New Substituted Pyrrolidinones and Their Use as Medicaments

A compound of the formula

• wherein:
• A denotes a 4- to 7-membered cycloalkyleneiminocarbonyl or cycloalkyleneiminosulphonyl group, while
• the cycloalkyleneimino moiety in the carbon skeleton may be substituted by one or two fluorine atoms, one or two C1-3-alkyl, C2-3-alkenyl, C2-3-alkynyl, hydroxy-C1-3-alkyl, C1-3-alkyloxy-C1-3-alkyl, phenyl-C1-3-alkyl, 1,1-diphenyl-C1-3-alkyl, heteroaryl-C1-3-alkyl, amino-C1-3-alkyl, C3-6-cycloalkylamino-C1-3-alkyl, phenylamino-C1-3-alkyl, C1-5-alkylamino-C1-3-alkyl, di-(C1-5-alkyl)-amino-C1-5-alkyl, N—(C3-6-cycloalkyl)-C1-3-alkylamino-C1-3-alkyl, a 4- to 7-membered cycloalkyleneimino-C1-3-alkyl, N—(C1-3-alkylcarbonyl)-C1-3-alkylamino-C1-3-alkyl, carboxy-C1-3-alkyl, C1-3-alkyloxycarbonyl-C1-3-alkyl, aminocarbonyl-C1-3-alkyl, C1-3-alkylaminocarbonyl-C1-3-alkyl, di-(C1-3-alkyl)-aminocarbonyl-C1-3-alkyl, a 4- to 7-membered cycloalkyleneiminocarbonyl-C1-3-alkyl, C1-5-alkyloxycarbonylamino-C1-3-alkyl, C1-3-alkylcarbonylamino-C1-3-alkyl, C1-5-alkylsulphonylamino-C1-3-alkyl, aminocarbonylamino-C1-3-alkyl, C1-5-alkylaminocarbonylamino-C1-3-alkyl, di-(C1-3-alkyl)-aminocarbonylamino-C1-3-alkyl, C1-5-alkylsulphonylamino, C1-5-alkylaminocarbonylamino, carboxy, C1-3-alkyloxycarbonyl, benzyloxycarbonyl, C1-3-alkylcarbonyl, aminocarbonyl, C1-3-alkylaminocarbonyl, di-(C1-3-alkyl)-aminocarbonyl, N—(C3-7-cycloalkyl)-C1-5-alkylaminocarbonyl, N-(phenyl-C1-3-alkyl)-C1-5-alkylaminocarbonyl, a 4- to 7-membered cycloalkyleneiminocarbonyl, aminocarbonyl-C1-3-alkylaminocarbonyl, hydroxy, C1-3-alkyloxy, allyloxy, propargyloxy, benzyloxy, amino, C1-3-alkylamino, di-(C1-3-alkyl)-amino, a 4- to 7-membered cycloalkyleneimino, trifluoromethylcarbonylamino, N—(C1-3-alkyl)-piperazin-4-yl-C1-3-alkyl, a phenyl or a 5- to 6-membered heteroaryl group, with the proviso that in the substitution of a methylene group adjacent to the imino group two heteroatoms are separated from one another by at least two carbon atoms, and/or
• a methylene group in the 3-position of a 5-membered cycloalkyleneimino group may be replaced by a sulphur atom, a sulphinyl or sulphonyl group or
• a methylene group in the 4-position of a 6- or 7-membered cycloalkyleneimino group may be replaced by an oxygen or sulphur atom, a carbonyl, sulphinyl or sulphonyl group or by an —NH group optionally substituted by a C1-3-alkyl, hydroxy, formyl or C1-3-alkylcarbonyl group, while additionally a methylene group adjacent to the previously mentioned optionally substituted —NH group may be replaced by a carbonyl, sulphinyl or sulphonyl group, with the proviso that
• during the substitution of the previously mentioned 6- to 7-membered cycloalkyleneimino groups, wherein a methylene group is replaced by an oxygen or sulphur atom, a sulphinyl or sulphonyl group, two heteroatoms are separated from one another by at least two carbon atoms,
