Aryl and biaryl piperdines with MCH modulatory activity
AssigneePharmacopeia Drug Discovery, Inc.
InventorsDouglas W. Hobbs, Tao Guo, Rachael C. Hunter, Huizhong Gu, Suresh D. Babu, Yuefei Shao
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Abstract
In one embodiment, this invention provides a novel class of compounds as antagonists of the MCH receptor, methods of preparing such compounds, pharmaceutical compositions containing one or more of the compounds, methods of preparing pharmaceutical formulations comprising one or more such compounds, and methods of treatment, prevention or amelioration or one or more of diseases associated with the MCH receptor. An illustrative inventive compound is shown below:
Claims27
A compound, including enantiomers, stereoisomers, rotamers, tautomers, and racemates of said compound, and pharmaceutically acceptable salts or solvates of said compound, said compound having the general structure shown in Formula I:
- wherein:
- Ar1:
- Z is a moiety selected from the group consisting of R4CO—;
- R4SO2—;
- R4N(R2′)CO—;
- R4′—;
- and R4′—O—C(O)—;
- R2 is H;
- alkyl;
- or alkyl (substituted with cycloalkyl);
- R2′ is H or alkyl;
- R3 is a moiety selected from the group consisting of H;
- alkyl;
- cycloalkyl;
- alkyl substituted with cycloalkyl;
- alkyl substituted with alkoxy;
- alkyl substituted with CF3;
- arylalkyl;
- alkylaryl;
- tetrahydrofuranyl;
- tetrahydropyranyl;
- R8SO2—;
- and
- n is a number 1 to 5;
- R4 is phenyl substituted with R7 or phenylalkyl substituted on the phenyl with R7;
- R4′ is a moiety selected from the group consisting of H;
- alkyl;
- cycloalkyl;
- alkyl substituted with cycloalkyl;
- alkyl substituted with alkoxy;
- alkyl substituted with CF3;
- arylalkyl;
- alkylaryl;
- tetrahydrofuranyl;
- and tetrahydropyranyl;
- R5 numbers 1-4 which may be the same or different and are independently selected from phenyl substituted with R7;
- R7 numbers 1-3 which may be the same or different and are independently selected from the group consisting of H;
- halogen;
- alkyl;
- OH;
- alkoxy;
- NH2, NH-alkyl;
- N(alkyl)2;
- CN;
- CF3;
- NO2;
- CF3O;
- —NH—C(O)-alkyl;
- —CH(O);
- —methylenedioxy;
- —CH2OH;
- benzofuran-2-yl;
- —O(alkyl);
- —C(O)alkyl;
- and indolyl;
- and
- R8 is selected from the group consisting of alkyl;
- arylalkyl;
- alkylaryl;
- aryl;
- —NH(alkyl);
- and —N(alkyl)2.
A compound, including enantiomers, stereoisomers, rotamers, tautomers, and racemates of said compound, and pharmaceutically acceptable salts, said compound having the general structure shown in Formula II:
- wherein:
- Ar1 is
- R2 is H;
- alkyl;
- or alkyl substituted with cycloalkyl;
- R3 is a moiety selected from the group consisting of H;
- alkyl;
- cycloalkyl;
- alkyl substituted with cycloalkyl;
- alkyl substituted with alkoxy;
- alkyl substituted with CF3;
- arylalkyl;
- alkylaryl;
- tetrahydrofuranyl;
- tetrahydropyranyl;
- R8SO2—;
- and
- n is a number from 1 to 5;
- R4 is phenyl substituted with R7 or phenylalkyl substituted on the phenyl with R7;
- R5 numbers 1-4 which may be the same or different and are independently selected from the group consisting of R7;
- phenyl substituted with R7;
- pyridyl substituted with R7;
- thiophenyl substituted with R7;
- pyrimidinyl substituted with R7;
- pyridazinyl substituted with R7;
- and pyrazinyl substituted with R7 as well as the N-oxides of the above-noted pyridyl, pyrimidinyl, pyridazinyl and pyrazinyl;
- R6 numbers 1-4 numbers 1-4 which may be the same or different and are independently selected from the group consisting of H;
- halogen;
- alkyl;
- OH;
- alkoxy;
- NH2;
- NH-alkyl;
- N(alkyl)2;
- CN;
- CF3;
- NO2;
- and CF3O;
- R7 numbers 1-3 which may be the same or different and are independently selected from the group consisting of H;
- halogen;
- alkyl;
- OH;
- alkoxy;
- NH2, NH-alkyl;
- N(alkyl)2;
- CN;
- CF3;
- NO2;
- CF3O;
- —NH—C(O)-alkyl;
- —CH(O);
- -methylenedioxy;
- —CH2OH;
- benzofuran-2-yl;
- —O(alkyl);
- —C(O)alkyl;
- and indolyl;
- and
- R8 is selected from the group consisting of alkyl;
- arylalkyl;
- alkylaryl;
- aryl;
- —NH(alkyl);
- and —N(alkyl)2.
A compound exhibiting MCH modulatory activity, including enantiomers, stereoisomers, rotamers, tautomers, and racemates of said compound, and pharmaceutically acceptable salts or solvates of said compound, said compound being selected from the group of compounds with structures listed below:
Dependencies are inferred from the claim text.