Patent Publication Number: US-9884814-B2

Title: Acylguanidines for treating osteoarthritis

Description:
The present invention relates to compounds of the formula I and in particular medicaments comprising at least one compound of the formula I for use in the treatment and/or prophylaxis of physiological and/or pathophysiological states in the triggering of which cathepsin D is involved, in particular for use in the treatment and/or prophylaxis of arthrosis, traumatic cartilage injuries, arthritis, pain, allodynia or hyperalgesia. 
     BACKGROUND OF THE INVENTION 
     Arthrosis is the most widespread joint disease worldwide, and radiological signs of arthrosis are found in the majority of over-65 year olds. In spite of this significant importance for the health system, the causes of arthrosis remain unclear to date, and effective preventative measures furthermore remain a distant aim. A reduction in the joint gap (caused by destruction of the joint cartilage), together with changes in the subchondral bone and osteophyte formation, are the radiological characteristics of the disease. For the patient, however, pain (load-dependent and nocturnal rest pain) with subsequent function impairments are to the fore. It is also these which force the patient into social isolation with corresponding secondary diseases. 
     The term arthrosis according to an unofficial definition in Germany denotes “joint wear” which exceeds the usual extent for the age. The causes are regarded as being excessive load (for example increased body weight), connatal or traumatic causes, such as malpositioning of the joints or also bone deformations due to bone diseases, such as osteoporosis. Arthrosis can likewise arise as a consequence of another disease, for example joint inflammation (arthritis) (secondary arthrosis), or accompany overload-induced effusion (secondary inflammation reaction) (activated arthrosis). The Anglo-American specialist literature differentiates between osteoarthrosis (osteoarthritis [OA]), in which the destruction of the joint surfaces can probably be attributed principally to the effects of load, and arthritis (rheumatoid arthritis [RA]), in which joint degeneration due to an inflammatory component is to the fore. 
     In principle, arthrosis is also differentiated according to its cause. Arthrosis alcaptonurica is based on increased deposition of homogenitic acid in joints in the case of previously existing alcaptonuria. In the case of haemophilic arthrosis, regular intra-articular bleeding occurs in the case of haemophilia (haemophilic joint). Arthrosis urica is caused by the mechanical influence of urate crystals (uric acid) on the healthy cartilage (W. Pschyrembel et al.: Klinisches Worterbuch mit klinischen Syndromen and einem Anhang Nomina Anatomica [Clinical Dictionary with Clinical Syndromes and a Nomina Anatomica Annex]. Verlag Walter de Gruyter &amp; Co, 253rd Edition, 1977). 
     The classical cause of arthrosis is dysplasia of joints. Using the example of the hip, it becomes clear that the zone with the greatest mechanical stress in the case of a physiological hip position represents a significantly larger area than in the case of a dysplastic hip. However, the stresses caused by the forces acting on the joint are substantially independent of the joint shape. They are essentially distributed over the main stress zone(s). A greater pressure will thus arise in the case of a relatively small zone than in the case of a larger one. The biomechanical pressure on the joint cartilage is thus greater in the case of a dysplastic hip than in the case of a physiological hip position. This rule is generally regarded as the cause of the increased occurrence of arthrotic changes in supporting joints which differ from the ideal anatomical shape. 
     If the consequences of an injury are responsible for premature wear, the term post-traumatic arthrosis is used. Further causes of secondary arthrosis that are being discussed are mechanical, inflammatory, metabolic, chemical (quinolones), trophic, hormonal, neurological and genetic reasons. In most cases, however, the diagnosis given is idiopathic arthrosis, by which the doctor means an apparent absence of a causal disease (H. I. Roach and S. Tilley, Bone and Osteoarthritis F. Bronner and M. C. Farach-Carson (Editors), Verlag Springer, Volume 4, 2007). 
     Medicinal causes of arthrosis can be, for example, antibiotics of the gyrase inhibitor type (fluoroquinolones, such as ciprofloxacin, levofloxacin). These medicaments result in complexing of magnesium ions in poorly vascularised tissues (hyaline joint cartilage, tendon tissue), which has the consequence that irreversible damage occurs to connective tissue. This damage is generally more pronounced in the growth phase in children and juveniles. Tendinopathies and arthropathies are known side effects of this class of medicaments. In adults, these antibiotics result in accelerated physiological degradation of the hyaline joint cartilage according to information from independent pharmacologists and rheumatologists (M. Menschik et al., Antimicrob. Agents Chemother. 41, 1997, pp. 2562-2565; M. Egerbacher et al., Arch. Toxicol. 73, 2000, pp. 557-563; H. Chang et al., Scand. J. Infect. Dis. 28, 1996, pp. 641-643; A. Chaslerie et al., Therapie 47, 1992, p. 80). Extended treatment with phenprocoumone can also favour arthrosis by decreasing bone density in the case of stresses of the joint internal structure. 
     Besides age, known risk factors for osteoarthrosis are mechanical overload, (micro)traumas, joint destabilisation caused by loss of the securing mechanisms, and genetic factors. However, neither the occurrence nor possible interventions have been fully explained (H. I. Roach and S. Tilley, Bone and Osteoarthritis F. Bronner and M. C. Farach-Carson (Editors), Verlag Springer, Volume 4, 2007). 
     In a joint affected by arthrosis, the content of nitrogen monoxide is increased in some cases. A similar situation has been observed due to high mechanical irritation of cartilage tissue (P. Das et al., Journal of Orthopaedic Research 15, 1997, pp. 87-93. A. J. Farrell et al. Annals of the Rheumatic Diseases 51, 1992, pp. 1219-1222; B. Fermor et al., Journal of Orthopaedic Research 19, 2001, pp. 729-737), whereas moderate mechanical stimulation tends to have a positive effect. The action of mechanical forces is thus causally involved in the progress of osteoarthrosis (X. Liu et al., Biorheology 43, 2006, pp. 183-190). 
     In principle, arthrosis therapy follows two aims: firstly freedom from pain under normal load and secondly the prevention of mechanical restrictions or changes in a joint. These aims cannot be achieved in the long term by pain treatment as a purely symptomatic therapy approach, since this cannot halt the progress of the disease. If the latter is to be achieved, the cartilage destruction must be stopped. Since the joint cartilage in adult patients cannot regenerate, the elimination of pathogenetic factors, such as joint dysplasia or malpositions, which result in increased point pressure on the joint cartilage, is in addition enormously important. 
     Finally, it is attempted to prevent or stop the degeneration processes in the cartilage tissue with the aid of medicaments. 
     An essential factor for the functioning state of the joint cartilage and thus the resistance thereof to stress is the extracellular matrix, which primarily consists of collagens, proteoglycans and water. The enzymes involved in degradation of the extracellular matrix include, in particular, the metalloproteases, aggrecanases and cathepsin enzymes. However, further enzymes can in principle also degrade cartilage matrix, for example plasmin, kallikrein, neutrophilelastase, tryptase and chymase. 
     Cathepsins belong to the papain superfamily of lysosomal proteases. Cathepsins are involved in normal proteolysis and the conversion of target proteins and tissues and in the initiation of proteolytic cascades and proenzyme activations. In addition, they are involved in MHC class II expression (Baldwin (1993) Proc. Natl. Acad. Sci., 90: 6796-6800; Mixuochi (1994) Immunol. Lett., 43: 189-193). However, abnormal cathepsin expression can result in severe diseases. Thus, increased cathepsin expression has been detected in cancer cells, for example in breast, lung, prostate, glioblastoma and head and neck cancer, and it has been shown that cathepsins are associated with inadequate therapy success in breast, lung, head and neck cancer, and in brain tumours (Kos et al. (1998) Oncol. Rep., 5: 1349-1361; Yan et al. (1998) Biol. Chem., 379:113-123; Mort et al.; (1997) Int. J. Biochem. Cell Biol., 29: 715-720; Friedrick et al. (1999) Eur. J Cancer, 35: 138-144). In addition, abnormal cathepsin expression is apparently involved in the development of inflammatory and non-inflammatory diseases, such as, for example, rheumatoid arthritis and osteoarthrosis (Keyszer (1995) Arthritis Rheum., 38: 976-984). 
     The molecular mechanism of cathepsin activity has not been fully explained. On the one hand, it has been found that, for example, induced cathepsin expression protects B cells from which serum is taken against apoptosis, and that treatment of the cells with antisense oligonucleotides of cathepsin B induces apoptosis (Shibata et al. (1998) Biochem. Biophys. Res. Commun., 251: 199-20; Isahara et at. (1999) Neuroscience, 91: 233-249). These reports suggest an anti-apoptotic role of cathepsins. However, they are in complete contrast to earlier reports, which describe cathepsins as apoptosis mediators (Roberts et al (1997) Gastroenterology, 113: 1714-1726; Jones et al. (1998) Am. J. Physiol., 275: G723-730). 
     Cathepsins are synthesised as inactive zymogens on ribosomes and transferred into the lysosomal system. After proteolytic cleaving-off of the N-terminal propeptide, the cathepsin concentration in the acidic environment of the lysosomes increases to 1 mM, and the cathepsins are released into the extracellular medium by the lysosomes. 
     In the case of cathepsins, a differentiation is made between the cysteine cathepsins B, C, H, F, K, L, O, S, V and W, the aspartyl cathepsins D and E, and the serine cathepsin G. 
     Examples of cathepsin inhibitors in clinical development are cathepsin K inhibitors for the treatment of arthrosis and cathepsin S inhibitors for the treatment of arthritis, neuropathic pain and psoriasis. 
     Besides cathepsin D, the aspartyl proteases also include the HIV aspartyl protease (HIV-1 protease), renin, pepsin A and C, BACE (Asp2, memapsin), plasmepsins and the aspartyl haemoglobinases (Takahashi, T. et al., Ed. Aspartic Proteinases Structure, Function, Biology and Biomedical Implications (Plenum Press, New York, 1995), Adams, J. et al., Ann. Rep. Med. Chem. 31, 279-288, 1996; Edmunds J. et al., Ann. Rep. Med. Chem. 31, 51-60, 1996; Miller, D. K. et al., Ann. Rep. Med. Chem 31, 249-268, 1996). Cathepsin D is normally involved in the degradation of intracellular or phagocytised proteins and thus plays an important role in protein metabolism (Helseth, et al., Proc. Natl. Acad. Sci. USA 81, 3302-3306, 1984), in protein catabolism (Kay, et al., Intracellular Protein Catabolism (eds. Katunuma, et al., 155-162, 1989) and in antigen processing (Guagliardi, et al., Nature, 343, 133-139, 1990; Van Noort, et al., J. Biol. Chem., 264, 14159-14164, 1989). 
     Increased cathepsin D levels are associated with a number of diseases. Thus, increased cathepsin D levels correlate with a poor prognosis in breast cancer and with increased cell invasion and an increased risk of metastases, and shorter relapse-free survival time after therapy and a lower survival rate overall (Westley B. R. et al., Eur. J. Cancer 32, 15-24, 1996; Rochefort, H., Semin. Cancer Biol. 1:153, 1990; Tandon, A. K. et al., N. Engl. J. Med. 322, 297, 1990). The cathepsin D secretion rate in breast cancer is promoted by overexpression of the gene and by modified processing of the protein. Increased levels of cathepsin D and other proteases, such as, for example, collagenase, produced in the immediate vicinity of a growing tumour, could degrade the extracellular matrix in the environment of the tumour and thus promote the detachment of tumour cells and invasion into new tissue via the lymph and circulation system (Liotta L. A., Scientific American February: 54, 1992; Liotta L. A. and Stetler-Stevenson W. G., Cancer Biol. 1:99, 1990; Liaudet E., Cell Growth Differ. 6:1045-1052, 1995; Ross J. S., Am. J. Clin. Pathol. 104:36-41, 1995; Dickinson A. J., J. Urol. 154:237-241, 1995). 
     Cathepsin D is in addition associated with degenerative changes in the brain, such as, for example, Alzheimer&#39;s disease. Thus, catepsin D is associated with cleavage of the amyloid-β precursor protein or of a mutant precursor which increases the expression of the amyloid protein in transfected cells (Cataldo, A. M. et al., Proc. Natl. Acad. Sci. 87: 3861, 1990; Ladror, U. S. et al., J. Biol. Chem. 269: 18422, 1994, Evin G., Biochemistry 34: 14185-14192, 1995). The amyloid-β protein, which is formed by proteolysis of the amyloid-β precursor protein, results in the formation of plaques in the brain and appears to be responsible for the development of Alzheimer&#39;s disease. Increased cathepsin D levels have also been found in the cerebrospinal fluid of Alzheimer&#39;s patients, and a high proteolytic activity of cathepsin D compared with the mutant amyloid-β precursor protein has been found (Schwager, A. L., et al. J. Neurochem. 64:443, 1995). In addition, a significant increase in cathepsin D activity is measured in biopsies from Huntington&#39;s disease patients (Mantle D., J. Neurol. Sci. 131: 65-70, 1995). 
     Cathepsin D is thought to play an essential role at various levels in the development of arthrosis. Thus, increased mRNA levels of cathepsin D are measured in the joint cartilage of the hip joint head in dogs with spontaneous arthrosis compared with healthy dogs (Clements D. N. et al., Arthritis Res. Ther. 2006; 8(6): R158; Ritchlin C. et al., Scand. J. Immunnol. 40: 292-298, 1994). Devauchelle V. et al. (Genes Immun. 2004, 5(8): 597-608) also show different expression rates of cathepsin D in human patients in the case of arthrosis compared with rheumatoid arthritis (see also Keyszer G. M., Arthritis Rheum. 38: 976-984, 1995). Cathepsin D also appears to play a role in mucolipidosis (Kopitz J., Biochem. J. 295, 2: 577-580, 1993). 
     The lysosomal endopeptidase cathepsin D is the most widespread pro-teinase in the chondrocytes (Ruiz-Romero C. et al., Proteomics. 2005, 5(12): 3048-59). In addition, the proteolytic activity of cathepsin D has been detected in the cultivated synovium from osteoarthrosis patients (Bo G. P. et al., Clin. Rheumatol. 2009, 28(2): 191-9), and increased proteolytic activity is also found in synovectomy tissue of patients with rheumatoid arthritis (Taubert H. et al., Autoimmunity. 2002, 35(3): 221-4). Lorenz et al. (Proteomics. 2003, 3(6): 991-1002) thus also write that, although the lysosomal and secreted aspartyl protease cathepsin D has not yet been studied in detail with respect to arthritis and arthrosis, in contrast to cathepsins B and L, Lorenz et al. found, however, higher protein levels of cathepsin D in the synovial tissue of patients with arthrosis compared with patients with rheumatoid arthritis. 
     Gedikoglu et al. (Ann. Rheum. Dis. 1986, 45(4): 289-92) have likewise detected an increased proteolytic activity of cathepsin D in synovial tissue and Byliss and Ali (Biochem. J. 1978, 171(1): 149-54) in the cartilage of patients with arthrosis. 
     In the case of arthrosis, a reduction in the pH occurs in regions of the cartilage. This reduction in the pH is of crucial importance for the under-standing of catabolic processes in the cartilage. 
     In the case of arthrosis, a direct correlation is thus also found between a low pH in the joint tissue and the severity and progress of the disease. At a pH of 5.5, autodigestion of the cartilage occurs. This can be inhibited virtually completely by pepstatin or ritonavir in explant cultures (for example from mouse, cow or human). This suggests an essential role, or even a key role, of cathepsin D in arthrosis, since pepstatin inhibits aspartyl proteases with one exception—BACE 1—and only these two aspartyl proteases have hitherto been identified in the cartilage tissue. Thus, Bo G. P. et al. (Clin. Rheumatol. 2009, 28(2): 191-9) also describe the important role of cathepsin D in pathological changes in joints. 
     The best-known aspartyl protease inhibitor is pepstatin, a peptide which was originally isolated from a  Streptomyces  culture. Pepstatin is effective against pepsin, cathepsin and renin. Many aspartyl protease inhibitors have therefore been modelled on the example of the structure of pepstatin (U.S. Pat. No. 4,746,648; Umezawa, H, et al., J Antibiot (Tokyo) 23: 259-62, 1970; Morishima, H., et al., J. Antibiot. (Tokyo) 23: 263-5, 1970; Lin, Ty and Williams, H R., J. Biol. Chem. 254: 11875-83, 1979; Jupp, R A, et al., Biochem. J. 265: 871-8, 1990; Agarwal, N S and Rich, D H, J. Med. Chem. 29: 2519-24, 1986; Baldwin, E T, et al., Proc. Natl. Acad. Sci., USA 90: 6796-800, 1993; Francis, S E et al., EMBO J 13: 306-17, 1994). 
     Aspartyl proteases and cathepsin D are frequently described as target proteins for active compounds for the treatment of neurodegenerative diseases, cognitive disorders, dementia, Alzheimer&#39;s, cancer, malaria, HIV infection and diseases of the cardiovascular system, and inhibitors of aspartyl proteases or cathepsin D are disclosed for the treatment of these diseases, such as, for example, in WO 2009013293, EP 1987834, EP 1872780, EP 1867329, EP 1745778, EP 1745777, EP 1745776, WO 1999002153, WO 1999055687, U.S. Pat. No. 6,150,416, WO 2003106405, WO 2005087751, WO 2005087215, WO 2005016876, US 2006281729, WO 2008119772, WO 2006074950, WO 2007077004, WO 2005049585, U.S. Pat. No. 6,251,928 and U.S. Pat. No. 6,150,416. 
     Peptide derivatives or guanidines as analgesics are known, for example, from WO 9524421. Further acylguanidines for the treatment of cancer and/or for treatment of neurodegenerative are known from WO 2010025448, WO 2011010013, WO 9920599 and WO 9736862, acylguanidines for the treatment of coagulation disorders are known from WO 9612499. Acylguanidines for the treatment of migraine are known from EP 1728784. Diazaheterocyclic guandines are known from U.S. Pat. No. 3,098,066. 
     WO 02236554 discloses acylguandines as 5-HT 7  receptor antagonists for the treatment of depression, schizophrenia and sleep disorders. 
     Although the known cathepsin D inhibitors and the two model compounds pepstatin and ritonavir effectively inhibit cathepsin D activity, they have, however, quite low selectivity for other aspartyl proteases. The role of the renin-angiotensin system (RAS) in the regulation of blood pressure and the fluid and electrolyte balance (Oparil, S. et al., N. Engl. J. Med. 1974; 291: 381-401/446-57) and the efficacy of renin and pepsin inhibitors in diseases of the cardiovascular system is adequately known, and thus numerous side effects can be expected, in particular on oral or systemic administration of these low-selectivity cathepsin D inhibitors, and systemic complications can also be expected on local application due to diffusion of the compounds. In addition, the peptidic compounds in particular have low stability and are therefore not suitable for oral or systemic administration. 
     The invention was based on the object of finding novel compounds having valuable properties, in particular those which can be used for the preparation of medicaments. 
     The object of the present invention was, in particular, to find novel active compounds and particularly preferably novel cathepsin D inhibitors which can be employed for the prevention and treatment of arthrosis and have, in particular, high selectivity for cathepsin D compared with renin and pepsin. In addition, the aim was to find novel cathepsin D inhibitors which are sufficiently stable, at least on local or intra-articular administration. 
     SUMMARY OF THE INVENTION 
     Surprisingly, it has been found that the acylguanidines according to the invention inhibit cathepsin D highly effectively and at the same time have high selectivity for cathepsin D compared with renin and pepsin, and thus few side effects can be expected on use thereof for the treatment of arthrosis. In addition, the compounds according to the invention have adequately good stability in synovial fluid, meaning that they are suitable for intra-articular administration and thus for the treatment of arthrosis. It has likewise surprisingly been found that the acylguanidines according to the invention are able to reduce inflammation-induced thermal hyperalgesia depending on the dose. 
     The invention relates to acylguanidines of the general formula I, 
                         
in which
     R 1 , R 2 , R 3  are selected, independently of one another, from the group consisting of H, a straight-chain or branched alkyl, alkenyl or alkynyl group having 1-10 C atoms which is unsubstituted or mono-, di- or trisubstituted by R 4 , R 5 , R 6 , a mono-, bi- or tricyclic cycloalkyl group having 3-20 C atoms which is unsubstituted or mono-, di- or trisubstituted by R 4 , R 5 , R 6 , a mono- or bicyclic cycloalkylalkyl group having 4-20 C atoms which is unsubstituted or mono-, di- or trisubstituted by R 4 , R 5 , R 6 , a mono- or bicyclic cycloalkylalkenyl group having 5-20 C atoms which is unsubstituted or mono-, di- or trisubstituted by R 4 , R 5 , R 6 , a mono- or bicyclic cycloalkylalkynyl group having 5-20 C atoms which is unsubstituted or mono-, di- or trisubstituted by R 4 , R 5 , R 6 , a mono- or bicyclic cycloalkenyl group having 5-20 C atoms which is unsubstituted or mono-, di- or trisubstituted by R 4 , R 5 , R 6 , a mono- or bicyclic cycloalkenylalkyl group having 5-20 C atoms which is unsubstituted or mono-, di- or trisubstituted by R 4 , R 5 , R 6 , a mono- or bicyclic heterocycloalkyl group having 1-14 C atoms and 1-7 heteroatoms selected, independently of one another, from N, O and S which is unsubstituted or mono-, di- or trisubstituted by R 4 , R 5 , R 6 , a mono- or bicyclic heterocycloalkylalkyl group having 2-20 C atoms and 1-7 heteroatoms selected, independently of one another, from N, O and S which is unsubstituted or mono-, di- or trisubstituted by R 4 , R 5 , R 6 , a mono- or bicyclic aryl group having 3-20 C atoms which is unsubstituted or mono-, di- or trisubstituted by R 4 , R 5 , R 6 , a mono- or bicyclic arylalkyl group having 4-20 C atoms which is unsubstituted or mono-, di- or trisubstituted by R 4 , R 5 , R 6 , a mono- or bicyclic arylalkenyl group having 5-20 C atoms which is unsubstituted or mono-, di- or trisubstituted by R 4 , R 5 , R 6 , a mono- or bicyclic arylalkynyl group having 5-20 C atoms which is unsubstituted or mono-, di- or trisubstituted by R 4 , R 5 , R 6 , a mono- or bicyclic heteroaryl group having 1-14 C atoms and having 1-7 heteroatoms selected, independently of one another, from N, O and S which is unsubstituted or mono-, di- or trisubstituted by R 4 , R 5 , R 6 , a mono- or bicyclic heteroarylalkyl group having 2-20 C atoms and having 1-7 heteroatoms selected, independently of one another, from N, O and S which is unsubstituted or mono-, di- or trisubstituted by R 4 , R 5 , R 6 , a mono- or bicyclic heteroarylalkenyl group having 3-20 C atoms and having 1-7 heteroatoms selected, independently of one another, from N, O and S which is unsubstituted or mono-, di- or trisubstituted by R 4 , R 5 , R 6 , and a heteroarylalkynyl group having 3-20 C atoms and having 1-7 heteroatoms selected, independently of one another, from N, O and S which is unsubstituted or mono-, di- or trisubstituted by R 4 , R 5 , R 6 , where, in each case independently of one another, the CH 2 —, CH═CH— or —C≡C— groups of the alkyl, alkenyl and alkynyl groups may be replaced by O, N, S, SO, SO 2 , NH, NCH 3 , —OCO—, —NHCONH—, —NHCO—, —NRSO 2 A—, —COO—, —CONN—, —NCH 3 CO— or —CONCH 3 — and/or 1-20H atoms may be replaced by F and/or Cl,   R 4 , R 5 , R 6  are selected, independently of one another, from the group consisting of H, A, ═O, ═S, EN, (CH 2 ) n Hal, (CH 2 ) n CH(Hal) 2 , (CH 2 ) n C(Hal) 3 , (CH 2 ) n OC(Hal) 3 , (CH 2 ) n N(C[Hal] 3 ) 2 , (CH 2 ) n OC(Hal) 3 , (CH 2 ) n NO 2 , (CH 2 ) n CN, (CH 2 ) n NR 7 R 8 , (CH 2 ) n O(CH 2 ) m NR 7 R 8 , (CH 2 ) n NR 7 (CH 2 ) n , NR 7 R 8 , (CH 2 ) n O(CH 2 ) m OR 7 , (CH 2 ) n NR 7 (CH 2 ) m OR 8 , (CH 2 ) n COOR 7 , (CH 2 ) n CH═O, (CH 2 ) n OR 7 , (CH 2 ) n CHOH(CH 2 ) n OR 7 , (CH 2 ) n COR 7 , (CH 2 ) n OOCR 7 , (CH 2 ) n CONR 7 R 8 , C(O)NHA, C(O)NHANH 2  (CH 2 ) n NR 7 COR 8 , (CH 2 ) n NR 7 CONR 7 R 8 , (CH 2 ) n NR 7 SO 2 R 7 , (CH 2 ) n SO 2 NR 7 R 8 , (CH 2 ) n SO 2 R 7 R 8 , (CH 2 ) n S(O) m R 7 , (CH 2 ) n OC(O)R 7 , (CH 2 ) n COR 7 , (CH 2 ) n CH═S, (CH 2 ) n SR 7 , CH═N-OA, CH 2 CH═N-OA, (CH 2 ) n NHOA, (CH 2 ) n CH═N—R 7 , (CH 2 ) n OC(O)NR 7 R 7 , (CH 2 ) n NR 7 COOR 8 , (CH 2 ) n N(R 7 )CH 2 CH 2 OR 9 , (CH 2 ) n N(R 7 )CH 2 CH 2 OCF 3 , (CH 2 ) n N(R 7 )C(R 9 )HCOOR 8 , (CH 2 ) n N(R 7 )C(R 9 )HCOR 8 , (CH 2 ) n N(R 7 )CH 2 CH 2 N(R 8 )CH 2 COOR 7 , (CH 2 ) n N(R 7 )CH 2 CH 2 NR 7 R 8 , CH═CHCOOR 9 , CH═CHCH 2 NR 7 R 8 , CH═CHCH 2 NR 7 R 8 , CH═CHCH 2 OR 9 , (CH 2 ) n N(COOR 9 )COOR 10 , (CH 2 ) n N(CONH 2 )COOR 9 , (CH 2 ) n N(CONH 2 )CONH 2 , (CH 2 ) n N(CH 2 COOR 9 )COOR 10 , (CH 2 ) n N(CH 2 CONH 2 )COOR 9 , (CH 2 ) n N(CH 2 CONH 2 )CONH 2 , (CH 2 ) n CHR 9 COR 10 , (CH 2 ) n CHR 9 COOR 10 , (CH 2 ) n CHR 9 CH 2 OR 10 , (CH 2 ) n OCN and (CH 2 ) n NCO,   R 7 , R 8  are, independently of one another, H or A and, in NR 7 R 8 , R 7  and R 8 , together with the N atom to which they are bonded, may form a 5-, 6- or 7-membered heterocycle, which may optionally contain one or two further heteroatoms selected from the group consisting of N, O and S,   R 9 , R 10  are selected, independently of one another, from the group consisting of H, Hal and A,   A is selected from the group consisting of alkyl, alkenyl, alkynyl and cycloalkyl,   n, m are, independently of one another, 0, 1, 2, 3, 4, or 5, and   Hal is, independently of one another, F, Cl, Br or I,
 
and physiologically acceptable salts, derivatives, solvates, prodrugs and stereoisomers thereof, including mixtures thereof in all ratios.
   

     The invention preferably relates to all above-mentioned compounds of the formula I in which
     R 1  is selected from the group consisting of: a straight-chain or branched alkyl group which is unsubstituted or mono-, di- or trisubstituted by R 4 , R 5 , R 6 , a mono-, bi- or tricyclic cycloalkyl group which is unsubstituted or mono-, di- or trisubstituted by R 4 , R 5 , R 6 , a mono- or bicyclic cycloalkylalkyl group which is unsubstituted or mono-, di- or trisubstituted by R 4 , R 5 , R 6 , a mono- or bicyclic aryl group which is unsubstituted or mono-, di- or trisubstituted by R 4 , R 5 , R 6 , a mono- or bicyclic arylalkyl group which is unsubstituted or mono-, di- or trisubstituted by R 4 , R 5 , R 6 , a mono- or bicyclic heteroaryl group which is unsubstituted or mono-, di- or trisubstituted by R 4 , R 5 , R 6  and a mono- or bicyclic heteroarylalkyl group which is unsubstituted or mono-, di- or trisubstituted by R 4 , R 5 , R 6  
 
and R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , A, n, m and Hal have the meanings indicated above, and physiologically acceptable salts, derivatives, solvates, prodrugs and stereoisomers thereof, including mixtures thereof in all ratios.
   

