Chemopreventive compounds and a preparation method and use there

Details Chemopreventive compounds and a preparation method and use there Chemopreventive compounds and a preparation method and use there

1995-06-15

1997-08-19

Bernhardt, Emily

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Having -c-, wherein x is chalcogen, bonded directly to...

514252, 544405, 544408, A61K 31495, C07D24118, C07D40912

Patent

active

056589131

DESCRIPTION:

BRIEF SUMMARY
This application is a 371 of PCT/KR 94/0144 filed Oct. 21, 1994.


BACKGROUND OF THE INVENTION

1. Field of the Invention
The present invention relates to a novel useful compound, a use thereof and a preparation method thereof. More particularly, it relates to a novel compound having chemopreventive activity and to a method for preparing the same and a composition comprising the same as an active ingredient.
2. Description of the Prior Art
A living body has functions to excrete xenobiotics by inactivating them or reducing lipophilicity thereof to transform into hydrophilic substances. These functions are performed by mediation of various enzymes and may be classified depending on the kind of enzymes into two groups: Phase I reaction(oxidation, reduction and hydrolysis, etc) and phase II reaction(conjugation). Sometimes, these functions are adversely performed to form a more reactive compound which may cause damages to macromolecules in the cells, thus inducing cancer formation.
Particularly, cytochromes P-450(CYP 450), which are present in smooth endoplasmic reticulum of hepatic cells and other cells, are an oxidation enzymes involved in phase I reaction. Cytochromes P-450 oxidize steroids, fatty acids and amines which are synthesized in a living body as well as metabolize medicines, chemical carcinogens and mutagens to more hydrophilic execretable substances.. Nevertheless, cytochromes P-450 sometimes activate xenobiotics, which causes damages to macromolecules and consequently induce a cancer formation(Black, S. D., Coon, M. J., P-450 cytochromes: Structure and function, Adv. Enzymol., 60:35-87(1987)). Cytochromes P450 are classified into gene families and sub families depending on the similarity of base sequence. Among the multiple forms of P-450, cytochrome P-450 2E1 has a very high substrate specificity to a wide spectrum of exogenous substances and enhances the toxicity of the exogenous substances by activating them.
For example, therapeutically effective dose of acetaminophen causes hepatotoxicity in a chronic alcoholics, because cytochrome P-450 2E1 activate acetaminophen with a high substrate specificity and the activated acetaminophen attacks macromolecules such as proteins to cause hepatic necrosis(Wrighton, S. A., Thomas, P. E., Molowa, D. T., Haniu, M, Guzelian P. S., Characterization of ethanol-inducible human liver N-nitrosodimethylamine demethylase, Biochemistry, 25; 6731-6735(1986)).
For the metabolism of carbon tetrachloride which cause hepatic necrosis, it is reported that an increase in the level of reactive metabolites is closely related to an increase of expression of cytochrome P-450 2E1 (Ansher, S. S. Dolan, P., Bueding E., Chemoprotective effects of two dithiolthiones and butylhydroxyanisole against carbon tertrachloride and acetaminophen toxicity, Hepatoloty, 3; 932-935(1983)). It also plays an important role in activating xenobiotics due to a high affinity to nitrosamine, a precursor carcinogen(Peng, R., Yang, C. S., The induction and competitive inhibition of a high affinity microsomal nitrosodimethylamine demethylase by ethanol, Carcinogenesis, 3; 1457-1461(1982)).
Benzene is known to induce a leucopenia, a leukemia and an agranulocytic anemia and it has been reported that cytochrome P-450 2E1 is involved in the metabolism of benzene(Lewis, J. G., Stewart, W., Adams, D. C., Role of oxygen radicals in induction of DNA damage by metabolite of benzene, Cancer Res., 48;4762-4765(1988)). Recently, it has been reported that this enzyme shows a very high substrate specificity to halothane, a inhaling anesthetic so that causes a hepatotoxicity. This is due to the fact that the increased trifluoroacetyl free radicals formed from intermediates form adducts with liver proteins to produce neoantigens(Kenna, J. G., Pohm, L. R., Factors affecting the expression of trifluoroacetylated microsomal protein neoantigen in rats treated with halothane, Drug Metab. Dispos., 18;788-792(1990)).
Moreover, cytochrome P-450 2E1 is closely related to hepatotoxicity enhancements by activating various low mo

REFERENCES:
patent: 3931166 (1976-01-01), Winter et al.
patent: 3989713 (1976-11-01), Winter et al.
patent: 4105661 (1978-08-01), Winter et al.
patent: 4123613 (1978-10-01), Bernardi et al.
Bourguignon et al, Chemical Abstracts, vol. 93, No. 150209 (1980).
Sato et al, Chemical Abstracts, vol. 118, No. 212 276 (1993).
Shimazaki et al, Heterocycles, 27, pp. 1643-1651 (1988).
The Pyrazines by G.B. Barlin, pp. 196-197 (1982).

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