Heterocyclic Hydroxamic Acids as Protein Deacetylase Inhibitors and Dual Protein Deacetylase-Protein Kinase Inhibitors and Methods of Use Thereof

摘要

The present invention relates to novel hydroxamic acids which are specific histone deacetylase (HDAC) inhibitors and/or TTK/Mps1 kinase inhibitors, including pharmaceutically acceptable salts thereof, which are useful for modulating HDAC and/or TTK/Mps1 kinase activity, pharmaceutical compositions comprising these compounds, and processes for their preparation.

主权项

1. A compound of formula (I): or a pharmaceutically acceptable salt thereof, wherein: Z is NH or CH2, X is O, S, SO, SO2, CO, CR2R3, NR4, SO2NR4, NR4SO2, CONR4, NR4CO, NR4CO2, NR4(CO)NR5 or a bond; M is CR6 or N; Q1 and Q2 are independently N or CH; Q3 is CR7 or Q3 is NR8 when R1 is not present; n is 0-6; Y is H, CN, Cl, Br, I, F, C1-C6 alkyl, haloalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, (CH2)n-aryl, (CH2)n-heteroaryl, OR9, SR9, COR9, COOR9, SOR9, SO2R9, SO2R10R11, NR10R11, NR10SO2R9, NR10COR9, NR10CO2R9, CONR10R11, CO2NR10R11, NR10(CO)NR11, each of which may be optionally substituted and where R10 and R11 taken together may form a heterocyclic ring which may be optionally substituted; R1 is H, C1-C6 alkyl, haloalkyl, aryl, aryl-alkyl, heteroaryl, heteroaryl-alkyl, heterocyclic, carbocyclic or absent, each of which may be optionally substituted; R2 is H, C1-C6 alkyl, hydroxy, alkoxy, aryl, (CH2)n-aryl, heteroaryl, (CH2)n-heteroaryl, cycloalkyl or heterocyclic, any of which is substituted or unsubstituted; R3 is H, C1-C6 alkyl, alkoxy, aryl, (CH2)n-aryl, heteroaryl, (CH2)n-heteroaryl, cycloalkyl or heterocyclic, any of which is substituted or unsubstituted; R4 is H, C1-C6 alkyl, aryl, (CH2)n-aryl, heteroaryl, (CH2)n-heteroaryl, cycloalkyl or heterocyclic, any of which is substituted or unsubstituted; R5 is H, C1-C6 alkyl, aryl, (CH2)n-aryl, heteroaryl, (CH2)n-heteroaryl, cycloalkyl or heterocyclic, any of which is substituted or unsubstituted; R6 is H, CN, Cl, Br, I, F, C1-C6 alkyl, haloalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, (CH2)n-aryl, (CH2)n-heteroaryl, OR9, SR9, COR9, COOR9, SOR9, SO2R9, SO2NR10R11, NR10R11, NR10SO2R9, NR10COR9, NR10CO2R9, CONR10R11, CO2NR10R11 or absent, where R10 and R11 taken together may form a 4-7 membered ring which may be optionally substituted; R7 is H, C1-C6 alkyl, aryl, (CH2)n-aryl, heteroaryl, (CH2)n-heteroaryl, cycloalkyl or heterocyclic, any of which is substituted or unsubstituted; R8 is H, C1-C6 alkyl, haloalkyl, aryl, aryl-alkyl, heteroaryl, heteroaryl-alkyl, heterocyclic, carbocyclic or absent, each of which may be optionally substituted; R9 is H, C1-C6 alkyl, aryl, (CH2)n-aryl, heteroaryl, (CH2)n-heteroaryl, cycloalkyl or heterocyclic, any of which is substituted or unsubstituted; R10 is H, C1-C6 alkyl, aryl, (CH2)n-aryl, heteroaryl, (CH2)n-heteroaryl, cycloalkyl or heterocyclic, any of which is substituted or unsubstituted; and R11 is H, C1-C6 alkyl, aryl, (CH2)n-aryl, heteroaryl, (CH2)n-heteroaryl, cycloalkyl or heterocyclic, any of which is substituted or unsubstituted.