Welcome to LookChem.com Sign In|Join Free

CAS

  • or

58-55-9

Post Buying Request

58-55-9 Suppliers

Recommended suppliersmore

  • Product
  • FOB Price
  • Min.Order
  • Supply Ability
  • Supplier
  • Contact Supplier

58-55-9 Usage

Chemical Description

Theophylline is a xanthine derivative used in the treatment of respiratory diseases.

Chemical Description

Theophylline, thymine, and uracil are nucleic acid bases, while 1-chloro-2,3-epoxypropane and methacryloyl chloride are used in the preparation of 2-propanol derivatives.

Description

Theophylline is a dimethylxanthine alkaloid that acts as a weak bronchodilator and is useful for chronic therapy. It is a competitive inhibitor of phosphodiesterase (PDE) and a non-selective antagonist of adenosine A receptors. Theophylline is naturally occurring in tea and is in the same family of bio chemicals as caffeine. It is an odorless white crystalline powder with a bitter taste.

Uses

Used in Pharmaceutical Industry:
Theophylline is used as a bronchodilator for the treatment of asthma and chronic obstructive pulmonary disease (COPD). It helps in inducing relaxation of bronchiole smooth muscle, which is precontracted with acetylcholine.
Used in Cosmetic Industry:
Theophylline is used as a tonic and skin conditioning agent, although its cosmetic activity is not clearly or definitively established. It is most often found in anti-cellulite products.
Physical properties of Theophylline:
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 (7.36 g/L at 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)

History

Theophylline was firstly extracted from tea leaves and chemically identified by the German biologist Albrecht Kossel. A cup of tea contains about 1?mg/mL theophylline. In 1895, a chemical synthesis of theophylline starting with 1,3-dimethyluric acid was described by Emil Fischer and Lorenz Ach. Theophylline was synthesized by Wilhelm Traube in 1900. Aminophylline, a derivative of theophylline ethylenediamine, is widely used due to its greater aqueous solubility.Theophylline was firstly used clinically as a diuretic in 1902. Twenty years later it was firstly reported by D.I.?Macht and G.C.?Ting for asthma treatment in pig bronchial smooth muscle. The first successful clinical use of theophylline in bronchial asthma was reported in 1922 by S.? Hirsch, who described that four patients responded well to the rectal administration of a mixture of 66.7% theophylline and 33.3% theobromine. He also tested the combination of theophylline with theobromine on bovine bronchial smooth muscle strips and noted smooth muscle relaxation. Thus he concluded that dimethylxanthines act by producing relaxation of bronchial smooth muscle. In 1937, two concurrent but independent clinical trials reported that methylxanthines were efficacious in asthma. The Food and Drug Administration approved the use of theophylline for asthma in the USA in 1940.There are more than 300 derivatives of theophylline. The main derivatives include aminophylline, dihydroxypropyl theophylline, and oxtriphylline.2. Doxofylline: 7-(1,3-dioxalan-2-ylmethyl) theophylline. It has antitussive and bronchodilator effects. In animal and human studies, it has shown similar efficacy to theophylline but with fewer side effects. Related research has showed that the effect of doxofylline on airway relaxation is 10–15 times that of aminophylline.3. Diprophylline: 7-(2,3-dihydroxypropyl)-1,3-dimethyl-3,7-dihydro-1H-purine- 2,6-dione. Diprophylline is the neutral preparation of theophylline. It causes less of nausea and gastric irritation.4. Oxtriphylline: choline theophyllinate; administered orally. Oxtriphylline is five times more soluble than aminophylline.

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.

Air & Water Reactions

Slightly soluble in water.

Reactivity Profile

Theophylline neutralizes acids in exothermic reactions to form salts plus water. May be incompatible with isocyanates, halogenated organics, peroxides, phenols (acidic), epoxides, anhydrides, and acid halides. Flammable gaseous hydrogen may be generated in combination with strong reducing agents, such as hydrides.

Hazard

Questionable carcinogen.

Fire Hazard

Flash point data for Theophylline are not available, however Theophylline is probably combustible.

Biological Activity

Bronchodilator, anti-inflammatory and immunomodulator. Antagonizes adenosine receptors and is a weak non-selective inhibitor of phosphodiesterases (PDEs).

Biochem/physiol Actions

Phosphodiesterase inhibitor; diuretic; cardiac stimulant; muscle relaxant; asthma medication.

Mechanism of action

In spite of a great deal of investigation, just how theophylline causes bronchodilation is not clearly understood. Inhibition of the enzyme PDE, which is responsible for the hydrolysis of cAMP and cyclic guanosine monophosphate (cGMP), generally is put forth as the mechanism of action; however, theophylline also is an adenosine antagonist and has been implicated in stimulation of the release of catecholamines. It has been clearly shown that theophylline does inhibit PDEs in vitro, and x-ray crystallographic studies have identified the binding residues that interact with the methylxanthines. Theophylline binds to a subpocket of the active site and appears to be sandwiched between a phenylalanine and a valine via hydrophobic bonds. Its binding affinity is reinforced by hydrogenbonding between a tyrosine and N-7 and a glutamine and O-6 of the xanthine ring system. There are more than 11 families of PDEs, and studies have shown that theophylline binds in a similar manner to both the PDE4 and PDE5 family isoforms.

Pharmacology

Smooth muscle relaxation, central nervous system (CNS) excitation, and cardiac stimulation are the principal pharmacological effects observed in patients treated with theophylline.The action of theophylline on the respiratory system is easily seen in the asthmatic by the resolution of obstruction and improvement in pulmonary function. Other mechanisms that may contribute to the action of theophylline in asthma include antagonism of adenosine, inhibition of mediator release, increased sympathetic activity, alteration in immune cell function, and reduction in respiratory muscle fatigue. Theophylline also may exert an antiinflammatory effect through its ability to modulate inflammatory mediator release and immune cell function. Inhibition of cyclic nucleotide phosphodiesterases is widely accepted as the predominant mechanism by which theophylline produces bronchodilation. Phosphodiesterases are enzymes that inactivate cAMP and cyclic guanosine monophosphate (GMP), second messengers that mediate bronchial smooth muscle relaxation.