     The invention furthermore preferably relates to all above-mentioned compounds of the formula I in which
     R 2  is selected from the group consisting of: H, a straight-chain or branched alkyl group which is unsubstituted or mono-, di- or trisubstituted by R 4 , R 5 , R 6 , a mono-, bi- or tricyclic cycloalkyl group which is unsubstituted or mono-, di- or trisubstituted by R 4 , R 5 , R 6 , a mono- or bicyclic cycloalkylalkyl group which is unsubstituted or mono-, di- or trisubstituted by R 4 , R 5 , R 6 , a mono- or bicyclic aryl group which is unsubstituted or mono-, di- or trisubstituted by R 4 , R 5 , R 6  and a mono- or bicyclic arylalkyl group which is unsubstituted or mono-, di- or trisubstituted by R 4 , R 5 , R 6  
 
and R 1 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , A, n, m and Hal have the meanings indicated above, and physiologically acceptable salts, derivatives, solvates, prodrugs and stereoisomers thereof, including mixtures thereof in all ratios.
   

     The invention furthermore preferably relates to all above-mentioned compounds of the formula I in which
     R 2  denotes H or a straight-chain or branched alkyl group which is unsubstituted or mono-, di- or trisubstituted by R 4 , R 5 , R 6 , a monocyclic cycloalkylalkyl group which is unsubstituted or mono-, di- or trisubstituted by R 4 , R 5 , R 6  or a monocyclic arylalkyl group which is unsubstituted or mono-, di- or trisubstituted by R 4 , R 5 , R 6  
 
and R 1 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , A, n, m and Hal have the meanings indicated above, and physiologically acceptable salts, derivatives, solvates, prodrugs and stereoisomers thereof, including mixtures thereof in all ratios.
   

     The invention furthermore preferably relates to all above-mentioned compounds of the formula I in which
     R 2  denotes H or a straight-chain or branched alkyl, cyclohexylmethyl, cyclohexylethyl, benzyl or phenylethyl, each of which is unsubstituted or mono-, di- or trisubstituted by R 4 , R 5 , R 6 ,
 
and R 1 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , A, n, m and Hal have the meanings indicated above, and physiologically acceptable salts, derivatives, solvates, prodrugs and stereoisomers thereof, including mixtures thereof in all ratios.
   

     The invention furthermore preferably relates to all above-mentioned compounds of the formula I in which
     R 2  denotes H or a straight-chain or branched alkyl, cyclohexylmethyl, cyclohexylethyl, benzyl or phenylethyl, each of which is unsubstituted or mono-, di- or trisubstituted by (CH 2 ) n OR 7  or Hal,
 
and R 1 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , A, n, m and Hal have the meanings indicated above, and physiologically acceptable salts, derivatives, solvates, prodrugs and stereoisomers thereof, including mixtures thereof in all ratios.
   

     The invention furthermore preferably relates to all above-mentioned compounds of the formula I in which
     R 2  denotes H or a straight-chain or branched alkyl, cyclohexylmethyl, cyclohexylethyl, benzyl or phenylethyl, which is unsubstituted or mono-, di- or trisubstituted by (CH 2 ) n OR 7  or Cl,
 
and R 1 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , A, n, m and Hal have the meanings indicated above, and physiologically acceptable salts, derivatives, solvates, prodrugs and stereoisomers thereof, including mixtures thereof in all ratios.
   

     The invention furthermore preferably relates to all above-mentioned compounds of the formula I in which
     R 3  is selected from the group consisting of: a straight-chain or branched alkyl group which is unsubstituted or mono-, di- or trisubstituted by R 4 , R 5 , R 6 , a mono-, bi- or tricyclic cycloalkyl group which is unsubstituted or mono-, di- or trisubstituted by R 4 , R 5 , R 6 , a mono- or bicyclic cycloalkylalkyl group which is unsubstituted or mono-, di- or trisubstituted by R 4 , R 5 , R 6 , a mono- or bicyclic heterocycloalkyl group which is unsubstituted or mono-, di- or trisubstituted by R 4 , R 5 , R 6 , a mono- or bicyclic heterocycloalkylalkyl group which is unsubstituted or mono-, di- or trisubstituted by R 4 , R 5 , R 6 , a mono- or bicyclic aryl group which is unsubstituted or mono-, di- or trisubstituted by R 4 , R 5 , R 6 , a mono- or bicyclic arylalkyl group which is unsubstituted or mono-, di- or trisubstituted by R 4 , R 5 , R 6 , a mono- or bicyclic heteroaryl group which is unsubstituted or mono-, di- or trisubstituted by R 4 , R 5 , R 6  and a mono- or bicyclic heteroarylalkyl group which is unsubstituted or mono-, di- or trisubstituted by R 4 , R 5 , R 6  
 
and R 1 , R 2 , R 4 , R 5 , R 6 , R 6 , R 7 , R 8 , R 9 , R 10 , A, n, m and Hal have the meanings indicated above, and physiologically acceptable salts, derivatives, solvates, prodrugs and stereoisomers thereof, including mixtures thereof in all ratios.
   

     The invention particularly preferably relates to all above-mentioned compounds of the formula I in which
     R 1  is selected from the group consisting of: a straight-chain or branched alkyl group which is unsubstituted or mono-, di- or trisubstituted by R 4 , R 5 , R 6 , a mono-, bi- or tricyclic cycloalkyl group which is unsubstituted or mono-, di- or trisubstituted by R 4 , R 5 , R 6 , a mono- or bicyclic cycloalkylalkyl group which is unsubstituted or mono-, di- or trisubstituted by R 4 , R 5 , R 6 , a mono- or bicyclic aryl group which is unsubstituted or mono-, di- or trisubstituted by R 4 , R 5 , R 6 , a mono- or bicyclic arylalkyl group which is unsubstituted or mono-, di- or trisubstituted by R 4 , R 5 , R 6 , a mono- or bicyclic heteroaryl group which is unsubstituted or mono-, di- or trisubstituted by R 4 , R 5 , R 6  and a mono- or bicyclic heteroarylalkyl group which is unsubstituted or mono-, di- or trisubstituted by R 4 , R 5 , R 6 ,   R 2  is selected from the group consisting of: H, a straight-chain or branched alkyl group which is unsubstituted or mono-, di- or trisubstituted by R 4 , R 5 , R 6 , a mono-, bi- or tricyclic cycloalkyl group which is unsubstituted or mono-, di- or trisubstituted by R 4 , R 5 , R 6 , a mono- or bicyclic cycloalkylalkyl group which is unsubstituted or mono-, di- or trisubstituted by R 4 , R 5 , R 6 , a mono- or bicyclic aryl group which is unsubstituted or mono-, di- or trisubstituted by R 4 , R 5 , R 6  and a mono- or bicyclic arylalkyl group which is unsubstituted or mono-, di- or trisubstituted by R 4 , R 5 , R 6 ,   R 3  is selected from the group consisting of: a straight-chain or branched alkyl group which is unsubstituted or mono-, di- or trisubstituted by R 4 , R 5 , R 6 , a mono-, bi- or tricyclic cycloalkyl group which is unsubstituted or mono-, di- or trisubstituted by R 4 , R 5 , R 6 , a mono- or bicyclic cycloalkylalkyl group which is unsubstituted or mono-, di- or trisubstituted by R 4 , R 5 , R 6 , a mono- or bicyclic heterocycloalkyl group which is unsubstituted or mono-, di- or trisubstituted by R 4 , R 5 , R 6 , a mono- or bicyclic heterocycloalkylalkyl group which is unsubstituted or mono-, di- or trisubstituted by R 4 , R 5 , R 6 , a mono- or bicyclic aryl group which is unsubstituted or mono-, di- or trisubstituted by R 4 , R 5 , R 6 , a mono- or bicyclic arylalkyl group which is unsubstituted or mono-, di- or trisubstituted by R 4 , R 5 , R 6 , a mono- or bicyclic heteroaryl group which is unsubstituted or mono-, di- or trisubstituted by R 4 , R 5 , R 6  and a mono- or bicyclic heteroarylalkyl group which is unsubstituted or mono-, di- or trisubstituted by R 4 , R 5 , R 6 ,
 
and R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , A, n, m and Hal have the meanings indicated above, and physiologically acceptable salts, derivatives, solvates, prodrugs and stereoisomers thereof, including mixtures thereof in all ratios.
   

     The invention very particularly preferably relates to all above-mentioned compounds of the formula I in which
     R 1  denotes a straight-chain or branched alkyl group, mono-, bi- or tricyclic cycloalkyl group, mono- or bicyclic cycloalkylalkyl group, mono- or bicyclic aryl group, mono- or bicyclic arylalkyl group, mono- or bicyclic heteroaryl group or mono- or bicyclic heteroarylalkyl group which is unsubstituted or mono-, di- or trisubstituted by (CH 2 ) n OR 7 , EN, Hal, OCF 3 , CF 3 , ═O, A, (CH 2 ) n CN, (CH 2 ) n NR 7 SO 2 R 7  or (CH 2 ) n SO 2 NR 7 R 8 ,   R 2  denotes H or a straight-chain or branched alkyl, monocyclic cycloalkylalkyl or monocyclic arylalkyl, each of which is unsubstituted or mono-, di- or trisubstituted by (CH 2 ) n OR 7  or Hal,   R 3  denotes a straight-chain or branched alkyl group, mono-, bi- or tricyclic cycloalkyl group, mono- or bicyclic cycloalkylalkyl group, mono- or bicyclic heterocycloalkyl group, mono- or bicyclic heterocycloalkylalkyl group, mono- or bicyclic aryl group, mono- or bicyclic arylalkyl group, mono- or bicyclic heteroaryl group or mono- or bicyclic heteroarylalkyl group which is unsubstituted or mono-, di- or trisubstituted by (CH 2 ) n OR 7 , EN, Hal, OCF 3 , CF 3 , (CH 2 ) n COOR 7 , ═O, A, (CH 2 ) n CN, (CH 2 ) n NR 7 SO 2 R 7 , (CH 2 ) n SO 2 NR 7 R 8 , (CH 2 ) n N(C[Hal] 3 ) 2 , (CH 2 ) n CHOH(CH 2 ) n OR 7  or (CH 2 ) n O(CH 2 ) m OR 7 ,
 
and R 7 , R 8 , A, n, m and Hal have the meanings indicated above, and physiologically acceptable salts, derivatives, solvates, prodrugs and stereoisomers thereof, including mixtures thereof in all ratios.
   

     The invention furthermore very particularly preferably relates to all above-mentioned compounds of the formula I in which
     R 1  denotes a straight-chain or branched alkyl group, mono-, bi- or tricyclic cycloalkyl group, mono- or bicyclic cycloalkylalkyl group, mono- or bicyclic aryl group, mono- or bicyclic arylalkyl group, mono- or bicyclic heteroaryl group, mono- or bicyclic heteroarylalkyl group which is unsubstituted or mono-, di- or trisubstituted by (CH 2 ) n OR 7 , EN, Hal, OCF 3 , CF 3 , ═O, A, (CH 2 ) n CN, (CH 2 ) n NR 7 SO 2 R 7 , (CH 2 ) n SO 2 NR 7 R 8 ,   R 2  H or a straight-chain or branched alkyl, cyclohexylmethyl, cyclohexylethyl, benzyl or phenylethyl, each of which is unsubstituted or mono-, di- or trisubstituted by (CH 2 ) n OR 7  or CI,   R 3  denotes a straight-chain or branched alkyl group, mono-, bi- or tricyclic cycloalkyl group, mono- or bicyclic cycloalkylalkyl group, mono- or bicyclic heterocycloalkyl group, mono- or bicyclic heterocycloalkylalkyl group, mono- or bicyclic aryl group, mono- or bicyclic arylalkyl group, mono- or bicyclic heteroaryl group or mono- or bicyclic heteroarylalkyl group which is unsubstituted or mono-, di- or trisubstituted by (CH 2 ) n OR 7 , EN, Hal, OCF 3 , CF 3 , (CH 2 ) n COOR 7 , ═O, A, (CH 2 ) n CN, (CH 2 ) n NR 7 SO 2 R 7 , (CH 2 ) n SO 2 NR 7 R 8 , (CH 2 ) n N(C[Hal] 3 ) 2 , (CH 2 ) n CHOH(CH 2 ) n OR 7  or (CH 2 ) n O(CH 2 ) m OR 7  
 
and R 7 , R 8 , A, n, m and Hal have the meanings given above, and physiologically acceptable salts, derivatives, solvates, prodrugs and stereoisomers thereof, including mixtures thereof in all ratios.
   

