ACETYLENE DERIVATIVES AS INHIBITORS OF HISTONE DEACETYLASE

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18 . The pharmaceutical composition of claim 23 wherein Ar 2 is thiophenyl, pyridinyl, quinolinyl, thiazolyl, benzthiazolyl, benzoxazolyl, furanyl, benzimidazolyl, benzothiophenyl, pyrrolyl, indolyl, isoindolyl, or isoquinolinyl optionally substituted with one or two substituents independently selected from alkyl, alkoxy, alkoxyalkyl, halo, haloalkyl, haloalkoxy, alkylamino, dialkylamino, hydroxy, hydroxyalkyl, hydroxyalkyloxy, aminoalkyl, aminoalkoxy, alkoxyalkyloxy, optionally substituted phenyl, optionally substituted heteroaryl, optionally substituted phenyloxyalkyl, optionally substituted heteroaralkyloxy, optionally substituted heteroaryloxyalkyl, optionally substituted heterocycloalkylalkyloxy, or optionally substituted heterocycloalkylallyl.

19 . The pharmaceutical composition of claim 23 wherein Ar 2 is thiazolyl, quinolinyl, oxazolyl, benzothiophenyl, indolyl, benzofuranyl, benzthiazolyl, or benzimidazolyl optionally substituted with a substitutent selected from halo, haloalkyl, alkoxy, haloalkoxyalkyl, aminoalkoxy, aminoalkyl, alkoxyalkyloxy, alkoxyalkyloxyalkyl, optionally substituted heterocycloalkyloxy, optionally substituted hetrocycloalkylalkyloxy, or phenyl optionally substituted with -(alkylene)NRR′ where R and R 1 are independently hydrogen or alkyl.

20 . A pharmaceutical composition comprising a compound selected from the group consisting of;

N-hydroxy-4-[3-(3-phenylacryloylamino)prop-1-ynyl]-benzamide,

N-hydroxy-4-[3-(4-phenylthiazol-2-ylcarbonylamino)prop-1-ynyl]-benzamide;

N-hydroxy-4-[3-S-(3-phenylacryloylamino)-but-1-ynyl]-benzamide;

N-hydroxy-4-[3-(4-methoxyquinolin-2-ylcarbonylamino)prop-ynyl]-benzamide;

N-hydroxy-4-{3-[2-(4-aminomethylphenyl)oxazol-5-ylcarbonylamino}prop-1ynyl]-benzamide hydrochloride;

N-hydroxy-4-[3S-(4-phenylthiazol-2-ylcarbonylamino)but-1-ynyl]-benzamide;

N-hydroxy-4-[3-(phenylcarbonylamino)prop-1-ynyl]-benzamide;

N-hydroxy-4-[3-(benzothiophen-2-ylcarbonylamino)prop-1-ynyl]-benzamide;

N-hydroxy-4-[3-(5-chlorobenzofuran-2-ylcarbonylamino)-prop-1-ynyl]-benzamide;

N-hydroxy-4-[3-(5-indol-2-ylcarbonylamino)prop-1-ynyl]-benzamide;

N-hydroxy-4-[3-(benzofuran-2-ylcarbonylamino)prop-1-ynyl]-benzamide;

N-hydroxy-4-[3S-(benzothiophen-2-ylcarbonylamino)but-1-ynyl]-benzamide;

N-hydroxy-4-[3-(indol-2-ylcarbonylamino)prop-1-ynyl]-benzamide;

N-hydroxy-4-{3-[3-(2,2,2-trifluoroethyloxymethyl)benzofuran-2-yl-carbonyl-amino]prop-1-ynyl}-benzamide;

N-hydroxy-4-[3-(benzthiazol-2-ylcarbonylamino)prop-1-ynyl]-benzamide;

N-hydroxy-4-[3-(4-trifluoromethylbenzothiophen-2-ylcarbonyl-amino)prop-1-ynyl]-benzamide;

N-hydroxy-4-[3-(benzimidazol-2-ylcarbonylamino)prop-1-ynyl]-benzamide;

