Substituted glycinamides, process for their manufacture and use thereof as medicaments

Abstract

The present invention relates to new substituted glycinamides of general formula (I) wherein D, M, R 3 , R 4 and R 5 are defined as in the specification, the tautomers, enantiomers, diastereomers, mixtures and salts thereof, particularly the physiologically acceptable salts thereof with inorganic or organic acids or bases, which have valuable properties.

1 . Compounds of general formula (I) 
     
       
         
         
             
             
         
       
     
     wherein 
     D denotes a substituted bicyclic ring system of formula (II), 
     
       
         
         
             
             
         
       
       wherein 
       K 1  and K 4  
 each independently of one another denote a —CH 2 , —CHR 7a , —CR 7b R 7c  or a —C(O) group, and 
 R 7a /R 7b /R 7c  
 each independently of one another denote a fluorine atom, a hydroxy, C 1-5 -alkyloxy, tetrahydrofuranyl, oxetanyl, amino, C 1-5 -alkylamino, di-(C 1-5 -alkyl)-amino, C 3-5 -cycloalkyleneimino or C 1-5 -alkylcarbonylamino group, a C 1-5 -alkyl group which may be substituted by 1-3 fluorine atoms, a hydroxy-C 1-5 -alkyl, C 1-5 -alkyloxy-C 1-5 -alkyl, amino-C 1-5 -alkyl, C 1-5 -alkylamino-C 1-5 -alkyl, di-(C 1-5 -alkyl)-amino-C 1-5 -alkyl, C 4-7 -cycloalkyleneimino-C 1-5 -alkyl, carboxy-C 0-5 -alkyl, C 1-5 -alkyloxycarbonyl-C 0-5 -alkyl, aminocarbonyl-C 0-5 -alkyl, C 1-5 -alkylaminocarbonyl-C 0-5 -alkyl, di-(C 1-5 -alkyl)-aminocarbonyl-C 0-5 -alkyl, C 4-7 -cycloalkyleneiminocarbonyl-C 0-5 -alkyl-group, 
 a phenyl group or a 5- or 6-membered heteroaryl group which may be substituted by 1-2 substituents selected from among a nitro, amino, hydroxy, methoxy, cyano, C 1-5 -alkyl group or a fluorine, chlorine or bromine atom,
 wherein the two groups R 7b /R 7c  cannot both simultaneously be bound to the cyclic carbon atom via a heteroatom, except if —C(R 7b R 7c )— corresponds to a —CF 2  group, 
 
 or 
 two groups R 7b /R 7c  together with the cyclic carbon atom may form a 3, 4, 5-, 6- or 7-membered saturated carbocyclic group or a cyclopentene, cyclohexene, oxetane, azetidine, thietane, tetrahydrofuran, pyrrolidine, tetrahydrothiophene, tetrahydropyran, piperidine, pentamethylene sulphide, hexamethyleneimine, 1,3-dioxolane, 1,4-dioxane, hexahydropyridazine, piperazine, thiomorpholine, morpholine, 2-imidazolidinone, 2-oxazolidinone, tetrahydro-2(1H)-pyrimidinone, [1,3]oxazinan-2-one ring,
 wherein the methylene groups thereof may be substituted by 1-2 C 1-3 -alkyl or CF 3 — groups, and/or 
 the methylene groups thereof, if they are not bound to a heteroatom, may be substituted by 1-2 fluorine atoms, and/or 
 wherein a —CH 2  group adjacent to an N atom may be replaced by a —CO group, and/or 
 the imino groups of which may be substituted in each case by a C 1-3 -alkyl or C 1-3 -alkylcarbonyl group, and/or 
 wherein the sulphur atom may be oxidised to form a sulphoxide or sulphone group, 
 
 
 
       K 2  and K 3  
 each independently of one another denote a —CH 2 , —CHR 8a , —CR 8b R 8c  or a —C(O)— group, and 
 R 8a /R 8b /R 8c  
 each independently of one another denote a C 1-5 -alkyl group which may be substituted by 1-3 fluorine atoms, a hydroxy-C 1-5 -alkyl, C 1-5 -alkyloxy-C 1-5 -alkyl, amino-C 1-5 -alkyl, C 1-5 -alkylamino-C 1-5 -alkyl, di-(C 1-5 -alkyl)-amino-C 1-5 -alkyl, C 4-7 -cycloalkyleneimino-C 1-5 -alkyl, carboxy-C 0-5 -alkyl, C 1-5 -alkyloxycarbonyl-C 0-5 -alkyl, aminocarbonyl-C 0-5 -alkyl, C 1-5 -alkylaminocarbonyl-C 0-5 -alkyl, di-(C 1-5 -alkyl)-aminocarbonyl-C 0-5 -alkyl, C 4-7 -cycloalkyleneiminocarbonyl-C 0-5 -alkyl group, 
 or two groups R 8b /R 8c  together with the cyclic carbon atom may form a 3, 4, 5-, 6- or 7-membered saturated carbocyclic group or a cyclopentene, cyclohexene, oxetane, azetidine, thietane, tetrahydrofuran, pyrrolidine, tetrahydrothiophene, tetrahydropyran, piperidine, pentamethylene sulphide, hexamethyleneimine, hexahydropyridazine, tetrahydro-2(1H)-pyrimidinone, [1,3]oxazinan-2-one ring,
 wherein the methylene groups thereof may be substituted by 1-2 C 1-3 -alkyl or CF 3 — groups, and/or 
 the methylene groups thereof, if they are not bound to a heteroatom, may be substituted by 1-2 fluorine atoms, and/or 
 wherein a —CH 2  group next to a nitrogen atom may be replaced by a —CO group, and/or 
 the imino groups of which may be substituted in each case by a C 1-3 -alkyl or C 1-3 -alkylcarbonyl group, and/or 
 wherein the sulphur atom may be oxidised to form a sulphoxide or sulphone group, 
 with the proviso that a heteroatom introduced by R 8b  or R 8c  may not be separated from X in formula (I) by only one carbon atom, and 
 
