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5-Methyl-2-phenyl-1,2-dihydropyrazol-3-one
- Iupac Name：5-methyl-2-phenyl-4H-pyrazol-3-one
- CAS No.: 89-25-8
- Molecular Weight：174.1992
- Modify Date.: 2022-11-25 02:26
- Introduction: Edaravone was marketed in Japan for improving neurologic recoveryfollowing acute brain infarction. Currently, several agents classified as neuroprotectantsand acting by diverse mechanisms (inhibition of glutamate release, blockade of calciumchannels, lazaroids) have been marketed for treating the outcomes of brain damage due totrauma, ischemia or cardiac arrest. Edavarone is the first antioxidant with free radicalscavenging activity to be introduced for this pathology. This previously described molecule(in particular as norantipyrine, one of three metabolites of antipyrine in mammals) can besimply prepared by direct cyclization of phenylhydrazine with alkylacetoacetate. Edarevoneis a lipophilic agent, readily accessible to brain tissue, that is capable of reducing edemain the brain following ischemia by blocking the arachidonic acid cascade triggeringperoxidative neurodegeneration. Interestingly, this agent has been shown to quench activeoxygen species in endothelial cell homogenate, as well as inhibiting in vitro lipid peroxidative disintegration of membranes, so making this compound effective duringreperfusion following ischemic injury. As an additional indication, phase III trials started with edaravone for increasing the chance of recovery after subarachnoid hemorrhage.
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1. Names and Identifiers
- 1.1 Name
- 5-Methyl-2-phenyl-1,2-dihydropyrazol-3-one
- 1.2 Synonyms
1-pheny-3-methyl-5-pyrazolone (PMP) 1-PHENYL-3-METHYL-2-PYRAZOLIN-5-ONE 1-PHENYL-3-METHYL-5- PYRAZOLONE 1-PHENYL-3-METHYL-5-OXO-2-PYRAZOLINE 1-PHENYL-3-METHYL-5-PYRAZALONE 1-PHENYL-3-METHYL-5-PYRAZOLE 1-PHENYL-3-METHYL-5-PYRAZOLONE 2,4-dihydro-5-methyl-2-phenyl-3h-pyrazol-3-on 2,4-dihydro-5-methyl-2-phenyl-3h-pyrazol-3-one 2-Pyrazolin-5-one, 3-methyl-1-phenyl- 3H-Pyrazol-3-one,2,4-dihydro-5-methyl- 3-methyl-1-phenyl-1H-pyrazol-5(4H)-one 3-methyl-1-phenyl-2-pyrazolin-5-on 3-METHYL-1-PHENYL-2-PYRAZOLIN-5ONE 3-Methyl-1-phenyl-2-pyrazolin-5-one 3-METHYL-1-PHENYL-2-PYRAZOLIN-5-ONE (EDARAVONE) 3-METHYL-1-PHENYL-2-PYRAZOLIN-5-ONE FOR SYNTHESIS 3-Methyl-1-phenyl-2-pyrazoline-5-one 3-METHYL-1-PHENYL-2-PYRAZOLINE-5-ONE / EDARAVONE 3-methyl-1-phenyl-4,5-dihydro-1H-pyrazol-5-one 3-methyl-1-phenyl-5-pyrazolon 3-Methyl-1-phenyl-5-pyrazolone 5-METHYL-2-PHENYL-1,2-DIHYDROPYRAZOL-3-ONE EDARAVONE 5-methyl-2-phenyl-2,4-dihydro-3H-pyrazol-3-one c.i. developer 1 Edaravone (MCI-186) EINECS 201-891-0 MFCD00003138 MONOPYRAZOLONE TIMTEC-BB SBB003801
- 1.3 CAS No.
- 89-25-8
- 1.4 CID
- 4021
- 1.5 EINECS(EC#)
- 201-891-0
- 1.6 Molecular Formula
- C10H10N2O (isomer)
- 1.7 Inchi
- InChI=1S/C10H10N2O/c1-8-7-10(13)12(11-8)9-5-3-2-4-6-9/h2-6H,7H2,1H3
- 1.8 InChkey
- QELUYTUMUWHWMC-UHFFFAOYSA-N
- 1.9 Canonical Smiles
- CC1=NN(C(=O)C1)C2=CC=CC=C2
- 1.10 Isomers Smiles
- CC1=NN(C(=O)C1)C2=CC=CC=C2
2. Properties
- 2.1 Density
- 1.12
- 2.1 Melting point
- 127-131℃
- 2.1 Boiling point
- 287℃ (265 mmHg)
- 2.1 Refractive index
- 0.00014 (25 C)
- 2.1 Flash Point
- 155.2 °C
- 2.1 Precise Quality
- 174.07900
- 2.1 PSA
- 32.67000
- 2.1 logP
- 1.29980
- 2.1 Solubility
- 3.30g/l
- 2.2 Appearance
- 1-phenyl-3-methyl-5-pyrazolone appears as white to off-white powder or crystals. (NTP, 1992)
- 2.3 Storage
- Ambient temperatures.
