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Cas Database

103-90-2

103-90-2

Identification

  • Product Name:Acetaminophen

  • CAS Number: 103-90-2

  • EINECS:203-157-5

  • Molecular Weight:151.165

  • Molecular Formula: C8H9NO2

  • HS Code:2924.29

  • Mol File:103-90-2.mol

Synonyms:Acetamide,N-(4-hydroxyphenyl)-;Acetanilide,4'-hydroxy- (7CI,8CI);4-(Acetylamino)phenol;4-(N-Acetylamino)phenol;4-Acetamidophenol;4-Acetaminophenol;4-Hydroxyacetanilide;4'-Hydroxyacetanilide;Alpiny;Alvedon;Anhiba;Apamid;Apamide;Banesin;Ben-u-ron;Bickie-mol;Biocetamol;Cetadol;Clixodyne;Daphalgan;Datril;Dirox;Enelfa;Eu-Med;Exdol;Gattaphen T;Homoolan;Jin Gang;Korum;Lestemp;Liquagesic;Lonarid;Lyteca;Lyteca Syrup;Minoset;Minoset Plus;Momentum;Multin;N-(4-Hydroxyphenyl)acetamide;N-Acetyl-4-aminophenol;N-Acetyl-4-hydroxyaniline;Pacemo;Pacemol;Panadol;Panadol Actifast;Panadol Extend;Panaleve;Panasorb;Panets;Panodil;Paracetamol;Paracetamol DC;Paracetamole;Parageniol;Paralen;Paramol;Paraspen;Parelan;Parmol;Pasolind N;Pedric;k*e*t*a*m*i*n*e ,kush available;

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Safety information and MSDS view more

  • Pictogram(s):HarmfulXn

  • Hazard Codes:Xn,T,F

  • Signal Word:Warning

  • Hazard Statement:H302 Harmful if swallowedH315 Causes skin irritation H317 May cause an allergic skin reaction H319 Causes serious eye irritation

  • First-aid measures: General adviceConsult a physician. Show this safety data sheet to the doctor in attendance.If inhaled Fresh air, rest. In case of skin contact Rinse and then wash skin with water and soap. In case of eye contact Rinse with plenty of water (remove contact lenses if easily possible). If swallowed Give one or two glasses of water to drink. SYMPTOMS: Symptoms of overexposure to this compound include nausea, vomiting, cyanosis from methemoglobinemia, injury to the liver, kidneys, central nervous system and heart, circulatory collapse, drowsiness, confusion, liver tenderness, low blood pressure, cardiac arrhythmias, jaundice, acute renal failure, death due to liver necrosis, metabolic acidosis, hepatic damage and cirrhosis. Other symptoms include changes in exocrine pancreas, diarrhea, irritability, somnolence, general anesthesia, fever and hepatitis. Diaphoresis and general malaise may occur. Exposure may lead to hematological reactions and, occasionally, skin rashes and other allergic reactions. The rash is usually erythematous or urticarial, but sometimes it is more serious and may be accompanied by drug fever and mucosal lesions. Exposure to large amounts may lead to pallor, anorexia, abdominal pain, abnormalities of glucose metabolism and hepatic encephalopathy. It may also lead to epigastric pain, sweating, paresthesias of distal extremities, muscular aching, weakness, dizziness, central nervous system depression (rare), pain in the upper right quadrant, enlarged liver, oliguria, anuria, coagulation defects and myocardiopathy characterized by ST segment abnormalities, T-wave flattening and pericarditis. This compound can cause purpura, generalized bleeding and hypoglycemia. It can also cause neutropenia, pancytopenia, leukopenia, thrombocytopenia and nephrotoxicity. Other symptoms may include wheezing, general discomfort, blood changes including many anemias (aplastic anemia), central nervous system stimulation, swollen tongue, rapid pulse, skin eruptions, chills, excitement, delirium, vascular collapse and convulsions. Irritation of the skin, eyes, mucous membranes and upper respiratory tract may occur. ACUTE/CHRONIC HAZARDS: This compound may be harmful by ingestion and inhalation. It may cause irritation of the skin, eyes, mucous membranes and upper respiratory tract. When heated to decomposition it emits toxic fumes of carbon monoxide, carbon dioxide and nitrogen oxides. Emergency and supportive measures. Spontaneous vomiting may delay the oral administration of antidote or charcoal and can be treated with metoclopramide or a serotonin receptor antagonist such as ondansetron. Provide general supportive care for hepatic or renal failure if it occurs. Emergency liver transplant may be necessary for fulminant hepatic failure. Encephalopathy, metabolic acidosis, hypoglycemia, and a progressive rise in the prothrombin time are indications of severe liver injury.

  • Fire-fighting measures: Suitable extinguishing media Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide. Special protective equipment for firefighters: Wear self contained breathing apparatus for fire fighting if necessary. Flash point data for this chemical are not available; however, it is probably combustible. Wear self-contained breathing apparatus for firefighting if necessary.

  • Accidental release measures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapours, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. For personal protection see section 8. Personal protection: particulate filter respirator adapted to the airborne concentration of the substance. Sweep spilled substance into covered containers. If appropriate, moisten first to prevent dusting. Do NOT let this chemical enter the environment. Personal precautions: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Discharge into the environment must be avoided. Methods and materials for containment and cleaning up: Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed containers for disposal.

  • Handling and storage: Avoid contact with skin and eyes. Avoid formation of dust and aerosols. Avoid exposure - obtain special instructions before use.Provide appropriate exhaust ventilation at places where dust is formed. For precautions see section 2.2. Provision to contain effluent from fire extinguishing. Store in an area without drain or sewer access.Keep container tightly closed in a dry and well-ventilated place. Keep in a dry place.

  • Exposure controls/personal protection:Occupational Exposure limit valuesBiological limit values Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and at the end of workday. Eye/face protection Safety glasses with side-shields conforming to EN166. Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU). Skin protection Wear impervious clothing. The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace. Handle with gloves. Gloves must be inspected prior to use. Use proper glove removal technique(without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands. The selected protective gloves have to satisfy the specifications of EU Directive 89/686/EEC and the standard EN 374 derived from it. Respiratory protection Wear dust mask when handling large quantities. Thermal hazards

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  • Manufacture/Brand:TRC
  • Product Description:Acetaminophen
  • Packaging:100mg
  • Price:$ 65
  • Delivery:In stock
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  • Manufacture/Brand:Tocris
  • Product Description:Acetaminophen ≥99%(HPLC)
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  • Manufacture/Brand:Tocris
  • Product Description:G-1 ≥98%(HPLC)
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  • Manufacture/Brand:TCI Chemical
  • Product Description:4'-Hydroxyacetanilide >98.0%(HPLC)(N)
  • Packaging:25g
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  • Manufacture/Brand:TCI Chemical
  • Product Description:4'-Hydroxyacetanilide >98.0%(HPLC)(N)
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  • Manufacture/Brand:SynQuest Laboratories
  • Product Description:N-Acetyl-4-aminophenol 99.0%
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  • Manufacture/Brand:SynQuest Laboratories
  • Product Description:N-Acetyl-4-aminophenol 99.0%
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  • Product Description:N-Acetyl-4-aminophenol 99.0%
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  • Manufacture/Brand:Sigma-Aldrich
  • Product Description:Paracetamol European Pharmacopoeia (EP) Reference Standard
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  • Manufacture/Brand:Sigma-Aldrich
  • Product Description:Paracetamol for equipment qualification European Pharmacopoeia (EP) Reference Standard
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Relevant articles and documentsAll total 297 Articles be found

Enhanced catalytic activity of natural hematite-supported ppm levels of Pd in nitroarenes reduction

Gholinejad, Mohammad,Shojafar, Mohammad,Sansano, José M.

