Inhibitors of histone demethylases

A compound of the general Formula (I)

• A is selected from —CHR2C(O)—, C1-8 alkylene, C2-8 alkenylene, C2-8 alkynylene, C3-10 cycloalkylene, heterocyclylene, heteroarylene and arylene, which alkylene, alkenylene, alkynylene, cycloalkylene, heterocyclylene, heteroarylene and arylene may optionally be substituted with one or more R3;
• Y is selected from —H, —NR6R7, —OR7, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C3-10 cycloalkyl, heterocyclyl, heteroaryl and aryl, which alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, heteroaryl and aryl may optionally be substituted with one or more R3 and may form a cyclic structure with R2;
• R1 is selected from —H, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C3-10 cycloalkyl, which alkyl, alkenyl, alkynyl and cycloalkyl may be optionally substituted with one or more selected from —OH, aryl, C1-6 alkoxy, heteroaryl, aryloxy, heteroaryloxy, F, and C3-6 cycloalkyl;
• or more preferably is selected from —H and C1-4 alkyl;
• or with -A-Y forms a nitrogen containing optionally substituted heterocyclic group where the optional substitution may be C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, or C3-10 cycloalkyl, which alkyl, alkenyl, alkynyl and cycloalkyl may be optionally substituted with one or more selected from —OH, aryl, C1-6 alkoxy, heteroaryl, aryloxy, heteroaryloxy, F, and C3-6 cycloalkyl;
• R2 is selected from —H, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, and C3-10 cycloalkyl, which alkyl, alkenyl, alkynyl and cycloalkyl may be optionally substituted with one or more selected from —OH, aryl, C1-6 alkoxy, heteroaryl, aryloxy, heteroaryloxy, F, and C3-6 cycloalkyl, and may form a cyclic structure with Y;
• each R3 is independently selected from C1-6 alkyl, C1-4 fluoroalkyl, C1-4 hydroxyalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, —Z-heterocyclyl, —Z-aryl, —Z-heteroaryl, —Z—NR6R7, —Z—C(═O)—NR6R7, —Z—NR6—C(═O)—R7, —Z—C(═O)—R7, —Z—OR7, halogen, —Z—SR7, —Z—SOR7, —Z—SO2R7, —Z—SO2NR6R7 and —Z—COOR7, wherein any heterocyclyl may be substituted with one or more R4, and wherein any heteroaryl and any aryl may be substituted with one or more R5;
• Z is selected from a single bond, C1-4 alkylene, heterocyclylene and C3-6 cycloalkylene;
• each R4 is independently selected from C1-6 alkyl, C1-4 fluoroalkyl, C1-4 hydroxyalkyl, C1-4 alkoxy, C3-10 cycloalkyl, —N(R1)2, carbamoyl, and —OH;
• each R5 is independently selected from C1-6 alkyl, C1-4 fluoroalkyl, C1-4 hydroxyalkyl, C1-4 alkoxy, C3-6 cycloalkyl, —CN, —F, —Cl, —Br, carbamoyl and —OH;
• each of R6 and R7 is independently selected from —H, C1-8 alkyl, C1-4 fluoroalkyl, C1-4 perfluoroalkyl, C1-4 hydroxyalkyl, C2-8 alkenyl, C2-8 alkynyl, C3-10 cycloalkyl, —Z-heterocyclyl, —Z-heteroaryl and —Z-aryl, which alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, heteroaryl and aryl may optionally be substituted with one or more independently selected R8;
• or, alternatively, R6 and R7 may together with the N-atom to which they are attached form an N-heterocyclic ring optionally substituted with one or more independently selected R8;
• each R8 is independently selected from C1-6 alkyl, C1-4 fluoroalkyl, C1-4 hydroxyalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, —Z-heterocyclyl, —Z-heteroaryl, —Z-aryl, —Z—NR10R11, —Z—C(═O)—NR10R11, —Z—OR9, halogen, —CN, —Z—SR9, —Z—SOR9, —Z—SO2R9 and —Z—COOR9, which alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclics, heteroaryl and aryl may optionally be substituted with one or more selected from C1-4 alkyl, C1-4 fluoroalkyl, C1-4 hydroxyalkyl, C3-6 cycloalkyl, —Z-heterocyclyl, —Z-heteroaryl, —Z-aryl, —Z—NR10R11, —Z—C(═O)—NR10R11, —Z—OR9, halogen, —CN, —Z—SR9, —Z—SOR9, —Z—SO2R9 and —Z—COOR9;
• wherein any heterocyclyl may be further substituted with one or more R4 as defined above, and wherein any heteroaryl and any aryl may be further substituted with one or more R5 as defined above, and
• each R9 is independently selected from —H, C1-8 alkyl, C1-4 fluoroalkyl, C1-4 hydroxyalkyl, C2-8 alkenyl, C2-8 alkynyl, C3-10 cycloalkyl, —Z-heterocyclyl, —Z-aryl, and —Z-heteroaryl, wherein any heterocyclyl may be substituted with one or more R4 as defined above, and wherein any heteroaryl and any aryl may be substituted with one or more R5 as defined above;
• each of R10 and R11 is independently selected from —H, C1-6 alkyl, C1-4 fluoroalkyl, C1-4 hydroxyalkyl, C2-8 alkenyl, C2-8 alkynyl, C3-10 cycloalkyl, heterocyclyl, heteroaryl, and aryl, wherein any heterocyclyl may be substituted with one or more R4 as defined above, and wherein any heteroaryl and any aryl may be substituted with one or more R5 as defined above, or, alternatively, R10 and R11 may together with the N-atom to which they are attached form an N-heterocyclic ring optionally substituted with one or more R4 as defined above;
• with the proviso that Y is not H when A is —CH2—;
• or an isomer or a mixture of isomers thereof, or a pharmaceutically acceptable salt, solvate or prodrug thereof.