Novel inhibitors of bone reabsorption and antagonists of vitronectin receptors

Abstract

The present invention relates to 5-membered ring heterocycles of the formula I, in which E, F, G, W, Y and Z have the meaning given in the patent claims, to their preparation and to their use as medicaments. The novel compounds are used as vitronectin receptor antagonists and as inhibitors of bone reabsorption.

1 . A compound of the formula I  
                   
       in which: 
 W is R 1 —A—B—D—C(R 16 ), R 1 —A—B—D—C(R 16 )═C,  
                 
 
 with it being possible for the ring systems  
                 
 
 to contain 1 or  
 2 heteroatoms from the group N, O and S, to be saturated or unsaturated, once or more than once, and be substituted by 1-3 substituents from R 16  or substituted, once or twice, by doubly bonded O or S;  
 Y is C═O, C═S or —CH 2 —;  
 Z is N(R 0 ), O, S or —CH 2 —;  
 A is a direct linkage, (C 1 -C 8 )-alkanediyl, —NR 2 —N═CR 2 —, —NR 2 —C(O)—NR 2 —, —NR 2 —C(O)O—, —NR 2 —C(O)S—, —NR 2 —C(S)—NR 2 —, —NR 2 —C(S)—O—, —NR 2 —C(S)—S—, —NR 2 —S(O) n —NR 2 —, —NR 2 —S(O) n —O—, —NR 2 —S(O) n —, (C 3 -C 12 )-cycloalkanediyl, —C≡C—, —NR 2 —C(O)—, —C(O)—NR 2 —, —(C 5 -C 14 )-arylene-C(O)—NR 2 —, —O—, —S(O)—, (C 5 -C 14 )-arylene-, —CO—, (C 5 -C 14 )-arylene-CO—, —NR 2 —, —SO 2 —NR 2 ,—C(O)O—, —O—C(O)—, —N═CR 2 —, —R 2 C═N—, —CR 2 ═CR 3 —or —(C 5 -C 14 )-arylene-S(O) n —, which in each case can be substituted by NR 2  and/or substituted, once or twice, by (C 1 -C 8 )-alkanediyl;  
 B is a direct linkage, (C 1 -C 8 )-alkanediyl, (C 5 -C 10 )-arylene, (C 3 -C 8 )-cycloalkanediyl, —C≡C—, —NR 2 —, —C(O)—, NR 2 —C(O)—, —C(O)—NR 2 —, —NR 2 —C(O)—NR 2 , —NR 2 —C(S)—NR 2 —, —OC(C)—, —C(O)O—, —S(C)—, —S(O) 2 —, —S(O)—NR 2 —, —S(O) 2 —NR 2 —, —NR 2 —S(O)—, —NR 2 —S(O) 2 —, —O—, —S— or —CR 2 ═CR 3 —, which in each case can be substituted once or twice by (C 1 -C 6 )-alkanediyl, or is a divalent radical of a 5- or 6-membered saturated or unsaturated ring which contains 1 or 2 nitrogen atoms and can be substituted, once or twice, by (C 1 -C 6 )-alkyl or doubly bonded oxygen or sulfur;  
 D is a direct linkage, (C 1 -C 8 )-alkanediyl, (C 5 -C 10 )-arylene, —O—, —NR 2 —, —CO—NR 2 —, —NR 2 —CO—, —NR 2 —C(O)—NR 2 —, —NR 2 —C(S)—NR 2 —, —OC(O)—, —C(O)—,—CO—,—CS—, —S(O)—, —S(O) 2 —, —S(O) 2 —NR 2 —, —NR 2 —S(O)—, —NR—S(O) 2 —, —S—, —CR═CR—, —C≡C—, —NR 2 —N═CR 2 —, —N═CR 2 , —R 2 C═N— or —CH(OH)—, which in each case can be substituted, once or twice, by (C 1 -C 8 )-alkanediyl, —CR 2 ═CR 3 —or (C 5 -C 6 )-arylene;  
 E is a direct linkage, (C 1 -C 6 )-alkanediyl, (C 2 -C 6 )-alkenediyll, (C 2 -C 6 )-alkynediyl, phenylene, phenylene-(C 1 -C 3 )-alkanediyl or (C 1 -C 3 )-alkanediyl-phenylene;  
 F is defined as D;  
 G is  
                 
