New indole derivatives as factor Xa inhibitors

Abstract

The present invention relates to compounds of formula I, in which R 0 ; R 1 ; R 2 ; R 3 ; R 4 ; R 5 ; R 6 ; R 7 ; Q; V, G and M have the meanings indicated in the claims. The compounds of formula I are valuable pharmacologically active compounds. They exhibit a strong antithrombotic effect and are suitable, for example, for the therapy and prophylaxis of cardiovascular disorders like thromboembolic diseases or restenoses. They are reversible inhibitors of the blood clotting enzymes factor Xa (FXa) and/or factor VIIa (FVIIa), and can in general be applied in conditions in which an undesired activity of factor Xa and/or factor VIIa is present or for the cure or prevention of which an inhibition of factor Xa and/or factor Vila is indicated. The invention furthermore relates to processes for the preparation of compounds of formula I, their use, in particular as pharmaceuticals for treating the foregoing conditions, and pharmaceutical preparations comprising them.

1 . A compound of the formula I,  
       
         
           
           
               
               
           
         
         wherein  
         R 0  is selected from the group consisting of 
 1) monocyclic and bicyclic 6- to 14-membered aryl radicals, said aryl radicals being substituted with one two or three substituents independently selected from the R 8  substituents defined below, provided that at least one R 8  is halogen, —C(O)—NH 2  or —O—(C 1 -C 8 )-alkyl;  
 2) monocyclic and bicyclic 4- to 14-membered heteroaryl radicals selected from the group consisting of pyridyl, pyrimidinyl, indolyl, isoindolyl, indazolyl, phthalazinyl, quinolyl, isoquinolyl, benzothiophen, quinazolinyl and phenylpyridyl radicals, said heteroaryl radicals being unsubstituted or substituted with one two or three substituents independently selected from the R 8  substituents defined below;  
 3) monocyclic or bicyclic 4- to 14-membered heteroaryl radicals containing one, two, three or four heteroatoms selected from the group consisting of nitrogen, sulfur and oxygen, said heteroaryl radicals being unsubstituted or substituted with one two or three substituents independently selected from the R 8  substituents defined below, as well as by a monocyclic or bicyclic 4- to 14-membered heteroaryl, containing one, two, three or four heteroatoms selected from the group consisting of nitrogen, sulfur and oxygen, which heteroaryl radical is unsubstituted or substituted with one two or three substituents independently selected from the R 8  substituents defined below;  
 
         R 8  is selected from the group consisting of halogen, —NO 2 ; —CN; —C(O)—NH 2 ; —OH; —NH 2 ; —OCF 3 ; monocyclic and bicyclic 4- to 14-membered aryl radicals, said aryl radicals being substituted with one, two, or three substituents independently selected from halogen and —O—(C 1 -C 8 )-alkyl; —(C 1 -C 8 )-alkyl, said alkyl being unsubstituted or substituted with up to three substituents independently selected from halogen, NH 2 , —OH and methoxy; and  
         —O—(C 1 -C 8 )-alkyl, said alkyl being unsubstituted or substituted with up to three substituents independently selected from halogen, NH 2 , —OH and methoxy;  
         Q is selected from the group consisting of 
 a direct bond; —C(O)—; —(C 0 -C 2 )-alkylene-C(O)—N R 10 —; —NR 10 —C(O)—NR 10 —;  
 —NR 10 —C(O)—; —SO 2 —; —(C 1 -C 6 )-alkylene, wherein alkylene is unsubstituted or substituted with up to three substituents independently selected from halogen,  
 —NH 2  and —OH; and (C 3 -C 6 )-cycloalkylene, wherein cycloalkylene is unsubstituted or substituted with up to three substituents independently selected from halogen,  
 —NH 2  and —OH;  
 
         R 1  is selected from the group consisting of 
 hydrogen; —(C 1 -C 4 )-alkyl radicals, said alkyl radicals being unsubstituted or substituted with one two or three substituents independently selected from the R 13  substituents defined below; and monocyclic or bicyclic 4- to 14-membered heteroaryl radicals said heteroaryl radical is unsubstituted or substituted with one two or three substituents independently selected from the R 14  substituents defined below;  
 
