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Usage

Uses

Used in Pharmaceutical Synthesis:
2-(naphthalen-2-yl)acetohydrazide is used as a reagent for the synthesis of various pharmaceutical compounds due to its unique chemical properties and the presence of the naphthalene ring structure, which can be exploited in the development of new drugs.
Used in Cancer Treatment Research:
In the field of oncology, 2-(naphthalen-2-yl)acetohydrazide is used as a potential therapeutic agent for the treatment of various types of cancer. Its specific mode of action and efficacy are under investigation, but its chemical structure suggests it may interact with biological targets relevant to cancer cell growth and proliferation.
Used in Neurological Disorder Research:
2-(naphthalen-2-yl)acetohydrazide is also being studied for its potential applications in the treatment of neurological conditions. 2-(naphthalen-2-yl)acetohydrazide's interaction with specific biological pathways or receptors in the nervous system could offer new avenues for managing or treating such disorders.
Used in Pesticide Development:
Due to its pesticidal properties, 2-(naphthalen-2-yl)acetohydrazide is used in the development of new pesticides. Its chemical structure may provide a basis for creating effective agents against pests that are resistant to existing pesticides.
Used in Antimicrobial Applications:
2-(naphthalen-2-yl)acetohydrazide is used as a potential antimicrobial agent, suggesting it may have utility in combating microbial infections. Its specific antimicrobial activity and spectrum are subjects of ongoing research, with the aim of identifying its potential use in medical or industrial settings.

Upstream product

• 2876-71-3 methyl 2-naphthylacetate 
• 581-96-4 2-naphthylacetic acid 
• 2876-70-2 ethyl 2-naphthylacetate 

Downstream Products

• 865811-81-0 cyclopropanecarboxylic acid N'-(2-naphthalen-2-yl-acetyl)-hydrazide 

Relevant academic research and scientific papers

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.

Preliminary SAR and biological evaluation of antitubercular triazolothiadiazine derivatives against drug-susceptible and drug-resistant Mtb strains

Following up the SAR study of triazolothiadiazoles for their antitubercular activities targeting Mt SD in our previous study, on the principle of scaffold hopping, the C3 and C6 positions of triazolothiadiazine were examined systematically to define a preliminary structure–activity relationship (SAR) with respect to biological activity. This study herein highlights the potential of two highly potent advanced leads 6c-3, 6g-3 and several other compounds with comparable potencies as promising new candidates for the treatment of TB (6c-3, MIC-H37Rv?=?0.25?μg/mL; MIC-MDRTB?=?2.0?μg/mL; MIC-RDRTB?=?0.25?μg/mL; Mt SD-IC50?=?86.39?μg/mL; and 6g-3, MIC-H37Rv?=?1.0?μg/mL; MIC-MDRTB?=?4.0?μg/mL; MIC-RDRTB?=?2.0?μg/mL; Mt SD-IC50?=?73.57?μg/mL). Compounds 6c-3 and 6g-3 possessed a para-nitro phenyl at the 6 position showed low Vero and HepG2 cells toxicity, turning out to be two excellent lead candidates for preclinical trials. In addition, in vitro Mt SD inhibitory assay indicates that Mt SD is at least one of the targets for their antitubercular activity. Thus, they may turn out to be promising multidrug-resistance-reversing agents.

Synthesis, spectral analysis and antibacterial evaluation of 5-substituted-1,3,4-oxadiazol-2-yl 4-(4-methylpiperidin-1-ylsulfonyl)benzyl sulfides

Owing to valuable biological activities of 1,3,4-oxadiazole, sulfamoyl and piperidine functionalities, some new 1-(4-{[(5-substituted-1,3,4-oxadiazol-2-yl) thio]methyl}benzene sulfonyl)-4-methylpiperidine (6a-o) derivatives have been introduced. The target molecules were synthesized from different aralkyl/aryl carboxylic acids, 1a-o, through a series of steps. First the compounds, 1a-o, were converted to heterocyclic 1,3,4-oxadiazole nucleophiles, 4a-o. Second an electrophile as 1-(4-bromomethylbenzenesulfonyl)-4-methylpiperidine (5) was synthesized from 4-methylpiperidine. Finally the target compounds, 6a-o, were prepared by reacting 4a-o with 5 in DMF and LiH. The final compounds were structurally elucidated by spectral data of IR, 1H-NMR and EI-MS. All the compounds were screened for their antibacterial evaluation and found to exhibit valuable results.

