43038-45-5

Usage

Uses

Used in Pharmaceutical Industry:
1-NAPHTHHYDRAZIDE is used as a reagent for the synthesis of various pharmaceutical compounds, contributing to the development of new drugs and therapeutic agents.
Used in Dye Industry:
1-NAPHTHHYDRAZIDE is used as a reagent in the production of dyes, playing a crucial role in the creation of colorants for various applications, including textiles, plastics, and printing inks.
Used in Biochemistry and Molecular Biology:
1-NAPHTHHYDRAZIDE is used as a reagent for detecting and quantifying specific types of biomolecules, such as lipids and ketones, aiding in research and diagnostic applications.
Used in Agriculture:
1-NAPHTHHYDRAZIDE is used as a plant growth regulator, potentially influencing plant development and crop yield, although its application in this field requires further research and validation.

InChI:InChI=1/C11H10N2O/c12-13-11(14)10-7-3-5-8-4-1-2-6-9(8)10/h1-7H,12H2,(H,13,14)

Upstream product

• 879-18-5 naphthalene-1-carbonic acid chloride 
• 2459-24-7 methyl 1-naphthoate 
• 90-11-9 1-Bromonaphthalene 
• 3007-97-4 ethyl 1-naphthoate 
• 86-55-5 1-naphthalenecarboxylic acid 

Downstream Products

• 64001-71-4 2-(naphthalen-1-yl)-1,3,4-oxadiazole 
• 6917-53-9 1-α-Naphthoyl-2-β-naphthoyl-hydrazin 
• 70491-78-0 Naphthalene-1-carboxylic acid N'-(3-oxo-3-phenyl-1-p-tolyl-propyl)-hydrazide 
• 70284-60-5 Naphthalene-1-carboxylic acid N'-(3-oxo-1,3-diphenyl-propyl)-hydrazide 
• 116082-89-4 5-[1]naphthyl-3H-[1,3,4]oxadiazole-2-thione 
• 807628-38-2 C₃₅H₃₅N₅O₅Si 
• 116082-89-4 5-(naphthalen-1-yl)-1,3,4-oxadiazole-2-thiol 
• 1292842-40-0 C₄₀H₃₀N₈S₂ 
• 1292842-41-1 C₄₀H₃₀N₈O₂S₂ 
• 1292842-42-2 C₄₀H₂₈N₁₀O₄S₂ 
• 1292842-43-3 C₄₄H₄₀N₁₀S₂ 
• 1292842-44-4 C₄₀H₃₀N₈O₂S₂ 
• 1292842-45-5 C₄₀H₂₈Cl₂N₈S₂ 
• 1292842-48-8 C₄₀H₃₀N₈O₂S₂ 

Relevant academic research and scientific papers

N-Amino-1,8-Naphthalimide is a Regenerated Protecting Group for Selective Synthesis of Mono-N-Substituted Hydrazines and Hydrazides

A new route to synthesis of various mono-N-substituted hydrazines and hydrazides by involving in a new C?N bond formation by using N-amino-1,8-naphthalimide as a regenerated precursor was invented. Aniline and phenylhydrazines are reproduced upon reacting these individually with 1,8-naphthalic anhydride followed by hydrazinolysis. The practicality and simplicity of this C?N dihalo alkanes; developed a synthon for bond formation protocol was exemplified to various hydrazines and hydrazides. N-amino-1,8-naphthalimide is suitable synthon for transformation for selective formation of mono-substituted hydrazine and hydrazide derivatives. Those are selective mono-amidation of hydrazine with acid halides; mono-N-substituted hydrazones from aldehydes; synthesis of N-aminoazacycloalkanes from acetohydrazide scaffold and inserted to hydroxy derivatives; distinct synthesis of N,N-dibenzylhydrazines and N-benzylhydrazines from benzyl halides; synthesis of N-amino-amino acids from α-halo esters. Ecofriendly reagent N-amino-1,8-naphthalimide was regenerated with good yields by the hydrazinolysis in all procedures.

