Identification

Name
Dyphylline
Accession Number
DB00651  (APRD00769)
Type
Small Molecule
Groups
Approved
Description

A theophylline derivative with broncho- and vasodilator properties. It is used in the treatment of asthma, cardiac dyspnea, and bronchitis. [PubChem]

Structure
Thumb
Synonyms
  • (+-)-7-(2,3-Dihydroxypropyl)theophylline
  • (+-)-Diprophylline
  • (+-)-Dyphylline
  • (±)-diprophylline
  • (±)-dyphylline
  • (1,2-Dihydroxy-3-propyl)thiophyllin
  • 1,3-Dimethyl-7-(2,3-dihydroxypropyl)xanthine
  • 7-(2,3-Dihydroxypropyl)-1,3-dimethylxanthine
  • 7-(2,3-Dihydroxypropyl)-3,7-dihydro-1,3-dimethyl-1H-purine-2,6-dione
  • 7-(2,3-Dihydroxypropyl)theophylline
  • 7-(beta,gamma-Dihydroxypropyl)theophylline
  • 7-(β,γ-dihydroxypropyl)theophylline
  • Dihydroxypropyl theopylin
  • Diprofilina
  • Diprophylline
  • Diprophyllinum
  • Dyphylline
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Protophylline Elixir 100mgElixir100 mgOralRougier Pharma Division Of Ratiopharm Inc1962-12-311999-09-27Canada
Protophylline Inj 500mg/2mlLiquid500 mgIntramuscular; IntravenousRougier Pharma Division Of Ratiopharm Inc1963-12-311999-09-27Canada
Protophylline Solution 100mgSolution100 mgOralRougier Pharma Division Of Ratiopharm Inc1965-12-311999-09-27Canada
Protophylline Sup 500mg AdultesSuppository500 mgRectalRougier Pharma Division Of Ratiopharm Inc1962-12-311999-09-27Canada
Protophylline Tab 200mgTablet200 mgOralRougier Pharma Division Of Ratiopharm Inc1962-12-311999-09-27Canada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
LufyllinTablet200 mg/1OralMeda Pharmaceuticals Ltd1976-08-312016-02-29Us
LufyllinTablet400 mg/1OralMeda Pharmaceuticals Ltd1976-08-312015-01-31Us
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Dilex-G 400Dyphylline (200 mg/1) + Guaifenesin (400 mg/1)TabletOralPoly Pharmaceuticals2006-09-082011-09-30Us
Dy GDyphylline (100 mg/5mL) + Guaifenesin (100 mg/5mL)LiquidOralCypress Pharmaceuticals, Inc.2001-10-312011-08-26Us
Dyphylline and GuaifenesinDyphylline (200 mg/1) + Guaifenesin (200 mg/1)TabletOralBreckenridge Pharmaceutical, Inc.2001-08-012012-02-29Us
Dyphylline GGDyphylline (200 mg/1) + Guaifenesin (200 mg/1)TabletOralPegasus Laboratories2006-12-182012-06-30Us
Dyphylline GgDyphylline (100 mg/15mL) + Guaifenesin (100 mg/15mL)ElixirOralSilarx Pharmaceuticals, Inc.1996-12-052011-06-02Us
Dyphylline GG ESDyphylline (200 mg/1) + Guaifenesin (300 mg/1)TabletOralBreckenridge Pharmaceutical, Inc.2008-02-012012-02-28Us
Jay-PhylDyphylline (100 mg/5mL) + Guaifenesin (50 mg/5mL)SyrupOralJaymac Pharmaceuticals Llc2006-05-022012-10-31Us
Lufyllin -GGDyphylline (100 mg/15mL) + Guaifenesin (100 mg/15mL)SolutionOralMeda Pharmaceuticals Ltd1968-06-012013-03-31Us
Theospect ImprovedDyphylline (200 mg/1) + Guaifenesin (200 mg/1)TabletOralPRN Pharmacal2000-01-132010-05-03Us
International/Other Brands
Corphyllin (Nippon Shinyaku) / Dilor (Savage)
Categories
UNII
263T0E9RR9
CAS number
479-18-5
Weight
Average: 254.2426
Monoisotopic: 254.101504956
Chemical Formula
C10H14N4O4
InChI Key
KSCFJBIXMNOVSH-UHFFFAOYSA-N
InChI
InChI=1S/C10H14N4O4/c1-12-8-7(9(17)13(2)10(12)18)14(5-11-8)3-6(16)4-15/h5-6,15-16H,3-4H2,1-2H3
IUPAC Name
7-(2,3-dihydroxypropyl)-1,3-dimethyl-2,3,6,7-tetrahydro-1H-purine-2,6-dione
SMILES
CN1C2=C(N(CC(O)CO)C=N2)C(=O)N(C)C1=O

