8-bis[(3-m-bromophenyl)-s-triazolo[3,4-b]-[1,3,4]thiadiazole-6-yl]octane 
• 947857-44-5 3-(3-bromophenyl)-6-(3,4-dichlorophenyl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole 
• 1122552-33-3 2,5-bis[3-(m-bromophenyl)-1,2,4-triazolo[3,4-b]-[1,3,4]thiadiazol-6-yl]thiophene 
• 1193086-61-1 ethyl 4-[(E)-2-{3-(3-bromophenyl)[1,2,4]triazolo[3,4-b][1,3,4]thiadiazol-6-yl}ethenyl]-1-phenyl-1H-pyrazole-3-carboxylate 

Relevant academic research and scientific papers

New heparanase-inhibiting triazolo-thiadiazoles attenuate primary tumor growth and metastasis

Compelling evidence ties heparanase, an endoglycosidase that cleaves heparan sulfate side (HS) chains of proteoglycans, with all steps of tumor development, including tumor initiation, angiogenesis, growth, metastasis, and chemoresistance. Moreover, heparanase levels correlate with shorter postoperative survival of cancer patients, encouraging the development of heparanase inhibitors as anti-cancer drugs. Heparanase-inhibiting heparin/heparan sulfate-mimicking compounds and neutralizing antibodies are highly effective in animal models of cancer progression, yet none of the compounds reached the stage of approval for clinical use. The present study focused on newly synthesized triazolo–thiadiazoles, of which compound 4-iodo-2-(3-(p-tolyl)-[1,2,4]triazolo[3,4b][1,3,4]thiadiazol-6-yl)phenol (4-MMI) was identified as a potent inhibitor of heparanase enzymatic activity, cell invasion, experimental metastasis, and tumor growth in mouse models. To the best of our knowledge, this is the first report showing a marked decrease in primary tumor growth in mice treated with small molecules that inhibit heparanase enzymatic activity. This result encourages the optimization of 4-MMI for preclinical and clinical studies primarily in cancer but also other indications (i.e., colitis, pancreatitis, diabetic nephropathy, tissue fibrosis) involving heparanase, including viral infection and COVID-19.

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.

Facile synthesis, biological evaluation and molecular docking studies of novel substituted azole derivatives

In this study, we synthesized the series of novel azole derivatives and evaluated for enzyme inhibition assays, corresponding kinetic analysis and molecular modeling. Among the investigated bioassays, the oxadiazole derivatives 4a-k were found potent α-glucosidase inhibitors while the Schiff base derivatives 7a-k exhibited considerable potential toward urease inhibition. The inhibition kinetics for the most active compounds were analyzed by the Lineweaver–Burk plots to investigate the possible binding modes of the synthesized compounds toward the tested proteins. Moreover, the detailed docking studies were performed on the synthesized library of 4a-k and 7a-k to study the molecular interaction and binding mode in the active site of the modeled yeast α-glucosidase and Jack Bean Urease, respectively. It could be inferred from docking results that theoretical studies are in close agreement to that of the experimental results. The structure of one of the compound 7k was characterized by the single crystal X-ray diffraction analysis in order to find out the predominant conformation of the molecules.

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.

Synthesis, anti-HIV activity and Molecular modeling study of 3-aryl-6-adamantylmethyl-[1,2,4] triazolo[3,4-b][1,3,4]thiadiazole derivatives

A series of novel 3-aryl-6-adamantylmethyl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles 6a-l were synthesized by a simple method with the aim of developing novel HIV non-nucleoside reverse transcriptase inhibitors. All the synthesized compounds were structurally confirmed by spectral analyses. The structure of 6a was unambiguously verified by X-ray structure determination. The synthesized compounds were evaluated for their anti-HIV activity and four analogs displayed moderate inhibitory activity with EC50 values ranging from 10.10 to 12.40 μg mL-1. Molecular docking of 6g with HIV-1 reverse transcriptase was studied to rationalize some structureactivity relationships (SARs).

Synthesis and antimicrobial evaluation of 5-aryl-1,2,4-triazole-3-thione derivatives containing a rhodanine moiety

Three series of 5-aryl-1,2,4-triazole-3-thione derivatives containing a rhodanine moiety (5a-k, 6a-i, and 7a-i) have been synthesized, characterized and evaluated for their antibacterial activity. Some of these displayed potent antibacterial activity against several Gram-positive and Gram-negative bacterial strains (including multidrug-resistant clinical isolates) with minimum inhibitory concentration (MIC) values in the range of 4-64 μg/mL and minimum bactericidal concentration (MBC) values in the range of 8-256 μg/mL. Compared with previously reported rhodanine derivatives, these compounds exhibited a broad spectrum of antibacterial activity by means of introducing 4-amino-5-aryl-1,2,4-triazole-3-thione moiety. Notably, compound 5f exhibited good antibacterial activity against Staphylococcus aureus RN 4220, S. aureus 209, S. aureus 503, Gram-negative bacteria (Escherichia coli 1924), and Candida albicans 7535 with MBC values of 8 or 16 μg/ml. All of the compounds synthesized in the current Letter were characterized by 1H NMR, 13C NMR, infrared and mass spectroscopy.