     All above-mentioned preferred, particularly preferred and very particularly preferred meanings of the above radicals of the compounds of the formula I should be understood in such a way that these preferred, particularly preferred and very particularly preferred meanings or embodiments can be combined with one another in any possible combination to give compounds of the formula I and preferred, particularly preferred and very particularly preferred compounds of the formula I of this type are likewise explicitly disclosed hereby. 
     Very particular preference is also given to the following compounds of the formula I selected from the group consisting of: 
                                    1.   (R)-3-(2,4-dichlorophenyl)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]-           guanidino}-N-[2-(3,4-dimethoxyphenyl)ethyl]propionamide,       2.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-(4-methoxy-           benzyl)-3-phenylpropionamide,       3.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-(1-ethylpropyl)propionamide trifluoroacetate,       4.   (R)-3-(2,4-dichlorophenyl)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]-           guanidino}-N-[2-(1,3-dioxo-1,3-dihydroisoindol-2-yl)ethyl]propion-amide,       5.   (S)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-[2-(1,3-           dioxo-1,3-dihydroisoindol-2-yl)ethyl]-3-(4-methoxyphenyl)propion-amide,       6.   (S)-3-(4-chlorophenyl)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]-           guanidino}-N-[2-(1,3-dioxo-1,3-dihydroisoindol-2-yl)ethyl]propion-amide,       7.   (S)-3-(2,4-dichlorophenyl)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]-           guanidino}-N-[2-(1,3-dioxo-1,3-dihydroisoindol-2-yl)ethyl]propion-amide,       8.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-[2-(3,4-           dimethoxyphenyl)ethyl]-3-phenylpropionamide,       9.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-[2-(1,3-           dioxo-1,3-dihydroisoindol-2-yl)ethyl]propionamide,       10.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-phenethyl-3-           phenylpropionamide,       11.   (R)-N-[2-(4-chlorophenyl)ethyl]-2-{N′-[2-(3,4-dimethoxyphenyl)-           acetyl]guanidino}-3-phenylpropionamide,       12.   (R)-N-[2-(2,4-dichlorophenyl)ethyl]-2-{N′-[2-(3,4-dimethoxyphenyl)-           acetyl]guanidino}-3-phenylpropionamide,       13.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-[2-(1,3-           dioxo-1,3-dihydroisoindol-2-yl)ethyl]-3-phenylpropionamide,       14.   (S)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-[2-(1,3-           dioxo-1,3-dihydroisoindol-2-yl)ethyl]-3-phenylpropionamide,       15.   (R)-N-[2-(2-bromo-4,5-dimethoxyphenyl)ethyl]-2-{N′-[2-(3,4-           dimethoxyphenyl)acetyl]guanidino}-3-phenylpropionamide,       16.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-3-phenyl-N-(4-           sulfamoylbenzyl)propionamide,       17.   (R)-N-(4-cyano-3-fluorobenzyl)-2-{N′-[2-(3,4-dimethoxyphenyl)-           acetyl]guanidino}-3-phenylpropionamide,       18.   (R)-N-(3,4-dimethoxybenzyl)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]-           guanidino}-3-(4-methoxyphenyl)propionamide,       19.   (R)-N-cyclohexylmethyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]-           guanidino}-3-phenylpropionamide trifluoroacetate,       20.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-(4-fluoro-           benzyl)-3-phenylpropionamide,       21.   (R)-N-(3,4-difluorobenzyl)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]-           guanidino}-3-phenylpropionamide,       22.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-(4-fluoro-3-           methoxybenzyl)-3-phenylpropionamide,       23.   (R)-N-(2-bromo-4,5-dimethoxybenzyl)-2-{N′-[2-(3,4-dimethoxy-           phenyl)acetyl]guanidino}-3-phenylpropionamide,       24.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-((1S,2R)-2-           hydroxyindan-1-yl)-3-phenylpropionamide,       25.   (R)-3-cyclohexyl-N-(3,4-dimethoxybenzyl)-2-{N′-[2-(3,4-dimethoxy-           phenyl)acetyl]guanidino}propionamide,       26.   (R)-N-benzyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-           methyl-3-phenylpropionamide,       27.   (R)-N-(3,4-dimethoxybenzyl)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]-           guanidino}-N-methyl-3-phenylpropionamide,       28.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-3-phenyl-propionamide,       29.   (R)-N-(3,4-dichlorobenzyl)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]-           guanidino}-3-phenylpropionamide,       30.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-3-phenyl-N-           pyridin-4-ylmethylpropionamide,       31.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-3-phenyl-N-           pyridin-2-ylmethylpropionamide,       32.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-3-phenyl-N-[3-           (1H-tetrazol-5-yl)benzyl]propionamide,       33.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-isobutyl-3-           phenylpropionamide,       34.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-(2,2-           dimethylpropyl)-3-phenylpropionamide,       35.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-(3-methyl-           butyl)-3-phenylpropionamide,       36.   (R)-N-(4-tert-butylcyclohexyl)-2-{N′-[2-(3,4-dimethoxyphenyl)-           acetyl]guanidino}-3-phenylpropionamide,       37.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-[3-(2-           methoxyethoxy)benzyl]-3-phenylpropionamide,       38.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-[3-(2-           hydroxyethoxy)benzyl]-3-phenylpropionamide,       39.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-(1-ethyl-           propyl)-3-phenylpropionamide,       40.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-isopropyl-3-           phenylpropionamide,       41.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-(2-ethyl-           butyl)-3-phenylpropionamide,       42.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-((S)-2-           methylbutyl)-3-phenylpropionamide,       43.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-((S)-2-methylbutyl)propionamide,       44.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanecarboxylic acid 4-fluoro-3-methoxybenzyl amide,       45.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanecarboxylic acid isobutyl amide,       46.   (2R,3R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-3-methyl-           pentanecarboxylic acid 4-fluoro-3-methoxybenzyl amide,       47.   (R)-N-(2-benzo-1,3-dioxol-5-ylethyl)-2-{N′-[2-(3,4-dimethoxy-           phenyl)acetyl]guanidino}-3-phenylpropionamide,       48.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-3-phenyl-N-(2-           pyridin-4-ylethyl)propionamide,       49.   (R)-N-(3,4-dimethoxybenzyl)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]-           guanidino}-3-hydroxypropionamide,       50.   (R)-3-tert-butoxy-N-(3,4-dimethoxybenzyl)-2-{N′-[2-(3,4-dimethoxy-           phenyl)acetyl]guanidino}propionamide,       51.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanecarboxylic acid 3,4-dimethoxybenzyl amide,       52.   (R)-N-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           3-phenylpropionamide,       53.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-isobutylpropionamide,       54.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-(3-methoxy-           benzyl)-3-phenylpropionamide,       55.   (R)-3-(2-chlorophenyl)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]-           guanidino}-N-[2-(3,4-dimethoxyphenyl)ethyl]propionamide,       56.   (R)-3-(4-chlorophenyl)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]-           guanidino}-N-[2-(3,4-dimethoxyphenyl)ethyl]propionamide,       57.   5-((R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-3-phenyl-           propionylamino)furan-2-carboxylic acid methyl ester,       58.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-3-phenyl-N-           thiophen-2-ylmethylpropionamide,       59.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-(3-ethoxy-           pyridin-2-ylmethyl)-3-phenylpropionamide,       60.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-(4-fluoro-3-methoxybenzyl)propionamide,       61.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-(4-fluoro-3-           methoxybenzyl)-4-phenylbutyramide,       62.   (1S,3S,4S)-4-((R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           3-phenylpropionylamino)-3-hydroxycyclohexanecarboxylic acid methyl ester,       63.   (R)-N-(3,5-dimethoxybenzyl)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]-           guanidino}-3-phenylpropionamide,       64.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-((R)-1-           hydroxymethyl-3-methylbutyl)-3-phenylpropionamide,       65.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-((S)-1-           hydroxymethyl-3-methylbutyl)-3-phenylpropionamide,       66.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-(4-methyl-           cyclohexyl)-3-phenylpropionamide,       67.   (2R,3R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-3-methyl-           pentanoic acid isobutyl amide,       68.   R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanecarboxylic acid ((S)-2-methylbutyl) amide,       69.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-[1-(4-fluoro-3-methoxyphenyl)cyclopropyl]propionamide,       70.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanecarboxylic acid [1-(4-fluoro-3-methoxyphenyl)cyclopropyl] amide,       71.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-[1-(4-fluoro-           3-methoxyphenyl)cyclopropyl]-3-phenylpropionamide,       72.   (R)-3,N-dicyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]-           guanidino}propionamide,       73.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanecarboxylic acid cyclohexyl amide,       74.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-3-phenyl-N-           (tetrahydropyran-4-yl)propionamide,       75.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanecarboxylic acid (tetrahydropyran-4-yl) amide,       76.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-(1-methyl-           piperidin-4-yl)-3-phenylpropionamide,       77.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanecarboxylic acid (1-methylpiperidin-4-yl) amide,       78.   (R)-N-(3,4-dimethoxybenzyl)-2-{N′-[2-(3,5-dimethoxyphenyl)acetyl]-           guanidino}-3-phenylpropionamide,       79.   (R)-2-{N′-[2-(3,5-dimethoxyphenyl)acetyl]guanidino}-N-(4-fluoro-3-           methoxybenzyl)-3-phenylpropionamide,       80.   (R)-3-cyclohexyl-2-{N′-[2-(3,5-dimethoxyphenyl)acetyl]guanidino}-           N-(4-fluoro-3-methoxybenzyl)propionamide,       81.   (R)-3-cyclohexyl-2-{N′-[2-(3,5-dimethoxyphenyl)acetyl]guanidino}-           N-isobutylpropionamide,       82.   (R)-N-cyclopropylmethyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]-           guanidino}-3-phenylpropionamide,       83.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-[(S)-1-(3-           methoxyphenyl)ethyl]-3-phenylpropionamide,       84.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-[(R)-1-(3-           methoxyphenyl)ethyl]-3-phenylpropionamide,       85.   (S)-3-cyclohexyl-N-cyclopropylmethyl-2-{N′-[2-(3,4-dimethoxy-           phenyl)acetyl]guanidino}propionamide,       86.   (S)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-[(S)-1-(3-methoxyphenyl)ethyl]propionamide,       87.   (S)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-[(R)-1-(3-methoxyphenyl)ethyl]propionamide,       88.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-3-phenyl-N-           (tetrahydropyran-4-ylmethyl)propionamide,       89.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-(3-methoxy-           propyl)-3-phenylpropionamide,       90.   (S)-3-cyclohexyl-N-cyclohexylmethyl-2-{N′-[2-(3,4-dimethoxy-           phenyl)acetyl]guanidino}propionamide,       91.   (S)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-(tetrahydropyran-4-ylmethyl)propionamide,       92.   (S)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-(3-methoxypropyl)propionamide,       93.   (R)-3-cyclohexyl-2-{N′-[3-(3,4-dimethoxyphenyl)propionyl]-           guanidino}-N-(4-fluoro-3-methoxybenzyl)propionamide,       94.   (R)-2-[N′-(2-benzo-1,3-dioxol-5-ylacetyl)guanidino]-3-cyclohexyl-N-           (4-fluoro-3-methoxybenzyl)propionamide,       95.   (R)-3-cyclohexyl-N-(4-fluoro-3-methoxybenzyl)-2-[N′-(4-methyl-           pentanoyl)guanidino]propionamide,       96.   (R)-3-cyclohexyl-N-(4-fluoro-3-methoxybenzyl)-2-[N′-(indane-2-           carbonyl)guanidino]propionamide,       97.   (R)-2-{N′-[2-(3-methoxyphenyl)acetyl]guanidino}-4-methylpentane-           carboxylic acid 3,4-dimethoxybenzyl amide,       98.   (R)-3-cyclohexyl-2-[N′-(2-cyclohexylacetyl)guanidino]-N-(4-fluoro-3-           methoxybenzyl)propionamide,       99.   (R)-2-{N′-[2-(2-bromo-4,5-dimethoxyphenyl)acetyl]guanidino}-3-           cyclohexyl-N-(4-fluoro-3-methoxybenzyl)propionamide,       100.   (R)-3-cyclohexyl-N-((S)-2-methylbutyl)-2-[N′-(3-phenylpropionyl)-           guanidino]propionamide,       101.   (R)-3-cyclohexyl-N-(4-fluoro-3-methoxybenzyl)-2-[N′-(3-phenyl-           propionyl)guanidino]propionamide,       102.   (R)-3-cyclohexyl-N-((S)-2-methylbutyl)-2-(N′-phenylacetyl-           guanidino)propionamide,       103.   (R)-2-[N′-(2-benzo-1,3-dioxol-5-ylacetyl)guanidino]-3-cyclohexyl-N-           isobutylpropionamide,       104.   (R)-2-[N′-(2-benzo-1,3-dioxol-5-ylacetyl)guanidino]-N-(3,4-           dimethoxybenzyl)-3-phenylpropionamide,       105.   (R)-N-(3,4-dimethoxybenzyl)-3-phenyl-2-[N′-(3-phenylpropionyl)-           guanidino]propionamide,       106.   (R)-3-cyclohexyl-2-[N′-(indane-2-carbonyl)guanidino]-N-isobutyl-           propionamide,       107.   (R)-N-(3,4-dimethoxybenzyl)-2-[N′-(indane-2-carbonyl)guanidino]-3-           phenylpropionamide,       108.   (R)-N-(3,4-dimethoxybenzyl)-2-{N′-[3-(3,4-dimethoxyphenyl)-           propionyl]guanidino}-3-phenylpropionamide,       109.   (R)-2-{N′-[2-(2-bromo-4,5-dimethoxyphenyl)acetyl]guanidino}-3-           cyclohexyl-N-isobutylpropionamide,       110.   (R)-2-{N′-[2-(2-bromo-4,5-dimethoxyphenyl)acetyl]guanidino}-N-           (3,4-dimethoxybenzyl)-3-phenylpropionamide,       111.   (R)-2-{N′-[2-(3-methoxyphenyl)acetyl]guanidino}-4-methylpentanoic           acid isobutyl amide,       112.   (R)-2-{N′-[2-(3-methoxyphenyl)acetyl]guanidino}-4-methylpentane-           carboxylic acid 4-fluoro-3-methoxybenzyl amide,       113.   (R)-3-cyclohexyl-2-{N′-[2-(3-methoxyphenyl)acetyl]guanidino}-N-           ((S)-2-methylbutyl)propionamide,       114.   (R)-3-cyclohexyl-N-(4-fluoro-3-methoxybenzyl)-2-{N′-[2-(3-methoxy-           phenyl)acetyl]guanidino}propionamide,       115.   (R)-N-(3,4-dimethoxybenzyl)-3-phenyl-2-(N′-phenylacetyl-           guanidino)propionamide,       116.   (R)-3-cyclohexyl-N-isobutyl-2-[N′-(4-methylpentanoyl)guanidino]-           propionamide,       117.   (R)-3-cyclohexyl-N-isobutyl-2-{N′-[2-(3-methoxyphenyl)acetyl]-           guanidino}propionamide,       118.   (R)-3-cyclohexyl-2-[N′-(2-cyclohexylacetyl)guanidino]-N-isobutyl-           propionamide,       119.   (R)-N-(3,4-dimethoxybenzyl)-2-[N′-(4-methylpentanoyl)guanidino]-           3-phenylpropionamide,       120.   (R)-2-[N′-(2-cyclohexylacetyl)guanidino]-N-(3,4-dimethoxybenzyl)-           3-phenylpropionamide,       121.   (R)-N-(3,4-dimethoxybenzyl)-2-{N′-[2-(3-methoxyphenyl)acetyl]-           guanidino}-3-phenylpropionamide,       122.   (R)-N-(3-methoxybenzyl)-2-{N′-[2-(3-methoxyphenyl)acetyl]-           guanidino}-3-phenylpropionamide,       123.   (R)-N-(4-fluoro-3-methoxybenzyl)-2-{N′-[2-(3-methoxyphenyl)-           acetyl]guanidino}-3-phenylpropionamide,       124.   (R)-2-[N′-(2-cyclohexylacetyl)guanidino]-N-(4-fluoro-3-methoxy-           benzyl)-3-phenylpropionamide,       125.   (R)-N-isobutyl-2-{N′-[2-(4-methoxyphenyl)acetyl]guanidino}-3-           phenylpropionamide,       126.   (R)-N-(3,4-dimethoxybenzyl)-2-{N′-[2-(4-methoxyphenyl)acetyl]-           guanidino}-3-phenylpropionamide,       127.   (R)-N-isobutyl-2-[N′-(2-phenoxyacetyl)guanidino]-3-phenylpropion-amide,       128.   (R)-N-(3,4-dimethoxybenzyl)-3-phenyl-2-{N′-[2-(4-trifluoromethyl-           phenyl)acetyl]guanidino}propionamide,       129.   (R)-3-phenyl-N-(4-sulfamoylbenzyl)-2-{N′-[2-(4-trifluoromethoxy-           phenyl)acetyl]guanidino}propionamide,       130.   (R)-N-(3,4-dimethoxybenzyl)-3-phenyl-2-{N′-[2-(4-trifluoromethoxy-           phenyl)acetyl]guanidino}propionamide,       131.   (R)-N-isobutyl-2-[N′-(3-methylbutyryl)guanidino]-3-phenylpropion-amide,       132.   (R)-N-[2-(3,4-dimethoxyphenyl)ethyl]-2-[N′-(3-methylbutyryl)-           guanidino]-3-phenylpropionamide,       133.   (R)-2-[N′-(3-methylbutyryl)guanidino]-3-phenyl-N-(4-sulfamoyl-           benzyl)propionamide,       134.   (R)-N-(3,4-dimethoxybenzyl)-2-[N′-(3-methylbutyryl)guanidino]-3-           phenylpropionamide,       135.   (R)-4-methyl-2-[N′-(3-methylbutyryl)guanidino]-pentanoic acid 3,4-           dimethoxybenzyl amide,       136.   (R)-N-isobutyl-2-(N′-isobutyrylguanidino)-3-phenylpropionamide,       137.   (R)-N-[2-(3,4-dimethoxyphenyl)ethyl]-2-(N′-isobutyrylguanidino)-3-           phenylpropionamide,       138.   (R)-2-(N′-isobutyrylguanidino)-3-phenyl-N-(4-sulfamoylbenzyl)-propionamide,       139.   (R)-N-(3,4-dimethoxybenzyl)-2-(N′-isobutyrylguanidino)-3-phenyl-propionamide,       140.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-(2-methyl-           sulfamoylbenzyl)-3-phenylpropionamide,       141.   (R)-N-(3,4-dimethoxybenzyl)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]-           guanidino}-3-phenylpropionamide,       142.   (R)-N-benzo-1,3-dioxol-5-ylmethyl-2-{N′-[2-(3,4-dimethoxyphenyl)-           acetyl]guanidino}-3-phenylpropionamide,       143.   (R)-N-(2,3-dimethoxybenzyl)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]-           guanidino}-3-phenylpropionamide,       144.   (R)-N-(3-bromobenzyl)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]-           guanidino}-3-phenylpropionamide,       145.   (R)-N-(3-chlorobenzyl)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]-           guanidino}-3-phenylpropionamide,       146.   (R)-N-benzyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-3-           phenylpropionamide,       147.   (R)-2-{N′-[2-(4-chlorophenyl)acetyl]guanidino}-N-[2-(3,4-dimethoxy-           phenyl)ethyl]-3-phenylpropionamide,       148.   (S)-3-(2,4-dichlorophenyl)-N-[2-(1,3-dioxo-1,3-dihydroisoindol-2-yl)-           ethyl]-2-{N′-[2-(3-phenoxyphenyl)acetyl]guanidino}propionamide,       149.   (S)-3-(4-chlorophenyl)-N-[2-(1,3-dioxo-1,3-dihydroisoindol-2-yl)-           ethyl]-2-{N′-[2-(3-phenoxyphenyl)acetyl]guanidino}propionamide,       150.   (R)-3-(2,4-dichlorophenyl)-N-[2-(1,3-dioxo-1,3-dihydroisoindol-2-yl)-           ethyl]-2-{N′-[2-(3-phenoxyphenyl)acetyl]guanidino}propionamide,       151.   (S)-N-[2-(1,3-dioxo-1,3-dihydroisoindol-2-yl)ethyl]-3-(4-methoxy-           phenyl)-2-{N′-[2-(3-phenoxyphenyl)acetyl]guanidino}propionamide,       152.   (R)-N-[2-(1,3-dioxo-1,3-dihydroisoindol-2-yl)ethyl]-2-{N′-[2-(3-           phenoxyphenyl)acetyl]guanidino}-3-phenylpropionamide,       153.   (S)-N-[2-(1,3-dioxo-1,3-dihydroisoindol-2-yl)ethyl]-2-{N′-[2-(3-           phenoxyphenyl)acetyl]guanidino}-3-phenylpropionamide,       154.   (R)-N-(3,4-dimethoxybenzyl)-2-{N′-[2-(2,4-dimethoxyphenyl)acetyl]-           guanidino}-3-phenylpropionamide,       155.   (R)-2-{N′-[2-(2,4-dimethoxyphenyl)acetyl]guanidino}-N-(4-fluoro-3-           methoxybenzyl)-3-phenylpropionamide,       156.   (R)-3-cyclohexyl-2-{N′-[2-(2,4-dimethoxyphenyl)acetyl]guanidino}-           N-isobutylpropionamide,       157.   (R)-3-cyclohexyl-2-{N′-[2-(2,4-dimethoxyphenyl)acetyl]guanidino}-           N-(4-fluoro-3-methoxybenzyl)propionamide,       158.   (R)-2-[N′-(2-adamantan-1-ylacetyl)guanidino]-N-(3,4-dimethoxy-           benzyl)-3-phenylpropionamide,       159.   2-[N′-(2-adamantan-1-ylacetyl)guanidino]-3-cyclohexyl-N-isobutyl-           propionamide,       160.   2-[N′-(2-adamantan-1-ylacetyl)guanidino]-3-cyclohexyl-N-(4-fluoro-           3-methoxybenzyl)propionamide,       161.   2-[N′-(2-adamantan-1-ylacetyl)guanidino]-N-(4-fluoro-3-methoxy-           benzyl)-3-phenylpropionamide,       162.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-(4-sulfamoylbenzyl)propionamide,       163.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanecarboxylic acid cyclopropylmethyl amide,       164.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanecarboxylic acid 4-sulfamoylbenzyl amide,       165.   (R)-3-cyclohexyl-N-cyclopropylmethyl-2-{N′-[2-(3,4-dimethoxy-           phenyl)acetyl]guanidino}propionamide,       166.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-[(S)-1-(3-methoxyphenyl)ethyl]propionamide,       167.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-[(R)-1-(3-methoxyphenyl)ethyl]propionamide,       168.   (R)-3-cyclohexyl-N-cyclohexylmethyl-2-{N′-[2-(3,4-dimethoxy-           phenyl)acetyl]guanidino}propionamide,       169.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-(tetrahydropyran-4-ylmethyl)propionamide,       170.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-(3-methoxypropyl)propionamide,       171.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-(tetrahydrothiopyran-4-yl)propionamide,       172.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-3-phenyl-N-           (tetrahydrothiopyran-4-yl)propionamide,       173.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanecarboxylic acid (tetrahydrothiopyran-4-yl) amide,       174.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-(tetrahydropyran-4-yl)propionamide,       175.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-(1-methylpiperidin-4-yl)propionamide,       176.   (R)-N-(5-chlorothiophen-2-ylmethyl)-2-{N′-[2-(3,4-dimethoxy-           phenyl)acetyl]guanidino}-3-phenylpropionamide,       177.   (R)-N-(5-chlorothiophen-2-ylmethyl)-3-cyclohexyl-2-{N′-[2-(3,4-           dimethoxyphenyl)acetyl]guanidino}propionamide,       178.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-(3-fluoro-4-           methoxybenzyl)-3-phenylpropionamide,       179.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-(3-fluoro-4-methoxybenzyl)propionamide,       180.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanecarboxylic acid 3-fluoro-4-methoxybenzyl amide,       181.   (R)-3-cyclohexyl-N-(3,4-difluorobenzyl)-2-{N′-[2-(3,4-dimethoxy-           phenyl)acetyl]guanidino}propionamide,       182.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanecarboxylic acid 3,4-difluorobenzyl amide,       183.   (R)-N-(6-chloropyridin-3-ylmethyl)-3-cyclohexyl-2-{N′-[2-(3,4-           dimethoxyphenyl)acetyl]guanidino}propionamide,       184.   (R)-N-((S)-sec-butyl)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)-           acetyl]guanidino}propionamide,       185.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-(trans-4-hydroxycyclohexyl)propionamide,       186.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanecarboxylic acid (6-chloropyridin-3-ylmethyl) amide,       187.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-(4-fluorobenzyl)propionamide,       188.   (R)-3-cyclohexyl-N-cyclopropyl-2-{N′-[2-(3,4-dimethoxyphenyl)-           acetyl]guanidino}propionamide,       189.   (R)-3-cyclohexyl-N-cyclopentyl-2-{N′-[2-(3,4-dimethoxyphenyl)-           acetyl]guanidino}propionamide,       190.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanecarboxylic acid 4-fluorobenzyl amide,       191.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanecarboxylic acid cyclopentyl amide,       192.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanecarboxylic acid ((S)-sec-butyl) amide,       193.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanecarboxylic acid ((R)-sec-butyl) amide,       194.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanecarboxylic acid (trans-4-hydroxycyclohexyl) amide,       195.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanecarboxylic acid (cis-4-hydroxycyclohexyl) amide,       196.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanecarboxylic acid (S)-indan-1-yl amide amide,       197.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanecarboxylic acid (R)-indan-1-ylamide amide,       198.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanecarboxylic acid (4-methoxyindan-2-yl) amide,       199.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanecarboxylic acid (5-methoxyindan-2-yl) amide,       200.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanecarboxylic acid 3-(1H-tetrazol-5-yl)benzyl amide,       201.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-diethoxyphenyl)acetyl]guanidino}-N-           (4-fluoro-3-methoxybenzyl)propionamide,       202.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-(cis-4-hydroxycyclohexyl)propionamide,       203.   (R)-N-((R)-sec-butyl)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)-           acetyl]guanidino}propionamide,       204.   (R)-N-(3,4-dimethoxybenzyl)-2-{N′-[2-(2,5-dimethoxyphenyl)acetyl]-           guanidino}-3-phenylpropionamide,       205.   (R)-2-{N′-[2-(2,5-dimethoxyphenyl)acetyl]guanidino}-N-(4-fluoro-3-           methoxybenzyl)-3-phenylpropionamide,       206.   (R)-3-cyclohexyl-2-{N′-[2-(2,5-dimethoxyphenyl)acetyl]guanidino}-           N-isobutylpropionamide,       207.   (R)-3-cyclohexyl-2-{N′-[2-(2,5-dimethoxyphenyl)acetyl]guanidino}-           N-(4-fluoro-3-methoxybenzyl)propionamide,       208.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-(S)-indan-1-ylpropionamide)propionamide,       209.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-(R)-indan-1-ylpropionamide,       210.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-(4-methoxyindan-2-yl)propionamide,       211.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-(5-methoxyindan-2-yl)propionamide,       212.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-[3-(1H-tetrazol-5-yl)benzyl]propionamide,       213.   (R)-N-(4-fluoro-3-methoxybenzyl)-2-{N′-[2-(4-fluoro-3-methoxy-           phenyl)acetyl]guanidino}-3-phenylpropionamide,       214.   (R)-3-cyclohexyl-2-{N′-[2-(4-fluoro-3-methoxyphenyl)acetyl]-           guanidino}-N-isobutylpropionamide,       215.   (R)-3-cyclohexyl-N-(4-fluoro-3-methoxybenzyl)-2-{N′-[2-(4-fluoro-3-           methoxyphenyl)acetyl]guanidino}propionamide,       216.   (R)-N-(4-fluoro-3-methoxybenzyl)-2-{N′-[2-(3-fluoro-4-methoxy-           phenyl)acetyl]guanidino}-3-phenylpropionamide,       217.   (R)-3-cyclohexyl-2-{N′-[2-(3-fluoro-4-methoxyphenyl)acetyl]-           guanidino}-N-isobutylpropionamide,       218.   (R)-3-cyclohexyl-N-(4-fluoro-3-methoxybenzyl)-2-{N′-[2-(3-fluoro-4-           methoxyphenyl)acetyl]guanidino}propionamide,       219.   (R)-N-(4-fluoro-3-methoxybenzyl)-3-phenyl-2-[N′-(2-tetrahydro-           pyran-4-ylacetyl)guanidino]propionamide,       220.   (R)-3-cyclohexyl-N-isobutyl-2-[N′-(2-tetrahydropyran-4-ylacetyl)-           guanidino]propionamide,       221.   (R)-3-cyclohexyl-N-(4-fluoro-3-methoxybenzyl)-2-[N′-(2-tetrahydro-           pyran-4-ylacetyl)guanidino]propionamide,       222.   (R)-3-cyclohexyl-2-{N′-[2-(2,6-difluoro-4-methoxyphenyl)acetyl]-           guanidino}-N-(4-fluoro-3-methoxybenzyl)propionamide,       223.   (R)-3-cyclohexyl-2-{N′-[2-(2,6-difluoro-4-methoxyphenyl)acetyl]-           guanidino}-N-isobutylpropionamide,       224.   (R)-3-cyclohexyl-2-[N′-(3,3-dimethylbutyryl)guanidino]-N-(4-fluoro-           3-methoxybenzyl)propionamide,       225.   (R)-3-cyclohexyl-2-[N′-(3,3-dimethylbutyryl)guanidino]-N-isobutyl-           propionamide.       226.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-diethoxyphenyl)acetyl]guanidino}-N-           isobutylpropionamide,       227.   (R)-2-{N′-[2-(3,4-diethoxyphenyl)acetyl]guanidino}-N-(4-fluoro-3-           methoxybenzyl)-3-phenylpropionamide,       228.   (R)-2-{N′-[2-(2-bromo-4-methoxyphenyl)acetyl]guanidino}-N-(4-           fluoro-3-methoxybenzyl)-3-phenylpropionamide, (R)-2-{N′-[2-(2-           bromo-4-methoxyphenyl)acetyl]guanidino}-3-cyclohexyl-N-isobutyl-           propionamide,       229.   (R)-2-{N′-[2-(2-bromo-4-methoxyphenyl)acetyl]guanidino}-3-cyclo-           hexyl-N-isobutylpropionamide,       230.   (R)-2-{N′-[2-(2-bromo-4-methoxyphenyl)acetyl]guanidino}-3-cyclo-           hexyl-N-(4-fluoro-3-methoxybenzyl)propionamide,       231.   (S)-2-benzyl-4-{N′-[(R)-1-(4-fluoro-3-methoxybenzylcarbamoyl)-2-           phenylethyl]guanidino}-4-oxobutyric acid methyl ester,       232.   (S)-2-benzyl-4-[N′-((R)-2-cyclohexyl-1-isobutylcarbamoylethyl)-           guanidino]-4-oxobutyric acid methyl ester,       233.   (S)-2-benzyl-4-{N′-[(R)-2-cyclohexyl-1-(4-fluoro-3-methoxybenzyl-           carbamoyl)ethyl]guanidino}-4-oxobutyric acid methyl ester,       234.   (R)-2-{N′-[2-(2-bromophenyl)acetyl]guanidino}-3-cyclohexyl-N-(4-           fluoro-3-methoxybenzyl)propionamide,       235.   (R)-2-{N′-[2-(2-bromophenyl)acetyl]guanidino}-3-cyclohexyl-N-           isobutylpropionamide,       236.   (R)-2-{N′-[2-(2-bromophenyl)acetyl]guanidino}-N-(4-fluoro-3-           methoxybenzyl)-3-phenylpropionamide,       237.   (R)-3-cyclohexyl-N-(4-fluoro-3-methoxybenzyl)-2-{N′-[2-((S)-5-oxo-           pyrrolidin-2-yl)acetyl]guanidino}propionamide,       238.   (R)-3-cyclohexyl-N-isobutyl-2-{N′-[2-((S)-5-oxopyrrolidin-2-yl)-           acetyl]guanidino}propionamide,       239.   (S)-2-benzyl-4-{N′-[(R)-2-cyclohexyl-1-(4-fluoro-3-methoxybenzyl-           carbamoyl)ethyl]guanidino}-4-oxobutyric acid,       240.   (R)-N-(3,4-dimethoxybenzyl)-3-phenyl-2-{N′-[2-(2,3,4-trimethoxy-           phenyl)acetyl]guanidino}propionamide,       241.   (R)-N-(4-fluoro-3-methoxybenzyl)-3-phenyl-2-{N′-[2-(2,3,4-           trimethoxyphenyl)acetyl]guanidino}propionamide,       242.   (R)-3-cyclohexyl-N-isobutyl-2-{N′-[2-(2,3,4-trimethoxyphenyl)-           acetyl]guanidino}propionamide,       243.   (R)-3-cyclohexyl-N-(4-fluoro-3-methoxybenzyl)-2-{N′-[2-(2,3,4-           trimethoxyphenyl)acetyl]guanidino}propionamide,       244.   (R)-2-{N′-[2-(3,4-difluorophenyl)acetyl]guanidino}-N-(3,4-dimethoxy-           benzyl)-3-phenylpropionamide,       245.   (R)-2-{N′-[2-(3,4-difluorophenyl)acetyl]guanidino}-N-(4-fluoro-3-           methoxybenzyl)-3-phenylpropionamide,       246.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-difluorophenyl)acetyl]guanidino}-N-           isobutylpropionamide,       247.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-difluorophenyl)acetyl]guanidino}-N-           (4-fluoro-3-methoxybenzyl)propionamide,       248.   (R)-N-cyclobutyl-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)-           acetyl]guanidino}propionamide,       249.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanecarboxylic acid cyclobutyl amide,       250.   (R)-2-{N′-[2-(1-ethylpiperidin-4-yl)acetyl]guanidino}-N-(4-fluoro-3-           methoxybenzyl)-3-phenylpropionamide,       251.   (R)-3-cyclohexyl-2-{N′-[2-(1-ethylpiperidin-4-yl)acetyl]guanidino}-N-           isobutylpropionamide,       252.   (R)-3-cyclohexyl-2-{N′-[2-(1-ethylpiperidin-4-yl)acetyl]guanidino}-N-           (4-fluoro-3-methoxybenzyl)propionamide,       253.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-(3-trifluoromethylbenzyl)propionamide,       254.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanoic acid 3-trifluoromethylbenzyl amide,       255.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-(4-fluoro-3-trifluoromethylbenzyl)propionamide,       256.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanecarboxylic acid 4-fluoro-3-trifluoromethylbenzyl amide,       257.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-(3-trifluoromethoxybenzyl)propionamide,       258.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanecarboxylic acid 3-trifluoromethoxybenzyl amide,       259.   (R)-3-cyclohexyl-N-(4-fluoro-3-trifluoromethoxybenzyl)-2-{N′-[2-(4-           fluoro-3-trifluoromethylphenyl)acetyl]guanidino}propionamide,       260.   (R)-3-cyclohexyl-N-(4-fluoro-3-trifluoromethylbenzyl)-2-{N′-[2-(4-           fluoro-3-trifluoromethylphenyl)acetyl]guanidino}propionamide,       261.   (R)-3-cyclohexyl-N-(4-fluoro-3-methoxybenzyl)-2-{N′-[2-(2,4,6-           trifluorophenyl)acetyl]guanidino}propionamide,       262.   (R)-3-cyclohexyl-N-(4-fluoro-3-trifluoromethoxybenzyl)-2-{N′-[2-           (2,4,6-trifluorophenyl)acetyl]guanidino}propionamide,       263.   (R)-3-cyclohexyl-N-(4-fluoro-3-trifluoromethylbenzyl)-2-{N′-[2-           (2,4,6-trifluorophenyl)acetyl]guanidino}propionamide,       264.   (R)-3-cyclohexyl-N-(4-fluoro-3-methoxybenzyl)-2-{N′-[2-(4-fluoro-3-           trifluoromethylphenyl)acetyl]guanidino}propionamide,       265.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-(4-fluoro-3-trifluoromethoxybenzyl)propionamide,       266.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanecarboxylic acid 4-fluoro-3-trifluoromethoxybenzyl amide,       267.   (R)-N-[(S)-1-(3-chlorophenyl)-2-oxopyrrolidin-3-yl]-3-cyclohexyl-2-           {N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}propionamide,       268.   (R)-N-[(R)-1-(3-chlorophenyl)-2-oxopyrrolidin-3-yl]-3-cyclohexyl-2-           {N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}propionamide,       269.   (R)-2-{N′-[2-(2-bromo-4,5-dimethoxyphenyl)acetyl]guanidino}-4-           methylpentanecarboxylic acid 3-(1H-tetrazol-5-yl)benzyl amide,       270.   (R)-2-{N′-[2-(2-bromo-4,5-dimethoxyphenyl)acetyl]guanidino}-3-           cyclohexyl-N-[3-(1H-tetrazol-5-yl)benzyl]propionamide,       271.   (R)-3-cyclohexyl-N-(4-fluoro-3-methoxybenzyl)-2-{N′-[2-(3-fluoro-4-           trifluoromethoxyphenyl)acetyl]guanidino}propionamide,       272.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-[4-(1H-tetrazol-5-yl)benzyl]propionamide,       273.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanoic acid 4-(1H-tetrazol-5-yl)benzyl amide,       274.   (R)-2-{N′-[2-(4-chlorophenyl)acetyl]guanidino}-3-cyclohexyl-N-           isobutylpropionamide,       275.   (R)-2-{N′-[2-(4-chlorophenyl)acetyl]guanidino}-3-cyclohexyl-N-(4-           fluoro-3-methoxybenzyl)propionamide,       276.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-[3-fluoro-4-(1H-tetrazol-5-yl)benzyl]propionamide,       277.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanoic acid 3-fluoro-4-(1H-tetrazol-5-yl)benzyl bamide,       278.   (R)-2-{N′-[2-(2-bromo-4-trifluoromethylphenyl)acetyl]guanidino}-3-           cyclohexyl-N-(4-fluoro-3-methoxybenzyl)propionamide,       279.   (R)-2-[N′-((2S,4R)-1-acetyl-4-methoxypyrrolidine-2-carbonyl)-           guanidino]-3-cyclohexyl-N-(4-fluoro-3-methoxybenzyl)propion-amide,       280.   (R)-3-cyclohexyl-N-(4-fluoro-3-methoxybenzyl)-2-[N′-(2-piperidin-1-           ylacetyl)guanidino]propionamide,       281.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-(3-sulfamoylbenzyl)propionamide,       282.   (R)-3-cyclohexyl-N-(4-fluoro-3-methoxybenzyl)-2-[N′-(2-morpholin-           4-ylacetyl)guanidino]propionamide,       283.   (R)-3-cyclohexyl-N-(4-fluoro-3-methoxybenzyl)-2-{N′-[2-(4-           sulfamoylphenyl)acetyl]guanidino}propionamide,       284.   (R)-3-cyclohexyl-N-(4-fluoro-3-methoxybenzyl)-2-{N′-[2-(2-fluoro-4-           methoxyphenyl)acetyl]guanidino}propionamide,       285.   (R)-3-cyclohexyl-2-{N′-[2-(2-fluoro-4-methoxyphenyl)acetyl]-           guanidino}-N-isobutylpropionamide,       286.   (R)-3-cyclohexyl-N-(4-fluoro-3-methoxybenzyl)-2-(N′-{2-[4-(5-           methyl-1,2,4-oxadiazol-3-yl)phenyl]acetyl}guanidino)propionamide,       287.   (R)-2-{N′-[2-(3-cyanophenyl)acetyl]guanidino}-3-cyclohexyl-N-(4-           fluoro-3-methoxybenzyl)propionamide,       288.   (R)-3-cyclohexyl-N-(4-fluoro-3-methoxybenzyl)-2-{N′-[2-(3-           methanesulfonylaminophenyl)acetyl]guanidino}propionamide,       289.   4-[((R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]-           guanidino}propionylamino)methyl]benzoic acid methyl ester,       290.   4-[((R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanoylamino)methyl]benzoic acid methyl ester,       291.   4-[((R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-3-phenyl-           propionylamino)methyl]benzoic acid methyl ester,       292.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-[3-(5-methyl-1,2,4-oxadiazol-3-yl)benzyl]propionamide,       293.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanoic acid 3-(5-methyl-1,2,4-oxadiazol-3-yl)benzyl amide,       294.   4-(2-{N′-[(R)-2-cyclohexyl-1-(4-fluoro-3-methoxybenzylcarbamoyl)-           ethyl]guanidino}-2-oxoethyl)-2-ethoxybenzoic acid ethyl ester,       295.   (R)-3-cyclohexyl-N-(4-fluoro-3-methoxybenzyl)-2-[N′-(2-pyridin-2-yl-           acetyl)guanidino]propionamide,       296.   (R)-3-cyclohexyl-N-(4-fluoro-3-methoxybenzyl)-2-[N′-(2-isobutoxy-           acetyl)guanidino]propionamide,       297.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanoic acid 4-(1,2,3-thiadiazol-4-yl)benzyl amide,       298.   (R)-2-{N′-[2-(4-chlorophenyl)acetyl]guanidino}-3-cyclohexyl-N-(3-           sulfamoylbenzyl)propionamide,       299.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-3-phenyl-N-(4-           (1,2,3-thiadiazol-4-yl)benzyl)propionamide,       300.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-[3-(5-methyl-           1,2,4-oxadiazol-3-yl)benzyl]-3-phenylpropionamide,       301.   (R)-3-cyclohexyl-N-(4-fluoro-3-methoxybenzyl)-2-{N′-[2-(4-tetrazol-           1-ylphenyl)acetyl]guanidino}propionamide,       302.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-[3-(2-methyl-           imidazol-1-yl)benzyl]-3-phenylpropionamide,       303.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-[3-(2-methylimidazol-1-yl)benzyl]propionamide,       304.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanecarboxylic acid 3-(2-methylimidazol-1-yl)benzyl amide,       305.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-3-phenyl-N-(3-           (1,2,4-triazol-1-yl)benzyl)propionamide,       306.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-(3-1,2,4-triazol-1-ylbenzyl)propionamide,       307.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanoic acid 3-(1,2,4-triazol-1-yl)benzyl amide,       308.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanecarboxylic acid 4-(5-hydroxy-1,3,4-oxadiazol-2-yl)benzyl amide,       309.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-[4-(5-           hydroxy-1,3,4-oxadiazol-2-yl)benzyl]-3-phenylpropionamide,       310.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-[4-(5-hydroxy-1,3,4-oxadiazol-2-yl)benzyl]propionamide,       311.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-[3-(5-hydroxy-1,3,4-oxadiazol-2-yl)benzyl]propionamide,       312.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanoic acid 3-(5-hydroxy-1,3,4-oxadiazol-2-yl)benzyl amide,       313.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-[3-(5-           hydroxy-1,3,4-oxadiazol-2-yl)benzyl]-3-phenylpropionamide,       314.   (R)-2-{N′-[2-(4-chlorophenyl)acetyl]guanidino}-3-cyclohexyl-N-[4-           (1H-tetrazol-5-yl)benzyl]propionamide,       315.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-(4-1,2,3-thiadiazol-4-ylbenzyl)propionamide,       316.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-[3-(2-methyl-2H-pyrazol-3-yl)benzyl]propionamide,       317.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanoic acid 3-(2-methyl-2H-pyrazol-3-yl)benzyl amide,       318.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-[3-(2-methyl-           2H-pyrazol-3-yl)benzyl]-3-phenylpropionamide,       319.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-[3-(1-methyl-1H-pyrazol-3-yl)benzyl]propionamide,       320.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanoic acid 3-(1-methyl-1H-pyrazol-3-yl)benzyl amide,       321.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-[3-(1-methyl-           1H-pyrazol-3-yl)benzyl]-3-phenylpropionamide,       322.   (R)-2-{N′-[2-(4-chloro-2-fluorophenyl)acetyl]guanidino}-3-           cyclohexyl-N-(4-fluoro-3-methoxybenzyl)propionamide,       323.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-(3-thiazol-2-ylbenzyl)propionamide,       324.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanoic acid 3-thiazol-2-ylbenzyl amide,       325.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-3-phenyl-N-(3-           thiazol-2-ylbenzyl)propionamide,       326.   (R)-2-[N′-((1S,4R)-2-bicyclo[2.2.1]hept-2-ylacetyl)guanidino]-3-           cyclohexyl-N-(4-fluoro-3-methoxybenzyl)propionamide,       327.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethylphenyl)acetyl]guanidino}-N-           (4-fluoro-3-methoxybenzyl)propionamide,       328.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-[4-fluoro-3-(5-hydroxy-1,3,4-oxadiazol-2-yl)benzyl]propionamide,       329.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanoic acid 4-fluoro-3-(5-hydroxy-1,3,4-oxadiazol-2-yl)benzyl amide,       330.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-[4-fluoro-3-           (5-hydroxy-1,3,4-oxadiazol-2-yl)benzyl]-3-phenylpropionamide,       331.   (R)-2-[N′-((1S,4R)-2-bicyclo[2.2.1]hept-2-ylacetyl)guanidino]-3-           cyclohexyl-N-[3-(1H-tetrazol-5-yl)benzyl]propionamide,       332.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethylphenyl)acetyl]guanidino}-N-           [3-(1H-tetrazol-5-yl)benzyl]propionamide,       333.   (R)-3-cyclohexyl-N-(4-fluoro-3-methoxybenzyl)-2-(N′-{2-[4-(2H-           tetrazol-5-yl)phenyl]acetyl}guanidino)propionamide,       334.   (R)-3-cyclohexyl-N-(4-fluoro-3-methoxybenzyl)-2-{N′-[2-(4-propyl-           cyclohexyl)acetyl]guanidino}propionamide,       335.   (R)-3-cyclohexyl-2-{N′-[2-(4-propylcyclohexyl)acetyl]guanidino}-N-           [3-(1H-tetrazol-5-yl)benzyl]propionamide,       336.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-[4-fluoro-3-           (2H-tetrazol-5-yl)benzyl]-3-phenylpropionamide,       337.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-[4-fluoro-3-(2H-tetrazol-5-yl)benzyl]propionamide,       338.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanoic acid 4-fluoro-3-(2H-tetrazol-5-yl)benzyl amide,       339.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-{(S)-1-[3-(1H-tetrazol-5-yl)phenyl]ethyl}propionamide,       340.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethylphenyl)acetyl]guanidino}-N-           {(S)-1-[3-(1H-tetrazol-5-yl)phenyl]ethyl}propionamide,       341.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-{(S)-1-[4-fluoro-3-(1H-tetrazol-5-yl)phenyl]ethyl}propionamide,       342.   (R)-N-[4-(bistrifluoromethylamino)benzyl]-3-cyclohexyl-2-{N′-[2-           (3,4-dimethoxyphenyl)acetyl]guanidino}propionamide,       343.   4-[((R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]-           guanidino}propionylamino)methyl]benzoic acid,       344.   3-[((R)-2-{N′-[2-(4-chlorophenyl)acetyl]guanidino}-3-cyclohexyl-           propionylamino)methyl]benzoic acid methyl ester,       345.   3-[((R)-2-{N′-[2-(4-chlorophenyl)acetyl]guanidino}-4-methyl-           pentanoylamino)methyl]benzoic acid methyl ester,       346.   (R)-N-[3-(bistrifluoromethylamino)benzyl]-3-cyclohexyl-2-{N′-[2-           (3,4-dimethoxyphenyl)acetyl]guanidino}propionamide,       347.   (R)-3-cyclohexyl-N-(4-fluoro-3-methoxybenzyl)-2-(N′-{2-[3-(2H-           tetrazol-5-yl)phenyl]acetyl}guanidino)propionamide,       348.   (R)-N-{1-[4-(bistrifluoromethylamino)phenyl]cyclopropyl}-3-           cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}propion-amide,       349.   (R)-3-cyclohexyl-N-((R)-2,3-dihydroxypropyl)-2-{N′-[2-(3,4-           dimethoxyphenyl)acetyl]guanidino}propionamide,       350.   (R)-3-cyclohexyl-N-((S)-2,3-dihydroxypropyl)-2-{N′-[2-(3,4-           dimethoxyphenyl)acetyl]guanidino}propionamide                    
and physiologically acceptable salts, derivatives, solvates, prodrugs and stereoisomers thereof, including mixtures thereof in all ratios.
 
