MXPA01007100A - &bgr;-PHENYLALANINE DERIVATIVES AS INTEGRIN ANTAGONISTS - Google Patents

Abstract

The present invention relates to compounds of general formula (1), wherein R4 is -SO2R4', -COOR4", -COR4', -CONR4'2 or -CSNR4'2;R4'is hydrogen, a substituted or unsubstituted alkyl or cycloalkyl residue, a substituted or unsubstituted aryl residue or a saturated or unsaturated, optionally substituted heterocyclic residue;R4"is a substituted or unsubstituted alkyl or cycloalkyl residue, a substituted or unsubstituted aryl residue or a saturated or unsaturated, optionally substituted heterocyclic residue;L is a sulphonamide, amide, ether, ester, keto, urea, thioether, sulphoxide or sulphone unit optionally extended by one or two methylene groups;and X is N, O or S;and their physiologically acceptable salts and stereoisomers. The present invention furthermore relates to a process for the preparation of the compounds of formula (1), a pharmaceutical composition containing at least one of these compounds, and the use of compounds of formula (1) for the production of a pharmaceutical composition having integrin-antagonistic action and in particular for the inhibition of angiogenesis and/or for the therapy and prophylaxis of cancer, osteolytic diseases such as osteoporosis, arteriosclerosis, restenosis and ophthalmic disorders.

Description

BETA-PHENYLALANIN DERIVATIVES AS INTEGRINE ANTAGONISTS Field of the Invention The present invention relates to β-phenylalanine derivatives, their preparation and use as pharmaceutical compositions, as integrin antagonists and in particular, for the production of pharmaceutical compositions for the treatment and prophylaxis of cancer, arteriosclerosis, restenosis, rheumatoid arthritis, conditions osteolytics, such as osteoporosis and ophthalmic diseases.

BACKGROUND OF THE INVENTION Integrins are heterodimeric transmembrane proteins located on the surface of cells, which play an important part in the adhesion of cells to an extracellular matrix. They recognize extracellular glycoproteins, such as fibronectin or vitronectin on the extracellular matrix by means of the RGD sequence that occurs in these proteins (RGD is the simple letter code for the amino acid sequence arginine-glycine-aspartate). In general, the interim ones, such as, for example, the REF: 130976 amino acid arginine-glycine-aspartate). In general, interim, such as, for example, the vitronectin receptor, which is also referred to as the avß3 receptor, or alternatively the avß5 receptor or the GpIIb / IIIa receptor, play an important part in biological processes such as migration cellular and cellular matrix adhesion and in this way, in diseases in which these processes are crucial stages. Examples that may be mentioned are cancer, osteoporosis, arteriosclerosis, restenosis (fresh occurrence of a stenosis after a surgical intervention as a result of damage to the vesicular wall) and ophthalmia (a certain type of inflammation of the eye). The vß3 receptor occurs, for example, in large amounts in the growth of endothelial cells and makes its adhesion to an extracellular matrix possible. In this way, the avß3 receptor plays an important part in angiogenesis, i.e. the formation of new blood vessels, which is a crucial requirement for tumor growth and formation of metastases in carcinomatous diseases. In addition, it is also responsible for the interaction between osteoclasts, i.e. cells that resorbed mineralized tissue, and the bone structure. The first stage in the degradation of bone tissue consists of the adhesion of osteoclasts to the bone. This cell-matrix interaction is carried out via the avß3 receptor, this is because the corresponding integrin plays an important part in this process. Osteolytic diseases such as osteoporosis are caused by an imbalance between bone formation and bone degradation, i.e. resorption of bone material caused by the addition of osteoclast predominations. It was possible to show that the blocking of the aforementioned receptors is an important starting point for the treatment of ailments of this type. If the adhesion of growing endothelial cells to an extracellular matrix is suppressed by blocking their corresponding integrin receptors, for example by a cyclic peptide or a monoclonal antibody, the endothelial cells die. Therefore, angiogenesis does not occur, which leads to a stoppage or regression of tumor growth (cf., for example, Brooks et al., Cell, Volume 79, 1157-1164, 1994). In addition, the invasive properties of the tumor cells and thus their ability to metastasize, are markedly reduced if their avß3 receptor is blocked by an antibody (Brooks et al., J. Clin. Invest., Volume 96, 1815, nineteen ninety five). Bone tissue degradation can obviously be suppressed by the blocking of the avß3 receptors of the osteoclasts, since they are then unable to accumulate in the bone to resorb their substance (WO 98/18461, p.1, 1, 24 a 2, 1, 13). As a result of the blocking of the vß3 receptor on the cells of the smooth vascular muscle of the aorta with the help of the integrin receptor antagonists, it is possible to suppress the migration of these cells in the neointima and in this way, the angioplasty that leads to artiosclerosis and restenosis (Brown et al., Cardiovascular Res., Volume 28, 1815, 1994). In recent years, therefore, compounds that act as antagonists of integrin receptors have been sought. For example, WO 98/00395 discloses the phenylalanine derivative for substituted (I), which exhibits an IC50 value of 0.13 nM in an avß3 receptor assay and an IC50 value of 0.16 nM in an avß5 receptor test: Acid-phenylcarboxylic acids having a phenyl residue which is linked to the phenyl group via a linker group and having a guanidine unit or an imitation of guanidine are described, for example in WO 97/36858, WO 97/36859 , WO 97/36860 and WO 97/36862. According to these filed patent applications, the linker group can be an amide, sulfonamide, ester, urea, ether, thioether, sulfoxide, sulfone or ketone unit which could be extended by an additional methylene group or can be a saturated alkylene bridge or unsaturated In particular, WO 97/36859, in addition to numerous substances comprised by a general formula, actually describes derivatives of 3-phenylpropionic acid, such as (II) or (III). While the (II) derivative of α-phenylalanine exhibits an IC 50 value of 0.18 nM with respect to its activity as an avß3 antagonist in in-vitro investigations, the succinic acid derivatives (III) have IC 50 values in the range of 38.7 to 141 nM in the same investigations: R = OH, OEt, NHCH2COOH WO 97/36862, in addition to numerous substances comprised by a general formula, actually describes β-substituted propionic acid derivatives, such as (IV) or (V). The derivative (IV) of the sulfonamide bridge exhibits an IC50 value of 16.7 nM with respect to its activity as an ovß3 antagonist in in-vitro investigations, while the amide bridge derivatives (V) have IC50 values in the range of 0.87 to 11.6 nM in the same investigations: R = methyl, isopropyl, phenyl, 3,5-difluorophenyl G = G = However, none of the filed patent applications mentioned above describe β-phenylalanine derivatives or their activity as avß3 antagonists. Β-phenylalanine derivatives as avß antagonists are described, for example, in US-5639765, WO 97/08145 and WO 97/36861, the binding of the carboxyl residue to the central group consisting of two phenyl units linked to each other via a linker group found in these compounds, if a central group is present at all of this type, via the amino group. for example, the compound (VI) described in WO 97/36861 exhibits an IC50 value of 1.66 nM with respect to its activity as an avß3 antagonist in in-vitro investigations.

It was the aim of the present invention to develop compounds exhibiting a high activity as integrin antagonists and in particular against the avß3 and / or avß5 receptor.

Brief Description of the Invention The present invention is achieved according to the invention by the β-phenylalanine derivatives defined below. In particular, it was obtained that the β-phenylalanine derivatives according to the invention have a very high activity as integrin antagonists, especially against the avß3 and / or avß5 receptor. The present invention relates to compounds of the general formula (1) where R1 is hydrogen, a substituted or unsubstituted alkyl or cycloalkyl residue, a substituted or unsubstituted aryl residue or a saturated or unsaturated, optionally substituted heterocyclic residue; R is hydrogen, a substituted or unsubstituted alkyl or cycloalkyl residue, a substituted or unsubstituted aryl residue, an optionally substituted, saturated or unsaturated heterocyclic residue, an optionally substituted alkenyl residue, an optionally substituted alkynyl residue, a hydroxyl residue or an alkoxy residue or binds to R3 with the formation of an optionally substituted carbocyclic or heterocyclic ring system that includes the carbon atom to which R is linked and may optionally contain heteroatoms; R3 is hydrogen, a substituted or unsubstituted alkyl or cycloalkyl residue, a substituted or unsubstituted aryl residue, a saturated or unsaturated heterocyclic residue, optionally substituted, an optionally substituted alkenyl residue, an optionally substituted alkynyl residue, a hydroxyl residue or an alkoxy residue or R2 is linked to the formation of an optionally substituted carbocyclic or heterocyclic ring system that includes the carbon atom to which R3 is linked and may optionally contain heteroatoms; R- is -S02R4 ', -COOR4", -COR4', -CONR'2 or -CSNR4'2; R 'is hydrogen, a substituted or unsubstituted alkyl, alkenyl or cycloalkyl residue, a substituted or unsubstituted aryl residue or a residue saturated or unsaturated heterocyclic, optionally substituted, R 4 'is a substituted or unsubstituted alkyl or cycloalkyl residue, a substituted or unsubstituted aryl residue or a saturated or unsaturated heterocyclic residue, optionally substituted; R "is hydrogen, an alkyl or substituted cycloalkyl residue or unsubstituted or a substituted or unsubstituted aryl residue; R 10 is hydrogen, a substituted or unsubstituted alkyl or cycloalkyl residue, a substituted or unsubstituted alkoxy residue or a halogen atom; R 11 is hydrogen, a substituted or unsubstituted alkyl or cycloalkyl residue, a substituted or unsubstituted alkoxy residue or a halogen atom; is - (CH2) mNHS02 (CH2) n-, - (CH2) mS02NH (CH2) n-, (CH2) mNHCO (CH2) n-, - (CH2) mCONH (CH2) n-, (CH2) mOCH2 (CH2) ) n-, - (CH2) mCH20 (CH2) n-, (CH2) mC00 (CH2) n-. - (CH2) mOOC (CH2) n-, (CH2) mCH2CO (CH2) n-, - (CH2) mCOCH2 (CH2) n-, -NHCONH-, - (CH2) mSCH2 (CH2) n-, - (CH2) ) mCH2S (CH2) n-, (CH2) mCH2SO (CH2) n-, - (CH2) mSOCH2 (CH2) n-, (CH2) mCH2S02 (CH2) n- or - (CH2) mS02CH2 (CH2) n-, where m and n are each an integer of 0 or 1 and m + n < 1; R6 is hydrogen, a substituted or unsubstituted alkyl or cycloalkyl residue, a substituted or unsubstituted aryl residue, a saturated or unsaturated heterocyclic residue, optionally substituted or linked to one of R7, R8 or R9, if present, with the formation of a optionally substituted heterocyclic ring system including the nitrogen atom to which R6 is bonded and may be saturated or unsaturated and / or may contain additional heteroatoms; X is N, O or S; R7 is absent, is -H, a substituted or unsubstituted alkyl or cycloalkyl residue, -N02-, -CN, -COR7 ', -COOR7', or is linked to one of R6, R8 or R9 with the formation of an optionally substituted heterocyclic ring system including X and may be saturated or unsaturated and / or may contain additional heteroatoms; R7 'is hydrogen, a substituted or unsubstituted alkyl or cycloalkyl residue, a substituted or unsubstituted aryl residue or a saturated or unsaturated, optionally substituted heterocyclic residue which may be saturated or unsaturated and / or may contain additional heteroatoms; Rc is hydrogen, a substituted or unsubstituted alkyl or cycloalkyl residue, a substituted or unsubstituted aryl residue, a saturated or unsaturated heterocyclic residue, optionally substituted or linked to one of R6, R7 or R9, if present, with the formation of a optionally substituted heterocyclic ring system including the nitrogen atom to which R8 is linked and may be saturated or unsaturated and / or may contain additional heteroatoms; R- is hydrogen, a substituted or unsubstituted alkyl or cycloalkyl residue, a substituted or unsubstituted aryl residue, a saturated or unsaturated heterocyclic residue, optionally substituted or linked to one of R6, R7 or R8, if present, with the formation of an optionally substituted heterocyclic ring system that includes the nitrogen atom to which R9 is linked and can be saturated or unsaturated and / or can contain additional heteroatoms; and their physiologically acceptable salts and stereoisomers. According to the invention, the preferred compounds of the formula (1) are those in which R1 is hydrogen, a C? -C6 alkyl residue, a C3_7 cycloalkyl residue, an aryl residue or a substituted derivative thereof; R2 is hydrogen, a C? _6 alkyl residue. a C3_7 cycloalkyl residue, an aryl residue, an alkenyl residue, an alkynyl residue or a substituted derivative thereof; a hydroxyl residue or a C6_6 alkoxy residue or is linked to R "with the formation of an optionally substituted carbocyclic or heterocyclic ring system including the carbon atom to which R2 is linked and may optionally contain heteroatoms; R3 is hydrogen, a C.sub.6 alkyl residue, a C3_7 cycloalkyl residue, an aryl residue, an alkenyl residue, an alkynyl residue or a substituted derivative thereof, a hydroxyl residue or a C? -6 alkoxy residue or binds to R2 with the formation of an optionally substituted carbocyclic or heterocyclic ring system that includes the carbon atom to which R- is linked and may optionally contain heteroatoms; R 'is -S02R4', -COOR4", -COR4 ', -CONR4'2 or -CSNR4'2; R 'is hydrogen, a C? -β alkyl residue, an optionally substituted C2_6 alkenyl residue, a C3_7 cycloalkyl residue, a substituted or unsubstituted aryl residue or a saturated or unsaturated, optionally substituted heterocyclic residue; R "is a C alquilo-β alkyl residue, a cycloalkyl residue C3_, a substituted or unsubstituted aryl residue or a saturated or unsaturated heterocyclic residue, optionally substituted; R- is hydrogen, a C? _6 alkyl residue, a C3_7 cycloalkyl residue, a C? _6 alkoxy residue or a substituted derivative thereof; R 10 is hydrogen, a C? _6 alkyl residue. a C3_7 cycloalkyl residue, a C6_6 alkoxy residue or a substituted derivative thereof or F, Cl, Br or I; 11 is a C C-6 alkyl residue, a C 3 cycloalkyl residue, an aryl residue or a substituted derivative thereof or F, Cl, Br or I; is -NHS02-, -CH2NHS02-, -NHS02CH2-, -S02NH-, CH2S02NH-, -S02NHCH2-, -NHCO-, -CH2NHCO-, -NHCOCH2-, -CONH-, -CH2CONH-, -CONHCH2-, -OCH2-, -CH2OCH2, -OCH2CH2-, -CH20- -CH2CH20-, -COO-, -CH2COO-, -COOCH2-, -OOC-, -OOCCH2-, -CH2OOC-, -CH2CO-, -COCH2-, - CH2CH2CO-, -COCH2CH2-, -CH2COCH2-, -NHCONH-, -SCH2-, -CH2S-, -CH2SCH2, -SCH2CH2-, -CH2CH2S-, -SOCH2- , - CH2SO-, -CH2SOCH2-, -SOCH2CH2-, -CH2CH2SO-, -S02CH2-, -CH2S02-, -CH2S02CH2-, -CH2CH2S02- or -S02CH2CH2-; R1 is hydrogen, a C? _6 alkyl residue. a C3.7 cycloalkyl residue, an aryl residue or a substituted derivative thereof or is linked to one of R7, R8 or R9, if present, with the formation of an optionally substituted heterocyclic ring system including the nitrogen atom at which R6 is linked and can be saturated or unsaturated and / or can contain additional heteroatoms; X is O, N or S; R7 is absent, is -H, a C? _6 alkyl residue, a C3_7 cycloalkyl residue, -N02, -CN, -COR7'-, COOR7 ', or is linked to one of R6, R8 or R9 with the formation of a optionally substituted heterocyclic ring system including X and may be saturated or unsaturated and / or may contain additional heteroatoms; R 'is hydrogen, a C? -6 alkyl residue. a C3_7 cycloalkyl residue, an aryl residue or a substituted derivative thereof; is hydrogen, a C? -β alkyl residue, a C3_ cycloalkyl residue, an aryl residue or a substituted derivative thereof or is linked to one of R6, R7 or R9, if present, with the formation of a heterocyclic ring system optionally substituted which includes the nitrogen atom to which R8 is linked and may be saturated or unsaturated and / or may contain additional heteroatoms; and R9 is hydrogen, an optionally substituted C6_6 alkyl residue, a C3_ cycloalkyl residue, an aryl residue or a substituted derivative thereof, an unsaturated heterocyclic residue, optionally substituted or linked to one of R6, R7 or R8, if present, with the formation of an optionally substituted heterocyclic ring system including the nitrogen atom to which R9 is bonded and can be saturated or unsaturated and / or can contain additional heteroatoms. Particularly, the preferred compounds of the formula according to the present invention are those in which R1 is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclobutyl , cyclopentyl, cyclohexyl, cycloheptyl, phenyl, benzyl, tolyl or a substituted derivative thereof; R2 is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, phenyl, benzyl, tolyl or a substituted derivative thereof, -OH, methoxy, ethoxy, propoxy, butoxy, pentoxy, hexoxy, benzyloxy or is linked to R3 with the formation of an optionally substituted carbocyclic or heterocyclic ring system of 3 to 6 members including the carbon atom to which R2 is bonded and may optionally contain heteroatoms; R3 is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, phenyl, benzyl, tolyl or a substituted derivative thereof, -OH, methoxy, ethoxy, propoxy, butoxy, pentoxy, hexoxy, or is linked to R2 with the formation of an optionally substituted 3 to 6 membered carbocyclic or heterocyclic ring system including the carbon atom to which R3 is bonded and can optionally contain heteroatoms; R4 is -S02R4 ', COOR4' or -COR 4 '; R4' is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, ciciohexilo, cycloheptyl, phenyl, benzyl, tolyl or a substituted derivative thereof, -C 6 H 2 (CH 3) 3, -C 6 (CH 3) 5, -CH 2 C 6 H 2 (CH 3) 3, 4-phenyl phenyl, 2-chlorophenyl, 3-chlorophenyl, 4- chlorophenyl, 2,3-dichlorophenyl, 2,4-dichlorophenyl, 3,4-dichlorophenyl, 2,5-dichlorophenyl, 3,5-dichlorophenyl, 2,6-dichlorophenol, 2-chlorophenylmethyl, 4-chlorophenylmethyl, 2,4 - dichlorophenylmethyl, 2, 6-dichlorophenylmethyl, 2-metoxicarbonilfenilmetilo, 3-trifluoromethylphenyl, 4-trifluoromethylphenyl, 3,5-bis (trifluoromethyl) phenyl, 4-trifluoromethoxyphenyl, phenylmethyl, 2-acetamido-4-methyl-thiazol-5-yl , phenylethyl, l-phenylpropyl, (S) - (+) - camphor-10-yl, (R) - (-) -canfor-10-yl, 2-phenylethenyl, 2-thiophenyl, 4-methoxyphenyl, 3, 5 -methoxyphenyl, 3-methylphenyl, 4-methylphenyl, 4-t-butylphenyl, 4 -pro pylphenyl, 2,5-dimethylphenyl, 2-methoxy-5-methylphenyl, 2,3,5,6-tetramethylphenyl, 2,3,4,5,6-pentamethylphenyl, 1-naphthyl, 2-naphthyl, 4-fluorophenyl, 2,4-difluorophenyl, 2-chloro-6-methylphenyl, 2-chloro-4-fluorophenyl, 2,5-dimethoxyphenyl, 3,4-dimethoxyphenyl, 3-chloro-6-methoxyphenyl, 2-trifluoromethylphenyl, 2-alkylsulfonylphenyl, 2-arylsulfonylphenyl, 3- (N-acet-il-6-methoxy) aniline, 4-acetamidophenyl, 2,2,2-trifluoroethyl, 5-chloro-3-methyl-benzothiazol-2-yl, N-methoxycarbonylpiperidin- 3- ilo, thiophen-2-yl, isoxazol-5-yl, 2-chloropyridin-3-yl, pyridin-3-yl, 5-methylisoxazol-3-yl, 1-adamantyl, 4-chlorophenoxymethyl, 2,2-dimethylethenyl, 2-chloropyridin-5-methyl, 5,7-dimethyl-1,3-, 4-triazaindolizin-2-yl, (S) -canphan-1-yl, (R) -canphan-1-yl, 8-quinolinyl; R4"is methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, ciciohexilo, cicioheptilo, phenyl, benzyl, or a substituted derivative thereof, -CH2C6H2 (CH3) 3, 2-chlorophenylmethyl, 4- chlorophenylmethyl, 2, 4-dichlorophenylmethyl, 2,6-dichlorophenylmethyl, 2-metoxicarbonilfenilmetilo, 3- trifluoromethylphenylmethyl, 4- trifluoromethylphenylmethyl, 3,5- bis (trifluoromethyl) phenylmethyl, 4 - trifluoromethoxyphenyl, 2-thiophenylmethyl, 4- metoxifenilometilo, 3, 5-dimethoxyphenylmethyl, 3- methylphenylmethyl, 4 -methyl-phenylmethyl, 4-t- -butylphenylmethyl, 4-propilfenilmetilo, 2,5- dimethylphenylmethyl, 2-methoxy-5-methylphenylmethyl , 2, 3, 5, 6-tetramethylphenylmethyl, 2,3,4,5,6-pentamethylphenylmethyl, 1-naphthylmethyl, 2-naphthylmethyl, 4-fluorophenylmethyl, 2,4-difluorophenylmethyl, 2-chloro-6-methylphenylmethyl, 2 -chloro-4-fluoro-phenylmethyl, 2,5-dimethoxyphenylmethyl, 3,4-dimethoxyphenylmethyl, 3-chloro-6-methoxyphenylmethyl, 2-trifluoromet ilfeni 1-methyl, 2,2,2-trifluoroethyl, isoxazol-5-ylmethyl, 2-chloropyridin-3-ylmethyl, pyridin-3-yl-1-methyl, 2-chloropyridin-5-met ilo; is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclopropylmethyl, cyclobutyl, cyclopentyl, ciciohexilo, cicioheptilo, 4-meth yl-cyclohexyl ester, 3, 3, 5- trimethylcyclohexyl, 5-met i 1-2 -hexyl, phenyl, benzyl, tolyl or a substituted derivative thereof, C 1 -C 4 alkylamino C 1-4 dialkylamino C 4 -C 4 alkyl, amino C 1 alkyl, C1_alkyloxyCalkyl- or (a) (a2) (a3) (a4) (a5) (aß) (a7) (aß) 09) (a 10) (a11) (a12) (a13) (a14) (a 15) (to 6) (to! 7) (to 18) (to 19) (a20) (a21) (a22) (a23) (a24) (a25) < a26) (a27) (a28) R10 is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, methoxy, ethoxy, propoxy, butoxy, pentoxy or hexoxy, fluorine, chlorine, bromine or iodine; .11 is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cydoheptyl, methoxy, ethoxy, propoxy, butoxy, pentoxy or hexoxy , fluorine, chlorine, bromine or iodine; is -NHS02-, -CH2NHS02-, -NHS02CH2-, -S02NH-, CH2S02NH-, -S02NHCH2-, -NHCO-, -CH2NHCO-, -NHCOCH2-, -CONH-, -CH2CONH-, -CONHCH2-, -OCH2 -, -CH2OCH2, - OCH2CH2-, -CH20- or -CH2CH20-; R < is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclopropylmethyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, 4-methylcyclohexyl, 3,3,5-trimethylcyclohexyl , 5-met i1-2 -hexyl, phenyl, benzyl, tolyl or a substituted derivative thereof, C4_4 alkylamino C4_4alkyl, dialkylamino C4_4_C1_alkyl, amino_C4_4alkyl, alkyloxy C? -alkyl C? -, one of the residues (al) to (a28) or binds to one of R7, R8 or R9, if present, with the formation of a 4- to 6-membered heterocyclic ring system optionally substituted which includes the nitrogen atom to which R6 is linked and may be saturated or unsaturated and / or may contain additional heteroatoms; X is N, 0 or S; R7 is absent, is -H, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, -N02, -CN, -COR7 ', -COOR7' or is linked to one of R6, R8 or R9 with the formation of an optionally substituted heterocyclic or carbocyclic 4- to 6-membered ring system including X and may be saturated or unsaturated and / or may contain additional heteroatoms; R7 'is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, phenyl, benzyl, tolyl or a substituted derivative thereof; R8 is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclopropylmethyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, 4-methylcyclohexyl, 3, 3, 5- trimethylcyclohexyl, 5-methyl-2-hexyl, phenyl, benzyl, tolyl or a substituted derivative thereof, C 1 -C 4 alkylamino, C 4 alkyl dialkylamino 4 C 4 alkyl, amino C 4 alkyl Alkyloxy C? _4-C? _4 alkyl, one of the residues (al) a (a28) or binds to one of R6, R7 or R9, if present, with the formation of a ring system of 4 to 6 optionally substituted heterocyclic members including the nitrogen atom to which R8 is bonded and may be saturated or unsaturated and / or may contain additional heteroatoms; and is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclopropylmethyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, 4-methylcyclohexyl, 3,3,5 -trimethylcyclohexyl, 5-methyl-2-hexyl, phenyl, benzyl, tolyl or a substituted derivative thereof, C 1-4 alkylamino C? _4 alkyl, dialkylamino C? _4-C? _4 alkyl, amino C? _4 alkyl, Alkyloxy C? _4-C? _4 alkyl, one of the residues (al) a (a28) or binds to one of R6, R7 or R8, if present, with the formation of a ring system of 4 to 6 members optionally substituted heterocyclic including the nitrogen atom to which R9 is linked and may be saturated or unsaturated and / or may contain additional heteroatoms. According to a preferred embodiment, the present invention relates to compounds of the formula (1) wherein R4 is -S02R4 '; R4 'is methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, phenyl, benzyl, tolyl or substituted derivative thereof, -C6H2 (CH3) 3, -C6 (CH3) 5. -CH2C6H2 (CH3) 3, 4-phenyl-phenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2,3-dichlorophenyl, 2-dichlorophenyl, 3,4-dichlorophenyl, 2,5-dichlorophenyl, 3, 5- dichlorophenyl, 2,6-dichlorophenyl, 2-chlorophenylmethyl, 4-chlorophenylmethyl, 2,4-dichlorophenylmethyl, 2,6-dichlorophenylmethyl, 2-methoxycarbonyl phenylmethyl, 3-trifluoromethylphenyl, 4-trifluoromethylphenyl, 3,5-bis (trifluoromethyl) ) phenyl, 4-trifluoromethoxyphenyl, phenylmethyl, 2-acetamido-4-methyl-thiazol-5-yl, phenylethyl, 1-phenylpropyl, (S) - (+) - camphor-10-yl, (R) - (- ) - camphor-10-yl, 2-phenylethenyl, 2-thiophenyl, 4-methoxyphenyl, 3,5-dimethoxyphenyl, 3-methylphenyl, 4-methylphenyl, 4-t-butylphenyl, 4-propylphenyl, 2,5-dimethylphenyl, 2-methoxy-5-methylphenyl, 2,3,5,6-tetramethylphenyl, 2, 3, 4, 5, 6-pentametylphenyl, 1-naphthyl, 2-naphthyl, 4-fluoro-phenyl, 2,4-difluorophenyl, 2-chloro-6-methyl-l-phenyl, 2-chloro-4-fluorophenyl, 2,5-dimethoxyphenyl, 3,4-dimethoxyphenyl, 3-chloro-6-methoxy-phenyl, 2-trifluo romet-ilphenyl, 2-alkylsulfonylphenyl, 2-aryl-sulfonylphenyl, 3- (N-acetyl-6-methoxy) aniline, 4-acetamidophenyl, 2,2,2-trifluoroethyl, 5-chloro-3-methyl-benzothiazole-2- ilo, N-methoxycarboni1-piperidin-3-yl, thiophen-2-yl, isoxazol-5-yl, 2-chloropyridin-3-yl, pyridin-3-yl, 5-methylisoxazol-3-yl, 1-adamantyl, 4-chlorophenoxymethyl, 2,2-dimethyletenyl, 2-chloropyridin-5-methyl, 5,7-dimeti 1-1, 3, 4-triazaindolizin-2-yl, (S) -canphan-1-yl, (R) -Canfan-1-yl or 8-quinolinyl; is -NHS02-, -CH2NHS02-, -NHS02CH2-; X is N or O; the other residues are as defined above. According to a further preferred embodiment, the present invention relates to compounds of the formula (1) wherein R4 is -COR4 '; R 4 is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, phenyl, benzyl, tolyl or a substituted derivative thereof, -C6H2 (CH3) 3, -C6 (CH3) 5, -CH2C6H2 (CH3) 3;, 4-phenylphenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2,3-dichlorophenyl, 2,4-dichlorophenyl, 3,4-dichlorophenyl, 2,5-dichlorophenyl, 3,5-dichlorophenyl, 2,6-dichlorophenyl, 2-chlorophenylmethyl, 4-chlorophenylmethyl, 2,4-dichlorophenylmethyl, 2,6-dichlorophenylmethyl, 2- methoxycarbonylphenylmethyl, 3- trifluoromethylphenyl, 4-trifluoromethylphenyl, 3,5-bis (trifluoromethyl) phenyl, 4-trifluoromethoxyphenyl, phenylmethyl,. 2-Acetamido-4-methyl-yl-thiazol-5-yl, phenylethyl, l-phenylpropyl, (S) - (+) - camphor-10-yl, (R) - (-) -camphor-10-yl, 2-Phenylethenyl, 2-thio-phenyl, 4-methoxyphenyl, 3,5-dimethoxyphenyl, 3-methylphenyl, 4-methylphenyl, 4-t-butylphenyl, 4-propylphenyl, 2,5-dimethylphenyl, 2-methoxy-5- methylphenyl, 2, 3, 5, 6-tetramethylphenyl, 2,3,4,5,6-pentamethylphenyl, 1-naphthyl, 2-naphthyl, 4-fluorophenyl, 2,4-difluorophenyl, 2-chloro-6-methylphenyl, 2-chloro-4-fluorophenyl, 2,5-dimethoxyphenyl, 3,4-dimethoxyphenyl, 3-chloro-6-methoxyphenyl, 2-trifluoromet-ilphenyl, 2-alkylsulfonylphenyl, 2-arylsulfonylphenyl, 3- (N-acetyl-6-) methoxy) aniline, 4-acetamidophenyl, 2,2,2-trifluoroethyl, 5-chloro-3-methylbenzothiazol-2-yl, N-methoxycarbonylpiperidin-3-yl, thiophen-2-yl, isoxazol-5-yl, 2-chloropyridin-3-yl, pyridin-3-yl, 5-methylisoxazol-3-yl, 1-adamantyl, 4-chlorophenoxymethyl, 2,2-dimethyletenyl, 2-chloropyridin-5-methyl, 5,7-dimeti-1 , 3,4-triazaindoli zin-2-yl, (S) -canfan-l-yl, (R) -canfan-1-yl or 8-quinolinyl; L is -NHS02-, -CH2NHS02- or -NHS02CH2-; X is N or O; and the other residues are as defined above. According to a preferred embodiment, the present invention relates to compounds of the formula (1) wherein R 4 is -COOR 4; is methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, phenyl, benzyl, or a substituted derivative thereof, CH2C6H2 (CH3) 2, 2-chlorophenylmethyl, 4- chlorophenylmethyl, 2, 4-dichlorophenylmethyl, 2,6-dichlorophenylmethyl, 2-metoxicarbonilfenilmetilo, 3-trifluoromethylphenylmethyl, 4-trifluoromet ylphenylmethyl, 3,5-bis (trifluoromethyl) phenylmethyl, 4 -trifluorometoxifenilo, 2-thiophenylmethyl, 4-methoxyphenylmethyl, 3, 5-dimethoxyphenylmethyl, 3-methylphenylmethyl, 4 -met ylphenylmethyl, 4-t -butylphenylmethyl, 4-propilfenilmetilo, 2,5-dimethylphenylmethyl, 2-methoxy-5-methylphenylmethyl, 2,3,5,6-tetramethylphenylmethyl, 2,3,4,5,6-pentamethylphenylmethyl, 1-naphthyl and yl, 2-naphthylmethyl, 4-fluorophenylmethyl, 2,4-difluorophenylmethyl, 2-chloro-6-methylphenylmethyl, 2-Chloro-4-fluoro-phenylmethyl, 2,5-dimethoxyphenylmethyl, 3,4-dimethoxyphenylmethyl, 3-chloro-6-methoxyphenylmethyl, 2-trifluoromethylphenylmethyl, 2,2,2-trifluoroethyl, isoxazol-5-ylmethyl, 2- chloro-pyridin-3-yl-methyl yl, pyridin-3-yl-methyl yl, 2-chloropyridin-5-methyl; L is -NHS02-, -CH2NHS02- or -NHS02CH2-; X is N or O; and the other residues are as defined above. According to a still further preferred embodiment, the present invention relates to compounds of the formula (1) wherein Rf is -S02R4; R 'is methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, ciciohexilo, cicioheptilo, phenyl, benzyl, tolyl or a substituted derivative thereof, - C 6 H 2 (CH 3) 3-, -C 6 (CH 3) 5, -CH 2 C 6 H 2 (CH 3) 3, 4-phenylphenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2,3-dichlorophenyl, 2,4-dichlorophenyl, 3 , 4- dichlorophenyl, 2, 5-dichlorophenyl, 3,5- dichlorophenyl, 2, 6-dichlorophenyl, 2-chlorophenylmethyl, 4-chlorophenylmethyl, 2,4-dichlorophenylmethyl, 2, 6-dichlorophenylmethyl, 2- metoxicarbonilfenilmetilo, 3 -trifluoromethylphenyl, 4-trifluoromethylphenyl, 3,5-bis (trifluoromethyl) phenyl, 4-trifluoromethoxyphenyl, phenylmethyl, 2 -acetamido-4-methyl-thiazol-5-yl, phenylethyl, l-phenylpropyl, (S) - (+ ) -canfor-10-ilo, (R) - (-) -canfor-10-yl, 2-phenylethenyl, 2-thiophenyl, 4-methoxyphenyl, 3,5-dimethoxyphenyl, 3-methylphenyl, 4-methylphenyl, 4-t-butylphenyl, 4-propylphenyl, 2, 5-dimethylphenyl, 2-methoxy-5-methylphenyl, 2,3,5,6-tetramethylphenyl, 2,3,4,5,6-pentamethylphenyl, 1-naphthyl, 2-naphthyl, 4-fluoro-phenyl, 2, 4- difluorophenyl, 2-chloro-6-methylphenyl, 2-chloro-4-fluorophenyl, 2,5-dimethoxyphenyl, 3,4-dimethoxyphenyl, 3-chloro-6-methoxy-phenyl, 2-trifluoromet-ilphenyl, 2-alkylsulfonylphenyl , 2- arylsulfonylphenyl, 3- (N-acetyl-6-methoxy) aniline, 4-acetamidophenyl, 2,2,2-trifluoroethyl, 5-chloro-3-methyl-benzothiazol-2-yl, N-methoxycarbonyl-piperidin-3-yl, thiophen-2-yl, isoxazol-5-yl, 2- chloropyridin-3-yl, pyridin-3-yl, 5-methylisoxazol-3-yl, 1-adamantyl, 4-chlorophenoxymethyl, 2,2-dimethylethenyl, 2-chloropyridin-5-methyl, 5,7-dimethyl -1, 3, -triazaindolizin-2-yl, (S) -canphan-1-yl, (R) -canphan-1-yl or 8-quinolinyl; is -NHCO-, -CH2NHCO- or -NHCOCH2-; X is N or O; The other waste is as defined above.

