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Mci-186

HCID 178954410
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Grundinformationen

CAS
1228765-67-0
Standard-SMILES
CC1=NN(c2ccccc2)C(=O)C1
InChIKey
QELUYTUMUWHWMC-UHFFFAOYSA-N
Summenformel
C10H10N2O
Durchschnittliche Molmasse
174,2 g/mol

Überblick

1-phenyl-3-methyl-5-pyrazolone appears as white to off-white powder or crystals. (NTP, 1992)

Namen und Bezeichner

Bevorzugter Name
Mci-186
IUPAC
5-methyl-2-phenyl-4H-pyrazol-3-one
Englischer Name
2,4-Dihydro-5-methyl-2-(phenyl-2,3,4,5,6-d5)-3H-pyrazol-3-one
Summenformel
C10H10N2O
Molmasse
174.2

Namen und Synonyme

MCI-186MCI 186RefChem:57584edaravone89-25-83-METHYL-1-PHENYL-2-PYRAZOLIN-5-ONERadicutNorphenazone1-Phenyl-3-methyl-5-pyrazoloneDeveloper ZMethylphenylpyrazoloneNorantipyrine
Weitere Namen anzeigen
MCI-186 D5D5-EdaravoneEdaravone D5Idalafeng-D55-Methyl-2-(phenyl-d5)-2,4-dihydro-3H-pyrazol-3-one2,4-Dihydro-5-methyl-2-(phenyl-2,3,4,5,6-d5)-3H-pyrazol-3-one3-methyl-1-[(2,3,4,5,6-2H?)phenyl]-4,5-dihydro-1H-pyrazol-5-oneEdaravone-D5: 5-methyl-2-(phenyl-d5)-2,4-dihydro-3H-pyrazol-3-one
C.I. Developer 1PhenylmethylpyrazolonePhenyl methyl pyrazoloneRadicava3-Methyl-1-phenyl-5-pyrazolone3-Methyl-1-phenyl-1H-pyrazol-5(4H)-one5-Methyl-2-phenyl-2,4-dihydro-3H-pyrazol-3-one5-methyl-2-phenyl-4H-pyrazol-3-one

Datenbank-Bezeichner

CAS
1228765-67-0
ChEMBL
CHEMBL290916
ChEBI
CHEBI:31530
UNII
S798V6YJRP
EC Number
201-891-0
Nikkaji
J37.341I

Eigenschaften

Berechnete Struktureigenschaften

XLogP
1,3
Polarare Oberfläche (TPSA)
32,7 Ų
H-Brücken-Donoren
0
H-Brücken-Akzeptoren
2
Frei drehbare Bindungen
1
Schwere Atome
13
Formalladung
0
Komplexität
241

Experimentelle und physikochemische Eigenschaften

Chemical ClassesNitrogen Compounds -> Pyrazoles
DrugsPharmaceuticals -> Listed in ZINC15
Cosmetics · 2 Einträge

Cosmetic ingredients (Phenyl Methyl Pyrazolone) -> CIR (Cosmetic Ingredient Review)

Hair dyeing

LogP1.44
Color/Form · 2 Einträge

MONOCLINIC PRISMS FROM WATER

WHITE POWDER OR CRYSTALS

Solubility · 3 Einträge

less than 1 mg/mL at 73 °F (NTP, 1992)

SOL IN HOT WATER & HOT ALCOHOL; SLIGHTLY SOL IN BENZENE; INSOL IN PETROLEUM ETHER

25.4 [ug/mL] (The mean of the results at pH 7.4)

Human Drugs · 2 Einträge

FDA approved drugs -> Active ingredient

FDA approved drugs -> Active ingredient

Boiling Point · 2 Einträge

549 °F at 105 mmHg (NTP, 1992)

191 °C @ 17 MM HG; 287 °C @ 105 MM HG

Sicherheit und Regulatorisches

Sicherheitsangaben dienen nur zur Orientierung und ersetzen weder das Sicherheitsdatenblatt (SDB) des Lieferanten noch geltende Vorschriften oder eine fachliche Bewertung.

