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US 2003/0166690 A1Published application
Use of compounds for decreasing activity of hormone-sensitive
AssigneeNero Nordisk A/S
InventorsSoren Ebdrup, Johannes Cornelis de Jong, Poul Jacobsen, Holger Claus Hansen, Per Vedso
Life of this patent
Estimating the term…
Abstract
Use of compounds to inhibit hormone-sensitive lipase, pharmaceutical compositions comprising the compounds, methods of treatment employing these compounds and compositions, and novel compounds. The present compounds are inhibitors of hormone-sensitive lipase and may be useful in the treatment and/or prevention of medical disorders where a decreased activity of hormone-sensitive lipase is desirable.
Claims46
Use of a compound of the general formula I
- 69
- wherein R1 is selected from hydrogen, C1-6-alkyl, C2-6-alkenyl and C3-10-cycloalkyl, each of which is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano and nitro;
- and
- R2 is selected from C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, each of which is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8heterocyclyl and C3-10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, perhalomethyl and perhalomethoxy;
- and
- wherein R2 is optionally covalently bound to R1 by an ether, thioether, C—C or C—N bond, to form a ring system with the N-atom to which R1 and R2 are bound;
- and
- X is O or S;
- and
- L is a group such that —C(═X)-L is a hydrolysable group;
- 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
- for inhibition of the lipolytic activity of hormone-sensitive lipase against triacylglycerols, diacylglycerols, cholesterol acyl esters or steroid acyl esters.
10 more elements
Use of a compound of the general formula I
- 70
- wherein R1 is selected from hydrogen, C1-6alkyl, C2-6-alkenyl and C3-10-cycloalkyl, each of which is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano and nitro;
- and
- R2 is selected from C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, each of which is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, Cam-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8heterocyclyl and C3-10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, perhalomethyl and perhalomethoxy;
- and
- wherein R2 is optionally covalently bound to R1 by an ether, thioether, C—C or C—N bond, to form a ring system with the N-atom to which R1 and R2 are bound;
- and
- X is O or S;
- and
- L is a group such that —C(═X)-L is a hydrolysable group;
- 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
- for the preparation of a medicament for the treatment of any disorder where it is desirable to
- modulate the plasma level of free fatty acids, glycerol, LDL-cholesterol, HDL-cholesterol, insulin and/or glucose;
- and/or
- modulate intracellular triacylglycerol and cholesterol ester stores, intracellular level of fatty acids, fatty acid esters such as diacylglycerols, phosphatidic acids, long chain acyl-CoA's as well as citrate or malonyl-CoA;
- and/or
- increase insulin sensitivity in adipose tissue, skeletal muscle, liver or pancreatic β cells;
- and/or
- modulate insulin secretion from pancreatic β cells.
17 more elements
A pharmaceutical composition comprising a compound of formula I
- 75
- wherein R1 is selected from hydrogen, C1-6-alkyl, C2-6-alkenyl and C3-10-cycloalkyl, each of which is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano and nitro;
- and
- R2 is selected from C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, each of which is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C34-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6alkyl, C2-6-alkenyl, perhalomethyl and perhalomethoxy;
- and
- wherein R2 is optionally covalently bound to R1 by an ether, thioether, C—C or C—N bond, to form a ring system with the N-atom to which R1 and R2 are bound;
- and
- X is O or S;
- and
- L is a group such that —C(═X)-L is a hydrolysable group;
- 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
9 more elements
Dependencies are inferred from the claim text.