1-(7-(hexahydropyrrolo [3,4-c] pyrrol-2 (1H)-yl) quinolin-4-yl) -3- (pyrazin-2-yl) urea derivatives and related compounds as glycogen synthase kinase 3 (GSK-3)

1. A heterocyclic compound of the general formula (I)

the stereoisomers, tautomers and/or physiologically tolerated acid addition salts thereof, wherein

A is selected from the group consisting of CR A1 R A2 and NR B ; where

R A1 and R A2 are independently of each other selected from the group consisting of hydrogen, C 1 -C 2 -alkyl, C 1 -C 2 -haloalkyl, NH 2 and OH; and

R B is selected from H, C 1 -C 4 -alkyl and C 1 -C 4 -haloalkyl;

X 1 is selected from the group consisting of CR 2 and N;

X 2 and X 3 are independently of each other selected from the group consisting of CR 2 ;

X 4 and X 7 are independently of each other selected from the group consisting of CR 1 , CR 3 and N;

X 5 and X 6 are independently of each other selected from the group consisting of CR 1 and CR 3 ;

With the proviso that only one of X 1 , X 4 and X 7 is N and that no more than two of X 4 , X 5 , X 6 and X 7 are CR 1 ;

G is a 5- or 6-membered heteroaromatic ring containing one nitrogen atom and optionally 1, 2 or 3 further nitrogen atoms as ring members, where the heteroaromatic ring is bonded to the group NR 4 via a carbon atom in α-position to the nitrogen ring atom and where the heteroaromatic ring optionally carries 1, 2, 3 or 4 substituents R 5 or 1, 2 or 3 substituents R 5 and 1 substituent R 1 ;

with the proviso that G carries one substituent R 1 if none of X 4 , X 5 , X 6 and X 7 is CR 1 ;

each R 1 is independently a 6-, 7-, 8-, 9-, 10-, 11-, 12-, 13- or 14-membered bicyclic or tricyclic saturated or unsaturated heterocyclic ring containing one nitrogen atom and optionally 1, 2 or 3 further heteroatoms selected from N, O and S as ring members and optionally carrying 1, 2 or 3 substituents R 6 ;

each R 2 is independently selected from the group consisting of hydrogen, OH, halogen, CN, C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 1 -C 6 -alkoxy, C 1 -C 6 -haloalkoxy and NR a R b ; or two radicals R 2 bonded at the carbon atoms of groups X 2 and X 3 , together with the carbon atoms to which they are bonded, form a 5- or 6-membered saturated or unsaturated ring which may contain 1 or 2 heteroatoms as ring members selected from the group consisting of N, O and S and which optionally carries 1, 2 or 3 substituents R 7 ;

each R 3 is independently selected from the group consisting of hydrogen, CN, NR a R b , OH, halogen, C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 3 -C 7 -cycloalkyl, C 3 -C 7 -halocycloalkyl, C 2 -C 4 -alkenyl, C 2 -C 4 -haloalkenyl, C 1 -C 6 -alkoxy, C 1 -C 6 -haloalkoxy, formyl, C 1 -C 6 -alkylcarbonyl, C 1 -C 6 -haloalkylcarbonyl, C 1 -C 6 -alkoxycarbonyl, C 1 -C 6 -haloalkoxycarbonyl, C 1 -C 6 -alkyl-NR a R b and an aromatic radical Ar, which is selected from the group consisting of phenyl and a 5- or 6-membered N- or C-bound heteroaromatic radical comprising one nitrogen atom and optionally 1, 2 or 3 further heteroatoms independently selected from O, S and N as ring members, wherein Ar is unsubstituted or carries one or two radicals R 8 and wherein Ar may also be bonded via a CH 2 group;

R 4 is selected from the group consisting of hydrogen, C 1 -C 4 -alkyl and C 1 -C 4 -haloalkyl;

R 5 , R 6 and R 7 , independently of each other and independently of each occurrence, have one of the meanings given for R 3 ;

each R 8 is independently selected from the group consisting of halogen, C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 3 -C 6 -cycloalkyl, C 3 -C 6 -halocycloalkyl, C 1 -C 6 -alkoxy, C 1 -C 6 -haloalkoxy, NR a R b , a phenyl group and an aromatic 5- or 6-membered C-bound heteroaromatic radical comprising one nitrogen atom and optionally 1, 2 or 3 further heteroatoms independently selected from O, S and N as ring members, wherein phenyl and the heteroaromatic radical are, independently of each other, unsubstituted or substituted by 1, 2, 3 or 4 radicals selected from halogen, cyano, C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy and C 1 -C 4 -haloalkoxy; and

R a and R b are independently of each other selected from the group consisting of hydrogen, C 1 -C 6 -alkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy, C 1 -C 4 -alkylcarbonyl and C 1 -C 4 -haloalkylcarbonyl;

or R a and R b form, together with the nitrogen atom to which they are bonded, a 3-, 4-, 5-, 6- or 7-membered saturated or unsaturated aromatic or non-aromatic N-heterocyclic ring, which may contain 1 further heteroatom or heteroatom containing group selected from the group consisting of O, S, SO, SO 2 and N as a ring member.