     In the following moiety of the formula I, R 2  may also stand for a radical of a natural or non-natural amino acid. 
     
       
         
         
             
             
         
       
     
     Thus, R 2  can stand for the radicals of the following amino acids:
         Natural amino acids: alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine, histidine, isoleucine, leucine, lysine, methionine, ornithine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine and valine   Non-natural amino acids, such as, for example, cyclopropylglycine, cyclobutylglycine, cyclopentylglycine, cyclohexylglycine, 3-oxetanylglycine, 3-oxetanylglycine, tetrahydrofuran-3-ylglycine, tetrahydrofuran-2-ylglycine, ethylsulfanylmethylglycine, 2-methylsulfanylethylglycine, 1-methylsulfanylethylglycine, norvaline, aminobutyric acid, tert-leucine, norleucine, naphthylalanine, O-methylserine, O-ethylserine and the like.       

     If the above-mentioned amino acids can occur in a plurality of enantiomeric forms, all these forms and also mixtures thereof (for example DL forms) are included above and below. 
     Furthermore, the abbreviations have the following meanings: 
     Boc ter-butoxycarbonyl 
     CBZ benzyloxycarbonyl 
     DNP 2,4-dinitrophenyl 
     FMOC 9-fluorenylmethoxycarbonyl 
     imi-DNP 2,4-dinitrophenyl in the 1-position of the imidazole ring 
     OMe methyl ester 
     POA phenoxyacetyl 
     DCCl dicyclohexylcarbodiimide 
     HOBt 1-hydroxybenzotriazole 
     Hal denotes fluorine, chlorine, bromine or iodine, in particular fluorine or chlorine. 
     —(C═O)— or ═O denotes carbonyl oxygen and stands for 
                         
or an oxygen atom bonded to a carbon atom by means of a double bond
 
     A stands for alkyl, alkenyl, alkynyl or cycloalkyl. 
     Alkyl is a saturated, unbranched (linear) or branched hydrocarbon chain and has 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 C atoms. Alkyl preferably denotes methyl, furthermore ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl or tert-butyl, furthermore also pentyl, 1-, 2- or 3-methylbutyl, 1,1-, 1,2- or 2,2-dimethylpropyl, 1-ethylpropyl, hexyl, 1-, 2-, 3- or 4-methylpentyl, 1,1-, 1,2-, 1,3-, 2,2-, 2,3- or 3,3-dimethylbutyl, 1- or 2-ethylbutyl, 1-ethyl-1-methylpropyl, 1-ethyl-2-methylpropyl, 1,1,2- or 1,2,2-trimethylpropyl, linear or branched heptyl, octyl, nonyl or decyl, further preferably, for example, trifluoromethyl. 
     With regard to the present invention, alkyl additionally also denotes cyclo-alkyl. 
     Alkenyl denotes an unsaturated hydrocarbon chain which has at least one double bond, preferably methenyl, ethenyl, propenyl, butenyl, pentenyl or hexenyl, furthermore branched alkenyl. 
     Alkynyl denotes an unsaturated hydrocarbon chain which has at least one triple bond, preferably methynyl, ethynyl, propynyl, butynyl, pentynyl or hexynyl, furthermore branched alkynyl. 
     Cyclic alkyl or cycloalkyl is a saturated cyclic hydrocarbon chain and has 3-10, preferably 3-7 C atoms and preferably denotes cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl. Cycloalkyl also denotes a partially unsaturated cyclic akyl, such as, for example, cyclohexenyl or cyclohexynyl. 
     Aryl denotes an aromatic or fully unsaturated cyclic hydrocarbon chain, for example unsubstituted phenyl, naphthyl or biphenyl, furthermore preferably phenyl, naphthyl or biphenyl, each of which is mono-, di- or trisubstituted by, for example, A, fluorine, chlorine, bromine, iodine, hydroxyl, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, nitro, cyano, formyl, acetyl, propionyl, trifluoromethyl, amino, methylamino, ethylamino, dimethylamino, diethylamino, benzyloxy, sulfonamido, methylsulfonamido, ethylsulfonamido, propylsulfonamido, butylsulfon-amido, dimethylsulfonamido, phenylsulfonamido, carboxyl, methoxycarbonyl, ethoxycarbonyl, aminocarbonyl. 
     Mono- or bicyclic saturated, unsaturated or aromatic heterocycle preferably denotes unsubstituted or mono-, di- or trisubstituted 2- or 3-furyl, 2- or 3-thienyl, 1-, 2- or 3-pyrrolyl, 1-, 2, 4- or 5-imidazolyl, 1-, 3-, 4- or 5-pyrazolyl, 2-, 4- or 5-oxazolyl, 3-, 4- or 5-isoxazolyl, 2-, 4- or 5-thiazolyl, 3-, 4- or 5-isothiazolyl, 2-, 3- or 4-pyridyl, 2-, 4-, 5- or 6-pyrimidinyl, furthermore preferably 1,2,3-triazol-1-, -4- or -5-yl, 1,2,4-triazol-1-, -3- or 5-yl, 1- or 5-tetrazolyl, 1,2,3-oxadiazol-4- or -5-yl, 1,2,4-oxadiazol-3- or -5-yl, 1,3,4-thiadiazol-2- or -5-yl, 1,2,4-thiadiazol-3- or -5-yl, 1,2,3-thiadiazol-4- or -5-yl, 3- or 4-pyridazinyl, pyrazinyl, 1-, 2-, 3-, 4-, 5-, 6- or 7-indolyl, 4- or 5-isoindolyl, 1-, 2-, 4- or 5-benzimidazolyl, 1-, 3-, 4-, 5-, 6- or 7-benzopyrazolyl, 2-, 4-, 5-, 6- or 7-benzoxazolyl, 3-, 4-, 5-, 6- or 7-benzisoxazolyl, 2-, 4-, 5-, 6- or 7-benzothiazolyl, 2-, 4-, 5-, 6- or 7-benzisothiazolyl, 4-, 5-, 6- or 7-benz-2,1,3-oxadiazolyl, 2-, 3-, 4-, 5-, 6-, 7- or 8-quinolyl, 1-, 3-, 4-, 5-, 6-, 7- or 8-isoquinolyl, 3-, 4-, 5-, 6-, 7- or 8-cinnolinyl, 2-, 4-, 5-, 6-, 7- or 8-quinazolinyl, 5- or 6-quinoxalinyl, 2-, 3-, 5-, 6-, 7- or 8-2H-benzo-1,4-oxazinyl, further preferably 1,3-benzodioxol-5-yl, 1,4-benzodioxan-6-yl, 2,1,3-benzothiadiazol-4- or -5-yl or 2,1,3-benz-oxadiazol-5-yl. 
     The heterocyclic radicals may also be partially or fully hydrogenated and also denote, for example, 2,3-dihydro-2-, -3-, -4- or -5-furyl, 2,5-dihydro-2-, -3-, -4- or 5-furyl, tetrahydro-2- or -3-furyl, 1,3-dioxolan-4-yl, tetrahydro-2- or -3-thienyl, 2,3-dihydro-1-, -2-, -3-, -4- or -5-pyrrolyl, 2,5-dihydro-1-, -2-, -3-, -4- or -5-pyrrolyl, 1-, 2- or 3-pyrrolidinyl, tetrahydro-1-, -2- or -4-imidazolyl, 2,3-dihydro-1-, -2-, -3-, -4- or -5-pyrazolyl, tetrahydro-1-, -3- or -4-pyrazolyl, 1,4-dihydro-1-, -2-, -3- or -4-pyridyl, 1,2,3,4-tetrahydro-1-, -2-, -3-, -4-, -5- or -6-pyridyl, 1-, 2-, 3- or 4-piperidinyl, 2-, 3- or 4-morpholinyl, tetrahydro-2-, -3- or -4-pyranyl, 1,4-dioxanyl, 1,3-dioxan-2-, -4- or -5-yl, hexahydro-1-, -3- or -4-pyridazinyl, hexahydro-1-, -2-, -4- or -5-pyrimidinyl, 1-, 2- or 3-piperazinyl, 1,2,3,4-tetrahydro-1-, -2-, -3-, -4-, -5-, -6-, -7- or -8-quinolyl, 1,2,3,4-tetrahydro-1-, -2-, -3-, -4-, -5-, -6-, -7- or -8-isoquinolyl, 2-, 3-, 5-, 6-, 7- or 8-3,4-dihydro-2H-benzo-1,4-oxazinyl, further preferably 2,3-methylenedioxyphenyl, 3,4-methylenedioxyphenyl, 2,3-ethylenedioxyphenyl, 3,4-ethylenedioxyphenyl, 3,4-(difluoromethylenedioxy)phenyl, 2,3-dihydrobenzofuran-5- or 6-yl, 2,3-(2-oxomethylenedioxyl)phenyl or also 3,4-dihydro-2H-1,5-benzodioxepin-6- or -7-yl, furthermore preferably 2,3-dihydrobenzofuranyl or 2,3-dihydro-2-oxofuranyl. 
     Heterocycle furthermore denotes, for example, 2-oxopiperidin-1-yl, 2-oxo-pyrrolidin-1-yl, 2-oxo-1H-pyridin-1-yl, 3-oxomorpholin-4-yl, 4-oxo-1H-pyridin-1-yl, 2,6-dioxopiperidin1-yl, 2-oxopiperazin-1-yl, 2,6-dioxopiperazin-1-yl, 2,5-dioxopyrrolidin-1-yl, 2-oxo-1,3-oxazolidin-3-yl, 3-oxo-2H-pyridazin-2-yl, 2-caprolactam-1-yl (=2-oxoazepan-1-yl), 2-hydroxy-6-oxopiperazin-1-yl, 2-methoxy-6-oxopiperazin-1-yl or 2-azabicyclo[2.2.2]octan-3-on-2-yl. 
     Heterocycloalkyl here denotes a fully hydrogenated or saturated heterocycle, heterocycloaklenyl (one or more double bonds) or heterocycloaklynyl (one or more triple bonds) denotes a partially or incompletely hydrogenated or unsaturated heterocycle, heteroaryl denotes an aromatic or fully unsaturated heterocycle. 
     Cycloalkylalkyl, cycloalkylalkenyl, cycloalkylalkynyl, heterocycloalkylalkyl, heterocycloalkylalkenyl, heterocycloalkylalkynyl, arylalkyl, arylalkenyl, arylalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl means that the respective ring system are bonded via an alkyl, alkenyl or alkynyl radical. 
     Thus, cycloalkylalkenyl having 5-12 C atoms denotes, for example, cyclopentylmethenyl, cyclohexylmethenyl, cyclohexylethenyl, cyclohexylpropenyl or cyclohexylbutenyl and cycloalkylalkynyl having 5-12 C atoms, denotes, for example, cyclopentylmethynyl, cyclohexylmethynyl, cyclohexylethynyl, cyclohexylpropynyl or cyclohexylbutynyl. 
     OA denotes alkoxy and is preferably methoxy, furthermore also ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy or tert-butoxy. 
     All physiologically acceptable salts, derivatives, solvates and stereoisomers of these compounds, including mixtures thereof in all ratios, are also in accordance with the invention. 
     Compounds of the general formula I may contain one or more centres of chirality, so that all stereoisomers, enentiomers, diastereomers, etc., of the compounds of the general formula I are also claimed in the present invention. 
     The invention also relates to the optically active forms (stereoisomers), the enantiomers, the racemates, the diastereomers and hydrates and solvates of these compounds. 
     Compounds of the formula I according to the invention may be chiral owing to their molecular structure and may accordingly occur in various enantiomeric forms. They may therefore be in racemic or optically active form. Since the pharmaceutical efficacy of the racemates or stereoisomers of the compounds according to the invention may differ, it may be desirable to use the enantiomers. In these cases, the end product, but also even the intermediates, may be separated into enantiomeric compounds by chemical or physical measures known to the person skilled in the art or already employed as such in the synthesis. 
     Pharmaceutically or physiologically acceptable derivatives are taken to mean, for example, salts of the compounds according to the invention and also so-called prodrug compounds. Prodrug compounds are taken to mean compounds of the formula I which have been modified with, for example, alkyl or acyl groups (see also amino- and hydroxyl-protecting groups below), sugars or oligopeptides and which are rapidly cleaved or liberated in the organism to form the effective compounds according to the invention. These also include biodegradable polymer derivatives of the compounds according to the invention, as described, for example, in Int. J. Pharm. 115 (1995), 61-67. 
     Suitable acid-addition salts are inorganic or organic salts of all physiologically or pharmacologically acceptable acids, for example halides, in particular hydrochlorides or hydrobromides, lactates, sulfates, citrates, tartrates, maleates, fumarates, oxalates, acetates, phosphates, methyl-sulfonates or p-toluenesulfonates. 
     Very particular preference is given to the hydrochlorides, the trifluoro-acetates or the bistrifluoroacetates of the compounds according to the invention. 
     Solvates of the compounds of the formula I are taken to mean adductions of inert solvent molecules onto the compounds of the formula I which form owing to their mutual attractive force. Solvates are, for example, hydrates, such as monohydrates or dihydrates, or alcoholates, i.e. addition compounds with alcohols, such as, for example, with methanol or ethanol. 
     It is furthermore intended that a compound of the formula I includes iso-tope-labelled forms thereof. An isotope-labelled form of a compound of the formula I is identical to this compound apart from the fact that one or more atoms of the compound have been replaced by an atom or atoms having an atomic mass or mass number which differs from the atomic mass or mass number of the atom which usually occurs naturally. Examples of isotopes which are readily commercially available and which can be incorporated into a compound of the formula I by well-known methods include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, fluorine and chlorine, for example  2 H,  3 H,  13 O,  14 O,  15 N,  18 O,  17 O,  31 P,  32 P,  35 S,  18 F and  36 Cl, respectively. A compound of the formula I, a prodrug thereof or a pharmaceutically acceptable salt of either which contains one or more of the above-mentioned isotopes and/or other isotopes of other atoms is intended to be part of the present invention. An isotope-labelled compound of the formula I can be used in a number of beneficial ways. For example, an isotope-labelled compound of the formula I into which, for example, a radioisotope, such as  3 H or  14 C, has been incorporated is suitable for medicament and/or substrate tissue distribution assays. These radioisotopes, i.e. tritium ( 3 H) and carbon-14 ( 14 O), are particularly preferred owing to their simple preparation and excellent detectability. Incorporation of heavier isotopes, for example deuterium ( 2 H), into a compound of the formula I has therapeutic advantages owing to the higher metabolic stability of this isotope-labelled compound. Higher metabolic stability translates directly into an increased in-vivo half-life or lower dosages, which under most circumstances would represent a preferred embodiment of the present invention. An isotope-labelled compound of the formula I can usually be prepared by carrying out the procedures disclosed in the synthesis schemes and the related description, in the example part and in the preparation part in the present text, replacing a non-isotope-labelled reactant with a readily available isotope-labelled reactant. 
     In order to manipulate the oxidative metabolism of the compound by way of the primary kinetic isotope effect, deuterium ( 2 H) can also be incorporated into a compound of the formula I. The primary kinetic isotope effect is a change in the rate of a chemical reaction that results from exchange of isotopic nuclei, which in turn is caused by the change in ground state energies necessary for covalent bond formation after this isotopic exchange. Exchange of a heavier isotope usually results in a lowering of the ground state energy for a chemical bond and thus causes a reduction in the rate in rate-limiting bond breakage. If the bond breakage occurs in or in the vicinity of a saddle-point region along the coordinate of a multi-product reaction, the product distribution ratios can be altered substantially. For explanation: if deuterium is bonded to a carbon atom in a non-exchangeable position, rate differences of k M /k D =2-7 are typical. If this rate difference is successfully applied to a compound of the formula I that is susceptible to oxidation, the profile of this compound in vivo can thereby be drastically modified and result in improved pharmacokinetic properties. 
     When discovering and developing therapeutic agents, the person skilled in the art attempts to optimise pharmacokinetic parameters while retaining desirable in-vitro properties. It is reasonable to assume that many compounds with poor pharmacokinetic profiles are susceptible to oxidative metabolism. In-vitro liver microsomal assays currently available provide valuable information on the course of oxidative metabolism of this type, which in turn permits the rational design of deuterated compounds of the formula I with improved stability through resistance to such oxidative metabolism. Significant improvements in the pharmacokinetic profiles of the compounds of the formula I are thereby obtained and can be expressed quantitatively in terms of increases in the in-vivo half-life (T/2), concentration at maximum therapeutic effect (C max ), area under the dose response curve (AUC), and F; and in terms of reduced clearance, dose and costs of materials. 
     The following is intended to illustrate the above: a compound of the formula I which has multiple potential sites of attack for oxidative metabolism, for example benzylic hydrogen atoms and hydrogen atoms bonded to a nitrogen atom, is prepared as a series of analogues in which various combinations of hydrogen atoms are replaced by deuterium atoms, so that some, most or all of these hydrogen atoms have been replaced by deuterium atoms. Half-life determinations enable favourable and accurate determination of the extent to which the improvement in resistance to oxidative metabolism has improved. In this way, it is determined that the half-life of the parent compound can be extended by up to 100% as the result of deuterium-hydrogen exchange of this type. 
     The replacement of hydrogen by deuterium in a compound of the formula I can also be used to achieve a favourable modification of the metabolite spectrum of the starting compound in order to diminish or eliminate undesired toxic metabolites. For example, if a toxic metabolite arises through oxidative carbon-hydrogen (C—H) bond cleavage, it can reasonably be assumed that the deuterated analogue will greatly diminish or eliminate production of the undesired metabolite, even if the particular oxidation is not a rate-determining step. Further information on the state of the art with respect to deuterium-hydrogen exchange is given, for example in Hanzlik et al., J. Org. Chem. 55, 3992-3997, 1990, Reider et al., J. Org. Chem. 52, 3326-3334, 1987, Foster, Adv. Drug Res. 14, 1-40, 1985, Gillette et al., Biochemistry 33(10), 2927-2937, 1994, and Jarman et al., Carcinogenesis 16(4), 683-688, 1993. 
     The invention also relates to mixtures of the compounds of the formula I according to the invention, for example mixtures of two diastereomers, for example in the ratio 1:1, 1:2, 1:3, 1:4, 1:5, 1:10, 1:100 or 1:1000. These are particularly preferably mixtures of two stereoisomeric compounds. However, preference is also given to mixtures of two or more compounds of the formula I. 
     The invention additionally relates to a process for the preparation of the compounds of the formula I, characterised in that
     a) a compound of the formula VII,   

     
       
         
         
             
             
         
       
         
         
           
             in which R 1  has the meanings indicated above, 
             is obtained by acylation of a pyrazole-1-carboxamidine of the formula XI 
           
         
       
    
     
       
         
         
             
             
         
       
         
         
           
             using an acid of the formula X or an acid derivative of the formula Xa using auxiliary bases or coupling reagents which are usual in such reactions, by methods known from the literature, 
           
         
       
    
     
       
         
         
             
             
         
       
         
         
           
             in which R 1  has the meanings indicated above and X denotes a halogen, alkyl- or aryloxycarbonyloxy, such as, for example, ethoxycarbonyloxy or p-nitrophenyloxycarbonyloxy, 
             and a compound of the formula VIII 
           
         
       
    
     
       
         
         
             
             
         
       
         
         
           
             in which R 1  has the meanings indicated above and R 11  denotes a protecting group for amines or imines, is obtained by reacting a guanidine of the formula IX, 
           
         
       
    
     
       
         
         
             
             
         
       
         
         
           
             in which R 11  has the meanings indicated above, with an acid of the formula X or an activated acid derivative of the formula Xa, 
           
         
       
    
     
       
         
         
             
             
         
       
         
         
           
             in which R 1  and X have the meanings indicated above, 
             and a compound of the formula III, 
           
         
       
    
     
       
         
         
             
             
         
       
         
         
           
             in which R 1  and R 11  have the meanings indicated above and L denotes a leaving group, such as, for example, a 1-pyrrazolyl or trifluoromethylsulfonylamino group, is prepared by either 
             in the case where L denotes a 1-pyrazolyl group, introducing a protecting group R 11  into a compound of the formula VII by the usual processes known from the literature, 
             or, in the case where L denotes a trifluoromethylsulfonylamino group, preparing a compound of the formula III by reaction of a compound of the formula VIII with trifluoromethanesulfonic anhydride by the usual methods known from the literature, 
             and a compound of the formula II, 
           
         
       
    
     
       
         
         
             
             
         
       
         
         
           
             in which R 2  and R 3  have the meanings indicated above, is prepared by preparing a compound of the formula IV, 
           
         
       
    
     
       
         
         
             
             
         
       
         
         
           
             in which R 2 , R 3  and R 11  have the meanings indicated above, by coupling an amino acid of the formula V, 
           
         
       
    
     
       
         
         
             
             
         
       
         
         
           
             in which R 3  and R 11  have the meanings indicated above, to an amine of the formula VI,
 
H 2 N—R 3   VI
 
             in which R 3  has the meanings indicated above, by processes known from the literature using coupling reagents which are usual in such reactions, 
             and a compound of the formula II is prepared by removing R 11  from a compound of the formula IV by processes known from the literature, 
             and then obtaining a compound of the formula Ia 
           
         
       
    
     
       
         
         
             
             
         
       
         
         
           
             in which R 1 , R 2 , R 3  and R 11  have the meanings indicated above, by reaction of an amine of the formula II with an acylguanidine of the formula III, 
             and a compound of the formula I is obtained by removing R 11 , a protecting group for amines or imines, such as a tert-butyloxycarbonyl (BOC group) or benzyloxycarbonyl group (Z group), from a compound of the formula Ia, by processes known from the literature. or 
           
         
         b) a compound of the formula VII is reacted with an amine of the formula II, or 
         c) the base of a compound of the formula I is converted into one of its salts by treatment with an acid, or 
         d) an acid of a compound of the formula I is converted into one of its salts by treatment with a base. 
       
    
     The synthesis of the compounds according to the invention is summarised in Scheme 1. 
     
