Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1994-01-05
1995-07-11
Chang, Ceila
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
549462, 549468, 549471, A61K 3134, C07D30778, C07D30785
Patent
active
054321956
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/JP92/00875 filed Jul. 8, 1992.
TECHNICAL FIELD
The present invention relates to a novel benzofuran derivative, expressed by the following general formula (I) and pharmacologically-acceptable salt thereof, which exhibits a therapeutic action for diseases caused by high Lp(a) concentration in blood and a lowering action for lipid concentration in blood and are useful for therapy and prevention of coronary diseases, cerebral infarction, hyperlipemia and arteriosclerosis. ##STR2## wherein R.sup.1 is hydrogen, halogen or alkyl; R.sup.2 is alkoxycarbonyl, aralkyloxycarbonyl, carboxy, hydroxyalkyl or acyloxyalkyl; Y is >CHOH, >CHOZ, >CH.sub.2 or >CO; and z is acyl.
BACKGROUND ART
Lp(a) was firstly found in blood of patients suffering from arteriosclerosis and has been considered to be a fatal factor for arteriosclerosis. Today, it has been known as a kind of lipoprotein having apoprotein B-100 (the same as LDL molecule) at the central part to which apoprotein (a) is bonded. (cf. Gendai Iryou, vol.22, no.7, 1990).
Lp(a) is detected only in Primates including human being. Therefore, it is difficult to subject to animal experiment using rodents and the like whereby its investigation of its behavior in animals has been delayed.
Lp(a) has the same fundamental structure as plasminogen and, accordingly, Lp(a) is supposed to participate in inhibition of decomposition of fibrin in blood resulting in inhibition of dissolution of thrombosis.
Lp(a) is distributed in the area where arteriosclerosis may take place in higher concentrations than other areas whereby Lp(a) is presumed to directly participate in arteriosclerosis. In addition, the concentration of Lp(a) in blood is not affected by conventional hypolipemic drugs and arteriosclerosis is observed even in the people with low lipid level. Consequently, the relation between Lp(a) and arteriosclerosis has been considered to be important.
It has been known that the Lp(a) of the patients of arteriosclerosis and hyperlipemia never lowers in blood by a diet therapy.
It has been known that high Lp(a) concentration in blood is dominated and decided by genetic factor.
Out of the above-given knowledges, it may be easily concluded that Lp(a) is directly related to arteriosclerosis and is based upon the inhibitory action of dissolution of thrombosis.
DISCLOSURE OF INVENTION
Since it has been found to be quite likely that Lp(a) is a lipoprotein which accelerates the arteriosclerosis, there has been attempts to prevent those disease by curing the diseases with high Lp(a) concentration in blood (cf. Arteriosclerosis, vol.10, no.5, pages 672-679, 1990). Nicotinic acid has been known as a substance which lowers the concentration of Lp(a) in blood though it exhibits adverse reactions such as flushing and, moreover, the main action is not so satisfactory (J. Internal Medicine 226 271-276 (1989)).
Incidentally, it has been widely known that, besides the lowering action of Lp(a) concentration, the substances which lower the lipid concentration in blood are useful for the therapy of arteriosclerosis. Accordingly, it is presumed that, if there is a substance which lowers the Lp(a) concentration and also lowers the lipid level in blood, such a substance would be far useful for the therapy of the above-given diseases.
As a result thereof, the present inventors have found that the compound expressed by the general formula (I) met with the requirement and have achieved the present invention.
The characteristic feature of the present invention is the structure per se of the compounds expressed by the general formula (I). The compounds of the present invention are novel which have not been described in any of the prior art literatures yet.
Examples of the halogen expressed by R.sup.1 in the general formula (I) are fluorine, chlorine, bromine and iodine.
Preferred examples of the alkyl are straight chain or branched having 1 to 7 carbon atoms and are, for example, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, tert-butyl, n-pentyl, iso-p
REFERENCES:
patent: 4918092 (1990-04-01), Frenette
Hackh's "Chemical Dictionary" McGraw-Hill, 1983, p. 16.
Clarkson et al. "The Role of individual Differences in Lipoprotein . . . of atherosclerosis" N.Y. Aca. Sci. vol. 454, pp. 28-43 (1985).
Eaton. "High density lipoprotein" J. Chron. Dis. 31 131-135 (1978).
Pike et al. "Nutrition au integrated approach" John Wiley & Sons. p. 534 (1984).
Journal of the Chemical Society, Perkin Transactions 1, No. 9, 1978, Letchworth GB, pp. 928-933, S. Jordan et al.-The synthesis and oxidation . . . Toliprolol.
Chokai Shoichi
Ohmachi Shinji
Taira Masafumi
Chang Ceila
Nippon Shinyaku Company Limited
LandOfFree
Benzofuran derivative and pharmaceutical composition does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Benzofuran derivative and pharmaceutical composition, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Benzofuran derivative and pharmaceutical composition will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-503752