• Elena Welchinskaya Bogomolets National Medical University in Kiev


Problemofthetreatmentof man’scancerandsearchoftheeffective, withalittletoxicityantitumourmedicalproducts,isonefromtheimportant taskatthecontemporaneous medicine and pharmaceutical chemistry. Chemicalmodificationofmolecularof5-bromouracilewithnextinvestigationoftoxicity and antitumour activityofits newderivativeswhichsynthesized is described. Physical-chemical, statistical pharmacological, toxicological methods were used. A strongly antitumour effect has been discovered for bis-derivative of 5-bromouracile for the first time. A new convenient methods for the preparation of new mono- and bis-derivatives of 5-bromouracile with 1,1,1-trifluoro-2-bromo-2-chloroethane (ftorotan) and 1,1-diethylcarboxy-2-chloro-2-trifluoromethylethylene is described. The reactions are catalyzed by the DB-18-crown-6-complex. It was tested on the heterotransplantates of man’s glioma cancer of brain (by Bogden’s under capsule-method). It is permits to consider the new bis-derivative of 5-bromouracile as physiological active with a perspective investigation as potential antitumour drugs for treatment of man in future.


Adjei, A. A. (1999). Review of pharmacology and clinical activity of new chemotherapy agents for the treatment of colorectal cancer. Clinical Pharmacology, Vol. 48, p. 265-277.

Abou – Gharbia, M. & Patel – Usha, R. (Eds.). (1988). Polycyclic aryl- and heteroarylpiperazinyl imides as 5-HT1A receptor ligands and potential anxiolytic agents: synthesis and structure-activity relationship studies. Journal of Medical Chemistry, Vol. 31 (7), p. 1382-1385.

Аlоnso, R., Shaw G. & Wright D. (1984). Thermal addition of heterocycles to bicyclic reagents. Journal Chemical Society Perkin Translation, l (12), p. 2795-2799.

Anderson, N. & Lokich, J. (1992). Controversial issues in 5-fluorouracil infusion use. Dose intensity, treatment duration, and cost comparisons. Cancer, 70, p. 998-1002.

Anttila, M. I., Sotaniemi, E. A. & Kairaluoma, M. I. (Eds.). (1983). Pharmacokinetics of ftorafur after intravenous and oral administration. Cancer Chemotherapy and Pharmacology, 10, p. 150–153.

Au, J. L., Wu, A. T. & Friedman, M. A. (Eds.) (1979). Pharmacokinetics and metabolism of ftorafur in man. Cancer Treatment Rep., 63, p. 343–350.

Baba, H., Kohnoe, S. & Endo, K. (Eds.) (2000). State of the treatment for gastrointestinal cancer. Gan To Kagaku Ryoho., Vol. 27, p. 1233-1246.

Barlow, R. (1959). Vvedenie v himicheskyy farmacologiy [Introduction to chemical pharmacology]. Moscow, Russia: Foreign literature.

Benz, C., Tills, T. & Tattelman, E. (Eds.) (1982). Optimal schedule of methotrexate and 5-fluorouracil in human breast cancer. Cancer Research, Vol. 42, p. 2081-2086.

Brody, G. L. & Sweet, R. B. (1963). Halothane anesthesia as a possible cause of massive hepatic necrosis. Anesthesiology, Vol. 24, p. 29–37.

Brown, B. R. & Sipes, I. G. (1977). Biotransformation and hepatotoxicity of halothane. Biochemical Pharmacology, Vol. 26, p. 2091–2094.

Longley, D. B. & Harkin, D. P. (2004). Mechanisms of action of 5-fluorouracil. Nature Revues Cancer, Vol. 4, p. 230-238.

Noordhuis, P. & Holwerda, U. (2004). 5-fluorouracil incorporation info RNA and DNA in relation to thymidilate synthetase inhibition human colorectal cancer. Annals of oncology, Vol. 15, p. 1025-1032. PMid:15205195

Perevodchikovoy, N. I. (Ed.) (2005). Chimioterapia rakovih zabolevaniy [Chemotherapy of cancerous diseases] (2nd edition). Moscow, Russia: Practical medicine.

Prozorovskiy, V. B., Prozorovskiy, V. P. & Demchenko, V. М. (1978). Ekspress-metod opredeleniya sredney effektivnosty dozy i ego oshibka [Express - method of middle effective dose determination and its mistake]. Pharmacology and toxicology, Vol. 41 (4), p. 407-509.

Sophinoy, Z. P., Sophina, A. B., Goldina, A. & Kmeina, A. (Eds.) (1979). Eksperimentalnay ocenka protivoopuholevyh preparatov v SSSR i SShA [The experimental value of the antitumour drugs in USSR and USA]. Moscow, Russia: Medicine.

Welchinska, H. V., Piecuszak, B. I. & Kovalenko, E. A. (Eds.) (2003). Biologicheskaya aktivnost bakterialnih lektinov i ih molekularnih kompleksov s geterotsyklicheskimy bis-adduktamy [Biological activity of bacterial lectins and their molecular complexes with heterocyclic bis-adducts]. Microbiological journal, Vol. 65 (6), p. 20-25.

Yagupolskiy, L. M. (1988). Aromaticheskie i geterocyklicheskie soedineniya s ftorsoderjashimy zamestitelyamy [Aromatic and heterocyclic compounds with fluorocontaining substitutes]. (p. 90–105). Kiev, Ukaine: Naukova dumka.