         R 2  is a direct bond or —(C 1 -C 4 )-alkylene; provided that:  
         a) R 1  and R 7  together with the atoms to which they are bonded can form a 4- to 7-membered cyclic group, which may contain 1, 2, 3 or 4 heteroatoms selected from the group consisting of nitrogen, sulfur and oxygen, said cyclic group being unsubstituted or substituted with one two or three substituents independently selected from the R 14  substituents defined below;  
         b) R 1 —N—R 2 —V can form a 4- to 7-membered cyclic group, which may contain 1, 2, 3 or 4 heteroatoms selected from the group consisting of nitrogen, sulfur and oxygen, said cyclic group being unsubstituted or substituted with one two or three substituents independently selected from the R 14  substituents defined below;  
         R 14  is selected from the group consisting of 
 halogen, —OH, ═O, —(C 1 -C 8 )-alkyl, —(C 1 -C 4 )-alkoxy, —NO 2 , —C(O)—OH, —CN, —NH 2 , —C(O)—O—(C 1 -C 4 )-alkyl, —(C 1 -C 8 )-alkylsulfonyl, —SO 2 , —C(O)—NH—(C 1 -C 8 )-alkyl, —C(O)—N—[(C 1 -C 8 )-alkyl] 2 , —NR 10 —C(O)—NH—(C 1 -C 8 )-alkyl, —C(O)—NH 2 —SR 10 , and —NR 10 —C(O)—NH-[(C 1 -C 8 )-alkyl] 2 , said R 10  being selected from hydrogen, —(C 1 -C 3 )-perfluoroalkyl and —(C 1 -C 6 )-alkyl;  
 
         V is selected from the group consisting of 
 a 3- to 7-membered cyclic group, which may contain 1, 2, 3 or 4 heteroatoms selected from the group consisting of nitrogen, sulfur and oxygen, said cyclic group being unsubstituted or substituted with one two or three substituents independently selected from the R 14  substituents defined above; a 6- to 14-membered aryl, said aryl being unsubstituted or substituted with one two or three substituents independently selected from the R 14  substituents defined above; and a monocyclic or bicyclic 4- to 14-membered heteroaryl, said heteroaryl being other than a piperadine radical and being unsubstituted or substituted with one two or three substituents independently selected from the R 14  substituents defined above;  
 
         G is selected from the group consisting of: 
 a direct bond, —(CH 2 ) m , —NR 10 —SO 2 —NR 10 —(CH 2 ) n —, —(CH 2 ) m —CH(OH)—(CH 2 ) n —, —(CH 2 ) m , —(CH 2 ) m —O—(CH 2 ) n —, —(CH 2 ) m —C(O)—NR 10 —(CH 2 ) n —, —(CH 2 )—SO 2 —(CH 2 ) n —, —(CH 2 ) m —NR 10 —C(O)—NR 10 —(CH 2 ) n —, —(CH 2 ) m —NR 10 —C(O)—(CH 2 ) n —, —(CH 2 ) m —C(O)—(CH 2 ) n , —(CH 2 )—S—(CH 2 ) n —, —(CH 2 ) n —, —SO 2 —NR 10 —(CH 2 ) n —, —(CH 2 ) m —NR 10 —SO 2 —(CH 2 ) n —, —(CH 2 ) m —NR 10 —, —(CH 2 ) m —C(O)—NR 10 —(CH 2 ) n — and —(CH 2 ) m —NR 10 —C(O)—O—(CH 2 ) n —,  
 
         n and m are independently selected from zero and the integers 1, 2, 3, 4, 5 and 6,  
         R 10  is hydrogen, —(C 1 -C 3 )-perfluoroalkyl or —(C 1 -C 6 )-alkyl,  
         M is selected from the group consisting of 
 hydrogen; —(C 1 -C 8 )-alkyl, said alkyl being unsubstituted or substituted with one two or three substituents independently selected from the R 14  substituents defined above; —C(O)—NR 11 R 12 ; —(CH 2 ) m —NR 10 ; —(C 6 -C 14 )-aryl, said aryl being unsubstituted or substituted with one two or three substituents independently selected from the R 14  substituents defined above; —(C 4 -C 14 )-heteroaryl, said heteroaryl being unsubstituted or substituted with one two or three substituents independently selected from the R 14  substituents defined above; (C 3 -C 7 )-cycloalkyl, said cycloalkyl being unsubstituted or substituted with one two or three substituents independently selected from the R 14  substituents defined above; a 3- to 7-membered cyclic residue, optionally containing 1, 2, 3 or 4 heteroatoms selected from nitrogen, sulfur and oxygen, said cyclic residue being unsubstituted or substituted with one two or three substituents independently selected from the R 14  substituents defined above;  
 
