Quinoline compounds suitable for treating disorders that respond to modulation of the serotonin-5-HT

1. A method for treating a cognitive dysfunction associated with Alzheimer's disease, a cognitive dysfunction associated with schizophrenia, or obesity, said method comprising administering an effective amount of the compound of formula (I) or a physiologically tolerated acid addition salt or a N-oxide thereof to a subject in need thereof

where in formula (I)

R is a radical selected from the group consisting of

wherein * indicates the binding site to the quinolinyl radical;

R 1 is hydrogen, C 1 -C 6 -alkyl, C 1 -C 6 -hydroxyalkyl, C 1 -C 6 -haloalkyl, C 1 -C 6 -alkoxy-C 1 -C 4 -alkyl, C 1 -C 6 -haloalkoxy-C 1 -C 4 -alkyl, C 3 -C 6 -cycloalkyl, C 3 -C 6 -halocycloalkyl, C 3 -C 6 -cycloalkyl-C 1 -C 4 -alkyl, aryl-C 1 -C 4 -alkyl, hetaryl-C 1 -C 4 -alkyl, C 3 -C 6 -alkenyl, C 3 -C 6 -haloalkenyl, formyl, C 1 -C 4 -alkylcarbonyl, C 1 -C 4 -alkoxycarbonyl, phenoxycarbonyl or benzyloxycarbonyl, where the phenyl rings in the last two mentioned moieties are unsubstituted or carry 1, 2 or 3 substituents, selected from halogen, C 1 -C 4 -alkyl or C 1 -C 4 -haloalkyl;

n is 0, 1 or 2;

m is 0, 1, 2 or 3;

R a , R ib are independently selected from the group consisting of halogen, CN, C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy, C(O)R aa , C(O)NR cc R bb and NR cc R bb ;

wherein R aa is hydrogen, C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy or C 1 -C 4 -haloalkoxy, and

R cc , R bb are independently selected from the group consisting of hydrogen and C 1 -C 4 -alkyl;

X is S(O) 2 ; which is located in the 3- or 4-position of the quinoline ring;

Ar is phenyl, which is unsubstituted or may carry 1, 2, 3 substituents R x , wherein

R x is halogen, CN, NO 2 , C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 1 -C 6 -hydroxyalkyl, C 1 -C 6 -alkoxy-C 1 -C 4 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -haloalkenyl, C 3 -C 6 -cyclo-alkyl, C 3 -C 6 -halocycloalkyl, C 1 -C 6 -alkoxy, C 1 -C 6 -hydroxyalkoxy, C 1 -C 6 -alkoxy-C 1 -C 4 -alkoxy, C 1 -C 6 -haloalkoxy, C 1 -C 6 -alkylthio, C 1 -C 6 -haloalkylthio, C 1 -C 6 -alkylsulfinyl, C 1 -C 6 -haloalkylsulfinyl, C 1 -C 6 -alkylsulfonyl, C 1 -C 6 -haloalkylsulfonyl, C 1 -C 6 -alkylcarbonyl, C 1 -C 6 -haloalkylcarbonyl, C 1 -C 6 -alkylcarbonylamino, C 1 -C 6 -haloalkyl-carbonylamino, carboxy, NH—C(O)—NR x1 R x2 , NR x1 R x2 , NR x1 R x2 —C 1 -C 6 -alkylene, O—NR x1 R x2 , wherein R x1 and R x2 in the last 4 mentioned radicals are independently of each other hydrogen, C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl or C 1 -C 6 -alkoxy or R x1 and R x2 in the last 4 mentioned radicals together with the nitrogen atom form an N-bound 5-, 6- or 7-membered, saturated heteromonocycle or an N-bound 7-, 8-, 9- or 10-membered, saturated heterobicycle which are unsubstituted or which carry 1, 2, 3 or 4 radicals selected from C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -hydroxyalkyl and C 1 -C 4 -alkoxy and wherein 2 radicals R x , which are bound to adjacent carbon atoms of Ar may form a saturated or unsaturated 5- or 6-membered carbocyclic or heterocyclic ring, which itself may carry a radical R x .

2. The method of claim 1 , wherein R 1 is hydrogen.

3. The method of claim 1 , wherein X is located in the 3-position of the quinolinyl moiety.

4. The method of claim 1 , wherein X is located in the 4-position of the quinolinyl moiety.

5. The method of claim 1 , wherein R x is selected from the group consisting of halogen, CN, C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy, C 3 -C 6 -cycloalkyl and a group NR x1 R x2 .

