Novel substituted thiophenecarboxamides, their preparation and their use as medicaments

A compound of the formula

• wherein:
• A is a group of the formula
• in which
• m is the number 1 or 2,
• R8a is in each case independently of one another a hydrogen or halogen atom or a C1-5-alkyl, hydroxy, hydroxy-C1-5-alkyl, C1-5-alkoxy, C1-5-alkoxy-C1-5-alkyl, amino, C1-5-alkylamino, di-(C1-5-alkyl)-amino, amino-C1-5-alkyl, C1-5-alkylamino-C1-5-alkyl, di-(C1-5-alkyl)-amino-C1-5-alkyl, aminocarbonyl, C1-5-alkylaminocarbonyl, di-(C1-5-alkyl)-aminocarbonyl or C1-5-alkylcarbonylamino group, where in the aforementioned substituted 5- to 7-membered groups A, the heteroatoms F, Cl, Br, I, O or N which may optionally be introduced as substituents with R8a, are not separated by exactly one carbon atom from a heteroatom from the group of N, O, S,
• R8b is in each case independently of one another a hydrogen atom or a C1-5-alkyl group,
• X1 is a carbonyl, thiocarbonyl, C═NR8c, C═N—OR8c, C═N—NO2, C═N—CN or sulphonyl group,
• R8c is in each case independently of one another a hydrogen atom, a C1-5-alkyl, C1-5-alkylcarbonyl, C1-5-alkyloxycarbonyl or C1-5-alkylsulphonyl group,
• X2 is an oxygen atom or an —NR8b-group, where R8b is as defined above,
• X3 is a carbonyl, thiocarbonyl, C═NR8c, C═N—OR8c, C═N—NO2, C═N—CN or sulphonyl group, where R8c is as defined above,
• X4 is an oxygen or sulphur atom or an —NR8c-group, where R8c is as defined above,
• Ar is an aromatic ring selected from the group of phenyl, pyridyl, pyrimidinyl, thienyl, thiazolyl, pyrazolyl, pyrrolyl,
• R1 is a hydrogen or a halogen atom, a C1-3-alkyl or C1-3-alkoxy group, where the hydrogen atoms of the C1-3-alkyl or C1-3-alkoxy group may optionally be wholly or partly replaced by fluorine atoms, or a C2-3-alkenyl, C2-3-alkynyl, nitrile, nitro or amino group,
• R2 is a hydrogen or halogen atom or a C1-3-alkyl group,
• R3 is a hydrogen atom or a C1-3-alkyl group,
• R4 and R5 are each independently of one another
• a hydrogen atom, a C2-6-alkenyl or C2-6-alkynyl group,
• a straight-chain or branched C1-6alkyl group,
• where 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 (1-5-alkyloxy group, where the hydrogen atoms of the C1-5-alkyloxy group may optionally be replaced wholly or partly by fluorine atoms, or an allyloxy, propargyloxy, benzyloxy, C1-5-alkylcarbonyloxy, C1-5-alkoxycarbonyloxy, carboxy-C1-5-alkyloxy, C1-5-alkyloxycarbonyl-C1-5-alkyloxy, mercapto, C1-5-alkylsulphanyl, C1-5-alkylsulphinyl, C1-5-alkylsulphonyl, carboxy, C1-5-alkyloxycarbonyl, aminocarbonyl, C1-5-alkylaminocarbonyl, di-(C1-5-alkyl)-aminocarbonyl, C3-6-cycloalkyleniminocarbonyl, aminosulphonyl, C1-5-alkylaminosulphonyl, di-(C1-5-alkyl)-aminosulphonyl, C3-6-cycloalkyleniminosulphonyl, di-(C1-5-alkyl)-phosphoryl, 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-cycloalkyl-carbonylamino group,
• a carboxy, aminocarbonyl, C1-5-alkylaminocarbonyl, C3-6-cycloalkylaminocarbonyl, di-(C1-5-alkyl)-aminocarbonyl, C1-5-alkoxycarbonyl, C4-6cycloalkyleniminocarbonyl group,
• a phenyl, heteroaryl, phenyl-C1-5-alkyl or heteroaryl-C1-5-alkyl group,
• which may optionally be substituted in the phenyl or heteroaryl moiety once to three times by identical or different substituents selected from the group consisting of halogen atoms, C1-5-alkyl, trifluoromethyl, amino, C1-5-alkylamino, 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, cycloalkylenimino, cycloalkyl-C1-5-alkyl or cycloalkylenimino-C1-3-alkyl group,
• in which in the case of 4- to 7-membered rings a methylene group in the cyclic moiety may optionally be replaced by an —N(R8c) group, an oxygen or sulphur atom or an —S(O)— or —S(O)2-group, where R8c is as defined above, or
• in which in the case of 4- to 7-membered rings two adjacent methylene groups in the cyclic moiety may together optionally be replaced by a —C(O)N(R8b)— or —S(O)2N(R8b)-group, where R8b is as defined above, or
• in which in the case of 6- to 7-membered rings three adjacent methylene groups in the cyclic moiety may together optionally be replaced by a substituted —OC(O)N(R8b)— or —N(R8b)C(O)N(R8b) or —N(R8b)S(O)2N(R8b)-group, where R8b is as defined above,
• with the proviso that a 3- to 7-membered cycloalkyl, cycloalkylenimino, cycloalkyl-C1-5-alkyl or cycloalkylenimino-C1-3-alkyl group as defined above, in which two heteroatoms from the group of oxygen and nitrogen are separated from one another by exactly one optionally substituted —CH2-group, is excluded,
• where a 3- to 7-membered cycloalkyl, cycloalkylenimino, cycloalkyl-C1-5-alkyl or cycloalkylenimino-C1-3-alkyl group as defined above may be substituted on one or two —CH2-groups by in each case one or two C1-3-alkyl groups, or