         R 11  and R 12  are independently selected from the group consisting of: 
 hydrogen; —(C 1 -C 6 )-alkyl, said alkyl being unsubstituted or substituted with one two or three substituents independently selected from the R 13  substituents defined below; —(C 6 -C 14 )-aryl-(C 1 -C 4 )-alkyl-, wherein said alkyl and said aryl are each independently unsubstituted or substituted with one two or three substituents independently selected from the R 13  substituents defined below; —(C 6 -C 14 )-aryl-, said aryl being unsubstituted or substituted with one two or three substituents independently selected from the R 13  substituents defined below;  
 —(C 4 -C 14 )-heteroaryl, said heteroaryl being unsubstituted or substituted with one two or three substituents independently selected from the R 13  substituents defined below; —(C 4 -C 14 )-heteroaryl-(C 1 -C 4 )-alkyl-, wherein said alkyl and said heteroaryl are each independently unsubstituted or substituted with one two or three substituents independently selected from the R 13  substituents defined below; or, alternatively,  
 
         R 11  and R 12, , together with the nitrogen atom to which they are bonded, form a saturated 5- to 7-membered monocyclic heterocyclic ring which, in addition to said nitrogen atom, may contain one or two identical or different ring heteroatoms selected from oxygen, sulfur and nitrogen; said heterocyclic ring being unsubstituted or substituted with one two or three substituents independently selected from the R 13  substituents defined below;  
         R 13  is selected from the group consisting of: 
 halogen; —NO 2 ; —CN; ═O; —OH; —(C 1 -C 8 )-alkyl; —(C 1 -C 8 )-alkoxy; —CF 3 ; phenyl; phenyloxy-; —C(O)—O—R 11 ; phenyl-(C 1 -C 4 )-alkoxy-; —C(O)—N—R 11 R 12 ; —NR 11 R 12 ; —NR 10 —SO 2 —R 10 ; —S—R 10 ; —SO n —R 10 ; wherein n is 1 or 2; —SO 2 —NR 11 R 12 ; —C(O)—R 10 ; —(C 0 -C 4 )-alkyl-C(O)—O—C(R 15 R 16 )—O—C(O)—R 17 ; —(C 0 -C 4 )-alkyl-C(O)—O—C(R 15 R 16 )—O—C(O)O—R 17 , and a residue of formula Va,  
                     
