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Celecoxib
- Iupac Name：4-[5-(4-methylphenyl)-3-(trifluoromethyl)pyrazol-1-yl]benzenesulfonamide
- CAS No.: 169590-42-5
- Molecular Weight：381.37217
- Modify Date.: 2022-11-07 06:16
- Introduction: Celecoxib is a nonsteroidal antiinflammatory drug (NSAID) firstlaunched as Celebrex in the US for the treatment of symptoms in patients withrheumatoid arthritis (RA) and osteoarthritis (OA). Celecoxib belongs to a newclass of 1, 5-diarylpyrazoles and can be synthesized by heat-promotedheterocyclization of a trifiuoro-l,3-dione with appropriate arylhydrazine.Celecoxib is a highly selective inhibitor of COX-2, the inducible form ofcyclooxygenase expressed during inflammatory processes; it does not block theconstitutive form COX-1, thus suppressing the gastric and intestinal toxicity ofmost non-selective NSAIDs. The potency ratio COX1/COX2 on purified humanenzymes was about 400. In several in vivo models of acute and chronicinflammation, Celecoxib demonstrated potent antiinflammatory activity withoutaffecting gastric or urinary prostaglandin PGE2. In several clinical studiesperformed with patients suffering from osteoarthritis or rheumatoid arthritis,Celecoxib was shown to be well tolerated and to relieve pain and inflammation more efficiently compared with other standard NSAIDs; the gastrointestinalsafety profile was significantly better than that of other NSAIDs. Interestingly,Celecoxib was approved for another indication in patients with familial adenomatous polyposis (FAP). A six-month clinical trialdemonstrated a 28% reduction in the number of colorectal polyps withCelecoxib, compared to a 5% reduction with placebo.
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1. Names and Identifiers
- 1.1 Name
- Celecoxib
- 1.2 Synonyms
1-(4-sulphamoylphenyl)-3-trifluoromethyl-5-(p-tolyl)-pyrazole 4-(5-p-tolyl-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzene sulfonamide 4-[5-(4-Methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide 4-[5-(4-methylphenyl)-3-(trifluoromethyl)pyrazol-1-yl]benzenesulfonamide 4-[5-(4-Methylphenyl)-3-trifluoromethyl)-1H-pyrazol-yl]benzenesulfonamide Celecoxib 4-5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-ylbenzenesulfonamide Benzenesulfonamide, 4-(5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)- Benzenesulfonamide, 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]- benzenesulfonamide, 4-5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl- Celebra Celebrex Celebrex,Celebra Celecox Celecoxib (200 mg) Celecoxib Solution, 100ppm celexicob Celocoxib CJ-016377 CP-598107 MFCD00941298 N-[4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1yl]phenylsulfonyl]benzensulfonamide PF-00345549 PHA-00846533 Solexa YM 177
- 1.3 CAS No.
- 169590-42-5
- 1.4 CID
- 2662
- 1.5 EINECS(EC#)
- 200-001-8
- 1.6 Molecular Formula
- C17H14F3N3O2S (isomer)
- 1.7 Inchi
- InChI=1S/C17H14F3N3O2S/c1-11-2-4-12(5-3-11)15-10-16(17(18,19)20)22-23(15)13-6-8-14(9-7-13)26(21,24)25/h2-10H,1H3,(H2,21,24,25)
- 1.8 InChkey
- RZEKVGVHFLEQIL-UHFFFAOYSA-N
- 1.9 Canonical Smiles
- CC1=CC=C(C=C1)C2=CC(=NN2C3=CC=C(C=C3)S(=O)(=O)N)C(F)(F)F
- 1.10 Isomers Smiles
- CC1=CC=C(C=C1)C2=CC(=NN2C3=CC=C(C=C3)S(=O)(=O)N)C(F)(F)F
2. Properties
- 2.1 Density
- 1.43
- 2.1 Melting point
- 157-159℃
- 2.1 Boiling point
- 529.0±60.0
- 2.1 Refractive index
- 1.606
- 2.1 Flash Point
- 273.7 °C
- 2.1 Precise Quality
- 381.07600
- 2.1 PSA
- 86.36000
- 2.1 logP
- 5.29500
- 2.1 Solubility
- DMSO: >20mg/mL
- 2.2 Appearance
- white powder
- 2.3 Storage
- Store at RT
- 2.4 Chemical Properties
- White to Pale Yellow Solid
- 2.5 Color/Form
- white to off-white
- 2.6 Decomposition
- Hazardous decomposition products formed under fire conditions: Carbon oxides, Nitrogen oxides (NOx), Sulfur oxides, Hydrogen fluoride.