• a 5- to 7-membered cycloalkenyleneiminocarbonyl or cycloalkenyleneiminosulphonyl group optionally substituted by one or two C1-3-alkyl, hydroxy-C1-3-alkyl, C1-5-alkoxy-C1-3-alkyl, amino-C1-3-alkyl, C1-3-alkylamino-C1-3-alkyl, di-(C1-3-alkyl)-amino-C1-3-alkyl, a 4- to 7-membered cycloalkyleneimino-C1-3-alkyl, C3-6-cycloalkylamino-C1-3-alkyl, phenyl, phenyl-C1-3-alkyl, heteroaryl, heteroaryl-C1-3-alkyl, aminocarbonyl, C1-3-alkylaminocarbonyl, di-(C1-3-alkyl)-aminocarbonyl or 4- to 7-membered cycloalkyleneiminocarbonyl groups, wherein the double bond is not bound to a nitrogen atom and may be fused to a 5- or 6-membered heteroaryl group,
• an aminocarbonyl or aminosulphonyl group optionally substituted by one or two C1-5-alkyl, C2-3-alkenyl, C2-3-alkynyl or C3-6-cycloalkyl groups,
• while the substituents may be identical or different and
• in each case one of the C1-5-alkyl groups may be substituted by one or two hydroxy-C1-3-alkyl, C1-3-alkoxy-C1-3-alkyl, benzyloxy-C1-3-alkyl, amino-C1-3-alkyl, C1-3-alkylamino-C1-3-alkyl, di-(C1-3-alkyl)-amino-C1-3-alkyl, a 4- to 7-membered cycloalkyleneimino-C1-3-alkyl, C1-5-alkyloxycarbonylamino-C1-3-alkyl, C3-6-cycloalkylamino-C1-3-alkyl, aminocarbonyl, C1-3-alkylamino-carbonyl, N—(C3-7-cycloalkyl)-C1-3-alkylaminocarbonyl, N-(phenyl-C1-3-alkyl)-C1-5-alkylaminocarbonyl, di-(C1-3-alkyl)-aminocarbonyl or a 4- to 7-membered cycloalkyleneiminocarbonyl group,
• or a group of formula
• which may be substituted in each case at a carbon atom by a C1-3-alkyl, C1-3-alkyloxy, C1-3-alkyloxycarbonyl, C1-5-alkyloxycarbonylamino-C1-3-alkyl, C1-3-alkyl-sulphonyl, C1-3-alkyl-sulphonyl-C1-3-alkyl, aminosulphonyl, C1-3-alkylsulphonyl-C1-3-alkyl, C1-3-alkylsulphonylamino-C1-3-alkyl, C1-3-alkylsulphonylamino, C1-3-alkylcarbonylamino-C1-3-alkyl, C1-3-alkylcarbonylamino, amino-C1-3-alkyl, C1-3-alkylamino-C1-3-alkyl, di-(C1-3-alkyl)-amino-C1-3-alkyl, hydroxy-C1-3-alkyl, C1-5-alkoxy-C1-3-alkyl, a 4- to 7-membered cycloalkyleneimino-C1-3-alkyl, morpholin-4-yl-C1-3-alkyl, piperazinyl-C1-3-alkyl, N—(C1-3-alkyl)-piperazin-4-yl-C1-3-alkyl, aminocarbonyl, C1-3-alkylaminocarbonyl or di-(C1-3-alkyl)-aminocarbonyl group and wherein
• m denotes the number 1 or 2,
• R1 denotes a hydrogen or halogen atom, a C1-3-alkyl or C1-3-alkoxy group, while the hydrogen atoms of the C1-3-alkyl or C1-3-alkoxy group may optionally be wholly or partly replaced by fluorine atoms, a C2-3-alkenyl, C2-3-alkynyl, nitrile, nitro or amino group,
• R2 denotes a hydrogen or halogen atom or a C1-3-alkyl group,
• X denotes a nitrogen atom or a CH— group,
• R3 denotes a hydrogen atom or a C1-3-alkyl group,
• R4 and R5 each independently of one another denote
• a hydrogen atom, a hydroxy group, an OR9 group, a C2-6-alkenyl or C2-6-alkynyl group,
• a straight-chain or branched C1-6-alkyl group,
