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Doxofylline

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Doxofylline Basic information
Product Name:Doxofylline
Synonyms:DOXOFYLLINE;DOXOPHYLLINE;2-(7’-teofillinmetil)-1,3-diossolano;Doxofyliine;7-(1,3-dioxolan-2-ylmethyl)-1,3-dimethyl-purine-2,6-dione;DOXOFYLLINE [7-(1,3-DIOXOLAN-2-YLMETHYL)-3,7-DIHYDRO-1,3-DIMETHYL-1H-PURINE-2,6-DIONE];MAXIVENT;Ansirnar
CAS:69975-86-6
MF:C11H14N4O4
MW:266.25
EINECS:274-239-6
Product Categories:ZYRTEC;Respiratory system;69975-86-6;API
Mol File:69975-86-6.mol
Doxofylline Structure
Doxofylline Chemical Properties
Melting point 144-146°C
Boiling point 409.46°C (rough estimate)
density 1.2896 (rough estimate)
refractive index 1.6000 (estimate)
RTECS XH5135000
storage temp. under inert gas (nitrogen or Argon) at 2-8°C
solubility DMSO (Slightly), Methanol (Slightly)
form Solid
pka0.42±0.70(Predicted)
color White to Off-White
Water Solubility Soluble
Merck 14,3438
InChIInChI=1S/C11H14N4O4/c1-13-9-8(10(16)14(2)11(13)17)15(6-12-9)5-7-18-3-4-19-7/h6-7H,3-5H2,1-2H3
InChIKeyHWXIGFIVGWUZAO-UHFFFAOYSA-N
SMILESN1(CC2OCCO2)C2=C(N(C)C(=O)N(C)C2=O)N=C1
CAS DataBase Reference69975-86-6(CAS DataBase Reference)
Safety Information
Hazard Codes Xi
Risk Statements 36/37/38
Safety Statements 26-36/37
HS Code 29399990
ToxicityLD50 in mice (mg/kg): 841 orally; 215.6 i.v.; in rats: 1022.4 orally, 445 i.p. (Franzone)
MSDS Information
Doxofylline Usage And Synthesis
DescriptionDoxofylline, a xanthine bronchodilator related to theophylline, is useful in the treatment of asthma and similar bronchospastic disorders. It has minimal activity on intestinal smooth muscle and the cardiovascular system, and is reportedly devoid of the behavioral effects of theophylline.
DescriptionDoxofylline is a methylxanthine bronchodilator that has been examined in clinical trials involving patients with either bronchial asthma or chronic obstructive pulmonary disease. Its mechanism of action is related to its ability to inhibit phosphodiesterase activity and, thus, increase cAMP. Compared to other xanthine derivatives, which have direct arrhythmogenic effects, doxofylline demonstrates decreased affinity towards adenosine A1 and A2 receptors, does not interfere with calcium influx into cells, and does not antagonize the action of calcium-channel blockers.
OriginatorABC S.p.A. (Italy)
UsesDoxofylline is a xanthine molecule that appears to be both bronchodilator and anti-inflammatory with an improved therapeutic window over conventional xanthines such as Theophylline and the evidence supporting the effects of Doxofylline in the treatment of lung diseases.
UsesH1 antihistamine
DefinitionChEBI: Doxofylline is an oxopurine that is a derivative of xanthine, methylated at N-1 and N-3 and carrying a 1,3-dioxolan-2-ylmethyl group at N-7, used in the treatment of asthma. It has a role as a bronchodilator agent, an antitussive and an anti-asthmatic drug. It is functionally related to a 7H-xanthine.
Brand nameMaxivent (Roberts Pharmaceutical);ANSIMAR.
Synthesis
2-Bromomethyl-1,3-dioxolane

4360-63-8

Theophylline

58-55-9

Doxofylline

69975-86-6

The general procedure for the synthesis of 7-((1,3-dioxolan-2-yl)methyl)-1,3-dimethyl-1H-purine-2,6(3H,7H)-dione from 2-bromomethyl-1,3-dioxolane and 1,3-dimethyl-1H-purine-2,6(3H,9H)-dione was carried out as follows: to a reactor, 13 kg (72.16 mol) of 1,3- dimethyl-1H-purine-2,6(3H,9H)-dione (theophylline), 8 L of acetone, 5.77 kg (144.32 mol) of sodium hydroxide and 0.7 kg (2.16 mol) of tetrabutyl ammonium bromide. After stirring for 10 min, 14.47 kg (86.64 mmol) of 2-bromomethyl-1,3-dioxolane (bromoacetaldehyde acetal) was added. The mixture was refluxed for 6.3 h and the progress of the reaction was monitored by thin-layer chromatography (unfolding reagent ratio acetone: dichloromethane = 3:1). Upon completion of the reaction, the solvent was removed by distillation under reduced pressure, washed three times with saturated sodium chloride solution, and the residue was recrystallized from anhydrous ethanol to give 17.28 kg (64.98 mol) of 7-((1,3-dioxolan-2-yl)methyl)-1,3-dimethyl-1H-purine-2,6(3H,7H)-dione (doxophyllotoxin) in 90% yield and purity over 98.5%.

References[1] Patent: CN105418612, 2016, A. Location in patent: Paragraph 0029; 0041; 0042
[2] Patent: CN105237538, 2016, A. Location in patent: Paragraph 0055; 0056; 0058
Tag:Doxofylline(69975-86-6) Related Product Information
Dimethyl sulfoxide Purine Dimethyl fumarate alpha-Amylcinnamaldehyde DIOXOPROMETHAZINE HCL Dimethyl ether ETHANE Dihydromyrcenol Aminophylline Dimethyl carbonate 1,4-Dioxane Selenium dioxide N,N-Dimethylformamide TERT-AMYL METHYL ETHER 9-(1,3-Dioxolan-2-ylMethyl)-3,9-dihydro-1,3-diMethyl-1H-purine-2,6-dione 2-Chlorophenyl cyclopentyl ketone 7-(2-HYDROXYETHYL)THEOPHYLLINE DIOXOPROMETHAZINE

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