       
         
         
             
             
         
       
     
     It is also possible to carry out the reactions stepwise in each case and to modify the sequence of the linking reactions of the building blocks with adaptation of the protecting-group concept. 
     The starting materials or starting compounds are generally known. If they are novel, they can be prepared by methods known per se. 
     If desired, the starting materials can also be formed in situ by not isolating them from the reaction mixture, but instead immediately converting them further into the compounds of the formula I. 
     The compounds of the formula I are preferably obtained by liberating them from their functional derivatives by solvolysis, in particular by hydrolysis, or by hydrogenolysis. Preferred starting materials for the solvolysis or hydrogenolysis are those which contain correspondingly protected amino, carboxyl and/or hydroxyl groups instead of one or more free amino, carboxyl and/or hydroxyl groups, preferably those which carry an amino-protecting group instead of an H atom which is connected to an N atom. Preference is furthermore given to starting materials which carry a hydroxyl-protecting group instead of the H atom of a hydroxyl group. Preference is also given to starting materials which carry a protected carboxyl group instead of a free carboxyl group. It is also possible for a plurality of identical or different protected amino, carboxyl and/or hydroxyl groups to be present in the molecule of the starting material. If the protecting groups present are different from one another, they can in many cases be cleaved off selectively. 
     The term “amino-protecting group” is generally known and relates to groups which are suitable for protecting (blocking) an amino group against chemical reactions, but which can easily be removed after the desired chemical reaction has been carried out elsewhere in the molecule. Typical of such groups are, in particular, unsubstituted or substituted acyl groups, furthermore unsubstituted or substituted aryl (for example 2,4-dinitophenyl) or aralkyl groups (for example benzyl, 4-nitrobenzyl, triphenylmethyl). Since the amino-protecting groups are removed after the desired reaction or reaction sequence, their type and size is, in addition, not crucial, but preference is given to those having 1-20, in particular 1-8, C atoms. The term “acyl group” is to be understood in the broadest sense in connection with the present process. It encompasses acyl groups derived from aliphatic, araliphatic, aromatic or heterocyclic carboxylic acids or sulfonic acids and, in particular, alkoxy-carbonyl, aryloxycarbonyl and especially aralkoxycarbonyl groups. Exam-pies of such acyl groups are alkanoyl, such as acteyl, propionyl, buturyl, aralkanoyl, such as phenylacetyl, aroyl, such as benzoyl or toluyl, aryoxyaklkanoyl, such as phenoxyacetyl, alkyoxycarbonyyl, such as methoxycarbonyl, ethoxycarbonyl, 2,2,2-trichloroethoxycarbonyl, BOC, 2-iodoethoxycaronyl, aralkoxycarbonyl. such as CBZ, 4-methoxybenzyloxycarbonyl or FMOC. Preferred acyl groups are CBZ, FMOC, benzyl and acetyl. 
     The term “acid-protecting group” or “carboxyl-protecting group” is likewise generally known and relates to groups which are suitable for protecting a —COOH group against chemical reactions, but which can easily be removed after the desired chemical reaction has been carried out elsewhere in the molecule. The use of esters instead of the free acids, for example of substituted and unsubstituted alkyl esters (such as methyl, ethyl, tert-butyl and substituted derivatives thereof), of substituted and unsubstituted benzyl esters or silyl esters, is typical. The type and size of the acid-protecting groups is not crucial, but preference is given to those having 1-20, in particular 1-10, C atoms. 
     The term “hydroxyl-protecting group” is likewise generally known and relates to groups which are suitable for protecting a hydroxyl group against chemical reactions, but which can easily be removed after the desired chemical reaction has been carried out elsewhere in the molecule. Typical of such groups are the above-mentioned unsubstituted or substituted aryl, aralkyl or acyl groups, furthermore also alkyl groups. The their type and size of the hydroxyl-protecting groups is not crucial, but preference is given to those having 1-20, in particular 1-10, C atoms. Examples of hyrdoxyl-protecting groups are, inter alia, benzyl, p-nitrobenzoyl, p-toluenesulfonyl and acetyl, where benzyl and acetyl are preferred. 
     Further typical examples of amino-, acid- and hydroxyl-protecting groups are found, for example, in “Greene&#39;s Protective Groups in Organic Synthesis”, fourth edition, Wiley-Interscience, 2007. 
     The functional derivatives of the compounds of the formula I to be used as starting materials can be prepared by known methods of amino-acid and peptide synthesis, as described, for example, in the said standard works and patent applications. 
     The compounds of the formula I are liberated from their functional derivatives, depending on the protecting group used, for example, with the aid of strong acids, advantageously using trifluoroacetic acid or perchloric acid, but also using other strong inorganic acids, such as hydrochloric acid or sulfuric acid, strong organic acids, such as trichloroacetic acid, or sulfonic acids, such as benzoyl- or p-toluenesulfonic acid. The presence of an additional inert solvent and/or a catalyst is possible, but is not always necessary. 
     Depending on the respective synthetic route, the starting materials can optionally be reacted in the presence of an inert solvent. 
     Suitable inert solvents are, for example, heptane, hexane, petroleum ether, DMSO, benzene, toluene, xylene, trichloroethylene-, 1,2-dichloroethanecarbon tetrachloride, chloroform or dichloromethane; alcohols, such as methanol, ethanol, isopropanol, n-propanol, n-butanol or tert-butanol; ethers, such as diethyl ether, diisopropyl ether (preferably for substitution on the indole nitrogen), tetrahydrofuran (THF) or dioxane; glycol ethers, such as ethylene glycol monomethyl or monoethyl ether, ethylene glycol dimethy-I ether (diglyme); ketones, such as acetone or butanone; amides, such as acetamide, dimethylacetamide, N-methylpyrrolidone (NMP) or dimethylformamide (DMF); nitriles, such as acetonitrile; esters, such as ethyl acetate, carboxylic acids or acid anhydrides, such as, for example, such as acetic acid or acetic anhydride, nitro compounds, such as nitromethane or nitrobenzene, optionally also mixtures of the said solvents with one another or mixtures with water. 
     The amount of solvent is not crucial; 10 g to 500 g of solvent can preferably be added per g of the compound of the formula I to be reacted. 
     It may be advantageous to add an acid-binding agent, for example an alkali metal or alkaline-earth metal hydroxide, carbonate or bicarbonate or other alkali or alkaline-earth metal salts of weak acids, preferably a potassium, sodium or calcium salt, or to add an organic base, such as, for example, on triethylamine, dimethylamine, pyridine or quinoline, or an excess of the amine component. 
     The resultant compounds according to the invention can be separated from the corresponding solution in which they are prepared (for example by centrifugation and washing) and can be stored in another composition after separation, or they can remain directly in the preparation solution. 
     The resultant compounds according to the invention can also be taken up in desired solvents for the particular use. 
     Suitable reaction temperatures are temperatures from 0 to 40° C., preferably 5 to 25° C. 
     The reaction duration depends on the reaction conditions selected. In general, the reaction duration is 0.5 hour to 10 days, preferably 1 to 24 hours. On use of a microwave, the reaction time can be reduced to values of 1 to 60 minutes. 
     The compounds of the formula I and also the starting materials for their preparation are, in addition, prepared by known methods, as described in the literature (for example in standard works, such as Houben-Weyl, Methoden der organischen Chemie [Methods of Organic Chemistry], Georg-Thieme-Verlag, Stuttgart), for example under reaction conditions which are known and suitable for the said reactions. Use can also be made here of variants known per se, which are not described here in greater detail. 
     Conventional work-up steps, such as, for example, addition of water to the reaction mixture and extraction, enable the compounds to be obtained after removal of the solvent. It may be advantageous, for further purification of the product, to follow this with a distillation or crystallisation or to carry out a chromatographic purification. 
     An acid of the formula I can be converted into the associated addition salt using a base, for example by reaction of equivalent amounts of the acid and base in an inert solvent, such as ethanol, and inclusive evaporation. Suitable bases for this reaction are, in particular, those which give physiologically acceptable salts. Thus, the acid of the formula I can be converted into the corresponding metal salt, in particular alkali or alkaline-earth metal salt, using a base (for example sodium hydroxide, potassium hydroxide, sodium carbonate or potassium carbonate) or into the corresponding ammonium salt. Organic bases which give physiologically acceptable salts, such as, for example, ethanolamine, are also suitable for this reaction. 
     On the other hand, a base of the formula I can be converted into the associated acid-addition salt using an acid, for example by reaction of equivalent amounts of the base and acid in an inert solvent, such as ethanol, with subsequent evaporation. Suitable acids for this reaction are, in particular, those which give physiologically acceptable salts. Thus, it is possible to use inorganic acids, for example sulfuric acid, nitric acid, hydrohalic acids, such as hydrochloric acid or hydrobromic acid, phosphoric acids, such as orthophosphoric acid, sulfamic acid, furthermore organic acids, in particular aliphatic, alicyclic, araliphatic, aromatic or heterocyclic, mono- or polybasic carboxylic, sulfonic or sulfuric acids, for example formic acid, acetic acid, propionic acid, pivalic acid, diethylacetic acid, malonic acid, succinic acid, pimelic acid, fumaric acid, maleic acid, lactic acid, tartaric acid, malic acid, citric acid, gluconic acid, ascorbic acid, nicotinic acid, isonicotinic acid, methane- or ethanesulfonic acid, ethanedisulfonic acid, 2-hydroxysulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, naphthalenemom- and disulfonic acids or laurylsulfuric acid. Salts with physiologically unacceptable acids, for example picrates, can be used for the isolation and/or purification of the compounds of the formula I. 
     It has been found that the compounds of the formula I are well tolerated and have valuable pharmacological properties, since they selectively inhibit aspartyl proteases and in particular cathepsin D. 
     The invention therefore furthermore relates to the use of compounds according to the invention for the preparation of a medicament for the treatment and/or prophylaxis of diseases which are caused, promoted and/or propagated by cathepsin D and/or by cathepsin D-promoted signal transduction. 
     The invention thus also relates, in particular, to a medicament comprising at least one compound according to the invention and/or one of its physiologically acceptable salts, derivatives, solvates, prodrugs and stereoisomers, including mixtures thereof in all ratios, for use in the treatment and/or prophylaxis of physiological and/or pathophysiological states. 
     Particular preference is given, in particular, to physiological and/or pathophysiological states which are connected to cathepsin D. 
     Physiological and/or pathophysiological states are taken to mean physiological and/or pathophysiological states which are medically relevant, such as, for example, diseases or illnesses and medical disorders, complaints, symptoms or complications and the like, in particular diseases. 
     The invention furthermore relates to a medicament comprising at least one compound according to the invention and/or one of its physiologically acceptable salts, derivatives, solvates, prodrugs and stereoisomers, including mixtures thereof in all ratios, for use in the treatment and/or prophylaxis of physiological and/or pathophysiological states selected from the group consisting of arthrosis, traumatic cartilage injuries and arthritis, in particular rheumatoid arthritis. 
     The invention furthermore relates to a medicament comprising at least one compound according to the invention and/or one of its physiologically acceptable salts, derivatives, solvates, prodrugs and stereoisomers, including mixtures thereof in all ratios, for use in the treatment and/or prophylaxis of physiological and/or pathophysiological states selected from the group consisting of Alzheimer&#39;s disease, Huntington&#39;s disease, mucolipidosis, cancer, in particular breast cancer, contact dermatitis, late-onset hypersensitivity reaction, inflammation, endometriosis, scarring, benign prostate hyperplasia, osteosarcoma, rickets, skin diseases, such as, for example, psoriasis, immunological diseases, autoimmune diseases and immunodeficiency diseases. 
     In this connection, brain cancer, lung cancer, squamous cell cancer, bladder cancer, stomach cancer, pancreatic cancer, liver cancer, kidney cancer, colorectal cancer, breast cancer, head cancer, neck cancer, oesophageal cancer, gynaecological cancer, thyroid cancer, lymphomas, chronic leukaemia and acute leukaemia are to be regarded as cancerous diseases, all of which usually count amongst the group of hyperproliferative diseases. 
     Pain is a complex sensory perception which, as an acute event, has the character of a warning and control signal, but as chronic pain has lost this and in this case (as chronic pain syndrome) should be regarded and treated today as an independent syndrome. Hyperalgesia is the term used in medicine for excessive sensitivity to pain and reaction to a stimulus which is usually painful. Stimuli which can trigger pain are, for example, pressure, heat, cold or inflammation. Hyperalgesia is a form of hyperaesthesia, the generic term for excessive sensitivity to a stimulus. Allodynia is the term used in medicine for the sensation of pain which is triggered by stimuli which do not usually cause pain. 
     The invention thus furthermore relates to a medicament comprising at least one compound according to the invention and/or one of its physiologically acceptable salts, derivatives, solvates, prodrugs and stereoisomers, including mixtures thereof in all ratios, for use in the treatment and/or prophylaxis of physiological and/or pathophysiological conditions, selected from the group consisting of pain, allodynia and hyperalgesia. 
     The invention thus particularly preferably relates to a medicament comprising at least one compound according to the invention and/or one of its physiologically acceptable salts, derivatives, solvates, prodrugs and stereoisomers, including mixtures thereof in all ratios, for use in the treatment and/or prophylaxis of physiological and/or pathophysiological conditions, selected from the group consisting of arthrosis, traumatic cartilage injuries, arthritis, pain, allodynia and hyperalgesia. 
     It is intended that the medicaments disclosed above include a corresponding use of the compounds according to the invention for the preparation of a medicament for the treatment and/or prophylaxis of the above physiological and/or pathophysiological states. 
     It is additionally intended that the medicaments disclosed above include a corresponding method for the treatment and/or prophylaxis of the above physiological and/or pathophysiological states in which at least one compound according to the invention is administered to a patient in need of such a treatment. 
     The compounds according to the invention preferably exhibit an advantageous biological activity which can easily be demonstrated in enzyme assays and animal experiments, as described in the examples. In such enzyme-based assays, the antibodies according to the invention preferably exhibit and cause an inhibiting effect, which is usually documented by IC 50  values in a suitable range, preferably in the micromolar range and more preferably in the nanomolar range. 
     The compounds according to the invention can be administered to humans or animals, in particular mammals, such as apes, dogs, cats, rats or mice, and can be used in the therapeutic treatment of the human or animal body and in the combating of the above-mentioned diseases. They can furthermore be used as diagnostic agents or as reagents. Furthermore, compounds according to the invention can be used for the isolation and investigation of the activity or expression of cathepsin D. In addition, they are particularly suitable for use in diagnostic methods for diseases in connection with disturbed cathepsin D activity. The invention therefore furthermore relates to the use of the compounds according to the invention for the isolation and investigation of the activity or expression of cathepsin D or as binders and inhibitors of cathepsin D. 
     For diagnostic purposes, the compounds according to the invention can, for example, be radioactively labelled. Examples of radioactive labels are  3 H,  14 C,  231 I and  125 I. A preferred labelling method is the iodogen method (Fraker et al., 1978). In addition, the compounds according to the invention can be labelled by enzymes, fluorophores and chemophores. Examples of enzymes are alkaline phosphatase, β-galactosidase and glucose oxidase, an example of a fluorophore is fluorescein, an example of a chemophore is luminol, and automated detection systems, for example for fluorescent colorations, are described, for example, in U.S. Pat. No. 4,125,828 and U.S. Pat. No. 4,207,554. 
     The compounds of the formula I can be used for the preparation of pharmaceutical preparations, in particular by non-chemical methods. In this case, they are brought into a suitable dosage form together with at least one solid, liquid and/or semi-liquid excipient or adjuvant and optionally in combination with one or more further active compound(s). 
     The invention therefore furthermore relates to pharmaceutical preparations comprising at least one compound of the formula I and/or physiologically acceptable salts, derivatives, solvates and stereoisomers thereof, including mixtures thereof in all ratios. In particular, the invention also relates to pharmaceutical preparations which comprise further excipients and/or adjuvants, and also to pharmaceutical preparations which comprise at least one further medicament active compound. 
     In particular, the invention also relates to a process for the preparation of a pharmaceutical preparation, characterised in that a compound of the formula I and/or one of its physiologically acceptable salts, derivatives, solvates and stereoisomers, including mixtures thereof in all ratios, is brought into a suitable dosage form together with a solid, liquid or semi-liquid excipient or adjuvant and optionally with a further medicament active compound. 
     The pharmaceutical preparations according to the invention can be used as medicaments in human or veterinary medicine. The patient or host can belong to any mammal species, for example a primate species, particularly humans; rodents, including mice, rats and hamsters; rabbits; horses, cattle, dogs, cats, etc. Animal models are of interest for experimental investigations, where they provide a model for the treatment of a human disease. 
     Suitable carrier substances are organic or inorganic substances which are suitable for enteral (for example oral), parenteral or topical administration and do not react with the novel compounds, for example water, vegetable oils (such as sunflower oil or cod-liver oil), benzyl alcohols, polyethylene glycols, gelatine, carbohydrates, such as lactose or starch, magnesium stearate, talc, lanolin or Vaseline. Owing to his expert knowledge, the person skilled in the art is familiar with which adjuvants are suitable for the desired medicament formulation. Besides solvents, for example water, physiological saline solution or alcohols, such as, for example, ethanol, propanol or glycerol, sugar solutions, such as glucose or mannitol solutions, or a mixture of the said solvents, gel formers, tablet assistants and other active-ingredient carriers, it is also possible to use, for example, lubricants, stabilisers and/or wetting agents, emulsifiers, salts for influencing the osmotic pressure, antioxidants, dispersants, antifoams, buffer substances, flavours and/or aromas or flavour correctants, preservatives, solubilisers or dyes. If desired, preparations or medicaments according to the invention may comprise one or more further active compounds, for example one or more vitamins. 
     If desired, preparations or medicaments according to the invention may comprise one or more further active compounds and/or one or more action enhancers (adjuvants). 
     The terms “pharmaceutical formulation” and “pharmaceutical preparation” are used as synonyms for the purposes of the present invention. 
     As used here, “pharmaceutically tolerated” relates to medicaments, precipitation reagents, excipients, adjuvants, stabilisers, solvents and other agents which facilitate the administration of the pharmaceutical preparations obtained therefrom to a mammal without undesired physiological side effects, such as, for example, nausea, dizziness, digestion problems or the like. 
     In pharmaceutical preparations for parenteral administration, there is a requirement for isotonicity, euhydration and tolerability and safety of the formulation (low toxicity), of the adjuvants employed and of the primary packaging. Surprisingly, the compounds according to the invention preferably have the advantage that direct use is possible and further purification steps for the removal of toxicologically unacceptable agents, such as, for example, high concentrations of organic solvents or other toxicologically unacceptable adjuvants, are thus unnecessary before use of the compounds according to the invention in pharmaceutical formulations. 
     The invention particularly preferably also relates to pharmaceutical preparations comprising at least one compound according to the invention in precipitated non-crystalline, precipitated crystalline or in dissolved or suspended form, and optionally excipients and/or adjuvants and/or further pharmaceutical active compounds. 
     The compounds according to the invention preferably enable the preparation of highly concentrated formulations without unfavourable, undesired aggregation of the compounds according to the invention occurring. Thus, ready-to-use solutions having a high active-ingredient content can be prepared with the aid of compounds according to the invention with aqueous solvents or in aqueous media. 
     The compounds and/or physiologically acceptable salts and solvates thereof can also be lyophilised and the resultant lyophilisates used, for example, for the preparation of injection preparations. 
     Aqueous preparations can be prepared by dissolving or suspending compounds according to the invention in an aqueous solution and optionally adding adjuvants. To this end, defined volumes of stock solutions comprising the said further adjuvants in defined concentration are advantageously added to a solution or suspension having a defined concentration of compounds according to the invention, and the mixture is optionally diluted with water to the pre-calculated concentration. Alternatively, the adjuvants can be added in solid form. The amounts of stock solutions and/or water which are necessary in each case can subsequently be added to the aqueous solution or suspension obtained. Compounds according to the invention can also advantageously be dissolved or suspended directly in a solution comprising all further adjuvants. 
     The solutions or suspensions comprising compounds according to the invention and having a pH of 4 to 10, preferably having a pH of 5 to 9, and an osmolality of 250 to 350 mOsmol/kg can advantageously be prepared. The pharmaceutical preparation can thus be administered directly substantially without pain intravenously, intra-arterially, intra-articularly, subcutaneously or percutaneously. In addition, the preparation may also be added to infusion solutions, such as, for example, glucose solution, isotonic saline solution or Ringer&#39;s solution, which may also contain further active compounds, thus also enabling relatively large amounts of active compound to be administered. 
     Pharmaceutical preparations according to the invention may also comprise mixtures of a plurality of compounds according to the invention. 
     The preparations according to the invention are physiologically well tolerated, easy to prepare, can be dispensed precisely and are preferably stable with respect to assay, decomposition products and aggregates throughout storage and transport and during multiple freezing and thawing processes. They can preferably be stored in a stable manner over a period of at least three months to two years at refrigerator temperature (2-8° C.) and at room temperature (23-27° C.) and 60% relative atmospheric humidity (R.H.). 
     For example, the compounds according to the invention can be stored in a stable manner by drying and when necessary converted into a ready-to-use pharmaceutical preparation by dissolution or suspension. Possible drying methods are, for example, without being restricted to these examples, nitrogen-gas drying, vacuum-oven drying, lyophilisation, washing with organic solvents and subsequent air drying, liquid-bed drying, fluidised-bed drying, spray drying, roller drying, layer drying, air drying at room temperature and further methods. 
     The term “effective amount” denotes the amount of a medicament or of a pharmaceutical active compound which causes in a tissue, system, animal or human a biological or medical response which is sought or desired, for example, by a researcher or physician. 
     In addition, the term “therapeutically effective amount” denotes an amount which, compared with a corresponding subject who has not received this amount, has the following consequence: improved treatment, healing, prevention or elimination of a disease, syndrome, disease state, complaint, disorder or prevention of side effects or also a reduction in the progress of a disease, complaint or disorder. The term “therapeutically effective amount” also encompasses the amounts which are effective for increasing normal physiological function. 
     On use of preparations or medicaments according to the invention, the compounds according to the invention and/or physiologically acceptable salts and solvates thereof are generally used analogously to known, commercially available preparations or preparations, preferably in dosages of between 0.1 and 500 mg, in particular 5 and 300 mg, per use unit. The daily dose is preferably between 0.001 and 250 mg/kg, in particular 0.01 and 100 mg/kg, of body weight. The preparation can be administered one or more times per day, for example two, three or four times per day. 
     However, the individual dose for a patient depends on a large number of individual factors, such as, for example, on the efficacy of the particular compound used, on the age, body weight, general state of health, sex, nutrition, on the time and method of administration, on the excretion rate, on the combination with other medicaments and on the severity and duration of the particular disease. 
     A measure of the uptake of a medicament active compound in an organism is its bioavailability. If the medicament active compound is delivered to the organism intravenously in the form of an injection solution, its absolute bioavailability, i.e. the proportion of the pharmaceutical which reaches the systemic blood, i.e. the major circulation, in unchanged form, is 100%. In the case of oral administration of a therapeutic active compound, the active compound is generally in the form of a solid in the formulation and must therefore first be dissolved in order that it is able to overcome the entry barriers, for example the gastrointestinal tract, the oral mucous membrane, nasal membranes or the skin, in particular the stratum corneum, or can be absorbed by the body. Data on the pharmacokinetics, i.e. on the bioavailability, can be obtained analogously to the method of J. Shaffer et al., J. Pharm. Sciences, 88 (1999), 313-318. 
     Furthermore, medicaments of this type can be prepared by means of one of the processes generally known in the pharmaceutical art. 
     Medicaments can be adapted for administration via any desired suitable route, for example by the oral (including buccal or sublingual), rectal, pulmonary, nasal, topical (including buccal, sublingual or transdermal), vaginal or parenteral (including subcutaneous, intramuscular, intravenous, intradermal and in particular intra-articular) routes. Medicaments of this type can be prepared by means of all processes known in the pharmaceutical art by, for example, combining the active compound with the excipient(s) or adjuvant(s). 
     Parenteral administration is preferably suitable for administration of the medicaments according to the invention. In the case of parenteral administration, intra-articular administration is particularly preferred. 
     The invention thus preferably also relates to the use of a pharmaceutical preparation according to the invention for intra-articular administration in the treatment and/or prophylaxis of physiological and/or pathophysiological states selected from the group consisting of arthrosis, traumatic cartilage injuries, arthritis, pain, allodynia or hyperalgesia. 
     Intra-articular administration has the advantage that the compound according to the invention can be administered directly into the synovial fluid in the vicinity of the joint cartilage and is also able to diffuse from there into the cartilage tissue. Pharmaceutical preparations according to the invention can thus also be injected directly into the joint gap and thus develop their action directly at the site of action as intended. The compounds according to the invention are also suitable for the preparation of medicaments to be administered parenterally having slow, sustained and/or controlled release of active compound. They are thus also suitable for the preparation of delayed-release formulations, which are advantageous for the patient since administration is only necessary at relatively large time intervals. 
     The medicaments adapted to parenteral administration include aqueous and non-aqueous sterile injection solutions comprising antioxidants, buff-ers, bacteriostatics and solutes, by means of which the formulation is rendered isotonic with the blood or synovial fluid of the recipient to be treated; as well as aqueous and non-aqueous sterile suspensions, which can comprise suspension media and thickeners. The formulations can be delivered in single-dose or multi-dose containers, for example sealed ampoules and vials, and stored in the freeze-dried (lyophilised) state, so that only the addition of the sterile carrier liquid, for example water for injection purposes, immediately before use is necessary. Injection solutions and suspensions prepared in accordance with the formulation can be prepared from sterile powders, granules and tablets. 
     The compounds according to the invention can also be administered in the form of liposome delivery systems, such as, for example, small unilamellar vesicles, large unilamellar vesicles and multilamellar vesicles. Liposomes can be formed from various phospholipids, such as, for example, cholesterol, stearylamine or phosphatidylcholines. 
     The compounds according to the invention can also be coupled to soluble polymers as targeted medicament excipients. Such polymers can encompass polyvinylpyrrolidone, pyran copolymer, polyhydroxypropylmethacrylamidophenol, polyhydroxyethylaspartamidophenol or polyethylene oxide polylysine, substituted by palmitoyl radicals. The compounds according to the invention can furthermore be coupled to a class of biodegradable polymers which are suitable for achieving slow release of a medicament, for example polylactic acid, poly-epsilon-caprolactone, polyhydroxybutyric acid, polyorthoesters, polyacetals, polydihydroxypyrans, polycyanoacrylates, polylactic-co-glycolic acid, polymers, such as conjugates between dextran and methacrylates, polyphosphoesters, various polysaccharides and polyamines and poly-ε-caprolactone, albumin, chitosan, collagen or modified gelatine and crosslinked or amphipathic block copolymers of hydrogels. 
     Suitable for enteral administration (oral or rectal) are, in particular, tablets, dragees, capsules, syrups, juices, drops or suppositories, and suitable for topical use are ointments, creams, pastes, lotions, gels, sprays, foams, aerosols, solutions (for example solutions in alcohols, such as ethanol or isopropanol, acetonitrile, DMF, dimethylacetamide, 1,2-propanediol or mixtures thereof with one another and/or with water) or powders. Also particularly suitable for topical uses are liposomal preparations. 
     In the case of formulation to give an ointment, the active compound can be employed either with a paraffinic or a water-miscible cream base. Alternatively, the active compound can be formulated to a cream with an oil-in-water cream base or a water-in-oil base. 
     Medicaments adapted to transdermal administration can be delivered as independent plasters for extended, close contact with the epidermis of the recipient. Thus, for example, the active compound can be supplied from the plaster by means of iontophoresis, as described in general terms in Pharmaceutical Research, 3(6), 318 (1986). 
     It goes without saying that, besides the constituents particularly mentioned above, the medicaments according to the invention may also comprise other agents usual in the art with respect to the particular type of pharmaceutical formulation. 
     The invention also relates to a set (kit) consisting of separate packs of
     a) an effective amount of a compound of the formula I and/or physiologically acceptable salts, derivatives, solvates, prodrugs and stereoisomers thereof, including mixtures thereof in all ratios, and   b) an effective amount of a further medicament active compound.   

     The set comprises suitable containers, such as boxes or cartons, individual bottles, bags or ampoules. The set may, for example, comprise separate ampoules each containing an effective amount of a compound of the formula I and/or pharmaceutically acceptable salts, derivatives, solvates, prodrugs and stereoisomers thereof, including mixtures thereof in all ratios, and an effective amount of a further medicament active compound in dissolved or lyophilised form. 
     Furthermore, the medicaments according to the invention can be used in order to provide additive or synergistic effects in certain known therapies and/or can be used in order to restore the efficacy of certain existing therapies. 
     Besides the compounds according to the invention, the pharmaceutical preparations according to the invention may also comprise further medicament active compounds, for example for use in the treatment of arthrosis, other cathepsin D inhibitors, NSAIDS, Cox-2 inhibitors, glucocorticoids, hyaluronic acid, azathioprine, methotrexate, anti-CAM antibodies, such as, for example, anti-ICAM-1 antibody, FGF-18. For the treatment of the other diseases mentioned, the pharmaceutical preparations according to the invention may also, besides the compounds according to the invention, comprise further medicament active compounds which are known to the person skilled in the art in the treatment thereof. 
     The cancer treatment disclosed here can be carried out as therapy with a compound of the present invention or in combination with an operation, irradiation or chemoherapy. Chemotherapy of this type can include the use of one or more active compounds of the following categories of antitumour active compounds: 
     (i) antiproliferative/antineoplastic/DNA-damaging active compounds and combinations thereof, as used in medical oncology, such as alkylating active compounds (for example cis-platin, parboplatin, cyclophosphamide, nitrogen mustard, melphalan, chlorambucil, busulphan and nitrosoureas); antimetabolites (for example antifolates such as fluoropyrimidines such as 5-fluorouracil and tegafur, raltitrexed, methotrexate, cytosine arabinoside, hydroxyurea and gemcitabine); antitumour antibiotics (for example anthra-cyclines, such as adriamycin, bleomycin, doxorubicin, daunomycin, epi-rubicin, idarubicin, mitomycin-C, dactinomycin and mithramycin); antimitotic active compounds (for example vinca alkaloids, such as vincristine, vinblastine, vindesine and vinorelbine, and taxoids, such as taxol and taxotere); topoisomerase inhibitors (for example epipodophyllotoxins, such as etoposide and teniposide, amsacrine, topotecan, irinotecan and camptothecin) and cell-differentiating active compounds (for example all-trans-retinoic acid, 13-cis-retinoic acid and fenretinide);
 
(ii) cytostatic active compounds, such as anti-oestrogens (for example tamoxifen, toremifene, raloxifene, droloxifene and iodoxyfene), oestrogen receptor regulators (for example fulvestrant), anti-androgens (for example bicalutamide, flutamide, nilutamide and cyproterone acetate), LHRH antagonists or LHRH agonists (for example goserelin, leuprorelin and buserelin), progesterones (for example megestrol acetate), aromatase inhibitors (for example anastrozole, letrozole, vorazole and exemestane) and inhibitors of 5α-reductase, such as finasteride;
 
(iii) active compounds which inhibit cancer invasion (for example metalloproteinase inhibitors, like marimastat, and inhibitors of urokinase plasminogen activator receptor function);
 
(iv) inhibitors of growth factor function, for example growth factor antibodies, growth factor receptor antibodies, for example the anti-erbb2 antibody trastuzumab [Herceptin™] and the anti-erbbl antibody cetuximab [C225]), farnesyl transferase inhibitors, tyrosine kinase inhibitors and serine/threonine kinase inhibitors, for example inhibitors of the epidermal growth factor family (for example EGFR family tyrosine kinase inhibitors, such as N-(3-chloro-4-fluorophenyl)-7-methoxy-6-(3-morpholinopropoxy) quinazolin-4-amine (gefitinib, AZD1839), N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)quinazolin-4-amine (erlotinib, OSI-774) and 6-acrylamido-N-(3-chloro-4-fluorophenyl)-7-(3-morpholinopropoxy)quinazolin-4-amine (Cl 1033), for example inhibitors of the platelet-derived growth factor family and, for example, inhibitors of the hepatocyte growth factor family;
 
(v) anti-angiogenic active compounds, such as those which inhibit the effects of vascular endothelial growth factor (for example the anti-vascular endothelial cell growth factor antibody bevacizumab [Avastin™], compounds which have been published in the international patent applications WO 97/22596, WO 97/30035, WO 97/32856 and WO 98/13354) and compounds which act by another mechanism (for example linomide, inhibitors of integrin αvβ3 function and angiostatin);
 
(vi) vessel-destroying agents, such as combretastatin A4 and compounds which have been published in the international patent applications WO 99/02166, WO 00/40529, WO 00/41669, WO 01/92224, WO 02/04434 and WO 02/08213;
 
(vii) antisense therapies, for example those directed to the targets mentioned above, such as ISIS 2503, an anti-Ras antisense;
 
(viii) gene therapy approaches, including, for example, approaches for replacement of abnormal, modified genes, such as abnormal p53 or abnormal BRCA1 or BRCA2, GDEPT approaches (gene-directed enzyme pro-drug therapy), such as those which use cytosine deaminase, thymidine kinase or a bacterial nitroreductase enzyme, and approaches which increase the tolerance of a patient to chemotherapy or radiotherapy, such as multi-drug resistance therapy; and
 
(ix) immunotherapy approaches, including, for example, ex-vivo and in-vivo approaches for increasing the immunogenicity of tumour cells of a patient, such as transfection with cytokines, such as interleukin 2, interleukin 4 or granulocyte macrophage colony stimulating factor, approaches for decreasing T-cell anergy, approaches using transfected immune cells, such as cytokine-transfected dendritic cells, approaches for use of cytokine-transfected tumour cells and approaches for use of anti-idiotypic antibodies.
 
