Sulfonyl-derivatives as novel inhibitors of histone deacetylase

1. A compound of formula (I),

or an N-oxide form, pharmaceutically acceptable addition salt or stereo-chemically isomeric form thereof, wherein

n is 1;

t is 0 and a direct bond is intended;

Q is

X is

Y is nitrogen;

Z is nitrogen;

R 1 is —C(O)NR 7 R 8 , —N(H)C(O)R 9 , —C(O)—C 1-6 alkanediylSR 9 , —NR 10 C(O)N(OH)R 9 , —NR 10 C(O)C 1-6 alkanediylSR 9 , —NR 10 C(O)C═N(OH)R 9 or another Zn-chelating-group wherein R 7 and R 8 are each independently selected from hydrogen, hydroxy, C 1-6 alkyl, hydroxyC 1-6 alkyl, aminoC 1-6 alkyl and aminoaryl;

R 9 is independently selected hydrogen, C 1-6 alkyl, C 1-6 alkylcarbonyl, arylC 1-6 alkyl, C 1-6 alkylpyrazinyl, pyridinone, pyrrolidinone and methylimidazolyl;

R 10 is independently selected from hydrogen and C 1-6 alkyl;

R 2 is hydrogen, halo, hydroxy, amino, nitro, C 1-6 alkyl, C 1-6 alkyloxy, trifluoromethyl, di(C 1-6 alkyl)amino, hydroxyamino or naphtalenylsulfonylpyrazinyl;

-L- is a direct bond;

each R 3 represents a hydrogen atom and one hydrogen atom is optionally replaced by aryl;

R 4 is hydrogen, hydroxy, amino, hydroxyC 1-6 alkyl, C 1-6 alkyl, C 1-6 alkyloxy, arylC 1-6 alkyl, aminocarbonyl, hydroxycarbonyl, aminoC 1-6 alkyl, aminocarbonylC 1-6 alkyl, hydroxycarbonylC 1-6 alkyl, hydroxyaminocarbonyl, C 1-6 alkyloxycarbonyl, C 1-6 alkylamino C 1-6 alkyl or di(C 1-6 alkyl)amino C 1-6 alkyl;

 is a radical selected from

wherein each s is independently 0, 1, 2, 3, 4 or 5;