 
 L is C(R 16 ) or N;  
 R 0  is H, (C 1 -C 8 )-alkyl which is optionally substituted, once or more than once, by fluorine, (C 3 -C 12 )-cycloalkyl, (C 3 -C 12 )-cycloalkyl-(C 1 -C 8 )-alkyl, (C 1 -C 14 )-aryl, (C 5 -C 14  )-aryl-(C 1 -C 8 )-alkyl or (C 1 -C 8 )-alkyl-C(O)—, (C 3 -C 12 )-cycloalkyl-C(O), (C 3 -C 12 )-cycloalkyl-(C 1 -C 6 )-alkyl-C(O), (C 5 -C 14 )-aryl-C(O)— or (C 5 -C 14 )-aryl-(C 1 -C 6 )-alkyl-C(O), with it being possible for the alkyl radicals to be substituted, once or more than once, by fluorine;  
 R 1  is R 2 —C(═NR 2 )NR 2 —, R 2 R 3 N—C(═NR 2 )—, R 2 R 3 N—C—(═NR 2 )—NR, or a 4 to 14-membered, monocyclic or polycyclic, aromatic or non-aromatic ring system which can optionally contain 1-4 heteroatoms from the group N, O and S and can optionally be substituted, once or more than once, by substituents from the group R 12 , R 13 , R 14  and R 15 ;  
 R 2  and R 3  are, independently of each other, H, (C 1 -C 10 )-alkyl, which is optionally substituted, once or more than once, by fluorine, (C 3 -C 12 )-cycloalkyl, (C 3 -C 12 )-cycloalkyl-(C 1 -C 8 )-alkyl, (C 5 -C 14 )-aryl, (C 5 -C 14 )-aryl-(C 1 -C 8 )-alkyl, H 2 N, R 8 ONR 9 , R 8 OR 9 , R 6 OC(O)R 9 , R 8 —(C 5 -C 14 )-aryl-R 9 , R 8 R 8 NR 9 , HO—(C 1 -C 8 )-alkyl-NR 8 R 9 , R 8 R 8 NC(O)R 9 , R 8 C(O)NR 8 R 9 , R 8 C(O)R 9 , R 8 R 8 N—C(═NR8)—, R 8 R 8 N—C(═NR 8 )—NR 8  or (C 1 -C 18 )-alkylcarbonyloxy-(C 1 -C 6 )-alkoxycarbonyl;  
 R 4 , R 5 , R 6  and R 7  are, independently of each other, H, fluorine, OH, (C 1 -C 8 )-alkyl, (C 3 -C 12 )-cycloalkyl, (C 3 -C 12 )-cycloalkyl-(C 1 -C 8 )-alkyl, or R 8 OR 9 , R 3 SR 9 , R 8 CO 2 R 9 , R 8 OC(O)R 9 , R 8 —(C 5 -C 14 )-aryl-R 9 , R 8 N(R 2 )R 9 , R 8 R 8 NR 9 , R 8 N(R 2 )C(O)OR 9 , R 8 S(O) n N(R 2 )R 9 , R 8 OC(O)N( R 2 )R 9 , to R 8 N(R 2 )C(O)N(R 2 )R 9 , R 8 N(R 2 )S(O) n N(R 2 )R 9 , R 8 S(O) n R 9 , R 8 SC(O)N(R 2 )R 9 , R 8 C(O)R 9 , R 8 N(R 2 )C(O)R 9  or R 8 N(R 2 )S(O) n R 9 ;  
 R 8  is H, (C 1 -C 8 )-alkyl, (C 3 -C 12 )-cycloalkyl, (C 3 -C 12 )-cycloalkyl-(C 1 -C 8 )-alkyl, (C 5 -C 14 )-aryl or (C 5 -C 14 )-aryl-(C 1 -C 8 )-alkyl, with it being possible for the alkyl radicals to be substituted, once or more than once, by fluorine;  
 R 9  is a direct linkage or (C 1 -C 8 )-alkanediyl;  
 R 10  is C(O)R 11 , C(S)R 11 , S(O) n R 11 , P(O) n R 11  or a four- to eight-membered, saturated or unsaturated heterocycle which contains 1, 2, 3 or 4 heteroatoms from the group N, O and S;  
 R 11  is OH, (C 1 -C 8 )-alkoxy, (C 5 -C 14 )-aryl-(C 1 -C 8 )-alkoxy, (C 5 -C 14 )-aryloxy, (C 1 -C 8 )-alkylcarbonyloxy-(C 1 -C 4 )-alkoxy, (C 5 -C 14 )-aryl-(C 1 -C 8 )-alkylcarbonyloxy-(C 1 -C 6 )-alkoxy, NH 2 , mono- or di(C 1 -C 8 -alkyl)amino, (C 5 -C 14 )-aryl-(C 1 -C 14 )-alkylamino, (C 1 -C 8 )-dialkylamino-carbonylmethyloxy, (C 5 -C 14 )-aryl-(C 1 -C 8 )-dialkylaminocarbonylmethyloxy or (C 5 -C 14 )-arylamino or an L- or D-armino acid;  