Pharmacology

Theophylline can reduce the tension of smooth muscle and dilate respiratory tract; It can promote the release of endogenous epinephrine and norepinephrine and relax airway smooth muscle; Inhibit the release of calcium ions from the endoplasmic reticulum of smooth muscle, reduce the concentration of intracellular calcium ions and produce respiratory tract dilation. Theophylline has a strong relaxation effect on smooth muscle, but it is not as good as β Receptor agonists. On October 27, 2017, the list of carcinogens published by the international agency for research on cancer of the World Health Organization was preliminarily sorted out for reference. Theophylline was included in the list of Category 3 carcinogens.

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.

Side effects

Theophylline has a narrow therapeutic index and produces side effects that can be severe, even life threatening. Importantly, the plasma concentration of theophylline cannot be predicted reliably from the dose. In one study, the oral dosage of theophylline required to produce therapeutic plasma levels (i.e., between 10 and 20 μg/mL) varied between 400 and 3,200 mg/day. Heterogeneity among individuals in the rate at which they metabolize theophylline appears to be the principal factor responsible for the variability in plasma levels. Such conditions as heart failure, liver disease, and severe respiratory obstruction will slow the metabolism of theophylline.

Safety Profile

Human poison by ingestion, parenteral, intravenous, and rectal routes. Experimental poison by multiple routes. An experimental teratogen. Human systemic effects: coma, convulsions or effect on seizure threshold, cyanosis, EKG changes, fever and other metabolic effects, heart arrhythmias, heart rate change, hyperglycemia, metabolic acidosis, nausea or vomiting, potassium-level changes, respiratory stimulation, salivary gland changes, somnolence, tremor. Experimental reproductive effects. Human mutation data reported. Used as a dturetic, cardtac stimulant, smooth muscle relaxant, and to treat asthma. When heated to decomposition it emits toxic fumes of NOx.

Synthesis

Theophylline, 1,3-dimethylxanthine (23.3.5), is present in small quantities in tea leaves. It is synthesized synthetically by the Traube method, a general method suggested for making purine bases. In the given example, reacting N,N-dimethylurea with cyanoacetic ether in the presence of acetic anhydride gives cyanoacetylmethylurea (23.3.1), which cyclizes into 6-amino-1,3-dimethyluracil (23.3.2). The resulting compound transforms into 5-nitroso-6-amino-1,3-dimethyluracil (23.3.3) upon reaction with nitric acid. Reduction of the nitroso group gives 5,6-diamino-1,3-dimethyluracil (23.3.4), the subsequent reaction of which with formamide gives the desired theophylline (23.3.5).

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.

Environmental Fate

Theophylline is readily broken down in the environment. It may undergo photolytic degradation in the air or when exposed to light. In moist soil, or aqueous environments, it undergoes rapid biodegradation.

Metabolism

Chemically, theophylline is 1,3-dimethylxanthine and contains both an acidic and a basic nitrogen (N-7 and N-9, respectively). Physiologically, it behaves as an acid (pKa = 8.6), and its poor aqueous solubility can be enhanced by salt formation with organic bases. Theophylline is metabolized by a combination of C-8 oxidation and N-demethylation to yield methyluric acid metabolites. The major urinary metabolite is 1,3-dimethyl uric acid, which is the product of the action of xanthine oxidase. Because none of the metabolites is uric acid itself, theophylline can be safely given to patients who suffer from gout.

Purification Methods

It crystallises from H2O as the monohydrate which becomes anhydrous above 100o. It is freely soluble in hot H2O, but its solubility at 15o is 0.44%. It complexes with heavy metals. It is a diuretic, vasodilator and a cardiac stimulant. [Lister Purines Part II, Fused Pyrimidines Brown Ed, Wiley-Interscience pp253-254 1971, ISBN 0-471-38205-1, Beilstein 26 H 455, 26 I 134, 26 II 263, 26 III/IV 2331.]

Toxicity evaluation

In acute overdoses, theophylline often causes severe emesis (75% in acute vs 30% in chronic). The emesis is often difficult to control with antiemetics. It is thought that theophylline causes increased gastric acid secretion and smooth muscle relaxation. Theophylline causes a release of endogenous catecholamines, and therefore is a cardiac stimulant. There is a positive inotropic and dose-dependent chronotropic response. Tachydysrhythmias, especially supraventricular tachycardia, are common due to adenosine receptor antagonism. Ventricular tachydysrhythmias can occur as well in acute overdose; however, they are rare at therapeutic concentrations. Rapid administration of aminophylline has resulted in sudden cardiac death. Hypokalemia, hypercalcemia, and hyperglycemia may contribute to arrhythmias as well. In cases of chronic toxicity, dysrhythmias occur at lower serum concentrations (40–80 mg ml-1) compared to acute overdose. Theophylline will stimulate the CNS respiratory center causing increased respiratory rate and can lead to respiratory alkalosis. Theophylline will cause CNS stimulation and vasoconstriction, similar to caffeine, and may lead to headache, anxiety, agitation, insomnia, tremor, irritability, hallucinations, and seizures. Methylxanthines exhibit weak diuretic effects by increasing cardiac output and renal vasodilation. Theophylline has a narrow therapeutic index, with 12–25% of overdose patients developing serious or life-threatening symptoms including arrhythmias and seizure. Toxicity can develop at lower serum concentrations for those treated chronically or older patients. Age greater than 60 years and chronic use are risk factors for increased morbidity and mortality.