, p. 2033 - 2043 (2020)

In this work, Pd NPs supported on amine-modified natural hematite have been prepared and characterized. Using this simple catalyst, nitroaromatic compounds as a major cause of industrial pollution were reduced to corresponding amines with ppm levels of Pd in the presence of designer surfactant TPGS-750-M and NaBH4 at room temperature in aqueous media. Synergistic effect between hematite and Pd is responsible for the observed enhanced catalytic activity. This catalyst was recycled for at least four times with a small decrease in the activity.

Influence of medium and temperature on the hydrolysis kinetics of propacetamol hydrochloride: Determination using derivative spectrophotometry

Barcia, Emilia,Martin, Alicia,Azuara, Ma. Luz,Negro, Sofia

, p. 277 - 280 (2005)

Propacetamol hydrochloride (PRO) is a water-soluble prodrug of paracetamol (PA) which can be parenterally administered as analgesic for the treatment of postoperative pain, acute trauma, and gastric and/or intestinal disorders where oral administration is not possible. In these circumstances, PRO can be administered in physiologic or glucose solutions since it is rapidly and quantitatively hydrolyzed into PA by plasma estearases. We have studied the degradation kinetics of PRO in 5% glucose and 0.9% saline solutions at 4 °C and 25 °C (storage and room temperatures, respectively). The analytic technique used to determine PRO and PA quantitatively was first-derivative spectrophotometry. The degradation process of PRO can be best fitted to a second-order kinetics with independence of the medium used (saline or glucose solution). The hydrolysis kinetics of PRO conversion into PA depends on the temperature but not on the assay medium (saline or glucose solution). The degradation rate constants obtained for PRO were approximately 4.5 times higher at 25 °C than at 4 °C. The values of t90% for PRO were 3.17 h and 3.61 h at 25 °C, and 13.42 h and 12.36 h at 4 °C when the tests were performed in 5% glucose and 0.9% saline solutions, respectively.

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Rosenmund et al.

, p. 324,327 (1953)

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Subphthalocyanines: Addressing water-solubility, nano-encapsulation and activation for optical imaging of B16 melanoma cells

Bernhard, Yann,Winckler, Pascale,Chassagnon, Remi,Richard, Philippe,Gigot, lodie,Perrier-Cornet, Jean-Marie,Decrau, Richard A.

, p. 13975 - 13978 (2014)

Water-soluble disulfonato-subphthalocyanines (SubPcs) or hydrophobic nano-encapsulated SubPcs are efficient probes for the fluorescence imaging of cells. 20 nm large liposomes (TEM and DLS) incorporated about 13% SubPc. Moreover, some of these fluorophores were found to be pH activatable.

Regioselective preparation of 5-hydroxypropranolol and 4′-hydroxydiclofenac with a fungal peroxygenase

Kinne, Matthias,Poraj-Kobielska, Marzena,Aranda, Elisabet,Ullrich, Rene,Hammel, Kenneth E.,Scheibner, Katrin,Hofrichter, Martin

, p. 3085 - 3087 (2009)

An extracellular peroxygenase of Agrocybe aegerita catalyzed the H2O2-dependent hydroxylation of the multi-function beta-adrenergic blocker propranolol (1-naphthalen-1-yloxy-3-(propan-2-ylamino)propan-2-ol) and the non-steroidal anti-inflammatory drug diclofenac (2-[2-[(2,6-dichlorophenyl)amino]phenyl]acetic acid) to give the human drug metabolites 5-hydroxypropranolol (5-OHP) and 4′-hydroxydiclofenac (4′-OHD). The reactions proceeded regioselectively with high isomeric purity and gave the desired 5-OHP and 4′-OHD in yields up to 20% and 65%, respectively. 18O-labeling experiments showed that the phenolic hydroxyl groups in 5-OHP and 4′-OHD originated from H2O2, which establishes that the reaction is mechanistically a peroxygenation. Our results raise the possibility that fungal peroxygenases may be useful for versatile, cost-effective, and scalable syntheses of drug metabolites.

Preparation of β-cyclodextrin functionalized reduced graphene oxide: Application for electrochemical determination of paracetamol

Fu, Li,Lai, Guosong,Yu, Aimin

, p. 76973 - 76978 (2015)

β-Cyclodextrin functionalized reduced graphene oxide (β-CD/RGO) was successfully prepared using a simple wet chemical method. The β-CD/RGO nanohybrid was characterized by UV-vis spectroscopy, FTIR, Raman spectroscopy, TEM and SEM. The results confirmed that β-CD had effectively covered the RGO surface. The β-CD/RGO nanohybrid modified glassy carbon electrode was employed for the sensitive electrochemical determination of paracetamol. Cyclic voltammetry measurements indicated that β-CD/RGO could significantly enhance the electrochemical response of paracetamol due to the outstanding electronic properties of RGO sheets and the high supramolecular recognition and enrichment capability of β-CD. The experimental factors were investigated and optimized. Under optimized conditions, the amperometric oxidation currents of paracetamol were linearly proportional to the concentration in the range of 0.01 to 0.8 mM with a detection limit of 2.3 μM (S/N = 3). Furthermore, the proposed sensor exhibited an excellent anti-interference property and acceptable reproducibility.

Spectrophotometric Determination of Aspirin by Transacetylation of 4-Aminophenol

Verma, Krishna K.,Jain, Archana

, p. 821 - 824 (1986)

Aspirin transacetylates 4-aminophenol, yielding acetaminophen (N-acetyl-4-aminophenol), which can be determined by its oxidation to an orange-yellow product either by iodylbenzene in acetone when the absorbance is measured at 430 nm or by photometric titration with 2-iodylbenzoate in acetone-water medium at 444 nm.Salicylic acid, salicylamide, oxyphenbutazone, caffeine, and sodium hydrogen carbonate do not interfere.Drug mixtures of acetaminophen and aspirin have been analyzed by determining acetaminophen alone directly with iodyl reagents and then determining acetaminophen plus aspirin after 4-aminophenol reaction; aspirin is found b y difference

Detection of N-acetyl-p-benzoquinone imine produced during the hydrolysis of the model phenacetin metabolite N-(pivaloyloxy)phenacetin

Novak,Pelecanou,Zemis

, p. 1424 - 1429 (1986)

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Assessment of cytochrome P450 (1A2, 2B6, 2C9 and 3A4) induction in cryopreserved human hepatocytes cultured in 48-well plates using the cocktail strategy

Gerin, Brigitte,Dell'aiera, Sylvie,Richert, Lysiane,Smith, Steven,Chanteux, Hugues

, p. 320 - 335 (2013)

1. A fast, straightforward and cost-effective assay was validated for the assessment of CYP induction in cryopreserved human hepatocytes cultured in 48-well plates. The cocktail strategy (in situ incubation) was used to assess the induction of CYP1A2, CYP2B6, CYP2C9 and CYP3A4 by using the recommended probe substrate, i.e. phenacetin, bupropion, diclofenac and midazolam, respectively. 2. Cryopreserved human hepatocytes were treated for 72 h with prototypical reference inducers, β-naphthoflavone (25 μM), phenobarbital (500 μM) and rifampicin (10 μM) as positive controls for CYP induction. The use of a cocktail strategy has been validated and compared to the classical approach (single incubation). The need of using phase II inhibitor (salicylamide) in CYP induction assay was also investigated. 3. By using three different batches of cryopreserved human hepatocytes and our conditions of incubations, we showed that there was no relevant drug-drug interaction using the cocktail strategy. The same conclusions were observed when a broad range of enzyme activity has to be assessed (wide range of reference inducers, i.e. EC50-Emax experiment). In addition, the interassay reproducibility assessment showed that the day-to-day variability was minimal. 4. In summary, the study showed that the conditions used (probe substrates, concentration of probe substrate and time of incubation) for the cocktail approach were appropriate for investigations of CYP induction potential of new chemical entities. In addition, it was also clear that the use of salicylamide in the incubation media was not mandatory and could generate drug-drug interactions. For this reason, we recommend to not use salicylamide in CYP induction assay.