Synthesis and effects of oxadiazole derivatives on tyrosinase activity and human SK-MEL-28 malignant melanoma cells

Melanin is a form of pigment that gives colour to human skin, hair and eyes. Whilst it protects against skin damage from the sun, accumulation of excessive amounts of epidermal melanin can lead to various dermatological disorders. This study aimed to evaluate the effects of three selected oxadiazoles on the o-diphenolase mushroom tyrosinase activity and their cytotoxic effects on SK-MEL-28 malignant melanoma cells. The results showed that compounds 1, 2 and 3 exhibited significant inhibition on the diphenolase activity of mushroom tyrosinase with IC50 values of 40.46 μM, 27.42 μM and 32.51 μM, respectively. Further kinetic studies revealed that compounds 1 (Ki = 3.8 μM) and 3 (Ki = 3.9 μM) exhibited a mixed-type inhibition while compound 2 (Ki = 0.7 μM) displayed a competitive-type inhibition as suggested by the Lineweaver-Burk plots. Molecular docking and dynamics simulations were also performed to understand the binding behaviour of compound 2 in the active site of tyrosinase. Finally, all three compounds displayed relatively low cytotoxicity to SK-MEL-28 cells up to 100 μM treatment via MTT assay.

Synthesis & characterization of 2-(substituted-phenyl)acetohydrazide analogs, 1,3,4-oxadiazoles, and 1,2,4-triazine Ring Systems: A novel class of potential analgesic and anti-inflammatory agents

The new series of 2-(substituted-phenyl)acetohydrazides analogs, S-alkylated 5-substituted-1,3,4-oxadiazoles-2-thione derivatives and 5-arylidene-3-substituted-1,2,4-triazines have been synthesized in good yields and characterized by IR, NMR, mass spectral and elemental analyses. All the synthesized compounds 4(a-d), 5(a-d), 7(a-b), and 8(a-f) are evaluated for their in vitro DPPH scavenging, antimicrobial activity, in vivo analgesic, anti-inflammatory activities. The results of the anti-inflammatory activity are supported by molecular docking study with mouse COX-1 (PDB ID: 2CZT) and COX-2 (PDB ID: 3LN1) enzymes to predict their putative interactions. Among all the assays conducted, the compounds 5-(4-bromophenyl)-3-(naphthalen-2-ylmethyl)-1,2,4-triazine (4d) and2-{[5-(diphenylmethyl)-1,3,4-oxadiazol-2-yl]sulfanyl}-N-(pyrazin-2-yl)acetamide (8a) have emerged as the most potent molecules.

SAR studies on 1,2,4-triazolo[3,4-b][1,3,4]thiadiazoles as inhibitors of Mtb shikimate dehydrogenase for the development of novel antitubercular agents

Shikimate dehydrogenase, an essential protein for the biosynthesis of the chorismate end product, is a highly promising therapeutic target, especially for the discovery and development of new-generation anti-TB agents. Following up the identification of one lead 3,6-disubstituted 1,2,4-triazolo[3,4-b][1,3,4]thiadiazole (1), targeting Mt SD in our previous study, an extensive SAR study for optimization of the lead compound was performed through systematic modification of the 3 and 6 positions. This study has successfully led to the discovery of two highly potent advanced leads 6d-4, 6c-4 and several other compounds with comparable potencies (6d-4, MIC-H37Rv = 0.5 μg mL-1; MIC-MDRTB = 4.0 μg mL-1; MIC-RDRTB = 0.5 μg mL-1; Mt SD-IC50 = 14.20 μg mL-1; and 6c-4, MIC-H37Rv = 0.5 μg mL-1; MIC-MDRTB = 4.0 μg mL-1; MIC-RDRTB = 1.0 μg mL-1; Mt SD-IC50 = 6.82 μg mL-1). These advanced lead compounds possess a para-halogen phenyl at the 3 position. In vitro Mt SD inhibitory assay indicates that Mt SD is the target for their antitubercular activity. Moreover, the BacT/ALERT 3D liquid culture technology and in vitro Mt SD inhibitory assay were initially applied.

Synthesis and SAR evaluation of 1,2,4-triazoles as A2A receptor antagonists

The synthesis and in vitro structure-activity relationships (SAR) of a series of triazoles as A2A receptor antagonists is reported. This resulted in the identification of potent, selective and permeable 1,2,4-triazoles such as 42 for further op