New compounds, their preparation and use
AssigneeNovo Nordisk A/S
InventorsJohn Patrick Mogensen, Per Sauerberg, Paul Stanley Bury, Lone Jeppesen, Ingrid Pettersson
Life of this patent
Estimating the term…
Abstract
The present invention relates to compounds of formula (I) 1 The compounds are useful in the treatment and/or prevention of conditions mediated by nuclear receptors, in particular the Peroxisome Proliferator-Activated Receptors (PPAR).
Claims80
A compound of formula (I)
- 40
- wherein
- X is hydrogen or
- X is C1-12-alkyl, C2-12-alkenyl, C2-12-alkynyl, aryl, heteroaryl, aralkyl, heteroaralkyl or heterocyclyl each of which is optionally substituted with one or more substituents selected from halogen, perhalomethyl, hydroxy, C1-6-alkyl, C2-6-alkenyl, C2-6-alkynyl, hydroxy, C1-6-alkoxy, C1-6-alkylthio, aryl, aryloxy, arylthio, acyl, aralkyl, aralkoxy, heteroaryl, heteroaralkyl, heteroaryloxy, heteroaralkoxy, C1-6-alkylthio, cyano, amino, C1-6-alkylamino, C1-6-dialkylamino, carboxy or C1-6-alkylester;
- and
- Y is hydrogen or
- Y is C1-12-alkyl, C2-12-alkenyl, C2-12-alkynyl, C4-12-alkenynyl, aryl, heteroaryl, aralkyl or heteroaralkyl each of which is optionally substituted with one or more substituents selected from halogen, C1-6-alkyl, perhalomethyl, hydroxy, aryl, heteroaryl, amino, carboxy or C1-6-alkylester;
- and
- Z is hydrogen, halogen, hydroxy or
- Z is C1-6-alkyl or C1-6-alkoxy each of which is optionally substituted with one or more substituents selected from C1-6-alkoxy, halogen, hydroxy, carboxy, amino or cyano;
- and
- Q is O, S or NR5, wherein R5 is hydrogen, C1-6-alkyl, C2-6-alkenyl, C2-6-alkynyl, C4-6-alkenynyl, aralkyl or heteroaralkyl and wherein R5 is optionally substituted with one or more substituents selected from halogen, hydroxy, C1-6-alkoxy, amino or carboxy;
- and
- Ar is arylene, heteroarylene or a divalent heterocyclic group each of which can be optionally substituted with one or more substituents selected from C1-6-alkyl, aryl or C1-6-alkoxy each of which can be optionally substituted with halogen, hydroxy, carboxy or C1-6-alkylester;
- and
- R1 is hydrogen, hydroxy or halogen;
- or R1 forms a bond together with R2;
- and
- R2 is hydrogen or C1-6-alkyl;
- or R2 forms a bond together with R1;
- and
- R3 is hydrogen, C1-6-alkyl, C2-4-alkenyl, C2-6-alkynyl, C4-6-alkenynyl, aryl, aralkyl, C1-6-alkoxyC1-6-alkyl, acyl, heterocyclyl, heteroaryl or heteroaralkyl groups optionally substituted with one or more substituents selected from halogen, perhalomethyl, hydroxy, cyano, carboxy or C1-6alkylester;
- and
- R4 is hydrogen, C1-6-alkyl, C2-6-alkenyl, C2-4-alkynyl, C4-6-alkenynyl or aryl;
- n is an integer ranging from 0 to 3;
- and
- m is an integer ranging from 0 to 1;
- or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof, or any tautomeric forms, stereoisomers, mixture of stereoisomers including a racemic mixture, or polymorphs.
