Inhibitors of histone demethylases

摘要

The present application discloses compounds capable of modulating the activity of histone demethylases (HDMEs), which are useful for prevention and/or treatment of diseases in which genomic dysregulation is involved in the pathogenesis, such as e.g. cancer. The present application also discloses pharmaceutical compositions comprising said compounds and the use of such compounds as a medicament. The compounds take the form;

主权项

1. A compound of Formula (I)wherein
A is —CH2C(O)—; Y is —NR6R7; p1 R1 is —H; 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(R10)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 hydroxyalkyl, C2-8 alkenyl, C2-8 alkynyl, C3-10 cycloalkyl, —Z-heterocyclyl, —Z-heteroaryl and —Z-aryl, wherein alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, heteroaryl and aryl may optionally be 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, wherein alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, 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; 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; and 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 a pharmaceutically acceptable salt thereof.