 
          wherein R 10 , R 11 ,R 12  are as defined above and R 15 , R 16  or R 17  are as defined below;  
         R 15  and R 16  are independently selected from hydrogen, and —(C 1 -C 6 )-alkyl, or, alternatively, together with the carbon atom to which they are bonded, form a 3- to 6 membered carbocyclic ring, said carbocyclic ring being unsubstituted or substituted with one, two or three substituents independently selected from the R 10  substituents defined above;  
         R 17  is selected from the group consisting of —(C 1 -C 6 )-alkyl, —(C 1 -C 8 )-cycloalkyl, and —(C 1 -C 6 )-alkyl-(C 1 -C 8 )-cycloalkyl, each said cycloalkyl ring being unsubstituted or substituted with one, two or three substituents independently selected from the R 10  substituents defined above;  
         R 3 , R 4 , R 5 , R 6  and R 7  are each independently selected from the group consisting of: 
 hydrogen; halogen; —(C 1 -C 4 )-alkyl, said alkyl being unsubstituted or substituted with one two or three substituents independently selected from the R 13  substituents defined above; —(C 1 -C 3 )-perfluoroalkyl; phenyl, said phenyl being unsubstituted or substituted with one, two or three substituents independently selected from the R 13  substituents defined above; —O—(C 1 -C 4 )-alkyl, said alkyl being unsubstituted or substituted with one two or three substituents independently selected from the R 13  substituents defined above; —NO 2 ; —CN; —OH; phenyloxy-, said phenyloxy being unsubstituted or substituted with one two or three substituents independently selected from the R 13  substituents defined above; benzyloxy-, said benzyloxy being unsubstituted or substituted with one two or three substituents independently selected from the R 13  substituents defined above; —C(O)—O—R 11 , wherein R 11  is as defined above; —C(O)—N—R 11 R 12 , wherein R 11  and R 12  are as defined above; —NR 11 R 12 , wherein R 11  and R 12  are as defined above; —NR 10 —SO 2 —R 10 , wherein R 10  is as defined above; —SR 10 , wherein R 10  is as defined above; —SO n —R 10 , wherein n is 1 or 2 and R 10  is as defined above; —SO 2 —NR 11 R 12 , wherein R 11  and R 12  are as defined above; —C(O)—R 10 , wherein R 10  is as defined above;  
 —C(O)—O—C(R 15 R 16 )—O—C(O)—R 17 , wherein R 15 , R 16  and R 17  are as defined above;  
 —C(O)—O—C(R 15 R 16 )—O—C(O)O—R 17 , wherein R 15 , R 16  and R 17  are as defined above; a residue of formula Va,  
                     wherein R 10  is as defined above;    
 a residue of formula Vb or Vc,  
                     
 
         —NR 10 —(C 1 -C 4 )-alkyl, said alkyl being unsubstituted or substituted with one two or three substituents independently selected from the R 13  substituents defined above; —O—CF 3 ;  
         and a residue selected from the group consisting of:  
         
           
             
             
                 
                 
             
           
           wherein R 10 , R 11 , R 12  and R 13  are as defined above;  
         
         in all its stereoisomeric forms and mixtures thereof in any ratio, and its physiologically tolerable salts.  
       
     
     
