Histone deacetylase inhibitors

1. A compound of formula (I):

or the tautomeric form, stereoisomer, pharmaceutically acceptable salt or composition or prodrug thereof;

wherein R 1 and R 2 represent substituted or unsubstituted groups selected from aryl, cycloalkyl, cycloalkenyl, arylalkenyl, heteroarylalkenyl, arylalkynyl, heterocyclyl and heteroaryl;

R represents H, or substituted or unsubstituted groups selected from linear or branched alkyl, aryl, heteroaryl and heterocyclyl;

X represents a group selected from —CONR 4 —, —NR 4 SO 2 —, —SO 2 NR 4 —, —SO 2 O—, —O—SO 2 —, —CONR 4 CONR 4 —, —NR 4 CO—, —OCONR 4 —, —NR 4 CONR 4 —, —NR 4 — and —O—;

R 4 represents H, or substituted or unsubstituted groups selected from alkyl, aryl, heterocyclyl, heteroaryl, cycloalkyl and cycloalkenyl;

Ar represents substituted or unsubstituted groups selected from aryl and heteroaryl;

R 3 represents a group selected from ortho substituted aniline, phenol, amino aryl, hydroxy aryl, amino heteroaryl and —OR 5 ;

R 5 represents a group selected from H, -COR 6 , substituted or unsubstituted groups selected from alkyl, aryl and heterocyclyl; R 6 represents substituted or unsubstituted groups selected from alkyl, aryl and heterocyclyl;

wherein n=0 or 1, o=0-1, p=1, q=0-3;

with the proviso that if X=—OCONH—, then n and p=1; and

when the groups R, R 1 , R 2 , R 4 and Ar have one or more substituents , the substituents are selected from halogens; hydroxy; nitro; cyano; azido; nitroso; amino; hydrazine; formyl; alkyl; alkenyl; alkynyl; haloalkyl group; haloalkoxy; aralkoxy; cycloalkyl; aryl; alkoxy; aryloxy; acyl; acyloxy; acyloxyacyl; heterocyclyl; heteroaryl; alkylamino; acylamino; alkoxycarbonyl; aryloxycarbonyl; alkylsulfonyl; arylsulfonyl; alkylsulfinyl; arylsulfinyl; alkylthio; arylthio; sulfamoyl; alkoxyalkyl and carboxylic acids and its derivatives; the substituents which in turn are optionally further substituted with hydroxy; halogens; nitro; cyano; azido; nitroso; amino; hydrazine; alkyl; alkoxy; aryl; cycloalkyl and heteroaryl.

2. A compound according to claim 1 wherein

R 1 and R 2 represent substituted or unsubstituted groups selected from aryl group comprising phenyl, naphthyl, indanyl and biphenyl; cycloalkyl group comprising cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cyclooctyl; arylalkenyl group comprising phenylethenyl and phenylpropenyl; heteroarylalkenyl group comprising thienylpropenyl, indolylpropenyl; arylalkynyl group comprising phenylethynyl and phenylpropynyl; heterocyclyl group comprising azetidinyl, acridinyl, benzodioxolyl, benzodioxanyl, benzofuranyl and carbazolyl; and heteroaryl group comprising pyridinyl, pyridazinyl, pyrimidyl, triazinyl, pyrrolyl, pyrazolyl, imidazolyl, pyrazinyl, pyrimidinyl, tetrazolyl, furyl, thienyl, thiazolyl, isoxazolyl, oxazolyl, quinolinyl, isoquinolinyl, indolyl, azaindolyl, benzothiazolyl, benzimidazolyl, benzothienyl, benzofuranyl and benzoxazolyl;

