Isoquinoline derivatives

1. A method of treating Alzheimer's disease in a patient comprising administering to the patient at least one compound of the formula (I):

wherein

R 1 is

H;

R 2 is

H;

R 3 is

H, NH-phenyl or NH-benzodioxolyl;

R 4 is

H,

halogen,

(C 1 -C 6 )alkyl;

R 5 is

H,

halogen,

(C 1 -C 6 )alkyl,

cyclopropyl, phenyl, benzofuran,

(C 1 -C 6 )alkylene-phenyl;

R 6 is

H,

(C 1 -C 8 )alkyl,

(C 1 -C 6 )alkylene-(C 10 )aryl,

(C 1 -C 6 )alkylene-CH[phenyl] 2 , (C 1 -C 6 )alkylene-phenyl;

R 7 is

H,

halogen,

(C 1 -C 6 )alkyl,

phenyl;

R 8 is

H,

halogen,

or (C 1 -C 6 )alkyl;

n is 1, 2, 3 or 4; and

L is

O or

O—(C 1 -C 6 )alkylene;

wherein in residues R 4 , R 5 , R 7 and R 8 one alkyl or alkylene hydrogen atom can be optionally substituted by OH, OCH 3 , COOH, COOCH 3 , NH 2 , NHCH 3 , N(CH 3 ) 2 , CONH 2 , CONHCH 3 or CON(CH 3 ) 2 , and in any residue one or more alkyl or alkylene hydrogen atoms can optionally be substituted by F;

and wherein phenyl or naphthyl groups are optionally substituted one or more times by (C 1 -C 4 )alkyl, O—(C 1 -C 4 )alkyl, O-phenyl, C(O)O—(C 1 -C 6 )alkyl, C(O)OH, C(O)—(C 1 -C 4 )alkyl, halogen, NO 2 , SO 2 NH 2 , CN, SO 2 —(C 1 -C 4 )alkyl, NH—SO 2 —(C 1 -C 4 )alkyl, NH 2 , NH—C(O)—(C 1 -C 4 )alkyl, (C 3 -C 8 )cycloalkyl, (C 1 -C 4 )alkyl-OH, C(O)N[(C 1 -C 4 )alkyl] 2 , C(O)NH 2 , N[(C 1 -C 4 )alkyl] 2 , (C 2 -C 4 )alkenylene-(C 6 -C 10 )aryl, wherein the (C 6 -C 10 )aryl may be further substituted with (C 1 -C 4 )alkyl, (C 1 -C 4 )alkylene-O—(C 1 -C 6 )alkyl, O—(C 1 -C 6 )alkyl-(C 6 -C 10 )aryl, or may be vicinal substituted by a O—(C 1 -C 4 )alkylene-O group whereby a 5-8-membered ring is formed together with the carbon atoms the oxygen atoms are attached to,

and wherein the benzofuran or benzodioxolyl groups are optionally substituted one or more times with (C 1 -C 4 )alkyl, O—(C 1 -C 4 )alkyl, halogen or (C 1 -C 4 )alkylene-O—(C 1 -C 4 )alkyl,

or a pharmaceutically acceptable salt and physiologically functional derivative thereof.

2. A method according to claim 1 , wherein in formula (I), R 3 is H, or NH-phenyl.

3. A method according to claim 1 , wherein in formula (I), R 8 is H, halogen or (C 1 -C 4 )alkyl.

4. A method according to claim 3 , wherein in formula (I), R 8 is H, Cl, F, methyl or ethyl.

5. A method according to claim 1 , wherein in formula (I), R 4 is H, halogen or (C 1 -C 4 )alkyl.

6. A method according to claim 5 , wherein in formula (I), R 4 is H.

7. A method according to claim 1 , wherein in formula (I), R 5 is H, halogen, (C 1 -C 6 )alkyl, phenyl, (C 1 -C 2 )alkylene-phenyl or benzofuran.

