128958-65-6

Usage

Uses

Used in Pharmaceutical Industry:
4-BENZYLOXYBENZHYDRAZIDE is used as a potential candidate in drug development for its strong antioxidant and anti-inflammatory properties, making it suitable for the treatment of diseases such as cancer and arthritis.
Used in Cancer Research:
4-BENZYLOXYBENZHYDRAZIDE is used as a potential therapeutic agent in cancer research, given its strong antioxidant and anti-inflammatory properties, which may contribute to the development of new cancer treatments.
Used in Antimicrobial Applications:
4-BENZYLOXYBENZHYDRAZIDE is used as an antibacterial and antifungal agent, demonstrating its potential in the development of new medical treatments for infectious diseases.
Used in Antioxidant and Anti-inflammatory Therapies:
4-BENZYLOXYBENZHYDRAZIDE is used as a therapeutic agent for its antioxidant and anti-inflammatory properties, which may be beneficial in the treatment of various diseases and conditions.

InChI:InChI=1/C14H14N2O2/c15-16-14(17)12-6-8-13(9-7-12)18-10-11-4-2-1-3-5-11/h1-9H,10,15H2,(H,16,17)

Upstream product

• 56441-55-5 ethyl 4-(benzyloxy)benzoate 
• 32122-11-5 4-benzyloxy-benzoic acid methyl ester 
• 100-39-0 benzyl bromide 
• 99-76-3 methyl 4-hydroxylbenzoate 
• 120-47-8 Ethyl 4-hydroxybenzoate 
• 100-44-7 benzyl chloride 
• 99-96-7 4-hydroxy-benzoic acid 
• 1486-51-7 p-(benzyloxy)benzoic acid 
• 100-51-6 benzyl alcohol 

Downstream Products

• 147807-60-1 1-<4-(benzyloxy)benzoyl>-2-(cyanoethyl)hydrazine 
• 741262-94-2 5-(4-benzyloxy-phenyl)-[1,3,4]oxadiazole-2-thiol 
• 851625-56-4 ((C₆H₅)CH₂O(C₆H₄)C(O)NNCH(C₆H₄)OCH₂(C₆H₅))2FeCl(H₂O) 
• 851625-52-0 ((C₆H₅)CH₂O(C₆H₄)C(O)NNCH(C₆H₅))2FeCl(H₂O) 
• 851625-54-2 ((C₆H₅)CH₂O(C₆H₄)C(O)NNCH(C₆H₄)Cl)2FeCl(H₂O) 
• 851625-53-1 ((C₆H₅)CH₂O(C₆H₄)C(O)NNCH(C₆H₄)OCH₃)2FeCl(H₂O) 
• 851625-49-5 ((C₆H₅)CH₂O(C₆H₄)C(O)NNCH₂)2FeCl(H₂O) 
• 851625-50-8 ((C₆H₅)CH₂O(C₆H₄)C(O)NNCHCH₃)2FeCl(H₂O) 
• 1003015-78-8 bis[N-4-ethylbenzylidene(4-benzyloxy)benzoylhydrazinato]nickel(II) 
• 1003015-77-7 bis[N-4-methylbenzylidene(4-benzyloxy)benzoylhydrazinato]nickel(II) 
• 947394-01-6 potassium benzyloxybenzoyldithiocarbazate 
• 947393-91-1 3-benzyloxyphenyl-4-amino-5-mercapto-l,2,4-triazole 
• 1285701-05-4 C₃₈H₂₆N₈O₂S₂ 
• 1285701-06-5 C₃₈H₂₆N₈O₂S₂ 

Relevant academic research and scientific papers

Ultrasound assisted synthesis of 4-(Benzyloxy)-N-(3-chloro-2-(substitutedphenyl)-4-oxoazetidin-1-yl) benzamide as challenging anti-tubercular scaffold