R represents H, or substituted or unsubstituted groups selected from linear or branched alkyl group comprising methyl, ethyl, n-propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, hexyl, heptyl and octyl; aryl group comprising phenyl, naphthyl, indanyl and biphenyl; heteroaryl group comprising pyridinyl, pyridazinyl, pyrimidyl, triazinyl, pyrrolyl, pyrazolyl, imidazolyl, pyrazinyl, pyrimidinyl, tetrazolyl, furyl, thienyl, thiazolyl, isoxazolyl, oxazolyl and quinolinyl; and heterocyclyl group comprising azetidinyl, acridinyl, benzodioxolyl, benzodioxanyl, benzofuranyl and carbazolyl;

R 4 is H, or substituted or unsubstituted groups selected from linear or branched alkyl group comprising methyl, ethyl, n-propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, hexyl, heptyl and octyl; aryl group comprising phenyl, naphthyl, indanyl and biphenyl; heterocyclyl group comprising azetidinyl, acridinyl, benzodioxolyl, benzodioxanyl, benzofuranyl and carbazolyl; heteroaryl group comprising pyridinyl, pyridazinyl, pyrimidyl, triazinyl, pyrrolyl, pyrazolyl, imidazolyl, pyrazinyl, pyrimidinyl, tetrazolyl, furyl, thienyl, thiazolyl, isoxazolyl, oxazolyl and quinolinyl; cycloalkyl group comprising cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cyclooctyl; and cycloalkenyl group comprising of cyclopentenyl, cyclohexenyl, cycloheptenyl and cyclooctenyl;

Ar represents substituted or unsubstituted groups selected from aryl group comprising phenylene, naphthylene, indanylene and biphenylene; and heteroaryl group comprising pyridinylene, pyridazinylene, pyrimidylene, triazinylene, pyrrolylene, pyrazolylene, imidazolylene, pyrazinylene and pyrimidinylene;

R 5 represents H, —COR 6 , or substituted or unsubstituted groups selected from linear or branched alkyl group comprising methyl, ethyl, n-propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, hexyl, heptyl and octyl; aryl group comprising phenyl, naphthyl, indanyl and biphenyl; and heterocyclyl group comprising azetidinyl, acridinyl, benzodioxolyl, benzodioxanyl, benzofuranyl and carbazolyl;

R 6 represents substituted or unsubstituted groups selected from linear or branched alkyl group comprising methyl, ethyl, n-propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, hexyl, heptyl, octyl; aryl group comprising phenyl, naphthyl, indanyl and biphenyl; and heterocyclyl group comprising azetidinyl, acridinyl, benzodioxolyl, benzodioxanyl, benzofuranyl and carbazolyl;

when the groups R, R 1 , R 2 , R 4 and Ar have one or more substituents, the substituents are selected from halogens comprising fluorine, chlorine, bromine and iodine; hydroxy; nitro; cyano; azido; nitroso; amino; hydrazine; formyl; alkyl; alkenyl; alkynyl; haloalkyl group comprising trifluoromethyl, trichloromethyl, dichloromethyl and difluoromethyl; haloalkoxy; aralkoxy group comprising benzyloxy and phenylethoxy; cycloalkyl; aryl; alkoxy; aryloxy; acyl; acyloxy; acyloxyacyl; heterocyclyl; heteroaryl; alkylamino group comprising monoalkylamino and dialkylamino; acylamino; alkoxycarbonyl; aryloxycarbonyl; alkylsulfonyl; arylsulfonyl; alkylsulfinyl; arylsulfinyl; alkylthio; arylthio; sulfamoyl; alkoxyalkyl groups and carboxylic acids and its derivatives comprising ester and amide; which in turn are optionally substituted by hydroxy; halogens; nitro; cyano; azido; nitroso; amino; hydrazine; alkyl; alkoxy; aryl; cycloalkyl and heteroaryl.

