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US 2017/0362191 A1Published application
Substituted Cyclohexylamine Compounds
AssigneeEpizyme, Inc.
InventorsMegan Alene Cloonan FOLEY, Kevin Wayne KUNTZ, Lorna Helen MITCHELL, Michael John MUNCHHOF
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Abstract
The present disclosure provides substituted cyclohexylamine compounds having Formula (I): and the pharmaceutically acceptable salts and solvates thereof, wherein R1, R2a, R2b, R3a, R3b, R4, R5, and R7 are defined as set forth in the specification. The present disclosure is also directed to the use of compounds of Formula I to treat a disorder responsive to the blockade of SMYD proteins such as SMYD3 or SMYD2. Compounds of the present disclosure are especially useful for treating cancer.
Claims26
A compound having Formula I:
- or a pharmaceutically acceptable salt or hydrate thereof,
- wherein:
- R1 is selected from the group consisting of ethyl and cyclopropyl;
- R2a, R2b, R3a, and R3b are each independently selected from the group consisting of hydrogen, C1-4 alkyl, alkyl, alkoxy, alkyoxyalkyl, aralkyl, and —C(═O)R6c;
- or
- R2a and R2b taken together form a C1-4 bridge;
- and R3a and R3b are independently selected from the group consisting of hydrogen, C1-4 alkyl, alkoxy, alkyoxyalkyl, aralkyl, and —C(═O)R6c;
- or
- R3a and R3b taken together form a C1-4 bridge;
- and R2a and R2b are independently selected from the group consisting of hydrogen, C1-4 alkyl, alkoxy, alkyoxyalkyl, aralkyl, and —C(═O)R6c;
- or
- R2a and R3b b taken together form a C1-4 bridge;
- and R2b and R3a are independently selected from the group consisting of hydrogen, C1-4 alkyl, alkoxy, alkyoxyalkyl, aralkyl, and —C(═O)R6c;
- or
- R2b and R3a taken together form a C1-4 bridge;
- and R2a and R3b are independently selected from the group consisting of hydrogen, C1-4 alkyl, alkoxy, alkyoxyalkyl, and —C(═O)R6c;
- or
- R4 is selected from the group consisting of hydrogen, optionally substituted C1-6 alkyl hydroxyalkyl, (amino)alkyl, (alkylamino)alkyl, (dialkylamino)alkyl, (heterocyclo)alkyl, —C(═O)R6a, and —S(═O)2R6b;
- R5 is selected from the group consisting of hydrogen, optionally substituted C1-6 alkyl, hydroxyalkyl, (amino)alkyl, (alkylamino)alkyl, (dialkylamino)alkyl, and (heterocyclo)alkyl;
- R6a is selected from the group consisting of optionally substituted C1-6 alkyl, alkoxy, amino, alkylamino, dialkylamino, cycloalkylamino, hydroxyalkyl, (amino)alkyl, (alkylamino)alkyl, (dialkylamino)alkyl, (cycloalkylamino)alkyl, (heterocyclo)alkyl, (amino)(hydroxy)alkyl, (aralkylamino)alkyl, optionally substituted C4-14 heterocyclo, optionally substituted C5-14 heteroaryl, and optionally substituted C3-12 cycloalkyl;
- R6b is selected from the group consisting of optionally substituted C1-6 alkyl, amino, alkylamino, dialkylamino, cycloalkylamino, hydroxyalkyl, (amino)alkyl, (alkylamino)alkyl, (dialkylamino)alkyl, (cycloalkylamino)alkyl, (heterocyclo)alkyl, (amino(hydroxy)alkyl, (aralkylamino)alkyl, optionally substituted C4-14 heterocyclo, optionally substituted C5-14 heteroaryl, and optionally substituted C3-12 cycloalkyl;
- R6c is selected from the group consisting of optionally substituted alkyl, amino, alkylamino, dialkylamino, cycloalkylamino, hydroxyalkyl, (amino)alkyl, (alkylamino)alkyl, (dialkylamino)alkyl, (cycloalkylamino)alkyl, (heterocyclo)alkyl, (amino)(hydroxy)alkyl, (aralkylamino)alkyl, optionally substituted C4-14 heterocyclo, optionally substituted C5-14 heteroaryl, and optionally substituted C3-12 cycloalkyl;
- and
- R7 is selected from the group consisting of hydrogen, C1-6 alkyl, hydroxyalkyl, (amino)alkyl, (alkylamino)alkyl, (dialkylamino)alkyl, alkoxyalkyl, and aralkyl,
- with the proviso that said compound having Formula I is not:
- N-(4-aminocyclohexyl)-5-cyclopropyl-N-methylisoxazole-3-carboxamide;
- N-((1s,4s)-4-aminocyclohexyl)-5-ethyl-N-(3-trifluoromethoxy)benzyl)isoxazole-3-carboxamide;
- N-(4-((3-(difluoromethoxy)benzyl)amino)cyclohexyl)-5-ethyl-N-(3-(trifluoromethoxy)benzyl)isoxazole-3-carboxamide;
- or
- 5-ethyl-N-(3-trifluoromethoxy)benzyl)-N-(4-((4-(trifluoromethoxy)benzyl) amino)cyclohexyl)isoxazole)-3-carboxamide.
27 more elements
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Dependencies are inferred from the claim text.