Identification

Name
Enprofylline
Accession Number
DB00824  (APRD00273)
Type
Small Molecule
Groups
Approved
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
International/Other Brands
Nilyph / Oxeze
Categories
UNII
DT7DT5E518
CAS number
41078-02-8
Weight
Average: 194.1906
Monoisotopic: 194.080375584
Chemical Formula
C8H10N4O2
InChI Key
SIQPXVQCUCHWDI-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.

TargetActionsOrganism
AcAMP-specific 3',5'-cyclic phosphodiesterase 4B
inhibitor
Human
AAdenosine receptor A2b
antagonist
Human
AcAMP-specific 3',5'-cyclic phosphodiesterase 4A
inhibitor
Human
UAdenosine receptor A1Not AvailableHuman
UAdenosine receptor A2aNot AvailableHuman
UAdenosine receptor A3Not AvailableHuman
Absorption

Rapidly absorbed from the digestive tract

Volume of distribution
Not Available
Protein binding

49%

Metabolism
Not Available
Route of elimination
Not Available
Half life

1.9 hours

Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

Synthesis Reference
Not Available
General References
Not Available
External Links
Human Metabolome Database
HMDB14962
KEGG Drug
D04006
PubChem Compound
1676
PubChem Substance
46505790
ChemSpider
1613
BindingDB
50001493
ChEBI
126237
ChEMBL
CHEMBL279898
Therapeutic Targets Database
DAP001375
PharmGKB
PA164749350
Wikipedia
Enprofylline
ATC Codes
Not Available
AHFS Codes
Not Available
PDB Entries
Not Available
FDA label
Not Available
MSDS
Not Available

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2RecruitingTreatmentChronic Obstructive Pulmonary Disease (COPD)1
4WithdrawnTreatmentAsthma Bronchial1

Pharmacoeconomics

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

Properties

State
Solid
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
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
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 chemical entities known as xanthines. These are purine derivatives with a ketone group conjugated at carbons 2 and 6 of the purine moiety.
Kingdom
Chemical entities
Super Class
Organic compounds
Class
Organoheterocyclic compounds
Sub Class
Imidazopyrimidines
Direct Parent
Xanthines
Alternative Parents
6-oxopurines / Alkaloids and derivatives / Pyrimidones / Vinylogous amides / Imidazoles / Heteroaromatic compounds / Ureas / Lactams / Azacyclic compounds / Organopnictogen compounds
show 4 more
Substituents
Xanthine / 6-oxopurine / Purinone / Alkaloid or derivatives / Pyrimidone / Pyrimidine / Azole / Imidazole / Heteroaromatic compound / Vinylogous amide
show 11 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
oxopurine (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 f...
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 ]
Details
2. Adenosine receptor A2b
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 ]
Details
4. Adenosine receptor A1
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 ]
Details
5. Adenosine receptor A2a
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 ]
Details
6. Adenosine receptor A3
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 October 02, 2017 04:46