Histone deacetylases (HDACs) inhibitors

摘要

Histone deacetylases inhibitors (HDACIs) and compositions comprising the same are disclosed. Methods of treating diseases and conditions wherein inhibition of HDAC provides a benefit are also disclosed. In one aspect, the invention relates to a compound having the structure;
or a pharmaceutically acceptable salt, a solvate or hydrate, a prodrug, or a metabolite thereof. In one embodiment of the invention, R1 is ethyl; R2 is 2-phenylethyl; R3 is hydrogen; R4 is fluoro; R5 is (2E)-3-N-hydroxyamino-3-oxo-propenyl; and R6 is hydrogen, or a salt thereof. In another embodiment of the invention, R1 is ethyl; R2 is 2-phenylethyl; R3 is hydrogen; R4 is (2E)-3-N-hydroxyamino-3-oxo-propenyl; R5 is chloro or fluoro; and R6 is hydrogen, or a salt thereof.

主权项

1. A compound having the structureor a pharmaceutically acceptable salt thereof,
(I) wherein: R1 is hydrogen, (C1-C6)alkyl, or (C3-C6)cycloalkyl; R2 is (C6-C18)aryl, (C6-C18)aryl(C3-C18)alkyl, (C3-C18)heteroaryl(C1-C6)alkyl, halo(C6-C18)aryl(C1-C6)alkyl, or (C1-C6)alkoxy(C6-C18)aryl(C1-C6)alkyl; R3 is N-hydroxyamino-oxo(C2-C6)alkenyl; R4 is hydrogen, halogen, N-hydroxyamino-oxo(C2-C6)alkenyl, or N-hydroxyaminocarbonyl(C6-C18)aryl(C1-C6)alkylene; R5 is hydrogen, halogen, N-hydroxy amino-oxo(C2-C6)alkenyl, N-hydroxyaminocarbonyl(C6-C18)aryl(C1-C6)alkylene, or amino(C6-C18)aryl-oxo(C2-C6)alkenyl; and R6 is hydrogen, N-hydroxyamino-oxo(C2-C6)alkenyl, N-hydroxyamino(C6-C18)aryl(C1-C6)alkylene, or N-hydroxyaminocarbonyl(C6-C18)aryl(C1-C6)alkylene; (II) or wherein: R1, R2, R4 and R6 are each as defined in (I) above; R3 is hydrogen or N-hydroxyamino-oxo(C2-C6)alkenyl; and R4 is N-hydroxyamino-oxo(C2-C6)alkenyl, or N-hydroxyaminocarbonyl(C6-C18)aryl(C1-C6)alkylene; (III) or wherein: R1, R2, R4 and R6 are each as defined in (I) above; R3 is as defined in (II) above; and R5 is N-hydroxyamino-oxo(C2-C6)alkenyl, N-hydroxyaminocarbonyl(C6-C18)aryl(C1-C6)alkylene, or amino(C6-C18)aryl-oxo(C2-C6)alkenyl; (IV) or wherein: R1, R2, R4, R5 are each as defined in (I) above; R3 is as defined in (II) above; and R6 is N-hydroxyamino-oxo(C2-C6)alkenyl, N-hydroxyamino(C6-C18)aryl(C1-C6)alkylene, or N-hydroxyaminocarbonyl(C6-C18)aryl(C1-C6)alkylene.