A compound according to any one of the preceding claims of formula (I)
- 42
- wherein
- X is hydrogen, C1-12-alkyl, C2-12-alkenyl, C2-12-alkynyl, aryl, heteroaryl, aralkyl, heteroaralkyl or heterocyclyl optionally substituted with one or more substituents selected from halogen, perhalomethyl, hydroxy, C1-6-alkyl, C2-6-alkenyl, C2-6-alkynyl, hydroxy, C1-6-alkoxy, C1-6-alkylthio, aryl, aryloxy, arylthio, acyl, aralkyl, aralkoxy, heteroaryl, heteroaralkyl, heteroaryloxy, heteroaralkoxy, C1-6-alkylthio, cyano, amino, C1-6-alkylamino, C1-6dialkylamino, carboxy or C1-6-alkylester;
- and
- Y is hydrogen, C1-12-alkyl, C2-12-alkenyl, C2-12-alkynyl, C4-12-alkenynyl, aryl, heteroaryl, aralkyl or heteroaralkyl optionally substituted with one or more substituents selected from halogen, C1-6-alkyl, perhalomethyl, hydroxy, aryl, heteroaryl, amino, carboxy or C1-6-alkylester;
- and
- Z is hydrogen, halogen, hydroxy, C1-6-alkyl or C1-6-alkoxy optionally substituted with one or more substituents selected from C1-6-alkoxy, halogen, hydroxy, carboxy, amino or cyano;
- and
- Q is O, S or NR5, wherein R5 is hydrogen, C1-6-alkyl, C2-6-alkenyl, C2-6alkynyl, C4-6alkenynyl, aralkyl or heteroaralkyl and wherein R5 is optionally substituted with one or more substituents selected from halogen, hydroxy, C1-6-alkoxy, amino or carboxy;
- and
- Ar is arylene, heteroarylene or a divalent heterocyclic group each of which can be optionally substituted with one or more substituents selected from C1-6-alkyl, aryl or C1-6-alkoxy each of which can be optionally substituted with halogen, hydroxy, carboxy or C1-6-alkylester;
- and
- R1 is hydrogen, hydroxy or halogen;
- or R1 forms a bond together with R2;
- and
- R2 is hydrogen or C1-6-alkyl;
- or R2 forms a bond together with R1;
- and
- R3 is hydrogen, C1-6-alkyl, C2-4-alkenyl, C2-6-alkynyl, C4-6-alkenynyl, aryl, aralkyl, C1-6-alkoxyC1-6-alkyl, acyl, heterocyclyl, heteroaryl or heteroaralkyl groups optionally substituted with one or more substituents selected from halogen, perhalomethyl, hydroxy, cyano, carboxy or C1-6-alkylester;
- and
- R4 is hydrogen, C1-6-alkyl, C2-6-alkenyl, C2-6-alkynyl, C4-6-alkenynyl or aryl;
- n is an integer ranging from 0 to 3;
- and
- m is an integer ranging from 0 to 1;
- or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof, or any tautomeric forms, stereoisomers, mixture of stereoisomers including a racemic mixture, or polymorphs.
A compound according to any one of the preceding claims wherein X is aryl, heteroaryl or heterocyclyl optionally substituted with one or more substituents selected from halogen, perhalomethyl, C1-6-alkoxy, C1-6-alkylthio, aryl, aryloxy, arylthio, aralkyl, aralkoxy, heteroaryl, heteroaralkyl, heteroaryloxy or heteroaralkoxy.
A compound according to any one of the preceding claims wherein X is aryl, heteroaryl or heterocyclyl each of which is optionally substituted with one or more substituents selected from halogen, perhalomethyl, C1-6-alkoxy, C1-6-alkylthio, aryl, aryloxy, arylthio, aralkyl, aralkoxy, heteroaryl, heteroaralkyl, heteroaryloxy or heteroaralkoxy.
A compound according to any one of the preceding claims wherein X is aryl optionally substituted with one or more substituents selected from halogen, perhalomethyl, C1-6-alkoxy, C1-6-alkylthio, aryl, aryloxy, arylthio, aralkyl, aralkoxy, heteroaryl, heteroaralkyl, heteroaryloxy or heteroaralkoxy.
A compound according to any one of the preceding claims wherein X is phenyl or naphthyl each of which is optionally substituted with one or more substituents selected from halogen or perhalomethyl.
A compound according to any one of the preceding claims wherein X is phenyl optionally substituted with one or more substituents selected from halogen.
A compound according to any one of the preceding claims wherein X is phenyl.
A compound according to any one of the preceding claims wherein X is heteroaryl optionally substituted with one or more substituents selected from halogen, perhalomethyl, C1-6-alkoxy, C1-6-alkylthio, aryl, aryloxy, arylthio, aralkyl, aralkoxy, heteroaryl, heteroaralkyl, heteroaryloxy or heteroaralkoxy.
A compound according to any one of the preceding claims wherein X is heterocyclyl optionally substituted with one or more substituents selected from halogen, perhalomethyl, C1-6-alkoxy, C1-6-alkylthio, aryl, aryloxy, arylthio, aralkyl, aralkoxy, heteroaryl, heteroaralkyl, heteroaryloxy or heteroaralkoxy.
