Tonapofylline

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

Identification

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Name
Tonapofylline
Accession Number
DB12569  (DB05640)
Type
Small Molecule
Groups
Investigational
Description

Tonapofylline has been used in trials studying the treatment of Heart Failure, Renal Insufficiency, and Congestive Heart Failure.

Structure
Thumb
Synonyms
Not Available
External IDs
BG-9928 / BG9928
Categories
UNII
83VNU4U44T
CAS number
340021-17-2
Weight
Average: 416.522
Monoisotopic: 416.242355526
Chemical Formula
C22H32N4O4
InChI Key
ZWTVVWUOTJRXKM-UHFFFAOYSA-N
InChI
InChI=1S/C22H32N4O4/c1-3-13-25-17-16(18(29)26(14-4-2)20(25)30)23-19(24-17)22-10-7-21(8-11-22,9-12-22)6-5-15(27)28/h3-14H2,1-2H3,(H,23,24)(H,27,28)
IUPAC Name
3-[4-(2,6-dioxo-1,3-dipropyl-2,3,6,7-tetrahydro-1H-purin-8-yl)bicyclo[2.2.2]octan-1-yl]propanoic acid
SMILES
CCCN1C2=C(NC(=N2)C23CCC(CCC(O)=O)(CC2)CC3)C(=O)N(CCC)C1=O

Pharmacology

Indication
Not Available
Pharmacodynamics
Not Available
Mechanism of action

Stimulation of A1 adenosine receptors in the kidney reduces glomerular filtration rate (GFR) via tubuloglomerular feedback and increases sodium reabsorption. Blocking A1 adenosine receptors would therefore maintain GFR and cause natriuresis. Tonapofylline is a xanthine derivative that binds with high affinity to A1 adenosine receptors from several species including human and acts as a competitive antagonist at these receptors.

TargetActionsOrganism
UAdenosine receptor A1Not 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
Not Available
Food Interactions
Not Available

References

General References
  1. Doggrell SA: BG-9928 (Biogen Idec). Curr Opin Investig Drugs. 2005 Sep;6(9):962-8. [PubMed:16187697]
External Links
PubChem Compound
216466
PubChem Substance
347828791
ChemSpider
187607
BindingDB
50199293
ChEMBL
CHEMBL414157

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableHepatic Impairment1
2TerminatedTreatmentHeart Failure / Impaired Renal Function1
2, 3CompletedTreatmentCongestive Heart Failure (CHF) / Impaired Renal Function1

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 Solubility0.118 mg/mLALOGPS
logP2.74ALOGPS
logP3.47ChemAxon
logS-3.6ALOGPS
pKa (Strongest Acidic)4.13ChemAxon
pKa (Strongest Basic)-0.69ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area106.6 Å2ChemAxon
Rotatable Bond Count8ChemAxon
Refractivity111.71 m3·mol-1ChemAxon
Polarizability47.37 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
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 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 / Carbocyclic fatty acids / Pyrimidones / Vinylogous amides / Imidazoles / Heteroaromatic compounds / Ureas / Lactams / Azacyclic compounds
show 7 more
Substituents
Xanthine / 6-oxopurine / Purinone / Carbocyclic fatty acid / Alkaloid or derivatives / Pyrimidone / Pyrimidine / Fatty acyl / Vinylogous amide / Heteroaromatic compound
show 17 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Humans
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
References
  1. Greenberg B, Thomas I, Banish D, Goldman S, Havranek E, Massie BM, Zhu Y, Ticho B, Abraham WT: Effects of multiple oral doses of an A1 adenosine antagonist, BG9928, in patients with heart failure: results of a placebo-controlled, dose-escalation study. J Am Coll Cardiol. 2007 Aug 14;50(7):600-6. Epub 2007 Jul 30. [PubMed:17692744]
  2. Vu CB, Kiesman WF, Conlon PR, Lin KC, Tam M, Petter RC, Smits G, Lutterodt F, Jin X, Chen L, Zhang J: Tricyclic imidazoline derivatives as potent and selective adenosine A1 receptor antagonists. J Med Chem. 2006 Nov 30;49(24):7132-9. [PubMed:17125265]

Drug created on October 20, 2016 16:56 / Updated on June 04, 2019 07:40