 R 12 , R 13 , R 14  and R 15  are, independently of each other, H, (C 1 -C 10 )-alkyl which is optionally substituted, once or more than once, by fluorine, (C 3 -C 12 )-cycioalkyl, (C 3 -C 12 )-cycloalkyl-(C 1 -C 8 )-alkyl, (C 5 -C 14 )-aryl, (C 5 -C 14 )-aryl-(C 1 -C 8 )-alkyl, H 2 N, R 8 ONR 9 , R 8 OR 9 , R 8 OC(O)R 9 , R 8 R 8 NR 9 , R 8 —(C 5 -C 14 )-aryl-R 9 , HO—(C 1 -C 8 )-alkyl-N(R 2 )R 9 , R 8 N(R 2 )C(O)R 9 , R 8 C(O)N(R 2 )R 9 , R 8 C(O)R 9 , R 2 R 3 N—C(═NR 2 )—NR 2 —, R 2 R 3 N—C(═NR 2 ), ═O or ═S; with it being possible for two adjacent substituents from the group R 12  to R 15  also together to be —OCH 2 O—, —OCH 2 CH 2 O— or —OC(CH 3 ) 2 O—;  
 R 16  is H, (C 1 -C 10 )-alkyl which is optionally substituted, once or more than once, by fluorine, (C 3 -C 12 )-cycloalkyl, (C 3 -C 12 )-cycloalkyl-(C 1 -C 8 )-alkyl, (C 5 -C 14 )-aryl, (C 5 -C 14 )-aryl-(C 1 -C 8 )-alkyl, (C 2 -C 20 )-alkenyl or (C 2 -C 10 )-alkynyl;  
 m is 1, 2, 3, 4, 5 or 6;  
 n is 1 or 2;  
 p and q are, independently of each other, 0 or 1; and the physiologically tolerated salts thereof,  
 with compounds being excluded in which R 1 —A—B—D—C—(R 16 ) or R 1 —A—B—D—C(R 16 )═C is R 1 —K—C(R 16 ) or R 1 —K—CH═C (R 16 ═H), where, in this case,  
 R 1  is X—NH—C(═NH)—(CH 2 ) p , X 1 —(NH—(CH 2 ) p  or 4-imidazolyl-CH 2 —, wherein p is an integer from 0 to 3,  
 X is hydrogen, (C 1 -C 6 )-alkyl, (C 1 -C 6 )-alkylcarbonyl, (C 1 -C 6 )-alkoxycarbonyl, (C 1 -C 18 )-alkylcarbonyloxy-(C 1 -C 6 )-alkoxycarbonyl, (C 6 -C 14 )-arylcarbonyl, (C 6 -C 14 )-aryloxycarbonyl, (C 6 -C 14 )-aryl-(C 1 -C 6 )-alkoxycarbonyl, hydroxyl, (C 1 -C 6 )-alkoxy, (C 6 -C 14 )-aryl-(C 1 -C 6 )-alkoxy or amino, with the aryl groups in X being pure carbocycies which are optionally substituted once or more than once.  
 X 1  is (C 4 -C 14 )-arylcarbonyl, (C 4 -C 14 )-aryloxycarbonyl, (C 4 -C 14 )-aryl-(C 1 -C 6 )-alkoxycarbonyl, (C 4 -C 14 )-aryl-(C 1 -C 6 )-alkoxy or R′—NH—C(═N—R″), where R′ and R″ have, independently of each other, the meanings of X and where the aryl groups in X 1  are pure carbocycles which are optionally substituted once or more than once,  
 K is (C 1 -C 6 )-alkanediyl, (C 3 -C 7 )-cycloalkanediyl, phenylene, phenylene-(C 1 -C 6 )-alkanediyl, (C 1 -C 6 )-alkanediylphenylene, phenylene-(C 2 -C 6 )-alkenediyl or a divalent radical of a 5- or 6-membered, saturated or unsaturated ring which contains 1 or 2 nitrogen atoms and can be substituted, once or twice, by (C 1 -C 6 )-alkyl or doubly bonded oxygen or sulfur.  
 
