Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Patent
1996-09-09
1998-02-17
Richter, Johann
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
536 64, 536 184, 552201, 514460, 514 25, 549417, C07H 15252, A61K 3170
Patent
active
057191301
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/JP95/00407 filed Mar. 10, 1995.
TECHNICAL FIELD
This invention relates to new anthracycline derivatives having a trifluoromethylated sugar which exhibit excellent anticancer or antitumor activities even at low dosages thereof and which are of low toxicity. This invention also relates to a pharmaceutical composition which comprises the new anthracycline derivative as an active ingredient. More particularly, this invention relates to such new anthracycline derivatives which exhibit anticancer or antitumor activities and are of low toxicity and which embrace 7-O-(2,6-dideoxy-2,6,6,6-tetrafluoro-.alpha.-L-talopyranosyl)daunomycinone or -adriamycinone as well as 7-O-(2,6-dideoxy-6,6,6-trifluoro-.alpha.-L-lyxo-hexopyranosyl)adriamycinon e. Furthermore, this invention relates to new intermediate compounds which are useful for the synthesis of the above-mentioned new anthracycline derivatives.
BACKGROUND ART OF THE INVENTION
As the antibiotics of the anthracycline type are known daunomycin which is referred to as daunorubicin in the specification of U.S. Pat. No. 3,616,242, and adriamycin which is referred to as doxorubicin in the specification of U.S. Pat. No. 3,590,028. These compounds, namely daunomycin and adriamycin have broad anticancer activities against experimental tumors and have found wide-spread clinical utilities as chemotherapeutic antitumor agents.
Thus, daunomycin and adriamycin can exhibit somewhat strong anticancer or antitumor activities against various kinds of cancers or tumors but are not necessarily satisfactory as the anticancer agent or antitumor agent. Namely, daunomycin and adriamycin have been used widely as the chemotherapeutic antitumor agents for clinical treatments of tumor-bearing patients, but they are also known to bring about serious side-effects such as leukocytopenia, alopecia, myocardiopathy and others, in many instances.
Hitherto, it has hence been attempted to produce newly various kinds of daunomycin-related compounds for the purpose of providing such daunomycin-related compounds which have much enhanced anticancer or antitumor activities but have low toxicities. As some results of the attempts made hitherto, there have been proposed several compounds which are known, for example, as aclacinomycins A and B; 4'-O-tetrahydropyranyl-adriamycin; and N-mono-benzyl- or N-di-benzyl-adriamycin.
Besides, U.S. Pat. No. 4,427,664 specification discloses 7-O-(3,4-di-O-acetyl-2,6-dideoxy-2-iodo-.alpha.-L-manno-hexopyranosyl)daun omycinone and 7-O-(3,4-di-O-acetyl-2,6-dideoxy-2-iodo-.alpha.-L-talo-hexopyranosyl)dauno mycinone.
The present inventors had proceeded with investigations in an attempt to provide such derivatives of daunomycin or adriamycin which have better anticancer or antitumor activities and lower toxicities than daunomycin or adriamycin. As parts of the outcomes of the investigations, the present inventors already synthesized some of the daunomycin derivatives and the adriamycin derivatives in which the sugar moiety of daunomycin and adriamycin has been modified chemically. For instance, the present inventors already reported 4'-O-tetrahydropyranyl-daunomycin or -adriamycin as well as 3'-deamino-3'-morpholinodaunomycin or -adriamycin.
Furthermore, the present inventors succeeded in synthesizing such anthracycline derivatives having anticancer or antitumor activities and represented by the following general formula (A) ##STR2## wherein R.sup.a means a hydrogen atom or a hydroxyl group, for example, 7-O-(2,6-dideoxy-2-fluoro-.alpha.-L-talopyranosyl)daunomycinone and 7-O-(2,6-dideoxy-2-fluoro-.alpha.-L-talo-pyranosyl)adriamycinone (Japanese Patent Application First Publication "Kokai" No. 145097/87 and European Patent No. 0230013).
The present inventors also succeeded in synthesizing such antitumor anthracycline derivatives represented by the general formula (B) ##STR3## wherein R' means a group --(CH.sub.2).sub.m H, where m is an integer of 1-6, or a group --(CH.sub.2).sub.n --COOH, where n is zero or an integer of 1-10 (Japanese Pate
REFERENCES:
patent: 5374746 (1994-12-01), Ok et al.
Takagi Yasushi
Takeuchi Tomio
Tsuchiya Tsutomu
Umezawa Sumio
Richter Johann
Stockton Laura L.
Zaidan Hojin Biseibutsu Kagaku Kenkyu Kai
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