Precautions

Theophylline should be used with caution in patientswith myocardial disease, liver disease, and acutemyocardial infarction. The half-life of theophylline isprolonged in patients with congestive heart failure.Because of its narrow margin of safety, extreme cautionis warranted when coadministering drugs, such as cimetidineor zileuton, that may interfere with the metabolismof theophylline. Indeed, coadministration of zileutonwith theophylline is contraindicated. It is alsoprudent to be careful when using theophylline in patientswith a history of seizures.

References

Fischer., Ber., 30, 553 (1897) Schwabe., Arch. Pharm., 245, 312 (1907)Biltz, Strufe.,Annalen, 404, 137, 170(1914)Yoshitomi., Chem. Abstr., 19,2303 (1925) Mossini., Boll. chim. farm., 75, 557 (1936)Deichmeister., Farm. Zhur., 13, 18 (1940) Deichmeister., Chem. Zentr., 1, 1280 (1942) Deniges., Bull. trav. soc. ph arm. Bordeaux, 79, 141 (1941)Lesser., Drug & Cosmetic Ind., 66, 276,340 (1950)

Check Digit Verification of cas no

The CAS Registry Mumber 58-55-9 includes 5 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 2 digits, 5 and 8 respectively; the second part has 2 digits, 5 and 5 respectively.
Calculate Digit Verification of CAS Registry Number 58-55:
(4*5)+(3*8)+(2*5)+(1*5)=59
59 % 10 = 9
So 58-55-9 is a valid CAS Registry Number.
InChI:InChI=1/C7H10N4O2/c1-10-5-4(8-3-9-5)6(12)11(2)7(10)13/h3-5H,1-2H3,(H,8,9)

58-55-9 Well-known Company Product Price

  • Brand
  • (Code)Product description
  • CAS number
  • Packaging
  • Price
  • Detail
  • TCI America

  • (T0179)  Theophylline  >98.0%(HPLC)(T)

  • 58-55-9

  • 25g

  • 120.00CNY

  • Detail
  • TCI America

  • (T0179)  Theophylline  >98.0%(HPLC)(T)

  • 58-55-9

  • 100g

  • 360.00CNY

  • Detail
  • TCI America

  • (T0179)  Theophylline  >98.0%(HPLC)(T)

  • 58-55-9

  • 500g

  • 890.00CNY

  • Detail

58-55-9SDS

SAFETY DATA SHEETS

According to Globally Harmonized System of Classification and Labelling of Chemicals (GHS) - Sixth revised edition

Version: 1.0

Creation Date: Aug 12, 2017

Revision Date: Aug 12, 2017

1.Identification

1.1 GHS Product identifier

Product name theophylline

1.2 Other means of identification

Product number -
Other names [13C]-Theophyllin

1.3 Recommended use of the chemical and restrictions on use

Identified uses For industry use only.
Uses advised against no data available

1.4 Supplier's details

1.5 Emergency phone number

Emergency phone number -
Service hours Monday to Friday, 9am-5pm (Standard time zone: UTC/GMT +8 hours).

More Details:58-55-9 SDS

58-55-9Synthetic route

1,3-dimethyl-4-amino-5-(formylamino)uracil
7597-60-6

1,3-dimethyl-4-amino-5-(formylamino)uracil

theophylline
58-55-9

theophylline

Conditions
ConditionsYield
With triethylamine; 1,3-bis[2,6-diisopropylphenyl]imidazolium chloride In water at 75℃; under 4500.45 Torr; for 0.916667h; Pressure; Temperature; Autoclave;97.7%
With sodium hydroxide; sodium chloride
With sodium hydroxide
at 250 - 260℃;
With sulfuric acid at 90℃; pH=5; pH-value; Temperature; Reagent/catalyst;
Methyl formate
107-31-3

Methyl formate

1,3-Dimethylxanthine potassium salt
57533-87-6

1,3-Dimethylxanthine potassium salt

A

theophylline
58-55-9

theophylline

B

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione
58-08-2

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione

Conditions
ConditionsYield
In methanolA 97.5%
B n/a
7-amino-1,3-dimethyl-3,7-dihydro-1H-purine-2,6-dione
81281-58-5

7-amino-1,3-dimethyl-3,7-dihydro-1H-purine-2,6-dione

theophylline
58-55-9

theophylline

Conditions
ConditionsYield
With hydrogenchloride; sodium nitrite In water at 5℃; for 1h;95%
7-(2,4-dimethoxybenzyl)-1,3-dimethyl-3,7-dihydropurine-2,6-dione

7-(2,4-dimethoxybenzyl)-1,3-dimethyl-3,7-dihydropurine-2,6-dione

theophylline
58-55-9

theophylline

Conditions
ConditionsYield
With trifluoroacetic acid In dichloromethane at 20℃;87%
(1,3-Dimethyl-2,6(1H,3H)-dioxopurin-7-yl)(phenyl)methyl acetate
226386-40-9

(1,3-Dimethyl-2,6(1H,3H)-dioxopurin-7-yl)(phenyl)methyl acetate

theophylline
58-55-9

theophylline

Conditions
ConditionsYield
With hydrogenchloride In methanol Ambient temperature;78%
1,2,3,6-tetrahydro-1,3-dimethyl-2,6-dioxo-9H-purine-9-carbonitrile
124093-03-4

1,2,3,6-tetrahydro-1,3-dimethyl-2,6-dioxo-9H-purine-9-carbonitrile

theophylline
58-55-9

theophylline

Conditions
ConditionsYield
In water for 1h; Reflux;77%
N-(1,3-dimethyl-6-nitro-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidin-5-yl)-formamide
624734-82-3

N-(1,3-dimethyl-6-nitro-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidin-5-yl)-formamide

theophylline
58-55-9

theophylline

Conditions
ConditionsYield
With iron; acetic acid for 0.5h; Heating;75%
2,2-dimethyl-propionic acid 1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-purin-7-ylmethyl ester
64210-71-5

