Substituted indol-5-ol derivatives and their therapeutical applications

1. A compound of the formula (I)

or a pharmaceutically acceptable derivative thereof, wherein;

R is selected from the group consisting of:

(i) hydrogen, amino, alkyl amino;

(ii) C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl; and

(iii) K—Ar;

Ar represents heteroaryl or aryl, each of which is substituted with from 0 to 4 substituents independently selected from the group consisting of:

(i) halogen, hydroxy, amino, amide, cyano, —COOH, —SO 2 NH 2 , oxo, nitro or alkoxycarbonyl; and

(ii) C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 3 -C 10 cycloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 2 -C 6 alkanoyl, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkoxy, mono- and di-(C 1 -C 6 alkyl)amino, C 1 -C 6 alkylsulfonyl, mono- and di-(C 1 -C 6 alkyl) sulfonamido and mono- and di-(C 1 -C 6 alkyl)aminocarbonyl; phenylC 0 -C 4 alkyl or (4- to 7-membered heterocycle)C 0 -C 4 alkyl, each of which is substituted with from 0 to 4 secondary substituents independently selected from the group consisting of halogen, hydroxy, cyano, oxo, imino, C 1 -C 4 alkyl, C 1 -C 4 alkoxy or C 1 -C 4 haloalkyl;

K is selected from the group consisting of:

(i) O, S, SO, SO2;

(ii) (CH2) m , m=0-3, —O(CH 2 ) p , p=1-3, —S(CH 2 ) p , p=1-3, —N(CH 2 ) p , p=1-3, —(CH2) p O, p=1-3;

(iii) NR 1

wherein R 1 represents hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, alkylthio, aryl, or arylalkyl; and

(iv) groups of the formula (Ia):

wherein:

R 2 represents hydrogen, C 1 -C 4 alkyl, or oxo;

X is CH, when R 3 is hydrogen; or X—R 3 is O; or X is N, wherein R 3 represents groups of hydrogen, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 10 aryl or heteroaryl, (C 3 -C 7 cycloalkyl)C 1 -C 4 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 alkylthio, C 2 -C 6 alkanoyl, C 1 -C 6 alkoxycarbonyl, C 2 -C 6 alkanoyloxy, mono- and di-(C 3 -C 8 cycloalkyl)aminoC 0 -C 4 alkyl, (4- to 7-membered heterocycle)C 0 -C 4 alkyl, C 1 -C 6 alkylsulfonyl, mono- and di-(C 1 -C 6 alkyl) sulfonamido, or mono- and di-(C 1 -C 6 alkyl)aminocarbonyl, each of which is substituted with from 0 to 4 substituents independently selected from the up consisting of: halogen, hydroxy, cyano, amino, —COOH and oxo;

Het is selected from any heterocycle, which is substituted with from 0 to 4 substituents independently selected from the group consisting of:

(i) C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl;

(ii) halogen, hydroxy, amino, amide, cyano, —COOH, —SO 2 NH 2 , oxo, nitro and alkoxycarbonyl, and

(iii) aryl;

R 11 and R 12 are independently selected from the group consisting of: Hydrogen, F, Cl, Br, CN, C 1 -C 4 alkyl, and C 1 -C 6 alkoxy;

R 13 , R 14 and R 15 are independently selected from the group consisting of Hydrogen, C 1 -C 4 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 10 aryl or heteroaryl, C 1 -C 6 alkoxy, C 1 -C 6 alkylthio, C 2 -C 6 alkanoyl, C 1 -C 6 alkoxycarbonyl, and C 2 -C 6 alkanoyloxy.

2. A pharmaceutical composition comprising at least one compound of claim 1 or its pharmaceutically acceptable salts, hydrates, solvates, crystal forms or individual diastereomers thereof, and a pharmaceutically acceptable carrier.

3. The composition according to claim 2 , further comprising an additional therapeutic agent.

4. The compound with the formula:

5. A pharmaceutical composition comprising at least one compound of claim 4 or its pharmaceutically acceptable salts, hydrates, solvates, crystal forms or individual diastereomers thereof, and a pharmaceutically acceptable carrier.

6. The composition according to claim 5 , further comprising an additional therapeutic agent.

7. The compound with the formula:

8. A pharmaceutical composition comprising at least one compound of claim 4 or its pharmaceutically acceptable salts, hydrates, solvates, crystal forms or individual diastereomers thereof, and a pharmaceutically acceptable carrier.

9. The composition according to claim 8 , further comprising an additional therapeutic agent.