 
 
       in all there should be no more than four groups selected from among R 7a , R 7b , R 7c , R 8a , R 8b  and R 8c  in formula (II), and 
       X denotes an oxygen or sulphur atom, a sulphene, sulphone or an
 NR 1  group, wherein 
 R 1  denotes a hydrogen atom or a hydroxy, C 1-3 -alkyloxy, amino, C 1-3 -alkylamino, di-(C 1-3 -alkyl)-amino, a C 1-5 -alkyl, C 2-5 -alkenyl-CH 2 , C 2-5 -alkynyl-CH 2 , C 3-6 -cycloalkyl, C 4-6 -cycloalkenyl, oxetan-3-yl, tetrahydrofuran-3-yl, benzyl, C 1-5 -alkyl-carbonyl, trifluoromethylcarbonyl, C 3-6 -cycloalkyl-carbonyl, C 1-5 -alkyl-sulphonyl, C 3-6 -cycloalkyl-sulphonyl, aminocarbonyl, C 1-5 -alkylaminocarbonyl, di-(C 1-5 -alkyl)-aminocarbonyl, C 1-5 -alkyloxycarbonyl, C 4-7 -cycloalkyleneiminocarbonyl group,
 wherein the methylene and methyl groups present in the above-mentioned groups may additionally be substituted by a C 1-3 -alkyl, carboxy, C 1-5 -alkoxycarbonyl group or by a hydroxy, C 1-5 -alkyloxy, amino, C 1-5 -alkylamino, C 1-5 -dialkylamino or C 4-7 -cycloalkyleneimino group, provided that the methylene or methyl groups are not directly bound to a heteroatom selected from among O, N or S, and/or 
 one to three hydrogen atoms may be replaced by fluorine atoms, provided that the methylene or methyl groups are not directly bound to a heteroatom selected from among O, N or S, 
 
 
       and wherein 
       A 1  denotes either N or Ce, 
       A 2  denotes either N or CR 11 , 
       A 3  denotes either N or CR 12 , 
       wherein R 10 , R 11 , and R 12  each independently of one another represent
 a hydrogen, fluorine, chlorine, bromine or iodine atom, or a C 1-5 -alkyl, CF 3 , C 2-5 -alkenyl, C 2-5 -alkynyl, a cyano, carboxy, C 1-5 -alkyloxycarbonyl, hydroxy, C 1-3 -alkyloxy, CF 3 O, CHF 2 O, CH 2 FO, amino, C 1-5 -alkylamino, di-(C 1-5 -alkyl)-amino or C 4-7 -cycloalkyleneimino group, or 
 
     
     D denotes one of the four groups (II-1), (II-2), (II-3) or (II-4) 
     
       
         
         
             
             
         
       
       wherein the groups A1, A2, A3, K1, K2, K3, K4 are as hereinbefore defined, and Anion in (II-4) denotes a fluoride, chloride, bromide, iodide, sulphate, hydrogen sulphate, phosphate, hydrogen phosphate, benzoate, salicylate, succinate, citrate or tartrate, 
     
     R 3  denotes a hydrogen atom or a C 1-3 -alkyl group, and 
     R 4  and R 5  each independently of one another represent
 a hydrogen atom, 
 a straight-chain or branched C 1-6 -alkyl, C 2-6 -alkenyl or C 2-6 -alkynyl group,
 wherein the hydrogen atoms of the methylene and/or methyl fragments of the straight-chain or branched C 1-6 -alkyl, C 2-6 -alkenyl or C 2-6 -alkynyl group may optionally be wholly or partly replaced by fluorine atoms, and/or 
 one or two hydrogen atoms of the straight-chain or branched C 1-6 -alkyl, C 2-6 -alkenyl or C 2-6 -alkynyl group in their methylene and/or methyl fragments may optionally each be replaced independently of one another by a C 3-7 -cycloalkyl group, a nitrile, hydroxy or C 1-5 -alkyloxy group,
 wherein the hydrogen atoms of the C 1-5 -alkyloxy group may optionally be 
 wholly or partly replaced by fluorine atoms, 
 