         2 . A compound of the formula I, as claimed in  claim 1 , wherein 
 R 0  is selected from the group consisting of phenyl, said phenyl being unsubstituted or substituted with one, two or three substituents independently selected from the R 8′  substituents defined below; bicyclic 5- to 14-membered heteroaryl radicals selected from the group consisting of indolyl, isoindolyl, benzofuranyl, benzothiophenyl, 1,3-benzodioxolyl, indazolyl, benzimidazolyl, benzoxazolyl, benzothiazolyl, quinolinyl, isoquinolinyl, chromanyl, isochromanyl, cinnolinyl, quinazolinyl, quinoxalinyl, phthalazinyl, pyridoimidazolyl, pyridopyridinyl, pyridopyrimidinyl, purinyl and pteridinyl, said heteroaryl radicals being unsubstituted or substituted with one, two or three substituents independently selected from the R 8′  substituents defined below; said heteroaryl radicals being optionally further substituted by an additional residue selected from the group consisting of pyridyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, pyrrolyl, 2-pyrrolyl, 3-pyrrolyl, furyl, 2-furyl, 3-furyl; thienyl, 2-thienyl, 3-thienyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, triazolyl, isothiazolyl, thiadiazolyl, tetrazolyl, pyrimidinyl, pyridazinyl and pyrazinyl, said additional residue being unsubstituted or substituted with one, two or three substituents independently selected from the R 8′  substituents defined below; a monocyclic 5- to 14-membered heteroaryl radical selected from the group consisting of pyridyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, pyrrolyl, 2-pyrrolyl, 3-pyrrolyl, furyl, 2-furyl, 3-furyl; thienyl, 2-thienyl, 3-thienyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, thiadiazolyl, isothiazolyl, triazolyl, tetrazolyl, pyridazinyl and pyrazinyl, said heteroaryl radical being unsubstituted or substituted with one, two or three substituents independently selected from the R 8′  substituents defined below said heteroaryl radical being optionally further substituted by a residue selected from the group consisting of pyridyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, pyrrolyl, 2-pyrrolyl, 3-pyrrolyl, furyl, 2-furyl, 3-furyl, thienyl, 2-thienyl, 3-thienyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, thiadiazolyl, isothiazolyl, triazolyl, tetrazolyl, pyridazinyl and pyrazinyl, said residue being unsubstituted or substituted with one, two or three substituents independently selected from the R 8′  substituents defined below;    R 8′  is selected from the group consisting of: 
 halogen, including F, Cl, Br and I; —C(O)—NH 2 ; —(C 1 -C 4 )-alkyl, said alkyl being unsubstituted or independently substituted by one, two or three substituents selected from halogen, —OH and methoxy; and —O—(C 1 -C 4 )-alkyl, said alkyl being-unsubstituted or independently substituted by one, two or three substituents selected from halogen and methoxy,  
   provided that at least one R 8′  is halogen, —C(O)—NH 2  or a —O—(C 1 -C 8 )-alkyl residue when R 0  is a monocyclic or bicyclic 6- to 14-membered aryl;    Q is selected from the group consisting of:    a direct bond; —C(O)—; —SO 2 —; —(C 1 -C 6 )-alkylene; and —(C 0 -C 2 )-alkylene-C(O)—NR 10 —;    R 1  is hydrogen or —(C 1 -C 2 )-alkyl;    R 2  is a direct bond or —(C 1 -C 2 )-alkylene; or, alternatively,    R 1 —N—R 2 —V, together, form a 5- to 7-membered cyclic radical selected from the group consisting of piperazine, pyridine, pyrimidine, pyrrolidine, pyrrolidinone, 1,2,3-triazine, 1,2,4-triazine, 1,3,5-triazine, 1,2,3-triazole, 1,2,4-triazole, tetrazine, tetrazole, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine, azepine, ketopiperazine, oxazole, isoxazole, isoxazolidine, 2-isoxazoline, morpholine, thiazole, isothiazole, thiadiazole or thiomorpholine, said cyclic radical being unsubstituted or substituted with one, two or three substituents independently selected from the R 14  substituents defined below;    R 14  is halogen, —(C 1 -C 4 )-alkyl or —NH 2 ;    V is selected from the group consisting of derivatives of 3- to 7-membered cyclic residues selected from the group consisting of aziridine, azirine, azetidine, pyrrole, pyrrolidine, pyridonyl, imidazole, pyrazole, 1,2,3-triazole, 1,2,4-triazole, tetrazole, pyridine, pyrimidine, pyrazine, 1,2,3-triazine, 1,2,4-triazine, 1,3,5-triazine, tetrazine, tetrazole, azepine, diazirine, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine, pyridazine, piperazine, pyrrolidinone, ketopiperazine, furan, pyran, dioxole, oxazole, isoxazole, 2-isoxazoline, isoxazolidine, morpholine, oxirane, oxaziridine, 1,3-dioxolene, 1,2-oxazine, 1,3-oxazine, 1,4-oxazine, oxaziridine, thiophene, thiopyran, thietan, thiazole, isothiazole, isothiazoline, isothiazolidine, 1,2-oxathiolan, thiopyran, 1,2-thiazine, 1,3-thiazole, 1,3-thiazine, 1,4-thiazine, thiadiazine and thiomorpholine, said cyclic residue being unsubstituted or substituted with one, two or three substituents independently selected from the R 14  substituents defined above; phenyl, which is unsubstituted or substituted with one, two or three substituents independently selected from the R 14  substituents defined above; and a bicyclic 5- to 14-membered heteroaryl selected from the group consisting of quinolyl, isoquinolyl and quinoxalinyl, said heteroaryl being unsubstituted or substituted with one, two or three substituents independently selected from the R 14  substituents defined above;    G is a direct bond, —(CH 2 ) m —, or —(CH 2 ) m —NR 10 —;    m is zero or an integer selected from 1, 2, 3 and 4;    R 10  is hydrogen, —(C 1 -C 3 )-perfluoroalkyl or —(C 1 -C 4 )-alkyl;    M is selected from the group consisting of 
 hydrogen; —(C 6 -C 14 )-heteroaryl, said heteroaryl being a residue selected from the group consisting of the derivatives of piperidine, piperazine, pyridine, pyrimidine, pyrrolidine, pyrrolidinone, pyridonyl, imidazole, pyridazine, pyrazine, 1,2,3-triazine, 1,2,4-triazine, 1,3,5-triazine, 1,2,3-triazole, 1,2,4-triazole, tetrazine, tetrazole, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine, azepine, ketopiperazine, oxazole, isoxazole, isoxazolidine, 2-isoxazoline, morpholine, thiazole, isothiazole, tetrahydropyran, thiadiazole and thiomorpholine, which are unsubstituted or substituted with one, two or three substituents independently selected from the R 14  substituents defined above; —(C 1 -C 6 )-alkyl, said alkyl being unsubstituted or substituted with one, two or three substituents independently selected from the R 14  substituents defined above; and (C 3 -C 6 )-cycloalkyl;  
   R 3 , R 4 , R 5 , R 6  and R 7  are independently selected from the group consisting of hydrogen; F; Cl; Br; —(C 1 -C 4 )-alkyl, said alkyl being unsubstituted or substituted by R 13  as defined below; —CF 3 ; phenyl, said phenyl being unsubstituted or substituted with one, two or three substituents independently selected from the R 13  substituents defined below; —O—(C 1 -C 4 )-alkyl, wherein alkyl is unsubstituted or substituted by R 13  as defined below; —NO 2 ; —CN; —OH; phenyloxy-, said phenyloxy being unsubstituted or substituted by R 13  as defined below; benzyloxy-, said benzyloxy being unsubstituted or substituted by R 13  as defined below; 
 —C(O)—O—R 11 ; —C(O)—N—R 11 R 12 ; —NR 11 R 12 ; —NR 10 —SO 2 —R 10 ; —SO n —R 10 , wherein n is 1 or 2;  
   —SO 2 —N R 11  R 12 ; —C(O)—R 10 ; —C(O)—O—C(R 15 R 16 )—O—C(O)—R 17 ; —C(O)—O—C(R 15 R 16 )—O—C(O)O—R 17 ; a residue of formula Va                          a residue of formula Vb or Vc,                          —O—CF 3 ; and a residue selected from the group consisting of                          R 13  is selected from the group consisting of 
 halogen; —NO 2 ; —CN, ═O; —OH; —(C 1 -C 8 )-alkoxy; —CF 3 ; —C(O)—O—R 11 ;  
 —C(O)—N—R 11 R 12 ; —NR 11 R 12 ; —NR 10 —SO 2 —R 10 ; —SO n —R 10 , wherein n is 1 or 2;  
 —SO 2 —NR 11 R 12 ; —C(O)—R 10 ; —(C 0 -C 4 )-alkyl-C(O)—O—C(R 15 R 16 )—O—C(O)—R 17 ;  
 —(C 0 -C 4 )-alkyl-C(O)—O—C(R 15 R 16 )—O—C(O)O—R 17 ; and a residue of formula Va,  
                     