• while the hydrogen atoms of the straight-chain or branched C1-6-alkyl group may optionally be wholly or partly replaced by fluorine atoms, and which may optionally be substituted by a C3-5-cycloalkyl group, a nitrile, hydroxy, a C1-5-alkyloxy group, while the hydrogen atoms of the C1-5-alkyloxy group may optionally be wholly or partly replaced by fluorine atoms, an allyloxy, propargyloxy, benzyloxy, C1-5-alkylcarbonyloxy, C1-5-alkyloxycarbonyloxy, carboxy-C1-5-alkyloxy, C1-5-alkyloxycarbonyl-C1-5-alkyloxy, mercapto, C1-5-alkylsulphanyl, C1-5-alkylsulphonyl, carboxy, C1-5-alkyloxycarbonyl, aminocarbonyl, C1-5-alkylaminocarbonyl, di-(C1-5-alkyl)-aminocarbonyl, C4-6-cycloalkyleneiminocarbonyl, aminosulphonyl, C1-5-alkylaminosulphonyl, di-(C1-5-alkyl)-aminosulphonyl, C4-6-cycloalkyleneiminosulphonyl, amino, C1-5-alkylamino, di-(C1-5-alkyl)-amino, C1-5-alkylcarbonylamino, C1-5-alkylsulphonylamino, N—(C1-5-alkylsulphonyl)-C1-5-alkylamino or C3-6-cycloalkylcarbonylamino group,
• while the 6- to 7-membered cyclic groups of the C4-6-cycloalkyleneiminocarbonyl group in the cyclic moiety a methylene group in the 4-position of a 6- or 7-membered cycloalkyleneimino group may be replaced by an oxygen or sulphur atom, by a carbonyl, sulphinyl, sulphonyl or —NR7 group and additionally a methylene group adjacent to an above-mentioned —NR7 group may be replaced by a carbonyl group,
• a phenyl or heteroaryl group
• which may optionally be mono- to trisubstituted in the phenyl or heteroaryl moiety by identical or different substituents selected from among halogen atoms, C1-5-alkyl, di-(C1-5-alkyl)-amino, hydroxy, C1-5-alkyloxy, mono-, di- or trifluoromethoxy, carboxy- and C1-5-alkyloxycarbonyl groups,
• a phenyl-C1-5-alkyl or heteroaryl-C1-5-alkyl group,
• which may optionally be mono- to trisubstituted in the phenyl or heteroaryl moiety by identical or different substituents selected from among halogen atoms, C1-5-alkyl, di-(C1-5-alkyl)-amino, hydroxy, C1-5-alkyloxy, mono-, di- or trifluoromethoxy, carboxy- and C1-5-alkyloxycarbonyl groups, and which may optionally be substituted in the C1-5-alkyl moiety by a hydroxy, a C1-5-alkyloxy group, while the hydrogen atoms of the C1-5-alkyloxy group may optionally be wholly or partly replaced by fluorine atoms, an allyloxy, propargyloxy, benzyloxy, C1-5-alkylcarbonyloxy, C1-5-alkyloxycarbonyloxy, carboxy-C1-5-alkyloxy, or a C1-5-alkyloxycarbonyl-C1-5-alkyloxy group,
• a 3- to 7-membered cycloalkyl, cycloalkyleneimino, cycloalkyl-C1-5-alkyl or cycloalkyleneimino-C1-3-alkyl group,
• wherein in 4- to 7-membered cyclic groups in the cyclic moiety a methylene group may optionally be replaced by an —N(R7) group, an oxygen or sulphur atom or a —S(O) or —S(O)2 group, or
• wherein in 4- to 7-membered cyclic groups in the cyclic moiety two adjacent methylene groups together may optionally be replaced by a —C(O)N(R8) or —S(O)2N(R8) group, or
• wherein in 6- to 7-membered cyclic groups in the cyclic moiety three adjacent methylene groups together may optionally be replaced by a substituted —OC(O)N(R8) or —N(R8)C(O)N(R8) or —N(R8)S(O)2N(R8) group,
• with the proviso that a 3- to 7-membered cycloalkyl, cycloalkyleneimino, cycloalkyl-C1-5-alkyl or cycloalkyleneimino-C1-3-alkyl group as hereinbefore defined wherein two heteroatoms selected from oxygen and nitrogen are separated from one another by precisely one optionally substituted —CH2 group, is excluded,