     
     
         2 . A compound of the formula I as claimed in    claim 1    in which: 
 W is R′—A—B—D—C(R 16 ), R 1 —A—B—D—C(R 16 )═C,  
                 
 
 where the ring systems  
                 
 
 contain 1 or 2 heteroatoms from the group N and O, can be saturated or unsaturated once, and can be substituted by 1 or 2 substituents from R 16 ;  
 Y is C═O, C═S or —CH 2 —;  
 Z is N(R 0 ), O or —CH 2 —;  
 A is a direct linkage, (C 1 -C 6 )-alkanediyl, —NR 2 —N═CR 2 —, —NR 2 —C(O)—NR 2 —, —NR 2 —C(O)O—, —NR 2 —C(O)S—, —NR 2 —C(S)—NR 2 —, —NR 2 —C(S)—O—, —NR 2 —C(S)—S—, —NR 2 —S(O),—NR 2 —, —NR 2 —S(O) n —O—, —NR 2 —S(O) n —, (C 3 -C 8 )-cycloalkanediyl, —C≡C—, —NR 2 —C(O)—, —C(O)—NR 2 —, —(C 5 -C 12 )-arylene-C(O)—NR 2 —, —O—, —S(O) n —, —(C 5 -C 12 )-arylene-, —CO—, —(C 5 -C 12 )-arylene-CO—, —NR 2 —, —SO 2 —NR 2 , —C(O)O—, —O—C(O)—, —N═CR 2 —, —R 2 C═N—, —CR 2 ═CR 3 —, —(C 5 -C 12 )-arylene-S(O) n —, which in each case can be substituted by NR 2  and/or be substituted, once or twice, by (C 1 -C 8 )-alkanediyl;  
 B is a direct linkage, (C 1 -C 6 )-alkanediyl, (C 5 -C 8 )-arylene, (C 3 -C 8 )-cycloalkanediyl, —C≡C—, —NR 2 —, —C(O)—, —NR 2 —C(O)—, —C(O)—NR 2 —, —NR 2 —C(O)—NR 2 —, —S(O)—, —S(O) 2 —, —S(O)—NR 2 —, —S(O) 2 —NR 2 —, —NR 2 —S(O)—, —NR 2 —S(O) 2 —, —O—, —CR 2 ═CR 3 —, which in each case can be substituted, once or twice, by (C 1 -C 6 )-alkanediyl;  
 D is a direct linkage, (C 1 -C 8 )-alkanediyl, (C 5 -C 8 )-arylene, —O—, —NR 2 —, —CO—NR 2 —, —NR 2 —CO—, —NR 2 —C(O)—NR 2 —, —NR 2 —C(S)—NR 2 —, —OC(O)—, —C(O)O—, —CO—, —CS—, —S(O)—, —S(O) 2 —, —S(O) 2 —NR 2 —, —NR 2 —S(O)—, —NR 2 —S(O) 2 —, —S—, —CR 2 ═CR 3 —, —C≡C—, —NR 2 —N═CR 2 —, —N═CR 2 , or —R 2 C═N—, which in each case can be substituted, once or twice, by (C 1 -C 6 )-alkanediyl, —CR 2 ═CR 3 — or (C 5 -C 6 )-arylene;  
 E is a direct linkage, (C 1 -C 4 )-alkanediyl, (C 2 -C 4 )-alkenediyl, (C 2 -C 4 )-alkynediyl, phenylene, phenylene-(C 1 -C 2 )-alkanediyl or (C 1 -C 2 )-alkanediylphenylene;  
 F is defined as D;  
 G is  
                 
