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4-(4-methanesulfonylphenyl)-3-phenyl-2,5-dihydrofuran-2-one

ChemBase ID: 415
Molecular Formular: C17H14O4S
Molecular Mass: 314.35566
Monoisotopic Mass: 314.06127993
SMILES and InChIs

SMILES:
S(=O)(=O)(c1ccc(C2=C(c3ccccc3)C(=O)OC2)cc1)C
Canonical SMILES:
O=C1OCC(=C1c1ccccc1)c1ccc(cc1)S(=O)(=O)C
InChI:
InChI=1S/C17H14O4S/c1-22(19,20)14-9-7-12(8-10-14)15-11-21-17(18)16(15)13-5-3-2-4-6-13/h2-10H,11H2,1H3
InChIKey:
RZJQGNCSTQAWON-UHFFFAOYSA-N

Cite this record

CBID:415 http://www.chembase.cn/molecule-415.html

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NAMES AND DATABASE IDS

NAMES AND DATABASE IDS

Names Database IDs
IUPAC name
4-(4-methanesulfonylphenyl)-3-phenyl-2,5-dihydrofuran-2-one
IUPAC Traditional name
rofecoxib
4-(4-methanesulfonylphenyl)-3-phenyl-2,5-dihydrofuran-2-one
Brand Name
Vioxx
Synonyms
MK 966
MK 996
rofecoxib
Rofecoxib
4-[4-(Methylsulfonyl)phenyl]-3-phenyl-2(5H)-furanone
3-(4-Methanesulfonylphenyl)-2-phenyl-2-buten-4-olide
3-Phenyl-4-[4-(Methylsulfonyl)phenyl]-2(5H)-furanone
MK 0966
Rhuma-cure
Vioxx
Rofecoxib (Vioxx)
Vioxx
Ceoxx
Ceeoxx
Rofecoxib
CAS Number
N/A
162011-90-7
PubChem SID
160963878
46504787
PubChem CID
5090

CALCULATED PROPERTIES

CALCULATED PROPERTIES

JChem ALOGPS 2.1
Acid pKa 14.839777  H Acceptors
H Donor LogD (pH = 5.5) 2.5609105 
LogD (pH = 7.4) 2.5609105  Log P 2.5609105 
Molar Refractivity 84.0801 cm3 Polarizability 33.193634 Å3
Polar Surface Area 60.44 Å2 Rotatable Bonds
Lipinski's Rule of Five true 
Log P 2.32  LOG S -4.47 
Solubility (Water) 1.06e-02 g/l 

PROPERTIES

PROPERTIES

Physical Property Safety Information Pharmacology Properties Product Information Bioassay(PubChem)
Solubility
Chloroform expand Show data source
Dimethyl formamide expand Show data source
DMSO expand Show data source
Insoluble expand Show data source
Apperance
Off-White Solid expand Show data source
Melting Point
207-209°C expand Show data source
Hydrophobicity(logP)
3.2 expand Show data source
Storage Condition
Refrigerator expand Show data source
MSDS Link
Download expand Show data source
Target
COX expand Show data source
Mechanism of Action
Cyclooxygenase-2 inhibitor expand Show data source
Salt Data
Free Base expand Show data source
Certificate of Analysis
Download expand Show data source
Application(s)
Nonsteroidal anti-inflammatory drug (NSAID) expand Show data source

