MXPA97010277A

MXPA97010277A - Substitute purin derivatives, procedures for the preparation, use and agents that contain them

Info

Publication number: MXPA97010277A
Application number: MXPA/A/1997/010277A
Authority: MX
Inventors: Breipohl Gerhard; Wehner Volkmar; Peyman Anuschirwan; Knolle Jochen; Carniato Denis; Gourvest Jeanfrancois; Richard Gadek Thomas
Original assignee: Hoechst Aktiengesellschaft
Priority date: 1996-12-20
Filing date: 1997-12-17
Publication date: 1999-01-11

Abstract

The object of the present invention are compounds of the formulas I and Ia, wherein X, Y, W, Wa, G and Ga possess the meanings indicated in the claims, as well as their physiologically tolerable salts and their prodrugs, their preparation, their use , especially as medicated active ingredients, and pharmaceutical preparations containing them. The compounds of the formula I are antagonists of vitronectin receptors and can be used, for example, as inhibitors of bone resorption and for the treatment of osteoporos

Description

SUBSTITUTE PURIN DERIVATIVES, PROCEDURES FOR PREPARATION, USE AND AGENTS THAT CONTAIN IT Object of the present invention are compounds of the formulas I and wherein X, Y, W, Wa, G and Ga possess the meanings indicated below, as well as their physiologically tolerable salts and their prodrugs, their preparation, their use and pharmaceutical preparations containing them. The compounds of the formula I are valuable medicated active ingredients. In particular, they are antagonists of vitronectin receptors and are suitable for the therapy and prophylaxis of diseases that are based on the reciprocal action between the vitronectin receptors and their ligands in the processes of cell-cell or cell-matrix interaction, or that they can be avoided, relieved or cured by an influence of this reciprocal action. The invention relates, inter alia, to the use of compounds of the formula I, as well as of their physiologically tolerable salts and of pharmaceutical preparations containing said compounds, as a curative agent for the prophylaxis, mitigation or cure of diseases which are conditioned, at least in part, by an unwanted measure of bone resorption, angiogenesis or cell proliferation of smooth vascular musculature, or an influence of these processes is intended for their therapy or prophylaxis. In particular, the compounds of the formula I are suitable, for example, as inhibitors of bone resorption, as inhibitors of tumor growth and of tumor metastasis, as anti-inflammatory, for the treatment or prophylaxis of cardiovascular diseases, such as, for example, arteriosclerosis or restenosis, or for the treatment or prophylaxis of nephropathies and retinopathies, such as, for example, diabetic retinopathy. The compounds of the formulas I and that according to the invention inhibit bone resorption by osteo-clasts. Osteopathies against which the compounds of the formula I can be used are, above all, osteoporosis, hypercalcemia, osteopenia, for example caused by metastasis, diseases of the teeth, hyperparathyroidism, periarticular erosions in rheumatoid arthritis and Paget's disease. In addition, the compounds of the formula I are used for the mitigation, prophylaxis or therapy of osteopathies that are caused by a therapy with glucocorticoids, steroids or corticosteroids or by a lack of hormone or sex hormones. All these diseases are characterized by bone loss, which is due to the imbalance between bone constitution and degradation. Human bones undergo a continuous and dynamic reconstitution process, which includes the resorption of bones and the constitution of bones. These processes are regulated by specialized cell types. The constitution of the bones is based on the deposition of bone matrix by the osteoblasts, the resorption of the bones is based on the degradation of the bone matrix by the osteoclasts. Most osteopathies are based on an altered balance between bone formation and bone resorption. Osteoporosis is characterized by a loss of bone matrix. The activated osteoclasts are plurinuclear cells with a diameter of up to 400 μ, which destroy the bone matrix. Activated osteoclasts are stored on the surface of the bone matrix and secrete proteolytic enzymes and acids in the so-called "sealing zone", the zone between its cell membrane and the bone matrix. The acidic environment and the proteases cause bone degradation. Studies have shown that the deposition of osteoclasts on bones is regulated by integrin receptors on the cell surface of osteoclasts. Integrins are a superfamily of receptors, to which they belong, among others, the fibringen receptor auDß3 on blood platelets and the vitronectin receptor ayßg. The avr3 vitronectin receptor is a glycoprotein that resides in the membrane, which is expressed on the cell surface of a series of cells, such as endothelial cells, smooth fiber vascular muscle cells, osteoclasts and tumor cells. The vitronectin avßt receptor that is expressed in the osteoclast membrane regulates the process of bone deposition and bone resorption and, consequently, contributes to osteoporosis. In this case, avß3 binds to bone matrix proteins, such as osteopontin, bone sialoprotein and thrombospontine, which contain the tripeptide motif Arg-Gly-Asp (or RGD). Horton et al. Disclose RGD peptides and a vitronectin receptor antibody (23C6), which inhibit the degradation of teeth by osteoclasts and the migration of osteoclasts (Horton et al., Exp. Cell. Res. 1991, 195, 368 ). Sato et al. describe in J. Cell Biol. 1990, 111, 1713 echistatin, an RGD peptide from snake venom, as a potent inhibitor of bone resorption in a tissue culture, and as an inhibitor of osteoclast adhesion to bone. Fischer et al. (Endo-crinology 1993, 132, 1411) could demonstrate in rats that echistatin also inhibits bone resorption in vivo. Wayne et al. (J. Clin. Invest. 1997, 99, 2284) were able to detect in rats the in vivo activity of the inhibition of bone resorption by a vitronectin receptor antagonist. The vitronectin avßt receptor on human cells of the smooth aortic fiber vascular musculature stimulates the migration of these cells to the neointima, which eventually leads to atherosclerosis and restenosis after angioplasty (Brown et al., Cardiovascular Res. 1994 , 28, 1815). Brooks et al. (Cell 1994, 79, 1157; J. Clin. Invest. 96 (1995) 1815), as well as Mitjans et al., J. Cell Science 1995, 108, 2825) demonstrated that antibodies against avß3 or ßj Puecien antagonists cause a contraction of the tumors, inducing apoptosis of the cells of the blood vessels during angiogenesis. Cheresh et al. (Science 1995, 270, 1500) describe anti-aß antibodies or avß antagonists that inhibit the angiogenesis processes induced by bFGF in rat eyes, which can be used therapeutically in the treatment of retinopathies. EP-A-0 528 586 and EP-A-0 528 587 disclose phenyl alanine derivatives substituted by aminoalkyl or heterocyclyl, WO 95/32710 being aryl derivatives as inhibitors of bone resorption by the osteoclasts. In WO 95/28426 RGD peptides are described as inhibitors of bone resorption, angiogenesis and restenosis. In WO 96/00574 and WO 96/26190, benzodiazepines are described as, inter alia, vitronectin receptor antagonists or integrin receptor antagonists. WO 96/00730 describes templates of fibrinogen receptor antagonists, especially benzodiazepines, which are linked in the nitrogen-bearing 5-membered ring as antagonists of vitronectin receptors. In EP-A-0 531 883 condensed 5-membered heterocycles which inhibit the binding of fibrinogen to thrombocytes are described. Object of the present invention are compounds of the formulas I and where: X means hydrogen, NR ° R6, fluorine, chlorine, bromine, OR6, SR, hydroxy-alkyl- ^ -Cg) -NH, (hydroxy-C1- (C1-Cg) alkyl) 2N, amino-alkyl- Cg-NH, (amino-C 1-6 -alkyl) 2 N, hydroxy-C 1 -C 6 J-O, hydroxyalkyl- (C 1 -C 6) -S or NH-CO-R 6; Y means R6, fluorine, chlorine, bromine, cyano, NR6R6 ', OR6, SR6 or hydroxy-alkyl- Cj ^ CgJ-NH; means a radical of formula II - (CR) 11D R2N -ICR 11D R2 < CR l (H); W means a radical of formula III -B- (CR1R '-ICR1R2) S- (CR1R ^ k -ICR1R2) t-D-E (III); means a radical of the formula lia W,? Aa means a radical of the Illa formula -B-ÍCR ^^^ A-ÍCR ^^^ CR ^^^ CR ^ 2) ^ (Illa); A, A ', independently of one another, mean a direct bond, -C (0) NR5, -NR5C (0) -, -C (0) -, -NR5- -0-, -S-, -SO- , -S02-, arylene- (C5-C14), being able to be replaced in the aryl radical of one to five carbon atoms by one to five heteroatoms, alkynylene- (C2-C4), alkenylene- (C2-C4) , or a divalent radical of a 3 to 7 membered ring, saturated or unsaturated, which may contain one or two heteroatoms, such as, for example, nitrogen, sulfur or oxygen, and which may be substituted once or twice with radicals of the series = 0, = S and R3; R, R, independently of one another, mean hydrogen, fluorine, chlorine, cyano, nitro, alkyl-4-C ^), cycloalkyl- (C3-C] _4), cycloalkyl- (C3-C1) -alkyl- - (C1-Cg), aryl- (C5-C14), aryl- (C5-C14) -alkyl- - (C ^ Cg), R6-0-R7, R6-S (0) p-R7 or R6R6'N -R7; R3, independently of one another, mean hydrogen, fluorine, chlorine, cyano, nitro, alkyl-1-C ^), cycloalkyl- (C3-C14), cycloalkyl- (C3-C14) -alkyl- (C1 -Cg), aryl- (C5-C14), aryl- (C5-C14) -alkyl- (C1-Cg), R6-0-R7, R6R6'N-R7, R6C (0) -0-R7, R6C (0) R7, R60C (0) R7, R6N (R6 ') - C (0 0)) 00RR7, R6S (0) N (R5) R7 , R60C (0) N (R5) R7, R6C (0) N (R5) R7, R < N (R6 ') C (0) N (R =) R7, R6N (R6') S (0) pN (R5) R7, R6S (0) pR7, R6SC (0) N (R5) R7, R6N (R6) ') C (0) R7 or R6N (R6') S (0) DR7, wherein alkyl may be unsaturated once or several times and, in addition, alkyl or aryl may be substituted once or several times with fluorine, chlorine, bromine, cyano, R ° R6'NR7, nitro, R6OC (0) R7, R6C (0) R7, R6N (R6 ') C (0) R7, R6N (R6') -S (0) pR7, R6 or R6-0-R7; R4 means C (0) R8, C (S) R8, S (0) pR8, P (0) R8R8 'or a saturated or unsaturated radical of a four to eight membered heterocycle, containing 1, 2, 3 or 4 heteroatoms of the series N, 0, S, such as, for example, tetrazolyl, imidazolyl, pyrazolyl, oxazolyl, thiadiazolyl; R5 mean, independently of one another, hydrogen, < cycloalkyl- (C3-C14), cycloalkyl- (C3-C14) -alkyl- (C1-Cg), aryl- (C5-C1) or aryl- - (C5-C14) -alki lo- (Ci-Cg); R6, R6 'signify, independently of one another, hydrogen, alkyl- (C? -C1g), cycloalkyl- (C3 ~ C14), cycloalkyl- (3 ~ C14) -alkyl- (C1-Cg), aryl- (C5-C1), in which from 1 to 5 carbon atoms can be replaced by heteroatoms such as N, O, S, or aryl- (C5-C1) - -alkyl-C2-Cg), where, on the aryl part, from 1 to 5 carbon atoms can be replaced by heteroatoms such as N, 0, S, or R6 and R6, together with the atoms that join them, form a ring system, especially a 4- to 8-member ring system, which may optionally also contain, additionally, one, two or three additional heteroatoms of the series N, O, S, and which may be saturated or unsaturated, especially saturated, such as, for example, , morpholine, thiomorpholine, piperazine, piperidine, pyrrolidine; R7 signifies, independently of one another, alkylene- (C1-C4) or a direct bond; R, R8 'signify, independently of one another, hydroxy, alkoxy-^Cg), aryl- (C5-C14) -alkoxy- (C1-Cg), aryloxy- (C5-C14), alkyl- (C1 -Cg) -carbonyloxy-(C1-C4) alkoxy, ary1- (C5-C14) -alkyl- (C] _- Cg) -carbonyloxy-alkoxy- (C ^ Cg), NR6R6 ', di-Calkyl- CCj ^ -CgJ-aminocarbonylmethyloxy, di- (ary1- (C5-C14) -alkyl-> Cj ^ -Cg) -amino) carbonyl ethyloxy, aryl- (C [j-C14) -amino, the radical of an amino acid , N- (alky1- (C1-C4)) -piperidin-4-yloxy, 2-methylsulfonyletoxy, 1,3-thiazol-2-ylmethyloxy, 3-pyridylmethyloxy. 2- (di- (C 1 -C 4) alkylamino) ethoxy or the radical Q "(CH 3) 3 N + -CH 2 -CH 2 O-, wherein Q" represents a physiologically tolerable anion; B means -0-, -S-, -NR5-, -NR5-C (0) -, -C (0) -NR5-, a direct bond or a divalent radical of a 3 to 7 membered ring, saturated or unsaturated, which may contain one or two heteroatoms, such as, for example, nitrogen, sulfur or oxygen, and which may be substituted once or twice with radicals of the series = 0, = S and R3; D means a direct bond, -NR6-, -C (0) -NR6-, -NR6- -C (0) -, -S (0) u-NR6-, -NR6-C (0) -NR6-, -NR6-C (S) -NR6-, -NR6-S (0) u-NR6-, -NR6-C (0) 0-, -NR6-N = CR6-, -NR6-S (0) u ~ , -aryl- (C5-C14) -CO-, -aryl- (C5-C14) -S (0) u-, -N = CR6-, -R6C = N- or -R6C = N-NR6-, being the divalent radicals represented by D linked to group E through the free bond on the right side; E means hydrogen, R6-C (= NR6) -NR6-, R6R6 'NC (= NR6) -, R6R6'NC (= NR6) -NR6- or a radical of a ring system of 4 to 11 members, monocyclic or polycyclic, aromatic or non-aromatic, which may optionally contain 1, 2, 3 or 4 heteroatoms of the series N, 0 and S, and which may optionally be substituted one, two or three times with radicals of the series R3, R5, = 0, = S and R6R6'NC (= NR6) -, such as, for example, the following radicals: n means zero, one, two, three, four or five; m means zero, one, two, three, four or five; i means zero or one; p mean, independently of one another, zero, one or two; q means zero, one or two; r means zero, one, two, three, four, five or six; s means zero, one, two, three, four or five; t means zero, one, two, three, four or five; k means zero or one; u means one or two; v means zero, one, two or three; in all its stereoisomeric forms and mixtures thereof in all ratios, and their physiologically tolerable salts, as well as their prodrugs; it may also be in place of the purine backbone shown in formulas I and II, a 3-deaza-pu-rine backbone, a 7-deaza-purine backbone or a 7-deaza-8-aza-purine backbone. All the radicals and indices that can appear several times in the compounds of formulas I and II, for example the radicals R1, R2 and R3 and the radicals R5, R6, R6 'and R7 which are derived from them, and the indices, which appear in the radicals G and W, but also all other radicals and indices, for which this is valid, can have in each case the indicated meanings, independently of one another. They can be the same or different. Likewise, the heteroatoms which may be present several times in the heterocycles, or the substituents which may be present several times in the radicals, may have the indicated meanings, independently of one another, and may be the same or different. The alkyl radicals appearing in the substituents can be straight chain or branched, saturated or unsaturated one or more times. This is also valid if the substituents carry other radicals or other radicals appear as substituents, for example, in alkoxy radicals, alkoxycarbonyl radicals or aralkyl radicals. The same is true for divalent alkylene radicals. Examples of suitable alkyl-t ^ -C ^ radicals are: methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, decyl, undecyl, dodecyl, tridecyl, hexadecyl, octadecyl, the n-isomers of these radicals, isopropyl, isobutyl, isopentyl, neopentyl, isohexyl, 3-methylpentyl, 2, 3, 4-trimethylhexyl, sec-butyl, tert-butyl, tert-pentyl. Preferred alkyl radicals are methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl and tere-butyl. Unsaturated alkyl radicals are, for example, alkenyl radicals, such as vinyl, 1-propenyl, allyl, butenyl, 3-methyl-2-butenyl, or alkynyl radicals, such as ethynyl, 1-propynyl or propargyl. The alkenylene radicals as well as alkynylene can be straight chain or branched. Examples of alkenylene radicals are vinylene or propenylene, from alkynylene, ethynylene or propylene glycol radicals. Cycloalkyl radicals can be monocyclic, bicyclic or tricyclic. Cycloalkyl oncyclic radicals are, in particular, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl, in addition to, for example, cyclononyl, cyclodecyl, cycloundecyl, cyclododecyl or cyclotetradecyl, which may also all be substituted with, for example, alkyl- ( C1-C4). As examples of substituted cycloalkyl radicals, there can be mentioned 4-methylcyclohexyl and 2,3-dimethylcyclopentyl. The bicyclic and tricyclic cycloalkyl radicals can be unsubstituted or can be substituted at arbitrary appropriate positions with one or more oxo groups and / or one or more (C 1 -C) alkyl radicals, the same or different, for example, methyl groups or groups isopropyl, preferably methyl groups. The free bond of the bicyclic or tricyclic radical can be found in the arbitrary position of the molecule, ie the radical can be linked through a bridgehead atom or a bridge atom. The free bond can also be found in an arbitrary stereochemical position, for example, in an exo position or in an endo position. Examples of basic bodies of bicyclic ring systems are norbornane (= bicyclo [2.2.1] heptane), bicyclo [2.2.2] octane and bicyclo [3.2. l] octane. An example of a system substituted with an oxo group is camphor (= 1,7,7-trimethyl-2-oxo-bicyclo [2.2.1] heptane).

Examples of basic bodies of tricyclic systems are the tuistano (= tricycle [4.4.0.0J 'a] dean, adamantane (= tricyclo [3.3.1.13, 7] decane), noradamantane (= trici-clo [3.3.1.03'7] nonane), the tricycle [2.2.1.O2 '6] -heptane, the tricycle [5.3.2.0 , 9] dodecane, the tricyclo- [5.4.0.02 '9] undecane or the tricycle [5.5.1.O3, 11] tridecane. Aryl- (C5-C14) comprises heterocyclic aryl- (C5-C14) radicals, in which ring carbon atoms are replaced by heteroatoms such as nitrogen, oxygen or sulfur, and carbocyclic aryl- (Cg-C14) radicals. Examples of carbocyclic aryl radicals are phenyl, naphthyl, biphenylyl, anthryl or fluorenyl, with 1-naphthyl, 2-naphthyl and, especially, phenyl being preferred. The aryl radicals, in particular the phenyl radicals, can be substituted once or several times, preferably once, twice or three times, with radicals, the same or different, of the alkyl-! C ^ Cg), especially (C 1 -C 4) alkyl, alkoxy-C 1 -Cg), especially (C 1 -C) -alkoxy, halogen, such as fluorine, chlorine and bromine, nitro, amino, trifluoromethyl, hydroxy , methylenedium-xi, cyano, hydroxycarbonyl, aminocarbonyl, alkoxy-C ^ C ^ j) - carbonyl, phenyl, phenoxy, benzyl, benzyloxy, (R'0) 2P (0) -, (R90) P (0) - 0- or tetrazolyl, R9 representing hydrogen, alkyl- ^ - C ^), aryl- (Cg-C14) or aryl- (Cg-C14) -alkyl- (C ^ -Cg). The same is valid for the corresponding arylene radicals. In monosubstituted phenyl radicals, the substituent may be in the 2-position, 3-position or 4-position, with 3 and 4 being preferred. If phenyl is substituted twice, then the substituents may be in positions 1, 2, 1,3 or 1,4, one with respect to the other. Referring to the binding site, the substituents can be found in position 2,3, in position 2,4, in position 2,5, in position 2,6, in position 3,4 or in position 3, 5. In the twice substituted phenyl radicals, it is preferred that the two substituents are arranged in the 3-position and in the 4-position with respect to the binding site. Aryl groups or arylene groups can also represent monocyclic or polycyclic aromatic ring systems, wherein the carbon atoms 1, 2, 3, 4, 6, 5 of the ring are replaced by heteroatoms, such as, for example, 2-pyridyl, 3-pyridyl, 4-pyridyl, pyrrolyl, furyl, thienyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, tetrazolyl, pyridyl, pyrazinyl, pyrimidinyl, indolyl, isoindolyl, indazolyl, phthalazinyl, quinolyl, isoquinolyl, quinoxalinyl, quinazo- Linillo, cinolinyl, β-carbolinyl, or a derivative of these radicals condensed with benzo or condensed with cyclopenta, cyclohexa or cyclohepta. These heterocycles can be substituted with the same substituents as the aforementioned carbocyclic aryl systems. In the series of these aryl groups or of the corresponding arylene groups, aromatic, oncyclic or bicyclic ring systems with 1, 2 or 3 heteroatoms of the series N, 0, S, which are unsubstituted or substituted with 1 , 2 or 3 substituents of the series alkyl- (Cj ^ -Cg), alkoxy- (C ^ -Cg), fluorine, chlorine, nitro, amino, trifluoromethyl, hydroxy, alkoxy- (C 1 -C 4) -carbonyl, phenyl , phenoxy, benzyloxy and benzyl. In this case, aromatic ring systems of 5 to 10 membered, monocyclic or bicyclic, with 1 to 3 heteroatoms of the series N, 0, S, which can be substituted with 1 to 2 substituents of the alkyl- ^ C ^ j), alkoxy-CCj ^ -C ^ j), phenyl, phenoxy, benzyl and benzyloxy. Examples of saturated and unsaturated rings, especially of saturated or unsaturated rings with 3 to 7 members, which may contain one or two heteroatoms, such as, for example, nitrogen, sulfur or oxygen, and which may possibly be substituted once or twice with = 0, = S or R3, are cyclopropane, cyclobutane, cyclopentane, cyclohexane, cycloheptane, cyclopentene, cyclohexene, cycloheptene, tetrahydropyran, 1,4-dioxacyclohexane, morpholine, thiomorpholine, piperazine, piperidine, pyrrolidine, dihydroisoxazole, tetrahydroisoxazole, 1,3-dioxolane, 1,2-dithiolane, 2,3-dihydrofuran, 2,5-dihydrofuran, tetrahydrofuran , 2, 3-dihydrothiophene, 2,5-dihydrothiophene, 2-imidazoline, 3-imidazoline, 4-imidazoline, 2-oxazoline, 3-oxazoline, 4-oxazoline, 2-thiazoline, 3-thiazoline, 4-thiazoline , tiazoli-dina, a-thiapyran, -piran and? -pirano. The radical of an amino acid representing R8 and / or R 'is obtained in the formally customary manner in the chemistry of the peptides, by removing a hydrogen atom from the amino group of the amino acid. To the free bond in the group to i, formally obtained in this case, the amino acid radical is then bound, for example in the group CO of the group CO-R8. The amino acids can be natural or non-natural amino acids. A-amino acids are preferred. The amino acids can be present in different stereochemical forms, for example as D- or L-amino acids, and in stereochemically homogeneous form or in the form of mixtures of stereoisomers. As amino acids can be mentioned, for example, (see Houben-Weyl, Methoden der organischen Chemie, volumes XV / 1 and 2, Editorial Georg Thieme, Stuttgart, 1974): Aad, Abu,? Abu, ABz, 2ABz, eAca, Ach, Acp, Adpd, Ahb, Aib, ßAib, Ala, ßAla,? AIa, Alg, All, Ama, Amt, Ape, Apm, Apr, Arg, Asn, Asp, Asu, Aze, Azi, Bai, Bph, Can, Cit, Cys, (Cys) 2, Cyta, Daad, Dab, Dadd, Dap, Dapm, Dasu, Djen, Dpa, Dtc, Fel, Gln, Glu, Gly, Guv, hAla, hArg, hCys, hGln, hGlu, His, hile, hLeu, hLys, hMet, hPhe, hPro, hSer, hThr, hTrp, hTyr, Hyl, Hyp, 3Hyp, lie, Ise, Iva, Kyn, Lant, Len, Leu, Lsg, Lys, ßLys,? Lys, M? T, Mim, Min, nArg, NIe, Nva, Oly, Orn, Pan, Pee, Pen, Phe, Phg, Foot, Pro,? Pro, Pse, Pya, Pyr, Pza, Qin, Ros, Sar, Sec, Sem, Ser, Thi, ßThi, Thr, Thy, Thx, Aunt, Tie, Tly, Trp, Trta, Tyr, Val, tert-butylgliac (Tbg), neopentylglycine (Npg), cyclohexylglycine (Chg), cyclohexilalanine (Cha), 2-thienylalanine (Thia), acid 2,2-diphenylaminoacetic, 2- (p-tolyl) -2-phenylaminoacetic acid, 2- (p-chlorophenyl) -aminoacetic acid; in addition: pyrrolidine-2-carboxylic acid; piperidin-2-carboxylic acid; 1, 2, 3, 4-tetrahydroisoquinoline-3-carboxylic acid; decahydroisoquinoline-3-carboxylic acid; octahydroindol-2-carboxylic acid; decahydroquinoline-2-carboxylic acid; octahydrocyclopenta [b] pyrrole-2-carboxylic acid; 2-azabicyclo [2.2.2] octane-3-carboxylic acid; 2-azabicyclo acid [2.2. l] heptan-3-carboxylic; 2-azabicyclo [3.1.0] hexane-3-carboxylic acid; 2-azaspiro [4.4] nonane-3-carboxylic acid; 2-azaspiro [4.5] decane-3-carboxylic acid; Spiro acid (bi-cyclo [2.2.1] heptane) -2,3-pyrrole idin-5-carboxylic acid; Spiro acid (bicyclo [2.2.2] octane) -2, 3-pi roline idin-5-carboxyl; 2-azatriciclo acid [4.3.0. I6, 9] decane-3-carboxylic acid; decahydrocyclohepta [b] pyrrole-2-carboxylic acid; decahydro-cycloocta [c] pyrrole-2-carboxylic acid; octahydrocyclopenta-ta [c] pyrrole-2-carboxylic acid; octahydroisoindole-1-carboxylic acid; 2, 3, 3a, 4, 6a-hexahydrocyclopenta [b] pyrrole-2-carboxylic acid; 2, 3, 3a, 4, 5, 7a-hexahydroindol-2-carbo-xylic acid; tetrahydrothiazole-4-carboxylic acid; isoxazo-li-din-3-carboxylic acid; pyrazolidin-3-carboxylic acid, hydroxypyrrolidine-2-carboxylic acid; which may eventually all be replaced (see the following formulas): . -.

