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Identification
NameDyphylline
Accession NumberDB00651  (APRD00769)
TypeSmall Molecule
GroupsApproved
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
External Identifiers Not Available
Approved 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
Approved Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Lufyllintablet200 mg/1oralMeda Pharmaceuticals Inc.1976-08-312016-02-29Us
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
CorphyllinNippon Shinyaku
DilorSavage
Brand mixtures
NameLabellerIngredients
Jay-phylJay Mac Pharmaceuticals Llc
SaltsNot Available
CategoriesNot Available
UNII263T0E9RR9
CAS number479-18-5
WeightAverage: 254.2426
Monoisotopic: 254.101504956
Chemical FormulaC10H14N4O4
InChI KeyInChIKey=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
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
  • N-substituted imidazole
  • Heteroaromatic compound
  • Vinylogous amide
  • Imidazole
  • Azole
  • Urea
  • Secondary alcohol
  • Lactam
  • 1,2-diol
  • Azacycle
  • Organoheterocyclic compound
  • Hydrocarbon derivative
  • Primary alcohol
  • Organooxygen compound
  • Organonitrogen compound
  • Alcohol
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationFor relief of acute bronchial asthma and for reversible bronchospasm associated with chronic bronchitis and emphysema.
PharmacodynamicsDyphylline, 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 actionThe 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.
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein binding84%
Metabolism