     The medicaments from Table 1 can preferably, but not exclusively, be combined with the compounds of the formula 1. 
     
       
         
           
               
               
               
             
               
                 TABLE 1 
               
               
                   
               
             
            
               
                 Alkylating active 
                 Cyclophosphamide 
                 Lomustine 
               
               
                 compounds 
                 Busulfan 
                 Procarbazine 
               
               
                   
                 Ifosfamide 
                 Altretamine 
               
               
                   
                 Melphalan 
                 Estramustine phosphate 
               
               
                   
                 Hexamethylmelamine 
                 Mechloroethamine 
               
               
                   
                 Thiotepa 
                 Streptozocin 
               
               
                   
                 chloroambucil 
                 Temozolomide 
               
               
                   
                 Dacarbazine 
                 Semustine 
               
               
                   
                 Carmustine 
                   
               
               
                 Platinum active 
                 Cisplatin 
                 Carboplatin 
               
               
                 compounds 
                 Oxaliplatin 
                 ZD-0473 (AnorMED) 
               
               
                   
                 Spiroplatin 
                 Lobaplatin (Aetema) 
               
               
                   
                 Carboxyphthalatoplatinum 
                 Satraplatin (Johnson 
               
               
                   
                 Tetraplatin 
                 Matthey) 
               
               
                   
                 Ormiplatin 
                 BBR-3464 
               
               
                   
                 Iproplatin 
                 (Hoffrnann-La Roche) 
               
               
                   
                   
                 SM-11355 (Sumitomo) 
               
               
                   
                   
                 AP-5280 (Access) 
               
               
                 Antimetabolites 
                 Azacytidine 
                 Tomudex 
               
               
                   
                 Gemcitabine 
                 Trimetrexate 
               
               
                   
                 Capecitabine 
                 Deoxycoformycin 
               
               
                   
                 5-Fluorouracil 
                 Fludarabine 
               
               
                   
                 Floxuridine 
                 Pentostatin 
               
               
                   
                 2-Chlorodesoxyadenosine 
                 Raltitrexed 
               
               
                   
                 6-Mercaptopurine 
                 Hydroxyurea 
               
               
                   
                 6-Thioguanine 
                 Decitabine (SuperGen) 
               
               
                   
                 Cytarabine 
                 Clofarabine (Bioenvision) 
               
               
                   
                 2-Fluorodesoxycytidine 
                 Irofulven (MGI Pharrna) 
               
               
                   
                 Methotrexate 
                 DMDC (Hoffmann-La Roche) 
               
               
                   
                 Idatrexate 
                 Ethynylcytidine (Taiho) 
               
               
                 Topoisomerase 
                 Amsacrine 
                 Rubitecan (SuperGen) 
               
               
                 inhibitors 
                 Epirubicin 
                 Exatecan mesylate (Daiichi) 
               
               
                   
                 Etoposide 
                 Quinamed (ChemGenex) 
               
               
                   
                 Teniposide or mitoxantrone 
                 Gimatecan (Sigma-Tau) 
               
               
                   
                 Irinotecan (CPT-11) 
                 Diflomotecan (Beaufour- 
               
               
                   
                 7-ethyl-10- 
                 Ipsen) 
               
               
                   
                 hydroxycamptothecin 
                 TAS-103 (Taiho) 
               
               
                   
                 Topotecan 
                 Elsamitrucin (Spectrum) 
               
               
                   
                 Dexrazoxanet (TopoTarget) 
                 J-107088 (Merck &amp; Co) 
               
               
                   
                 Pixantrone (Novuspharrna) 
                 BNP-1350 (BioNumerik) 
               
               
                   
                 Rebeccamycin analogue 
                 CKD-602 (Chong Kun Dang) 
               
               
                   
                 (Exelixis) 
                 KW-2170 (Kyowa Hakko) 
               
               
                   
                 BBR-3576 (Novuspharrna) 
                   
               
               
                 Antitumour 
                 Dactinomycin (Actinomycin 
                 Amonafide 
               
               
                 antibiotics 
                 D) 
                 Azonafide 
               
               
                   
                 Doxorubicin (Adriamycin) 
                 Anthrapyrazole 
               
               
                   
                 Deoxyrubicin 
                 Oxantrazole 
               
               
                   
                 Valrubicin 
                 Losoxantrone 
               
               
                   
                 Daunorubicin (Daunomycin) 
                 Bleomycin sulfate 
               
               
                   
                 Epirubicin 
                 (Blenoxan) 
               
               
                   
                 Therarubicin 
                 Bleomycinic acid 
               
               
                   
                 Idarubicin 
                 Bleomycin A 
               
               
                   
                 Rubidazon 
                 Bleomycin B 
               
               
                   
                 Plicamycinp 
                 Mitomycin C 
               
               
                   
                 Porfiromycin 
                 MEN-10755 (Menarini) 
               
               
                   
                 Cyanomorpholinodoxorubicin 
                 GPX-100 (Gem 
               
               
                   
                 Mitoxantron (Novantron) 
                 Pharmaceuticals) 
               
               
                 Antimitotic active 
                 Paclitaxel 
                 SB 408075 
               
               
                 compounds 
                 Docetaxel 
                 (GlaxoSmithKline) 
               
               
                   
                 Colchicine 
                 E7010 (Abbott) 
               
               
                   
                 Vinblastine 
                 PG-TXL (Cell Therapeutics) 
               
               
                   
                 Vincristine 
                 IDN 5109 (Bayer) 
               
               
                   
                 Vinorelbine 
                 A 105972 (Abbott) 
               
               
                   
                 Vindesine 
                 A 204197 (Abbott) 
               
               
                   
                 Dolastatin 10 (NCI) 
                 LU 223651 (BASF) 
               
               
                   
                 Rhizoxin (Fujisawa) 
                 D 24851 (ASTA Medica) 
               
               
                   
                 Mivobulin (Warner-Lambert) 
                 ER-86526 (Eisai) 
               
               
                   
                 Cemadotin (BASF) 
                 Combretastatin A4 (BMS) 
               
               
                   
                 RPR 109881A (Aventis) 
                 Isohomohalichondrin-B 
               
               
                   
                 TXD 258 (Aventis) 
                 (PharmaMar) 
               
               
                   
                 Epothilone B (Novartis) 
                 ZD 6126 (AstraZeneca) 
               
               
                   
                 T 900607 (Tularik) 
                 PEG-Paclitaxel (Enzon) 
               
               
                   
                 T 138067 (Tularik) 
                 AZ10992 (Asahi) 
               
               
                   
                 Cryptophycin 52 (Eli Lilly) 
                 !DN-5109 (Indena) 
               
               
                   
                 Vinflunine (Fabre) 
                 AVLB (Prescient 
               
               
                   
                 Auristatin PE (Teikoku 
                 NeuroPharma) 
               
               
                   
                 Hormone) 
                 Azaepothilon B (BMS) 
               
               
                   
                 BMS 247550 (BMS) 
                 BNP-7787 (BioNumerik) 
               
               
                   
                 BMS 184476 (BMS) 
                 CA-4-prodrug (OXiGENE) 
               
               
                   
                 BMS 188797 (BMS) 
                 Dolastatin-10 (NrH) 
               
               
                   
                 Taxoprexin (Protarga) 
                 CA-4 (OXiGENE) 
               
               
                 Aromatase 
                 Aminoglutethimide 
                 Exemestan 
               
               
                 inhibitors 
                 Letrozole 
                 Atamestan (BioMedicines) 
               
               
                   
                 Anastrazole 
                 YM-511 (Yamanouchi) 
               
               
                   
                 Formestan 
                   
               
               
                 Thymidylate 
                 Pemetrexed (Eli Lilly) 
                 Nolatrexed (Eximias) 
               
               
                 Synthase 
                 ZD-9331 (BTG) 
                 CoFactor ™ (BioKeys) 
               
               
                 inhibitors 
                   
                   
               
               
                 DNA antagonists 
                 Trabectedin (PharmaMar) 
                 Mafosfamide (Baxter 
               
               
                   
                 Glufosfamide (Baxter 
                 International) 
               
               
                   
                 International) 
                 Apaziquone (Spectrum 
               
               
                   
                 Albumin + 32P 
                 Pharmaceuticals) 
               
               
                   
                 (isotope solutions) 
                 O6-benzylguanine 
               
               
                   
                 Thymectacin (NewBiotics) 
                 (Paligent) 
               
               
                   
                 Edotreotid (Novartis) 
                   
               
               
                 Farnesyl transferas 
                 Arglabin (NuOncology Labs) 
                 Tipifarnib (Johnson &amp; 
               
               
                 inhibitors 
                 Lonafarnib (Schering-Plough 
                 Johnson) 
               
               
                   
                 BAY-43-9006 (Bayer) 
                 Perillyl alcohol (DOR 
               
               
                   
                   
                 BioPharma) 
               
               
                 Pump inhibitors 
                 CBT-1 (CBA Pharma) 
                 Zosuquidar trihydrochloride 
               
               
                   
                 Tariquidar (Xenova) 
                 (Eli Lilly) 
               
               
                   
                 MS-209 (Schering AG) 
                 Biricodar dicitrate (Vertex) 
               
               
                 Histone acetyl transferase 
                 Tacedinaline (Pfizer) 
                 Pivaloyloxymethyl butyrate 
               
               
                 inhibitors 
                 SAHA (Aton Pharma) 
                 (Titan) 
               
               
                   
                 MS-275 (Schering AG) 
                 Depsipeptide (Fujisawa) 
               
               
                 Metalloproteinase 
                 Neovastat (Aeterna 
                 CMT-3 (CollaGenex) 
               
               
                 inhibitors 
                 Laboratories) 
                 BMS-275291 (Celltech) 
               
               
                 Ribonucleoside 
                 Marimastat (British Biotech) 
                 Tezacitabine (Aventis) 
               
               
                 reductase 
                 Gallium maltolate (Titan) 
                 Didox (Molecules for 
               
               
                 inhibitors 
                 Triapin (Vion) 
                 Health) 
               
               
                 TNF-alpha 
                 Virulizin (Lorus Therapeutics 
                 Revimid (Celgene) 
               
               
                 agonists/ 
                 CDC-394 (Celgene) 
                   
               
               
                 antagonists 
                   
                   
               
               
                 Endothelin-A receptor 
                 Atrasentan (Abbot) 
                 YM-598 (Yamanouchi) 
               
               
                 antagonists 
                 ZD-4054 (AstraZeneca) 
                   
               
               
                 Retinoic acid 
                 Fenretinide (Johnson &amp; 
                 Alitretinoin (Ligand) 
               
               
                 receptor agonists 
                 Johnson) 
                   
               
               
                   
                 LGD-1550 (ligand) 
                   
               
               
                 Immunomodulators 
                 Interferon 
                 Dexosome therapy (Anosys 
               
               
                   
                 Oncophage (Antigenics) 
                 Pentrix (Australian Cancer 
               
               
                   
                 GMK (Progenics) 
                 Technology) 
               
               
                   
                 Adenocarcinoma vaccine 
                 JSF-154 (Tragen) 
               
               
                   
                 (Biomira) 
                 Cancer vaccine (Intercell) 
               
               
                   
                 CTP-37 (AVI BioPharma) 
                 Norelin (Biostar) 
               
               
                   
                 JRX-2 (Immuno-Rx) 
                 BLP-25 (Biomira) 
               
               
                   
                 PEP-005 (Peplin Biotech) 
                 MGV (Progenics) 
               
               
                   
                 Synchrovax vaccines (CTL 
                 !3-Alethin (Dovetail) 
               
               
                   
                 Immuno) 
                 CLL-Thera (Vasogen) 
               
               
                   
                 Melanoma vaccines (CTL 
                   
               
               
                   
                 Immuno) 
                   
               
               
                   
                 p21-RAS vaccine (GemVax) 
                   
               
               
                 Hormonal and 
                 Oestrogens 
                 Prednisone 
               
               
                 antihormonal 
                 Conjugated oestrogens 
                 Methylprednisolone 
               
               
                 active compounds 
                 Ethynyloestradiol 
                 Prednisolone 
               
               
                   
                 Chlorotrianisene 
                 Aminoglutethimide 
               
               
                   
                 Idenestrol 
                 Leuprolide 
               
               
                   
                 Hydroxyprogesterone 
                 Goserelin 
               
               
                   
                 caproate 
                 Leuporelin 
               
               
                   
                 Medroxyprogesterone 
                 Bicalutamide 
               
               
                   
                 Testosterone 
                 Flutamide 
               
               
                   
                 Testosterone propionate 
                 Octreotide 
               
               
                   
                 Fluoxymesterone 
                 Nilutamide 
               
               
                   
                 Methyltestosterone 
                 Mitotan 
               
               
                   
                 Diethylstilbestrol 
                 P-04 (Novogen) 
               
               
                   
                 Megestrol 
                 2-Methoxyoestradiol  
               
               
                   
                 Tamoxifen 
                 (En_treMed) 
               
               
                   
                 Toremofin 
                 Arzoxifen (Eli Lilly) 
               
               
                   
                 Dexamethasone 
                   
               
               
                 Photodynamic 
                 Talaporfin (Light Sciences) 
                 Pd bacteriopheophorbide 
               
               
                 active compounds 
                 Theralux (Theratechnologies 
                 (Yeda) 
               
               
                   
                 Motexafin-Gadolinium 
                 Lutetium texaphyrin 
               
               
                   
                 (Pharmacyclics) 
                 (Pharmacyclics) 
               
               
                   
                   
                 Hypericin 
               
               
                 Tyrosine kinase 
                 Imatinib (Novartis) 
                 Kahalide F (PharmaMar) 
               
               
                 inhibitors 
                 Leflunomide(Sugen/Pharmacia) 
                 CEP-701 (Cephalon) 
               
               
                   
                 ZDI839 (AstraZeneca) 
                 CEP-751 (Cephalon) 
               
               
                   
                 Erlotinib (Oncogene Science 
                 MLN518 (Millenium) 
               
               
                   
                 Canertjnib (Pfizer) 
                 PKC412 (Novartis) 
               
               
                   
                 Squalamine (Genaera) 
                 Phenoxodiol O 
               
               
                   
                 SU5416 (Pharmacia) 
                 Trastuzumab (Genentech) 
               
               
                   
                 SU6668 (Pharmacia) 
                 C225 (ImClone) 
               
               
                   
                 ZD4190 (AstraZeneca) 
                 rhu-Mab (Genentech) 
               
               
                   
                 ZD6474 (AstraZeneca) 
                 MDX-H210 (Medarex) 
               
               
                   
                 Vatalanib (Novartis) 
                 2C4 (Genentech) 
               
               
                   
                 PKI166 (Novartis) 
                 MDX-447 (Medarex) 
               
               
                   
                 GW2016 (GlaxoSmithKline) 
                 ABX-EGF (Abgenix) 
               
               
                   
                 EKB-509 (Wyeth) 
                 IMC-1C11 (ImClone) 
               
               
                   
                 EKB-569 (Wyeth) 
                   
               
               
                 Various other 
                 SR-27897 (CCK-A inhibitor, 
                 BCX-1777 (PNP inhibitor, 
               
               
                 active compounds 
                 Sanofi-Synthelabo) 
                 BioCryst) 
               
               
                   
                 Tocladesine (cyclic AMP 
                 Ranpirnase (ribonuclease 
               
               
                   
                 agonist, Ribapharm) 
                 stimulant, Alfacell) 
               
               
                   
                 Alvocidib (CDK inhibitor, 
                 Galarubicin (RNA synthesis 
               
               
                   
                 Aventis) 
                 inhibitor, Dong-A) 
               
               
                   
                 CV-247 (COX-2 inhibitor, Ivy 
                 Tirapazamine (reducing 
               
               
                   
                 Medical) 
                 agent, SRI International) 
               
               
                   
                 P54 (COX-2 inhibitor, 
                 N-Acetylcysteine 
               
               
                   
                 Phytopharm) 
                 (reducing agent, 
               
               
                   
                 CapCell ™ (CYP450 
                 Zambon) 
               
               
                   
                 stimulant, Bavarian Nordic) 
                 R-Flurbiprofen (NF-kappaB 
               
               
                   
                 GCS-IOO (gal3 antagonist, 
                 inhibitor, Encore) 
               
               
                   
                 GlycoGenesys) 
                 3CPA (NF-kappaB 
               
               
                   
                 G17DT immunogen (gastrin 
                 inhibitor, Active Biotech) 
               
               
                   
                 inhibitor, Aphton) 
                 Seocalcitol (vitamin D 
               
               
                   
                 Efaproxiral (oxygenator, 
                 receptor agonist, Leo) 
               
               
                   
                 Allos Therapeutics) 
                 131-I-TM-601 (DNA 
               
               
                   
                 PI-88 (heparanase inhibitor, 
                 antagonist, 
               
               
                   
                 Progen) 
                 TransMolecular) 
               
               
                   
                 Tesmilifen (histamine 
                 Eflornithin (ODC inhibitor, 
               
               
                   
                 antagonist, YM 
                 ILEX Oncology) 
               
               
                   
                 BioSciences) 
                 Minodronic acid 
               
               
                   
                 Histamine (histamine H2 
                 (osteoclast inhibitor, 
               
               
                   
                 receptor agonist, Maxim) 
                 Yamanouchi) 
               
               
                   
                 Tiazofurin (IMPDH inhibitor, 
                 Indisulam (p53 stimulant, 
               
               
                   
                 Ribapharm) 
                 Eisai) 
               
               
                   
                 Cilengitide (integrin 
                 Aplidin (PPT inhibitor, 
               
               
                   
                 antagonist, 
                 PharmaMar) 
               
               
                   
                 Merck KGaA) 
                 Rituximab (CD20 antibody, 
               
               
                   
                 SR-31747 (IL-1 antagonist, 
                 Genentech) 
               
               
                   
                 Sanofi-Synthelabo) 
                 Gemtuzumab (CD33 
               
               
                   
                 CCI-779 (mTOR kinase 
                 antibody, Wyeth Ayerst) 
               
               
                   
                 inhibitor, Wyeth) 
                 PG2 (haematopoiesis 
               
               
                   
                 Exisulind (PDE-V inhibitor, 
                 promoter, Pharmagenesis) 
               
               
                   
                 Cell Pathways) 
                 Immunol ™ (triclosan 
               
               
                   
                 CP-461 (PDE-V inhibitor, 
                 mouthwash, Endo) 
               
               
                   
                 Cell Pathways) 
                 Triacetyluridine (uridine 
               
               
                   
                 AG-2037 (GART inhibitor, 
                 prodrug, Wellstat) 
               
               
                   
                 Pfizer) 
                 SN-4071 (sarcoma agent, 
               
               
                   
                 WX-UK1 (plasminogen 
                 Signature BioScience) 
               
               
                   
                 activator inhibitor, Wilex) 
                 TransMID-107 ™ 
               
               
                   
                 PBI-1402 (PMN stimulant, 
                 (immunotoxin, KS 
               
               
                   
                 ProMetic LifeSciences) 
                 Biomedix) 
               
               
                   
                 Bortezomib (proteasome 
                 PCK-3145 (apoptosis promoter, 
               
               
                   
                 inhibitor, Millennium) 
                 Procyon) 
               
               
                   
                 SRL-172 (T-cell stimulant, 
                 Doranidazole (apoptosis 
               
               
                   
                 SR Pharma) 
                 promoter, Pola) 
               
               
                   
                 TLK-286 (glutathione-S 
                 CHS-828 (cytotoxic agent, 
               
               
                   
                 transferase inhibitor, Telik) 
                 Leo) 
               
               
                   
                 PT-100 (growth factor 
                 trans-Retinoic acid 
               
               
                   
                 agonist, Point Therapeutics) 
                 (differentiator, NIH) 
               
               
                   
                 Midostaurin (PKC inhibitor, 
                 MX6 (apoptosis promoter, 
               
               
                   
                 Novartis) 
                 MAXIA) 
               
               
                   
                 Bryostatin-1 (PKC stimulant, 
                 Apomine (apoptosis 
               
               
                   
                 GPC Biotech) 
                 promoter, ILEX Oncology) 
               
               
                   
                 CDA-II (apoptosis promoter, 
                 Urocidin (apoptosis 
               
               
                   
                 Everlife) 
                 promoter, Bioniche) 
               
               
                   
                 SDX-101 (apoptosis promoter, 
                 Ro-31-7453 (apoptosis 
               
               
                   
                 Salmedix) 
                 promoter, La Roche) 
               
               
                   
                 Ceflatonin (apoptosis promoter, 
                 Brostallicin (apoptosis 
               
               
                   
                 ChemGenex) 
                 promoter, Pharmacia) 
               
               
                   
               
            
           
         
       
     
     Even without further embodiments, it is assumed that a person skilled in the art will be able to use the above description in the broadest scope. The preferred embodiments should therefore merely be regarded as descriptive disclosure which is absolutely not limiting in any way. 
     The following examples are thus intended to explain the invention without limiting it. Unless indicated otherwise, percent data denote percent by weight. All temperatures are indicated in degrees Celsius. “Conventional work-up”: water is added if necessary, the pH is adjusted, if necessary, to values between 2 and 10, depending on the constitution of the end product, the mixture is extracted with ethyl acetate or dichloromethane, the phases are separated, the organic phase is dried over sodium sulfate, filtered and evaporated, and the product is purified by chromatography on silica gel and/or by crystallisation. 
     Rf values on silica gel; mass spectrometry: EI (electron impact ionisation): M + , FAB (fast atom bombardment): (M+H) + , THF (tetrahydrofuran), NMP (N-methlpyrrolidone), DMSO (dimethyl sulfoxide), EA (ethyl acetate), MeOH (methanol), TLC (thin-layer chromatography) 
     The following substances have been synthesised and characterised. However, the preparation and characterisation of the substances can also be carried out by other methods for the person skilled in the art. 
    
    
     EXAMPLE 1 
     Illustrative Compounds of the Formula I 
     
       
         
           
               
               
               
               
             
               
                 TABLE 2 
               
               
                   
               
               
                 Compound 
                   
                 CathD 
                 LC/MS 
               
               
                 No. 
                 Structure 
                 IC 50  nM 
                 (M + H) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
            
               
                 1 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 300 
                 617 
               
               
                   
               
               
                 2 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 190 
                 505 
               
               
                   
               
               
                 3 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 140 
                 461 
               
               
                   
               
               
                 4 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 110 
                 626 
               
               
                   
               
               
                 5 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3400 
                 588 
               
               
                   
               
               
                 6 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2600 
                 592 
               
               
                   
               
               
                 7 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 3300 
                 626 
               
               
                   
               
               
                 8 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 82 
                 549 
               
               
                   
               
               
                 9 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                 482 
               
               
                   
               
               
                 10 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 580 
                 489 
               
               
                   
               
               
                 11 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 950 
                 523 
               
               
                   
               
               
                 12 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 950 
                 557 
               
               
                   
               
               
                 13 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 180 
                 558 
               
               
                   
               
               
                 14 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                 558 
               
               
                   
               
               
                 15 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 120 
                 628 
               
               
                   
               
               
                 16 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 82 
                 554 
               
               
                   
               
               
                 17 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 730 
                 518 
               
               
                   
               
               
                 18 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 160 
                 565 
               
               
                   
               
               
                 19 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 400 
                 481 
               
               
                   
               
               
                 20 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 270 
                 493 
               
               
                   
               
               
                 21 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 370 
                 511 
               
               
                   
               
               
                 22 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 50 
                 523 
               
               
                   
               
               
                 23 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 260 
                 614 
               
               
                   
               
               
                 24 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                 517 
               
               
                   
               
               
                 25 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 120 
                 541 
               
               
                   
               
               
                 26 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 1400 
                 489 
               
               
                   
               
               
                 27 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 1300 
                 549 
               
               
                   
               
               
                 28 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                 385 
               
               
                   
               
               
                 29 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 1000 
                 543. 
               
               
                   
               
               
                 30 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 1900 
                 476 
               
               
                   
               
               
                 31 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                 476 
               
               
                   
               
               
                 32 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 110 
                 543 
               
               
                   
               
               
                 33 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 170 
                 441 
               
               
                   
               
               
                 34 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 660 
                 455 
               
               
                   
               
               
                 35 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 280 
                 455 
               
               
                   
               
               
                 36 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 230 
                 523 
               
               
                   
               
               
                 37 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 130 
                 549 
               
               
                   
               
               
                 38 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 100 
                 535 
               
               
                   
               
               
                 39 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 170 
                 455 
               
               
                   
               
               
                 40 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 290 
                 427 
               
               
                   
               
               
                 41 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                 469 
               
               
                   
               
               
                 42 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 230 
                 455 
               
               
                   
               
               
                 43 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 31 
                 461 
               
               
                   
               
               
                 44 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 24 
                 489 
               
               
                   
               
               
                 45 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 240 
                 407 
               
               
                   
               
               
                 46 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 26 
                 489 
               
               
                   
               
               
                 47 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 760 
                 533 
               
               
                   
               
               
                 48 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                 490 
               
               
                   
               
               
                 49 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 1500 
                 475 
               
               
                   
               
               
                 50 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 330 
                 531 
               
               
                   
               
               
                 51 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 67 
                 501 
               
               
                   
               
               
                 52 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 140 
                 467 
               
               
                   
               
               
                 53 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 72 
                 447 
               
               
                   
               
               
                 54 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 78 
                 505 
               
               
                   
               
               
                 55 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 400 
                 583 
               
               
                   
               
               
                 56 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 310 
                 583 
               
               
                   
               
               
                 57 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 1900 
                 509 
               
               
                   
               
               
                 58 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 890 
                 481 
               
               
                   
               
               
                 59 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                 520 
               
               
                   
               
               
                 60 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 17 
                 529 
               
               
                   
               
               
                 61 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 74 
                 537 
               
               
                   
               
               
                 62 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 1900 
                 541 
               
               
                   
               
               
                 63 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 260 
                 535 
               
               
                   
               
               
                 64 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 1800 
                 485 
               
               
                   
               
               
                 65 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 1100 
                 485 
               
               
                   
               
               
                 66 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 210 
                 481 
               
               
                   
               
               
                 67 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 150 
                 407 
               
               
                   
               
               
                 68 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 330 
                 421 
               
               
                   
               
               
                 69 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 15 
                 555 
               
               
                   
               
               
                 70 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 86 
                 515 
               
               
                   
               
               
                 71 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 130 
                 549 
               
               
                   
               
               
                 72 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 97 
                 473 
               
               
                   
               
               
                 73 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 210 
                 433 
               
               
                   
               
               
                 74 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 680 
                 469 
               
               
                   
               
               
                 75 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 440 
                 435 
               
               
                   
               
               
                 76 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                 482 
               
               
                   
               
               
                 77 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                 448 
               
               
                   
               
               
                 78 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 700 
                 535 
               
               
                   
               
               
                 79 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 470 
                 523 
               
               
                   
               
               
                 80 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 98 
                 529 
               
               
                   
               
               
                 81 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 180 
                 447 
               
               
                   
               
               
                 82 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 900 
                 439 
               
               
                   
               
               
                 83 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 130 
                 519 
               
               
                   
               
               
                 84 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 420 
                 519 
               
               
                   
               
               
                 85 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 530 
                 445 
               
               
                   
               
               
                 86 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 320 
                 525 
               
               
                   
               
               
                 87 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                 525 
               
               
                   
               
               
                 88 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2400 
                 483 
               
               
                   
               
               
                 89 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 1100 
                 457 
               
               
                   
               
               
                 90 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 1300 
                 487 
               
               
                   
               
               
                 91 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 1700 
                 489 
               
               
                   
               
               
                 92 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 1800 
                 463 
               
               
                   
               
               
                 93 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 57 
                 543 
               
               
                   
               
               
                 94 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 270 
                 513 
               
               
                   
               
               
                 95 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 940 
                 449 
               
               
                   
               
               
                 96 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 490 
                 495 
               
               
                   
               
               
                 97 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2000 
                 471 
               
               
                   
               
               
                 98 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 140 
                 475 
               
               
                   
               
               
                 99 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 8.6 
                 607 
               
               
                   
               
               
                 100 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 570 
                 415 
               
               
                   
               
               
                 101 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 230 
                 483 
               
               
                   
               
               
                 102 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 250 
                 515 
               
               
                   
               
               
                 103 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 59 
                 431 
               
               
                   
               
               
                 104 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 440 
                 519 
               