Heterocycles based on the aforementioned radicals are known, for example, from US-A-4,344,949; US-A-4,374,847; US-A-4,350,704; EP-A 29,488; EP-A 31,741; EP-A 46,953; EP-A 49,605; EP-A 49,658; EP-A 50,800; EP-A 51,020; EP-A 52,870; EP-A 79,022; EP-A 84,164; EP-A 89,637; EP-A 90,341; EP-A 90,362; EP-A 105,102; EP-A 109,020; EP-A 111,873; EP-A 271,865 and EP-A 344,682. In addition, the amino acids can also be present as esters or amides, such as, for example, as methyl ester, ethyl ester, isopropyl ester, isobutyl alcohol, tert-butyl ester, benzyl ester, unsubstituted amide, methylamide, ethylamide, semicarbazide u? -amino-alkyl- (C2-Cg) -amide. The functional groups of amino acids can be protected. Suitable protecting groups, such as, for example, urethane protecting groups, carboxyl protecting groups and side chain protecting groups, are described in Hubbuch, Kontakte (Merck) 1979, nd 3, pages 14 to 23, and in Büllesbach, Kontakte (Merck), 1980, nd 1, pages 23 to 35. They can be mentioned in particular: Aloe, Pyoc, Fmoc, Tcboc, Z, Boc, Ddz, Bpoc, Adoc, Msc, Moc, Z (N02), Z (Haln ), Bobz, Iboc, Adpoc, Mboc, Acm, tere-butyl, OBzl, ONbzl, OMbzl, Bzl, Mob, Foot, Trt. The compounds of the formulas I and that according to the invention are optionally present as E / Z isomers. Both the pure E isomers and the pure Z isomers, as well as the E / Z isomer mixtures in all ratios are the object of the present invention. The compounds of the formulas I and II can contain optically active carbon atoms which, independently of one another, can have the R or S configurations. They can be in the form of pure enantiomers or pure diastereomers, or in the form of mixtures of enantiomers, for example in the form of racemates, or mixtures of diastereoisomers. Both the pure enantiomers and the mixtures of enantiomers in all the ratios, as well as the diastereomers and the mixtures of diastereomers in all the ratios are object of the present invention. The diastereoisomers, including the E / Z isomers, can be separated into their individual isomers, for example, by chromatography. The racemates can be separated in the chiral phases, for example by chromatography, or they can be separated into the two enantiomers by splitting the racemate. In the case of the presence of mobile hydrogen atoms, the present invention also comprises all tautomeric forms of the compounds of formulas I and II. The physiologically tolerable salts of the compounds of the formulas I and II are, in particular, pharmaceutically usable or non-toxic salts, physiologically usable. Of the compounds of the formulas I and the one containing acidic groups, for example carboxy, the salts are usable, such as, for example, alkali metal salts or alkaline earth metal salts, for example, sodium salts, salts of potassium, magnesium salts and calcium salts, as well as salts with quaternary ammonium ions and acid addition salts physiologically tolerable with ammonia and physiologically tolerable organic amines, such as, for example, triethylamine, ethanolamine or tris- (2-hydroxy) ethyl) - amine. The compounds of the formulas I and the one containing basic groups, for example one or more amino groups, amidino groups. or guanidino groups, form salts by the addition of acids, for example with inorganic acids, such as hydrochloric acid, sulfuric acid or phosphoric acid, or with carboxylic acids and organic sulfonic acids, such as acetic acid, citric acid, benzoic acid, maleic acid , fumaric acid, tartaric acid, methanesulfonic acid or p-toluenesulfonic acid. A physiologically tolerable Q ~ anion, which is contained in the compounds of formulas I and when R8 QI and / or R ° represent the 2-trimethylammonium-ethoxy radical, it is in particular a monovalent anion or an equivalent of a polyvalent anion of an inorganic or organic acid, non-toxic, physiologically usable, especially also pharmaceutically usable, for example the anion or an anion equivalent of one of the aforementioned acids, which come into consideration for the formation of salts by the addition of acids. That is, Q "may represent, for example, one of the anions (or an anion equivalent) of the chloride, sulfate, phosphate, acetate, citrate, benzoate, maleate, fumarate, tartrate, methanesulfonate and p-toluenesulphonate series. The salts can be obtained by customary methods, known to the person skilled in the art, from the compounds of the formulas I and the, for example, by bringing together the compounds of the formulas I and the one with an acid or a base inorganic or organic, in a solvent or dispersing agent, or also by cation exchange or exchange of anions from other salts The present invention also comprises all the salts of the compounds of the formulas I and the one which, on account of of their limited physiological tolerability, they are not directly appropriate for use in medicines, but they can be considered, for example, as intermediate products for carrying out other chemical modifications of the compounds of the formulas I and the, or as starting material for the preparation of physiologically tolerable salts. The present invention also comprises all the solvates of compounds of the formulas I and the, for example, hydrates or adducts with alcohols, as well as derivatives of the compounds of the formulas I and the, for example, esters, prodrugs and metabolites which they act like the compounds of formulas I and la. Subject of the invention are, in particular, prodrugs of the compounds of the formulas I and that which are converted into compounds of the formulas I and under physiological conditions. Suitable prodrugs for the compounds of the formulas I and II, ie derivatives of the compounds of the formulas I and the chemically modified ones, with the improved properties in the desired manner, are known to those skilled in the art. More detailed data on prodrugs are found, for example, in Fleisher et al., Advanced Drug Delivery Reviews 19 (1996) 115-130; Design of Prodrugs, compiler H. Bundgaard, Elsevier, 1985; H. Bundgaard, Drugs of the Future 16 (1991) 443; Saulnier et al., Bioorg. Med. Chem. Lett. 4 (1994) 1985; Safadi et al., Pharmaceutical Res. 10 (1993) 1350. As prodrugs for the compounds of the formulas I and especially include prodrugs of esters of acidic groups, for example of carboxylic acid groups, in particular of a COOH group represented by R, as well as acyl prodrugs and carbamate prodrugs of acylated nitrogen groups, such as amino groups, amidino groups or guanidino groups, especially the groups R6-C (= NR6) -NR6-, R6R6 'NC (= NR6) -, R6R6'NC (= NR6) -NR6- and the ring system of 4 to 11 members, monocyclic or polycyclic, aromatic or non-aromatic, represented by E. In the prodrugs of acyl or in the prodrugs of carbamate, one atom of hydrogen which is found in a nitrogen atom in these groups is replaced one or several times, for example twice, by an acyl group or a carbamate group. Suitable acyl groups and carbamate groups for the acyl prodrugs and the carbamate prodrugs are, for example, the groups R6-CO and R60-CO, in which R6 has the meanings indicated above, ie hydrogen, alkyl-1 ^ -C ^), cycloalkyl- (C3 ~ C1), cycloalkyl- (C3-C14) -alkyl- (C1-Cg), aryl- (C ~ C14), wherein from 1 to 5 carbon atoms they may be replaced by heteroatoms such as N, O, S, or aryl-, wherein from 1 to 5 carbon atoms in the alkyl part may be replaced by heteroatoms such as N, O, S, not taking into consideration the combinations of meanings of the substituents which, in individual cases, lead to non-stable compounds, for example to non-stable free carbamic acids. The preparation of these prodrugs can be carried out by customary procedures familiar to the person skilled in the art, for the preparation of acylamines and carbamates. Furthermore, the present invention is not limited to the compounds according to formulas I and that with a main purine skeleton, but also comprises the compounds which, instead of the main purine backbone shown in formulas I and II, present a skeleton of 3-deaza-purine, 7-deaza-purine or 7-deaza-8-aza-purine, ie, compounds of the formulas Ib and le, Id and le, as well as If and Ig. (you) All the preceding and following explanations on the compounds of the formulas I and II are equally valid for the compounds of the formulas Ib and le, Id and le, If and Ig. Accordingly, unless otherwise indicated, when referring to compounds of formulas I and II, the deaza and deaza-aza analogs of formulas Ib and le, Id and le, If and Ig are also included. Preferably, in the compounds according to the invention, the purine skeleton, which is in fact shown in formulas I and that, in which there are nitrogen atoms in the 3-position and 7-position, and a carbon atom in the position, is present. 8 with the group Y attached to him. In the compounds of formulas I and X, X preferably represents hydrogen, NR6R6 ', hydroxy-alkyl-IC ^ -Cg) or NH-CO-R6, particularly preferably represents hydrogen, NR6R6 or NH-CO-R6 , and very especially preferred, represents hydrogen or NH. And it preferably represents hydrogen. R4 preferably represents C (0) R8. Also preferred are the compounds of the formulas I and that according to the invention, in which R3 represents R6R6'N-R7, R6OC (0) N (R5) R7, R6S (0) pN (R5) R7, R6C (0) N (R5) R7 or R6N (R6 ') C (0) N (R ^) R7, here representing p 1 or 2, especially compounds in which R3 represents R6OC (0) N (R ^) R7 or R ° S (0) _N (R5) R7 (with p = 1 or 2); in this case, compounds in which a lipophilic radical is contained in RJ are particularly preferred, for example compounds in which R6 and / or R6 ', for example in the group R6OC (0) N (R5) R7 , represent (C4-C14) alkyl, aryl- (C5-C1) -alkyl- (C1-C4), for example benzyl, cycloalkyl- (C? -C ^) or cycloalkyl- (C5-C14) -alkyl- (C1-C4), with preferred cycloalkyl radicals being here, especially the 1-adamantyl radical and the 2-adamantyl radical. A preferred group of compounds according to the invention is formed by compounds of the formulas I and the, wherein: X means hydrogen, NH2, OH or NH-CO-R6; And it means hydrogen; G means a radical of formula II - (CR1R2) n-A- (CR1R2) m- (CR1R3) - (CR1R2) q-R4 (II); W means a radical of formula III -B- (CR1R2) r-A '- (CR1R2) s- (CR1R3) k- (CR1R2) t-D-E (III); means a radical of the formula Wa means a radical of the Illa formula -B- (CR1R2) n-A- (CR1R2) m- (CR1R3) - (CR1R2) q-R4 (Illa); A, A ', independently of one another, mean a direct bond, -C (0) NR5-, -NR5C (0) -, -C (0) -, -NR5-, -0-, -S-, - SO-, -S02-, arylene- (C5-C14), being able to be replaced in the aryl radical of one to five carbon atoms by one to five heteroatoms, alkynylene- (C2-C4), alkenylene- (C2-C4) or a divalent radical of a 3 to 7 membered ring, saturated or unsaturated, which may contain one or two heteroatoms, such as, for example, nitrogen, sulfur or oxygen, and which may be substituted once or twice with = 0 , = S or R3; R, R, independently of one another, mean H, fluorine, chlorine, CN, nitro, alkyl- (C ^ -C ^), cycloalkyl- (C3 ~ C14), cycloalkyl- (C3-C12) -alkyl- ( C1-Cg), aryl- (C5-C14), aryl- (C5-C14) -alkyl- (C1-Cg), R6-0-R7, R6-S (0) p-R7 or R6R6'N- R7; R, independently of one another, mean H, fluorine, chlorine, CN, nitro, alkyl- (C? -C14), cycloalkyl- RN (R) S (0) pR, wherein alkyl may be unsaturated once or several times and, in addition, alkyl or aryl may be substituted once or several times with fluorine, chlorine, bromine, CN, R6N (R5) R7, R6R6'NR7 , nitro, R6OC (0) R7, R6C (0) R7, R6N (R5) C (0) R7, R6N (R5) S (0) pR7, R6, R6-0-R7; R4 means C (0) R8, C (S) R8, S (0) pR8, P (0) R8R8 ', a L- or D-amino acid, or a four to eight membered heterocycle, saturated or unsaturated, containing 1, 2, 3, 6, 4 heteroatoms of the N, 0, S series, such as, for example, tetrazolyl, imidazolyl, pyrazolyl , oxazolithiadiazolyl; R5 means H, (C1-C1) alkyl- (C3-C14) cycloalkyl, (C3-C14) -Calkyl-alkyl- (C1-Cg), aryl- (C5-C14) or ari1- (C5-C14) ) -alkyl- (Ci-Cg); R6, R6 'denote, independently of one another, H, alkyl- (C1-Cg), cycloalkyl- (C3-C14).

, (C3-C14) -cycloalkyl- (C1-Cg) alkyl, (C5-C14) aryl, wherein from 1 to 5 carbon atoms may be replaced by heteroatoms, or aryl- (C5-C14) -alkyl-ΔCj ^ -C), in which the aryl part 1-5 carbon atoms can be replaced by heteroatoms, or R6 and R6, together with the atoms that join them, form a ring system, which eventually can also contain other heteroatoms of the N, 0, S series, such as, for example, morpholine, piperazine, piperidine, pyrrolidine; they mean, independently of one another, alkylene- (C1-C4) or a direct bond; R8, R8 'signify, independently of one another, OH, alkoxy-fCj ^ -Gg), aryl- (C5-C14) -alkoxy- (C1-Cg), aryloxy- (C5-C14), alkyl- -C) -carbonyloxy-(C1-C4) alkoxy, ary1- (C5-C14) -alkyl-fCj ^ -C) -carbonyloxy-alkoxy- (C ^ C), NR6R6 ', dialkyl- ^ Cj ^ -CgJ -aminocarbonylmethoxy, aryl- (C5-C14) -dialkyl- (C1-Cg) -amino) carbonylmethyloxy, or an L- or D-amino acid; B means O, S, NR5, -NR5-C (0) -, -C (0) -NR5-, a direct bond or a divalent radical of a 3 to 7 membered ring, saturated or unsaturated, which may contain one or two heteroatoms, such as, for example, nitrogen, sulfur or oxygen, and which may be substituted one or two • 3 times with = 0, = S or R, • D means a direct bond, -NR6-, -C (0) -NR6-, E means hydrogen, R6-C (= NR6) NR6-, R6R6 'NC (= NR6) -, R6R6'NC (= NR6) -NR6- or a ring system of 4 to 11 members, monocyclic or polycyclic, aromatic or non-aromatic, which can optionally contain 1-4 heteroatoms of the series N, 0 and S, and which may possibly be substituted one to three times with R, R5, = 0, = S or R6R6 'NC (= NR6) -, such as, for example, the radicals indicated in the previous definition of E with their structural formulas; n means zero, one, two, three, four or five; m means zero, one, two, three, four or five; i means zero or one; p mean, independently of one another, zero, one or two; q mean, independently of one another, zero, one or two; r means zero, one, two, three, four, five or six; s means zero, one, two, three, four or five; t means zero, one, two, three, four or five; k means zero or one; u means one or two; v means, in the radicals indicated in the previous definition of E, the numbers zero, one, two or three; in all its stereoisomeric forms and mixtures thereof in all ratios, and their physiologically tolerable salts, not being included in this group of preferred compounds are the analogous compounds with a 3-de-aza-purine skeleton, a 7-deaza skeleton -purine or a skeleton of 7-deaza-8-aza-purine.

An additional group of preferred compounds are compounds of the formulas I and the, wherein: X means hydrogen, NR6R6 ', hydroxy-alkyl- ^ - Cg) -NH or NH-CO-R6; And it means hydrogen; G means a radical of formula II - (CR1R2) n-A- (CR1R2) rn- (CR1R3) r (CR1R2) q-R4 (II); W means a radical of formula III -B- (CR1R2) r-A '- (CR1R2) s- (CR1R3) k- (CR1R2) t-D-E (III); Ga means a radical of the formula lia - (CR1R2) r-A '- (CR1R2) S- (CR1R3) k- (CR1R2) t-D-E (Ha); Wa means a radical of the Illa formula -B- (CR1R2) n-A- (CR1R2) m- (CR1R3) i- (CR1R2) q-R4 (Illa); A, A ', independently of one another, mean a direct bond, -C (0) NR5, -NR5C (0) -, -C (O) -, -NR5-, -0-, -S-, -SO -, -S0 -, alkynylene- (C2-C4), alkenylene- (C2-C4) or arylene- (C5-C14), being able to be replaced in the aryl radical of one to three carbon atoms by one to three heteroatoms of the series 0, N, S; R 1, R 2, independently of one another, mean hydrogen, fluorine, cyano, C 1 -C 4 alkyl, aryl- (C 5 -C 6), aryl- (C 5 -C 6) -alkyl- (C 1 -C 4), R 6- 0-R7 or R6R6'N-R7; R .3, independently of one another, mean hydrogen, alkyl-C 1 -C 2), cycloalkyl- (C 3 -C 14), cycloalkyl- (C 3 -C 1) -alkyl- (C 1 -Cg), aryl- (C 5) -C1), aryl- - (C5-C14) -alkyl (C1-Cg), R6R6'N-R7, R6C (0) R7, R6S (0) pN (R5) R7, R6OC (0) N (R5) R7, R6C (0) N (R5) R7, R6N (R6) C (0) N (R5) R7, R6N (R6 ') S (0) pN (R5) R7 or RN (R') C (0) R7, wherein unsaturated alkyl may be one or more times and, in addition, alkyl or aryl may be substituted once or several times with fluorine, chlorine, bromine, cyano, R6R6'NR7, nitro, R60C (0) R7, R6C (0) R7 , R6N (R6 ') C (-0) R7, R6N (R6') S (0) pR7, R6 or R6OR7; R4 means C (0) R8; R5 signifies, independently of one another, hydrogen or (C1-C4) alkyl; R °, R ° signify, independently of one another, hydrogen, cycloalkyl- (C3-C14), cycloalkyl- (C3-C14) -alkyl- (C1-Cg), aryl- (C5-C14), where one to three carbon atoms can be replaced by one to three heteroatoms of the series N, O, S, or aryl- (Cg-C1) -alkyl- (C1-Cg) , where, in the aryl part, one to three carbon atoms can be replaced by one to three heteroatoms of the series N, O, S, or R6 and R6, together with the atoms that join them, form a system of rings, which may optionally also contain further heteroatoms of the N, S, O series, such as, for example, morpholine, piperazine, piperidine, pyrrolidine; R 'signify, independently of one another, alkylene- (C1-C) or a direct bond; R, R8 'signify, independently of one another, hydroxy, alkoxy-C!), Aryl- (C5-C1) -alkoxy- (C1-C4), aryloxy- (C5-C14), alkyl -fC ^ -C) -carboni loxi-alkoxy- (C1-C4), ari1- (C5-C14) -alkyl-iC ^ C. ^) -carbonyloxy-alkoxy- 0 ^ -0 ^) or the radical of a amino acid; means -O-, -S-, -NR-, a direct bond or a divalent radical of a 3 to 7 membered ring, saturated or unsaturated, which may contain one or two heteroatoms, such as, for example, nitrogen, sulfur or oxygen, and which can be substituted once or twice with radicals of the series = 0, = S and R3; means a direct bond, -NR6-, -C (0) -NR6-, -NR6-C (0) -, -NR6-C (0) -NR6-, -NR6-C (0) 0-, - NR6-N = CR6-, -R6C = N-NR6-, -N = CR6- or -R6C = N-, the divalent radicals represented by D being linked to group E via the free bond on the right side; means hydrogen, R6-C (= NR6) -NR6 '-, R6R6'NC (= NR6') -, R6R6'N-C (= NR6 ') -NR6- or a radical of the series which may optionally be substituted one to three times with radicals of the series R3, R5, = 0, = S and R6R6 * N-C (= NR6) -; n means one, two, three or four; m means zero or one; i means zero or one; q means zero or one; p mean, independently of one another, zero, one or two; r means zero, one, two, three, four or five; s means zero, one or two; t means zero, one or two; k means zero or one; v means zero, one, two or three; in all its stereoisomeric forms and mixtures thereof in all ratios, and their physiologically tolerable salts, as well as their prodrugs.

