83-07-8

Usage

Uses

Used in Pharmaceutical Applications:
4-Aminoantipyrine is used as a non-steroidal anti-inflammatory drug, a non-narcotic analgesic, an antirheumatic drug, and a peripheral nervous system drug. It serves as an EC 1.14.99.1 (prostaglandin-endoperoxide synthase) inhibitor, an antipyretic, a drug metabolite, and a marine xenobiotic metabolite.
Used in Diagnostics:
4-Aminoantipyrine is used as a coupling reagent for Trinder's reagent in colorimetric hydrogen peroxide detection assays. It forms highly stable dyes by coupling with Trinder's reagent in the presence of peroxidase and H2O2, making it suitable for use in test strip and solution diagnostics.
Used in Environmental Analysis:
4-Aminoantipyrine is the most widely used analytical reagent for the estimation of phenol. It is used as a reagent for glucose determination in the presence of peroxidase and phenol. Additionally, it is used as an indicator for trace phenol determinations in water. Phenolic compounds are determined by buffering the sample to a pH of 10.0 and adding 4-aminoantipyrine to produce a yellow or amber-colored complex in the presence of ferricyanide ion. The color is intensified through extraction of the complex into chloroform, allowing for the quantitative measurement of phenol concentration in the sample.

Preparation

synthesis of 4-aminoantipyrine: Antipyrine is nitrosated by sodium nitrite, reduced by ammonium bisulfite and ammonium sulfite, hydrolyzed by sulfuric acid, and finally neutralized with liquid ammonia to obtain 4-aminoantipyrine.

Purification Methods

It crystallises from EtOH or EtOH/ether. [Beilstein 25 III/IV 3554.]

InChI:InChI=1/C11H13N3O/c1-8-10(12)11(15)14(13(8)2)9-6-4-3-5-7-9/h3-7H,12H2,1-2H3

Upstream product

• 885-11-0 1,5-dimethyl-4-nitroso-2-phenyl-1,2-dihydro-pyrazol-3-one 
• 135182-38-6 4-<(2,2,2-Trichlor-1,1-dimethylethoxycarbonyl)amino>antipyrin 
• 7664-93-9 sulfuric acid 
• 1759-26-8 (1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)-sulfamic acid 
• 64-17-5 ethanol 
• 64-19-7 acetic acid 
• 7647-01-0 hydrogenchloride 
• 30672-29-8 1,5-dimethyl-4-nitro-2-phenyl-1H-pyrazole-3(2H)-one 
• 94332-50-0 4-N-(3,4-methylenedioxybenzalidine)-aminoantipyrine 
• 302929-07-3 5-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-ylimino)-barbituric acid 
• 1055-31-8 1,5,5'-trimethyl-2,2'-diphenyl-1,2,2',4'-tetrahydro-4,4'-azanylylidene-bis-pyrazol-3-one 
• 7732-18-5 water 
• 129-89-5 Melubrin 
• 58-15-1 aminopyrine 

Downstream Products

• 70318-34-2 N-(2-pyridinemethylene)-1,5-dimethyl-2-phenyl-1,2-dihydro-pyrazol-3-one 
• 92968-42-8 N-(2-furanylmethylene)-1,5-dimethyl-2-phenyl-1,2-dihydro-pyrazol-3-one 
• 2139-47-1 nifenazone 
• 101896-02-0 4-(1,3-dioxoisoindolin-2-yl)antipyrine 
• 19357-14-3 N-antipyrine-phthalamic acid 
• 4346-22-9 1,5-dimethyl-4-(5-nitro-furan-2-ylmethyleneamino)-2-phenyl-1,2-dihydro-pyrazol-3-one 
• 846042-53-3 pyridine-2,3-dicarboxylic acid mono-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-ylamide) 
• 302929-07-3 5-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-ylimino)-barbituric acid 
• 1055-31-8 1,5,5'-trimethyl-2,2'-diphenyl-1,2,2',4'-tetrahydro-4,4'-azanylylidene-bis-pyrazol-3-one 
• 67523-71-1 4-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-ylimino)-3-phenyl-4H-isoxazol-5-one 
• 100949-94-8 1,5-dimethyl-2-phenyl-4-pyrrolidino-1,2-dihydro-pyrazol-3-one 
• 92296-04-3 4-(2-bromo-propionylamino)-1,5-dimethyl-2-phenyl-1,2-dihydro-pyrazol-3-one 
• 102157-48-2 1,5-dimethyl-2-phenyl-4-(3-phenyl-propylamino)-1,2-dihydro-pyrazol-3-one 
• 102173-45-5 chloro-phenyl-acetic acid-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-ylamide) 