Pharmacology

Indication

For relief of acute bronchial asthma and for reversible bronchospasm associated with chronic bronchitis and emphysema.

Pharmacodynamics

Dyphylline, a xanthine derivative, is a bronchodilator used for relief of acute bronchial asthma and for reversible bronchospasm associated with chronic bronchitis and emphysema. Dyphylline is a xanthine derivative with pharmacologic actions similar to theophylline and other members of this class of drugs. Its primary action is that of bronchodilation, but it also exhibits peripheral vasodilatory and other smooth muscle relaxant activity to a lesser degree.

Mechanism of action

The bronchodilatory action of dyphylline, as with other xanthines, is thought to be mediated through competitive inhibition of phosphodiesterase with a resulting increase in cyclic AMP producing relaxation of bronchial smooth muscle as well as antagonism of adenosine receptors.

TargetActionsOrganism
AcAMP-specific 3',5'-cyclic phosphodiesterase 4B
inhibitor
Human
AcAMP-specific 3',5'-cyclic phosphodiesterase 4A
inhibitor
Human
AcAMP-specific 3',5'-cyclic phosphodiesterase 4C
inhibitor
Human
AcAMP-specific 3',5'-cyclic phosphodiesterase 4D
inhibitor
Human
AAdenosine receptor A1
antagonist
Human
AAdenosine receptor A2a
antagonist
Human
AHigh affinity cAMP-specific 3',5'-cyclic phosphodiesterase 7A
inhibitor
Human
AcAMP-specific 3',5'-cyclic phosphodiesterase 7B
inhibitor
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding

84%

Metabolism

Hepatic

Route of elimination

Dyphylline exerts its bronchodilatory effects directly and, unlike the­ophylline, is excreted unchanged by the kidneys without being metabolized by the liver. Approximately 88% of a single oral dose can be recovered from the urine unchanged.

Half life

2 hours (range 1.8 - 2.1 hours)

Clearance
Not Available
Toxicity

LD50=1954 mg/kg (orally in mice)

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

Interactions

Drug Interactions
DrugInteraction
AbacavirDyphylline may decrease the excretion rate of Abacavir which could result in a higher serum level.
AcarboseAcarbose may decrease the excretion rate of Dyphylline which could result in a higher serum level.
AceclofenacAceclofenac may decrease the excretion rate of Dyphylline which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Dyphylline which could result in a higher serum level.
AcetaminophenAcetaminophen may decrease the excretion rate of Dyphylline which could result in a higher serum level.
Acetylsalicylic acidAcetylsalicylic acid may decrease the excretion rate of Dyphylline which could result in a higher serum level.
AclidiniumDyphylline may decrease the excretion rate of Aclidinium which could result in a higher serum level.
AcrivastineDyphylline may decrease the excretion rate of Acrivastine which could result in a higher serum level.
AcyclovirAcyclovir may decrease the excretion rate of Dyphylline which could result in a higher serum level.
AdefovirAdefovir may decrease the excretion rate of Dyphylline which could result in a higher serum level.
Food Interactions
Not Available

References

Synthesis Reference

Jones, J.W. and Maney, P.V.; U.S. Patent 2,575,344; November 20,1951; assigned to the State of Iowa.

