603-00-9

Basic information

• Product Name: PROXYPHYLLINE
• Synonyms: 1,3-Dimethyl-7-(2-hydroxypropyl)xanthine;1H-Purine-2,6-dione, 3,7-dihydro-1,3-dimethyl-7-(2-hydroxypropyl)-;1H-Purine-2,6-dione, 3,7-dihydro-7-(2-hydroxypropyl)-1,3-dimethyl-;2-Hydroxypropyl-7-theophylline;3,7-dihydro-1,3-dimethyl-7-(2-hydroxypropyl)-1h-purine-6-dione;3,7-Dihydro-7-(2-hydroxypropyl)-1,3-dimethyl-1H-purine-2,6-dione;3,7-dihydro-7-(2-hydroxypropyl)-1,3-dimethyl-1h-purine-6-dione;7-(2-Hydroxypropyl)-1,3-dimethyl-3,7-dihydro-1H-purine-2,6-dione
• CAS NO: 603-00-9
• Molecular Formula: C₁₀H₁₄N₄O₃
• Molecular Weight: 238.24
• EINECS: 210-028-7
• Product Categories: Heterocycles;Intermediates & Fine Chemicals;Metabolites & Impurities;Pharmaceuticals
• Mol File: 603-00-9.mol
• Article Data: 5

Chemical Properties

• Melting Point: 134-136°C
• Boiling Point: 487.2ºC
• Flash Point: 248.5ºC
• Appearance: /
• Density: 1.46 g/cm³
• Vapor Pressure: 2.63E-10mmHg at 25°C
• Refractive Index: 1.664
• Storage Temp.: Refrigerator
• Solubility: Solution S is clear (2.2.1) and colourless (2.2.2, Method II).
• PKA: 14.55±0.20(Predicted)
• Water Solubility: 285.7g/L(temperature not stated)
• Merck: 14,7905
• CAS DataBase Reference: PROXYPHYLLINE(CAS DataBase Reference)
• NIST Chemistry Reference: PROXYPHYLLINE(603-00-9)
• EPA Substance Registry System: PROXYPHYLLINE(603-00-9)

Safety Data

• Hazard Codes: Xn
• Statements: 22
• Safety Statements: 36
• WGK Germany: 3
• RTECS: XH5907500
• Hazardous Substances Data: 603-00-9(Hazardous Substances Data)

Usage

Chemical Properties

White Solid

Uses

A metabolite of Theophylline in human plasma.

Biological Activity

ki: 82 nm for bovine brain a1 adenosine receptorproxyphylline is an a1 adenosine receptor antagonist.the a1 adenosine receptor, the best characterized purinergic receptor family, can mediate responses via multiple pertussis toxin-sensitive gtp binding proteins to various different effectors.

in vitro

previous study showed that proxyphylline could selectively antagonize a1 adenosine receptors versus a2 adenosine receptors (ki = 850 μm for platelets) [1].

in vivo

in a previous study, rats that were allodynic following the vincristine injections were randomly allocated into four groups. theoesberiven f (a combination of proxyphylline and melilotus extract) was administered to rats. results showed that the decreased paw withdrawal threshold induced by vincristine injection was increased by theoesberiven f treatment and the increased withdrawal frequency to cold stimuli was also reduced by theoesberiven f treatment [2].

Purification Methods

Crystallise it from EtOH, aqueous MeOH or EtOAc. Roth Archiv Pharmazie 292 234 1959, Zelnik et al. Bull Soc Chim Fr 1733 1956, Beilstein 26 III/IV 2366.]

references

[1] u. schwabe, d. ukena and m. j. lohse. xanthine derivatives as antagonists at a1 and a2 adenosine receptors. naunyn-schmiedeberg's arch.pharmacol. 330,212-221 (1985).[2] s. bang, y. s. kim and s. r. jeong. anti-allodynic effect of theoesberiven f in a vincristine-induced neuropathy model. exp. ther. med. 12(2), 799-803 (2016). [3] selvig k. pharmacokinetics of proxyphylline in adults after intravenous and oral administration. eur j clin pharmacol. 1981 jan;19(2):149-55.

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

Upstream product

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

Downstream Products

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

Relevant articles and documents

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.

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.

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.