Rolofylline

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

Identification

Name
Rolofylline
Accession Number
DB12670  (DB05360)
Type
Small Molecule
Groups
Investigational
Description

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

Structure
Thumb
Synonyms
Not Available
External IDs
KW 3902 / KW-3902 / MK-7418
Categories
UNII
7805S5HIHX
CAS number
136199-02-5
Weight
Average: 356.47
Monoisotopic: 356.221226158
Chemical Formula
C20H28N4O2
InChI Key
PJBFVWGQFLYWCB-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[[email protected]@H]4CC2C[[email protected]](C3)C4)C(=O)N(CCC)C1=O

Pharmacology

Indication
Not Available
Structured Indications
Not Available
Pharmacodynamics
Not 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.

TargetActionsOrganism
UAdenosine receptor A1Not 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
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
AlphaprodineThe risk or severity of adverse effects can be increased when Alphaprodine is combined with Rolofylline.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
DPDPEThe risk or severity of adverse effects can be increased when DPDPE is combined with Rolofylline.Investigational
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
MeptazinolThe risk or severity of adverse effects can be increased when Meptazinol is combined with Rolofylline.Experimental
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
NicomorphineThe risk or severity of adverse effects can be increased when Nicomorphine is combined with Rolofylline.Experimental
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
PhenazocineThe risk or severity of adverse effects can be increased when Phenazocine is combined with Rolofylline.Experimental
PhenoperidineThe risk or severity of adverse effects can be increased when Phenoperidine is combined with Rolofylline.Experimental
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
Sodium phosphateRolofylline may increase the nephrotoxic activities of Sodium phosphate.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
TilidineThe risk or severity of adverse effects can be increased when Tilidine is combined with Rolofylline.Experimental
TramadolThe risk or severity of adverse effects can be increased when Tramadol is combined with Rolofylline.Approved, Investigational
Food Interactions
Not Available

References

Synthesis Reference
Not Available
General References
Not Available
External Links
ChemSpider
10122604
ATC Codes
Not Available
AHFS Codes
Not Available
PDB Entries
Not Available
FDA label
Not Available
MSDS
Not Available

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedTreatmentHeart Failure, Unspecified1
3CompletedTreatmentCongestive Heart Failure (CHF)3

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Not Available
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.125 mg/mLALOGPS
logP4.11ALOGPS
logP3.27ChemAxon
logS-3.4ALOGPS
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 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 xanthines. These are purine derivatives with a ketone group conjugated at carbons 2 and 6 of the purine moiety.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Imidazopyrimidines
Sub Class
Purines and purine derivatives
Direct Parent
Xanthines
Alternative Parents
6-oxopurines / Alkaloids and derivatives / Pyrimidones / Vinylogous amides / Imidazoles / Heteroaromatic compounds / Ureas / Lactams / Azacyclic compounds / Organooxygen compounds
show 3 more
Substituents
Xanthine / 6-oxopurine / Purinone / Alkaloid or derivatives / Pyrimidone / Pyrimidine / Azole / Imidazole / Heteroaromatic compound / Vinylogous amide
show 10 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not 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 September 01, 2017 12:23