• R4 and R5 together with the carbon atom to which they are bonded form a C3-8-cycloalkyl or C3-8-cycloalkenyl group,
• where one of the methylene groups of a C4-8-cycloalkyl group may be replaced by an oxygen or sulphur atom or an —N(R8c)— or a carbonyl, sulphinyl or sulphonyl group, where R8c is as defined above, and/or
• two directly adjacent methylene groups of a C4-8-cycloalkyl group may together be replaced by a —C(O)N(R8b)— or —S(O)2N(R8b)-group, where R8b is as defined above, and/or
• three directly adjacent methylene groups of a C6-8-cycloalkyl group may together be replaced by a —OC(O)O—, —OC(O)N(R8b)—, —N(R8b)C(O)N(R8b)— or —N(R8b)S(O)2N(R8bb)-group, where R8b is as defined above,
• where 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-alkyl-sulphanyl, C1-5-alkylsulphonyl, carboxy, C1-5-alkyloxycarbonyl, aminocarbonyl, C1-5-alkylaminocarbonyl, di-(C1-5-alkyl)-aminocarbonyl, C3-6-cycloalkyleniminocarbonyl, aminosulphonyl, C1-5-alkylaminosulphonyl-, di-(C1-5-alkyl)-aminosulphonyl, C3-6-cycloalkyleniminosulphonyl, amino-, C1-5-alkylamino, di-(C1-5-alkyl)-amino, C1-5-alkylcarbonylamino, C1-5-alkyl-sulphonylamino, N—(C1-5-alkylsulphonyl)-C1-5-alkylamino or C3-6-cycloalkylcarbonylamino group,
• where 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-cycloalkyleniminocarbonyl, aminosulphonyl, C1-5-alkylaminosulphonyl, di-(C1-5-alkyl)-aminosulphonyl, C3-6-cycloalkyleniminosulphonyl group,
• and 1 to 2 carbon atoms of a C4-8-cycloalkenyl group which are not linked by a double bond to another carbon atom 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-alkyl-sulphonylamino, N—(C1-5-alkylsulphonyl)-C1-5-alkylamino or C3-6-cycloalkylcarbonylamino group,
• with the proviso that such a C3-8-cycloalkyl or C3-8-cycloalkenyl group which is formed together from R4 and R5,
• in which two heteroatoms in the ring selected from the group of oxygen and nitrogen are separated from one another by exactly one optionally substituted —CH2-group, and/or
• in which one or both methylene groups in the ring which are directly connected to the carbon atom to which the groups R4 and R5 are attached are replaced by a heteroatom from the group of oxygen, nitrogen and sulphur, and/or
• in which a substituent which is linked to the cyclic group, and which is distinguished by a heteroatom from the group of oxygen, nitrogen, sulphur and halogen atom being directly linked to the cyclic group, is separated from another heteroatom from the group of oxygen, nitrogen and sulphur, with the exception of the sulphone group, by exactly one optionally substituted methylene group, and/or
• in which two oxygen atoms are directly connected together,
• is excluded,
• where, unless otherwise mentioned, the term “heteroaryl group” mentioned above in the definitions means a monocyclic 5- or 6-membered heteroaryl group, where
• the 6-membered heteroaryl group comprises one, two or three nitrogen atoms and
• the 5-membered heteroaryl group comprises an imino group which is optionally substituted by a C1-3-alkyl, phenyl or phenyl-C1-3-alkyl group, or an oxygen or sulphur atom or
• an imino group which is 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-cycloalkylenimino-C1-3-alkyl or phenyl-C1-3-alkyl group, or an oxygen or sulphur atom and additionally a nitrogen atom or
• an imino group which is optionally substituted by a C1-3-alkyl or phenyl-C1-3-alkyl group, and two or three nitrogen atoms,
• and additionally a phenyl ring which is 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-cycloalkylenimino group may be fused to the aforementioned monocyclic heteroaryl groups via two adjacent carbon atoms,
• and the linkage takes place via a nitrogen atom or via a carbon atom of the heterocyclic moiety or of a fused phenyl ring,
• where, unless otherwise mentioned, the term “halogen atom” mentioned above in the definitions means an atom from the group of fluorine, chlorine, bromine and iodine,
• where the alkyl, alkenyl, alkynyl and alkoxy groups which are present in the aforementioned definitions and which have more than two carbon atoms may, unless otherwise mentioned, be straight-chain or branched, and the alkyl groups in the aforementioned dialkylated groups, for example the dialkylamino groups, may be identical or different,
• and where the hydrogen atoms in the methyl or ethyl groups present in the aforementioned definitions may, unless otherwise mentioned, be wholly or partly replaced by fluorine atoms,
• or a tautomer or salt thereof.