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

Identification
NameRolofylline
Accession NumberDB12670  (DB05360)
TypeSmall Molecule
GroupsInvestigational
Description

Rolofylline is under clinical development by pharmaceutical company NovaCardia for the treatment of congestive heart failure.

Structure
Thumb
SynonymsNot Available
External IDs KW 3902 / KW-3902 / MK-7418
Product Ingredients Not Available
ProductsNot Available
International BrandsNot Available
Brand mixturesNot Available
Categories
UNII7805S5HIHX
CAS number136199-02-5
WeightAverage: 356.47
Monoisotopic: 356.221226158
Chemical FormulaC20H28N4O2
InChI KeyPJBFVWGQFLYWCB-QUYAXPHCSA-N
InChI
InChI=1S/C20H28N4O2/c1-3-5-23-16-15(17(25)24(6-4-2)19(23)26)21-18(22-16)20-10-12-7-13(11-20)9-14(20)8-12/h12-14H,3-11H2,1-2H3,(H,21,22)/t12-,13+,14?,20?
IUPAC Name
1,3-dipropyl-8-[(1R,5S)-tricyclo[3.3.1.0^{3,7}]nonan-3-yl]-2,3,6,7-tetrahydro-1H-purine-2,6-dione
SMILES
CCCN1C2=C(NC(=N2)C23C[C@@H]4CC2C[[email protected]](C3)C4)C(=O)N(CCC)C1=O
Pharmacology
IndicationNot Available
Structured Indications Not Available
PharmacodynamicsNot Available
Mechanism of action

Rolofylline is an adenosine A1-receptor antagonist. Plasma adenosine levels are elevated in patients with heart failure and adenosine A1 receptors in the kidney mediate vasoconstriction of afferent arterioles, reabsorption of sodium and water in proximal tubules, and tubuloglomerular feedback in the juxtaglomerular apparatus. Accordingly, inhibition of these receptors would be expected to increase renal blood flow and enhance diuresis. The effects of Rolofylline on renal function are consistent with those obtained with another adenosine A1-receptor antagonist in both experimental and human heart failure.