- 2.7 pKa
- 9.68±0.10(Predicted)
- 2.8 Water Solubility
- DMSO: >20mg/mL
- 2.9 Stability
- Stable under recommended storage conditions.
- 2.10 StorageTemp
- 2-8°C
3. Use and Manufacturing
- 3.1 General Description
- Celecoxib (Celebrex) was the first selective COX-2 inhibitordrug introduced into the market in 1998 for use in thetreatment of RA, OA, acute pain, and menstrual pain. Thereal benefit is that it has caused fewer GI complicationswhen compared with other conventional NSAIDs. It hasalso been approved for reducing the number of adenomatouscolorectal polyps in familial adenomatous polyposis (FAP).Celecoxib is well absorbed and undergoes rapid oxidativemetabolism via CYP2C9 to give its inactive metabolites. Thus, a potential drug interaction exists betweencelecoxib and warfarin because the active isomer ofwarfarin is primarily degraded by CYP2C9.
- 3.2 Usage
- expectorant, gastric stimulant, insecticide
4. Safety and Handling
- 4.1 Symbol
- GHS08
- 4.1 Hazard Codes
- Xn
- 4.1 Signal Word
- Danger
- 4.1 Risk Statements
- R20/21/22
- 4.1 Safety Statements
- S22;S24/25;S28;S37/39
- 4.1 Exposure Standards and Regulations
- The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl celecoxib, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.
- 4.2 Octanol/Water Partition Coefficient
- log Kow = 3.47 /Estimated/
- 4.3 Hazard Class
- IRRITANT
- 4.3 Hazard Declaration
- H360D
- 4.3 DisposalMethods
- SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.
- 4.4 RIDADR
- UN 2811
- 4.4 Caution Statement
- P201-P308 + P313
- 4.4 Formulations/Preparations
- Celecoxib is the active ingredient in the drug Celebrex produced by GD Searle LLC (oral capsules)
- 4.5 WGK Germany
- 3
- 4.5 RTECS
- DB2944937
- 4.5 Safety
-
Hazard Codes of Celecoxib (CAS NO.169590-42-5):?
Xn
Risk Statements: 20/21/22?
R20/21/22: Harmful by inhalation, in contact with skin and if swallowed.
Safety Statements: 22-24/25-28-37/39?
S22: Do not breathe dust.?
S24/25: Avoid contact with skin and eyes.?
S28: After contact with skin, wash immediately with plenty of soap-suds.?
S37/39: Wear suitable gloves and eye/face protection.
5. MSDS
2.Hazard identification
2.1 Classification of the substance or mixture
Reproductive toxicity, Category 1B
2.2 GHS label elements, including precautionary statements
| Pictogram(s) |  |
| Signal word | Danger |
| Hazard statement(s) | H360 May damage fertility or the unborn child |
| Precautionary statement(s) | |
| Prevention | P201 Obtain special instructions before use. P202 Do not handle until all safety precautions have been read and understood. P280 Wear protective gloves/protective clothing/eye protection/face protection. |
| Response | P308+P313 IF exposed or concerned: Get medical advice/ attention. |
| Storage | P405 Store locked up. |
| Disposal | P501 Dispose of contents/container to ... |
2.3 Other hazards which do not result in classification
none
6. Synthesis Route
169590-42-5Total: 29 Synthesis Route
8. Other Information
- 8.0 Merck
- 14,1956
- 8.1 Indications and Usage
- Celecoxib and Rofecoxib are two currently used COX-2 inhibitors. Successfully developed by GD Searle & Pfizer Co. (U.S.,) released in 1999, trade name: Celebrex.
