2-aminoquinoline derivatives

1. A compound of general formula [I]:

wherein:

R 1 and R 2 are each independently selected from the group consisting of:

(1) optionally hydroxyl- or halogen-substituted lower alkyl,

(2) optionally R 9 -substituted 3 to 6-membered cycloalkyl, and

(3) optionally R 9 -substituted 4 to 6-membered heterocycloalkyl, or

(4) R 1 and R 2 together form a 4 to 11-membered crosslinking, non-crosslinking or spiro ring aliphatic nitrogen-containing heterocycle, with the nitrogen atom to which they bind, one or two optional hydrogen atoms in the aliphatic nitrogen-containing heterocycle being optionally substituted with R 9 ;

R 3 , R 4 , R 6 and R 7 are each independently selected from the group consisting of:

(1) hydrogen,

(2) hydroxyl,

(3) halogen, and

(4) optionally halogen-substituted lower alkyl;

R 5 stands for:

(1) hydrogen, or

(2) optionally halogen-substituted lower alkyl;

each R 8 is independently selected from the group consisting of:

(1) halogen,

(2) lower alkyl, and

(3) lower alkyloxy;

R 9 is selected from the group consisting of hydroxyl, amino, mono-lower alkylamino, di-lower alkylamino, optionally hydroxyl- or halogen-substituted lower alkyl, (lower alkyloxycarbonyl)amino, lower alkyloxycarbonyl-(lower alkyl)amino, lower alkylcarbonylamino, lower alkylcarbonyl(lower alkyl)amino, mono-lower alkylcarbamoyl-(lower alkyl)amino, di-lower alkylcarbamoyl(lower alkyl)amino, lower alkylsulfonylamino, lower alkylsulfonyl(lower alkyl)amino, oxo and 2-oxopyrrolidinyl; and

n is 0, 1, 2, 3 or 4;

or a pharmaceutically acceptable salt thereof.

2. The compound according to claim 1 , wherein: R 1 is lower alkyl, and R 2 is selected from the group consisting of optionally hydroxyl-substituted lower alkyl, tetrahydrofuranyl and optionally R 9 -substituted pyrrolidinyl, or a pharmaceutically acceptable salt thereof.

3. The compound according to claim 1 , wherein: the 4 to 11-membered crosslinking, non-crosslinking or spiro ring aliphatic nitrogen-containing heterocycle formed by R 1 and R 2 together with the nitrogen atom to which they bind is represented by a formula (A):

wherein R a is R 9 or two R a s together form —(CH 2 )x-(NH)—(CH 2 )y-, hydrogen in the substituent group may optionally be substituted with lower alkyl, lower alkylcarbonyl or oxo, x and y are each independently selected from 0, 1, 2, 3 or 4, provided that 3≦x+y≦4, and m is selected from 0, 1 or 2; or a pharmaceutically acceptable salt thereof.

4. The compound according to claim 3 , wherein:

R a is selected from the group consisting of lower alkylcarbonyl(lower alkyl)amino, lower alkylsulfonyl(lower alkyl)amino, lower alkyloxycarbonyl(lower alkyl)amino, and di-lower alkylcarbamoyl(lower alkyl)amino, and

m=1;

or a pharmaceutically acceptable salt thereof.

5. The compound according to claim 3 , wherein: m=2, and the two R a s together form a group selected from the group consisting of:

wherein: R 10 is selected from lower alkyl and lower alkylcarbonyl;

or a pharmaceutically acceptable salt thereof.

6. The compound according to claim 3 , wherein: the aliphatic nitrogen-containing heterocycle represented by the formula (A) is selected from the group consisting of:

1-methyl-2-oxo-1,7-diazaspiro[4.4]nonan-7-yl, 7-methyl-8-oxo-2,7-diazaspiro[4.4]nonan-2-yl, 3-[acetyl(methyl)amino]pyrrolidin-1-yl, 3-[propionyl(methyl)amino]pyrrolidin-1-yl, 3-[isobutyryl(methyl)-amino]pyrrolidin-1-yl, 3-[methanesulfonyl(methyl)amino]pyrrolidin-1-yl, 3-[methoxycarbonyl(methyl) amino]pyrrolidin-1-yl, 3-{[(dimethylamino)carbonyl](methyl)amino}pyrrolidin-1-yl, 6-acetyldecahydro-pyrrolo[3,4-d[azepin-2-yl, and 2-oxo]1.3′]bipyrrolidinyl-1′-yl;

or a pharmaceutically acceptable salt thereof.