 
 L is C(R 16 ) or N;  
 R 0  is H, (C 1 -C 6 )-alkyl, (C 3 -C 8 )-cycloalkyl, (C 3 -C 8 )-cycloalkyl-(C 1 -C 6 )-alkyl, (C 5 -C 12 )-aryl, (C 5 -C 12 )-aryl-(C 1 -C 6 )-alkyl, (C 1 -C 8 )-alkyl-C(O), (C 3 -C 8 )-cycloalkyl-C(O), (C 3 -C 8 )-cycloalkyl-(C 1 -C 4 )-alkyl-C(O), (C 5 -C 12 )-aryl-C(O) or (C 5 -C 12 )-aryl-(C 1 -C 14 )-alkyl-C(O), where the alkyl radicals can be substituted, once or more than once, by fluorine;  
 R 1  is R 2 —C(═NR 2 )NR 3 —, R 2 R 3 N—C(═NR 2 )—, R 2 R 3 N—C(═NR 2 )—NR 2 , or a 4-10-membered, monocyclic or polycyclic, aromatic or non-aromatic ring system which can optionally contain 1-4 heteroatoms from the group N, O and S and can optionally be substituted, once or more than once, by substituents from the group R 12 , R 13 , R 14  and R 15 ;  
 R 2  and R 3  are, independently of each other, H, (C 1 -C 8 )-alkyl which is optionally substituted, once or more than once, by fluorine, (C 3 -C 8 )-cycloalkyl, (C 3 -C 8 )-cycloalkyl-(C 1 -C 6 )-alkyl, ( C 5 -C 12 )-aryl, (C 5 -C 12 )-aryl-(C 1 -C 6 )-alkyl, H 2 N, R 8 ONR 9 , R 8 OR 9 , R 8 OC(O)R 9 , R 8 —(C 5 -C 12 )-aryl-R 9 , R 8 R 8 NR 9 , HO—(C 1 -C 8 )-alkyl-NR 8 R 9 , R 8 R 8 NC(O)R 9 , R 8 C(O)NR 8 R 9 , R 8 C(O)R 9 , R 8 R 8 N—C(═NR 8 )—, R 8 R 8 N—C(═NR 8 )—NR 8 — or (C 1 -C 10 )-alkylcarbonyloxy-(C 1 -C 4 )-alkoxycarbonyl;  
 R 4 , R 5 , R 6  and R 7  are, independently of each other, H, fluorine, OH, (C 1 -C 8 )-alkyl, (C 5 -C 12 )-cycloalkyl, (C 5 -C 12 )-cycloalkyl-(C 1 -C 8 )-alkyl, or R 8 OR 9 , R 8 SR 9 , R 8 CO 2 R 9 , R 8 OC(O)R 9 , R 8 —(C 5 -C 12 )-aryl-R 9 , R 8 N(R 2 )R 9 , R 8 R 8 NR 9 , R 8 N(R 2 )C(O)OR 9 , R 8 S(O) n N(R 2 )R 9 , R 8 OC(O)N(R 2 )R 9 , R 8 C(O)N(R 2 )R 9 , R 8 N(R 2 )C(O)N(R 2 )R 9 , R 8 N(R 2 )S(O) n N(R 2 )R 9 , R 8 S(O) n R 9 , R 8 SC(O)N(R 2 )R 9 , R 8 C(O)R 9 , R 8 N(R 2 )C(O)R 9 , R 8 N(R 2 )S(O) n R 9 ;  
 R 8  is H, (C 1 -C 6 )-alkyl, (C 5 -C 12 )-cycloalkyl, (C 5 -C 12 )-cycloalkyl-(C 1 -C 6 )-alkyl, (C 5 -C 12 )-aryl or (C 5 -C 12 )-aryl-(C 1 -C 6 )-alkyl, where the alkyl radicals can be substituted, once or more than once, by fluorine;  
 R 9  is a direct linkage or (C 1 -C 6 )-alkanediyi;  
 R 10  is C(O)R 11 , C(S)R 11 , S(O) n R 11 , P(O) n R 11  or a 4- to 8-membered, saturated or unsaturated heterocycle which contains 1, 2, 3 or 4 heteroatoms from the group N, O and S;  
 R 11  is OH, (C 1 -C 6 )-alkoxy, (C 5 -C 12 )-aryl-(C 1 -C 6 )-alkoxy, (C 5 -C 12 )-aryloxy, (C 1 -C 6 )-alkylcarbonyloxy-(C 1 -C 4 )-alkoxy, (C 5 -C 12 )-aryl-(C 1 -C 6 )-alkylcarbonyloxy-(C 1 -C 6 )-alkoxy, NH 2 , mono- or di(C 1 -C 6 -alkyl)amino, (C 5 -C 12 )-aryl-(C 1 -C 6 )-alkylamino or (C 1 -C 6 )-dialkylaminocarbonylmethyloxy;  
 R 12 , R 13 , R 14  and R 15  are, independently of each other, H, (C 1 -C 8 )-alkyl, which is optionally substituted, once or more than once, by fluorine, (C 3 -C 8 )-cycloalkyl, (C 3 -C 8 )-cycloalkyl-(C 1 -C 6 )-alkyl, (C 5 -C 12 )-aryl, (C 5 -C 12 )-aryl-(C 1 -C 6 )-alkyl, H 2 N, R 8 ONR 9 , R 8 OR 9 , R 8 OC(O)R 9 , R 8 —(C 5 -C 12 )-aryl-R 9 , R 8 R 8 NR 9 , HO—(C 1 -C 8 )-alkyl-N(R 2 )R 9 , R 8 N(R 2 )C(O)R 9 , R 8 C(O)N(R 2 )R 9 , R 8 C(O)R 9 , R 2 R 3 N—C(═NR 2 )—, R 2 R 3 N—C(═NR 3 )—NR 2 —, ═O or ═S; where two adjacent substituents from the group R 12  to R 15  can also together be —OCH 2 O—, —OCH 2 CH 2 O— or —OC(CH 3 ) 2 O—;  
 R 16  is H, (C 1 -C 8 )-alkyl which is optionally substituted, once or more than once, by fluorine, (C 3 -C 8 )-cycloalkyl, (C 3 -C 8 )-cycloalkyl-(C 1 -C 6 )-alkyl, (C 5 -C 12 )-aryl, (C 5 -C 12 )-aryl-(C 1 -C 6 )-alkyl, (C 2 -C 8 )-alkenyl or (C 2 -C 8 )-alkynyl;  
 m is 3,4 or 5;  
 n is 1 or 2; and  
 p and q are, independently of each other, 0 or 1. And the physiologically tolerated salts thereof.  
 
