124980-06-9

Basic information

• Product Name: 4-AMINO-5-(3-FLUOROPHENYL)-4H-1,2,4-TRIAZOLE-3-THIOL
• Synonyms: BUTTPARK 25\07-94;4-AMINO-5-(3-FLUOROPHENYL)-4H-1,2,4-TRIAZOLE-3-THIOL;AKOS TOT-0027;A4390/0187369;ZINC02635301
• CAS NO: 124980-06-9
• Molecular Formula: C₈H₇FN₄S
• Molecular Weight: 210.23
• Mol File: 124980-06-9.mol

Chemical Properties

• Appearance: /
• CAS DataBase Reference: 4-AMINO-5-(3-FLUOROPHENYL)-4H-1,2,4-TRIAZOLE-3-THIOL(CAS DataBase Reference)
• NIST Chemistry Reference: 4-AMINO-5-(3-FLUOROPHENYL)-4H-1,2,4-TRIAZOLE-3-THIOL(124980-06-9)
• EPA Substance Registry System: 4-AMINO-5-(3-FLUOROPHENYL)-4H-1,2,4-TRIAZOLE-3-THIOL(124980-06-9)

Safety Data

• Hazardous Substances Data: 124980-06-9(Hazardous Substances Data)

Upstream product

• 75-15-0 carbon disulfide 
• 499-55-8 3-fluoro-benzoic acid hydrazide 
• 455-38-9 3-fluorobenzoic acid 
• 451-02-5 ethyl 3-fluorobenzoate 
• 455-68-5 methyl 3-fluorobenzoate 
• 2231-57-4 Thiocarbohydrazide 
• 166093-17-0 C₈H₆FN₂OS₂^(1-)*K⁽¹⁺⁾ 
• 1711-07-5 3-fluorobenzoyl chloride 

Downstream Products

• 1293362-48-7 methyl 3-(3-(3-fluorophenyl)-5-thioxo-1H-1,2,4-triazol-4-ylimino)cholanate 

Relevant articles and documents

Synthesis, characterization and antimicrobial evaluation of some new schiff, mannich and acetylenic mannich bases incorporating a 1,2,4-triazole nucleus

A series of Schiff and Mannich bases derived from 4-amino-5-(3-fluorophenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione were synthesized. The alkylation of 4-phenyl-5-(3-fluorophenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione with propargyl bromide afforded the corresponding thiopropargylated derivative which upon treatment with the appropriate secondary amines in the presence of CuCl2 furnished the desired acetylenic Mannich bases. The synthesized compounds were characterized on the basis of their spectral (IR, 1H- and 13C-NMR) data and evaluated for their biological activities. Some of the compounds were found to exhibit significant antimicrobial activity.

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, 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.

METHODS FOR TREATING VIRAL INFECTION

A method effective in treating a viral infection involves administering a therapeutically effective amount of at least one compound capable of inhibiting expression of at least a portion of a virus genome containing an internal ribosomal entry site, or a pharmaceutically acceptable salt thereof. The compound has an azole moiety comprising a five member heterocyclic ring containing at least one nitrogen atom, a hydrophobic moiety bonded to the heterocyclic ring of the azole, and a donor / acceptor moiety bonded to the heterocyclic ring having at least one of hydrogen bond donor and a hydrogen bond acceptor.

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, crystal structure and antiproliferative activity of 6-adamantyl-3-aryl[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles

A series of 3,6-disubstituted [1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles 5a - l bearing an adamantyl moiety were synthesized by condensation of 4-amino-5-aryl-2H-1,2,4-triazole-3(4H)-thiones 4a - l with adamantyl-1- carboxylic acid in the presence of POCl3. The structures of the newly synthesized compounds were established using spectroanalytical techniques and verified further by the crystal structure determination of compounds 5a and 5j. The compounds were screened for their antiproliferative activity against a large panel of human cell lines.

Design, synthesis, and urease inhibition studies of a series of 4-amino-5-aryl-3H-1,2,4-triazole-3-thiones

A series of 4-amino-5-aryl-3H-1,2,4-triazole-3-thiones was synthesized by reaction of aryl hydrazides with CS2 and hydrazine hydrate. The synthesized compounds were characterized by spectroanalytical techniques, and their urease inhibition activity was evaluated using jack bean urease. All but one of the synthesized compounds were active, and two of them were found to be more potent than the standard, with 50% inhibition concentration (IC 50) values of 17.5 ± 0.52 and 4.3 ± 0.169 μM, respectively (standard IC 50 = 21.0 ± 0.11 μM). Tentative statements regarding the role of different functional groups in binding to the enzyme active site are also presented.

Synthesis of novel triazole derivatives of methyl 3-oxocholanate using microwave irradiation

An efficient rapid method for the synthesis of new triazole derivatives derived from methyl 3-oxocholanate under microwave irradiation has been developed. These new compounds were characterised by 1H NMR, IR, ESI-MS spectra and elemental analyses. Some of these triazoles were tested for antibacterial activity against Staphylococcus aureus, Candida albicans and Escherichia coli.