Oxidation of human cytochrome P450 1A2 substrates by Bacillus megaterium cytochrome P450 BM3

Kim, Dong-Hyun,Kim, Keon-Hee,Kim, Dooil,Jung, Heung-Chae,Pan, Jae-Gu,Chi, Youn-Tai,Ahn, Taeho,Yun, Chul-Ho

, p. 179 - 187 (2010)

Cytochrome P450 enzymes (P450s or CYPs) are good candidates for biocatalysis in the production of fine chemicals, including pharmaceuticals. Despite the potential use of mammalian P450s in various fields of biotechnology, these enzymes are not suitable as biocatalysts due to their low stability, low catalytic activity, and limited availability. Recently, wild-type and mutant forms of bacterial P450 BM3 (CYP102A1) from Bacillus megaterium have been found to metabolize various. It has therefore been suggested that CYP102A1 may be used to generate the metabolites of drugs and drug candidates. In this report, we show that the oxidation reactions of typical human CYP1A2 substrates (phenacetin, ethoxyresorufin, and methoxyresorufin) are catalyzed by both wild-type and mutant forms of CYP102A1. In the case of phenacetin, CYP102A1 enzymes show only O-deethylation product, even though two major products are produced as a result of O-deethylation and 3-hydroxylation reactions by human CYP1A2. Formation of the metabolites was confirmed by HPLC analysis and LC-MS to compare the metabolites with the actual biological metabolites produced by human CYP1A2. The results demonstrate that CYP102A1 mutants can be used for cost-effective and scalable production of human CYP1A2 drug metabolites. Our computational findings suggest that a conformational change in the cavity size of the active sites of the mutants is dependent on activity change. The modeling results further suggest that the activity change results from the movement of several specific residues in the active sites of the mutants.

Identification of human cytochrome P450s that metabolise anti-parasitic drugs and predictions of in vivo drug hepatic clearance from in vitro data

Li, Xue-Qing,Bjoerkman, Anders,Andersson, Tommy B.,Gustafsson, Lars L.,Masimirembwa, Collen

, p. 429 - 442 (2003)

Objective: Knowledge about the metabolism of anti-parasitic drugs (APDs) will be helpful in ongoing efforts to optimise dosage recommendations in clinical practise. This study was performed to further identify the cytochrome P450 (CYP) enzymes that metabolise major APDs and evaluate the possibility of predicting in vivo drug clearances from in vitro data. Methods: In vitro systems, rat and human liver microsomes (RLM, HLM) and recombinant cytochrome P450 (rCYP), were used to determine the intrinsic clearance (CLint) and identify responsible CYPs and their relative contribution in the metabolism of 15 commonly used APDs. Results and discussion: CLint determined in RLM and HLM showed low (r2=0.50) but significant (Pint values were scaled to predict in vivo hepatic clearance (CLH) using the 'venous equilibrium model'. The number of compounds with in vivo human CL data after intravenous administration was low (n=8), and the range of CL values covered by these compounds was not appropriate for a reasonable quantitative in vitro-in vivo correlation analysis. Using the CLH predicted from the in vitro data, the compounds could be classified into three different categories: high-clearance drugs (> 70% liver blood flow; amodiaquine, praziquantel, albendazole, thiabendazole), low-clearance drugs (int drug categories. The identified CYPs for some of the drugs provide a basis for how these drugs are expected to behave pharmacokinetically and help in predicting drug-drug interactions in vivo.

SELECTIVE ACYLATIONS OF AMINOPHENOLS AND HYDROXYALKYLPHENOLS WITH 1-ACETYL-v-TRIAZOLOPYRIDINE.

Paradisi, Mario Paglialunga,Zecchini, Giampiero Pagani,Torrini, Ines

, p. 5029 - 5032 (1986)

The title triazolide serves as a convenient reagent for highly chemoselective acetylations of aminophenols and hydroxyalkylphenols.

Ytterbium triflate mediated selective deprotection of acetates

Sharma,Ilangovan

, p. 1963 - 1965 (1999)

Ytterbium triflate mediated selective deprotection of acetates in isopropyl alcohol at reflux temperature is reported. Unlike hafnium triflate, under the present reaction conditions aryl acetates also undergo deacetylation instead of Fries migration.

Reagents with a Crystalline Coat

Schwenger, Alexander,Frey, Wolfgang,Richert, Clemens

, p. 13706 - 13709 (2016)

Tetrakis(dimethoxyphenyl)adamantane (TDA) readily forms crystalline inclusion complexes with reactive, toxic, or malodorous reagents, such as benzoyl chloride, acetyl chloride, cyclohexyl isocyanide, phosphorus trichloride, and trimethylsilyl chloride. The crystals are stable and largely free of the problematic properties of the free reagents. When exposed to solvents such as DMSO or MeOH, the reagents react, and a large portion of the TDA precipitates. The TDA-coated reagents may lead to a safer way of storing, handling, and delivering reagents, and ultimately to synthetic protocols that do not require fume hoods.

Mechanism of Decomposition of N-Hydroxyacetaminophen, a Postulated Toxic Metabolite of Acetaminophen

Gemborys, Mark W.,Mudge, Gilbert H.

, p. 304 - 308 (1980)

The decomposition of N-hydroxyacetaminophen (N-acetyl-N-hydroxy-p-aminophenol, 2) a postulated toxic metabolite of acetaminophen (N-acetyl-p-aminophenol, 1) in aqueous solution is quantitatively accounted for by the appearance of equimolar amounts of p-nitrosophenol and acetaminophen.The rate of decomposition depends on initial concentration and varies with pH.Antioxidants decrease the rate of decomposition and change the products.In the presence of cysteine, N-acetyl-3-(S-cysteine)-p-aminophenol, an in vivo metabolite of acetaminophen, is a product of decomposition.

The anticarcinogen 3,3'-diindolylmethane is an inhibitor of cytochrome P-450.

Stresser,Bjeldanes,Bailey,Williams

, p. 191 - 201 (1995)

Dietary indole-3-carbinol inhibits carcinogenesis in rodents and trout. Several mechanisms of inhibition may exist. We reported previously that 3,3'-diindolylmethane, an in vivo derivative of indole-3-carbinol, is a potent noncompetitive inhibitor of trout cytochrome P450 (CYP) 1A-dependent ethoxyresorufin O-deethylase with Ki values in the low micromolar range. We now report a similar potent inhibition by 3,3'-diindolylmethane of rat and human CYP1A1, human CYP1A2, and rat CYP2B1 using various CYP-specific or preferential activity assays. 3,3'-Diindolylmethane also inhibited in vitro CYP-mediated metabolism of the ubiquitous food contaminant and potent hepatocarcinogen, aflatoxin B1. There was no inhibition of cytochrome c reductase. In addition, we found 3,3'-diindolylmethane to be a substrate for rat hepatic microsomal monooxygenase(s) and tentatively identified a monohydroxylated metabolite. These observations indicate that 3,3'-diindolylmethane can inhibit the catalytic activities of a range of CYP isoforms from lower and higher vertebrates in vitro. This broadly based inhibition of CYP-mediated activation of procarcinogens may be an indole-3-carbinol anticarcinogenic mechanism applicable to all species, including humans.

Retrorsine, but not monocrotaline, is a mechanism-based inactivator of P450 3A4

Dai, Jieyu,Zhang, Fan,Zheng, Jiang

, p. 49 - 56 (2010)

Retrorsine (RTS) and monocrotaline (MCT) cause severe toxicities via P450-mediated metabolic activation. The screening of mechanism-based inhibitors showed RTS inactivated 3A4 in the presence of NADPH. Unlike RTS, MCT failed to inhibit P450 3A4 and other enzymes tested. Further studies showed the loss of P450 3A4 activity occurred in a time- and concentration-dependent way, which was not recovered after dialysis. Dextromethorphan, a P450 3A4 substrate, protected the enzyme from the inactivation. Exogenous nucleophile glutathione (GSH) and reactive oxygen species scavengers catalase and superoxide dismutase did not protect P450 3A4 from the inactivation. GSH trapping experiments showed both P450 3A4 and 2C19 converted RTS and MCT to the corresponding electrophilic metabolites which could be trapped by GSH to form 7-GSH-DHP conjugate. We conclude that RTS and MCT are metabolically activated by P450 3A4 and 2C19, and that RTS, but not MCT, is a mechanism-based inactivator of P450 3A4.