Design, Synthesis, and Pharmacological Evaluation of First-in-Class Multitarget N-Acylhydrazone Derivatives as Selective HDAC6/8 and PI3Kα Inhibitors

Targeting histone deacetylases (HDACs) and phosphatidylinositol 3-kinases (PI3Ks) is a very promising approach for cancer treatment. This manuscript describes the design, synthesis, in vitro pharmacological profile, and molecular modeling of a novel class of N-acylhydrazone (NAH) derivatives that act as HDAC6/8 and PI3Kα dual inhibitors. The surprising selectivity for PI3Kα may be related to differences in the conformation in the active site. Cellular studies showed that these compounds act in HDAC6 inhibition and the PI3/K/AKT/mTOR pathway. The compounds that are selective for inhibition of HDAC6/8 and inhibit PI3Kα show potential for the treatment of cancer.

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.

New gold (I) complexes with 5-aromatic ring-1, 3, 4-oxadiazole-2-thione and triphenylphosphine as potential multifunctional materials

Three new gold (I) complexes (4a, 4b, 4c) with 5-aromatic ring-1, 3, 4-oxadiazole-2-thione and triphenylphosphine as ligands were synthesized. Structures of 4a and 4b were determined through X-ray single-crystal diffraction, and it displayed that 4a and 4b had the same metal coordination pattern, wherein the ligand was coordinated by the sulfur atom to the central metal ion of gold (I). The optical properties of these gold (I) complexes were studied both in solution and in solid-state. In DMSO, 4a and 4b peaked at 415 nm and 443 nm, respectively, and the CIE coordinates of 4a and 4b in the solid-state were in the green area namely, (0.26, 0.46) and (0.24, 0.41). HOMO/LUMO levels and bandgaps of 4a, 4b and 4c were assessed by UV spectrum estimation, electrochemical method, and theoretical calculations. The observation hinted that the photophysical properties and energy levels of these gold (I) complexes can be adjusted by the introduction of different substituent aromatic rings at the 5-position of the 1, 3, 4-oxadiazole-2-thiol moiety. The findings of good optical, electrochemical and thermal properties of these new gold (I) complexes demonstrated their potential in the future studies as multifunctional materials.

Synthesis and structural study of some N-acyl-4-allylsemicarbazides and the product of their cyclization with a potential antimicrobial activity

In this paper semicarbazide (2a-2h) and 1,2,4-trazole (3a-3h) derivatives with allyl group were synthesized. All compounds were tested in vitro for their antimicrobial activity showing different activity to E. coli, S. aureus, S. epidermidis, M. smegmatis, M. phlei and M. tuberculosis H37Ra. The antimicrobial activity is showed 2g against S. epidermidis, 3g against E. coli and S. epidermidis and 3h against E. coli. The crystal structure of determinations of 2b, 2d, 3b, 3c and 3e were undertaken in order to confirm the synthesis pathway and identification of their tautomeric forms in the crystalline state. Theoretical calculations showed that the physico-chemicals (logP) and electronic properties (MEP distribution, energy localization of HOMO and LUMO orbitals) are related to observed antimicrobial activity of investigated compounds. The molecular docking study carried out for the most active against M. tuberculosis compound 3b using the M. tuberculosis cytochrome P450 CYP121 showed that this compound binds to the active site of P450 by hydrogen bonds via water molecule with the amino acid residue of Met86A and molecule of hem.