3. A compound according to claim 1 , which is selected from:

N-(2-Aminophenyl)-4-((3-(3,4-difluorophenyl)-2-(4-fluorophenyl)acrylamido)methyl)benzamide;

N-(2-Aminophenyl)-4-((3-(4-methoxyphenyl)-2-(phenyl)acrylamido)methyl)benzamide;

N-(2-Aminophenyl)-4-((3-(2-fluorophenyl)-2-(4-chlorophenyl)acrylamido)methyl)benzamide;

N-(2-Aminophenyl)-4-((3-(4-fluoro-3-trifluoromethylphenyl)-2-(4-trifluoromethylphenyl)acrylamido)methyl)benzamide;

N-(2-Aminophenyl)-4-((3-(4-fluoro-3-trifluoromethylphenyl)-2-(4-nitrophenyl)acrylamido)methyl)benzamide;

N-(2-Aminophenyl)-4-((3-(4-methylthiophenyl)-2-(4-fluorophenyl)acrylamido)methyl)benzamide;

N-(2-Aminophenyl)-4-((3-(5-nitrothiophen-2-yl)-2-(4-fluorophenyl)acrylamido)methyl)benzamide;

N-(2-Aminophenyl)-4-((3-(3,4,5-trimethoxyphenyl)-2-(4-fluorophenyl)acrylamido)methyl)benzamide;

N-(2-Aminophenyl)-4-((3-(2-chloro-4-fluorophenyl)-2-(phenyl)acrylamido)methyl)benzamide;

N-(2-Aminophenyl)-4-((3-(4-fluorophenyl)-2-(phenyl)acrylamido) methyl)benzamide;

N-(2-Aminophenyl)-4-((3-(4-methoxyphenyl)-2-(4-fluorophenyl)acrylamido)methyl)benzamide;

N-(2-Aminophenyl)-4-((3-phenyl-2-phenylacrylamido)methyl)benzamide;

N-(2-Aminophenyl)-4-((3-(2,4,6-trifluorophenyl)-2-(4-fluorophenyl)acrylamido)methyl)benzamide;

N-(2-Aminophenyl)-4-((3-(cyclopropyl)-2-(4-fluorophenyl)acrylamido)methyl)benzamide;

N-2-Aminophenyl)-4-((3-(pyridin-4-yl)-2-(4-fluorophenyl)acrylamido)methyl)benzamide;

N-(2-Aminophenyl)-4-((3-(4-methylthiophenyl)-2-(4-methoxyphenyl)acrylamido)methyl)benzamide;

N-(2-Aminophenyl)-4-((3-(3,5-dimethoxyphenyl)-2-(4-fluorophenyl)acrylamido)methyl)benzamide;

N-(2-Aminophenyl)-4-((3-(4-methylthiophenyl)-2-(thiophen-2-yl)acrylamido)methyl)benzamide;

N-(2-Aminophenyl)-4-((3-(3,4-dimethoxyphenyl)-2-(4-fluorophenyl)acrylamido)methyl)benzamide;

N-(2-Aminophenyl)-4-((3-(4-fluoro-3-methoxyphenyl)-2-(4-fluorophenyl)acrylamido)methyl)benzamide;

N-(2-Aminophenyl)-4((3-(4-methylthiophenyl)-2-(4-trifluoromethylphenyl)acrylamido)methyl)benzamide;

N-(2-Aminophenyl)-4-((3-(quinolin-4-yl)-2-(4-fluorophenyl)acrylamido)methyl)benzamide;

N-(2-Aminophenyl)-4-((3-(4-methylthiophenyl)-2-(2-chlorophenyl)acrylamido)methyl)benzamide;

N-(2-Aminophenyl)-4-((3-(4-methylthiophenyl)-2-(2-fluorophenyl)acrylamido)methyl)benzamide;

N-(2-Aminophenyl)-4-((3-(4-methylthiophenyl)-2-(4-methylphenyl)acrylamido)methyl)benzamide;

N-(2-Aminophenyl)-4-((3-(4-methylthiophenyl)-2-(thiophen-3-yl)acrylamido)methyl)benzamide;

N-(2-Aminophenyl)-4-((3-(3,4-dimethoxyphenyl)-2-(4-methoxyphenyl)acrylamido)methyl)benzamide;