A series of ten novel derivatives of 4-(benzyloxy)-N-(3-chloro-2-(substituted phenyl)-4-oxoazetidin-1-yl) benzamide 6a–j were synthesized in good yield from the key compound 4-(benzyloxy)-N’-(substituted benzylidene) benzo hydrazide, called Schiff’s bases 5a–j, by Staudinger reaction ([2 + 2] ketene-imine cycloaddition reaction) with chloro acetyl chloride in the presence of catalyst tri ethylamine and solvent dimethyl formamide (DMF), by using ultra-sonication as one of the green chemistry tools. All the synthesised compounds were evaluated for in vitro anti-tubercular activity against Mycobacterium tuberculosis (MTB) and most of them showed promising activity with an IC50 value of less than 1 μg/mL. To establish the safety, all the synthesized compounds were further tested for cytotoxicity against the human cancer cell line HeLa and all 6a–j compounds were found to be non-cytotoxic in nature. The molecular docking study was carried out with essential enzyme InhA (FabI/ENR) of Mycobacterium responsible for cell wall synthesis which suggests that 6a and 6e are the most active derivatives of the series. The theoretical evaluation of cell permeability based on Lipinski’s rule of five has helped to rationalize the biological results and hence the synthesized azetidinone derivatives 6a–j were also analyzed for physicochemical evaluation that is, absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties and the results showed that all the derivatives could comply with essential features required for a potential lead in the anti-tubercular drug discovery process.

Ultrasound- and molecular sieves-assisted synthesis, molecular docking and antifungal evaluation of 5-(4-(benzyloxy)-substituted phenyl)-3-((phenylamino)methyl)-1,3,4-oxadiazole-2(3h)-thiones

A novel series of 5-(4-(benzyloxy)substituted phenyl)-3-((phenyl amino)methyl)-1,3,4-oxadiazole-2(3H)-thione Mannich bases 6a-o were synthesized in good yield from the key compound 5-(4-(benzyloxy)phenyl)-1,3,4-oxadiazole-2(3H)-thione by aminomethylation with paraformaldehyde and substituted amines using molecular sieves and sonication as green chemistry tools. The antifungal activity of the new products was evaluated against seven human pathogenic fungal strains, namely, Candida albicans ATCC 24433, Candida albicans ATCC 10231, Candida glabrata NCYC 388, Cryptococcus neoformans ATCC 34664, Cryptococcus neoformans PRL 518, Aspergillus fumigatus NCIM 902 and Aspergillus niger ATCC 10578. The synthesized compounds 6d, 6f, 6g, 6h and 6j exhibited promising antifungal activity against the tested fungal pathogens. In molecular docking studies, derivatives 6c, 6f and 6i showed good binding at the active site of C. albicans cytochrome P450 enzyme lanosterol 14 α-demethylase. The in vitro antifungal activity results and docking studies indicated that the synthesized compounds have potential antifungal activity and can be further optimized as privileged scaffolds to design and develop potent antifungal drugs.

4-Alkyl-1,2,4-triazole-3-thione analogues as metallo-β-lactamase inhibitors

In Gram-negative bacteria, the major mechanism of resistance to β-lactam antibiotics is the production of one or several β-lactamases (BLs), including the highly worrying carbapenemases. Whereas inhibitors of these enzymes were recently marketed, they only target serine-carbapenemases (e.g. KPC-type), and no clinically useful inhibitor is available yet to neutralize the class of metallo-β-lactamases (MBLs). We are developing compounds based on the 1,2,4-triazole-3-thione scaffold, which binds to the di-zinc catalytic site of MBLs in an original fashion, and we previously reported its promising potential to yield broad-spectrum inhibitors. However, up to now only moderate antibiotic potentiation could be observed in microbiological assays and further exploration was needed to improve outer membrane penetration. Here, we synthesized and characterized a series of compounds possessing a diversely functionalized alkyl chain at the 4-position of the heterocycle. We found that the presence of a carboxylic group at the extremity of an alkyl chain yielded potent inhibitors of VIM-type enzymes with Ki values in the μM to sub-μM range, and that this alkyl chain had to be longer or equal to a propyl chain. This result confirmed the importance of a carboxylic function on the 4-substituent of 1,2,4-triazole-3-thione heterocycle. As observed in previous series, active compounds also preferentially contained phenyl, 2-hydroxy-5-methoxyphenyl, naphth-2-yl or m-biphenyl at position 5. However, none efficiently inhibited NDM-1 or IMP-1. Microbiological study on VIM-2-producing E. coli strains and on VIM-1/VIM-4-producing multidrug-resistant K. pneumoniae clinical isolates gave promising results, suggesting that the 1,2,4-triazole-3-thione scaffold worth continuing exploration to further improve penetration. Finally, docking experiments were performed to study the binding mode of alkanoic analogues in the active site of VIM-2.

