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Identification
NameKW-3902
Accession NumberDB05360
TypeSmall Molecule
GroupsInvestigational
Description

KW-3902 is a compounds that is under clinical development by pharmaceutical company, NovaCardia. It is used for the treatment of congestive heart failure.

Structure
Thumb
SynonymsNot Available
External Identifiers 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
SaltsNot Available
Categories
UNIINot Available
CAS numberNot Available
WeightAverage: 356.4619
Monoisotopic: 356.22122616
Chemical FormulaC20H28N4O2
InChI KeyInChIKey=PJBFVWGQFLYWCB-UHFFFAOYSA-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)
IUPAC Name
1,3-dipropyl-8-{tricyclo[3.3.1.0³,⁷]nonan-3-yl}-2,3,6,7-tetrahydro-1H-purine-2,6-dione
SMILES
CCCN1C2=C(NC(=N2)C23CC4CC2CC(C3)C4)C(=O)N(CCC)C1=O
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as alkaloids and derivatives. These are naturally occurring chemical compounds that contain mostly basic nitrogen atoms. This group also includes some related compounds with neutral and even weakly acidic properties. Also some synthetic compounds of similar structure are attributed to alkaloids. In addition to carbon, hydrogen and nitrogen, alkaloids may also contain oxygen, sulfur and more rarely other elements such as chlorine, bromine, and phosphorus.
KingdomOrganic compounds
Super ClassAlkaloids and derivatives
ClassNot Available
Sub ClassNot Available
Direct ParentAlkaloids and derivatives
Alternative Parents
Substituents
  • Alkaloid or derivatives
  • Xanthine
  • Purinone
  • 6-oxopurine
  • Purine
  • Imidazopyrimidine
  • Pyrimidone
  • Pyrimidine
  • Heteroaromatic compound
  • Vinylogous amide
  • Imidazole
  • Azole
  • Urea
  • Lactam
  • Azacycle
  • Organoheterocyclic compound
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationInvestigated for use/treatment in congestive heart failure and kidney disease.
PharmacodynamicsNot Available
Mechanism of actionKW-3902 (rolofylline),is an adenosine A1-receptor antagonist, on diuresis and renal function compared with placebo in patients with acute decompensated heart failure (ADHF). 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 KW-3902 on renal function are consistent with those obtained with another adenosine A1-receptor antagonist in both experimental and human heart failure.
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
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9531
Caco-2 permeable-0.6414
P-glycoprotein substrateSubstrate0.7637
P-glycoprotein inhibitor IInhibitor0.7726
P-glycoprotein inhibitor IINon-inhibitor0.7673
Renal organic cation transporterNon-inhibitor0.6473
CYP450 2C9 substrateNon-substrate0.7638
CYP450 2D6 substrateNon-substrate0.8117
CYP450 3A4 substrateSubstrate0.6349
CYP450 1A2 substrateInhibitor0.7733
CYP450 2C9 inhibitorNon-inhibitor0.6371
CYP450 2D6 inhibitorNon-inhibitor0.8456
CYP450 2C19 inhibitorNon-inhibitor0.6767
CYP450 3A4 inhibitorInhibitor0.5975
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.6423
Ames testNon AMES toxic0.5956
CarcinogenicityNon-carcinogens0.8656
BiodegradationNot ready biodegradable0.9972
Rat acute toxicity3.2033 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8659
hERG inhibition (predictor II)Inhibitor0.6043
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
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
Polarizability40.67 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
General References
  1. Dittrich HC, Gupta DK, Hack TC, Dowling T, Callahan J, Thomson S: The effect of KW-3902, an adenosine A1 receptor antagonist, on renal function and renal plasma flow in ambulatory patients with heart failure and renal impairment. J Card Fail. 2007 Oct;13(8):609-17. [PubMed:17923351 ]
External Links
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot 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
Molecular Weight:
36511.325 Da
Comments
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Drug created on November 18, 2007 11:24 / Updated on September 16, 2013 17:26