Identification

Name
Nimesulide
Accession Number
DB04743
Type
Small Molecule
Groups
Approved, Investigational, Withdrawn
Description

Nimesulide is a relatively COX-2 selective, non-steroidal anti-inflammatory drug (NSAID) with analgesic and antipyretic properties. Its approved indications are the treatment of acute pain, the symptomatic treatment of osteoarthritis and primary dysmenorrhoea in adolescents and adults above 12 years old. Due to concerns about the risk of hepatotoxicity, nimesulide has been withdrawn from market in many countries.

Structure
Thumb
Synonyms
Not Available
External IDs
R 805 / R-805
International/Other Brands
Ainex / Aulin / Coxtal / Eskaflam / Mesulid / Nilsid / Nimalox / Nimside / Nise / Octaprin / Sintalgin / Sulide
Categories
UNII
V4TKW1454M
CAS number
51803-78-2
Weight
Average: 308.31
Monoisotopic: 308.046692194
Chemical Formula
C13H12N2O5S
InChI Key
HYWYRSMBCFDLJT-UHFFFAOYSA-N
InChI
InChI=1S/C13H12N2O5S/c1-21(18,19)14-12-8-7-10(15(16)17)9-13(12)20-11-5-3-2-4-6-11/h2-9,14H,1H3
IUPAC Name
N-(4-nitro-2-phenoxyphenyl)methanesulfonamide
SMILES
CS(=O)(=O)NC1=C(OC2=CC=CC=C2)C=C(C=C1)[N+]([O-])=O

Pharmacology

Indication

For the treatment of acute pain, the symptomatic treatment of osteoarthritis and primary dysmenorrhoea in adolescents and adults above 12 years old.

Pharmacodynamics

Food, gender and advanced age have negligible effects on nimesulide pharmacokinetics.

Mechanism of action

The therapeutic effects of Nimesulide are the result of its complete mode of action which targets a number of key mediators of the inflammatory process such as: COX-2 mediated prostaglandins, free radicals, proteolytic enzymes and histamine.

TargetActionsOrganism
AProstaglandin G/H synthase 2
inhibitor
Human
UGroup IIE secretory phospholipase A2Not AvailableHuman
ULactotransferrinNot AvailableHuman
Absorption

Rapidly absorbed following oral administration.

Volume of distribution
Not Available
Protein binding

>97.5%

Metabolism

Hepatic. Extensive biotransformation, mainly to 4-hydroxynimesulide (which also appears to be biologically active).

Route of elimination

Renal (50%), fecal (29%)

Half life

1.8–4.7 hours

Clearance
Not Available
Toxicity

Oral TDLO (human): 1.429 mg/kg; Oral TDLO (woman): 2 mg/kg; Oral LD50 (rat): 200 mg/kg; Oral LD50 (mouse): 392 mg/kg

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe risk or severity of bleeding and hemorrhage can be increased when Nimesulide is combined with (R)-warfarin.
(S)-WarfarinThe risk or severity of bleeding and hemorrhage can be increased when Nimesulide is combined with (S)-Warfarin.
4-hydroxycoumarinThe risk or severity of bleeding and hemorrhage can be increased when Nimesulide is combined with 4-hydroxycoumarin.
AbafunginThe therapeutic efficacy of Abafungin can be increased when used in combination with Nimesulide.
AbciximabNimesulide may increase the anticoagulant activities of Abciximab.
AcebutololNimesulide may decrease the antihypertensive activities of Acebutolol.
AceclofenacThe risk or severity of adverse effects can be increased when Nimesulide is combined with Aceclofenac.
AcemetacinThe risk or severity of adverse effects can be increased when Nimesulide is combined with Acemetacin.
AcenocoumarolThe risk or severity of bleeding and hemorrhage can be increased when Nimesulide is combined with Acenocoumarol.
AcepromazineThe risk or severity of hypotension can be increased when Acepromazine is combined with Nimesulide.
Food Interactions
Not Available

References

Synthesis Reference

Bernard Pirotte, Geraldine Piel, Philippe Neven, Isabelle Delneuville, Joszef Geczy, "Water-soluble nimesulide salt and its preparation, aqueous dolution containing it, nimesulide-based combinations and their uses." U.S. Patent US5756546, issued November, 1991.