N-hydroxy-4-[3-(5-fluorobenzothiophen-2-ylcarbonylamino)prop-1-ynyl]-benzamide;

N-hydroxy-4-[3-(3-N,N-dimethylaminomethylbenofuran-2-ylcarbonylamino)prop-1-ynyl]-benzamide hydrochloride;

N-hydroxy-4-{3-[1-(2-N,N-dimethylaminoethyl)benzimidazol-2-ylcarbonyl-amino]prop-1-ynyl}benzamide;

N-hydroxy-4-[3-(4-methoxybenzofuran-2-ylcarbonylamino)prop-1-ynyl]-benzamide;

N-hydroxy-4-[3-(4-N,N-dimethylaiinoethoxybenzofuran-2-ylcarbonylamino-)prop-1-ynyl]-benzamide hydrochloride,

N-hydroxy-4-[3-(4-methoxyindol-2-ylcarbonylamino)prop-1-ynyl]-benzamide;

N-hydroxy-4-[3-(4-N,N-dimethylaminoet-hoxyindol-2-yl-carbonylamino)prop-1-ynyl]-benzamide;

N-hydroxy-4-[3-(5-methoxyindol-2-ylcarbonylamino)prop-1-ynyl]-benzamide;

N-hydroxy-4-[3-(5-N,N-dimethylaminoethoxyindol-2-ylcarbonyl-amino)prop-1-nynl]-benzamide hydrochloride;

N-hydroxy-4-{3-[3-(2-methoxyethyloxymethyl)-benzofuran-2-yl-carbonylamino]prop-1-ynyl}benzamide;

N-hydroxy-4-{3-[3-(2-methoxyethyloxy)indol-2-yl-carbonylamino]prop-1-ynyl}-benzamide;

N-hydroxy-4-[3-(5-tetrahydropyran-4-yloxybenzofuran-2-yl-carbonylamino)prop-1-ynyl]benzamide;

N-hydroxy-4-(3-[5-(2-pyrrolidin-1-ylethoxy)benzofuran-2-yl-carbonylamino]prop-1-ynyl}benzamide hydrochloride;

N-hydroxy-4-{3-[5-(2-methoxyethyloxy)benzofuran-2-yl-carbonylamino]prop-1-ynyl}-benzamide;

N-hydroxy-4-{3-[4-(N,N-dimethylaminoethyloxy)quinolin-2-yl-carbonlyamino]prop-1-ynyl}benzamide hydrochloride;

N-hydroxy-4-{3-[5-(1-(2,2,2-trifluoroethyl)piperidin-4-yloxy)benzofuran-2-ylcarbonyl-amino]prop-1-ynyl}benzamide;

N-hydroxy-4-{3-[5-(1-cyclopropypiperidin-4-yloxy)benzofuran-2-yl-carbonylamino]-prop-1-ynyl}benzamide hydrochloride;

N-hydroxy-4-{3-[5-(tetrahydropyran-4-ylmethyloxy)benzofuran-2-ylcarbonylamino]-prop-1-ynyl}benzamide;

N-hydroxy-4-{3-[5-(2-morpholin-4-ylethyloxy)benzofuran-2-yl-carbonylamino]prop-1-ynyl}benzamide hydrochloride;

N-hydroxy-4-{3-[3-(4-chlorophenyl)ureido]prop-1-ynyl}benzamide;

N-hydroxy-4-{3-[3-(4-trifluoromethylphenyl)ureido]prop-1-ynyl}benzamide;

N-hydroxy-4-{3-[3-(phenyl)ureido]prop-1-ynyl}benzamide;

N-hydroxy-4-{3-[3-(2-trifluoromethyoxyphenyl)ureido]prop-1-ynyl}benzamide;

N-hydroxy-4-[3-methyl-3-(3-phenylacryloylamino)but-1-ynyl]-benzamide;

N-hydroxy-4-[3-methyl-3-(4-phenylthiazol-2-ylcarbonylamino)but-1-ynyl]-benzamide;

N-hydroxy-4-[3-methyl-3-(benzithiazol-2-ylcarbonylamino)but-1-ynyl]-benzamide;

N-hydroxy-4-[3-methyl-3-(benzofuran-2-ylcarbonylamino)but-1-ynyl]-benzamide; or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable excipient.

