Identification
NameEnprofylline
Accession NumberDB00824  (APRD00273)
TypeSmall Molecule
GroupsApproved
Description

Enprofylline is a derivative of theophylline which shares bronchodilator properties. Enprofylline is used in asthma, chronic obstructive pulmonary disease, and in the management of cerebrovascular insufficiency, sickle cell disease, and diabetic neuropathy. Long-term enprofylline administration may be associated with elevation in liver enzyme levels and unpredictable blood levels.

Structure
Thumb
Synonyms
3-n-Propylxanthine
3-Propyl-3,7-dihydro-purine-2,6-dione
3-Propylxanthine
3,7-dihydro-3-Propyl-1H-purine-2,6-dione
Enprofilina
Enprofylline
Enprofyllinum
External IDs Not Available
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 Brands
NameCompany
NilyphNot Available
OxezeNot Available
Brand mixturesNot Available
Categories
UNIIDT7DT5E518
CAS number41078-02-8
WeightAverage: 194.1906
Monoisotopic: 194.080375584
Chemical FormulaC8H10N4O2
InChI KeySIQPXVQCUCHWDI-UHFFFAOYSA-N
InChI
InChI=1S/C8H10N4O2/c1-2-3-12-6-5(9-4-10-6)7(13)11-8(12)14/h4H,2-3H2,1H3,(H,9,10)(H,11,13,14)
IUPAC Name
3-propyl-2,3,6,7-tetrahydro-1H-purine-2,6-dione
SMILES
CCCN1C2=C(NC=N2)C(=O)NC1=O
Pharmacology
Indication

Used in the management of symptoms of asthma. Also used in the treatment of peripheral vascular diseases and in the management of cerebrovascular insufficiency, sickle cell disease, and diabetic neuropathy.

Structured Indications Not Available
Pharmacodynamics

Enprofylline is a synthetic dimethylxanthine derivative structurally related to theophylline and caffeine. It antagonizes erythrocyte phosphodiesterase, increasing cAMP activity.

Mechanism of action

Enprofylline inhibits erythrocyte phosphodiesterase, resulting in an increase in erythrocyte cAMP activity. Subsequently, the erythrocyte membrane becomes more resistant to deformity. Along with erythrocyte activity, enprofylline also decreases blood viscosity by reducing plasma fibrinogen concentrations and increasing fibrinolytic activity.

TargetKindPharmacological actionActionsOrganismUniProt ID
cAMP-specific 3',5'-cyclic phosphodiesterase 4BProteinyes
inhibitor
HumanQ07343 details
Adenosine receptor A2bProteinyes
antagonist
HumanP29275 details
cAMP-specific 3',5'-cyclic phosphodiesterase 4AProteinyes
inhibitor
HumanP27815 details
Adenosine receptor A1ProteinunknownNot AvailableHumanP30542 details
Adenosine receptor A2aProteinunknownNot AvailableHumanP29274 details
Adenosine receptor A3ProteinunknownNot AvailableHumanP0DMS8 details
Related Articles
Absorption

Rapidly absorbed from the digestive tract

Volume of distributionNot Available
Protein binding

49%

MetabolismNot Available
Route of eliminationNot Available
Half life

1.9 hours

ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
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
2RecruitingTreatmentChronic Obstructive Pulmonary Disease (COPD)1
4WithdrawnTreatmentAsthma Bronchial1
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point (°C)287-289 °CPhysProp
water solubility1200 mg/LNot Available
logP0.33SANGSTER (1993)
Predicted Properties
PropertyValueSource
Water Solubility5.68 mg/mLALOGPS
logP0.35ALOGPS
logP-0.11ChemAxon
logS-1.5ALOGPS
pKa (Strongest Acidic)7.83ChemAxon
pKa (Strongest Basic)-0.77ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area78.09 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity49.31 m3·mol-1ChemAxon
Polarizability18.72 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.8963
Caco-2 permeable-0.6282
P-glycoprotein substrateSubstrate0.6567
P-glycoprotein inhibitor INon-inhibitor0.7819
P-glycoprotein inhibitor IINon-inhibitor0.9559
Renal organic cation transporterNon-inhibitor0.796
CYP450 2C9 substrateNon-substrate0.7883
CYP450 2D6 substrateNon-substrate0.8691
CYP450 3A4 substrateNon-substrate0.5557
CYP450 1A2 substrateNon-inhibitor0.9046
CYP450 2C9 inhibitorNon-inhibitor0.907
CYP450 2D6 inhibitorNon-inhibitor0.9303
CYP450 2C19 inhibitorNon-inhibitor0.912
CYP450 3A4 inhibitorNon-inhibitor0.9561
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9259
Ames testNon AMES toxic0.73
CarcinogenicityNon-carcinogens0.9402
BiodegradationNot ready biodegradable0.7406
Rat acute toxicity2.6371 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.6953
hERG inhibition (predictor II)Non-inhibitor0.7663
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Taxonomy
DescriptionThis compound belongs to the class of chemical entities known as xanthines. These are purine derivatives with a ketone group conjugated at carbons 2 and 6 of the purine moiety.
KingdomChemical entities
Super ClassOrganic compounds
ClassOrganoheterocyclic compounds
Sub ClassImidazopyrimidines
Direct ParentXanthines
Alternative Parents6-oxopurines / Alkaloids and derivatives / Pyrimidones / Vinylogous amides / Imidazoles / Heteroaromatic compounds / Ureas / Lactams / Azacyclic compounds / Organopnictogen compounds
SubstituentsXanthine / 6-oxopurine / Purinone / Alkaloid or derivatives / Pyrimidone / Pyrimidine / Azole / Imidazole / Heteroaromatic compound / Vinylogous amide
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptorsoxopurine (CHEBI:126237 )