 an allyloxy, propargyloxy, phenylmethyloxy, phenethyloxy, C 1-5 -alkylcarbonyloxy, C 1-5 -alkyloxycarbonyloxy, carboxy-C 1-5 -alkyloxy, C 1-5 -alkyloxycarbonyl-C 1-5 -alkyloxy, C 1-5 -alkyloxy-C 2-5 -alkyloxy, mercapto, C 1-5 -alkylsulphanyl, C 1-5 -alkylsulphinyl, C 1-5 -alkylsulphonyl, carboxy, C 1-5 -alkyloxycarbonyl, aminocarbonyl, C 1-5 -alkylaminocarbonyl, di-(C 1-5 -alkyl)-aminocarbonyl, C 1-5 -alkyl-aminocarbonyloxy, di-(C 1-5 -alkyl)-aminocarbonyloxy, C 4-7 -cycloalkyleneiminocarbonyl, aminosulphonyl, C 1-5 -alkylaminosulphonyl, di-(C 1-5 -alkyl)-aminosulphonyl, C 4-7 -cycloalkyleneiminosulphonyl, di-(C 1-5 -alkyl)-phosphoryl, amino, C 1-5 -alkylamino, di-(C 1-5 -alkyl)-amino, C 1-5 -alkylcarbonylamino, trifluoracetylamino, C 1-5 -alkyloxy-C 1-5 -alkylcarbonylamino, phenylcarbonylamino, C 1-5 -alkylaminocarbonylamino, di-(C 1-5 -alkyl)-aminocarbonylamino, C 1-5 -alkyloxy-carbonylamino, phenylmethyloxy-carbonylamino, C 1-5 -alkyloxy-C 2-5 -alkyloxy-C 1-2 -alkylcarbonylamino, C 1-5 -alkylsulphonylamino, N—(C 1-5 -alkylsulphonyl)-C 1-5 -alkylamino, C 3-6 -cycloalkylcarbonylamino group, 4-morpholinocarbonylamino, or a morpholinyl, thiomorpholinyl, pyrrolidinyl, piperidinyl, piperazinyl, tetrahydrofuranyl, tetrahydropyranyl group,
 wherein the above-mentioned carbo- and heterocycles in the ring may each be substituted by 1 to 4 C 1-3 -alkyl or C 1-3 -alkylcarbonyl groups or may each be substituted by 1 or 2 oxo groups, and/or 
 the above-mentioned phenyl and heteroaryl groups may be replaced by 1 or 2 substituents selected from among fluorine, chlorine, bromine, methyl, methoxy, amino or trifluoromethyl or two adjacent carbon atoms of a phenyl ring may be substituted by a —CH 2 —O—CH 2  group, and/or the above-mentioned alkyl groups may be substituted by a cyano-C 1-5 -alkyloxycarbonyl or carboxy group, 
 wherein the above-mentioned carboxylic acid or sulphonic acid amide may optionally be additionally substituted at the nitrogen by a C 1-5 -alkyl group, 
 
 and/or the hydrogen atoms of the sp 2 -hybridised carbon atoms of the straight-chain or branched C 2-6 -alkenyl group may optionally be wholly or partly replaced by fluorine atoms, 
 
 a carboxy, aminocarbonyl, C 1-5 -alkylaminocarbonyl, C 3-6 -cycloalkylaminocarbonyl, di-(C 1-5 -alkyl)-aminocarbonyl, C 1-5 -alkyloxycarbonyl, C 4-7 -cycloalkyleneiminocarbonyl group, 
 a phenyl, mono- or bicyclic heteroaryl, phenyl-C 1-5 -alkyl or mono- or bicyclic heteroaryl-C 1-5 -alkyl group,
 which may optionally be mono- to trisubstituted in the phenyl or heteroaryl moiety by identical or different substituents selected from among fluorine, chlorine, bromine and iodine atoms, and C 1-5 -alkyl, trifluoromethyl, benzyl, amino, nitro, C 1-5 -alkyl-amino, di-(C 1-5 -alkyl)-amino, hydroxy, C 1-5 -alkyloxy, mono-, di- or trifluoromethoxy, carboxy- and C 1-5 -alkyloxycarbonyl group, or two adjacent carbon atoms of a phenyl ring may be substituted by a —CH 2 —O—CH 2  group, 
 
 or 
 a C 3-7 cycloalkyl, morpholinyl, thiomorpholinyl, pyrrolidinyl, piperidinyl, piperazinyl, tetrahydrofuranyl, tetrahydropyranyl group,
 which may optionally be substituted by one to two groups selected independently of one another from among C 1-3 -alkyl, acetyl, C 1-5 -alkyloxycarbonyl, and hydroxycarbonyl, or 
 