8. A method according to claim 1 , wherein in formula (I), R 7 is H, halogen, (C 1 -C 4 )alkyl, or phenyl.

9. A method according to claim 1 , wherein in formula (I), R 7 is H, fluoro, chloro, bromo, methyl, ethyl, or phenyl.

10. A method according to claim 1 , wherein in formula (I), n is 1, 2 or 3.

11. A method according to claim 10 , wherein in formula (I), n is 1.

12. A method according to claim 1 , wherein in formula (I), R 6 is H, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkylene-(C 10 )aryl or (C 1 -C 6 )alkylene-phenyl.

13. A method according to claim 12 , wherein in formula (I), R 6 is H, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkylene-(C 10 )aryl or (C 1 -C 6 )alkylene-phenyl.

14. A method according to claim 1 , wherein in formula (I), L is attached to the 3-position or to the 4-position of the piperidine ring.

15. A method according to claim 1 , wherein in formula (I), L is attached to the 4-position of the piperidine ring.

16. A method according to claim 1 , wherein in formula (I), L is O-methylene, O-ethylene or O.

17. A method according to claim 16 , wherein in formula (I), L is O.

18. A method according to claim 1 , wherein in formula (I),

R 1 is H;

R 2 is hydrogen;

R 3 is H, NH-phenyl or NH-benzodioxolyl;

R 4 is H, halogen or (C 1 -C 6 )alkyl;

R 5 is H, (C 1 -C 6 )alkyl, halogen, phenyl, (C 1 -C 6 )alkylene-phenyl or benzofuran;

R 6 is H, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkylene-(C 10 )aryl or (C 1 -C 6 )alkylene-phenyl;

R 7 is H, halogen, (C 1 -C 6 )alkyl, or phenyl;

n is 1, 2 or 3, and

L is O,O-methylene or O-ethylene.

19. A method according to claim 1 , wherein in formula (I),

R 1 is H;

R 2 is H;

R 3 is H, halogen, or NH-phenyl or NH-benzodioxolyl;

R 4 is H, halogen or (C 1 -C 4 )alkyl;

R 5 is H, (C 1 -C 6 )alkyl, halogen, phenyl, (C 1 -C 6 )alkylene-phenyl or benzofuran;

R 6 is H, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkylene-phenyl or (C 1 -C 6 )alkylene-(C 10 )aryl;

R 7 is H, halogen, (C 1 -C 6 )alkyl, or phenyl;

n is 1, 2or 3; and

L is O.

20. A method according to claim 1 , wherein in formula (I),

R 1 is H;

R 2 is H;

R 3 is H or NH-phenyl;

R 4 is H, halogen or (C 1 -C 4 )alkyl;

R 5 is H, (C 1 -C 4 )alkyl, halogen, phenyl, or (C 1 -C 2 )alkylene-phenyl;

R 6 is H, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkylene-phenyl or (C 1 -C 6 )alkylene-(C 10 )aryl;

R 7 is H, halogen, (C 1 -C 4 )alkyl, or phenyl;

R 8 is H, halogen or (C 1 -C 4 )alkyl;

n is 1; and

L is O.

21. A method according to claim 1 comprising administering to a patient a pharmaceutical composition comprising a pharmaceutically effective amount of at least one compound of formula (I), or a pharmaceutically acceptable salt thereof, a physiologically functional derivative thereof and physiologically tolerated excipients and carriers.

22. A method according to claim 21 wherein the pharmaceutical composition further comprises additional additives or other active ingredients.

23. A method according to claim 1 , wherein in formula (I), R 3 is

24. A method according to claim 1 , wherein in formula (I), R 5 is hydrogen, fluoro, chloro, bromo, iodo, (p-methoxy)-phenyl, N-aniline, phenyl, benzyl, methyl, ethyl, cyclopropyl, 4-methoxy-anilin, N-acetyl or a substituent of the group consisting of

25. A method according to claim 1 wherein in formula (I), R 6 is H, methyl, ethyl, propyl, butyl, s-butyl, pentyl, 3-methyl-butyl, isopropyl, benzyl or a substituent of the group consisting of