- 2.4 Chemical Properties
- Off white to light yellow powder
- 2.5 Color/Form
- MONOCLINIC PRISMS FROM WATER|WHITE POWDER OR CRYSTALS
- 2.6 PH
- 4.0-4.4 (H2O, 20℃)(saturated aqueous solution)
- 2.7 pKa
- 2.73±0.50(Predicted)
- 2.8 Water Solubility
- H2O: 3 g/L (20 oC)
- 2.9 Spectral Properties
- MAX ABSORPTION (ALCOHOL): 280 NM SHOULDER (LOG E= 3.6) INDEX OF REFRACTION: 1.637; MAX ABSORPTION (ALCOHOL): 245 NM (LOG E= 1.1)
IR: 15451 (Sadtler Research Laboratories IR Grating Collection)
UV: 985 (Sadtler Research Laboratories Spectral Collection)
MASS: 136 (Aldermaston, Eight Peak Index of Mass Spectra, UK)
- 2.10 Stability
- Stable under normal temperatures and pressures.
- 2.11 StorageTemp
- 2-8°C
3. Use and Manufacturing
- 3.1 Definition
- ChEBI: A pyrazolone that is 2,4-dihydro-3H-pyrazol-3-one which is substituted at positions 2 and 5 by phenyl and methyl groups, respectively.
- 3.2 Methods of Manufacturing
- CONDENSATION OF PHENYLHYDRAZINE WITH ETHYL ACETOACETATE|BY CONDENSATION OF PHENYLHYDRAZINE WITH ETHYLACETOACETATE.
- 3.3 Purification Methods
- Crystallise the pyrazolone from hot H2O, EtOH or EtOH/water (1:1). It complexes with metals. [Veibel et al. Acta Chim Scand 6 1066 1952, Beilstein 24 II 9, 24 III/IV 71.] 5-Methyl-2-phenyl-1,2-dihydropyrazol-3-one Preparation Products And Raw materials Preparation Products
- 3.4 Usage
- antioxidant, lipoxygenase inhibitor
4. Safety and Handling
- 4.1 Symbol
- GHS07
- 4.1 Hazard Codes
- Xi
- 4.1 Signal Word
- Warning
- 4.1 Risk Statements
- R36/37/38
- 4.1 Safety Statements
- S26;S36
- 4.1 Hazard Declaration
- H302-H315-H319-H335
- 4.1 RIDADR
- NONH for all modes of transport
- 4.1 Safety Profile
- Moderately toxic by ingestion andintraperitoneal routes. An eye irritant. When heated todecomposition it emits toxic fumes of NOx.
- 4.2 Caution Statement
- P261-P305 + P351 + P338
- 4.2 WGK Germany
- 1
- 4.2 RTECS
- UQ9625000
- 4.2 Report
-
NCI Carcinogenesis Bioassay (feed); No Evidence: mouse, rat NCITR* ?? National Cancer Institute Carcinogenesis Technical Report Series. (Bethesda, MD 20014) No. NCI-CG-TR-141 ,1978. . Reported in EPA TSCA Inventory.
- 4.3 Safety
-
Moderately toxic by ingestion and intraperitoneal routes. An eye irritant. When heated to decomposition it emits toxic fumes of NOx.
Safety Information of Norphenazone (CAS NO.89-25-8):
Hazard Codes: 
Xi
Risk Statements: 36/37/38:? Irritating to eyes, respiratory system and skin?
Safety Statements: 26-36
26:? In case of contact with eyes, rinse immediately with plenty of water and seek medical advice?
36:? Wear suitable protective clothing?
WGK Germany:?1
- 4.4 Specification
-
?Norphenazone, its CAS NO. is 89-25-8, the synonyms are 2,4-dihydro-5-methyl-2-phenyl-3h-pyrazol-3-one ; 5-Methyl-2-phenyl-1,2-dihydropyrazol-3-one?.