6. The method of claim 1 , wherein m is 0.

7. The method of claim 1 , wherein n is 0.

8. The method of claim 1 , where the compound of formula (I) is a compound of the formula (Ia.a)

wherein R is a radical R-12 or R-16

wherein R 1 is hydrogen and wherein Ar is as defined in claim 1 .

9. The method of claim 8 where R in formula (Ia.a) is a radical of the formula R-16b,

wherein R 1 is hydrogen.

10. The method of claim 1 , where the compound of formula (I) is a compound of the formula (Ia.a)

wherein m is 0, n is 0 and wherein R is a radical R-16b

wherein R 1 is hydrogen or methyl

and wherein Ar is selected from the group consisting of phenyl, 3-fluorophenyl, 4-fluorophenyl, 3-trifluoromethylphenyl, 3-trifluoromethoxyphenyl, 3-difluoromethylphenyl, 4-(oxazol-5-yl)phenyl, 3-(oxazol-2-yl)phenyl, 3-(oxazol-4-yl)phenyl and 3-(oxazol-5-yl)phenyl.

11. The method of claim 1 , where the compound of formula (I) or a physiologically tolerated acid addition salt or a N-oxide thereof is administered as a pharmaceutical composition comprising the compound of formula (I) or a physiologically tolerated acid addition salt or a N-oxide thereof together with at least one physiologically acceptable carrier or auxiliary substance.

12. The method of claim 1 , wherein R x is selected from the group consisting of halogen, C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 1 -C 6 -hydroxyalkyl, C 1 -C 6 -alkoxy, C 1 -C 6 -alkoxy-C 1 -C 4 -alkyl, C 1 -C 6 -haloalkoxy, C 2 -C 6 -alkenyl, C 2 -C 6 -haloalkenyl and a group NR x1 R x2 .

13. The method of claim 1 , wherein the compound of formula (I), or a physiologically tolerated acid addition salt or a N-oxide thereof, is selected from the group consisting of:

8-(Hexahydropyrrolo[3,4-b]pyrrol-5(1H)-yl)-3-(phenylsulfonyl)quinoline;

Benzyl 6-(3-(phenylsulfonyl)quinolin-8-yl)-3,6-diazabicyclo[3.2.0]heptane-3-carboxylate;

tert-butyl 2-(3-(phenylsulfonyl)quinolin-8-yl)hexahydro-1H-pyrrolo[3,4-c]pyridine-5(6H)-carboxylate;

3-(Phenylsulfonyl)-8-(1H-pyrrolo[3,4-c]pyridin-2(3H,3aH,4H,5H,6H,7H,7aH)-yl)quinoline;

(1R,5S)-tert-butyl 3-(3-(phenylsulfonyl)quinolin-8-yl)-3,6-diazabicyclo[3.2.0]heptane-6-carboxylate;

8-((1S,5S)-3,6-diazabicyclo[3.2.0]heptan-3-yl)-3-(phenylsulfonyl)quinoline;

(3aS,6aS)-ethyl 1-(3-(phenylsulfonyl)quinolin-8-yl)hexahydropyrrolo[3,4-b]pyrrole-5(1H)-carboxylate;

tert-butyl 5-(3-(4-fluorophenylsulfonyl)quinolin-8-yl)hexahydropyrrolo[3,4-b]pyrrole-1(2H)-carboxylate;

tert-butyl 5-(3-(phenylsulfonyl)quinolin-8-yl)octahydro-1,5-naphthyridine-1(2H)-carboxylate;

1-(3-(phenylsulfonyl)quinolin-8-yl)decahydro-1,5-naphthyridine;

tert-butyl 2-(3-(4-fluorophenylsulfonyl)quinolin-8-yl)hexahydro-1H-pyrrolo[3,4-c]pyridine-5(6H)-carboxylate;

8-((3aS,6aS)-hexahydropyrrolo[3,4-b]pyrrol-1(2H)-yl)-3-(phenylsulfonyl)quinoline;

3-(4-fluorophenylsulfonyl)-8-(1H-pyrrolo[3,4-c]pyridin-2(3H,3aH,4H,5H,6H,7H,7aH)-yl)quinoline;

3-(4-fluorophenylsulfonyl)-8-(hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)quinoline;

tert-butyl 5-(3-(3-(trifluoromethoxy)phenylsulfonyl)quinolin-8-yl)hexahydropyrrolo[3,4-c]pyrrole-2(1H)-carboxylate;

8-(hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)-3-(3-(trifluoromethoxy)phenylsulfonyl)quinoline;

tert-butyl 5-(3-(3-(5-(tert-butoxycarbonyl)hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)phenylsulfonyl)quinolin-8-yl)hexahydropyrrolo[3,4-c]pyrrole-2(1H)-carboxylate;

