PYRAZOLE AMINOPYRIMIDINE DERIVATIVES AS LRRK2 MODULATORS
First Claim
Patent Images
1. A compound selected from:
- N2-(1′
,5-dimethyl-1′
H-1,4′
-bipyrazol-4-yl)-N4-methyl-5-(trifluoromethyl)pyrimidine-2,4-diamine;
N2-(1′
,3-dimethyl-1′
H-1,4′
-bipyrazol-4-yl)-N4-methyl-5-(trifluoromethyl)pyrimidine-2,4-diamine;
4-(cyclopropylamino)-2-((5-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)amino)pyrimidine-5-carbonitrile;
4-(cyclopropylamino)-2-((3-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)amino)pyrimidine-5-carbonitrile;
2-((1-(1-cyanopropyl)-5-methyl-1H-pyrazol-4-yl)amino)-4-(cyclopropylamino)pyrimidine-5-carbonitrile;
N2-(1-(1-fluoro-2-methylpropan-2-yl)-3-methyl-1H-pyrazol-4-yl)-N4-methyl-5-(trifluoromethyl)pyrimidine-2,4-diamine;
2-((5-chloro-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)amino)-4-(ethylamino)pyrimidine-5-carbonitrile;
5-bromo-N2-(1,5-dimethyl-1H-pyrazol-4-yl)-N4-methylpyrimidine-2,4-diamine;
2-methyl-2-(3-methyl-4-((4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-1H-pyrazol-1-yl)propan-1-ol;
1-((5-chloro-4-((4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-1H-pyrazol-1-yl)methyl)cyclopropanol;
N2-(3-chloro-1-(2-(4-ethyl-4H-1,2,4-triazol-3-yl)propan-2-yl)-1H-pyrazol-4-yl)-N4-methyl-5-(trifluoromethyl)pyrimidine-2,4-diamine;
N2-(3-chloro-1-(2-(1-ethyl-1H-1,2,4-triazol-3-yl)propan-2-yl)-1H-pyrazol-4-yl)-N4-methyl-5-(trifluoromethyl)pyrimidine-2,4-diamine;
N2-(3-chloro-1-(2-(1-ethyl-1H-1,2,4-triazol-3-yl)propan-2-yl)-1H-pyrazol-4-yl)-N4-methyl-5-(trifluoromethyl)pyrimidine-2,4-diamine;
N2-(3-chloro-1-(2-(1-ethyl-1H-1,2,4-triazol-3-yl)propan-2-yl)-1H-pyrazol-4-yl)-N4-methyl-5-(trifluoromethyl)pyrimidine-2,4-diamine;
N4-methyl-N2-(3-methyl-1-(3-methyloxetan-3-yl)-1H-pyrazol-4-yl)-5-(trifluoromethyl)pyrimidine-2,4-diamine;
N2-(1-(2-(1,4-dimethyl-1H-imidazol-2-yl)propan-2-yl)-3-methyl-1H-pyrazol-4-yl)-N4-methyl-5-(trifluoromethyl)pyrimidine-2,4-diamine;
N2-(1-(2-(1,4-dimethyl-1H-imidazol-2-yl)propan-2-yl)-3-methyl-1H-pyrazol-4-yl)-N4-methyl-5-(trifluoromethyl)pyrimidine-2,4-diamine;
N4-methyl-N2-(3-methyl-1-(2-(5-methyloxazol-2-yl)propan-2-yl)-1H-pyrazol-4-yl)-5-(trifluoromethyl)pyrimidine-2,4-diamine;
N4-ethyl-N2-(3-methyl-1-(3-methyloxetan-3-yl)-1H-pyrazol-4-yl)-5-(trifluoromethyl)pyrimidine-2,4-diamine;
N4-ethyl-N2-(1-((2-methoxyethyl)sulfonyl)-3-methyl-1H-pyrazol-4-yl)-5-(trifluoromethyl)pyrimidine-2,4-diamine;
N2-(1-((2-methoxyethyl)sulfonyl)-3-methyl-1H-pyrazol-4-yl)-N4-methyl-5-(trifluoromethyl)pyrimidine-2,4-diamine;
