181695-72-7 Usage
Description
Valdecoxib, also known as Bextra, is a second-generation COX-2 inhibitor and a diaryl substituted isoxazole compound. It is a metabolite of parecoxib and is used as a nonsteroidal anti-inflammatory drug (NSAID) for the treatment of various conditions. Valdecoxib is a white crystalline powder that is relatively insoluble in water but soluble in methanol, ethanol, and organic solvents. It is approximately 28,000-fold more selective against human recombinant COX-2 than human recombinant COX-1, making it a potent and selective inhibitor of prostaglandin synthesis.
Used in Pharmaceutical Industry:
Valdecoxib is used as an anti-inflammatory, analgesic, and antipyretic agent for the treatment of various conditions such as arthritis, rheumatism, and menstrual pain. It is particularly effective in relieving symptoms like inflammation, swelling, stiffness, and joint pain. Valdecoxib was used for the treatment of arthritis from 2001 until 2005, when it was withdrawn due to concerns of an associated increased risk of heart attack and stroke.
Used as a Cyclooxygenase 2 Inhibitor:
In the pharmaceutical industry, Valdecoxib is used as a selective cyclooxygenase 2 inhibitor, playing a crucial role in managing inflammation and pain. Its high selectivity for COX-2 over COX-1 helps reduce the risk of side effects commonly associated with non-selective NSAIDs.
Used as a Non-Steroidal Anti-Inflammatory Drug (NSAID):
Valdecoxib is used as a non-steroidal anti-inflammatory drug, providing relief from inflammation and pain associated with various conditions such as arthritis and rheumatism.
Used as a Non-Narcotic Analgesic:
As a non-narcotic analgesic, Valdecoxib is used to manage mild to moderate pain without the risk of addiction associated with narcotic pain relievers.
Used as an Antirheumatic Drug:
Valdecoxib is used as an antirheumatic drug, helping to reduce the symptoms of rheumatoid arthritis and improve the quality of life for patients suffering from this condition.
Used as an Antipyretic:
In addition to its anti-inflammatory and analgesic properties, Valdecoxib is also used as an antipyretic, helping to reduce fever and associated discomfort.
Originator
Pharmacia (Searle) (USA)
Preparation
The step for the synthesis of valdecoxib: Deoxybenzoin is converted to the corresponding oxime by treatment with hydroxylamine under basic conditions with sodium acetate in aqueous ethanol or in toluene in presence of potassium hydroxide in absolute ethanol. The treatment of the oxime under nitrogen with two equivalents of butyllithium in tetrahydrofuran is followed by cyclization in ethyl acetate or acetic anhydride to the isoxazoline derivative. Finally, treatment of the isoxazoline with cold chlorosulfuric acid followed by reaction of the intermediate with aqueous ammonia afforded valdecoxib.
Biochem/physiol Actions
Valdecoxib is reported to elicit anti-inflammatory, analgesic and antipyretic functionality. It acts as a substrate for the liver enzyme cytochrome P450 2C9(CYP2C9) and cytochrome P450 3A4 (CYP3A4).
Pharmacokinetics
Valdecoxib is freely soluble in alkaline aqueous solutions. At recommended doses, the mean oral bioavailability for
valdecoxib is 83%, and the time to peak concentration is approximately 3 hours. Time to peak plasma concentration
was delayed by 1 to 2 hours when administered with a high-fat meal. Protein binding is very high at 98%. Valdecoxib
exhibits linear pharmacokinetics over the usual clinical dose range. Valdecoxib is extensively metabolized in humans.
The primary metabolite for valdecoxib involved CYP2C9 hydroxylation of the 5-Me group, which was further
metabolized to the inactive carboxylate, and N-hydroxylation at the sulfonamide moiety. Oxidative breakdown of the
N-hydroxy sulfonamide function group led to the formation of the corresponding sulfinic acid and sulfonic acid
metabolites. The O-and N-glucuronides were the major urinary metabolites. Only 3% of the administered dose was
recovered in urine as unchanged valdecoxib.
Clinical Use
Valdecoxib is approved for the relief of the signs and symptoms of osteoarthritis and adult rheumatoid arthritis and
for the treatment of primary dysmenorrhea. Valdecoxib is contraindicated for the treatment of postoperative pain
immediately following coronary artery bypass graft surgery.
Clinical claims and research
Valdecoxib is a substrate of CYP3A4 but no metabolism interference was seen with commonly used synthetic narcotics, alfentanil and fentanyl. Clinical studies have shown that valdecoxib is as effective as naproxen in treating osteoarthritis, rheumatoid arthritis and dysmenornhoea. The efficacy of valdecoxib was also demonstrated in managing postoperative pain (oral and orthopedic surgery) with effective analgesia and time to rescue medication superior to those obtained with rofecoxib. Several clinical trials showed that valdecoxib has a better upper gastrointestinal safety profile compared to naproxen, ibuprofen or diclofenac and does not affect platelet function. Less abdominal pain, dyspepsia and constipation were observed with valdecoxib than with naproxen. Valdecoxib is contraindicated in patients with a history of allergic reactions to sulfonamides due to reported anaphylactic and skin reactions.
