Organic compounds -- part of the class 532-570 series – Organic compounds – Carboxylic acid esters
Patent
1993-06-17
1995-05-30
Killos, Paul J.
Organic compounds -- part of the class 532-570 series
Organic compounds
Carboxylic acid esters
549365, 552290, C07C 6976
Patent
active
054203333
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
The present invention relates to a compound (hereinafter referred as Compound (I) of the present invention ) represented by Formula (I): ##STR3## wherein R.sup.1 is a lower alkyl, cycloalkyl, cycloalkyl-lower alkyl, aryl or aralkyl group which is optionally substituted,
R.sup.2 is a group represented by the formula: --COOR': (wherein R' is a lower alkyl or aralkyl which is optionally substituted), lower alkyl or halogenated lower alkyl, or,
R.sup.1 and R.sup.2, together with adjacent carbonyl group, form a cyclohexanone ring represented by the formula: ##STR4##
R.sup.3 is a phenyl group optionally being substituted, and, ring A is a benzene nucleus which is optionally substituted, or a heterocyclic ring containing S or O optionally being substituted], and pharmaceutically acceptable salts thereof. The present invention also provides anti-hyperlipemic agents containing these compounds.
PRIOR ART
Hyperlipemia is believed to be one of the major causes of a geriatric disease arteriosclerosis. Among the hyperlipemic diseases, hypercholesterolemia is particularly in close relationship with arteriosclerosis. Cholesterol is present in blood in either one of the forms of very low density lipoprotein (hereinafter referred as VLDL), low density lipoprotein (LDL) and high density lipoprotein (HDL). VLDL and LDL enhance deposition of cholesterol in an arterial wall thereby causing arteriosclerosis, while HDL prevents the deposition and exhibits therapeutic and prophylactic effects against arteriosclerosis, as reported in Annals of Internal Medicine, 90, 85, (1979). Accordingly, an anti-hyperlipemic agent capable of reducing selectively VLDL and LDL cholesterols is desired in the field of treatment and prophylaxis of arteriosclerosis.
Drugs directed to the purpose described above were disclosed, for example, in Japanese Patent Publication Nos. H3-72422, H3-157351, H2-72136 and H1-135766.
PROBLEMS TO BE SOLVED BY THE INVENTION
Among factors causing atherosclerosis which is most significant in arteriosclerotic diseases, the behavior of LDL cholesterol in blood is quite important. Especially, permeation of LDL into arterial walls and incorporation of LDL by macrophages in the wall, and resulting formation of foam cells and accumulation of cholesterols in intima and blood vessel failures are very important. It is believed that oxidized LDLs are exclusively incorporated into macrophages (D. Steinberg, S. Parthasarathy, T. E. Carew, J. C. Khoo and J. L. Witztum, N. Engl. J. Med., 320, 915 (1989)). Thus, an anti-hyperlipemic agent having anti-oxidizing effect on LDLs in addition to the ability of reducing VLDL and LDL cholesterols selectively as mentioned above is desirable. However, no such agents have been reported.
DETAILED DESCRIPTION OF THE INVENTION
It has been found surprisingly that Compounds (I) and pharmaceutically acceptable salts thereof according to the present invention have anti-oxidizing effect on LDLs in addition to the ability of reducing VLDL and LDL cholesterols selectively.
Compounds (I) of the present invention can readily be converted into desirable salts by a known manner.
Pharmaceutically acceptable salts of Compounds (I) include alkaline metal salts such as sodium and potassium salts, alkaline earth metal salts such as calcium and magnesium salts, and quaternary ammonium salts such as tetramethylammonium salt. Throughout the specification, the terms have the meanings as described below.
In the definition of group R.sup.1 in Formula (I), "a lower alkyl group which is optionally substituted" means a straight or branched C.sub.1 -C.sub.6 alkyl which may have one or more substituents. "A straight or branched C.sub.1 -C.sub.6 alkyl" includes methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, n-pentyl, i-pentyl, neopentyl, s-pentyl, t-pentyl, 1-ethylpropyl, n-hexyl, neohexyl, i-hexyl, s-hexyl and t-hexyl. The substituent may be hydroxyl, halogen atom (F, Cl, Br, I), amino, cyano, nitro, nitroso, hydrazino, hydroxyamino, thiol and lower alkoxy groups. The
REFERENCES:
patent: 4771072 (1988-09-01), Iwasaki et al.
patent: 4840951 (1989-06-01), Iwasaki et al.
Broom et al., "A General Route to Substituted Naphthols", J. C. S. Chem. Comm., 1978, pp. 162-164.
Ichihashi Teruhisa
Kida Shiro
Mizui Takuji
Mori Sachio
Takechi Shozo
Killos Paul J.
Shionogi & Co. Ltd.
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