N-(2-Aminophenyl)-4-((3-(3,4-dimethoxyphenyl)-2-(2-fluorophenyl)acrylamido)methyl)benzamide;

N-(2-Aminophenyl)-4-((3-(3,4-dimethoxyphenyl)-2-(4-methylphenyl)acrylamido)methyl)benzamide;

N-(2-Aminophenyl)-4-((3-(3,4-dimethoxyphenyl)-2-(2-chlorophenyl)acrylamido)methyl)benzamide;

N-(2-Aminophenyl)-4-((3-(3,4-dimethoxyphenyl)-2-phenylacrylamido)methyl)benzamide;

N-(2-Aminophenyl)-4-((3-(3,4-dimethoxyphenyl)-2-(3-fluorophenyl)acrylamido)methyl)benzamide;

N-(2-Aminophenyl)-4-(3-(4-carbmethoxyphenyl)-2-(3-chlorophenyl)acrylamido)methyl)benzamide;

N-(2-Aminophenyl)-4-((3-(4-carbmethoxyphenyl)-2-(2-fluorophenyl)acrylamido)methyl)benzamide;

N-(2-Aminophenyl)-4-((3-(4-carbmethoxyphenyl)-2-(4-methoxyphenyl)acrylamido)methyl)benzamide;

N-(2-Aminophenyl)-4-((3-(4-carbmethoxyphenyl)-2-(thiophen-2-yl)acrylamido)methyl)benzamide;

N-(2-Aminophenyl)-4-((3-(3,4-dimethoxyphenyl)-2-(thiophen-2-yl)acrylamido)methyl)benzamide;

N-(2-Aminophenyl)-4-((3-(4-carbmethoxyphenyl)-2-(3,4-difluorophenyl)acrylamido)methyl)benzamide;

N-(2-Aminophenyl)-4-((3-(2,4dimethoxyphenyl)-2-phenylacrylamido)methyl)benzamide;

N-(2-Aminophenyl)-4-((2-(3,4-dimethoxyphenyl)-3-phenylacrylamido)methyl)benzamide;

N-(2-Aminophenyl)-4-((3-(3,4-dimethoxyphenyl)-2-(pyridin-3-yl)acrylamido)methyl)benzamide;

N-(2-Aminophenyl)-4-((3-(3,4-dimethoxyphenyl)-2-(4-methylphenyl)acrylamido))benzamide;

N-(2-Aminophenyl)-4-((3-(3,4-difluorophenyl)-2-(4-methoxyphenyl)acrylamido)methyl)benzamide;

N-(2-Aminophenyl)-4-((3-(4-fluorophenyl)-2-(4-methoxyphenyl)acrylamido)methyl)benzamide;

N-(2-Aminophenyl-4-((3-(4-fluorophenyl)-2-[benzo[d][1,3dioxo-5-yl]acrylamido)methyl)benzamide;

N-(2-Aminophenyl)-4-((3-(4-methylthiophenyl)-2-(3,4-dimethoxyphenyl)acrylamido)methyl)benzamide;

N-(2-Aminophenyl-4-((3-(4-methylthiophenyl)-2-(3,4-methylenedioxyphenyl)acrylamido)methyl)benzamide;

4-((2-(4-Fluorophenyl)-3-(3,4,5-trimethoxyphenyl)acrylamido)methyl)-N-hydroxybenzamide;

4-((2-(4-Methoxyphenyl)-3-(4-fluorophenyl)acrylamido)methyl)-N-hydroxybenzamide;

4-((2-(4-Trifluoromethyllphenyl)-3-(4-fluorophenyl)acrylamido)methyl)-N-hydroxybenzamide;

4-2-(Phenyl)-3-(4-fluorophenyl)acrylamido)methyl)-N-hydroxybenzamide;

4-((2-(4-Fluorophenyl)-3-(4-methylthiophenyl)acrylamido)methyl)-N-hydroxybenzamide;

