83-07-8

Basic information

• Product Name: 4-Aminoantipyrine
• Synonyms: 4-Amine-2,3-dimethyl-lphenyl-5-pyrazolone-[5],Ampyrone;4-amino-1,2-dihydro-1,5-dimethyl-2-phenyl-3h-pyrazol-3-on;4-amino-1,2-dihydro-1,5-dimethyl-2-phenyl-3H-Pyrazol-3-one;4-Amino-1,5-dimethyl-2-phenyl-1,2-dihydro-3H-pyrazol-3-one;4-amino-2,3-dimethyl-1-phenyl-3-pyrazolin-5-on;4-Amminoantipirina;Aminoantipyrin;Aminoazophenazone
• CAS NO: 83-07-8
• Molecular Formula: C11H13N3O
• Molecular Weight: 203.24
• EINECS: 201-452-3
• Product Categories: Drug bulk;Pyridines, Pyrimidines, Purines and Pteredines;Antibiotic Explorer;Heterocycles;Intermediates & Fine Chemicals;Metabolites & Impurities;Pharmaceuticals;PYRAMIDON;Heterocycles, Metabolites & Impurities, Pharmaceuticals, Intermediates & Fine Chemicals;reagent
• Mol File: 83-07-8.mol
• Article Data: 14

Chemical Properties

• Melting Point: 105-110 °C(lit.)
• Boiling Point: 340 C
• Flash Point: 140.7 °C
• Appearance: Yellow to yellow-brown/Powder or Crystals
• Density: 0.8
• Vapor Pressure: 0.000659mmHg at 25°C
• Refractive Index: 1.4930 (estimate)
• Storage Temp.: Store at RT.
• Solubility: H2O: 0.1 g/mL, clear
• PKA: pK1: 4.94(+1) (25°C)
• Water Solubility: ca. 500 g/L (20 ºC)
• Stability: Stable. May be light sensitive.
• Merck: 14,591
• BRN: 181635
• CAS DataBase Reference: 4-Aminoantipyrine(CAS DataBase Reference)
• NIST Chemistry Reference: 4-Aminoantipyrine(83-07-8)
• EPA Substance Registry System: 4-Aminoantipyrine(83-07-8)

Safety Data

• Hazard Codes: Xn
• Statements: 22-36/37/38-20/21/22
• Safety Statements: 26-36-36/37/39
• WGK Germany: 3
• RTECS: CD2480000
• F: 8-9-23
• TSCA: Yes
• Hazardous Substances Data: 83-07-8(Hazardous Substances Data)

Usage

Chemical Properties

Amber crystalline powder

Uses

4-Aminoantipyrine is a metabolite of aminopyrine, having both analgesic and anti-inflammatory properties. It readily forms metal complexes due to its amino nitrogen, a strong coordination site.4-aminoantipyrine forms Schiff bases when treated with aldehydes/ketones, which are used in chemosensing applications.Coupling Reagent for Trinder's reagent in colorimetric hydrogen peroxide detectionassays.Forms highly stable dyes by coupling with Trinder's reagent in presence of Peroxidase and H2O2. Therefore suitable for use in test strip and solution diagnostics.

Application

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. It is also used as indicator for trace phenol determinations in water.Phenolic compounds were 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 colour is intensified through extraction of the complex into chloroform. Measurement of this colour quantitatively determines the phenol concentration of the sample.

Definition

ChEBI: 4-aminoantipyrine is a pyrazolone, a member of the class of pyrazoles that is antipyrine substituted at C-4 by an amino group. It is a metabolite of aminopyrine and of metamizole. It has a role as a non-steroidal anti-inflammatory drug, a non-narcotic analgesic, an antirheumatic drug, a peripheral nervous system drug, an EC 1.14.99.1 (prostaglandin-endoperoxide synthase) inhibitor, an antipyretic, a drug metabolite and a marine xenobiotic metabolite. It is a primary amino compound and a pyrazolone. It derives from an antipyrine.

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.

General Description

4-Aminoantipyrine forms heterocyclic Schiff bases, by reaction with various aldehydes and oximes. These Schiff bases form stable complexes with transition metals.

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

• 30672-29-8 1,5-dimethyl-4-nitro-2-phenyl-1H-pyrazole-3(2H)-one 
• 519-98-2 4-methylaminoantipyrine 
• 58-15-1 aminopyrine 
• 60-80-0 antipyrine 
• 885-11-0 1,5-dimethyl-4-nitroso-2-phenyl-1,2-dihydro-pyrazol-3-one 
• 7732-18-5 water 
• 129-89-5 Melubrin 
• 7664-93-9 sulfuric acid 
• 1759-26-8 (1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)-sulfamic acid 
• 1055-31-8 1,5,5'-trimethyl-2,2'-diphenyl-1,2,2',4'-tetrahydro-4,4'-azanylylidene-bis-pyrazol-3-one 
• 302929-07-3 5-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-ylimino)-barbituric acid 
• 7647-01-0 hydrogenchloride 
• 94332-50-0 4-N-(3,4-methylenedioxybenzalidine)-aminoantipyrine 
• 64-17-5 ethanol 

Downstream Products

• 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 
• 13489-06-0 1,5-dimethyl-2-phenyl-4-(2-thioxo-5,6-dihydro-2H-[1,3]thiazin-4-ylamino)-1,2-dihydro-pyrazol-3-one 
• 53857-11-7 1,9a-dihydro-1,6,9a-trimethyl-2-phenylpyrazolo<3,4-c><1,4>benzoxazin-3(2H)-one 
• 51978-59-7 6-ethyl-1,2,4,10-tetrahydro-1-methyl-2-phenyl-3H-pyrazolo<3,4-c><1,5>benzoxazepin-3-one 
• 16087-01-7 3-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)-2,4-dioxo-3,4-dihydro-2H-benzo[e][1,3]oxazine-6-carboxylic acid methyl ester 
• 16087-02-8 3-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)-2,4-dioxo-3,4-dihydro-2H-benzo[e][1,3]oxazine-6-carboxylic acid ethyl ester 
• 16087-03-9 3-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)-2,4-dioxo-3,4-dihydro-2H-benzo[e][1,3]oxazine-6-carboxylic acid propyl ester 
• 14780-48-4 6-acetylamino-3-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)-benzo[e][1,3]oxazine-2,4-dione 
• 65172-82-9 4-(4-ethyl-4H-furo[3,2-b]indol-2-ylmethyleneamino)-1,5-dimethyl-2-phenyl-1,2-dihydro-pyrazol-3-one 
• 70318-34-2 N-(2-pyridinemethylene)-1,5-dimethyl-2-phenyl-1,2-dihydro-pyrazol-3-one 
• 39197-04-1 4-[bis-(2-hydroxy-ethyl)-amino]-1,5-dimethyl-2-phenyl-1,2-dihydro-pyrazol-3-one 
• 119426-88-9 2,3-dihydro-3-(2,5-dihydro-2,3-dimethyl-5-oxo-1-phenyl-1H-pyrazol-4-yl)-2-thioxoquinazolin-4(1H)-one 
• 83330-02-3 Biphenyl-2,2'-dicarboxylic acid 2-[(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)-amide] 2'-[(4-nitro-phenyl)-amide] 

Relevant articles and documents

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.

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.