According to a still further preferred embodiment, the present invention relates to compounds of the formula (1) wherein R 4 is -S02R 4 '; R4 is methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, ciciohexilo, cicioheptilo, phenyl, benzyl, tolyl or a substituted derivative thereof, -C6H2 (CH3) 3, -C6 (CH3) 5, -CH2C6H2 (CH3) 3, -phenylphenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2,3-dichlorophenyl, 2,4-dichlorophenyl, 3,4- dichlorophenyl, 2, 5-dichlorophenyl, 3,5- dichlorophenyl, 2, 6-dichlorophenyl, 2- chlorophenylmethyl, 4-chlorophenylmethyl, 2,4-dichlorophenylmethyl, 2, 6-dichlorophenylmethyl, metoxicarbonilfenilmetilo 2-, 3-trifluoromethylphenyl, 4-trifluoromethylphenyl, 3,5-bis (trifluoromethyl) phenyl, 4-trifluoromethoxyphenyl, phenylmethyl, 2-acetamido-4-methyl-thiazol-5-yl, phenylethyl, l-phenylpropyl, (S) - (+) - camphor -10-yl, (R) - (-) -canfor-10-yl, 2-phenylethenyl, 2-thiophenyl, 4-methoxyphenyl, 3,5-dimethoxyphenyl, 3-methylphenyl, 4-methylphenyl, 4-t-butylphenyl , 4-propylphenyl, 2,5-dimethylphenyl, 2-methoxy-5-methylphenyl, 2,3,5,6-tetramethylphenyl, 2, 3, 4, 5, 6-pentamethylphenyl, 1-naphthyl, 2-naphthyl, 4 -fluorophenyl, 2,4-difluorophenyl, 2-chloro-6-methylphenyl, 2-chloro-4-fluorophenyl, 2,5-dimethoxyphenyl, 3,4-dimethoxyphenyl, 3-chloro-6-methoxy-phenyl, 2-trifluoromethylphenyl , 2-alkylsulfonylphenyl, 2-arylsulfonylphenyl, 3- (N-acetyl-6-methoxy) aniline, 4-acetamidophenyl, 2,2,2-trifluoroethyl, 5-chloro-3-methyl-benzothiazol-2-yl, N-methoxycarbonyl-1-piperidin-3-yl, thiophen-2-yl, isoxazol-5-yl, 2-chloropyridin-3-yl, pyridin-3-yl, 5-methylisoxazol-3-yl, 1-adamantyl , 4-chlorophenoxymethyl, 2,2-dimethyleten ilo, 2-chloropyridin-5-methyl, 5,7-dimethyl-1, 3, 4-triazaindolizin-2-yl, (S) -canfan-1-yl, (R) -canfan-l-yl or 8- quinolinyl; L is -OCH2-, -CH20-, -CH20CH2-, -CH2CH20- or -OCH2CH2-; X is N or O; and the other residues are as defined above. According to a still further preferred embodiment, the present invention relates to compounds of the formula (1) wherein R 4 is -S02R 4 '; R 'is methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, phenyl, benzyl, tolyl or a substituted derivative thereof, - C 6 H 2 (CH 3) 3, -C 6 (CH 3) 5, -CH 2 C 6 H 2 (CH 3) 3, 4-phenylphenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2,3-dichlorophenyl, 2,4-dichlorophenyl, 3, 4- dichlorophenyl, 2,5-dichlorophenyl, 3,5-dichlorophenyl, 2,6-dichlorophenyl, 2-chlorophenylmethyl, 4-chlorophenylmethyl, 2,4-dichlorophenylmethyl, 2,6-dichlorophenylmethyl, 2-methoxycarbonyl phenylmethyl, 3-trifluoromethylphenyl, 4 -trifluoromet ilphenyl, 3,5-bis (trifluoromethyl) phenyl, 4-trifluoromethoxyphenyl, phenylmethyl, 2 -acetamido-4-methyl-thiazol-5-yl, phenylethyl, l-phenylpropyl, (S) - (+) - camphor- 10-yl, (R) - (-) -canfor-10-yl, 2-phenylethenyl, 2-thiophenyl, 4-methoxyphenyl, 3,5-dimethoxyphenyl, 3-methylphenyl, 4-methylphenyl, 4-t-butylphenyl, 4-propylphenyl, 2,5-dimethylphenyl, 2-methoxy-5-methylpheni lo, 2,3,5,6-tetramethylphenyl, 2, 3, 4, 5, 6-pentamet-ilphenyl, 1-naphthyl, 2-naphthyl, 4-fluorophenyl, 2,4-difluorophenyl, 2-chloro-6-methylphenyl , 2-chloro-4-fluorophenyl, 2,5-dimethoxyphenyl, 3,4-dimethoxyphenyl, 3-chloro-6-methoxy-phenyl, 2-trifluoromethylphenyl, 2-alkylsulfonylphenyl, 2-arylsulfonylphenyl, 3- (N-acetyl) 6-methoxy) aniline, 4-acetamidophenyl, 2, 2, 2-trifluoroethyl, 5-chloro-3-meth i 1-benzothiazol-2-yl, N-methoxycarbonyl-piperidin-3-yl, thiophen-2-yl , isoxazol-5-yl, 2-chloropyridin-3-yl, pyridin-3-yl, 5-methylisoxazol-3-yl, 1-adamantyl, 4-chlorophenoxymethyl, 2,2-dimethyletenyl, 2-chloropyridin-5- methyl, 5,7-dimethyl-1,3-, 4-triazaindolizin-2-yl, (S) -canphan-1-yl, (R) -canphan-1-yl or 8-quinolinyl; L is -NHS02-, -CH2NHS02- or -NHS02CH2-; X is N or O; R7 and R9 together form an ethylene group that is bonded to the nitrogen atom to which R7 is bonded to the nitrogen atom to which R9 is linked; and the other residues are as defined above. The present invention also relates to a process for the preparation of the compounds of the formula (1) 0) comprising the steps: a) reaction of a β-amino acid of the formula (2) wherein P is - (CH2) mN02, - (CH2) pO-C6-alkyl, - (CH2) mS02P ', - (CH2) mC0P', - (CH2) mCH20-C6_6 alkyl, wherein m in each case it is an integer of 0 or 1; P 'is -OH, -O-C C-C6 alkyl, and the other residues are as defined above; with a compound R4-A to give a compound of the formula (3), wherein R4 is -S02R4 ', -COOR4"or -COR4'; R4 'and R4" are as defined above; A is -Cl, -Br, -I, -O-triflyl, -O-tosyl, -O-alkyl C? -6. -O-CO-alkyl C? _6, -O-CO-O-alkyl C? _6, OC (CH3) = CH2; and the other residues are as defined above; b) conversion of residue P to residue Q, where Q is - (CH2) mNH2, - (CH2) mOH, - (CH2) mCH2OH, - (CH2) mS02A, - (CH2) mC0A, A is as defined above; m is an integer of 0 or 1; c) reaction of the compound obtained from step b) with a compound of the formula (4) wherein S is AS02 (CH2) n-, NH2 (CH2) n-, ACO (CH2) n-, HOCH2 (CH2) n-, M (CH2) n-, MCH2 (CH2) n-. HSCH2 (CH2) n- or HS (CH2) n-, where n is an integer of 0 or 1; M is a residue that includes Mg, Li, Cd or Sn; A is as defined above; and C is -N02 or X, R7, R8, R9 and R11 are as defined above; to give a compound of the formula (5) wherein the waste is as defined above; d) if appropriate, the conversion of C, if C is a nitro group, into a unit of urea, thiourea or optionally cyclic guanidine with the obtaining of compound (1); and e) if appropriate, the removal of the protecting groups and / or derivation of the nitrogen atoms, which are present at preferred times within the preparation process, and / or conversion of the compound obtained in the free acid and / or the conversion of the compound obtained in one of its physiologically acceptable salts, by reaction with a suitable inorganic or organic base or acid.

Preferably, in the process according to the invention, the β-amino acid of the formula (2) is obtained by the reaction of the malonic acid with a benzaldehyde derivative of the formula (2a) wherein R10 and P are as defined above, in the presence of ammonia, ammonium or amines compounds and, if appropriate, the subsequent substitution at position a with respect to the terminal carboxyl group. Furthermore, according to a preferred embodiment of the invention, the process comprises the conversion of the nitro group in step d) by reduction to the amino group, the subsequent reaction with a carboxylic acid ester derivative and, if appropriate, the removal of the protecting groups present and / or the reaction with a compound containing at least one amino group. The present invention further relates to a pharmaceutical composition containing at least one of the compounds according to the invention described above. The present invention also relates to the use of the compounds according to the invention described above, for the production of a pharmaceutical composition having the antagonistic action of integrin. The present invention also relates to the use of the compounds according to the invention, described above for the production of a pharmaceutical composition for the inhibition of angiogenesis and / or the therapy and prophylaxis of cancer, osteolytic diseases, such as osteoporosis, arteriosclerosis, restenosis, rheumatoid arthriand ophthalmic diseases.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS The invention is explained more exactly below, with reference to the preferred embodiments, to which, however, it is not restricted in any way. In the following description, the bivalent substituents are indicated in such a way that their respective left end is connected to the indicated left group of the corresponding substituent in formula (1), and its respective right end is connected to the indicated right group of the corresponding substituent in the Formula 1). Yes, for example, the residue L is - (CH2) mNHS02 (CH2) n- in the formula (1), the nitrogen atom is connected to the phenylene group located to the left of the residue L in the formula (1) by means of the group (CH2) m. The compounds according to the invention are characterized in that, as a main structural element, they have two phenyl units connected via a linker group L, a phenylene group which has the residue derived from a β-amino acid, while the other phenylene group carries a urea group, thiourea group or guanidine group optionally incorporated in a cyclic ring system. The phenylene units linked by a linker group L, in addition, can carry additional substituents in addition to the residues mentioned above. The carboxyl terminal unit included in the residue derived from a β-amino acid may be present as a free carboxylic acid or as an ester. In the case where the carboxyl terminal unit is esterified, basically all the esters of carboxylic acids obtained according to conventional processes and in which they can be metabolized into the free carboxylic acid in the human or animal body, such as the esters of Suitable alkyl, cycloalkyl esters, aryl esters and heterocyclic analogs thereof can be used according to the invention, wherein alkyl esters, cycloalkyl esters and aryl esters are preferred and the alcohol residue can carry additional substituents. C este _6 alkyl esters, such as methyl ester, ethyl ester, propyl ester, isopropyl ester, butyl ester, isobutyl ester, t-butyl ester, pentyl ester, isopentyl ester, neopentyl ester hexyl ester, cyclopropyl ester, cyclopropylmethyl ester, cyclobutyl ester, cyclopentyl ester, cyclohexyl ester or aryl ester, such as phenyl ester, benzyl ester or tolyl ester are particularly preferred.

The aforementioned esters can be used as prodrugs for the treatment of the diseases mentioned at the beginning, such as cancer, osteoporosis, arteriosclerosis, restenosis, rheumatoid arthritis or ophthalmia, since they are easily converted into an animal and in man into the corresponding carboxylic acid . However, for the treatment of the aforementioned conditions, the compounds of the general formula (1) according to the invention are preferably used in a form in which the carboxyl terminal unit is present as a free carboxylic acid. For use in medicine, the compounds of the general formula (1) according to the invention can also be used in the form of their physiologically acceptable salts. The physiologically acceptable salts are understood according to the invention as non-toxic salts, which are generally accessible by the reaction of the compounds of the general formula (1) according to the invention with an inorganic or organic base or acid and They use conventionally for this purpose. Examples of the preferred salts of the compounds of the general formula (1) according to the invention are the corresponding alkali metal salts, e.g. the salt of lithium, potassium or sodium, the corresponding alkaline earth metal salt, such as magnesium or calcium salt, a quaternary ammonium salt, such as, for example, the triethylammonium salt, acetate, benzenesulfonate, benzoate, dicarbonate, disulfate, ditartrate, borate, bromide, carbonate, chloride, citrate, dihydrochloride, fumarate, gluconate, glutamate, hexyl-resorcinate, hydrobromide, hydrochloride, hydroxynaphthoate, iodide, isothionate, lactate, laurate, malate, maleate, mandelate, mesylate, methyl bromide, methylnitrate, methylisulfate, nitrate, oleate, oxalate, palmitate, pantothenate, phosphate, diphosphate, polygalacturonate, salicylate, stearate, sulfate, succinate, tartrate, tosylate and valerate, and other salts used for medical purposes. The residue linked to one of the two central phenylene units and derived from a β-amino acid can alternatively carry one or two additional substituents at the a-position with respect to the carboxyl group. These substituents in each case can be selected from the group consisting of hydrogen, a substituted or unsubstituted alkyl or cycloalkyl residue, a substituted or unsubstituted aryl residue, a saturated or unsaturated heterocyclic residue, optionally substituted, an optionally substituted alkenyl residue, an alkynyl residue optionally substituted, a hydroxyl residue or an alkoxy residue. The alkyl residue may preferably be a C6_6 alkyl such as, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl or hexyl. The cycloalkyl residue may preferably be a C3- cycloalkyl such as, for example, cyclopropyl, cyclopropylmethyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl. The aryl residue can preferably be phenyl, benzyl or tolyl. The heterocyclic residue may preferably be pyrrole, pyridine, tetrahydrofuran, furan, thiophene, tetrahydrothiophene, thiooxazole, benzofuran, quinoline, isoquinoline or pyrimidine. The alkenyl residue can be a terminal or internal alkene E or Z unit. The alkoxy residue may preferably be a C6-C6 alkoxy residue such as, for example, methoxy, ethoxy, propoxy, butoxy, pentoxy, hexoxy or benzyloxy. The aforementioned residues can alternatively be substituted by one or more C? _6 alkyl residue, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl or hexyl, C3_ cycloalkyl residues, such as cyclopropyl , cyclopropylmethyl, cyclobutyl, cyclopentyl or cyclohexyl, aryl residues, such as phenyl, benzyl, tolyl, naphthyl, heterocyclic residues, such as pyrrole, pyridine, tetrahydrofuran, furan, thiophene, tetrahydrothiophene, oxazole, thiazole, thiooxazole, benzofuran, benzoxazole, benzothiazole, quinoline, isoquinoline or functional groups, such as a double bond to a heteroatom, such as oxygen, sulfur or nitrogen, an optionally substituted amino group, a nitro group, a halogen group, a hydroxyl, a group ether, a sulfide group, a mercaptan group, a cyano group, an isonitrile group, an alkenyl group, an alkynyl group, an aldehyde group, a keto group, a carboxyl group, an ester group, an amide group, a sulfoxide group or a sulfone group. In addition, one or more saturated or unsaturated rings may be additionally fused to the cyclic residues mentioned above with the formation of, for example, a naphthyl, benzofuranyl, benzoxazolyl, benzothiazolyl, quinolinyl or isoquinolinyl unit or a partially or fully hydrogenated analogue thereof. The two substituents at position a with respect to the terminal carboxyl group, if present, can be further bonded to one another and thus, together form a carbocyclic or heterocyclic ring system together with the carbon atom a of the residue derived from a amino acid a. This ring system can optionally carry additional substituents and / or contain additional heteroatoms. According to the invention, the fore-ring system, if present, is preferably a 3-6 membered carbocyclic or heterocyclic ring system, such as, for example, a cyclopropane ring, cyclobutane ring, cyclopentane ring, cyclohexane ring, ring dihydrofuran, tetrahydrofuran ring, dihydropyran ring, tetrahydropyran ring, dioxane ring, dihydrothiophene ring, tetrahydrothiophene ring or a substituted derivative thereof. In the groups according to the invention, the amino group included in the residue derived from a β-amino acid is replaced by one of the residues -S02R4 ', -COOR4", -COR4', -CONR4'2 or -CSNR4'2, wherein R4 'may be hydrogen, a substituted or unsubstituted alkyl, alkenyl or cycloalkyl residue, a substituted or unsubstituted aryl residue or a saturated or unsaturated, optionally substituted heterocyclic residue and R4"may be a substituted or unsubstituted alkyl or cycloalkyl residue, an substituted or unsubstituted aryl residue or a saturated or unsaturated, optionally substituted heterocyclic residue. In this context, the alkyl residue is preferably a C? -6 alkyl such as, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, the alkenyl residue is preferably a C2_6 alkenyl having a double bond, such as for example ethenyl, propenyl, butenyl, the cycloalkyl residue is a C3_ cycloalkyl such as, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, the aryl residue is an aryl such as phenyl, benzyl, tolyl or a substituted derivative thereof such as -CeH2 (CH3) 3, -C6 (CH3) 5, CH 2 C 6 H 2 (CH 3) 3, 4-phenylphenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2,3-dichlorophenyl, 2,4-dichlorophenyl, 3,4-dichlorophenyl, 2,5-dichlorophenyl, 3, 5- dichlorophenyl, 2,6-dichlorophenyl, 2-chlorophenylmethyl 4-chlorophenylmethyl, 2,4-dichloro-phenyl-methyl, 2,6-dichlorophenylmethyl, 2-methoxycarbonylphenyl-methyl, 3-trifluoromethylphenyl, 4-trifluoromethylphenyl, 3, 5-bis (trifluoromethyl) -phenyl, 4-trifluoromethoxyphenyl, phenylmethyl, 2-acetamido-4-methyl-thiazol-5-yl, phenylethyl, l-phenylpropyl, (S) - (+) - camphor-10-yl , (R) - (-) -canfor-10-yl, 2-phenylethenyl, 2-thiophenyl, 4-methoxyphenyl, 3,5-dimethoxyphenyl, 3-methylphenyl, 4-methylphenyl, 4-t-butylphenyl, 4-propylphenyl , 2,5-dimethylphenyl, 2-methoxy-5-methylphenyl, 2,3,5,6-tetramethylphenyl, 2, 3, 4, 5, β-pentamethylphenyl, 1-naphthyl, 2-naphthyl, 4-fluorophenyl, 2 , 4-difluorophenyl, 2-chloro-6-methylphenyl, 2-chloro-4-fluorophenyl, 2,5-dimethoxyphenyl, 3,4-dimethoxyphenyl, 3-chloro-6-methoxyphenyl, 2-trifluoromethylphenyl, 2 -alkyl-sulfonylphenyl, 2-arylsulfonylphenyl, 3- (N-acetyl-6-methoxy) aniline, 4-acetamidophenyl, 2,2,2-trifluoroethyl, 5-chloro-3-methyl-benzothiazol-2-yl, N- methoxycarboni1-piperidin-3-yl, t-ofen-2-yl, isoxazol-5-yl, 2-chloropyridin-3-yl, pyridin-3-yl, 5-methylisoxazol-3-yl, 1-adamantyl, 4- chlorophenoxymethyl, 2,2-dimethyletenyl, 2-chloropyridin-5-methyl, 5,7-dimethyl-1,3-, 4-triazaindolizin-2-yl, (S) -canfan-1-yl, (R) -canfan- 1-yl or 8-quinolinyl. R4"preferably represents a C6_6 alkyl group such as, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, a C3_7 cycloalkyl, such as, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, phenyl, benzyl, or a substituted derivative thereof, -CH 2 CdH 2 (CH 3) 3, 2-chlorophenylmethyl, 4-chlorophenylmethyl, 2,4-dichlorophenylmethyl, 2, β-dichloro-phenylmethyl, 2- methoxycarbonyl phenylmethyl, 3-trifluoromethylphenylmethyl, 4-trifluoromethylphenylmethyl, 3,5-bis (trifluoromethyl) phenylmethyl, 4-trifluoromethoxyphenyl, 2-thiophenylmethyl, 4-methoxyphenylmethyl, 3,5-dimethoxyphenylmethyl, 3-methylphenylmethyl, 4-methylphenylmethyl, 4- t-butylphenyl-methyl, 4-propylphenylmethyl, 2,5-dimethylphenylmethyl, 2-methoxy-5-methylphenylmethyl, 2,3,5,6-tetramethylphenylmethyl, 2,3,4,5,6-pentamethylphenylmethyl, 1- Naphthylmethyl, 2-naphthylmethyl, 4-fluorophenylmethyl, 2,4-difluorophenylmethyl, 2-chloro-6-methylphenylmethyl, 2-clo ro-4-fluorophenylmethyl, 2,5-dimethoxyphenylmethyl, 3,4-dimethoxyphenylmethyl, 3-chloro-6-methoxy-phenylmethyl, 2-trifluoromethylphenylmethyl, 2,2,2-trifluoroethyl, isoxazol-5-yl-methyl, 2- chloropyridin-3-yl-methyl, pyridin-3-yl-methyl, 2-chloropyridin-5-methyl.