Exploration of a library of triazolothiadiazole and triazolothiadiazine compounds as a highly potent and selective family of cholinesterase and monoamine oxidase inhibitors: Design, synthesis, X-ray diffraction analysis and molecular docking studies

There is a high demand for the collection of small organic molecules (especially N-heterocycles) with diversity and complexity in the process of drug discovery. This need for privileged scaffolds in medicinal research gives an impetus for the development of nitrogen-containing compounds which are widely encountered in natural products, drugs and pharmaceutically active compounds. In this context, a diverse library of new triazolothiadiazole (4a-l) and triazolothiadiazine (5a-p) compounds was designed, synthesized and evaluated as potent and selective inhibitors of electric eel acetylcholinesterase (EeAChE) and horse serum butyrylcholinesterase (hBChE) by Ellman's method using neostigmine and donepezil as standard inhibitors. Among the screened triazolothiadiazoles, 4j emerged as a lead candidate showing the highest inhibition with an outstanding IC50 value of 0.117 ± 0.007 μM against AChE, which is ～139-fold greater inhibitory efficacy as compared to neostigmine, whereas 4k displayed ～506-fold strong inhibition with IC50 of 0.056 ± 0.001 μM against BChE. In the triazolothiadiazine series, 5j and 5e depicted a clear selectivity towards EeAChE with IC50 values of 0.065 ± 0.005 and 0.075 ± 0.001 μM, respectively, which are ～250- and ～218-fold stronger inhibition as compared to neostigmine (IC50 = 16.3 ± 1.12 μM). In addition, the synthesized compounds were also tested for their monoamine oxidase (MAO-A and MAO-B) inhibition, where 4a from the triazolothiadiazole series delivered the highest potency against MAO-A with an IC50 value of 0.11 ± 0.005 μM which is ～33-fold higher inhibition as compared to the standard inhibitor, clorgyline (IC50 = 3.64 ± 0.012 μM), whereas compound 5c from the triazolothiadiazine series turned out to be a lead inhibitor with an IC50 value of 0.011 ± 0.001 μM which is ～330-fold stronger inhibition. Moreover, compounds 4b (triazolothiadiazole series) and 5o (triazolothiadiazine series) were identified as lead inhibitors against MAO-B. Molecular modelling studies were performed against human AChE and BChE to observe the binding site interactions of these compounds.

Synthesis and biological activities of some new 3,6-disubstituted 1,2,4-triazolo[3,4-b]1,3,4-thiadiazole derivatives

A series of aromatic hydrazides 3a-j were prepared by refluxing esters 2a-j with hydrazine hydrate in methanol, which were prepared by the esterification of 1a-j. Acetohydrazides 3a-j upon treatment with carbon disulfide and methanolic potassium hydroxide yielded potassium dithiocarbazate salts 4a-j, which on refluxing with hydrazine hydrate yielded substituted 4-amino-5-aryl-3H-1,2,4-triazole-3-thiones 5a-j. The target compounds 6a-j were synthesized by condensing furan-3-carboxylic acid in the presence of polyphosphoric acid under reflux. The structures of newly synthesized compounds were characterized by IR, 1H NMR, 13C NMR, elemental analysis and mass spectrometric studies. All the synthesized compounds were screened for their urease, acetylcholine esterase inhibition, antioxidant and alkaline phosphatase inhibition activity. Almost all of the compounds 6a-j showed good to excellent activities against urease and acetylcholine esterase more than the reference drugs. Compounds 6f and 6g were more potent scavenger of free radicals than the reference n-propyl gallate. Compound 6b and 6h showed excellent activities of alkaline phosphatase as compare to the reference KH 2PO4.

Some pyridyl- and thiophenyl- Substituted 1,2,4-triazolo[3,4-b]1,3,4- thiadiazole derivatives as potent antibacterial

The target compounds 6-11a-e were synthesized by condensing 4-amino-5-aryl-3H-1,2,4-triazole-3-thiones 5a-f with various aromatic carboxylic acids in the presence of phosphorous oxychloride. The structures of newly synthesized compounds were characterized by IR, 1H NMR, 13C NMR, elemental analysis and mass spectrometric studies. All the synthesized compounds were screened for their antibacterial activity. Almost all the tested compounds were potent against four different strains of bacteria when compared with that of reference drug ciprofloxacin. Compounds 6c, 6e, 8d, 9b, 9e, 11a and 11b showed nearly equal or lower MIC values than standard drug, against all four tested bacterial strains but rest of the compounds showed excellent antibacterial activities.