Substituted indol-5-ol derivatives and their therapeutical applications

1. A method of treating cancer comprising a tumor cell, comprising contacting the tumor cell with a composition comprising a compound of formula (I):

or its pharmaceutically acceptable salts, hydrates, solvates, and individual diastereomers thereof, wherein R is selected from the group consisting of:

(i) hydrogen, amino, and alkyl amino;

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

(iii) K—Ar, wherein:

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

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

(2) 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 and (4- to 7-membered heterocycle)C 0 -C 4 alkyl, each of which is substituted with from 0 to 4 secondary substituents independently chosen from halogen, hydroxy, cyano, oxo, imino, C 1 -C 4 alkyl, C 1 -C 4 alkoxy and C 1 -C 4 haloalkyl;

K is selected from the group consisting of:

1) O, S, SO, and SO 2 ;

2) (CH 2 ) 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, and —(CH 2 ) p O, p=1-3; and

3) NR 1 , wherein R 1 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, alkylthio, aryl, and arylalkyl; and

(iv) groups of the formula (Ia):

 wherein:

R 2 is selected from the group consisting of hydrogen, C 1 -C 4 alkyl, and oxo; and

X is CH, when R 3 is hydrogen; or X—R 3 is O; or X is N;

R 3 is selected from the group consisting of hydrogen, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 10 aryl and 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)amino C 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, and mono- and di-(C 1 -C 6 alkyl)aminocarbonyl, each of which is substituted with from 0 to 4 substituents independently chosen from halogen, hydroxy, cyano, amino,—COOH or oxo; and

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

(i) C 1 C 6 alkyl, C 2 C 6 alkenyl, and 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; and

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. The method of claim 1 , in which the concentration of the compound in the pharmaceutical composition results in administration to a patient of a dosage of between 0.01-100 mg/kg body weight/day.

3. The method of claim 1 , wherein the cancer is breast cancer, gastric cancer, chronic myelogenous leukemia, acute myelogenous leukemia, pancreatic carcinoma, thyroid cancer or endometrial carcinoma.

4. A method of claim 3 , in which the cancer is chronic myeogenous leukemia (CML).

5. A method of treating cancer comprising a tumor cell, comprising contacting the tumor cell with a composition comprising a compound having the formula:

or its pharmaceutically acceptable salts, solvates, and individual diastereomers thereof.

6. The method of claim 5 , in which the concentration of the compound in the pharmaceutical composition results in administration to a patient of a dosage of between 0.01-100 mg/kg body weight/day.

7. The method of claim 5 , wherein the cancer is breast cancer, gastric cancer, chronic myelogenous leukemia, acute myelogenous leukemia, pancreatic carcinoma, thyroid cancer or endometrial carcinoma.

8. A method of claim 7 , in which the cancer is chronic myeogenous leukemia (CML).

9. A method of treating cancer comprising a tumor cell, comprising contacting the tumor cell with a composition comprising a compound having the formula:

or its pharmaceutically acceptable salts, hydrates, solvates, and individual diastereomers thereof.

10. The method of claim 9 , in which the concentration of the compound in the pharmaceutical composition results in administration to a patient of a dosage of between 0.01-100 mg/kg weight/day.

11. The method of claim 9 , wherein the cancer is breast cancer, gastric cancer, chronic myelogenous leukemia, acute myelogenous leukemia, pancreatic carcinoma, thyroid cancer or endometrial carcinoma.

12. A method of claim 11 , in which the cancer is chronic myeogenous leukemia (CML).

13. A method of claim 11 , in which the cancer is pancreatic carcinoma.

14. A method of claim 7 , in which the cancer is pancreatic carcinoma.