IP Library › Patent Application 14772602

Patent Application

App. No. 14/772,602

USE OF INDOLE COMPOUNDS FOR FAT REDUCTION AND SKIN AND SOFT TISSUE TIGHTENING

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Patent No.: US None
App. No.: 14/772,602

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Abstract

The present invention relates to indole compounds and compositions and uses thereof, including uses of the indole compounds and compositions for the reduction or removal of localized fat deposits and/or tightening of skin and soft tissue laxity in subjects. The indole compounds can be employed, for example, in the cosmetic sector or for producing pharmaceutical products.

Claims (147)

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):

wherein

R 1 is hydrogen, C 1-6 alkyl, hydroxyl, or —(CH 2 ) x —CONH 2 ;

R 2 , R 3 , R 4 , R 5 , R 6 , and R 7 are independently selected from hydrogen, C 1-6 alkyl, C 1-6 alkoxy, amino, substituted amino, halogen, heteroaryl, substituted heteroaryl, —(CH 2 ) x —C(O)—OC 1-6 alkyl, —(CH 2 ) x —OH, —(CH 2 ) x —CN, —OCH 2 C 6 H 5 , —OCOCH 3 , —(CH 2 ) x —CONH 2 , —CHO, —(CH 2 ) x —COOH, —(CH 2 ) x —COOC 1-6 alkyl, —(CH 2 ) y —CO—COOH, and —(CH 2 ) y —C(H)(OH)—COOH; or

any two adjacent R 4 , R 5 , R 6 , and R 7 , together with the atoms they attach to, form a five to seven-membered carbocyclic ring; or

R 2 and R 3 , together with the atoms they attach to, form an unsubstituted or substituted five to seven-membered heterocyclyl ring;

x is a number from zero to six; and

y is a number from zero to six;

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):

wherein

R 1 is hydrogen, C 1-6 alkyl, hydroxyl, or —(CH 2 ) x —CONH 2 ;

any two adjacent R 4 , R 5 , R 6 , and R 7 , together with the atoms they attach to, form a five to seven-membered carbocyclic ring; or

R 2 and R 3 , together with the atoms they attach to, form an unsubstituted or substituted five to seven-membered heterocyclyl ring;

x is a number from zero to six; and

y is a number from zero to six;

or a pharmaceutically acceptable salt thereof.

3 . A method for treating an adipose tissue disorder an adipose tissue tumor or in a subject comprising locally administering to the subject a compound of Formula (I):

wherein

R 1 is hydrogen, C 1-6 alkyl, hydroxyl, or —(CH 2 ) x —CONH 2 ;

any two adjacent R 4 , R 5 , R 6 , and R 7 , together with the atoms they attach to, form a five to seven-membered carbocyclic ring; or

R 2 and R 3 , together with the atoms they attach to, form an unsubstituted or substituted five to seven-membered heterocyclyl ring;

x is a number from zero to six; and

y is a number from zero to six;

or a pharmaceutically acceptable salt thereof.

4 . A method for decreasing 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):

wherein

R 1 is hydrogen, C 1-6 alkyl, hydroxyl, or —(CH 2 ) x —CONH 2 ;

any two adjacent R 4 , R 5 , R 6 , and R 7 , together with the atoms they attach to, form a five to seven-membered carbocyclic ring; or

R 2 and R 3 , together with the atoms they attach to, form an unsubstituted or substituted five to seven-membered heterocyclyl ring;

x is a number from zero to six; and

y is a number from zero to six;

or a pharmaceutically acceptable salt thereof.

5 . A method for preventing or reducing a skin condition associated with aging in a subject comprising locally administering to the subject a compound of Formula (I):

wherein

R 1 is hydrogen, C 1-6 alkyl, hydroxyl, or —(CH 2 ) x —CONH 2 ;

any two adjacent R 4 , R 5 , R 6 , and R 7 , together with the atoms they attach to, form a five to seven-membered carbocyclic ring; or

R 2 and R 3 , together with the atoms they attach to, form an unsubstituted or substituted five to seven-membered heterocyclyl ring;

x is a number from zero to six; and

y is a number from zero to six;

or a pharmaceutically acceptable salt thereof.

6 . A method for treating sleep apnea in a subject comprising locally administering a compound of Formula (I),

wherein the sleep apnea is caused by a fat deposit around a trachea in the subject; and

the administration of the compound is to the fat deposit around the trachea; and

wherein Formula (I) is:

wherein

R 1 is hydrogen, C 1-6 alkyl, hydroxyl, or —(CH 2 ) x —CONH 2 ;

any two adjacent R 4 , R 5 , R 6 , and R 7 , together with the atoms they attach to, form a five to seven-membered carbocyclic ring; or

R 2 and R 3 , together with the atoms they attach to, form an unsubstituted or substituted five to seven-membered heterocyclyl ring;

x is a number from zero to six; and

y is a number from zero to six;

or a pharmaceutically acceptable salt thereof.

7 . The method of any of claims 1 - 6 , wherein the compound is of Formula (II):

wherein

R 1 is hydrogen, C 1-6 alkyl, or hydroxy;

R 2 , R 3 , R 4 , R 5 , R 6 , and R 7 are independently selected from hydrogen, C 1-6 alkyl, C 1-6 alkoxy, amino, substituted amino, halogen, —(CH 2 ) x —C(O)—OC 1-6 alkyl, —(CH 2 ) x —OH, —(CH 2 ) x —CN, —OCH 2 C 6 H 5 , —CHO, —(CH 2 ) x —COOH, —(CH 2 ) x —COOC 1-6 alkyl, —(CH 2 ) y —CO—COOH, and —(CH 2 ) y —C(H)(OH)—COOH; or

any two adjacent R 4 , R 5 , R 6 , and R 7 , together with the atoms they attach to, form a five to seven-membered carbocyclic ring;

x is a number from zero to six; and

y is a number from zero to six;

or a pharmaceutically acceptable salt thereof.

