• M. I. Romanenko
  • M. V. Nazarenko
  • D. G. Ivanchenko
  • O. A. Pakhomova
  • A. Yu. Cherchesova



xanthine, organicsynthesis, NMR-spectroscopy



It has been foundearlier[1-5]that 8-substituted of 7-(2-hydroxy-3-R-oxypropyl-1)-3-methylxanthine show rather high diuretic, anti-inflammatory, analgesic, antioxidant and hypolipidemic action.Meanwhile, works of international researchers reveal data on synthesis of other equivalents of7-(2-hydroxy-3-R-propyl-1)-xanthine, which demonstratebroncholytic, antiasthmatic and antianaphylacticeffects[6-8] and can be used as anti-inflammatory medicines[9].

The aim of this work is to develop unique methods for synthesizing8-aminoderivativesof 7-(2-hydroxy-3-i-propoxypropyl-1)-3-methylxanthines, the potential bioactive compounds yet undescribed in scientific works, and to study their physical and chemical peculiarities.

Materials and Methods of Research

Themeltingpointhasbeendeterminedwiththehelpofanopencapillary methodwithTAPdevice(M).Elementalanalysishasbeenperformedwiththe help of the instrument ElementarVario L cube, NMR-spectra have been taken on a spectrometer Bruker SF-400 (operating frequency of 400 MHz, solvent DMSO-d6, internal standard – TMS).These data correspond to thecalculated elemental analysis.

Results and their discussion

Similarly to the method of synthesizing 7-(3-aryloxy-2-hydroxypropyl-1)-8-bromoxanthines[11], described earlier,8-bromo-7-(2-hydroxy-3-i-propoxypropyl-1)-3-methylxanthine, undescribed before(2) (scheme 1) was synthesized through the reaction of 8-bromo-3-methylxanthine(1) [10] with isopropoxymethyloxirane in butanol-1in the presence of N,N-dimethylbenzylamine.

The presence of a substitute in position 7 of molecule of 8-bromo-3-methylxanthine, and the data of PMR-spectroscopy only attest to the fact that obtained bromalcohol (2) in contrast to the initial compound (1) is not dissolvedat room temperature in water solution of ammonia.

Presence of bromine atom in position 8 allows to put in variousO-, N-, S-containing substitutes in xanthine molecule and consequently expect to see changes and manifestation of a certain biological effect in obtained derivatives.

It has been found that short-period boiling of bromalcohol (2) with primary amines in water or waterdioxaneleads to a formation of relevant 8-aminosubstituted 7-(2-hydroxy-3-i-propoxypropyl-1)-3-methylxanthine(3-12). The structure of synthesized aminalcohols 3-12 has been proved based on their PMR spectra analysis.


For further synthetic research, along with convenient synthones there have also been elaborated easy-to-apply laboratory methods for synthesizing8-amino-7-(2-hydroxy-3-i-propoxypropyl-1)-3-methylxanthines, which are potential bioactive compounds.

The structure of synthesized compounds has been proved by elemental analysis, IR- and NMR-spectroscopydata. 


Shkoda, O. S., Romanenko, N. I., Samura, I. B., Samura, B.A., & Sapronova, A. Yu. (2007) Syntez ta biolohichni vlastyvosti 8-aminozamishchenykh 7-β-hydroksy-γ-(3-metylfenok-si)propil-3-metyl ksantynu [The synthesis and biological properties of 8-aminosubstituted of 7-β-hydroxy-γ-(3’-methylphyenoxypropyl)-3-methylxanthine]. Visnyk farmatsii, 1, 3–8. [in Ukrainian].

Shkoda, O. S., Romanenko, M. I., Ivanchenko, D. H., Samura, B. B., Samura, I. B., Samura, B. A., et al. (2007) [Synthesis and pharmacological action of 8-aminosubstituted of 7-β-hydroxy-γ-(o-methylphenoxy)-propyl-3-methylxanthine]. Farmatsevtychnyi chasopys, 1, 36–40. [in Ukrainian].

Ostapenko, A. O., Belaj, I. M., Romanenko, N. I. (2011) Gipogliceridemicheskaya aktivnost' 8-r-7-(2-gidroksi-3-izoproksi)propil-3-metilksantinov [Hypoglyceridemic activity of 8-R-7-(2-hydroxyisopropoxy)propyl-3-methylxanthynes]. Aktualni pytannia farmatsevtychnoi i medychnoi nauky ta praktyky, 2, 9–12. [in Ukrainian].