               
                   
               
               
                 105 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 1300 
                 489 
               
               
                   
               
               
                 106 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 140 
                 413 
               
               
                   
               
               
                 107 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 440 
                 501 
               
               
                   
               
               
                 108 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 110 
                 549 
               
               
                   
               
               
                 109 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 55 
                 526 
               
               
                   
               
               
                 110 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 90 
                 614 
               
               
                   
               
               
                 111 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 380 
                 377 
               
               
                   
               
               
                 112 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 160 
                 459 
               
               
                   
               
               
                 113 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 240 
                 431 
               
               
                   
               
               
                 114 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 110 
                 499 
               
               
                   
               
               
                 115 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2300 
                 475 
               
               
                   
               
               
                 116 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 590 
                 367 
               
               
                   
               
               
                 117 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 310 
                 417 
               
               
                   
               
               
                 118 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 560 
                 393 
               
               
                   
               
               
                 119 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                 455 
               
               
                   
               
               
                 120 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 1300 
                 481 
               
               
                   
               
               
                 121 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 1800 
                 505 
               
               
                   
               
               
                 122 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 1900 
                 475 
               
               
                   
               
               
                 123 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 980 
                 493 
               
               
                   
               
               
                 124 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2000 
                 469 
               
               
                   
               
               
                 125 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2700 
                 411 
               
               
                   
               
               
                 126 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 1500 
                 505 
               
               
                   
               
               
                 127 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                 397 
               
               
                   
               
               
                 128 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 1700 
                 543 
               
               
                   
               
               
                 129 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                 578 
               
               
                   
               
               
                 130 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2200 
                 559 
               
               
                   
               
               
                 131 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                 347 
               
               
                   
               
               
                 132 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                 445 
               
               
                   
               
               
                 133 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                 460 
               
               
                   
               
               
                 134 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                 441 
               
               
                   
               
               
                 135 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 1900 
                 407 
               
               
                   
               
               
                 136 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                 333 
               
               
                   
               
               
                 137 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                 441 
               
               
                   
               
               
                 138 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                 446 
               
               
                   
               
               
                 139 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                 427 
               
               
                   
               
               
                 140 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 210 
                 568 
               
               
                   
               
               
                 141 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 58 
                 535 
               
               
                   
               
               
                 142 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 200 
                 519 
               
               
                   
               
               
                 143 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 280 
                 535 
               
               
                   
               
               
                 144 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 130 
                 554 
               
               
                   
               
               
                 145 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 130 
                 510 
               
               
                   
               
               
                 146 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 120 
                 475 
               
               
                   
               
               
                 147 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 360 
                 524 
               
               
                   
               
               
                 148 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                 659 
               
               
                   
               
               
                 149 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2000 
                 625 
               
               
                   
               
               
                 150 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 480 
                 559 
               
               
                   
               
               
                 151 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                 620 
               
               
                   
               
               
                 152 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 1600 
                 590 
               
               
                   
               
               
                 153 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                 590 
               
               
                   
               
               
                 154 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 390 
                 535 
               
               
                   
               
               
                 155 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 240 
                 523 
               
               
                   
               
               
                 156 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 48 
                 447 
               
               
                   
               
               
                 157 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 46 
                 529 
               
               
                   
               
               
                 158 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                 533 
               
               
                   
               
               
                 159 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 960 
                 445 
               
               
                   
               
               
                 160 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 620 
                 527 
               
               
                   
               
               
                 161 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2100 
                 521 
               
               
                   
               
               
                 162 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 49 
                 560 
               
               
                   
               
               
                 163 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 400 
                 405 
               
               
                   
               
               
                 164 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 270 
                 520 
               
               
                   
               
               
                 165 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                 445 
               
               
                   
               
               
                 166 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                 525 
               
               
                   
               
               
                 167 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                 525 
               
               
                   
               
               
                 168 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                 487 
               
               
                   
               
               
                 169 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                 489 
               
               
                   
               
               
                 170 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                 463 
               
               
                   
               
               
                 171 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                 491 
               
               
                   
               
               
                 172 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                 485 
               
               
                   
               
               
                 173 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                 451 
               
               
                   
               
               
                 174 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                 475 
               
               
                   
               
               
                 175 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                 488 
               
               
                   
               
               
                 176 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                 516 
               
               
                   
               
               
                 177 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                 522 
               
               
                   
               
               
                 178 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                 523 
               
               
                   
               
               
                 179 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                 529 
               
               
                   
               
               
                 180 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                 489 
               
               
                   
               
               
                 181 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                 517 
               
               
                   
               
               
                 182 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                 477 
               
               
                   
               
               
                 183 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                 517 
               
               
                   
               
               
                 184 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                 447 
               
               
                   
               
               
                 185 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                 489 
               
               
                   
               
               
                 186 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                 476 
               
               
                   
               
               
                 187 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                 499 
               
               
                   
               
               
                 188 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                 431 
               
               
                   
               
               
                 189 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                 459 
               
               
                   
               
               
                 190 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                 459 
               
               
                   
               
               
                 191 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                 419 
               
               
                   
               
               
                 192 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 260 
                 407 
               
               
                   
               
               
                 193 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 420 
                 407 
               
               
                   
               
               
                 194 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 650 
                 449 
               
               
                   
               
               
                 195 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 450 
                 449 
               
               
                   
               
               
                 196 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 11 
                 467 
               
               
                   
               
               
                 197 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 450 
                 467 
               
               
                   
               
               
                 198 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 260 
                 497 
               
               
                   
               
               
                 199 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 280 
                 497 
               
               
                   
               
               
                 200 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 370 
                 509 
               
               
                   
               
               
                 201 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 72 
                 557 
               
               
                   
               
               
                 202 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 220 
                 489 
               
               
                   
               
               
                 203 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 110 
                 447 
               
               
                   
               
               
                 204 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 1200 
                 535 
               
               
                   
               
               
                 205 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 610 
                 523 
               
               
                   
               
               
                 206 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                 447 
               
               
                   
               
               
                 207 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 110 
                 529 
               
               
                   
               
               
                 208 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 11 
                 507 
               
               
                   
               
               
                 209 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 320 
                 507 
               
               
                   
               
               
                 210 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 210 
                 537 
               
               
                   
               
               
                 211 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 260 
                 537 
               
               
                   
               
               
                 212 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 92 
                 549 
               
               
                   
               
               
                 213 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 230 
                 511 
               
               
                   
               
               
                 214 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 170 
                 435 
               
               
                   
               
               
                 215 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 63 
                 517 
               
               
                   
               
               
                 216 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 360 
                 511 
               
               
                   
               
               
                 217 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 230 
                 435 
               
               
                   
               
               
                 218 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 120 
                 516 
               
               
                   
               
               
                 219 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 760 
                 471 
               
               
                   
               
               
                 220 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 1100 
                 395 
               
               
                   
               
               
                 221 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 190 
                 477 
               
               
                   
               
               
                 222 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 41 
                 535 
               
               
                   
               
               
                 223 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 91 
                 453 
               
               
                   
               
               
                 224 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                 449 
               
               
                   
               
               
                 225 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                 367 
               
               
                   
               
               
                 226 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 140 
                 475 
               
               
                   
               
               
                 227 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 370 
                 551 
               
               
                   
               
               
                 228 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 250 
                 572 
               
               
                   
               
               
                 229 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 43 
                 496 
               
               
                   
               
               
                 230 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 42 
                 578 
               
               
                   
               
               
                 231 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 1600 
                 549 
               
               
                   
               
               
                 232 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 770 
                 473 
               
               
                   
               
               
                 233 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 450 
                 555 
               
               
                   
               
               
                 234 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 250 
                 548 
               
               
                   
               
               
                 235 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 230 
                 466 
               
               
                   
               
               
                 236 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 970 
                 541 
               
               
                   
               
               
                 237 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                 476 
               
               
                   
               
               
                 238 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 &gt; 
                 394 
               
               
                   
               
               
                 239 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                 541 
               
               
                   
               
               
                 240 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 1300 
                 565 
               
               
                   
               
               
                 241 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 430 
                 553 
               
               
                   
               
               
                 242 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 120 
                 477 
               
               
                   
               
               
                 243 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 66 
                 559 
               
               
                   
               
               
                 244 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 1500 
                 511 
               
               
                   
               
               
                 245 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 900 
                 499 
               
               
                   
               
               
                 246 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 340 
                 423 
               
               
                   
               
               
                 247 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 200 
                 505 
               
               
                   
               
               
                 248 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 120 
                 445 
               
               
                   
               
               
                 249 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 410 
                 405 
               
               
                   
               
               
                 250 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                 498 
               
               
                   
               
               
                 251 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                 422 
               
               
                   
               
               
                 252 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                 504 
               
               
                   
               
               
                 253 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 220 
                 549 
               
               
                   
               
               
                 254 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 460 
                 509 
               
               
                   
               
               
                 255 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 280 
                 567 
               
               
                   
               
               
                 256 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 440 
                 527 
               
               
                   
               
               
                 257 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 280 
                 565 
               
               
                   
               
               
                 258 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 530 
                 525 
               
               
                   
               
               
                 259 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 240 
                 609 
               
               
                   
               
               
                 260 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 320 
                 593 
               
               
                   
               
               
                 261 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 57 
                 523 
               
               
                   
               
               
                 262 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 310 
                 577 
               
               
                   
               
               
                 263 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 230 
                 561 
               
               
                   
               
               
                 264 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 84 
                 555 
               
               
                   
               
               
                 265 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 530 
                 583 
               
               
                   
               
               
                 266 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 620 
                 543 
               
               
                   
               
               
                 267 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 290 
                 585 
               
               
                   
               
               
                 268 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 200 
                 585 
               
               
                   
               
               
                 269 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 240 
                 588 
               
               
                   
               
               
                 270 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 140 
                 628 
               
               
                   
               
               
                 271 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 380 
                 571 
               
               
                   
               
               
                 272 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 44 
                 549 
               
               
                   
               
               
                 273 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 510 
                 509 
               
               
                   
               
               
                 274 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 110 
                 421 
               
               
                   
               
               
                 275 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 51 
                 504 
               
               
                   
               
               
                 276 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 81 
                 567 
               
               
                   
               
               
                 277 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 690 
                 527 
               
               
                   
               
               
                 278 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 74 
                 616 
               
               
                   
               
               
                 279 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                 520 
               
               
                   
               
               
                 280 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                 476 
               
               
                   
               
               
                 281 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 13 
                 560 
               
               
                   
               
               
                 282 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 1400 
                 478 
               
               
                   
               
               
                 283 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 110 
                 548 
               
               
                   
               
               
                 284 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 35 
                 517 
               
               
                   
               
               
                 285 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 80 
                 435 
               
               
                   
               
               
                 286 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 61 
                 551 
               
               
                   
               
               
                 287 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 56 
                 494 
               
               
                   
               
               
                 288 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 20 
                 562 
               
               
                   
               
               
                 289 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 90 
                 539 
               
               
                   
               
               
                 290 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 470 
                 499 
               
               
                   
               
               
                 291 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 350 
                 533 
               
               
                   
               
               
                 292 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 120 
                 563 
               
               
                   
               
               
                 293 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 390 
                 523 
               
               
                   
               
               
                 294 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 24 
                 585 
               
               
                   
               
               
                 295 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 230 
                 470 
               
               
                   
               
               
                 296 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 100 
                 465 
               
               
                   
               
               
                 297 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 240 
                 525 
               
               
                   
               
               
                 298 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 48 
                 535 
               
               
                   
               
               
                 299 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 230 
                 559 
               
               
                   
               
               
                 300 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 780 
                 557 
               
               
                   
               
               
                 301 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 52 
                 537 
               
               
                   
               
               
                 302 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2000 
                 555 
               
               
                   
               
               
                 303 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 490 
                 561 
               
               
                   
               
               
                 304 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 2400 
                 521 
               
               
                   
               
               
                 305 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 830 
                 542 
               
               
                   
               
               
                 306 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 93 
                 548 
               
               
                   
               
               
                 307 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 440 
                 508 
               
               
                   
               
               
                 308 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                 525 
               
               
                   
               
               
                 309 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 700 
                 559 
               
               
                   
               
               
                 310 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 47 
                 565 
               
               
                   
               
               
                 311 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 89 
                 565 
               
               
                   
               
               
                 312 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 380 
                 525 
               
               
                   
               
               
                 313 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 530 
                 559 
               
               
                   
               
               
                 314 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 200 
                 524 
               
               
                   
               
               
                 315 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 45 
                 565 
               
               
                   
               
               
                 316 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 100 
                 561 
               
               
                   
               
               
                 317 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 320 
                 521 
               
               
                   
               
               
                 318 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 400 
                 555 
               
               
                   
               
               
                 319 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 41 
                 561 
               
               
                   
               
               
                 320 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 230 
                 521 
               
               
                   
               
               
                 321 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 240 
                 555 
               
               
                   
               
               
                 322 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 49 
                 522 
               
               
                   
               
               
                 323 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 67 
                 564 
               
               
                   
               
               
                 324 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 220 
                 524 
               
               
                   
               
               
                 325 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 290 
                 558 
               
               
                   
               
               
                 326 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 110 
                 487 
               
               
                   
               
               
                 327 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 47 
                 497 
               
               
                   
               
               
                 328 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 170 
                 583 
               
               
                   
               
               
                 329 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 550 
                 543 
               
               
                   
               
               
                 330 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 630 
                 577 
               
               
                   
               
               
                 331 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 550 
                 507 
               
               
                   
               
               
                 332 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 100 
                 517 
               
               
                   
               
               
                 333 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 42 
                 537 
               
               
                   
               
               
                 334 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 130 
                 517 
               
               
                   
               
               
                 335 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 470 
                 537 
               
               
                   
               
               
                 336 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 550 
                 561 
               
               
                   
               
               
                 337 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 88 
                 567 
               
               
                   
               
               
                 338 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 280 
                 527 
               
               
                   
               
               
                 339 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 45 
                 563 
               
               
                   
               
               
                 340 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 49 
                 531 
               
               
                   
               
               
                 341 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 13 
                 581 
               
               
                   
               
               
                 342 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 340 
                 632 
               
               
                   
               
               
                 343 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                 525 
               
               
                   
               
               
                 344 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                 514 
               
               
                   
               
               
                 345 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                 473 
               
               
                   
               
               
                 346 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                 632 
               
               
                   
               
               
                 347 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                 537 
               
               
                   
               
               
                 348 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                 658 
               
               
                   
               
               
                 349 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                 465 
               
               
                   
               
               
                 350 
                 
                   
                     
                     
                         
                         
                     
                   
                 
                   
                 465 
               
               
                   
               
            
           
         
       
     
