Treatment for obesity

Patent metadata

Field	Value
Publication number	US-9226910-B2
Application number	US-201414334694-A
Country	US
Kind code	B2
Filing date	Jul 18, 2014
Priority date	Jul 18, 2013
Publication date	Jan 5, 2016
Grant date	Jan 5, 2016

Abstract

The present invention relates to a method for treating or preventing obesity in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of certain carbamate compounds. The invention further relates to methods for reducing body weight and/or reducing food intake in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of certain carbamate compounds.

First claim

We claim:

1. A method for treating obesity in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of Formula (I):

or a pharmaceutically acceptable salt or ester thereof;
wherein R is a member selected from the group consisting of alkyl of 1 to 8 carbon atoms, halogen, alkoxy of 1 to 3 carbon atoms, nitro, hydroxy, trifluoromethyl, and thioalkoxy of 1 to 3 carbon atoms;
x is an integer of 0 to 3, with the proviso that R may be the same or different when x is 2 or 3;
R 1 and R 2 are independently selected from the group consisting of hydrogen, alkyl of 1 to 8 carbon atoms, aryl, arylalkyl, cycloalkyl of 3 to 7 carbon atoms; or
R 1 and R 2 can be joined to form a 5 to 7-membered heterocycle that is unsubstituted or substituted with one or more alkyl or aryl groups, wherein the heterocycle can comprise 1 to 2 nitrogen atoms and 0 to 1 oxygen atom, wherein the nitrogen atoms are not directly connected with each other or with the oxygen atom;
wherein the subject reduces body weight, thereby treating the obesity.

2. A method for reducing body weight or body weight gain in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of Formula (I):

or a pharmaceutically acceptable salt or ester thereof;
wherein R is a member selected from the group consisting of alkyl of 1 to 8 carbon atoms, halogen, alkoxy of 1 to 3 carbon atoms, nitro, hydroxy, trifluoromethyl, and thioalkoxy of 1 to 3 carbon atoms;
x is an integer of 0 to 3, with the proviso that R may be the same or different when x is 2 or 3;
R 1 and R 2 are independently selected from the group consisting of hydrogen, alkyl of 1 to 8 carbon atoms, aryl, arylalkyl, cycloalkyl of 3 to 7 carbon atoms; or
R 1 and R 2 can be joined to form a 5 to 7-membered heterocycle that is unsubstituted or substituted with one or more alkyl or aryl groups, wherein the heterocycle can comprise 1 to 2 nitrogen atoms and 0 to 1 oxygen atom, wherein the nitrogen atoms are not directly connected with each other or with the oxygen atom;
wherein the subject reduces body weight.

3. A method for reducing food intake in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of Formula (I):

or a pharmaceutically acceptable salt or ester thereof;
wherein R is a member selected from the group consisting of alkyl of 1 to 8 carbon atoms, halogen, alkoxy of 1 to 3 carbon atoms, nitro, hydroxy, trifluoromethyl, and thioalkoxy of 1 to 3 carbon atoms;
x is an integer of 0 to 3, with the proviso that R may be the same or different when x is 2 or 3;
R 1 and R 2 are independently selected from the group consisting of hydrogen, alkyl of 1 to 8 carbon atoms, aryl, arylalkyl, cycloalkyl of 3 to 7 carbon atoms; or
R 1 and R 2 can be joined to form a 5 to 7-membered heterocycle that is unsubstituted or substituted with one or more alkyl or aryl groups, wherein the heterocycle can comprise 1 to 2 nitrogen atoms and 0 to 1 oxygen atom, wherein the nitrogen atoms are not directly connected with each other or with the oxygen atom;
wherein the subject reduces food intake.

4. The method of claim 1 , wherein x=0.

5. The method of claim 1 , wherein R 1 and R 2 are hydrogen and x=0.

6. The method of claim 1 , wherein the compound of Formula I is an enantiomer of Formula I substantially free of other enantiomers or an enantiomeric mixture wherein one enantiomer of Formula I predominates.

7. The method of claim 6 , wherein the enantiomer of Formula I predominates to the extent of about 90% or greater.

8. The method of claim 6 , wherein the enantiomer of Formula I predominates to the extent of about 98% or greater.

9. The method of claim 6 , wherein the enantiomer of Formula I is an enantiomer of Formula Ia:

or a pharmaceutically acceptable salt or ester thereof.

10. The method of claim 9 , wherein the enantiomer of Formula Ia is the (R) or (D) enantiomer.

11. The method of claim 9 , wherein the enantiomer of Formula Ia is the (S) or (L) enantiomer.

12. The method of claim 9 , wherein the enantiomer of Formula Ia predominates to the extent of about 90% or greater.

13. The method of claim 9 , wherein the enantiomer of Formula Ia predominates to the extent of about 98% or greater.

14. The method of claim 6 , wherein the enantiomer of Formula I substantially free of other enantiomers is the compound of Formula Ib or an enantiomeric mixture wherein the compound of Formula Ib predominates:

or a pharmaceutically acceptable salt or ester thereof.

15. The method of claim 14 , wherein the compound of Formula Ib predominates to the extent of about 90% or greater.

16. The method of claim 14 , wherein the compound of Formula Ib predominates to the extent of about 98% or greater.

17. The method of claim 1 , wherein the effective amount of the compound of Formula I is from about 0.01 mg/kg/dose to about 150 mg/kg/dose.

18. The method of claim 1 , wherein the effective amount of the compound of Formula I is from about 1 mg/day to about 7000 mg/day.

19. The method of claim 1 , wherein the compound of Formula I is administered orally.

20. The method of claim 1 , wherein the compound of Formula I is administered in the form of a capsule or tablet.

21. The method of claim 1 , wherein the compound of Formula I is administered in the form of a capsule at a dose of about 10 mg to about 1000 mg without any excipients.

Assignees

• Jazz Pharmaceuticals Internat Iii Ltd
• Sk Biopharmaceuticals Co Ltd

Inventors

• Khayrallah Moise A
• Bream Gary
• Butts Stephen E

Classifications

• A61P3/04

  Anorexiants; Antiobesity agents · CPC title

• A61K9/0053

  Mouth and digestive tract, i.e. intraoral and peroral administration · CPC title

• A61K9/48

  Preparations in capsules, e.g. of gelatin, of chocolate {(A61K9/0004 takes precedence; bite capsules A61K9/0056)} · CPC title

• A61K31/27 Primary

  of carbamic or thiocarbamic acids, meprobamate, carbachol, neostigmine · CPC title