R4"represents particularly preferably methyl, ethyl, propyl, isopropyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, phenyl or benzyl. According to the invention, the group Amino included in the residue derived from a β-amino acid is particularly preferably substituted by -S02R4 ', COOR4"or -COR4', wherein R4 'and R4" are as defined above In this context, particularly preferred compounds are those that the residue derived from a β-amino acid does not have the substituent at position a with respect to the carboxyl unit and the amino group included in this residue is replaced by -S02R4 ', -COOR4"or -COR4', where R4 'and R 4' are as defined above In addition to one of the residues mentioned above, the nitrogen atom of the amino group located at the β-position can have a substituent which can be selected from the group consisting of hydrogen or, a substituted or unsubstituted alkyl or cycloalkyl residue, a substituted or unsubstituted aryl residue, a saturated or unsaturated heterocyclic residue, optionally substituted or can be linked to each other and thus, form a heterocyclic ring system together with the one or more atoms of nitrogen to which they are linked. In this context, substituents that can be selected from the group consisting of hydrogen, a C6_6 alkyl such as, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl or hexyl, are preferred. a C3_7 cycloalkyl such as, for example, cyclopropyl, cyclopropylmethyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl, an aryl such as, for example, phenyl, benzyl or tolyl, a heterocyclic residue such as, for example, pyrrolidine, piperidine, piperazine, pyrrole, pyridine, tetrahydrofuran, furan, thiophene, tetrahydrothiophene, imidazolidine, imidazole, oxazolidine, oxazole, thiazolidine, thiazole, thiooxazole, benzofuran, benzoxazole, benzothiazole, benzimidazole, quinoline, isoquinoline, tetrahydroquinoline, tetrahydroisoquinoline, triazole, tetrazole, pyrimidine, purine, cytosine, thymine, uracil, adenine, guanine or xanthine and can alternatively be substituted by one or more C? -6 alkyl residues such as methyl, ethyl, propyl, isopropy it, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl or hexyl, C3_ cycloalkyl residues such as cyclopropyl, cyclopropylmethyl, cyclobutyl, cyclopentyl (or cyclohexyl, aryl residues such as phenyl, benzyl, tolyl, naphthyl, indolyl, heterocyclic residues) such as pyrrolidine, piperidine, piperazine, pyrrole, pyridine, tetrahydrofuran, furan, thiophene, tetrahydrothiophene, imidazolidine, imidazole, oxazolidine, oxazole, thiazolidine, thiazole, thiooxazole, benzofuran, benzoxazole, benzothiazole, benzimidazole, quinoline, isoquinoline, tetrahydroquinoline, tetrahydroisoquinoline, triazole, tetrazole, pyrimidine, purine, cytosine, thymine, uracil, adenine, guanine or xanthine, or functional groups such as a double bond to a heteroatom such as oxygen, sulfur or nitrogen, an optionally substituted amino group, a nitro group, a halogen, a hydroxyl group, an ether group, a sulfide group, a mercaptan group, a cyano group, an isonitrile group, an alkenyl group, an alkynyl group, an aldehyde group, a keto group, a carboxyl group, an ester group, an amide group, a sulfoxide group or a sulfone group. One or more additionally saturated or unsaturated rings may additionally be fused to the aforementioned cyclic residues with the formation of, for example, a naphthyl, indolyl, benzofuranyl, benzoxazolyl, benzothiazolyl, benzimidazolyl, quinolinyl or isoquinolinyl unit or a partial or full analogue. hydrogenated thereof. Particularly, preferably, the additional substituent on the nitrogen atom of the amino group β is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclopropylmethyl, cyclobutyl, cyclopentyl, cyclohexyl, 4-methyl-cyclohexyl, 3,3,5-trimethylcyclohexyl, 5-methyl-2-hexyl, phenyl, benzyl, tolyl or a substituted derivative thereof, alkylamino C? _4-C? -4 alkyl, dialkylamino C? _-C C _4 alkyl, C? -4 aminoalkyl, C? _4 alkyloxy-C alquilo _4 alkyl, (a11) (a12) (a13) (a14) (a15) (al 6) (a! 7) (al8) (a 19) (a20) (225) (a26) (a27) (a28) The residue derived from a β-amino acid is linked to one of the two central phenylene units which are linked via a linker group L, and such a phenylene unit will be referred to herein as a phenylene unit A. Apart from the residue derived from a β-amino acid and the linker group L, preferably the phenylene unit A does not carry additional substituents, but may contain one or more residues which are selected from the group consisting of hydrogen, a substituted or unsubstituted alkyl or cycloalkyl residue, a substituted or unsubstituted alkoxy residue or a halogen atom. The alkyl residue or residues are preferably C.sub.6 -alkyl residues such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl. The cycloalkyl residue (s) are preferably C3_7 cycloalkyl residues such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl. The alkoxy residue (s) are preferably C.sub.1-6 alkoxy residues such as methoxy, ethoxy, propoxy, butoxy, pentoxy or hexoxy and the halogen atom (s) are preferably F, Cl, Br or I.

The phenylene unit A is linked to a second central phenylene unit, which will be referred to herein as a phenylene B unit, via a linker group L. In addition to the linker group L, the phenylene unit B carries a substituent additional that is selected from the group consisting of a guanidine, urea or thiourea unit, which is optionally incorporated into a cyclic ring system. In addition, the phenylene unit B preferably does not carry substituents, but may contain one or more residues which are selected from the group consisting of hydrogen, a substituted or unsubstituted alkyl or cycloalkyl residue, a substituted or unsubstituted alkoxy residue or a halogen atom . The alkyl residue (s) are preferably C?-6 alkyl such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl. The cycloalkyl residue (s) are preferably C3_7 cycloalkyl residues such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl. The alkoxy residue (s) are preferably C.sub.1-6 alkoxy residues such as methoxy, ethoxy, propoxy, butoxy, pentoxy or hexoxy and the halogen atom (s) are preferably F, Cl, Br or I. The two central phenylene units may be , 3-or 1,4-linked with respect to the linker group L and the residue derived from a β-amino acid or the guanidine, urea or thiourea unit, ie the residue derived from a β-amino acid and the linking group L, can be substituted on the phenylene A unit in the meta or para position with respect to the other, and at the same time the linker group L and the guanidine or thiourea unit on the unit of phenylene B can be substituted in the meta or para position with respect to each other, wherein each combination of the substitution patterns mentioned above, is possible for the phenylene unit A central-linker L- phenylene B of the compounds according to the invention. According to the present invention, the compounds whose phenylene A-linker L-phenylene B unit according to the above definition are composed of a p-substituted phenylene unit A and a p-substituted phenylene B unit, p-substituted phenylene unit A and a m-substituted phenylene B unit, an m-substituted phenylene unit A and a m-substituted phenylene B unit. According to the present invention, the compounds whose phenylene unit A-L-phenylene B linker according to the above definition, consist of an m-substituted phenylene unit A and a m-substituted phenylene B unit are particularly preferred. According to the present invention, the linker group L is selected from the group consisting of the elements - (CH2) mNHS02 (CH2) n-, - (CH2) mS02NH (CH2) n-, (CH2) mNHCO (CH2) n -, (CH2) mC0NH (CH2) n-, (CH2) m0CH2 (CH2) n-, - (CH2) mCH20 (CH2) n-, - (CH2) mCOO (CH2) n-, - (CH2) m00C ( CH2) n_, - (CH2) mCH2CO (CH2) n-, - (CH2) mCOCH2 (CH2) n-, -NHCONH-, (CH2) mSCH2 (CH2) n-, - (CH2) mCH2S (CH2) n- , - (CH2) mCH2SO (CH2) "-, - (CH2) mSOCH2 (CH2) n, - (CH2) mCH2S02 (CH2) n- or (CH2) mS02CH2 (CH2) n-, where m and n in each case are an integer of 0 or 1 and m + n is = 1 According to the invention, the linker group L is preferably -NHS02-, CH2NHS02-, -NHS02CH2-, -S02NH-, -CH2S02NH-, -S02NHCH2-, -NHCO-, -CH2NHC0-, -NHCOCH2, -CONH- , CH2C0NH-, CONHCH2-, 0CH2-, -CH2OCH2, -OCH2CH2, -CH20-, -CH2CH20-, -COO-, -CH2COO-, -COOCH2-, -OOC-, -OOCCH2-, -CH2OOC-, -CH2CO -, -COCH2-, -CH2CH2CO-, -COCH2CH2-, CH2COCH2-, -NHCONH-, -SCH2-, -CH2S-, -CH2SCH2, -SCH2CH2-, CH2CH2S-, -SOCH2-, -CH2SO-, -CH2SO-CH2-, -SOCH2CH2-, -CH2CH2SO-, -S02CH2-, CH2S02-, -CH2S02CH2-, -CH2CH2S02- or -S02CH2CH2-. Particularly preferred linker groups L herein are -NHS02-, -CH2NHS02-, NHS02CH2-, -S02NH-, -CH2S02NH-, -S02NHCH2-, -NHCO-, -CH2NHCO-, -NHCOCH2-, -CONH-, - CH2CONH-, CONHCH2-, -OCH2-, -CH2OCH2-, -OCH2CH2-, -CH20- or -CH2CH20-. The central phenylene B unit carries as a substituent a residue selected from the group consisting of a guanidine, urea or thiourea unit.

