Identification

Name
Antrafenine
Accession Number
DB01419
Type
Small Molecule
Groups
Approved
Description

Antrafenine is a piperazine derivative drug that acts as an analgesic and anti-inflammatory drug with similar efficacy to naproxen. It is not widely used as it has largely been replaced by newer drugs.

Structure
Thumb
Synonyms
Not Available
International/Other Brands
Stakane
Categories
UNII
21FS93Y6OE
CAS number
55300-29-3
Weight
Average: 588.5435
Monoisotopic: 588.195995326
Chemical Formula
C30H26F6N4O2
InChI Key
NWGGKKGAFZIVBJ-UHFFFAOYSA-N
InChI
InChI=1S/C30H26F6N4O2/c31-29(32,33)20-4-3-5-22(18-20)40-14-12-39(13-15-40)16-17-42-28(41)24-6-1-2-7-25(24)38-26-10-11-37-27-19-21(30(34,35)36)8-9-23(26)27/h1-11,18-19H,12-17H2,(H,37,38)
IUPAC Name
2-{4-[3-(trifluoromethyl)phenyl]piperazin-1-yl}ethyl 2-{[7-(trifluoromethyl)quinolin-4-yl]amino}benzoate
SMILES
FC(F)(F)C1=CC(=CC=C1)N1CCN(CCOC(=O)C2=CC=CC=C2NC2=C3C=CC(=CC3=NC=C2)C(F)(F)F)CC1

Pharmacology

Indication

Antrafenine is used as an anti-inflammatory and analgesic agent for the relief of mild to moderate pain.

Pharmacodynamics

Its mode of action is not fully understood; however, its ability to inhibit prostaglandin synthesis may be involved in the anti-inflammatory effect.

Mechanism of action

Antrafenine is believed to be associated with the inhibition of cyclooxygenase activity. Two unique cyclooxygenases have been described in mammals. The constitutive cyclooxygenase, COX-1, synthesizes prostaglandins necessary for normal gastrointestinal and renal function. The inducible cyclooxygenase, COX-2, generates prostaglandins involved in inflammation. Inhibition of COX-1 is thought to be associated with gastrointestinal and renal toxicity while inhibition of COX-2 provides anti-inflammatory activity.

TargetActionsOrganism
UProstaglandin G/H synthase 1
inhibitor
Human
UProstaglandin G/H synthase 2
inhibitor
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
Not Available
Pathways
PathwayCategory
Antrafenine Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe risk or severity of gastrointestinal bleeding can be increased when Antrafenine is combined with (R)-warfarin.
(S)-WarfarinThe risk or severity of gastrointestinal bleeding can be increased when Antrafenine 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 Antrafenine is combined with 1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic Acid.
4-hydroxycoumarinThe risk or severity of gastrointestinal bleeding can be increased when Antrafenine is combined with 4-hydroxycoumarin.
AbacavirAntrafenine may decrease the excretion rate of Abacavir which could result in a higher serum level.
AbciximabThe risk or severity of bleeding and hemorrhage can be increased when Antrafenine is combined with Abciximab.
AcarboseAntrafenine may decrease the excretion rate of Acarbose which could result in a higher serum level.
AcebutololAntrafenine may decrease the antihypertensive activities of Acebutolol.
AceclofenacThe risk or severity of adverse effects can be increased when Aceclofenac is combined with Antrafenine.
AcemetacinThe risk or severity of adverse effects can be increased when Acemetacin is combined with Antrafenine.
Food Interactions
Not Available

References

Synthesis Reference

Giudicelli, D.P.R.L., Najer, H., Manory, P.M.J. and Dumas, A.P.F.; January 27,1976; assigned to Synthelabo US. Patent 3,935,229.

General References
Not Available
External Links
Human Metabolome Database
HMDB0015488
PubChem Compound
68723
PubChem Substance
46507354
ChemSpider
61973
ChEBI
135841
ChEMBL
CHEMBL345524
PharmGKB
PA164784000
Wikipedia
Antrafenine