General References
Not Available
External Links
Human Metabolome Database
HMDB0014789
KEGG Drug
D00691
KEGG Compound
C07819
PubChem Compound
3182
PubChem Substance
46504443
ChemSpider
3070
BindingDB
82016
ChEBI
4728
ChEMBL
CHEMBL1752
Therapeutic Targets Database
DAP000596
PharmGKB
PA164748027
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Dyphylline
ATC Codes
R03DA51 — Diprophylline, combinationsR03DA01 — DiprophyllineR03DB01 — Diprophylline and adrenergics
MSDS
Download (65.7 KB)

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
  • Teva pharmaceuticals usa inc
  • Savage laboratories inc div altana inc
  • Meda pharmaceuticals inc
Packagers
  • Breckenridge Pharmaceuticals
  • Great Southern Laboratories
  • Lunsco Inc.
  • Meda AB
  • Novartis AG
  • Savage Labs
Dosage forms
FormRouteStrength
TabletOral
LiquidOral
ElixirOral
SyrupOral
TabletOral200 mg/1
TabletOral400 mg/1
SolutionOral
ElixirOral100 mg
LiquidIntramuscular; Intravenous500 mg
SolutionOral100 mg
SuppositoryRectal500 mg
TabletOral200 mg
Prices
Unit descriptionCostUnit
Afinitor 10 mg tablet247.58USD tablet
Afinitor 5 mg tablet234.75USD tablet
Lufyllin-400 tablet4.62USD tablet
Lufyllin 200 mg tablet3.15USD tablet
Dyphylline gg es tablet0.78USD tablet
Dyphylline gg tablet0.69USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)155-157Jones, J.W. and Maney, P.V.; U.S. Patent 2,575,344; November 20,1951; assigned to the State of Iowa.
water solubility3.33E+005 mg/L (at 25 °C)MERCK INDEX (1996)
logP-1.9Not Available
logS-0.17ADME Research, USCD
Predicted Properties
PropertyValueSource
Water Solubility14.3 mg/mLALOGPS
logP-0.98ALOGPS
logP-1.9ChemAxon
logS-1.2ALOGPS
pKa (Strongest Acidic)13.91ChemAxon
pKa (Strongest Basic)-0.97ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area98.9 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity62.09 m3·mol-1ChemAxon
Polarizability24.65 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.964
Blood Brain Barrier-0.6357
Caco-2 permeable-0.7332
P-glycoprotein substrateSubstrate0.5999
P-glycoprotein inhibitor INon-inhibitor0.9775
P-glycoprotein inhibitor IINon-inhibitor0.9792
Renal organic cation transporterNon-inhibitor0.9289
CYP450 2C9 substrateNon-substrate0.8343
CYP450 2D6 substrateNon-substrate0.8429
CYP450 3A4 substrateNon-substrate0.5446
CYP450 1A2 substrateNon-inhibitor0.9046
CYP450 2C9 inhibitorNon-inhibitor0.907
CYP450 2D6 inhibitorNon-inhibitor0.946
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.978
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9758
Ames testNon AMES toxic0.799
CarcinogenicityNon-carcinogens0.8576
BiodegradationNot ready biodegradable0.6129
Rat acute toxicity1.8401 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9489
hERG inhibition (predictor II)Non-inhibitor0.8734
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
GC-MS Spectrum - EI-BGC-MSsplash10-001i-9000000000-d159f2e06ae5688fe714
GC-MS Spectrum - EI-BGC-MSsplash10-001i-9000000000-d159f2e06ae5688fe714
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
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0a4i-0090000000-333eda23b5db828349a1
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0a4i-0390000000-b965183e8f0f1617c518
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-001i-0910000000-65b3ffefd28585f62d32
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0089-3900000000-e0a54464bc16e628c820
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-05gj-9700000000-b192c58457f7957424f1
LC-MS/MS Spectrum - LC-ESI-IT , positiveLC-MS/MSsplash10-001i-0920000000-973a36ebf151db89ccdc
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0a59-2970000000-4ad8ef9bfa86cda3d221
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0089-2900000000-1b3e2d3408802f411886