     
     
         3 . A compound of the formula I as claimed in    claim 1    in which:  
       W is R 1 —A—E—D—C(R 16 ), R 1 —A—B—D—C(R 16 )═C or  
                 

 Y is C═O, C═S or —CH 2 —;  
 Z is N(R 0 ) or —CH 2 —;  
 A is a direct linkage, (C 1 -C 6 )-alkanediyl, —NR 2 —N═CR 2 —, —NR 2 —C(O)—NR 2 —, —NR 2 —C(O)O—, —NR 2 —C(O)S—, —NR 2 —S(O)N—NR 2 —, —NR 2 —S(O) n —, (C 3 -C 6 )-cycloalkanediyl, —C≡C—, —NR 2 —C(O)—, —C(O)—NR 2 —, (C 5 -C 10 )-arylene-C(O)—NR 2 —, —O—, (C 5 -C 10 )-arylene-, —CO—, —(C 5 -C 10  )-arylene-CO—, —NR 2 —, —C(O)O—, —N═CR 2 —, —R 2 C═N— or —CR 2 ═CR 3 —, which in each case can be substituted by NR 2  andlor be substituted, once or twice, by (C 1 -C 6 )-alkanediyl;  
 B is a direct linkage, (C 1 -C 6 )-alkanediyl, (C 5 -C 6 )-arylene, (C 5 -C 6 )-cycloalkanediyl, —C≡C—, —NR 2 —C(O)—, —C(O)—NR 2 —, —NR 2 —S(O) 2 —, —O— or —CR 2 ═CR 3 —, which in each case can be substituted, once or twice, by (C 1 -C 6 )-alkanediyl;  
 D is a direct linkage, (C 1 -C 6 )-alkanediyl, (C 5  -C 6 )-arylene, —O—, —NR 2 —, —NR 2 —CO—, —NR 2 —C(O)—NR 2 —, —NR 2 —C(S)—NR 2 —, —OC(O)—, —C(O)—, —S(O) 2 —NR 2 —, —NR 2 —S(O)—, —NR 2 —S(O) 2 —, —N═CR 2 — or —R 2 C═N—, which in each case can be substituted, once or twice, by (C 1 -C 6 )-alkanediyl;  
 E is a direct linkage, (C 1 -C 4 )-alkanediyl or (C 2 -C 4 )-alkenediyl;  
 F is a direct linkage, (C 1 -C 6 )-alkanediyl, —O—, —CO—NR 2 —, —NR 2 —CO—, —NR 2 —C(O)—NR 2 —, —OC(O)—, —C(O)O—, —CO—, —S(O) 2 —, —S(O) 2 —NR 2 —, —NR 2 —S(O) 2 —, —CR 2 ═CR 3 —, —C≡C—, —N═CR 2 — or —R 2 C═N—, which in each case can be substituted, once or twice, by (C 1 -C 6 )-alkanediyl;  
 G is  
                 
 
 L is C(R 16 ) or N;  
 R 0  is H, (C 1 -C 6 )-alkyl, (C 3 -C 6 )-cycloalkyl, (C 3 -C 6 )-cycloalkyl-(C 1 -C 4 )-alkyi, (C 5 -C 10 )-aryl, (C 5 -C 10 )-aryl-(C 1 -C 4 )-alkyl, (C 1 -C 6 )-alkyl-C(O)—, (C 5 -C 6 )-cycloalkylmethyl-C(O)—, phenyl-C(O) or benzyl-C(O), where the alkyl radicals can be substituted by 1-6 fluorine atoms;  
 R 1  is R 2 —C(═NR 2 )NR 2 —, R 2 R 3 N—C(═NR 2 )—,  
                 