8-(hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)-3-(3-(hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)phenylsulfonyl)quinoline;

tert-butyl 2-(3-(3-(trifluoromethoxy)phenylsulfonyl)quinolin-8-yl)hexahydro-1H-pyrrolo[3,4-c]pyridine-5(6H)-carboxylate;

8-(1H-pyrrolo[3,4-c]pyridin-2(3H,3aH,4H,5H,6H,7H,7aH)-yl)-3-(3-(trifluoromethoxy)phenylsulfonyl)quinoline;

tert-butyl 5-(3-(3-(trifluoromethyl)phenylsulfonyl)quinolin-8-yl)hexahydropyrrolo[3,4-b]pyrrole-1(2H)-carboxylate;

8-(hexahydropyrrolo[3,4-b]pyrrol-5(1H)-yl)-3-(3-(trifluoromethyl)phenylsulfonyl)quinoline;

(3aR,6aS)-tert-butyl 5-(3-(3-(trifluoromethyl)phenylsulfonyl)quinolin-8-yl)hexahydropyrrolo[3,4-c]pyrrole-2(1H)-carboxylate;

8-((3aR,6aS)-hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)-3-(3-(trifluoromethyl)phenylsulfonyl)quinoline;

(3aS,6aS)-ethyl-1-(3-(3-fluorophenylsulfonyl)quinolin-8-yl)hexahydropyrrolo[3,4-b]pyrrole-5(1H)-carboxylate;

3-(3-Fluoro-benzenesulfonyl)-8-(3aS,6aS)-hexahydropyrrolo[3,4-b]pyrrol-1-yl-quinoline;

(1S,5R)-tert-butyl 3-(3-(3-fluorophenylsulfonyl)quinolin-8-yl)-3,6-diazabicyclo[3.2.0]heptane-6-carboxylate;

8-(1R,5R)-3,6-Diaza-bicyclo[3.2.0]hept-3-yl-3-(3-fluoro-benzenesulfonyl)-quinoline;

3-(3-Fluoro-benzenesulfonyl)-8-(hexahydro-pyrrolo[3,4-b]pyrrol-5-yl)-quinoline;

3-(3-Fluoro-benzenesulfonyl)-8-(3aR,6aS)-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl-quinoline;

3-(3-fluorophenylsulfonyl)-8-(tetrahydro-1H-pyrrolo[3,4-b]pyridin-6(2H,7H,7aH)-yl)quinoline;

8-((1S,5S)-3,6-diazabicyclo[3.2.0]heptan-3-yl)-3-(3-fluorophenylsulfonyl)quinoline;

5-(3-(3-fluorophenylsulfonyl)quinolin-8-yl)octahydro-1H-pyrrolo[3,4-c]pyridin-2-ium chloride;

8-(5-benzyl-1H-pyrrolo[3,4-c]pyridin-2(3H,3aH,4H,5H,6H,7H,7aH)-yl)-3-(3-fluorophenylsulfonyl)quinoline;

3-(3-Fluoro-benzenesulfonyl)-8-(octahydro-pyrrolo[3,4-c]pyridin-2-yl)-quinoline;

8-((3aS,6aS)-1-benzyl hexahydropyrrolo[3,4-b]pyrrol-5(1H)-yl)-3-(3-fluorophenylsulfonyl)quinoline;

3-(3-Fluoro-benzenesulfonyl)-8-((3aR,6aS)-5-methyl-hexahydropyrrolo[3,4-c]pyrrol-2-yl)-quinoline;

3-(4-fluorophenylsulfonyl)-8-(hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)quinoline;

3-(4-fluorophenylsulfonyl)-8-(hexahydropyrrolo[3,4-b]pyrrol-5(1H)-yl)quinoline;

8-(5-benzylhexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)-3-(phenylsulfonyl)-quinoline;

8-(5-methyl-1H-pyrrolo[3,4-c]pyridin-2(3H,3aH,4H,5H,6H,7H,7aH)-yl)-3-(phenylsulfonyl)quinoline;

2-(3-(phenylsulfonyl)quinolin-8-yl)dodecahydro-1H-pyrido[4,3-b]indole;

8-(hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)-3-(phenylsulfonyl)quinoline; and

8-(1H-pyrrolo[3,4-c]pyridin-2(3H,3aH,4H,5H,6H,7H,7aH)-yl)-3-(3-(trifluoromethyl)phenylsulfonyl)quinolone.