4-((2-(4-Fluorophenyl)-3-(4-methoxyphenyl)acrylamido)methyl)-N-hydroxybenzamide;

4-((2-(4-Fluorophenyl)-3-(2,4,6-trifluorophenyl)acrylamido)methyl)-N-hydroxybenzamide;

4-((2-(Pyridin-3-yl)-3-(4-methylthiophenyl)acrylamido)methyl)-N-hydroxybenzamide;

4-((2-(2-Chlorophenyl)-3-(4-methylthiophenyl)acrylamido)methyl)-N-hydroxybenzamide;

4-((2-(4-Methoxyphenyl)-3-(4-methylthiophenyl)acrylamido)methyl)-N-hydroxybenzamide;

4-((2-(4-Methylphenyl)-3-(4-methylthiophenyl)acrylamido)methyl)-N-hydroxybenzamide;

4-((2-(Thiophen-3-yl)-3-(4-methylthiophenyl)acrylamido)methyl)-N-hydroxybenzamide;

4-((2-(4-Fluorophenyl)-3-(4-fluoro-3-methoxyphenyl)acrylamido)methyl)-N-hydroxybenzamide;

4-((2-(4-Fluorophenyl)-3-(cyclopropyl)acrylamido)methyl)-N-hydroxybenzamide;

4-((2-(4-Methylphenyl)-3-(3,4-dimethoxyphenyl)acrylamido)methyl)-N-hydroxybenzamide;

4-((2-(4-Fluorophenyl)-3-(3,4-dimethoxyphenyl)acrylamido)methyl)-N-hydroxybenzamide;

4-((2-(4-Methoxyphenyl)-3-(3,4-dimethoxyphenyl)acrylamido)methyl)-N-hydroxybenzamide;

4-((2-(4-Methylphenyl)-3-(3,4-dimethoxyphenyl)acrylamido))-N-hydroxybenzamide;

4-((2-Phenyl-3-(3,4-dimethoxyphenyl)acrylamido)methyl)-N-hydroxybenzamide;

4-((2-[Benzo[d]-1,3dioxo-5-yl]-3-(4-fluorophenyl)acrylamido))-N-hydroxybenzamide;

4-((2-[Benzo[d]-1,3dioxo-5-yl]-3-(4-fluorophenyl)acrylamido)methyl)-N-hydroxybenzamide;

4-((2-(3,4-Dimethoxyphenyl)-3-(4-methylthiophenyl)acrylamido)methyl)-N-hydroxybenzamide;

4-((2-[Benzo[d]-1,3-dioxo-5-yl]-3-(4-methylthiophenyl)acrylamido)methyl)-N-hydroxybenzamide;

4-((2-(4-Methoxyphenyl)-3-(pyridin-3-yl)acrylamido)methyl)-N-hydroxybenzamide;

4-((2-(4-Fluorophenyl)-3-(pyridin-3-yl)acrylamido)methyl)-N-hydroxybenzamide;

4-((2-(4-Methoxyphenyl)-3-(3,4-difluorophenyl)acrylamido)methyl)-N-hydroxybenzamide;

4-((2-Phenyl-3-(4-methylthiophenyl)acrylamido)methyl)-N-hydroxybenzamide;

(1E)-N-(4-(3-(Hydroxyamino)-3-oxoprop-1-enyl)benzyl)-2,3-diphenyl acrylamide;

(1E)-N-(4-(3-(Hydroxyamino)-3-oxoprop-1-enyl)benzyl)-2-(4-fluorophenyl)-3-(4-methylthiophenyl)acrylamide;

(1E)-N-(4-(3-(Hydroxyamino)-3-oxoprop-1-enyl)benzyl)-2-(4-fluorophenyl)-3-(3,4-dimethoxyphenyl)acrylamide;

(1E)-N-(4-(3-(Hydroxyamino)-3-oxoprop-1-enyl)benzyl)-2-(2-fluorophenyl)-3-(3,4-dimethoxyphenypacrylamide;