8 . The method of any of claims 1 - 6 , wherein the compound is of Formula (III):

wherein

R 1 is hydrogen, C 1-6 alkyl, or hydroxy;

any two adjacent R 4 , R 5 , R 6 , and R 7 , together with the atoms they attach to, form a five to seven-membered carbocyclic ring;

x is a number from zero to six; and

y is a number from zero to six;

or a pharmaceutically acceptable salt thereof;

provided that at least one of R 2 , R 3 , R 4 , R 5 , R 6 , and R 7 is bromo.

9 . The method of any of claims 1 - 6 , wherein the compound is of Formula (IV):

wherein

R 1 is hydrogen, C 1-6 alkyl, or hydroxy;

any two adjacent R 4 , R 5 , R 6 , and R 7 , together with the atoms they attach to, form a five to seven-membered carbocyclic ring;

x is a number from zero to six; and

y is a number from zero to six;

or a pharmaceutically acceptable salt thereof;

provided that at least one of R 2 , R 3 , R 4 , R 5 , R 6 , and R 7 is —CHO or —(CH 2 ) x —COOH.

10 . The method of any of claims 1 - 6 , wherein the compound is of Formula (V):

wherein

R 1 is hydrogen or C 1-6 alkyl;

R 2 , R 3 , 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 , halogen, —CHO, —(CH 2 ) x —COOH; and

x is a number from zero to six;

or a pharmaceutically acceptable salt thereof.

11 . The method of any of claims 1 - 6 , wherein the compound is of Formula (VI):

wherein

R 1 is hydrogen or C 1-6 alkyl;

R 4 , R 5 , R 6 , and R 7 are independently selected from hydrogen, C 1-6 alkyl, C 1-6 alkoxy, amino, substituted amino, halogen, heteroaryl, substituted heteroaryl, —(CH 2 ) x —C(O)—OC 1-6 alkyl, —(CH 2 ) x —OH, —(CH 2 ) x —CN, —OCH 2 C 6 H 5 , —OCOCH 3 , —(CH 2 ) x —CONH 2 , —CHO, —(CH 2 ) x —COOH, —(CH 2 ) x —COOC 1-6 alkyl, —(CH 2 ) y —CO—COOH, and —(CH 2 ) y —C(H)(OH)—COOH;

R 8 , R 10 , and R 11 are independently selected from hydrogen, halogen, —(CH 2 ) x —C(O)—OC 1-6 alkyl, —(CH 2 ) x —OH, —(CH 2 ) x —CN, —OCH 2 C 6 H 5 , —OCOCH 3 , —(CH 2 ) x —CONH 2 , —CHO, —(CH 2 ) x —COOH, —(CH 2 ) x —COOC 1-6 alkyl, —(CH 2 ) y —CO—COOH, —(CH 2 ) y —C(H)(OH)—COOH, phenyl, and substituted phenyl; wherein the substituted phenyl is substituted with 1-4 substituents selected from hydroxyl, C 1-6 alkoxy, and C 1-6 alkyl;

R 9 is hydrogen or C 1-6 alkyl;

x is a number from zero to six; and

y is a number from zero to six;

or a pharmaceutically acceptable salt thereof.

12 . The method of any of claims 1 - 6 , wherein the compound is of Formula:

Compound

Structure

Chemical Name

1H-indole-2-carbaldehyde

4-(1H-indol-3-yl)butanoic acid

1H-indole-2-carboxylic acid

5-bromo-1H-indole

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

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

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

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

13 . The method of any of claims 1 - 6 , wherein the compound is of Formula:

1H-indole-2-carbaldehyde

14 . The method of any of claims 1 - 6 , wherein the compound is of Formula:

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

15 . The method of any of claims 1 - 14 , wherein the administering step is by injection, transdermal pump, transdermal patch, or a subdermal depot.

16 . The method of any of claims 1 - 14 , wherein the administering step is by subcutaneous injection or intradermal injection.

17 . The method of any of claims 1 - 14 , wherein the subject is a mammal.

18 . The method of any of claims 1 - 14 , wherein the subject is a human.

19 . The method of any of claims 1 - 14 , further comprising administering to the mammal a second therapeutic agent.

20 . A kit comprising a container, wherein the container comprises a compound of Formula (I):

wherein

R 1 is hydrogen, C 1-6 alkyl, hydroxyl, or —(CH 2 ) x —CONH 2 ;

any two adjacent R 4 , R 5 , R 6 , and R 7 , together with the atoms they attach to, form a five to seven-membered carbocyclic ring; or

R 2 and R 3 , together with the atoms they attach to, form an unsubstituted or substituted five to seven-membered heterocyclyl ring;

x is a number from zero to six; and

y is a number from zero to six;

or a pharmaceutically acceptable salt thereof.

21 . A syringe comprising a compound of Formula (I):

wherein

R 1 is hydrogen, C 1-6 alkyl, hydroxyl, or —(CH 2 ) x —CONH 2 ;

any two adjacent R 4 , R 5 , R 6 , and R 7 , together with the atoms they attach to, form a five to seven-membered carbocyclic ring; or

R 2 and R 3 , together with the atoms they attach to, form an unsubstituted or substituted five to seven-membered heterocyclyl ring;

x is a number from zero to six; and

y is a number from zero to six;

or a pharmaceutically acceptable salt thereof.