each R 5 is independently selected from hydrogen; halo; hydroxy; amino; nitro; trihaloC 1-6 alkyl; trihaloC 1-6 alkyloxy; C 1-6 alkyl; C 1-6 alkyl substituted with aryl and C 3-10 cycloalkyl; C 1-6 alkyloxy; C 1-6 alkyloxyC 1-6 alkyloxy; C 1-6 alkylcarbonyl; C 1-6 alkyloxycarbonyl; C 1-6 alkylsulfonyl; cyanoC 1-6 alkyl; hydroxyC 1-6 alkyl; hydroxyC 1-6 alkyloxy; hydroxyC 1-6 alkylamino; aminoC 1-6 alkyloxy; di(C 1-6 alkyl)amino carbonyl; di(hydroxyC 1-6 alkyl)amino; (aryl)(C 1-6 alkyl)amino; di(C 1-6 alkyl)amino C 1-6 alkyloxy; di(C 1-6 alkyl)amino C 1-6 alkylamino; di(C 1-6 alkyl)amino C 1-6 alkylamino C 1-6 alkyl; arylsulfonyl; arylsulfonylamino; aryloxy; aryloxyC 1-6 alkyl; arylC 2-6 alkenediyl; di(C 1-6 alkyl)amino; di(C 1-6 alkyl)aminoC 1-6 alkyl; di(C 1-6 alkyl)amino(C 1-6 alkyl)amino; di(C 1-6 alkyl)amino(C 1-6 alkyl)aminoC 1-6 alkyl; di(C 1-6 alkyl)aminoC 1-6 alkyl(C 1-6 alkyl)amino; di(C 1-6 alkyl)aminoC 1-6 alkyl(C 1-6 alkyl)aminoC 1-6 alkyl; aminosulfonylamino(C 1-6 alkyl)amino; aminosulfonylamino(C 1-6 alkyl)aminoC 1-6 alkyl; di(C 1-6 alkyl)aminosulfonylamino(C 1-6 alkyl)amino; di(C 1-6 alkyl)aminosulfonylamino(C 1-6 alkyl)aminoC 1-6 alkyl; cyano; thiophenyl; thiophenyl substituted with di(C 1-6 alkyl)aminoC 1-6 alkyl(C 1-6 alkyl)aminoC 1-6 alkyl, di(C 1-6 alkyl)aminoC 1-6 alkyl, C 1-6 alkylpiperazinylC 1-6 alkyl, hydroxyC 1-6 alkylpiperazinylC 1-6 alkyl, hydroxyC 1-6 alkyloxyC 1-6 alkylpiperazinylC 1-6 alkyl, di(C 1-6 alkyl)aminosulfonylpiperazinylC 1-6 alkyl, C 1-6 alkyloxypiperidinyl, C 1-6 alkyloxypiperidinylC 1-6 alkyl, morpholinylC 1-6 alkyl, hydroxyC 1-6 alkyl(C 1-6 alkyl)aminoC 1-6 alkyl, or di(hydroxyC 1-6 alkyl)aminoC 1-6 alkyl; furanyl; furanyl substituted with hydroxyC 1-6 alkyl; benzofuranyl; imidazolyl; oxazolyl; oxazolyl substituted with aryl and C 1-6 alkyl; C 1-6 alkyltriazolyl; tetrazolyl; pyrrolidinyl; pyrrolyl; piperidinylC 1-6 alkyloxy; morpholinyl; C 1-6 alkylmorpholinyl; morpholinylC 1-6 alkyloxy; morpholinylC 1-6 alkyl; morpholinylC 1-6 alkylamino; morpholinylC 1-6 alkylaminoC 1-6 alkyl; piperazinyl; C 1-6 alkylpiperazinyl; C 1-6 alkylpiperazinylC 1-6 alkyloxy; piperazinylC 1-6 alkyl; naphtalenylsulfonylpiperazinyl; naphtalenylsulfonylpiperidinyl; naphtalenylsulfonyl: C 1-6 alkylpiperazinylC 1-6 alkyl; C 1-6 alkylpiperazinylC 1-6 alkylamino; C 1-6 alkylpiperazinylC 1-6 alkylaminoC 1-6 alkyl; C 1-6 alkylpiperazinylsulfonyl; aminosulfonylpiperazinylC 1-6 alkyloxy; amino sulfonylpiperazinyl; amino sulfonylpiperazinylC 1-6 alkyl; di(C 1-6 alkyl)amino sulfonylpiperazinyl; di(C 1-6 alkyl)aminosulfonylpiperazinylC 1-6 alkyl; hydroxyC 1-6 alkylpiperazinyl; hydroxyC 1-6 alkylpiperazinylC 1-6 alkyl; C 1-6 alkyloxypiperidinyl; C 1-6 alkyloxypiperidinylC 1-6 alkyl; piperidinylaminoC 1-6 alkylamino; piperidinylaminoC 1-6 alkylaminoC 1-6 alkyl; (C 1-6 alkylpiperidinyl)(hydroxyC 1-6 alkyl)aminoC 1-6 alkylamino; (C 1-6 alkylpiperidinyl)(hydroxyC 1-6 alkyl)aminoC 1-6 alkylamino C 1-6 alkyl; hydroxyC 1-6 alkyloxyC 1-6 alkylpiperazinyl; hydroxyC 1-6 alkyloxyC 1-6 alkylpiperazinylC 