GHS-Klassifizierung

GHS Classification · 6 Einträge

This chemical does not meet GHS hazard criteria for 7.7% (16 of 209) of reports.

Warning

H302 (26.8%): Harmful if swallowed [Warning Acute toxicity, oral]

P261, P264, P264+P265, P270, P271, P272, P273, P280, P301+P317, P302+P352, P304+P340, P305+P351+P338, P319, P321, P330, P332+P317, P333+P317, P337+P317, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 209 reports by companies from 25 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Warning

Gefahrenhinweise

Regulatory Information · 3 Einträge

Chemical: 3H-Pyrazol-3-one, 2,4-dihydro-5-methyl-2-phenyl-

Status: Active Update: 15-10-2018 https://echa.europa.eu/registration-dossier/-/registered-dossier/22541

3H-Pyrazol-3-one, 2,4-dihydro-5-methyl-2-phenyl-: Does not have an individual approval but may be used under an appropriate group standard

Other Safety InformationIMAP assessments - 3H-Pyrazol-3-one, 2,4-dihydro-5-methyl-2-phenyl-: Human health tier II assessment
Fire HazardsFlash point data for this chemical are not available. It is probably combustible. (NTP, 1992)
Health HazardsSYMPTOMS: Symptoms of exposure to this compound may include irritation of the skin, eyes and mucous membranes.
Hazards Summary · 1 Eintrag

Emergency treatment: Irritants; [HSDB] A skin, eye, and mucous membrane irritant; [CAMEO] Causes no to mild skin and eye irritation in rabbits; Not sensitizing to guinea pig skin; [IUCLID] No teratogenicity observed in experimental animals, but reduced birth weight and fetal loss seen at high doses; [REPROTOX] No evidence for carcinogenicity in mice or rats; [NTP] A mild eye irritant; Causes changes in liver and spleen in intravenous studies of dogs; [RTECS]

Chemie und Industrie

Pharmakologische Informationen

ATC Code · 2 Einträge

N - Nervous system

QN - Nervous system

Protein BindingEdaravone is 92% bound to human serum proteins, mainly to albumin, with no concentration dependence in the range of 0.1 to 50 micromol/L.
PharmacodynamicsEdaravone works to delay the disease progression of neurological disorders such as ischemic stroke and ALS by limiting the extent of neuronal damage or death.
Mechanism of Action · 1 Eintrag

Oxidative stress and reactive oxygen species (ROS) production have been implicated in various neurological disorders, such as amyotrophic lateral sclerosis (ALS) and cerebral ischemia. Oxidative stress caused by excess ROS damages endothelial cells in the cerebral vasculature as well as neuronal cell membranes, leading to neuronal cell death. Edaravone is a free radical scavenger that scavenges and suppresses the generation of hydroxyl radicals and peroxynitrite radicals. The exact mechanism of action of edaravone in ALS has not been fully elucidated; however, edaravone is thought to mediate therapeutic effects via its antioxidant properties. Since oxidative stress has been implicated in the pathophysiology of ALS and cerebral ischemia, inhibiting lipid peroxidation, suppressing endothelial cell damage induced by lipid peroxides, and scavenging free radicals may lead to neuroprotective effects. Edaravone has no effect on superoxide production. It is suggested that edaravone may also possess anti-inflammatory properties, as it inhibited neutrophil activation and suppressed inducible nitric oxide synthase (iNOS) and neuronal nitric oxide synthase (nNOS) expression in animal models. It was also shown to ameliorate ROS-induced inflammatory oxidative stress after ischemic brain reperfusion.