N2-(1-((2-methoxyethyl)sulfonyl)-5-methyl-1H-pyrazol-4-yl)-N4-methyl-5-(trifluoromethyl)pyrimidine-2,4-diamine;
N2-(5-chloro-1-(2-(4-methyl-4H-1,2,4-triazol-3-yl)propan-2-yl)-1H-pyrazol-4-yl)-N4-ethyl-5-(trifluoromethyl)pyrimidine-2,4-diamine;
N4-methyl-N2-(5-methyl-1-(2-(1-methyl-1H-pyrazol-3-yl)propyl)-1H-pyrazol-4-yl)-5-(trifluoromethyl)pyrimidine-2,4-diamine;
N4-methyl-N2-(5-methyl-1-(2-(1-methyl-1H-pyrazol-3-yl)propyl)-1H-pyrazol-4-yl)-5-(trifluoromethyl)pyrimidine-2,4-diamine;
N4-methyl-N2-(3-methyl-1-(2-(pyrimidin-2-yl)propan-2-yl)-1H-pyrazol-4-yl)-5-(trifluoromethyl)pyrimidine-2,4-diamine;
N2-(3-chloro-1-(2-(5-methyl-1,3,4-oxadiazol-2-yl)propan-2-yl)-1H-pyrazol-4-yl)-N4-ethyl-5-(trifluoromethyl)pyrimidine-2,4-diamine;
N4-ethyl-N2-(3-methyl-1-(2-(5-methyl-1,3,4-oxadiazol-2-yl)propan-2-yl)-1H-pyrazol-4-yl)-5-(trifluoromethyl)pyrimidine-2,4-diamine;
N4-ethyl-N2-(1-(2-(5-ethyl-1,3,4-oxadiazol-2-yl)propan-2-yl)-3-methyl-1H-pyrazol-4-yl)-5-(trifluoromethyl)pyrimidine-2,4-diamine;
N4-ethyl-N2-(1-(2-(1-isopropyl-1H-1,2,4-triazol-3-yl)propan-2-yl)-3-methyl-1H-pyrazol-4-yl)-5-(trifluoromethyl)pyrimidine-2,4-diamine;
N2-(3-chloro-1-(2-(4-methyl-4H-1,2,4-triazol-3-yl)propan-2-yl)-1H-pyrazol-4-yl)-N4-ethyl-5-(trifluoromethyl)pyrimidine-2,4-diamine;
N2-(3-chloro-1-(2-(1-methyl-1H-1,2,4-triazol-3-yl)propan-2-yl)-1H-pyrazol-4-yl)-N4-ethyl-5-(trifluoromethyl)pyrimidine-2,4-diamine;
N4-methyl-N2-(5-methyl-1-(2-(1-methyl-1H-pyrazol-3-yl)ethyl)-1H-pyrazol-4-yl)-5-(trifluoromethyl)pyrimidine-2,4-diamine;
N4-ethyl-N2-(3-methyl-1-(2-(1-methyl-1H-pyrazol-3-yl)propan-2-yl)-1H-pyrazol-4-yl)-5-(trifluoromethyl)pyrimidine-2,4-diamine;
N4-ethyl-N2-(3-methyl-1-(2-(1-methyl-1H-pyrazol-5-yl)propan-2-yl)-1H-pyrazol-4-yl)-5-(trifluoromethyl)pyrimidine-2,4-diamine;
N4-methyl-N2-(3-methyl-1-(2-(1-methyl-1H-pyrazol-3-yl)ethyl)-1H-pyrazol-4-yl)-5-(trifluoromethyl)pyrimidine-2,4-diamine;
N2-(1-(3-fluorotetrahydro-2H-pyran-4-yl)-3-methyl-1H-pyrazol-4-yl)-N4-methyl-5-(trifluoromethyl)pyrimidine-2,4-diamine;
N2-(1-(3-fluorotetrahydro-2H-pyran-4-yl)-3-methyl-1H-pyrazol-4-yl)-N4-methyl-5-(trifluoromethyl)pyrimidine-2,4-diamine;
N2-(1-(3-fluorotetrahydro-2H-pyran-4-yl)-5-methyl-1H-pyrazol-4-yl)-N4-methyl-5-(trifluoromethyl)pyrimidine-2,4-diamine;
N2-(1-((3R)-3-fluorotetrahydro-2H-pyran-4-yl)-5-methyl-1H-pyrazol-4-yl)-N4-methyl-5-(trifluoromethyl)pyrimidine-2,4-diamine3-methyl-3-(3-methyl-4-((4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-1H-pyrazol-1-yl)butanenitrile;
