86540-95-6

Usage

Uses

Used in Respiratory Medicine:
(S)-Proxyphylline is used as a bronchodilator for treating asthma, COPD, and other respiratory conditions. It helps in relaxing the muscles in the airways, allowing for easier breathing.
Used in Neonatology:
(S)-Proxyphylline is used as a respiratory stimulant for treating apnea of prematurity in premature infants, stimulating their breathing and improving their overall respiratory function.

InChI:InChI=1/C10H14N4O3/c1-6(15)4-14-5-11-8-7(14)9(16)13(3)10(17)12(8)2/h5-6,15H,4H2,1-3H3/t6-/m0/s1

Upstream product

• 10226-64-9 7-Acetonyltheophylline 
• 127-00-4 1-Chloro-2-propanol 
• 58-55-9 theophylline 
• 4254-15-3 (S)-1,2-Propanediol 
• 68696-86-6 N⁷-tosyltheophylline 
• 57-55-6 propylene glycol 
• 75-56-9 methyloxirane 
• 19686-73-8 1-bromo-2-propanol 

Downstream Products

• 137138-15-9 Propoxyphyllintosylat 
• 137138-18-2 7-<2-(1-Methyl-2-phenyl-ethylamino)-propyl>-theophyllin 

Relevant academic research and scientific papers

Chemoenzymatic Synthesis of Proxyphylline Enantiomers

A novel synthetic route for preparation of proxyphylline enantiomers using a kinetic resolution (KR) procedure as the key step is presented. The reactions were catalyzed by immobilized Candida antarctica lipase B in acetonitrile. Three types of reactions were examined: (i) enantioselective transesterification of racemic proxyphylline with vinyl acetate as well as (ii) hydrolysis and (iii) methanolysis of its esters. The influence of reaction conditions on the substrate conversion and enantiomeric purity of the products were investigated. Studies on analytical scale reactions revealed that the titled API enantiomers could be successfully obtained with excellent enantiomeric excess (up to >99% ee). The process was easily conducted on a 5 g scale at 100 g/L. In a preparative-scale reaction, unreacted (S)-(+)-butanoate (97% ee) and (R)-(-)-alcohol (96% ee) were obtained after 2 days in yields of 45% and 46%, respectively. When the reaction time was extended to 6 days, (S)-(+)-butanoate was isolated in >99% ee and acceptable high enantioselectivity (E = 90). Importantly, the KR's products could be conveniently isolated by exploiting varying solubility of the ester/alcohol in acetonitrile at room temperature. In addition, a chiral preference of the CAL-B active site for the R-enantiomer was rationalized by in sillico docking studies.

N 7-Tosyltheophylline (TsTh): A highly efficient reagent for the one-pot synthesis of n 7-alkyltheophyllines from alcohols

A convenient and highly efficient one-pot N-alkylation of theophylline from alcohols via N 7-tosyltheophylline (TsTh) is described. In this protocol, the treatment of primary and/or secondary alcohols with a mixture of TsTh and 1,8-diazabicyclo[5.4.0]undec-7-ene in refluxing acetonitrile affords the corresponding N 7-alkyltheophylline in good to excellent yields; the reaction was optimized for solvent and base. This methodology is highly efficient for various structurally diverse primary and secondary alcohols. A plausible mechanism for the one-pot N-alkylation of theophylline with alcohols via TsTh has been suggested. Georg Thieme Verlag Stuttgart New York.

Method for treating benign prostate hyperplasia

A method of treating and/or preventing renal dysfunction in a patient, such as renal colic or contrast nephropathy by administering to a patient, a compound of the formula: is described herein. Administration of dyphylline in a sustained release oral dosage form is preferred.

Method of kidney treatment

A method of treating and/or preventing renal dysfunction in a patient, such as renal colic or contrast nephropathy by administering to a patient, a compound of the formula: is described herein. Administration of dyphylline in a sustained release oral dosage form is preferred.

Potentiation of cADPR-induced Ca2+-release by methylxanthine analogues

Caffeine and other methylxanthines are known to induce Ca2+-release from intracellular stores via the ryanodine receptor. In the present work, a range of caffeine analogues, in which methyl groups at the 1 and 7 positions were replaced with alkyl chains containing different functional groups (oxo, hydroxyl, propargyl, ester, and acids), were synthesized. These compounds were then screened for their ability to potentiate Ca2+-release induced by cADPR (an endogenous modulator of ryanodine receptors) in sea urchin egg homogenates. Two of the synthesized methylxanthines, 1,3-dimethyl-7-(7- hydroxyoctyl)xanthine (37) and 3-methyl-7-(7-oxooctyl)-1-propargylxanthine (66), were shown to be more potent than caffeine in potentiating cADPR- induced Ca2+-release, while 1,3-dimethyl-7-(5-ethylcarboxypentyl)xanthine (14) was shown to be more efficacious. The development of new methylxanthine analogues may lead to a better understanding of ryanodine receptor function and could possibly provide novel therapeutic agents.

Optical resolution, absolute configuration, and activity of the enantiomers of proxyphylline

The enantiomers of proxyphylline have been separated via their corresponding camphanates. Synthesis of (+)-proxyphylline from theophylline and (S)-propylene oxide derived from (S)-lactic acid established the absolute configuration of the (+) and (-) isomer as S and R, respectively. The activity of the enantiomers as cyclic nucleotide phosphodiesterase inhibitors was tested in human lung tissue homogenate. No differences were found either between the two enantiomers or between the enantiomers and racemic proxyphylline.