 
     R 4  and R 5  together with the carbon atom to which they are bound,
 form a C 3-7 -cycloalkyl or C 5-7 -cycloalkenyl group, 
 wherein one of the methylene groups of a C 4-7 -cycloalkyl group may be replaced by an oxygen or sulphur atom or an —NH, —N(C 1-5 -alkyl), —N(C 1-4 -alkylcarbonyl), —N(C 1-4 -alkyloxycarbonyl)- or a carbonyl, sulphinyl or sulphonyl group, and/or 
 two directly adjacent methylene groups of a C 4-7 -cycloalkyl group may together be replaced by a —C(O)NH, —C(O)N(C 1-5 -alkyl), —S(O) 2 NH, or —S(O) 2 N(C 1-5 -alkyl) group, and/or 
 1 to 3 carbon atoms of a C 3-7 -cycloalkyl group may each optionally be substituted independently of one another by one or two fluorine atoms or one or two C 1-5 -alkyl groups or a hydroxy, C 1-5 -alkyloxy, formyloxy, C 1-5 -alkylcarbonyloxy, C 1-5 -alkylsulphanyl, C 1-5 -alkylsulphonyl, aminosulphonyl, C 1-5 -alkylaminosulphonyl, di-(C 1-5 -alkyl)-aminosulphonyl, C 4-7 -cycloalkyleneiminosulphonyl, amino, C 1-5 -alkylamino, di-(C 1-5 -alkyl)-amino, C 1-5 -alkylcarbonylamino, C 1-5 -alkylsulphonylamino, N—(C 1-5 -alkylsulphonyl)-C 1-5 -alkylamino, C 3-6 -cycloalkylcarbonylamino, Nitril, carboxy-C 1-5 -alkyl, C 1-5 -alkyloxycarbonyl-C 1-5 -alkyl, carboxy, C 1-5 -alkyloxycarbonyl, aminocarbonyl, C 1-5 -alkylaminocarbonyl, di-(C 1-5 -alkyl)-aminocarbonyl or C 4-7 -cycloalkyleneiminocarbonyl group, and/or 
 1 to 2 carbon atoms of a C 5-7 -cycloalkenyl group may optionally be substituted independently of one another by in each case a C 1-5 -alkyl, nitrile, carboxy-C 1-5 -alkyl, C 1-5 -alkyloxycarbonyl-C 1-5 -alkyl, carboxy, C 1-5 -alkyloxycarbonyl, aminocarbonyl, C 1-5 -alkylaminocarbonyl, di-(C 1-5 -alkyl)-aminocarbonyl, C 3-6 -cycloalkyleneiminocarbonyl, aminosulphonyl, C 1-5 -alkylaminosulphonyl, di-(C 1-5 -alkyl)-aminosulphonyl, C 3-6 -cycloalkyleneiminosulphonyl groups or 1-2 fluorine atoms, and/or 
 1 to 2 carbon atoms of a C 4-7 -cycloalkenyl group which are not bound to another carbon atom by a double bond, may optionally be substituted independently of one another by a hydroxy, C 1-5 -alkyloxy, C 1-5 -alkylcarbonyloxy, C 1-5 -alkylsulphanyl, C 1-5 -alkylsulphonyl, amino, C 1-5 -alkylamino, di-(C 1-5 -alkyl)-amino, C 1-5 -alkylcarbonylamino, C 1-5 -alkylsulphonylamino, N—(C 1-5 -alkylsulphonyl)-C 1-5 -alkylamino or C 3-6 -cycloalkylcarbonylamino groups, 
 with the proviso that a C 3-7 -cycloalkyl or C 5-7 -cycloalkenyl group of this kind formed from R 4  and R 5  together,
 wherein two heteroatoms in the cyclic group selected from among oxygen and nitrogen are separated from one another by precisely one optionally substituted —CH 2  group, and/or 
 wherein one or both methylene groups of the cyclic group which are joined directly to the carbon atom to which the groups R 4  and R 5  are linked, 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 fluorine is bound directly to the cyclic group, is separated from one other 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 atoms in the ring form an —O—O or —S—O— bond, 
 
 is excluded, 
 
     M denotes a thiophene ring according to formula (III), 
     
       
         
         
             
             
         
       
       which is bound to the carbonyl group in formula (I) via the 2-position and which is substituted the in 5-position by R 2  and optionally additionally by R 6 , wherein 
       R 2  denotes a hydrogen, fluorine, chlorine, bromine or iodine atom or a methoxy, C 1-2 -alkyl, formyl, NH 2 CO or ethynyl group, 
       R 6  denotes a hydrogen, fluorine, chlorine, bromine or iodine atom or a C 1-2 -alkyl or amino group, 
     
     wherein, unless otherwise stated, the term “heteroaryl group” mentioned hereinbefore in the definitions denotes a monocyclic 5- or 6-membered heteroaryl group, wherein
 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 C 1-3 -alkyl group, or an oxygen or sulphur atom, or
 an imino group optionally substituted by a C 1-3 -alkyl group or an oxygen or sulphur atom and additionally one or two nitrogen atoms, or 
 an imino group optionally substituted by a C 1-3 -alkyl group and three nitrogen atoms, 
 
 and moreover a phenyl ring optionally substituted by a fluorine, chlorine or bromine atom, a C 1-3 -alkyl, hydroxy, C 1-3 -alkyloxy group, amino, C 1-3 -alkylamino, di-(C 1-3 -alkyl)-amino or C 3-6 -cycloalkyleneimino group phenyl ring 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, 
 
     and wherein, 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, 
     and wherein the alkyl, alkenyl, alkynyl and alkyloxy groups contained in the previously 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 otherwise stated, may be wholly or partly replaced by fluorine atoms, 
     the tautomers, enantiomers, diastereomers, mixtures and salts thereof. 
   
   
       2 . Compounds of general formula (I) according to  claim 1 , wherein 
     D denotes a substituted bicyclic ring system of formula (II), 
     
       
         
         
             
             
         
       
       wherein 
       K 1  and K 4  
 each independently of one another denote a —CH 2 , —CHR 7a , —CR 7b R 7c  or a —C(O) group, wherein 
 R 7a /R 7b /R 7c  
 each independently of one another denote a fluorine atom, a hydroxy, C 1-5 -alkyloxy group, a C 1-5 -alkyl group which may be substituted by 1-3 fluorine atoms, a hydroxy-C 1-5 -alkyl, C 1-5 -alkyloxy-C 1-5 -alkyl group, or a phenyl group which may be substituted by 1-2 substituents selected from among a nitro, amino, hydroxy-methoxy, cyano, C 1-5 -alkyl group or a fluorine, chlorine or bromine atom, or a 5- or 6-membered heteroaryl group,
 wherein the two groups R 7b /R 7c  cannot both simultaneously be bound to the cyclic carbon atom via a heteroatom, except if —C(R 7b R 7c )— corresponds to a —CF 2  group, or 
 
 two groups R 7b /R 7c  may form, together with the cyclic carbon atom, a 3-, 4-, 5-, 6- or 7-membered saturated carbocyclic group or a cyclopentene, cyclohexene, oxetane, tetrahydrofuran or tetrahydropyran ring,
 wherein the methylene groups thereof may be substituted by 1-2 C 1-3 -alkyl or CF 3 — groups, and/or 
 the methylene groups thereof, if they are not bound to a heteroatom, may be substituted by 1-2 fluorine atoms, and 
 