Especially preferred are the compounds of the formulas I and the, wherein: X means hydrogen, NR6R6 'or NH-CO-R6; And it means hydrogen; G means a radical of formula II - (CR1R2) n-A- (CR1R2) m- (CR1R3) - (CR1R2) q-R4 (II); W means a radical of formula III -B-ÍCR1R2) r-A '- (CR1R2) S- (CR1R3) k- (CR1R2) t-D-E (III); Ga means a radical of the formula - < CR1R2) r-A '- (CR1R2) S- (CR1R3) k- (CR1R2) t-D-E (lia); Wa means a radical of the Illa formula -B- (CR1R2) n-A- (CR1R2) m- (CR1R3) r (CR1R2) q-R < ("Ta).

A, A ', independently of one another, mean a direct bond, -C (0) NR5-, -NR5C (0) - or arylene- (C5-Cg), and one to two carbon atoms may be replaced in the aryl radical. carbon by nitrogen atoms; R1, R2 signify hydrogen; R3 signifies, independently of one another, hydrogen, alkyl-C ^ Q), cycloalkyl- (C3"C14), cycloalkyl- (C3-C14) -alkyl- (C1-Cg), aryl- (C5-) C14), aryl- (C5-C14) -alkyl (C1-Cg), R6R6'N-R7, R6OC (0) N (R5) R7, R6C (0) N (R5) R7, R6N (R6 ' ) C (0) N (R5) R7, R6C (0) R7 R RN (R6) C (0) R, wherein unsaturated alkyl may be one or more times and, in addition, wherein alkyl or aryl may be substituted one or more times with fluorine, chlorine, bromine, cyano, R6R6'NR7, R6C (0) R7, R6N (R6 ') C (0) R7, R6 or R60R7; R4 means C (0) R8; R5 signifies, independently of one another, hydrogen or alkyl-1Cj--C.j); R6, R6 signify, independently of one another, hydrogen, alkyl- (C-Cg), cycloalkyl- (C3"C1), cycloalkyl- (C3-C12) -alkyl- (C1-Cg), aryl- (C5) -C14), where one to three carbon atoms can be replaced by one to three heteroatoms of the series N, S, O, or, where, in the aryl part, one to three carbon atoms can be replaced by one to three heteroatoms of the series N, S, O; R means a direct link; they mean, independently of one another, hydroxy, alkoxy- (C1-C4), aryl- (C5-C1) -alkoxy- (C1-C), aryloxy- - (C5-C14), alky1- (Cj_-Cg) -carboni loxy-alkoxy- (C 1 -C 4), aryl- (C 5 -C 14) -alkyl- (C 1 -C 4) -carboni loxy-alkoxy- (C 1 -C 4) or the radical of an amino acid; B means -O-, -S-, -NR-, a direct bond or a divalent radical of a 3 to 7 membered ring, saturated or unsaturated, which may contain one or two heteroatoms, such as, for example, nitrogen, sulfur or oxygen, and which may be substituted once or twice with radicals of the series = 0, = S and R, D means a direct bond, -NR6-, -C (0) -NR6- or -NR6- -C (O) -; means hydrogen, R6-C (= NR6) -NR6 '-, R6R6' N-C (= NR6 ') -, R6R6'N-C (= NR6') -NR6- or a radical of the series which may optionally be substituted one to three times with radicals of the series R3, R5, = 0, = S and R6R6 * N-C (= NR6) -; r means zero, one, two, three, four or five; s means zero or one; t means zero or one; k means zero or one; n means one, two, three or four; m means zero or one; i means zero or one; q means zero or one; in all its stereoisomeric forms and mixtures thereof in all ratios, and their physiologically tolerable salts, as well as their prodrugs.

In addition, the compounds of the formula I are especially preferred, in which: X means hydrogen, NR6R6 'or NH-CO-R6; And it means hydrogen; G means a radical of formula II - (CRR2) n-A- (CR1R2) m- (CR1R3) l- (CR1R2) q-R4 (II); W means a radical of formula III -B- (CR1R2) r-A '- (CR1R2) 8- (CR1R3) k- (CR1R2) t-D-E (III); A, A 'mean a direct link; R1, R2 signify, independently of one another, hydrogen, (C1-C) alkyl, aryl- (C5-Cg) or aryl- (C5-Cg) - -alkyl-ICj ^ -C.j); R3, independently of one another, means hydrogen, (C1-C1g) alkyl, (C3-C14) cycloalkyl, (C3-C14) -alkyl- (C1-Cg) alkyl, (C5-C14) aryl- , aryl- - (C5-C14) -alkyl- (C1-Cg), R6R6'N-R7, R6OC (0) N (R5) R7, R6S02N (R5) R7, R6C (0) N (R5) R7 , R6N (R6 ') C (0) N (R5) R7, R6C (0) R7 or R6N (R6') C (0) R7, wherein unsaturated alkyl may be one or more times and, in addition, may be alkyl or aryl substituted one or more times with fluorine, chlorine, bromine, cyano, R6R6'NR7, R6C (0) R7, R6N (R6 ') C (0) R7, R6 or R6OR7; R4 means C (0) R8; R5 signifies, independently of one another, hydrogen or (C1-C4) alkyl; R6, R6 signify, independently of one another, hydrogen, alkyl-CCj-C ^ g), cycloalkyl- (C3-C12), cycloalkyl- (C3-C12) -alkyl- (C1-Cg), aryl- ( C5-C14), where from 1 to 3 carbon atoms can be replaced by 1 to 3 heteroatoms of the N, S, 0, or aryl- (C5-C14) -alkyl- (C1-Cg) series, in where, in the aryl radicals, from 1 to 3 carbon atoms can be replaced by 1 to 3 heteroatoms of the series N, S, 0, and R6 and R6 can also form, together with the atoms that join them, a system of rings which may optionally also contain additional heteroatoms, in particular one, two or three heteroatoms of the N, S, O series; R 'means a direct link; R8 signifies, independently of one another, hydroxy, alkoxy- (C1-C4), aryl- (C5-C14) -alkoxy- (C1-C4), aryloxy- - (C5-C1), alkyl- (C1-Cg) -carbonyloxy-alkoxy- (C1-C) or ary1- (C5-C14) -alkyl 1- (C1-C4) -carbonyloxy-alkoxy- (C? -C4) B means 1,4-piperidinediyl or 1,4-piperazindiyl, in the case of the radical 1, 4-piperidinedi-ilp being attached, the nitrogen atom of the piperidine to the purine skeleton; D means a direct bond, -NR6-, -C (0) -NR6- -NR ° -C (0) -; means hydrogen, R6-C (= NR6) NR6 'R6R6' N-C (= NR6 ') -, R6R6 'N-C (= NR6) -NRc or a radical of the series which can optionally be substituted one to three times with radicals of the series R- R- = 0, = S and R6R6'N-C (= NR6) -; r means zero, one or two; s means zero or one; t means zero or one; k means zero or one; n means zero, one or two; m means zero or one; i means zero or one; q means zero or one; in all its stereoisomeric forms and mixtures thereof in all ratios, and their physiologically tolerable salts, as well as their prodrugs.

Very especially preferred are the compounds of the formula I, wherein: X means hydrogen; And it means hydrogen; G means a radical of formula II - (CR1R2) n-A- (CR1R2) m- (CR1R3) r (CR1R2) q-R4 di); W means a radical of formula III -B- (CR1R2) r-A '- (CR1R2) s- (CR1R3) k- (CR1R2) t-D-E (III); A, A1 means a direct link; 1 T R, R? they mean, independently of one another, hydrogen or (C 1 -C 2) alkyl, especially hydrogen; R3 means R6R6'N-R7, R6OC (0) N (R5) R7, R6S02N (R5) R7, R6C (0) N (R5) R7 or R6N (R6 ') C (0) N (R5) R7, in special R6OC (0) N (R5) R7; R4 means C (0) R8; R5 means hydrogen or (C1-C2) alkyl, especially hydrogen; R, R6 'signify, independently of one another, hydrogen, (C3-C12) -cycloalkyl- (C1-Cg) alkyl, (C5-C14) aryl, wherein from 1 to 3 carbon atoms may be replaced by 1 to 3 heteroatoms of the series N, S, 0, or aryl- (Ccj-C14) -alkyl- (C1-Cg), where, in the aryl radicals, from 1 to 3 carbon atoms can be replaced by 1 to 3 heteroatoms of the series N, S, 0, and Rfi ° and Rfi 'may also form, together with the atoms joining them, a ring system which may optionally also contain additional heteroatoms, especially one, two or three heteroatoms of the series N, S, 0; 7 R means a direct link; R8 means hydroxy, alkoxy- (C1-C4), aryl- (C5-C14) -alkoxy- (C1-C4), aryloxy- (C5-C14), alkyl- (Cj-Cg) -carbonyl- oxy- (C 1 -C 4) alkoxy or (C 5 -C 1) aryl- (C 1 -C 4) alkyloxycarbonyloxy-alkoxy-C 2 -C 4), especially hydroxy or (C 1 -C 4) alkoxy; B means 1,4-piperidinediyl, the nitrogen atom of piperidine being attached to the purine skeleton; D means -NR6- or -C (0) -NR6-, the nitrogen atom being linked in the group -C (0) -NR6- to the group E; E means R6R6'N-C (= NR6 ') - or a radical of the series R ~ which may optionally be substituted one to three times with radicals of the series R3, R5, = 0, = S and R6R6'N-C (= NR6) -; r means zero or one; s means zero; t means zero; k means zero; n means one; m means zero; i means one; q means zero; in all its stereoisomeric forms and mixtures thereof in all ratios, and their physiologically tolerable salts, as well as their prodrugs.

Especially preferred compounds according to the invention are the compounds of the formula Ih, wherein R3 represents R6R6'N-R7, R6OC (0) N (R5) R7, R6S02N- (R5) R7, R6C (0) N (R5) R7 or R6N (R6 ') C (0) N (R5) R7, in particular represents R6OC (0) N (R5) R7, and Rh represents the carboxylic acid group COOH or represents a carboxylic acid derivative, for example an ester, such as for example an alkyl- (C1-C4) ester, that is to say for example the group COO-alkyl- (C ^ -C); in all its stereoisomeric forms and mixtures thereof in all ratios, and their physiologically tolerable salts, as well as their prodrugs. In the compounds of the formula Ih, in which R 'represents a direct bond, the stereochemical center (h) in the formula Ih preferably has the configuration S. The compounds of the formula Ih in 7, which R represents a direct bond, can be referred to as 2-amino-3- (6- (4- (1, 4, 5, 6-tetrahydropyrimidin-2-yl-carbamoyl) -piperidin-1-yl) - purin-9-yl) -propionic, optionally substituted in the 2-amino group, and their derivatives, for example their esters. Especially preferred is 2S-benzyloxycarboni lamino-3- (6- (4- (1, 4,5,6-tetrahydropy-rimidin-2-yl-carbamsyl) -piperidin-1-yl) -purin-9-yl ) -propionic of the formula Ik and its physiologically tolerable salts, as well as its prodrugs. The compounds of the formulas I and II can be prepared in a general manner, for example in the course of a convergent synthesis, by linking two or more fragments, which can be derived retrosynthetically from the formulas I and II. In the preparation of the compounds of the formulas I and, in general, in the course of the synthesis, it may be advantageous or necessary to employ in the form of precursors the functional groups which, in the respective stage of the synthesis, could lead to reactions unwanted or secondary reactions, precursors that are later transformed into the desired functional groups, or temporarily block the functional groups by a strategy of protecting groups adapted to the problem of synthesis, which is known to the person skilled in the art (Greene, Wuts, Protective Groups in Organic Synthesis, Wiley, 1991). Objects of the present invention are also processes for the synthesis of the compounds of the formula I, which are characterized in that one or more of the following steps are carried out for the constitution of the compounds of the formula I. a) A compound of formula IV, wherein Ll represents a customary leaving group, known to the person skilled in the art, for example chlorine, bromine, iodine, OTos or OMes, preferably chlorine or bromine, and X and Y are defined as above, but the functional groups may optionally be also present in the form of precursors or may be provisionally protected with a protecting group, is reacted with a compound of the formula V L2-ICR »11 D R2 1 D2 _ / D1 D3V rDl o2 _D10 A-fCR1 R < CR R INCR1 R ') q-R < V > where R R1, R2, R3, A, n, m, i and q are defined as above, R 10 is defined as the group R was defined before, but is optionally protected with a protecting group, for example for R 4 = COOH, with a terebutyl protecting group or a methyl or ethyl protecting group, L2 means hydroxy or a leaving group known to the person skilled in the art, for example chlorine, bromine, iodine, OTos, OMes or OTf, to give a compound of formula VI, where R rrepnrreeflseßnnttaa - Í (CPRRX ^ RR ^) n-_AA-- ((TCRRX ^ RR¿ ^) 1 m-_ ((CGRX! RR J3) 11.-_ (/ -CGRRi! R) I q -RD? 1? 0 and, for that matter, the above meanings are valid, the reaction being carried out according to methods known to the person skilled in the art (see bibliographical sources in J. March, Advanced Organic Chemistry, fourth edition, Wiley, 1992). It is preferred to work in an appropriate organic solvent or diluent, for example DCM, CHC13, THF, diethyl ether, n-heptane, n-hexane, n-pentane, cyclohexane, diisopropyl ether, methyl tert-butyl ether, acetonitrile, DMF, DMSO, dioxane, toluene, benzene, acetic acid ethyl ester, or a mixture of these solvents, optionally with the addition of a base, such as, for example, butyl lithium, lithium diisopropylamide (LDA), sodium hydride, sodium amide , potassium tert-butylate, CaC03 # Cs2C ?, triethylamine, diisopropylethylamine or complex bases (sodium amide / R12ONa, representing R12 alkyl- (C2-C 6) or CH3CH2OCH2CH2.) For L2 = OH, the reaction can be carried out, for example, according to the conditions described for the Mitsunobu reaction (Hughes, Organic Reactions 42 (1992) 335-656), for example by reaction with triphenylphosphine and DEAD in THF. a2) The compound of the formula VI is reacted with a compound of the formula VII, H-B- (CR1R2) r-A '- (CR1R2) S- (CR1R3) k- (CR1R ^ -R13 (VII) wherein R 13 represents -D-E or a group R 14 which can be converted to D-E and which is optionally provided with appropriate protecting groups and for which the above meanings are otherwise valid. R 14 represents, for example, an amino group -NHR, optionally protected, it being possible to use as protective group, for example, the protecting group Boc, a protected carboxylic acid ester, an aldehyde -C (0) H, a keto group -C (0) R6, or a protected mercapto group. In such a case, a compound of the formula VIII is obtained wherein R15 represents -B-ICR ^ 2) r-A '- (CR1R2) s- (CR1R3) k- - (CR1R2) t-R13 and for which, in addition, the above meanings are valid. The reaction is carried out according to methods known to the person skilled in the art (see bibliographical sources in J. March, Advanced Organic Chemistry, fourth edition, Wiley, 1992), preferably in an appropriate organic solvent or diluent, for example DCM, CHCl3, THF, diethyl ether, n-heptane, n-hexane, n-pentane, cyclohexane, diisopropyl ether, methyl tert-butyl ether, acetonitrile, DMF, DMSO, dioxane, toluene, benzene, ethyl acetate, or mixtures of these solvents, optionally with the addition of a base, such as, for example, butyllithium, lithium diisopropyl-amide (LDA), sodium hydride, sodium amide, potassium tert-butylate, CaCO, Cs 2 C 3, triethylamine , diisopropyl-1 or ethylamine or complex bases (sodium amide / R ^ ONa, representing R12 alkyl- (C2-Cg) or CH3CH2OCH2CH2), also being able, in the case of B = NR6, to serve as a base an excess of VII . a3) Optionally the protective groups are separated in R13 and / or R1 ^ in the compound of formula VIII by known methods (Greene, Wuts, Protective Groups in Organic Synthesis, Wiley, 1991). For example, if R 13 represents an amino group protected with Boc, then the Boc group can be separated, for example, by reaction with trifluoroacetic acid. a4) Then, optionally R13 in the compound of formula VIII is reacted by known procedures to give the group D-E, for example by one of the following procedures. a4.1) By reaction of compounds with R 3 = NHR 6 with lH-pyrazole-1-carboxamidine or cyanamide, a guanidine is obtained (see Bernatowicz et al., J. Org. Chem. 57 (1992) 2497). a4.2) By reaction of compounds with R13 = NHR6 with a monocycle or polycycle of the type wherein L3 represents a substitutable nucleophilic leaving group, such as, for example, halogen or SH, SCH3, SOCH3, S02CH3 or HN-N02, compounds with the terminal group are obtained (for the procedure, see, for example, AF Mckay et al., J. Med. Chem. 6 (1963) 587; MN Buchman et al., J. Am. Chem. Soc. 71 (1949) 766; Jung et al., J. Med. Chem. 34 (1991) 1110; or G. Sorba et al., Eur. J. Med. Chem. 21 (1986), 391). a4.3) By reaction of compounds with R13 = NHR6 with compounds of the type in which L3 represents a substitutable nucleophilic leaving group, such as, for example, halogen or SH, SCH3, SOCH3, S02CH or HN-NO2, compounds are obtained with the terminal group (for the procedure, see, for example, Miller, Synthesis 1986, 777; or Brimble, J. Chem. Soc. Perkin Trans. 1 (1990) 311). a4.4) By reaction of compounds with R 13 NHR ° with a monocycle or polycycle of the type wherein L3 represents a substitutable nucleophilic leaving group, such as, for example SCH3, compounds with the terminal group are obtained (for the procedure, see, for example, T. Hiroki et al., Synthesis (1984) 703; Purkayastha et al., Indian J. Chem. Sect. B 30 (1991) 646). a4.5) Compounds, where -D-E means the radical of an aminoguanidinyl imine of the type or a cyclic aminoguanidinylimine of the type they can be prepared, for example, by condensation of compounds of the formula with ketones or aldehydes of type 0 = C (R6) -, or with the corresponding acetals or ketals, by methods of the literature, for example, analogously to N. Desideri et al., Arch. Pharm. 325 (1992) 773-777 or A. Alves et al. Eur. J. Med. Chem. Chim. Ther. 21 (1986) 297-304, whereby the aminoguanidinyl imines may optionally be obtained as mixtures of E / Z isomers which can be separated by standard chromatographic methods. a4.6) Compounds, where -D-E represents R6-C (= NR6) -NR6-N = C (R6) - or a radical containing a monocycle or a polycycline of the type they are obtained analogously to a4.5). a4.7) Compounds, in which -D- represents -S (0) 2NR6-, can be prepared, for example, by oxidizing compounds with R13 = SH, by procedures known from the literature (see Houben-Weyl, Methoden der organischen Chemie, volume E12 / 2, Editorial Georg Thieme, Stuttgart 1985, pages 1058 et seq.), To give sulphonic acids (R13 = SO3H), from which the compounds are then prepared with -D- = -S (0) 2NR6-, for example, directly or through corresponding sulfonic acid halides, by hard-bonding an amide bond, protecting groups sensitive to oxidation of the molecule, such as, for example, amino groups, amidino groups or guanidino groups , in case they were necessary for the realization of the oxidation, by means of appropriate protective groups. a4.8) Compounds, in which -D- represents -S (0) NR6, can be prepared, for example, by converting compounds with RJ = SH in the corresponding sulphide and then oxidizing with meta-chloroperbenzoic acid to the sulfinic acids (R13 = S02H) (see Houben-Weyl, Methoden der organischen Chemie, volume Ell / 1, Georg Thieme, Stuttgart, 1974) , pages 618 et seq.), from which the corresponding sulfinic acid amides can be prepared by methods known from the literature. Generally, other methods known from the literature can also be used for the preparation of compounds of the formulas I and the con -D- = -S (0) uNR6- (u = 1, 2) (see Houben-Weyl, Methoden der organischen Chemie, volume Ell / 1, Georg Thieme Editorial, Stuttgart, 1985, pages 618 et seq., or volume Ell / 2, Stuttgart 1985, pages 1055 et seq.). a4.9) Compounds, where -D-E- represents R R * N- C (N = R) -NR6-C (0) - or the radical of a cyclic acylguanidine of the type they can be prepared, for example, by reacting a compound, wherein R13 represents -C (0) -L4 and L4 represents an easily substitutable nucleophilic leaving group, with the corresponding guanidine or guanidine derivative of the type or with guanidine or cyclic guanidine derivative of type The activated acid derivatives, indicated above, with the group L4 (0) C-, in which L4 can mean, for example, an alkoxy group, preferably a methoxy group, a phenoxy group, a phenylthio group, a methylthio group, a 2-pyridylthio group or a nitrogenous heterocycle, preferably 1-izolyl, are advantageously obtained, in a manner known per se, from the carboxylic acid chlorides (L4 = Cl) on which they are based, which, in turn, are they can be prepared, again in a manner known per se, from the carboxylic acids on which they are based, for example with thionyl chloride. In addition to the carboxylic acid chlorides (L4 = Cl), other acid derivatives activated with the group of the type L4 (0) C- can also be prepared, in a manner known per se, directly from the carboxylic acids in which they are based (L 4 = OH), such as, for example, the methyl ester (L 4 = OCH 3) by treatment with gaseous HCl in methanol, the izolides (L 4 = 1-izolyl) by treatment with carbonyldiizole (see Staab, Angew. Int. Ed. Engl 1, 351-367 (1962)) or the mixed anhydrides (L4 = C2H5OC (0) 0 or TosO) with Cl-COOC H5 or tosyl chloride, in the presence of triethylamine in an inert solvent. Activation of the carboxylic acids can also be carried out with carbodiis, such as dicyclohexylcarbodii (DCC1) or with 0- ((cyano (ethoxycarbo-nyl) methylene) amino) -1, 3,3-tetramethyluronium tetrafluoroborate ( "TOTU") (Kdnig et al., Proc. 21st Europ. Peptide Symp., 1990 (compilers Giralt, Andreu), Escom, Leiden, 1991, page 143) and other activation reagents common in peptide chemistry (a series of methods suitable for the preparation of activated derivatives of carboxylic acids, with indication of the bibliographic sources, are given in J. March, Advanced Organic Chemistry, third edition (John Wiley &Sons, 1985), page 350). The reaction of an activated derivative of carboxylic acid with the group of the type L4 (0) C-, with the respective guanidine or guanidine derivative is preferably carried out, in a manner known per se, in an inert, polar organic solvent, protic or aprotic, the reaction of the methyl esters (La = OMe) with the respective guanidines in methanol, isopropanol or THF being advantageously carried out at temperatures from 20 [deg.] C. to the boiling point of these solvents. In the majority of the reactions of compounds with the group L4 (0) C- with salt-free guanidines, advantageously work is carried out in inert aprotic solvents, such as THF, dimethoxyethane, dioxane, but water can also be used as a solvent using a base, such as, for example, NaOH, in the case of the reaction of compounds with the group L4 (0) C- with guanidines. If L 4 is Cl, advantageously, addition of an acid acceptor, for example in the guanidine form or excess guanidine derivative, is used to fix the halogenated hydrazide. a4.10) Compounds, in which -D-E represents R6-C (= NR6) --NNRR66 - CC ((00) - or a radical containing a monocycle or polycyclic of the type can be obtained analogously to a4.9). a4.11) Compounds, in which -D-E represents the radical of a sulfonylguanidine or a sulfoxilguanidine of the type R6R6'N-C (= NR6) - • NR6-S (0) u- (u = 1, 2) or it can be prepared, according to methods known from the literature, by reacting compounds of the formulas R6R6'N-C (= NR6) -NHR6 O with compounds in which R13 represents S (0) u-L5 (u = 1, 2) and L5 means, for example, Cl or NH2, for example analogously to S. Birtwell et al., J. Chem. Soc (1946) 491, or Houben-Weyl, Methoden der organischen Chemie, volume E4, Georg Thieme Editorial, Stuttgart, 1983, pages 620 et seq. a4.12) Compounds, where -DE represents R6-C (N = R6) -N NRR66-SS ((00)) uu-- ((uu == 11, 22)) or the radical containing a monocycle or polycycle of the type (u = 1, 2), can be obtained analogously to a4.11). a4.13) Compounds, in which -D- represents -NR6-C (0) -, can be prepared, for example, by reacting a compound with the radical R13 = -NHR6, with an appropriate carbonic acid derivative , preferably phosgene, diphosgene (trichloromethyl ester of chloroformic acid), triphosgene (bis (tert-trichloromethyl ester) of carbonic acid), ethyl ester of chloroformic acid, chloroformic acid i-butyl ester, bis- (1-hydroxy) carbonate lH-benzotriazolyl) or N, N'-carbonyldiyl idazole, in a solvent inert to the reagents used, preferably DMF, THF or toluene, at temperatures between -20 ° C and the boiling point of the solvent, preferably between 0 ° C and 60"C, to give 1 or first a compound in which Rí J represents meaning L6, according to the carbonic acid derivative used, for example a hydroxy, halogen group, such as, for example, chloro, ethoxy, isobutoxy, benzotriazole-1-oxy or 1-imidazolyl. Then, the subsequent reaction of these derivatives with R6R6 'N-C (= NR6) -NR6? OR R6-C (N = R6) -NHR6, or with the compound containing a monocycle or a polycycle of the type is carried out as described above for the preparation of acylguanidines or acylguanidine derivatives in a4.9). a4.14) Compounds of the formula I, in which -D-E represents a bis-aminotriazole radical or a bis-amino-oxadiazole radical, can be prepared, for example, according to P.J. Garrett et al., Tetrahedron 49 (1993) 165, or R. Lee Webb et al., J. Hete-rocyclic Chem. 24 (1987) 275. a4.15) Compounds of the formula I, wherein -DE represents a urea group or a thiourea group, can be synthesized by known procedures, such as those summarized, for example, in C Ferri, Reaktionen der organischen Synthese, Georg Thieme, Stuttgart 1978, for example by the reaction of the corresponding amines with isocyanates or isothiocyanates. a5) After the reaction of R 11J in the compound of the formula VIII to give the group D-E, optionally still other protective groups are removed by known methods (see Greene, Wuts, see above). a6) Possibly, the compounds of formula I obtained are converted into their salts, especially into their pharmaceutically usable or non-toxic and physiologically tolerable salts, and / or into prodrugs.