7. The compound according to claim 1 , wherein: R 8 is a fluorine atom or a methoxy group, or a pharmaceutically acceptable salt thereof.

8. The compound according to claim 1 , wherein: selected from the group consisting of:

(1) 5-(4-fluorophenyl)-N-[2-(1-methyl-2-oxo-1,7-diazaspiro[4,4]nonan-7-yl)-6-quinolinyl]-2-pyrimidinecarboxamide,

(2) 5-(4-fluorophenyl)-N-[2-(7-methyl-8-oxo-2,7-diazaspiro[4,4]-nonan-2-yl)-6-quinolinyl]-2-pyrimidinecarboxamide,

(3) N-(2-[(3R)-3-[isobutyryl(methyl)amino]-1-pyrrolidinyl]-6-quinolinyl)-5-phenyl-2-pyrimidine carboxamide,

(4) N-[2-(6-acetyldecahydropyrrolo[3,4-d]azepin-2-yl)-6-quinolinyl]-5-phenyl-2-pyrimidine carboxamide,

(5) N-[2-[(3R)-3-[acetyl(methyl)amino]-1-pyrrolidinyl]-6-quinolinyl)-5-phenyl-2-pyrimidine carboxamide,

(6) 5-phenyl-N-(2-[(3R)-3-[propionyl(methyl)amino]-1-pyrrolidinyl]-6-quinolinyl)-2-pyrimidine carboxamide,

(7) N-(2-[(3R)-3-[methanesulfonyl(methyl)amino]-1-pyrrolidinyl]-6-quinolinyl)-5-phenyl-2-pyrimidine carboxamide,

(8) N-(2-[(3R)-3-[methoxycarbonyl(methyl)amino-1-pyrrolidinyl]-6-quinolinyl)-5-phenyl-2-pyrimidine carboxamide,

(9) N-(2-[(3R)-3-[[(dimethylamino)carbonyl)](methyl)amino]-1-pyrrolidinyl]-6-quinolinyl)-5-phenyl-2-pyrimidinecarboxamide,

(10) N-(2-[isopropyl(methyl)amino]-6-quinolinyl)-5-phenyl-2-pyrimidinecarboxamide,

(11) 5-(4-fluorophenyl)-N-(2-[(3R)-3-[isobutyryl(methyl)amino]-1-pyrrolidinyl]-6-quinolinyl)-2-pyrimidinecarboxamide,

(12) N-(2-[(3R)-3-[acetyl(methyl)amino]-1-pyrrolidinyl]-6-quinolinyl)-5-(4-fluorophenyl)-2-pyrimidine carboxamide,

(13) 5-(4-fluorophenyl)-N-(2-[methyl(tetrahydro-3-furanyl)amino]-6-quinolinyl)-2-pyrimidine carboxamide and

(14) 5-(3-fluorophenyl)-N-(2-[(3R)-3-[isobutyryl(methyl)amino]-1-pyrrolidinyl]-6-quinolinyl)-2-pyrimidine carboxamide,

or a pharmaceutically acceptable salt thereof.

9. A method for treating obesity in a human subject in need of such treatment comprising administering to the human subject of a therapeutically effective amount of a compound according to claim 1 , or a pharmaceutically acceptable salt thereof.

10. A pharmaceutical composition comprising a compound according to claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

11. A process for preparing the compound of general formula [I] of claim 1 , wherein: R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 and n have the same significations as given in claim 1 ,

which comprises the step of subjecting a compound of a general formula [II]:

 wherein R 1 , R 2 , R 3 , R 4 and R 5 are as defined in claim 1 ;

and a compound of a general formula [III]

 wherein R 6 , R 7 , R 8 and n are as defined in claim 1 ;

to an amidation reaction.