- 4.5 Toxicity
- LD50 orl-rat: 3500 mg/kg LONZA# 08FEB79
5. MSDS
2.Hazard identification
2.1 Classification of the substance or mixture
Skin irritation, Category 2
Skin sensitization, Category 1
Hazardous to the aquatic environment, long-term (Chronic) - Category Chronic 4
2.2 GHS label elements, including precautionary statements
| Pictogram(s) |  |
| Signal word | Warning |
| Hazard statement(s) | H315 Causes skin irritation H317 May cause an allergic skin reaction H413 May cause long lasting harmful effects to aquatic life |
| Precautionary statement(s) | |
| Prevention | P264 Wash ... thoroughly after handling. P280 Wear protective gloves/protective clothing/eye protection/face protection. P261 Avoid breathing dust/fume/gas/mist/vapours/spray. P272 Contaminated work clothing should not be allowed out of the workplace. P273 Avoid release to the environment. |
| Response | P302+P352 IF ON SKIN: Wash with plenty of water/... P321 Specific treatment (see ... on this label). P332+P313 If skin irritation occurs: Get medical advice/attention. P362+P364 Take off contaminated clothing and wash it before reuse. P333+P313 If skin irritation or rash occurs: Get medical advice/attention. |
| Storage | none |
| Disposal | P501 Dispose of contents/container to ... |
2.3 Other hazards which do not result in classification
none
7. Synthesis Route
89-25-8Total: 23 Synthesis Route
9. Other Information
- 9.0 Usage
- 3-Methyl-1-phenyl-2-pyrazolin-5-one used as reagent for detection of reducing carbohydrates by ESI/MALDI -MS.
- 9.1 Storage Conditions
- CONDENSATION OF PHENYLHYDRAZINE WITH ETHYL ACETOACETATE|BY CONDENSATION OF PHENYLHYDRAZINE WITH ETHYLACETOACETATE.
- 9.2 Dissociation Constants
- 7.0
- 9.3 Reactive Group
- Amides and Imides
- 9.4 Reactivity Profile
- 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.
- 9.5 Special Reports
- DHEW/NCI; Bioassay of 1-Phenyl-3-methyl-5-pyrazolone for Possible Carcinogenicity (1978) Technical Rpt Series No. 141 DHEW Pub No. (NIH) 78-1396
- 9.6 Fire Hazards
- Flash point data for this chemical are not available. It is probably combustible. (NTP, 1992)
- 9.7 Nonfire Spill Response
- 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. STORAGE PRECAUTIONS: You should store this material in a refrigerator. (NTP, 1992)
- 9.8 Personal Protective Equipment
- 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)
- 9.9 Livertox Summary
- Edaravone is a free radical scavenger and neuroprotective agent used for therapy of amyotrophic lateral sclerosis. Edaravone is associated with a low rate of serum aminotransferase elevations during therapy but has not been linked to instances of clinically apparent, acute liver injury.
- 9.10 Drug Classes
- Amyotrophic Lateral Sclerosis Agents
- 9.11 Mesh
- Substances that eliminate free radicals. Among other effects, they protect PANCREATIC ISLETS against damage by CYTOKINES and prevent myocardial and pulmonary REPERFUSION INJURY. (See all compounds classified as Free Radical Scavengers.)|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. (See all compounds classified as Neuroprotective Agents.)
- 9.12 Absorption
- The peak plasma concentration of the parent drug is reached at the end of infusion, without accumulation of the drug with multiple dosing regimen. The mean Cmax value in healthy male adults is 888ng/mL for intravenous infusion. The values of AUC and Cmax are increased in a dose-proportional relationship. The oral bioavailability in mouse studies is 38% of the I.V. delivery.|About 0.7-0.9% of the dose is excreted as unchanged drug and 71.0-79.9% of the dose is excreted as metabolites (mostly as glucuronide conjugates) through mainly renal elimination.|The mean Vd value following an intravenous infusion of a single 30mg dose is 18.5L/kg.|The mean total plasma drug clearance following an intravenous infusion of a single 30mg dose is 0.1L/min.
- 9.13 Metabolism
- Multiple renal and hepatic uridine diphosphate glucuronosyltransferase (UGT) isoforms catalyze glucuronidation reaction of edaravone to form glucuronide conjugates. Edaravone is also metabolized into sulfate conjugates via sulfotransferase activity, which is the main metabolite form predominantly found circulating in plasma. It is predicted that the sulfate conjugate is hydrolyzed back to edaravone, which is then converted to the glucuronide conjugate in the human kidney before excretion into the urine. These metabolites have no pharmacological activity.
- 9.14 Biological Half Life
- The mean terminal elimination half-life of edaravone is 4.5 to 6 hours and the half-lives of its metabolites are 2 to 2.8 hours.