2,2-dimethyl-propionic acid 1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-purin-7-ylmethyl ester

theophylline
58-55-9

theophylline

Conditions
ConditionsYield
68%
7-(2-acetamido-4,6-di-O-acetyl-2,3-dideoxy-D-threo-hex-2-enopyranosyl)theophylline
80035-38-7, 80035-40-1, 80035-42-3

7-(2-acetamido-4,6-di-O-acetyl-2,3-dideoxy-D-threo-hex-2-enopyranosyl)theophylline

A

theophylline
58-55-9

theophylline

B

7-(methyl 2-acetamido-6-O-acetyl-2,3,4-trideoxy-α-D-threo-hex-2-enopyranosid-4-yl)theophylline
70800-68-9

7-(methyl 2-acetamido-6-O-acetyl-2,3,4-trideoxy-α-D-threo-hex-2-enopyranosid-4-yl)theophylline

C

7-(methyl 2-acetamido-6-O-acetyl-2,3,4-trideoxy-β-D-erythro-hex-2-enopyranosid-4-yl)theophylline
70675-25-1

7-(methyl 2-acetamido-6-O-acetyl-2,3,4-trideoxy-β-D-erythro-hex-2-enopyranosid-4-yl)theophylline

Conditions
ConditionsYield
With boron trifluoride diethyl etherate In methanol for 0.25h; Heating;A n/a
B 54%
C 12%
formic acid
64-18-6

formic acid

4,5-Diamino-1,3-dimethyluracil
5440-00-6

4,5-Diamino-1,3-dimethyluracil

theophylline
58-55-9

theophylline

Conditions
ConditionsYield
at 110 - 300℃; for 2.33333h;51%
With hydrogenchloride; sodium hydroxide at 90℃; Yield given;
7-azido-1,3-dimethylpteridine-2,4(1H,3H)-dione
124093-02-3

7-azido-1,3-dimethylpteridine-2,4(1H,3H)-dione

theophylline
58-55-9

theophylline

Conditions
ConditionsYield
In N,N-dimethyl acetamide for 0.25h; Reflux;50%
7-(2-acetamido-4,6-di-O-acetyl-2,3-dideoxy-D-threo-hex-2-enopyranosyl)theophilline
80035-41-2, 80035-43-4

7-(2-acetamido-4,6-di-O-acetyl-2,3-dideoxy-D-threo-hex-2-enopyranosyl)theophilline

theophylline
58-55-9

theophylline

Conditions
ConditionsYield
With boron trifluoride diethyl etherate In methanol Product distribution;48%
1,3-dimethyl-5-bromo-6-methylaminopyrimidine-2,4-dione
98333-72-3

1,3-dimethyl-5-bromo-6-methylaminopyrimidine-2,4-dione

theophylline
58-55-9

theophylline

Conditions
ConditionsYield
With sodium azide In N,N-dimethyl-formamide Ambient temperature;47%
4,5-Diamino-1,3-dimethyluracil
5440-00-6

4,5-Diamino-1,3-dimethyluracil

Vilsmeier reagent
3724-43-4, 149409-22-3

Vilsmeier reagent

theophylline
58-55-9

theophylline

Conditions
ConditionsYield
In toluene 1.) RT, 2.) reflux;44%
3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione
58-08-2

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione

A

theophylline
58-55-9

theophylline

B

theobromine /
83-67-0

theobromine /

Conditions
ConditionsYield
With sodium thiophenolate at 250℃; for 1.5h;A 37%
B 21%
6-amino-5-bromo-1,3-dimethylpyrimidine-2,4(1H,3H)-dione
7150-04-1

6-amino-5-bromo-1,3-dimethylpyrimidine-2,4(1H,3H)-dione

theophylline
58-55-9

theophylline

Conditions
ConditionsYield
for 7h; Reflux;35%
3,7-Dihydro-1,3-dimethyl-2,6-dioxo-1H-purin-7-carbonsaeure-ethylester
101774-91-8

3,7-Dihydro-1,3-dimethyl-2,6-dioxo-1H-purin-7-carbonsaeure-ethylester

A

theophylline
58-55-9

theophylline

B

(E)-1,2-diphenyl-ethene
103-30-0

(E)-1,2-diphenyl-ethene

3,4,5,7-Tetrahydro-1,3-dimethyl-2,6-dioxo-anti-10,syn-11-diphenyl-4,5-ethano-1H-purin-7-carbonsaeure-ethylester
130195-61-8

3,4,5,7-Tetrahydro-1,3-dimethyl-2,6-dioxo-anti-10,syn-11-diphenyl-4,5-ethano-1H-purin-7-carbonsaeure-ethylester

Conditions
ConditionsYield
In dichloromethane at 25 - 30℃; for 12h; Irradiation;A 8%
B 23%
C 6%
(E)-1,2-diphenyl-ethene
103-30-0

(E)-1,2-diphenyl-ethene

3,7-Dihydro-1,3-dimethyl-2,6-dioxo-1H-purin-7-carbonsaeure-ethylester
101774-91-8

3,7-Dihydro-1,3-dimethyl-2,6-dioxo-1H-purin-7-carbonsaeure-ethylester

A

theophylline
58-55-9

theophylline

3,4,5,7-Tetrahydro-1,3-dimethyl-2,6-dioxo-syn-10,anti-11-diphenyl-4,5-ethano-1H-purin-7-carbonsaeure-ethylester
130149-72-3

3,4,5,7-Tetrahydro-1,3-dimethyl-2,6-dioxo-syn-10,anti-11-diphenyl-4,5-ethano-1H-purin-7-carbonsaeure-ethylester

3,4,5,7-Tetrahydro-1,3-dimethyl-2,6-dioxo-anti-10,syn-11-diphenyl-4,5-ethano-1H-purin-7-carbonsaeure-ethylester
130195-61-8

3,4,5,7-Tetrahydro-1,3-dimethyl-2,6-dioxo-anti-10,syn-11-diphenyl-4,5-ethano-1H-purin-7-carbonsaeure-ethylester

