7640-37-1

Upstream product

• 100-48-1 pyridine-4-carbonitrile 
• 55-22-1 pyridine-4-carboxylic acid 
• 1570-45-2 isonicotinic acid ethylester 
• 1453-82-3 isonicotinamide 
• 88057-93-6 (piperidin-1-yl)(pyridin-4-yl)methanethione 
• 17332-42-2 N-cyclohexylpyridine-4-carbothioamide 
• 13841-66-2 butyl isonicotinate 
• 53-91-8 {3-hydroxy-4-[(E)-(isonicotinoylhydrazono)methyl]-2-methylpyridin-5-yl}methylphosphate 
• 302-01-2 hydrazine 
• 2459-09-8 4-pyridinecarboxylic acid, methyl ester 
• 872-85-5 pyridine-4-carbaldehyde 
• 39178-35-3 isonicotinoyl chloride hydrochloride 
• 536-75-4 4-Ethylpyridine 
• 14254-57-0 4-(chlorocarbonyl)pyridine 

Downstream Products

• 103033-32-5 isonicotinic acid-[2-(tetra-O-acetyl-β-D-glucopyranosyloxy)-benzylidenehydrazide] 
• 91803-29-1 isonicotinic acid-(1-[4]pyridyl-ethylidenehydrazide) 
• 14152-90-0 isonicotinic acid-(3-phenyl-propylidenehydrazide) 
• 17346-05-3 isonicotinic acid bibenzyl-α-ylidenehydrazide 
• 106273-71-6 isonicotinic acid-(4-sulfamoyl-benzylidenehydrazide) 
• 92852-66-9 isonicotinic acid-(3-ethoxy-4-hydroxy-benzylidenehydrazide) 
• 52540-96-2 2-hydroxy-3-(isonicotinoylhydrazono-methyl)-benzoic acid 
• 108956-06-5 isonicotinic acid-(2-hydroxy-4-nitro-benzylidenehydrazide) 
• 95812-37-6 isonicotinic acid-[([1]naphthyl-phenyl-methylene)-hydrazide] 
• 75847-68-6 isonicotinic acid-(3-methylsulfanyl-propylidenehydrazide) 
• 91959-21-6 4-(5-cyclohexyl-[1,3,4]oxadiazol-2-yl)-pyridine 
• 102240-54-0 isonicotinic acid-(1-phenyl-octylidenehydrazide) 
• 107922-70-3 isonicotinic acid-[1-(3,4-dihydroxy-phenyl)-ethylLiDenehydrazide] 

Relevant academic research and scientific papers

Design, docking, synthesis, and characterization of novel N'(2-phenoxyacetyl) nicotinohydrazide and N'(2-phenoxyacetyl)isonicotinohydrazide derivatives as anti-inflammatory and analgesic agents

Inflammation is the complex biological response of vascular tissues, which is partly determined by prostaglandins (PLA2). The cyclooxygenase (COX) enzyme exists in two isoforms: COX-1 and COX-2 and by the action of this, the PGs are produced. Besides, nonsteroidal anti-inflammatory drugs (NSAIDs) are therapeutic agents useful in the treatment of inflammation. Encouraged by this, the new derivatives of N'(2-phenoxyacetyl)nicotinohydrazide 9(a-e) and N'(2-phenoxyacetyl)isonicotinohydrazide 10(a-e) were designed, synthesized, characterized, and identified as remarkable anti-inflammatory and analgesic agents. These compounds were prepared in a series of steps starting with different phenol derivatives. Among the series, compound (10e) showed the highest IC50 value for COX-1 inhibition, whereas compounds (9e) and (10e) exhibited the highest COX-2SI. Further, molecular Docking Studies have been performed for the potent compound to check the three-dimensional geometrical view of the ligand binding to the targeted enzymes.