Biological Half-LifeThe mean terminal elimination half-life of edaravone is approximately 4.5 to nine hours. The half-lives of its metabolites range from three to six hours.
Metabolism/Metabolites · 1 Eintrag

The metabolites of edaravone have not been fully characterized. Edaravone is metabolized to a sulfate conjugate and a glucuronide conjugate, which are not pharmacologically active. The glucuronide conjugation of edaravone involves multiple uridine diphosphate glucuronosyltransferase (UGT) isoforms (UGT1A1, UGT1A6, UGT1A7, UGT1A8, UGT1A9, UGT1A10, UGT2B7, and UGT2B17). In human plasma, edaravone is mainly detected as the sulfate conjugate, which is presumed to be formed by sulfotransferases. Oral edaravone results in 1.3- and 1.7-fold higher exposures for both sulfate and glucuronide metabolites, respectively, when compared to intravenously-administered edaravone because of first-pass metabolism.

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Melting Point · 3 Einträge

261 to 266 °F (NTP, 1992)

127 °C

128.9 °C

Vapor Pressure · 2 Einträge

less than 0.01 mmHg at 68 °F (NTP, 1992)

LESS THAN 0.01 MM @ 20 °C

Refractive IndexMAX ABSORPTION (ALCOHOL): 280 NM SHOULDER (LOG E= 3.6) INDEX OF REFRACTION: 1.637; MAX ABSORPTION (ALCOHOL): 245 NM (LOG E= 1.1)
Physical Description · 2 Einträge

1-phenyl-3-methyl-5-pyrazolone appears as white to off-white powder or crystals. (NTP, 1992)

White solid; [Merck Index] Light yellow odorless powder; [Alfa Aesar MSDS]

Physikochemische Eigenschaften

Löslichkeit
Chloroform (Slightly), DMSO (Slightly), Methanol (Slightly)
Aggregatzustand
Solid
Farbe
White to Off-White
Reactive GroupAmides and Imides
Special ReportsDHEW/NCI; Bioassay of 1-Phenyl-3-methyl-5-pyrazolone for Possible Carcinogenicity (1978) Technical Rpt Series No. 141 DHEW Pub No. (NIH) 78-1396
Reactivity Profile · 1 Eintrag

Amines are chemical bases. They neutralize acids to form salts plus water. These acid-base reactions are exothermic. The amount of heat that is evolved per mole of amine in a neutralization is largely independent of the strength of the amine as a base. Amines may be incompatible with isocyanates, halogenated organics, peroxides, phenols (acidic), epoxides, anhydrides, and acid halides. Flammable gaseous hydrogen is generated by amines in combination with strong reducing agents, such as hydrides.

Air and Water ReactionsInsoluble in water.
Hazard Classes and Categories · 2 Einträge

Acute Tox. 4 (26.8%)

Skin sensitisation - category 1

Sicherheit und Schutzausrüstung

Fire FightingFires involving this material can be controlled with a dry chemical, carbon dioxide or Halon extinguisher. (NTP, 1992)
First Aid · 1 Eintrag

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop.

Nonfire Spill Response · 1 Eintrag

SMALL SPILLS AND LEAKAGE: Should a spill occur while you are handling this chemical, FIRST REMOVE ALL SOURCES OF IGNITION, then you should dampen the solid spill material with ethanol and transfer the dampened material to a suitable container. Use absorbent paper dampened with ethanol to pick up any remaining material. Seal the absorbent paper, and any of your clothes, which may be contaminated, in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with ethanol followed by washing with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned.

Protective Action Criteria (PAC) · 3 Einträge

5.7 [mg/m3]

63 [mg/m3]

380 [mg/m3]

Personal Protective Equipment (PPE) · 1 Eintrag

RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with an organic vapor/acid gas cartridge (specific for organic vapors, HCl, acid gas and SO2) with a dust/mist filter. (NTP, 1992)

Toxikologische Informationen

Hepatotoxicity · 1 Eintrag

Serum aminotransferase elevations occur in a small proportion of patients on edaravone therapy, but the frequency, timing of onset, duration and severity of these elevations has not been defined. The rates of abnormal liver tests during edaravone therapy were said to be similar to those during placebo treatment. Most elevations resolved spontaneously, and there were no reports of drug discontinuation for serum enzyme elevations. Clinically apparent liver injury due to edaravone was not reported in the prelicensure trials and has not been reported with subsequent clinical use of edaravone, but the numbers of patients treated have been few. Thus, clinically apparent liver injury from edaravone must be rare if it occurs at all.