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Metal ion binding
Specific Function:
Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes. May be involved in mediating central nervous system effects of therapeutic agents ranging from antidepressants to antiasthmatic and anti-inflammatory agents.
Gene Name:
PDE4B
Uniprot ID:
Q07343
Uniprot Name:
cAMP-specific 3',5'-cyclic phosphodiesterase 4B
Molecular Weight:
83342.695 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
antagonist
General Function:
G-protein coupled adenosine receptor activity
Specific Function:
Receptor for adenosine. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase.
Gene Name:
ADORA2B
Uniprot ID:
P29275
Uniprot Name:
Adenosine receptor A2b
Molecular Weight:
36332.655 Da
References
  1. Holgate ST: The Quintiles Prize Lecture 2004. The identification of the adenosine A2B receptor as a novel therapeutic target in asthma. Br J Pharmacol. 2005 Aug;145(8):1009-15. [PubMed:15980878 ]
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Metal ion binding
Specific Function:
Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.
Gene Name:
PDE4A
Uniprot ID:
P27815
Uniprot Name:
cAMP-specific 3',5'-cyclic phosphodiesterase 4A
Molecular Weight:
98142.155 Da
References
  1. Featherstone RL, Chambers DJ: Long-term hypothermic lung preservation: does adenosine A1 receptor antagonism have a role in ischemic preconditioning protection? Interact Cardiovasc Thorac Surg. 2004 Mar;3(1):182-7. [PubMed:17670210 ]
  2. Dulloo AG, Seydoux J, Girardier L: Peripheral mechanisms of thermogenesis induced by ephedrine and caffeine in brown adipose tissue. Int J Obes. 1991 May;15(5):317-26. [PubMed:1885257 ]
  3. Dar MS: Central adenosinergic system involvement in ethanol-induced motor incoordination in mice. J Pharmacol Exp Ther. 1990 Dec;255(3):1202-9. [PubMed:2262902 ]
  4. Ukena D, Schirren CG, Schwabe U: Effects of enprofylline on A1 and A2 adenosine receptors. Eur J Pharmacol. 1985 Oct 29;117(1):25-33. [PubMed:3002801 ]
  5. Berg G, Andersson RG, Ryden G: Effects of different phosphodiesterase-inhibiting drugs on human pregnant myometrium: an in vitro study. Arch Int Pharmacodyn Ther. 1987 Dec;290(2):288-92. [PubMed:3446047 ]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
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
References
  1. Linden J, Thai T, Figler H, Jin X, Robeva AS: Characterization of human A(2B) adenosine receptors: radioligand binding, western blotting, and coupling to G(q) in human embryonic kidney 293 cells and HMC-1 mast cells. Mol Pharmacol. 1999 Oct;56(4):705-13. [PubMed:10496952 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Identical protein binding
Specific Function:
Receptor for adenosine. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase.
Gene Name:
ADORA2A
Uniprot ID:
P29274
Uniprot Name:
Adenosine receptor A2a
Molecular Weight:
44706.925 Da
References
  1. Linden J, Thai T, Figler H, Jin X, Robeva AS: Characterization of human A(2B) adenosine receptors: radioligand binding, western blotting, and coupling to G(q) in human embryonic kidney 293 cells and HMC-1 mast cells. Mol Pharmacol. 1999 Oct;56(4):705-13. [PubMed:10496952 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
G-protein coupled adenosine receptor activity
Specific Function:
Receptor for adenosine. The activity of this receptor is mediated by G proteins which inhibits adenylyl cyclase. Possible role in reproduction.
Gene Name:
ADORA3
Uniprot ID:
P0DMS8
Uniprot Name:
Adenosine receptor A3
Molecular Weight:
36184.175 Da
References
  1. Linden J, Thai T, Figler H, Jin X, Robeva AS: Characterization of human A(2B) adenosine receptors: radioligand binding, western blotting, and coupling to G(q) in human embryonic kidney 293 cells and HMC-1 mast cells. Mol Pharmacol. 1999 Oct;56(4):705-13. [PubMed:10496952 ]
Drug created on June 13, 2005 07:24 / Updated on July 18, 2017 16:53