In addition, methods for the synthesis of the compounds of the formula la, which are characterized in that one or more of the following steps are carried out for the constitution of the compounds of the formula la are also subject of the present invention. bl) A compound of the formula IV is reacted with a compound of the formula IX wherein R1, R2, R3, A ', r, s, k, t, R13 and L2 are defined as above, to give a compound of formula X, wherein R16 represents - (CR: R2) rA '- (CR1R2) s- (CR1R3) k - (CR1R2) tR13, Ll, X and Y are defined as above and, otherwise, the meanings are valid before indicated. The reaction is carried out by methods known to those skilled in the art (see literature sources in J. March, Advanced Organic Chemistry, fourth edition, Wiley, 1992), preferably in an appropriate organic solvent or diluent, for example DCM, CHCl3, THF , diethyl ether, n-heptane, n-hexane, n-pentane, cyclohexane, diisopropyl ether, methyl tert-butyl ether, acetonitrile, DMF, DMSO, dioxane, toluene, benzene, ethyl acetate, or mixtures of these solvents, optionally with the addition of a base, such as, for example, lithium butyl lithium diisopropylamide (LDA), sodium hydride, sodium amide, potassium tert-butylate, CaC0, Cs2CO3, triethylamine, diisopropyl- ethylamine or complex bases (sodium amide / R12ONa, representing R12 alkyl? - (C2-C6) or CH3CH2OCH2CH2). For L2 = OH, the reaction can be carried out, for example, under the conditions described for the Mitsunobu reaction (Hughes, Organic Reactions 42 (1992) 335-656), for example, by reaction with triphenylphosphine and DEAD in THF. b2) The compound of formula X is reacted with a compound of formula XI, H-B- (CR1R2) n-A- (CR1R2) m- (CR1R3) i- (CR1R2) q-R10 (XI); wherein R1, R2, R3, R10, A, B, n, m, i and q are defined as above, to give a compound of formula XII, wherein R, X and Y are defined as above, R17 represents -B- (CR1R2) nA- (CR1R2) m- (CR1R3) i- (CR1R2) q -R10 and, otherwise, the meanings indicated above are valid . b3) For the further synthesis of the compounds of the formula, the following is then proceeded analogously to steps a3) to a6) in the synthesis of the compounds of the formula I. In the process for the synthesis of the compounds of the formula I it is also possible to carry out step a2) before al). In the process for the synthesis of the compounds of the formula la can also be carried out step b2) before the bl). The introduction of the substituents on the carbon at position 6 of the purine backbone can be carried out, for example, by the Stille coupling, as described, for example, in Langli et al., Tetrahedron 52 (1996) 5625; Gundersen, Tetrahedron Lett. 35 (1994) 3153, or by Heck coupling, as described, for example, in Koyama et al., Nucleic Acids Res., Symp. Ser. 11 (1982) 41. A substituent X can also be introduced at the 2-position of the purine backbone at the end of the synthesis of the compounds of the formulas I and the, by known methods, such as those described, for example, in DA Nugiel, J. Org. Chem. 62 (1997) 201-203; N. S. Gray, Tetrahe-dron Lett. 38 (1997) 1161 and in the literature cited therein. A substituent represented by Y in the 8-position can be introduced by known methods, such as those described, for example, in E. J. Reist et al., J. Org. Chem. 33 (1968) 1600; J. L. Kelley et al., J. Med. Chem. 33 (1990) 196; or E. Vanotti et al., Eur. J. Chem. 29 (1994) 287. The compounds of the formulas I and the according to the invention and their physiologically tolerable salts can be administered to the animal, preferably to the mammal, and in particular to the human being, as a medicine, alone, in mixtures among themselves or in the form of pharmaceutical preparations which allow enteral or parenteral use, and which contain as an active component an effective dose of at least one compound of the formula I or of the formula la, or one of its salts, or one of its prodrugs, together with the correct and pharmaceutically usual support substances and / or additives. The pharmaceutical preparations normally contain from about 0.5 to 90% by weight of the therapeutically active compounds. The medicaments can be administered, for example, in the form of pills, tablets, varnished tablets, dragees, granules, hard and soft gelatin capsules, solutions, syrups, emulsions, suspensions or mixtures for aerosols. The administration can also be carried out rectally, for example in the form of suppositories, or parenterally, for example in the form of solutions for injection or solutions for infusion, microcapsules or rods, percutaneously, for example in the form of ointments or tinctures, or nasally, for example in the form of nasal sprays. The preparation of the pharmaceutical preparations is carried out in a manner known per se, using pharmaceutically inert inorganic or organic support substances. For the preparation of pills, tablets, dragees and hard gelatine capsules, for example, lactose, corn starch or its derivatives, talc, stearic acid or its salts, etc. can be used. Supporting substances for soft gelatin capsules and suppositories are, for example, fats, waxes, semi-solid and liquid polyols, natural or hardened oils, etc. Suitable support substances for the preparation of solutions and syrups are, for example, water, sucrose, invert sugar, glucose, polyols, etc. Water is suitable as support substances for the preparation of solutions for injection, alcohols, glycerol, polyols, vegetable oils, etc. Suitable carriers for microcapsules, implants or rods are copolymers of glycolic acid and lactic acid. The pharmaceutical preparations may contain, together with the active ingredients and carrier substances, additives, such as, for example, fillers, spreaders, disintegrants, binders, lubricants, crosslinkers, stabilizers, emulsifiers, preservatives, sweeteners, dyes, agents flavors or flavorings, thickeners, diluents, buffer substances, in addition to dissolving solvents or inducers, or agents to achieve a deposition effect, as well as salts for the variation of osmotic pressure, coating agents or antioxidants. They may also contain two or more compounds of the formulas I or the and / or their physiologically tolerable salts, in addition to, together with at least one compound of the formulas I or the one or of one of its salts, still one or more other substances therapeutically active The dose can vary between wide limits and has to be adapted in each particular case to the individual peculiarities. In the case of oral administration, the daily dose is generally from about 0.01 to 100 mg / kg, preferably 0.1 to 5 mg / kg, especially 0.3 to 0.5 mg / kg of body weight , for the achievement of more effective results. Also in the case of intravenous application, the daily dose is generally from about 0.01 to 100 mg / kg, preferably 0.05 to 10 mg / kg of body weight. The daily dose can be subdivided, especially in the case of the application of greater amounts, in several partial administrations, for example in 2, 3 or 4. It may even be necessary, depending on the individual behavior, to deviate upwards or downwards. below the indicated daily dose. In addition to the active drug ingredients, the compounds of the formulas I and II can also be used for diagnostic purposes, for example for in vitro diagnostics, and as an auxiliary agent in biochemical investigations, in which an inhibition of the vitronectin receptor is attempted or an influence of cell-cell or cell-matrix interactions. In addition, they can serve as intermediates for the preparation of other compounds, especially other medicament active ingredients which are obtainable from the compounds of the formulas I and II, for example by modification or by introduction of radicals or groups.

Abbreviations used: AcOH acetic acid Boc tert-butoxycarbonyl DCC1 dicyclohexylcarbodiimide DCM dichloromethane DEAD diethylazodicarboxylate DIPEA diisopropylethylamine DMF dimethylformamide DMSO dimethylsulfoxide AE ethyl acetate FAB bombardment by fast atoms HOOBt 3-hydroxy-4-oxo-3,4-dihydro-2, 3-benzotriazine MeOH methanol Month methylsulfonyl TA room temperature Tf trifluoromethylsulfonyl THF tetrahydrofuran Tos p-toluenesulfonyl Z benzyloxycarbonyl Examples The compounds of formulas I and that which contain in the 6-position of the purine skeleton an amino group which is not a component of a ring, can also be considered as derivatives of adenine (= 6-amino-purine) and be designated as such in the denomination of the compounds. 2 Purine 2 The substituents which are attached to the nitrogen atom of the amino group in the 6-position of adenine are provided in this designation form with the addition N. The substituents which are attached to the nitrogen atom of the ring in the 9-position are provided with the addition N9. In the name of the substitute-te is indicated, at the beginning, in which position in the substitute-te the substituent is attached to the nitrogen atom N6 or N, according to the chosen designation form. The same is true for the compounds which are designated as N9-substituted derivatives of the purine.

Example 1 N6- (1- (5-guanidinopenti1)) -N9- (3- (2S-acid (benzyloxycarbonylamino) propionic) -adenine la) N9- (3- (2S- (benzyloxycarbonylamino) -tert-butyl) -6-chloropurine propionate 2.63 g (17 mmol) of 6-chloropurine and 4.46 g (16.5 mmol) of triphenylphosphine were suspended under argon in 50 ml of absolute THF. To this mixture was added, at RT, 2.56 ml (16.3 mmol) of DEAD and stirred for 15 minutes at RT, forming a clear solution. To this solution was added 3.78 g (12.8 mmol) of tert-butyl ester of N-benzyloxycarboni 1-L-serine (prepared according to M. Schultz, H. Kunz, Tetrahedron: Asymmetry 4 (1993) 1205- 1220), dissolved in 50 ml of absolute THF, for 1.5 h. Then, it was stirred for 2 h more at RT. The solvent was removed by evaporation, the residue was triturated with ether and chromatographed on silica gel (toluene: AE 98: 2 to 7: 3), obtaining 2.85 g (51%) of pure product. 1 H-NMR (200 MHz, DMSO): d = 1.30 (s, 9H, C (CH 3) 3); 4.48-4.73 (m, 3H, N-CH2-CH (NHZ)); 4.98 (s, 2H, CH2-aryl); 7.19-7.40 (m, 5H, aryl-H); 7.87 (d, 1H, NH); 8.61 + 8.77 (2 s, 2H, C6-H + C8-H). MS (FAB): m / e = 432.1 (100%; (M + H) +); 376.0 (60). lb) N6- (1- (5- (tert-butyloxycarbonylamino) pentyl)) -N- (3- (2S-propylate (benzyloxycarbonylamino) -tert-butyl)) -ade-nine To a solution of 431 mg (1 mmol) of (2S- (benzyloxycarbonylamino) -tert-butyl) -6-chloropurine N- (3-propiolate) (Example 1) and 404 mg (2 mmol) of - (tert-butyloxycarbo-nylamino) -l-pentylamine in 5 ml of absolute DMF was added 0.170 ml (1 mmol) of DIPEA and 5 mg of potassium iodide, and the mixture was stirred for 72 h at 40 ° C. evaporated and the residue was chromatographed on silica gel (toluene: EA 7: 3 to 1: 2), obtaining 190 mg (32%) of pure product MS (FAB): m / e = 598.3 (100 %; (M + H) +). lc) N6- (1- (5-aminopentyl)) -N9- (3- (2- (benzyloxycarbonyl-amino) propionic acid)) -adenine 190 mg (0.32 mmol) of N6- (1- (5- (tert-butyloxycarbonylamino) pentyl)) -N- (3- (2S-benzyloxycarbonylamino) -tert-butyl) -adenine propionate (Example lb) were dissolved in 2 ml of 90% trifluoroacetic acid and stirred for 2 h at RT, concentrated by evaporation to dryness and the residue coevaporated twice with acetic acid, then dissolved in water and lyophilized. 134 mg (95%). MS (ES +): m / e = 442.3 (20%; (M + H) +), 308.2 (35).

Id) N6- (1- (5-guanidinopentyl)) - N9- (3- (2S- (benzyloxycarbonylamino) propionic acid)) -adenine 34 mg (0.077 mmol) of N6- (1- (5-aminopentyl) -N9- (3- (2S- (benzyloxycarbonylamino) propionic acid)) -adenine (Example le) were dissolved in 1.5 ml of water and 0.5 ml of DMF were mixed with 0.033 ml (0.193 mmol) of DIPEA and 13.5 mg (0.092 mmol) of 1H-pyrazole-1-carboxy-midin hydrochloride and stirred for 40 h at RT. the solvent was removed by evaporation, the residue was taken up in water and lyophilized, for further purification, it was chromatographed on silica gel (DCM: methanol: acetic acid: water 15: 5: 1: 1) Yield: 70% MS (FAB): m / e = 484.2 (100%; (M + H) +).

Example 2 N6- (1- (4-guanidinobutyl)) -N9- (3- (2S- (benzyloxycarbonylamino) propionic acid)) -adenine 2a) N6- (1- (4- (tert-butyloxycarbonylamino) butyl)) - N9- (3 - (2S- (benzyloxycarbonylamino) -tert-butyl propionate)) -adenine Synthesis analogous to lb, from 431 mg (1 mmol) of N - (3S-benzyloxycarbonyllamino) -tert-butyl) -6-chloropurine N-propionate (Example la) and 376 mg (2 mmol) of 4- (tert-butyloxycarbonylamino) -l-butylamine. Yield: 214 mg (37%). 1 H-NMR (200 MHz, DMSO): d = 1.30 (s, 9H, C (CH 3) 3); 1.38 (s, 9H, C (CH3) 3); 1.41 (m, 2H, CH2); 1.57 (m, 2H, CH2); 3.46 (m, 2H, CH2-NH-Boc); 2.92 (t, 2H, C2-NH-CH2); 4.31-4.58 (m, 3H, N1-CH2-CH (NHZ)); 5.01 (s, 2H, CH2-aryl); 6.99 (t, 1H, C2-NH); 7.10-7.38 (m, 5H, aryl-H); 7.75 (m, 1H, NH-Boc); 7.91 (d, 1H, NH-Z); 8.02 + 8.20 (2 s, 2H, C6-H + C8-H). MS (ES +): m / e = 584.3 (100%; (M + H) +). 2b) N6- (1- (4-aminobutyl)) - N9- (3- (2S- (benzyloxycarbo-nyl-amino) propionic acid)) -adenine Synthesis analogous to Example LE, starting from N6- q - (1- (4-tert-butyloxycarbonyllamino) bu i 1) -N7- (3- (2S- (benzyloxycarbonylamino) -tert-butyl propionate)) - adenine (Example 2a). Yield: 96%. MS (ES +): m / e = 428.2 (100%; (M + H) +), 294.1 (70). 2c) N6- (1- (4-guanidinobutyl)) - N9- (3- (2S- (benzyloxycarbonylamino) propionic acid) -adenine Synthesis analogous to Example Id, starting from N - (1- (4-aminobutyl)) -N- (3- (2S- (benzyloxycarbonyllamino) -propionic acid)) -adenine (Example 2b). Yield: 76%. MS (ES +): m / e = 470.1 (20%; (M + H) +).

Example 3 r N6- (1- (3-guanidinopropy1)) -N9- (3- (2S- (benzyloxycarbo-nil-amino) propionic acid)) -adenine 3a) N6- (l- (3- (tert-butyloxycarbonylamino) propyl)) - N9 - (3- (2S- (benzyloxycarbonylamino) -tert-butyl) -adine propionate Synthesis analogous to lb, starting from 60 mg (0.14 mmol) of N9- (3S-benzyloxycarbonylamino) -6-chloropurine-6-propionate (Example la) and 30 mg (0.17 mmol) of 3- (tert-butyloxycarbonylamino) -l-propylamine.

Yield: 30 mg (38%). 1 H-NMR (200 MHz, DMSO): d = 1.28 (s, 9H, C (CH 3) 3); 1.36 (s, 9H, C (CH3) 3); 1.68 (m, 2H, CH2-CH2-CH2); 1.41 (m, 2H, CH2); 2.98 (t, 2H, C2-NH-CH2); 3.46 (t, 2H, CH2-NH-Boc); 4.29-4.59 (m, 3H, N1-CH2-CH (NHZ)); 5.00 (s, 2H, CH2-aryl); 6.82 (t, 1H, C2-NH); 7.21-7.40 (m, 5H, aryl-H); 7.72 (m, 1H, NH-Boc); 7.91 (d, 1H, NH-Z); 8.03 + 8.20 (2 s, 2H, C6-H + C8-H). MS (ES +): m / e = 570.3 (100%; (M + H) +). 3b) N6- (1- (3-aminopropyl)) - N9- (3- (2S- (benzyloxycarbo-nylamino) propionic acid)) -adenine Synthesis analogous to Example LE, starting from N - (l-- (3- (tert-buti-loxycarbonyl-lamino) propi 1)) -N- (3- (2S- (benzyloxycarbonylamino) -tert-butyl propionate)) - adenine (Example 3a). Performance: 100%. MS (ES +): m / e = 414.2 (100%; (M + H) +), 280.1 (30). 3c) N6- (1- (3-guanidinopropyl)) - N9- (3- (2S (benzyloxycarbonylamino) propionic acid) -adenine Synthesis analogous to Example Id, starting from N6- (1- (3-aminopropyl)) -N9- (3- (2S- (benzyloxycarbonylamino) -propionic acid)) -adenine (Example 3b). Yield: 66%. MS (ES +): m / e = 456.3 (20%; (M + H) +), 130.1 (100).