Mode of action
Valdecoxib is a nonsteroidal anti-inflammatory drug (NSAID) that exhibits anti-inflammatory, analgesic and antipyretic properties in animal models. The mechanism of action is believed to be due to inhibition of prostaglandin synthesis primarily through inhibition of cyclooxygenase-2 (COX-2). At therapeutic plasma concentrations in humans valdecoxib does not inhibit cyclooxygenase-1 (COX-1).
references
[1] talley j j, brown d l, carter j s, et al. 4-[5-methyl-3-phenylisoxazol-4-yl]-benzenesulfonamide, valdecoxib: a potent and selective inhibitor of cox-2. journal of medicinal chemistry, 2000, 43(5): 775-777.[2] nussmeier n a, whelton a a, brown m t, et al. complications of the cox-2 inhibitors parecoxib and valdecoxib after cardiac surgery. new england journal of medicine, 2005, 352(11): 1081-1091.
Check Digit Verification of cas no
The CAS Registry Mumber 181695-72-7 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,8,1,6,9 and 5 respectively; the second part has 2 digits, 7 and 2 respectively.
Calculate Digit Verification of CAS Registry Number 181695-72:
(8*1)+(7*8)+(6*1)+(5*6)+(4*9)+(3*5)+(2*7)+(1*2)=167
167 % 10 = 7
So 181695-72-7 is a valid CAS Registry Number.
InChI:InChI=1/C16H14N2O3S/c1-11-15(12-7-9-14(10-8-12)22(17,19)20)16(18-21-11)13-5-3-2-4-6-13/h2-10H,1H3,(H2,17,19,20)
181695-72-7Relevant articles and documents
NHC-palladium-catalyzed ionic liquid-accelerated regioselective oxyarylation of alkynes with diaryl ethers?
Cen, Liying,He, Dan,Jiang, Huanfeng,Li, Jianxiao,Lin, Zidong,Wu, Wanqing
, p. 1983 - 1988 (2022/04/03)
The first NHC-palladium-catalyzed regioselective oxyarylation of oxime ether in a task-specific ionic liquid via C(sp3)-O and C(sp2)-O bond cleavage of two different types of ethers for the assembly of structurally diverse 4-arylisoxazoles is described. Both the basic ionic liquid [C3NH2mim]Br and NHC-Pd catalyst IPr-Pd-Im-Cl2 played an important role in this transformation. Notably, this new approach provides a practical and straightforward route to access a broad range of privileged 4-arylisoxazole structures with good yields and excellent regioselectivities. Significantly, this catalytic system can be recycled up to eight times without significant loss of catalytic activity.
Parecoxib sodium, injection preparation and preparation method
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Paragraph 0052-0059; 0087, (2020/12/08)
The invention discloses parecoxib sodium, an injection preparation and a preparation method. The preparation method of the parecoxib sodium is as follows: 5-methyl-3,4-diphenylisoxazole is used as theraw material; sulfonation and amination are carried out in sequence, so that a valdecoxib intermediate is obtained; then, the valdecoxib intermediate is subjected to acylation reaction and salt forming reaction, so that crude parecoxib sodium is obtained; the crude parecoxib sodium is dissolved and decolourized, so that the finished parecoxib sodium is obtained; the finished parecoxib sodium is the parecoxib sodium A crystal form; and the parecoxib sodium preparation for injection is prepared by adding accessories into the parecoxib sodium A crystal form. The preparation method of the parecoxib sodium in the invention is simple in synthetic route and moderate in reaction condition; raw materials are available at low prices; and furthermore, the impurity content of the prepared parecoxib sodium is low.
Preparation method of parecoxib sodium
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Paragraph 0043; 0046-0047; 0052; 0055-0056; 0061; 0064-0065, (2019/10/04)
The invention belongs to the technical field of drug preparation, and specifically relates to a preparation method of parecoxib sodium. The preparation method comprises sulfonation reactions, amination reactions, propionylation reactions, and salt forming reactions. In sulfonation reactions, 5-methyl-3,4-diphenyl isoxazole is taken as the primary raw material and directly carries out reactions with chlorosulfonic acid, after reactions, and the reaction system is poured into water to carry out quenching to obtain suspension of reaction products. All used reagents are common reagents; the preparation method only uses third kind solvents, which are regulated by International Council for Harmonization (ICH) and are harmless for human body; the operation of the preparation method and post treatment is simple, the repeatability is good, the yield is high, and the cost is low. The purity of prepared parecoxib sodium can reach 99.9% or more. The quality of prepared parecoxib sodium is higher than the standards made by a plant that develops parecoxib sodium. The preparation method is suitable for industrial production of pharmaceutical enterprises.