Conditions
ConditionsYield
In dichloromethane at 25 - 30℃; for 12h; Irradiation;A 8%
B 23%
C 6%
N-(1,3-dimethyl-5-nitro-2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-yl)formamide

N-(1,3-dimethyl-5-nitro-2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-yl)formamide

theophylline
58-55-9

theophylline

Conditions
ConditionsYield
With acetic acid; zinc for 0.666667h; Reflux;20%
With iron; acetic acid at 119℃; for 0.516667h; Temperature; Reflux;
With iron; acetic acid at 122℃; for 0.533333h; Temperature; Reflux;
isoalantolactone
470-17-7

isoalantolactone

8-bromotheophylline
10381-75-6

8-bromotheophylline

A

theophylline
58-55-9

theophylline

B

1,3-dimethyl-7-(((3R,3aR,4aS,8aR,9aR)-8a-methyl-5-methylene-2-oxododecahydronaphtho[2,3-b]furan-3-yl)methyl)-1H-purine-2,6(3H,7H)dione

1,3-dimethyl-7-(((3R,3aR,4aS,8aR,9aR)-8a-methyl-5-methylene-2-oxododecahydronaphtho[2,3-b]furan-3-yl)methyl)-1H-purine-2,6(3H,7H)dione

C

1,3-dimethyl-8-(((4aS,8aR,9aS)-8a-methyl-5-methylene-2-oxo-2,4,4a,5,6,7,8,8a,9,9a-decahydronaphtho[2,3-b]furan-3-yl)methyl)-1H-purine-2,6(3H,7H)dione

1,3-dimethyl-8-(((4aS,8aR,9aS)-8a-methyl-5-methylene-2-oxo-2,4,4a,5,6,7,8,8a,9,9a-decahydronaphtho[2,3-b]furan-3-yl)methyl)-1H-purine-2,6(3H,7H)dione

D

1,3-dimethyl-8-((E)-((3aR,4aS,8aR,9aR)-8a-methyl-5-methylene-2-oxodecahydronaphtho[2,3-b]furan-3(2H)ylidene)methyl)-1H-purine-2,6(3H,7H)dione

1,3-dimethyl-8-((E)-((3aR,4aS,8aR,9aR)-8a-methyl-5-methylene-2-oxodecahydronaphtho[2,3-b]furan-3(2H)ylidene)methyl)-1H-purine-2,6(3H,7H)dione

Conditions
ConditionsYield
With palladium diacetate; triethylamine; tris-(o-tolyl)phosphine In N,N-dimethyl-formamide at 120℃; for 20h; Heck Reaction; Inert atmosphere; Molecular sieve; Sealed tube;A n/a
B 17%
C 6%
D 20%
3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione
58-08-2

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione

A

theophylline
58-55-9

theophylline

B

theobromine /
83-67-0

theobromine /

C

paraxanthine
611-59-6

paraxanthine

Conditions
ConditionsYield
With hepatic cytochrome P450 Enzymatic reaction;A 7%
B 12%
C n/a
1,3,5-Triazine
290-87-9

1,3,5-Triazine

4,5-Diamino-1,3-dimethyluracil
5440-00-6

4,5-Diamino-1,3-dimethyluracil

theophylline
58-55-9

theophylline

6-Amino-1,3-dimethylbarbituric acid
6642-31-5

6-Amino-1,3-dimethylbarbituric acid

theophylline
58-55-9

theophylline

Conditions
ConditionsYield
With formic acid; sodium nitrite anschliessendes Erhitzen mit Na2S2O4 auf 200grad;
With formic acid; sodium nitrite anschliessendes Erhitzen mit Na2S2O4 auf 200grad;
4,5-Diamino-1,3-dimethyluracil
5440-00-6

4,5-Diamino-1,3-dimethyluracil

theophylline
58-55-9

theophylline

1,3-dimethyl-4-amino-5-(formylamino)uracil
7597-60-6

1,3-dimethyl-4-amino-5-(formylamino)uracil

potassium ethoxide
917-58-8

potassium ethoxide

theophylline
58-55-9

theophylline

8-chlorotheophylline
85-18-7

8-chlorotheophylline

theophylline
58-55-9

theophylline

Conditions
ConditionsYield
With water; zinc
With tetralin; iodine
With sodium hydroxide; palladium-barium carbonate at 105℃; under 29420.3 Torr; Hydrogenation;
bei der elektrochemischen Reduktion an einer Quecksilber-Kathode;
bei der elektrolytischen Reduktion an Bleikathoden;
5-acetylamino-6-amino-1,3-dimethyl-1H-pyrimidine-2,4-dione
10184-41-5

5-acetylamino-6-amino-1,3-dimethyl-1H-pyrimidine-2,4-dione

theophylline
58-55-9

theophylline

7-(hydroxymethyl)theophylline
31542-43-5

7-(hydroxymethyl)theophylline

A

formaldehyd
50-00-0

formaldehyd

B

theophylline
58-55-9

theophylline

Conditions
ConditionsYield
at 165 - 170℃;
6-amino-1,3-dimethyl-5-phenylazouracilate
122707-25-9

