87239-93-8

Upstream product

• 24398-88-7 ethyl 3-bromobenzoate 
• 1711-09-7 3-bromobenzoyl chloride 
• 585-76-2 m-bromobenzoic acid 
• 618-89-3 methyl 3-bromobenzoate 
• 75-15-0 carbon disulfide 
• 39115-96-3 3-bromo-benzoic acid hydrazide 

Downstream Products

• 87239-96-1 4-amino-5-(3-bromophenyl)-4H-1,2,4-triazole-3-thiol 
• 111827-93-1 N-[3-(3-Bromo-phenyl)-5-thioxo-1,5-dihydro-[1,2,4]triazol-4-yl]-benzamide 
• 111828-16-1 [4-Amino-5-(3-bromo-phenyl)-4H-[1,2,4]triazol-3-ylsulfanyl]-acetic acid hydrazide 
• 1427500-98-8 3-(3-bromophenyl)-6-(furan-3-yl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole 
• 87239-96-1 4-amino-5-(3-bromophenyl)-2,3-dihydro-4H-1,2,4-triazole-3-thione 
• 1427468-60-7 3-(3-bromophenyl)-6-(thiophen-2-ylmethyl)-[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 
• 1427468-57-2 3-(3-bromophenyl)-6-(3,5-difluoropyridin-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 
• 947921-72-4 3-(3-bromophenyl)-6-(pyridin-2-yl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole 

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.

Dithiocarbamate as a valuable scaffold for the inhibition of metallo-β-lactmases

The ‘superbug’ infection caused by metallo-β-lactamases (MβLs) has grown into an emergent health threat. Given the clinical importance of MβLs, a novel scaffold, dithiocarbamate, was constructed. The obtained molecules, DC1, DC8 and DC10, inhibited MβLs NDM-1, VIM-2, IMP-1, ImiS and L1 from all three subclasses, exhibiting an IC50 50 0.22 μM). DC1-2, DC4, DC8 and DC10 restored antimicrobial effects of cefazolin and imipenem against E. coli-BL21, producing NDM-1, ImiS or L1, and DC1 showed the best inhibition of E. coli cells, expressing the three MβLs, resulting in a 2-16-fold reduction in the minimum inhibitory concentrations (MICs) of both antibiotics. Kinetics and isothermal titration calorimetry (ITC) assays showed that DC1 exhibited a reversible, and partially mixed inhibition, of NDM-1, ImiS and L1, with Ki values of 0.29, 0.14 and 5.06 μM, respectively. Docking studies suggest that the hydroxyl and carbonyl groups of DC1 form coordinate bonds with the Zn (II) ions, in the active center of NDM-1, ImiS and L1, thereby inhibiting the activity of the enzymes. Cytotoxicity assays showed that DC1, DC3, DC7 and DC9 have low toxicity in L929 mouse fibroblastic cells, at a dose of up to 250 μM. These studies revealed that the dithiocarbamate is a valuable scaffold for the development of MβLs inhibitors.

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.

Synthesis and evaluation of novel azoles as potent antifungal agents

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.

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.

THE ACIDITIES AND THE TAUTOMERIC STRUCTURE OF 5-ARYL-2-MERCAPTO-1,3,4-OXADIAZOLES

The acidity constants of a series of substituted 5-phenyl-2-mercapto-1,3,4-oxadiazoles were determined by potentiometric and spectrophotometric methods in 80percent (vol.) ethanol-water at 25 deg C.The data obtained by the two methods are in good agreement.The pKa values correlate with the ?*XC6H4 constants of the substituted phenyl group (p = -0.985, r = 0.936), however, a better correlation of the pKa data with the Hammett substituent constants ?X (p = -0.983, r = 0.959) was obtained.These linear correlations exclude the possibility of the presence of the thiol tautomer 1 in eqiulibrium with the thioamide tautomer 2 and indicate that the ionization of the compounds takes place in the form of the thioamide tautomer 2.According to the results of the HMO calculations, the thioamide form 2 is more stable than the thiol tautomer 1.A satisfactory correlation between the observed pKa values and the difference between the ?-electronic energies (ΔE?) of the thioamide tautomer and of the common resonance-stabilized anion was obtained, thus supporting the assigned tautomeric structure 2 for the series under study.