1-6 alkyl; (hydroxyC 1-6 alkyl)(C 1-6 alkyl)amino; (hydroxyC 1-6 alkyl)(C 1-6 alkyl)amino C 1-6 alkyl; hydroxyC 1-6 alkylaminoC 1-6 alkyl; di(hydroxyC 1-6 alkyl)amino C 1-6 alkyl; pyrrolidinylC 1-6 alkyl; pyrrolidinylC 1-6 alkyloxy; pyrazolyl; thiopyrazolyl; pyrazolyl substituted with two substituents selected from C 1-6 alkyl or trihaloC 1-6 alkyl; pyridinyl; pyridinyl substituted with C 1-6 alkyloxy, aryloxy or aryl; pyrimidinyl; tetrahydropyrimidinylpiperazinyl; tetrahydropyrimidinylpiperazinylC 1-6 alkyl; quinolinyl; indolyl; phenyl; phenyl substituted with one, two or three substituents independently selected from halo, amino, nitro, C 1-6 alkyl, C 1-6 alkyloxy, hydroxyC 1-4 alkyl, trifluoromethyl, trifluoromethyloxy, hydroxyC 1-4 alkyloxy, C 1-4 alkylsulfonyl, C 1-4 alkyloxyC 1-4 alkyloxy, C 1-4 alkyloxycarbonyl, amino C 1-4 alkyloxy, di(C 1-4 alkyl)amino C 1-4 alkyloxy, di(C 1-4 alkyl)amino, di(C 1-4 alkyl)amino carbonyl, di(C 1-4 alkyl)amino C 1-4 alkyl, di(C 1-4 alkyl)amino C 1-4 alkylamino C 1-4 alkyl, di(C 1-4 alkyl)amino(C 1-4 alkyl)amino, di(C 1-4 alkyl)amino(C 1-4 alkyl)amino C 1-4 alkyl, di(C 1-4 alkyl)amino C 1-4 alkyl(C 1-4 alkyl)amino, di(C 1-4 alkyl)amino C 1-4 alkyl(C 1-4 alkyl)amino C 1-4 alkyl, aminosulfonylamino(C 1-4 alkyl)amino, aminosulfonylamino(C 1-4 alkyl)amino C 1-4 alkyl, di(C 1-4 alkyl)amino sulfonylamino(C 1-4 alkyl)amino, di(C 1-4 alkyl)amino sulfonylamino(C 1-4 alkyl)amino C 1-6 alkyl, cyano, piperidinylC 1-4 alkyloxy, pyrrolidinylC 1-4 alkyloxy, amino sulfonylpiperazinyl, aminosulfonylpiperazinylC 1-4 alkyl, di(C 1-4 alkyl)amino sulfonylpiperazinyl, di(C 1-4 alkyl)amino sulfonylpiperazinylC 1-4 alkyl, hydroxyC 1-4 alkylpiperazinyl, hydroxyC 1-4 alkylpiperazinylC 1-4 alkyl, C 1-4 alkyloxypiperidinyl, C 1-4 alkyloxypiperidinylC 1-4 alkyl, hydroxyC 1-4 alkyloxyC 1-4 alkylpiperazinyl, hydroxyC 1-4 alkyloxyC 1-4 alkylpiperazinylC 1-4 alkyl, (hydroxyC 1-4 alkyl)(C 1-4 alkyl)amino, (hydroxyC 1-4 alkyl)(C 1-4 alkyl)amino C 1-4 alkyl, di(hydroxyC 1-4 alkyl)amino, di(hydroxyC 1-4 alkyl)aminoC 1-4 alkyl, furanyl, furanyl substituted with —CH═CH—CH═CH—, pyrrolidinylC 1-4 alkyl, pyrrolidinylC 1-4 alkyloxy, morpholinyl, morpholinylC 1-4 alkyloxy, morpholinylC 1-4 alkyl, morpholinylC 1-4 alkylamino, morpholinylC 1-4 alkylamino C 1-4 alkyl, piperazinyl, C 1-4 alkylpiperazinyl, C 1-4 alkylpiperazinylC 1-4 alkyloxy, piperazinylC 1-4 alkyl, C 1-4 alkylpiperazinylC 1-4 alkyl, C 1-4 alkylpiperazinylC 1-4 alkylamino, C 1-4 alkylpiperazinylC 1-4 alkylamino C 1-6 alkyl, tetrahydropyrimidinylpiperazinyl, tetrahydropyrimidinylpiperazinylC 1-4 alkyl, piperidinylamino C 1-4 alkylamino, piperidinylamino C 1-4 alkylamino C 1-4 alkyl, (C 1-4 alkylpiperidinyl)(hydroxyC 1-4 alkyl)amino C 1-4 alkylamino, (C 1-4 alkylpiperidinyl)(hydroxyC 1-4 alkyl)amino C 1-4 alkylamino C 1-4 alkyl, pyridinylC 1-4 alkyloxy, hydroxyC 1-4 alkylamino, hydroxyC 1-4 alkylamino C 1-4 alkyl, di(C 1-4 alkyl)amino C 1-4 alkylamino, aminothiadiazolyl, aminosulfonylpiperazinylC 1-4 alkyloxy, and thiophenylC 1-4 alkylamino;