A compound according to any one of the preceding claims wherein Y is hydrogen, C1-12-alkyl or aryl.
A compound according to any one of the preceding claims wherein Y is hydrogen or methyl.
A compound according to any one of the preceding claims wherein Y is hydrogen.
A compound according to any one of the preceding claims wherein Z is hydrogen or C1-6-alkoxy.
A compound according to any one of the preceding claims wherein Z is hydrogen.
A compound according to any one of the preceding claims wherein Q is O.
A compound according to any one of the preceding claims wherein Ar is arylene optionally substituted with one or more substituents selected from C1-6-alkyl or C1-6-alkoxy each of which can be optionally substituted with carboxy.
A compound according to any one of the preceding claims wherein Ar is phenylene.
A compound according to any one of the preceding claims wherein R1 is hydrogen or R1 forms a bond together with R2.
A compound according to any one of the preceding claims wherein R1 is hydrogen.
A compound according to any one of the preceding claims wherein R2 is hydrogen or R2 forms a bond together with R1.
A compound according to any one of the preceding claims wherein R2 is hydrogen.
A compound according to any one of the preceding claims wherein R3 is C1-6-alkyl.
A compound according to any one of the preceding claims wherein R3 is C12-alkyl.
A compound according to any one of the preceding claims wherein R4 is hydrogen.
A compound according to any one of the preceding claims wherein n is 1.
A compound according to any one of the preceding claims wherein m is 1.
A compound according to any one of the preceding claims wherein alkyl is methyl or ethyl.
A compound according to any one of the preceding claims wherein alkenyl is vinyl or 1-propenyl.
A compound according to any one of the preceding claims wherein alkynyl is 1-propynyl.
A compound according to any one of the preceding claims wherein alkenynyl is 1-pentene-4-yne.
A compound according to any one of the preceding claims wherein alkoxy is methoxy, ethoxy, isopropoxy or cyclopropoxy.
A compound according to any one of the preceding claims wherein aryl is phenyl or naphthyl optionally substituted with halogen.
A compound according to any one of the preceding claims wherein arylene is phenylene.
A compound according to any one of the preceding claims wherein halogen is chlorine.
A compound according to any one of the preceding claims wherein perhalomethyl is trifluoromethyl.
A compound according to any one of the preceding claims wherein heteroaryl is furan, pyrrole, pyridine, indole or benzofuran.
A compound according to any one of the preceding claims wherein heteroarylene is furan, pyrrole, pyridine, indole or benzofuran.
A compound according to any one of the preceding claims wherein aralkyl is benzyl.
A compound according to any one of the preceding claims wherein aryloxy is phenoxy.
A compound according to any one of the preceding claims wherein aralkoxy is benzyloxy.
A compound according to any one of the preceding claims wherein n is an integer ranging from 1 to 3 and m is 1.
A compound according to any of the preceding claims wherein the substituents Z and Y are arranged in a trans-configuration.
A compound according to any of the preceding claims wherein the substituents Z and Y are arranged in a cis-configuration.
A pharmaceutical composition comprising, as an active ingredient, a compound according to any one of the preceding compound claims or a pharmaceutically acceptable salt thereof together with a pharmaceutically acceptable carrier or diluent.
A pharmaceutical composition useful in the treatment and/or prevention of conditions mediated by nuclear receptors, in particular the Peroxisome Proliferator-Activated Receptors (PPAR), the composition comprising, as an active ingredient, a compound according to any one of the preceding compound claims or a pharmaceutically acceptable salt thereof together with a pharmaceutically acceptable carrier or diluent.
A pharmaceutical composition useful in the treatment and/or prevention of diabetes and/or obesity, the composition comprising, as an active ingredient, a compound according to any one of the preceding compound claims or a pharmaceutically acceptable salt thereof together with a pharmaceutically acceptable carrier or diluent.
Use of a compound according to any one of the preceding compound claims or a pharmaceutically acceptable salt thereof for the preparation of a medicament.
Use of a compound according to any one of the preceding compound claims or a pharmaceutically acceptable salt thereof for the preparation of a medicament useful in the treatment and/or prevention of conditions mediated by nuclear receptors, in particular the Peroxisome Proliferator-Activated Receptors (PPAR).
Use of a compound according to any one of the preceding compound claims or a pharmaceutically acceptable salt thereof for the preparation of a medicament for treatment and/or prevention of diabetes and/or obesity.
Dependencies are inferred from the claim text.