Example 4 N6- (l- (4- (4,5-Dihydro-lH-imidazol-2-ylamino) butyl)) - N9- - (3- (2S- (benzyloxycarbonylamino) propionic acid)) -adenine 153 mg (0.36 mmol) of N6- (1- (4-aminobutyl)) - N9 - (3- (2S- (benzyloxycarbonylamino) propionic acid)) -adenine (Example 2b) and 88 mg (0.36) mmol) of 2- (methyl mercapto) -2-imidazoline hydroiodide were dissolved in 2 ml of water and adjusted to pH 9.0 with IN NaOH. It was stirred for 100 h at 50 ° C. Then, the solution was brought to pH 1.5 with IN HCl, the solvent was removed by evaporation and the residue was chromatographed several times on silica gel (DCM: MeOH 9: 1 to 1: 2, in each case with 0, 1% AcOH, 0.1% H20), then with DCM: MeOH: H 0: AcOH 8: 2: 0.4: 0.4. Yield: 7 mg (4%) MS (FAB): m / e = 496.2 (M + H +, 100%); 518.2 (M + Na +, 50).

Example 5 N6- (1- (3-guanidinopropyl)) -N9- (4- (2S- (benzyloxycarbonylamino) butyric acid)) -adenine 5a) N9- (4- (2S- (benzyloxycarbon-n-lamino) butyric) -6-chloropurine tert-butyl ester Synthesis analogous to Example la, from 6-chloropurine and tert-butyl ester of N-benzyloxycarbonyl-L-homoserine. Performance: 24%. ^ -NMR (200 MHz, DMSO): d = 1.34 (s, 9H, C (CH3) 3); 2.08-2.43 (m, 2H, N-CH2-CH2-CH); 3.81-3.93 (m, 1H, CH-NHZ); 4.39 (t, 2H, N9-CH2); 5.02 (s, 2H, CH2-aryl); 7.26-7.42 (m, 5H, aryl-H); 7.87 (d, 1H, NH); 8.63 + 8.75 (2 s, 2H, C6-H + C8-H). MS (FAB): m / e = 446.1 (100%; (M + H) +); 390.1 (65). 5b) N6- (1- (3- (tert-butyloxycarbonylamino) propyl)) - N9 - (4- (tert-butyl ester of 2S- (benzyloxycarbonylamino) butyric acid) -adenine Synthesis analogous to lb, from 50 mg (0.11 mmol) of N9- (4- (tert-butyl ester of 2S- (benzyloxycarbonylamino) butyric acid) -6-chloropurine (Example 5a) and 38 mg ( 0.22 mmol) of 3- (tert-butyloxycarbonylamino) -1-propylamine Yield: 26 mg (41%) MS (ES +): m / e = 584.3 (100%; (M + H) + ). 5c) N - (1- (3-aminopropyl)) - N - (4- (2- (benzyloxycarbon-ni-lamino) butyric acid) -adenine Synthesis analogous to Example LE, starting from N - (l- q - (3- (tert-butyl-icarbonylamino) propyl)) - N '- (4- (2S- (benzyloxycarbonylamino) butyric acid tert-butyl ester) - adenine (Example 5b) Yield: 94% MS (FAB): m / e = 428.3 (100%; (M + H) +). 5d) N6- (1- (3-guanidinopropyl)) - N9- (4- (2S- (benzyloxycarbonylamino) butyric acid)) -adenine Synthesis analogous to Example Id, starting from N6- (1- (3-aminopropyl)) -N9- (4- (2- (benzyloxycarbonylamino) -butyric acid) -adenine (Example 5c) Yield: 71%. (FAB): m / e = 470.3 (70%; (M + H) +). 5e) N-benzyloxycarboni 1-L-homoserine 6 g (50.4 mmol) of L-homoserine were largely dissolved in 50 ml of DMF and mixed, at 0 ° C and in portions, with 12.56 g (50.4 mmol) of N-benzyloxycarbonyl-oxy) -succinimide. It was stirred for 1 h at 0 ° C, and then for 48 h at RT. The solvent was distilled off and the residue was partitioned between EA and a saturated NaCl solution. The organic phase was washed with saturated NaCl solution, with 5% citric acid and again with saturated NaCl solution, dried, filtered and concentrated. The crystalline residue was mixed with stirring in ether, filtered with suction, and washed with ether and pentane. Yield: 9.55 g (75%). 1 H-NMR (200 MHz, DMSO): d = 1.61-1.95 (m, 2H, CH 2 -CH 2 -OH); 3.42 (m, 2H, CH2-OH); 4.08 (m, 1H, CH-NH-Z); 4.57 (s, broad, 1H, OH); 5.02 (s, 2H, CH2-phenyl); 7.32 (m, 5H, aryl-H); 7.49 (d, 1H, NH-Z).

MS (C1 +): m / e = 236.1 (M + H + -H20, 20%); 192.1 (50); 91.0 (100). 5f) N-benzyloxycarbonyl-L-homoserine tert-butyl ester 3.8 g (15 mmol) of ZL-homoserin and 3.42 g (15 mmol) of benzyltriethylammonium chloride were dissolved in 110 ml of N-methyl-2-pyrrolidone under argon and mixed successively with 53.9 g ( 390 mmol) of K2C03 and 98.7 g (720 mmol) of tere-butyl bromide. It was stirred for 22 h at 55 ° C. The reaction mixture was poured into 1.5 liter of ice / water, extracted twice with toluene, the organic phase was washed twice with saturated NaCl solution, dried, filtered and concentrated by evaporation.For further purification, the product was chromatographed on silica gel (n-heptane: EA 7: 3 to 1: 1) Yield: 2.0 g (43.1%). MHz, CDCl 3): d = 1.45 (s, 9H, tBu), 1.51-1.74 + 2.03-2.26 (m, 2H, CH2-CH2-OH), 3.01 (s) , width, 1H, OH), 3.70 (m, 2H, CH2-OH), 4.41 (m, 1H, CH-NH-Z), 5.12 (s, 2H, CH2-phenyl); 60 (d, 1H, NH-Z), 7.36 (m, 5H, aryl-H), MS (C1 +): m / e = 310.3 (M + H +, 50%), 254.2 ( 100).

Example 6 N6- (1- (4-guanidinobutyl)) - N9- (4- (2S- (benzyloxycarbonylamino) butyric acid)) -adenine 6a I6- (1- (4- (tert-butyloxycarbonylamino) butyl)) - N9- (4- (tert-butyl ester of 2S- (benzyloxycarbonylamino) butyr-co)) -adenine Synthesis analogous to lb, from 50 mg (0.11 mmol) of N9- (4- (2S- (benzyloxycarbonylamino) butyric acid tert -butyl ester)) -6-chloropurine (Example 5a) and 41 mg ( 0.22 mmol) of 4- (tert-butyloxycarbonylamino) -l-butylamine. Yield: 38 mg (58%).

MS (ES +): m / e = 598.3 (100%; (M + H) +) 6b) N6- (1- (4-aminobutyl)) - N9- (4- (2- (benzyloxycarbonyl-amino) butyric acid)) -adenine Synthesis analogous to Example le, starting from N6- (l- q - (4- (tert-butyloxycarbonylamino) butyl)) - N '- (4- (tert-butyl ester of 2S- (benzyloxycarbonylamino) butyric acid)) - adenine (Example 6a). Performance: 100%. MS (FAB): m / e = 442.3 (100%; (M + H) +). 6c) N6- (1- (4-guanidinobutyl)) - N - (4- (2S- (benzyloxycarbonylamino) butyric acid)) -adenine Synthesis analogous to Example Id, starting from N6- (l- - (4-aminobutyl) -N9- (3- (2S- (benzyloxycarbonylamino) -butyric acid)) -adenine (Example 6b) Yield: 65%. MS (ES +): m / e = 484.3 (5%; (M + H) +), 350.2 (10), 333.2 (5), 130.0 (100).

Example 7 N6- (1- (3-guanidinopropyl)) -N9- (3-propionic acid) -adenine 7a) N9- (tert-butyl ester of 3-propionic acid) -6-chloropurine .45 g (0.1 mol) of 6-chloropurine, 43.5 ml (0.3 mol) of tere-butyl acrylate and 1.34 ml (7 mmol) of sodium methanolate 5.22 N (in MeOH ) were dissolved in 400 ml of absolute MeOH and boiled under reflux for 4.5 h, with repeated addition of 2.6 ml (14 mmol) of 5.22 N sodium methanolate (in MeOH). For working up, it was suction filtered, the solvent was removed by evaporation, and the residue was chromatographed on silica gel (+ 10% H20) (toluene: EA 3: 1). Yield: 1.35 g (5%). 1 H-NMR (200 MHz, DMSO): d = 1.29 (s, 9H, C (CH 3) 3); 2.95 (t, 2H, CH2C (0)); 4.50 (t, 2H, N-CH2); 8.70 + 8.79 (2 s, 2H, C6-H + C8-H). MS (ES +): m / e = 283.1 (70%; (M + H) +); 227.0 (100). 7b) N6- (1- (3- (tert-butyloxycarbonylamino) propyl)) - N9- (tert-butyl ester of 3-propionic acid) -adenine Synthesis analogous to lb, from 282 mg (1.0 mmol) of N9- (tert-butyl ester of 3-propionic acid) -6-chloropurine (Example 7a) and 209 mg (1.2 mmol) of 3- (tert-buti loxycarboni lamino) - 1-propi sheet. Performance : 160 mg (38%). MS (ES +): m / e = 421.2 (100%; (M + H) +), 365.2 (60), 321.2 (50), 265.1 (30). 7c) N6- (1- (3-aminopropyl)) -N9- (3-propionic acid) -adenine Synthesis analogous to Example le, starting from N - (l - (3- (tert-butyloxycarbonylamino) propyl)) -N- (tert-butyl ester of 3-propionic acid) -adenine (Example 7b).

Performance: 100%. 1 H-NMR (200 MHz, DMSO): d = 1.88 (t, 2H, CH 2 -CH 2 -CH 2 -); 2.80-2.93 (m, 4H, NH-CH2 + CH2-C (0)); 3.56 (m, 2H, CH2-NH2); 4.38 (t, 2H, N9-CH2); 7.72 (s, broad, 2H, NH2); 7.95 (t, 1H, NH); 8.15 + 8.23 (2 s, 2H, C6-H + C8-H). MS (ES +): m / e = 265.1 (100%; (M + H) +); 248.1 (40), 176.0 (30) 7d) N6- (1- (3-guanidinopropyl)) - N9- (3-propionic acid) - adenine Synthesis analogous to Example Id, from N6- (1- (3-aminopropyl) -N9- (3-propionic acid) -adenine (Example 7c) Yield: 41% 1 H-NMR (200 MHz, D20) d = 1.95 (t, 2H, CH2-CH2-CH2-), 2.71 (t, 2H, CH2-C (0)), 3.24 (t, 2H, Gua-CH2), 3, 65 (m, 2H, CH2-NH2), 4.40 (t, 2H, N9-CH2), 8.00 + 8.15 (2 s, 2H, C6-H + C8-H). ): m / e = 307.1 (100%; (M + H) +), 290.1 (30).

Example 8 N6- (l-4- (guanidinobutyl)) -N9- (3-propionic acid) -adenine 8a) N6- (1- (4- (tert-butyloxycarbonylamino) butyl)) -N9- (tert-butyl ester of 3-propionic acid) -adenine Synthesis analogous to lb, from 141 mg (0.5 mmol) of N9- (tert-butyl ester of 3-propionic acid) -6-chloropurine (Example 7a) and 104 mg (0.55 mmol) of 4- (tert-butyloxycarboni lamino) -l-butylamine. Yield: 130 mg (60%). 1 H-NMR (200 MHz, DMSO): d = 1.32 (s, 9H, C (CH 3) 3); 1.35 (s, 9H, C (CH3) 3); 1.40 (t, 2H, CH2); 1.57 (t, 2H, CH2); 2.84 (t, 2H, -CH2-C (0)); 2.95 (t, 2H, C2-NH-CH2); 3.45 (m, 2H, CH2-NH-Boc); 4.34 (t, 2H, N9-CH2); 6.78 (t, 1H, C2-NH); 7.70 (m, 1H, NH-Boc); 8.08 + 8.19 (2 s, 2H, C6-H + C8-H). MS (ES +): m / e = 435.2 (100%; (M + H) +), 379.2 (20), 335.2 (55), 279.1 (50). 8b) N6- (1- (4-aminobutyl)) - N9- (3-propionic acid) -adenine Synthesis analogous to Example le, starting from N6- (l- - (4- (tert-butyloxycarbonylamino) butyl)) -N9- (tert-butyl ester of 3-propionic acid) -adenine (Example 8a).

Performance: 100%. 1 H-NMR (200 MHz, DMSO): d = 1.50-1.70 (m, 4H, -CH 2 -CH 2 -); 2.74-2.91 (m, 4H, NH-CH2 + CH2-C (0)); 3.50 (m, 2H, CH2-NH2); 4.36 (t, 2H, N9-CH2); 7.64 (s, broad, 2H, NH2); 7.90 (t, 1H, NH); 8.11 + 8.21 (2 s, 2H, C6-H + C8-H). MS (FAB): m / e = 279.2 (100%; (M + H) +). 8c) N6- (1- (4-guanidinobutyl)) -N9- (3-propionic acid) -ade-nine Synthesis analogous to Example Id, starting from N6- (1- (4-aminobutyl)) -N9- (3-propionic acid) -adenine (Example 8b). Performance: 65%. MS (ES +): m / e = 321.1 (100%; (M + H) +).

Example 9 N - (1- (5-guanidinopentyl)) - N - (3-propionic acid) -adenine 9a) N6- (1- (5- (tert-butyloxycarbonyllamino) butyl)) -N9- (tert-butyl ester of 3-propionic acid) -adenine Synthesis analogous to lb, from 282 mg (1.0 mmol) of N9- (tert-butyl ester of 3-propionic acid) -6-chloropurine (Example 7a) and 243 mg (1.2 mmol) of 5- (tert-Butyloxycarbonyl-1-amino) -1-pentylamine. Yield: 219 mg (41%). MS (ES +): m / e = 449.3 (100%; (M + H) +). 9b) N6- (1- (5-aminopentyl)) -N- (3-propionic acid) -adenine Synthesis analogous to Example LE, starting from N6- (l- - (5- (erc-buti loxycarbonyl lamino) pentyl)) -N9- (tert-butyl ester of 3-propionic acid) -adenine (Example 9a) . Performance: 100%. XH-NMR (200 MHz, DMSO): d = 1.39 (m, 2H, CH2); 1.50-1.67 (m, 4H, 2 x CH2); 2.79 (dt, 2H, NH-CH2); 2.89 (m, 2H, CH2-C (0)); 3.48 (m, 2H, CH2-NH2); 4.37 (t, 2H, N9-CH2); 7.67 (s, width, 2H, NH2); 8.04 (t, 1H, NH); 8.13 + 8.25 (2 s, 2H, C6-H + C8-H). MS (ES +): m / e = 293.1 (100%; (M + H) +). 9c) N6- (1- (5-guanidinopentyl)) - N9- (3-propionic acid) adenine Synthesis analogous to Example Id, starting from N6- (1- (5-aminopentyl)) -N9- ( 3-propionic acid) -adenine (Example 9b). Yield: 37%. 1 H-NMR (200 MHz, DMSO): d = 1.38-1.79 (m, 6H, 3 x CH 2); 2.80 (t, 2H, NH-CH2); 3.12 (m, 2H, CH2-C (0)); 3.58 (m, 2H, CH2-Gua); 4.43 (t, 2H, N9-CH2); 8.07 + 8.21 (2 s, 2H, C6-H + C8-H). MS (FAB): m / e = 335.2 (100%; (M + H) +).

Example 10 N6- (2-acetic acid) -N9- (1- (5-aminopentyl)) -adenine 10a) N - (tert-butyl ester of 2-acetic acid) -adenine 155 mg (1 mmol) of 6-chloropurine and 420 mg (2 mmol) of glycine tert-butyl ester hydrochloride (80% strength) were dissolved in 5 ml of absolute DMF, mixed with 0.17 ml of DIPEA and the tip of a potassium iodide spatula, and were stirred for 6 h at 50 ° C. The solvent was removed by evaporation and the residue was chromatographed on silica gel (toluene: AE 1: 1 to 1: 2). Yield: 76 mg (31%), MS (ES +): 250.0 (M + H, 10%); 193.9 (95), 163.9 (100). 10b) N6- (2-acetic acid) -N9- (1- (5- (tert-butyloxycarbonyl-amino) pentyl)) -adenine 75 mg (0.3 mmol) of N6- (tert-butyl ester of 2-acetic acid) -adenine (Example 10a), 214 mg (0.6 mmol) of 5- (tert-butyloxycarbonylamino) pentyl ester of acid 4 toluene sulfonic acid and 42 mg (0.3 mmol) of K2CÜ3 were dissolved in 6 ml of absol. DMF. and they were shaken for 5 days at RT. The solvent was removed by evaporation and the residue was chromatographed on silica gel (toluene: EA 7: 3 to 1: 2). Yield: 92 mg (71%).

MS (ES +): 435.3 (M + H, 25%); 349.3 (100). 10c) N6- (2-acetic acid) -N9- (1- (5-aminopentyl)) - adenine Analogous synthesis. to Example 1, from N6- (2-acetic acid) -N9- (1- (5- (tert-bu-yloxycarbonyl-lamino) -pentyl)) -adenine (Example 10b). Yield: 93%. MS (ES +): m / e = 279.2 (15%; (M + H) +), 249.1 (100).

Example 11 N6- (2- (N- (2-aminoethyl) -acetamido)) - N9- (2-acetic acid) - adenine lia) N9- (tert-butyl ester of 2-acetic acid) -adenine 6.76 g (0.05 mol) of adenine were suspended in 300 ml of absolute DMF under N2, then, 2.4 g (0.06 mol) of NaH dispersion was added and stirred for 2 h at RT. In the space of 30 min they were added, drop by drop, 14.7 ml (0.1 mol) of tert-butyl ester of bromoacetic acid, forming a clear solution. It was stirred for an additional 5 h at RT. The solvent was removed by evaporation, the residue was stirred with 500 ml of water, filtered with suction and crystallized from ethanol. Yield: 5.1 g (41%). XH-NMR (200 MHz, DMSO): d = 1.42 (s, 9H, tBu); 4.95 (s, 2H, N9-CH2); 7.22 (s, broad, 2H, N6H2); 8.10 + 8.15 (2 s, 2H, C6-H + C8-H). MS (ES +): m / e = 250.1 (M + H +, 65%), 194.0 (100). 11b) N6- (ethyl ester of 2-acetic acid) -N9- (tert-butyl ester of 2-acetic acid) -adenine 978 mg (3 mmol) of NaH and 250 mg (1 mmol) of N9- (tert-butyl ester of 2-acetic acid) -adenine (Example lia) were suspended in 10 ml of absolute DMF and 0.12 ml of chloroacetic acid ethyl ester was added dropwise over 10 min. Then, it was stirred for 6 h at 50 ° C, then the same amount of CSCO3 was added again and it was stirred for 6 h at 50 ° C. The solvent was removed by evaporation and the residue was partitioned between water and EA. The organic phase was dried and evaporated. Performance: 16%. l-NMR (200 MHz, 'DMSO): d = 1.20 (t, 3H, CH2-CH3); 1.41 (s, 9H, tBu); 4.00-4.28 (m, 4H, CH2-CH3 + N6-CH2); 4.98 (s, 2H, N9-CH2); 8.09 (s, broad, 1H, N6H); 8.15 + 8.21 (2 s, 2H, C6-H + C8-H). MS (ES +): m / e = 336.3 (M + H +, 100%); 280.3 (60). 11c) N6- (2-acetic acid) -N9- (tert-butyl ester of 2-acetic acid) -adenine 249 mg (0.74 mmol) of N6- (2-acetic acid ethyl ester) -N9- (2-acetic acid-tert-butyl ester) adenine (Example 11b) were dissolved in 6 ml of dioxane: water : triethylamine and stirred for 4 days at RT. The solvent was removed by evaporation and the residue was chromatographed on silica gel (DCM: MeOH 95: 5 to 90:10). Performance: 36%. MS (ES +): m / e = 308.3 (M + H +, 100%). lld $ I6- (2- (N- (2-tert-butyloxycarbonylaminoethyl) -acetamido)) - N - (tert-butyl ester of 2-acetic acid) -adenine 80 mg (0.26 mmol) of N6- (2-acetic acid) -N9- (tert-butyl ester of 2-acetic acid) -adenine (Example 11c) and 42 mg (0.26 mmol) of 2-tert. -butyloxycarbonylaminoethylamine were dissolved under argon in 5 ml of absolute DMF, mixed with O'C with 85 mg (0.26 mmol) of TOTU and 0.13 ml (0.78 mmol) of DIPEA and stirred for 10 min. O'C, and for 2.5 ha the TA. It was diluted to 100 ml with EA, then washed with saturated potassium hydrogencarbonate solution, dried and concentrated. It was chromatographed on silica gel (DCM: MeOH 98: 2 to 90:10). Yield: 5%. MS (ES +): m / e = 450.3 (M + H +, 100%). lie) N6- (2- (N- (2-aminoethyl) -acetamido)) - N - (2-acetyl-co-acid) Synthesis analogous to Example le, starting from N6- (2 - (N- (2-tert-butyloxycarboni laminoeti 1) -acetamido)) -N9- (tert-butyl ester of 2-acetic acid) -adenine (Example fight). Performance: 80%. MS (ES +): m / e = 293.1 (100%; (M + H) +).

