Inhibitors of histone deacetylase

1. A compound of formula I:

wherein

and the ring containing W 1 and W to which it is fused together form an optionally substituted 1,3,4,9-tetrahydro-2H-b-carbolin-2-yl or an optionally substituted 1,3,4,4a,9,9a-hexahydro-2H-b-carbolin-2-yl substituent;

W 2 is a bond or [—C(R 1 )(R 2 )—] p ;

R 1 and R 2 are independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclic, and substituted heterocyclic;

p is 1, 2, 3 or 4;

wherein Ar 2 -G-C(O)NHOH, is 5-[-G-C(O)NHOH]-pyrimid-2-ylene

G is a bond; or

a tautomer, stereoisomer, prodrug, or pharmaceutically acceptable salt thereof.

2. The compound according to claim 1 , wherein W 2 is a bond.

3. The compound according to claim 2 , wherein said compound is:

[N-hydroxy-2-(1,3,4,9-tetrahydro-2H-b-carbolin-2-yl)pyrimidine-5-carboxamide],

[N-hydroxy-2-(6-methoxy-1,3,4,9-tetrahydro-2H-b-carbolin-2-yl)pyrimidine-5-carboxamide],

[N-hydroxy-2-(8-methyl-1,3,4,9-tetrahydro-2H-b-carbolin-2-yl)pyrimidine-5-carboxamide],

[N-hydroxy-2-(7-fluoro-1,3,4,9-tetrahydro-2H-b-carbolin-2-yl)pyrimidine-5-carboxamide],

[N-hydroxy-2-(6-fluoro-1,3,4,9-tetrahydro-2H-b-carbolin-2-yl)pyrimidine-5-carboxamide],

[N-hydroxy-2-(6-benzyloxy-1,3,4,9-tetrahydro-2H-b-carbolin-2-yl)pyrimidine-5-carboxamide],

[N-hydroxy-2-(7-methyl-1,3,4,9-tetrahydro-2H-b-carbolin-2-yl)pyrimidine-5-carboxamide],

[N-hydroxy-2-(6-methyl-1,3,4,9-tetrahydro-2H-b-carbolin-2-yl)pyrimidine-5-carboxamide],

[N-hydroxy-2-{6-[3-(morpholin-4-ylmethyl)phenyl]-1,3,4,9-tetrahydro-2H-b-carbolin-2-yl}pyrimidine-5-carboxamide],

[N-hydroxy-2-{6-[3-((4-methylpiperazin-1-yl)methyl)phenyl]-1,3,4,9-tetrahydro-2H-b-carbolin-2-yl}pyrimidine-5-carboxamide],

[N-hydroxy-2-{6-[4-((4-methylpiperazin-1-yl)methyl)phenyl]-1,3,4,9-tetrahydro-2H-b-carbolin-2-yl}pyrimidine-5-carboxamide],

[N-hydroxy-2-{6-[2-((4-methylpiperazin-1-yl)methyl)phenyl]-1,3,4,9-tetrahydro-2H-b-carbolin-2-yl}pyrimidine-5-carboxamide],

[N-hydroxy-2-{9-[2-pyrrolidin-1-ylethyl]-1,3,4,9-tetrahydro-2H-b- carbolin-2-yl}pyrimidine-5-carboxamide],

[N-hydroxy-2-[9-(2-piperidin-1-ylethyl)-1,3,4,9-tetrahydro-2H-b-carbolin-2-yl]pyrimidine-5-carboxamide],

[N-hydroxy-2-[9-(2-morpholin-4-ylethyl)-1,3,4,9-tetrahydro-2H-b- carbolin-2-yl]pyrimidine-5-carboxamide],

[N-hydroxy-2-[9-(phenylsulfonyl)-1,3,4,9-tetrahydro-2H-b-carbolin-2-yl]pyrimidine-5-carboxamide],

[N-hydroxy-2-(9-methyl-1,3,4,9-tetrahydro-2H-b-carbolin-2-yl)pyrimidine-5-carboxamide],

[N-hydroxy-2-(9-benzyl-1,3,4,9-tetrahydro-2H-b-carbolin-2-yl)pyrimidine-5-carboxamide],

[2-(9-acetyl-1,3,4,9-tetrahydro-2H-b-carbolin-2-yl)-N-hydroxypyrimidine-5-carboxamide],

[N-hydroxy-2-{9-[2-pyrrolidin-1-ylmethyl]-1,3,4,9-tetrahydro-2H-b-carbolin-2-yl}pyrimidine-5-carboxamide],

[N-hydroxy-2-[9-(2-hydroxyethyl)-1,3,4,9-tetrahydro-2H-b-carbolin-2-yl]pyrimidine-5-carboxamide],

[N-hydroxy-2-[9-(1-methylpiperidin-3-yl)-1,3,4,9-tetrahydro-2H-b-carbolin-2-yl]pyrimidine-5-carboxamide] or

[N-hydroxy-2-(6-methyl-1,3,4,4a,9,9a-hexahydro-2H-b-carbolin-2-yl)pyrimidine-5-carboxamide].

