Oxadiazolopyridine derivatives for use as ghrelin O-acyl transferase (GOAT) inhibitors
AssigneeBoehringer Ingelheim International GmbH
InventorsCédrickx Godbout, Thomas Trieselmann, Viktor Vintonyak
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Abstract
The present invention relates to compounds of general formula I, wherein the groups R1, R2 and n are defined as in claim 1, which have valuable pharmacological properties, in particular bind to ghrelin O-acyl transferase (GOAT) and modulate its activity. The compounds are suitable for treatment and prevention of diseases which can be influenced by this receptor, such as metabolic diseases, in particular obesity.
Claims37
A method for treating obesity, type 2 diabetes mellitus, and/or insulin resistance, the method comprising administering to a patient in need thereof a pharmaceutically effective amount of a compound of formula (I)
- wherein
- X is CH or N;
- R1 is selected from the group consisting of CH3—CH2OH CH3, —CH2OH and Cl;
- R2 is independently of each other selected from the group consisting of H, F, Cl, Br, I, CN, C1-6-alkyl, C3-7-cycloalkyl, OH, —O—(C1-6-alkyl), —O—(C3-7-cycloalkyl), —O—(C1-3-alkyl)-(C3-7-cyclo alkyl) —O—(C1-3-alkyl)-(C3-7-cycloalkyl), —O-heterocyclyl, —O—(C1-3-alkyl)-heterocyclyl, —O-aryl, —O-heteroaryl, —S—(C1-3-alkyl), —SO—(C1-3-alkyl), —SO21-3-alkyl) —SO2-(C1-3alkyl), —NH2, —NH—(C1-6-alkyl), —NH—(C3-6-cycloalkyl), —NH—(C1-3-alkyl)-heterocyclyl, —NH—(C1-6-alkyl-C(═O)—NH2—C(═O)—NH2—C(═O)—NH—(C1-3-alkyl) —NH—(C1-6-alkyl)-C(═O)—NH2, —C(═O)—NH2, —C(═O)—NH—(C1-3-alkyl), —C(═O)—N(C1-3-alkyl)2, —C(═O)OH, —C(═O)—O—(C1-4-alkyl), —C(═O)—(C1-4-alkyl), alkyl) —C1-3-alkyl-C(═O)—O—(C1-4-alkyl), heterocyclyl, heteroaryl and 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl,
- wherein each alkyl or cycloalkyl group is optionally independently substituted with one or more substituents selected from the group consisting of F, CN and OH, and
- wherein each heterocyclyl group is selected from the group consisting of a mono- or spirocyclic 4-7-membered cycloalkyl group, in which 1, 2 or 3 CH2-groups are independently of each other replaced by O, S, NH or C═O, and
- wherein each heterocyclyl group is optionally substituted with 1 or 2 substituents independently of each other selected from the group consisting of F, OH and C1-3-alkyl,
- wherein each aryl group is selected from the group consisting of phenyl and naphthyl, and
- wherein each heteroaryl group is selected from the group consisting of a 5-membered aromatic cycle containing 1 or 2 heteroatoms independently selected from the group consisting of N, O and S or from a 6-membered aromatic cycle containing 1 or 2 N, and
- wherein each aryl or heteroaryl group is optionally substituted with 1 or 2 substituents independently selected from the group consisting of F, CN and C1-3-alkyl, which is optionally substituted with one or more F;
- or, if two groups R2 are attached to adjacent C atoms of the pyridine or pyrimidine group, they may be linked with each other and together form a O—CH2—O— —O—CH2—O—, —O—CH2—CH2—O— or —O—CH2—CH2—CH2—O— bridge, in which 1 or 2H 2 H atoms may be replaced with F or C1-3-alkyl;
- and
- n is 1, 2 or 3;
- wherein each of the above-mentioned alkyl groups may be substituted with one or more F;
- or a pharmaceutically acceptable salt thereof.
