Photoreactive benzamide probes for histone deacetylase 2
View Patent ↗The design, modeling, synthesis, biological evaluation, and photoaffinity labeling studies of a series of photoreactive potent and selective HDACs 1 and 2 benzamide based probes are disclosed herein.
1. A compound of formula (I):
or a salt, hydrate or solvate thereof, wherein:
X is selected from the group consisting of azido, phenyl and thiophenyl;
each Y is independently selected from the group consisting of hydrogen, alkyl and substituted alkyl; and
R 1 , R 2 and R 3 are independently selected from the group consisting of hydrogen, azido, azidoalkyl, azidoalkoxy, and azidoalkylamidyl, wherein at least one of R 1 , R 2 and R 3 is selected from the group consisting of azido, azidoalkyl, azidoalkoxy, and azidoalkylamidyl.
2. The compound of claim 1 , wherein one or two of R 1 , R 2 and R 3 is selected from the group consisting of azido, azidoalkyl, azidoalkoxy, and azidoalkylamidyl.
3. The compound of claim 1 , wherein R 1 is selected from the group consisting of hydrogen and azido.
4. The compound of claim 1 , wherein R 2 is selected from the group consisting of hydrogen, azido, azidoalkoxy, and azidoalkylamidyl.
5. The compound of claim 1 , wherein R 3 is selected from the group consisting of hydrogen and azidoalkyl.
6. The compound of claim 1 , wherein each Y is hydrogen.
7. The compound of claim 1 , wherein the compound is selected from the group consisting of:
N-(4-amino-[1,1′-biphenyl]-3-yl)-4-azidobenzamide;
N-(2-amino-5-(thiophen-2-yl)phenyl)-4-azidobenzamide;
N-(2-amino-5-(thiophen-2-yl)phenyl)-3-azido-5-(azidomethyl)benzamide;
N-(4-amino-[1,1′-biphenyl]-3-yl)-3-azido-5-(azidomethyl)benzamide;
N-(4-amino-[1,1′-biphenyl]-3-yl)-3-azido-4-(2-azidoethoxyl)benzamide;
N-(2-amino-5-(thiophen-2-yl)phenyl)-3-azido-4-(2-azidoethoxyl)benzamide; and
N-(2-amino-5-azidophenyl)-4-(3-azidopropanamido)benzamide.
8. A compound of formula (II):
or a salt, hydrate or solvate thereof, wherein:
X is selected from the group consisting of phenyl and thiophenyl;
each Y is independently selected from the group consisting of hydrogen, alkyl and substituted alkyl; and
R 1 , R 2 and R 3 are independently selected from the group consisting of hydrogen, azido, azidoalkyl, azidoalkoxy, and azidoalkylamidyl, wherein at least one of R 1 , R 2 and R 3 is selected from the group consisting of azido, azidoalkyl, azidoalkoxy, and azidoalkylamidyl.
9. The compound of claim 8 , wherein R 1 is selected from the group consisting of hydrogen and azido.
10. The compound of claim 8 , wherein R 2 is hydrogen.
11. The compound of claim 8 , wherein R 3 is selected from the group consisting of hydrogen and azidoalkyl.
12. The compound of claim 8 , wherein each Y is hydrogen.
13. The compound of claim 8 , wherein the compound is selected from the group consisting of:
3-azidobenzyl 4-((4-amino-[1,1′-biphenyl]-3-yl)carbamoyl)benzylcarbamate;
3-azido-5-(azidomethyl)benzyl 4-((4-amino-[1,1′-biphenyl]-3-yl)carbamoyl)benzylcarbamate; and
3-azido-5-(azidomethyl)benzyl 4-((2-amino-5-(thiophen-2-yl)phenyl)carbamoyl)benzylcarbamate.