Cherchesova, A. Yu., Romanenko, M. I., Samura, A. B., & Taran, A. V. (2011) Syntez i vyvchennia diuretychnoi dii pokhidnykh 7-β-hidroksy-γ-(4-khlorofenoksy)propil-3-metyl-8-tioksantynu [Synthesis and study of the diuretic action of 7-β-hydroxy-γ-(4'-chlorophenoxy)propyl-3-methyl-8-thioxanthine derivatives]. Aktualni pytannia farmatsevtychnoi i medychnoi nauky ta praktyky, 2, 41–44. [in Ukrainian].

Cherchesova, A. Yu., Romanenko, M. I., Martynyuk, O. A., Kremzer, A. A., Samura, B. A., & Taran, A. V. (2011) Syntez, fizyko-khimichni ta biolohichni vlastyvosti 8-ilidenhidrazynopokhidnykh 7-β-hidroksy-γ-(p-khlorofenoksy)propilksantyniv [Synthesis, physical, chemical and biological properties of ilidenhydrazynoderivatives of 8-7-β-hydroxy-γ-(p-hlorofenoxy)propylxanthines]. Aktualni pytannia farmatsevtychnoi i medychnoi nauky ta praktyky,3, 90–94. [in Ukrainian].

Czarnecki, R., Librowski, T., & Pawlowski, M. (2001) Antianaphylactic and antiasthmatic properties of new piperazinyl 7-(β-hydroxypropyl)theophylline derivatives in guinea pigs. Pol. J. Pharmacol., 53, P. 131–136.

Danila, G., Profire, L., & Costuleanu, M. (2000) Researches on pharmacological properties of some new xanthine derivatives. Rev. Med. Chir. Soc. Med. Nat. Iasi., 104(4), 131–136.

Profire, L., Sunel, V., Lupascu, D., Baican, M. C., Bibire, N., & Vasile, C. (2010) New theophylline derivatives with potential pharmacological activity. Farmacia, 58(2), 170–176.

Danila, G., Profire, L., & Costuleanu, M. (2002) Xanthine derivative compounds potential activity in inflammatory process. Rev. Med. Chir. Soc. Med. Nat. Iasi., 107(2), 391–396.

Romanenko, M. I., Cherchesova, A. Yu., Martyniuk, O. A., Ivanchenko, D. G. (2011) Syntez 8-bromo-7-β-hidroksy-γ-(4′-khlorofenoksy)propilksantyniv i vyvchennia yikh reaktsii z diaminamy ta aminokyslotamy [Synthesis of 8-bromo-7-β-hydroxy-γ-(4'-chlorophenoxy)propylxanthines and studying their reactions with diamines and amino acids]. Zaporozhskij medicinskij zhurnal, 13(1), 90–93. [in Ukrainian].

Romanenko, M. I., Cherchesova, A. Yu., Martyniuk, O. A., Riabytskyi, O. B., Vasiuk, S. A., & Korzhova, A. S. (2013) Syntez, spektralni ta stereokhimichni vlastyvosti benzylidenhidrazydiv 7-β-hidroksy-γ-(p-khlorofenoksy)propilteofilinil-8-tiootstovoi kysloty [Synthesis, spectral and stereochemical properties of 7-β-hydroxy-γ-(p-chlorophenoxy)propyl-theophyllinyl-8-thioacetic acid benzyliden hydrazides]. Aktualni pytannia farmatsevtychnoi i medychnoi nauky ta praktyky, 1, 63–68. [in Ukrainian].

How to Cite

Romanenko MI, Nazarenko MV, Ivanchenko DG, Pakhomova OA, Cherchesova AY. SYNTHESISAND PHYSICAL-CHEMICAL PROPERTIES OF 8-AMINO-7-(2-HYDROXY-3-i-PROPOXYPROPYL-1)-3-METHYLXANTHINES. Current issues in pharmacy and medicine: science and practice [Internet]. 2014Nov.12 [cited 2024Jun.21];(3). Available from:



Pharmacognosy and chemistry of natural compounds