Development of potent nanosized isatin-isonicotinohydrazide hybrid for management of Mycobacterium tuberculosis

Inspired by the antitubercular activity of isoniazid (INH) and 5-bromoisatin, isatin–INH hybrid (WF-208) has been synthesized as a potent agent against multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains of M. tuberculosis. In silico molecular docking studies indicated that DprE1, a critical enzyme in the synthesis of M. tuberculosis cell wall, is a potential enzymatic target for WF-208. The synthesized WF-208 was incorporated into a nanoparticulate system to enhance stability of the compound and to sustain its antimicrobial effect. Nanosized spherical niosomes (hydrodynamic diameter of ca. 500–600 nm) could accommodate WF-208 at a high encapsulation efficiency of 74.2%, and could impart superior stability to the compound in simulated gastric conditions. Interestingly, WF-208 had minimal inhibitory concentrations (MICs) of 7.8 and 31.3 μg/mL against MDR and XDR M. tuberculosis, respectively, whereas INH failed to demonstrate bacterial growth inhibition at the range of the tested concentrations. WF-208-loaded niosomes exhibited a 4-fold increase in the anti-mycobacterial activity as compared to the free compound (MIC of 1.9 vs. 7.8 μg/mL) against H37Rv M. tuberculosis, after three weeks of incubation with WF-208-loaded niosomes. Incorporation of the compound into nanosized vesicles allowed for a further increase in stability, potency and sustainability of the anti-mycobacterial activity, thus, providing a promising strategy for management of tuberculosis.

Pleuromutilin derivative with 1, 3, 4-oxadiazole side chain and preparation and application thereof

The invention belongs to the field of medicinal chemistry, and particularly relates to a pleuromutilin derivative with a 1, 3, 4-oxadiazole side chain and preparation and application thereof The pleuromutilin derivative with the 1, 3, 4-oxadiazole side chain is a compound shown in a formula 2 or a pharmaceutically acceptable salt thereof, and a solvent compound, an enantiomer, a diastereoisomer and a tautomer of the compound shown in the formula 2 or the pharmaceutically acceptable salt thereof or a mixture of the solvent compound, the enantiomer, the diastereoisomer and the tautomer in any proportion, including a racemic mixture. The pleuromutilin derivative has good antibacterial activity, is especially suitable for being used as a novel antibacterial agent for systemic system infection of animals or human beings, and has good water solubility.

Discovery, synthesis and in combo studies of Schiff’s bases as promising dipeptidyl peptidase-IV inhibitors

Abstract: Diabetes mellitus is a main global health apprehension. Macrovascular illnesses, neuropathy, retinopathy, and nephropathy are considered some of its severe hitches. Gliptins are a group of hypoglycemic agents that inhibit dipeptidyl peptidase-IV (DPP-IV) enzyme and support blood glucose-lowering effect of incretins. In the current research, synthesis, characterization, docking, and biological evaluation of fourteen Schiff’s bases 5a–f and 9a–h were carried out. Compound 9f revealed the best in vitro anti-DPP-IV activity of 35.7% inhibition at a concentration of 100?μM. Compounds 9c and 9f with the highest in vitro DPP-IV inhibition were subjected to the in vivo glucose-lowering test using vildagliptin as a positive inhibitor. Vildagliptin, 9c, and 9f showed significant reduction in the blood glucose levels of the treated mice after 30?min of glucose administration. Moreover, induced fit docking showed that these derivatives accommodated the enzyme binding site with comparable docking scores. Schiff’s bases can serve as promising lead for the development of new DPP-IV inhibitors. Graphical Abstract: [Figure not available: see fulltext.].

