56441-55-5

Usage

Uses

Used in Pharmaceutical Industry:
ETHYL 4-(BENZYLOXY)BENZOATE is used as a key intermediate in the synthesis of various pharmaceuticals. Its unique chemical structure allows it to be a building block for the development of new drugs, contributing to the advancement of medicine.
Used in Perfumery Industry:
In the perfumery industry, ETHYL 4-(BENZYLOXY)BENZOATE is utilized as a component in the creation of fragrances. Its sweet aroma makes it a valuable addition to the formulation of various scented products, enhancing their appeal and longevity.
Used in Flavor Industry:
ETHYL 4-(BENZYLOXY)BENZOATE is also employed in the flavor industry, where it serves as an ingredient in the production of flavors for food and beverages. Its sweet scent adds depth and complexity to the taste profiles of various products, enriching the overall sensory experience.
Used in Organic Synthesis:
As an ester, ETHYL 4-(BENZYLOXY)BENZOATE is commonly used in the synthesis of various organic compounds. Its reactivity and functional groups make it a versatile building block for the creation of a wide range of chemical products, including specialty chemicals and materials.

InChI:InChI=1/C16H16O3/c1-2-18-16(17)14-8-10-15(11-9-14)19-12-13-6-4-3-5-7-13/h3-11H,2,12H2,1H3

Upstream product

• 120-47-8 Ethyl 4-hydroxybenzoate 
• 100-39-0 benzyl bromide 
• 4397-53-9 p-benzyloxybenzaldehyde 
• 64-17-5 ethanol 
• 260783-80-0 N,N,N--trimethyl--1--phenylmethanaminium trifluoromethanesulfonate 
• 100-44-7 benzyl chloride 
• 1486-51-7 p-(benzyloxy)benzoic acid 

Downstream Products

• 1486-51-7 p-(benzyloxy)benzoic acid 
• 958870-41-2 4-(phenylmethoxy)-benzenecarbothioic acid O-ethyl ester 
• 343335-76-2 (1R,2S,5R)-menthyl 4-benzyloxybenzoate 
• 38970-50-2 [(1S)-endo]-borneyl 4-hydroxybenzoate 
• 74754-58-8 Cholest-5-en-3β-yl 4-hydroxybenzoate 
• 169968-84-7 (1R,2S,5R)-2-isopropyl-5-methylcyclohexyl 4-hydroxybenzoate 
• 343335-73-9 4-[(1R,2S,5R)-menthoxycarbonyl]phenyl phenylpropiolate 
• 626199-91-5 cholesteryl 4-benzyloxybenzoate 
• 373389-77-6 4-(cholesteryloxycarbonyl)phenyl phenylpropiolate 
• 107301-15-5 1-[5-(4-Benzyloxy-phenyl)-[1,2,4]oxadiazol-3-ylmethyl]-6,7-dimethoxy-3,4-dihydro-isoquinoline 
• 107301-29-1 1-[5-(4-Benzyloxy-phenyl)-[1,2,4]oxadiazol-3-ylmethyl]-6,7-diethoxy-3,4-dihydro-isoquinoline 
• 107301-39-3 4-(2-Imino-9,10-dimethoxy-6,7-dihydro-2H-pyrimido[6,1-a]isoquinolin-4-yl)-phenol; hydrochloride 
• 107301-53-1 4-(9,10-Diethoxy-2-imino-6,7-dihydro-2H-pyrimido[6,1-a]isoquinolin-4-yl)-phenol; hydrochloride 
• 120-47-8 Ethyl 4-hydroxybenzoate 

Relevant academic research and scientific papers

Design, synthesis, and biological activity evaluation of 2-(benzo[b]thiophen-2-yl)-4-phenyl-4,5-dihydrooxazole derivatives as broad-spectrum antifungal agents

To discover antifungal compounds with broad-spectrum and stable metabolism, a series of 2-(benzo[b]thiophen-2-yl)-4-phenyl-4,5-dihydrooxazole derivatives was designed and synthesized. Compounds A30-A34 exhibited excellent broad-spectrum antifungal activity against Candida albicans with MIC values in the range of 0.03–0.5 μg/mL, and against Cryptococcus neoformans and Aspergillus fumigatus with MIC values in the range of 0.25–2 μg/mL. In addition, compounds A31 and A33 showed high metabolic stability in human liver microsomes in vitro, with the half-life of 80.5 min and 69.4 min, respectively. Moreover, compounds A31 and A33 showed weak or almost no inhibitory effect on the CYP3A4 and CYP2D6. The pharmacokinetic evaluation in SD rats showed that compound A31 had suitable pharmacokinetic properties and was worthy of further study.

Transition-Metal-Free and Base-Promoted Carbon-Heteroatom Bond Formation via C-N Cleavage of Benzyl Ammonium Salts

A facile and general method for constructing carbon-heteroatom (C-P, C-O, C-S, and C-N) bonds via C-N cleavage of benzyl ammonium salts under transition-metal-free conditions was reported. The combination of t-BuOK and 18-crown-6 enabled a wide range of substituted benzyl ammonium salts to couple readily with different kinds of heteroatom nucleophiles, i.e. hydrogen phosphoryl compounds, alcohols, thiols, and amines. Good functional group tolerance was demonstrated. The scale-up reaction and one-pot synthesis were also successfully performed.

