Organic compounds -- part of the class 532-570 series – Organic compounds – Oxygen containing
Patent
1986-07-02
1987-10-20
Lone, Werren B.
Organic compounds -- part of the class 532-570 series
Organic compounds
Oxygen containing
C07C 35205
Patent
active
047015705
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The present invention relates to an antitumor agent and a process for treatment of tumors, using it.
BACKGROUND ART
Synthetic chemical materials and antibiotics have been employed as low molecular antitumor agents. However, in general, many of these materials are highly toxic and can cause side effects.
The development of an antitumor agent that has low toxicity to normal cells and causes few side effects has therefore been considered desirable.
DISCLOSURE OF INVENTION
It is an object of the present invention to provide an antitumor agent that has superior antitumor effects and that substantially does not show any toxicity to normal cells or display any side effects.
The present invention provides an antitumor agent containing, as an active ingredient, 2,7,11-cembratriene-4,6-diol represented by the following formula: ##STR1##
BEST MODE OF CARRYING OUT THE INVENTION
The active ingredient of the antitumor agent according to the present invention is 2,7,11-cembratriene-4,6-diol (hereinafter referred to as CBT) represented by Formula [I] below: ##STR2## CBT has two diastereoisomers, i.e., 1S,2E,4S,6R,7E,11E-2,7,11-cembratriene-4,6-diol (hereinafter referred to as .alpha.-CBT) represented by Formula [II] below, and 1S,2E,4R,6R,7E,11E-2,7,11-cembratriene-4,6-diol (hereinafter referred to as .beta.-CBT) represented by Formula [III] below. Since both .alpha.-CBT and .beta.-CBT show antitumor effects, as will be apparent in Examples which follow, the antitumor agent, according to the present invention, may contain, as an active ingredient, at least one of .alpha.-CBT and .beta.-CBT. In this specification and the appended claims, the terms "2,7,11-cembratriene-4,6-diol" and "CBT" mean .alpha.-CBT and/or .beta.-CBT. CBT is often represented in a duvatriene form. Accordingly, 4,8,13-duvatriene-1,3-diols, represented by Formulas [IV] and [V] below respectively, are the same compounds as .alpha.-CBT and .beta.-CBT. It is to be understood that the compounds represented in the duvatriene form are encompassed within the scope of the present invention. ##STR3##
It is known that CBT is contained in resinous materials on the surface of tobacco leaves. It is also known that CBT is associated with tobacco quality and its flavor during smoking. No pharmacological properties of CBT are known except that it has the effect of preventing the growth of powdery mildew on tobacco (Japanese Patent Disclosure No. 58-157704. In this Disclosure, CBT is represented in the duvatriene form). The present inventors have found for the first time that CBT has an antitumor effect, and the present invention was completed based on this finding.
CBT may be produced, for example, in the following manner: Fresh or dry tobacco leaves are immersed in an organic solvent such as hexane, ether, chloroform, or dichloromethane for a short period of time (for example, 10 seconds to 60 seconds). The immersing temperature is normally between 10.degree. C. and 30.degree. C. The weight ratio of tobacco leaves to the organic solvent is preferably from 2:1 to 1:1. The immersing procedure may be repeated two or more times. The immersion extracts resinous materials found on the surface of the tobacco leaves. This extract is recovered by filtration and is then condensed by evaporating the organic solvent at a reduced pressure and a temperature of 40.degree. C. or lower. The extract is conveniently condensed to a volume of about 1/25 to 1/200 of the original volume.
The condensate is shaken after the addition of a hexane/methanol/water solvent mixture, to transfer CBT to the methanol/water layer. The methanol/water layer is then condensed in the same manner as the extract. The condensate is purified by silica gel chromatography using a hexane/ethyl acetate mixture as an eluting solvent. The removal of the solvent from the eluate at a reduced pressure and a temperature of 40.degree. C. or lower leaves CBT (with a purity of about 80% or higher). The CBT can then be directly used as the active ingredient of an antitumor agent according to the pre
REFERENCES:
Roberts et al., "Chemical Abstracts", vol. 55, p553h (1962).
Roberts et al, "J. Organic Chem.", vol. 27, Nov. 1962, pp. 3989-3995.
Fuchs et al., "Chemical Abstracts", vol. 99, pp. 209,808 (1983).
Heemann et al., "Chemical Abstracts", vol. 99, pp. 172,787.
Chemical Abstract 103(19):155572g, Y. Saito et al., Carcinogenesis (London), pp. 1189-1194, 1985.
Chemical Abstract 88(17):116228b (1977).
Chemical Abstract 100(19):k53845n (1984).
Mizusaki Shigenobu
Saito Yutaka
Yoshida Daisuke
Japan Tobacco Inc.
Lone Werren B.
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