(1E)-N-(4-(3-(Hydroxyamino)-3-oxoprop-1-enyl)benzyl)-2-(2-phenyl)-3-(4-fluorophenyl)acrylamide;

(1E)-N-(4-(3-(Hydroxyamino)-3-oxoprop-1-enyl)benzyl)-2-(4-fluorophenyl)-3-(3,5-dimethoxyphenyl)acrylamide;

(1E)-N-(4-(3-(Hydroxyamino)-3-oxoprop-1-enyl)benzyl)-2-(4-fluorophenyl)-3-(3,4,5-trimethoxyphenyl)acrylamide;

(1E)-N-(4-(3-(Hydroxyamino)-3-oxoprop-1-enyl)benzyl)-3-(4-fluorophenyl)-2-(4-methoxyphenyl)acrylamide;

3-(3,4-Dimethoxyphenyl)-2-(4-methoxyphenyl)allyl-4-(2-aminophenylcarbamoyl)benzylcarbamate;

3-(3,4-Dimethoxyphenyl)-2-(4-methylphenyl)allyl-4(2-aminophenylcarbamoyl)benzylcarbamate and

the pharmaceutically acceptable salts thereof.

4. A process for the preparation of a compound of formula (I) according to claim 1 , comprising reacting the compounds of formulae 1d or 1g with R 3 NH 2 ;

wherein Y is —OH, —O-Alkyl and R, R 1 , R 2 , R 3 , Ar, o, q are as defined for formula (I).

5. A pharmaceutical composition comprising a compound of formula (I), according to claim 1 , as an active ingredient, along with a pharmaceutically acceptable carrier, diluent, excipient or solvate.

6. A pharmaceutical composition according to claim 5 , wherein the composition is in the form of a tablet, capsule, powder, syrup, solution, aerosol or suspension.

7. A method for inhibiting HDAC in a cell comprising treating the cell with an effective amount of a compound according to claim 1 .

8. A method for the treatment of a condition mediated by HDAC selected from lung cancer, colon cancer and glioma, comprising administering to a subject suffering from said condition mediated by HDAC, a therapeutically effective amount of a compound according to claim 1 .

9. A method for the treatment of cancer selected from lung cancer, colon cancer and glioma, comprising administering to a subject suffering from said cancer, a therapeutically effective amount of a compound according to claim 1 .

10. A pharmaceutical composition comprising a compound of formula (I), according to claim 3 , as an active ingredient, along with a pharmaceutically acceptable carrier, diluent, excipient or solvate.

11. A method for the treatment of a condition mediated by HDAC selected from B-cell lymphoma, T-cell lymphoma, leukemia, breast cancer, lung cancer, ovarian cancer, prostate cancer, head cancer, neck cancer, renal cancer, gastric cancer, colon cancer, pancreatic cancer and brain cancer, comprising administering to a subject suffering from said condition mediated by HDAC, a therapeutically effective amount of a compound according to claim 1 .

12. A method for inhibiting HDAC in a cell comprising treating the cell with an effective amount of a compound according to claim 3 .

13. A method for the treatment of a condition mediated by HDAC selected from lung cancer, colon cancer and glioma, comprising administering to a subject suffering from said condition mediated by HDAC, a therapeutically effective amount of a compound according to claim 3 .

14. A method for the treatment of cancer selected from lung cancer, colon cancer and glioma, comprising administering to a subject suffering from said cancer, a therapeutically effective amount of a compound according to claim 3 .

15. A method for the treatment of a condition mediated by HDAC selected from B-cell lymphoma, T-cell lymphoma, leukemia, breast cancer, lung cancer, ovarian cancer, prostate cancer, head cancer, neck cancer, renal cancer, gastric cancer, colon cancer, pancreatic cancer and brain cancer, comprising administering to a subject suffering from said condition mediated by HDAC, a therapeutically effective amount of a compound according to claim 3 .