Silicon-grafted Ag/AgX/rGO nanomaterials (X = Cl or Br) as dip-photocatalysts for highly efficient p-nitrophenol reduction and paracetamol production

Attia, Yasser A.,Mohamed, Yasser M.A.

, (2019)

In this work, plasmonic Ag/AgX/rGO (X?=?Cl or Br) nano-photocatalysts were grafted with silicon by adding trimethylsilyl chloride as silicon precursor. The synthesized Ag/AgX/rGO-Si hybrids showed a large improvement of photocatalytic activity towards the synthesis of p-aminophenol (PAP) as well as paracetamol (acetaminophen; APAP) through the photoreduction of p-nitrophenol (PNP). The prepared catalysts Ag/AgX/rGO were characterized using SEM, XRD, FTIR and the reduction reaction of p-nitrophenol was monitored by UV–Vis measurements, GC/MS and 1HNMR data. From the results, it was demonstrated that the rate order of reduction process of the PNP to PAP and to APAP under visible light irradiation of the samples was as follows; Ag/AgBr/rGO-Si?>?Ag/AgCl/rGO-Si?>?Ag/AgBr/rGO?>?Ag/AgCl/rGO. The reaction mechanism had been postulated that was supported with the spectroscopic data. In addition, the catalysts were recovered from the reaction medium and re-used in three cycles that indicated the reusability and stability of the catalysts. This study was featured by the following; i) fast reaction, ii) the reduction of p-nitrophenol to paracetamol was performed in a facile one-pot reaction compared to previous approaches that tends to reduce the production cost, and iii) investigations on the catalytic properties of Ag/AgX/rGO in organic transformations open the door to find a benefice of these catalysts in other organic reactions and in the development in the synthesis of pharmaceutical products.

Amidation of phenol derivatives: A direct synthesis of paracetamol (acetaminophen) from hydroquinone

Joncour, Roxan,Duguet, Nicolas,Metay, Estelle,Ferreira, Amadeo,Lemaire, Marc

, p. 2997 - 3002 (2014)

A direct synthesis of paracetamol (acetaminophen) from hydroquinone has been developed using ammonium acetate as an amidating agent. The reaction proceeds in acetic acid at elevated temperatures without any metallic catalyst. Under these conditions, paracetamol was obtained with high yield and selectivity (>95%). The reaction has also been carried out on the multi-gram scale (44 g of hydroquinone) and a potential process has been proposed based on the recycling of the solvent and by-products. This amidation protocol has also been extended to other phenol derivatives. This journal is the Partner Organisations 2014.

Introduction of a hydroxy group at the para position and N-iodophenylation of N-arylamides using phenyliodine(III) bis(trifluoroacetate)

Itoh, Naoki,Sakamoto, Takeshi,Miyazawa, Etsuko,Kikugawa, Yasuo

, p. 7424 - 7428 (2002)

The reaction of anilides with phenyliodine(III) bis(trifluoroacetate) (PIFA) in trifluoroacetic acid (TFA), TFA-CHCl3, or hexafluoroisopropyl alcohol (HFIP) is described. When the acyl group of the anilide is highly electronegative, such as trifluoroacetyl, or the phenyl group is substituted with an electron-withdrawing group, the 4-iodophenyl group is transferred from PIFA to the amide nitrogen to afford acetyldiarylamines. On the other hand, when the acyl group contains an electron-donating function, such as 4-methoxyphenyl, or the phenyl group is substituted with an electron-donating group, a trifluoroacetoxy group is transferred to the para position of the anilide aromatic ring. This group is hydrolyzed during workup to produce the corresponding phenol.

A Realistic Model for Heme-containing Catalases and Peroxidases: the X-Ray Structural Characterisation of a Non-porphyrin Iron(III) Macrocyclic Complex, and the Mechanism of Its Peroxidation of Aromatic Substrates

Cairns, Colin J.,Heckman, Roger A.,Melnyk, Alexandra C.,Davis, William M.,Busch, Daryle H.

, p. 2505 - 2510 (1987)

In acidic buffered aqueous solution the complex dichloroheptadeca-1(17),13,15-triene>iron(III) tetrafluoroborate, BF4, exhibits both catalase- and peroxidase-like activity.The predominant cation in aqueous buffered solution at pH 4.65 is the mixed species 2+.The catalase- and peroxidase-like activity is proposed to occur via a high oxidation state intermediate rather than through involvement of free hydroxyl radicals.Quantitative compliance with the algebraic forms of theoretical rate laws fails to distinguish between these possibilities.However, the kinetics of dioxygen evolution in the presence of hydroxyl radical traps leads to the elimination of the hydroxyl radical model.In addition, the peroxidase-like reactivity of substituted benzenes toward the 2+-H2O2 model system parallels that expected for an electrophilic oxidant, and not that of free OH radicals.Parallel experiments with Fenton's reagent support this view.An X-ray structural determination on the dichloro complex indicates that the macrocycle adopts a folded conformation allowing the two chloride ligands to occupy cis positions in the co-ordination sphere.This stereochemistry is proposed to be retained in aqueous solution, and may allow bidentate co-ordination of hydrogen peroxide,a structural feature that may be critical to the catalase- and peroxidase-like activity.The iron(III) complex crystallises in the orthorhombic system, a=10.046(2), b=13.322(2), c=15.262(3) Angstroem, space group Pnma, with four molecules per unit cell.Final residuals had values of 0.042 and 0.043, for R and R', respectively, upon convergence for 1525 observed reflections.Both the cationic, macrocyclic complex and the BF4 anion display crystallographically imposed mirror symmetry.The iron(III) ion displays an approximately octahedral geometry, with co-ordination angles ranging from 77 to 95 deg.An analysis of associated torsion angles suggests that the folded conformation of the macrocycle is almost strain free.

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Sundberg,Smith

, p. 295,296,300 (1971)

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Oxygen activation by the iron(II)-2-mercaptobenzoic acid complex. A model for microsomal mixed function oxygenases.

Ullrich

, p. 699 - 704 (1969)

-

Cerium(IV) sulfate tetrahydrate: A catalytic and highly chemoselective deprotection of THP, MOM, and BOM ethers

González-Calderón, Davir,González-González, Carlos A.,Fuentes-Benítez, Aydeé,Cuevas-Yá?ez, Erick,Corona-Becerril, David,González-Romero, Carlos

, p. 7164 - 7166 (2013)

Tetrahydropyranyl (THP), methoxymethyl (MOM), and benzyloxymethyl (BOM) phenyl/alkyl ethers were efficiently cleaved to the corresponding parent hydroxyl compounds in good yields using catalytic amounts of Ce(SO 4)2·4H2O by microwave-assisted or conventional heating in methanol solution. Intramolecular and competitive experiments demonstrated the chemoselective deprotection of THP ethers in the presence of triisopropylsilyl (TIPS) and tert-butyldiphenylsilyl (TBDPS) phenyl ethers.

Aluminium chloride hexahydrate (AlCl3.6H2o): An efficient, facile, mild, and highly chemoselective catalytic deprotection of tert-butyldimethylsilyl (tbs) ethers

Gonzalez-Calderon, Davir,Benitez-Puebla, Luis J.,Gonzalez-Gonzalez, Carlos A.,Garcia-Eleno, Marco A.,Fuentes-Benitez, Aydee,Cuevas-Yanez, Erick,Corona-Becerril, David,Gonzalez-Romero, Carlos

, p. 1258 - 1265 (2014)

tert-Butyldimethylsilyl (TBS) phenyl / alkyl ethers were cleaved to the corresponding efficiently parent hydroxyl compounds in good yields using catalytic amounts of AlCl3.6H2O by conventional or microwave-assisted heating in methanol or isopropanol solution. Intramolecular and competitive experiments demonstrated the chemoselective deprotection of TBS ethers in the presence of triisopropylsilyl and tert-butyldiphenylsilyl ethers.