- 9.15 First Aid
- 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. SKIN: IMMEDIATELY flood affected skin with water while removing and isolating all contaminated clothing. Gently wash all affected skin areas thoroughly with soap and water. If symptoms such as redness or irritation develop, IMMEDIATELY call a physician and be prepared to transport the victim to a hospital for treatment. INHALATION: IMMEDIATELY leave the contaminated area; take deep breaths of fresh air. If symptoms (such as wheezing, coughing, shortness of breath, or burning in the mouth, throat, or chest) develop, call a physician and be prepared to transport the victim to a hospital. Provide proper respiratory protection to rescuers entering an unknown atmosphere. Whenever possible, Self-Contained Breathing Apparatus (SCBA) should be used; if not available, use a level of protection greater than or equal to that advised under Protective Clothing. INGESTION: DO NOT INDUCE VOMITING. If the victim is conscious and not convulsing, give 1 or 2 glasses of water to dilute the chemical and IMMEDIATELY call a hospital or poison control center. Be prepared to transport the victim to a hospital if advised by a physician. If the victim is convulsing or unconscious, do not give anything by mouth, ensure that the victim's airway is open and lay the victim on his/her side with the head lower than the body. DO NOT INDUCE VOMITING. IMMEDIATELY transport the victim to a hospital. (NTP, 1992)
- 9.16 Mesh Entry Terms
- 1 Phenyl 3 methyl 5 pyrazolone
- 9.17 Production
- 25,000 - 100,000 lb|(1976) 5.90X10+6 GRAMS (SALES)|(1979) PROBABLY GREATER THAN 2.27X10+6 GRAMS
- 9.18 Manufacturing Info
- Synthetic dye and pigment manufacturing|3H-Pyrazol-3-one, 2,4-dihydro-5-methyl-2-phenyl-: ACTIVE
- 9.19 Use Classification
- Human drugs -> Rare disease (orphan)|Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients|Cosmetics -> Hair dyeing
- 9.20 Merck
- 14,6713
- 9.21 BRN
- 609575
- 9.22 Description
- Edaravone was marketed in Japan for improving neurologic recovery following acute brain infarction. Currently, several agents classified as neuroprotectants and acting by diverse mechanisms (inhibition of glutamate release, blockade of calcium channels, lazaroids) have been marketed for treating the outcomes of brain damage due to trauma, ischemia or cardiac arrest. Edavarone is the first antioxidant with free radical scavenging activity to be introduced for this pathology. This previously described molecule (in particular as norantipyrine, one of three metabolites of antipyrine in mammals) can be simply prepared by direct cyclization of phenylhydrazine with alkylacetoacetate. Edarevone is a lipophilic agent, readily accessible to brain tissue, that is capable of reducing edema in the brain following ischemia by blocking the arachidonic acid cascade triggering peroxidative neurodegeneration. Interestingly, this agent has been shown to quench active oxygen species in endothelial cell homogenate, as well as inhibiting in vitro lipid peroxidative disintegration of membranes, so making this compound effective during reperfusion following ischemic injury. As an additional indication, phase III trials started with edaravone for increasing the chance of recovery after subarachnoid hemorrhage.
- 9.23 Description
- MCI-186 is a free radical scavenger with diverse protective effects in vivo. Most notably, it reduces damage due to ischemia-reperfusion injury in lung, liver, and brain in animal models of transplant, infection, traumatic brain injury, and stroke.1,2,3,4 MCI-186 provides these protective effects, at least in part, by reducing reactive oxygen species, inhibiting apoptosis, and blocking nonenzymatic peroxidation and lipoxygenase activity.3,5,6
- 9.24 Chemical Properties
- Off white to light yellow powder
- 9.25 Originator
- Mitsubishi Pharma (Japan)
- 9.26 Uses
- antioxidant, lipoxygenase inhibitor
- 9.27 Uses
- Edaravone inhibits the disease activity in rheumatoid arthritis.
- 9.28 Definition
- ChEBI: A pyrazolone that is 2,4-dihydro-3H-pyrazol-3-one which is substituted at positions 2 and 5 by phenyl and methyl groups, respectively.
- 9.29 Brand name
- Radicut
- 9.30 General Description
-
A free radical scavenger and antioxidant that reduces post-ischemic brain injury. Inhibits iron-dependent peroxidation in rat brain homogenates (IC50 = 15 μM). Inhibits mitochondrial permeability transition pore.
10. Computational chemical data
- Molecular Weight: 174.1992g/mol
- Molecular Formula: C10H10N2O
- Compound Is Canonicalized: True
- XLogP3-AA: 1.3
- Exact Mass: 174.079312947
- Monoisotopic Mass: 174.079312947
- Complexity: 241
- Rotatable Bond Count: 1
- Hydrogen Bond Donor Count: 0
- Hydrogen Bond Acceptor Count: 2
- Topological Polar Surface Area: 32.7
- Heavy Atom Count: 13
- Defined Atom Stereocenter Count: 0
- Undefined Atom Stereocenter Count: 0
- Defined Bond Stereocenter Count: 0
- Undefined Bond Stereocenter Count: 0
- Isotope Atom Count: 0
- Covalently-Bonded Unit Count: 1
- CACTVS Substructure Key Fingerprint: AAADccBzIAAAAAAAAAAAAAAAAAAAAQAAAAAwAAAAAAAAAAABAAAAHgAIAAAACAiBkAAywIIAAACoASVyUACSBAAhAgAaiAEwZIgIIDLAkZGEIAhgjADIyAcQAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA==
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12. Realated Product Infomation
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