Celecoxib is a nonsteroidal, anti-inflammatory agent with significant analgesic and anti-inflammatory effects, causing the lowest incidence of upper gastrointestinal tract ulcers and other complications. Used clinically to treat acute and chronic osteoarthritis and rheumatoid arthritis, with an anti-inflammatory analgesic role, relieving the signs and symptoms of osteoarthritis and rheumatoid arthritis.
- 8.2 Clinical Research
- 50 Clinical trials on more than 130,000 subjects in 23 countries have been conducted on Celecoxib. Regarding anti-inflammatory and analgesic effects towards osteoarthritis (OA) and rheumatoid arthritis (RA): subjects ages 18-93 had been diagnosed with OA or RA for at least three months, and the disease was in an active or relapsed state. Diagnoses were made according to the criteria of the American College of Rheumatology (ACR.) Visual analog scales (VAS) and American Pain Society (APS) test tables were used to evaluate joint pain, and the WOMAC and health assessment questionnaire (HAQ) impaired function indices were used to evaluate joint pain, stiffness, and function loss. Extensive clinical trials have shown that Celecoxib is effective against OA and RA joint pain.
Clinical trials on the efficacy of Celecoxib against OA have concluded: by VAS evaluation, 100 and 200 mg bid have the same effect on reducing signs and symptoms of OA as with 500 mg bid of naproxen, greater than with placebos, although the effects of 200 mg bid are not significantly greater than those with 100 mg bid. The effects on OA pain last 24-48h, equivalent to 500 mg bid of naproxen. Using the WOMAC (pain, joint stiffness, and impaired function) indices, 100 and 200 mg bid had the same effects as 500 mg bid of naproxen. 200 mg qd and 100 mg bid had similar effects on OA symptoms.
For RA: 100 and 200 mg bid significantly relieved RA symptoms in clinical trials, equivalent to 500 mg bid of naproxen. 100, 200, and 400 mg bid had similar effects on the number of RA patients suffering from joint swelling and pain/tenderness, all equivalent to 500 mg bid of naproxen.
- 8.3 Side Effects
- Occasional gastrointestinal reactions. Small effects on renal function and platelets. Acute overdose can cause fatigue, drowsiness, nausea, vomiting, and upper abdominal pain, which can be relieved with treatment. Gastrointestinal bleeding is possible. In rare cases, hypertension, acute renal failure, respiratory depression, and comas may occur.
- 8.4 Warnings and Precautions
- Anyone who is allergic to any ingredient in Celecoxib or who is known to be allergic to sulfa drugs should not take it.
It should be avoided in patients with asthma, urticaria, or acute rhinitis.
Lactating women should not take it.
May slow down metabolism and increase serum concentration in combination with leukotriene antagonist zafirlukast, antifungal agent fluconazole, and lipid-lowering statin drug fluvastatin.
Celecoxib can increase blood concentration of beta blockers, antidepressants and antipsychotic drugs, so care should be taken when using these drugs.
- 8.5 Chemical Properties
- White to Pale Yellow Solid
- 8.6 Uses
- expectorant, gastric stimulant, insecticide
- 8.7 Uses
- For relief and management of osteoarthritis (OA), rheumatoid arthritis (RA), juvenile rheumatoid arthritis (JRA), ankylosing spondylitis, acute pain, primary dysmenorrhea and oral adjunct to usual care for patients with familial adenomatous polyposis
- 8.8 Uses
- A selective cyclooxygenase-2 (COX-2) inhibitor. Anti-inflammatory. Used in treatment of familial adenomatous polyposis
- 8.9 Brand name
- Celebrex (Searle).