A method for treating a disease or condition which is mediated by inhibiting the activity of the ghrelin O-acyl transferase (GOAT), the method comprising administering a compound of formula (I)
- wherein
- X is CH or N;
- R1 is selected from the group consisting of CH3—CH2OH CH3, —CH2OH and Cl;
- R2 is independently of each other selected from the group consisting of H, F, Cl, Br, I, CN, C1-6-alkyl, C3-7-cycloalkyl, OH, —O—(C1-6-alkyl), —O—(C3-7-cycloalkyl), —O—(C1-3-alkyl)-(C3-7-cycloalkyl), —O-heterocyclyl, —O—(C1-3-alkyl)-heterocyclyl, —O-aryl, —O-heteroaryl, —S—(C1-3-alkyl), —SO—(C1-3-alkyl), —SO21-3-alkyl) —SO2—(C1-3-alkyl), —NH2, —NH—(C1-6-alkyl), —NH—(C3-6-cycloalkyl), —NH—(C1-3-alkyl)-heterocyclyl, —NH—(C1-6-alkyl)-C(═O )—NH2, —C(═O)—NH2, —C(═O)—NH—(C1-3-alkyl), —C(═O)—N(C1-3-alkyl)2, —C(═O)OH, —C(═O)—O—(C1-4-alkyl), —C(═O)—(C1-4-alkyl), alkyl) —C1-3-alkyl—C(═O)—O—(C1-4-alkyl), heterocyclyl, heteroaryl and 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl,
- wherein each alkyl or cycloalkyl group is optionally independently substituted with one or more substituents selected from the group consisting of F, CN and OH, and
- wherein each heterocyclyl group is selected from the group consisting of a mono- or spirocyclic 4-7-membered cycloalkyl group, in which 1, 2 or 3 CH2-groups are independently of each other replaced by O, S, NH or C═O, and
- wherein each heterocyclyl group is optionally substituted with 1 or 2 substituents independently of each other selected from the group consisting of F, OH and C1-3-alkyl,
- wherein each aryl group is selected from the group consisting of phenyl and naphthyl, and
- wherein each heteroaryl group is selected from the group consisting of a 5-membered aromatic cycle containing 1 or 2 heteroatoms independently selected from the group consisting of N, O and S or from a 6-membered aromatic cycle containing 1 or 2 N, and
- wherein each aryl or heteroaryl group is optionally substituted with 1 or 2 substituents independently selected from the group consisting of F, CN and C1-3-alkyl, which is optionally substituted with one or more F;
- or, if two groups R2 are attached to adjacent C atoms of the pyridine or pyrimidine group, they may be linked with each other and together form a O—CH2—O— —O—CH2—O—, —O—CH2—CH2—O— or —O—CH2—CH2—CH2—O— bridge, in which 1 or 2H 2 H atoms may be replaced with F or C1-3-alkyl;
- and
- n is 1, 2 or 3;
- wherein each of the above-mentioned alkyl groups may be substituted with one or more F;
- or a pharmaceutically acceptable salt thereof,
- to a patient in need thereof.
A method for treating obesity, type 2 diabetes mellitus, and/or insulin resistance, the method comprising administering to a patient in need thereof a pharmaceutically effective amount of a compound of formula
A method for treating obesity, type 2 diabetes mellitus, and/or insulin resistance, the method comprising administering to a patient in need thereof a pharmaceutically effective amount of a compound of formula
A method for treating obesity, type 2 diabetes mellitus, and/or insulin resistance, the method comprising administering to a patient in need thereof a pharmaceutically effective amount of a compound of formula
A method for treating obesity, type 2 diabetes mellitus, and/or insulin resistance, the method comprising administering to a patient in need thereof a pharmaceutically effective amount of a compound of formula
A method for treating obesity, type 2 diabetes mellitus, and/or insulin resistance, the method comprising administering to a patient in need thereof a pharmaceutically effective amount of a compound of formula
A method for treating obesity, type 2 diabetes mellitus, and/or insulin resistance, the method comprising administering to a patient in need thereof a pharmaceutically effective amount of a compound of formula
A method for treating obesity, type 2 diabetes mellitus, and/or insulin resistance, the method comprising administering to a patient in need thereof a pharmaceutically effective amount of a compound of formula
Dependencies are inferred from the claim text.