This guanidine, urea or thiourea unit can be either an open chain or a constituent of a cyclic system. The two nitrogen atoms of the respective unit, which are only linked via single bonds, can carry additional substituents R6, R8 and R9. These substituents can be independently of one another or simultaneously hydrogen, a substituted or unsubstituted alkyl or cycloalkyl residue, a substituted or unsubstituted aryl residue, a saturated or unsaturated heterocyclic residue, optionally substituted or can be linked to each other and thus form a Heterocyclic ring system together with the nitrogen atom (s) to which it is bound. In this context, the preferred substituents are selected from the group consisting of hydrogen, a Ci-β alkyl such as, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl or hexyl. , a C3-7 cycloalkyl such as, for example, cyclopropyl, cyclopropylmethyl; cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl, an aryl such as, for example, phenyl, benzyl or tolyl, a heterocyclic residue such as, for example, pyrrolidine, piperidine, piperazine, pyrrole, pyridine, tetrahydrofuran, furan, thiophene, tetrahydrothiophene, imidazolidine , imidazole, oxazolidine, oxazole, thiazolidine, thiazole, thiooxazole, benzofuran, benzoxazole, benzothiazole, benzimidazole, quinoline, isoquinoline, tetrahydroquinoline, tetrahydroisoquinoline, triazole, tetrazole, pyrimidine, purine, cytosine, thymine, uracil, adenine, guanine or xanthine and can alternatively substituted by one or more C? _6 alkyl residues such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl or hexyl, C3_7 cycloalkyl residues such as cyclopropyl, cyclopropylmethyl, cyclobutyl, cyclopentyl or cyclohexyl, aryl residues such as phenyl, benzyl, tolyl, naphthyl, indolyl, heterocyclic residues such as pyrrolidine, piperidine, piperaz ina, pyrrole, pyridine, tetrahydrofuran, furan, thiophene, tetrahydrothiophene, imidazolidine, imidazole, oxazolidine, oxazole, thiazolidine, thiazole, thiooxazole, benzofuran, benzoxazole, benzothiazole, benzimidazole, quinoline, isoquinoline, tetrahydroquinoline, tetrahydroisoquinoline, triazole, tetrazole, pyrimidine, purine, cytosine, thymine, uracil, adenine, guanine or xanthine, or functional groups such as a double bond to a heteroatom such as oxygen, sulfur or nitrogen, an optionally substituted amino group, a nitro group, a halogen, a hydroxyl group, an ether group, a sulfide group, a mercaptan group, a cyano group, an isonitrile group, an alkenyl group, an alkynyl group, an aldehyde group, a keto group, a carboxyl group, an ester group, an amide group, a group sulfoxide or a sulfone group. One or more additionally saturated or unsaturated rings can be further fused to the cyclic residues mentioned above with the formation of, for example, a naphthyl, indolyl, benzofuranyl, benzoxazolyl, benzothiazolyl, benzimidazolyl, quinolinyl or isoquinolinyl unit or a partially or completely hydrogenated analogue thereof. Particularly preferred substituents are hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclopropylmethyl, cyclobutyl, cyclopentyl, cyclohexyl, 4-methylcyclohexyl, 3,3, 5-trimethylcyclohexyl, 5-methyl-2-hexyl, phenyl, benzyl, tolyl or a substituted derivative thereof, C? -4 alkylamino C? _4 alkyl, C dial -4 dialkylamino C alquilo _4 alkyl, amino C ?- 4-C 1 -4 alkyl, C 4 -4 alkyloxy C 4 -4 alkyl or one of the residues mentioned above (al) a (a 28). The two residues R8 and R9 on the terminal nitrogen atom of the corresponding guanidine unit, urea or thiourea can be bonded to one another and thus, with the nitrogen atom, form a heterocyclic system which can be selected, for example, from the following list, not strict: wherein the ring systems shown may carry one or more residues which are selected from the group consisting of hydrogen, C? _6 alkyl, such as, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl or hexyl, a C3.7 cycloalkyl, such as, for example, cyclopropyl, cyclopropylmethyl, cyclobutyl, cyclopentyl or cyclohexyl, an aryl such as, for example, phenyl, benzyl or tolyl, a heterocyclic residue such as, for example, pyrrolidine, piperidine, piperazine, pyrrole, pyridine, tetrahydrofuran, furan, thiophene, tetrahydrothiophene, imidazolidine, imidazole, oxazolidine, oxazole, thiazolidine, thiazole, thiooxazole, benzofuran, benzoxazole, benzothiazole, benzimidazole, quinoline, isoquinoline, tetrahydroquinoline, tetrahydroisoquinoline , triazole, tetrazole, pyrimidine, purine, cytosine, thymine, uracil, adenine, guanine or xanthine, or an alkene E or Z terminal or internal unit, and can alternatively be replaced by one or more C? -6 alkyl residues such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl or hexyl, C3_7 cycloalkyl residues, such as cyclopropyl, cyclopropylmethyl, cyclobutyl, cyclopentyl or cyclohexyl, aryl residues such as phenyl, benzyl, tolyl, naphthyl, indolyl, heterocyclic residues such as pyrrolidine, piperidine, piperazine, pyrrole, pyridine, tetrahydrofuran, furan, thiophene, tetrahydrothiophene, imidazolidine, imidazole, oxazolidine, oxazole, thiazolidine, thiazole, thiooxazole, benzofuran, benzoxazole, benzothiazole, benzimidazole, quinoline, isoquinoline, tetrahydroquinoline, tetrahydroisoquinoline, triazole, tetrazole, pyrimidine, purine, cytosine, thymine, uracil, adenine, guanine or xanthine, or functional groups such as a double bond to a heteroatom such as oxygen , sulfur or nitrogen, an optionally substituted amino group, a nitro group, a halogen group, a hydroxyl group, an ether group, a sulfide group, or a mercaptan group, a cyano group, an isonitrile group, an alkenyl group, an alkynyl group, an aldehyde group, a keto group, a carboxyl group, an ester group, an amide group, a sulfoxide group or a sulfone group. One or more additionally saturated or unsaturated rings can further be fused to the cyclic residues mentioned above with the formation of, for example, a naphthyl, indolyl, benzofuranyl, benzoxazolyl, benzothiazolyl, benzimidazolyl, quinolinyl or isoquinolinyl unit or a partially or fully hydrogenated analog of the same. Of the ring systems shown above, ring systems of four to six members are preferred. As mentioned above, the urea, thiourea or guanidine unit may be open chain or incorporated in a cyclic system and thus, may be a constituent of one of the following preferred functional units: R * R * R * R * R 'R' I I - N N ^ o T R * "? M", 'R' N where the above list is not a strict enumeration of all possible structural units. According to the invention, in addition to the above-preferred structural units, their analogs are also included, in which one or more of the 4 to 6 member ring systems are fused to the heterocycle, such as, for example, the corresponding benzofused analogs of the aforementioned structural units. In the structural units shown above, R6, R8 and R9 are as defined above. According to this invention, compounds of the general formula are particularly preferred (1), where X represents N u 0, i.e. guanidine or urea derivatives, and the other substituents are as defined above. According to one embodiment of the present invention, the urea derivatives are particularly preferred, wherein X represents 0 and the other substituents are as defined above, while according to another embodiment of the present invention, guanidine compounds are particularly preferred, wherein X represents N and the other substituents are as defined above. Further, in the above structural units R7 may be absent, or may be hydrogen, a substituted or unsubstituted alkyl or cycloalkyl residue, such as, for example, a C ?_6 alkyl such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl , t-butyl, pentyl, isopentyl, neopentyl, hexyl or a C3-7 cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, -N02, -CN, -COR7'- or -COOR7 ', wherein R7' can be hydrogen , a substituted or unsubstituted alkyl or cycloalkyl residue, a substituted or unsubstituted aryl residue or a saturated or unsaturated, optionally substituted heterocyclic residue, which may be saturated or unsaturated and / or may contain additional heteroatoms, and is preferably a C? -6 alkyl? such as, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, a C3_ cycloalkyl such as, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, an aryl as, for example, phenyl, benzyl, tolyl, or a substituted derivative thereof. Particularly preferred compounds of formula (1) according to the invention are those in which the amino group included in the residue derived from a β-amino acid carries a residue -S02R4 ', wherein R4' is preferably methyl, ethyl, propyl , isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, phenyl, benzyl, tolyl or a substituted derivative thereof, -C6H2 (CH3) 3, -C6 (CH 3) 5, -CH 2 C 6 H 2 (CH 3) 3, 4-phenylphenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2,3-dichlorophenyl, 2,4-dichlorophenyl, 3,4-dichlorophenyl, 2, 5- dichlorophenyl, 3,5-dichlorophenyl, 2,6-dichlorophenyl, 2-chlorophenylmethyl, 4-chlorophenylmethyl, 2-dichlorophenylmethyl, 2,6-dichlorophenylmethyl, 2-methoxycarbonylphenylmethyl, 3-trifluoromethylphenyl, 4-trifluoromethylphenyl, 3,5- bis (trifluoromethyl) phenyl, 4-trifluoromethoxyphenyl, phenylmethyl, 2-acetamido-4-methyl-thiazol-5-yl, phenylethyl, l-phenylpyr ropyl, (S) - (+) -canfor-10-yl, (R) - [-) -canfor-10-yl, 2-phenylethenyl, 2-thiophenyl, 4-methoxyphenyl, 3,5-dimethoxyphenyl, 3- methylphenyl, 4-methylphenyl, 4-t-butylphenyl, 4-propylphenyl, 2,5-dimethylphenyl, 2-methoxy-5-methylphenyl, 2,3,5,6-tetramethylphenyl, 2, 3, 4, 5, 6 pentamethylphenyl, 1-naphthyl, 2-naphthyl, 4-fluorophenyl, 2,4-difluorophenyl, 2-chloro-6-methylphenyl, 2-chloro-4-fluorophenyl, 2,5-dimethoxyphenyl, 3,4-dimethoxyphenyl, 3- chloro-6-methoxyphenyl, 2-trifluoromethylphenyl, 2-alkylsulfonylphenyl, 2-arylsulfonylphenyl, 3- (N-acetyl-6-methoxy) aniline, 4-acetamidophenyl, 2,2,2-trifluoroethyl, 5-chloro-3-methyl -benzothiazol-2-yl, N-methoxycarbonylpiperidin-3-yl, thiophen-2-yl, isoxazol-5-yl, 2-chloropyridin-3-yl, pyridin-3-yl, 5-methylisoxazol-3-yl, -adamino, 4-chloro-phenoxymethyl, 2,2-dimethyletenyl, 2-chloropyridin-5-methyl, 5,7-dimethyl-1,3-, 4-triazaindolizin-2-yl, (S) -canfan-1-yl , (R) -canfan-l-yl or 8-quinolinyl, the linker group L is -NHS02-, -CH2NHS02-, -NH S02CH2-, and the residue located on the phenylene unit is an open-chain or cyclic guanidine or urea unit, wherein the particularly preferred guanidine units are a cyclic guanidine unit such as, for example, a unit 4, -dihydro-lH-imidazol-2-yl-amino or an open chain guanidine unit such as the unsubstituted guanidinyl residue and particularly the preferred urea units are open chain units, such as unit 3- (C? _4 alkyl) ) - solid, 3-pyridin-4-yl-ureido, 3-pyridin-3-yl-methyl-ureido, 3-pyridin-4-yl-methyl-ureido and 3 (lH-benzimidazol-2-yl) -ureido . In addition, the particularly preferred compounds of the formula (1) according to the present invention are those in which the amino group included in the residue derived from a β-amino acid carries a residue -S02R4'-, wherein R4 'is preferably methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, phenyl, benzyl, tolyl or a substituted derivative thereof, -C6H2 (CH3) 3, -C6 (CH3) 5. -CH 2 C 6 H 2 (CH 3) 3, 4-phenylphenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2,3-dichlorophenyl, 2,4-dichlorophenyl, 3,4-dichlorophenyl, 2,5-dichlorophenyl, 3, 5 -dichlorophenyl, 2,6-dichlorophenyl, 2-chlorophenylmethyl 4-chlorophenylmethyl, 2,4-dichlorophenylmethyl, 2,6-dichlorophenylmethyl, 2-methoxycarbonylphenylmethyl, 3-trifluoromethylphenyl, 4-trifluoromethylphenyl, 3,5-bis (trifluoromethyl) phenyl , 4-trifluoromethoxyphenyl, phenylmethyl, 2-acetamido-4-met-il-thiazol-5-yl, phenylethyl, l-phenylpropyl, (S) - (+) - camphor-10-yl, (R) - (-) - camphor-10-yl, 2-phenylethenyl, 2-thiophenyl, 4-methoxyphenyl, 3,5-dimethoxyphenyl, 3-methylphenyl, 4-methylphenyl, 4-t-butylphenyl, 4-propylphenyl, 2,5-dimethylphenyl, 2- methoxy-5-methylphenyl, 2,3,5,6-tetramethylphenyl, 2, 3, 4, 5, 6-pentamethylphenyl, 1-naphthyl, 2-naphthyl, 4-fluorophenyl, 2-difluorophenyl, 2-chloro- 6-methylphenyl, 2-chloro-4-fluorophenyl, 2,5-dimethoxyphenyl, 3,4-dimethoxyphenyl, 3-chloro-6-methoxyphenyl, 2-trifluoromet-ilphenyl, 2 -alkylsulfonylphenyl, 2-arylsulfonylphenyl, 3- (N-acetyl-6-methoxy) aniline, 4-acetamidophenyl, 2,2,2-trifluoroethyl, 5-chloro-3-methyl-benzothiazol-2-yl, N-methoxycarbonyl -piperidin-3-yl, thiophen-2-yl, isoxazol-5-yl, 2-chloro-iridin-3-yl, pyridin-3-yl, 5-methylisoxazol-3-yl, 1-adamantyl, 4-chlorophenoxymethyl , 2, 2-dimethyl-ethenyl, 2-chloropyridin-5-methyl, 5,7-dimethyl-1,3,4-triazaindolizin-2-yl, (S) -canphan-1-yl, (R) -Canfan-1-yl or 8-quinolinyl, the linking group L is -NHCO-, -CH 2 NHCO-, -NHCOCH 2 - or -OCH 2 -, -CH 2 -, - CH 2 OCH 2 -, -CH 2 CH 20 -, -OCH 2 CH 2 - , and the residue located on the phenylene unit is an open chain or cyclic guanidine or urea unit, wherein a cyclic guanidine unit such as, for example, a 4,5-dihydro-lH-imidazole unit is particularly preferred. 2-yl-amino or an open-chain guanidine unit such as, for example, the guanidino residue. In addition, the particularly preferred compounds of the formula (1) according to the present invention are those in which the amino group included in the residue derived from a β-amino acid carries a residue -COR 4'-, wherein R 4 'is preferably hydrogen , methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, phenyl, benzyl, tolyl or a substituted derivative thereof, -CeH2 ( CH 3) 3, -C 6 (CH 3) 5, CH 2 C 6 H 2 (CH 3) 3, 4-phenylphenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2,3-dichlorophenyl, 2,4-dichlorophenyl, 3,4-dichlorophenyl , 2, 5-dichlorophenyl, 3, 5-dichlorophenyl, 2,6-dichlorophenyl, 2-chlorophenylmethyl, 4-chlorophenylmethyl, 2,4-dichlorophenylmethyl, 2,6-dichlorophenylmethyl, 2-methoxycarbonylphenylmethyl, 3-trifluoromethylphenyl, 4-trifluoromethylphenyl , 3, 5-bis (trifluoromethyl) phenyl, 4-trifluoromethoxyphenyl, phenylmethyl, 2-acetamido-4-methyl-thiazole-5 -yl, phenylethyl, l-phenylpropyl, (S) - (+) - camphor-10-yl, (R) - (-) -canfor-10-yl, 2-phenylethenyl, 2-thiophenyl, 4-methoxyphenyl, 3,5-dimethoxyphenyl, 3-methylphenyl, 4-methylphenyl, 4-t-butylphenyl, 4-propylphenyl, 2,5-dimethylphenyl, 2-methoxy-5-methylphenyl, 2, 3, 5,6-tetramethylphenyl, 1- Naphthyl, 2-naphthyl, 4-fluorophenyl, 2,4-difluorophenyl, 2-chloro-6-methylphenyl, 2-chloro-4-fluorophenyl, 2,5-dimethoxyphenyl, 3,4-dimethoxyphenyl, 3-chloro-6- methoxyphenyl, 2-trifluoromethylphenyl, 2-alkylsulfonylphenyl, 2-arylsulfonylphenyl, 3- (N-acetyl-6-methoxy) aniline, 4-acetamidophenyl, 2,2,2-trifluoroethyl, 5-chloro-3-methyl-benzothiazole-2 -yl, N-methoxycarbonyl-piperidin-3-yl, thiophen-2-yl, isoxazol-5-yl, 2-chloropyridin-3-yl, pyridin-3-yl, 5-methylisoxazol-3-yl, 1-adamantyl , 4-chlorophenoxymethyl, 2,2-dimethylethenyl, 2-chloropyridin-5-methyl, 5,7-dimethyl-1,3,4-triazaindolizin-2-yl, (S) -canphan-1-yl, (R) -canfan-l-yl or 8-quinolinyl, the linker group L is -NHS02-, -CH2NHS02-, -NHS02CH2-, and the residue located on the phenylene unit is an open or cyclic chain guanidine unit, wherein a cyclic guanidine unit such as, for example, a 4,5-dihydro-lH- unit is particularly preferred. imidazol-2-yl-amino. In addition, the particularly preferred compounds of the formula (1) according to the present invention are those in which the amino group included in the residue derived from a β-amino acid carries a residue -COOR 4", wherein R 4" is preferably methyl , ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, phenyl, benzyl, or a substituted derivative thereof, -CH2CßH2 (CH3) 3 , 2-chlorophenylmethyl, 4-chloro-phenylmethyl, 2,4-dichlorophenylmethyl, 2,6-dichlorophenylmethyl, 2-methoxycarbonyl phenylmethyl, 3-trifluoromethylphenylmethyl, 4-trifluoromethylphenylmethyl, 3,5-bis (trifluoromethyl) phenylmethyl, 4-trifluoromethoxyphenyl, 2-thiophenylmetyl, 4-methoxyphenylmethyl, 3,5-dimethoxyphenylmethyl, 3-methylphenylmethyl, 4-methylphenylmethyl, 4-t-butylphenylmethyl, 4-propylphenylmethyl, 2,5-dimethylphenylmethyl, 2-methoxy-5-methylphenylmethyl, 2, 3,5,6-tetramethylphenylmethyl, 2, 3, 4, 5, 6-p entamethylphenylmethyl, 1-naphthylmethyl, 2-naphthylmethyl, 4-fluorophenylmethyl, 2,4-difluorophenylmethyl, 2-chloro-6-methyl-phenylmethyl, 2-chloro-4-fluorophenylmethyl, 2,5-dimethoxyphenylmethyl, 3,4- di- methoxyphenylmethyl, 3-chloro-6-methoxyphenylmethyl, 2-trifluoromethylphenylmethyl, 2,2,2-trifluoroethyl, isoxazol-5-ylmethyl, 2-chloropyridin-3-yl-methyl, pyridin-3-yl-methyl, 2-chloropyridin-5-methyl, the linker group L is -NHS02-, -CH2NHS02-, -NHS02CH2-, and the residue located on the phenylene unit is an open chain or cyclic guanidine or urea unit, the particularly preferred guanidine units are a cyclic guanidine unit such as, for example, a unit 4,5-dihydro-1H-imidazol-2-ylamino or an open chain guanidine unit such as, for example, the guanidine residue and the particularly preferred urea units are open chain units such as units 3- ( alkyl C? _4) -ureido, 3-pyridin-4-yl-ureido, 3-pyridin-3-yl-methyl-ureido, 3-pyridin-4-ylmethyl-uredio and 3 (lH-benzimidazol-2-yl- The present invention comprises the individual enantiomers or diastereomers and the corresponding racemates, diastereomeric mixtures and salts of the compounds defined in claim 1. In addition, All possible tautomeric forms of the compounds described above are also included according to the present invention. The present invention further comprises the pure E and Z isomers of the compounds of the general formula (1) and their E / Z mixtures in all ratios. The diastereomeric mixtures or E / Z mixtures can be separated into the individual isomers by chromatographic procedures. The racemates can be separated into the respective enantiomers either by chromatographic procedures on the chiral phases or by resolution. The compounds described above can be separated from the commercially available starting materials. The main steps of the preparation processes according to the invention are the reaction of a β-amino acid of the formula (2) wherein P is - (CH2) mN02, - (CH2) mO-C6-6 alkyl, - (CH2) mS02P ', - (CH2) mC0P', - (CH2) mCH20-C6-C6 alkyl. where m in each case is an integer of 0 or 1; P 'is -OH, -O-alkyl C? .6, and the other residues are as defined above; with a compound R4-A to give a compound of the formula (3), wherein R4 is -S02R4 ', -COOR4", or -COR4'; R4 'and R4" are as defined above; A is -Cl, -Br, -I, -0- triflyl, -0-tosyl, -O-C6-alkyl, -O-CO-C6-alkyl. -O-CO-O-alkyl C? -6, -OC (CH3) = CH2; and the other residues are as defined above; the conversion of residue P into residue Q, where Q is - (CH2) mNH2, - (CH2) m0H, - (CH2) mCH20H, - (CH2) mS02A, - (CH2) mC0A, A is as defined above; m is an integer of 0 or 1; the reaction of the compound (3) obtained above with a compound of the formula (4) where S is AS02 (CH2) n-. NH2 (CH2) n-, ACO (CH2) n-, HOCH2 (CH2) n-, M (CH2) "-, MCH2 (CH2) n-, HSCH2 (CH2) n- or HS (CH2) n-, where n is an integer of 0 or 1; M is a residue that includes Mg, Li, Cd or Sn; A is as defined above; and C is N02 or X, R7, R8, R9 and R11 are as defined above; to give a compound of the formula (5) (5) where the waste is as defined above; if the conversion of C is appropriate, if C is a nitro group, in a unit of urea, thiourea or optionally cyclic guanidine with the obtaining of compound (1); and if appropriate the removal of the protecting groups and / or derivation of the nitrogen atoms, which are present, at preferred times within the preparation process, and / or the conversion of the obtained compound into the free acid and / or conversion of the compound obtained in one of its physiologically acceptable salts by reaction with a base or inorganic or organic acid. The β-amino acid derivatives of the formula (2) are commercially available or are simply accessible by standard chemical processes, such as are known to the person skilled in the art and are described in standard works, such as Houben-Weyl , Methoden der organischen Chemie [Methods of Organic Chemistry], Georg Thieme-Ver Stuttgart. In particular, reference is made to the process of preparation for the β-amino acid derivatives described by Rodionow et al., J. Am. Chem. Soc. 51, 1929, 844-846, Kunz et al., Angew. Chem. 101, 1989, 1042-1043 and Ishihara et al., Bull. Chem. Soc. Jpn., 68, 6, 1995, 1721-1730. According to a preferred embodiment of the present invention, the derivatives of the β-amino acid of the formula (2) are obtained by the reaction of the malonic acid with a benzaldehyde derivative of the formula (2a) wherein R10 and P are as defined above, in the presence of ammonia, ammonium or amine compounds. Instead of malonic acid, an ester may also be used, if appropriate with the addition of a base suitably used for these purposes, such as NaH or a sodium alkoxide, preferably sodium methoxide, sodium ethoxide. An ammonium compound, such as, for example, ammonium acetate is preferably used as the nitrogen compound. The benzaldehyde derivatives (2a) are either commercially available or are accessible in a simple manner by standard chemical processes, such as are known to one skilled in the art and are described in standard works such as Houben-Weyl, Methoden der Organischen Chemie [Methods of Organic Chemistry], Georg Thieme-Ver Stuttgart. According to a preferred embodiment of the present invention, the compound of the formula (2a) employed is a nitrobenzaldehyde derivative such as 3- or 4-nitrobenzaldehyde or an alkoxybenzaldehyde derivative such as 3- or 4-methoxybenzaldehyde. According to a preferred embodiment of the present invention, the β-amino acid of formula (2) is obtained by the reaction of approximately equimolar amounts of malonic acid, ammonium acetate and 3-nitrobenzaldehyde or 3-methoxybenzaldehyde in a solvent such as isopropanol. with heating from 50 to 110 ° C for several hours, preferably 2 to 6 hours, preferably under reflux of the solvent, in surrounding atmosphere (i.e. in air or under normal pressure). For the following reaction steps, the carboxyl group is blocked by a conventional protecting group P. Protective groups of this type are known to the person skilled in the art and do not need to be expressly mentioned here. Particularly preferably, the carboxyl group is esterified, P is C6_6 alkyl such as, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, a C3_7 cycloalkyl, such as, for example, cyclopropyl, cyclopropylmethyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, an aryl such as, for example, phenyl, benzyl or tolyl or a substituted derivative thereof. In addition, the preparation process according to the invention for the compounds of the general formula (1) can be carried out in a solid phase. In this case the carboxyl residue can be linked to any solid phase conventionally used for reactions of this type, such as a polystyrene resin, for example a polystyrene resin of Wang. According to a preferred embodiment according to the invention, the The carboxyl group of the above β-amino acid is esterified by reaction with an alcohol, such as ethanol. This can be carried out under conditions known to the person skilled in the art, such as acid catalysis and, if appropriate, addition of a dehydrating agent, such as dicyclohexylcarbodiimide. However, preferably, the β-amino acid is suspended in the appropriate alcohol, such as ethanol, which is present in excess, HCl is passed for a period of about 30 minutes to about 2 hours and the mixture is then heated in a surrounding atmosphere for several hours, preferably about 1 to 6 hours and particularly preferably about 3 to 5 hours, at about 50 to about 100 ° C, preferably at reflux of the alcohol. In this manner, the accessible protected carboxyl amino acids are reacted with a sulphonation, carbamoylation or acylation reagent to obtain the corresponding sulfonamide, carbamate or amide derivatives. The sulfonation reagent preferably used is a sulfonyl chloride of the formula R '-S02C1 or a carbamoyl chloride of the formula R4"-OCOC1, wherein R4' is a C? -? 0 alkyl such as methyl, ethyl, propyl , isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, heptyl, octyl, nonyl, decyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or camphor-10-yl, an aryl such as phenyl, benzyl, tolyl, mesityl or substituted derivatives thereof such as -C6H2 (CH3) 3-, -Ce (CH3) 5, -CH2C6H2 (CH3) 3, 4-phenylphenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2, 3-dichlorophenyl, 2,4-dichlorophenyl, 3,4-dichlorophenyl, 2,5-dichlorophenyl, 3,5-dichlorophenyl, 2,6-dichlorophenyl, 2-chlorophenylmethyl, 4-chlorophenylmethyl, 2,4-dichlorophenylmethyl, 2, 6-Dichlorophenylmethyl, 2-methoxycarbonylphenylmethyl, 3-trifluoromethylphenyl, 4-trifluoromethylphenyl, 3,5-bis (trifluoromethyl) phenyl, 4- trifluoromethoxyphenyl, phenylmethyl, 2-acetamido-4-methylthia zol-5-yl, phenylethyl, l-phenylpropyl, (S) - (+) - camphor-10-yl, (R) - (-) -canfor-10-yl, 2-phenylethenyl, 2-thiophenyl, 4- methoxyphenyl, 3, 5-dimethoxyphenyl, 3-methylphenyl, 4-methylphenyl, 4-t-butylphenyl, 4-propylphenyl, 2,5-dimethylphenyl, 2-methoxy-5-methylphenyl, 2, 3, 5,6-tetramethylphenyl, 1-naphthyl, 2-naphthyl, 4-fluorophenyl, 2,4-difluorophenyl, 2-chloro-6-methylphenyl, 2-chloro-4-fluorophenyl, 2,5-dimethoxyphenyl, 3,4-dimethoxyphenyl, 3-chloro- 6-methoxyphenyl, 2-trifluoromethylphenyl, 2-alkylsulfonylphenyl, 2-arylsulfonylphenyl, 3- (N-acetyl-6-methoxy) aniline, 4-acetamidophenyl, 2,2,2-trifluoroethyl, 5-chloro-3-methylbenzothiazole-2 -yl, N-methoxycarbonyl-1-piperidin-3-yl, thiophen-2-yl, isoxazol-5-yl, 2-chloropyridin-3-yl, pyridin-3-yl, 5-methylisoxazol-3-yl, 1-adamantyl, 4-chlorophenoxymethyl, 2,2-dimethylethenyl, 2-chloropyridin-5-methyl, 5,7-dimethyl -l, 3, 4 -triazaindoli zin-2-yl, (S) -canfan-l-yl, (R) -canphan-l-yl, 8-quinolinyl, or a heterocyclic analog of the cyclic residues mentioned above and in where R4 'is a C6_6 alkyl such as, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, a C3_7 cycloalkyl such as, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, an aryl such as phenyl, benzyl, or a substituted derivative thereof such as -CH 2 C 6 H 2 (CH 3) 3, 2-chlorophenylmethyl, 4-chlorophenylmethyl, 2,4-dichlorophenylmethyl, 2,6-dichlorophenylmethyl , 2-methoxycarbonylphenylmethyl, 3-trifluoromethylphenylmethyl, 4-trifluoromethylphenylmethyl, 3,5-bis (trifluoromethyl) phenylmethyl, 4-trifluoromethoxyphenyl, 2-thiophenylmethyl, 4-methoxyphenylmethyl, 3,5-dimethoxy phenylmethyl, 3-methylphenylmethyl, 4-methylphenylmethyl, 4-t-butylphenylmethyl, 4-propylphenylmethyl, 2,5-dimethylphenylmethyl, 2-methoxy-5-methylphenylmethyl, 2,3,5,6-tetramethylphenylmethyl, 2,3,4, 5,6-pentamethylphenylmethyl, 1-naphthylmethyl, 2-naphthylmethyl, 4-fluorophenylmethyl, 2,4-difluorophenylmethyl, 2-chloro-6-methylphenylmethyl, 2-chloro-4-fluorophenylmethyl, 2,5-dimethoxyphenylmethyl, 3, 4- dimethoxyphenylmethyl, 3-chloro-6-methoxyphenylmethyl, 2-trifluoromethylphenylmethyl, 2,2,2-trifluoroethyl, isoxazol-5-ylmethyl, 2-chloropyridin-3-ylmethyl, pyridin-3-ylmethyl, 2- chloropyridin-5-methyl. Instead of the sulfonyl or carbamoyl chlorides mentioned above, the corresponding fluorides, bromides or iodides can also be used. As an acylating reagent, the appropriate carbonyl halides or carboxylic anhydrides are reacted with the amino group, wherein the appropriate C 1 -C 6 alkyl chlorides such as methyl chloride, ethyl chloride, propyl chloride, isopropyl chloride, butyl chloride, isobutyl chloride, t-butyl chloride, pentyl chloride, isopentyl chloride, neopentyl chloride, hexyl chloride, C3_ cycloalkyl chlorides, such as cyclopropyl chloride, cyclobutyl chloride, cyclopentyl chloride, chloride of cyclohexyl, aryl chlorides such as phenyl chloride, benzyl chloride, tolylcarboxylic acid chloride or substituted derivatives thereof, are preferred according to the invention. For the preparation of the urea or thiourea derivatives, the amino group is first reacted preferably with a carbonic acid derivative thiocarbonic acid, such as chloroformic acid ester or thiophosgene and then with a desired amine. The above reactions and their implementation are well known to those skilled in the art and are described in detail in standard works such as, for example, Houben-Weyl, Methoden der organischen Chemie [Methods of Organic Chemistry], Georg Thieme-Verlag, Stuttgart. According to a preferred embodiment of the invention, the protected ß carboxyl amino acid of the formula (2) is treated with an equimolar amount or a slight excess of the appropriate sulfonation agent, for example phenylsulfonyl chloride or acylating agent, for example chloride of mesitylacetyl, with cooling, preferably at 0 ° C, in a solvent such as pyridine or dioxane in a surrounding atmosphere, in the presence of a base such as amine, preferably triethylamine or diisopropylethylamine and stirring at this temperature for a period of about 10 hours. minutes to approximately 2 hours. In the case of sulfonation, stirring is continued at room temperature for several hours, preferably about 2 to 6 hours. Prior to the construction of the linker group L, the residue P of the compound of the formula (3) must be converted into a Q group that can participate in a nucleophilic substitution, either as a nucleophilic reagent or as a substrate. If P includes a nitro group, this is reduced to the corresponding amino group, this reduction can be carried out according to the present invention, preferably by the addition of tin (II) chloride to a solution of the compound of the formula (3) in a solvent, such as ethanol and the subsequent heating to about 50 to 110 ° C, preferably under reflux of the solvent, for several hours, preferably about 1 to 4 hours, in a surrounding atmosphere. If P includes an ether group, the release of the corresponding hydroxyl group is preferably carried out by the addition of a Lewis acid, such as boron tribromide in a solvent, such as dichloromethane with cooling, preferably at -78 ° C, and subsequent agitation for several hours, preferably 6 to 24 hours, at room temperature. If P includes a group of sulfonic acid or carboxylic acid, the conversion to the corresponding sulfonyl halide or carbonyl is preferably carried out. This can be carried out in a manner known to the person skilled in the art, for example by the reaction of the corresponding sulfonic or carboxylic acid with thionyl chloride. The compound prepared in this way is then reacted with a compound of the formula (4) where is AS02 (CH2) n-. NH2 (CH2) n-, AC0 (CH2) n-, H0CH2 (CH2) n-, M (CH2) n-, MCH2 (CH2) n-, HSCH2 (CH2) n- or HS (CH2) n-, where n is an integer of 0 or 1; M is a residue that includes Mg, Li, Cd or Sn; A is as defined above; and C is -N02 or X, R7, R8, R9 and R11 are as defined above; to give a compound of the formula (5) (5) where the waste is as defined above. This reaction formally represents the substitution of a leaving group in one of the initiator compounds by a nucleophilic unit in the other initiator compound in each case. According to a preferred embodiment of the present invention, the reagents are mixed in approximately equimolar amounts in the presence of a base such as pyridine or sodium hydride and optionally in a solvent such as, for example, tetrahydrofuran (THF) or dimethylformamide (DMF). ) in a surrounding atmosphere at room temperature or with cooling, preferably at about 0 ° C, and stirred for several hours, preferably about 1 h at about 24 hours, at room temperature or with cooling, for example at 0 ° C. The compounds of the formula (5) thus obtained are converted into the compounds of the formula (1) according to the invention by conversion of the terminal nitro group into a cyclic or open chain guanidine, urea or thiourea unit. For this purpose, the nitro group is preferably first converted according to the invention into an amino group by the addition of a customary reducing agent, such as tin (II) chloride, if appropriate in the presence of solvents such as ethanol, by stirring the reaction mixture with heating at about 50 to 110 ° C, preferably at reflux of the solvent, in a surrounding atmosphere for about 2 hours. The amino group thus obtained is then converted to a guanidine, urea or thiourea unit. For this purpose, the above amino group is preferably first reacted with a carbonic acid ester derivative or thiocarbonic acid ester in a solvent, such as dimethylformamide (DMF) in the presence of mercury (II) chloride with cooling, preferably at about 0 ° C, and stirring for about 10 minutes for up to about 3 hours with cooling, preferably at about 0 ° C, and if appropriate, then at room temperature. The derivative of the carbonic acid ester or thiocarbonic acid ester used can preferably be phosgene, triphosgene, thiophosgene, esters of chloroformic acid or derivatives of thiopseudourea, commercially available esters of chloroformic acid are preferred for the preparation of urea derivatives, it prefers thiophosgene for the preparation of the thiourea derivatives and the thiopseudourea derivatives are preferred for the preparation of the guanidine derivatives. The carbamates or isothiocyanates formed in this way can be converted into the corresponding urea, thiourea and guanidine derivatives by reaction with the appropriate amines. The amines that can be used are substances of the formula HNRR ', wherein R and R' independently of one another or simultaneously are hydrogen, a substituted or unsubstituted alkyl or cycloalkyl residue, a substituted or unsubstituted aryl residue, a saturated or unsaturated heterocyclic residue , optionally substituted, an alkylamine residue, an alkylamide residue or are bonded to each other and together with the nitrogen atom form an optionally substituted heterocyclic ring system which may be saturated or unsaturated and / or may contain additional heteroatoms. With respect to the preferred residues on the amine, reference is made to the above description of the compounds according to the invention. According to the invention, the carbamate or isothiocyanate is preferably reacted with an amine at room temperature with stirring for about 1 to 5 hours, preferably about 2 to 3 hours, in the presence of an auxiliary base, such as diisopropylethylamine in a solvent such as dimethylformamide (DMF). In the case of the preparation of the cyclic guanidine derivatives, the corresponding isothiocyanate is preferably first heated in ethanol for several hours, preferably approximately 12 to 24 hours, and then heated with a diamine such as diaminoethane in a solvent, such as toluene, dimethylformamide (DMF) or a mixture of the two. According to a further preferred embodiment of the present invention, it is also possible to generate the group of the guanidine, urea or thiourea above in the above manner, initially on the compound of the formula (4) and react the compound of the formula ( 4) thus obtained subsequently in the manner described above with the compound of the formula (3). The compounds obtained according to the processes explained above can be further derived by removing the protective groups that might be present, continuing the substitution of the nitrogen atoms, which are present, at the preferred positions in the preparation process, and / or conversion of the compound obtained in the free acid and / or its physiologically acceptable salts. For example, the t-butoxymethoxycarbonyl groups used conveniently conveniently used as protecting groups for the nitrogen atoms are stirred in an acid medium, for example by the addition of trifluoroacetic acid. Possible alkylating agents for the derivatization of the nitrogen atoms are reactants conventionally used for this purpose in this step, whereby, for example, a substituted or unsubstituted alkyl or cycloalkyl residue, a substituted aryl residue can be linked to the nitrogen atom. or unsubstituted or a saturated or unsaturated, optionally substituted heterocyclic residue. With respect to the substituents preferably linked to the respective nitrogen atoms, reference is made to the above description of the compounds according to the invention. The above reactions and their implementation are well known to those skilled in the art and are described in detail in standard works, such as, for example, Houben-Weyl, Methoden der organischen Chemie [Methods of Organic Chemistry], Georg Thieme Verlag, Stutgart. The ester derivatives according to the invention can be converted into the corresponding free carboxylic acids in a customary manner, such as, for example, by hydrolysis of the basic ester. If desired, the compounds according to the invention can be converted into their physiologically acceptable salts. This can be effected either by reaction with an organic or inorganic base, such as, for example, an alkali metal hydroxide or alkaline earth metal hydroxide, such as KOH, NAOH, LiOH, Mg (OH) 2 or Ca (OH) 2, as a result of which the carboxyl terminal group is deprotonated and the corresponding carboxylate is formed, or by reaction with an organic or inorganic acid, such as, for example, hydrochloric acid, sulfuric acid, phosphoric acid, mandelic acid, oleic acid , linoleic acid or p-toluenesulfonic acid, as a result of which one or more of the nitrogen atoms present are protonated. The steps of the preparation process according to the invention described above can be carried out in a normal atmosphere, i.e. in air and without the use of absolute solvents, i.e. essentially anhydrous.

The compounds according to the invention exhibit a very good antagonistic action against the integrin receptors, in particular the avß3 receptor or the avß5 receptor. This makes them suitable for use as pharmaceutical compositions, in particular for the treatment and prophylaxis of arteriosclerosis, restenosis, osteolytic conditions, such as osteoporosis, cancer and ophthalmic diseases. In addition, they are suitable for the reduction and inhibition of angiogenesis and consequently are suitable for the prophylaxis and treatment of conditions and diseases such as cancer or rheumatoid arthritis. The compounds according to the invention can be used as components of active compounds for the production of pharmaceutical compositions against the diseases mentioned above. For this purpose, they can be converted into customary formulations such as tablets, coated tablets, aerosols, pills, granules, syrups, emulsions, suspensions and solutions using inert, non-toxic, pharmaceutically suitable excipients or solvents. The compounds according to the invention are preferably used herein in such an amount that their concentration in the total mixture is about 0.5 to about 90% by weight, being dependent, inter alia, on the corresponding indication of the pharmaceutical composition. The aforementioned formulations are prepared, for example, by spreading the active compounds using solvents and / or excipients having the above properties, where, if appropriate, emulsifying agents or dispersing agents have to be additionally added and, in the case of water as a solvent, alternatively an organic solvent. The pharmaceutical compositions according to the invention can be administered in a customary manner. The present invention is illustrated below with the aid of the non-restrictive examples and comparison examples.

Eg emplos In the following examples, all quantitative data, unless stated otherwise, refer to percentages by weight. Mass determinations were carried out by high performance liquid chromatography-mass spectrometry (HPLC-MS) using the electronic spray ionization (ESI) method.