 
 with Y′ being NR 2 , O or S.  
 R 2  and R 3  are, independently of each other, H, (C 1 -C 6 )-alkyl which is optionally substituted, once or more than once, preferably 1-6 times, by fluorine, (C 3 -C 6 )-cycloalkyl, (C 3 -C 6 )-cycloalkyl-(C 1 -C 4 )-alkyl, (C 5 -C 10 )-aryl, (C 5 -C 10 )-aryl-(C 1 -C 4 )-alkyl, H 2 N, R 8 OR 9 , R 8 —(C 5 -C 10 )-aryl-R 9 , R 8 NHR 9 , R 8 R 8 NR 9 , R 8 NHC(O)R 9 , R 8 C(O)—, H 2 N—C(═NH) or H 2 N—C(═NH)—NH—;  
 R 4 , R 5 , R 6  and R 7  are, independently of each other, H, fluorine, OH, (C 1 -C 6 )-alkyl, (C 6 -C 12 )-cycloalkyl, (C 6 -C 12 )-cycloalkyl-(C 1 -C 6 )-alkyl, or R 8 OR 9 , R 8 CO 2 R 9 , R 8 OC(O)R 9 , R 8 -(C 5 -C 10 )-aryl-R 9 , R 8 NHR 9 , R 8 R 8 NR 9 , R 8 NHC(O)OR 9 , R 8 S(O) n NHR 9 , R 8 OC(O)NHR 9 , R 8 C(O)NHR 9 , R 8 C(O)R 9 , R 8 NHC(O)NHR 9 , R 8 NHS(O) n NHR 9 , R 8 NHC(O)R 9 , R 8 NHS(O) n R 9 ;  
 R 8  is H, (C 1 -C 6 )-alkyl, (C 6 -C 12 )-cycloalkyl, (C 6 -C 12 )-cycloalkyl-(C 1 -C 4 )-alkyl, (C 5 -C 10 )-aryl or (C 5 -C 10 )-aryl-(C 1 -C 4 )-alkyl, where the alkyl radicals can be substituted by 1-6 fluorine atoms;  
 R 9  is a direct linkage or (C 1 -C 6 )-alkanediyl;  
 R 10  is C(O)R 11 , S(O) n R 11  or P(O) n R 11 :  
 R 11  is OH, (C 1 -C 6 )-alkoxy, (C5-C 10 )-aryl-(C 1 -C 6 )-alkoxy, (C 5 -C 10 )-aryloxy, (C 1 -C 6 )-alkylcarbonyloxy-(C 1 -C 4 )-alkoxy, (C 5 -C 10 )-aryl-(C 1 -C 4 )-alkylcarbonyloxy-(C 1 -C 4 )-alkoxy, NH 2  or mono- or di(C 1 -C 6 -alkyl)-amino;  
 R 12 , R 13  and R 14  are H, (C 1 -C 6 )-alkyl, which is optionally substituted, once or more than once, by fluorine, (C 3 -C 6 )-cycloalkyl, (C 3 -C 6 )-cycloalkyl-(C 1 -C 4 )-alkyl, (C 5 -C 10 )-aryl, (C 5 -C 10 )-aryl-(C 1 -C 4 )-alkyl, H 2 N, R 8 OR 9 , R 8 OC(O)R 9 , R 8 -(C 5 -C 10 )-aryl-R 9 , R 8 R 8 NR 9 , R 8 NHC(O)R 9 , R 8 C(O)NHR 9 , H 2 N—C(═NH)—, H 2 N—C(═NH)—NH— or ═O; where two adjacent substituents from the group R 12  to R 14  can also together be —OCH 2 O— or —OCH 2 CH 2 O—;  
 R 16  is H, (C 1 -C 6 )-alkyl which can be substituted 16 times by fluorine, (C 3 -C 6 )-cycloalkyl, (C 3 -C 6 )-cycloalkyl-(C 1 -C 4 )-alkyl, phenyl, phenyl-(C 1 -C 4 )-alkyl or (C 2 -C 6 )-alkenyl;  
 m is 3,4 or 5;  
 n is 1 or 2; and  
 p and q are, independently of each other, 0 or 1, and the physiologically tolerated salts thereof.  
 
     
     
         4 . A compound of the formula I as claimed in    claim 1    , in which: 
 W is R 1 —A—E—D—C(R 16 ) or R 1 —A—B—D—CH═C,  
 Y is C═O or C═S;  
 Z is N(R 0 );  
 A is a direct linkage, (C 1 -C 4 )-alkanediyl, —NR 2 —N═CR 2 —, —NR 2 —C(O)—NR 2 —, —NR 2 —C(O)O—, —NR 2 —S(O) n —, —NR 2 —S(O) n —NR 2 —, —NR 2 —CO—, —NR 2 — or —N═CR 2 , which in each case can be substituted by NH and/or be substituted, once or twice, by (C 1 -C 4 )-alkanediyl;  
 B is a direct linkage, (C 1 -C 4 )-alkanediyl, phenylene, a divalent radiical of pyridine, thiophene or furane, cyclohexanediyl, —C≡C—, —CR 2 ═CR 3 —, —C(O)—NR 2 — or —NR 2 —C(O)—, which in each case can be substituted, once or twice, by (C 1 -C 4 )-alkanediyl;  
 D is a direct linkage, (C 1 -C 4 )-alkanediyl, phenylene, —O—, —NR 2 —, —NR 2 —CO—, —NR 2 —C(O)—NR 2 —, —R 2 N—S(O) 2 —NR 2 —, —NR 2 —S(O) 2 —, —NR 2 —S(O)—, —N═CR 2 — or —R 2 C═N—, which in each case can be substituted, once or twice, by (C 1 -C 4 )-alkanediyl;  
 E is a direct linkage or (C 1 -C 4 )-alkanediyl;  
 F is a direct linkage, (C 1 -C 6 )-alkanediyl, —O—, —CO—NR 2 —, —NR 2 —CO—, —NR 2 —C(O)—NR 2 —, —S(O) 2 —NR 2 —, —NR 2 —S(O) 2 —, —CR 2 ═CR 3 —, —C≡C—, —N═CR 2 — or —R 2 C═N—, which in each case can be substituted, once or twice, by (C 1 -C 4 )-alkanediyl;  
 G is  
                 