Intensification of paracetamol (acetaminophen) synthesis from hydroquinone using ultrasound

Mane, Swapnil N.,Gadalkar, Sagar M.,Rathod, Virendra K.

, p. 106 - 110 (2018)

Paracetamol (acetaminophen) is one of the most frequently used analgesic and antipyretic drugs. This work deals with ultrasound assisted synthesis (UAS) of paracetamol from hydroquinone using ammonium acetate as an amidating agent. The optimization of various reaction and ultrasound parameters was performed to minimize the energy and time requirement. UAS of paracetamol was achieved at a lower temperature (60 °C) and the time (150 min) without formation of salt as a byproduct, making reaction green and inherently safer. On the other hand, the conventional process requires high reaction temperature (220 °C) and time (15 h). The quantification of the product was done by using high performance liquid chromatography (HPLC). Optimization of parameters revealed that the percent yield of 57.72% can be obtained in 150 min by performing the reaction in the ultrasound bath at 22 kHz frequency, 60 °C temperature, hydroquinone to ammonium acetate and acetic acid in a molar ratio of 1:6:5, 125 W power, 50% duty cycle and agitation speed of 300 RPM. Hence, ultrasound assisted synthesis can be considered as a process intensification tool for the synthesis of paracetamol and possibly other pharmaceutical compounds.

-

Freifelder

, p. 1092 (1962)

-

Aromatic hydroxylation by a new cupric nitrate-H2O2-phosphate buffer system

Nasreen, Aayesha,Adapa, Srinivas R.

, p. 373 - 376 (2000)

-

-

Feldstein et al.

, p. 1656 (1961)

-

A population approach to enzyme characterization and identification: Application to phenacetin O-deethylation

Belle,Ring,Allerheiligen,Heathman,O'Brien,Sinha,Roskos,Wrighton

, p. 1531 - 1536 (2000)

Purpose. To determine the enzyme kinetics (EK) and identify the human cytochrome(s) P450 (CYP) involved in the deethylation of phenacetin to acetaminophen using a population-based method. Methods. A sparse data set was generated from incubations containing human liver microsomes (n = 19) with phenacetin. Estimates of the EK parameters were obtained by fitting the concentration-velocity data to Michaelis-Menten models by using nonlinear mixed effects modeling. Relationships between the EK parameters and the CYP activities determined for these liver microsomes were examined. Results. A two-enzyme kinetic model with a saturated, low KM enzyme and an unsaturated, high KM enzyme capable of forming acetaminophen best fit the data. The population estimates of the EK parameters were Vmax1, 911 pmol/min/mg protein; KM1, 11.3 μM; and Clint2 0.4 μl/min/mg. The coefficients of variation for interliver variability in Vmax1 and residual error of the model were 39% and 15%, respectively. When the selective catalytic activities were examined as potential covariates, 7-ethoxyresorufin O-deethylation (CYP1A2) activity was found to be associated with the low KM enzyme, however, the high KM enzyme(s) could not be identified. Conclusions. The population approach characterized the EK parameters and identified the low KM enzyme responsible for phenacetin O-deethylation as CYP1A2. Population modeling of EK provides valuable information on inter- and intraliver variability in CYP dependent activities.

Synthesis and evaluation in vitro of 4-acetamidophenyl phosphate

Taniguchi,Nakano

, p. 577 - 580 (1981)

-

Evaluation of the impact of 16-dehydropregnenolone on the activity and expression of rat hepatic cytochrome P450 enzymes

Ramakrishna, Rachumallu,Bhateria, Manisha,Singh, Rajbir,Bhatta, Rabi Sankar

, p. 183 - 192 (2016)

16-dehydropregnenolone (DHP) is a promising novel antihyperlipidemic agent developed and patented by Central Drug Research Institute (CDRI), India. The purpose of the present study was to investigate whether DHP influences the activities and mRNA expression of hepatic drug-metabolizing cytochrome P450 (CYP) enzymes (CYP1A2, CYP2C11, CYP2D2, CYP2E1 and CYP3A1) in Sprague-Dawley (SD) rats. A cocktail suspension of CYP probe substrates which contained caffeine (CYP1A2), tolbutamide (CYP2C11), dextromethorphan (CYP2D2), chlorzoxazone (CYP2E1) and dapsone (CYP3A1) was administered orally on eighth- or fifteenth-day to rats pre-treated with DHP intragastrically at a dose of 36 and 72?mg/kg for one week and two weeks. The concentrations of probe drugs in plasma were estimated by liquid chromatography-tandem mass spectrometry (LC–MS/MS). Alongside, the effect of DHP on CYPs activity and mRNA expression levels were assayed in isolated rat liver microsomes and by real-time reverse transcription-polymerase chain reaction (RT-PCR), respectively. DHP had significant inducing effects on CYP1A2, 2C11, 2D2 and 2E1 with no effect on CYP3A1 in dose- and time-dependent manner, as revealed from the pharmacokinetic profiles of the probe drugs in rats. In-vitro microsomal activities and mRNA expression results were in good agreement with the in-vivo pharmacokinetic results. Collectively, the results unveiled that DHP is an inducer of rat hepatic CYP enzymes. Hence, intense attention should be paid when DHP is co-administered with drugs metabolized by CYP1A2, 2C11, 2D2 and 2E1, which might result in drug-drug interactions and therapeutic failure.

Large scale Biginelli reaction via water-based biphasic media: A green chemistry strategy

Bose, Ajay K.,Manhas, Maghar S.,Pednekar, Suhas,Ganguly, Subhendu N.,Dang, Hoang,He, William,Mandadi, Arun

, p. 1901 - 1903 (2005)

An important stage in process development is kilo scale preparation of the target compound. For this reason, a procedure involving water-based biphasic reaction media has been developed for conducting some exothermic reactions on a large scale. This protocol is illustrated by the energy-efficient and rapid preparation of dihydropyrimidinones by a solvent-free, green chemistry procedure applied to the Biginelli reaction using p-toluenesulfonic acid as catalyst. 2005 Elsevier Ltd.

IMMUNOCHEMICAL MODELING OF LIGAND-RECEPTOR REACTIONS. COMMUNICATION V. PROPERTIES OF ANTIBODIES RAISED AGAINST THE TRIETHYLAMMONIUM DETERMINANT

Burkin, A. A.,Zoryan, V. G.

, p. 83 - 86 (1995)

The properties of antibodies to immunogens determined by triethylammonium were studied.The immunochemical method is suggested for determining the ligands of a cholinergic receptor with a predominantly antidepolarizing type of action.

Preparation of an organic–inorganic hybrid based on synergy of Br?nsted and Lewis acid centres as heterogeneous magnetic nanocatalyst for ultrafast synthesis of acetaminophen

Kooti,Nasiri

, (2018)

A heterogeneous nanocatalyst based on a Cu(II) complex containing phosphotungstic acid and N/O-donor ligands supported on cobalt ferrite nanoparticles was successfully prepared. The synthesized nanocatalyst was characterized using various techniques. The magnetic nanocatalyst was examined as an efficient and synergistic catalyst for ultrafast synthesis of acetaminophen at room temperature and under solventless conditions. The examined synergistic nanocatalyst, which has both Lewis and Br?nsted acidic sites, could be easily separated from the reaction system and reused several times without significant loss of its activity. The synthesized acetaminophen was also fully characterized.