Development of Novel (+)-Nootkatone Thioethers Containing 1,3,4-Oxadiazole/Thiadiazole Moieties as Insecticide Candidates against Three Species of Insect Pests

To improve the insecticidal activity of (+)-nootkatone, a series of 42 (+)-nootkatone thioethers containing 1,3,4-oxadiazole/thiadiazole moieties were prepared to evaluate their insecticidal activities against Mythimna separata Walker, Myzus persicae Sulzer, and Plutella xylostella Linnaeus. Insecticidal evaluation revealed that most of the title derivatives exhibited more potent insecticidal activities than the precursor (+)-nootkatone after the introduction of 1,3,4-oxadiazole/thiadiazole on (+)-nootkatone. Among all of the (+)-nootkatone derivatives, compound 8c (1 mg/mL) exhibited the best growth inhibitory (GI) activity against M. separata with a final corrected mortality rate (CMR) of 71.4%, which was 1.54- and 1.43-fold that of (+)-nootkatone and toosendanin, respectively; 8c also displayed the most potent aphicidal activity against M. persicae with an LD50 value of 0.030 μg/larvae, which was closer to that of the commercial insecticidal etoxazole (0.026 μg/larvae); and 8s showed the best larvicidal activity against P. xylostella with an LC50 value of 0.27 mg/mL, which was 3.37-fold that of toosendanin and slightly higher than that of etoxazole (0.28 mg/mL). Furthermore, the control efficacy of 8s against P. xylostella in the pot experiments under greenhouse conditions was better than that of etoxazole. Structure-activity relationships (SARs) revealed that in most cases, the introduction of 1,3,4-oxadiazole/thiadiazole containing halophenyl groups at the C-13 position of (+)-nootkatone could obtain more active derivatives against M. separata, M. persicae, and P. xylostella than those containing other groups. In addition, toxicity assays indicated that these (+)-nootkatone derivatives had good selectivity to insects over nontarget organisms (normal mammalian NRK-52E cells and C. idella and N. denticulata fries) with relatively low toxicity. Therefore, the above results indicate that these (+)-nootkatone derivatives could be further explored as new lead compounds for the development of potential eco-friendly pesticides.

Synthesis, in silico, in vitro and in vivo evaluations of isatin aroylhydrazones as highly potent anticonvulsant agents

In this study, a series of new isatin aroylhydrazones (5a-e and 6a-e) was synthesized and evaluated for their anticonvulsant activities. The (Z)-configuration of compounds was confirmed by 1H NMR. In vivo studies using maximal electroshock (MES) and pentylenetetrazole (PTZ) models of epilepsy in mice revealed that while most of compounds had no effect on chemically-induced seizures at the higher dose of 100 mg/kg but showed significant protection against electrically-induced seizures at the lower dose of 5 mg/kg. Certainly, N-methyl analogs 6a and 6e were found to be the most effective compounds, displaying 100% protection at the dose of 5 mg/kg. Protein binding and lipophilicity (logP) of the selected compounds (6a and 6e) were also determined experimentally. In silico evaluations of title compounds showed acceptable ADME parameters, and drug-likeness properties. Distance mapping and docking of the selected compounds with different targets proposed the possible action of them on VGSCs and GABAA receptors. The cytotoxicity evaluation of 6a and 6e against SH-SY5Y and Hep-G2 cell lines indicated safety profile of compounds on the neuronal and hepatic cells.

Design, synthesis, in vitro and in vivo evaluation against MRSA and molecular docking studies of novel pleuromutilin derivatives bearing 1, 3, 4-oxadiazole linker

A class of pleuromutilin derivatives containing 1, 3, 4-oxadiazole were designed and synthesized as potential antibacterial agents against Methicillin-resistant staphylococcus aureus (MRSA). The ultrasound-assisted reaction was proposed as a green chemistry method to synthesize 1, 3, 4-oxadiazole derivatives (intermediates 85–110). Among these pleuromutilin derivatives, compound 133 was found to be the strongest antibacterial derivative against MRSA (MIC = 0.125 μg/mL). Furthermore, the result of the time-kill curves displayed that compound 133 could inhibit the growth of MRSA in vitro quickly (- 4.36 log10 CFU/mL reduction). Then, compound 133 (- 1.82 log10 CFU/mL) displayed superior in vivo antibacterial efficacy than tiamulin (- 0.82 log10 CFU/mL) in reducing MRSA load in mice thigh model. Besides, compound 133 exhibited low cytotoxicity to RAW 264.7 cells. Molecular docking studies revealed that compound 133 was successfully localized in the binding pocket of 50S ribosomal subunit (ΔGb = -10.50 kcal/mol). The results indicated that these pleuromutilin derivatives containing 1, 3, 4-oxadiazole might be further developed into novel antibiotics against MRSA.

