Compounds for the treatment of addiction

Patent metadata

Field	Value
Publication number	US-9610299-B2
Application number	US-201514659042-A
Country	US
Kind code	B2
Filing date	Mar 16, 2015
Priority date	Jul 1, 2011
Publication date	Apr 4, 2017
Grant date	Apr 4, 2017

Abstract

Disclosed are novel compounds having the structure of Formula (I):

which are useful for treating mammals for dependence upon substances of addiction, for example addiction to a dopamine-producing agent such as cocaine, morphine, amphetamines, nicotine, and/or alcohol. Also disclosed are pharmaceutical compositions comprising a therapeutically effective amount of a compound of Formula (I) and methods of using the compounds of Formula (I) in the treatment of addiction to a dopamine-producing agent.

First claim

What is claimed is:

1. A method of treating obesity comprising administering a compound of Formula (Ia):

wherein:
R 1 is hydrogen, optionally substituted C 1-6 alkyl, —CH 2 OH, —CH 2 OP(O)(OR 20 )(OR 21 ), —C(O)R 22 , or —SO 2 R 23 ;
R 2 is hydrogen, optionally substituted C 1-6 alkyl, cycloalkyl, or halo;
each of R 3 , R 4 , R 5 , R 6 , R 9 , R 10 , R 11 , R 12 and R 13 is independently hydrogen, hydroxyl, —OP(O)(OR 20 )(OR 21 ), —CH 2 OH, —CH 2 OP(O)(OR 20 )(OR 21 ), optionally substituted alkyl, optionally substituted alkylene, optionally substituted alkynyl, optionally substituted alkoxy, optionally substituted cycloalkyl, aminocarbonyl, acyl, acylamino, —O—(C 1 to C 6 -alkyl)-O—(C 1 to C 6 -alkyl), cyano, halo, —SO 2 NR 24 R 25 , or —NR 24 R 25 ;
R 7 is hydrogen or optionally substituted C 1-6 alkyl;
each of R 20 and R 21 is independently Na + , Li + , K + , hydrogen, or C 1-6 alkyl; or R 20 and R 21 can be combined to represent a single divalent cation Zn 2+ , Ca 2+ , or Mg 2+ ;
each of R 22 and R 23 is independently optionally substituted alkyl, optionally substituted alkoxy, optionally substituted cycloalkyl, optionally substituted aryl, or —NR 24 R 25 ; and
each of R 24 and R 25 is independently hydrogen or C 1-6 alkyl or when combined together with the nitrogen to which they are attached form a heterocycle; or a pharmaceutically acceptable salt or prodrug thereof, to a human patient in need thereof.

2. A method of treating obesity comprising administering a compound selected from the group consisting of:
2,6-dichloro-4-(2-methoxyethoxy)-N-(4-(2-oxo-1,2-dihydropyridin-4-yl) benzyl)benzamide;
2,6-dichloro-N-[4-(2-oxo-1,2-dihydro-pyridin-4-yl)-benzyl]-benzamide;
2-chloro-3-fluoro-N-(4-(2-oxo-1,2-dihydropyridin-4-yl)benzyl)benzamide;
2-chloro-6-methyl-N-(4-(2-oxo-1,2-dihydropyridin-4-yl)benzyl)benzamide;
2,6-dimethyl-N-(4-(2-oxo-1,2-dihydropyridin-4-yl)benzyl)benzamide;
2,6-dichloro-N-[4-(6-methyl-2-oxo-1,2-dihydro-pyridin-4-yl)-benzyl]-benzamide;
2-chloro-3,6-difluoro-N-(4-(2-oxo-1,2-dihydropyridin-4-yl)benzyl)benzamide;
2,6-dichloro-N-(3-methyl-4-(2-oxo-1,2-dihydropyridin-4-yl)benzyl)benzamide);
2,6-dichloro-N-(4-(1-methyl-2-oxo-1,2-dihydropyridin-4-yl)benzyl)benzamide;
2,6-difluoro-N-(4-(2-oxo-1,2-dihydropyridin-4-yl)benzyl)benzamide;
2-chloro-6-fluoro-N-(4-(2-oxo-1,2-dihydropyridin-4-yl)benzyl)benzamide;
2,6-dichloro-N-(2-fluoro-4-(2-oxo-1,2-dihydropyridin-4-yl)benzyl)benzamide;
2,6-dichloro-N-(4-(5-fluoro-2-oxo-1,2-dihydropyridin-4-yl)benzyl)benzamide; and
phosphoric acid mono-(4-{4-[(2,6-dichloro-benzoylamino)-methyl]-phenyl}-2-oxo-2H-pyridin-1-ylmethyl) ester; or
a pharmaceutically acceptable salt, single stereoisomer, mixture of stereoisomers, or tautomer thereof, to a patient in need thereof.

3. The method of claim 1 wherein the compound is:

or a pharmaceutically acceptable salt, ester, or tautomer thereof.

Assignees

• Gilead Sciences Inc

Inventors

• Cannizzaro Carina E
• Graupe Michael
• Guerrero Juan A
• Lu Yafan
• Strickley Robert G
• Venkataramani Chandrasekar
• Zablocki Jeff

Classifications

• A61P25/30

  for treating abuse or dependence · CPC title

• A61P25/32

  Alcohol-abuse · CPC title

• A61P3/04

  Anorexiants; Antiobesity agents · CPC title

• A61P25/34

  Tobacco-abuse · CPC title

• A61P25/36

  Opioid-abuse · CPC title