Effects of artemisinin antimalarials on Cytochrome P450 enzymes in vitro using recombinant enzymes and human liver microsomes: Potential implications for combination therapies

Ericsson, Therese,Sundell, Jesper,Torkelsson, Angelica,Hoffmann, Kurt-Jürgen,Ashton, Michael

, p. 615 - 626 (2014)

1. Cytochrome P450 enzyme system is the most important contributor to oxidative metabolism of drugs. Modification, and more specifically inhibition, of this system is an important determinant of several drug-drug interactions (DDIs). 2. Effects of the antimalarial agent artemisinin and its structural analogues, artemether, artesunate and dihydroartemisinin, on seven of the major human liver CYP isoforms (CYP1A2, 2A6, 2B6, 2C9, 2C19, 2D6 and 3A4) were evaluated using recombinant enzymes (fluorometric assay) and human liver microsomes (LC-MS/MS analysis). Inhibitory potency (IC50) and mechanisms of inhibition were evaluated using nonlinear regression analysis. In vitro-in vivo extrapolation using the [I]/Ki ratio was applied to predict the risk of DDI in vivo. 3. All compounds tested inhibited the enzymatic activity of CYPs, mostly through a mixed type of inhibition, with CYP1A2, 2B6, 2C19 and 3A4 being affected. A high risk of interaction in vivo was predicted if artemisinin is coadministrated with CYP1A2 or 2C19 substrates. 4. With respect to CYP1A2 inhibition in vivo by artemisinin compounds, our findings are in line with previously published data. However, reported risks of interaction may be overpredicted and should be interpreted with caution.

Human cytochromes p450 mediating phenacetin 0-deethylation in vitro: Validation of the high affinity component as an index of CYP1A2 activity

Venkatakrishnan, Karthik

, p. 1502 - 1507 (1998)

Phenacetin 0-deethylation, widely used as an index reaction for cytochrome P450 1A2 (CYP1A2) activity, displays biphasic kinetics in human liver microsomes. CYP1A2 has been identified as contributing to the high affinity component, but is not verified as the sole contributor to the high affinity phase. In addition, the human CYP isoforms accounting for the low affinity phase have not been identified. We have used heterologously expressed human CYP isoforms to identify, kinetically characterize, and predict the relative contribution of the major human liver CYP isoforms mediating phenacetin 0-deethylation. CYP1A2 (Km 31 /J.M) is the only high affinity phenacetin 0-deethylase in human liver microsomes, while CYPs 2A6 (Km 4098 pM), 2C9 (Km 566 μM), 2C19 (Km 656 μM), 2D6 (Km 1021 μM), and 2E1 (Km 1257 μM) all contribute to the low affinity phase of the reaction. Considering the relative abundance of the various CYPs in human liver, CYP1A2 accounts for 86% of net reaction velocity at a substrate concentration of 100 fM, while CYP2C9 becomes the primary phenacetin 0-deethylase at substrate concentrations of 865 /M and higher and accounts for 31% of the net Vmsst of the reaction. Predictions from kinetic studies on heterologously expressed CYPs are consistent with chemical inhibition studies on human liver microsomes with sulfaphenazole and a-naphthoflavone that suggest a greater role for CYP2C9, and a smaller role for CYP1A2, at higher substrate concentrations. Thus CYP1A2 is the only high affinity human liver phenacetin 0-deethylase, thereby validating the use of the high affinity component as an index of CYP1A2 activity in human liver microsomes.

In vitro evaluations for pharmacokinetic drug-drug interactions of a novel serotonin-dopamine activity modulator, brexpiprazole

Sasabe, Hiroyuki,Koga, Toshihisa,Furukawa, Masayuki,Matsunaga, Masayuki,Sasahara, Katsunori,Hashizume, Kenta,Oozone, Yoshihiro,Amunom, Immaculate,Torii, Mikako,Umehara, Ken,Kashiyama, Eiji,Takeuchi, Kenji

, p. 522 - 535 (2021)

Brexpiprazole, a serotonin-dopamine activity modulator, is indicated for the treatment of schizophrenia and also adjunctive therapy to antidepressants for the treatment of Major Depressive Disorder. To determine the drug–drug interaction risk for cytochrome P450, and SLC and ABC transporters, brexpiprazole and its metabolite, DM-3411 were assessed in this in?vitro investigation. Brexpiprazole exhibited weak inhibitory effects (IC50 >13 μmol/L) on CYP2C9, CYP2C19, CYP2D6 and CYP3A4 activities, but had moderate inhibitor activity on CYP2B6 (IC50 8.19 μmol/L). The ratio of systemic unbound concentration (3.8 nmol/L) to the Ki value was sufficiently low. DM-3411 had comparable inhibitory potentials with brexpiprazole only for CYP2D6 and CYP3A4. The mRNA expressions of CYP1A2, CYP2B6 and CYP3A4 were not changed by the exposure of brexpiprazole to human hepatocytes. Brexpiprazole and DM-3411 exhibited weak or no inhibitory effects for hepatic and renal transporters (OATPs, OATs, OCTs, MATE1, and BSEP), except for MATE-2K (0.156 μmol/L of DM-3411), even for which the ratio to systemic unbound concentration (5.3 nmol/L) was sufficiently low. Brexpiprazole effected the functions of P-gp and BCRP with IC50 values of 6.31 and 1.16 μmol/L, respectively, however, the pharmacokinetic alteration was not observed in the clinical concomitant study on P-gp and BCRP substrates. These in?vitro data suggest that brexpiprazole is unlikely to cause clinically relevant drug interactions resulting from the effects on CYPs or transporters mediating the absorption, metabolism, and/or disposition of co-administered drugs.

N-hydroxylation of p-acetophenetidide as a factor in nephrotoxicity.

Calder,Creek,Williams,Funder,Green,Ham,Tange

, p. 499 - 502 (1973)

-

Paracetamol oxidation: synthesis and reactivity of N-acetyl-p-benzoquinoneimine

Blair,Boobis,Davies,Cresp

, p. 4947 - 4950 (1980)

-

Functionalized nanomagnetic graphene by ion liquid containing phosphomolybdic acid for facile and fast synthesis of paracetamol and aspirin

Nasiri, Elahe,Kooshki, Feridoon,Kooti, Mohammad,Rezaeinasab, Rezvan

, (2021)

A nanocomposite has been synthesized by supporting of polyaniline-modified polyoxometalate-paired poly(ionic liquid) on the surface of magnetic graphene and characterized by various techniques. The fabricated nanocomposite was found to be a versatile catalyst for the synthesis of paracetamol and aspirin drugs showing high activity and selectivity. The observed high catalytic activity of the newly synthesized catalyst, in the preparation of these two important drugs, can be attributed to the presence of graphene, which provides high surface area for the supporting of polyaniline–polyoxometalate pair and also to the strong acidity of the solid acid. This catalytic system has several advantages, such as simple experimental process, easy separation of the product, solvent-free condition, efficient isolation, and recovery of the magnetic catalyst as well as high reusability.

KHF2: A mild and selective desilylating agent for phenol tert-butyldimethylsilyl (TBDMS) ethers

Lakshman, Mahesh K.,Tine, Fatou A.,Khandaker, Tashrique A.,Basava, Vikram,Agyemang, Nana B.,Benavidez, Michael S.A.,Ga?i, Marikone,Guerrera, Lisa,Zajc, Barbara

, p. 381 - 385 (2017)

TBDMS (t-BuMe2Si, tert-butyldimethylsilyl) ethers of a variety of phenols have been deprotected with KHF2 in MeOH, at room temperature. Carboxylic ester and labile phenolic acetate were unaffected under these conditions. In competition reactions between TBDMS ethers of a phenol and two primary benzylic alcohols, the phenolic ether underwent cleavage whereas the alcohol ethers remained intact. From a substrate containing both a phenolic hydroxyl group and a secondary, doubly benzylic hydroxyl group protected as TBDMS ethers, the phenol was rapidly and selectively released. Cleavage of TBDMS, TBDPS, and TIPS ethers of a phenol was also compared. TBDMS and TBDPS ethers underwent cleavage at room temperature within 30 minutes, whereas removal of the TIPS ether required 2.5 hours. Ease of cleavage appears to be TBDMS ≈ TBDPS > TIPS. At 60°C, TBDMS ethers of primary benzylic, allylic, and unactivated alcohols can be efficiently desilylated over a prolonged period (13-17 h). Thus, KHF2 proves to be a mild and effective reagent for the selective desilylation of phenol TBDMS ethers at room temperature.