- 8.10 Biological Activity
- Selective cyclooxygenase-2 (COX-2) inhibitor (IC 50 values are 15 and 0.04 μ M for COX-1 and COX-2 respectively). Anti-inflammatory with shorter plasma half-life in vivo than SC 58121 (5-(4-Fluorophenyl)-1-[4-(methylsulfonyl)phenyl]-3-(trifluoromethyl)-1H-pyrazole ). Displays chemopreventive activity in in vivo tumor models.
- 8.11 Indications and Usage
- Celecoxib and Rofecoxib are two currently used COX-2 inhibitors. Successfully developed by GD Searle & Pfizer Co. (U.S.,) released in 1999, trade name: Celebrex.
Celecoxib is a nonsteroidal, anti-inflammatory agent with significant analgesic and anti-inflammatory effects, causing the lowest incidence of upper gastrointestinal tract ulcers and other complications. Used clinically to treat acute and chronic osteoarthritis and rheumatoid arthritis, with an anti-inflammatory analgesic role, relieving the signs and symptoms of osteoarthritis and rheumatoid arthritis.
- 8.12 Description
- Celecoxib is a nonsteroidal antiinflammatory drug (NSAID) first launched as Celebrex in the US for the treatment of symptoms in patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Celecoxib belongs to a new class of 1, 5-diarylpyrazoles and can be synthesized by heat-promoted heterocyclization of a trifiuoro-l,3-dione with appropriate arylhydrazine. Celecoxib is a highly selective inhibitor of COX-2, the inducible form of cyclooxygenase expressed during inflammatory processes; it does not block the constitutive form COX-1, thus suppressing the gastric and intestinal toxicity of most non-selective NSAIDs. The potency ratio COX1/COX2 on purified human enzymes was about 400. In several in vivo models of acute and chronic inflammation, Celecoxib demonstrated potent antiinflammatory activity without affecting gastric or urinary prostaglandin PGE2. In several clinical studies performed with patients suffering from osteoarthritis or rheumatoid arthritis, Celecoxib was shown to be well tolerated and to relieve pain and inflammation more efficiently compared with other standard NSAIDs; the gastrointestinal safety profile was significantly better than that of other NSAIDs. Interestingly, Celecoxib was approved for another indication in patients with familial adenomatous polyposis (FAP). A six-month clinical trial demonstrated a 28% reduction in the number of colorectal polyps with Celecoxib, compared to a 5% reduction with placebo.
- 8.13 Originator
- Searle (US)
- 8.14 Indications
- Celecoxib is indicated for the treatment of osteoarthritis and rheumatoid arthritis. Its use is contraindicated in individuals with hypersensitivity to sulfonamides or other NSAIDs. It should be used with caution in persons with hepatic disease. Interactions occur with other drugs that induce CYP2C9 (e.g. rifampin rifampin) or compete for metabolism by this enzyme (e.g. fluconazole, leflunomide). The most common adverse reactions to celecoxib are mild to moderate GI effects such as dyspepsia, diarrhea, and abdominal pain. Serious GI and renal effects have occurred rarely.
- 8.15 Manufacturing Process
- 4-(5-(4-Methylphenyl)-3-trifluoromethyl-N-pyrazol-1-yl)benzenesulfonamide To a solution of ethyl trifluoroacetate (1.90 ml, 16.0 mmol) in 7 ml of methyl tert-butyl ether was added 25% NaOMe (3.62 ml, 16.8 mmol). Next 4- chloroaceteophenone (2.08 ml, 16.0 mmol) in 2 ml of methyl tert-butyl ether was added. The mixture was stirred at room temperature overnight. To above solution was added 100 ml of 90% EtOH, followed by 4 N HCl (4.0 ml, 16 mmol) and 4-sulphonamidophenylhydrazine hydrochloride (3.58 g, 16 mmol). The mixture was heated to reflux for 3 hours. The mixture was concentrated. When 30 ml of water was added, a solid formed. The solid was filtered and washed with 20 ml of 60% EtOH to give 4.50 g of white solid. The filtrate was evaporated and taken up in ethyl acetate (100 ml), washed with saturated NaHCO3, and brine, dried over MgSO4, and concentrated. Heptane was added at boiling point of the mixture. After cooling down to 0°C, 1.01 g more product was obtained. The combined yield of the 4-(5-(4-methylphenyl)-3- trifluoromethyl-N-pyrazol-1-yl)benzenesulfonamide (Celecoxib) was 86%.
