Rofecoxib Chemical Properties

Melting point:

207°C

Boiling point:

577.6±50.0 °C(Predicted)

Density 

1.333±0.06 g/cm3(Predicted)

storage temp. 

Refrigerator

solubility 

DMSO: soluble5mg/mL, clear (warmed)

form 

powder

color 

white to beige

Water Solubility 

9mg/L(25 ºC)

Merck 

14,8248

CAS DataBase Reference

162011-90-7(CAS DataBase Reference)

Safety Information

Hazard Codes 

Xn

Risk Statements 

22

WGK Germany 

3

RTECS 

LU5135000

Hazardous Substances Data

162011-90-7(Hazardous Substances Data)

Rofecoxib Usage And Synthesis

Description

Rofecoxib ts a non-steroidal anti-inflammatory drug (NSAID) launched in Mexico, its first market, for the management of acute pain and the treatment of osteoarthritis (OA) and primary dysmenorrhea. Rofecoxib can be obtained by several different ways; one example is by arylation of a 4-bromofuranone with a phenylboronic acid under Suzuki conditions. Rofecoxib is a highly selective inhibitor of COX-2, the inducible isoform of cyclooxygenase and therefore exhibits a potent antiinflammatory activity without concomitant gastric or renal toxicities linked to the non-specific COX-1/2 inhibitors. In several clinical studies in patients with knee or hip osteoarthritis, Rofecoxib was evaluated at 12.5-50 mg doses once daily: it demonstrated efficacy for all primary and secondary endpoints at doses considerably weaker than those for classical non-specific NSAIDs, with good tolerance and less adverse effects. Selective COX-2 inhibitors potentially have a large spectrum of activity including new indications such as Alzheimer's disease, colorectal cancer, irritable bowel disease or urinary incontinence.

Chemical Properties

Off-White (Pale Yellow) Crystalline Powder

Originator

Merck (US)

Uses

A selective cyclooxygenase-2 (COX-2) inhibitor. Use as an anti-inflammatory, analgesic.

Uses

antipsychotic

Uses

Labeled Rizatriptan, intended for use as an internal standard for the quantification of Rizatriptan by GC- or LC-mass spectrometry.

Definition

ChEBI: A butenolide that is furan-2(5H)-one that is substituted by a phenyl group at position 3 and by a p-(methylsulfonyl)phenyl group at position 4. A selective cyclooxygenase 2 inhibitor, it was used from 1999 to 2004 for the tr atment of ostoarthritis, but was withdrawn following concerns about an associated increased risk of heart attack and stroke.

Indications

Rofecoxib is approved for the treatment of osteoarthritis, dysmenorrhea, and acute pain. The most common adverse reactions to rofecoxib are mild to moderate GI irritation (diarrhea, nausea, vomiting, dyspepsia, abdominal pain). Lower extremity edema and hypertension occur relatively frequently (about 3.5%). It is not metabolized by CYP2C9, so rofecoxib should not be subject to some of the interactions seen with celecoxib. However, its metabolism is increased by the coadministration of rifampin, which acts as a nonspecific inducer of hepatic metabolism.

brand name

Vioxx (Merck).

Mechanism of action

Rofecoxib is excreted primarily in the urine (72%) as metabolites. Less than 1% is excreted in the urine as unchanged drug, whereas approximately 14% is excreted in the feces as unchanged drug. Although the metabolism of rofecoxib has not been fully determined, the microsomal cytochrome P450 system appears to play only a minor role—a major difference in the metabolic routes of rofecoxib and celecoxib. The major metabolic route appears to form reduction of the dihydrofuranone ring system by cystolic enzymes to the to cis- and trans- dihydro derivatives. Also isolated is the glucuronide of a hydroxy derivative that results from CYP2C9 oxidative metabolism. None of the isolated metabolites of rofecoxib possess pharmacological activity as COX-1 or COX-2 inhibitors.

Pharmacokinetics

Rofecoxib has been synthesized by a number of synthetic routes that have been summarized elsewhere. It was the second selective COX-2 inhibitor to be marketed. Rofecoxib is well absorbed from the GI tract on oral administration, with peak plasma levels generally being attained within 2 to 3 hours of dosing. Bioavailability averages 93% following administration of a single dose. The area under the plasma concentration–time curve is increased in patients older than 65 years compared to younger adults and is increased slightly in black and Hispanic patients compared with white patients, but the difference is not considered to be clinically significant.

Clinical Use

Rofecoxib was indicated for the relief of the signs and symptoms of osteoarthritis, for the management of acute pain in adults, and for the treatment of primary dysmenorrhea.

Rofecoxib(162011-90-7)Related Product Information

• Nimesulide
• Meloxicam
• Parecoxib
• Tamsulosin hydrochloride
• 2(5H)-Furanone
• ROFECOXIB-D5
• 4-Methyi Sulfonyl Acetophenone, Rofecoxib,
• 3-(3,4-Difluorophenyl)-4-(4-(methylsulfonyl)phenyl)-2(5H)-furanone
• Rofecoxib
• Phenylacetone
• Furazolidone
• Furaltadone
• Diphenyl ether
• Phenylacetic acid
• PHENYL VALERATE
• PHENYL RESIN