Search International and National Patent Collections
Some content of this application is unavailable at the moment.
If this situation persists, please contact us atFeedback&Contact
1. (WO1991009017) QUINOLINE DERIVATIVES, THEIR PRODUCTION AND USE
Note: Text based on automatic Optical Character Recognition processes. Please use the PDF version for legal matters

CLAIMS

1. A quinoline derivative of the formula ( I)


wherein each phenyl ring of A and B can have one or more
Rl
I
substituents; X is -N=C- (Rl is a hydrogen atom, a lower
R
I
alkyl group or a lower alkoxy group) or -N-CO- (R? is a hydrogen atom or a lower alkyl group); Y is -(CH2)m~(m is 0, 1 or 2) or -CH=CH-; Z is a group of the formula:




wherein each phenyl ring of C and D can have one or more substituents, R3 and R are each a hydrogen or halogen atom, or a lower alkyl, lower alkoxy, lower acyloxy, lower alkoxycarbonyloxy, N,N-di-lower alkylcarbamoyloxy, optionally esterified carboxy or hydroxyl group, R5 is a halogen atom, or a lower alkyl, lower alkoxy, lower acyloxy, lower alkoxycarbonyloxy, N,N-di-lower
alkylcarbamyloxy, optionally esterified carboxy or
hydroxyl group, R and R7 are each a hydrogen atom or a lower alkyl group, and n, o and p are each 1 or 2; J. is 0 or 1, or its salt.

2. The compound of claim 1 wherein the phenyl ring A is substituted by one or two lower alkyl groups, the phenyl ring B is substituted one or
Rl
I
two halogen atoms, X is -N=C- (Rl=hydrogen atom) and Y is

-(CH2)m (m=0 or 1) or -CH=CH-, or its salt.

3. The compound of claim 2 wherein the phenyl ring A is substituted by two methyl groups and the phenyl ring B is substituted by a chlorine atom.

4. The compound of claim 1 or 2 wherein Z is


in which R3 is a hydroxyl group, a lower alkoxy group, a hydrogen atom or a halogen atom, R4 and R5 are a lower alkyl group, a lower alkoxy group, a hydroxyl group or a halogen atom, and o and n are 1 or 2.


wherein the ring C may be substituted by a halogen atom and R6 is a lower alkyl group.

6. The compound of claim 1 or 2 wherein Z is


in which the ring D may be substituted by one hydroxyl group and one to three lower alkyl groups, R is a lower alkyl group and p is 1 or 2.

7. The compound of claim 1 which is 4-(2-chloropheriyl)-3- (4-hydroxy-2 , 3 ,5-trimethylbenzamido)-6 , 8-dimethylquinoline,

4- ( 2-chlorophenyl)-3-( 2, 4-difluorophenylacetylamino)-6 , 8-dimethylquinoline,
4-( 2-chlorophenyl)-3-( 3 ,4-dimethoxycinnamoylamino)-6 , 8-dimethylquinoline,
4-( 2-chlorophenyl)-3-( 3 , 4-dihydroxycinnamoylamino)-6 , 8-dimethylquinoline, 4-(2-chlorophenyl)-3-(2, 3-dihyd:roxycinnamolyamino)-6 , 8-dimethylquinoline,
4-( 2-chlorophenyl)-3-(4-hydroxy-3,5-dimethoxycinnamoylamino)•

6 ,8-dimethylquinoline,
4-(2-chlorophenyl)-6 , 8-dimethyl-3-( 3-methyl-4H-l,4-benzothiazin-2-ylcarbonyl)aminoquinoline,
4-(2-chlorophenyl)-3-( 7-fluoro-3-methyl-4H-l,4-banzothiazin- 2-ylcarbonyl)amino-6 , 8-dimethylquinoline,
4-( 2-chlorophenyl)-3-( 6-hydroxy-2,5,7, 8-tetramethylchroman- 2-ylcarbonyl)amino-6, 8-dimethylquinoline, or
4-(2-chlorophenyl)-3-( 2, 3-dihydro-5-hydroxy-2,4,6,7-tetramethylbenzofuran-2-ylcarbonyl )amino-6 , 8-dimethylquinoline, or a salt thereof.

8. An inhibitory composition for acyl-CoA: cholesterol acyltransferase which comprises an effective inhibitory amount of a compound of the formula (I) in claim 1 or a salt thereof and a pharmaceutically acceptable carrier, diluent or excipient.

9. The inhibitory composition of claim 8 in which the compound of the formula (I) or its salt is a compound as claimed in claim 7 or its salt.

10. A process for the production of a quinoline
derivative of the formula (I) as defined in claim 1 or its salt, which comprises reacting a compound of the formula (II):



wherein the symbols have the same meanings as defined in the formula (I ) ,
or its salt with a compound of the formula (III):

Z-(Y),e-C00H (III)

wherein the symbols have the same meaning as defined in the formula (I ) ,
and if desired, reducing the resultant compound (I) where

Y is -CH*=CH- to the corresponding compound where Y is

-CH2CH2-,
and further if desired, converting the resultant compound

(I) into the corresponding salt.

11. A process for the production of a quinoline
derivative of the formula (I) as defined in claim 1 or its salt where Z

is wherein the phenyl ring C Ls as

defined in the formula (I) and i is 0, which comprises reacting a compound (II) in claim 10 or its salt with diketene to obtain a compound of the formula (IV):

NHCOCH2COCH3 (IV)


wherein the symbols have the same meanings as defined in the formula (I)
and then reacting the compound (IV) with a compound of the formula (V) :


wherein the phenyl ring C is as defined in the formula (I), and if desired, converting the resultant compound (I) into the corresponding salt.

12. A use of a quinoline derivative or its salt as defined in any one of claims 1 - 7 for preventing or. treating hypercholesterolemia, atherosclerosis and diseases caused thereby.

13. A use of a quinoline derivative or its salt as defined in any one of claims 1 to 7 for the production of a medicine for use in the prevention or treatment of disorders or diseases associated with acyl-CoA :
cholesterol acyltransferase.