Identification
NameRilapladib
Accession NumberDB05119  (DB05256)
TypeSmall Molecule
GroupsInvestigational
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
SynonymsNot Available
External IDs GSK 659032 / SB 659032 / SB-659032
Product Ingredients Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
Categories
UNIIO14CWE893Z
CAS number412950-08-4
WeightAverage: 735.81
Monoisotopic: 735.255404085
Chemical FormulaC40H38F5N3O3S
InChI KeyNNBGCSGCRSCFEA-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
PharmacodynamicsNot 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.

TargetKindPharmacological actionActionsOrganismUniProt ID
Platelet-activating factor acetylhydrolaseProteinunknownNot AvailableHumanQ13093 details
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organismsNot Available
PathwaysNot Available
Pharmacogenomic Effects/ADRs Not Available
Interactions
Drug Interactions Not Available
Food InteractionsNot Available
References
Synthesis ReferenceNot Available
General ReferencesNot Available
External Links
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Clinical Trials
Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedDiagnosticAtherosclerosis / Healthy Volunteers1
1CompletedTreatmentAtherosclerosis2
1WithdrawnTreatmentAlzheimer's Disease (AD)1
2CompletedTreatmentAlzheimer's Disease (AD)1
2CompletedTreatmentAtherosclerosis1
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental PropertiesNot 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 featuresNot Available
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassBiphenyls and derivatives
Direct ParentBiphenyls and derivatives
Alternative ParentsHydroquinolones / Trifluoromethylbenzenes / Hydroquinolines / Alkylarylthioethers / Fluorobenzenes / Vinylogous thioesters / Pyridines and derivatives / Piperidines / Aryl fluorides / Vinylogous amides
SubstituentsBiphenyl / Dihydroquinolone / Trifluoromethylbenzene / Quinoline / Dihydroquinoline / Aryl thioether / Fluorobenzene / Alkylarylthioether / Halobenzene / Aryl fluoride
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot 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 sn-2 position. It is inactive against long-chain phospholipids.
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 June 11, 2017 21:00