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23 . A pharmaceutical composition comprising a therapeutically effective amount of a compound having the structure of Formula (I):

wherein:

R is hydrogen;

Ar 1 is phenylene and the triple bond attached to Ar 1 is in the para position relative to the —CONHOH group, wherein said Ar 1 is optionally substituted with one or two substituents independently selected from alkyl, halo, alkoxy. Haloalkoxy or haloalkyl;

X and Y are a bond,

R 1 and R 2 are hydrogen or alkyl;

Z is —CONH—;

Ar 2 is heteroaryl:

and individual stereoisomers, individual geometric isomers, or mixtures thereof; or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient.

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25 . A pharmaceutical composition comprising a therapeutically effective amount of

or pharmaceutically acceptable salts thereof and a pharmaceutically acceptable excipient.

26 . A pharmaceutical composition comprising a therapeutically effective amount of

or pharmaceutically acceptable salts thereof and a pharmaceutically acceptable excipient.

27 . A method for treating a disease in an animal mediated by HDAC which method comprises administering to the animal a pharmaceutical composition comprising a therapeutically effective amount of a compound having the structure of Formula (I):

wherein:

R is hydrogen:

Ar 1 is phenylene and the triple bond attached to Ar 1 is in the para position relative to the —CONHOH group. Wherein said Ar 1 is optionally substituted with one or two substituents independently selected from alkyl, halo, alkoxy, haloalkoxy, or haloalkyl;

X and Y are a bond;

R 1 and R 2 are hydrogen or alkyl;

Z is —CONH—;

Ar 2 is heteroaryl;

and individual stereoisomers. Individual geometric isomers, or mixtures thereof; or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient.

28 . The method of claim 27 wherein the disease is cancer and the animal is a human.

29 . A method for treating cancer which method comprises administering to the animal a pharmaceutical composition comprising a therapeutically effective amount of having the structure of Formula (I):

wherein:

R is hydrogen,

Ar 1 is phenylene and the triple bond attached to Ar 1 is in the para position relative to the —CONHOH groups wherein said Ar 1 is optionally substituted with one or two substituents independently selected from alkyl, halo, alkoxy, haloalkoxy, or haloalkyl;

X and Y are a bond;

R 1 and R 2 are hydrogen or alkyl;

Z is —CONH—:

Ar 2 is heteroaryl;

and individual stereoisomers, individual geometric isomers, or mixtures thereof; or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient in combination will one or more compound(s) independently selected from an estrogen receptor modulator, an androgen receptor modulator, retinoid receptor modulator, a cytotoxic agent, another antiproliferative agent, a prenyl-protein transferase inhibitor, an HMG-CoA reductase inhibitor, an IIIV protease inhibitor, a reverse transcriptase inhibitor, or angiogenesis inhibitor.

30 . A method for treating cancer which method comprises administering to the animal a pharmaceutical composition comprising a therapeutically effective amount of having the structure of Formula (I):

wherein:

R is hydrogen:

Ar 1 is phenylene and the triple bond attached to Ar 1 is in the para position relative to the —CONHOH group. Wherein said Ar 1 is optionally substituted with one or two substituents independently selected from alkyl halo, alkoxy. Haloalkoxy. Or haloalkyl:

X and Y are a bond;

R 1 and R 2 are hydrogen or alkyl;

Z is —CONH—;

Ar 2 is heteroaryl;

and individual stereoisomers, individual geometric isomers, or mixtures thereof; or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient in combination with radiation therapy and one or more compound(s) independently selected from an estrogen receptor modulator, an androgen receptor modulator, retinoid receptor modulator, a cytotoxic agent, another antiproliferative agent, a prenyl-protein transferase inhibitor, an HMG-COA reductase inhibitor, an HIV protease inhibitor, a reverse transcriptase inhibitor, or an angiogenesis inhibitor.