Quinoline derivatives, their production and use as ACAT inhibito

Details Quinoline derivatives, their production and use as ACAT inhibito Quinoline derivatives, their production and use as ACAT inhibito

1991-02-01

1994-11-08

Tsang, Cecilia

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Having -c-, wherein x is chalcogen, bonded directly to...

514313, 546153, 546159, A61K 3147, C07D21538

Patent

active

053627423

DESCRIPTION:

BRIEF SUMMARY
BACKGROUND OF THE INVENTION

1. Field of the Invention
This invention relates to novel quinoline derivatives, their production and use. The compounds of this invention possess excellent inhibitory action against acyl-CoA: cholesterol acyltransferase (ACAT). Especially, the compounds of this invention inhibit the absorption of cholesterol through the intestinal tract of a mammal and also restrain the accumulation of cholesterol ester at the arterial wall, and accordingly are useful as a drug for preventing and treating hypercholesterolemia, atherosclerosis and various diseases caused thereby (e.g., ischemic cardiac diseases such as myocardial infarction, cerebrovascular disturbance such as cerebral infarction, cerebral apoplexy, etc.).
2. Description of the Prior Art
U.S. Pat. No. 3,798,226 mentions specifically 6-chloro-4-phenyl-3-phenylacetamidoquinoline (Compound A), and 6-chloro-3-(p-chlorophenylacetamido)-4-phenylquinoline (Compound B), which possess antitrichomonas or antiulcer action.
There has not been any report that the above mentioned compounds possess pharmacological activity useful as a drug for arteriosclerosis such as ACAT inhibitory activity and blood cholesterol lowering activity, and these points have not been studied so far.
Therefore, it has not been known that the compounds A and B and their analogue compounds are useful as a drug for atherosclerosis.


SUMMARY OF THE INVENTION

The inventors of this invention studied the physiological activities of the above mentioned compounds A and B and their analogue compounds, and found that new compounds which are not described concretely in the above mentioned publications, possess potent ACAT inhibitory activity and are useful as a drug for atherosclerosis.
Thus, this invention relates to ##STR5## wherein each phenyl ring of A and B can have one or more substituents; X is ##STR6## (R.sup.1 is a hydrogen atom, a lower alkyl group or a lower alkoxy group) or ##STR7## (R.sup.2 is a hydrogen atom or a lower alkyl group); Y is --(CH2).sub.m --(m is 0, 1 or 2) or --CH.dbd.CH--, Z is a group of the formula: ##STR8## wherein each ring of C and D can have one or more substituents, R.sup.3 and R.sup.4 are each a hydrogen atom, a halogen atom, or a lower alkyl, lower alkoxy, lower acyloxy, lower alkoxycarbonyloxy, N,N-di-lower alkylcarbamoyloxy, optionally esterified carboxy or hydroxyl group, R.sup.5 is a halogen atom, or a lower alkyl, lower alkoxy, lower acyloxy, lower alkoxycarbonyloxy, N,N-di lower alkylcarbamoyloxy, optionally esterified carboxy or hydroxyl group, R.sup.6 and R.sup.7 are each a hydrogen atom, or a lower alkyl group, and n, o and p are each 1 or 2; l is 0 or 1; or its salt; formula (I), or its salt.


DESCRIPTION OF THE PREFERRED EMBODIMENT

Examples of the halogen atoms represented by R.sup.3, R.sup.4 and R.sup.5 in the formula (I) are fluorine, chlorine, bromine or iodine atom, preferably fluorine atom.
Preferably, the lower alkyl groups for R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6 and R.sup.7 are straight or branched chain ones having 1-6 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neo-pentyl, hexyl and the like.
Preferably, the lower alkoxy groups for R.sup.2, R.sup.4 and R.sup.5 are straight or branched chain ones having 1-6 carbon atoms, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentyloxy, isopentyloxy, neopentyloxy and hexyloxy.
The preferable lower acyloxy groups for R.sup.3, R.sup.4 and R.sup.5 are straight or branched chain ones having 1-6 carbon atoms, such as formyloxy, acetoxy, propionyloxy, isobutyloxy, butyryloxy, isobutyryloxy, valeryloxy, isovaleryloxy, pivaloyloxy, hexanoyloxy and the like.
The preferable lower alkoxycarbonyloxy groups for R.sup.3, R.sup.4 and R.sup.5 are ones containing straight or branched chain alkyl groups having 1-6 carbon atoms, such as methoxycarbonyloxy, ethoxycarbonyloxy, propoxycarbonyloxy, isopropoxycarbonyloxy, butoxycarbonyloxy, isobutoxycarbonyloxy, sec-but

REFERENCES:
patent: 3798226 (1974-03-01), Meguro

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