41078-02-8

Basic information

• Product Name: ENPROFYLLINE
• Synonyms: 3-Propylxanthfine;Enprofyllilie;3-Propyl 3,7-dihydro-1H-purine-2,6-dione;3-Propyl-7H-purine-2,6(1H,3H)-dione;3-propyl-7H-purine-2,6-dione;3-propyl-7H-purine-2,6-quinone;1H-Purine-2,6-dione, 3,9-dihydro-3-propyl-;3-Propyl-1H-purine-2,6(3H,7H)-dione
• CAS NO: 41078-02-8
• Molecular Formula: C₈H₁₀N₄O₂
• Molecular Weight: 194.19
• EINECS: 255-201-8
• Mol File: 41078-02-8.mol

Chemical Properties

• Appearance: white/solid
• Density: 1.367 g/cm³
• Refractive Index: 1.583
• Storage Temp.: 2-8°C
• Solubility: DMSO: soluble
• CAS DataBase Reference: ENPROFYLLINE(CAS DataBase Reference)
• NIST Chemistry Reference: ENPROFYLLINE(41078-02-8)
• EPA Substance Registry System: ENPROFYLLINE(41078-02-8)

Safety Data

• Hazard Codes: Xn
• Statements: 20/21/22
• Safety Statements: 36
• WGK Germany: 3
• RTECS: UO8439700
• Hazardous Substances Data: 41078-02-8(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
ENPROFYLLINE is used as a bronchodilator for the symptomatic treatment of asthma and chronic obstructive pulmonary disease (COPD). It helps in relaxing the smooth muscles in the airways, thereby reducing bronchial hyperresponsiveness and improving respiratory function.
Used in Cerebrovascular Insufficiency Treatment:
ENPROFYLLINE is used as a therapeutic agent for managing cerebrovascular insufficiency. Its adenosine receptor antagonism and cAMP phosphodiesterase inhibition properties contribute to improved blood flow and oxygenation in the brain, alleviating symptoms associated with this condition.
Used in Sickle Cell Disease Management:
ENPROFYLLINE is used as a treatment option for sickle cell disease, where it helps in reducing the frequency and severity of painful crises. Its bronchodilator and vasodilator effects can improve blood flow and oxygenation, mitigating the complications of the disease.
Used in Diabetic Neuropathy Management:
ENPROFYLLINE is used as a therapeutic agent for the management of diabetic neuropathy. Its ability to improve blood flow and reduce inflammation can help alleviate the pain and discomfort associated with this condition.
Used in Respiratory Medicine:
ENPROFYLLINE is used as a bronchodilator in respiratory medicine, specifically for the treatment of asthma and chronic obstructive pulmonary disease (COPD). Its adenosine receptor antagonism and cAMP phosphodiesterase inhibition properties help in reducing bronchial hyperresponsiveness and improving lung function in patients with these conditions.

InChI:InChI=1/C8H10N4O2/c1-2-3-12-6-5(9-4-10-6)7(13)11-8(12)14/h4H,2-3H2,1H3,(H,9,10)(H,11,13,14)

Upstream product

• 53681-47-3 6-amino-1-propyl-1H-pyrimidine-2,4-dione 
• 76194-07-5 5,6-diamino 1-n-propyl-1,3-dihydropyrimidine-2,4-dione 
• 76194-05-3 1-propyl-6-amino-5-nitrosouracil 
• 14036-06-7 diethoxymethyl acetate 
• 76194-09-7 6-amino-5-formamido-1-n-propyl-2,4-(1H,3H)-pyrimidinedione 