 
 
       K 2  and K 3  
 each independently of one another represent a —CH 2 , —CHR 8a , —CR 8b R 8c  or a —C(O)— group, and 
 R 8a /R 8b /R 8c  
 each independently of one another denote a C 1-5 -alkyl group which may be substituted by 1-3 fluorine atoms, a hydroxy-C 1-5 -alkyl, C 1-5 -alkyloxy-C 1-5 -alkyl group, 
 or two groups R 8b /R 8c  may form, together with the cyclic carbon atom, a 3-, 4-, 5-, 6- or 7-membered carbocyclic group or a cyclopentene, cyclohexene, oxetane, tetrahydrofuran, tetrahydropyran ring,
 wherein the methylene groups thereof may be substituted by 1-2 C 1-3 -alkyl or CF 3 — groups, and/or the methylene groups thereof, if they are not bound to a heteroatom, may be substituted by 1-2 fluorine atoms, 
 with the proviso that a heteroatom introduced by R 8b  or R 8c  must not be separated from X in formula (I) by only one carbon atom, and 
 
 
 
       in all in formula (II) there should be no more than four groups selected from among R 7a , R 7b , R 7c , R 8a , R 8b  and R 8c , and 
       X denotes an oxygen or sulphur atom, a sulphene, sulphone
 or an NR 1  group, wherein 
 R 1  denotes a hydrogen atom or
 a C 1-5 -alkyl, C 2-5 -alkenyl-CH 2 , C 2-5 -alkynyl-CH 2 , C 3-6 -cycloalkyl, C 4-6 -cycloalkenyl, oxetan-3-yl, tetrahydrofuran-3-yl, benzyl, C 1-5 -alkyl-carbonyl, trifluoromethylcarbonyl, C 3-6 -cycloalkyl-carbonyl, C 1-5 -alkyl-sulphonyl, C 3-6 -cycloalkyl-sulphonyl, aminocarbonyl, C 1-5 -alkylaminocarbonyl, di-(C 1-5 -alkyl)-aminocarbonyl, C 1-5 -alkyloxycarbonyl, C 4-7 -cycloalkyleneiminocarbonyl group,
 wherein the methylene and methyl groups present in the above-mentioned groups may additionally be substituted by a C 1-3 -alkyl, carboxy, C 1-5 -alkoxycarbonyl group or by a hydroxy, C 1-5 -alkyloxy, amino, C 1-5 -alkylamino, C 1-5 -dialkylamino or C 4-7 -cycloalkyleneimino group, provided that the methylene or methyl groups are not directly bound to a heteroatom selected from among O, N or S, and/or 
 one to three hydrogen atoms may be replaced by fluorine atoms, provided that the methylene or methyl groups are not directly bound to a heteroatom selected from among O, N or S, 
 
 
 
       and wherein 
       A 1 , A 2 , and A 3  are each defined as described in the 1st embodiment, or 
     
     D denotes one of the four groups (II-1a), (II-2a), (II-3) or (II-4) 
     
       
         
         
             
             
         
       
       wherein the groups A1, A2, A3, K1, K2, K3, K4 are as hereinbefore defined, and Anion in (II-4) denotes a fluoride, chloride, bromide, iodide, sulphate, hydrogen sulphate, phosphate, hydrogen phosphate, benzoate, salicylate, succinate, citrate or tartrate, 
       and 
     
     R 3  denotes a hydrogen atom, and 
     R 4 , R 5  and M are each defined as described in the 1st embodiment, 
     the tautomers, enantiomers, diastereomers, mixtures and salts thereof. 
   
   
       3 . Compounds of general formula (I) according to  claim 1 , wherein 
     D denotes a substituted bicyclic ring system of formula (II), 
     
       
         
         
             
             
         
       
       wherein 
       K1, K2, K3 and K4 are defined as in  claim 1 , and 
       X denotes an NR 1  group, wherein
 R 1  denotes a hydrogen atom or
 a C 1-5 -alkyl, C 2-5 -alkenyl-CH 2 , C 2-5 -alkynyl-CH 2 , C 3-6 -cycloalkyl, C 4-6 -cycloalkenyl group,
 wherein the methylene and methyl groups present in the above-mentioned groups may additionally be substituted by a C 1-3 -alkyl, carboxy, C 1-5 -alkoxycarbonyl group or by a hydroxy, C 1-5 -alkyloxy, amino, C 1-5 -alkylamino, C 1-5 -dialkylamino or C 4-7 -cycloalkyleneimino group, provided that the methylene or methyl groups are not directly bound to a heteroatom selected from among O, N or S, and/or 
 one to three hydrogen atoms may be replaced by fluorine atoms, so long as the methylene or methyl groups are not directly bound to the nitrogen atom, 
 
 
 
       and wherein 
       A 1  denotes either N or CR 10 , 
       A 2  denotes either N or CR 11 , 
       A 3  denotes either N or CR 12 , 
       wherein R 10 , R 11  and R 12  each independently of one another represent
 a hydrogen, fluorine, chlorine, bromine atom or a C 1-5 -alkyl, CF 3 , a cyano, carboxy, C 1-5 -alkyloxycarbonyl, hydroxy, C 1-3 -alkyloxy, CF 3 O, CHF 2 O, CH 2 FO— group, or 
 
     
     D denotes one of the four groups (II-1a), (II-2a), (II-3) or (II-4) 
     
       
         
         
             
             
         
       
       wherein the groups A1, A2, A3, K1, K2, K3, K4 are as hereinbefore defined, and Anion in (II-4) may be selected from among fluoride, chloride, bromide, iodide, sulphate, phosphate, benzoate, salicylate, succinate, citrate and tartrate, and 
     
     R 3 , R 4 , R 5  and M are each defined as in 1, wherein R 6  denotes a hydrogen atom, 
     the tautomers, enantiomers, diastereomers, mixtures and salts thereof. 
   