the central

 moiety is optionally bridged with a methylene, ethylene or propylene bridge;

each R 5 optionally replaces the hydrogen on the nitrogen; and

aryl in the above is phenyl, or phenyl substituted with one or more substituents each independently selected from halo, C 1-6 alkyl, C 1-6 alkyloxy, trifluoromethyl, cyano or hydroxycarbonyl.

2. A compound as claimed in claim 1 wherein

R 7 and R 8 are each independently selected from hydrogen, hydroxy, hydroxyC 1-6 alkyl, aminoC 1-6 alkyl and aminoaryl;

R 2 is hydrogen, halo, hydroxy, amino, nitro, C 1-6 alkyl, C 1-6 alkyloxy, trifluoromethyl, hydroxyamino or naphtalenylsulfonylpyrazinyl;

R 4 is hydrogen, hydroxy, amino, hydroxyC 1-6 alkyl, C 1-6 alkyloxy, arylC 1-6 alkyl, aminocarbonyl, hydroxycarbonyl, aminoC 1-6 alkyl, aminocarbonylC 1-6 alkyl, hydroxycarbonylC 1-6 alkyl, hydroxyamino carbonyl, C 1-6 alkyloxycarbonyl, C 1-6 alkylaminoC 1-6 alkyl or di(C 1-6 alkyl)aminoC 1-6 alkyl;

each R 5 is independently selected from hydrogen; halo; hydroxy; amino; nitro; trihaloC 1-6 alkyl; trihaloC 1-6 alkyloxy; C 1-6 alkyl; C 1-6 alkyloxy; C 1-6 alkyloxyC 1-6 alkyloxy; C 1-6 alkylcarbonyl; C 1-6 alkylsulfonyl; cyanoC 1-6 alkyl; hydroxyC 1-6 alkyl; hydroxyC 1-6 alkyloxy; hydroxyC 1-6 alkylamino; amino C 1-6 alkyloxy; di(C 1-6 alkyl)amino carbonyl; di(hydroxyC 1-6 alkyl)amino; di(C 1-6 alkyl)aminoC 1-6 alkyloxy; di(C 1-6 alkyl)aminoC 1-6 alkylamino; arylsulfonyl; arylsulfonylamino; aryloxy; arylC 2-6 alkenediyl; di(C 1-6 alkyl)amino; cyano; thiophenyl; thiophenyl substituted with di(C 1-6 alkyl)aminoC 1-6 alkyl(C 1-6 alkyl)aminoC 1-6 alkyl, di(C 1-6 alkyl)aminoC 1-6 alkyl, C 1-6 alkylpiperazinylC 1-6 alkyl or di(hydroxyC 1-6 alkyl)aminoC 1-6 alkyl; furanyl; imidazolyl; C 1-6 alkyltriazolyl; tetrazolyl; piperidinylC 1-6 alkyloxy; morpholinyl; C 1-6 alkylmorpholinyl; morpholinylC 1-6 alkyloxy; morpholinylC 1-6 alkyl; C 1-6 alkylpiperazinylC 1-6 alkyloxy; C 1-6 alkylpiperazinylC 1-6 alkyl; C 1-6 alkylpiperazinylsulfonyl; aminosulfonylpiperazinylC 1-6 alkyloxy; aminosulfonylpiperazinyl; aminosulfonylpiperazinylC 1-6 alkyl; di(C 1-6 alkyl)aminosulfonylpiperazinyl; di(C 1-6 alkyl)aminosulfonylpiperazinylC 1-6 alkyl; hydroxyC 1-6 alkylpiperazinyl; hydroxyC 1-6 alkylpiperazinylC 1-6 alkyl; C 1-6 alkyloxypiperidinyl; C 1-6 alkyloxypiperidinylC 1-6 alkyl; hydroxyC 1-6 alkyloxyC 1-6 alkylpiperazinyl; hydroxyC 1-6 alkyloxyC 1-6 alkylpiperazinylC 1-6 alkyl; (hydroxyC 1-6 alkyl)(C 1-6 alkyl)amino; (hydroxyC 1-6 alkyl)(C 1-6 alkyl)amino C 1-6 alkyl; pyrrolidinylC 1-6 alkyloxy; pyrazolyl; thiopyrazolyl; pyrazolyl substituted with two substituents selected from C 1-6 alkyl or trihaloC 1-6 alkyl; pyridinyl; pyridinyl substituted with C 1-6 alkyloxy or aryl; pyrimidinyl; quinolinyl; phenyl; phenyl substituted with one, two or three substituents independently selected from halo, amino, C 1-6 alkyl, C 1-6 alkyloxy, hydroxyC 1-4 alkyl, trifluoromethyl, trifluoromethyloxy, hydroxyC 1-4 alkyloxy, C 1-4 alkyloxyC 1-4 alkyloxy, aminoC 1-4 alkyloxy, di(C 1-4 alkyl)aminoC 1-4 alkyloxy, di(C 1-4 alkyl)amino, piperidinylC 1-4 alkyloxy, pyrrolidinylC 1-4 alkyloxy, aminosulfonylpiperazinyl, amino sulfonylpiperazinylC 1-4 alkyl, di(C 1-4 alkyl)amino sulfonylpiperazinyl, di(C 1-4 alkyl)amino sulfonylpiperazinylC 1-4 alkyl, hydroxyC 1-4 alkylpiperazinyl, hydroxyC 1-4 alkylpiperazinylC 1-4 alkyl, C 1-4 alkyloxypiperidinyl, C 1-4 alkyloxypiperidinylC 1-4 alkyl, hydroxyC 1-4 alkyloxyC 1-4 alkylpiperazinyl, hydroxyC 1-4 alkyloxyC 1-4 alkylpiperazinylC 1-4 alkyl, (hydroxyC 1-4 alkyl)(C 1-4 alkyl)amino, (hydroxyC 1-4 alkyl)(C 1-4 alkyl)amino C 1-4 alkyl, pyrrolidinylC 1-4 alkyloxy, morpholinylC 1-4 alkyloxy, morpholinylC 1-4 alkyl, C 1-4 alkylpiperazinylC 1-4 alkyloxy, C 1-4 alkylpiperazinylC 1-4 alkyl, hydroxyC 1-4 alkylamino, di(hydroxyC 1-4 alkyl)amino, di(C 1-4 alkyl)amino C 1-4 alkylamino, aminothiadiazolyl, aminosulfonylpiperazinylC 1-4 alkyloxy, or thiophenylC 1-4 alkylamino.

