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US 2003/0144261 A1Published application
MCH antagonists for the treatment of obesity
AssigneeSchering Corporation
InventorsAnandan Palani, Sherry A. Shapiro, Mark D. McBriar, Jing Su
Life of this patent
Estimating the term…
Abstract
The present invention discloses compounds, which are novel antagonists for melanin-concentrating hormone (MCH), as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising such MCH antagonists as well as methods of using them to treat obesity, metabolic disorders, eating disorders such as hyperphagia, and diabetes.
Claims33
A compound of formula I:
- 83
- or a pharmaceutically acceptable salt or solvate of said compound, wherein:
- X is a single bond, —C—, —CH— or alkylene, and when X is a single bond, R6 is absent and the carbon atom marked 1 is directly attached to N of N—Y;
- Y is a single bond, —C—, —CH— or alkylene, and when Y is a single bond, R5 is absent and the carbon atom marked 7 is directly attached to N of N—X;
- R1 is aryl or heteroaryl, wherein each of said aryl or heteroaryl can be unsubstituted or optionally independently substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group consisting of CN, CF3, halogen, alkyl, cycloalkyl, cycloalkylalkyl, haloalkyl, haloalkoxy, alkoxy and OH;
- R2 is H, alkyl, aryl or aralkyl wherein each of said aryl, or aralkyl can be unsubstituted or optionally independently substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group consisting of halogen, alkyl, cycloalkyl, cycloalkylalkyl, haloalkyl, haloalkoxy, alkoxy and OH;
- R3 is H, alkyl, aryl or aralkyl wherein each of said aryl or aralkyl can be unsubstituted or optionally independently substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group consisting of CF3, halogen, alkyl, cycloalkyl, cycloalkylalkyl, haloalkyl, haloalkoxy, alkoxy and OH;
- R4 is selected from the group consisting of -alkylene-N(R7)2, —N(H)alkylene-N(R7)2, —O-alkylene-N(R7)2,
- 84
- wherein each R7 in said —N(R7)2, can be the same or different each R7 is H, alkyd, cycloalkyl or aryl, wherein each of said alkyl, aryl or cycloalkyl can be unsubstituted or optionally independently substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group consisting of halogen, alkyl, cycloalkyl, cycloalkylalkyl, haloalkyl, haloalkoxy, alkoxy and OH;
- or each R7 can be joined together and with the nitrogen to which they are attached to form a 3 to 7-membered heterocyclyl ring;
- n is 0 or 1;
- p is 0 to 5 and when p is >1, the number of p moieties can be the same or different;
- R5 is H or 1 or 2 substituents independently selected from alkyl or cycloalkyl;
- R6 is H or 1 or 2 substituents independently selected from alkyl or cycloalkyl;
- and
- R8 is H, OH, alkoxy, alkyl, cycloalkyl, aryl, —N(H)R7, —N(H)C(O)alkyl, —N(H)C(O)aryl, —N(H)C(O)N(H)alkyl, —N(H)C(O)N(H)aryl, —N(H)S(O2)alkyl or —N(H)S(O2)aryl;
- with the proviso that the carbons shown marked 1 and 6 on the aromatic ring, along with X—R6, can optionally form a 4 to 8 membered ring system.
15 more elements
A compound of formula II:
- 111
- or a pharmaceutically acceptable salt or solvate of said compound, wherein:
- Y is a single bond, —C—, —CH— or alkylene, and when Y is a single bond, R5 is absent and the carbon atom marked 7 is directly attached to N of N—X;
- Z is a single bond, —C—, —CH— or alkylene, and when Z is a single bond, R6 is absent and the carbon atom marked 1 is directly attached to the carbon atom marked 8:
- R1 is aryl or heteroaryl, wherein each of said aryl or heteroaryl can be unsubstituted or optionally independently substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group consisting of CN, CF3, halogen, alkyl, cycloalkyl, cycloalkylalkyl, haloalkyl, haloalkoxy, alkoxy and OH;
- R2 is H, alkyl, aryl or aralkyl wherein each of said aryl or aralkyl can be unsubstituted or optionally independently substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group consisting of halogen, alkyl, cycloalkyl, cycloalkylalkyl, haloalkyl, haloalkoxy, alkoxy and OH;
- R3 is H, alkyl, aryl or aralkyl wherein each of said aryl or aralkyl can be unsubstituted or optionally independently substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group consisting of CF3, halogen, alkyl, cycloalkyl, cycloalkylalkyl, haloalkyl, haloalkoxy, alkoxy and OH;
- R5 is H or 1 or 2 substituents independently selected from alkyl or cycloalkyl;
- R6 is H or 1 or 2 substituents independently selected from alkyl or cycloalkyl;
- R10 is selected from the group consisting -alkylene(R7)2,
- 112
- n is 0 or 1;
- p is 0 to 5 and when p is >1, the number of p moieties can be the same or different;
- and
- R8 is H, OH, alkoxy, alkyl, cycloalkyl, aryl, —N(H)R7, —N(H)C(O)alkyl, —N(H)C(O)aryl, —N(H)C(O)N(H)alkyl, —N(H)C(O)N(H)aryl, —N(H)S(O2)alkyl or —N(H)S(O2)aryl;
- with the proviso that the carbons shown marked 1 and 6 on the aromatic ring, along with X—R6, can optionally form a 4 to 8 membered ring system.
13 more elements
Dependencies are inferred from the claim text.