Example 12 N - (4- (2S- (benzyloxycarbonylamino) butyric acid)) - N - (1- (3-guanidinopropy 1)) -adenine 12a) N9- (1- (3-tert-butyloxycarbonyllamino) propyl)) -6-chloropu-brane 154.6 mg (1 mmol) of 6-chloropurine were dissolved in 2.5 ml of absolute DMF and mixed, with stirring, with 331.7 mg (2.4 mmol) of K2C03 and 285.8 mg (1, 2 mmol) of N- (3-bromspropyl) carbamic acid tert-butyl ester. The mixture was stirred for 11 h at RT, the solvent was evaporated off, the residue was taken up in EA and washed twice with saturated NaHCO 3 solution, then with NaCl solution, dried, filtered and concentrated. The residue was chromatographed on silica gel (EA: n-heptane 8: 2). Yield: 267 mg (86%). 1 H-NMR (200 MHz, DMSO): d = 1.37 (s, 9H, tBu); 2.00 (tt, 2H, CH2-CH2-CH2); 2.95 (dt, 2H, CH2-NH); 4.30 (t, 2H, N9-CH2); 6.91 (t, broad, 1H, NH); 8.70 + 8.78 (2 s, 2H, C6-H + C8-H). MS (ES +): m / e = 312.2 (100%; (M + H) +); 256.1 (20). 12b) N6- (4- (2S- (benzyloxycarbonylamino) butyric acid)) -N9 - (1-3- (tert-butyloxycarbonyllamino) propyl)) -adenine 370 mg (1.19 mmol) of N9- (1- (3-tert-butyloxycarbo-nylamino)? Ropil)) -6-chloropurine (Example 12a) were dissolved in 10 ml of absolute DMF and 5 ml of DIPEA. 449 mg (1.8 mmol) of 2S-benzyloxycarbonylamino-4-aminobutyric acid were added at RT and stirred for 50 h at 65 βC. The solvent was removed by evaporation and the residue was partitioned between EA and saturated NaCl solution (20% KHSO4). The organic phase was washed with water, dried, filtered and concentrated. The residue was chromatographed on silica gel (EA: MeOH 8: 2). Yield: 331 mg (53%). 1 H-NMR (200 MHz, DMSO): d = 1.39 (s, 9H, tBu); 1.73-2.21 (m, 2H, CH2-CH (NH-Z)); 1.90 (m, 2H, CH2-CH2-CH2); 2.92 (dt, 2H, CH2-NHBoc); 3.15 (dt, 2H, N6H-CH2); 3.88-4.10 (m, 1H, CH- -NHZ); 4.14 (t, 2H, N9-CH2); 5.03 (s, 2H, CH2-phenyl); 6.91 (t, broad, 1H, NH-Boc); 7.37 (s, 5H, aryl-H); 7.55-7.81 (m, 2H, NH-Z + N6H-CH2); 8.13 + 8.19 (2 s, 2H, C6-H + C8-H). MS (ES +): m / e = 528.2 (100%; (M + H) +). 12c) N6- (4- (2S- (benzyloxycarbonylamino) butyric acid)) -N9 - (1- (3-aminopropyl)) -adenine mg (0.06 mmol) of N6- (3- (2S- (benzyloxycarbonylamino) ropionic acid)) - N - (1- (3- (tert-butyloxycarbonylamino) -propyl)) - adenine (Example 12b) they were dissolved in 2 ml of 90% trifluoroacetic acid, stirred for 70 min at RT, concentrated and the residue was stirred several times with ether. The residue was dissolved in water and lyophilized. Performance: 100%. MS (ES +): m / e = 428.2 (100%; (M + H) +); 294.1 (90). 12d) N6- (4- (2S- (benzyloxycarbonylamino) butyric acid)) -N9 - (1- (3-guanidinylpropyl)) -adenine Synthesis analogous to Example Id, starting from N6- (3- q - (2S- (benzyloxycarbonylamino) propionic acid)) - N - (l- (3-aminopropyl)) -adenine (Example 12c). Performance: 77%.

MS (ES +): m / e = 470.3 (25%; (M + H) +); 336.2 (100).

Example 13 N6- (4- (2S- (benzyloxycarbonylamino) butyric acid)) - N9- (1- (3- (4,5-dihydro-lH-imidazol-2-ylamino) -propyl)) -adenine Synthesis analogous to Example 4, starting with N6- (3- (2S- (benzyloxycarbonylamino) propionic acid)) -N9- (1- (3-aminopropyl)) -adenine (Example 12c). Performance: 63%. MS (ES +): m / e = 496.3 (100%; (M + H) +).

Example 14 N - (3- (2S- (benzyloxycarbonylamino) propionic acid)) - N - (1- (5-guanidinopenti1)) -adenine 14a) N - (1- (5- (tert-butyloxycarbonylamino) pentyl)) -6-chloro-purine Synthesis analogous to Example 12a, from 6-chloropurine and tert-butyl ester of N- (5-tosyloxy-pentyl) carbamic acid. Yield: 66%. 1 H-NMR (200 MHz, DMSO): d = 1.11-1.48 (m, 4H, 2 x CH 2); 1.35 (S, 9H, tBu); 1.87 (tt, 2H, CH2); 2.97 (dt, 2H, CH2-NHBoc); 4.28 (t, 2H, N9-CH2); 6.72 (t, broad, 1H, NH); 8.71 + 8.78 (2 s, 2H, C6-H + C8-H). MS (ES +): m / e = 340.2 (100%; (M + H) +); 284.1 (50). 14b) N6- (3- (2S- (benzyloxycarbonylamino) propionic acid)) - N9- (1- (5- (tert-butyloxycarbonylamino) pentyl)) -adenine Synthesis analogous to Example 12b, starting from N9- (l- (5- (tert-butyloxycarbonyllamino) pentyl)) -6-chloropurine and 2S-benzyloxycarbonylamino-3-aminopropionic acid. Yield: 23%. XH-NMR (200 MHz, DMSO): d = 1.10-1.49 (m, 4H, 2 x CH2); 1.36 (s, 9H, tBu); 1.62-1.88 (m, 2H, CH2); 2.87 (dt, 2H, CH2-NHBoc); 3.68-4.98 (m, 5H, N9-CH2 + CH2-CH-NHZ); 5.00 (s, 2H, CH2-phenyl); 6.75 (t, broad, 1H, NH); 8.02 + 8.20 (2 s, 2H, C6-H + C8-H). MS (FAB): m / e = 542.3 (100%; '(M + H) +). 14c) N - (3- (2S- (benzyloxycarbonylamino) propionic acid)) - N9- (1- (5-aminopentyl)) -adenine Synthesis analogous to Example 12c, starting from N6 - (3- (2S- (benzyloxycarbonylamino) propionic acid)) -N9- (1- (5- (tert-butyloxycarbonylamino) pentyl)) -adenine (Example 14b) . Performance: 100%. 1 H-NMR (200 MHz, DMSO): d = 1.18-1.40 + 1.44-1.65 + 1.71-1.93 (2 m, 6H 3 x CH2); 2.77 (dt, 2H, CH2-NHBoc); 3.64-4.35 (m, 5H, N9-CH2 + CH2CH-NHZ); 5.00 (s, 2H, CH2-phenyl); 7.66 (m, 3H, NH 3 +); 8.20 + 8.24 (2 s, 2H, C6-H + C8-H). MS (ES +): m / e = 442.3 (40%; (M + H) +); 308.2 (100). 14d) N6- (3- (2S- (benzyloxycarbonylamino) propionic acid)) - N9- (1- (5-guanidinylpentyl)) -adenine Synthesis analogous to Example Id, starting from N6- (3-- (2S- (benzyloxycarbonyllamino) propionic acid)) -N9- (1- (5-aminopentyl)) -adenine (Example 14c). Performance: 90%. MS (ES +): m / e = 484.3 (70%; (M + H) +); 350.2 (60).

Example 15 N6- (3- (2S- (benzyloxycarbonylamino) propionic acid)) -N9-- (1- (5- (4,5-dihydro-lH-imidazol-2-ylamino) pentyl)) -adenine Synthesis analogous to Example 4, starting from N6- (3 - (2S- (benzyloxycarbonylamino) propionic acid)) - N - (1- (5-aminopentyl)) -adenine (Example 14c). Performance: 75%. MS (ES +): m / e = 510.3 (40%; (M + H) +); 376.2 (100).

Example 16 N6- (3- (2S- (benzyloxycarbonyl-lamino) propionic acid) -N9- (1- (3-guanidinylpropyl)) -adenine 16a) N - (3- (2S- (benzyloxycarbonylamino) propionic acid)) - N9- (1- (3- (tert-butyloxycarbonylamino) propi1)) -adenine Synthesis analogous to Example 12b, starting from N9 - (l- (3-tert-butyloxycarbonyllamino) propyl)) -6-chloropurine (Example 12a) and 2S-benzyloxycarbonylamino-3-aminopro-pionic acid. Yield: 27%. 1 H-NMR (200 MHz, DMSO): 6 = 1.37 (s, 9H, tBu); 1.90 (m, 2H, CH2-CH2-CH2); 2.92 (dt, 2H, CH2-NHBoc); 3.86 (m, broad, 2H, CH2-CH (NH-Z)); 4.13 (t, 2H, N9-CH2); 4.40 (m, 1H, CH-NHZ); 5.01 (s, 2H, CH2-phenyl); 6.92 (t, broad, 1H, NH-Boc); 7.33 (s, 5H, aryl-H); 7.55-7.75 (m, 2H, NH-Z + N6H-CH2); 8.16 + 8.22 (2 s, 2H, C6-H + C8-H). MS (ES +): m / e = 514.3 (100%; (M + H) +). 16b) N6- (3- (2S- (benzyloxycarbonylamino) propionic acid)) - N9- (1- (3-aminopropy1) -adenine Synthesis analogous to Example 12c, starting from N6 - (3- (2S- (benzyloxycarbonylamino) propionic acid)) -N- (1- (3- (tert-butyloxycarbonylamino) propyl)) -adenine (Example 16a). Performance: 100%. MS (ES +): m / e = 414.2 (100%; (M + H) +); 280.2 (70). 16c) N6- (3- (2S- (benzyloxycarbonylamino) propionic acid)) - q -N '- (1- (3-guanidinylpropyl)) -adenine Synthesis analogous to Example Id, starting from N - (3- q - (2S- (benzyloxycarbonylamino) propionic acid)) - N - (1- (3-a-propyl) -adenine (Example 16b) Yield: 98%.

MS (ES +): m / e = 456.3 (40%; (M + H) +); 322.2 (100).

Example 17 N - (3- (2S- (benzyloxycarbonylamino) propionic acid)) -N9- (1- (4-guanidinylbutyl) -adenine 17a) N - (1- (4-tert-butyloxycarbonylamino) butyl)) - 6-chloro-purine Synthesis analogous to Example 12a, from 6-chloropurine and N- (4-tosyloxy-butyl) carbamic acid tert-butyl ester. Yield: 66%. 1 H-NMR (200 MHz, DMSO): d = 1.30 (m, 2H, CH 2); 1.35 (s, 9H, tBu); 1.86 (tt, 2H, CH2); 2.93 (dt, 2H, CH2-NHBoc); 4.31 (t, 2H, N2-CH2); 6.79 (t, broad, 1H, NH); 8.72 + 8.78 (2 s, 2H, C6-H + C8-H). MS (ES +): m / e = 326.2 (80%; (M + H) +); 270.1 (100). 17b) N6- (3- (2S- (benzyloxycarbonylamino) α-ropionic acid)) - N9- (1- (4- (tert-buty-ls-xicarboni-lamino) buti)) -adenine Synthesis analogous to Example 12b, starting from N9 - (l- (4- tert-but i loxy carboni lamino) butyl)) -6-chloropurine (Example 17a) and 2S-benzyloxycarbonylamino-3-aminopro-pionic acid. Performance: 33%. 1 H-NMR (200 MHz, DMSO): d = 1.30 (m, 2H, CH 2); 1.35 (s, 9H, tBu); 1.75 (, 2H, CH2); 2.91 (dt, 2H, CH2-NHBoc); 3.71-4.34 (m, 5H, CH2-CH (NH-Z) + N9-CH2); 5.01 (s, 2H, CH2-phenyl); 6.89 (t, broad, 1H, NH-Boc); 7.35 (s, 5H, aryl-H); 7.46-7.73 (, 2H, NH-Z + N6H-CH2); 8.10 (broad) + 8.20 (2 s, 2H, C6-H + C8-H). MS (FAB): m / e = 528.4 (100%; (M + H) +). 17c) N6- (3- (2S- (benzyloxycarbonylamino) propionic acid)) - N9- (1- (4-aminobutyl)) -adenine Synthesis analogous to Example 12c, starting from N6- (3- (2S- (benzyloxycarbonylamino) propionic acid)) -N9-. - (1- (4- (tert-butyloxycarbonylamino) butyl)) -adenine (Example 17b). Performance: 100%. 1 H-NMR (200 MHz, DMSO): d = 1.48 (m, 2H, CH 2); 1.87 (m, 2H, CH2); 2.80 (dt, 2H, CH2-NH2); 3.69-4.02 (m, 2H, CH2-CH (NH-Z); 4.20 (t, 2H, N9-CH2); 4.36 (m, 1H, CH (NH-Z)); 5.01 (s, 2H, CH2-phenyl), 7.33 (s, 5H, aryl-H), 7.64 (s, broad, 4H, NH3 + + N6H-CH2), 8.10 (broad) + 8.20 (2 s, 2H, C6-H + C8-H) MS (ES +): m / e = 428.3 (50%; (M + H) +); 294.2 (100). 17d) N6- (3- (2S- (benzyloxycarbonylamino) propionic acid)) - N9- (1- (4-guanidinylbutyl)) - adenine Synthesis analogous to Example Id, starting from N 6 - (3- (2 S- (benzyloxycarbonylamino) propionic acid)) -N 9 - (1- (4-aminobutyl)) -adenine (Example 17c). Performance: 78%. MS (ES +): m / e = 470.2 (50%; (M + H) +); 336.2 (100).

Example 18 N6- (3- (2S- (benzyloxycarbonylamino) propionics)) -N9 - (l- (4- (4,5-dihydro-lH-imidazol-2-yl) amino) l3util) -adenine Synthesis analogous to Example 4, starting from N6 - (3- (2S- (benzyloxycarbonylamino) propionic acid)) -N9 - (1- (4-aminobutyl)) -adenine (Example 17c). Yield: 41%. MS (ES +): m / e = 496.3 (60%; (M + H) +); 362.2 (100).

Example 19 2S-Benzyloxycarbonylamino-3- (6- (4- (1,4,5,6-tetrahi-dropirimidin-2-ylcarbamoyl) -? Iperidin-1-yl) -purin-9-yl) -propionic acid 19a) 2S-Benzyloxycarbonylamino-3- (6- (4-carboxy-piperidin-1-yl) -purin-9-yl) -propionic acid butyl ester 260 mg (0.6 mmol) of the 2S-benzyloxycarbonylamino-3- (6-chloro-? Urin-9-yl) -α-ropionic acid tert-butyl ester (Example la), 116.3 mg (0.9 mmol) ) of piperidine-4-carboxylic acid and 310 mg (2.4 mmol) of DIPEA in 4 ml of absolute DMF were stirred for 16 h at 60 ° C. Then, an additional 310 mg of DIPEA was added and it was stirred again for 24 h at 60 ° C. The solvent was removed by evaporation and the residue was partitioned between EA and water. The organic phase was washed again with KHS? 4 / K2S? 4 solution, then with NaCl solution, dried, filtered and concentrated. The residue was chromatographed on silica gel (EA). Yield: 219 mg (69%). MS (ES +): m / e = 525.3 (100%; (M + H) +). 19b) 2S-Benzyloxycarbonyl-amino-3- (6- (1,4-, 5,6,6-tetrahydropyrimidin-2-iCarbamoyl-1) -piperidin-1-yl) -purin-9-tert-butyl ester -il) propionic 126 mg (0.24 mmol) of 2S-benzyloxycarbonylamino-3- (6- (4-carboxy-piperidin-1-y1) -purin-9-yl) -propionic acid tert-butyl ester (Example 19a), 39.3 mg (0.29 mmol) of 2-amino-1,4,5,6-tetrahydropyrimidine hydrochloride, 86.6 mg (0.264 mmol) of TOTU (0- ((ethoxycarbonyl) cyanomethyleneamino) tetrafluoroborate) -N, N, N ', N' -tetramethyluronium (Konig et al., Proceedings of the 21st European Peptide Symposium 1990, compilers E. Giralt and D. Andreu, ESCOM, Leiden, page 143) and 124 mg of DIPEA were added successively to 3 ml of absolute DMF.The mixture was stirred for 3 h at RT, then an additional 28 mg of DIPEA was added and the mixture was stirred for 12 h at RT The reaction mixture was adjusted to pH 6 with glacial acetic acid / toluene (1: 1), the reaction solution was concentrated, the residue was partitioned between EA and saturated NaHCO3 solution, the organic phase was washed with NaCl, dried and concentrated.The residue was chromatographed on silica gel (EA: MeOH; TEA 85: 15: 1,5). Immuno: 70 mg MS (ES +): m / e = 606.4 (60%; (M + H) +); 416.3 (40); 275.7 (100) 19c) 2S-Benzyloxycarbonylamino-3- (6- (4- (1, 4, 5, 6-tetrahydropyrimidin-2-ylcarbamoyl) -piperidin-1-yl) -purin-9-yl) -propionic acid 80 mg tert-butyl ester of 2S-benzyl-oxycarboni lamino-3- (6- (4- (1,4,5,6-tetrahydropyrimidin-2-ylcarbamoyl) -pi-eridin-1-yl) - purin-g-il) propionic (Example ig) were dissolved in 16 ml of 5% trifluoroacetic acid, previously cooled, and stirred, first for 30 min at O'C, and then for 30 min at RT. The trifluoroacetic acid was removed by rotary evaporation, the residue coevaporated three times with toluene, stirred in ethanol / ether (1: 2), washed with ether and dried in vacuo. Yield: 5 mg. MS (ES +): m / e = 550.3 (60%; (M + H) +); 416.3 (100).

Example 20 2S-benzyloxycarbonylamino-3- (1- (9- (2-guanidinoethyl) -gH-purin-6-yl) -lH-imidazol-4-yl) -propionic acid 20a) N9- (1- (2- (tert-butyloxycarbonylamino) ethyl)) -6-chloro-purine The synthesis was carried out analogously to Example 12a, starting from 6-chloropurine and tert-butyl acid ester N- (2-tosyloxyethyl) carbamic. Performance: 36%. ^ -NMR (200 MHz, DMSO): d = 1.24 (s, 9H, tBu); 3.40 (dt, 2H, CH2-NHBoc); 4.35 (t, 2H, N9-CH2); 6.91 (t, broad, 1H, NH); 8.60 + 8.78 (2 s, 2H, C6-H + C8-H). MS (FAB): m / e = 298.2 (100%; (M + H) +). 20b) 2S-benzyloxycarbonylamino-3- (1- (9- (2- (tert-butyloxycarbonylamino) ethyl) -9H-purin-6-yl) -lH-imidazol-4-yl) -pro-ionic acid The synthesis was carried out analogously to Example 12b, starting with N9- (1- (2- (tert-butyloxycarbonylamino) ethyl)) -6-chloropurine (Example 21a) and Na-Z-L-histidine. Performance: 33%. MS (ES +): m / e = 551.3 (100%; (M + H) +). 20c) 3- (1- (9- (2-aminoethyl) -9H-purin-6-yl) -lH-imidazol-4-yl) -2S-benzyloxycarbonylamino-propionic acid The synthesis was carried out analogously to Example 12c, starting from 2S-benzyloxycarbonylamino-3- (1- (g- (2- (tert-butyloxycarbonylamino) ethyl) -gH-purin-6-yl) -lH-imide zol-4-yl) -propionic (Example 20b). Performance: 100%.

MS (ES +): m / e = 451.3 (70%; (M + H) +); 1 H-NMR (200 MHz, DMSO): d = 2.87-3.15 (m, 2H, Im-CH 2); 3.38--3.51 (m, 2H, CH2-NH2); 4.36 (m, 1H, CH-NHZ); 4.60 (t, 2H, N9-CH2); 5.00 (s, 2H, CH2-phenyl); 7.28 (s, 5H, aryl-H); 7.62 (d, 1H, NH-Z); 8.23 + 9.05 (2 s, 2H, Im-H); 8.71 + 8.88 (2 s, 2H, C6-H + C8-H). 20d) 2S-benzyloxycarbonylamino-3- (1- (9- (2-guanidino-ethyl) -9H-purin-6-yl) -lH-imidazol-4-yl) -propionic acid The synthesis was carried out analogously to Example Id, starting from 3- (1- (9- (2-aminoethyl) -9H-purin-6-yl) -lH-imidazol-4-yl) -2S-benzyloxycarbonylamino- acid. propionic (Example 20c). Performance: 38%. MS (ES +): m / e = 493.3 ((M + H) +); Example 21 2R-benzyloxycarbonylamino-3- (6- (N- (4-guanidinocyclohexyl) amino) -purin-9-yl) -propionic acid 21a) N9- (3- (2R- (benzyloxycarbonylamino) -propionate) butyl) -6-chloropurine The synthesis was carried out analogously to Example la from 6-chloropurine and tert-butyl ester of N-benzyl-oxycarbonyl-D-serine. MS (FAB): m / e = 432.2 (100%; (M + H) +); 376.1 (30). 21b) 2R-Benzyloxycarbonylamino-3- (6- (N- (4- (tert-buty-loxycarbonylamino) -cyclohexy-1-amino) -purin-g-yl) -propionic acid tert-butyl ester The synthesis was carried out analogously to Example lb, starting from 4-amino-l- (tert-buty-loxycarbonyl-lamino) -cyclohexa-no and N- (3- (2R- (benzyloxycarbonyl-lamino) -terc-butyl propionate ) -6-chloropurine (Example 21a) Yield: 55% MS (FAB): m / e = 610.3 (100%; (M + H) +). 21c) 3- (6- (N- (4-aminocyclohexyl) amino) -purin-g-yl) -2R-benzyloxycarbonylamino-propionic acid The synthesis was carried out analogously to Example le, starting from tert-butyl ester of 2R-benzyloxycarbonyl-nylamino-3- (6- (N- (4- (tert-butyloxycarbonyllamino) cyclohexylamino) -purin-9 -il) -propionic (Example 21b) Yield: 100% MS (ES +): m / e = 454.2 (50%, (M + H) +). 21d) 2R-Benzyloxycarbonylamino-3- (6- (N- (4-guanidinocyl-clohexyl) amino) -purin-9-yl) -propionic acid The synthesis was carried out analogously to Example Id, starting from 3- (6- (N- (4-aminocyclohexyl) amino) -purin-g-yl) -2R-benzyloxycarbonylamino-propionic acid (Example 21c). Performance: 80%. MS (ES +): m / e = 4g6.3 (50%, (M + H) +).