TargetKindPharmacological actionActionsOrganismUniProt ID
Adenosine receptor A1ProteinunknownNot AvailableHumanP30542 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
DrugInteractionDrug group
AlfentanilThe risk or severity of adverse effects can be increased when Alfentanil is combined with Rolofylline.Approved, Illicit
AlphacetylmethadolThe risk or severity of adverse effects can be increased when Alphacetylmethadol is combined with Rolofylline.Experimental, Illicit
BezitramideThe risk or severity of adverse effects can be increased when Bezitramide is combined with Rolofylline.Experimental, Illicit, Withdrawn
BuprenorphineThe risk or severity of adverse effects can be increased when Buprenorphine is combined with Rolofylline.Approved, Illicit, Investigational, Vet Approved
ButorphanolThe risk or severity of adverse effects can be increased when Butorphanol is combined with Rolofylline.Approved, Illicit, Vet Approved
CarfentanilThe risk or severity of adverse effects can be increased when Carfentanil is combined with Rolofylline.Illicit, Vet Approved
CodeineThe risk or severity of adverse effects can be increased when Codeine is combined with Rolofylline.Approved, Illicit
DextromoramideThe risk or severity of adverse effects can be increased when Dextromoramide is combined with Rolofylline.Experimental, Illicit
DextropropoxypheneThe risk or severity of adverse effects can be increased when Dextropropoxyphene is combined with Rolofylline.Approved, Illicit, Withdrawn
DezocineThe risk or severity of adverse effects can be increased when Dezocine is combined with Rolofylline.Approved
DihydrocodeineThe risk or severity of adverse effects can be increased when Dihydrocodeine is combined with Rolofylline.Approved, Illicit
DihydroetorphineThe risk or severity of adverse effects can be increased when Dihydroetorphine is combined with Rolofylline.Experimental, Illicit
DihydromorphineThe risk or severity of adverse effects can be increased when Dihydromorphine is combined with Rolofylline.Experimental, Illicit
DiphenoxylateThe risk or severity of adverse effects can be increased when Diphenoxylate is combined with Rolofylline.Approved, Illicit
EthylmorphineThe risk or severity of adverse effects can be increased when Ethylmorphine is combined with Rolofylline.Approved, Illicit
EtorphineThe risk or severity of adverse effects can be increased when Etorphine is combined with Rolofylline.Illicit, Vet Approved
FentanylThe risk or severity of adverse effects can be increased when Fentanyl is combined with Rolofylline.Approved, Illicit, Investigational, Vet Approved
HeroinThe risk or severity of adverse effects can be increased when Heroin is combined with Rolofylline.Approved, Illicit
HydrocodoneThe risk or severity of adverse effects can be increased when Hydrocodone is combined with Rolofylline.Approved, Illicit
HydromorphoneThe risk or severity of adverse effects can be increased when Hydromorphone is combined with Rolofylline.Approved, Illicit
KetobemidoneThe risk or severity of adverse effects can be increased when Ketobemidone is combined with Rolofylline.Approved
Levomethadyl AcetateThe risk or severity of adverse effects can be increased when Levomethadyl Acetate is combined with Rolofylline.Approved
LevorphanolThe risk or severity of adverse effects can be increased when Levorphanol is combined with Rolofylline.Approved
LofentanilThe risk or severity of adverse effects can be increased when Lofentanil is combined with Rolofylline.Illicit
MethadoneThe risk or severity of adverse effects can be increased when Methadone is combined with Rolofylline.Approved
Methadyl AcetateThe risk or severity of adverse effects can be increased when Methadyl Acetate is combined with Rolofylline.Approved, Illicit
MorphineThe risk or severity of adverse effects can be increased when Morphine is combined with Rolofylline.Approved, Investigational
NalbuphineThe risk or severity of adverse effects can be increased when Nalbuphine is combined with Rolofylline.Approved
NormethadoneThe risk or severity of adverse effects can be increased when Normethadone is combined with Rolofylline.Approved, Illicit
OpiumThe risk or severity of adverse effects can be increased when Opium is combined with Rolofylline.Approved, Illicit
OxycodoneThe risk or severity of adverse effects can be increased when Oxycodone is combined with Rolofylline.Approved, Illicit, Investigational
OxymorphoneThe risk or severity of adverse effects can be increased when Oxymorphone is combined with Rolofylline.Approved, Investigational, Vet Approved
PentazocineThe risk or severity of adverse effects can be increased when Pentazocine is combined with Rolofylline.Approved, Vet Approved
PethidineThe risk or severity of adverse effects can be increased when Pethidine is combined with Rolofylline.Approved
PiritramideThe risk or severity of adverse effects can be increased when Piritramide is combined with Rolofylline.Investigational
RemifentanilThe risk or severity of adverse effects can be increased when Remifentanil is combined with Rolofylline.Approved
SufentanilThe risk or severity of adverse effects can be increased when Sufentanil is combined with Rolofylline.Approved, Investigational
TapentadolThe risk or severity of adverse effects can be increased when Tapentadol is combined with Rolofylline.Approved
TramadolThe risk or severity of adverse effects can be increased when Tramadol is combined with Rolofylline.Approved, Investigational
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
2CompletedTreatmentHeart Failure, Unspecified1
3CompletedTreatmentCongestive Heart Failure (CHF)3
Properties
StateNot Available
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.125 mg/mLALOGPS
logP4.11ALOGPS
logP3.27ChemAxon
logS-3.5ALOGPS
pKa (Strongest Acidic)7.83ChemAxon
pKa (Strongest Basic)-0.72ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area69.3 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity99.06 m3·mol-1ChemAxon
Polarizability40.66 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET featuresNot Available
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as xanthines. These are purine derivatives with a ketone group conjugated at carbons 2 and 6 of the purine moiety.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassImidazopyrimidines
Sub ClassPurines and purine derivatives
Direct ParentXanthines
Alternative Parents6-oxopurines / Alkaloids and derivatives / Pyrimidones / Vinylogous amides / Imidazoles / Heteroaromatic compounds / Ureas / Lactams / Azacyclic compounds / Organooxygen compounds
SubstituentsXanthine / 6-oxopurine / Purinone / Alkaloid or derivatives / Pyrimidone / Pyrimidine / Azole / Imidazole / Heteroaromatic compound / Vinylogous amide
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Purine nucleoside binding
Specific Function:
Receptor for adenosine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase.
Gene Name:
ADORA1
Uniprot ID:
P30542
Uniprot Name:
Adenosine receptor A1
Molecular Weight:
36511.325 Da
Drug created on October 20, 2016 17:33 / Updated on June 11, 2017 21:36