Example 1 Scheme of general synthesis: NH4OAc (la) (ih) 0) a) 2-propanol, reflux; b) HCl, ethanol; c) PhS02Cl, Et3N; d) SnCl 2, ethanol; e) 3-N02-C6H4S02Cl; f) SnCl 2, ethanol; g) HgCl2, 1,3-bis (tert-butyloxycarbonyl) -2-methyl-2-thiopseudourea; h) TFA, dichloromethane, i) LiOH 3-amino-3- (3-nitro phenyl) propionic acid hydrochloride (la) 151 g of 3-nitrobenzaldehyde, 94 g of ammonium acetate and 127 g of malonic acid were heated under reflux for 5 h in 1 l of isopropanol. The solution was filtered and the precipitate was washed with 0.7 1 hot isopropanol. The crude product was dried in vacuo, suspended in 1.5 1 of water, treated with hydrochloric acid and filtered, and the filtrate was concentrated (yield: 146 g).

^ -NMR (400 MHz, D4-MeOH): 3.09 (m, 2H), 4.88 (m, HI), 7.74 (t, ÍH), 7.90 (d, ÍH), 8.33 (d, ÍH), 8.43 (s) , ÍH).

Ethyl 3-amino-3- (3-nitro phenyl) -propionate hydrochloride (lb) 60 g of (la) were suspended in 660 ml of ethanol, and gaseous HCl was passed for 1 hour. The reaction mixture was then heated to reflux for 4 h and then cooled and concentrated. 62 g of a white solid were obtained.

^ -RMN (400 MHz, D4-MEOH); 1.22 (t, 3H), 3.12 (dd, ÍH), 3.20 (dd, ÍH), 4.18 (q, 2H), 4.95 (t, ÍH), 7.77 (t, ÍH), 7.94 (d, ÍH), 8.35 (d, ÍH), 8.43 (s, ÍH). 3-Bencensulf onylamino-3- (3-nitro phenyl) -propionate ethyl (le) 8.1 g of phenylsulfonyl chloride were added at 0 ° C to a solution of 10 g of (lb) in 100 ml of pyridine. After a reaction time of 15 min, 6.3 ml of triethylamine was added and the mixture was stirred at room temperature. After 5 h, it was concentrated, treated with IN HCl, extracted with dichloromethane, dried with MgSO 4 and concentrated. Chromatographic purification (dichloromethane / methanol = 5: 1) yielded 11.4 of a white solid.

XH-NMR (400 MHz, CDC13); 1.16 (t, 3H), 2.80 (m, 2H), 4.05 (q, 2H), 4.87 (q, ÍH), 6.06 (d, ÍH), 7.35-7.50 (m, 5H), 7.71 (d, 2H) ? 7.92 (s, ÍH), 8.03 (d, ÍH).

Ethyl 3- (3-amino-phenyl) -3-benzenesulfonylamino-propionate (Id) 4. 77 g of tin (II) chloride were added to a solution of 2.0 g of (le) in 60 ml of ethanol, and the reaction mixture was heated to reflux for 2 h. After cooling, the solution was hydrolyzed by pouring it on ice and adjusted to pH = 8 using a solution of NaHCO 3 (5%). It was then extracted with dichloromethane and the organic phase was washed with NaCl, dried with MgSO 4 and concentrated. 1.79 g of a yellow oil was obtained. ^ -RMN (400 MHz, CDC13); 1.14 (t, 3H), 2.72 (dd, ÍH), 2.81 (dd, ÍH), 4.02 (q, 2H), 4.65 (q, ÍH), 5.66 (d, ÍH), 6.41 (m, ÍH), 6.48 (m, 2H), 6.96 (t, ÍH), 7.40 (m, 2H), 7.50 (m, ÍH), 7.75 (m, 2H). 3 - . 3 -Ben cen sul fonm lam i no- 3- (3- [3-ni phenyl sul phonyl amino] phenol) -propi ona to e ti l o 382 mg of 3-n-t-robennesulfonyl chloride were added at 0 ° C to a solution of 500 mg of (Id) in 4 ml of pyridine. After a reaction time of 1 h at 0 ° C and 2 h at room temperature, the mixture was concentrated, treated with IN HCl and extracted with dichloromethane. After drying with MgSO4, the solvent was removed and 649 mg of a solid was obtained.

XH-NMR (400 MHz, CDC13); 1.02 (t, 3H), 2.50 (dd, ÍH), 2.59 (dd, ÍH), 3.88 (q, 2H), 4.52 (q, ÍH), 5.70 (d, ÍH), 6.49 (s, ÍH), 6.82 -6.90 (m, 3H), 7.06 (t, ÍH), 7.34 (t, 2H), 7.44 (t, ÍH), 7.59 (t, ÍH), 7.64 (d, 2H), 7.96 (d, ÍH), 8.31 (d, ÍH), 8.49 (m, ÍH).

Ethyl 3- (3- [3-amino-3-ylsulfonyl-amido] -phenyl) -3-benzenesulfonylamino-propionate (lf) 1. 27 g of tin (II) chloride were added to a solution of 600 mg of (le) in 9 ml of ethanol, and the reaction mixture was heated to reflux for 2 h. After cooling, the solution was hydrolysed by pouring it on ice and the pH = 8 was adjusted using a solution of NaHCO3 (5%). It was then extracted with dichloromethane, and the organic phase was washed with NaCl, dried with MgSO4 and concentrated. 394 mg of a yellow, viscous residue was obtained.

XH-NMR (400 MHz, CDC13); 1.14 (t, 3H), 2.65 (dd, ÍH), 2.73 (dd, ÍH), 4.01 (q, 2H), 4.63 (q, ÍH), 5.81 (d, ÍH), 6.32 (s, ÍH), 6.79 (d, 2H), 6.88 (d, ÍH), 6.99 (t, ÍH), 7.05-7.14 (m, 3H), 7.22 (t, ÍH), 7.39 (m, 2H), 7.51 (t, ÍH), 7.71 (d, 2H). 3-Benzylsulphonylamino-3- (3- (3- [N, N'-bis-t-butoxycarbonyl-guanidino] -phenylsulphonylamino) -phenyl) -propione (or g) 0. 16 ml of triethylamine, 195 mg of l, 3-bis (t-butoxycarbonyl) -2-met il-2-thiopseudourea and 132 mg of mercuric chloride were added at 0 ° C to a solution of 281 mg of (lf) in 10 ml of DMF. After a reaction time of 30 min at 0 ° C, the mixture was stirred at room temperature for an additional 1.5 h. 15 ml of ethyl acetate were added and the mixture was stirred for 30 minutes before the precipitate was filtered. The solution was concentrated and reused without further purification.

XH-NMR (400 MHz, CDC13); 1.12 (t, 3H), 1.52 (s, 9H), 1.54 (s, 9H), 2.65 (dd, ÍH), 2.72 (d, IH), 3.99 (q, 2H), 4.66 (m, ÍH), 5.78 (m, ÍH), 6.72 (m, ÍH), 6.85 (d, ÍH), 6.96-7.07 (m, 3H), 7.33-7.49 (m, 5H), 7.65 (d, 2H), 7.78 (m, ÍH ), 8.12 (s, ÍH). 3-Bencensul foni lamino-3 - (3- [3-guanidinof eni l sulf oni lamino] -phenyl) -propi on to ethyl o (lh) 2 ml of trifluoroacetic acid were added to a solution of 246 mg of (lg) in 2 ml of methylene chloride. The reaction was stirred at room temperature for 4 h and the solvent was then stirred in a rotary evaporator. 100 mg of a viscous oil was obtained by means of chromatographic purification (dichloromethane / methanol 1: 1).

Mass spectrometry: 546 (MH +).

Salt of 3-benzenesulfonylamino-3- [3- (guanidino-benzenesulphonylamino) -phenyl] -3-propionic acid, trifluoroacetic acid (1): 98 mg of lithium hydroxide monohydrate was added to a solution of 98 mg of (lh) in 14 ml of water, and the reaction mixture was stirred at room temperature for 70 h. The solution was acidified to pH = 2 using trifluoroacetic acid and concentrated. The crude product was purified by RP chromatography (RP 18 water / acetonitrile). 42 mg of a white solid were obtained.

Elemental analysis for C22H23N5OnS2 x 2.0 TFA x 2.0 H20: calculated: C 39.95; H, 3.74; N 8.96 found: C 39.7; H 3.7; N, 9.1.

Mass spectrometry: 518 (MH +).

Example 2 Scheme of generated syn thesis: (id) (2b) (2) a) 3-H2N (C = NH) NHC6H4COOH (2a), iBuOCOCl, N-methylmorpholine; b) LiOH.

Acid hydride 3 - ((aminoiminoe ti l) amino) benzoi co (2a) 49.4 g of 3-aminobenzoic acid were added to a solution of 108.7 g of 3,5-dimethyl-pyrazolyl-1-carboxamidine nitrate and 54.7 g of diisopropylamine in 360 ml of dioxane and 180 ml of water. The reaction solution was heated to reflux for 18 h. After cooling, it was filtered and the crystallizate was washed with dioxane / water (2: 1) and dried in vacuo. The product was dissolved in water and treated with hydrochloric acid, and the hydrochloride salt was obtained after filtration as a solid product (yield: 29.7 g).

Melting point: 261 ° C.

XH-NMR (400 MHz, D4-MeOH); 7.51 (d, ÍH), 7.59 (t, ÍH), 7.91 (s, ÍH), 8.00 (d, ÍH). 3 - . 3 -Ben censul fon i lami no- 3- [3 - (3 - guani dino -ben zoi l amino) -feni l] -propi ona t o de e ti l o (2b) 0. 16 ml of N-methylmorpholine and isobutyl chloroformate were added to a solution of 310 mg of (2a) in 5 ml of DMF. The solution was stirred at 0 ° C for minutes, then a solution of 500 mg of (Id) in 5 ml of DMF was added at 0 ° C. The reaction mixture was heated to RT overnight and then concentrated. A viscous oil was obtained (yield: 502 mg) by chromatographic purification (dichloromethane / methanol = 3: 1).

Mass spectrometry: 510 (MH +).

Sa l of the acid 3-ben censulon fon i lamino -3- [3- (3-guanidino-benzoi lamino) -phenyl] -propionic, trifl uoroa-acetic acid (2): 64 mg of lithium hydroxide monohydrate were added to a solution of 204 mg of (2b) in 8 ml of water. The reaction mixture was stirred at room temperature for 48 h. The solution was then acidified to pH = 2 using trifluoroacetic acid and concentrated. The crude product was purified by RP chromatography (RP18 water / acetonitrile). A white solid was obtained (yield: 11 mg).

Mass spectrometry: 482 (MH +) Example 3 _5.sgue.na of general synthesis: (1b) (3a-7a) (3b-7b) (3cJc) d) OHN .1-0 H f. x e) (3d-7d) (3eJe) (3f-7 (3-7) a) RCOC1, iPr2EtN; b) SnCl 2, ethanol; c) 3-N02-C6H4S02Cl; d) SnCl 2, ethanol; e) HgCl2, 1,3-bis (tert-butoxycarbonyl) -2-methyl-2-thiopseudourea; f) TFA, dichloromethane, g) LiOH.

Ethyl 3- (2, 4, 6-trimethylphenylacetylamino) -3- (3-nitrophenyl) -propionate (3a): 3.57 g of mesityl-acetyl chloride and 5.27 g of diisopropylethylamine were added at 0 ° C to a solution of 5.0 g of (lb) in 50 ml of dioxane. The reaction mixture was stirred at 0 ° C for 1 h, and then allowed to warm to room temperature. The solution was added to water and acidified with IN HCl, extracted with dichloromethane, dried with MgSO4 and concentrated. Chromatographic purification on silica gel (dichloromethane / methanol = 20: 1) gave a white solid (yield: 6.0 g).

XH-NMR (400 MHz, CDC13); 1.09 (t, 3H), 2.28 (s, 6H), 2. 30 (s, 3H), 2.76 (m, 2H), 3.65 (m, 2H), 3.97 (m, 2H), . 48 (m, ÍH), 6.55 (d, ÍH), 6.97 (s, 2H), 7.49 (m, 2H), 7.95 (m, ÍH), 8.10 (d, ÍH). 3- (3-amino-phen-1) -3- (2, 4, 6 -methyltrimethylamine) -propylate of thiol (3b): 12. 5 of tin chloride (II) were added to a solution of 6.0 g of (3a) in 180 ml of ethanol, and heated to reflux for 2 h. The reaction mixture was hydrolysed on ice after cooling and neutralized with NaHCO3 solution (5%), then filtered through a little silica gel and washed with dichloromethane.

The organic phase was dried with MgSO 4 and concentrated. 1.5 g of a white solid was obtained.

^ -RMN (400 MHz, CDC13); 1.11 (t, 3H), 2.25 (s, 6H), 2.29 (s, 3H), 2.69 (m, 2H), 3.61 (m, 2H), 3.98 (m, 2H), . 33 (m, ÍH), 6.21 (d, ÍH), 6.42 (s, ÍH), 6.46 (d, ÍH), 6.53 (d, ÍH), 6.92 (s, 2H), 7.04 (t, ÍH). 3- (3- [3-nitr oben cen sulfonil amino] -phenyl) -3- (2,4,6-trimethylphenylacetylamino) -propionate ethyl (3c): 3-Nitrobenzenesulfonyl chloride at 0 ° C was added to a solution of 1.5 g of (3b) in 12 ml of pyridine. After a reaction time of 2.5 h, the mixture was concentrated, treated with IN HCl and extracted with dichloromethane. After drying with MgSO, the solvent was removed and 2.02 g of a solid were obtained.

H-NMR (400 MHz, CDC13); 1.07 (t, .3H), 2.23 (s, 6H), 2.30 (s, 3H), 2.63 (m, 2H), 3.63 (m, 2H), 3.94 (m, 2H), 5.27 (m, ÍH), 6.43 (d, ÍH), 6.87-6.95 (m, 5H), 7.14-7.19 (m, 2H), 7.62 (t, ÍH), 7.98 (d, ÍH), 8.37 (d, ÍH), 8.59 (s, ÍH). 3- (3- [3-N-aminobenzenesulfonyl] -phenyl] -3- (2,, 6-trimethyl-phenylacetyl-amino) -propionate ethyl ester (3d) 3. 8 g of tin (II) chloride were added to a solution of 2.0 g of (3c) in 30 ml of ethanol, and the reaction mixture was heated to reflux for 2 h. After cooling the solution, it was hydrolyzed by pouring it on ice and neutralized with NaHCO3 solution (5%). The mixture was filtered through a little silica gel, washed with dichloromethane, dried with MgSO 4 and concentrated. A yellowish crystalline product was obtained (yield: 1.4 g).

XH-NMR (400 MHz, CDC13); 1.09 (t, 3H), 2.25 (s, 6H), 2.29 (s, 3H), 2.68 (m, 2H), 3.63 (s, 2H), 3.97 (m, 4H), 5.30 (m, 1H), 6.44 (d, HH), 6.48 (s, HH), 6.73 (d, HH), 6.78 (d, HH), 6.88 (m, 2H), 6.93 (s, 2H), 7.07-7.19 (m, 4H). 3- (2,4-, 6-trimethyl-phenylacetylamino) -3- (3- [3-N, N'-bis (t-butoxycarbonyl) -guanidino-benzenesulphonylamino] -phenyl) -propionate ethyl (3e) 0. 12 ml of triethylamine, 195 mg of i, 3-bis (t-butoxycarbonyl) -2-met il-2-thiopseudourea and 132 mg of mercuric chloride were added at 0 ° C to a solution of 250 mg of (3d) in 10 ml of DMF. The reaction mixture was stirred at 0 ° C for 30 min and at room temperature for 2.5 h. 15 ml of ethyl acetate were added and the mixture was stirred for 30 min before the precipitate was removed by filtration. The solution was concentrated and reused without purification. Mass spectrometry: 766 (MH +).

Ethyl 3- (3- [3-guanidinobenzenesulfonylamino] -phenyl) -3- (2,4,6-trimethylphenyl-acetylamino) -propionate (3f): 3 ml of trifluoroacetic acid were added to a solution of 266 mg of (3e) in 3 ml of methylene chloride. The reaction mixture was stirred at room temperature for 4 h and concentrated. After chromatographic purification (methylene chloride / methanol = 5: 1), a viscous oil was obtained (yield: 228 mg).

Mass spectrometry: 566 (MH +). 3- (3- [3-Guanidinobenzenesulphonylamino] -phenyl) -3- (2,4,6-trimethyl-lal-eti-lamino) -propionic acid, trifluoroacetic acid (3): 64 mg of lithium hydroxide monohydrate they were added to a solution of 228 mg of (3f) in 30 ml of water and 30 ml of tetrahydrofuran. The reaction mixture was stirred at room temperature for 24 h. The crude product was dried in vacuo and purified by chromatography (acetonitrile / water = 7: 1), 0.1 ml of trifluoroacetic acid was added and the mixture was concentrated. A white solid was obtained (yield: 100 mg). Mass spectrometry: 538 (MH +).

* H-NMR (400 MHz, D4-MeOH); 2.18 (s, 6H), 2.23 (s, 3H), 2. 73 (m, 2H), 3.60 (m, 2H), 5.18 (m, ÍH), 6.84 (s, 2H), 6. 97 (d, ÍH), 7.04 (d, ÍH), 7.10 (s, ÍH), 7.20 (t, ÍH), 7.39 (d, ÍH), 7.51 (m, 2H), 7.68 (d, ÍH).

Example 4 3-Benzoylamino-3- (3-nitrophenyl) -propionate ethyl (4a): Corresponding to Example 3a, 5.0 g of (Ib) were acetylated by the addition of benzoyl chloride. A white solid was obtained (yield: 3.3 g).

XH-NMR (400 MHz, CDC13); 1.20 (t, 3H), 3.02 (m, 2H), 4.13 (q, 2H), 5.71 (m, ÍH), 7.31-8.68 (m, 10H) 3- (3-Aminophenyl) -3-benzoylamino-propione to ethyl (4b): Corresponding to Example 3b, 3 g of (4a) were reduced using tin (II) dichloride. A white solid was obtained (yield: 2.6 g). XH-NMR (400 MHz, CDC13); 1.19 (t, 3H), 2.91 (dd, ÍH), 3.00 (dd, ÍH), 4.11 (q, 2H), 5.54 (s, ÍH), 6.58 (d, ÍH), 6.54 (s, ÍH), 6.73 (s, ÍH), 7.12 (t, ÍH), 7.41-7.52 (m, 4H), 7.84 (d, 2H). 3-Benzoi lamino-3- (3- (-3-nor troben censul foni l amino) -feni l) -propi ona to eti lo (4 c): Corresponding to Example 3c, 2.60 g of (4b) were reacted with 3-nitrophenylsulfonyl chloride. A solid was obtained (yield: 1.76 g).

XH-NMR (400 MHz, CDC13); 1.18 (t, 3H), 2.90 (m, 2H), 4.09 (q, 2H), 5.49 (m, ÍH), 7.00 (d, ÍH), 7.05 (s, ÍH), 7.11 (s, ÍH), 7.15 (d, ÍH), 7.23 (d, ÍH), 7.45-7.57 (m, 4H), 7.70 (d, ÍH), 7.80 (d, 2H), 7.95 (d, ÍH), 8.27 (d, ÍH), 8.58 (s, ÍH).

Ethyl 3- (3- (-3-nitrobenzenesulphonylamino) -phenyl) -propionate (4c): Corresponding to Example 3c, 2.60 g of (4b) were reacted with 3-nitrophenylsulphonyl chloride. A solid was obtained (yield: 1.76 g).

H-NMR (400 MHz, CDC13); 1.18 (t, 3H), 2.90 (m, 2H), 4.09 (q, 2H), 5.49 (, ÍH), 7.00 (d, ÍH), 7.05 (s, ÍH), 7.11 (s, ÍH), 7.15 ( d, ÍH), 7.23 (d, ÍH), 7.45-7.57 (m, 4H), 7.70 (d, ÍH), 7.80 (d, 2H), 7.95 (d, ÍH), 8.27 (d, ÍH), 8.58 (Yes H) . 3- (3- (3-Aminobenzenesulphonylamino) -phenyl) -3-benzoylamino-propionate ethyl (4d): Corresponding to Example 3d, 1.76 g of (4c) were treated with tin (II) chloride • A yellowish solid was obtained (yield: 779 mg).

XH-NMR (400 MHz, CDC13); 1.20 (t, 3H), 2.93 (m, 2H), 3.98 (s, 2H), 4.12 (q, 2H), 5.52 (m, ÍH), 6.48 (s, ÍH), 6.67 (d, ÍH), 6.84 (d, ÍH), 6.90 (s, ÍH), 7.08-7.14 (m, 3H), 7.20 (t, ÍH), 7.28 (m, ÍH), 7.45-7.56 (m, 3H), 7.65 (d, ÍH) ), 7.84 (d, 2H). 3 - . 3-Benz or i-lamino-3- (3- [3-N, N '-bis (t-butoxycarbonyl) guanidino-benzenesulfonyl ami no] -phenyl) -ethyl propionate (4e): Corresponding to Example 3e, 1.76 g of (4d) were treated with mercuric chloride and 1,3-bis (tert-butoxycarbonyl) -2-methyl-2-thiopseudourea. 864 mg of the desired product were obtained.

Mass spectrometry: 710 (MH +) 3-Benzoylamino-3- (3- (3-guanidinobenzenesulphonylamino) -phenyl) -propionate ethyl (4f): 6 ml of trifluoroacetic acid were added to a solution of 521 mg of (4e) in 6 ml of dichloromethane. The mixture was stirred at room temperature for 4 h, concentrated and purified by chromatography (dichloromethane / methanol = 5: 1). An oil was obtained (yield: 229 mg).

Mass spectrometry: 510 (MH +). 3-Benzoylamino-3- [3- (3-guanidinoben benzylammonium amino) -pheni] -propionic acid (4): 94 mg of lithium hydroxide monohydrate were added to a solution of 298.5 mg of (4f) in 30 ml of water and 30 ml of THF. The reaction mixture was stirred at room temperature for 20 h and then concentrated. Chromatographic purification on silica gel (acetonitrile / water = 7: 1) gave a white solid (yield: 155 mg).

Mass spectrometry: 482 (MH +) XH-NMR (400 MHz, D4-MeOH); 2.81 (m, 2H), 5.38 (m, HH), 6.91 (m, HH), 7.18 (m, 2H), 7.34 (s, HH), 7.61 (s, HH), 7.45-7.58 (m, 5H) , 7.72 (d, ÍH), 7.86 (d, 2H).

Example 5 3- (2,4-Dichlorophenylacetylamino) -3- (-3-nitrophenyl) propionate ethyl (5a): Corresponding to Example 3a, 5.0 g of (lb) were subjected to acetylation by the addition of 2,4-dichlorophenylacetyl chloride. A white solid was obtained (yield: 3.1 g).

H-NMR (400 MHz, CDC13); 1.15 (t, 3H), 2.87 (m, 2H), 3. 73 (s, 2H), 4.05 (q, 2H), 5.47 (m, ÍH), 6.99 (d, ÍH), 7. 18 (d, ÍH), 7.29 (m, ÍH), 7.47 (s, ÍH), 7.50 (d, ÍH), 7.59 (d, ÍH), 8.11 (m, 2H). 3- (3-aminophenyl) -3- (2,4-dichlorophenylacetylamino) -propionate ethyl (5b): Corresponding to Example 3b, 3.1 g of (5a) were reduced using tin dichloride (II). A white solid was obtained (yield: 0.9 g).

XH-NMR (400 MHz, CDC13); 1.15 (t, 3H), 2.75 (dd, ÍH), 2.84 (dd, ÍH), 3.64 (s, 2H), 4.03 (q, 2H), 5.31 (m, ÍH), 6. 55 (m, 4H), 7.08 (t, ÍH), 7.27 (m, 2H), 7.43 (s, ÍH). 3- (2, 4-di-chloro-phenylamino) -3- (3-13-nitropheni-sulphonylamino) -phen-1-propionate of ethyl or (5c) Corresponding to Example 3c, 900 mg of (5b) were reacted with 3-nitoprophenylsulfonyl chloride. A solid was obtained (yield: 1.18 g).XH-NMR (400 MHz, CDC13); 1.12 (t, 3H), 2.75 (m, 2H), 3. 70 (s, 2H), 4.01 (m, 2H), 5.28 (m, ÍH), 6.85 (d, ÍH), 6. 91 (d, ÍH), 7.00 (m, 2H), 7.18 (m, 2H), 7.28 (m, 2H), 7. 62 (t, ÍH), 7.99 (d, ÍH), 8.37 (d, ÍH), 8.58 (s, ÍH). 3- (3- [3-aminophenylsulfonylamino] -phenyl) -3- (2,4-dichlorophenylacetylamino) -propionate ethyl (5d) Corresponding to Example 3d, 1.18 g of (5c) were treated with tin (II) chloride. 820 mg of a yellowish solid was obtained.

XH-NMR (400 MHz, CDC13); 1.14 (t, 3H), 2.79 (m, 2H), 3.99 (s, 2H), 4.03 (q, 2H), 5.30 (m, ÍH), 6.41 (s, ÍH), 6.73-6.83 (m, 3H) , 6.87 (s, ÍH), 6.98 (d, ÍH), 7.11-7.33 (m, 6H), 7.43 (d, 1H). 3- (2,4-diol or phenylacetylamino) -3- (3- [3-N, N'-bis Cibui oxycarbonyl) -guanidino-benzenesulfonyl amino] -phenyl) -propionate ethyl (5e): Corresponding to Example 3e, 300 mg of (5d) were treated with mercuric chloride and 1,3-bis (tert-butoxycarbonyl) -2-met il-2-thiopseudourea. 611 mg of the desired product were obtained.

Mass spectrometry: 792 (MH +) 3- (2,4-Dichlorophenylacetylamino) -3- (3- [3-guanidino-benzenesulfonyl-amino] -phenyl) -propionic acid ethyl ester (5f) Corresponding to Example 4f, 432 mg of (5e) were treated with trifluoroacetic acid. An oil was obtained (292 mg).

Mass spectrometry: 592 (MH +). 3- (2,4-Dichlorophenyl) -acetylamino) -3- [3- (3-guan-id-non-benzene-sulphonylamino) -phenyl] -propionic acid (5): Corresponding to Example 4, 292 mg of (5f) were hydrolysed using lithium hydroxide. A white solid (106 mg) was obtained.

Mass spectrometry: 564 (MH +) XH-NMR (400 MHz, D4-MeOH); 2.69 (m, 2H), 3.73 (s, 2H), . 18 (m, ÍH), 6.78 (d, ÍH), 7.05 (d, ÍH), 7.12 (t, ÍH), 7. 27 (d, ÍH), 7.33 (m, 2H), 7.40 (d, ÍH), 7.46 (m, 2H), 7.54 (t, ÍH), 7.71 (d, ÍH).

