Darapladib

This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.

Identification

Name
Darapladib
Accession Number
DB06311
Type
Small Molecule
Groups
Investigational
Description
Not Available
Structure
Thumb
Synonyms
Not Available
External IDs
480848 / SB-480848
Categories
UNII
UI1U1MYH09
CAS number
356057-34-6
Weight
Average: 666.78
Monoisotopic: 666.265160306
Chemical Formula
C36H38F4N4O2S
InChI Key
WDPFJWLDPVQCAJ-UHFFFAOYSA-N
InChI
InChI=1S/C36H38F4N4O2S/c1-3-42(4-2)20-21-43(22-25-8-12-27(13-9-25)28-14-16-29(17-15-28)36(38,39)40)33(45)23-44-32-7-5-6-31(32)34(46)41-35(44)47-24-26-10-18-30(37)19-11-26/h8-19H,3-7,20-24H2,1-2H3
IUPAC Name
N-[2-(diethylamino)ethyl]-2-(2-{[(4-fluorophenyl)methyl]sulfanyl}-4-oxo-1H,4H,5H,6H,7H-cyclopenta[d]pyrimidin-1-yl)-N-{[4'-(trifluoromethyl)-[1,1'-biphenyl]-4-yl]methyl}acetamide
SMILES
CCN(CC)CCN(CC1=CC=C(C=C1)C1=CC=C(C=C1)C(F)(F)F)C(=O)CN1C2=C(CCC2)C(=O)N=C1SCC1=CC=C(F)C=C1

Pharmacology

Indication

Investigated for use/treatment in atherosclerosis.

Pharmacodynamics
Not Available
Mechanism of action

Darapladib is a selective lipoprotein-associated phospholipase A2 (Lp-PLA2) inhibitor. Lp-PLA2 is an enzymatic upstream mediator of inflammatory processes. Evidence from experimental settings show that the breakdown products from oxidized low density lipoprotein C (LDL-C)such as lysophosphatidylcholine species and oxidized nonesterified fatty acids are pro-inflammatory and pro-apoptotic. These products are suspected to cause athlerosclerosis progression and plaque vulnerability, which leads to increased risk of cardiovascular problems.

TargetActionsOrganism
UCytosolic phospholipase A2Not 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
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Not Available
Food Interactions
Not Available

References

General References
  1. Mohler ER 3rd, Ballantyne CM, Davidson MH, Hanefeld M, Ruilope LM, Johnson JL, Zalewski A: The effect of darapladib on plasma lipoprotein-associated phospholipase A2 activity and cardiovascular biomarkers in patients with stable coronary heart disease or coronary heart disease risk equivalent: the results of a multicenter, randomized, double-blind, placebo-controlled study. J Am Coll Cardiol. 2008 Apr 29;51(17):1632-41. doi: 10.1016/j.jacc.2007.11.079. [PubMed:18436114]
External Links
ChemSpider
8115230
BindingDB
50125265
ChEMBL
CHEMBL204021
ZINC
ZINC000003842798
PharmGKB
PA165884699
Wikipedia
Darapladib

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedBasic ScienceAtherosclerosis1
1CompletedDiagnosticAsthma / Atherosclerosis1
1CompletedTreatmentAtherosclerosis10
1CompletedTreatmentAtherosclerosis / Healthy Volunteers1
2CompletedTreatmentAtherosclerosis2
2CompletedTreatmentAtherosclerosis / Coronary Artery Disease1
2CompletedTreatmentAtherosclerosis / Dyslipidemia1
2CompletedTreatmentDiabetic Retinopathy (DR)1
3CompletedTreatmentAcute Coronary Syndromes (ACS)1
3CompletedTreatmentAtherosclerosis1
3CompletedTreatmentEndothelial Dysfunction1
Not AvailableCompletedNot AvailableCoronary Heart Disease (CHD)1

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 Solubility0.000692 mg/mLALOGPS
logP6.4ALOGPS
logP7.31ChemAxon
logS-6ALOGPS
pKa (Strongest Acidic)16.27ChemAxon
pKa (Strongest Basic)8.31ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area56.22 Å2ChemAxon
Rotatable Bond Count14ChemAxon
Refractivity181.08 m3·mol-1ChemAxon
Polarizability67.93 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
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 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
Trifluoromethylbenzenes / Alkylarylthioethers / Pyrimidones / Fluorobenzenes / Aryl fluorides / Vinylogous amides / Tertiary carboxylic acid amides / Heteroaromatic compounds / Trialkylamines / Amino acids and derivatives
show 7 more
Substituents
Biphenyl / Trifluoromethylbenzene / Aryl thioether / Fluorobenzene / Halobenzene / Alkylarylthioether / Pyrimidone / Aryl fluoride / Aryl halide / Pyrimidine
show 26 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Phospholipase a2 activity
Specific Function
Selectively hydrolyzes arachidonyl phospholipids in the sn-2 position releasing arachidonic acid. Together with its lysophospholipid activity, it is implicated in the initiation of the inflammatory...
Gene Name
PLA2G4A
Uniprot ID
P47712
Uniprot Name
Cytosolic phospholipase A2
Molecular Weight
85238.2 Da
References
  1. Riley RF, Corson MA: Darapladib, a reversible lipoprotein-associated phospholipase A2 inhibitor, for the oral treatment of atherosclerosis and coronary artery disease. IDrugs. 2009 Oct;12(10):648-55. [PubMed:19790016]

Drug created on March 19, 2008 10:23 / Updated on March 01, 2020 19:38

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