Ring-annulated dihydropyrrolo[2,1-α]isoquinolines

1. A ring-annulated dihydropyrrolo[2,1-a]isoquinoline derivative according to formula I

or a pharmaceutically acceptable salt thereof wherein

R1 is phenyl, (2-5C)heteroaryl, (3-6C)cycloalkyl, (1-6C)alkyl, (2-5C)heterocycloalkyl or (2-5C)heterocycloalkenyl, each optionally substituted with one or more (1-3C)alkyl or halogen; or

R1 is halogen;

R2 is H or (1-4C)alkyl;

R3 is hydroxyl, (1-3C)alkoxy; (1-3C)alkylthio or (1-4C)alkyl;

R4 is (1-5C)heteroaryl, (2-5C)heterocycloalkyl or (2-5C)heterocycloalkenyl, each optionally substituted with one or more hydroxy, cyano, halogen, (1-3C)alkoxy or (1-6C)alkyl, the alkyl group optionally substituted with one or more hydroxy or fluorine; or

R4 is halogen, nitro, cyano, amino, carboxylic acid or N-hydroxy-imidamide; or

R4 is (1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, (3-6C)cycloalkyl, (1-6C)alkoxy, (1-6C)alkylthio, (1-6C)alkylOC(O)(1-6C)alkyl, each optionally substituted with one or more hydroxy, oxo, cyano or fluorine; or

R4 is —NH(CO)R6, —NHSO2R6, —NHR6, —C(O)N(R7)R8, —C(O)OR6, —S(O)R6 or —SO2R6;

R5 is H or halogen;

R6 is (1-6C)alkyl, (2-6C)alkenyl or (2-5C)heteroaryl, each optionally substituted with one or more (1-3C)alkyl, (1-3C)alkoxy, hydroxy or halogen; or

R6 is (di)[(1-4C)alkyl]amino(1-4C)alkyl, (di)[(1-4C)alkyl]aminoC(O)(1-4C)alkyl or (2-5C)heterocycloalkyl(1-4C)alkyl, the heterocycloalkyl group optionally substituted with one or more (1-4C)alkyl, oxo, hydroxy, fluorine or (di)[(1-4C)alkyl]amino(1-4C)alkyl;

Y is a bond, Y is (CH 2 ) n or Y is X(CH 2 ) m , wherein one or more of the hydrogen atoms in the (CH 2 ) n or (CH 2 ) m groups in Y may optionally be substituted with (1-3C)alkyl, fluorine or hydroxy;

X is O, S or NR9;

R7 is H or (1-6C)alkyl, optionally substituted with one or more hydroxyl groups;

R8 is H, or (1-6C)alkyl, (1-6C)alkenlyl or (2-5C)heteroaryl, each optionally substituted with one or more (1-3C)alkyl, (1-3C)alkoxy, hydroxy or halogen; or

R8 is (2-5C)heterocycloalkyl(1-4C)alkyl, the heterocycloalkyl group optionally substituted with (1-4C)alkyl or (di)[(1-4C)alkyl]amino(1-4C)alkyl; or

R7 and R8 can form, together with the interconnecting nitrogen, a (2-5)heterocycloalkyl group, optionally substituted with hydroxy, (1-6C)alkoxycarbonyl or (1-6C)alkyl, the alkyl group optionally substituted with one or more hydroxy or fluorine;

R9 is hydrogen or R10-carbonyl;

R10 is (1-3C)alkyl, optionally substituted with halogen;

n is 0-4;

m is 2 or 3.

2. The compound according to claim 1 wherein R4 is (1-5C) heteroaryl, optionally substituted with (1-3C)alkyl or halogen; or R4 is nitro, (1-6C)alkyl, (1-6C)alkoxy, (1-6C)alkylthio, or —NH(CO)R6.

3. The compound according to claim 1 wherein R5 is H.

4. The compound according to claim 1 wherein R6 is (1-3C)alkyl.

5. The compound according to claims 1 wherein R3 is (1-3C)alkoxy.

6. The compound according to claims 1 wherein Y is (CH 2 ) n or Y is X(CH 2 ) m , wherein one or more of the hydrogen atoms in the (CH 2 ) n or (CH 2 ) m groups in Y may optionally be substituted with (1-3C)alkyl.

7. The compound according to claim 1 wherein Y is (CH 2 ) 3 .

8. The compound according to claim 1 wherein Y is X(CH 2 ) 2 .

9. The compound according to claim 1 wherein R1 is thienyl or thiazolyl.

10. A pharmaceutical composition made by combining a compound according to claim 1 , or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable excipients.

11. A pharmaceutical composition which comprises a compound according to claim 1 or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable excipients.

12. A pharmaceutical composition according to claim 11 , which further comprises at least one additional therapeutically active agent.