Example 6 3- (3-Nitro-phenyl) -3-phenylpropionylamino-propionic acid (6a): Corresponding to Example 3a, 5.0 g of (lb) were added to the acetylation with the addition of 3-phenylpropionyl. A white solid was obtained (yield: 6.7 g).

XH-NMR (400 MHz, CDC13); 1.16 (t, 3H), 2.59 (t, 2H), 2.75 (dd, ÍH), 2.85 (dd, ÍH), 4.05 (q, 2H), 5.45 (m, 2H), 6.75 (d, ÍH), 7.20 (m, 3H), 7.25 (m, 2H), 7.45 (d, 2H), 8.06 (s, ÍH), 8.10 (m, ÍH). 3- (3-Aminophenyl) -3-phenylpropionylamino-propionate ethyl (6b): Corresponding to Example 3b, 3.0 g of (6a) was reduced using tin (II) dichloride. A white solid was obtained (yield: 1.2 g).

XH-NMR (400 MHz, CDC13); 1.17 (t, 3H), 2.51 (t, 2H), 2.68 (dd, ÍH), 2.84 (dd, ÍH), 2.98 (t, 2H), 3.62 (s, 2H), 4.04 (q, 2H), 5.30 (m, ÍH), 6.39 (d, ÍH), 6.45 (s, ÍH), 6.55 (d, ÍH), 7.07 (t, ÍH), 7.20 (m, 3H), 7.29 (m, 2H).

Ethyl 3- (3- [3-nitrof in ilsulfonyl amino] -phenyl) -3- phenylpropionylamino-propionate (6c): Corresponding to Example 3c, 1.2 g of (6b) was reacted with 3-nitrophenylsulfonyl chloride. A solid was obtained (yield: 1.54 g).

XH-NMR (400 MHz, CDC13); 1.12 (t, 3H), 2.57 (m, 2H), 2.65 (dd, ÍH), 2.75 (dd, ÍH), 2.98 (m, 2H), 4.00 (m, 2H), 5.26 (m, ÍH), 6.70 (d, ÍH), 6.76 (s, ÍH), 6.88 (d, ÍH), 6.97 (d, 2H), 7.14 (t, ÍH), 7.21 (m, 2H), 7.23-7.32 (m, 3H), 7.45 (s, ÍH), 7.61 (t, ÍH), 8.34 (d, ÍH), 8.59 (s, ÍH).

Ethyl 3- (3- [3-amino-phenylsulphonylamino] -phenyl) -3-phenylpropionylamino-propionate (6d) Corresponding to Example 3d, 1.53 g of (6c) were treated with tin (II) chloride. A yellowish solid was obtained (yield: 1.1 g).

XH-NMR (400 MHz, CDC13); 1.16 (t, 3H), 2.57 (t, 2H), 2. 68 (dd, ÍH), 2.71 (dd, 2H), 2.98 (t, 2H), 4.02 (s, 2H), 4.04 (q, 2H), 5.30 (m, ÍH), 6.33 (s, ÍH), 6.61 (d, ÍH), 6.73 (d, ÍH), 6.83 (d, ÍH), 6.90 (m, 2H), 6.97 (s, ÍH), 7.08-7.29 (m, 8H). 3- (3- [3-N, N'-bis (t-butoxycarbonyl) guanidino-benzenesulphonylamino] -phenyl) -3-phenylpropionylamino-propionate ethyl (6e): Corresponding to Example 3e, 500 mg of (6d) were treated with mercuric chloride and l, 3-bis (tert-butoxycarbonyl) -2-methyl-2-thiopseudourea. 1.16 g of the desired product were obtained.

Mass spectrometry: 738 (MH +).

Ethyl 3- (3- [3- guanidino-benzenesulfonyl amino] -phenyl) -3-phenylpropionylamino-propionate (6f): Corresponding to Example 4f, 1.16 g of (6e) were treated with trifluoroacetic acid. An oil was obtained (yield: 410 mg).

Mass spectrometry: 538 (MH +) 3- (3- [3-Guanidol non-benzene sulphonylamino] -phenyl) -3-phenylpropionylamino-propionic acid (6): Corresponding to Example 4, 410 mg of (6f) was hydrolysed using lithium hydroxide. A white solid was obtained (yield: 221 mg).

Mass spectrometry: 510 (MH +).

XH-NMR (400 MHz, D4-MeOH); 2.49 (t, 2H), 2.61 (m, 2H), 2.89 (t, 2H), 5.15 (dd, ÍH), 6.83 (t, ÍH), 6.98 (d, ÍH), 7.10 (t, ÍH), 7.15 -7.24 (m, 5H), 7.28 (s, ÍH), 7.37 (s, ÍH), 7.47 (d, ÍH), 7.55 (t, ÍH), 7.72 (d, ÍH).

Example 7 Ethyl 3- (3-N-trophenyl) -3- (2-phenyl-butylamino) -propionate (la): Corresponding to Example 3a, 5.0 g of (lb) were added to the acetylation with the addition of 2-phenylbutyryl. A white solid was obtained (yield: 6.3 g).

^ -R N (400 MHz, CDC13); 0.89 (t, 3H), 1.11 (m, 3H), 1.82 (m, HH), 2.18 (m, HH), 2.80 (m, 2H), 3.33 (t, HH), 3.99, and 4.02 (q, 2H) , 5.43 (m, HH), 6.78 (m, HH), 7.26-8.13 (m, 9H) (mixture of diastereomers). 3- (3-Amino phenyl) -3- (2-phenylbutyl-ylamino) -propionate ethyl (Ib): Corresponding to Example 3b, 6.3 g of (7a) were reduced using tin dichloride (II). A white solid was obtained (yield: 3.9 g).

XH-NMR (400 MHz, CDC13); 0.88 (m, 3H), 1.09 and 1.15 (t, 3H), 1.80 (m, ÍH), 2.19 (m, ÍH), 2.61-2.85 (m, 2H), 3.27 (m, ÍH), 3.95 and 4.03 ( q, 2H), 5.28 (m, ÍH), 6.41-6.59 (m, 3H), 6.97 and 7.07 (t, 1H), 7.25-7.37 (mixture of diastereomers).

Ethyl 3- (3- [3-Nitrofenyl-sulfonylamino] -phenyl) -3- (2-phenylbutyrylamino) -propionate (7c): Corresponding to Example 3c, 3.9 g of (7b) was reacted with 3-nitrophenylsulfonyl chloride. A solid was obtained (yield: 5.0 g).

XH-NMR (400 MHz, CDC13): 0.86 and 0.89 (t, 3H), 1.06 and 1.10 (t, 3H), 1.82 (m, ÍH), 2.16 (m, ÍH), 2.66 and 2.73 (m, 2H) , 3.33 and 3.34 (t, ÍH), 3.93 (m, 2H), 5.24 (m, ÍH), 6.43-8.60 (m, 15H) (mixture of diastereomers).

Ethyl 3- (3- [3-aminophenylsulfonylamino] -phenyl) -3- (2-phenylbutyrylamino) -propionate (Id): Corresponding to Example 3d, 5 g of (7c) were treated with tin (II) chloride. A yellowish solid was obtained (yield: 1.8 g).

Mass spectrometry: 510 (MH +). 3- (3- [3-, N'-bis (t-butoxycarbonyl) guanidino-ben-cen-sulphonyl amino] -phenyl) -3- (2-phenyl-butylamino) -propionate (ethyl): Corresponding to Example 3e ,. 700 mg of (7d) were treated with mercuric chloride and l, 3-bis (t-butoxycarbonyl) -2-methyl-2-thiopseudourea. 1.45 g of the desired product were obtained.

Mass spectrometry: 752 (MH +). Ethyl 3- (3- [3-guanidino-benzenesulfonylamino] -phenyl) -3- (2-phenylbutyrylamino) -propionate (lf): Corresponding to Example 4f, 1.45 g of (7c) were treated with trifluoroacetic acid. An oil was obtained (yield: 630 mg).

Mass spectrometry: 552 (MH +). 3- (3- 13 -guanidino-benzene sulphonylamino] -phenyl) -3- (2-phenylbutyrylamino) -propionic acid (1): Corresponding to Example 4, 630 mg of (7f) were hydrolysed using lithium hydroxide. A white solid was obtained (yield: 320 mg).

Mass spectrometry: 524 (MH +) XH-NMR (400 MHz, D4-MeOH): 0.82 and 0.91 (t, 3H), 1.70-2.15 (m, 2H), 2.67 (m, 2H), 3.42 (t, ÍH), 5.15 (m, ÍH) , 6.75-7.73 (m, 13H) (mixture of diastereomers).

Example 8 Scheme of general synthesis: (8) (8) a) 2-propanol, reflux; b) HCl, ethanol; c) PhS02Cl, Et3N; d) BBr3; e) NaH, 3-N02-C6H4CH2Br; f) SnCl 2, ethanol; g) HgCl2, 1, 3-bis (tert-butyloxycarbonyl) -2-met il-2-thiopseudourea; h) TFA, dichloromethane, i) LiOH. 3-Amino-3- (3-methoxy phenyl) -propionic acid (8a): Corresponding to Example la, 200 g of 3-methoxybenzaldehyde were reacted with ammonium acetate and malonic acid. A white solid was obtained (yield: 135.5 g).

XH-NMR (400 MHz, Di-trifluoroacetic acid): 3.31 (dd, ÍH), 3.54 (dd, ÍH), 4.03 (s, 3H), 5.00 (m, ÍH), 7.19 (m, '3H), 7.52 (t, ÍH).

Ethyl 3-amino-3- (3-methoxy phenyl) -propionate hydrochloride (8b): Corresponding to Example lb, 60 g of (8a) were treated with hydrochloric acid in ethanol. A crystalline, white product was obtained (yield: 75 g).

^ -RN (400 MHz, D4-MeOH): 1.17 (t, 3H), 3.01 (dd, ÍH), 3.14 (dd, ÍH), 3.82 (s, 3H), 4.14 (m, 2H), 4.70 (m , ÍH), 6.98 (d, ÍH), 7.06 (m, 2H), 7.37 (t, ÍH). 3-Benzenesulfonylamino-3- (3-methoxy phenyl) -propionate ethyl (8c): Corresponding to Example 1, 10 g of (8b) were treated with phenylsulfonyl chloride and triethylamine. A yellowish solid was obtained (yield: 13.2 g).

XH-NMR (400 MHz, CDC13): 1.15 (t, 3H), 2.78 (m, 2H), 3. 68 (s, 3H), 4.02 (q, 2H), 4.75 (q, ÍH), 5.75 (d, ÍH), 6. 60 (s, ÍH), 6.69 (m, 2H), 7.08 (t, ÍH), 7.38 (m, 2H), 7.47 (t, ÍH), 7.71 (d, 2H). 3-Bencensul foni lamino-3- (3-hydroxy feni l) -propi ona to me ti l o (8d): A solution of BBr3 in dichloromethane (IM) was added at -78 ° C to a solution of 2.0 g of (8c) in 50 ml of dichloromethane. After stirring at room temperature for 3 hours, the solution was cooled to -78 ° C and then 100 ml of methanol was added. The mixture was stirred at room temperature overnight and then concentrated.

Chromatographic purification (dichloromethane / methanol = 40: 1) gave a white solid (yield 1.74 g).

XH-NMR (400 MHz, CDC13): 2.78 (m, 2H), 3.57 (s, 3H), 4.71 (m, HH), 5.11 (s, HH), 5.78 (d, HH), 6.60 (s, ÍH) ), 6.65 (m, 2H), 7.06 (t, ÍH), 7.40 (m, 2H), 7.50 (m, ÍH), 7.74 (d, 2H). 3 - . 3 - . 3 - . 3 -Ben census fon i l amino - [3 - (3-ni troben ci l oxy) -feni l] -propione to meti lo (8e): 1.5 g of (8d) in 30 ml of THF were added to a suspension of sodium hydride (0.2 g, 60% in paraffin oil) in 10 ml of THF. The reaction mixture was stirred at room temperature for 20 h. After the addition of 75 ml of a saturated solution of NH C1, the mixture was extracted using ethyl acetate. The combined organic phases were dried with MgSO 4, concentrated and purified by chromatography on silica gel (cyclohexane / ethyl acetate = 2: 1). 459 mg of the corresponding benzyl ether were obtained.

XH-NMR (400 MHz, CDC13): 2.79 (m, 2H), 3.57 (s, 3H), 4. 75 (m, ÍH), 5.03 (s, 2H), 5.78 (d, ÍH), 6.78 (m, 3H), 7. 16 (t, ÍH), 7.41 (m, 2H), 7.51 (m, ÍH), 7.58 (t, ÍH), 7.75 (m, 3H), 8.21 (d, ÍH), 8.29 (s, ÍH). [3- (3-Am i nobenzyl) -phenyl] -3-benzenesulphonyl-propionate methyl (8f): Corresponding to Example 3d, 442 mg of (8e) were treated with tin (II) chloride. A yellowish solid was obtained (yield: 387 mg).

XH-NMR (400 MHz, CDC13): 2.79 (m, 2H), 3.56 (s, 3H), 3.72 (br.s, 2H), 4.73 (m, ÍH), 4.83 (s, 2H), 5.69 (d , ÍH), 6.67 (m, 3H), 6.74 (m, 3H), 7.08 (t, ÍH), 7.17 (t, ÍH), 7.38 (m, 2H), 7.48 (m, ÍH), 7.71 (d, 2H). 3-Benzenesulfonyl amino-3- (3- [3-N, N'-bis (t-bu toxicarbonyl) guanidino-benzyl-oxy] -phenyl) -propionate of methyl (8g): Corresponding to Example 3e, 382 mg of (8f) were treated with mercuric chloride and l, 3-bis (tert-butoxycarbonyl) -2-methyl-2-thiopseudourea. 563 mg of the desired product were obtained.

Mass spectrometry: 683 (MH +) 3-Benzene sulfonyl amino -3- (3- [3-guanidinyl-benzyl lox i] -phenyl) -propionate methyl (8h): Corresponding to Example 4f, 536 mg of (8g) were treated with trifluoroacetic acid. An oil was obtained (yield: 471 mg).

Mass spectrometry: 483 (MH +). 3-Benzenesulfonylamino-3- [3- (3-guanidino-benzyloxy) -phenyl] -propionic acid (8): Corresponding to Example 4g, 471 mg of (8h) were hydrolysed using lithium hydroxide. A white solid was obtained (yield: 253 mg).

XH-NMR (400 MHz, D4-MeOH): 2.57 (m, 2H), 4.66 (m, ÍH), . 05 (s, 2H), 6.67 (d, ÍH), 6.76 (d, ÍH), 6.84 (s, ÍH), 7. 00 (t, ÍH), 7.19 (d, ÍH), 7.28 (s, ÍH), 7.35-7.49 (m, 5H), 7.67 (d, 2H).

Example 9 Scheme of general synthesis: (9b) (9C) (9) a) thiophosgene; b) ethanol, reflux; c) 1,2-diaminoethane, toluene, reflux; d) LiOH. 3-Benzenesulfonylamino-3- (3- [3-isothiocyanato-phenylsul-phinylamino] -phenyl) -propionate-ethyl ester (9a): A solution of 935 mg of NaHCO 3 in 20 ml of water was added to a solution of 800 mg of (lf) in 20 ml of ethyl acetate. Then the solution was treated with 207 mg of thiophosgene and stirred for 1 h. After separation of the two phases, the organic phase was washed with water, dried with MgSO 4 and concentrated. After chromatographic purification (dichloromethane / methanol = 40: 1), the product (9a) was obtained (yield: 636 mg).

* H-NMR (400 MHz, CDC13): 1.13 (s, 3H), 2.62 (dd, ÍH), 2.69 (dd, ÍH), 3.99 (q, 2H), 4.66 (m, ÍH), 5.91 (d, ÍH), '6.74 (s, ÍH), 6.90-6.97 (m, 3H), 7.11 (t, ÍH), 7.36-7.55 (m, 5H), 7.62 (m, 2H), 7.72 (d, 2H). 3-Benzene sulphonyl amino -3- (3 - [3-ethoxy ti oca rboni l aminof in the phylum-amino] -pheni) -propi ona to e ti l o (9b): 200 mg of compound (9a) was heated overnight in 5 ml of ethanol. The reaction mixture was concentrated. The product was obtained in a yield of 215 mg.

: H-NMR (400 MHz, CDC13): 1.13 (s, 3H), 1.35 (m, 3H), 2. 64 (dd, ÍH), 2.75 (dd, ÍH), 4.02 (m, 2H), 4.55 (m, 2H), 4.64 (m, ÍH), 5.89 (d, ÍH), 6.74 (s, ÍH), 6.82 (d, ÍH), 6.90 (d, ÍH), 7.08 (t, ÍH), 7.17 (s, ÍH), 7.39-7.47 (m, 3H), 7.48-7.65 (m, 3H), 7.73 (d, 2H ), 8.80 (s, ÍH). 3 - . 3 -Ben cen sulfonyl ami no -3-. { Ethyl 3- (4, 5-dihydro-1H-imide zol-2-yl-amino) -phenylsulfonylamino] -phenyl)) -propionate (9c): 215 mg of compound (9b) and 33 mg of 1,2-diaminomethane were heated overnight in a mixture of 5 ml of toluene and 1 ml of DMF. The reaction mixture was concentrated, and, after chromatographic purification (dichloromethane / methanol = 1: 1), compound (9c) was obtained in a yield of 66 mg.

Mass spectrometry: 572 (MH +).

XH-NMR (400 MHz, CDC13): 1.11 (s, 3H), 2.59 (dd, 1H), 2.66 (dd, 1H), 3.55 (s, 4H), 3.95 (m, 2H), 4.63 (m, 1H) ), 6.70 (d, ÍH), 6.83 (d, ÍH), 6.90-6.97 (m, 2H), 7.23 (d, ÍH), 7.29 (m, 2H), 7.39-7.49 (m, 4H), 7.54 ( d, 2H). 3-Benzenesulfonylamino-3- acid. { 3- [3- (4, 5-dihydro-1H-imide zol-2-ylamino) -phenyl-sulphonyl] -phenyl} -propionic (9): Corresponding to Example 4g, 6 mg of (9c) was hydrolysed using lithium hydroxide. A white solid was obtained (yield: 47 mg).

Mass spectrometry: 544 (MH +) : H-NMR (400 MHz, D4-MeOH): 2.52 (dd, ÍH), 2.61 (dd, ÍH), 3.71 (s, 4H), 4.63 (dd, ÍH), 6.68 (d, ÍH), 6.78- 6.96 (m, 2H), 7.17 (s, ÍH), 7.37-7.55 (m, 6H), 7.66 (m, 3H).

Examples 10-47 Scheme of Synthesis Generated (101) (1 (M7> a) C3H5C0C1, iPr2EtN; b) SnCl2, Ethanol; c) 3-N02-C6H4CS02C1; d) SnCl 2, ethanol; e) HgCl2, 1,3-bis (tert-butyloxycarbonyl) -2-methyl-2-thiopseudourea; f) Pd (PPh3) 4, Bu3SnH; g) acid chloride, pyridine; trifluoroacetic acid; lithium hydroxide. 3- (Allyloxycarbonylamino) -3- (3-nitro phenyl) -propionate ethyl (10a): At 41.2 g of (lb) in 350 ml of dichloromethane, 48.8 g of diisopropylethylamine and 24.8 g of allyloxycarbonyl chloride were added in 150 ml of dichloromethane at 0 ° C. After stirring for 30 min, the mixture was washed with water, dried with MgSO 4 and concentrated to give a white solid (yield: 56.4 g).

XH-NMR (400 MHz, CDC13): 1.18 (t, 3H), 2.90 (d, 2H), 4. 11 (q, 2H), 4.58 (m, 2H), 5.15-5.40 (m, 3H), 5.90 (m, ÍH), 6.05 (m, ÍH), 7.55 (t, ÍH), 7.70 (d, ÍH), 8.12 (d, ÍH), 8.19 (s, ÍH). 3- (Allyloxycarbonylamino) -3- (3-aminophenyl) -propionate ethyl (10b): 64.6 g of tin (II) chloride were added to a solution of 18.8 g of (10a) in 245 ml of ethanol, and the mixture was heated to reflux for 2 h. The reaction mixture was hydrolyzed with 300 ml of 2N NaOH solution, then filtered through silica gel and washed with dichloromethane. The organic phase was dried with MgSO 4 and concentrated to yield 13.1 g of a white solid.

XH-NMR (400 MHz, CDC13): 1.19 (t, 3H), 2.80 (m, 2H), 4. 06 (q, 2H), 4.57 (m, 2H), 5.07 (m, ÍH), 5.20 (d, ÍH), . 29 (d, ÍH), 5.70 (m, ÍH), 5.89 (m, ÍH), 6.57 (d, ÍH), 6.62 (s, ÍH), 6.68 (d, ÍH), 7.11 (t, ÍH). 3- (Allyloxycarbonylamino) -3- (3- [3-nitro-phenylsul-phinylamino] -phenyl) -propionic acid ethyl ester (10c): 3-Nitrophenylsulfonyl chloride at 0 ° C was added to a solution of 11.6 g of (10b) in 110 ml of pyridine. After a reaction time of 2 h, the mixture was concentrated, treated with IN HCl and extracted with dichloromethane. After drying with MgSO 4, the solvent was removed and the crude product was purified by chromatography on silica gel (dichloromethane / methanol = 40: 1) to give 17.8 g of a solid. 3- (Allyloxycarbonylamino) -3- (3- [3-amino-phenylsulfonyl-amino] -phenyl) -propione-ethyl ester (lOd): 43.5 g of tin (II) chloride were added to a solution of 17.8 g of (10c) in 165 ml of ethanol, and the mixture was heated to reflux for 2 h. The reaction mixture was hydrolyzed with 200 ml of 2N NaOH solution, then filtered through silica gel and washed with dichloromethane. The organic phase was dried with MgSO 4 and concentrated to yield 9.2 g of a solid.

XH-NMR (400 MHz, CDC13): 1.18 (t, 3H), 2.80 (m, 2H), 3.95 (br.s, 2H), 4.08 (q, 2H), 4.54 (m, 2H), 5.08 (m , ÍH), 5.22 (d, ÍH), 5.30 (d, ÍH), 5.78 (m, ÍH), 5.90 (m, ÍH), 6.58 (s, ÍH), 6.75 (d, ÍH), 6.88 (d, ÍH), 6.95 (s, ÍH), 7.05 (d, ÍH), 7.11 (d, ÍH), 7.15-7.22 (m, 3H). 3- (Allyloxycarbonylamino) -3- (3- [3-N, N'-bis (t-butoxycarbonyl) -guanidinobenzenesulphonylamino] -phenyl) -propionate ethyl (lOe): 4.8 g of triethylamine, 8.2 g of 1,3-bis (t-butoxycarbonyl) -2-methyl-2-thiopseudourea and 7.7 g of mercuric chloride at 0 ° C were added to a solution of 10.6 g of (lOd) in 329 ml of DMF. The reaction mixture was stirred at 0 ° C for 30 min and at room temperature for 2 h. After treatment with ethyl acetate, the precipitate was removed by filtration and the solution was concentrated. Purification was carried out by chromatography on silica gel (dichloromethane / methanol = 40: 1) to yield 7.5 g.

XH-NMR (400 MHz, CDC13): 1.16 (t, 3H), 1.52 (s, 9H), 1. 56 (s, 9H), 2.77 (m, 2H), 4.05 (q, 2H), 4.53 (m, 2H)) . 05 (m, ÍH), 5.21 (d, ÍH), 5.30 (d, ÍH), 5.72 (m, ÍH), . 90 (m, ÍH), 6.82 (m, ÍH), 7.05 (m, 3H), 7.19 (d, ÍH), 7. 35 (m, 2H), 7.80 (d, ÍH), 8.12 (s, ÍH), 10.25 (s, ÍH), 11.82 (s, ÍH). 3 - . 3 -Amino-3- (3 - [3-N, N '-bi s (t -bu toxi carboni l) -guanidinoben censul foni lamino-feni l) -propi ona to e ti lo (1 0 f): To a solution of (lOe) in 140 ml of dichloromethane was added 1.5 g of acetic acid, 100 mg of tetracis- (triphenylphosphine) -palladium and 3.3 g of tributyl tin hydride. After stirring for 2.5 h at room temperature, the same amount of tetracis- (triphenyl-phosphin) -palladium and tributyltin hydride was added and the reaction mixture was stirred for 2 d. The mixture was washed with a solution of NaHCO 3, dried with MgSO 4 and concentrated. Purification by chromatography on silica gel yielded 3.0 g.

H-NMR (400 MHz, CDC13): 1.20 (t, 3H), 1.50 (s, 9H), 1. 55 (s, 9H), 2.55 (m, 2H), 4.11 (q, 2H), 4.32 (t, ÍH), 7. 05 (d, ÍH), 7.11 (m, 2H), 7.19 (d, ÍH), 7.36 (t, ÍH), 7. 42 (d, ÍH), 7.89 (d, ÍH), 8.02 (s, ÍH), 10.25 (s, ÍH), 11.80 (s, ÍH). 3- (4-chlorofenyl sulfonylamino) -3- (3- [3-guanidinobenzenesulphonylamino] -phenyl] -propionic acid (10): To a solution of 200 mg of (lOf) in 1 ml of pyridine, 86 mg of 4-chlorophenylsulfonyl chloride was added at 0 ° C. The mixture was stirred for 4 h and evaporated. The crude material was treated with IN HCl and extracted with dichloromethane and the solution was dried with MgSO 4 and then concentrated. The crude product was treated with 2 ml of dichloromethane and 2 ml of trifluoroacetic acid. After stirring for 2 h at room temperature, the mixture was concentrated. The crude product was dissolved in 10 ml of THF and 10 ml of water and 190 mg of lithium hydroxide were added. The mixture was stirred for 4 h at room temperature and then evaporated. Purification by chromatography on silica gel (dichloromethane / methanol 2: 1) and RP-HPLC yielded a pure white solid.