2-((3-methyl-4-((4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-1H-pyrazol-1-yl)methyl)butanenitrile;
3-methyl-3-(3-methyl-4-(4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)-1H-pyrazol-1-yl)butanenitrile;
2-(5-((4-(ethylamino)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-1-methyl-1H-pyrazol-3-yl)-2-methylpropanenitrile;
2-methyl-2-(1-methyl-5-((4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-1H-pyrazol-3-yl)propanenitrile;
2-((1-(2-cyanopropan-2-yl)-3-methyl-1H-pyrazol-4-yl)amino)-4-(cyclopropylamino)pyrimidine-5-carbonitrile;
2-((1-(2-cyanopropan-2-yl)-3-methyl-1H-pyrazol-4-yl)amino)-4-(cyclopropylamino)pyrimidine-5-carbonitrile;
2-((1-(2-cyanopropan-2-yl)-3-methyl-1H-pyrazol-4-yl)amino)-4-(ethylamino)pyrimidine-5-carbonitrile;
2-methyl-2-(3-methyl-4-((4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-1H-pyrazol-1-yl)butanenitrile; and
5-((4-(ethylamino)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-1-methyl-1H-pyrazole-3-carbonitrile,or a pharmaceutical salt thereof.
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Abstract
Pyrazole compounds that are modulators of LRRK2, methods of making the compounds, and methods for using the compounds for treatment of diseases associated with LRRK2 receptor, such as Parkinson'"'"'s disease.
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Citations
7 Claims
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1. A compound selected from:
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N2-(1′
,5-dimethyl-1′
H-1,4′
-bipyrazol-4-yl)-N4-methyl-5-(trifluoromethyl)pyrimidine-2,4-diamine;N2-(1′
,3-dimethyl-1′
H-1,4′
-bipyrazol-4-yl)-N4-methyl-5-(trifluoromethyl)pyrimidine-2,4-diamine;4-(cyclopropylamino)-2-((5-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)amino)pyrimidine-5-carbonitrile; 4-(cyclopropylamino)-2-((3-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)amino)pyrimidine-5-carbonitrile; 2-((1-(1-cyanopropyl)-5-methyl-1H-pyrazol-4-yl)amino)-4-(cyclopropylamino)pyrimidine-5-carbonitrile; N2-(1-(1-fluoro-2-methylpropan-2-yl)-3-methyl-1H-pyrazol-4-yl)-N4-methyl-5-(trifluoromethyl)pyrimidine-2,4-diamine; 2-((5-chloro-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)amino)-4-(ethylamino)pyrimidine-5-carbonitrile; 5-bromo-N2-(1,5-dimethyl-1H-pyrazol-4-yl)-N4-methylpyrimidine-2,4-diamine; 2-methyl-2-(3-methyl-4-((4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-1H-pyrazol-1-yl)propan-1-ol; 