• while a 3- to 7-membered cycloalkyl, cycloalkyleneimino, cycloalkyl-C1-5-alkyl or cycloalkyleneimino-C1-3-alkyl group as hereinbefore defined may be substituted at one or two —CH2 groups by one or two C1-3-alkyl groups in each case,
• with the proviso that R4 and R5 may not simultaneously be defined as hydroxy or OR9 groups, or
• R4 and R5 together with the carbon atom to which they are bound form a C3-8-cycloalkyl or C3-8-cycloalkenyl group,
• while one of the methylene groups of a C4-8-cycloalkyl group may be replaced by an oxygen or sulphur atom or a —N(R7), or a carbonyl, sulphinyl or sulphonyl group, and/or
• two directly adjacent methylene groups of a C4-8-cycloalkyl group may together be replaced by a —C(O)N(R8) or —S(O)2N(R8) group, and/or
• three directly adjacent methylene groups of a C6-8-cycloalkyl group may together be replaced by a —OC(O)N(R8), —N(R8)C(O)N(R8) or —N(R8)S(O)2N(R8) group,
• while 1 to 3 carbon atoms of a C3-8-cycloalkyl group may optionally be substituted independently of one another by in each case one or two identical or different halogen atoms or C1-5-alkyl, nitrile, hydroxy, C1-5-alkyloxy, C1-5-alkylcarbonyloxy, carboxy-C1-5-alkyl, C1-5-alkyloxycarbonyl-C1-5-alkyl, C1-5-alkylsulphanyl, C1-5-alkylsulphonyl, carboxy, C1-5-alkyloxycarbonyl, aminocarbonyl, C1-5-alkylaminocarbonyl, di-(C1-5-alkyl)-aminocarbonyl, C3-6-cycloalkyleneiminocarbonyl, aminosulphonyl, C1-5-alkylaminosulphonyl, di-(C1-5-alkyl)-aminosulphonyl, C3-6-cycloalkyleneiminosulphonyl, amino, C1-5-alkylamino, di-(C1-5-alkyl)-amino, C1-5-alkylcarbonylamino, C1-5-alkylsulphonylamino, N—(C1-5-alkylsulphonyl)-C1-5-alkylamino or C3-6-cycloalkylcarbonylamino groups,
• while 1 to 2 carbon atoms of a C3-8-cycloalkenyl group may optionally be substituted independently of one another by in each case a C1-5-alkyl, nitrile, carboxy-C1-5-alkyl, C1-5-alkyloxycarbonyl-C1-5-alkyl, carboxy, C1-5-alkyloxycarbonyl, aminocarbonyl, C1-5-alkylaminocarbonyl, di-(C1-5-alkyl)-aminocarbonyl, C3-6-cycloalkyleneiminocarbonyl, aminosulphonyl, C1-5-alkylaminosulphonyl, di-(C1-5-alkyl)-aminosulphonyl, C3-6-cycloalkyleneiminosulphonyl groups,
• and 1 to 2 carbon atoms of a C4-8-cycloalkenyl group which are not linked to another carbon atom by a double bond, may optionally be substituted independently of one another by a fluorine atom or a hydroxy, C1-5-alkyloxy, C1-5-alkylcarbonyloxy, C1-5-alkylsulphanyl, C1-5-alkylsulphonyl, amino, C1-5-alkylamino, di-(C1-5-alkyl)-amino, C1-5-alkylcarbonylamino, C1-5-alkylsulphonylamino, N—(C1-5-alkylsulphonyl)-C1-5-alkylamino or C3-6-cycloalkylcarbonylamino groups,
• with the proviso that a C3-8-cycloalkyl or C3-8-cycloalkenyl group of this kind formed from R4 and R5 together,
• wherein two heteroatoms in the cyclic group comprising oxygen and nitrogen are separated from one another by precisely one optionally substituted —CH2 group, and/or
• wherein one or both methylene groups of the cyclic group which are directly connected to the carbon atom to which the groups R4 and R5 are bound, are replaced by a heteroatom selected from among oxygen, nitrogen and sulphur, and/or