 
 R 0  is H, (C 1 -C 6 )-alkyl, trifluoromethyl, pentafluoroethyl, (C 5 -C 6 )-cycloalkyl, (C 5 -C 6 )-cycloalkyl-(C 1 -C 2 )-alkyl, optionally substituted phenyl or benzyl which is optionally substituted on the phenyl radical;  
                 
 
 R 2  and R 3  are, independently of each other, H, (C 1 -C 6 )-alkyl, trifluoromethyl, pentafluoroethyl, (C 5 -C 6 )-cycloalkyl, (C 5 -C 6 )-cycloalkyl-(C 1 -C 2 )-alkyl, phenyl, benzyl, H 2 N, R 8 OR 9 , R 8 —(C 5 -C 10 )-aryl-R 9 , R 8 NHR 9 , R 8 R 8 NR 9 , R 8 NHC(O)R 9 , H 2 N—C(═NH) or H 2 C—C(═NH)—NH—;  
 R 4 , R 5 , R 8  and R 7  are, independently of each other, H, fluorine, OH, (C 1 -C 6 )-alkyl, (C 10 -C 12 )-cycloalkyl, (C 10 -C 12 )-cycloalkyl-(C 1 -C 6 )-alkyl, or R 8 0R 9 , R 8 -(C 5 -C 10 )-aryl-R 9 , R 8 R 8 NR 9 , R 8 NHC(O)OR 9 , R 8 S(O) n NHR 9 , R 8 OC(O)NHR 9  or R 8 C(O)NHR 9 ;  
 R 8  is H, (C 1 -C 6 )-alkyl, (C 10 -C 12 )-cycloalkyl, (C 10 -C 12 )-Cycloalkyl-(C 1 -C 2 )-alkyl, (C 5 -C 10 )-aryl or (C 5 -C 10 )-aryl-(C 1 -C 2 )-alkyl;  
 R 9  is a direct linkage or (C 1 -C 6 )-alkanediyl,  
 R 10  is C(O)R 11 ;  
 R 11  is OH, (C 1 -C 6 )-alkoxy, phenoxy, benzyloxy, (C 1 -C 4 )-alkylcarbonyloxy-(C 1 -C 4 )-alkoxy, NH 2 , mono- or di(C 1 -C 8 -alkyl)amino;  
 R 16  is H, (C 1 -C 4 )-alkyl, trifluoromethyl, pentafluoroethyl, (C 5 -C 6 )-cycloalkyl, (C 5 -C 6 )-cycloalkyl-(C 1 -C 2 )-alkyl, phenyl or benzyl;  
 n is 1 or 2; and  
 p and q are, independently of each other, 0 or 1, and the physiologically tolerated salts thereof.  
 
     
     
         5 . A process for preparing a compound of formula I as claimed in    claim 1    wherein F is C(O)NR 2 , comprising linking a compound of formula II  
                 
 
       wherein M is hydroxycarbonyl, (C 1 -C 6 )-alkoxycarbonyl, or an activated carboxylic acid derivative, and W, Z, Y, and E are as defined in    claim 1   , with HNR 2 —G, wherein G and R 2  are as defined in    claim 1   .  
     
     
         6 . A pharmaceutical composition comprising a vitronectin receptor antagonistic amount of the compound of    claim 1   , and a pharmaceutically acceptable carrier.  
     
     
         7 . A method of treating a disease or condition associated with vitronectin receptor binding comprising administering to a mammal the composition of    claim 6   .  
     
     
         8 . A method of treating a disease or condition associated with the interaction between vitronectin receptors and their ligands in cell-cell or cell-matrix interaction processes, comprising the administration of the compound of    claim 1    to a mammal, wherein said disease or condition is selected from the group consisting of reabsorption by osteoclasts, tumor growth and tumor metastasis, inflammation, cardiovascular disease, nephropathies and retinopathies.