1-((5-chloro-4-((4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-1H-pyrazol-1-yl)methyl)cyclopropanol; N2-(3-chloro-1-(2-(4-ethyl-4H-1,2,4-triazol-3-yl)propan-2-yl)-1H-pyrazol-4-yl)-N4-methyl-5-(trifluoromethyl)pyrimidine-2,4-diamine; N2-(3-chloro-1-(2-(1-ethyl-1H-1,2,4-triazol-3-yl)propan-2-yl)-1H-pyrazol-4-yl)-N4-methyl-5-(trifluoromethyl)pyrimidine-2,4-diamine; N2-(3-chloro-1-(2-(1-ethyl-1H-1,2,4-triazol-3-yl)propan-2-yl)-1H-pyrazol-4-yl)-N4-methyl-5-(trifluoromethyl)pyrimidine-2,4-diamine; N2-(3-chloro-1-(2-(1-ethyl-1H-1,2,4-triazol-3-yl)propan-2-yl)-1H-pyrazol-4-yl)-N4-methyl-5-(trifluoromethyl)pyrimidine-2,4-diamine; N4-methyl-N2-(3-methyl-1-(3-methyloxetan-3-yl)-1H-pyrazol-4-yl)-5-(trifluoromethyl)pyrimidine-2,4-diamine; N2-(1-(2-(1,4-dimethyl-1H-imidazol-2-yl)propan-2-yl)-3-methyl-1H-pyrazol-4-yl)-N4-methyl-5-(trifluoromethyl)pyrimidine-2,4-diamine; N2-(1-(2-(1,4-dimethyl-1H-imidazol-2-yl)propan-2-yl)-3-methyl-1H-pyrazol-4-yl)-N4-methyl-5-(trifluoromethyl)pyrimidine-2,4-diamine; N4-methyl-N2-(3-methyl-1-(2-(5-methyloxazol-2-yl)propan-2-yl)-1H-pyrazol-4-yl)-5-(trifluoromethyl)pyrimidine-2,4-diamine; N4-ethyl-N2-(3-methyl-1-(3-methyloxetan-3-yl)-1H-pyrazol-4-yl)-5-(trifluoromethyl)pyrimidine-2,4-diamine; N4-ethyl-N2-(1-((2-methoxyethyl)sulfonyl)-3-methyl-1H-pyrazol-4-yl)-5-(trifluoromethyl)pyrimidine-2,4-diamine; N2-(1-((2-methoxyethyl)sulfonyl)-3-methyl-1H-pyrazol-4-yl)-N4-methyl-5-(trifluoromethyl)pyrimidine-2,4-diamine; N2-(1-((2-methoxyethyl)sulfonyl)-5-methyl-1H-pyrazol-4-yl)-N4-methyl-5-(trifluoromethyl)pyrimidine-2,4-diamine; N2-(5-chloro-1-(2-(4-methyl-4H-1,2,4-triazol-3-yl)propan-2-yl)-1H-pyrazol-4-yl)-N4-ethyl-5-(trifluoromethyl)pyrimidine-2,4-diamine; N4-methyl-N2-(5-methyl-1-(2-(1-methyl-1H-pyrazol-3-yl)propyl)-1H-pyrazol-4-yl)-5-(trifluoromethyl)pyrimidine-2,4-diamine; N4-methyl-N2-(5-methyl-1-(2-(1-methyl-1H-pyrazol-3-yl)propyl)-1H-pyrazol-4-yl)-5-(trifluoromethyl)pyrimidine-2,4-diamine; N4-methyl-N2-(3-methyl-1-(2-(pyrimidin-2-yl)propan-2-yl)-1H-pyrazol-4-yl)-5-(trifluoromethyl)pyrimidine-2,4-diamine; N2-(3-chloro-1-(2-(5-methyl-1,3,4-oxadiazol-2-yl)propan-2-yl)-1H-pyrazol-4-yl)-N4-ethyl-5-(trifluoromethyl)pyrimidine-2,4-diamine; N4-ethyl-N2-(3-methyl-1-(2-(5-methyl-1,3,4-oxadiazol-2-yl)propan-2-yl)-1H-pyrazol-4-yl)-5-(trifluoromethyl)pyrimidine-2,4-diamine; N4-ethyl-N2-(1-(2-(5-ethyl-1,3,4-oxadiazol-2-yl)propan-2-yl)-3-methyl-1H-pyrazol-4-yl)-5-(trifluoromethyl)pyrimidine-2,4-diamine; N4-ethyl-N2-(1-(2-(1-isopropyl-1H-1,2,4-triazol-3-yl)propan-2-yl)-3-methyl-1H-pyrazol-4-yl)-5-(trifluoromethyl)pyrimidine-2,4-diamine; N2-(3-chloro-1-(2