Example 22 2R-benzyloxycarbonyl lamino-3- (6- (N- (3-guanidinomethyl-benzyl) amino) -purin-g-yl) -propionic acid 22a) 2R-benzyloxycarbonylamino-no-3- (6- (N- (3-tert-buoxycarbonyl-1-anomethyl-benzyl) -amino) -purin-g-yl) -propionic acid tertiary butyl ester The synthesis was carried out analogously to Example lb, starting from 3-aminomethyl-l- (tert-butyloxycarbonylaminomethyl) -benzene and N - (3 - (2R- (benzyloxycarbonylamino) - tert -butyl) -ropionate -6- chloropurine (Example 21a) Yield: 51%.

MS (ES +): m / e = 632.3 (100%; (M + H) +). 22b) 3- (6- (N- (3-aminomethylbenzyl) amino) purin-g-yl) -2R-benzyloxycarboni lamino-propionic acid The synthesis was carried out analogously to Example le, starting from the tert-butyl ester of 2R-benzyloxycarbo-nylamino-3- (6- (N- (3-tert-butyloxycarbonylaminomethylbenzyl) amino) -purin-g-il ) -propionic (Example 22a). Performance: 100%. MS (ES +): m / e = 476.2 ((M + H) +, 50%); 342.2 (70). 22c) 2R-benzyloxycarbonylamino-3- (6- (N- (3-guanidinomethyl-benzyl) amino) -purin-g-yl) -propionic acid The synthesis was carried out analogously to Example Id, starting from 3- (6- (N- (3-aminomethylbenzyl) amino)? Urin-9-yl) -2R-benzyloxycarbonylamino-propionic acid (Example 22b). Performance: 30%. MS (ES +): m / e = 518.3 ((M + H) +, 20%).

EXAMPLE 23 3- (6- ((4-Benzimidazol-2-ylamino) -butyl) -amino) -purin-g-yl) -2S-benzyloxycarbonylamino-propionic acid 23a) l- (4-tert-butyloxycarbonylamino-butyl) acid ) -3- (2-nitro-phenyl) -thiourea To 0, g7 g (5.15 mmol) of 4- (tert-butyloxycarbonyl-aminobutyl) -l-amine in 25 ml of absolute DMF was added, to O'C and dropwise, 0, g28 g (5, 15 mmol) of 2-nitrophenyl isothiocyanate in 5 ml of absol. DMF. Then, it was stirred for 1 h at O'C. The solvent was distilled off and the residue was chromatographed on silica gel (EA: n-heptane 1: 2 to 1: 1). Yield: 1.8 g (g5%). MS (ES +): m / e = 369.2 ((M + H) +, 100%). 23b) 3- (2-amino-phenyl) -l- (4-tert-butyloxycarbonylamino-butyl) -thiourea 1.78 g (4.8 mmol) of l- (4-tert-butyloxycarbonylamino-butyl) -3- (2-nitro-phenyl) -thiourea (Example 23a) were dissolved in 120 ml of methanol and hydrogenated (1 bar) at RT for 3 h over 1 g of Pd / C. The catalyst was removed by filtration, the filtrate was concentrated and chromatographed on silica gel (EA: n-heptane 1: 1). Yield: 1.4 g. 23c) 4- (benzimidazol-2-ylamino) -l- (tert-butyloxycarboni lamino) -butane To 1.4 g (4.14 mmol) of 3- (2-amino-phenyl) -l - (4-tert-butyloxycarbonylamino-butyl) -thiourea (Example 23b) in 30 ml of ethanol was added 1.79. g (8.28 mmol) of yellow mercury oxide and 27 mg of sulfur flower, and the reaction mixture was heated for 3 h at 50-55 ° C. It was filtered with suction and washed with ethanol. The filtrate was concentrated and the product was chromatographed on silica gel (DCM: methanol 9: 5, then 9: 1). Performance: 43%. MS (ES +): m / e = 305.2 ((M + H) +, 100%). 23d) 4- (benzimidazol-2-ylamino) -l-amino-butane 198 mg (0.65 mmol) of 4- (benzimidazol-2-ylamino) -l- (tert-butyloxycarbonylamino) -butane (Example 23c) were dissolved in O'C in 20 ml of 95% trifluoroacetic acid and stirred for 2 h at O'C, and then concentrated at RT for 30 min. The residue was coevaporated three times with toluene, then, it was stirred with ether, washed with pentane and dried in vacuo. Performance: 100%. MS (ES +): m / e = 205.2 ((M + H) +, 100%). 23e) 3- (6- ((4- (Benzimidazol-2-ylamino) -butyl) -amino) -purin-g-yl) -2S-benzyloxycarbonyl-amino-propionic acid tert-butyl ester The synthesis was carried out analogously to Example lb, starting from 4- (benzimidazol-2-ylamino) -l-amino-butane (Example 23d) and N9- (3- (2S- (benzyloxycarbonyl-1-amino) -tert-butyl) -6-chloropurine propionate (Example 1). 32%. MS (ES +): m / e = 600.3 (100%; (M + H) +). 23f) 3- (6- ((4- (Benzimidazol-2-ylamino) -butyl) -amino) -purin-g-yl) -2S-benzyloxycarboni-lamino-propionic acid Synthesis was carried out analogously to Example le, from 3- (6- ((4- (benzimidazol-2-ylamino) -butyl) -amino) -purin-g-yl) tert-butyl ester - 2S-benzyloxycarbonylamino-propionic (Example 23e). Performance: 100%. MS (ES +): m / e = 544.2 ((M + H) +, 70%).

Example 24 2S-Benzyloxycarbonylamino-3- (6- (4- ((4,5-dihydro-1H-imidazol-2-ylamino) -methyl) -piperidin-1-yl) -purin-g-yl) - - acid propionic 24a) 3- (6- (4- (Aminomethyl) -piperidin-1-yl) -purin-9-yl) -2S-benzyloxycarbonylamino-propionic acid tert-butyl ester The synthesis was carried out analogously to Example lb, qa from 4- (aminomethyl) -piperidine and N - (3- (propionate of 2S- (benzyloxycarboni lamino) -tert-butyl) -6-chloropurine (Example la). Yield: g6,4%. MS (ES +): m / e = 510.3 (100%; (M + H) +). 24b) 3- (6- (4- (Aminomethyl) -piperidin-1-yl) -purin-g-yl) -2S-benzylcarbonylamino-propionic acid The synthesis was carried out analogously to Example le, from the tert-butyl ester of 3- (6- (4- (aminomethyl) -piperidin-1-yl) -purin-9-yl) -2S-benzyloxycarbonylamino- -propionic (Example 24a). Performance: 100%. MS (ES +): m / e = 454.3 ((M + H) +, 30%). 24c) 2S-Benzyloxycarbonylamino-3- (6- (4- ((4,5-dihydro-lH-imidazol-2-ylamino) methyl) -piperidin-1-yl) -purin-g-yl) acid - propionic The synthesis was carried out analogously to Example 4, starting from 3- (6- (4- (aminomethyl) -? Iperidin-1-yl) -purin-g-yl) -2S-benzyloxycarbonylamino-propionic acid (Example 24b) . Yield: 5%. MS (ES +): m / e = 522.3 ((M + H) +, 40%).

EXAMPLE 25 2R-Benzyloxycarbonylamino-3- (6- (4- ((4,5-dihydro-lH-imidazol-2-ylamino) -methyl) -piperidin-1-yl) -purin-g-yl) acid -propionics The synthesis was carried out analogously to Example 24, starting with N9- (3- (2R- (benzyloxycarbonylamino) -tert-butyl) -6-chloropurine propionate (Example 21a) MS (ES +): m / e = 522 , 3 ((M + H) +, 20%).

Example 26 2S-Benzyloxycarboni lamino-3- (6- (4- (guanidinomethyl) -piperidin-1-yl) -purin-9-yl) -propionic acid The synthesis was carried out analogously to Example Id, starting from 3- (6- (4- (aminomethyl) -piperidin-1-yl) -purin-g-yl) -2S-benzyloxycarbonylamino-propionic acid (Example 24b). Performance: 74%. MS (ES +): m / e = 4g6.3 ((M + H) +, 40%).

EXAMPLE 27 2S-benzyloxycarboni lamino-3- (6- (3- (3-benzlureido) -phenylsulphane) -α-urin-g-yl) -propionic acid 27a) 3- (6- (3-Amino-phenylsulfa-nyl) -purin-g-yl) -2S-benzyloxycarbonylamino-propionic acid tert-butyl ester 0.602 mmol of 3-mercaptoaniline were stirred for 12 h together with 0.602 mmol of N- (3S- (benzyloxycarbonylamino) -tert-butyl) -6-chloropurine N- (3-propionate (Example la) in DMF and DIPEA. The reaction solution was concentrated, the residue was partitioned between EA and saturated NaHCO solution, the phases were separated, the organic phase was washed with half saturated NaHC03 solution with NaCl solution, dried, concentrated and the product was chromatographed on silica gel (EA: heptane 1: 1) Yield: ig? mg MS (ES +): m / e = 521.3 ((M + H) +, 100%) 27b) 2S-benzyloxycarbonylamino-3- (6- (3- (3-benzylureido) -phenylsulfanyl) -purin-g-yl) -propionic acid tert-butyl ester To 180 mg of 3- (6- (3-amino-phenylsulfaphyl) -purin-g-yl) -2S-benzyloxycarbonylamino-non-propionic acid tert-butyl ester (Example 27a) in 3 ml of absolute acetonitrile were added , by syringe, 46.1 mg of benzyl isocyanate in 1 ml of acetonitrile. The mixture was stirred for 48 h at RT, concentrated and the residue was chromatographed on silica gel (DCM: AE 7: 3 to 1: 1). Yield: 205 mg. MS (ES +): m / e = 654.4 ((M + H) +, 100%). 27c) 2S-benzyloxycarbonylamino-3- (6- (3- (3-benzylurei-do) -phenylsulfanyl) -purin-g-yl) -propionic acid The synthesis was carried out analogously to Example LE, starting from the tert-butyl ester of 2S-benzyloxycarboni lamino-3- (6- (3- (3-benzlureido) -phenylsulfañyl) -purin-g-il) - propionic (Example 27b). Performance: 100%. MS (ES +): m / e = 5g8.4 ((M + H) +, 100%).

EXAMPLE 28 2S-neopentyloxycarbonylamino-3- (6- (4- (1,4,6,6-tetrahydropyrimidin-2-ylcarbamoyl) -piperidin-1-yl) -purin-g-yl) - - acid propionic 28a) 2S-amino-3- (6- (4-carboxy-piperidin-1-yl) -purin-g-yl) -propionic acid tert-butyl ester 1.7 g of 2S-benzyl-oxycarbonylamino-3- (6- (4-carboxy-piperidin-1-yl) -purin-9-yl) -propionic acid tert-butyl ester (Example 19a) were dissolved in 200 ml of AcOH and hydrogenated over Pd / C at 1 atm of H2 pressure. The catalyst was removed by filtration, the solvent was removed by distillation and the residue lyophilized, Yield: 100%. MS (ES +): m / e = 391.3 ((M + H) +, 100%). 28b) 2S-neopentyloxycarbonyl-amino-3- (6- (4-carboxy-piperidin-1-yl) -purin-g-yl) -propionic acid tert-butyl ester 3g? mg (1 mmol) of 2S-amino-3- (6- (4-carboxy-piperidin-1-yl) -purin-9-yl) -propionic acid tert-butyl ester (Example 20a) in 4 ml of DMF were mixed in O'C with 230 mg (1 mmol) of N- (neopentyloxycarbonyloxy) -succinimide and 0.17 ml of DIPEA and, after slow heating, they were stirred for 12 h at RT. The reaction mixture was concentrated and the residue was chromatographed (Lobar-C, DCM: MeOH: AcOH: H20 90: 10: 1: 1). Yield: 540 mg. MS (ES +): m / e = 505.4 ((M + H) +, 100%). 28c) 2S-neopenti loxycarboni tert-butyl ester 1-amino-3- (6- (4- (1, 4,5,6-tetrahydropyrimidin-2-ylcarbamoyl) -piperidin-1-yl) -purin- g-il) -propionic 505 mg (1 mmol) of 2S-neopentyloxycarbonyl-3- (6- (4-carboxy-piperidin-1-yl) -purin-g-yl) -propionic acid tert-butyl ester (Example 28b) dissolved in 10 ml of acetonitrile, mixed with 250 mg of DCC1 and 184 mg of pentafluorophenol and then stirred for 30 minutes at RT. It was filtered, the mother liquor was concentrated, it was taken up in 5 ml of DMF, mixed with 200 mg of 2-amino-1,4,5,6-tetrahidopyrimidine and stirred for 12 h at RT. The solvent was distilled off in vacuo and the residue was chromatographed (Lobar-C, DCM: MeOH: AcOH: H2O g, 8: 0, 8: 0, 8). Yield: 270 mg. MS (ES +): m / e = 586.5 ((M + H) +, 100%). 28d) 2S-neo? -cyloxycarbonylamino-3- (6- (4- (1, 4,5,6-tetrahydropyrimidin-2-ylcarbamoyl) -piperidin-1-yl) -purin-9-yl) -propionic acid The synthesis was carried out analogously to Example 19c, starting from tert-butyl ester of 2S-neopentyl-oxycarbonylamino-3- (6- (4- (1, 4, 5, 6-tetrahydropyrimidin-2-Icarbamoyl) 1) -piperidin-1-yl) -purin-9-yl) -propionic acid (Example 28c). Yield: 94%. MS (ES +): m / e = 530.4 ((M + H) +, 20%). 3 Example 2g 2S- (1-adamantylmethyl loxycarbonylamino) -3- (6- (4 - (1,4,5,6-tetrahydropyrimidin-2-ylcarbamoyl) -piperidin-1-yl) -purin- g-il) -propionics 2ga) 2S- (1-adamantylmethyloxycarbonylamino) -3- (6- (4-carboxy-iperidin-1-yl) -purin-g-yl) -propionic acid tert-butyl ester The synthesis was carried out analogously to Example 28b, starting from N- (1-adamantylmethyloxycarbonyloxy) -succinimide and tert-butyl ester of 2S-amino-3- (6- (4-carboxy-piperidin-1-yl) - purin-g-il) -propionic (Example 28a). Performance: 85%. MS (ES +): m / e = 583.4 ((M + H) +, 100%). 2gb) 2S- (1-adamantylmethyloxycarbonylamino) -3- (6- (4- (1, 4,5,6-tetrahydropyrimidin-2-iCarbamoyl) -piperidin-1-yl) tert-butyl ester purin-g-il) -propionic The synthesis was carried out analogously to Example 28c, starting from the tert-butyl ester of 2S- (1-adamantylmethyloxycarbonylamino) -3- (6- (4-carboxy-piperidin-1-yl) -purin-g-yl) -propionic (Example 2ga). Performance: 75%. MS (ES +): m / e = 664.5 ((M + H) +, 30%). 29c) 2S- (l-adamantylmethyloxycarbonylamino) -3- (6 - (4- (1,4,5,6-tetrahydropyrimidin-2-ylcarbamoyl) -piperidin-1-yl) -purin-g-yl) -propionic The synthesis was carried out analogously to the example IGC, starting from tert-butyl ester of 2S- (l-adamantyl-tylmethyloxycarbonylamino) -3- (6- (4- (1, 4, 5,6-tetrahydropyrim-din-2) - i 1 carbamoyl) -piperidin-1-yl) -purin-g-yl) -propionic (Example 29b). Performance: 100%. MS (ES +): m / e = 608.4 ((M + H) +, 10%).

Pharmacological research With the test method according to which, for example, the antagonistic action of the compounds according to the invention on the avr3 vitronectin receptor can be determined, the inhibition of the quistrine binding to the human vitronectin receptor (VnR) is described below. ) (ELISA-avp3 test, the test method is abbreviated to "K / VnR" in the enumeration of the test results).

Purification of quistrine Quertrine is purified by the methods of Dennis et al., Such as those described in Proc. Nati Acad. Sci. USA 198g, 87, 2471-2475 and in PROTEINS: Structure, Function and Genetics 1993, 15, 312-321.

Purification of the human vitronectin receptor The human vitronectin receptor is obtained from the placenta of humans by the method of Pytela et al., Methods Enzymol. 1987, 144, 475. The human vitronectin receptor avß3 can also be obtained from some cell lines (eg, from 293 cells, a human embryonic kidney cell line) that are cotransfected with DNA sequences for the two av and 33 subunits of the vitronectin receptor. The subunits were extracted with octylglycoside and then chromatographed on Concanavalin A, Heparin-Sepharose and S-300.

Monoclonal antibodies Murine monoclonal antibodies, specific for the β3 subunit of the vitronectin receptor, are prepared by the method of Newman et al., Blood, 1985, 227-232 or by a similar procedure. The rabbit anti-mouse Fab 2 Fe conjugate on horseradish peroxidase (Fe HRP anti-mouse) was purchased from Peí Freeze (catalog no. 715 305-1).

ELISA test The ability of the substances to inhibit the binding of quistrine to the vitronectin receptor can be detected with an ELISA assay. To this purpose, 96-well Nunc microtiter plates are covered with a quistrine solution (0.002 mg / ml), according to the method of Dennis et al., As described in PROTEINS: Structure, Function and Genetics 1993, 15, 312-321. The plates are then washed twice with PBS / 0.05% Tween-20 and blocked by incubation (for 60 min) with cattle serum albumin (0.5% BSA, RIA quality or better) in Tris-HCl (50 mM), NaCl (100 mM), MgCl2 (1 mM), CaCl2 (1 mM), MnCl2 (1 mM), pH 7. Solutions of known inhibitors and test substances are prepared at concentrations from 2 x 10"12 up to 2 x 10" 6 mol / 1 in assay buffer (BSA (0.5%, RIA quality or higher) in Tris-HCl (50 mM), NaCl (100 mM), MgCl2 (1 mM), CaCl2 (1 mM), MnCl2 (lmM). The blocked plates are emptied and 0.025 ml of this solution, containing a defined concentration (2 x 10"12 to 2 x 10" 6 mol / 1) of a known inhibitor or a test substance, is added to each well. In each well of the plate, 0.025 ml of a solution of the vitronectin receptor is pipetted into the assay buffer (0.03 mg / ml) and the plate is incubated in a shaker for 60-180 min at room temperature. Meanwhile, a solution (6 ml / plate) of a mouse monoclonal antibody is prepared, specific for the β3 subunit of the vitronectin receptor, in assay buffer (0.0015 mg / ml). To this solution is added a second rabbit antibody (0.001 ml of standard solution / 6 ml of the solution of monoclonal anti-ß mouse antibodies), which represents a conjugate Fe HRP anti-mouse antibody, and this anti-mouse antibody mixture. Mouse ß3 and conjugate Fe HRP rabbit anti-mouse antibody is allowed to incubate during the incubation time of the receptor inhibitor. The test plates are washed four times with PBS solution, containing 0.05% Tween-20, 0.05 ml / well of the antibody mixture is pipetted in each case in each well of the plate and incubated for 60-180 min. The plate is washed four times with PBS / 0.05% Tween-20 and then developed with 0.05 ml / well of a PBS solution containing 0.67 mg / ml of o-phenylenediamine and H202 at 0.012%. Alternatively, o-phenylenediamine can be used in a buffer (pH 5) containing Na 3 P 4 and citric acid. The color development is stopped with H2SO 1 N (0.05 ml / well). The absorption of each well is measured at 492-405 nm and the data is evaluated according to standard methods.