3. A compound as claimed in claim 1 wherein

R 1 is —C(O)NR 7 R 8 , —C(O)—C 1-6 alkanediylSR 9 , —NR 10 C(O)N(OH)R 9 , —NR 10 C(O)C 1-6 alkanediylSR 9 , —NR 10 C(O)C═N(OH)R 9 or another Zn-chelating-group wherein R 7 and R 8 are each independently selected from hydrogen, hydroxy, hydroxyC 1-6 alkyl, and aminoC 1-6 alkyl;

R 2 is hydrogen, halo, hydroxy, amino, nitro, C 1-6 alkyl, C 1-6 alkyloxy, trifluoromethyl or di(C 1-6 alkyl)amino;

R 4 is hydrogen, hydroxy, amino, hydroxyC 1-6 alkyl, C 1-6 alkyl, C 1-6 alkyloxy, arylC 1-6 alkyl, aminocarbonyl, aminoC 1-6 alkyl, C 1-6 alkylaminoC 1-6 alkyl or di(C 1-6 alkyl)aminoC 1-6 alkyl;

 is a radical selected from (a-1), and;

each s is independently 0, 1, 2, 3 or 4; and

R 5 is hydrogen; halo; hydroxy; amino; nitro; trihaloC 1-6 alkyl; trihaloC 1-6 alkyloxy; C 1-6 alkyl; C 1-6 alkyloxy; C 1-6 alkylcarbonyl; C 1-6 alkyloxycarbonyl; C 1-6 alkylsulfonyl; hydroxyC 1-6 alkyl; aryloxy; di(C 1-6 alkyl)amino; cyano; thiophenyl; furanyl; furanyl substituted with hydroxyC 1-6 alkyl; benzofuranyl; imidazolyl; oxazolyl; oxazolyl substituted with aryl and C 1-6 alkyl; C 1-6 alkyltriazolyl; tetrazolyl; pyrrolidinyl; pyrrolyl; morpholinyl; C 1-6 alkylmorpholinyl; piperazinyl; C 1-6 alkylpiperazinyl; hydroxyC 1-6 alkylpiperazinyl; C 1-6 alkyloxypiperidinyl; pyrazoly; pyrazolyl substituted with one or two substituents selected from C 1-6 alkyl or trihaloC 1-6 alkyl; pyridinyl; pyridinyl substituted with C 1-6 alkyloxy, aryloxy or aryl; pyrimidinyl; quinolinyl; indole; phenyl; or phenyl substituted with one or two substituents independently selected from halo, C 1-6 alkyl, C 1-6 alkyloxy or trifluoromethyl;

the central

 moiety is optionally bridged with an ethylene bridge.