4. A compound of formula I:

wherein

and the ring containing W 1 and W to which it is fused together form an optionally substituted 1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl or an optionally substituted 1,1a,3,4,4a,5-hexahydro-2H-pyrido[4,3-b]indol-2-yl substituent;

W 2 is a bond or [-C(R 1 )(R 2 )—] p ;

R 1 and R 2 are independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclic, and substituted heterocyclic;

p is 1, 2, 3 or 4;

wherein Ar 2 -G-C(O)NHOH, is 5-[-G-C(O)NHOH]-pyrimid-2-ylene G is a bond; or

a tautomer, stereoisomer, prodrug, or pharmaceutically acceptable salt thereof.

5. The compound according to claim 4 , wherein W 2 is a bond.

6. The compound according to claim 5 , wherein said compound is:

[N-hydroxy-2-(1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl)pyrimidine-5-carboxamide],

[N-hydroxy-2-(8-methyl-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl)pyrimidine-5-carboxamide],

[2-(8-chloro-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl)-N-hydroxypyrimidine-5-carboxamide],

[2-(8-bromo-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl)-N-hydroxypyrimidine-5-carboxamide],

[N-hydroxy-2-[8-(trifluoromethoxy)-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl]pyrimidine-5-carboxamide],

[N-hydroxy-2-(8-phenyl-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl)pyrimidine-5-carboxamide].

[N-hydroxy-2-(8-fluoro-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl)pyrimidine-5-carboxamide],

[N-hydroxy-2-(8-methoxy-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl)pyrimidine-5-carboxamide],

[N-hydroxy-2-(7-fluoro-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl)pyrimidine-5-carboxamide],

[N-hydroxy-2-(7-methyl-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl)pyrimidine-5-carboxamide],

[N-hydroxy-2-(7,8-dimethyl-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl)pyrimidine-5-carboxamide],

[N-hydroxy-2-(7-chloro-8-methyl-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl)pyrimidine-5-carboxamide],

[N-hydroxy-2-(7-bromo-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl)pyrimidine-5-carboxamide],

[N-hydroxy-2-(8-trifluoromethyl-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl)pyrimidine-5-carboxamide],

[N-hydroxy-2-(9-chloro-8-methyl-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl)pyrimidine-5-carboxamide],

[N-hydroxy-2-(8-nitro-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl)pyrimidine-5-carboxamide].

[N-hydroxy-2-(8-(N-acetamido)-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl)pyrimidine-5-carboxamide],

[N-hydroxy-2-(8-(N-methylsulfonamido)-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl)pyrimidine-5-carboxamide],

[N-hydroxy-2-(8-amino-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl)pyrimidine-5-carboxamide],

[N-hydroxy-2-{8-isopropyl-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl}pyrimidine-5-carboxamide],

[N-hydroxy-2-{8-tert-butyl-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl}pyrimidine-5-carboxamide],

[N-hydroxy-2-{7-phenyl-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl}pyrimidine-5-carboxamide],

[N-hydroxy-2-{5-acetyl-8-methyl-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl}pyrimidine-5-carboxamide],

[N-hydroxy-2-(8-methyl-1,3,4,4a,5,9b-hexahydro-2H-pyrido[4,3-b]indol-2-yl)pyrimidine-5-carboxamide] or

[N-hydroxy-2-{8-[(4-methylpiperazin-1-yl)methyl]-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl}pyrimidine-5-carboxamide].

7. The compound according to claim 4 , wherein said compound is:

[N-hydroxy-2-{8-[3-(pyrrolidin-1-ylmethyl)phenyl]-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl}pyrimidine-5-carboxamide],

[N-hydroxy-2-{8-(pyridin-3-yl)-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl}pyrimidine-5-carboxamide],

[N-hydroxy-2-{8-[4-(pyrrolidin-1-ylmethyl)phenyl]-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl}pyrimidine-5-carboxamide],

[N-hydroxy-2-{8-(pyrimidin-5-yl)-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl}pyrimidine-5-carboxamide],

[N-hydroxy-2-{8-[3-(morpholin-4-ylmethyl)phenyl]-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl}pyrimidine-5-carboxamide],

[N-hydroxy-2-{8-[3-(piperidin-1-ylmethyl)phenyl]-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl}pyrimidine-5-carboxamide],

[N-hydroxy-2-{8-[3-(N,N-dimethylaminomethyl)phenyl]-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl}pyrimidine-5-carboxamide],

[N-hydroxy-2-{8-[3-((4-hydroxymethylpiperidin-1-yl)methyl)phenyl]-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl}pyrimidine-5-carboxamide],