The following test results were obtained, Compound K / VnR K / VnR of the example inhibition at 10 μM (in%) IC50 (μM) 1 75 1.1 2 80 0.7 3 77 2.2 4 93 0.15 12 86 0.58 13 92 0.19 14 84 0.65 14 c 22 15 92 0.21 16 85 0.54 16 b 2 17 g2 0.17 18 g5 0.075 19 g7 0.004 23 g3 0.16 24 g5 0.052 ßg 0.345 26 91 0.36

Claims

Claims.- Compounds of formulas I and the, where: means hydrogen, NR6R6, fluorine, chlorine, bromine, OR6, SR6, hydroxy-alkyl- (C1-Cg) -NH, (hydroxy-alkyl- - (C1-Cg)) 2N, amino-alkyl-IC ^^ - CgJ -NH, (amino-alkyl- (C1-Cg)) 2N, hydroxy-C1-C6-S6, hydroxy-C1-C6-S or NH-CO-R6; means R6, fluorine, chlorine, bromine, cyano, NR6R ', OR6, SR6 or hydroxy-alkyl-C ^ CgJ-NH; means a radical of formula II - (CR1R2) n-A- (CR1R2) m- (CR> 11DR3 ^ \ - fCR> 11DR2 * \) q_-QR4"(ID; W stands for a radical of formula III -B-ÍCR1R2) r-A '- (CR1R2) S- (CR1R3) k- (CR1R2) t-D-E (III); Ga means a radical of the formula Ha Wa means a radical of the Illa formula (Illa); A, A ', independently of one another, mean a direct bond, -C (0) NR5, -NR5C (0) -, -C (0) -, -NR5- -0-, -S-, -SO- , -S02-, arylene- (C5-C14), being able to be replaced in the aryl radical of one to five carbon atoms by one to five heteroatoms, alkynylene- (C2-C4), alqueni wood- (C2J-C4), or a divalent radical of a 3 to 7 membered ring, saturated or unsaturated, which may contain one or two heteroatoms, and which may be substituted once or twice with radicals of the series = 0, = S and R3; R-1-, R, independently of one another, mean hydrogen, fluorine, chlorine, cyano, nitro, alkyl-fC ^ -C ^ Q), cycloalkyl- (C3-C14), cycloalkyl- (C3-C14) -alkyl - aryl- (C5-C14), aryl- (C5-C14) -alkyl- - (C], - C8), R6-0-R7, R6-S (0) p-R7 or R6R6'N-R7; R, independently of one another, mean hydrogen, fluorine, chlorine, cyano, nitro, alkyl-C ^ -Cj ^ g), cycloalkyl- (C3-C14), cycloalkyl- (C3-C14) -alkyl- (C1 -CQ), aryl- (C5-C14), aryl- (C5-C14) -alkyl- (C1-C8), R6-0-R7, R6R6'N-R7, R6C (0) -0-R7, R6C (0) R7, R6OC (0) R7, R6N (R6 ') - C (0) 0R7, R6S (0) pN (R5) R7, R6OC (0) N (R5) R7, R6C (0) N (R5 ) R7, R6N (R6 ') C (0) N (R ^) R7, R6N (R6') S (0) pN (R5) R7, R6S (0) pR7, R6SC (0) N (R5) R7, R6N (R6 ') C (0) R7 or R6N (R6') S (0) pR7, it being possible for alkyl to be unsaturated once or several times and, in addition, being able to be alkyl or aryl substituted once or several times with fluorine, chlorine, bromine , cyano, R6R NR7, nitro, R6OC (0) R7, R6C (0) R7, R6N (R6 ') C (0) R7, R6N (R6') - S (0) pR7, R6 or R6-0-R7; R4 means C (0) R8, C (S) R8, S (0) pR8, P (0) R8R8 'or a saturated or unsaturated radical of a four to eight membered heterocycle, containing 1, 2, 3 or 4 heteroatoms of the series N, 0, S; R5 signifies, independently of one another, hydrogen, (C1-C1) alkyl- 'cycloalkyl- (C3"C1), cycloalkyl- (C3-C14) -alkyl- (C1-C8), aryl- (C5-C14) or aryl- - (C5-C1) -alkyl- R6, R6 'signify, independently of one another, hydrogen, (C1-C18) alkyl, (C3-C14) cycloalkyl, (C3-C14) cycloalkyl- (C1-C8) alkyl, aryl- ( C5-C14), in which from 1 to 5 carbon atoms can be replaced by heteroatoms such as N, O, S, or aryl- (C ~ C14) - -alkyl- (C1-C), wherein, in the aryl part, from 1 to 5 carbon atoms can be replaced by heteroatoms such as N, O, S, or R6 and R6, together with the atoms that join them, form a ring system, which can eventually also contain heteroatoms additional series N, O, S, and that may be saturated or unsaturated; R7 signifies, independently of one another, alkylene- (1-C4) or a direct bond; R8, R8 signify, independently of one another, hydroxy, (C1-C8) alkoxy, aryl- (C5-C14) -alkoxy- (C1-C8), aryloxy- (C5-C14), alkyl- (C1- C8) -carbonyloxy-(C1-C4) alkoxy, ary1- (C5-C14) -alkylcarbonyloxy-alkoxy- (C1-C8), NR6R6 ', di- ((C1-C8) alkyl-amino) carbonylmethyl loxydi- (aryl- (C5-C14) -alkyl 1- (C1-C8) -amino) carbony1-methyloxy, aryl- (C5-C14) -amino, the radical of an amino acid, N- (alkyl- (C1-C4)) ^ piperidin-4-yloxy, 2-methylsulfonyletoxy, 1,3-thiazol-2-ylmethyloxy, 3-pyridylmethyloxy. 2- (di- (C 1 -C 4) alkylamino) ethoxy or the radical Q "(CH) 3N + -CH 2 -CH 2-0-, wherein Q" represents a physiologically tolerable anion; B means -O-, -S-, -NR5-, -NR5-C (0) -, -C (0) -NR5-, a direct bond or a divalent radical of a ring of 3 to 7 members, saturated or unsaturated, which may contain one or two heteroatoms, and which may be substituted once or twice with radicals of the series = 0, = S and R3; D means a direct bond, -NR6-, -C (0) -NR6-, -NR6- -C (0) -, -S (0) u-NR6-, -NR6-C (0) -NR6-, -NR6-C (S) -NR6-, -NR6-S (0) u-NR6-, -NR6-C (0) 0-, -NR6-N = CR6-, -NR6-S (0) u- , -aryl- (C5-C14) -CO-, -aryl- (C5-C1) -S (0) u-, -N = CR6-, -R6C = N- or -R6C = N-NR6-, being the divalent radicals represented by D linked to group E through the free bond on the right side; E means hydrogen, R6-C (= NR6) -NR6-, R6R6 'NC (= NR6) -, R6R6'NC (= NR6) -NR6- or a radical of a ring system of 4 to 11 members, monocyclic or polycyclic, aromatic or non-aromatic, which may optionally contain 1, 2, 3 6 4 heteroatoms of the series N, 0 and S, and which may optionally be substituted one, two or three times with radicals of the series R3, R, = 0, = S and R6R6'NC (= NR6) -; n means zero, one, two, three, four or five; m means zero, one, two, three, four or five; i means zero or one; p mean, independently of one another, zero, one or two; q means zero, one or two; r means zero, one, two, three, four, five or six; s means zero, one, two, three, four or five; t means zero, one, two, three, four or five; means zero or one; u means one or two; in all its stereoisomeric forms and mixtures thereof in all ratios, and their physiologically tolerable salts, as well as their prodrugs; it may also be in place of the purine backbone shown in formulas I and II, a 3-deaza-pu-rine backbone, a 7-deaza-purine backbone or a 7-deaza-8-aza-purine backbone. 2a.- Compounds of formulas I and according to claim 1, in which shydrogenase is hydrogen, NR6R6 ', hydroxy-alkyl-1-Cgj-NH or NH-CO-R6; And it means hydrogen; G means a radical of formula II - (CR1R2) n-A- (CR1R2) m- (CR1R3) - (CR1R2) q -R4 (II): W means a radical of the formula III -B- (CR1R2) r-A '- (CR1R2) s- (CR1R3) k- (CR1R2) t-D-E (III); Ga means a radical of the formula lia - (CR1R2) r-A '- (CR1R2) s- (CR1R3) k- (CR1R2) t-D-e (| the > a means a radical of the Illa formula -B- (CR1R2) n-A- (CR1R2) m- (CR1R3) - (CR1R2) q-R4 (Illa); A, A ', independently of one another, mean a direct bond, -C (0) NR5-, -NR5C (0) -, -C (O) -, -NR5-, -O-, -S-, - SO-, -S02-, alkynylene- (C2-C4), alkenylene- (C2-C4) or arylene or (C5-Ci4), being able to be replaced in the aryl radical of one to three carbon atoms by one to three heteroatoms of the series 0, N, S; Rx 1, R "), independently of one another, mean hydrogen, fluorine, cyano, alkyl- (C1-C), aryl- (C5-Cg), aryl- (C5-C6) -alkyl (C1-C4), R6-0-R7 or R6R6'N-R7; R3, independently of one another, mean hydrogen, (C1-C18) alkyl, (C3-C14) cycloalkyl, (C3-C1) -cycloalkyl- (C1-C8) alkyl, (C5-C14) aryl , aryl- - (C5-C14) -alkyl- (C1-C8), R6R6'N-R7, R6C (0) OR7, R6S (0) pN (R5) R7, R6OC (0) N (R5) R7 , R6C (0) N (R5) R7, R6N (R6) C (0) N (R5) R7, R6N (R6 ') S (0) pN (R5) R7 or RN (R6') C (0) R7 wherein unsaturated alkyl may be one or more times and, in addition, alkyl or aryl may be substituted once or several times with fluorine, chlorine, bromine, cyano, R6R6'NR7, nitro, R6OC (0) R7, R6C (0) R7, R6N (R6 ') C (0) R7, R6N (R6') S (0) pR7, R6 or R6OR7; R4 means C (0) R8; R5 signifies, independently of one another, hydrogen or (C1-C4) alkyl; CIR, Rs stand for, independently of one another, hydrogen, (C1-C18) alkyl, (C3-C14) cycloalkyl, (C3-C14) cycloalkyl- (C1-C8) alkyl, aryl- (C5) -C14), in which from one to three carbon atoms can be replaced by one to three heteroatoms of the series N, S, O, or aryl-, wherein, in the aryl part, from one to three carbon atoms can be replaced by one to three heteroatoms of the series N, S, O, or R6 and R6, together with the atoms that join them, form a ring system, which eventually can also contain additional heteroatoms of the N, S series, OR; they mean, independently of one another, alkyne- - (C1-C2) or a direct bond; they mean, independently of one another, hydroxy, alkoxy- (C1-C4), aryl- (C5-C14) -alkoxy- (C1-C4), aryloxy- (C5-C14), alkyl- (C? ~ C8) -carbony loxy-alkoxy- (C1-C4), ary1- (C5-C14) -alkyloxy-alkoxy- (C1-C4) or the radical of an amino acid; means -O-, -S-, -NR ° -, a direct bond or a divalent radical of a 3 to 7 membered ring, saturated or unsaturated, which may contain one or two heteroatoms, and which may be substituted one or two sometimes with radicals of the series = 0, = S and R3; means a direct bond, -NR-, -C (0) -NRD-, -NR6- -C (O) -, -NR6-C (0) -NR6-, -NR6-C (0) 0-, - NR6-N = CR6-, the divalent radicals represented by D being linked to group E via the free bond on the right side; means hydrogen, R6-C (= NR6) -NR6 '-, R6R6' N-C (= NR6) -, R6R6'N-C (= NR6) -NR6- or a radical of the series which may optionally be substituted one to three times with radicals of the series R3, R5, = 0, = S and R6R6 'N-C (= NR6) -; n means one, two, three or four; m means zero or one; i means zero or one; q means zero or one; p mean, independently of one another, zero, one or two; r means zero, one, two, three, four or five; s means zero, one or two; t means zero, one or two; k means zero or one; v means zero, one, two or three; in all its stereoisomeric forms and mixtures thereof in all ratios, and their physiologically tolerable salts, as well as their prodrugs. 3a.- Compounds of formulas I and according to claim 1 and / 6 2a, wherein X means hydrogen, NR6R6 'or NH-CO-R6; And it means hydrogen; G means a radical of formula II W means a radical of the formula III -B- (CR1R2) r-A '- (CR1R2) s- (CR1R3) k- (CR1R2) t-D-E. (III); Ga means a radical of the formula Ha - (CR1R2) r-A '- (CR1R2) S- (CR1R3) k- (CR1R2) t-D-E (Ha); Wa means a radical of the Illa formula -B- (CR1R2) n-A- (CR1R2) m- (CR1R3) i- (CR1R2) q-R4 (Illa); A, A ', independently of one another, mean a direct bond, -C (0) NR5-, -NR5C (0) - or arylene- (C5-Cg), and one to two carbon atoms may be replaced in the aryl radical. carbon by nitrogen atoms; R, R2 signify hydrogen; R3 signifies, independently of one another, hydrogen, cycloalkyl- (C3-C14), cycloalkyl- (C3-C14) -alkyl- (C1-C8), aryl- (C5-C14), aryl- (C5-) C14) -alkyl- (C1-C8), R6R6'N-R7, R6OC (0) N (R5) R7, R6C (0) N (R5) R7, R6N (R6 ') C (0) N (R5) R7, R6C (0) R7 or R6N- i 7 (R °) C (0) R', where unsaturated alkyl may be present one or more times and, in addition, alkyl or aryl may be substituted once or several times with fluorine, chlorine, bromine, cyano, R6R6'NR7, R6C (0) R7, R6N (R6 ') C (0) R7, R6 or R60R7; R4 means C (0) R8; R5 signifies, independently of one another, hydrogen or (C1-C4) alkyl; R6, R6 denote, independently of one another, hydrogen, (C1-C8) alkyl, (C3-C12) cycloalkyl, (C3-C12) cycloalkyl- (C1-C8) alkyl, aryl- (C5-C14), wherein from one to three carbon atoms can be replaced by one to three heteroatoms of the series N, S, O, or aryl- (C5-C14) -alkyl- (C1-C8), in where, on the aryl part, from one to three carbon atoms can be replaced by one to three heteroatoms of the N, S, O series; R7 means a direct link; R8 signifies, independently of one another, hydroxy, alkoxy- (C1-C4), aryl- (C5-C14) -alkoxy- (C1-C4), aryloxy- (C5-C14), alkyl- (C1-C8) -carbonyloxy-(C1-C4) alkoxy, ary1- (C5-C14) -alkyl 1- (C1-C4) -carboni or the radical of an amino acid; B means -0-, -S-, -NR5-, a direct bond or a divalent radical of a 3 to 7 membered ring, saturated or unsaturated, which may contain one or two heteroatoms, and which may be substituted one or two sometimes with radicals of the series = 0, = S and R3; D means a direct bond, -NR6-, -C (0) -NR6- or -NR6-C (0) -; E means hydrogen, R6-C (= NR6) -NR6 '-, R6R6' N-C (= NR6 ') -, R6R6'N-C (= NR6') - NR6- or a radical of the series which may optionally be substituted one to three times with radicals of the series R3, R5, = 0, = S and R6R6'N-C (= NR6) -; r means zero, one, two, three, four or five; s means zero or one; t means zero or one; k means zero or one; n means one, two, three or four; m means zero or one; i means zero or one; q means zero or one; in all its stereoisomeric forms and mixtures thereof in all ratios, and their physiologically tolerable salts, as well as their prodrugs. 4a.- Compounds of the formula I according to claim 1 and / or 2a, wherein X means hydrogen, NR6R6 'or NH-CO-R6; And it means hydrogen; means a radical of formula II W means a radical of formula III B-ÍCR > 11 RD2'I A'-ÍCR > 11 (III); R1, R2 signify, independently of one another, hydrogen, (C1-C4) alkyl, aryl- (C5-Cg) or aryl- (C5-Cg) - -alkyl-ΔCj ^ -C.j); R3, independently of one another, mean hydrogen, (C1-C18) alkyl, (C3-C14) cycloalkyl, (C3-C1) -cycloalkyl- (C1-C8) alkyl, aryl- (C5-C1) , aryl- - (C5-C14) -alkyl- (C1-C8), R6R6'N-R7, R6OC (0) N (R5) R7, R6S02N (R5) R7, R6C (0) N (R5) R7 , R6N (R6 ') C (0) N (R5) R7, R6C (0) R7 or R6N (R6') C (0) R7, wherein unsaturated alkyl may be one or more times and, in addition, may be alkyl or aryl substituted one or more times with fluorine, chlorine, bromine, cyano, R6R6'NR7, R6C (0) R7, R6N (R6) C (0) R 'R6OR7; means C (0) R R5 signifies, independently of one another, hydrogen or (C1-C4) alkyl; R6, R6 signify, independently of one another, hydrogen, (C1-C18) alkyl, (C3-C12) cycloalkyl, (C3-C12) cycloalkyl- (C1-C8) alkyl, aryl- (C5) -C14), in which from 1 to 3 carbon atoms can be replaced by 1 to 3 heteroatoms of the series N, S, 0, or aryl- (C5-C14) -alkyl- (C1-C8), in where in the aryl radicals, from 1 to 3 carbon atoms can be replaced by 1 to 3 heteroatoms of the series N, S, 0, and R6 and R6 can also form, together with the atoms that join them, a ring system which may optionally also contain additional heteroatoms of the series N, S, O; R7 means a direct link; R8 signifies, independently of one another, hydroxy, (C1-C4) alkoxy, aryl- (C5-C14) -alkoxy- (C1-C4), aryloxy- (C5-C14), alkyl- (C1-C8) -carbonyloxy-(C1-C4) alkoxy or ary1- (C5-C14) -alkyl 1- (C1-C4) -carbonyl i-alkoxy- (C1-C4); B means 1,4-piperidinediyl or 1,4-piperazindiyl, in the case of the 1-4-piperidinedilyl radical, the nitrogen atom of the piperidine is attached to the purine backbone; D means a direct bond, -NR6-, -C (0) -NR6- or -NR6-C (0) -; E means hydrogen, R6-C (= NR6) -NR6 '-, R6R6'N-C (= NR6') -, R6R6'N-C (= NR6 ') -NR6- or a radical of the series which may optionally be substituted one to three times with radicals of the series R3, R5, = 0, = S and R6R6 'N-C (= NR6) -; r means zero, one or two; s means zero or one; t means zero or one; k means zero or one; n means zero, one or two; m means zero or one; i means zero or one; q means zero or one; in all its stereoisomeric forms and mixtures thereof in all ratios, and their physiologically tolerable salts, as well as their prodrugs. 5a.- Compounds of the formula I according to one or several of the claims la a 4a, wherein X means hydrogen; And it means hydrogen; G means a radical of formula II - (CR1R2) n-A- (CR1R2) m- (CR1R3) r (CR1R2) q -R4 (||); means a radical of formula III -B- (CR1R2) r-A '- (CR1R2) S- (CR1R3) k- (CR1R2) t-D-E (III); A, A 'mean a direct link; R * i-, R? ") denote, independently of one another, hydrogen or alkyl? - (C1-C2); R3 means R6R6'N-R7, R6OC (0) N (R5) R7, R6S02N (R5) R7, R6C (0) N (R5) R7 or R6N (R6 ') C (0) N (R5) R7; R4 means C (0) R8; R5 means hydrogen or (C1-C2) alkyl; R ° signify, independently of one another, hydrogen, alkyl-C 1 -C 5), cycloalkyl- (C 3 -C 12), cycloalkyl- (C 3 -C 12) -alkyl- (C 1 -C) -aryl- ( C5-C14), wherein from 1 to 3 carbon atoms can be replaced by 1 to 3 heteroatoms of the series N, S, 0, or aryl- (C5-C1) -alkyl- (C1-C), in where in the aryl radicals, from 1 to 3 carbon atoms can be replaced by 1 to 3 heteroatoms of the series N, S, 0, and R ° and R ° can also form, together with the atoms that join them, a system of rings which may optionally also contain additional heteroatoms of the series N, S, 0; means a direct link; means hydroxy, alkoxy- (C? -C), aryl-? C? -Cj ^) -alkoxy- - (C1-C4), aryloxy- (C5-C14), alkyl-t ^ -C) -carbonyloxy- -alkoxy -ICj ^ -Cj) oaryl- (C5-C14) -alkyl- (C1-C4) -carboni1-oxy-alkoxy- (C1-C4); B means 1,4-piperidinediyl, the nitrogen atom of piperidine being attached to the purine skeleton; D means -NR6- or -C (0) -NR-, the nitrogen atom being linked in the group -C (0) -NR6- to the group E; E means R6R6'N-C (= NR6 ') - or a radical of the series which may optionally be substituted one to three times with radicals of the series R3, R5, = 0, = S and R6R6 'N-C (= NR6) -; r means zero or one; s means zero; t means zero; k means zero; n means one; m means zero; i means one; q means zero; in all its stereoisomeric forms and mixtures thereof in all ratios, and their physiologically tolerable salts, as well as their prodrugs. 6a.- Compounds of the formula Ih wherein R3 represents R6R6'N-R7, R60C (0) N (R5) R7, R6S02N- (R5) R7, R6C (0) N (R5) R7 or R6N (R6 ') C (0) N (R5) R7, and Rh represents the carboxylic acid group COOH or represents a carboxylic acid derivative; in all its stereoisomeric forms and mixtures thereof in all ratios, and their physiologically tolerable salts, as well as their prodrugs. 7a.- 2S-benzyloxycarbonylamino-3- (6- (4 - (1,4, 5,6-tetrahydropyrimidin-2-yl-carbamoyl) -? I? Eridin-1-yl) -purin-g- acid il) -propionic and its physiologically tolerable salts, as well as its prodrugs. 8a.- Process for the preparation of a compound of the formulas I and according to one or more of the claims la to 7a, characterized in that two or more fragments that can be derived retrosynthetically from the formulas I or la. 9a.- Process according to claim 8, characterized in that, for the preparation of a compound of the formula I, a compound of the formula IV, wherein Ll represents a leaving group and X and Y are defined as in claim la a 7a, but the functional groups may also be in the form of precursors or in protected form, reacted in steps with a compound of the formula V and with a compound of formula VII H-B- (CR1R) r-A '- (CR1R2) s- (CR1R3) k- (CR1R2) t-R13 (VII) to give a compound of formula VIII, 15 where in formulas V, VII and VIII L2 represents a labile group; the radical R11 represents - (CR1R2) n-A- (CR1R2) m- (CR1R3) i - (CR * R2) q - RR10. the radical R15 represents -B- (CR * R2) r-A '- (CR1R2) s- (CR1R3) k- (CRXR2) t -RR! 3. R has the meanings indicated in claims la to 7a, the groups represented by R4 being also able to be shown in protected form; RiJ has the meanings of the group D-E indicated in claims la to 7a, it being possible to present groups 1-5 included in D-E also in protected form, or R represents a group that can be transformed into the group -D-E; R, R2, R3, A, A ', B, X, Y, n, m, i, q, r, s, k and t have the meanings indicated in claims 1 to 7a; and, then, eventually the groups R10 and R13 are transformed into the R and D-E groups; or, for the preparation of a compound of the formula la, a compound of the formula IV is reacted, in stages, with a compound of the formula IX L2-ICR1R2) r-A '- (CR1R ^ -ICR1R3) k- (CR1R2) t-R13 (IX) and with a compound of formula XI H-B- (CR1R2) n-A- (CR1R2) m- (CR1R3) i- (CR1R2) q -R10 (XI) to give a compound of formula XII 17 N N ^ -Y (XII) N N I R16 wherein in the formulas IX, XI and XII the radical R6 represents - (CR1R2) r-A '- (CR1R2) s- (CR1R3) k- (CR1R2) tR13 the radical R17 represents -B- (CR1R2 ) nA- (CR1R2) m- (CR1R3) i- (CR1R2) qR 10. R1, R2, R3, R10, R13, A, A ', B, X, Y, L2, n, m, i, q, r, s, k and t are defined as above for formulas VII and VIII; and then, optionally, groups R10 and R3 are transformed into groups R and D-E. 10a.- Compounds of formulas I and according to one or more of claims 1 to 7a, and / or their physiologically tolerable salts and / or their prodrugs, for use as a medicament. The compounds of the formulas I and the one according to one or more of the claims 7a, and / or their physiologically tolerable salts and / or their prodrugs, as inhibitors of the bone resorption by the osteoclasts, as inhibitors of the growth of tumors or metastasization of tumors, as antiinflammatories, for the therapy or prophylaxis of cardiovascular diseases, for the therapy or prophylaxis of nephropathies or retinopa-aunts, or as antagonists of vitronectin receptors for therapy or prophylaxis of diseases that they are based on the reciprocal action between vitronectin receptors and their ligands in cell-cell or cell-matrix interaction processes. 12a.- Pharmaceutical preparation containing at least one compound of the formulas I or according to one or more of the claims la to 7a, and / or their physiologically tolerable salts and / or their prodrugs, together with support substances and / or additives pharmaceutically irreproachable.