6-amino-1,3-dimethyl-5-phenylazouracilate

theophylline
58-55-9

theophylline

Conditions
ConditionsYield
With nickel at 140℃; under 66195.7 Torr; Hydrogenation;
theophylline
58-55-9

theophylline

C7H4(2)H4N4O2

C7H4(2)H4N4O2

Conditions
ConditionsYield
With deuterium In water-d2 at 55℃; under 1500.15 Torr; for 36h; Glovebox;100%
theophylline
58-55-9

theophylline

4-(methoxymethoxy)-3-nitrobenzyl bromide
99132-02-2

4-(methoxymethoxy)-3-nitrobenzyl bromide

methoxymethylphidolopin
99131-99-4

methoxymethylphidolopin

Conditions
ConditionsYield
With potassium carbonate In N,N-dimethyl-formamide Ambient temperature;99%
theophylline
58-55-9

theophylline

1,2-dichloro-ethane
107-06-2

1,2-dichloro-ethane

7-(2-chloroethyl)-3,7-dihydro-1,3-dimethyl-1H-purine-2,6-dione
5878-61-5

7-(2-chloroethyl)-3,7-dihydro-1,3-dimethyl-1H-purine-2,6-dione

Conditions
ConditionsYield
With sodium hydroxide; Aliquat 336 for 4h; Heating;99%
With sodium hydroxide In water; isopropyl alcohol at 78 - 80℃; for 76.5h; Heating;90%
In water; dimethyl sulfoxide
theophylline
58-55-9

theophylline

benzyl 2-bromopropionate
3017-53-6

benzyl 2-bromopropionate

benzyl 2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)propanoate

benzyl 2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)propanoate

Conditions
ConditionsYield
With caesium carbonate In N,N-dimethyl-formamide at 20℃; for 2h; Inert atmosphere; Schlenk technique;99%
methyl bromide
74-83-9

methyl bromide

theophylline
58-55-9

theophylline

A

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione
58-08-2

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione

B

3-benzyladenine
7280-81-1

3-benzyladenine

Conditions
ConditionsYield
With solution aqueuse d'hydroxide de sodium; tetrabutylammomium bromide In dichloromethane 1)20 deg C, 12h 2)40 deg C, 3h;A 98%
B n/a
theophylline
58-55-9

theophylline

1,3-dibromo-propane
109-64-8

1,3-dibromo-propane

7-(3-bromo-propyl)-1,3-dimethyl-3,7-dihydro-purine-2,6-dione
23146-06-7

7-(3-bromo-propyl)-1,3-dimethyl-3,7-dihydro-purine-2,6-dione

Conditions
ConditionsYield
With sodium hydroxide; Aliquat 336 for 2h; Heating;98%
With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 24h;91%
With triethylamine In N,N-dimethyl-formamide at 60℃;77%
theophylline
58-55-9

theophylline

C7H(2)H7N4O2
1220356-90-0

C7H(2)H7N4O2

Conditions
ConditionsYield
With palladium 10% on activated carbon; hydrogen; water-d2 at 160℃; for 24h;97%
theophylline
58-55-9

theophylline

1,3-Dimethylxanthine potassium salt
57533-87-6

1,3-Dimethylxanthine potassium salt

Conditions
ConditionsYield
With potassium hydroxide In water for 0.166667h;97%
ethyl bromide
74-96-4

ethyl bromide

theophylline
58-55-9

theophylline

7-ethyl-1,3-dimethyl-3,7-dihydro-purine-2,6-dione
23043-88-1

7-ethyl-1,3-dimethyl-3,7-dihydro-purine-2,6-dione

Conditions
ConditionsYield
With sodium hydroxide; tetrabutylammomium bromide In dichloromethane at 40℃; for 24h;96%
With potassium hydroxide at 100℃;
theophylline
58-55-9

theophylline

p-toluenesulfonyl chloride
98-59-9

p-toluenesulfonyl chloride

N7-tosyltheophylline
68696-86-6

N7-tosyltheophylline

Conditions
ConditionsYield
With triethylamine In acetonitrile Reflux;96%
theophylline
58-55-9

theophylline

fluoroiodomethane
373-53-5

fluoroiodomethane

7-(fluoromethyl)-1,3-dimethyl-3,7-dihydro-1H-purine-2,6-dione

7-(fluoromethyl)-1,3-dimethyl-3,7-dihydro-1H-purine-2,6-dione

Conditions
ConditionsYield
With caesium carbonate In acetonitrile at 20℃; for 6h; chemoselective reaction;96%
pyridine
110-86-1

pyridine

theophylline
58-55-9

theophylline

8-pyridinium theophyllinate
52943-89-2

8-pyridinium theophyllinate

Conditions
ConditionsYield
With chloramine-B for 0.166667h; Ambient temperature;95%
theophylline
58-55-9

theophylline

6-thiotheophylline
2398-70-1

6-thiotheophylline

Conditions
ConditionsYield
With Lawessons reagent; aluminum oxide for 0.166667h; microwave irradiation;95%
4-chlorobutyl bromide
6940-78-9

4-chlorobutyl bromide

theophylline
58-55-9

theophylline

7-(4-chlorobutyl)theophylline
59663-15-9

7-(4-chlorobutyl)theophylline

Conditions
ConditionsYield
Stage #1: theophylline With sodium hydride In N,N-dimethyl-formamide at 20℃; for 0.166667h;
Stage #2: 4-chlorobutyl bromide In N,N-dimethyl-formamide at 20℃; for 24h; Further stages.;
95%
theophylline
58-55-9

theophylline

methyl iodide
74-88-4

methyl iodide

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione
58-08-2

3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione

Conditions
ConditionsYield
With sodium hydride In dimethyl sulfoxide for 0.75h;95%
With sodium hydride In dimethyl sulfoxide at 20℃; for 24h; Reagent/catalyst;90%
theophylline
58-55-9

theophylline

Di-tert-butyl acetylenedicarboxylate
66086-33-7

Di-tert-butyl acetylenedicarboxylate

triphenylphosphine
603-35-0

triphenylphosphine

di-tert-butyl 2-(theophylline-7-yl)-3-(triphenylphosphoranylidene)-butanedioate
1268809-87-5

di-tert-butyl 2-(theophylline-7-yl)-3-(triphenylphosphoranylidene)-butanedioate

Conditions
ConditionsYield
In diethyl ether at -5 - 20℃; for 10h; chemoselective reaction;95%
triphenyl phosphite
101-02-0

triphenyl phosphite

theophylline
58-55-9

theophylline

dimethyl acetylenedicarboxylate
762-42-5

dimethyl acetylenedicarboxylate

dimethyl (2RS,3SR)-2-(diphenoxyphosphinyl)-3-(1,2,3,6-tetrahydro-1,3-dimethyl-2,6-dioxo-7H-purine-7-yl)succinate

dimethyl (2RS,3SR)-2-(diphenoxyphosphinyl)-3-(1,2,3,6-tetrahydro-1,3-dimethyl-2,6-dioxo-7H-purine-7-yl)succinate