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.

Development and application of a high-throughput screening assay for identification of small molecule inhibitors of the P. falciparum reticulocyte binding-like homologue 5 protein

The P. falciparum parasite, responsible for the disease in humans known as malaria, must invade erythrocytes to provide an environment for self-replication and survival. For invasion to occur, the parasite must engage several ligands on the host erythrocyte surface to enable adhesion, tight junction formation and entry. Critical interactions include binding of erythrocyte binding-like ligands and reticulocyte binding-like homologues (Rhs) to the surface of the host erythrocyte. The reticulocyte binding-like homologue 5 (Rh5) is the only member of this family that is essential for invasion and it binds to the basigin host receptor. The essential nature of Rh5 makes it an important vaccine target, however to date, Rh5 has not been targeted by small molecule intervention. Here, we describe the development of a high-throughput screening assay to identify small molecules which interfere with the Rh5-basigin interaction. To validate the utility of this assay we screened a known drug library and the Medicines for Malaria Box and demonstrated the reproducibility and robustness of the assay for high-throughput screening purposes. The screen of the known drug library identified the known leukotriene antagonist, pranlukast. We used pranlukast as a model inhibitor in a post screening evaluation cascade. We procured and synthesised analogues of pranlukast to assist in the hit confirmation process and show which structural moieties of pranlukast attenuate the Rh5 – basigin interaction. Evaluation of pranlukast analogues against P. falciparum in a viability assay and a schizont rupture assay show the parasite activity was not consistent with the biochemical inhibition of Rh5, questioning the developability of pranlukast as an antimalarial. The high-throughput assay developed from this work has the capacity to screen large collections of small molecules to discover inhibitors of P. falciparum Rh5 for future development of invasion inhibitory antimalarials.

Boron-Catalyzed O-H Bond Insertion of α-Aryl α-Diazoesters in Water

A catalytic, metal-free O-H bond insertion of α-diazoesters in water in the presence of B(C6F5)3·nH2O (2 mol %) was developed, affording a series of α-hydroxyesters in good to excellent yields. The reaction features easy operation and wide substrate scope, and importantly, no metal is needed as compared with the conventional methods. Significantly, this approach further expands the applications of B(C6F5)3 under water-tolerant conditions.

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.

Nonsymmetrical cholesterol dimers constituting regioisomeric oxadiazole and thiadiazole cores: an investigation of the structure-property correlation

Three series of chiral nonsymmetrical dimers were prepared by connecting promesogenic cholesterol to a bent structure derived from a substituted 1,3,4-oxadiazole or 1,2,4-oxadiazole or 1,3,4-thiadiazole moiety. These two mesogenic segments are interconnected through spacers of varying lengths and parity. The structures of the bent achiral unit were systematically varied with different central heterocyclic cores to understand the influence of bent angles on the thermal and gelation behavior. The bent angle of the achiral unit, which is determined by the heterocyclic core, has a major role in the stabilization of frustrated phases. Dimers based on the 1,3,4-oxadiazole unit with a more bent structure stabilized frustrated phases like blue phases and twist grain boundary phases. The bent system with a wider bent angle preferred to stabilize chiral nematic and smectic A phases. It is interesting to note that an increased bent structure reduced the mesophase stability as in the case of dimers based on the 1,3,4-oxadiazole unit, where many compounds exhibited monotropic phases. In the case of dimers with a wider bent angle, enantiotropic mesomorphism was observed. All the compounds showed blue light emission in the solution. Among these chiral dimers, only the compounds based on the 1,3,4-oxadiazole unit showed the gelation ability, which emphasizes how small structural changes like bent angle, dipole moment and the type of heteroatom in the heterocyclic unit affect the macroscopic self-assembly.

Synthesis and anticonvulsant activity evaluation of 4-butyl-5-(4- alkoxyphenyl)-2H-1,2,4-triazole-3(4H)-ones

A series of 4-butyl-5-(4-alkoxyphenyl)-2H-1,2,4-triazole-3(4H)-ones (6a-6u) was designed and synthesized. The anticonvulsant effects and neurotoxicity of the compounds were evaluated with maximal electroshock test and rotarod test. Among the synthetic compounds, 4-butyl-5-(4-(2-fluorinebenzyl)phenyl)-2H-1,2,4- triazole-3 (4H)-one (6k) was the most potent with ED50 value of 27.4 mg/kg and protective index (PI = TD50/ED50) value of 12.0. Besides the anti-MES efficacy, the potency of compound 6k against seizures induced by pentylenetetrazole (PTZ), 3-mercaptopropionic acid (3-MP), and bicuculline (BIC) was also established, which suggested that the mechanisms of action including enhancing of GABAergic activity might be involved in its anticonvulsant activity.