  and R 10 , R 11 ,R 12 ,R 15 , R 16  and R 17  are as defined in  claim 1  above,  
 in all its stereoisomeric forms and mixtures thereof in any ratio, and its physiologically tolerable salts.  
   
     
     
         3 . A compound of the formula I as claimed in  claim 1 , wherein 
 R 0  is phenyl, said phenyl being unsubstituted or substituted with one or two substituents independently selected from the R 8″  substituents defined below; or a monocyclic 4- to 14-membered heteroaryl radical selected from the group consisting of thienyl, thiadiazolyl, isoxazolyl and thiazolyl, said heteroaryl radical being substituted by a residue selected from the group consisting of thienyl, 2-thienyl and 3-thienyl, wherein said residue is unsubstituted or substituted with one or two substituents independently selected from the R 8″  substituents defined below;    R 8″  is selected from the group consisting of F, Cl, Br, —O—CH 3 , —C(O)—NH 2  and —O—CF 3 ;    Q is a direct bond, —C(O)—, —SO 2 —, methylene or ethylene;    R 1  is hydrogen;    R 2  is a direct bond or methylene, or, alternatively,    R 1 —N—R 2 —V together form a 5- to 7-membered cyclic group selected from the group consisting of pyrrolidine, piperidine and piperazine;    R 13  is selected from the group consisting of 
 —C(O)—O—R 11 ; —C(O)—N—R 11 R 12 ; —NR 11 R 12 ; —NR 10 —SO 2 —R 10 ; —SO n —R 10 , wherein n is 1 or 2;  
 —SO 2 —NR 11 R 12 ; —C(O)—R 10 ; —(C 0 -C 4 )-alkyl-C(O)—O—C(R 15 R 16 )—O—C(O)—R 17 ;  
 —(C 0 -C 4 )-alkyl-C(O)—O—C(R 15 R 16 )—O—C(O)O—R 17 ; and a residue of formula Va,  
                     