[N-hydroxy-2-{8-[3-(thiomorpholin-4-ylmethyl)phenyl]-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl}pyrimidine-5-carboxamide],

[N-hydroxy-2-{8-[3-(N,N-di(2-hydroxyethyl)aminomethyl)phenyl]-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl}pyrimidine-5-carboxamide],

[N-hydroxy-2-{8-[3-((4-methylpiperazin-1-yl)methyl)phenyl]-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl}pyrimidine-5-carboxamide],

[N-hydroxy-2-{8-[3-(piperazin-1-ylmethyl)phenyl]-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl}pyrimidine-5-carboxamide],

[N-hydroxy-2-{8-[3-((4-(methylsulfonyl)piperazin-1-yl)methyl)phenyl]-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl}pyrimidine-5-carboxamide],

[N-hydroxy-2-{8-[3-((4-acetylpiperazin-1-yl)methyl)phenyl]-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl}pyrimidine-5-carboxamide],

[N-hydroxy-2-{8-[4-(morpholin-4-ylmethyl)phenyl]-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl}pyrimidine-5-carboxamide],

[N-hydroxy-2-{8-[4-(thiomorpholin-4-ylmethyl)phenyl]-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl}pyrimidine-5-carboxamide],

[N-hydroxy-2-{8-[4-((4-methylpiperazin-1-yl)methyl)phenyl]-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl}pyrimidine-5-carboxamide],

[N-hydroxy-2-{8-[4-(hydroxymethyl)phenyl]-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl}pyrimidine-5-carboxamide],

[N-hydroxy-2-{8-[5-((4-methylpiperazin-1-yl)methyl)-2-furyl]-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl}pyrimidine-5-carboxamide],

[N-hydroxy-2-{8-[5-(morpholin-4-yl)methyl-2-furyl]-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl}pyrimidine-5-carboxamide],

[N-hydroxy-2-{8-[5-((4-methylpiperazin-1-yl)methyl)-thien-2-yl]-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl}pyrimidine-5-carboxamide],

[N-hydroxy-2-{8-[3-(hydroxymethyl)phenyl]-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl}pyrimidine-5-carboxamide],

[N-hydroxy-2-{8-[4-methoxyphenyl]-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl}pyrimidine-5-carboxamide],

[N-hydroxy-2-{8-[4-methylphenyl]-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl}pyrimidine-5-carboxamide],

[N-hydroxy-2-{8-[4-(N-acetamido)phenyl]-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl}pyrimidine-5-carboxamide],

[N-hydroxy-2-{8-(fur-2-yl)-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl}pyrimidine-5-carboxamide],

[N-hydroxy-2-{8-[3-(pyrrolidin-1-ylcarbonyl)phenyl]-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl}pyrimidine-5-carboxamide],

[N-hydroxy-2-{7-[3-(pyrrolidin-1-ylmethyl)phenyl]-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl}pyrimidine-5-carboxamide],

[N-hydroxy-2-{8-[3-aminophenyl]-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl}pyrimidine-5-carboxamide],

[N-hydroxy-2-{8-[3-fluorophenyl]-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl}pyrimidine-5-carboxamide],

[N-hydroxy-2-{8-[4-fluorophenyl]-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl}pyrimidine-5-carboxamide],

[N-hydroxy-2-{8-[fur-3-yl]-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl}pyrimidine-5-carboxamide],

[N-hydroxy-2-{8-[1H-pyrrol-2-yl]-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl}pyrimidine-5-carboxamide],

[N-hydroxy-2-{8-[3-(methylthio)phenyl]-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl}pyrimidine-5-carboxamide],

[N-hydroxy-2-{8-[4-dimethylaminophenyl]-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl}pyrimidine-5-carboxamide],

[N-hydroxy-2-{8-[3-(methylsulfinyl)phenyl]-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl}pyrimidine-5-carboxamide],

[N-hydroxy-2-{8-[3-(N-acetamidomethyl)phenyl]-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl}pyrimidine-5-carboxamide],

[N-hydroxy-2-{8-[3-(N-methylsulfonamidomethyl)phenyl]-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl}pyrimidine-5-carboxamide],

[N-hydroxy-2-{8-[3-(N-acetamido)phenyl]-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl}pyrimidine-5-carboxamide],

[N-hydroxy-2-{8-[3-(N-methylsulfonamido)phenyl]-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl}pyrimidine-5-carboxamide],

[N-hydroxy-2-{8-[3-(1H-tetrazol-5-yl)phenyl]-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl}pyrimidine-5-carboxamide] or

[N-hydroxy-2-{8-[thien-2-yl]-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl}pyrimidine-5-carboxamide].

8. A pharmaceutical composition comprising an effective amount of one or more compounds according to claim 1 or claim 4 and a pharmaceutically inert carrier.