1,2,4-Triazole-3-thione compounds with a 4-ethyl alkyl/aryl sulfide substituent are broad-spectrum metallo-β-lactamase inhibitors with re-sensitization activity

Metallo-β-lactamases (MBLs) are important contributors of Gram-negative bacteria resistance to β-lactam antibiotics. MBLs are highly worrying because of their carbapenemase activity, their rapid spread in major human opportunistic pathogens while no clinically useful inhibitor is available yet. In this context, we are exploring the potential of compounds based on the 1,2,4-triazole-3-thione scaffold as an original ligand of the di-zinc active sites of MBLs, and diversely substituted at its positions 4 and 5. Here, we present a new series of compounds substituted at the 4-position by a thioether-containing alkyl chain with a carboxylic and/or an aryl group at its extremity. Several compounds showed broad-spectrum inhibition with Ki values in the μM to sub-μM range against VIM-type enzymes, NDM-1 and IMP-1. The presence of the sulfur and of the aryl group was important for the inhibitory activity and the binding mode of a few compounds in VIM-2 was revealed by X-ray crystallography. Importantly, in vitro antibacterial susceptibility assays showed that several inhibitors were able to potentiate the activity of meropenem on Klebsiella pneumoniae clinical isolates producing VIM-1 or VIM-4, with a potentiation effect of up to 16-fold. Finally, a selected compound was found to only moderately inhibit the di-zinc human glyoxalase II, and several showed no or only moderate toxicity toward several human cells, thus favourably completing a promising behaviour.

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.

Design of Hydrazide-Bearing HDACIs Based on Panobinostat and Their p53 and FLT3-ITD Dependency in Antileukemia Activity

Here, we present a new series of hydrazide-bearing class I selective HDAC inhibitors designed based on panobinostat. The cap, linker, and zinc-binding group were derivatized to improve HDAC affinity and antileukemia efficacy. Lead inhibitor 13a shows picomolar or low nanomolar IC50 values against HDAC1 and HDAC3 and exhibits differential toxicity profiles toward multiple cancer cells with different FLT3 and p53 statuses. 13a indirectly inhibits the FLT3 signaling pathway and down-regulates master antiapoptotic proteins, resulting in the activation of pro-caspase3 in wt-p53 FLT3-ITD MV4-11 cells. While in the wt-FLT3 and p53-null cells, 13a is incapable of causing apoptosis at a therapeutic concentration. The MDM2 antagonist and the proteasome inhibitor promote 13a-triggered apoptosis by preventing p53 degradation. Furthermore, we demonstrate that apoptosis rather than autophagy is the key contributing factor for 13a-triggered cell death. When compared to panobinostat, 13a is not mutagenic and displays superior in vivo bioavailability and a higher AUC0-inf value.

Photoconductive bent-core liquid crystalline radicals with a paramagnetic polar switchable phase

A series of self-organizing bent-core derivatives 1[12,n], containing a highly π-delocalized stable radical as the central angular structural element, is described. The planarity of the open-shell core permits efficient π-π stacking, which results in the formation of B2 and soft crystalline phases above 100 °C. Optical, XRD and dielectric analyses of 1[12,12] indicate that the ground state of the observed B2 phase is polar antiferroelectric of type SmCAPA exhibiting tristable electro-optical switching. SQUID and EPR measurements revealed strong antiferromagnetic spin-spin exchange interactions below the isotropic phase, which have been estimated at θ = -46 cm-1 with the Curie-Weiss law. Transient photoconductivity was observed in the B2 phase with a hole carrier mobility μh of 1.4 × 10-4 cm2 V-1 s-1

BENZOTHIAZOLE AND PYRIDOTHIAZOLE COMPOUNDS AS SUMO ACTIVATORS

Provided are SUMO activators, which can enhance SUMOylation of SERCA2a, which are useful in the treatment of heart failure, cardiovascular diseases, cancer, neurodegenerative disorders, viral infection, bacterial infection, liver disease, inflammation, and other diseases.

1-substituted benzoyl-4-fatty acyl semicarbazide derivative, preparation method and application thereof as antibacterial agent

The invention belongs to the technical field of antibacterial agents, and relates to a 1-substituted benzoyl-4-fatty acyl semicarbazide derivative, a preparation method and application thereof as an antibacterial agent. The compound is shown in a formula

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.