Fused Pyrimidine-Based Hydroxamate Derivatives

摘要

The present invention relates to fused R1 pyrimidine-based hydroxamate compounds of formula (I), comprising a hydroxamate group, that are inhibitors of histone deacetylase (HDAC) and kinases. More particularly, the present invention relates to hydroxamate substituted purine or 5H-pyrrolo[3,2-d]pyrimidine derivatives, methods for their preparation, pharmaceutical compositions containing these compounds and uses of these compounds in the treatment of disorders/conditions/diseases involving, relating to or associated with enzymes having histone deacetylase, non-histone deacetylase and kinase activities/functions and/or via unspecified/multi-targeted mechanisms.

主权项

1. A compound of Formula (I); wherein X, Y and Z are independently selected from N, CHR3 or CR3, wherein at least one of X, Y or Z is N; is a single or double bond, as valency allows; R1 and R2 are independently selected from the group consisting of a bond, halogen, optionally substituted alkyl, optionally substituted amino, optionally substituted alkyloxy, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl and optionally substituted heteroaryl; R3 and R4 are independently selected from the group consisting of a bond, hydrogen, halogen, optionally substituted alkyl, optionally substituted amino, optionally substituted alkyloxy, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl and optionally substituted heteroaryl; at least one of R1, R2, R3 or R4 is further independently substituted by an hydroxamate group -L1-R5-L2-R6-L3-CON(Ra)ORb, wherein; Ra and Rb are independently selected from the group consisting of a bond, hydrogen, optionally substituted alkyl, optionally substituted acyl and optionally substituted amino acid residue; L1, L2 and L3 are independently selected from the group consisting of a bond, optionally substituted alkyl, optionally substituted alkenyl and optionally substituted alkynyl; R5 and R6 are independently selected from the group consisting of a bond, O, S, NRc, S(O)n, optionally substituted amide, optionally substituted urea, optionally substituted carbonylurea, optionally substituted thiourea, optionally substituted sulfonamide, optionally substituted aminosulfonamide, optionally substituted sulfonylurea, optionally substituted oxime, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl and optionally substituted heteroaryl; wherein;
Rc is independently selected from the group consisting of a bond, hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl and optionally substituted acyl; andn is an integer from 0 to 2; or a pharmaceutically acceptable form or prodrug thereof.