Toxicity SummarySafe in the present practices of use and concentration. Ingredient, concentration, and use information are available in documents discoverable at https://cir-reports.cir-safety.org
Ongoing Test Status · 1 Eintrag

The following link will take the user to the National Toxicology Program (NTP) Test Agent Search Results page, which tabulates all of the "Standard Toxicology & Carcinogenesis Studies", "Developmental Studies", and "Genetic Toxicity Studies" performed with this chemical. Clicking on the "Testing Status" link will take the user to the status (i.e., in review, in progress, in preparation, on test, completed, etc.) and results of all the studies that the NTP has done on this chemical. [http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=89-25-8]

Carcinogen Classification · 6 Einträge

1-Phenyl-3-methyl-5-pyrazolone

TR-141: Bioassay of 1-Phenyl-3-methyl-5-pyrazolone for Possible Carcinogenicity (CASRN 89-25-8) (1978 )

06/29/78

No Evidence

No Evidence

No Evidence

Drug Induced Liver Injury · 6 Einträge

Drug Induced Liver Injury Rank (DILIrank 2.0)

Edaravone

vNo-DILI-concern

0

No match

DOI:10.1016/j.drudis.2016.02.015

Non-Human Toxicity Excerpts... Levels of Evidence of Carcinogenicity: Male Rats: Negative; Female Rats: Negative; Male Mice: Negative; Female Mice: Negative.
National Toxicology Program Studies · 1 Eintrag

A bioassay of 1-phenyl-3-methyl-5-pyrazolone for possible carcinogenicity was conducted using Fischer 344 rats and B6C3Fl mice. l-Phenyl-3-methyl-5-pyrazolone was admin in the feed, at either of two concn, to groups of 49 or 50 male and 50 female animals of each species. The high and low concn of 1-phenyl-3-methyl-5-pyrazolone utilized were, respectively, 5,000 and 2,500 ppm for rats and 15,000 and 7,500 ppm for mice. Twenty animals of each species and sex were placed on test as controls. After a 103 wk period of chemical admin, there was an additional observation period of 2 wk for rats. A 102 wk period of chemical admin was followed by an additional 2 wk observation period for mice. In both species adequate numbers of animals survived sufficiently long to be at risk from late developing tumors. ... Under the conditions of this bioassay, there was no evidence for the carcinogenicity of 1-phenyl-3-methyl-5-pyrazolone to Fischer 344 rats or B6C3Fl mice. ... Levels of Evidence of Carcinogenicity: Male Rats: Negative; Female Rats: Negative; Male Mice: Negative; Female Mice: Negative.

MeSH Pharmacological Classification · 2 Einträge

Substances that eliminate free radicals. Among other effects, they protect PANCREATIC ISLETS against damage by CYTOKINES and prevent myocardial and pulmonary REPERFUSION INJURY.

Drugs intended to prevent damage to the brain or spinal cord from ischemia, stroke, convulsions, or trauma. Some must be administered before the event, but others may be effective for some time after. They act by a variety of mechanisms, but often directly or indirectly minimize the damage produced by endogenous excitatory amino acids.

Absorption, Distribution and Excretion · 4 Einträge

One study investigated the absorption of edaravone in healthy adults, who either received a single oral (105 mg/mL) or intravenous (60 mg/60 min) dose. The mean Cmax (CV%) and Tmax were 1656 (44.3) ng/mL and 0.5 hours, respectively, following oral administration. The absolute oral bioavailability is about 57% because of first-pass metabolism. The mean Cmax (CV%) and Tmax were 1253 (18.3) ng/mL and one hour, respectively, following intravenous administration. When intravenously administered, the maximum plasma concentration (Cmax) of edaravone was reached by the end of infusion. The Cmax and area under the concentration-time curve (AUC) of edaravone increases more than dose-proportional over the dose range of 30 to 300 mg. Edaravone does not accumulate in plasma with once-daily or multiple-dose administration. The Cmax and AUC decreased when the oral suspension formulation of edaravone was administered with a high-fat meal.

