Lefradafiban

Identification

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Name
Lefradafiban
Accession Number
DB04863
Type
Small Molecule
Groups
Investigational
Description

Lefradafiban is an oral platelet glycoprotein IIb/IIIa receptor antagonist being investigated in the treatment of angina.

Structure
Thumb
Synonyms
  • Lefradafiban
  • lefradafibán
Categories
UNII
0R4888YXR5
CAS number
149503-79-7
Weight
Average: 439.4611
Monoisotopic: 439.174335547
Chemical Formula
C23H25N3O6
InChI Key
PGCFXITVMNNKON-ROUUACIJSA-N
InChI
InChI=1S/C23H25N3O6/c1-30-20(27)12-17-11-18(25-22(17)28)13-32-19-9-7-15(8-10-19)14-3-5-16(6-4-14)21(24)26-23(29)31-2/h3-10,17-18H,11-13H2,1-2H3,(H,25,28)(H2,24,26,29)/t17-,18-/m0/s1
IUPAC Name
methyl 2-[(3S,5S)-5-(4-{4-[(1Z)-amino[(methoxycarbonyl)imino]methyl]phenyl}phenoxymethyl)-2-oxopyrrolidin-3-yl]acetate
SMILES
COC(=O)C[C@@H]1C[C@@H](COC2=CC=C(C=C2)C2=CC=C(C=C2)C(\N)=N\C(=O)OC)NC1=O

Pharmacology

Indication

For the treatment of unstable angina.

Pharmacodynamics

Lefradafiban, an orally active prodrug of fradafiban, is a novel glycoprotein (IIb/IIIa) inhibitor for the treatment of unstable angina. Development was discontinued in 2000 due to lack of efficacy.

Mechanism of action

GPIIb/IIIa inhibitors, such as lefradafiban, block the final common pathway of platelet aggregation.

TargetActionsOrganism
UIntegrin alpha-IIbNot AvailableHumans
UIntegrin beta-3Not AvailableHumans
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
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
Patent BlueThe therapeutic efficacy of Lefradafiban can be decreased when used in combination with Patent Blue.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

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  • Action
    Action

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Food Interactions
Not Available

References

General References
  1. Akkerhuis KM, van Den Brand MJ, van Der Zwaan C, Peels HO, Suryapranata H, van Der Wieken LR, Stibbe J, Hoffmann J, Baardman T, Deckers JW, Simoons ML: Pharmacodynamics and safety of lefradafiban, an oral platelet glycoprotein IIb/IIIa receptor antagonist, in patients with stable coronary artery disease undergoing elective angioplasty. Heart. 2001 Apr;85(4):444-50. [PubMed:11250974]
  2. Doggrell SA: Clinical trials with glycoprotein IIb/IIIa antagonists - No benefit without bleeding? Drugs Today (Barc). 2001 Aug;37(8):509-531. [PubMed:12743636]
External Links
PubChem Compound
9576916
PubChem Substance
175426872
ChemSpider
7851357
ChEBI
60634
ChEMBL
CHEMBL2105032

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentHealthy Volunteers3

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 Solubility0.0088 mg/mLALOGPS
logP2.57ALOGPS
logP1.66ChemAxon
logS-4.7ALOGPS
pKa (Strongest Acidic)14ChemAxon
pKa (Strongest Basic)0.71ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area129.31 Å2ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity115.47 m3·mol-1ChemAxon
Polarizability47.13 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9954
Blood Brain Barrier+0.5605
Caco-2 permeable-0.7001
P-glycoprotein substrateSubstrate0.5684
P-glycoprotein inhibitor INon-inhibitor0.8028
P-glycoprotein inhibitor IIInhibitor0.509
Renal organic cation transporterNon-inhibitor0.7191
CYP450 2C9 substrateNon-substrate0.7478
CYP450 2D6 substrateNon-substrate0.8114
CYP450 3A4 substrateSubstrate0.582
CYP450 1A2 substrateNon-inhibitor0.6713
CYP450 2C9 inhibitorNon-inhibitor0.7755
CYP450 2D6 inhibitorNon-inhibitor0.8675
CYP450 2C19 inhibitorNon-inhibitor0.6173
CYP450 3A4 inhibitorNon-inhibitor0.5688
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.6038
Ames testNon AMES toxic0.643
CarcinogenicityNon-carcinogens0.8891
BiodegradationNot ready biodegradable0.9819
Rat acute toxicity2.5767 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9859
hERG inhibition (predictor II)Non-inhibitor0.8247
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

Taxonomy

Description
This compound belongs to the class of organic compounds known as biphenyls and derivatives. These are organic compounds containing to benzene rings linked together by a C-C bond.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Biphenyls and derivatives
Direct Parent
Biphenyls and derivatives
Alternative Parents
Phenoxy compounds / Phenol ethers / Alkyl aryl ethers / Pyrrolines / Cyclic carboximidic acids / Methyl esters / Lactims / Organic carbonic acids and derivatives / Propargyl-type 1,3-dipolar organic compounds / Azacyclic compounds
show 7 more
Substituents
Biphenyl / Phenoxy compound / Phenol ether / Alkyl aryl ether / Pyrroline / Methyl ester / Cyclic carboximidic acid / Carboxylic acid ester / Carbonic acid derivative / Lactim
show 19 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
methyl ester, pyrrolidin-2-ones (CHEBI:60634)

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Metal ion binding
Specific Function
Integrin alpha-IIb/beta-3 is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. It recognizes the sequence R-G-D in a wide array of ligands. It recogn...
Gene Name
ITGA2B
Uniprot ID
P08514
Uniprot Name
Integrin alpha-IIb
Molecular Weight
113375.96 Da
References
  1. Akkerhuis KM, van Den Brand MJ, van Der Zwaan C, Peels HO, Suryapranata H, van Der Wieken LR, Stibbe J, Hoffmann J, Baardman T, Deckers JW, Simoons ML: Pharmacodynamics and safety of lefradafiban, an oral platelet glycoprotein IIb/IIIa receptor antagonist, in patients with stable coronary artery disease undergoing elective angioplasty. Heart. 2001 Apr;85(4):444-50. [PubMed:11250974]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Virus receptor activity
Specific Function
Integrin alpha-V/beta-3 (ITGAV:ITGB3) is a receptor for cytotactin, fibronectin, laminin, matrix metalloproteinase-2, osteopontin, osteomodulin, prothrombin, thrombospondin, vitronectin and von Wil...
Gene Name
ITGB3
Uniprot ID
P05106
Uniprot Name
Integrin beta-3
Molecular Weight
87056.975 Da
References
  1. Akkerhuis KM, van Den Brand MJ, van Der Zwaan C, Peels HO, Suryapranata H, van Der Wieken LR, Stibbe J, Hoffmann J, Baardman T, Deckers JW, Simoons ML: Pharmacodynamics and safety of lefradafiban, an oral platelet glycoprotein IIb/IIIa receptor antagonist, in patients with stable coronary artery disease undergoing elective angioplasty. Heart. 2001 Apr;85(4):444-50. [PubMed:11250974]

Drug created on October 19, 2007 16:06 / Updated on August 02, 2019 07:41