Relevant academic research and scientific papers

N-demethylation of N-methyl-4-aminoantipyrine, the main metabolite of metamizole

Metamizole is an old analgesic used frequently in some countries. Active metabolites of metamizole are the non-enzymatically generated N-methyl-4-aminoantipyrine (4-MAA) and its demethylation product 4-aminoantipyrine (4-AA). Previous studies suggested that 4-MAA demethylation can be performed by hepatic cytochrome P450 (CYP) 3A4, but the possible contribution of other CYPs remains unclear. Using human liver microsomes (HLM), liver homogenate and HepaRG cells, we could confirm 4-MAA demethylation by CYPs. Based on CYP induction (HepaRG cells) and CYP inhibition (HLM) we could identify CYP2B6, 2C8, 2C9 and 3A4 as major contributors to 4-MAA demethylation. The 4-MAA demethylation rate by HLM was 280 pmol/mg protein/h, too low to account for in vivo 4-MAA demethylation in humans. Since peroxidases can perform N-demethylation, we investigated horseradish peroxidase and human myeloperoxidase (MPO). Horse radish peroxidase efficiently demethylated 4-MAA, depending on the hydrogen peroxide concentration. This was also true for MPO; this reaction was saturable with a Km of 22.5 μM and a maximal velocity of 14 nmol/min/mg protein. Calculation of the entire body MPO capacity revealed that the demethylation capacity by granulocyte/granulocyte precursors was approximately 600 times higher than the liver capacity and could account for 4-MAA demethylation in humans. 4-MAA demethylation could also be demonstrated in MPO-expressing granulocyte precursor cells (HL-60). In conclusion, 4-MAA can be demethylated in the liver by several CYPs, but hepatic metabolism cannot fully explain 4-MAA demethylation in humans. The current study suggests that the major part of 4-MAA is demethylated by circulating granulocytes and granulocyte precursors in bone marrow.

Synthesis and biological evaluation of new pyrazolone Schiff bases as monoamine oxidase and cholinesterase inhibitors

In the current work, Schiff base derivatives of antipyrine were synthesized. The chemical characterization of the compounds was confirmed using IR, 1H NMR, 13C NMR and mass spectroscopies. The inhibitory potency of synthesized compounds was investigated towards acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), and monoamine oxidases A and B (MAO-A and MAO-B) enzymes. Some of the compounds displayed significant inhibitory activity against AChE and MAO-B enzymes, respectively. According to AChE enzyme inhibition assay, compounds 3e and 3g were found as the most potent derivatives with IC50 values of 0.285 μM and 0.057 μM, respectively. Also, compounds 3a (IC50 = 0.114 μM), 3h (IC50 = 0.049 μM), and 3i (IC50 = 0.054 μM) were the most active derivatives against MAO-B enzyme activity. So as to understand inhibition type, enzyme kinetics studies were carried out. Furthermore, molecular docking studies were performed to define and evaluate the interaction mechanism between compounds 3g and 3h and related enzymes. ADME (Absorption, Distribution, Metabolism, and Excretion) and BBB (Blood, Brain, Barier) permeability predictions were applied to estimate pharmacokinetic profiles of synthesized compounds.

Photocatalytic hydrogenation of nitroarenes: supporting effect of CoOx on TiO2 nanoparticles

Cobalt oxide visible light-active photo-catalysts supported on TiO2 nanoparticles with varying amount of cobalt oxide [3% CoOx/TiO2 (A), 4% CoOx/TiO2 (B), 5% CoOx/TiO2 (C)] were synthesized by solid-state method followed by calcination. The as-synthesized catalysts were characterized by various techniques such as powder XRD, TEM, EDX, UV-Vis-DRS and XPS analysis. The photocatalytic activity of the as-synthesized materials was studied for the reduction of nitroarenes to the corresponding amines using hydrazine monohydrate as the reductant. Cobalt(ii) oxide is responsible for the reduction of nitroarenes and then, cobalt(iii) is reduced back to the original compound by hydrazine hydrate, thus ascertaining the catalytic nature of this hydrogenation process. XPS suggests the presence of Co(ii) in CoOx/TiO2.

Synthetic process of 4-ampyrone product

The invention provides a synthetic process of a 4-ampyrone product, which comprises the following steps of: preparing antipyrine and sulfuric acid with concentration of 40 to 60% into solution; enabling the solution and sodium nitrite solution to simultaneously flow into a nitrosation reactor, controlling flow rates of the solution and the sodium nitrite solution, and controlling a reaction temperature to be 45 to 50 DEG C; performing a reaction with stirring; testing a reaction endpoint by iodine powder and starch test paper to regulate a water flow rate; enabling nitroso antipyrine generated by nitrosation to immediately flow into a reducing pot to react with a reducing agent ammonium hydrogen sulfite prepared in the pot and aqueous solution of ammonium sulfite; carrying out sampling and measuring a pH value and a reduction degree; heating to a temperature of 90 to 100 DEG C; after hydrolysis, cooling to a temperature of 80 to 85 DEG C; neutralizing to pH of 7 to 7.5 by liquid ammonia; carrying out standing and layering. The process provided by the invention is simple, convenient to operate and high in yield.