Design, synthesis, antibacterial evaluation, and computational studies of hybrid oxothiazolidin–1,2,4-triazole scaffolds

Bacterial infections are a serious threat to human health due to the development of resistance against the presently used antibiotics. The problem of growing and widespread antibiotic resistance is only getting worse with the shortage of new classes of antibiotics, creating a substantial unmet medical need in the treatment of serious bacterial infections. Therefore, in the present work, we report 18 novel hybrid thiazolidine–1,2,4-triazole derivatives as DNA gyrase inhibitors. The derivatives were synthesized by multistep organic synthesis and characterized by spectroscopic methods (1H and 13C nuclear magnetic resonance and mass spectroscopy). The derivatives were tested for DNA gyrase inhibition, and the result emphasized that the synthesized derivatives have a tendency to inhibit the function of DNA gyrase. Furthermore, the compounds were also tested for antibacterial activity against three Gram-positive (Bacillus subtilis [NCIM 2063], Bacillus cereus [NCIM 2156], Staphylococcus aureus [NCIM 2079]) and two Gram-negative (Escherichia coli [NCIM 2065], Proteus vulgaris [NCIM 2027]) bacteria. The derivatives showed a significant-to-moderate antibacterial activity with noticeable antibiofilm efficacy. Quantitative structure–activity relationship (QSAR), ADME (absorption, distribution, metabolism, elimination) calculation, molecular docking, radial distribution function, and 2D fingerprinting were also performed to elucidate fundamental structural fragments essential for their bioactivity. These studies suggest that the derivatives 10b and 10n have lead antibacterial properties with significant DNA gyrase inhibitory efficacy, and they can serve as a starting scaffold for the further development of new broad-spectrum antibacterial agents.

N-acylhydrazones confer inhibitory efficacy against New Delhi metallo-β-lactamase-1

The expression of β-lactamases, especially metallo-β-lactamases (MβLs) in bacteria is one of the main causes of drug resistance. In this work, an effective N-acylhydrazone scaffold as MβL inhibitor was constructed and characterized. The biological activity assays indicated that the synthesized N-acylhydrazones 1–11 preferentially inhibited MβL NDM-1, and 1 was found to be the most effective inhibitor with an IC50 of 1.2 μM. Analysis of IC50 data revealed a structure–activity relationship, which is that the pyridine and hydroxylbenzene substituents at 2-position improved inhibition of the compounds on NDM-1. ITC and enzyme kinetics assays suggested that it reversibly and competitively inhibited NDM-1 (Ki = 0.29 ± 0.05 μM). The synthesized N-acylhydrazones showed synergistic antibacterial activities with meropenem, reduced 4–16-fold MIC of meropenem on NDM-1- producing E. coli BL21 (DE3), while 1 restored 4-fold activity of meropenem on K. pneumonia expressing NDM-1 (NDM-K. pneumoniae). The mice experiments suggested that 1 combined meropenem to fight against NDM-K. pneumoniae infection in the spleen and liver. Cytotoxicity assays showed that 1 and 2 have low cytotoxicity. This study offered a new framework for the development of NDM-1 inhibitors.

A CONTINUOUS FLOW SYNTHESIS METHOD FOR THE MANUFACTURE OF ISONIAZID

A multistep continuous flow synthesis method for the manufacture of isonicotinyl-hydrazide (Isoniazid) comprising reacting 4-cyano pyridine with NaOH at a specified molar ratio and temperature range to produce the intermediate isonicotinamide, which intermediate is reacted with hydrazine hydrate, without isolation thereof, at a specified molar ratio and temperature range to produce isonicotinyl-hydrazide (Isoniazid) in a yield greater than about 90%.