   
       4 . Compounds of general formula (I) according to  claim 1 , wherein
 D, R 3  and M are each defined as in  claim 1 , and   R 4  denotes a straight-chain or branched C 3-6 -alkenyl or C 3-6 -alkynyl group,
 a straight-chain or branched C 1-6 -alkyl group,
 wherein the hydrogen atoms of the straight-chain or branched C 1-6 -alkyl group may optionally be wholly or partly replaced by fluorine atoms, 
 and wherein optionally one to two hydrogen atoms may be replaced independently of one another by a C 3-7 -cycloalkyl, hydroxy, C 1-5 -alkyloxy, phenylmethyloxy, phenethyloxy, carboxy-C 1-5 -alkyloxy, C 1-5 -alkyloxycarbonyl-C 1-5 -alkyloxy, C 1-5 -alkyloxy-C 2-5 -alkyloxy, C 1-5 -alkylsulphanyl, C 1-5 -alkylsulphinyl, C 1-5 -alkylsulphonyl, carboxy, C 1-5 -alkyloxycarbonyl, aminocarbonyl, C 1-5 -alkylaminocarbonyl, di-(C 1-5 -alkyl)-aminocarbonyl, C 1-5 -alkyl-aminocarbonyloxy, di-(C 1-5 -alkyl)-aminocarbonyloxy, C 4-7 -cycloalkyleneiminocarbonyl, amino, C 1-5 -alkylamino or di-(C 1-5 -alkyl)-amino group C 1-5 -alkylcarbonylamino, trifluoracetylamino, C 1-5 -alkyloxy-C 1-5 -alkylcarbonylamino, phenylcarbonylamino, C 1-5 -alkylaminocarbonylamino, di-(C 1-5 -alkyl)-aminocarbonylamino, C 1-5 -alkyloxy-carbonylamino, phenylmethyloxy-carbonylamino, C 1-5 -alkyloxy-C 2-5 -alkyloxy-C 1-2 -alkylcarbonylamino, C 1-5 -alkylsulphonylamino, C 3-6 -cycloalkylcarbonylamino group, 4-morpholinocarbonylamino-group,
 wherein the above-mentioned carbo- and heterocycles in the ring may each be substituted by 1 to 4 C 1-3 -alkyl or C 1-3 -alkylcarbonyl groups or may each be substituted by 1 or 2 oxo groups, and/or 
 the above-mentioned phenyl and heteroaryl groups may be replaced by 1 to 2 substituents selected from among fluorine, chlorine, bromine, methyl, methoxy, or trifluoromethyl, or two adjacent carbon atoms of a phenyl ring may be substituted by a —CH 2 —O—CH 2  group, and/or 
 the above-mentioned alkyl groups may be substituted by a cyano-C 1-5 -alkyloxycarbonyl or carboxy group, 
 wherein the above-mentioned carboxylic acid or sulphonic acid amide may optionally additionally be substituted at the nitrogen by a C 1-5 -alkyl group, 
 
 
 a phenyl, phenyl-C 1-2 -alkyl, heteroaryl-C 1-2 -alkyl or C-linked heteroaryl group, wherein the heteroaryl group is selected from among imidazolyl, furanyl, thiophenyl, thiazolyl, pyrazolyl, tetrazolyl, benzimidazolyl, indolyl, pyrimidinyl, pyrazinyl-oxazolyl, 1,2,4-triazolyl and pyridinyl, and which may optionally be mono- to disubstituted in the phenyl or heteroaryl moiety by identical or different substituents selected from among chlorine or fluorine atoms or C 1-3 -alkyl, benzyl, hydroxy, amino, CF 3 , CH 3 O— or CHF 2 O— groups, 
   R 5  denotes a hydrogen atom, a straight-chain or branched C 1-4 -alkyl group, wherein the hydrogen atoms of the straight-chain or branched C 1-4 -alkyl groups may optionally be wholly or partly replaced by fluorine atoms, or a propargyl or C 1-3 alkyloxy-C 1-3 -alkyl group, or   R 4  and R 5  together with the carbon atom to which they are bound,
 form a C 5-6 -cycloalkenyl or C 3-7 -cycloalkyl group, 
 wherein one of the methylene groups of a C 4-7 -cycloalkyl group may be replaced by an oxygen or sulphur atom or an —NH—, —N(C 1-5 -alkyl), —N(C 1-4 -alkylcarbonyl), carbonyl, sulphinyl or a sulphonyl group, or two immediately adjacent methylene groups of a C 4-7 -cycloalkyl group may together be replaced by a —C(O)NH, —C(O)N(C 1-5 -alkyl), —S(O) 2 NH— or —S(O) 2 N(C 1-5 -alkyl) group, 
 and/or 1 to 2 carbon atoms of a C 3-7 -cycloalkyl group may optionally be substituted independently of one another by in each case one or two fluorine atoms or one or two C 1-5 -alkyl groups or a hydroxy, C 1-5 -alkyloxy, formyloxy, amino, C 1-5 -alkylamino, di-(C 1-5 -alkyl)-amino, C 1-5 -alkylcarbonylamino, C 3-6 -cycloalkylcarbonylamino, nitrile, carboxy, C 1-5 -alkyloxycarbonyl, aminocarbonyl, C 1-5 -alkylaminocarbonyl, di-(C 1-5 -alkyl)-aminocarbonyl or C 4-7 -cycloalkyleneiminocarbonyl group, 
 with the proviso that a C 3-7 -cycloalkyl group of this kind, formed from R 4  and R 5  together,
 wherein two heteroatoms in the cyclic group selected from among oxygen and nitrogen are separated from one another by precisely one optionally substituted —CH 2  group, and/or 
 wherein one or both methylene groups of the cyclic group which are joined directly to the carbon atom to which the groups R 4  and R 5  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 fluorine atom is bound directly to the cyclic group, is separated from another heteroatom selected from among oxygen, nitrogen and sulphur by precisely one optionally substituted methylene group, and/or 
 wherein two atoms in the ring form a —O—O or —S—O— bond, 
 
