Use of indole compounds for fat reduction and skin and soft tissue tightening

1. A method for non-surgical reduction or removal of one or more localized fat deposits in a subject having localized fat accumulation comprising administering to a target site in the fat deposit a compound of Formula (I-1), Formula (I-2), or Formula (I-3), wherein Formula (I-1) is represented by:

wherein

R 1 is hydrogen or C 1-6 alkyl;

R 2 is —(CH 2 ) x —COOH;

R 3 is hydrogen or C 1-6 alkyl;

R 4 , R 6 , and R 7 are independently selected from hydrogen, C 1-6 alkyl, C 1-6 alkoxy, halogen, and —OCH 2 C 6 H 5 ;

R 5 is halogen; and

x is zero;

or a pharmaceutically acceptable salt thereof;

Formula (I-2) is represented by:

wherein

R 1 is hydrogen or C 1-6 alkyl;

R 2 is hydrogen or C 1-6 alkyl;

R 3 is —CHO; and

R 4 , R 5 , R 6 , and R 7 are independently selected from hydrogen, C 1-6 alkyl, C 1-6 alkoxy, halogen, and —OCH 2 C 6 H 5 ;

or a pharmaceutically acceptable salt thereof; and

Formula (I-3) is represented by:

wherein

R 1 is hydrogen or C 1-6 alkyl;

R 2 is —CHO or —(CH 2 )—COOH;

R 3 , R 4 , R 5 , R 6 , and R 7 are independently selected from hydrogen, C 1-6 alkyl, C 1-6 alkoxy, halogen, and —OCH 2 C 6 H 5 ; and

x is zero;

or a pharmaceutically acceptable salt thereof.

2. A method for reducing a subcutaneous fat deposit in a subject having subcutaneous fat deposit comprising administering to a target site in the subcutaneous fat deposit a compound of formula (I-1), formula (I-2), or formula (I-3), wherein formula (I-1) is represented by:

wherein

R 1 is hydrogen or C 1-6 alkyl;

R 2 is —(CH 2 ) x —COOH;

R 3 is hydrogen or C 1-6 alkyl;

R 4 , R 6 , and R 7 are independently selected from hydrogen, C 1-6 alkyl, C 1-6 alkoxy, halogen, and —OCH 2 C 6 H 5 ;

R 5 is halogen; and

x is zero;

or a pharmaceutically acceptable salt thereof;

formula (I-2) is represented by:

wherein

R 1 is hydrogen or C 1-6 alkyl;

R 2 is hydrogen or C 1-6 alkyl;

R 3 is —CHO; and

R 4 , R 5 , R 6 , and R 7 are independently selected from hydrogen, C 1-6 alkyl, C 1-6 alkoxy, halogen, and —OCH 2 C 6 H 5 ;

or a pharmaceutically acceptable salt thereof; and

formula (I-3) is represented by:

wherein

R 1 is hydrogen or C 1-6 alkyl;

R 2 is —CHO or —(CH 2 ) x —COOH;

R 3 , R 4 , R 5 , R 6 , and R 7 are independently selected from hydrogen, C 1-6 alkyl, C 1-6 alkoxy, halogen, and —OCH 2 C 6 H 5 ; and

x is zero;

or a pharmaceutically acceptable salt thereof.

3. A method selected from:

(i) a method for treating an adipose tissue disorder or an adipose tissue tumor in a subject comprising locally administering to the subject a compound of Formula (I-1), Formula (I-2), or Formula (I-3), wherein Formula (I-1) is represented by:

 wherein

R 1 is hydrogen or C 1-6 alkyl;

R 2 is —(CH 2 ) x —COOH;

R 3 is hydrogen or C 1-6 alkyl;

R 4 , R 6 , and R 7 are independently selected from hydrogen, C 1-6 alkyl, C 1-6 alkoxy, halogen, and —OCH 2 C 6 H 5 ;

R 5 is halogen; and

x is zero;

or a pharmaceutically acceptable salt thereof;

Formula (I-2) is represented by:

 wherein

R 1 is hydrogen or C 1-6 alkyl;

R 2 is hydrogen or C 1-6 alkyl;

R 3 is —CHO; and

R 4 , R 5 , R 6 , and R 7 are independently selected from hydrogen, C 1-6 alkyl, C 1-6 alkoxy, halogen, and —OCH 2 C 6 H 5 ;

or a pharmaceutically acceptable salt thereof; and

Formula (I-3) is represented by:

 wherein

R 1 is hydrogen or C 1-6 alkyl;

R 2 is —CHO or —(CH 2 ) x —COOH;

R 3 , R 4 , R 5 , R 6 , and R 7 are independently selected from hydrogen, C 1-6 alkyl, C 1-6 alkoxy, halogen, and —OCH 2 C 6 H 5 ; and

x is zero;

or a pharmaceutically acceptable salt thereof; and

(ii) a method for decreasing a submental fat deposit under a skin area in a subject comprising administering to a target site in the fat deposit a compound of Formula (I-1), Formula (I-2), or Formula (I-3), wherein Formula (I-1) is represented by:

 wherein

R 1 is hydrogen or C 1-6 alkyl;

R 2 is —(CH 2 ) x —COOH;

R 3 is hydrogen or C 1-6 alkyl;

R 4 , R 6 , and R 7 are independently selected from hydrogen, C 1-6 alkyl, C 1-6 alkoxy, halogen, and —OCH 2 C 6 H 5 ;