US5756546
General References
Not Available
External Links
KEGG Drug
D01049
PubChem Compound
4495
PubChem Substance
46507721
ChemSpider
4339
BindingDB
50056999
ChEBI
44445
ChEMBL
CHEMBL56367
Therapeutic Targets Database
DPR000079
PharmGKB
PA137179528
HET
NIM
Drugs.com
Drugs.com Drug Page
Wikipedia
Nimesulide
ATC Codes
M02AA26 — NimesulideM01AX17 — Nimesulide
PDB Entries
1zwp / 2oth / 3e9x / 3n8x / 3ql6 / 4eix
MSDS
Download (23.5 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailablePain1
2CompletedPreventionCancer, Breast1
3RecruitingTreatmentAcute and Chronic Inflammation / Indigestion1
4CompletedTreatmentKnee Osteoarthritis (Knee OA)1
4CompletedTreatmentPharyngitis1
4WithdrawnTreatmentUpper Respiratory Tract Infections1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)143-144.5 °CPhysProp
logP2.60SANGSTER (1993)
Predicted Properties
PropertyValueSource
Water Solubility0.0182 mg/mLALOGPS
logP2.56ALOGPS
logP1.79ChemAxon
logS-4.2ALOGPS
pKa (Strongest Acidic)6.86ChemAxon
pKa (Strongest Basic)-8.9ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area101.22 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity76.31 m3·mol-1ChemAxon
Polarizability28.87 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9952
Blood Brain Barrier+0.6341
Caco-2 permeable-0.55
P-glycoprotein substrateNon-substrate0.8267
P-glycoprotein inhibitor INon-inhibitor0.5634
P-glycoprotein inhibitor IINon-inhibitor0.8129
Renal organic cation transporterNon-inhibitor0.8943
CYP450 2C9 substrateNon-substrate0.6235
CYP450 2D6 substrateNon-substrate0.8055
CYP450 3A4 substrateSubstrate0.5257
CYP450 1A2 substrateInhibitor0.9107
CYP450 2C9 inhibitorInhibitor0.8948
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.7628
CYP450 3A4 inhibitorNon-inhibitor0.8309
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.8952
Ames testAMES toxic0.6488
CarcinogenicityNon-carcinogens0.6116
BiodegradationNot ready biodegradable0.9901
Rat acute toxicity3.0832 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Strong inhibitor0.5345
hERG inhibition (predictor II)Non-inhibitor0.5574
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-000x-0291000000-646d9ba99afae997e8ed
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-000x-0291000000-d80621f80ce111da876f
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-001i-0910000000-a5c76988cf3380fc5b30
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0udi-0900000000-d75eef7fee376750fef9
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0udi-0900000000-3e21c4ed858c88f9fc59
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0a4i-0459000000-055f5763b37c21230aaa
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0ue9-2920000000-2d4d6a28e043baa5549a

Taxonomy

Description
This compound belongs to the class of organic compounds known as diphenylethers. These are aromatic compounds containing two benzene rings linked to each other through an ether group.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Diphenylethers
Direct Parent
Diphenylethers
Alternative Parents
Diarylethers / Sulfanilides / Nitrobenzenes / Nitroaromatic compounds / Phenoxy compounds / Phenol ethers / Organic sulfonamides / Organosulfonamides / Aminosulfonyl compounds / Organic oxoazanium compounds
show 6 more
Substituents
Diphenylether / Diaryl ether / Sulfanilide / Nitrobenzene / Phenoxy compound / Nitroaromatic compound / Phenol ether / Organic sulfonic acid amide / Organosulfonic acid amide / Organic sulfonic acid or derivatives
show 20 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
C-nitro compound, aromatic ether, sulfonamide (CHEBI:44445)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Prostaglandin-endoperoxide synthase activity
Specific Function
Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Constitutively expressed in some tissues in physiological conditions, such as the endothelium, kidney and...
Gene Name
PTGS2
Uniprot ID
P35354
Uniprot Name
Prostaglandin G/H synthase 2
Molecular Weight
68995.625 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  2. Rainsford KD: Nimesulide -- a multifactorial approach to inflammation and pain: scientific and clinical consensus. Curr Med Res Opin. 2006 Jun;22(6):1161-70. [PubMed:16846549]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Phospholipase a2 activity
Specific Function
PA2 catalyzes the calcium-dependent hydrolysis of the 2-acyl groups in 3-sn-phosphoglycerides. Has a preference for arachidonic-containing phospholipids.
Gene Name
PLA2G2E
Uniprot ID
Q9NZK7
Uniprot Name
Group IIE secretory phospholipase A2
Molecular Weight
15988.525 Da
References
  1. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Serine-type endopeptidase activity
Specific Function
Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate.Lactotransferrin is a major iron-binding and multifu...
Gene Name
LTF
Uniprot ID
P02788
Uniprot Name
Lactotransferrin
Molecular Weight
78181.225 Da
References
  1. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Uesawa Y, Takeuchi T, Mohri K: Integrated analysis on the physicochemical properties of dihydropyridine calcium channel blockers in grapefruit juice interactions. Curr Pharm Biotechnol. 2012 Jul;13(9):1705-17. [PubMed:22039822]

Drug created on September 11, 2007 11:49 / Updated on October 01, 2018 13:55