4. A compound as claimed in claim 1 wherein R 10 is hydrogen; R 2 is hydrogen, nitro, C 1-6 alkyloxy, trifluoromethyl, di(C 1-6 alkyl)amino, hydroxyamino or naphtalenylsulfonylpyrazinyl; each R 3 represents a hydrogen atom; R 4 is hydrogen, hydroxyC 1-6 alkyl, aminocarbonyl, hydroxyaminocarbonyl or di(C 1-6 alkyl)aminoC 1-6 alkyl;

is a radical selected from (a-1), (a-20)and; each s is independently 0, 1, 2 or 5; and each R 5 is independently selected from hydrogen; halo; nitro; trihaloC 1-6 alkyl; trihaloC 1-6 alkyloxy; C 1-6 alkyl; C 1-6 alkyloxy; C 1-6 alkylsulfonyl; (aryl)(C 1-6 alkyl)amino; arylsulfonyl; aryloxy; arylC 2-6 alkenediyl; di(C 1-6 alky)amino; thiophenyl; thiophenyl substituted with di(C 1-6 alkyl)aminoC 1-6 alkyl(C 1-6 alkyl)aminoC 1-6 alkyl, di(C 1-6 alkyl)aminoC 1-6 alkyl, C 1-6 alkylpiperazinylC 1-6 alkyl, hydroxyC 1-6 alkylpiperazinylC 1-6 alkyl, hydroxyC 1-6 alkyloxyC 1-6 alkylpiperazinylC 1-6 alkyl, di(C 1-6 alkyl)aminosulfonylpiperazinylC 1-6 alkyl, C 1-6 alkyloxypiperidinylC 1-6 alkyl, morpholinylC 1-6 alkyl, hydroxyC 1-6 alkyl(C 1-6 alkyl)aminoC 1-6 alkyl, or di(hydroxyC 1-6 alkyl)aminoC 1-6 alkyl; furanyl; oxazolyl; pyrrolyl; pyrazolyl; pyridinyl; pyridinyl substituted with C 1-6 alkyloxy; quinolinyl; indolyl; phenyl; phenyl substituted with one, two or three substituents independently selected from halo, amino, C 1-6 alkyl, C 1-6 alkyloxy, hydroxyC 1-4 alkyl, trifluoromethyl, trifluoromethyloxy, di(C 1-4 alkyl)aminoC 1-4 alkyloxy, di(C 1-4 alkyl)amino, di(C 1-4 alkyl)aminoC 1-4 alkyl, di(C 1-4 alkyl)aminoC 1-4 alkyl(C 1-4 alkyl)amino, di(C 1-4 alkyl)aminoC 1-4 alkyl(C 1-4 alkyl)aminoC 1-4 alkyl, hydroxyC 1-4 alkylpiperazinylC 1-4 alkyl, hydroxyC 1-4 alkyloxyC 1-4 alkylpiperazinylC 1-4 alkyl, di(hydroxyC 1-4 alkyl)aminoC 1-4 alkyl, pyrrolidinylC 1-4 alkyl, pyrrolidinylC 1-4 alkyloxy, morpholinylC 1-4 alkyloxy, morpholinylC 1-4 alkyl, and C 1-4 alkylpiperazinylC 1-4 alkyl, or the central

moiety is optionally bridged with a methylene bridge.