 is excluded, 
   
     the tautomers, enantiomers, diastereomers, mixtures and salts thereof. 
   
   
       5 . Compounds of general formula (I) according to  claim 1 , wherein
 D denotes a substituted bicyclic ring system of formula (II),   
     
       
         
         
             
             
         
       
       
         wherein 
         K 1  and K 4  
 each independently of one another represent a —CH 2 , —CHR 7a  or a —CR 7b R 7c -group, wherein 
 R 7a /R 7b /R 7c  
 each independently of one another denote a C 1-2 -alkyl group 
 or a phenyl group which may be substituted by 1 or 2 substituents selected from among a nitro, amino, hydroxyl, methoxy, cyano, C 1-5 -alkyl group or a fluorine, chlorine or bromine atom, 
 
 
         K 2  and K 3  
 each denote a —CH 2  group 
 
         X denotes an NR 1  group, wherein
 R 1  denotes a hydrogen atom or
 a C 1-5 -alkyl, C 2-4 -alkenyl-CH 2 , C 2-4 -alkynyl-CH 2  or C 3-6 -cycloalkyl group, wherein the methylene and methyl groups present in the previously mentioned C 2-5 -alkyl groups may be substituted by one to three fluorine atoms, as long as the methylene or methyl groups are not directly bound to the nitrogen atom, 
 
 
         and wherein 
         A 1  denotes either N or CR 10 , 
         A 2  denotes either N or CR 11 , 
         A 3  denotes either N or CR 12 ,
 wherein R 10 , R 11  and R 12  each independently of one another represent 
 a hydrogen, fluorine or chlorine atom, or a C 1-3 -alkyl, CF 3 , hydroxy or CH 3 O— group, 
 
         or 
       
       D denotes one of the groups (II-3) or (II-4) 
     
     
       
         
         
             
             
         
       
       
         wherein the groups A1, A2, A3, K1, K2, K3, K4 are as hereinbefore defined, and the anion in (II-4) may be selected from among fluoride, chloride, bromide, iodide, sulphate, phosphate, benzoate, salicylate, succinate, citrate or tartrate, and 
       
       R 3  denotes a hydrogen atom, 
       R 4  denotes a straight-chain or branched C 3-6 -alkenyl or C 3-6 -alkynyl group,
 a straight-chain or branched C 1-4 -alkyl group,
 wherein the hydrogen atoms of the straight-chain or branched C 1-4 -alkyl group may optionally be partially replaced by up to four fluorine atoms, 
 and wherein optionally one to two hydrogen atoms may be replaced independently of one another by a C 3-7 -cycloalkyl, hydroxy, C 1-5 -alkyloxy, phenylmethyloxy, C 1-5 -alkylsulphanyl, C 1-5 -alkylsulphinyl, C 1-5 -alkylsulphonyl, carboxy, C 1-5 -alkyloxycarbonyl, aminocarbonyl, C 1-5 -alkylaminocarbonyl, di-(C 1-5 -alkyl)-aminocarbonyl, C 4-7 -cycloalkyleneiminocarbonyl, amino, C 1-5 -alkylamino or di-(C 1-5 -alkyl)-amino, C 1-5 -alkylcarbonylamino, carboxy-C 1-5 -alkylcarbonylamino or a C 1-5 -alkyloxycarbonyl-C 1-5 -alkylcarbonylamino group,
 wherein the above-mentioned phenyl groups may be replaced by 1 or 2 substituents selected from fluorine, chlorine, bromine, methyl, methoxy, or trifluoromethyl, or wherein the above-mentioned carboxylic acid amide may optionally be additionally substituted at the nitrogen by a C 1-5 -alkyl group, 
 
 
 a phenyl, phenyl-C 1-2 -alkyl, heteroaryl-C 1-2 -alkyl or C-linked heteroaryl group, wherein the heteroaryl group is selected from among imidazolyl, furanyl, thiophenyl, thiazolyl, pyrazolyl, tetrazolyl, benzimidazolyl, indolyl, pyrimidinyl, pyrazinyl, oxazolyl, and pyridinyl, and which may optionally be mono- to disubstituted in the phenyl or heteroaryl moiety by identical or different substituents selected from among chlorine or fluorine atoms or C 1-3 -alkyl, CF 3 , HO, CH 3 O or CHF 2 O— groups, 
 