2. The heterocyclic compound according to claim 1 , wherein one or two of X 4 , X 5 , X 6 and X 7 are CR 1 .

3. The heterocyclic compound according to claim 1 , wherein none of X 4 , X 5 , X 6 and X 7 is CR 1 and G carries a substituent R1.

4. The heterocyclic compound according to claim 1 , wherein X 1 is N.

5. The heterocyclic compound according to claim 4 , wherein X 4 is CR 1 or CR 3 .

6. The heterocyclic compound according to claim 1 , wherein R 1 is a 7-, 8-, 9- or 10-membered bicyclic saturated heterocyclic ring containing one nitrogen atom and optionally 1, 2 or 3 further heteroatoms selected from N and O as ring members and optionally carrying 1, 2 or 3 substituents R 6 which are as defined in claim 1 .

7. The heterocyclic compound according to claim 6 , wherein R 1 is a 7-, 8-, 9- or 10- membered bicyclic saturated heterocyclic ring bound via a nitrogen ring atom, optionally containing one further heteroatom selected from N and O as ring member and optionally carrying 1, 2 or 3 substituents R 6 .

8. The heterocyclic compound according to claim 1 , wherein R 6 is selected from C 1 -C 4 -alkyl, C 1 -C 4 fluoroalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -fluoroalkoxy, C 1 -C 4 -alkylcarbonyl, C 1 -C 4 -fluoroalkylcarbonyl, C 1 -C 4 -alkoxycarbonyl and C 1 -C 4 -fluoroalkoxycarbonyl.

9. The heterocyclic compound according to claim 1 , wherein R 1 is selected from one of the following formulae

and the stereoisomers thereof;

where

Y 1 is O or NR 61 ;

R 61 is H or has one of the meanings of R 6 given in claim 1 ; and

# is the attachment point to the remainder of the molecule.

10. The heterocyclic compound according to claim 1 , wherein each R 3 is independently selected from hydrogen, halogen, C 1 -C 4 -alkyl, C 1 -C 4 -fluoroalkyl, C 1 -C 4 -alkoxy and C 1 -C 4 -fluoroalkoxy.

11. The heterocyclic compound according to claim 1 , wherein each R 2 is independently selected from hydrogen, halogen, C 1 -C 4 -alkyl and C 1 -C 4 -fluoroalkyl.

12. The heterocyclic compound according to claim 1 , wherein one of groups X 1 , X 2 and X 3 is CH and one of groups X 1 , X 2 and X 3 is CR 2 , where R 2 has one of the meanings given in claim 1 .

13. The heterocyclic compound according to claim 1 , wherein X 1 is N, X 2 and X 3 are CR 2 , preferably CH, one of X 5 and X 6 is CR 1 and the other is CR 3 , preferably CH, X 4 and X 7 are CR 3 , preferably CH, and G carries no substituent R 1 ; or X 1 is N, X 2 and X 3 are CR 2 , preferably CH, X 4 , X 5 and X 7 are CR 3 , preferably CH, X 6 is CR 3 , preferably C-methoxy, and G carries one substituent R 1 .

14. The heterocyclic compound according to claim 1 , wherein G is a 6-membered heteroaromatic ring selected from pyridin-2-yl, pyrazin-2-yl, pyrimidin-2-yl, pyrimidin-4-yl, pyridazin-3-yl and triazin-2-yl, which may carry 1, 2, or 3 substituents R 5 which are as defined in claim 1 or which may carry 1 or 2 substituents R 5 which are as defined in claim 1 and one substituent R 1 which is defined in claim 1 .

15. The heterocyclic compound according to claim 14 , wherein G is a 6-membered heteroaromatic ring selected from pyridin-2-yl and pyrazin-2-yl, which may carry 1, 2, or 3 substituents R 5 which are as defined in claim 1 or which may carry 1 or 2 substituents R 5 which are as defined in claim 1 and one substituent R 1 which is as defined in claim 1 .

16. The heterocyclic compound according to claim 15 , wherein G carries the substituent R 1 in the 6-position.

17. The heterocyclic compound according to claim 1 , wherein A is CH 2 , NH or NCH 3 .

18. The heterocyclic compound according to claim 1 , wherein R 4 is H or CH 3 .

19. A pharmaceutical composition comprising at least one heterocyclic compound as defined in claim 1 , a stereoisomer, tautomer and/or physiologically tolerated acid addition salt thereof and optionally at least one physiologically acceptable carrier and/or auxiliary substance.