Microwave initiated reactions: Pechmann coumarin synthesis, Biginelli reaction, and acylation

Manhas, Maghar S.,Ganguly, Subhendu N.,Mukherjee, Somdatta,Jain, Amit K.,Bose, Ajay K.

, p. 2423 - 2425 (2006)

An energy-efficient protocol has been developed for solvent-free reactions that are mildly exothermic but not spontaneous. The exothermic reaction mixture-on several g-scale-is exposed for about 30 s to low power (about 200 W) microwaves and then the microwave oven is switched off. After this short burst of energy, the exothermic reaction gets initiated and proceeds on its own to completion. A number of coumarins were synthesized by the Pechmann reaction using this strategy.

Process modeling of reduction and acetylation reactions by spectrophotometric and chemometrics methods

Hemmateenejad, Bahram,Shadabipour, Parisa,Mohamadizadeh, Moahamad Reza

, p. 147 - 154 (2014)

Achieving high levels of chemoselectivity is a pivotal feature of chemical synthesis. Although significant progress has been made in this regards, lots of challenges lie ahead. Herein, multivariate curve resolution-alternating least square (MCR-ALS) was employed to overcome the spectral overlapping of the reactants and products in the model reactions of methyl-(4-formyl) benzoate by NaBH4 and acetylation of p-aminophenol by acetyl chloride. The first-order ultraviolet/visible absorbance spectra were recorded during the addition of different quantities of reagent to the substrate. The absorbing species, coexisting in the system, were detected through employing factor analysis. The soft-modeling analysis of the evolutionary absorbance data by MCR-ALS revealed that both model reactions proceed through a two-step consecutive manner. Using the obtained concentration profiles, one can obtain an idea about the suitable molar ratio of reagent/substrate for selective production of one of the reaction products. Moreover, the pure spectrum of the intermediate species could be estimated.

Kinetics and inhibition by fluvoxamine of phenacetin O-deethylation in V79 cells expressing human CYP1A2

Gjervig Jensen,Enghusen Poulsen,Doehmer,Loft

, p. 286 - 288 (1995)

The kinetics of phenacetin O-deethylation and its inhibition by fluvoxamine was investigated in a V79 cell line (V79MZh1A2) transfected with human CYP1A2. In four sets of experiments the apparent Km values for phenacetin O-deethylation ranged from 35 to 95 μM and the Ki for fluvoxamine-mediated inhibition of the reaction ranged from 2.7 to 14.5 nM, i.e. comparable to values obtained in human liver microsomes. The kinetic performance of the V79MZh1A2 cell line demonstrates its usefulness as an analytical tool in a variety of toxicological and drug metabolism studies involving CYP1A2.

Large-scale crystallization of a pure metastable polymorph by reaction coupling

Lee, Hung Lin,Lin, Hong Yu,Lee, Tu

, p. 539 - 545 (2014)

A maximum of more than 40 g of acetaminophen Form II crystals with a yield of 65 mol % is made reproducibly in a 500 mL reactor by coupling the acetylation of p-aminophenol with the neutralization of acetic acid before the crystallization of acetaminophen Form II crystals. This novel working principle involves a sudden drop of the solubility of acetaminophen from the acetic acid-water environment to the acetate-water system in addition to temperature cooling but without agitation. This particular processing pathway is capable of maintaining a large supersaturation for quite some time for the system to enter the metastable zone of Form II with respect to the acetate-water system. The large amount of Form II crystals so produced are then isolated by filtration and oven drying to prevent Form II crystals in the mother liquor from transforming to the thermodynamically stable Form I crystals by the Ostwalds rule of stages.

Acetylshikonin is a novel non-selective cytochrome P450 inhibitor

Shon, Jong Cheol,Phuc, Nguyen Minh,Kim, Won Cheol,Heo, Jae Kyung,Wu, Zhexue,Lee, Hyunyoung,Liu, Kwang-Hyeon

, p. 553 - 556 (2017)

Acetylshikonin is a biologically active compound with anti-cancer and anti-inflammatory activity, which is isolated from the roots of Lithospermum erythrorhizoma. An inhibitory effect of acetylshikonin against CYP2J2 activity was discovered recently. Based on this result, this study was expanded to evaluate the inhibitory effects of acetylshikonin against nine different cytochrome P450 (P450) isoforms in human liver microsomes (HLMs) using substrate cocktails incubation assay. Acetylshikonin showed a strong inhibitory effect against all P450s tested with IC50 values of 1.4–4.0 μ m. Pre-incubation of acetylshikonin with HLMs and NADPH did not alter the inhibition potency, indicating that acetylshikonin is not a mechanism-based inhibitor. SKF-525A, a widely used non-specific P450 inhibitor, had no inhibitory activity against CYP1A2, 2A6, 2E1 and 2J2, while it showed an inhibitory effect against CYP2B6, CYP2C19 and 2D6 with IC50 values of 2.5, 3.6 and 0.5 μ m, respectively. Our findings indicate that acetylshikonin may be a novel general P450 inhibitor, which could replace SKF-525A.

Direct Synthesis of Paracetamol via Site-Selective Electrochemical Ritter-type C-H Amination of Phenol

Banerjee, Prabal,Saha, Debarshi,Taily, Irshad Maajid

supporting information, (2022/04/07)

The synthesis of paracetamol still relies on multistep protocols involving the utilization of a stoichiometric amount of oxidizing/reducing or other corrosive agents. Herein we report a regioselective electrochemical Ritter-type reaction at the C(sp2)-H of unprotected phenol toward the environmentally benign and direct synthesis of paracetamol. The reaction proceeds under exogenous oxidant- and catalyst-free conditions. The protocol is scalable, can be deployed to a variety of phenols, and offers a sustainable alternative for the synthesis of paracetamol.

Pyridazine N-Oxides as Photoactivatable Surrogates for Reactive Oxygen Species

Basistyi, Vitalii S.,Frederich, James H.

supporting information, p. 1907 - 1912 (2022/03/27)

A method for the photoinduced evolution of atomic oxygen from pyridazine N-oxides was developed. This underexplored oxygen allotrope mediates arene C-H oxidation within complex, polyfunctional molecules. A water-soluble pyridazine N-oxide was also developed and shown to promote photoinduced DNA cleavage in aqueous solution. Taken together, these studies highlight the utility of pyridazine N-oxides as photoactivatable O(3P) precursors for applications in organic synthesis and chemical biology.

Iron-catalyzed arene C-H hydroxylation

Cheng, Lu,Wang, Huihui,Cai, Hengrui,Zhang, Jie,Gong, Xu,Han, Wei

, p. 77 - 81 (2021/10/05)

The sustainable, undirected, and selective catalytic hydroxylation of arenes remains an ongoing research challenge because of the relative inertness of aryl carbon-hydrogen bonds, the higher reactivity of the phenolic products leading to over-oxidized by-products, and the frequently insufficient regioselectivity. We report that iron coordinated by a bioinspired L-cystine-derived ligand can catalyze undirected arene carbon-hydrogen hydroxylation with hydrogen peroxide as the terminal oxidant. The reaction is distinguished by its broad substrate scope, excellent selectivity, and good yields, and it showcases compatibility with oxidation-sensitive functional groups, such as alcohols, polyphenols, aldehydes, and even a boronic acid. This method is well suited for the synthesis of polyphenols through multiple carbon-hydrogen hydroxylations, as well as the late-stage functionalization of natural products and drug molecules.

