Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1996-08-12
1998-02-17
Richter, Johann
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
549405, 549408, 549410, A61K 3135, C07D31172
Patent
active
057191808
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/JP94/02046 filed Dec. 6, 1994.
TECHNICAL FIELD
The present invention relates to novel chroman derivatives. The chroman derivatives of the present invention have vitamin E activities and antioxidation activity, and are useful as medicaments and ingredients of pharmaceutical composition and the like.
BACKGROUND ART
Vitamin E is known to have various physiological activities such as anti-sterile activity, anti-amyotrophic activity, and anti-hemolytic activity. The physiological activities are considered to be based on its anti-oxidation activity.
Tocopherol and tocotrienol, which are naturally occurring vitamin Es, are structurally characterized in that the benzene ring moiety of the chroman ring is substituted with methyl groups. Such vitamin E derivatives as tocopheramine (J. Am. Chem. Soc., 64, 1082-1084, 1942), tocopherothiol, and thio-tocopherol are known. All of these vitamin E derivatives have methyl groups at 5-, 7-, and 8-positions of the respective chroman rings. A vitamin E derivative having dihydrobenzofran ring, instead of the chroman ring, is also known. The compound also has methyl groups at 4-, 5-, and 7-positions of the dihydrobenzofrun ring, which corresponds to 5-, 6-, and 8-positions of the chroman ring, respectively. Each of the above-described compounds are reported to have vitamin E activities.
Compounds introduced with a hydroxymethyl group or a formyl group at 5-position of a chroman ring (Chemiker-Zeitung, 115, pp. 113-116, 1991). However, no pharmacological activity of these compounds is described in the publication.
DISCLOSURE OF INVENTION
The inventors of the present invention conducted molecular designs to provide vitamin E derivatives having excellent pharmacological activities. As a result of syntheses of various compounds, the inventors found that compounds having a chroman ring, in which a methyl group at 8-position is subjected to an oxidation derivatization or a methyl group at 8-positionn is replaced with a hydrogen atom, had various physiological activities including unique anti-oxidation activity and preventive activity against dysembryoplasia. The present invention was achieved on the basis of these findings.
The present invention thus provides chroman derivatives represented by the following formula (I): ##STR2## wherein X represents H, --CH.sub.2 OH, --CHO, --COOH, --COOCH.sub.3, --CH.dbd.NOH, --CONH.sub.2, --COCH.sub.3, --CH(OH)CH.sub.3, Br, or CN; Y represents a hydroxyl group which may optionally have a protective group; R represents an alkyl group, alkenyl group, or aralkyl group; provided that, where X is hydrogen atom, R is an alkyl group, alkenyl group, or aralkyl group each having 16 or more carbon atoms. According to an embodiment of the present invention, the chroman derivatives wherein Y is a non-protected hydroxyl group are provided.
According to other embodiments of the present invention, there are provided a vitamin E-like active medicament comprising the chroman derivative as an active ingredient; the vitamin E-like active medicament used for therapeutic and preventive treatments of sterility; the vitamin E-like active medicament used for therapeutic and preventive treatments of ischemic disorders; the vitamin E-like active medicament used for therapeutic and preventive treatments of arterial sclerosis; the vitamin E-like active medicament used for activation of microcirculation; the vitamin E-like active medicament used for prevention of fetal abnormality; and the chroman derivatives used as antioxidants.
BEST MODE FOR CARRYING OUT THE INVENTION
In the above formula (I), examples of the alkyl groups represented by R include straight- or branched-chain lower or middle alkyl groups. Examples of the lower alkyl group include straight- or branched-chain alkyl groups having 1 to 5 carbon atoms such as, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, and neopentyl groups. As the middle alkyl group, for example, straight- or branched-chain middle alkyl groups hav
REFERENCES:
patent: 3789086 (1974-01-01), Frick et al.
Nair et al., Archives of Biochemistry and Biophysics 114, 488-493, 1966.
Slover et al., The Journal of the American Oil Chemists Society, vol. 44, pp. 161-166, Mar. 1967.
Akaike Masashi
Shudo Koichi
Richter Johann
Shudo Koichi
Stockton Laura L.
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