  wherein R 10 , R 11 ,R 12 ,R 15 , R 16  or R 17  are as defined in  claim 1  above;  
   R 14  is halogen, methyl, ethyl or —NH 2 ;    V is a cyclic residue selected from the group consisting of compounds derived from isoquinoline, quinoline, quinazoline, azetidine, tetrahydropyrane, piperazine and isoxazole, said cyclic residue being substituted with one or two substituents independently selected from the R 14  substituents defined above; and phenyl, which is unsubstituted or substituted with one or two substituents independently selected from the R 14  substituents defined above;    G is a direct bond, —(CH 2 ) m —, or —(CH 2 ) m —NR 10 —, wherein m is zero, 1 or 2, and R 10  is hydrogen or —(C 1 -C 4 )-alkyl;    M is selected from hydrogen, (C 2 -C 4 )-alkyl, imidazolyl, pyrazolyl, pyrrolidinyl, 
 tetrahydropyranyl, piperidinyl, pyridinyl, pyrimidyl, pyrazinyl, pyridazinyl, and (C 3 -C 6 )-cycloalkyl, which cyclic residues are unsubstituted or substituted with one or two substituents independently selected from the R 14  substituents defined above; and  
   R 3 , R 4 , R 5 , R 6  and R 7  are independently selected from the group consisting of hydrogen; F; Cl; —(C 1 -C 4 )-alkyl, wherein alkyl is unsubstituted or substituted by R 13 , as defined above; phenyl, which is unsubstituted or substituted with one, two or three substituents independently selected from the R 13  substituents defined above; —O—(C 1 -C 4 )-alkyl, wherein alkyl is unsubstituted or substituted by R 13 , as defined above; —C(O)—O—R 11 ; —C(O)—N—R 11 R 12 ; —NR 11 R 12 ; —NR 10 —SO 2 —R 10 ; 
 —SO 2 —NR 11 R 12 ; —C(O)—R 10 ; —C(O)—O—C(R 15 R 16 )—O—C(O)—R 17 , wherein R 15 , R 16  and R 17  are as defined in  claim 1  above; —C(O)—O—C(R 15 R 16 )—O—C(O)O—R 17 , wherein R 15 , R 16  and R 17  are as defined in  claim 1  above; a residue of formula Va  
                     a residue of formula Vb or Vc,                          and a residue selected from the group consisting of:                          in all its stereoisomeric forms and mixtures thereof in any ratio, and its physiologically acceptable salts.    
   
     
     