DETAILS

DETAILS

DrugBank DrugBank TRC TRC
DrugBank - DB00533 external link
Item Information
Drug Groups withdrawn; investigational
Description On September 30, 2004, Merck voluntarily withdrew rofecoxib from the market because of concerns about increased risk of heart attack and stroke associated with long-term, high-dosage use.
Indication For the treatment of osteoarthritis, rheumatoid arthritis, acute pain in adults, and primary dysmenorrhea, as well as acute treatment of migraine attacks with or without auras.
Pharmacology Rofecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, is classified as a nonsteroidal anti-inflammatory drug (NSAID). Unlike celecoxib, rofecoxib lacks a sulfonamide chain and does not require CYP450 enzymes for metabolism. Like other NSAIDs, rofecoxib exhibits anti-inflammatory, analgesic, and antipyretic activity. NSAIDs appear to inhibit prostaglandin synthesis via the inhibition of cyclooxygenase (COX), which are responsible for catalyzing the formation of prostaglandins in the arachidonic acid pathyway. There are at least two isoenzymes, COX-1 and COX-2, that have been identified. Although the exact mechanisms have not been clearly established, NSAIDs exert their anti-inflammatory, analgesic, and antipyretic primarily through the inhibition of COX-2. The inhibition of COX-1 is principally responsible for the negative effects on the GI mucosa. As rofecoxib is selective for COX-2, it may be potentially associated with a decreased risk of certain adverse events, but more data is needed to fully evaulate the drug.
Toxicity No overdoses of rofecoxib were reported during clinical trials. Administration of single doses of rofecoxib 1000 mg to 6 healthy volunteers and multiple doses of 250 mg/day for 14 days to 75 healthy volunteers did not result in serious toxicity.
Affected Organisms
Humans and other mammals
Biotransformation Hepatic. Metabolism of rofecoxib is primarily mediated through reduction by cytosolic enzymes. The principal metabolic products are the cis-dihydro and trans-dihydro derivatives of rofecoxib, which account for nearly 56% of recovered radioactivity in the urine. An additional 8.8% of the dose was recovered as the glucuronide of the hydroxy derivative, a product of oxidative metabolism. The biotransformation of rofecoxib and this metabolite is reversible in humans to a limited extent (< 5%). These metabolites are inactive as COX-1 or COX-2 inhibitors. Cytochrome P450 plays a minor role in metabolism of rofecoxib.
Absorption The mean oral bioavailability of rofecoxib at therapeutically recommended doses of 12.5, 25, and 50 mg is approximately 93%.
Half Life 17 hours
Protein Binding 87%
References
Bombardier C, Laine L, Reicin A, Shapiro D, Burgos-Vargas R, Davis B, Day R, Ferraz MB, Hawkey CJ, Hochberg MC, Kvien TK, Schnitzer TJ: Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. VIGOR Study Group. N Engl J Med. 2000 Nov 23;343(21):1520-8, 2 p following 1528. [Pubmed]
Bresalier RS, Sandler RS, Quan H, Bolognese JA, Oxenius B, Horgan K, Lines C, Riddell R, Morton D, Lanas A, Konstam MA, Baron JA: Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial. N Engl J Med. 2005 Mar 17;352(11):1092-102. Epub 2005 Feb 15. [Pubmed]
Curfman GD, Morrissey S, Drazen JM: Expression of concern reaffirmed. N Engl J Med. 2006 Mar 16;354(11):1193. Epub 2006 Feb 22. [Pubmed]
Fitzgerald GA: Coxibs and cardiovascular disease. N Engl J Med. 2004 Oct 21;351(17):1709-11. Epub 2004 Oct 6. [Pubmed]
Karha J, Topol EJ: The sad story of Vioxx, and what we should learn from it. Cleve Clin J Med. 2004 Dec;71(12):933-4, 936, 938-9. [Pubmed]
Baron JA, Sandler RS, Bresalier RS, Lanas A, Morton DG, Riddell R, Iverson ER, Demets DL: Cardiovascular events associated with rofecoxib: final analysis of the APPROVe trial. Lancet. 2008 Nov 15;372(9651):1756-64. Epub 2008 Oct 14. [Pubmed]
Matheson AJ, Figgitt DP: Rofecoxib: a review of its use in the management of osteoarthritis, acute pain and rheumatoid arthritis. Drugs. 2001;61(6):833-65. [Pubmed]
Hillson JL, Furst DE: Rofecoxib. Expert Opin Pharmacother. 2000 Jul;1(5):1053-66. [Pubmed]
External Links
Wikipedia
RxList
Drugs.com
Toronto Research Chemicals - V670000 external link
A selective cyclooxygenase-2 (COX-2) inhibitor. Use as an anti-inflammatory, analgesic.

REFERENCES

REFERENCES

From Suppliers Google Scholar IconGoogle Scholar PubMed iconPubMed Google Books IconGoogle Books
  • • Bombardier C, Laine L, Reicin A, Shapiro D, Burgos-Vargas R, Davis B, Day R, Ferraz MB, Hawkey CJ, Hochberg MC, Kvien TK, Schnitzer TJ: Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. VIGOR Study Group. N Engl J Med. 2000 Nov 23;343(21):1520-8, 2 p following 1528. Pubmed
  • • Bresalier RS, Sandler RS, Quan H, Bolognese JA, Oxenius B, Horgan K, Lines C, Riddell R, Morton D, Lanas A, Konstam MA, Baron JA: Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial. N Engl J Med. 2005 Mar 17;352(11):1092-102. Epub 2005 Feb 15. Pubmed
  • • Curfman GD, Morrissey S, Drazen JM: Expression of concern reaffirmed. N Engl J Med. 2006 Mar 16;354(11):1193. Epub 2006 Feb 22. Pubmed
  • • Fitzgerald GA: Coxibs and cardiovascular disease. N Engl J Med. 2004 Oct 21;351(17):1709-11. Epub 2004 Oct 6. Pubmed
  • • Karha J, Topol EJ: The sad story of Vioxx, and what we should learn from it. Cleve Clin J Med. 2004 Dec;71(12):933-4, 936, 938-9. Pubmed
  • • Baron JA, Sandler RS, Bresalier RS, Lanas A, Morton DG, Riddell R, Iverson ER, Demets DL: Cardiovascular events associated with rofecoxib: final analysis of the APPROVe trial. Lancet. 2008 Nov 15;372(9651):1756-64. Epub 2008 Oct 14. Pubmed
  • • Matheson AJ, Figgitt DP: Rofecoxib: a review of its use in the management of osteoarthritis, acute pain and rheumatoid arthritis. Drugs. 2001;61(6):833-65. Pubmed
  • • Hillson JL, Furst DE: Rofecoxib. Expert Opin Pharmacother. 2000 Jul;1(5):1053-66. Pubmed
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  • • Ehrich, E.W. et al., Clin. Pharmacol. Ther. (St. Louis), 1999, 65, 336-347, (pharmacol)
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