       R 5  denotes a hydrogen atom, a straight-chain or branched C 1-4 -alkyl group, a propargyl or C 1-3 -alkyloxy-C 1-3 -alkyl group, or 
       R 4  and R 5  together with the carbon atom to which they are bound form
 a C 5-6 -cycloalkenyl or C 3-7 -cycloalkyl group, 
 wherein one of the methylene groups of a C 4-7 -cycloalkyl group may be replaced by an oxygen or sulphur atom or a sulphonyl group, or 
 1 to 2 carbon atoms of a C 3-7 -cycloalkyl group may optionally be substituted independently of one another by in each case one or two fluorine atoms, or one or two C 1-5 -alkyl groups, or a hydroxy, C 1-5 -alkyloxy, formyloxy, nitrile, carboxy, C 1-5 -alkyloxycarbonyl, aminocarbonyl, C 1-5 -alkylaminocarbonyl, di-(C 1-5 -alkyl)-aminocarbonyl or C 4-7 -cycloalkyleneiminocarbonyl group, 
 with the proviso that a C 3-7 -cycloalkyl group of this kind formed from R 4  and R 5  together,
 wherein one of the methylene groups of the cyclic group which is linked directly to the carbon atom to which the groups R 4  and R 5  are bound, is replaced by an oxygen or sulphur atom, 
 
 is excluded, and 
 
       M denotes a thiophene ring according to formula (III), 
     
     
       
         
         
             
             
         
       
       
         which is bound to the carbonyl group in formula (I) via the 2-position and is substituted by R 2  in the 5-position, where 
         R 2  denotes a chlorine or bromine atom or an ethynyl group, and 
         R 6  denotes a hydrogen atom, 
       
     
     wherein the alkyl, alkenyl, alkynyl and alkyloxy groups contained in the previously 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, 
     the tautomers, enantiomers, diastereomers, mixtures and salts thereof. 
   
   
       6 . Compounds of general formula (I) according to  claim 1 , wherein the group 
     D denotes a substituted bicyclic ring system of formula (II), 
     
       
         
         
             
             
         
       
       wherein 
       K 1  and K 4  
 each independently of one another represent a —CH 2 , —CHR 7a  or a —CR 7b R 7c -group, where 
 R 7a /R 7b /R 7c  
 each independently of one another denote a C 1-2 -alkyl group, 
 
 
       K 2  and K 3  
 each denote a —CH 2  group, 
 
       X denotes an NR 1  group, wherein
 R 1  denotes a hydrogen atom or
 a C 1-5 -alkyl or C 3-6 -cycloalkyl group,
 wherein in the methylene and methyl groups present in the above-mentioned groups one to three hydrogen atoms may be replaced by fluorine atoms, provided that the methylene or methyl groups are not directly bound to the nitrogen atom, 
 
 
 
       and wherein 
       A 1  denotes CR 10 , 
       A 2  denotes CR 11 , 
       A 3  denotes CR 12 ,
 where R 10 , R 11  and R 12  each independently of one another represent 
 a hydrogen, fluorine or chlorine atom, or a C 1-3 -alkyl, CF 3 , HO, CH 3 O— group, 
 
       or 
     
     D denotes the group (II-4) 
     
       
         
         
             
             
         
       
       wherein the groups A1, A2, A3, K1, K2, K3, K4 are as hereinbefore defined, and the anion in (II-4) may be selected from among fluoride, chloride, bromide, iodide, sulphate, phosphate, benzoate, salicylate, succinate, citrate or tartrate, 
     
     the tautomers, enantiomers, diastereomers, mixtures and salts thereof. 
   
   
       7 . Compounds of general formula (I) according to  claim 1 , wherein neither
 R 4  nor R 5  may represent a hydrogen atom,   the tautomers, enantiomers, diastereomers, mixtures and salts thereof.   
   
   
       8 . Compounds of general formula (I) according to  claim 1 , wherein 
     R 4  and R 5  together with the carbon atom to which they are bound,
 form a C 5-6 -cycloalkenyl or C 3-7 -cycloalkyl group, 
 wherein one of the methylene groups of a C 4-7 -cycloalkyl group may be replaced by an oxygen or sulphur atom,
 with the proviso that a C 3-7 -cycloalkyl group of this kind formed from R 4  and R 5  together,
 wherein one of the methylene groups of the cyclic group, which is linked directly to the carbon atom, to which the groups R 4  and R 5  are bound, is replaced by an oxygen or sulphur atom, 
 
 is excluded, 
 
 
     the tautomers, enantiomers, diastereomers, mixtures and salts thereof. 
   
   
       9 . Physiologically acceptable salts of the compounds according to  claim 1 . 
   
   
       10 . Pharmaceutical compositions comprising a compound according to  claim 1  or a physiologically acceptable salt thereof optionally together with one or more inert carriers and/or diluents. 
   
   
       11 . Use of a compound according to  claim 1  or a physiologically acceptable salt thereof for preparing a pharmaceutical composition with an inhibitory effect on factor Xa and/or an inhibitory effect on related serine proteases. 
   
   
       12 . Process for preparing a pharmaceutical composition according to  claim 10 , wherein a compound according to  claim 1  or a physiologically acceptable salt thereof is incorporated in one or more inert carriers and/or diluents by a non-chemical method.