Rilapladib

Identification

Name
Rilapladib
Accession Number
DB05119  (DB05256)
Type
Small Molecule
Groups
Investigational
Description

Rilapladib is the third genomics-derived small molecule drug arising from the Human Genome Sciences-GlaxoSmithKline collaboration to enter clinical development. It is a lipoprotein-associated phospholipase A2 (Lp-PLA2) inhibitor. Lp-PLA2 is an enzyme associated with the formation of atherosclerotic plaques.

Structure
Thumb
Synonyms
Not Available
External IDs
GSK 659032 / SB 659032 / SB-659032
Categories
UNII
O14CWE893Z
CAS number
412950-08-4
Weight
Average: 735.81
Monoisotopic: 735.255404085
Chemical Formula
C40H38F5N3O3S
InChI Key
NNBGCSGCRSCFEA-UHFFFAOYSA-N
InChI
InChI=1S/C40H38F5N3O3S/c1-51-22-21-46-19-17-32(18-20-46)47(24-27-9-11-28(12-10-27)29-13-15-31(16-14-29)40(43,44)45)37(50)25-48-35-8-3-2-6-33(35)36(49)23-38(48)52-26-30-5-4-7-34(41)39(30)42/h2-16,23,32H,17-22,24-26H2,1H3
IUPAC Name
2-(2-{[(2,3-difluorophenyl)methyl]sulfanyl}-4-oxo-1,4-dihydroquinolin-1-yl)-N-[1-(2-methoxyethyl)piperidin-4-yl]-N-{[4'-(trifluoromethyl)-[1,1'-biphenyl]-4-yl]methyl}acetamide
SMILES
COCCN1CCC(CC1)N(CC1=CC=C(C=C1)C1=CC=C(C=C1)C(F)(F)F)C(=O)CN1C(SCC2=C(F)C(F)=CC=C2)=CC(=O)C2=C1C=CC=C2

Pharmacology

Indication

Investigated for use/treatment in atherosclerosis and cardiovascular disorders.

Structured Indications
Not Available
Pharmacodynamics
Not Available
Mechanism of action

Rilapladib is a Lp-PLA2 inhibitor. Lp-PLA2 has been found to be enriched in the highly atherogenic lipoprotein subfraction of small dense LDL, which is susceptible to oxidative modification. Moreover, enzyme levels are increased in patients with hyperlipidaemia, stroke, Type 1 and Type 2 diabetes mellitus, as well as in post-menopausal women. As such, plasma Lp-PLA2 levels tend to be elevated in those individuals who are considered to be at risk of developing accelerated atherosclerosis and clinical cardiovascular events. Thus, inhibition of the Lp-PLA2 enzyme would be expected to stop the build up of this fatty streak (by inhibition of the formation of lysophosphatidylcholine), and so be useful in the treatment of atherosclerosis.

TargetActionsOrganism
UPlatelet-activating factor acetylhydrolaseNot AvailableHuman
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
Not Available
Food Interactions
Not Available

References

General References
Not Available
External Links
PubChem Compound
9918381
PubChem Substance
347827712
ChemSpider
8094027
ChEMBL
CHEMBL2104981

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedDiagnosticAtherosclerosis / Healthy Volunteers1
1CompletedTreatmentAtherosclerosis2
1WithdrawnTreatmentAlzheimer's Disease (AD)1
2CompletedTreatmentAlzheimer's Disease (AD)1
2CompletedTreatmentAtherosclerosis1

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 Solubility0.000509 mg/mLALOGPS
logP6.34ALOGPS
logP8.08ChemAxon
logS-6.2ALOGPS
pKa (Strongest Acidic)13.77ChemAxon
pKa (Strongest Basic)8.4ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area53.09 Å2ChemAxon
Rotatable Bond Count13ChemAxon
Refractivity206.32 m3·mol-1ChemAxon
Polarizability72.71 Å3ChemAxon
Number of Rings6ChemAxon
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
Hydroquinolones / Trifluoromethylbenzenes / Hydroquinolines / Alkylarylthioethers / Fluorobenzenes / Vinylogous thioesters / Pyridines and derivatives / Piperidines / Aryl fluorides / Vinylogous amides
show 12 more
Substituents
Biphenyl / Dihydroquinolone / Trifluoromethylbenzene / Quinoline / Dihydroquinoline / Aryl thioether / Fluorobenzene / Alkylarylthioether / Halobenzene / Aryl fluoride
show 32 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Phospholipid binding
Specific Function
Modulates the action of platelet-activating factor (PAF) by hydrolyzing the sn-2 ester bond to yield the biologically inactive lyso-PAF. Has a specificity for substrates with a short residue at the...
Gene Name
PLA2G7
Uniprot ID
Q13093
Uniprot Name
Platelet-activating factor acetylhydrolase
Molecular Weight
50076.99 Da

Drug created on October 21, 2007 16:23 / Updated on December 01, 2017 15:35