Hepatic

Route of eliminationDyphylline 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 life2 hours (range 1.8 - 2.1 hours)
ClearanceNot Available
ToxicityLD50=1954 mg/kg (orally in mice)
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
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 )
Pharmacoeconomics
Manufacturers
  • Teva pharmaceuticals usa inc
  • Savage laboratories inc div altana inc
  • Meda pharmaceuticals inc
Packagers
Dosage forms
FormRouteStrength
Syruporal
Tabletoral200 mg/1
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.
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point155-157Jones, 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 FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
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
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 ReferencesNot Available
External Links
ATC CodesR03DA51R03DA01R03DB01
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (65.7 KB)
Interactions
Drug Interactions
Drug
AcebutololThe risk or severity of adverse effects can be increased when Acebutolol is combined with Dyphylline.
AdenosineThe therapeutic efficacy of Adenosine can be decreased when used in combination with Dyphylline.
AlprazolamThe therapeutic efficacy of Alprazolam can be decreased when used in combination with Dyphylline.
AmphetamineThe risk or severity of adverse effects can be increased when Amphetamine is combined with Dyphylline.
AtomoxetineAtomoxetine may increase the hypertensive activities of Dyphylline.
BenzphetamineThe risk or severity of adverse effects can be increased when Benzphetamine is combined with Dyphylline.
BromazepamThe therapeutic efficacy of Bromazepam can be decreased when used in combination with Dyphylline.
CamazepamThe therapeutic efficacy of Camazepam can be decreased when used in combination with Dyphylline.
ChlordiazepoxideThe therapeutic efficacy of Chlordiazepoxide can be decreased when used in combination with Dyphylline.
ChlormezanoneThe therapeutic efficacy of Chlormezanone can be decreased when used in combination with Dyphylline.
ChlorphentermineThe risk or severity of adverse effects can be increased when Chlorphentermine is combined with Dyphylline.
CinolazepamThe therapeutic efficacy of Cinolazepam can be decreased when used in combination with Dyphylline.
ClenbuterolThe risk or severity of adverse effects can be increased when Clenbuterol is combined with Dyphylline.
ClobazamThe therapeutic efficacy of Clobazam can be decreased when used in combination with Dyphylline.
ClonazepamThe therapeutic efficacy of Clonazepam can be decreased when used in combination with Dyphylline.
ClotiazepamThe therapeutic efficacy of Clotiazepam can be decreased when used in combination with Dyphylline.
CloxazolamThe therapeutic efficacy of Cloxazolam can be decreased when used in combination with Dyphylline.
DobutamineThe risk or severity of adverse effects can be increased when Dobutamine is combined with Dyphylline.
DopamineThe risk or severity of adverse effects can be increased when Dopamine is combined with Dyphylline.
DoxofyllineThe risk or severity of adverse effects can be increased when Dyphylline is combined with Doxofylline.
DronabinolDronabinol may increase the tachycardic activities of Dyphylline.
EpinephrineThe risk or severity of adverse effects can be increased when Epinephrine is combined with Dyphylline.
EsmololEsmolol may decrease the activities of Dyphylline.
FenoterolThe risk or severity of adverse effects can be increased when Fenoterol is combined with Dyphylline.
FludiazepamThe therapeutic efficacy of Fludiazepam can be decreased when used in combination with Dyphylline.
FlunitrazepamThe therapeutic efficacy of Flunitrazepam can be decreased when used in combination with Dyphylline.
FormoterolThe risk or severity of adverse effects can be increased when Dyphylline is combined with Formoterol.
HalazepamThe therapeutic efficacy of Halazepam can be decreased when used in combination with Dyphylline.
IndacaterolThe risk or severity of adverse effects can be increased when Dyphylline is combined with Indacaterol.
IobenguaneThe therapeutic efficacy of Iobenguane can be decreased when used in combination with Dyphylline.
IsoprenalineThe risk or severity of adverse effects can be increased when Isoprenaline is combined with Dyphylline.
KetazolamThe therapeutic efficacy of Ketazolam can be decreased when used in combination with Dyphylline.
LabetalolThe risk or severity of adverse effects can be increased when Labetalol is combined with Dyphylline.
LinezolidLinezolid may increase the hypertensive activities of Dyphylline.
LithiumThe serum concentration of Lithium can be decreased when it is combined with Dyphylline.
LorazepamThe therapeutic efficacy of Lorazepam can be decreased when used in combination with Dyphylline.
MephentermineThe risk or severity of adverse effects can be increased when Mephentermine is combined with Dyphylline.
MetaraminolThe risk or severity of adverse effects can be increased when Metaraminol is combined with Dyphylline.
MethamphetamineThe risk or severity of adverse effects can be increased when Methamphetamine is combined with Dyphylline.
MethotrexateThe serum concentration of Dyphylline can be increased when it is combined with Methotrexate.
MethoxamineThe risk or severity of adverse effects can be increased when Methoxamine is combined with Dyphylline.
MidodrineThe risk or severity of adverse effects can be increased when Midodrine is combined with Dyphylline.
NadololNadolol may decrease the activities of Dyphylline.
NaphazolineThe risk or severity of adverse effects can be increased when Naphazoline is combined with Dyphylline.
NorepinephrineThe risk or severity of adverse effects can be increased when Norepinephrine is combined with Dyphylline.
OlodaterolThe risk or severity of adverse effects can be increased when Dyphylline is combined with Olodaterol.
OrciprenalineThe risk or severity of adverse effects can be increased when Orciprenaline is combined with Dyphylline.
OxymetazolineThe risk or severity of adverse effects can be increased when Oxymetazoline is combined with Dyphylline.
PancuroniumThe risk or severity of adverse effects can be increased when Dyphylline is combined with Pancuronium.
PhenmetrazineThe risk or severity of adverse effects can be increased when Phenmetrazine is combined with Dyphylline.
PhentermineThe risk or severity of adverse effects can be increased when Phentermine is combined with Dyphylline.
PhenylephrineThe risk or severity of adverse effects can be increased when Phenylephrine is combined with Dyphylline.
PhenylpropanolamineThe risk or severity of adverse effects can be increased when Phenylpropanolamine is combined with Dyphylline.
ProbenecidThe serum concentration of Dyphylline can be increased when it is combined with Probenecid.
QuazepamThe therapeutic efficacy of Quazepam can be decreased when used in combination with Dyphylline.
QuinineThe serum concentration of Dyphylline can be increased when it is combined with Quinine.
RiociguatDyphylline may increase the hypotensive activities of Riociguat.
RitodrineThe risk or severity of adverse effects can be increased when Ritodrine is combined with Dyphylline.
SalmeterolThe risk or severity of adverse effects can be increased when Salmeterol is combined with Dyphylline.
Tedizolid PhosphateTedizolid Phosphate may increase the hypertensive activities of Dyphylline.
TemazepamThe therapeutic efficacy of Temazepam can be decreased when used in combination with Dyphylline.
TerbutalineThe risk or severity of adverse effects can be increased when Terbutaline is combined with Dyphylline.
TofisopamThe therapeutic efficacy of Tofisopam can be decreased when used in combination with Dyphylline.
TriazolamThe therapeutic efficacy of Triazolam can be decreased when used in combination with Dyphylline.
Food InteractionsNot Available

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
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
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
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
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
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
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
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 brain.
Gene Name:
PDE7B
Uniprot ID:
Q9NP56
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 ]
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Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23