Cu2+-selective colorimetric signaling by sequential hydrolysis and oxidative coupling of a Schiff base

A new Cu2+-selective probe was developed based on the Cu2+-induced sequential hydrolysis and oxidative coupling reactions of 4-aminoantipyrine-appended 8-hydroxyquinoline derivative 1. Cu2+-assisted hydrolysis of the enamine moiety of Schiff base 1 afforded its constituents, 4-aminoantipyrine and 8-hydroxyquinoline-2-carboxaldehyde. The Cu2+-induced oxidative coupling between these in situ generated compounds afforded a quinoneimine dye. Prominent naked-eye-detectable selective signaling of Cu2+ions, assisted by EDTA, was realized through a color change from faint yellow to pink with a detection limit of 1.81 × 10?6M.

Preparation of human drug metabolites using fungal peroxygenases

The synthesis of hydroxylated and O- or N-dealkylated human drug metabolites (HDMs) via selective monooxygenation remains a challenging task for synthetic organic chemists. Here we report that aromatic peroxygenases (APOs; EC 1.11.2.1) secreted by the agaric fungi Agrocybe aegerita and Coprinellus radians catalyzed the H2O2-dependent selective monooxygenation of diverse drugs, including acetanilide, dextrorphan, ibuprofen, naproxen, phenacetin, sildenafil and tolbutamide. Reactions included the hydroxylation of aromatic rings and aliphatic side chains, as well as O- and N-dealkylations and exhibited different regioselectivities depending on the particular APO used. At best, desired HDMs were obtained in yields greater than 80% and with isomeric purities up to 99%. Oxidations of tolbutamide, acetanilide and carbamazepine in the presence of H218O2 resulted in almost complete incorporation of 18O into the corresponding products, thus establishing that these reactions are peroxygenations. The deethylation of phenacetin-d1 showed an observed intramolecular deuterium isotope effect [(kH/kD) obs] of 3.1 ± 0.2, which is consistent with the existence of a cytochrome P450-like intermediate in the reaction cycle of APOs. Our results indicate that fungal peroxygenases may be useful biocatalytic tools to prepare pharmacologically relevant drug metabolites.

Scavenging activity of aminoantipyrines against hydroxyl radical

The pyrazolone derivatives antipyrine and 4-(N,N-dimethyl)-aminoantipyrine (aminopyrine) have long been used as analgesic, antipyretic and anti-inflammatory drugs. However, in spite of its recognized therapeutic benefits, the use of pyrazolones has been associated with agranulocytosis. Though the oxidation of aminopyrine by neutrophil-generated hypochlorous acid (HOCl), leading to the formation of a cation radical, has been considered responsible for the potential bone marrow toxicity, the reaction mechanisms of pyrazolones against other reactive oxygen species (ROS) remains elusive. Thus, the reactions of 4-aminoantipyrine and methylated derivatives with hydroxyl radicals (HO?) were studied as a model of their reactivity against ROS. The results show that 4-(N,N-dimethyl)-aminoantipyrine (aminopyrine) undergoes demethylation when reacting with HO· radical, leading to 4-(N-methyl)-aminoantipyrine, which is further demethylated to 4-aminoantipyrine. In addition, it was also observed that another favorable reaction of 4-aminoantipyrines in these conditions is the hydroxylation on the aromatic ring, a reaction that is common to aminopyrine, 4-(N-methyl)-aminoantipyrine, and 4-aminoantipyrine. Whether these reaction mechanisms give rise to harmful reactive intermediates requires further chemico-biological evaluation.

Efficient cleavage of carboxylic tert-butyl and 1-adamantyl esters, and N-Boc-amines using H2SO4 in CH2Cl2

A new procedure for the deprotection of carboxylic tert-butyl and 1-adamantyl esters, and N-Boc-amines using H2SO4 in CH2Cl2 is described. The proposed method is simple, cheap, eco-friendly and represents a valid alternative to existing ones, with special significance in large scale applications.

The cleavage of the 2,2,2-trichloro-1,1-dimethylethoxycarbonyl protective group by tin(II) tris(benzenethiolate)

The cleavage of the 2,2,2-trichloro-1,1-dimethylethoxycarbonyl (trichloro-tert-butoxycarbonyl, TCBOC) protective group for amino and hydroxy functions by tin(II) tris[benzenethiolate] in the presence of tetrabutylammonium cobalt(II) phthalocyanine-5,12,19,26-tetrasulfonate is reported. This combination is superior to previously used deblocking reagents for the TCBOC-group.