• wherein a substituent bound to the cyclic group, which is characterised in that a heteroatom selected from among oxygen, nitrogen, sulphur and halogen atom is bound directly to the cyclic group, is separated from another heteroatom selected from among oxygen, nitrogen and sulphur, with the exception of the sulphone group, by precisely one optionally substituted methylene group, and/or
• wherein two oxygen atoms are directly joined together,
• is excluded,
• R7 in each case independently of one another denotes a hydrogen atom, a hydroxy, a formyl, a C1-5-alkyl, C1-5-alkylcarbonyl, C1-5-alkyloxycarbonyl or C1-5-alkylsulphonyl group,
• R8 in each case independently of one another denotes a hydrogen atom or a C1-5-alkyl group,
• R9 denotes a straight-chain or branched C1-6-alkyl group,
• while the hydrogen atoms of the straight-chain or branched C1-6-alkyl group may optionally be wholly or partly replaced by fluorine atoms, and which may optionally be substituted by a C3-5-cycloalkyl group, a hydroxy, a C1-5-alkyloxy group, while the hydrogen atoms of the C1-5-alkyloxy group may optionally be wholly or partly replaced by fluorine atoms, an allyloxy, propargyloxy, benzyloxy, C1-5-alkylcarbonyloxy, C1-5-alkyloxycarbonyloxy, carboxy-C1-5-alkyloxy, C1-5-alkyloxycarbonyl-C1-5-alkyloxy, carboxy, C1-5-alkyloxycarbonyl, aminocarbonyl, C1-5-alkylaminocarbonyl, di-(C1-5-alkyl)-aminocarbonyl, C4-6-cycloalkyleneiminocarbonyl, C1-5-alkyloxycarbonylamino, amino, C1-5-alkylamino, di-(C1-5-alkyl)-amino, C1-5-alkylcarbonylamino, C1-5-alkylsulphonylamino, N—(C1-5-alkylsulphonyl)-C1-5-alkylamino or C3-6-cycloalkylcarbonylamino group,
• while the 6- to 7-membered cyclic groups of the C4-6-cycloalkyleneiminocarbonyl group in the cyclic moiety a methylene group in the 4-position of a 6- or 7-membered cycloalkyleneimino group may be replaced by an oxygen or sulphur atom, by a carbonyl, sulphinyl, sulphonyl or —NR7 group and additionally a methylene group adjacent to an above-mentioned —NR7 group may be replaced by a carbonyl group,
• with the proviso that replacement of hydrogen atoms of the first carbon atom of the straight-chain or branched C1-6-alkyl group by substituents from the group comprising oxygen, sulphur or nitrogen is excluded,
• a phenyl, heteroaryl, phenyl-C1-5-alkyl or heteroaryl-C1-5-alkyl group,
• which may optionally be mono- to trisubstituted in the phenyl or heteroaryl moiety by identical or different substituents selected from among halogen atoms, C1-5-alkyl, di-(C1-5-alkyl)-amino, hydroxy, C1-5-alkyloxy, mono-, di- or trifluoromethoxy, carboxy- and C1-5-alkyloxycarbonyl groups,
• a 3- to 7-membered cycloalkyl, cycloalkyl-C1-5-alkyl or cycloalkyleneimino-C2-3-alkyl group,
• wherein in 4- to 7-membered cyclic groups in the cyclic moiety a methylene group may optionally be replaced by a —N(R7) group, an oxygen or sulphur atom or a —S(O) or —S(O)2 group, or
• wherein in 4- to 7-membered cyclic groups in the cyclic moiety two adjacent methylene groups together may optionally be replaced by a —C(O)N(R8) or —S(O)2N(R8) group, or