Downstream Products

• 7464-76-8 3-Propyl-1,7-dimethylxanthine 
• 251918-41-9 [2-(2,6-dioxo-3-propyl-1,2,3,6-tetrahydro-purin-7-yl)-ethyl]-carbamic acid benzyl ester 
• 251918-42-0 [3-(2,6-dioxo-3-propyl-1,2,3,6-tetrahydro-purin-7-yl)-propyl]-carbamic acid benzyl ester 
• 251918-43-1 [4-(2,6-dioxo-3-propyl-1,2,3,6-tetrahydro-purin-7-yl)-butyl]-carbamic acid benzyl ester 
• 137296-34-5 3,7-dihydro-7-(4-methoxybenzyl)-1-(2-propenyl)-3-propyl-1H-purine-2,6-dione 
• 137296-35-6 1-But-3-enyl-7-(4-methoxy-benzyl)-3-propyl-3,7-dihydro-purine-2,6-dione 
• 137296-28-7 1-(2-Hydroxy-ethyl)-7-(4-methoxy-benzyl)-3-propyl-3,7-dihydro-purine-2,6-dione 
• 137296-24-3 [7-(4-Methoxy-benzyl)-2,6-dioxo-3-propyl-2,3,6,7-tetrahydro-purin-1-yl]-acetonitrile 
• 137296-27-6 7-(4-Methoxy-benzyl)-1-(3-oxo-butyl)-3-propyl-3,7-dihydro-purine-2,6-dione 
• 137296-32-3 7-(4-Methoxy-benzyl)-1-(2-methoxy-ethyl)-3-propyl-3,7-dihydro-purine-2,6-dione 
• 137296-29-8 1-(3-Hydroxy-propyl)-7-(4-methoxy-benzyl)-3-propyl-3,7-dihydro-purine-2,6-dione 
• 137296-26-5 7-(4-Methoxy-benzyl)-1-(2-oxo-propyl)-3-propyl-3,7-dihydro-purine-2,6-dione 
• 137296-25-4 3-[7-(4-Methoxy-benzyl)-2,6-dioxo-3-propyl-2,3,6,7-tetrahydro-purin-1-yl]-propionitrile 
• 1026686-34-9 1-(2-Ethoxy-ethyl)-7-(4-methoxy-benzyl)-3-propyl-3,7-dihydro-purine-2,6-dione 

Relevant articles and documents

Compounds for inhibition of ceramide-mediated signal transduction

Novel, heterocyclic compounds having at least one ring nitrogen, disclosed side chains and, in some embodiments, an oxygen ortho to the ring nitrogen inhibit inflammatory responses associated with TNF-α and fibroblast proliferation in vivo and in vitro. The compounds of the invention neither appreciably inhibit the activity of cAMP phosphodiesterase nor the hydrolysis of phosphatidic acid, and are neither cytotoxic nor cytostatic. Preferred compounds of the invention are esters. Methods for the use of the novel compounds to inhibit ceramide-mediated intracellular responses in stimuli in vivo (particularly TN-α) are also described. The methods are expected to be of use in reducing inflammatory responses (for example, after angioplasty), in limiting fibrosis (for example, of the liver in cirrhosis), in inhibiting cell senescence, cell apoptosis and UV induced cutaneous immune suppression. Compounds having enhanced water solubility are also described.

Compounds for ceramide-mediated signal transduction

Novel isoquinoloine compounds inhibit inflammatory responses associated with TNF-α and fibroblast proliferation in vivo and in vitro. The compounds of the invention neither appreciably inhibit the activity of cAMP phosphodiesterase nor the hydrolysis of phosphatidic acid, and are neither cytotoxic nor cytostatic. Preferred compounds of the invention are esters. Methods for the use of the novel compounds to inhibit ceramide-mediated intracellular responses to stimuli in vivo (particularly TNF-α) are also described. The methods are expected to be of use in reducing inflammatory responses (for example, after angioplasty), in limiting fibrosis (for example, of the liver in cirrhosis), in inhibiting cell senescence, cell apoptosis and UV induced cutaneous immune suppression.

Compounds for inhibition of ceramide-mediated signal transduction

Novel, heterocyclic compounds having at least one ring nitrogen, disclosed side chains and, in some embodiments, an oxygen ortho to the ring nitrogen inhibit inflammatory responses associated with TNF-α and fibroblast proliferation in vivo and in vitro. The compounds of the invention neither appreciably inhibit the activity of cAMP phosphodiesterase nor the hydrolysis of phosphatidic acid, and are neither cytotoxic nor cytostatic. Preferred compounds of the invention are esters. Methods for the use of the novel compounds to inhibit ceramide-mediated intracellular responses in stimuli in vivo (particularly TN-α) are also described. The methods are expected to be of use in reducing inflammatory responses (for example, after angioplasty), in limiting fibrosis (for example, of the liver in cirrhosis), in inhibiting cell senescence, cell apoptosis and UV induced cutaneous immune suppression. Compounds having enhanced water solubility are also described.