In Japanese and Caucasian healthy volunteer studies, edaravone was excreted mainly in the urine as its glucuronide conjugate (60-80% of the dose up to 48 hours). Approximately 6-8% of the dose was recovered in the urine as the sulfate conjugate, and <1% of the dose was recovered in the urine as the unchanged drug. _In vitro_ studies suggest that the sulfate conjugate of edaravone is hydrolyzed back to edaravone, which is then converted to the glucuronide conjugate in the kidney before excretion into the urine.

After intravenous administration, edaravone has a mean volume of distribution of 63.1 L, suggesting substantial tissue distribution. Edaravone has an apparent volume of distribution of 164 L following oral administration. Edaravone readily crosses the blood-brain barrier.

Following intravenous administration, the total clearance of edaravone is estimated to be 35.9 L/h. The apparent total clearance of edaravone is estimated to be 67.9L/h following oral administration.

Verwendung und Herstellung

Uses · 5 Einträge

CIR ingredient: Phenyl Methyl Pyrazolone

Used as an intermediate for dyes and drugs, reagent to detect cyanide, and developer for diazotized direct dyes; [HSDB] Used in the treatment of strokes; [Merck Index] Used for synthesis in the chemical industry and in the textile processing industry; [IUCLID] Used in hair dyes; [ExPub: EC]

Textiles (Printing, Dyeing, or Finishing) [Category: Industry]

INTERMEDIATE FOR DYES & DRUGS; SENSITIVE REAGENT FOR DETECTION OF CYANIDE

CHEM INT FOR DYES (EG, FOR PYRAZOLONE PIGMENTS), DRUGS (EG, ANTIPYRINE & AMINOPYRINE), DEVELOPER FOR DIAZOTISED DIRECT DYES, REAGENT FOR DETECTION OF CYANIDE

U.S. Exports · 2 Einträge

(1977) No Data

(1979) No Data

U.S. Imports · 2 Einträge

(1977) 6.01X10+7 GRAMS (PRINCPL CUSTMS DISTS)

(1979) 1.55X10+8 GRAMS (PRINCPL CUSTMS DISTS)

U.S. Production · 2 Einträge

(1976) 5.90X10+6 GRAMS (SALES)

(1979) PROBABLY GREATER THAN 2.27X10+6 GRAMS

Methods of Manufacturing · 2 Einträge

CONDENSATION OF PHENYLHYDRAZINE WITH ETHYL ACETOACETATE

BY CONDENSATION OF PHENYLHYDRAZINE WITH ETHYLACETOACETATE.

Household ProductsInformation on 99 consumer products that contain Phenyl methyl pyrazolone in the following categories is provided:
Use ClassificationCosmetics -> Hair dyeing
General Manufacturing Information3H-Pyrazol-3-one, 2,4-dihydro-5-methyl-2-phenyl-: ACTIVE
Anwendungen · 1 Eintrag

VerwendenEdaravone D5 is the labelled compound of Edaravone(E335000). synthesized and used for relative quant. anal. of oligosaccharides by mass spectrometry (MS). Edaravone inhibits the disease activity in rheumatoid arthritis. Edaravone can significantly enhance IR flap viability and protect flap vessels, which is related to scavenging oxygen free radicals, reducing the consumption of SOD, reducing the extent of lipid peroxidation and inflammation, and protecting functional structure of vessels in the early stages of reperfusion. It also shows protective effects against STZ-induced cognitive impairment, oxidative stress, cholinergic dysfunction and altered protein expressions. Its acts like a free radical scavenger, decreased apoptotic cell death, oxidative damage to DNA and lipids, and angiogene