^ -RMN (400 MHz, CD3OD): 2.58 (dd, ÍH), 2.67 (dd, ÍH), 4. 65 (dd, ÍH), 6.67 (d, ÍH), 6.86 (d, ÍH), 6.93 (t, ÍH), 7. 11 (s, ÍH), 7.34 (m, 3H), 7.45 (d, ÍH), 7.52 (d, ÍH), 7.58 (m, 2H), 7.69 (d, ÍH). 3- (3,4-Dichlorophenylcarbonyl amino) -3- (3- [3-gua n-id-notbenze-sulphonylamino] -phenyl) -propionic acid (11): Corresponding to Example 10; XH-NMR (400 MHz, CD3OD): 2.78 (m, 2H), 5.34 (t, ÍH), 6. 88 (m, ÍH), 7.15 (m, 2H), 7.32 (s, 1H), 7.41 (s, ÍH), 7. 45 (d, ÍH), 7.52 (t, ÍH), 7.63 (d, ÍH), 7.70 (d, ÍH), 7.74 (d, ÍH), 7.99 (s, ÍH). 3- (I-Butyloxycarbonylamino) -3- (3- [3-guanidinobenzenesulphonylamino] -phenyl) -propionic acid (12): Corresponding to Example 10; Mass spectrometry: 478 (MH +). 3- (1-naphthylsulfonylamino) -3- (3- [3-guanidinobenzenesulphonylamino] -phenyl) -propionic acid (13): Corresponding to Example 10: Mass spectrometry: 568 (MH +) 3- (4-tert-Butylphenylsulphonylamino) -3- (3- [3-guanidinobenzenesulphonylamino] -phenyl) -propionic acid (14): Corresponding to Example 10: Mass spectrometry: 574 (MH +). 3- (4-Fluorophenylsulfonyl amino) -3- (3- [3-guanidinobenzenesulphonylamino] -phenyl) -propionic acid (15): Corresponding to Example 10: Mass spectrometry: 536 (MH +). 3- (3,5-bis-trifluoromethylphenylsulphonylamino) -3- (3- [3-guanidin-nobenzene-sulphonylamino] -phenyl) -propionic acid (16) Corresponding to Example 10 Mass spectrometry: 554 (MH +) 3- (2, 3,, 5, 6 -pen tamet-il-phenylsulfonyl-amino) -3- (3- [3-guanidinobenzenesulphonylamino] -phenyl) -propionic acid (11), Corresponding to Example 10 Mass spectrometry: 558 (MH +). 3- (4-Methoxy-phenylsul-phinylamino) -3- (3- [3-guanidinobenzenesulphonylamino] -phenyl) -propionic acid (18): Corresponding to Example 10 Mass spectrometry: 548 (MH +). . 3- (3,4-dichlorof in ilsulf onyl amino) -3- (3- [3-guanidinobenzenesulfonyl amino] -phenyl) -propionic acid (19): Corresponding to Example 10: Mass spectrometry: 586/588 (MH +). 3- (4-Trifluoromethylphenylsulphonylamino) -3- (3- [3-guanidinobenzenesulphonylamino] -phenyl) -propionic acid (20): Corresponding to Example 10: Mass spectrometry: 586 (MH +). 3- (4-Trifluoromethoxy phenylsulphonylamino) -3- (3- [3-guanidinobenzenesulphonylamino] -phenyl) -propionic acid (21): Corresponding to Example 10: Mass spectrometry: 602 (MH +). 3- (3,5-dichloro-enylsulfonylamine) -3- (3- [3-guanidinobenzenesulphonylamino] -phenyl) -propionic acid (22): Corresponding to Example 10: Mass spectrometry: 586/588 (MH +] 3- (4- (1-propyl) -phenylsulfonyl amino) -3- (3- [3-guanidinobenzenesulphonylamino] -phenyl) -propionic acid (23): Corresponding to Example 10: Mass spectrometry: 560 (MH +). 3- (2-Thienylsulphonylamino) -3- (3- [3-guanidinobenzenesulphonylamino] -phenyl) -propionic acid (24): Corresponding to Example 10: Mass spectrometry: 524 (MH +). 3- (Phenylethenylsulfonyl amino) -3- (3- [3-guanidinobenzenesulphonylamino] -phenyl) -propionic acid (25): Corresponding to Example 10: Mass spectrometry: 544 (MH +) 3- (Benzylsulphonylamino) -3- (3- [3-guanidinobenzenesulphonylamino] -phenyl) -propionic acid (26): Corresponding to Example 10 Mass spectrometry: 532 (MH + 3- (2,6-dichlorobenzylsulphonylamino) -3- (3- [3- guanidinobenzenesulphonylamino] -phenyl) -propionic acid (21): Corresponding to Example 10: Mass spectrometry: 600/602 (MH +). 3- (4-Chlorobenzylsulphonylamino) -3- (3- [3-guanidinobenzenesulphonylamino] -phenyl) propionic acid (28): Corresponding to Example 10: Mass spectrometry: 566 (MH +) 3- (2-Thienylcarbonylamino) -3- (3- [3-guanidinobenzenesulphonylamino] -phenyl) -propionic acid (29): Corresponding to Example 10: Mass spectrometry: 488 (MH +). 3- (4-Methoxyphenylcarbonylamino) -3- (3- [3-guanidinobenzenesulphonylamino] -phenyl) -propionic acid (30): Corresponding to Example 10: Mass spectrometry: 512 (MH +) 3- (Ethyloxycarbonylamino) -3- (3- [3-guanidinobenzenesulphonylamino] -phenyl) -propionic acid (31): Corresponding to Example 10 Mass spectrometry: 450 (MH +). 3- (2,4,6-Trimethylphenylcarbonylkylamino) -3- (3- [3-guanidinobenzenesulphonylamino] -phenyl) -propionic acid (32): Corresponding to Example 10: Mass spectrometry: 524 (MH +). 3- (4- Fluorophen-Ie-rbon-lamino) -3- (3- [3-guanidinobenzenesulphonylamino] -phenyl) -propionic acid (33): Corresponding to Example 10: Mass spectrometry: 500 (MH +). 3- (Cyclopropylcarbonylamino) -3- (3- [3-guanidinobenzenesulphonylamino] -phenyl) -propionic acid (34): Corresponding to Example 10: Mass spectrometry: 446 (MH +). 3- (4-F-enylf-enylcarbonylamino) -3- (3- [3- guanidinobenzenesulphonylamino] -phenyl) -propionic acid (35): Corresponding to Example 10: Mass spectrometry: 558 (MH +). 3- (Adamantylcarbonylamino) -3- (3- [3-guanidinobenzenesulphonylamino] -phenyl) -propionic acid (36): Corresponding to Example 10: Mass spectrometry: 540 (MH +) 3- (4-Trifluoromethoxyphenylcarbonylamino) -3- (3- [3-guanidinobenzenesulphonylamino] -phenyl) -propionic acid (31): Corresponding to Example 10 Mass spectrometry: 566 (MH +) 3- (2, -dichloro-p-Icarbonyl-amino) -3- (3- [3- guanidinobenzenesulphonylamino] -phenyl) -propionic acid (38): Corresponding to Example 10: Mass spectrometry: 550/552 (MH +). 3- (3-Chlorofenylcarbonylamino) -3- (3- [3-guanidinoben-sulphonyl-amy] -phenyl) -propionic acid (39): Corresponding to Example 10: Mass spectrometry: 516 (MH +). 3- (2-Naphthylcarbonylamino) -3- (3- [3-guanidinobenzenesulphonylamino] -phenyl) -propionic acid (40): Corresponding to Example 10: Mass spectrometry: 532 (MH +). 3- (4-Methyl f-enylcarbonylamino) -3- (3- [3-guanidinobenzenesulphonylamino] -phenyl) -propionic acid (41): Corresponding to Example 10: Mass spectrometry: 496 (MH +). 3- (3-Methyl f-enylcarbonylamino) -3- (3- [3-guanidinobenzenesulphonylamino] -phenyl) -propionic acid (42): Corresponding to Example 10: Mass spectrometry: 496 (MH +). 3- (4-trifluoromethyl-ethylcarbonylamino) -3- (3- [3-guanidinoben-sulphonyl-amino] -phenyl) -propionic acid (43): Corresponding to Example 10: Mass spectrometry: 550 (MH +). 3- (Cyclohexylcarbonylamino) -3- (3- [3-guanidinobenzenesulphonylamino] -phenyl) -propionic acid (44): Corresponding to Example 10: Mass spectrometry: 488 (MH +) 3- (Cyclopentylcarbonylamino) -3- (3- [3-guanidinobenzenesulphonylamino] -phenyl) -propionic acid (45): Corresponding to Example 10: Mass spectrometry: 474 (MH +). 3- (3-Methoxy-f-4-carbonylamino) -3- (3- [3- guanidinoben-sulphonyl-amino] -phenyl) -propionic acid (46): Corresponding to Example 10: Mass spectrometry: 512 (MH +).

Acid 3- (1 -prop i read rbon i lam ino) -3- (3- [3-guanidinobenzenesulphonylamino] -phenyl) -propionic acid (41): Corresponding to Example 10: Mass spectrometry: 464 (MH +).

Examples 48-58 In the following examples all retention times are indicated in minutes and were determined by high performance liquid chromatography (HPLC) on a RP column (Eurospher 100, C18, ID 4 mm) by means of UV absorption. An eluent mixture of 0.1% acetonitrile / water concentration was used with the following method: 0 min = 10% acetonitrile, 13 min = 80% acetonitrile, 15 min = 80% acetonitrile, 17 min = 10% acetonitrile.

Example 48 Acid (3R, S) -3-benzyloxycarbonylamino-3-. { 3- [3- (3-propyl-ureido) -phenylsulfonyl amino] -pheni I} -propioni co 1. 2 g of Wang polystyrene resin (Rapp-Polymere, Tübingen, loading 1.08 mmol / g) were swollen in dimethylformamide (DMF). The solvent is filtered off with suction and a solution of 841 mg of (3R, S) -3- (9-flourenylmethoxycarbonylamino) -3- (3-nitrophenyl) -propionaurea in 15 ml of dimethylformamide (DMF) is added. After stirring at room temperature for 15 min the suspension is treated with 350 μl of pyridine and 540 mg of 2,6-dichlorobenzolyl chloride. It is stirred overnight at room temperature. The resin is then washed with dimethylformamide (DMF), methanol, dichloromethane. The resin is treated with 15 ml of a 20% piperidine solution in dimethylformamide (DMF). Then it is washed 3 times with dimethylformamide (DMF) and an additional solution of 15 ml of piperidine at 20% concentration in dimethylformamide (DMF). After stirring for 20 min, it is washed with dimethylformamide (DMF) and tetrahydrofuran (THF). The resin is treated with a solution of 450 μl of diisopropyl-ethylamine in 500 μl of tetrahydrofuran (THF) and a solution of 330 mg of benzyl chloroformate (acylation / sulfonation reagent) in 500 μl of tetrahydrofuran (THF). It is stirred overnight at room temperature. The resin is then washed with dimethylformamide (DMF), methanol, tetrahydrofuran (THF).

The resin is treated with a solution of 5400 mg of tin (II) chloride dihydrate in 12 ml of N-met ilpyrrolidone (NMP) and stirred overnight at room temperature. The resin is then washed with dimethylformamide (DMF), methanol, tetrahydrofuran (THF), dichloromethane.

The resin is treated with a solution of 450 μl of diisopropylethylamine in 500 μl of tetrahydrofuran (THF) and a solution of 430 mg of 3-nitrobenzenesulfonyl chloride in 500 μl of tetrahydrofuran (THF). It is stirred overnight at room temperature. The resin is then washed with dimethylformamide (DMF), methanol, tetrahydrofuran (THF). The resin is treated with a solution of 5400 mg of tin (II) chloride dihydrate in 12 ml of N-methylpyrrolidone (NMP) and stirred overnight at room temperature. The resin is then washed with dimethylformamide (DMF), methanol, tetrahydrofuran (THF), dichloromethane. The resin is treated with a solution of 500 μl of diisopropylethylamine in 12 ml of tetrahydrofuran / dichloromethane 1: 1 and a solution of 2757 mg of 4-nitrophenyl chloroformate in 12 ml of tetrahydrofuran / dichloromethane 1: 1. After 45 min of stirring at room temperature, the resin is washed with tetrahydrofuran (THF) and dimethylformamide (DMF) and a solution of 943 mg of propylamine (amine reagent) and 2780 μl of diisopropylethylamine in 20 ml of N is added. -methylpyrrolidone (NMP). After stirring for 10 h the resin is washed with dimethylformamide (DMF), methanol, tetrahydrofuran (THF), dichloromethane. For the removal of the product, the resin is stirred with tetrahydrofuran / dichloromethane 1: 1 for 1 h, filtered and the filtrate concentrated in vacuo and purified on silica gel. 148 mg of the title compound are obtained.

Mass spectrometry (ESI): 555. Retention time (HPLC): Rt = 8.1.

XH-NMR (400 MHz, methanol) d = 7.90 (s, 1H), 7.43 (d, 1H), 7.33-7.25 (m, 7H), 7.18 (s, 1H), 7.15 (d, 1H), 7.04 ( d, ÍH), 6.97 (d, ÍH), 5.04 (dd, ÍH, H-3), 5.03 (s, 2H), 3.12 (t, 2H), 2.72 (dd, ÍH, H-2a), 2.65 ( dd, ÍH, H-2b), 1.52 (tq, 2H), 0.93 (t, 3H). The following compounds can be prepared in analogy to example 48.

Example 49 Acid (3R, S) -3-iso-butyloxycarbonylamino-3-. { 3- [3- (3-propyl-ureido) -phenylsulfonyl-amino] -phenyl} -propionic Mass spectrometry (ESI): 521. Retention time (HPLC): Rt = 8.4 Example 50 Acid (3R, S) -3- (4-chlor-benzenesulfonamino) -3-. { 3- [3- (3-propyl-ureido) -phenylsul fonyl-amino] -phenyl} -propionic Mass spectrometry (ESI): 596. Retention time (HPLC): R = 8.6.

Example 51 Acid (3R, S) -3- (3,4-dichlorbenzenesulfonamino) -3-. { 3- [3- (3-propyl-ureido) -phenylsulfonyl-amino] -phenyl} -propionic Mass spectrometry (ESI): 594. Retention time (HPLC): Rt = 9.3 Example 52 Acid (3R, S) -3-benzyloxycarbonylamino-3-. { 3- [3- (3-pyridin-4-yl-ureido) -phenylsulfonyl-amino] -phenyl} -propionic Mass spectrometry (ESI): 590. Retention time (HPLC): Rt = 7.1 Example 53 Acid (3R, S) -3-benzyloxycarbonylamino-3-. { 3- [3- (3-pyridin-3-ylmethyl-ureido) -phenyl-sulfonylamino] -phenyl} -propionic Mass spectrometry (ESI): 604. Retention time (HPLC): Rt = 6.7 Example 54 Acid (3R, S) -3-benzyloxycarbonylamino-3-. { 3- [3- (3-pyridin-4-ylmethyl-ureido) -phenyl-sulfonylamino] -phenyl} -propionic Mass spectrometry (ESI): 604. Retention time (HPLC): Rt = 6.7 Example 55 (3R, S) -3- (3,4-Dichloro-benzenecarbonylamino-3. {3- [3- (3-pyridin-4-ylmethyl-ureido) -phenylsulphonylamino] -phenyl} -propionic acid Mass spectrometry (ESI): 643. Retention time (HPLC): Rt = 7.2 Example 56 Acid (3R, S) -3- (3,4-isobutyloxycarbonylamino) -3-. { 3- [3- (3-pyridin-4-ylmethyl-ureido) -phenylsulfonylamino] -phenyl} • propionic Mass spectrometry (ESI): 570. Retention time (HPLC): Rt = 7.2 Example 57 Acid (3R, S) -3- (4-chlorobenzenesulfonylamino) -3-. { 3- [3- (3-pyridin-4-ylmethyl-ureido) -phenylsulfonylamino] -phenyl} -propionic Mass spectrometry (ESI): 644. Retention time (HPLC): Rt = 6.6 Example 58 (3R, S) -3-benzyloxycarbonylamino-3- (3. {3- [3- (1H-benzoimidezol-2-yl) -ureido] -phenylsulfonylamino] -phenyl) -propiomatic acid Mass spectrometry (ESI): 629. Retention time (HPLC): Rt = 10 Biological investigations avß3 of human A375 cells was purified analogously to a procedure that was described by Wong et al. (Molecular Pharmacology, 50, 529-537 (nineteen ninety six)). 10 μl of avß3 (5 ng) in TBS pH 7.6, 2 mM CaCl2, 1 mM MgCl 2, 1% n-octyl glucopyranoside (Sigma); 10 μl of TBS pH 7.6, 2 mM CaCl 2, 1 mM MgCl 2, 1 mM MnCl 2 were incubated in each case at room temperature for 1 h. Accounts of 25 μl of WGA SPA (Amersham, 4 mg / ml) and 10 μl of echistatin (0.1 μCi, Amersham, chloramine T-brand) were then added in each case. After 16 hours at room temperature, the samples were measured in a scintillation measuring device (Wallac 1450).

The results of the test are shown in Table 1 below. Table 1 It is noted that in relation to this date, the best method known to the applicant to carry out the aforementioned invention, is that which is clear from the present description of the invention.

Claims (15)

CLAIMS Having described the invention as above, the content of the following claims is claimed as property.

1. The compounds of the general formula (1) characterized because R1 is hydrogen, a substituted or unsubstituted alkyl or cycloalkyl residue, a substituted or unsubstituted aryl residue or a saturated or unsaturated, optionally substituted heterocyclic residue; R2 is hydrogen, a substituted or unsubstituted alkyl or cycloalkyl residue, a substituted or unsubstituted aryl residue, an optionally substituted, saturated or unsaturated heterocyclic residue, an optionally substituted alkenyl residue, an optionally substituted alkynyl residue, a hydroxyl residue or an alkoxy residue or binds to R3 with the formation of an optionally substituted carbocyclic or heterocyclic ring system that includes the carbon atom to which R2 is linked and may optionally contain heteroatoms; R3 is hydrogen, a substituted or unsubstituted alkyl or cycloalkyl residue, a substituted or unsubstituted aryl residue, a saturated or unsaturated heterocyclic residue, optionally substituted, an optionally substituted alkenyl residue, an optionally substituted alkynyl residue, a hydroxyl residue or an alkoxy residue or R2 is linked to the formation of an optionally substituted carbocyclic or heterocyclic ring system that includes the carbon atom to which R3 is linked and may optionally contain heteroatoms; R4 is -S02R4 ', -COOR4", -COR4', -CONR4'2 or -CSNR4'2, R4 'is hydrogen, a substituted or unsubstituted alkyl, alkenyl or cycloalkyl residue, a substituted or unsubstituted aryl residue or a heterocyclic residue saturated or unsaturated, optionally substituted, is a substituted or unsubstituted alkyl or cycloalkyl residue, a substituted or unsubstituted aryl residue or a saturated or unsaturated heterocyclic residue, optionally substituted, R- is hydrogen, a substituted or unsubstituted alkyl or cycloalkyl residue or a residue substituted or unsubstituted aryl;,? or is hydrogen, a substituted or unsubstituted alkyl or cycloalkyl residue, a substituted or unsubstituted alkoxy residue or a halogen atom; R 11 is hydrogen, a substituted or unsubstituted alkyl or cycloalkyl residue, a substituted or unsubstituted alkoxy residue or a halogen atom; is - (CH2) mNHS02 (CH2) n-, - (CH2) mS02NH (CH2) n-, (CH2) mNHCO (CH2) n-, - (CH2) mCONH (CH2) n-, (CH2) mOCH2 (CH2) ) n-, - (CH2) mCH20 (CH2) n-, (CH2) mCOO (CH2) n-, - (CH2) mpOC (CH2) n-, (CH2) mCH2CO (CH2) n-, - (CH2) mCOCH2 (CH2) n-, -NHCONH-, - (CH2) mSCH2 (CH2) n-, - (CH2) mCH2S (CH2) n-. (CH2) mCH2SO (CH2) n-, - (CH2) mSOCH2 (CH2) n-, (CH2) mCH2S02 (CH2) n- or - (CH2) mS02CH2 (CH2) n-, where myns on each one an e ro of O olym + n = l; R6 is hydrogen, a substituted or unsubstituted alkyl or cycloalkyl residue, a substituted or unsubstituted aryl residue, a saturated or unsaturated heterocyclic residue, optionally substituted or linked to one of R7, R8 or R9, if present, with the formation of a optionally substituted heterocyclic ring system including the nitrogen atom to which R6 is bonded and may be saturated or unsaturated and / or may contain additional heteroatoms; X is N, O or S; R7 is absent, is -H, a substituted or unsubstituted alkyl or cycloalkyl residue, -N02-, -CN, -COR7 ', -COOR7', or is linked to one of R6, R8 or R9 with the formation of an optionally substituted heterocyclic ring system including X and may be saturated or unsaturated and / or may contain additional heteroatoms; R7 'is hydrogen, a substituted or unsubstituted alkyl or cycloalkyl residue, a substituted or unsubstituted aryl residue or a saturated or unsaturated heterocyclic residue, optionally substituted which may be saturated or unsaturated and / or may contain additional heteroatoms; R8 is hydrogen, a substituted or unsubstituted alkyl or cycloalkyl residue, a substituted or unsubstituted aryl residue, a saturated or unsaturated heterocyclic residue, optionally substituted or linked to one of R6, R7 or R9, if present, with the formation of a optionally substituted heterocyclic ring system including the nitrogen atom to which R8 is bonded and may be saturated or unsaturated and / or may contain additional heteroatoms; R9 is hydrogen, a substituted or unsubstituted alkyl or cycloalkyl residue, a substituted or unsubstituted aryl residue, a saturated or unsaturated heterocyclic residue, optionally substituted or linked to one of R6, R7 or R8, if present, with the formation of a optionally substituted heterocyclic ring system including the nitrogen atom to which R9 is linked and may be saturated or unsaturated and / or may contain additional heteroatoms; and their physiologically acceptable salts and stereoisomers.

2. The compounds according to claim 1, characterized in that R1 is hydrogen, a C? -C6 alkyl residue, a C3- cycloalkyl residue, an aryl residue or a substituted derivative thereof; R2 is hydrogen, a C? -6 alkyl residue, a C3- cycloalkyl residue, an aryl residue, an alkenyl residue, an alkynyl residue or a substituted derivative thereof; a hydroxyl residue or a C6_6 alkoxy residue or is linked to R3 with the formation of an optionally substituted carbocyclic or heterocyclic ring system including the carbon atom to which R2 is linked and may optionally contain heteroatoms; R3 is hydrogen, a C6_6 alkyl residue, a C3 cycloalkyl residue. , an aryl residue, an alkenyl residue, an alkynyl residue or a substituted derivative thereof; a hydroxyl residue or a C6-C6 alkoxy residue or is linked to R2 with the formation of an optionally substituted carbocyclic or heterocyclic ring system including the carbon atom to which R3 is linked and may optionally contain heteroatoms; R4 is -S02R4 ', -COOR4", -COR4', -CONR4'2 or -CSNR4'2; R4 'is hydrogen, a C? -6 alkyl residue, an optionally substituted C2_6 alkenyl residue, a C3_ cycloalkyl residue, a substituted or unsubstituted aryl residue or a saturated or unsaturated, optionally substituted heterocyclic residue; R4"is a C? -6 alkyl residue, a C3- cycloalkyl residue, a substituted or unsubstituted aryl residue or an optionally substituted saturated or unsaturated heterocyclic residue, R5 is hydrogen, a C? _6 alkyl residue, a C3- cycloalkyl residue 7, an aryl residue or a substituted derivative thereof, R10 is hydrogen, a C6_6 alkyl residue, a C3- cycloalkyl residue, a C6_6 alkoxy residue or a substituted derivative thereof or F, Cl, Br or I; R11 is hydrogen a C6_6 alkyl residue, a C3_7 cycloalkyl residue, a C6_6 alkoxy residue or a substituted derivative thereof or F, Cl, Br or I; L is -NHS02-, -CH2NHS02-, -NHS02CH2- , -S02NH-, CH2S02NH-, -S02NHCH2-, -NHCO-, -CH2NHC0-, -NHCOCH2-, -CONH-, -CH2CONH-, -CONHCH2-, -OCH2-, -CH2OCH2, - OCH2CH2-, -CH20- -CH2CH20-, -COO ?, -CH2COO-, -COOCH2-, -OOC-, -OOCCH2-, -CH2OOC-, -CH2CO-, -COCH2-, - CH2CH2CO-, -COCH2CH2-, -CH2COCH2-, -NHCONH -, -SCH2-, -CH2S-, -CH2SCH2, -SCH2CH2-, -CH2CH2S-, -SOCH2-, - CH2SO-, -CH2SOCH2-, -SOCH2CH2-, -CH2C H2SO-, -S02CH2-, -CH2S02-, -CH2S02CH2-, -CH2CH2S02- or -S02CH2CH2-; R6 is hydrogen, a C? -6 alkyl residue, a C3-7 cycloalkyl residue, an aryl residue or a substituted derivative thereof or is linked to one of R7, R8 or R9, if present, with the formation of a system of optionally substituted heterocyclic ring including the nitrogen atom to which R6 is linked and may be saturated or unsaturated and / or may contain additional heteroatoms; X is 0, N or S; R7 is absent, is -H, a C6_6 alkyl residue, a C3-7 cycloalkyl residue, -N02, -CN, -COR7'-, COOR7 ', or is linked to one of R6, R8 or R9 with the formation of an optionally substituted heterocyclic ring system including X and may be saturated or unsaturated and / or may contain additional heteroatoms; R7 'is hydrogen, a C? -6 alkyl residue, a C3_ cycloalkyl residue, an aryl residue or a substituted derivative thereof; R8 is hydrogen, a C? _6 alkyl residue, a C3- cycloalkyl residue, an aryl residue or a substituted derivative thereof or is linked to one of R6, R7 or R9, if present, with the formation of a ring system optionally substituted heterocyclic including the nitrogen atom to which R8 is linked and may be saturated or unsaturated and / or may contain additional heteroatoms; and R9 is hydrogen, an optionally substituted C6_6 alkyl residue, a C3_7 cycloalkyl residue, an aryl residue or a substituted derivative thereof, an unsaturated heterocyclic residue, optionally substituted or linked to one of R6, R7 or R8, if present, with the formation of an optionally substituted heterocyclic ring system including the nitrogen atom to which R9 is bonded and can be saturated or unsaturated and / or can contain additional heteroatoms.