Conditions
ConditionsYield
In acetonitrile at 20℃; for 24h; diastereoselective reaction;95%
theophylline
58-55-9

theophylline

1-bromomethyl-4-nitro-benzene
100-11-8

1-bromomethyl-4-nitro-benzene

1,3-dimethyl-7-(4-nitrobenzyl)xanthine
7278-47-9

1,3-dimethyl-7-(4-nitrobenzyl)xanthine

Conditions
ConditionsYield
With potassium carbonate In N,N-dimethyl-formamide at 20℃; Inert atmosphere; Schlenk technique;95%
With potassium carbonate In N,N-dimethyl-formamide at 100℃; for 4h;
theophylline
58-55-9

theophylline

propynoic acid methyl ester
922-67-8

propynoic acid methyl ester

methyl 2,3-bis(1,3-dimethyl-2,6-dioxo-2,3-dihydro-1H-purin-7(6H)-yl)propanoate

methyl 2,3-bis(1,3-dimethyl-2,6-dioxo-2,3-dihydro-1H-purin-7(6H)-yl)propanoate

Conditions
ConditionsYield
With triphenylphosphine In acetonitrile at 20℃; for 2h;95%
theophylline
58-55-9

theophylline

1-chloro-3-phenyl-2-propyne
3355-31-5

1-chloro-3-phenyl-2-propyne

7-phenylpropargyl-1,3-dimethylxanthine
21622-50-4

7-phenylpropargyl-1,3-dimethylxanthine

Conditions
ConditionsYield
With potassium carbonate In N,N-dimethyl-formamide at 20℃; Inert atmosphere; Schlenk technique;95%
theophylline
58-55-9

theophylline

xanthene-9-carboxylic acid
82-07-5

xanthene-9-carboxylic acid

1,3-dimethyl-7-(9H-xanthen-9-yl)-3,7-dihydro-1H-purine-2,6-dione

1,3-dimethyl-7-(9H-xanthen-9-yl)-3,7-dihydro-1H-purine-2,6-dione

Conditions
ConditionsYield
With 2,4,6-trimethyl-pyridine; tert-butylammonium hexafluorophosphate(V) In dichloromethane for 2.5h; Molecular sieve; Electrochemical reaction;95%
theophylline
58-55-9

theophylline

8-bromotheophylline
10381-75-6

8-bromotheophylline

Conditions
ConditionsYield
With bromine In water; acetic acid at 50℃; for 4h;94.5%
With bromine at 150℃; zuletzt auf 150grad;
With ethanol; bromine
theophylline
58-55-9

theophylline

isopropyl alcohol
67-63-0

isopropyl alcohol

8-(1-hydroxy-1-methyl-ethyl)-1,3-dimethyl-3,7(9)-dihydro-purine-2,6-dione
61639-78-9

8-(1-hydroxy-1-methyl-ethyl)-1,3-dimethyl-3,7(9)-dihydro-purine-2,6-dione

Conditions
ConditionsYield
With acetone at 25℃; for 80h; Product distribution; Mechanism; Irradiation;94%
With acetone at 25℃; for 80h; Irradiation;94%
theophylline
58-55-9

theophylline

8-bromo-1,3-dimethyl-7-(thiiran-2-ylmethyl)-3,7-dihydro-1H-purine-2,6-dione
122773-84-6

8-bromo-1,3-dimethyl-7-(thiiran-2-ylmethyl)-3,7-dihydro-1H-purine-2,6-dione

7-[(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)methyl]-1,3-dimethyl-6,7-dihydro[1,3]thiazolo[2,3-f]purine-2,4(1H,3H)-dione
1239919-39-1

7-[(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)methyl]-1,3-dimethyl-6,7-dihydro[1,3]thiazolo[2,3-f]purine-2,4(1H,3H)-dione

Conditions
ConditionsYield
With potassium hydroxide In ethanol for 3h; Reflux;94%
theophylline
58-55-9

theophylline

diethyl 2-vinylcyclopropane-1,1-dicarboxylate
7686-78-4

diethyl 2-vinylcyclopropane-1,1-dicarboxylate

(E)-diethyl 2-(4-(1,3-dimethyl-2,6-dioxo-2,3-dihydro-1H-purin-7(6H)-yl)but-2-en-1-yl)malonate

(E)-diethyl 2-(4-(1,3-dimethyl-2,6-dioxo-2,3-dihydro-1H-purin-7(6H)-yl)but-2-en-1-yl)malonate

Conditions
ConditionsYield
With tris(dibenzylideneacetone)dipalladium(0) chloroform complex; (2S,3S)-(+)-1,4-bis(diphenylphosphino)-2,3-O-isopropylidene-2,3-butanediol In 1,4-dioxane at 30℃; for 18h; Inert atmosphere; Schlenk technique; Sealed tube;94%
theophylline
58-55-9

theophylline

benzyl bromide
100-39-0

benzyl bromide

7-benzyltheophylline
1807-85-8

7-benzyltheophylline

Conditions
ConditionsYield
With potassium carbonate In N,N-dimethyl-formamide at 20℃; Inert atmosphere; Schlenk technique;93%
With potassium carbonate In N,N-dimethyl-formamide at 20℃; Inert atmosphere; Schlenk technique;93%
With potassium carbonate In N,N-dimethyl-formamide at 35℃; for 16h;87%
theophylline
58-55-9

theophylline

1-chloroacetophenone
532-27-4

1-chloroacetophenone

1,3-dimethyl-7-(2-oxo-2-phenylethyl)-3,7-dihydropurine-2,6-dione
78491-57-3

1,3-dimethyl-7-(2-oxo-2-phenylethyl)-3,7-dihydropurine-2,6-dione

Conditions
ConditionsYield
With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 2h; Alkylation;93%