5. A compound as claimed in claim 1 wherein R 10 is hydrogen; R 2 is hydrogen, nitro, C 1-6 alkyloxy, trifluoromethyl, di(C 1-6 alkyl)amino, hydroxyamino or naphtalenylsulfonylpyrazinyl; each R 3 represents a hydrogen atom; R 4 is hydrogen, hydroxyC 1-6 alkyl, aminocarbonyl, hydroxyaminocarbonyl or di(C 1-6 alkyl)aminoC 1-6 alkyl;

is a radical selected from (a-1), (a-20), and (a-21) each s is independently 0, 1, 2 or 5; and each R 5 is independently selected from hydrogen; halo; nitro; trihaloC 1-6 alkyl; trihaloC 1-6 alkyloxy; C 1-6 alkyl; C 1-6 alkyloxy; C 1-6 alkylsulfonyl; (aryl)(C 1-6 alkyl)amino; arylsulfonyl; aryloxy; arylC 2-6 alkenediyl; di(C 1-6 alky)amino; thiophenyl; thiophenyl substituted with di(C 1-6 alkyl)aminoC 1-6 alkyl(C 1-6 alkyl)aminoC 1-6 alkyl, di(C 1-6 alkyl)aminoC 1-6 alkyl, C 1-6 alkylpiperazinylC 1-6 alkyl, hydroxyC 1-6 alkylpiperazinylC 1-6 alkyl, hydroxyC 1-6 alkyloxyC 1-6 alkylpiperazinylC 1-6 alkyl, di(C 1-6 alkyl)aminosulfonylpiperazinylC 1-6 alkyl, C 1-6 alkyloxypiperidinylC 1-6 alkyl, morpholinylC 1-6 alkyl, hydroxyC 1-6 alkyl(C 1-6 alkyl)aminoC 1-6 alkyl, or di(hydroxyC 1-6 alkyl)aminoC 1-6 alkyl; furanyl; oxazolyl; pyrrolyl; pyrazolyl; pyridinyl; pyridinyl substituted with C 1-6 alkyloxy; quinolinyl; indolyl; phenyl; phenyl substituted with one, two or three substituents independently selected from halo, amino, C 1-6 alkyl, C 1-6 alkyloxy, hydroxyC 1-4 alkyl, trifluoromethyl, trifluoromethyloxy, di(C 1-4 alkyl)aminoC 1-4 alkyloxy, di(C 1-4 alkyl)amino, di(C 1-4 alkyl)aminoC 1-4 alkyl, di(C 1-4 alkyl)aminoC 1-4 alkyl(C 1-4 alkyl)amino , di(C 1-4 alkyl)aminoC 1-4 alkyl(C 1-4 alkyl)aminoC 1-4 alkyl, hydroxyC 1-4 alkylpiperazinylC 1-4 alkyl, hydroxyC 1-4 alkyloxyC 1-4 alkylpiperazinylC 1-4 alkyl, di(hydroxyC 1-4 alkyl)aminoC 1-4 alkyl, pyrrolidinylC 1-4 alkyl, pyrrolidinylC 1-4 alkyloxy, morpholinylC 1-4 alkyloxy, morpholinylC 1-4 alkyl, and C 1-4 alkylpiperazinylC 1-4 alkyl, or the central

moiety is optionally bridged with a methylene bridge.

6. A compound as claimed in claim 1 , wherein R 1 is —C(O)NH(OH); R 2 is hydrogen; each R 3 represents a hydrogen atom; R 4 is hydrogen;

is a radical selected from (a-1) and (a-20); each s is independently 0 or 1; and each R 5 is independently selected from hydrogen; thiophenyl; thiophenyl substituted with di(C 1-6 alkyl)aminoC 1-6 alkyl, or C 1-6 alkylpiperazinylC 1-6 alkyl; furanyl; phenyl; phenyl substituted with one substituents independently selected from di(C 1-4 alkyl)aminoC 1-4 alkyloxy, di(C 1-4 alkyl)amino, di(C 1-4 alkyl)aminoC 1-4 alkyl, di(C 1-4 alkyl)aminoC 1-4 alkyl(C 1-4 alkyl)aminoC 1-4 alkyl, pyrrolidinylC 1-4 alkyl, pyrrolidinylC 1-4 alkyloxy and C 1-4 alkylpiperazinylC 1-4 alkyl.

7. A compound according to claim 1 , which is No. 142

.

8. A pharmaceutical composition comprising pharmaceutically acceptable carriers and as an active ingredient a therapeutically effective amount of a compound as claimed in claim 1 .

9. A combination of an anti-cancer agent and a HDAC inhibitor as claimed claim 1 .