N-Sulphonylpyrroles and Their Use as Histone Deacetylase Inhibitors

A compound of formula I

• in which
• R1 is hydrogen, 1-4C-alkyl, halogen, or 1-4C-alkoxy,
• R2 is hydrogen or 1-4C-alkyl,
• R3 is hydrogen or 1-4C-alkyl,
• R4 is hydrogen, 1-4C-alkyl, halogen, or 1-4C-alkoxy,
• R5 is hydrogen, 1-4C-alkyl, halogen, or 1-4C-alkoxy,
• R6 is -T1-Q1, in which
• T1 is a bond or 1-4C-alkylene,
• either
• Q1 is substituted by R61 and/or R62, and is Aa1, Hh1, Ha1, Ha2, Ha3, Ha4 or Ah1,
• or
• Q1 is unsubstituted, and is Ha2, Ha3 or Ha4,
• in which
• R61 is 1-4C-alkyl, phenyl-1-4C-alkyl, 1-4C-alkoxy, hydroxyl, trifluoromethyl, cyano, halogen, completely or predominantly fluorine-substituted 1-4C-alkoxy, hydroxy-1-4C-alkyl, 1-4C-alkoxy-1-4C-alkyl, 1-4C-alkylsulphonylamino, tolylsulphonylamino, phenylsulphonylamino, 1-4C-alkylcarbonylamino, carbamoyl, sulphamoyl, mono- or di-1-4C-alkylaminocarbonyl, mono- or di-1-4C-alkylaminosulphonyl, -T2-N(R611)R612, —U-T3-N(R613)R614, -T4-Het3, or —V-T5-Het4, in which
• T2 is a bond or 1-4C-alkylene,
• R611 is hydrogen, 1-4C-alkyl, 3-7C-cycloalkyl, 3-7C-cycloalkylmethyl, hydroxy-2-4C-alkyl, 1-4C-alkoxy-2-4C-alkyl, 1-4C-alkylcarbonyl, or 1-4C-alkylsulphonyl,
• R612 is hydrogen or 1-4C-alkyl,
• or R611 and R612 together and with inclusion of the nitrogen atom, to which they are bonded, form a heterocyclic ring Het1, in which
• Het1 is morpholino, thiomorpholino, S-oxo-thiomorpholino, S,S-dioxo-thiomorpholino, piperidino, pyrrolidino, piperazino, or 4N-(1-4C-alkyl)-piperazino,
• is —O— (oxygen) or —C(O)NH—,
• T3 is 2-4C-alkylene,
• R613 is hydrogen, 1-4C-alkyl, 3-7C-cycloalkyl, 3-7C-cycloalkylmethyl, hydroxy-2-4C-alkyl. 1-4C-alkoxy-2-4C-alkyl, 1-4C-alkylcarbonyl, or 1-4C-alkylsulphonyl.
• R614 is hydrogen or 1-4C-alkyl,
• or 613 and R614 together and with inclusion of the nitrogen atom, to which they are bonded, form a heterocyclic ring Het2, in which
• Het2 is morpholino, thiomorpholino, S-oxo-thiomorpholino, S,S-dioxo-thiomorpholino, piperidino, pyrrolidino, piperazino, or 4N-(1-4C-alkyl)-piperazino,
• T4 is a bond or 1-4C-alkylene,
• Het3 is 1N-(1-4C-alkyl)-piperidinyl or 1N-(1-4C-alkyl)-pyrrolidinyl,
• V is —O— (oxygen) or —C(O)NH—,
• T5 is a bond or 1-4C-alkylene,
• Het4 is 1N-(1-4C-alkyl)-piperidinyl or 1N-(1-4C-alkyl)-pyrrolidinyl,
• R62 is 1-4C-alkyl, 1-4C-alkoxy or halogen,
• Aa1 is a bisaryl radical made up of two aryl groups, which are independently selected from the group consisting of phenyl and naphthyl, and which are linked together via a single bond,
• Hh1 is a bisheteroaryl radical made up of two heteroaryl groups, which are independently selected from the group consisting of monocyclic 5- and 6-membered heteroaryl radicals comprising one or two heteroatoms, each of which is selected from the group consisting of nitrogen, oxygen and sulfur, and which are linked together via a single bond,
• Ah1 is an arylheteroaryl radical made up of an aryl group selected from the group consisting of phenyl and naphthyl, and a heteroaryl group selected from the group consisting of monocyclic 5- and 6-membered heteroaryl radicals comprising one or two heteroatoms, each of which is selected from the group consisting of nitrogen, oxygen and sulfur, whereby said aryl and heteroaryl groups are linked together via a single bond, and whereby Ah1 is bonded via said heteroaryl moiety to the parent molecular group,
• Ha1 is a heteroarylaryl radical made up of a heteroaryl group selected from the group consisting of monocyclic 5- and 6-membered heteroaryl radicals comprising one or two heteroatoms, each of which is selected from the group consisting of nitrogen, oxygen and sulfur, and an aryl group selected from the group consisting of phenyl and naphthyl, whereby said heteroaryl and aryl groups are linked together via a single bond, and whereby Ha1 is bonded via said aryl moiety to the parent molecular group,
• Ha2 is a heteroarylaryl radical made up of a heteroaryl group selected from the group consisting of fused bicyclic 9- and 10-membered heteroaryl radicals comprising one, two or three heteroatoms, each of which is selected from the group consisting of nitrogen, oxygen and sulfur, and an aryl group selected from the group consisting of phenyl and naphthyl, whereby said heteroaryl and aryl groups are linked together via a single bond, and whereby Ha2 is bonded via said aryl moiety to the parent molecular group,
• Ha3 is a heteroarylaryl radical made up of a heteroaryl group selected from the group consisting of monocyclic 5-membered heteroaryl radicals comprising three or four heteroatoms, each of which is selected from the group consisting of nitrogen, oxygen and sulfur, and an aryl group selected from the group consisting of phenyl and naphthyl, whereby said heteroaryl and aryl groups are linked together via a single bond, and whereby Ha3 is bonded via said aryl moiety to the parent molecular group,
• Ha4 is a heteroarylaryl radical made up of a heteroaryl group selected from the group consisting of partially saturated fused bicyclic 9- and 10-membered heteroaryl radicals comprising a heteroatom-free benzene ring and one or two heteroatoms, each of which is selected from the group consisting of nitrogen, oxygen and sulfur, and an aryl group selected from the group consisting of phenyl and naphthyl, whereby said heteroaryl and aryl groups are linked together via a single bond, and whereby Ha4 is bonded via said aryl moiety to the parent molecular group,
• R7 is hydroxyl, or Cyc1, in which
• Cyc1 is a ring system of formula Ia
• in which
• A is C (carbon),
• B is C (carbon),
• R71 is hydrogen, halogen, 1-4C-alkyl, or 1-4C-alkoxy,
• R72 is hydrogen, halogen, 1-4C-alkyl, or 1-4C-alkoxy,
• M with inclusion of A and B is either a ring Ar2 or a ring Har2, in which
• Ar2 is a benzene ring,
• Har2 is a monocyclic 5- or 6-membered unsaturated heteroaromatic ring comprising one to three heteroatoms, each of which is selected from the group consisting of nitrogen, oxygen and sulfur,
• or a salt thereof.