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US 2009/0156825 A1Published application
Fluorescent compounds that bind to histone deacetylase
OwnerRichard W. Heidebrecht, JR., Astrid M. Kral +1inventors
InventorsRichard W. Heidebrecht, JR., Astrid M. Kral, Thomas A. Miller
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Abstract
The present invention relates to a novel class of fluorescent compounds that bind to histone deacetylases. The fluorescent compounds can be used to determine binding association and dissociation rates of histone deacetylase inhibitors via fluorescence polarization.
Claims10
A compound represented by the following structural Formula
- wherein A is aryl, heteroaryl or H, optionally substituted with halo, methyl, methoxy, amino, hydroxyl or halomethyl;
- R1 and R2 are independently selected from H, OH, halo, NH2, C1-C4 alkyl, or C1-C4 alkoxy;
- R3 is independently selected from H, OH, NH2, nitro, CN, amide, carboxyl, C1-C7 alkoxy, C1-C7 alkyl, C1-C7 haloalkyl, C1-C7 haloalkyloxy, C1-C7 hydroxyalkyl, C1-C7 alkenyl, C1-C7 alkyl-C(═O)O—, C1-C7 alkyl-C(═O)—, C1-C7 alkynyl, halo, hydroxyalkoxy, C1-C7 alkyl-NHSO2—, C1-C7 alkyl-SO2NH—, C1-C7 alkylsulfonyl, C1-C7 alkylamino or di(C1-C7)alkylamino;
- R4 is selected from —NR6R7;
- R5 is independently selected from H, OH, NH2, nitro, CN, amide, carboxyl, C1-C2 alkoxy, C1-C2 alkyl, C1-C2 haloalkyl, C1-C2 haloalkyloxy, C1-C2 hydroxyalkyl, C1-C2 alkenyl, C1-C2 alkyl-C(═O)O—, C1-C2 alkyl-C(═O)—, C1-C2 alkynyl, halo, hydroxyalkoxy, C1-C2 alkyl-NHSO2—, C1-C2 alkyl-SO2NH—, C1-C2 alkylsulfonyl, C1-C2 alkylamino or di(C1-C2)alkylamino;
- R6 is independently selected from H or C1-C4 alkyl;
- R7 is selected from —(CRa2)sC(O)(CRa2)qR12, or —(CRa2)C(O)O(CRa2)qR12;
- R12 is selected from C1-C4 alkyl, C3-C6 cycloalkyl, heteroaryl, aryl or heterocyclic, wherein the alkyl, cycloalkyl, heteroaryl, heterocyclic or aryl is attached to a fluorophore through a linker, and optionally substituted OH, NH2, nitro, CN, amide, carboxyl, C1-C7 alkoxy, C1-C7 alkyl, C1-C7 haloalkyl, C1-C7 haloalkyloxy, C1-C7 hydroxyalkyl, C1-C7 alkenyl, C1-C7 alkyl-C(═O)O—, C1-C7 alkyl-C(═O)—, C1-C7 alkynyl, halo, hydroxyalkoxy, C1-C7 alkyl-NHSO2—, C1-C7 alkyl-SO2NH—, C1-C7 alkylsulfonyl, C1-C7 alkylamino or di(C1-C7)alkylamino, aryl, heterocyclic or cycloalkyl;
- Ra is independently selected from H or C1-C4 alkyl;
- p is 1, 2, 3 or 4;
- s and q are independently 0, 1, 2, 3, or 4;
- L1 is (CH2)r, ethenyl or cyclopropyl, wherein r is 0, 1 or 2;
- X is OH or NH2;
- Z is C or N;
- or a stereoisomer or pharmaceutically acceptable salt thereof.
12 more elements
A compound represented by the following structural Formula
- Wherein,
- R25 is F-L-, where L is a linker, and F is a fluorophore;
- R26 to R29 is independently selected from H, C1-C4 alkyl, CN, azido, C1-C4 cyanoalkyl, nitro, halo, C1-C4 haloalkyl, amino, amide, carboxyl, C1-C4 alkoxycarbonyl, C1-C4 alkylaminocarbonyl, hydroxyl, C1-C4 alkoxy, aryl-C1-C4-alkoxy, C1-C4 haloalkyloxy, C1-C4 hydroxyalkyl, C1-C4 alkenyl, C1-C4 alkyl-C(═O)O—, C1-C4 alkyl-C(═O)—, C1-C4 alkynyl, hydroxyalkoxy, C1-C4 alkyl-NHSO2—, C1-C4 alkyl-SO2NH—, C1-C4 alkylsulfonyl, C1-C4 alkylamino or di(C1-C4)alkylamino;
- R30 is selected from H or C1-C4 alkyl;
- n is 4, 5, 6, 7 or 8;
- or a stereoisomer or pharmaceutically acceptable salt thereof.
3 more elements
A compound selected from:
- 5-{[({4-[({[(4-{[(4-aminobiphenyl-3-yl)amino]carbonyl}benzyl)amino]carbonyl}oxy)methyl]benzyl}amino)carbonothioyl]amino}-2-(6-hydroxy-3-oxo-3H-xanthen-9-yl)benzoic acid;
- 5-({[(4-{[8-(hydroxyamino)-8-oxooctanoyl]amino}benzyl)amino]carbonothioyl}amino)-2-(6-hydroxy-3-oxo-3H-xanthen-9-yl)benzoic acid;
- 5-{[({4-[({[(4-{[(2-aminophenyl)amino]carbonyl}benzyl)amino]carbonyl}oxy)methyl]benzyl}amino)carbonothioyl]amino}-2-(6-hydroxy-3-oxo-3H-xanthen-9-yl)benzoic acid.
- or a stereoisomer or pharmaceutically acceptable salt thereof.
1 more element
Dependencies are inferred from the claim text.