58-55-9Relevant articles and documents

Coordination polymers as potential solid forms of drugs: Three zinc(ii) coordination polymers of theophylline with biocompatible organic acids

Lou, Benyong,He, Fengdan

, p. 309 - 316 (2013)

The biocompatible organic acids such as acetic acid (Hac), benzoic acid (Hbz) and nicotinic acid (Hnit), have been employed as second ligands to assemble biocompatible coordination polymers of theophylline (Hthp), respectively. As a result, three coordination polymers [Zn2(thp) 2(ac)(OH)]n (1), [Zn2(thp)2(bz)(OH)] n (2) and [Zn(thp)(nit)]∞ (3) have been synthesized through hydrothermal and mechanochemical reactions. Theophylline could be released rapidly in simulated gastroenteric fluid (phosphate-buffered solution, PBS) and slow release of theophylline could be achieved from the three polymers in pure water at 37 °C with continuous stirring.

-

Kostareva et al.

, (1976)

-

Isolation and characterization of 1,3-dimethylisoguanine from the Bermudian sponge Amphimedon viridis

Mitchell,Whitehill,Trapido-Rosenthal,Ireland

, p. 727 - 728 (1997)

The new compound 1,3-dimethylisoguanine has been isolated and characterized from the Bermudian sponge Amphimedon viridis. Chemical conversion of the natural product to theophylline and 2D NMR methods were used to determine the position of the methyl groups on the purine ring. Analysis of the mass spectral fragmentation pattern allowed assignment of the purine ring as isoguanine.

SERS multiplexing of methylxanthine drug isomersviahost-guest size matching and machine learning

Chio, Weng-I Katherine,Dinish, U. S.,Jones, Tabitha,Lee, Tung-Chun,Liu, Jia,Olivo, Malini,Parkin, Ivan P.,Perumal, Jayakumar

supporting information, p. 12624 - 12632 (2021/10/06)

Multiplexed detection and quantification of structurally similar drug molecules, methylxanthine MeX, incl. theobromine TBR, theophylline TPH and caffeine CAF, have been demonstratedviasolution-based surface-enhanced Raman spectroscopy (SERS), achieving highly reproducible SERS signals with detection limits down to ~50 nM for TBR and TPH, and ~1 μM for CAF. Our SERS substrates are formed by aqueous self-assembly of gold nanoparticles (Au NPs) and supramolecular host molecules, cucurbit[n]urils (CBn,n= 7, 8). We demonstrate that the binding constants can be significantly increased using a host-guest size matching approach, which enables effective enrichment of analyte molecules in close proximity to the plasmonic hotspots. The dynamic range and the robustness of the sensing scheme can be extended using machine learning algorithms, which shows promise for potential applications in therapeutic drug monitoring, food processing, forensics and veterinary science.

Synthesis of a new class of bisheterocycles via the Heck reaction of eudesmane type methylene lactones with 8-bromoxanthines

Patrushev, Sergey S.,Rybalova, Tatyana V.,Ivanov, Igor D.,Vavilin, Valentin A.,Shults, Elvira E.

, p. 2717 - 2726 (2017/04/14)

The eudesmane-type methylene lactones (isoalantolactone, alantolactone, 4,15-epoxyisoalantolactone, 2′,2′-dichloro-4H-spiro[cyclopropane-1′,4-eudesma-11(13)-en-8β,12-olide], and alantolactone) react with 8-bromoxanthines (8-bromocaffeine, 8-bromotheobromine, 8-bromo-3-butyltheobromine, 8-bromotheophylline, 8-bromo-9-butyltheophylline) under Heck reaction conditions to produce the target (E)-13-(2,6-dioxo-2,3-dihydro-1H-purin-8-yl)eudesma-4(15),11(13)-dien-8β,12-olides and the subsequent endocyclic isomers - 11-(2,6-dioxo-2,3-dihydro-1H-purin-8-yl)-13-normethyleudecma-4(15)-7(11)-dien-8α,12-olides. It was revealed that the yield and product ratio depends on the reaction conditions and the structure of methylene lactone. The effectiveness of Pd(OAc)2–caffeine catalytic system has been demonstrated in this reaction. The electric eel acetylcholinesterase inhibitory activity of the eudecmanolide-xanthine hybrids was evaluated. Among the new type bisheterocycles compound 27 with butyl and 2-oxodecahydronaphtho[2,3-b]furan-3(2H)-ylidene)methyl substituents at C-7 and C-8 of the xanthine core showed moderate activity with IC50 value of 40?μM.

Fragment Discovery for the Design of Nitrogen Heterocycles as Mycobacterium tuberculosis Dihydrofolate Reductase Inhibitors

Shelke, Rupesh U.,Degani, Mariam S.,Raju, Archana,Ray, Mukti Kanta,Rajan, Mysore G. R.

, p. 602 - 613 (2016/08/28)

Fragment-based drug design was used to identify Mycobacterium tuberculosis (Mtb) dihydrofolate reductase (DHFR) inhibitors. Screening of ligands against the Mtb DHFR enzyme resulted in the identification of multiple fragment hits with IC50 values in the range of 38–90 μM versus Mtb DHFR and minimum inhibitory concentration (MIC) values in the range of 31.5–125 μg/mL. These fragment scaffolds would be useful for anti-tubercular drug design.

Post a RFQ

Enter 15 to 2000 letters.Word count: 0 letters

Attach files(File Format: Jpeg, Jpg, Gif, Png, PDF, PPT, Zip, Rar,Word or Excel Maximum File Size: 3MB)

1

What can I do for you?
Get Best Price

Get Best Price for 58-55-9