Identification

Name
Alclofenac
Accession Number
DB13167
Type
Small Molecule
Groups
Approved, Withdrawn
Description

Alclofenac is a non-steroidal anti-inflammatory drug. It was withdrawn from the market in the United Kingdom in 1979.

Structure
Thumb
Synonyms
  • (4-Allyloxy-3-chlorphenyl)essigsäure
  • [4-(allyloxy)-3-chlorophenyl]acetic acid
  • 3-Chloro-4-(2-propenyloxy)benzeneacetic acid
  • Alclofenac
  • Alclofénac
  • Alclofenaco
  • Alclofenacum
  • Alclophenac
External IDs
MY-101 / W 7320 / W-7320
International/Other Brands
Allopydin / Epinal / Medifenac / Mervan / Neosten / Neoston / Prinalgin / Reufenac / Zumaril
Categories
UNII
M9CP5H21N8
CAS number
22131-79-9
Weight
Average: 226.66
Monoisotopic: 226.0396719
Chemical Formula
C11H11ClO3
InChI Key
ARHWPKZXBHOEEE-UHFFFAOYSA-N
InChI
InChI=1S/C11H11ClO3/c1-2-5-15-10-4-3-8(6-9(10)12)7-11(13)14/h2-4,6H,1,5,7H2,(H,13,14)
IUPAC Name
2-[3-chloro-4-(prop-2-en-1-yloxy)phenyl]acetic acid
SMILES
OC(=O)CC1=CC(Cl)=C(OCC=C)C=C1

Pharmacology

Indication

Alclofenac is indicated in rheumatology, in particular for the treatment of rheumatoid arthritis, ankylosing spondylitis and, as an analgesic, in painful arthritic pathologies.

Pharmacodynamics
Not Available
Mechanism of action

Alclofenac is an inhibitor of prostaglandin H2 synthase. The inhibition of the enzyme occurs through the reversible block of cyclooxygenase enzyme. Therefore, it prevents the production of inflammatory mediators (and pain) as prostacyclins and prostaglandins. Aclofenac has the ability to inhibit the biosynthesis of prostaglandins which may be an important factor in the action of these drugs, but in addition, the effect of these agents in displacing endogenous anti-inflammatory substances from plasma protein binding sites is thought to be an equally important effect in their mechanism of action

TargetActionsOrganism
AProstaglandin G/H synthase 2
antagonist
Human
Absorption

The absorption of alclofenac from the gastrointestinal tract is irregular. After oral or rectal administration maximum plasma concentrations are reached within 1-4 hours.

Volume of distribution

The volume of distribution is 0.1 L / kg

Protein binding

The binding to plasma proteins is 90-99%.

Metabolism

the main metabolic product is alclofenac itself and alclofenac glucuronide

Route of elimination

Alclofenac is excreted in the urine mainly as glucuronide and as unchanged active substance.

Half life

The plasma half-life varies between 1.5 and 5.5 hours.

Clearance

For oral dose of 500mg: Renal clearance constant (av) 35ml/min Overall clearance constant (av) 37-69ml/min

Toxicity

The lethal dose orally: 1100 (mice), 1050 (rats) mg / kg ;
under the skin: 600 (mice), 630 (rats) mg / kg intraperitoneally: 550 (mice), 530 (rats) 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 Alclofenac is combined with (R)-warfarin.
(S)-WarfarinThe risk or severity of bleeding and hemorrhage can be increased when Alclofenac is combined with (S)-Warfarin.
1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic AcidThe risk or severity of renal failure, hyperkalemia, and hypertension can be increased when Alclofenac is combined with 1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic Acid.
1-benzylimidazoleThe risk or severity of hypertension can be increased when 1-benzylimidazole is combined with Alclofenac.
2,5-Dimethoxy-4-ethylamphetamineThe risk or severity of hypertension can be increased when 2,5-Dimethoxy-4-ethylamphetamine is combined with Alclofenac.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of hypertension can be increased when Alclofenac is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3,4-MethylenedioxyamphetamineThe risk or severity of hypertension can be increased when 3,4-Methylenedioxyamphetamine is combined with Alclofenac.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of hypertension can be increased when 4-Bromo-2,5-dimethoxyamphetamine is combined with Alclofenac.
4-hydroxycoumarinThe risk or severity of bleeding and hemorrhage can be increased when Alclofenac is combined with 4-hydroxycoumarin.
4-MethoxyamphetamineThe risk or severity of hypertension can be increased when 4-Methoxyamphetamine is combined with Alclofenac.
Food Interactions
Not Available

References

General References
  1. Wiggins LF: The chemical and biological background to alclofenac. Curr Med Res Opin. 1975;3(5):241-8. [PubMed:241593]
  2. Lambotte F: Therapeutic activity of 4-allyloxy-3-chlorophenylacetic acid. Arzneimittelforschung. 1970 Apr;20(4):569-71. [PubMed:4911592]
  3. Thomas GM, Rees P, Dippy JE, Maddock J: Simultaneous pharmacokinetics of alclofenace in plasma and synovial fluid in patients with rheumatoid arthritis. Curr Med Res Opin. 1975;3(5):264-7. [PubMed:241595]
  4. Selinsky BS, Gupta K, Sharkey CT, Loll PJ: Structural analysis of NSAID binding by prostaglandin H2 synthase: time-dependent and time-independent inhibitors elicit identical enzyme conformations. Biochemistry. 2001 May 1;40(17):5172-80. [PubMed:11318639]
  5. Brogden RN, Heel RC, Speight TM, Avery GS: Alclofenac: a review of its pharmacological properties and therapeutic efficacy in rheumatoid arthritis and allied rheumatic disorders. Drugs. 1977 Oct;14(4):241-59. [PubMed:21068]
External Links
KEGG Drug
D01252
PubChem Compound
30951
PubChem Substance
347829274
ChemSpider
28714
ChEBI
31183
ChEMBL
CHEMBL94081
Wikipedia
Alclofenac
ATC Codes
M01AB06 — Alclofenac

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

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

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.288 mg/mLALOGPS
logP3.01ALOGPS
logP2.79ChemAxon
logS-2.9ALOGPS
pKa (Strongest Acidic)3.71ChemAxon
pKa (Strongest Basic)-4.9ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area46.53 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity57.8 m3·mol-1ChemAxon
Polarizability22.28 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

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

Taxonomy

Description
This compound belongs to the class of organic compounds known as phenol ethers. These are aromatic compounds containing an ether group substituted with a benzene ring.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Phenol ethers
Sub Class
Not Available
Direct Parent
Phenol ethers
Alternative Parents
Phenoxy compounds / Chlorobenzenes / Alkyl aryl ethers / Aryl chlorides / Monocarboxylic acids and derivatives / Carboxylic acids / Organochlorides / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
Substituents
Phenoxy compound / Phenol ether / Alkyl aryl ether / Chlorobenzene / Halobenzene / Aryl chloride / Monocyclic benzene moiety / Aryl halide / Monocarboxylic acid or derivatives / Ether
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
aromatic ether, monocarboxylic acid, monochlorobenzenes (CHEBI:31183)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
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. Thomas GM, Rees P, Dippy JE, Maddock J: Simultaneous pharmacokinetics of alclofenace in plasma and synovial fluid in patients with rheumatoid arthritis. Curr Med Res Opin. 1975;3(5):264-7. [PubMed:241595]

Drug created on February 11, 2017 11:07 / Updated on December 16, 2018 07:00