3. The compounds according to claim 1, characterized in that: R1 is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, phenyl, benzyl, tolyl or a substituted derivative thereof; R2 is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, phenyl, benzyl, tolyl or a substituted derivative thereof, -OH, methoxy, ethoxy, propoxy, butoxy, pentoxy, hexoxy, benzyloxy or is linked to R3 with the formation of an optionally substituted carbocyclic or heterocyclic ring system of 3 to 6 members including the carbon atom to which R2 is bonded and may optionally contain heteroatoms; R is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, phenyl, benzyl, tolyl or a substituted derivative thereof, -OH, methoxy, ethoxy, propoxy, butoxy, pentoxy, hexoxy, or is linked to R2 with the formation of an optionally substituted 3 to 6 membered carbocyclic or heterocyclic ring system including the carbon atom to which R3 is bonded and can optionally contain heteroatoms; R4 is -S02R4 ', COOR4"or -COR4'; R4 'is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, phenyl, benzyl, tolyl or a substituted derivative thereof, -C6H2 (CH3) 3, -C6 (CH3) 5, -CH2C6H2 (CH3) 3, 4-phenylphenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl , 2,3-dichlorophenyl, 2,4-dichlorophenyl, 3,4-dichlorophenyl, 2,5-dichlorophenyl, 3,5-dichlorophenyl, 2,6-dichlorophenyl, 2-chlorophenylmethyl, 4-chlorophenylmethyl, 2,4-dichlorophenylmethyl , 2,6-dichlorophenylmethyl, 2-methoxycarbonylphenylmethyl, 3-trifluoromethylphenyl, 4-trifluoromethylphenyl, 3,5-bis (trifluoromethyl) phenyl, 4-trifluoromethoxyphenyl, phenylmethyl, 2-acetamido-4-methyl-thiazol-5-yl, phenylethyl , l-phenylpropyl, (S) - (+) - camphor-10-yl, (R) - (-) -canfor-10-yl, 2-phenylethenyl, 2-thiophenyl, 4-methoxyphenyl, 3,5-dimethoxyphenyl , 3-methylphenyl, 4-methylphenyl, 4-t-butylphenyl, 4-propylphenyl, 2 , 5-dimethylphenyl, 2-methoxy-5-methylphenyl, 2,3,5,6-tetramethylphenyl, 2, 3, 4, 5, 6-pentamethylphenyl, 1-naphthyl, 2-naphthyl, 4-fluorophenyl, 2,4 -difluorophenyl, 2-chloro-6-methylphenyl, 2-chloro-4-fluorophenyl, 2,5-dimethoxyphenyl, 3,4-dimethoxyphenyl, 3-chloro-6-methoxyphenyl, 2-trifluoromethylphenyl, 2-phenylsulfonylphenyl, 2- arylsulfonylphenyl, 3- (N-acetyl-6-methoxy) aniline, 4-acetamidophenyl, 2,2,2-trifluoroethyl, 5-chloro-3-methyl-benzothiazol-2-yl, N-methoxycarbonylpiperidin-3-yl, thiophen -2-yl, isoxazol-5-yl, 2-chloropyridin-3-yl, pyridin-3-yl, 5-methylisoxazol-3-yl, 1-adamantyl, 4-chlorophenoxymethyl, 2,2-dimethylethyl, 2-chloropyridin -5-methyl, 5,7-dimethyl-1, 3, 4-triazaindolizin-2-yl, (S) -canphan-1-yl, (R) -canphan-1-yl or 8-quinolinyl; is methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, phenyl, benzyl, or a substituted derivative thereof, -CH2C6H2 (CH3 ) 3, 2-chlorophenylmethyl, 4-chlorophenyl-methyl, 2,4-dichlorophenylmethyl, 2,6-dichlorophenylmethyl, 2-methoxycarbonylphenylmethyl, 3-trifluoromethylphenylmethyl, 4-trifluoromethylphenylmethyl, 3,5-bis (trifluoromethyl) phenylmethyl, 4-trifluoromethoxyphenyl , 2-thiophenylmethyl, 4-methoxyphenylmethyl, 3,5-dimethoxyphenylmethyl, 3-methylphenylmethyl, 4-methyl-phenylmethyl, 4-t-butylphenylmethyl, 4-propylphenylmethyl, 2,5-dimethylphenylmethyl, 2-methoxy-5-methylphenylmethyl, 2 , 3,5,6-tetramethylphenylmethyl, 2,3,4,5,6-pentamethylphenylmethyl, 1-naphthylmethyl, 2-naphthylmethyl, 4-fluorophenylmethyl, 2,4-difluorophenylmethyl, 2-chloro-6-methylphenylmethyl, 2-chloro -4-fluoro-phenylmethyl, 2,5-dimethoxyphenylmethyl, 3,4-dimethoxyphenylmethyl, 3-chloro-6-methoxyphenylmethyl, 2-trifluoromethylphenyl methyl, 2,2,2-trifluoroethyl, isoxazol-5-ylmethyl, 2-chloropyridin-3-yl-methyl, pyridin-3-yl-methyl, 2-chloropyridin-5-methyl; is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclopropylmethyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, 4-methylcyclohexyl, 3, 3, 5- trimethylcyclohexyl, 5-methy1-2-hexyl, phenyl, benzyl, tolyl or a substituted derivative thereof, C4-4 alkylaminoC1-4alkyl dialkylaminoC4-4C1-4alkyl, aminoC1-4alkyl, alkyloxyC ? -4-alkyl C? _4 or (a6) (a7) (aß) (a9) (a10) (a11) (a12) (a13) (a14) (a15) (a! 6) (al7) íal 8) (a 19) (a20) (a21) (a22) (a23) Ía24) (a25) (a26) (a27) (a28) R10 is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, methoxy, ethoxy, propoxy, butoxy, pentoxy or hexoxy, fluorine, chlorine, bromine or iodine; R11 is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, methoxy, ethoxy, propoxy, butoxy, pentoxy or hexoxy, fluorine, chlorine, bromine or iodine; L is -NHS02-, -CH2NHS02-, -NHS02CH2-, -S02NH-, CH2S02NH-, -S02NHCH2-, -NHCO-, -CH2NHCO-, -NHCOCH2-, -CONH-, -CH2CONH-, -CONHCH2-, - OCH2-, -CH2OCH2, -OCH2CH2-, -CH20- or -CH2CH20-; R6 is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclopropylmethyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, 4-methylcyclohexyl, 3,3,5-trimethylcyclohexyl, 5-methyl-2-hexyl, phenyl, benzyl, tolyl or a substituted derivative thereof, C 4 -C 4 alkylamino C 4 alkyl, dialkylamino C 4 -C 4 C 4 alkyl, amino -alkyl C? _4, alkyloxy Cj.-4-alkyl C? _4, one of the residues (al) a (a28) or binds to one of R7, R8 or R9, if present, with the formation of a system of optionally substituted heterocyclic 4- to 6-membered ring including the nitrogen atom to which R6 is bonded and may be saturated or unsaturated and / or may contain additional heteroatoms; X is N, 0 or S; R7 is absent, is -H, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, -N02, -CN, -COR7 ', -COOR7' or is linked to one of R6, R8 or R9 with the formation of an optionally substituted heterocyclic or carbocyclic 4- to 6-membered ring system including X and may be saturated or unsaturated and / or may contain additional heteroatoms; R7 'is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, phenyl, benzyl, tolyl or a substituted derivative thereof; R8 is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclopropylmethyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, 4-methylocyclohexyl, 3.3, 5 trimethylcyanohexyl, 5-methyl-2-hexyl, phenyl, benzyl, tolyl or a substituted derivative thereof, C 1 -C 4 alkylamino C 4 alkyl, C 4 -4 dialkylamino C 4 alkyl, amino C 4 alkyl 4 , C alquilo -4 alkyloxy C C _4 alkyl, one of the residues (a) a (a28) or binds to one of R6, R7 or R9, if present, with the formation of a ring system of 4 to 6 optionally substituted heterocyclic members including the nitrogen atom to which R8 is bonded and may be saturated or unsaturated and / or may contain additional heteroatoms; and is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclopropylmethyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, 4-methylcyclohexyl, 3, 3, 5- trimethylcyclohexyl, 5-methyl-2-hexyl, phenyl, benzyl, tolyl or a substituted derivative thereof, C 1-4 alkylamino C 1-4 alkyl, C 1-4 dialkylamino C 1-4 alkyl, C 1-4 amino-alkyl C4-4alkyloxyC4alkyl4, one of the residues (al) to (a28) or binds to one of R6, R7 or R8, if present, with the formation of a ring system of 4 to 6 optionally substituted heterocyclic members including the nitrogen atom to which R9 is bonded and may be saturated or unsaturated and / or may contain additional heteroatoms.

4. The compounds according to claim 3, characterized in that: R4 is -S02R4 '; R4 'is methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, phenyl, benzyl, tolyl or substituted derivative thereof, -C6H2 (CH 3) 3, -C 6 (CH 3) 5, -CH 2 C 6 H 2 (CH 3) 3, 4-phenyl-phenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2,3-dichlorophenyl, 2,4-dichlorophenyl, 3 , 4- dichlorophenyl, 2,5-dichlorophenyl, 3,5-dichlorophenyl, 2,6-dichlorophenyl, 2-chlorophenyl, 4-chlorophenylmethyl, 2,4-dichlorophenylmethyl, 2,6-dichlorophenylmethyl, 2-methoxycarbonylphenylmethyl, 3-trifluoromethylphenyl , 4-trifluoromethylphenyl, 3,5-bis (trifluoromethyl) phenyl, 4-trifluoromethoxyphenyl, phenylmethyl, 2-acetamido-4-methyl-thiazol-5-yl, phenylethyl, l-phenylpropyl, (S) - (+) -canfor -10-yl, (R) - (-) -canfor-10-yl, 2-phenylethenyl, 2-thiophenyl, 4-methoxyphenyl, 3,5-dimethoxyphenyl, 3-methylphenyl, 4-methylphenyl, 4-t-butylphenyl , 4-propylphenyl, 2,5-dimethylphenyl, 2-methoxy-5-methylphenyl, 2,3, 5,6-tetramethylphenyl, 2, 3, 4, 5, 6-pentamethylphenyl, 1-naphthyl, 2-naphthyl, 4-fluorophenyl, 2,4-difluorophenyl, 2-chloro-6-methylphenyl, 2-chloro-4 - fluorophenyl, 2,5-dimethoxyphenyl, 3,4-dimethoxyphenyl, 3-chloro-6-methoxy-phenyl, 2-trifluoromethylphenyl, 2-alkylsulfonylphenyl, 2-aryl-sulfonylphenyl, 3- (N-acetyl-6-methoxy) aniline, 4-acetamidophenyl, 2, 2, 2-trifluoroethyl, 5-chloro-3-methyl-benzothiazol-2-yl, N-methoxycarbonyl-1-piperidin-3-yl, thiophen-2-yl, isoxazol-5-yl, 2- chloropyridin-3-yl, pyridin-3-yl, 5-methylisoxazol-3-yl, 1-adamantyl, 4-chlorophenoxymethyl, 2,2-dimethylethenyl, 2-chloropyridin-5-methyl, 5,7-dimethyl- 1, 3, 4-triazaindolizin-2-yl, (S) -canphan-1-yl, (R) -canphan-1-yl or 8-quinolinyl; L is -NHS02-, -CH2NHS02-, -NHS02CH2-; is N or O; the other residues are as defined in claim 3.

The compounds according to claim 3, characterized in that:R4 is -COR4 '; R is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, phenyl, benzyl, tolyl or a substituted derivative thereof, -C6H2 (CH3) 3, -C6 (CH3) 5, -CH2C6H2 (CH3) 3, 4-phenyl phenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2,3-dichlorophenyl, 2,4-dichlorophenyl, 3,4-dichlorophenyl, 2,5-dichlorophenyl, 3,5-dichlorophenyl, 2,6-dichlorophenyl, 2-chlorophenylmethyl, 4-chlorophenylmethyl, 2,4-dichlorophenylmethyl, 2,6-dichlorophenylmethyl, 2- methoxycarbonylphenylmethyl, 3- trifluoromethylphenyl, 4-trifluoromethylphenyl, 3,5-bis (trifluoromethyl) phenyl, 4-trifluoromethoxyphenyl, phenylmethyl, 2 -acetamido-4-methyl-1-thiazo-5-yl, phenylethyl, l-phenylpropyl, (S) - (+) -canfor-10-yl, (R) - (-) -canfor-10-yl, 2-phenylethenyl, 2-thiophenyl, 4-methoxyphenyl, 3,5-dimethoxyphenyl, 3-methylphenyl, 4-methylphenyl, 4-t -butylphenyl, 4-propylphenyl, 2,5-dimethylphenyl, 2-methoxy-5-m ethylphenyl, 2,3,5,6-tetramethylphenyl, 2, 3, 4, 5, 6-pentamet-ilphenyl, 1-naphthyl, 2-naphthyl, 4-fluoro-phenyl, 2,4-difluorophenyl, 2-chloro-6-met ilphenyl, 2-chloro-4-fluorophenyl, 2,5-dimethoxyphenyl, 3,4-dimethoxyphenyl, 3-chloro-6-methoxyphenyl, 2-trifluoromethylphenyl, 2-phenylsulfonylphenyl, 2-arylsulfonylphenyl, 3- (N-acetyl) -6-methoxy) aniline, 4-acetamidophenyl, 2,2,2-trifluoroethyl, 5-chloro-3-methyl-benzothiazol-2-yl, N-methoxycarboni Ipiperidin-3-yl, thiophen-2-yl, isoxazole-5 -yl, 2- chloropyridin-3-yl, pyridin-3-yl, 5-methylisoxazol-3-yl, 1-adamantyl, 4-chlorophenoxymethyl, 2,2-dimethylethenyl, 2-chloropyridin-5-methyl, 5, 7- dimethyl-1, 3, 4-triazaindolizin-2-yl, (S) -canphan-1-yl, (R) -canphan-1-yl, or 8-quinolinyl; L is -NHS02-, -CH2NHS02- or NHS02CH2-; X is N or O; and the other residues are as defined in claim 1.

6. The compounds according to claim 3, characterized in that: R4 is -COOR4"; R4" is methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t- butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, phenyl, benzyl, or a substituted derivative thereof, -CH2CßH2 (CH3) 3, 2-chlorophenylmethyl, 4-chlorophenyl-methyl, 2, 4-Dichlorophenylmethyl, 2,6-dichlorophenylmethyl, 2-methoxycarbonylphenylmethyl, 3-trifluoromethylphenylmethyl, 4-trifluoromethylphenylmethyl, 3,5-bis (trifluoromethyl) phenylmethyl, 4-trifluoromethoxyphenyl, 2-thiophenylmethyl, 4-methoxyphenylmethyl, 3,5-dimethoxyphenylmethyl, 3- methylphenylmethyl, 4-methyl-phenylmethyl, 4-t-butylphenylmethyl, 4-propylphenylmethyl, 2,5-dimethylphenylmethyl, 2-methoxy-5-methylphenylmethyl, 2,3,5,6-tetramethylphenylmethyl, 2,3,4 , 5,6-pentamethylphenylmethyl, 1-naphthylmethyl, 2-naphthylmethyl, 4-fluorophenylmethyl, 2 , 4- difluorophenylmethyl, 2-chloro-6-methylphenylmethyl, 2-chloro-4-fluoro-phenylmethyl, 2,5-dimethoxyphenylmethyl, 3,4-dimethoxyphenylmethyl, 3-chloro-6-methoxyphenylmethyl, 2-trifluoromethylphenyl-methyl, 2 , 2,2-trifluoroethyl, isoxazol-5-ylmethyl, 2-chloropyridin-3-yl-methyl, pyridin-3-yl-methyl, 2-chloropyridin-5-methyl; L is -NHS02-, -CH2NHS02- or NHS02CH2-; X is N or O; and the other residues are as defined in claim 3.

7. The compounds according to claim 3, characterized in that: R4 is -S02R4 '; R4 'is methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, phenyl, benzyl, tolyl or a substituted derivative thereof, -C6H2 (CH3) 3, -C6 (CH3) 5, -CH2C6H2 (CH3) 3. 4-phenylphenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2,3-dichlorophenyl, 2,4-dichlorophenyl, 3 , 4- dichlorophenyl, 2,5-dichlorophenyl, 3,5-dichlorophenyl, 2,6-dichlorophenyl, 2-chlorophenylmethyl, 4-chlorophenylmethyl, 2,4-dichlorophenylmethyl, 2,6-dichlorophenylmethyl, 2- methoxycarbonyl phenylmethyl, 3- trifluoromethylphenyl, 4-trifluoromet ilphenyl, 3,5-bis (trifluoromethyl) phenyl, 4-trifluoromethoxyphenyl, phenylmethyl, 2-acetamido-4-methyl-thiazol-5-yl, phenylethyl, l-phenylpropyl, (S) - (+) - camphor -10-ilo, (R) - (-) -canfor-10-yl, 2-phenylethenyl, 2-thiophenyl, 4-methoxyphenyl, 3,5-dimethoxyphenyl, 3-methylphenyl, 4-methylphenyl, 4-t-butylphenyl, 4-propylphenyl, 2, 5-dimethylphenyl, 2-methoxy-5-methylphenyl, 2,3,5,6-tetramethylphenyl, 2,3,4,5,6-pentamethylphenyl, 1-naphthyl, 2-naphthyl, 4-fluorophenyl, 2, 4- difluorophenyl, 2-chloro-6-methylphenyl, 2-chloro-4-fluorophenyl, 2,5-dimethoxyphenyl, 3,4-dimethoxyphenyl, 3-chloro-6-methoxyphenyl, 2-trifluoromethylphenyl, 2-phenylsulfonylphenyl, 2- Arylsulfonylphenyl, 3- (N-acetyl-6-methoxy) aniline, 4-acetamidophenyl, 2,2,2-trifluoroethyl, 5-chloro-3-methyl-benzothiazol-2-yl, N-methoxycarbonylpiperidin-3-yl, thiophen -2-yl, isoxazol-5-yl, 2-chloropyridin-3-yl, pyridin-3-yl, 5-methylisoxazol-3-yl, 1-adamantyl, 4-chlorophenoxymethyl, 2,2-dimethylethyl, 2-chloropyridin -5-methyl, 5,7-dimethyl-1,3-, 4-triazaindolizin-2-yl, (S) -canphan-1-yl, (R) -canphan-1-yl or 8-quinolinyl; L is -NHCO-, -CH2NHCO- or NHCOCH2-; X is N or O; and the other residues are as defined in claim 3.

8. The compounds according to claim 3, characterized in that: R4 is -S02R4 '; R4 'is methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, phenyl, benzyl, tolyl or a substituted derivative thereof, - C 6 H 2 (CH 3) 3, -C 6 (CH 3) 5, -CH 2 C 6 H 2 (CH 3) 3, 4-phenyl phenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2,3-dichlorophenyl, 2,4-dichlorophenyl, 3 , 4-dichlorophenyl, 2, 5-dichlorophenyl, 3,5-dichlorophenyl, 2,6-dichlorophenyl, 2-chlorophenylmethyl, 4-chlorophenylmethyl, 2,4-dichlorophenylmethyl, 2,6-dichlorophenylmethyl, 2-methoxycarbonylphenylmethyl, 3-t rifluoromethylphenyl, 4-trifluoromethylphenyl, 3,5-bis (trifluoromethyl) phenyl, 4-trifluoromethoxyphenyl, phenylmethyl, 2 -acetamido-4-methyl-thiazol-5-yl, phenylethyl, l-phenylpropyl, (S) - (+) -canfor-10-yl, (R) - (-) -canfor-10-yl, 2-phenylethenyl, 2-thiophenyl, 4-methoxyphenyl, 3,5-dimethoxyphenyl, 3-methylphenyl, 4-methylphenyl, 4-t -butylphenyl, 4-propylphenyl, 2,5-dimethylphenyl, 2-methoxy-5-methylphenyl, 2,3 , 5,6-tetramethylphenyl, 2, 3, 4, 5, 6-pentamethylphenyl, 1-naphthyl, 2-naphthyl, 4-fluorophenyl, 2,4-difluorophenyl, 2-chloro-6-methylphenyl, 2-chloro- 4-fluorophenyl, 2,5-dimethoxyphenyl, 3,4-dimethoxyphenyl, 3-chloro-6-methoxyphenyl, 2-trifluoromethylphenyl, 2-phenylsulfonylphenyl, 2-arylsulfonylphenyl, 3- (N-acetyl-6-methoxy) aniline, -acetamidophenyl, 2, 2, 2-trifluoroethyl, 5-chloro-3-methyl-benzothiazol-2-yl, N-methoxycarboni Ipiperidin-3-yl, thiophen-2-yl, isoxazol-5-yl, 2-chloropyridin-3 -yl, pyridin-3-yl, 5-methylisoxazol-3-yl, 1-adamantyl, 4-chlorophenoxymethyl, 2,2-dimethylethenyl, 2-chloropyridin-5-methyl, 5,7-dimethyl-1,3, 4-triazaindolizin-2-yl, (S) -canphan-1-yl, (R) -canphan-1-yl or 8-quinolinyl; L is -OCH2-, -CH20- or CH2OCH2-, -CH2CH20- or OCH2CH2-; X is N or O; and the other residues are as defined in claim 3.

9. The compounds according to claim 3, characterized in that: Rf is -S02R; R. ' is methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, phenyl, benzyl, tolyl or a substituted derivative thereof, -C6H2 ( CH 3) 3, -C 6 (CH 3) 5, -CH 2 C 6 H 2 (CH 3) 3, 4-phenylphenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2,3-dichlorophenyl, 2,4-dichlorophenyl, 3,4- dichlorophenyl, 2,5-dichlorophenyl, 3,5-dichlorophenyl, 2,6-dichlorophenyl, 2-chlorophenylmethyl, 4-chlorophenylmethyl, 2,4-dichlorophenylmethyl, 2,6-dichlorophenylmethyl, 2-methoxycarbonylphenylmethyl, 3-trifluoromethylphenyl, 4- trifluoromethylphenyl, 3,5-bis (trifluoromethyl) phenyl, 4-trifluoromethoxyphenyl, phenylmethyl, 2-acetamido-4-methyl-thiazol-5-yl, phenylethyl, l-phenylpropyl, (S) - (+) - camphor-10- ilo, (R) - (-) -canfor-10-yl, 2-phenylethenyl, 2-thiophenyl, 4-methoxyphenyl, 3,5-dimethoxyphenyl, 3-methylphenyl, 4-methylphenyl, 4-t-butylphenyl, 4-propylphenyl, 2,5-dimethylphenyl, 2-methoxy-5-methylphenyl, 2,3,5,6-tetramethylphenyl, 2, 3, 4, 5, 6 pentamethylphenyl, 1-naphthyl, 2-naphthyl, 4-fluorophenyl, 2,4-difluorophenyl, 2-chloro-6-methylphenyl, 2-chloro-4-fluorophenyl, 2,5-dimethoxyphenyl, 3,4-dimethoxyphenyl, 3- chloro-6-methoxyphenyl, 2-trifluoromethylphenyl, 2-phenylsulfonylphenyl, 2-arylsulfonylphenyl, 3- (N-acetyl-6-methoxy) aniline, 4-acetamidophenyl, 2,2,2-trifluoroethyl, 5-chloro-3-methyl -benzothiazol-2-yl, N-methoxycarbonylpiperidin-3-yl, thiophen-2-yl, isoxazol-5-yl, 2-chloropyridin-3-yl, pyridin-3-yl, 5-methylisoxazol-3-yl, α-adamantyl, 4-chlorophenoxymethyl, 2,2-dimethyletenyl, 2-chloropyridin-5-methyl, 5,7-dimethyl-1,3,4-triazaindolizin-2-yl, (S) -canphan-1-yl, ( R) -Canf an-l-yl or 8-quinolinyl; L is -NHS02-, -CH2NHS02- or NHS02CH2-; X is N or O; R7 and R9 together form an ethylene group that is bonded to the nitrogen atom to which R7 is bonded to the nitrogen atom to which R9 is linked; and the other residues are as defined in claim 3.

10. The process for the preparation of compounds of the formula (1) characterized in that it comprises the steps: a) reaction of a β-amino acid of the formula (2) (2) wherein P is - (CH2) mN02, - (CH2) m0-alkylo-6, - (CH2) mS02P ', - (CH2) mCOP', - (CH2) mCH20-C6-6 alkyl, wherein m in each case is an integer of 0 or 1; P 'is -OH, -O-alkyl C? _6, and the other residues are as defined above; with a compound R4-A to give a compound of the formula (3), wherein R4 is -S02R4 ', -COOR4"or -COR4'; R4 'and R4" are as defined above; A is -Cl, -Br, -I, -O-triflyl, -O-tosyl, -O-alkyl C? -6. -O-CO-alkyl C? _6, -O-CO-O-alkyl C? _6, OC (CH3) = CH2; and the other residues are as defined above; b) conversion of residue P to residue Q, where Q is - (CH2) mNH2, - (CH2) mOH, - (CH2) mCH2OH, - (CH2) mS02A, - (CH2) mCOA, A is as defined previously; m is an integer of 0 or 1; c) reaction of the compound obtained from step b) with a compound of the formula (4) wherein S is AS02 (CH2) n-, NH2 (CH2) n-, ACO (CH2) n-, HOCH2 (CH2) "-, (CH2) n-, MCH2 (CH2) n-. HSCH2 (CH2) n- or HS (CH2) n-, where n is an integer of 0 or 1; M is a residue that includes Mg, Li, Cd or Sn; A is as defined above; and C is -N02 or X, R7, R8, R9 and R11 are as defined according to claim 1; to give a compound of the formula (5) wherein the residues are as defined in accordance with claim 1; d) if appropr, the conversion of C, if C is a nitro group, into a unit of urea, thiourea or optionally cyclic guanidine with the obtaining of compound (1); and e) if appropr, the removal of the protecting groups and / or derivation of the nitrogen atoms, which are present, at preferred times within the preparation process, and / or conversion of the compound obtained in the free acid and / or the conversion of the compound obtained in one of its physiologically acceptable salts, by reaction with a suitable inorganic or organic base or acid. The process according to claim 10, characterized in that the β-amino acid of the formula (2) is obtained by the reaction of malonic acid with a benzaldehyde derivative of the formula (2a) wherein R10 and P are as defined in accordance with claim 10, in the presence of ammonia, ammonium or amines compounds and, if appropr, the subsequent substitution at position a with respect to the terminal carboxyl group. 12. The compliance process, with claim 10, characterized in that it comprises the conversion of the nitro group in step d) by reduction to the amino group, the subsequent reaction with a carbonic acid derivative and, if appropr, the removal of the protective groups present and / or the reaction with a compound containing at least one amino group.

13. The pharmaceutical composition, characterized in that it comprises at least one compound according to one of claims 1 to 9. The use of compounds according to one of claims 1 to 9 for the production of a pharmaceutical composition having antagonistic action of integrin. The use of the compounds according to one of claims 1 to 10 for the production of a pharmaceutical composition for the inhibition of angiogenesis and / or for cancer therapy and prophylaxis, osteolytic diseases, such as osteoporosis, arteriosclerosis, restenosis , rheumatoid arthritis and ophthalmic diseases.