         4 . A compound of  claim 1  selected from the group consisting of: 
 {1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indol-2-yl}-[4-(pyridin-4-ylamino)-piperidin-1-yl]-methanone;    {1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-nitro-1H-indol-2-yl}-[4-(pyridin-4-ylamino)-piperidin-1-yl]-methanone;    {1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-7-methyl-1H-indol-2-yl}-[4-(pyridin-4-ylamino)-piperidin-1-yl]-methanone;    {1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indol-2-yl}-(4-isopropylamino-piperidin-1-yl)-methanone;    {1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-7-methyl-1H-indol-2-yl}-(4-isopropylamino-piperidin-1-yl)-methanone;    {1-[5-(5-Chloro-thiophen-2-yl]isoxazol-3-ylmethyl]-1H-indol-2-yl}-(4-pyrrolidin-1-yl-piperidin-1-yl)-methanone;    [1,4′]Bipiperidinyl-1′-yl-{1-[5-(5-chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indol-2-yl}-methanone;    1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indole-2-carboxylic acid (3-pyridin-4-yl-4,5-dihydro-isoxazol-5-ylmethyl)-amide;    {1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indol-2-yl}-(4-pyridin-4-ylmethyl-piperazin-1-yl)-methanone;    (4-Isopropylamino-piperidin-1-yl)-[1-(3-methoxy-benzyl)-1H-indol-2-yl]-methanone;    [1-(3-Methoxy-benzyl)-1H-indol-2-yl]-[4-(pyridin-4-ylamino)-piperidin-1-yl]-methanone;    (4-Isopropylamino-piperidin-1-yl)-[1-(4-methoxy-phenyl)-1H-indol-2-yl]-methanone;    1    (4-Isopropylamino-piperidin-1-yl)-[1-(4-methoxy-benzyl)-1H-indol-2-yl]-methanone;    [1-(3,5-Dichloro-benzyl)-1H-indol-2-yl]-(4-isopropylamino-piperidin-1-yl)-methanone;    [1-(3-Chloro-benzyl)-1H-indol-2-yl]-(4-isopropylamino-piperidin-1-yl)-methanone;    1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indole-2-carboxylic acid (4-methyl-piperazin-1-yl)-amide;    {1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indol-2-yl}-[4-(pyridin-4-yloxy)-piperidin-1-yl]-methanone;    1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indole-2-carboxylic acid [4-(1H-imidazol-4-yl)-phenyl]-amide;    1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indole-2-carboxylic acid (4-pyridin-3-yl-thiazol-2-yl)-amide;    1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indole-2-carboxylic acid [3-(pyrrolidine-1-carbonyl)-4,5-dihydro-isoxazol-5-ylmethyl]-amide;    11-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indole-2-carboxylic acid (4-isopropyl-piperazin-1-yl)-amide;    1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-i ndole-2-carboxylic acid (4-ethyl-piperazin-1-yl)-amide;    S-1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indole-2-carboxylic acid (1-ethyl-pyrrolidin-3-yl)-amide;    R-1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indole-2-carboxylic acid (1-ethyl-pyrrolidin-3-yl)-amide;    R-1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indole-2-carboxylic acid (1-isopropyl-pyrrolidin-3-yl)-amide;    S-1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indole-2-carboxylic acid (1-isopropyl-pyrrolidin-3-yl)-amide;    
     
     
         5 . A process for the preparation of a compound of the formula I as claimed in  claim 1 , which comprises condensing a compound of the formula 14 
       
         
           
           
               
               
           
         
       
       with a compound of the formula HR 8′  to give a compound of the formula 15 and optionally converting the compound of the formula 15 into a compound of the formula I, wherein the residue R 8′  is —N(R 1 )—R 2 —V-G-M, wherein each of R 1 , R 2 , V, G, and M are as defined in  claim 1 , but wherein said R 8′  functional groups can also be present in the form of precursor groups that are subsequently transformed into the final functional groups present in —N(R 1 )—R 2 —V-G-M; wherein the residue R 50  denotes the group -Q-R O , as Q and R 0  are defined in  claim 1 , or a precursor group which is subsequently transformed into the group -Q-R O ; the group —C(O)—R 49  is a carboxylic acid group or derivative thereof; and the groups R 1e , R 1a , R 1b , R 1c  and R 1d  in the formulae 14 and 15 have the meanings corresponding to the definitions of R 7 , R 6 , R 5 , R 4 , and R 3 , respectively, in formula I as defined above in  claim 1  or contain such functional groups in protected form or in the form of precursor groups.  
     
     
         6 . A pharmaceutical preparation, comprising an effective amount of at least one compound of formula I as claimed in  claim 1  and a pharmaceutically acceptable carrier.  
     
     
         7 . A method for inhibition of factor Xa and/or factor VIIa or for influencing fibrinolysis comprising administering to a patient in need thereof an effective amount of a composition of  claim 6 .  
     
     
         8 . The method as claimed in  claim 7  for influencing a condition selected from the group consisting of inflammatory response, fibrinolysis, cardiovascular disorders,, restenoses,, acute myocardial infarction, unstable angina, acute vessel closure associated with thrombolytic therapy, certain viral infections or cancer, coronary heart disease, myocardial infarction, angina pectoris, and vascular restenosis.