R 5 is halogen; and

x is zero;

or a pharmaceutically acceptable salt thereof;

Formula (I-2) is represented by:

 wherein

R 1 is hydrogen or C 1-6 alkyl;

R 2 is hydrogen or C 1-6 alkyl;

R 3 is —CHO; and

R 4 , R 5 , R 6 , and R 7 are independently selected from hydrogen, C 1-6 alkyl, C 1-6 alkoxy, halogen, and —OCH 2 C 6 H 5 ;

or a pharmaceutically acceptable salt thereof; and

Formula (I-3) is represented by:

 wherein

R 1 is hydrogen or C 1-6 alkyl;

R 2 is —CHO or —(CH 2 ) x —COOH;

R 3 , R 4 , R 5 , R 6 , and R 7 are independently selected from hydrogen, C 1-6 alkyl, C 1-6 alkoxy, halogen, and —OCH 2 C 6 H 5 ; and

x is zero;

or a pharmaceutically acceptable salt thereof.

4. The method of claim 3 , wherein the method is for decreasing a submental fat deposit under a skin area in a subject comprising administering to a target site in the fat deposit a compound of Formula (I-1) or Formula (I-2), wherein Formula (I-1) is represented by:

wherein

R 1 is hydrogen or C 1-6 alkyl;

R 2 is —(CH 2 ) x —COOH;

R 3 is hydrogen or C 1-6 alkyl;

R 4 , R 6 , and R 7 are independently selected from hydrogen, C 1-6 alkyl, C 1-6 alkoxy, halogen, and —OCH 2 C 6 H 5 ;

R 5 is halogen; and

x is zero;

or a pharmaceutically acceptable salt thereof; and

Formula (I-2) is represented by:

wherein

R 1 is hydrogen or C 1-6 alkyl;

R 2 is hydrogen or C 1-6 alkyl;

R 3 is —CHO; and

R 4 , R 5 , R 6 , and R 7 are independently selected from hydrogen, C 1-6 alkyl, C 1-6 alkoxy, halogen, and —OCH 2 C 6 H 5 ;

or a pharmaceutically acceptable salt thereof.

5. The method of claim 1 , wherein the compound is of Formula (II):

wherein

R 1 is hydrogen or C 1-6 alkyl;

R 2 is hydrogen or C 1-6 alkyl;

R 3 is —CHO;

R 4 is —OCH 2 C 6 H 5 ; and

R 5 , R 6 , and R 7 are independently selected from hydrogen, C 1-6 alkyl, C 1-6 alkoxy, and halogen;

or a pharmaceutically acceptable salt thereof.

6. The method of claim 1 , wherein the compound is of Formula (III):

wherein

R 1 is hydrogen or C 1-6 alkyl;

R 2 is —(CH 2 ) x —COOH;

R 3 is hydrogen or C 1-6 alkyl;

R 4 , R 6 , and R 7 are independently selected from hydrogen, C 1-6 alkyl, C 1-6 alkoxy, halogen, and —OCH 2 C 6 H 5 ;

R 5 is bromo; and

x is zero;

or a pharmaceutically acceptable salt thereof.

7. The method of claim 1 , wherein the compound is of Formula (IV):

wherein

R 1 is hydrogen or C 1-6 alkyl;

R 2 is —CHO or —(CH 2 ) x —COOH;

R 3 is hydrogen, C 1-6 alkyl, or C 1-6 alkoxy;

R 4 , R 5 , R 6 , and R 7 are independently selected from hydrogen, C 1-6 alkyl, C 1-6 alkoxy, and halogen; and

x is zero;

or a pharmaceutically acceptable salt thereof.

8. The method of claim 1 , wherein the compound is of Formula (V):

wherein

R 1 is hydrogen or C 1-6 alkyl;

R 2 is hydrogen or C 1-6 alkyl;

R 3 is —CHO; and

R 4 , R 5 , R 6 , and R 7 are independently selected from hydrogen, C 1-6 alkyl, C 1-6 alkoxy, —OCH 2 C 6 H 5 , and halogen;

or a pharmaceutically acceptable salt thereof.

9. A method for non-surgical reduction or removal of one or more localized fat deposits in a subject having localized fat accumulation comprising administering to a target site in the fat deposit a compound in Table 1A below, or a pharmaceutically acceptable salt thereof:

TABLE 1A

Compound

Structure

Chemical Name

 2

1H-indole-2-carbaldehyde

29

1H-indole-2-carboxylic acid

38

5-bromo-1H-indole

40

5-bromo-1H-indole-2-carboxylic acid

41

2-(5-bromo-1H-indol-3-yl)acetic acid

43

4-(benzyloxy)-1H-indole-3-carbaldehyde

44

6-(benzyloxy)-1H-indole-3-carbaldehyde.

10. The method of claim 1 , wherein the compound is of Formula:

11. The method of claim 1 , wherein the compound is of Formula:

12. The method of claim 1 , wherein the administering step is by injection, transdermal pump, transdermal patch, or a subdermal depot.

13. The method of claim 1 , wherein the administering step is by subcutaneous injection or intradermal injection.

14. The method of claim 1 , wherein the subject is a mammal.

15. The method of claim 1 , wherein the subject is a human.

16. The method of claim 1 , further comprising administering to the subject a second therapeutic agent.