• wherein in 6- to 7-membered cyclic groups in the cyclic moiety three adjacent methylene groups together may optionally be replaced by a substituted —OC(O)N(R8) or —N(R8)C(O)N(R8) or —N(R8)S(O)2N(R8) group,
• with the proviso that a 3- to 7-membered cycloalkyl, cycloalkyl-C1-5-alkyl or cycloalkyleneimino-C2-3-alkyl group as hereinbefore defined wherein two heteroatoms selected from oxygen and nitrogen are separated from one another by precisely one optionally substituted —CH2 group, is excluded,
• while a 3- to 7-membered cycloalkyl, cycloalkyl-C1-5-alkyl or cycloalkyleneimino-C2-3-alkyl group as hereinbefore defined may be substituted at one or two —CH2 groups by one or two C1-3-alkyl groups in each case,
• B denotes a group of general formula
• Y denotes a nitrogen atom or a CH— group,
• R6 denotes a hydrogen, a halogen atom, a nitrile group, a C2-3-alkenyl, C2-3-alkynyl, a C1-3-alkyl group, or a C1-3-alkoxy group, while the hydrogen atoms of the C1-3-alkyl or C1-3-alkoxy group may optionally be wholly or partly replaced by fluorine atoms,
• while, unless otherwise stated, by the “heteroaryl group” mentioned hereinbefore in the definitions is meant a monocyclic 5- or 6-membered heteroaryl group, while
• the 6-membered heteroaryl group contains one, two or three nitrogen atoms and
• the 5-membered heteroaryl group contains an imino group optionally substituted by a C1-3-alkyl, phenyl or phenyl-C1-3-alkyl group, or an oxygen or sulphur atom or
• an imino group optionally substituted by a C1-3-alkyl, phenyl, amino-C2-3-alkyl, C1-3-alkylamino-C2-3-alkyl, di-(C1-3-alkyl)-amino-C2-3-alkyl, a C3-6-cycloalkyleneimino-C1-3-alkyl or phenyl-C1-3-alkyl group or an oxygen or sulphur atom and additionally a nitrogen atom or
• an imino group optionally substituted by a C1-3-alkyl or phenyl-C1-3-alkyl group and two or three nitrogen atoms,
• and moreover a phenyl ring optionally substituted by a fluorine, chlorine or bromine atom, a C1-3-alkyl, hydroxy, C1-3-alkyloxy group, amino, C1-3-alkylamino, di-(C1-3-alkyl)-amino or C3-6-cycloalkyleneimino group may be fused to the above-mentioned monocyclic heteroaryl groups via two adjacent carbon atoms
• and the bond is effected via a nitrogen atom or a carbon atom of the heterocyclic moiety or a fused-on phenyl ring,
• while, unless otherwise stated, by the term “halogen atom” mentioned hereinbefore in the definitions is meant an atom selected from among fluorine, chlorine, bromine and iodine,
• while the alkyl, alkenyl, alkynyl and alkoxy groups contained in the afore-mentioned definitions which have more than two carbon atoms may unless otherwise stated be straight-chain or branched and the alkyl groups in the previously mentioned dialkylated groups, for example the dialkylamino groups, may be identical or different,
• and the hydrogen atoms of the methyl or ethyl groups contained in the foregoing definitions, unless stated to the contrary, may be wholly or partly replaced by fluorine atoms,
• or a tautomer or salt thereof.