-(4-methyl-4H-1,2,4-triazol-3-yl)propan-2-yl)-1H-pyrazol-4-yl)-N4-ethyl-5-(trifluoromethyl)pyrimidine-2,4-diamine; N2-(3-chloro-1-(2-(1-methyl-1H-1,2,4-triazol-3-yl)propan-2-yl)-1H-pyrazol-4-yl)-N4-ethyl-5-(trifluoromethyl)pyrimidine-2,4-diamine; N4-methyl-N2-(5-methyl-1-(2-(1-methyl-1H-pyrazol-3-yl)ethyl)-1H-pyrazol-4-yl)-5-(trifluoromethyl)pyrimidine-2,4-diamine; N4-ethyl-N2-(3-methyl-1-(2-(1-methyl-1H-pyrazol-3-yl)propan-2-yl)-1H-pyrazol-4-yl)-5-(trifluoromethyl)pyrimidine-2,4-diamine; N4-ethyl-N2-(3-methyl-1-(2-(1-methyl-1H-pyrazol-5-yl)propan-2-yl)-1H-pyrazol-4-yl)-5-(trifluoromethyl)pyrimidine-2,4-diamine; N4-methyl-N2-(3-methyl-1-(2-(1-methyl-1H-pyrazol-3-yl)ethyl)-1H-pyrazol-4-yl)-5-(trifluoromethyl)pyrimidine-2,4-diamine; N2-(1-(3-fluorotetrahydro-2H-pyran-4-yl)-3-methyl-1H-pyrazol-4-yl)-N4-methyl-5-(trifluoromethyl)pyrimidine-2,4-diamine; N2-(1-(3-fluorotetrahydro-2H-pyran-4-yl)-3-methyl-1H-pyrazol-4-yl)-N4-methyl-5-(trifluoromethyl)pyrimidine-2,4-diamine; N2-(1-(3-fluorotetrahydro-2H-pyran-4-yl)-5-methyl-1H-pyrazol-4-yl)-N4-methyl-5-(trifluoromethyl)pyrimidine-2,4-diamine; N2-(1-((3R)-3-fluorotetrahydro-2H-pyran-4-yl)-5-methyl-1H-pyrazol-4-yl)-N4-methyl-5-(trifluoromethyl)pyrimidine-2,4-diamine 3-methyl-3-(3-methyl-4-((4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-1H-pyrazol-1-yl)butanenitrile; 2-((3-methyl-4-((4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-1H-pyrazol-1-yl)methyl)butanenitrile; 3-methyl-3-(3-methyl-4-(4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)-1H-pyrazol-1-yl)butanenitrile; 2-(5-((4-(ethylamino)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-1-methyl-1H-pyrazol-3-yl)-2-methylpropanenitrile; 2-methyl-2-(1-methyl-5-((4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-1H-pyrazol-3-yl)propanenitrile; 2-((1-(2-cyanopropan-2-yl)-3-methyl-1H-pyrazol-4-yl)amino)-4-(cyclopropylamino)pyrimidine-5-carbonitrile; 2-((1-(2-cyanopropan-2-yl)-3-methyl-1H-pyrazol-4-yl)amino)-4-(cyclopropylamino)pyrimidine-5-carbonitrile; 2-((1-(2-cyanopropan-2-yl)-3-methyl-1H-pyrazol-4-yl)amino)-4-(ethylamino)pyrimidine-5-carbonitrile; 2-methyl-2-(3-methyl-4-((4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-1H-pyrazol-1-yl)butanenitrile; and 5-((4-(ethylamino)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-1-methyl-1H-pyrazole-3-carbonitrile, or a pharmaceutical salt thereof. - View Dependent Claims (2, 3, 4, 5, 6)
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7. The invention as described hereinabove.
Specification