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 / N-substituted imidazoles / Vinylogous amides / Heteroaromatic compounds / Secondary alcohols / Lactams / 1,2-diols / Ureas
show 6 more
Substituents
Xanthine / 6-oxopurine / Purinone / Alkaloid or derivatives / Pyrimidone / N-substituted imidazole / Pyrimidine / Azole / Imidazole / Heteroaromatic compound
show 16 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
oxopurine, propane-1,2-diols (CHEBI:4728)

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]
  3. Iancu L, Shneur A, Cohen H: Trials with xanthine derivatives in systemic treatment of psoriasis. Dermatologica. 1979;159(1):55-61. [PubMed:225216]
  4. Hariton C: Ocular hypotension induced by topical dopaminergic drugs and phosphodiesterase inhibitors. Eur J Pharmacol. 1994 Jun 2;258(1-2):85-94. [PubMed:7925603]
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. 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]
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  4. Iancu L, Shneur A, Cohen H: Trials with xanthine derivatives in systemic treatment of psoriasis. Dermatologica. 1979;159(1):55-61. [PubMed:225216]
  5. Hariton C: Ocular hypotension induced by topical dopaminergic drugs and phosphodiesterase inhibitors. Eur J Pharmacol. 1994 Jun 2;258(1-2):85-94. [PubMed:7925603]
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
PDE4C
Uniprot ID
Q08493
Uniprot Name
cAMP-specific 3',5'-cyclic phosphodiesterase 4C
Molecular Weight
79900.795 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]
  3. Iancu L, Shneur A, Cohen H: Trials with xanthine derivatives in systemic treatment of psoriasis. Dermatologica. 1979;159(1):55-61. [PubMed:225216]
  4. Hariton C: Ocular hypotension induced by topical dopaminergic drugs and phosphodiesterase inhibitors. Eur J Pharmacol. 1994 Jun 2;258(1-2):85-94. [PubMed:7925603]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Ubiquitin protein ligase binding
Specific Function
Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.
Gene Name
PDE4D
Uniprot ID
Q08499
Uniprot Name
cAMP-specific 3',5'-cyclic phosphodiesterase 4D
Molecular Weight
91114.1 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]
  3. Hariton C: Ocular hypotension induced by topical dopaminergic drugs and phosphodiesterase inhibitors. Eur J Pharmacol. 1994 Jun 2;258(1-2):85-94. [PubMed:7925603]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
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. Schwabe U, Ukena D, Lohse MJ: Xanthine derivatives as antagonists at A1 and A2 adenosine receptors. Naunyn Schmiedebergs Arch Pharmacol. 1985 Sep;330(3):212-21. [PubMed:2997628]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
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. Schwabe U, Ukena D, Lohse MJ: Xanthine derivatives as antagonists at A1 and A2 adenosine receptors. Naunyn Schmiedebergs Arch Pharmacol. 1985 Sep;330(3):212-21. [PubMed:2997628]
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 have a role in muscle signal transduction.
Gene Name
PDE7A
Uniprot ID
Q13946
Uniprot Name
High affinity cAMP-specific 3',5'-cyclic phosphodiesterase 7A
Molecular Weight
55504.475 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
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 the control of cAMP-mediated neural activity and cAMP metabolism in the ...
Gene Name
PDE7B
Uniprot ID
Q9NP56
Uniprot Name
cAMP-specific 3',5'-cyclic phosphodiesterase 7B
Molecular Weight
51834.855 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]

Drug created on June 13, 2005 07:24 / Updated on November 02, 2018 04:48