- 8.16 Therapeutic Function
- Antiinflammatory
- 8.17 General Description
- Celecoxib (Celebrex) was the first selective COX-2 inhibitordrug introduced into the market in 1998 for use in thetreatment of RA, OA, acute pain, and menstrual pain. Thereal benefit is that it has caused fewer GI complicationswhen compared with other conventional NSAIDs. It hasalso been approved for reducing the number of adenomatouscolorectal polyps in familial adenomatous polyposis (FAP).Celecoxib is well absorbed and undergoes rapid oxidativemetabolism via CYP2C9 to give its inactive metabolites. Thus, a potential drug interaction exists betweencelecoxib and warfarin because the active isomer ofwarfarin is primarily degraded by CYP2C9.
- 8.18 Biochem/physiol Actions
- Celecoxib is a non-steroidal, anti-inflammatory drug (NSAID) and a cyclooxygenase-2 (COX-2) selective inhibitor. Celecoxib is at least 10-20 times more selective for COX-2 over COX-1.
- 8.19 Pharmacokinetics
- Celecoxib is well absorbed from the GI tract, with peak plasma concentrations generally being attained within 3 hours of administration. Peak plasma levels in geriatric patients may be increased, but dosage adjustments in elderly patients generally are not required unless the patient weighs less than 50 kg.
- 8.20 Clinical Use
- Celecoxib is currently indicated for the relief of signs and symptoms of osteoarthritis and rheumatoid arthritis and to reduce the number of adenomatous colorectal polyps in familial adenomatous polyposis as an adjunct to usual care.
Celecoxib is synthesized by condensing 4-methyl-acetophenone and ethyltrifluoroacetate with sodium methoxide and the resulting butanedione derivative cyclized with 4-hydrazinophenylsulfonamide. It was the first NSAID to be marketed as a selective COX-2 inhibitor.
- 8.21 Metabolism
- Celecoxib is excreted in the urine and feces primarily as inactive metabolites, with less than 3% of an administered dose being excreted as unchanged drug. Metabolism occurs primarily in the liver by CYP2C9 and involves hydroxylation of the 4-methyl group to the primary alcohol, which is subsequently oxidized to its corresponding carboxylic acid, the major metabolite (73% of the administered dose). The carboxylic acid is conjugated, to a slight extent, with glucuronic acid to form the corresponding glucuronide. None of the isolated metabolites have been shown to exhibit pharmacological activity as inhibitors of either COX-1 or COX-2. Celecoxib also inhibits CYP2D6; thus, the potential of celecoxib to alter the pharmacokinetic profiles of other drugs inhibited by this isoenzyme exists. Celecoxib, however, does not appear to inhibit other CYP isoforms, such as CYP2C19 or CYP3A4. Other drug interactions related to the metabolic profile of celecoxib have been noted, particularly with other drugs that inhibit CYP2C.
9. Computational chemical data
- Molecular Weight: 381.37217g/mol
- Molecular Formula: C17H14F3N3O2S
- Compound Is Canonicalized: True
- XLogP3-AA: 3.4
- Exact Mass: 381.07588236
- Monoisotopic Mass: 381.07588236
- Complexity: 577
- Rotatable Bond Count: 3
- Hydrogen Bond Donor Count: 1
- Hydrogen Bond Acceptor Count: 7
- Topological Polar Surface Area: 86.4
- Heavy Atom Count: 26
- 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: AAADccB7MYBAAAAAAAAAAAAAAAAAAWAAAAAwYAAAAAAAAAAB0AAAHQQYQAAADAiBXhAywZIIAAKiAyRiRHDSBDAhAgAYmDgwZJgIIOLA0dGEpAhgiADIyAcQgMAOQAQAAAAAAACACAAAAAAAAAAAAAAAAA==
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11. Realated Product Infomation
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