Theophylline

Base Information

• Chemical Name: Theophylline
• CAS No.: 58-55-9
• Deprecated CAS: 46157-00-0,56645-32-0,75448-53-2,111079-49-3,1024160-72-2,111079-49-3,75448-53-2
• Molecular Formula: C7H8N4O2
• Molecular Weight: 180.166
• Hs Code.: 29395900
• European Community (EC) Number: 200-385-7,807-662-7
• ICSC Number: 0678
• NSC Number: 757346,2066
• UN Number: 1544
• UNII: 0I55128JYK
• DSSTox Substance ID: DTXSID5021336
• Nikkaji Number: J492.514I,J2.333G
• Wikipedia: Theophylline
• Wikidata: Q407308
• NCI Thesaurus Code: C61968
• RXCUI: 91178
• Pharos Ligand ID: U3SDZU3L3UYH
• Metabolomics Workbench ID: 37911
• ChEMBL ID: CHEMBL190
• Mol file: 58-55-9.mol

Synonyms:1,3 Dimethylxanthine;1,3-Dimethylxanthine;3,7-Dihydro-1,3-dimethyl-1H-purine-2,6-dione;Accurbron;Aerobin;Aerolate;Afonilum Retard;Anhydrous, Theophylline;Aquaphyllin;Armophylline;Bronchoparat;Bronkodyl;Constant T;Constant-T;ConstantT;ct, theo von;Elixophyllin;Euphylong;Glycinate, Theophylline Sodium;Glycine Theophyllinate;Lodrane;Monospan;Nuelin;Nuelin S.A.;Quibron T SR;Quibron T-SR;Quibron TSR;Slo Phyllin;Slo-Phyllin;SloPhyllin;Sodium Glycinate, Theophylline;Somophyllin T;Somophyllin-T;SomophyllinT;Sustaire;Synophylate;Theo 24;Theo Dur;theo von ct;Theo-24;Theo-Dur;Theo24;Theobid;Theocin;Theoconfin Continuous;Theodur;Theolair;Theolix;Theon;Theonite;Theopek;Theophyllinate, Glycine;Theophylline;Theophylline Anhydrous;Theophylline Sodium Glycinate;Theospan;Theostat;Theovent;Uniphyl;Uniphyllin;Uniphylline;von ct, theo

Chemical Property of Theophylline

Chemical Property:

• Appearance/Colour: white to light yellow crystal powder
• Vapor Pressure: 2.72E-06mmHg at 25°C
• Melting Point: 271-273 °C
• Refractive Index: 1.737
• Boiling Point: 454.091 °C at 760 mmHg
• PKA: 8.77(at 25℃)
• Flash Point: 228.426 °C
• PSA: 72.68000
• Density: 1.466 g/cm³
• LogP: -1.03970
• Storage Temp.: 2-8°C
• Solubility.: 0.1 M HCl: soluble
• Water Solubility.: 8.3 g/L (20 ºC)
• XLogP3: 0
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 0
• Exact Mass: 180.06472551
• Heavy Atom Count: 13
• Complexity: 267

Purity/Quality:

98% ^*data from raw suppliers

Theophylline ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xn, T, F, Xi
• Hazard Codes: Xn,T,F,Xi
• Statements: 22-39/23/24/25-23/24/25-11-36/37/38
• Safety Statements: 7-16-36/37-45-36-26-24/25

MSDS Files:

SDS file from LookChem

Total 1 MSDS from other Authors

Useful:

• Drug Classes: Antiasthmatic Agents
• Canonical SMILES: CN1C2=C(C(=O)N(C1=O)C)NC=N2
• Recent ClinicalTrials: Theophylline Effects in the Fontan Circulation
• Recent EU Clinical Trials: A randomised, double-blind placebo controlled trial of the effectiveness of low dose oral theophylline as an adjunct to inhaled corticosteroids in preventing exacerbations of chronic obstructive pulmonary disease
• Recent NIPH Clinical Trials: Influence of habitual exercise training on sweat gland function
• Inhalation Risk: A nuisance-causing concentration of airborne particles can be reached quickly when dispersed.
• Effects of Short Term Exposure: The substance may cause effects on the heart and central nervous system. This may result in cardiac dysrhythmia and convulsions. The effects may be delayed.
• Description: Theophylline is a methylxanthine that acts as a weak bronchodilator. It is useful for chronic therapy and is not helpful in acute exacerbations.Theophylline is a methylxanthine alkaloid that is a competitive inhibitor of phosphodiesterase (PDE; Ki = 100 μM). It is also a non-selective antagonist of adenosine A receptors (Ki = 14 μM for A1 and A2). Theophylline induces relaxation of feline bronchiole smooth muscle precontracted with acetylcholine (EC40 = 117 μM; EC80 = 208 μM). Formulations containing theophylline have been used in the treatment of asthma and chronic obstructive pulmonary disease (COPD).
• Physical properties: Appearance: white, crystalline powder, odorless, with a bitter taste. Solubility: freely soluble in solutions of alkali hydroxides and in ammonia; sparingly soluble in alcohol, in chloroform, and in ether; slightly soluble in water. Water solubility, 7.36?g/L (20?°C); density, 1.62?g/cm3 ; melting point, 270–274?°C; boiling point, 390.1?°C (760? mmHg); flash point, 189.7?°C; vapor pressure, 2.72E-06? mmHg (25?°C).
• Uses: theophylline is tonic and skin conditioning. Its cosmetic activity is not clearly or definitively established. It is most often found in anti-cellulite products. Theophylline is in the same family of bio chemicals as caffeine. It is naturally occurring in tea.
• Indications: Twenty years ago theophylline (Theo-Dur, Slo-bid, Uniphyl, Theo-24) and its more soluble ethylenediamine salt, aminophylline, were the bronchodilators of choice in the United States. Although the β2-adrenoceptor agonists now fill this primary role, theophylline continues to have an important place in the therapy of asthma because it appears to have antiinflammatory as well as bronchodilator activity.
• Clinical Use: The principal use of theophylline is in the management of asthma. It is also used to treat the reversible component of airway obstruction associated with chronic obstructive pulmonary disease and to relieve dyspnea associated with pulmonary edema that develops from congestive heart failure.
• Drug interactions: Potentially hazardous interactions with other drugs Antibacterials: increased concentration with azithromycin, clarithromycin, erythromycin, ciprofloxacin, norfloxacin and isoniazid; decreased plasma levels of erythromycin if erythromycin taken orally; increased risk of convulsions if given with quinolones; rifampicin accelerates metabolism of theophylline. Antidepressants: concentration increased by fluvoxamine - avoid or halve theophylline dose and monitor levels; concentration reduced by St John’s wort - avoid. Antiepileptics: metabolism increased by carbamazepine, phenobarbital and primidone; concentration of both drugs increased with fosphenytoin and phenytoin. Antifungals: concentration increased by fluconazole and ketoconazole. Antivirals: metabolism of theophylline increased by ritonavir; concentration possibly increased by aciclovir. Calcium-channel blockers: concentration increased by diltiazem and verapamil and possibly other calcium-channel blockers. Deferasirox: concentration of theophylline increased. Febuxostat: use with caution. Interferons: reduced metabolism of theophylline. Tacrolimus: may increase tacrolimus levels. Ulcer-healing drugs: metabolism inhibited by cimetidine; absorption possibly reduced by sucralfate.

Technology Process of Theophylline

There total 95 articles about Theophylline which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 97.7%

1,3-dimethyl-4-amino-5-(formylamino)uracil (7597-60-6) → theophylline (58-55-9,75448-53-2)

Guidance literature:

With triethylamine; 1,3-bis[2,6-diisopropylphenyl]imidazolium chloride; In water; at 75 ℃; for 0.916667h; under 4500.45 Torr; Pressure; Temperature; Autoclave;

Reference yield: 97.5%

Methyl formate (107-31-3) + 1,3-Dimethylxanthine potassium salt (57533-87-6) → theophylline (58-55-9,75448-53-2) + 3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione (58-08-2,138455-22-8,95789-13-2)

Guidance literature:

In methanol;

Reference yield: 95.0%

7-amino-1,3-dimethyl-3,7-dihydro-1H-purine-2,6-dione (81281-58-5) → theophylline (58-55-9,75448-53-2)

Guidance literature:

With hydrogenchloride; sodium nitrite; In water; at 5 ℃; for 1h;

upstream raw materials:

1,3,5-Triazine

4,5-Diamino-1,3-dimethyluracil

6-Amino-1,3-dimethylbarbituric acid

formamide

Downstream raw materials:

7-(2-hydroxyethyl)theophylline

1,3-dimethyl-7-(morpholinomethyl)xanthine

proxyphylline

7-[(2-hydroxy-2-phenyl)ethyl]theophylline

Refernces

• 1、 Hignite,Huffman,Azarnoff. "Synthesis of theophylline-8-13C". . p. 475 - 478,476,477. Retrieved 1978.
• 2、 Bergmann, Felix,Rahat, Miriam,Frank, Arie,Deutsch, Joseph. "Comparison of the Mass Spectra of 6-Thiotheophyllines and 6-Sulfinyltheophyllines". . p. 565 - 568. Retrieved 1982.
• 3、 Rathod,Patel,Das,Tipparaju,Shinde,Anderson, Robert F.. "Inhibition of radical-induced DNA strand breaks by water-soluble constituents of coffee: Phenolics and caffeine metabolites". . p. 480 - 487. Retrieved 2013.
• 4、 -. "Synthesis method of theophylline". Paragraph 0030; 0033; 0034; 0037; 0038; 0041; 0053-0056. . Retrieved 2020/12/29.
• 5、 -. "A coffee because of the intermediate 1, 3-dimethyl-4-amino-5-Carbamoyl [...] closed-loop reaction method". Paragraph 0040; 0041. . Retrieved 2017/01/05.