Structure-Activity Relationships of Nitro-Substituted Aroylhydrazone Iron Chelators with Antioxidant and Antiproliferative Activities

Aroylhydrazone iron chelators such as salicylaldehyde isonicotinoyl hydrazone (SIH) protect various cells against oxidative injury and display antineoplastic activities. Previous studies have shown that a nitro-substituted hydrazone, namely, NHAPI, displayed markedly improved plasma stability, selective antitumor activity, and moderate antioxidant properties. In this study, we prepared four series of novel NHAPI derivatives and explored their iron chelation activities, anti- or pro-oxidant effects, protection against model oxidative injury in the H9c2 cell line derived from rat embryonic cardiac myoblasts, cytotoxicities to the corresponding noncancerous H9c2 cells, and antiproliferative activities against the MCF-7 human breast adenocarcinoma and HL-60 human promyelocytic leukemia cell lines. Nitro substitution had both negative and positive effects on the examined properties, and we identified new structure-activity relationships. Naphthyl and biphenyl derivatives showed selective antiproliferative action, particularly in the breast adenocarcinoma MCF-7 cell line, where they exceeded the selectivity of the parent compound NHAPI. Of particular interest is a compound prepared from 2-hydroxy-5-methyl-3-nitroacetophenone and biphenyl-4-carbohydrazide, which protected cardiomyoblasts against oxidative injury at 1.8 ± 1.2 μM with 24-fold higher selectivity than SIH. These compounds will serve as leads for further structural optimization and mechanistic studies.

HISTONE DEACETYLASE INHIBITORS AND USES THEREOF

Provided herein are compounds of the formula (I) as well as pharmaceutically acceptable salts thereof, wherein the substituents are as those disclosed in the specification. These compounds, and the pharmaceutical compositions containing them, are useful for the treatment of cancer.

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.

Aroylhydrazone iron chelators: Tuning antioxidant and antiproliferative properties by hydrazide modifications

Aroylhydrazones such as salicylaldehyde isonicotinoyl hydrazone (SIH) are tridentate iron chelators that may possess antioxidant and/or antineoplastic activities. Their main drawback, their low stability in plasma, has recently been partially overcome by exchanging the aldimine hydrogen for an unbranched alkyl group. In this study, ten analogs of methyl- and ethyl-substituted SIH derivatives with modified hydrazide scaffolds were synthesized to further explore their structure-activity relationships. Their iron-chelation efficiencies, anti- or pro-oxidant potentials, abilities to induce protection against model oxidative injury on the H9c2 cell line derived from rat embryonic cardiac tissue, cytotoxicities on the same H9c2 cells and antiproliferative activities on MCF-7 human breast adenocarcinoma and HL-60 human promyelotic leukemia cell lines were evaluated. Compounds derived from lipophilic naphthyl and biphenyl hydrazides displayed highly selective antiproliferative activities against both MCF-7 and HL-60 cell lines, and they showed markedly improved stabilities in plasma compared to SIH. Of particular interest is a hydrazone prepared from 2-hydroxypropiophenone and pyridazin-4-carbohydrazide that showed a considerable antiproliferative effect and protected cardiomyoblasts against oxidative stress with a five-fold higher selectivity compared to the parent compound SIH. Thus, this work highlighted new structure-activity relationships among antiproliferative and antioxidant aroylhydrazones and identified new lead compounds for further development.

Development of Allosteric Hydrazide-Containing Class i Histone Deacetylase Inhibitors for Use in Acute Myeloid Leukemia

One of the biggest hurdles yet to be overcome for the continued improvement of histone deacetylase (HDAC) inhibitors is finding alternative motifs equipotent to the classic and ubiquitously used hydroxamic acid. The N-hydroxyl group of this motif is highly subject to sulfation/glucoronidation-based inactivation in humans; compounds containing this motif require much higher dosing in clinic to achieve therapeutic concentrations. With the goal of developing a second generation of HDAC inhibitors lacking this hydroxamate, we designed a series of potent and selective class I HDAC inhibitors using a hydrazide motif. These inhibitors are impervious to glucuronidation and demonstrate allosteric inhibition. In vitro and ex vivo characterization of our lead analogues' efficacy, selectivity, and toxicity profiles demonstrate that they possess low nanomolar activity against models of acute myeloid leukemia (AML) and are at least 100-fold more selective for AML than solid immortalized cells such as HEK293 or human peripheral blood mononuclear cells.