Method for promoting iron-catalyzed oxidation of aromatic compound carbon - hydrogen bond to synthesize phenol by ligand

-

Paragraph 0080-0081; 0128, (2021/09/21)

The method comprises the following steps: iron is used as - a catalyst metal; a sulfur-containing amino acid or cystine-derived dipeptide is a ligand; and under the common action of hydrogen peroxide as an oxidizing agent, an aromatic compound is synthesized to prepare a phenol. Under the action of an acid as an accelerant and hydrogen peroxide as an oxidizing agent, the aryl carbon - hydrogen bond is directly hydroxylated to form a phenolic compound, and the method for preparing the phenol by the catalytic oxidation reaction has a plurality of advantages. The reaction raw materials, the oxidant and the promoter are wide in source, low in price, environment-friendly and good in stability. The aromatic compound carbon - hydrogen bonds directly participate in the reaction to react in one step to form phenol. The reaction condition is mild, the functional group compatibility and the application range are wide. The reaction selectivity is good; under the optimized reaction conditions, the target product separation yield can reach 85%.

Process route upstream and downstream products

Process route

glutathion
70-18-8

glutathion

N-acetyl-p-benzoquinoneimine
50700-49-7

N-acetyl-p-benzoquinoneimine

4-acetaminophenol
103-90-2,8055-08-1

4-acetaminophenol

S-(5'-Acetamido-2'-hydroxyphenyl)glutathion
64889-81-2

S-(5'-Acetamido-2'-hydroxyphenyl)glutathion

Conditions
Conditions Yield
In water; benzene; at 37 ℃; Product distribution;
4-Hydroxyacetophenone
99-93-4

4-Hydroxyacetophenone

N-Methyl 4-hydroxy benzamide
27642-27-9

N-Methyl 4-hydroxy benzamide

4-acetaminophenol
103-90-2,8055-08-1

4-acetaminophenol

4-hydroxyacetophenone oxime
34523-34-7

4-hydroxyacetophenone oxime

Conditions
Conditions Yield
With hydroxylamine sulfate; at 80 ℃; for 2.5h;
85%
15%
With hydroxylamine sulfate; at 80 ℃; for 2.5h;
15%
83%
N-(4-[1-<sup>(2)</sup>H]ethoxyphenyl)acetamide

N-(4-[1-(2)H]ethoxyphenyl)acetamide

1-deuterio-acetaldehyde
4122-13-8

1-deuterio-acetaldehyde

4-acetaminophenol
103-90-2,8055-08-1

4-acetaminophenol

Conditions
Conditions Yield
With Vitamin C; Agrocybe aegerita peroxygenase; dihydrogen peroxide; at 20 ℃; for 0.00277778h; pH=7; aq. phosphate buffer; Enzymatic reaction;
4-acetamidophenyl benzoate
537-52-0

4-acetamidophenyl benzoate

N-butylbenzamide
2782-40-3

N-butylbenzamide

4-acetaminophenol
103-90-2,8055-08-1

4-acetaminophenol

Conditions
Conditions Yield
With N-butylamine; In benzene; for 14h; Yield given; Ambient temperature;
4-acetamidophenyl benzoate
537-52-0

4-acetamidophenyl benzoate

N-butylamine
109-73-9,85404-21-3

N-butylamine

N-butylbenzamide
2782-40-3

N-butylbenzamide

4-acetaminophenol
103-90-2,8055-08-1

4-acetaminophenol

Conditions
Conditions Yield
In benzene; for 14h; Yields of byproduct given; Ambient temperature;
N-[4-(1,3-Dioxo-1,3-dihydro-isoindol-2-ylmethoxy)-phenyl]-acetamide
150423-22-6

N-[4-(1,3-Dioxo-1,3-dihydro-isoindol-2-ylmethoxy)-phenyl]-acetamide

4-acetaminophenol
103-90-2,8055-08-1

4-acetaminophenol

Conditions
Conditions Yield
With buffer; In methanol; acetonitrile; at 25 ℃; Rate constant; Mechanism; pH 9.0, μ=0.15;
N-[4-(1,1,3-Trioxo-1,3-dihydro-1λ<sup>6</sup>-benzo[d]isothiazol-2-ylmethoxy)-phenyl]-acetamide
134697-04-4

N-[4-(1,1,3-Trioxo-1,3-dihydro-1λ6-benzo[d]isothiazol-2-ylmethoxy)-phenyl]-acetamide

4-acetaminophenol
103-90-2,8055-08-1

4-acetaminophenol

saccharin
81-07-2

saccharin

Conditions
Conditions Yield
With buffer; In methanol; acetonitrile; at 25 ℃; Rate constant; Mechanism; pH 9.0, μ=0.15;
N-sulfonoxyacetanilide pyridinium salt
91631-52-6

N-sulfonoxyacetanilide pyridinium salt

4-acetaminophenol
103-90-2,8055-08-1

4-acetaminophenol

2-(acetylamino)phenol
614-80-2

2-(acetylamino)phenol

4-sulfonoxyacetanilide pyridinium salt

4-sulfonoxyacetanilide pyridinium salt

2-sulfonoxyacetanilide pyridinium salt

2-sulfonoxyacetanilide pyridinium salt

Conditions
Conditions Yield
With potassium chloride; In water; acetonitrile; at 40 ℃; Further byproducts given;
37 % Chromat.
40 % Chromat.
6.7 % Chromat.
1.8 % Chromat.
With potassium chloride; In water; acetonitrile; at 40 ℃; Further byproducts given;
1.8 % Chromat.
40 % Chromat.
6.7 % Chromat.
39 % Chromat.
N-sulfonoxyacetanilide pyridinium salt
91631-52-6

N-sulfonoxyacetanilide pyridinium salt

N-(2-chlorophenyl)acetamide
533-17-5

N-(2-chlorophenyl)acetamide

4-acetaminophenol
103-90-2,8055-08-1

4-acetaminophenol

N-(4-chlorophenyl)acetamide
539-03-7

N-(4-chlorophenyl)acetamide

2-(acetylamino)phenol
614-80-2

2-(acetylamino)phenol

Conditions
Conditions Yield
With potassium chloride; In water; acetonitrile; at 40 ℃; Further byproducts given;
1.8 % Chromat.
39 % Chromat.
2.5 % Chromat.
N-sulfonoxyacetanilide pyridinium salt
91631-52-6

N-sulfonoxyacetanilide pyridinium salt

N-(2-chlorophenyl)acetamide
533-17-5

N-(2-chlorophenyl)acetamide

4-acetaminophenol
103-90-2,8055-08-1

4-acetaminophenol

2-(acetylamino)phenol
614-80-2

2-(acetylamino)phenol

4-sulfonoxyacetanilide pyridinium salt

4-sulfonoxyacetanilide pyridinium salt

Conditions
Conditions Yield
With potassium chloride; In water; acetonitrile; at 40 ℃; Further byproducts given;
1.8 % Chromat.
39 % Chromat.
6.7 % Chromat.

Global suppliers and manufacturers

Global( 464) Suppliers
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  • Business Type
  • Contact Tel
  • Emails
  • Main Products
  • Country
  • Shanghai Upbio Tech Co.,Ltd
  • Business Type:Lab/Research institutions
  • Contact Tel:+86-21-52196435
  • Emails:upbiocn@hotmail.com
  • Main Products:87
  • Country:China (Mainland)
  • DB BIOTECH CO., LTD
  • Business Type:Trading Company
  • Contact Tel:86--1829 2989 553
  • Emails:info@db-biotech.com
  • Main Products:87
  • Country:China (Mainland)
  • Chemwill Asia Co., Ltd.
  • Business Type:Manufacturers
  • Contact Tel:021-51086038
  • Emails:sales@chemwill.com
  • Main Products:55
  • Country:China (Mainland)
  • Hangzhou Dingyan Chem Co., Ltd
  • Business Type:Manufacturers
  • Contact Tel:86-571-86465881,86-571-87157530,86-571-88025800
  • Emails:sales@dingyanchem.com
  • Main Products:95
  • Country:China (Mainland)
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