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
PropertyValueSource
melting point (°C)88-90Giudicelli, D.P.R.L., Najer, H., Manory, P.M.J. and Dumas, A.P.F.; January 27,1976; assigned to Synthelabo US. Patent 3,935,229.
Predicted Properties
PropertyValueSource
Water Solubility0.00284 mg/mLALOGPS
logP6.3ALOGPS
logP8.39ChemAxon
logS-5.3ALOGPS
pKa (Strongest Acidic)16.69ChemAxon
pKa (Strongest Basic)7.04ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area57.7 Å2ChemAxon
Rotatable Bond Count10ChemAxon
Refractivity147.01 m3·mol-1ChemAxon
Polarizability55.48 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9969
Blood Brain Barrier+0.9132
Caco-2 permeable-0.5721
P-glycoprotein substrateSubstrate0.5792
P-glycoprotein inhibitor IInhibitor0.8917
P-glycoprotein inhibitor IIInhibitor0.9464
Renal organic cation transporterNon-inhibitor0.5702
CYP450 2C9 substrateNon-substrate0.8703
CYP450 2D6 substrateNon-substrate0.6674
CYP450 3A4 substrateNon-substrate0.5172
CYP450 1A2 substrateInhibitor0.7622
CYP450 2C9 inhibitorInhibitor0.7438
CYP450 2D6 inhibitorNon-inhibitor0.7155
CYP450 2C19 inhibitorInhibitor0.7394
CYP450 3A4 inhibitorInhibitor0.6383
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.9305
Ames testNon AMES toxic0.6823
CarcinogenicityNon-carcinogens0.8812
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.7506 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8133
hERG inhibition (predictor II)Inhibitor0.8583
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 GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
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 phenylpiperazines. These are compounds containing a phenylpiperazine skeleton, which consists of a piperazine bound to a phenyl group.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Diazinanes
Sub Class
Piperazines
Direct Parent
Phenylpiperazines
Alternative Parents
N-arylpiperazines / 4-aminoquinolines / Aminobenzoic acids and derivatives / Benzoic acid esters / Trifluoromethylbenzenes / Aniline and substituted anilines / Dialkylarylamines / Benzoyl derivatives / Aminopyridines and derivatives / N-alkylpiperazines
show 14 more
Substituents
Phenylpiperazine / N-arylpiperazine / Aminoquinoline / 4-aminoquinoline / Aminobenzoic acid or derivatives / Trifluoromethylbenzene / Benzoate ester / Quinoline / Benzoic acid or derivatives / Benzoyl
show 31 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Prostaglandin-endoperoxide synthase activity
Specific Function
Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Involved in the constitutive production of prostanoids in particular in the stomach and platelets. In gas...
Gene Name
PTGS1
Uniprot ID
P23219
Uniprot Name
Prostaglandin G/H synthase 1
Molecular Weight
68685.82 Da
References
  1. Hassan SM, Olivesi A, Fish A, Turner P: A comparison of antrafenine and aspirin on platelet aggregation and frusemide-induced diuresis. Postgrad Med J. 1982 Jan;58(675):17-9. [PubMed:7088753]
  2. Berry H, Coquelin JP, Gordon A, Seymour D: Antrafenine, naproxen and placebo in osteoarthritis: a comparative study. Br J Rheumatol. 1983 May;22(2):89-94. [PubMed:6342700]
  3. James MJ, Cook-Johnson RJ, Cleland LG: Selective COX-2 inhibitors, eicosanoid synthesis and clinical outcomes: a case study of system failure. Lipids. 2007 Sep;42(9):779-85. Epub 2007 Jun 2. [PubMed:17541796]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
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. Albertini R, Aimbire F, Villaverde AB, Silva JA Jr, Costa MS: COX-2 mRNA expression decreases in the subplantar muscle of rat paw subjected to carrageenan-induced inflammation after low level laser therapy. Inflamm Res. 2007 Jun;56(6):228-9. [PubMed:17607546]
  2. Dhir A, Naidu PS, Kulkarni SK: Neuroprotective effect of nimesulide, a preferential COX-2 inhibitor, against pentylenetetrazol (PTZ)-induced chemical kindling and associated biochemical parameters in mice. Seizure. 2007 Dec;16(8):691-7. Epub 2007 Jul 2. [PubMed:17604186]
  3. Kumar P, Padi SS, Naidu PS, Kumar A: Cyclooxygenase inhibition attenuates 3-nitropropionic acid-induced neurotoxicity in rats: possible antioxidant mechanisms. Fundam Clin Pharmacol. 2007 Jun;21(3):297-306. [PubMed:17521299]
  4. White WB: Cardiovascular effects of the selective cyclooxygenase-2 inhibitors. Subcell Biochem. 2007;42:145-58. [PubMed:17612049]
  5. Hassan-Alin M, Naesdal J, Nilsson-Pieschl C, Langstrom G, Andersson T: Lack of Pharmacokinetic Interaction between Esomeprazole and the Nonsteroidal Anti-Inflammatory Drugs Naproxen and Rofecoxib in Healthy Subjects. Clin Drug Investig. 2005;25(11):731-40. [PubMed:17532719]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]

Drug created on July 24, 2007 02:34 / Updated on November 02, 2018 05:00