COMPOUNDS FOR INHIBITION OF CERAMIDE-MEDIATED SIGNAL TRANSDUCTION

Novel, heterocyclic compounds having at least one ring nitrogen, disclosed side chains and, in some embodiments, an oxygen ortho to the ring nitrogen inhibit inflammatory responses associated with TNF-alpha and fibroblast proliferation in vivo and in vitro. The compounds of the invention neither appreciably inhibit the activity of cAMP phosphodiesterase nor the hydrolysis of phosphatidic acid, and are neither cytotoxic nor cytostatic. Preferred compounds of the invention are esters. Methods for the use of the novel compounds to inhibit ceramide-mediated intracellular responses to stimuli in vivo (particularly TNF-alpha) are also described. The methods are expected to be of use in reducing inflammatory responses (for example, after angioplasty), in limiting fibrosis (for example, of the liver in cirrhosis), in inhibiting cell senescence, cell apoptosis and UV induced cutaneous immune suppression.

Substituted xanthines, pteridinediones, and related compounds as potential antiinflammatory agents. Synthesis and biological evaluation of inhibitors of tumor necrosis factor α

A series of analogues of pentoxifylline metabolites were prepared in the purine, pteridine, [1,2,5]-thiadiazolo[3,4-d]pyrimidine, and quinazoline ring systems and evaluated for their ability to inhibit the production of tumor necrosis factor-α (TNFα) in human peripheral blood monocytes stimulated with bacterial lipopolysaccharide (LPS). The more active compounds were also tested for inhibition of cyclic AMP phosphodiesterase type IV (PDE IV) from human neutrophils in order to help determine their mechanism of action. Selected compounds which showed good activity in the in vitro TNFα assay were evaluated in an in vivo LPS-induced leukopenia model in mice. The most potent compounds in the TNFα assay, 6, 31, and 58, inhibited TNFα production at an IC50 of approximately 5 μM for each. Compound 58 was a very poor inhibitor of PDE IV but was the most active at preventing the leukopenia induced by TNFα in mice, providing more than 60% protection at 50 mg/kg. Thus, compounds such as 58, which are good inhibitors of TNFα production but are devoid of PDE IV inhibitory properties, may have potential as new antiinflammatory agents.

Effects of Alkyl Substitutions of Xanthine Skeleton on Bronchodilation

Structure-activity relationships in a series of 1,3,7-trialkyl-xanthine were studied with guinea pigs.Relaxant actions in the tracheal muscle were increased with alkyl chain length at the 1- and 3-positions of the xanthine skeleton, but decreased by alkylation at the 7-position.Positive chronotropic actions in the right atrium were potentiated with 3-alkyl chain length but tended to decrease with 1-alkylation and diminish by 7-substitution.Consequently, while the 1- and 3-substitutions were equally important for the tracheal smooth muscle relaxation, the substitution at the 1-position was more important than the 3-substitution for bronchoselectivity.The 7-alkylation may be significant to cancel heart stimulation.There were good correlations between the smooth muscle relexant action and the cyclic AMP-PDE inhibitory activity in 3-substituents and the affinity for adenosine (A1)receptors in 1-,3-, and 7-substituents.This suggests that not only the cyclic AMP-PDE inhibitory activity but also the adenosine antagonistic activity is important in the bronchodilatory effects of alkylxanthines.Among these xanthine derivatives, 1-butyl-3-propylxanthine and its 7-methylated derivative showed high bronchoselectivity in the in vitro and in vivo experiments compared to theophylline and enprofylline and may be new candidates for bronchodilator.

Process for preparing a purine derivative

A method for the preparation of enprofylline is disclosed, which method comprises (a) treating 6-amino-1-n-propyl-2,4-(1H,3H)-pyrimidinedione in formic acid with sodium nitrite in the presence of a catalyst to the formation of 6-amino-5-formamido-1-n-propyl-2,4-(1H,3H)-pyrimidinedione and (b) performing a ring-closure reaction on the formed 6-amino-5-formamido-1-n-propyl-2,4-(1H,3H)-pyrimidinedione to the formation of 3,7-dihydro-3-n-propyl-1H-purin-2,6-dione.

Method and pharmaceutical preparation for treating chronic obstructive airway disease and cardiac disease, and intermediates for the preparation of therapeutically active xanthine derivatives

A method for the treatment of chronic obstructive airway disease or cardiac disease, characterized by the administration of a compound of the formula STR1 wherein R is n-propyl, n-butyl or isobutyl or a therapeutically acceptable salt thereof.