Methods and compositions for the treatment of body weight related disorders

Patent metadata

Field	Value
Publication number	US-9233941-B2
Application number	US-201414270130-A
Country	US
Kind code	B2
Filing date	May 5, 2014
Priority date	Feb 2, 2007
Publication date	Jan 12, 2016
Grant date	Jan 12, 2016

Abstract

The present invention relates to methods for reducing body weight in an animal in need thereof via administration of a therapeutically effective amount of a compound having a general tripartite structure A-B-C. In the tripartite structure A, B, and C are identical or non-identical structures, for example, but not limited to, heterocyclic, phenyl or benzyl ring structures with or without substitutions and are described in detail herein. The methods may utilize particular compounds, for example, having a piperidinyl, a pyrrolinyl or pyridinyl A ring, a thiazole B ring, and a phenyl C ring which may be further substituted independently. Also provided are methods for increasing thermogenesis without reducing lean body mass during weight loss in an animal by administering of a therapeutically effective amount of the compounds described.

First claim

What is claimed is:

1. A method for reducing body weight in an animal in need thereof, comprising the step of administering to the animal, in a pharmaceutically acceptable medium, a therapeutically effective amount of a compound having the chemical structure is:

wherein R 1 is H, Et, OMe or n-propyl;
Y is CH or

R 2 is OH, OMe, or NH-i-Pr;
R 3 is H, F, or CI; and
R 4 is H, Me, CI, Br, F, OH, OBz, OCH 2 COOMe, OCH 2 COOH, NH 2 , NH-i-Pr, NHCOMe, NHSO 2 Me, NHBn,

 OMe, NHBoc,

 NHTs,

 wherein when R 1 is ethyl or n-propyl and R 3 is H R 4 is Cl,Br, F, OH, OBz, OCH 2 COOMe, OCH 2 COOH, NH 2 , NH-i-Pr, NHCOMe, NHSO 2 Me, NHBn,

 OMe, NHBoc,

 NHTs

 or a pharmaceutically acceptable salt or a stereoisomer thereof or a combination thereof.

2. The method of claim 1 , wherein the chemical structure is:

or a pharmaceutically acceptable salt or a stereoisomer thereof or a combination thereof.

3. The method of claim 1 , wherein said compound is administered in a composition which is in the form of a food, an animal feed material, or a medicine.

4. The method of claim 1 , wherein the compound increases the expression of uncoupling protein 1, uncoupling protein 2 or uncoupling protein 3.

5. The method of claim 1 , wherein the animal has a weight-related condition selected from the group consisting of obesity, hypertension, arteriosclerosis, asthma, hyperlipidemia, hyperinsulinemia, non-alcoholic fatty liver and type 2 diabetes caused by insulin resistance.

6. The method of claim 1 , further comprising providing to the animal a second therapy selected from a lifestyle modification, an antihyperglycemic agent, insulin, glucagon-like peptide (GLP), a dipeptidyl peptidase-4 inhibitor, a thiazolidinedione, a lipid lowering compound, and a combination of two or more thereof.

7. A method for increasing thermogenesis without reducing lean body mass during weight loss in an animal, comprising the step of administering to the animal, in a pharmaceutically acceptable medium, a therapeutically effective amount of a compound having the structure:

wherein R 1 is H, Et, OMe or n-propyl;
Y is CH or

R 2 is OH, OMe, or NH-i-Pr;
R 3 is H, F, or CI; and
R 4 is H, Me, CI, Br, F, OH, OBz, OCH 2 COOMe, OCH 2 COOH, NH 2 , NH-i-Pr,
NHCOMe, NHSO 2 Me, NHBn,

 OMe, NHBoc,

 NHTs,

 wherein when R 1 is ethly or n-propyl and R 3 is H R 4 is Cl,Br, F, OH, OBz, OCH 2 COOMe, OCH 2 COOH NH 2 NH-i-Pr, NHCOMe, NHSO 2 Me, NHBn,

 OMe, NHBoc,

 NHTs,

 or a pharmaceutically acceptable salt or a stereoisomer thereof or a combination thereof.

8. The method of claim 7 , wherein said compound is administered in a composition which is in the form of a food, an animal feed material, or a medicine.

9. The method of claim 7 , wherein the compound increases the expression of uncoupling protein 1, uncoupling protein 2 or uncoupling protein 3.

10. The method of claim 7 , wherein the animal has a weight-related condition selected from the group consisting of obesity, hypertension, arteriosclerosis, asthma, hyperlipidemia, hyperinsulinemia, non-alcoholic fatty liver and type 2 diabetes caused by insulin resistance.

11. The method of claim 7 , further comprising providing to the animal a second therapy selected from a lifestyle modification, an antihyperglycemic agent, insulin, glucagon-like peptide (GLP), a dipeptidyl peptidase-4 inhibitor, a thiazolidinedione, a lipid lowering compound, and a combination of two or more thereof.

Assignees

• Uesugi Motonari
• Wakil Salih J
• Abu-Elheiga Lutfi
• Watanabe Mizuki
• Baylor College Medicine

Inventors

• Uesugi Motonari
• Wakil Salih J
• Abu-Elheiga Lutfi
• Watanabe Mizuki

Classifications

• A61K31/427 Primary

  not condensed and containing further heterocyclic rings · CPC title

• C07D471/04

  Ortho-condensed systems · CPC title

• C07D401/14

  containing three or more hetero rings · CPC title

• C07D213/06

  containing only hydrogen and carbon atoms in addition to the ring nitrogen atom · CPC title

• C07D213/16

  containing only one pyridine ring · CPC title