Substituted indole derivatives

1. A Method for the treatment of a disease or condition in which PKC activation plays a role or is implicated, in a subject in need thereof which comprises administering to the subject an effective amount of a compound of formula (I) or a pharmaceutically acceptable salt or hydrate thereof,

Wherein

X is CH or N;

R is H or PO 3 H 2 ;

R1 is H; or C 1-4 alkyl;

R2 is H; or C 1-4 alkyl;

R3 is H; C 1-4 alkyl; CN; HaI; or OH; and

R4 and R5 are independently from each other H, or C 1-4 alkyl; or R4 and R5 form together with the carbon atom to which they are attached a 3-6 membered cycloalkyl group;

wherein the disease or condition is selected from psoriasis, acute or chronic rejection of organ or tissue allo- or xenografts and graft-versus-host disease and host-versus-graft disease.

2. The method according to claim 1 , comprising administering to the subject an effective amount of a compound of Formula (I) or a pharmaceutically acceptable salt or hydrate thereof,

wherein

X is CH;

R is H;

R1 is H;

R2 is H; or C 1-4 alkyl;

R3 is H; or C 1-4 alkyl; and

R4 and R5 are independently from each other H; or R4 and R5 form together with the carbon atom to which they are attached a 3-6 membered cycloalkyl group.

3. The method according to claim 1 , comprising administering to the subject an effective amount of a compound of Formula (I) or a pharmaceutically acceptable salt or hydrate thereof,

wherein

X is N;

R is PO 3 H 2 ;

R1 is H;

R2 is H; or C 1-4 alkyl;

R3 is H; and

R4 and R5 are independently from each other H; or R4 and R5 form together with the carbon atom to which they are attached a 3-6 membered cycloalkyl group.

4. The method according to claim 1 , comprising administering to the subject an effective amount of a compound of formula (III)

or a pharmaceutically acceptable salt or hydrate thereof.

5. The method according to claim 1 , comprising administering to the subject an effective amount of a compound of Formula (I), which is phosphoric acid mono-[3-[3-(4,7-diaza-spiro[2.5]oct-7-yl)-isoquinolin-1-yl]-4-(7-methyl-1H-indol-3-yl)-2,5-dioxo-2,5-dihydro-pyrrol-1-ylmethyl]ester, mono-hydrate.

6. The method in accordance to claim 1 , comprising administering to the subject an effective amount of a compound of Formula (I) which is 3-[3-(4,7-diaza-spiro[2.5]oct-7-yl)-isoquinolin-1-yl]-1-hydroxymethyl-4-(7-methyl-1H-indol-3-yl)-pyrrole-2,5-dione or a pharmaceutically acceptable salt thereof.

7. The method in accordance to claim 1 , comprising administering to the subject an effective amount of a compound of Formula (I) which is phosphoric acid mono-{3-(1H-indol-3-yl)-4-[2-(4-methyl-piperazin-1-yl)-quinazolin-4-yl]-2,5-dioxo-2,5-dihydro-pyrrol-1-ylmethyl}ester or a pharmaceutically acceptable salt thereof.