                     TABLE 3               The following compounds are also in accordance with the invention,       where the numbering of the respective compound corresponds to the       corresponding structure having the same numbering from Table 2,                                        1.   (R)-3-(2,4-dichlorophenyl)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]-           guanidino}-N-[2-(3,4-dimethoxyphenyl)ethyl]propionamide,       2.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-(4-methoxy-           benzyl)-3-phenylpropionamide,       3.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-(1-ethylpropyl)propionamide trifluoroacetate,       4.   (R)-3-(2,4-dichlorophenyl)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]-           guanidino}-N-[2-(1,3-dioxo-1,3-dihydroisoindol-2-yl)ethyl]propion-           amide,       5.   (S)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-[2-(1,3-           dioxo-1,3-dihydroisoindol-2-yl)ethyl]-3-(4-methoxyphenyl)propion-           amide,       6.   (S)-3-(4-chlorophenyl)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]-           guanidino}-N-[2-(1,3-dioxo-1,3-dihydroisoindol-2-yl)ethyl]propion-           amide,       7.   (S)-3-(2,4-dichlorophenyl)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]-           guanidino}-N-[2-(1,3-dioxo-1,3-dihydroisoindol-2-yl)ethyl]propion-           amide,       8.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-[2-(3,4-           dimethoxyphenyl)ethyl]-3-phenylpropionamide,       9.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-[2-(1,3-           dioxo-1,3-dihydroisoindol-2-yl)ethyl]propionamide,       10.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-phenethyl-3-           phenylpropionamide,       11.   (R)-N-[2-(4-chlorophenyl)ethyl]-2-{N′-[2-(3,4-dimethoxyphenyl)-           acetyl]guanidino}-3-phenylpropionamide,       12.   (R)-N-[2-(2,4-dichlorophenyl)ethyl]-2-{N′-[2-(3,4-dimethoxyphenyl)-           acetyl]guanidino}-3-phenylpropionamide,       13.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-[2-(1,3-           dioxo-1,3-dihydroisoindol-2-yl)ethyl]-3-phenylpropionamide,       14.   (S)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-[2-(1,3-           dioxo-1,3-dihydroisoindol-2-yl)ethyl]-3-phenylpropionamide,       15.   (R)-N-[2-(2-bromo-4,5-dimethoxyphenyl)ethyl]-2-{N′-[2-(3,4-           dimethoxyphenyl)acetyl]guanidino}-3-phenylpropionamide,       16.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-3-phenyl-N-(4-           sulfamoylbenzyl)propionamide,       17.   (R)-N-(4-cyano-3-fluorobenzyl)-2-{N′-[2-(3,4-dimethoxyphenyl)-           acetyl]guanidino}-3-phenylpropionamide,       18.   (R)-N-(3,4-dimethoxybenzyl)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]-           guanidino}-3-(4-methoxyphenyl)propionamide,       19.   (R)-N-cyclohexylmethyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]-           guanidino}-3-phenylpropionamide trifluoroacetate,       20.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-(4-fluoro-           benzyl)-3-phenylpropionamide,       21.   (R)-N-(3,4-difluorobenzyl)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]-           guanidino}-3-phenylpropionamide,       22.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-(4-fluoro-3-           methoxybenzyl)-3-phenylpropionamide,       23.   (R)-N-(2-bromo-4,5-dimethoxybenzyl)-2-{N′-[2-(3,4-dimethoxy-           phenyl)acetyl]guanidino}-3-phenylpropionamide,       24.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-((1S,2R)-2-           hydroxyindan-1-yl)-3-phenylpropionamide,       25.   (R)-3-cyclohexyl-N-(3,4-dimethoxybenzyl)-2-{N′-[2-(3,4-dimethoxy-           phenyl)acetyl]guanidino}propionamide,       26.   (R)-N-benzyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-           methyl-3-phenylpropionamide,       27.   (R)-N-(3,4-dimethoxybenzyl)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]-           guanidino}-N-methyl-3-phenylpropionamide,       28.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-3-phenyl-           propionamide,       29.   (R)-N-(3,4-dichlorobenzyl)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]-           guanidino}-3-phenylpropionamide,       30.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-3-phenyl-N-           pyridin-4-ylmethylpropionamide,       31.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-3-phenyl-N-           pyridin-2-ylmethylpropionamide,       32.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-3-phenyl-N-[3-           (1H-tetrazol-5-yl)benzyl]propionamide,       33.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-isobutyl-3-           phenylpropionamide,       34.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-(2,2-           dimethylpropyl)-3-phenylpropionamide,       35.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-(3-methyl-           butyl)-3-phenylpropionamide,       36.   (R)-N-(4-tert-butylcyclohexyl)-2-{N′-[2-(3,4-dimethoxyphenyl)-           acetyl]guanidino}-3-phenylpropionamide,       37.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-[3-(2-           methoxyethoxy)benzyl]-3-phenylpropionamide,       38.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-[3-(2-           hydroxyethoxy)benzyl]-3-phenylpropionamide,       39.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-(1-ethyl-           propyl)-3-phenylpropionamide,       40.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-isopropyl-3-           phenylpropionamide,       41.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-(2-ethyl-           butyl)-3-phenylpropionamide,       42.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-((S)-2-           methylbutyl)-3-phenylpropionamide,       43.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-((S)-2-methylbutyl)propionamide,       44.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanecarboxylic acid 4-fluoro-3-methoxybenzyl amide,       45.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanecarboxylic acid isobutyl amide,       46.   (2R,3R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-3-methyl-           pentanecarboxylic acid 4-fluoro-3-methoxybenzyl amide,       47.   (R)-N-(2-benzo-1,3-dioxol-5-ylethyl)-2-{N′-[2-(3,4-dimethoxy-           phenyl)acetyl]guanidino}-3-phenylpropionamide,       48.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-3-phenyl-N-(2-           pyridin-4-ylethyl)propionamide,       49.   (R)-N-(3,4-dimethoxybenzyl)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]-           guanidino}-3-hydroxypropionamide,       50.   (R)-3-tert-butoxy-N-(3,4-dimethoxybenzyl)-2-{N′-[2-(3,4-dimethoxy-           phenyl)acetyl]guanidino}propionamide,       51.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanecarboxylic acid 3,4-dimethoxybenzyl amide,       52.   (R)-N-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           3-phenylpropionamide,       53.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-isobutylpropionamide,       54.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-(3-methoxy-           benzyl)-3-phenylpropionamide,       55.   (R)-3-(2-chlorophenyl)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]-           guanidino}-N-[2-(3,4-dimethoxyphenyl)ethyl]propionamide,       56.   (R)-3-(4-chlorophenyl)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]-           guanidino}-N-[2-(3,4-dimethoxyphenyl)ethyl]propionamide,       57.   5-((R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-3-phenyl-           propionylamino)furan-2-carboxylic acid methyl ester,       58.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-3-phenyl-N-           thiophen-2-ylmethylpropionamide,       59.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-(3-ethoxy-           pyridin-2-ylmethyl)-3-phenylpropionamide,       60.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-(4-fluoro-3-methoxybenzyl)propionamide,       61.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-(4-fluoro-3-           methoxybenzyl)-4-phenylbutyramide,       62.   (1S,3S,4S)-4-((R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           3-phenylpropionylamino)-3-hydroxycyclohexanecarboxylic acid           methyl ester,       63.   (R)-N-(3,5-dimethoxybenzyl)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]-           guanidino}-3-phenylpropionamide,       64.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-((R)-1-           hydroxymethyl-3-methylbutyl)-3-phenylpropionamide,       65.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-((S)-1-           hydroxymethyl-3-methylbutyl)-3-phenylpropionamide,       66.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-(4-methyl-           cyclohexyl)-3-phenylpropionamide,       67.   (2R,3R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-3-methyl-           pentanoic acid isobutyl amide,       68.   R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanecarboxylic acid ((S)-2-methylbutyl) amide,       69.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-[1-(4-fluoro-3-methoxyphenyl)cyclopropyl]propionamide,       70.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanecarboxylic acid [1-(4-fluoro-3-methoxyphenyl)cyclopropyl]           amide,       71.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-[1-(4-fluoro-           3-methoxyphenyl)cyclopropyl]-3-phenylpropionamide,       72.   (R)-3,N-dicyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]-           guanidino}propionamide,       73.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanecarboxylic acid cyclohexyl amide,       74.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-3-phenyl-N-           (tetrahydropyran-4-yl)propionamide,       75.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanecarboxylic acid (tetrahydropyran-4-yl) amide,       76.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-(1-methyl-           piperidin-4-yl)-3-phenylpropionamide,       77.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanecarboxylic acid (1-methylpiperidin-4-yl) amide,       78.   (R)-N-(3,4-dimethoxybenzyl)-2-{N′-[2-(3,5-dimethoxyphenyl)acetyl]-           guanidino}-3-phenylpropionamide,       79.   (R)-2-{N′-[2-(3,5-dimethoxyphenyl)acetyl]guanidino}-N-(4-fluoro-3-           methoxybenzyl)-3-phenylpropionamide,       80.   (R)-3-cyclohexyl-2-{N′-[2-(3,5-dimethoxyphenyl)acetyl]guanidino}-           N-(4-fluoro-3-methoxybenzyl)propionamide,       81.   (R)-3-cyclohexyl-2-{N′-[2-(3,5-dimethoxyphenyl)acetyl]guanidino}-           N-isobutylpropionamide,       82.   (R)-N-cyclopropylmethyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]-           guanidino}-3-phenylpropionamide,       83.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-[(S)-1-(3-           methoxyphenyl)ethyl]-3-phenylpropionamide,       84.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-[(R)-1-(3-           methoxyphenyl)ethyl]-3-phenylpropionamide,       85.   (S)-3-cyclohexyl-N-cyclopropylmethyl-2-{N′-[2-(3,4-dimethoxy-           phenyl)acetyl]guanidino}propionamide,       86.   (S)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-[(S)-1-(3-methoxyphenyl)ethyl]propionamide,       87.   (S)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-[(R)-1-(3-methoxyphenyl)ethyl]propionamide,       88.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-3-phenyl-N-           (tetrahydropyran-4-ylmethyl)propionamide,       89.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-(3-methoxy-           propyl)-3-phenylpropionamide,       90.   (S)-3-cyclohexyl-N-cyclohexylmethyl-2-{N′-[2-(3,4-dimethoxy-           phenyl)acetyl]guanidino}propionamide,       91.   (S)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-(tetrahydropyran-4-ylmethyl)propionamide,       92.   (S)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-(3-methoxypropyl)propionamide,       93.   (R)-3-cyclohexyl-2-{N′-[3-(3,4-dimethoxyphenyl)propionyl]-           guanidino}-N-(4-fluoro-3-methoxybenzyl)propionamide,       94.   (R)-2-[N′-(2-benzo-1,3-dioxol-5-ylacetyl)guanidino]-3-cyclohexyl-N-           (4-fluoro-3-methoxybenzyl)propionamide,       95.   (R)-3-cyclohexyl-N-(4-fluoro-3-methoxybenzyl)-2-[N′-(4-methyl-           pentanoyl)guanidino]propionamide,       96.   (R)-3-cyclohexyl-N-(4-fluoro-3-methoxybenzyl)-2-[N′-(indane-2-           carbonyl)guanidino]propionamide,       97.   (R)-2-{N′-[2-(3-methoxyphenyl)acetyl]guanidino}-4-methylpentane-           carboxylic acid 3,4-dimethoxybenzyl amide,       98.   (R)-3-cyclohexyl-2-[N′-(2-cyclohexylacetyl)guanidino]-N-(4-fluoro-3-           methoxybenzyl)propionamide,       99.   (R)-2-{N′-[2-(2-bromo-4,5-dimethoxyphenyl)acetyl]guanidino}-3-           cyclohexyl-N-(4-fluoro-3-methoxybenzyl)propionamide,       100.   (R)-3-cyclohexyl-N-((S)-2-methylbutyl)-2-[N′-(3-phenylpropionyl)-           guanidino]propionamide,       101.   (R)-3-cyclohexyl-N-(4-fluoro-3-methoxybenzyl)-2-[N′-(3-phenyl-           propionyl)guanidino]propionamide,       102.   (R)-3-cyclohexyl-N-((S)-2-methylbutyl)-2-(N′-phenylacetyl-           guanidino)propionamide,       103.   (R)-2-[N′-(2-benzo-1,3-dioxol-5-ylacetyl)guanidino]-3-cyclohexyl-N-           isobutylpropionamide,       104.   (R)-2-[N′-(2-benzo-1,3-dioxol-5-ylacetyl)guanidino]-N-(3,4-           dimethoxybenzyl)-3-phenylpropionamide,       105.   (R)-N-(3,4-dimethoxybenzyl)-3-phenyl-2-[N′-(3-phenylpropionyl)-           guanidino]propionamide,       106.   (R)-3-cyclohexyl-2-[N′-(indane-2-carbonyl)guanidino]-N-isobutyl-           propionamide,       107.   (R)-N-(3,4-dimethoxybenzyl)-2-[N′-(indane-2-carbonyl)guanidino]-3-           phenylpropionamide,       108.   (R)-N-(3,4-dimethoxybenzyl)-2-{N′-[3-(3,4-dimethoxyphenyl)-           propionyl]guanidino}-3-phenylpropionamide,       109.   (R)-2-{N′-[2-(2-bromo-4,5-dimethoxyphenyl)acetyl]guanidino}-3-           cyclohexyl-N-isobutylpropionamide,       110.   (R)-2-{N′-[2-(2-bromo-4,5-dimethoxyphenyl)acetyl]guanidino}-N-           (3,4-dimethoxybenzyl)-3-phenylpropionamide,       111.   (R)-2-{N′-[2-(3-methoxyphenyl)acetyl]guanidino}-4-methylpentanoic           acid isobutyl amide,       112.   (R)-2-{N′-[2-(3-methoxyphenyl)acetyl]guanidino}-4-methylpentane-           carboxylic acid 4-fluoro-3-methoxybenzyl amide,       113.   (R)-3-cyclohexyl-2-{N′-[2-(3-methoxyphenyl)acetyl]guanidino}-N-           ((S)-2-methylbutyl)propionamide,       114.   (R)-3-cyclohexyl-N-(4-fluoro-3-methoxybenzyl)-2-{N′-[2-(3-methoxy-           phenyl)acetyl]guanidino}propionamide,       115.   (R)-N-(3,4-dimethoxybenzyl)-3-phenyl-2-(N′-phenylacetyl-           guanidino)propionamide,       116.   (R)-3-cyclohexyl-N-isobutyl-2-[N′-(4-methylpentanoyl)guanidino]-           propionamide,       117.   (R)-3-cyclohexyl-N-isobutyl-2-{N′-[2-(3-methoxyphenyl)acetyl]-           guanidino}propionamide,       118.   (R)-3-cyclohexyl-2-[N′-(2-cyclohexylacetyl)guanidino]-N-isobutyl-           propionamide,       119.   (R)-N-(3,4-dimethoxybenzyl)-2-[N′-(4-methylpentanoyl)guanidino]-           3-phenylpropionamide,       120.   (R)-2-[N′-(2-cyclohexylacetyl)guanidino]-N-(3,4-dimethoxybenzyl)-           3-phenylpropionamide,       121.   (R)-N-(3,4-dimethoxybenzyl)-2-{N′-[2-(3-methoxyphenyl)acetyl]-           guanidino}-3-phenylpropionamide,       122.   (R)-N-(3-methoxybenzyl)-2-{N′-[2-(3-methoxyphenyl)acetyl]-           guanidino}-3-phenylpropionamide,       123.   (R)-N-(4-fluoro-3-methoxybenzyl)-2-{N′-[2-(3-methoxyphenyl)-           acetyl]guanidino}-3-phenylpropionamide,       124.   (R)-2-[N′-(2-cyclohexylacetyl)guanidino]-N-(4-fluoro-3-methoxy-           benzyl)-3-phenylpropionamide,       125.   (R)-N-isobutyl-2-{N′-[2-(4-methoxyphenyl)acetyl]guanidino}-3-           phenylpropionamide,       126.   (R)-N-(3,4-dimethoxybenzyl)-2-{N′-[2-(4-methoxyphenyl)acetyl]-           guanidino}-3-phenylpropionamide,       127.   (R)-N-isobutyl-2-[N′-(2-phenoxyacetyl)guanidino]-3-phenylpropion-           amide,       128.   (R)-N-(3,4-dimethoxybenzyl)-3-phenyl-2-{N′-[2-(4-trifluoromethyl-           phenyl)acetyl]guanidino}propionamide,       129.   (R)-3-phenyl-N-(4-sulfamoylbenzyl)-2-{N′-[2-(4-trifluoromethoxy-           phenyl)acetyl]guanidino}propionamide,       130.   (R)-N-(3,4-dimethoxybenzyl)-3-phenyl-2-{N′-[2-(4-trifluoromethoxy-           phenyl)acetyl]guanidino}propionamide,       131.   (R)-N-isobutyl-2-[N′-(3-methylbutyryl)guanidino]-3-phenylpropion-           amide,       132.   (R)-N-[2-(3,4-dimethoxyphenyl)ethyl]-2-[N′-(3-methylbutyryl)-           guanidino]-3-phenylpropionamide,       133.   (R)-2-[N′-(3-methylbutyryl)guanidino]-3-phenyl-N-(4-sulfamoyl-           benzyl)propionamide,       134.   (R)-N-(3,4-dimethoxybenzyl)-2-[N′-(3-methylbutyryl)guanidino]-3-           phenylpropionamide,       135.   (R)-4-methyl-2-[N′-(3-methylbutyryl)guanidino]-pentanoic acid 3,4-           dimethoxybenzyl amide,       136.   (R)-N-isobutyl-2-(N′-isobutyrylguanidino)-3-phenylpropionamide,       137.   (R)-N-[2-(3,4-dimethoxyphenyl)ethyl]-2-(N′-isobutyrylguanidino)-3-           phenylpropionamide,       138.   (R)-2-(N′-isobutyrylguanidino)-3-phenyl-N-(4-sulfamoylbenzyl)-           propionamide,       139.   (R)-N-(3,4-dimethoxybenzyl)-2-(N′-isobutyrylguanidino)-3-phenyl-           propionamide,       140.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-(2-methyl-           sulfamoylbenzyl)-3-phenylpropionamide,       141.   (R)-N-(3,4-dimethoxybenzyl)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]-           guanidino}-3-phenylpropionamide,       142.   (R)-N-benzo-1,3-dioxol-5-ylmethyl-2-{N′-[2-(3,4-dimethoxyphenyl)-           acetyl]guanidino}-3-phenylpropionamide,       143.   (R)-N-(2,3-dimethoxybenzyl)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]-           guanidino}-3-phenylpropionamide,       144.   (R)-N-(3-bromobenzyl)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]-           guanidino}-3-phenylpropionamide,       145.   (R)-N-(3-chlorobenzyl)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]-           guanidino}-3-phenylpropionamide,       146.   (R)-N-benzyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-3-           phenylpropionamide,       147.   (R)-2-{N′-[2-(4-chlorophenyl)acetyl]guanidino}-N-[2-(3,4-dimethoxy-           phenyl)ethyl]-3-phenylpropionamide,       148.   (S)-3-(2,4-dichlorophenyl)-N-[2-(1,3-dioxo-1,3-dihydroisoindol-2-yl)-           ethyl]-2-{N′-[2-(3-phenoxyphenyl)acetyl]guanidino}propionamide,       149.   (S)-3-(4-chlorophenyl)-N-[2-(1,3-dioxo-1,3-dihydroisoindol-2-yl)-           ethyl]-2-{N′-[2-(3-phenoxyphenyl)acetyl]guanidino}propionamide,       150.   (R)-3-(2,4-dichlorophenyl)-N-[2-(1,3-dioxo-1,3-dihydroisoindol-2-yl)-           ethyl]-2-{N′-[2-(3-phenoxyphenyl)acetyl]guanidino}propionamide,       151.   (S)-N-[2-(1,3-dioxo-1,3-dihydroisoindol-2-yl)ethyl]-3-(4-methoxy-           phenyl)-2-{N′-[2-(3-phenoxyphenyl)acetyl]guanidino}propionamide,       152.   (R)-N-[2-(1,3-dioxo-1,3-dihydroisoindol-2-yl)ethyl]-2-{N′-[2-(3-           phenoxyphenyl)acetyl]guanidino}-3-phenylpropionamide,       153.   (S)-N-[2-(1,3-dioxo-1,3-dihydroisoindol-2-yl)ethyl]-2-{N′-[2-(3-           phenoxyphenyl)acetyl]guanidino}-3-phenylpropionamide,       154.   (R)-N-(3,4-dimethoxybenzyl)-2-{N′-[2-(2,4-dimethoxyphenyl)acetyl]-           guanidino}-3-phenylpropionamide,       155.   (R)-2-{N′-[2-(2,4-dimethoxyphenyl)acetyl]guanidino}-N-(4-fluoro-3-           methoxybenzyl)-3-phenylpropionamide,       156.   (R)-3-cyclohexyl-2-{N′-[2-(2,4-dimethoxyphenyl)acetyl]guanidino}-           N-isobutylpropionamide,       157.   (R)-3-cyclohexyl-2-{N′-[2-(2,4-dimethoxyphenyl)acetyl]guanidino}-           N-(4-fluoro-3-methoxybenzyl)propionamide,       158.   (R)-2-[N′-(2-adamantan-1-ylacetyl)guanidino]-N-(3,4-dimethoxy-           benzyl)-3-phenylpropionamide,       159.   2-[N′-(2-adamantan-1-ylacetyl)guanidino]-3-cyclohexyl-N-isobutyl-           propionamide,       160.   2-[N′-(2-adamantan-1-ylacetyl)guanidino]-3-cyclohexyl-N-(4-fluoro-           3-methoxybenzyl)propionamide,       161.   2-[N′-(2-adamantan-1-ylacetyl)guanidino]-N-(4-fluoro-3-methoxy-           benzyl)-3-phenylpropionamide,       162.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-(4-sulfamoylbenzyl)propionamide,       163.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanecarboxylic acid cyclopropylmethyl amide,       164.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanecarboxylic acid 4-sulfamoylbenzyl amide,       165.   (R)-3-cyclohexyl-N-cyclopropylmethyl-2-{N′-[2-(3,4-dimethoxy-           phenyl)acetyl]guanidino}propionamide,       166.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-[(S)-1-(3-methoxyphenyl)ethyl]propionamide,       167.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-[(R)-1-(3-methoxyphenyl)ethyl]propionamide,       168.   (R)-3-cyclohexyl-N-cyclohexylmethyl-2-{N′-[2-(3,4-dimethoxy-           phenyl)acetyl]guanidino}propionamide,       169.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-(tetrahydropyran-4-ylmethyl)propionamide,       170.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-(3-methoxypropyl)propionamide,       171.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-(tetrahydrothiopyran-4-yl)propionamide,       172.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-3-phenyl-N-           (tetrahydrothiopyran-4-yl)propionamide,       173.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanecarboxylic acid (tetrahydrothiopyran-4-yl) amide,       174.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-(tetrahydropyran-4-yl)propionamide,       175.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-(1-methylpiperidin-4-yl)propionamide,       176.   (R)-N-(5-chlorothiophen-2-ylmethyl)-2-{N′-[2-(3,4-dimethoxy-           phenyl)acetyl]guanidino}-3-phenylpropionamide,       177.   (R)-N-(5-chlorothiophen-2-ylmethyl)-3-cyclohexyl-2-{N′-[2-(3,4-           dimethoxyphenyl)acetyl]guanidino}propionamide,       178.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-(3-fluoro-4-           methoxybenzyl)-3-phenylpropionamide,       179.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-(3-fluoro-4-methoxybenzyl)propionamide,       180.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanecarboxylic acid 3-fluoro-4-methoxybenzyl amide,       181.   (R)-3-cyclohexyl-N-(3,4-difluorobenzyl)-2-{N′-[2-(3,4-dimethoxy-           phenyl)acetyl]guanidino}propionamide,       182.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanecarboxylic acid 3,4-difluorobenzyl amide,       183.   (R)-N-(6-chloropyridin-3-ylmethyl)-3-cyclohexyl-2-{N′-[2-(3,4-           dimethoxyphenyl)acetyl]guanidino}propionamide,       184.   (R)-N-((S)-sec-butyl)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)-           acetyl]guanidino}propionamide,       185.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-(trans-4-hydroxycyclohexyl)propionamide,       186.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanecarboxylic acid (6-chloropyridin-3-ylmethyl) amide,       187.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-(4-fluorobenzyl)propionamide,       188.   (R)-3-cyclohexyl-N-cyclopropyl-2-{N′-[2-(3,4-dimethoxyphenyl)-           acetyl]guanidino}propionamide,       189.   (R)-3-cyclohexyl-N-cyclopentyl-2-{N′-[2-(3,4-dimethoxyphenyl)-           acetyl]guanidino}propionamide,       190.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanecarboxylic acid 4-fluorobenzyl amide,       191.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanecarboxylic acid cyclopentyl amide,       192.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanecarboxylic acid ((S)-sec-butyl) amide,       193.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanecarboxylic acid ((R)-sec-butyl) amide,       194.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanecarboxylic acid (trans-4-hydroxycyclohexyl) amide,       195.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanecarboxylic acid (cis-4-hydroxycyclohexyl) amide,       196.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanecarboxylic acid (S)-indan-1-yl amide amide,       197.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanecarboxylic acid (R)-indan-1-ylamide amide,       198.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanecarboxylic acid (4-methoxyindan-2-yl) amide,       199.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanecarboxylic acid (5-methoxyindan-2-yl) amide,       200.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanecarboxylic acid 3-(1H-tetrazol-5-yl)benzyl amide,       201.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-diethoxyphenyl)acetyl]guanidino}-N-           (4-fluoro-3-methoxybenzyl)propionamide,       202.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-(cis-4-hydroxycyclohexyl)propionamide,       203.   (R)-N-((R)-sec-butyl)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)-           acetyl]guanidino}propionamide,       204.   (R)-N-(3,4-dimethoxybenzyl)-2-{N′-[2-(2,5-dimethoxyphenyl)acetyl]-           guanidino}-3-phenylpropionamide,       205.   (R)-2-{N′-[2-(2,5-dimethoxyphenyl)acetyl]guanidino}-N-(4-fluoro-3-           methoxybenzyl)-3-phenylpropionamide,       206.   (R)-3-cyclohexyl-2-{N′-[2-(2,5-dimethoxyphenyl)acetyl]guanidino}-           N-isobutylpropionamide,       207.   (R)-3-cyclohexyl-2-{N′-[2-(2,5-dimethoxyphenyl)acetyl]guanidino}-           N-(4-fluoro-3-methoxybenzyl)propionamide,       208.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-(S)-indan-1-ylpropionamide)propionamide,       209.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-(R)-indan-1-ylpropionamide,       210.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-(4-methoxyindan-2-yl)propionamide,       211.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-(5-methoxyindan-2-yl)propionamide,       212.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-[3-(1H-tetrazol-5-yl)benzyl]propionamide,       213.   (R)-N-(4-fluoro-3-methoxybenzyl)-2-{N′-[2-(4-fluoro-3-methoxy-           phenyl)acetyl]guanidino}-3-phenylpropionamide,       214.   (R)-3-cyclohexyl-2-{N′-[2-(4-fluoro-3-methoxyphenyl)acetyl]-           guanidino}-N-isobutylpropionamide,       215.   (R)-3-cyclohexyl-N-(4-fluoro-3-methoxybenzyl)-2-{N′-[2-(4-fluoro-3-           methoxyphenyl)acetyl]guanidino}propionamide,       216.   (R)-N-(4-fluoro-3-methoxybenzyl)-2-{N′-[2-(3-fluoro-4-methoxy-           phenyl)acetyl]guanidino}-3-phenylpropionamide,       217.   (R)-3-cyclohexyl-2-{N′-[2-(3-fluoro-4-methoxyphenyl)acetyl]-           guanidino}-N-isobutylpropionamide,       218.   (R)-3-cyclohexyl-N-(4-fluoro-3-methoxybenzyl)-2-{N′-[2-(3-fluoro-4-           methoxyphenyl)acetyl]guanidino}propionamide,       219.   (R)-N-(4-fluoro-3-methoxybenzyl)-3-phenyl-2-[N′-(2-tetrahydro-           pyran-4-ylacetyl)guanidino]propionamide,       220.   (R)-3-cyclohexyl-N-isobutyl-2-[N′-(2-tetrahydropyran-4-ylacetyl)-           guanidino]propionamide,       221.   (R)-3-cyclohexyl-N-(4-fluoro-3-methoxybenzyl)-2-[N′-(2-tetrahydro-           pyran-4-ylacetyl)guanidino]propionamide,       222.   (R)-3-cyclohexyl-2-{N′-[2-(2,6-difluoro-4-methoxyphenyl)acetyl]-           guanidino}-N-(4-fluoro-3-methoxybenzyl)propionamide,       223.   (R)-3-cyclohexyl-2-{N′-[2-(2,6-difluoro-4-methoxyphenyl)acetyl]-           guanidino}-N-isobutylpropionamide,       224.   (R)-3-cyclohexyl-2-[N′-(3,3-dimethylbutyryl)guanidino]-N-(4-fluoro-           3-methoxybenzyl)propionamide,       225.   (R)-3-cyclohexyl-2-[N′-(3,3-dimethylbutyryl)guanidino]-N-isobutyl-           propionamide.       226.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-diethoxyphenyl)acetyl]guanidino}-N-           isobutylpropionamide,       227.   (R)-2-{N′-[2-(3,4-diethoxyphenyl)acetyl]guanidino}-N-(4-fluoro-3-           methoxybenzyl)-3-phenylpropionamide,       228.   (R)-2-{N′-[2-(2-bromo-4-methoxyphenyl)acetyl]guanidino}-N-(4-           fluoro-3-methoxybenzyl)-3-phenylpropionamide, (R)-2-{N′-[2-(2-           bromo-4-methoxyphenyl)acetyl]guanidino}-3-cyclohexyl-N-isobutyl-           propionamide,       229.   (R)-2-{N′-[2-(2-bromo-4-methoxyphenyl)acetyl]guanidino}-3-cyclo-           hexyl-N-isobutylpropionamide,       230.   (R)-2-{N′-[2-(2-bromo-4-methoxyphenyl)acetyl]guanidino}-3-cyclo-           hexyl-N-(4-fluoro-3-methoxybenzyl)propionamide,       231.   (S)-2-benzyl-4-{N′-[(R)-1-(4-fluoro-3-methoxybenzylcarbamoyl)-2-           phenylethyl]guanidino}-4-oxobutyric acid methyl ester,       232.   (S)-2-benzyl-4-[N′-((R)-2-cyclohexyl-1-isobutylcarbamoylethyl)-           guanidino]-4-oxobutyric acid methyl ester,       233.   (S)-2-benzyl-4-{N′-[(R)-2-cyclohexyl-1-(4-fluoro-3-methoxybenzyl-           carbamoyl)ethyl]guanidino}-4-oxobutyric acid methyl ester,       234.   (R)-2-{N′-[2-(2-bromophenyl)acetyl]guanidino}-3-cyclohexyl-N-(4-           fluoro-3-methoxybenzyl)propionamide,       235.   (R)-2-{N′-[2-(2-bromophenyl)acetyl]guanidino}-3-cyclohexyl-N-           isobutylpropionamide,       236.   (R)-2-{N′-[2-(2-bromophenyl)acetyl]guanidino}-N-(4-fluoro-3-           methoxybenzyl)-3-phenylpropionamide,       237.   (R)-3-cyclohexyl-N-(4-fluoro-3-methoxybenzyl)-2-{N′-[2-((S)-5-oxo-           pyrrolidin-2-yl)acetyl]guanidino}propionamide,       238.   (R)-3-cyclohexyl-N-isobutyl-2-{N′-[2-((S)-5-oxopyrrolidin-2-yl)-           acetyl]guanidino}propionamide,       239.   (S)-2-benzyl-4-{N′-[(R)-2-cyclohexyl-1-(4-fluoro-3-methoxybenzyl-           carbamoyl)ethyl]guanidino}-4-oxobutyric acid,       240.   (R)-N-(3,4-dimethoxybenzyl)-3-phenyl-2-{N′-[2-(2,3,4-trimethoxy-           phenyl)acetyl]guanidino}propionamide,       241.   (R)-N-(4-fluoro-3-methoxybenzyl)-3-phenyl-2-{N′-[2-(2,3,4-           trimethoxyphenyl)acetyl]guanidino}propionamide,       242.   (R)-3-cyclohexyl-N-isobutyl-2-{N′-[2-(2,3,4-trimethoxyphenyl)-           acetyl]guanidino}propionamide,       243.   (R)-3-cyclohexyl-N-(4-fluoro-3-methoxybenzyl)-2-{N′-[2-(2,3,4-           trimethoxyphenyl)acetyl]guanidino}propionamide,       244.   (R)-2-{N′-[2-(3,4-difluorophenyl)acetyl]guanidino}-N-(3,4-dimethoxy-           benzyl)-3-phenylpropionamide,       245.   (R)-2-{N′-[2-(3,4-difluorophenyl)acetyl]guanidino}-N-(4-fluoro-3-           methoxybenzyl)-3-phenylpropionamide,       246.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-difluorophenyl)acetyl]guanidino}-N-           isobutylpropionamide,       247.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-difluorophenyl)acetyl]guanidino}-N-           (4-fluoro-3-methoxybenzyl)propionamide,       248.   (R)-N-cyclobutyl-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)-           acetyl]guanidino}propionamide,       249.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanecarboxylic acid cyclobutyl amide,       250.   (R)-2-{N′-[2-(1-ethylpiperidin-4-yl)acetyl]guanidino}-N-(4-fluoro-3-           methoxybenzyl)-3-phenylpropionamide,       251.   (R)-3-cyclohexyl-2-{N′-[2-(1-ethylpiperidin-4-yl)acetyl]guanidino}-N-           isobutylpropionamide,       252.   (R)-3-cyclohexyl-2-{N′-[2-(1-ethylpiperidin-4-yl)acetyl]guanidino}-N-           (4-fluoro-3-methoxybenzyl)propionamide,       253.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-(3-trifluoromethylbenzyl)propionamide,       254.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanoic acid 3-trifluoromethylbenzyl amide,       255.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-(4-fluoro-3-trifluoromethylbenzyl)propionamide,       256.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanecarboxylic acid 4-fluoro-3-trifluoromethylbenzyl amide,       257.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-(3-trifluoromethoxybenzyl)propionamide,       258.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanecarboxylic acid 3-trifluoromethoxybenzyl amide,       259.   (R)-3-cyclohexyl-N-(4-fluoro-3-trifluoromethoxybenzyl)-2-{N′-[2-(4-           fluoro-3-trifluoromethylphenyl)acetyl]guanidino}propionamide,       260.   (R)-3-cyclohexyl-N-(4-fluoro-3-trifluoromethylbenzyl)-2-{N′-[2-(4-           fluoro-3-trifluoromethylphenyl)acetyl]guanidino}propionamide,       261.   (R)-3-cyclohexyl-N-(4-fluoro-3-methoxybenzyl)-2-{N′-[2-(2,4,6-           trifluorophenyl)acetyl]guanidino}propionamide,       262.   (R)-3-cyclohexyl-N-(4-fluoro-3-trifluoromethoxybenzyl)-2-{N′-[2-           (2,4,6-trifluorophenyl)acetyl]guanidino}propionamide,       263.   (R)-3-cyclohexyl-N-(4-fluoro-3-trifluoromethylbenzyl)-2-{N′-[2-           (2,4,6-trifluorophenyl)acetyl]guanidino}propionamide,       264.   (R)-3-cyclohexyl-N-(4-fluoro-3-methoxybenzyl)-2-{N′-[2-(4-fluoro-3-           trifluoromethylphenyl)acetyl]guanidino}propionamide,       265.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-(4-fluoro-3-trifluoromethoxybenzyl)propionamide,       266.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanecarboxylic acid 4-fluoro-3-trifluoromethoxybenzyl amide,       267.   (R)-N-[(S)-1-(3-chlorophenyl)-2-oxopyrrolidin-3-yl]-3-cyclohexyl-2-           {N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}propionamide,       268.   (R)-N-[(R)-1-(3-chlorophenyl)-2-oxopyrrolidin-3-yl]-3-cyclohexyl-2-           {N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}propionamide,       269.   (R)-2-{N′-[2-(2-bromo-4,5-dimethoxyphenyl)acetyl]guanidino}-4-           methylpentanecarboxylic acid 3-(1H-tetrazol-5-yl)benzyl amide,       270.   (R)-2-{N′-[2-(2-bromo-4,5-dimethoxyphenyl)acetyl]guanidino}-3-           cyclohexyl-N-[3-(1H-tetrazol-5-yl)benzyl]propionamide,       271.   (R)-3-cyclohexyl-N-(4-fluoro-3-methoxybenzyl)-2-{N′-[2-(3-fluoro-4-           trifluoromethoxyphenyl)acetyl]guanidino}propionamide,       272.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-[4-(1H-tetrazol-5-yl)benzyl]propionamide,       273.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanoic acid 4-(1H-tetrazol-5-yl)benzyl amide,       274.   (R)-2-{N′-[2-(4-chlorophenyl)acetyl]guanidino}-3-cyclohexyl-N-           isobutylpropionamide,       275.   (R)-2-{N′-[2-(4-chlorophenyl)acetyl]guanidino}-3-cyclohexyl-N-(4-           fluoro-3-methoxybenzyl)propionamide,       276.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-[3-fluoro-4-(1H-tetrazol-5-yl)benzyl]propionamide,       277.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanoic acid 3-fluoro-4-(1H-tetrazol-5-yl)benzyl amide,       278.   (R)-2-{N′-[2-(2-bromo-4-trifluoromethylphenyl)acetyl]guanidino}-3-           cyclohexyl-N-(4-fluoro-3-methoxybenzyl)propionamide,       279.   (R)-2-[N′-((2S,4R)-1-acetyl-4-methoxypyrrolidine-2-carbonyl)-           guanidino]-3-cyclohexyl-N-(4-fluoro-3-methoxybenzyl)propion-           amide,       280.   (R)-3-cyclohexyl-N-(4-fluoro-3-methoxybenzyl)-2-[N′-(2-piperidin-1-           ylacetyl)guanidino]propionamide,       281.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-(3-sulfamoylbenzyl)propionamide,       282.   (R)-3-cyclohexyl-N-(4-fluoro-3-methoxybenzyl)-2-[N′-(2-morpholin-           4-ylacetyl)guanidino]propionamide,       283.   (R)-3-cyclohexyl-N-(4-fluoro-3-methoxybenzyl)-2-{N′-[2-(4-           sulfamoylphenyl)acetyl]guanidino}propionamide,       284.   (R)-3-cyclohexyl-N-(4-fluoro-3-methoxybenzyl)-2-{N′-[2-(2-fluoro-4-           methoxyphenyl)acetyl]guanidino}propionamide,       285.   (R)-3-cyclohexyl-2-{N′-[2-(2-fluoro-4-methoxyphenyl)acetyl]-           guanidino}-N-isobutylpropionamide,       286.   (R)-3-cyclohexyl-N-(4-fluoro-3-methoxybenzyl)-2-(N′-{2-[4-(5-           methyl-1,2,4-oxadiazol-3-yl)phenyl]acetyl}guanidino)propionamide,       287.   (R)-2-{N′-[2-(3-cyanophenyl)acetyl]guanidino}-3-cyclohexyl-N-(4-           fluoro-3-methoxybenzyl)propionamide,       288.   (R)-3-cyclohexyl-N-(4-fluoro-3-methoxybenzyl)-2-{N′-[2-(3-           methanesulfonylaminophenyl)acetyl]guanidino}propionamide,       289.   4-[((R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]-           guanidino}propionylamino)methyl]benzoic acid methyl ester,       290.   4-[((R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanoylamino)methyl]benzoic acid methyl ester,       291.   4-[((R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-3-phenyl-           propionylamino)methyl]benzoic acid methyl ester,       292.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-[3-(5-methyl-1,2,4-oxadiazol-3-yl)benzyl]propionamide,       293.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanoic acid 3-(5-methyl-1,2,4-oxadiazol-3-yl)benzyl amide,       294.   4-(2-{N′-[(R)-2-cyclohexyl-1-(4-fluoro-3-methoxybenzylcarbamoyl)-           ethyl]guanidino}-2-oxoethyl)-2-ethoxybenzoic acid ethyl ester,       295.   (R)-3-cyclohexyl-N-(4-fluoro-3-methoxybenzyl)-2-[N′-(2-pyridin-2-yl-           acetyl)guanidino]propionamide,       296.   (R)-3-cyclohexyl-N-(4-fluoro-3-methoxybenzyl)-2-[N′-(2-isobutoxy-           acetyl)guanidino]propionamide,       297.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanoic acid 4-(1,2,3-thiadiazol-4-yl)benzyl amide,       298.   (R)-2-{N′-[2-(4-chlorophenyl)acetyl]guanidino}-3-cyclohexyl-N-(3-           sulfamoylbenzyl)propionamide,       299.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-3-phenyl-N-(4-           (1,2,3-thiadiazol-4-yl)benzyl)propionamide,       300.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-[3-(5-methyl-           1,2,4-oxadiazol-3-yl)benzyl]-3-phenylpropionamide,       301.   (R)-3-cyclohexyl-N-(4-fluoro-3-methoxybenzyl)-2-{N′-[2-(4-tetrazol-           1-ylphenyl)acetyl]guanidino}propionamide,       302.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-[3-(2-methyl-           imidazol-1-yl)benzyl]-3-phenylpropionamide,       303.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-[3-(2-methylimidazol-1-yl)benzyl]propionamide,       304.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanecarboxylic acid 3-(2-methylimidazol-1-yl)benzyl amide,       305.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-3-phenyl-N-(3-           (1,2,4-triazol-1-yl)benzyl)propionamide,       306.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-(3-1,2,4-triazol-1-ylbenzyl)propionamide,       307.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanoic acid 3-(1,2,4-triazol-1-yl)benzyl amide,       308.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanecarboxylic acid 4-(5-hydroxy-1,3,4-oxadiazol-2-yl)benzyl           amide,       309.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-[4-(5-           hydroxy-1,3,4-oxadiazol-2-yl)benzyl]-3-phenylpropionamide,       310.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-[4-(5-hydroxy-1,3,4-oxadiazol-2-yl)benzyl]propionamide,       311.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-[3-(5-hydroxy-1,3,4-oxadiazol-2-yl)benzyl]propionamide,       312.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanoic acid 3-(5-hydroxy-1,3,4-oxadiazol-2-yl)benzyl amide,       313.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-[3-(5-           hydroxy-1,3,4-oxadiazol-2-yl)benzyl]-3-phenylpropionamide,       314.   (R)-2-{N′-[2-(4-chlorophenyl)acetyl]guanidino}-3-cyclohexyl-N-[4-           (1H-tetrazol-5-yl)benzyl]propionamide,       315.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-(4-1,2,3-thiadiazol-4-ylbenzyl)propionamide,       316.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-[3-(2-methyl-2H-pyrazol-3-yl)benzyl]propionamide,       317.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanoic acid 3-(2-methyl-2H-pyrazol-3-yl)benzyl amide,       318.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-[3-(2-methyl-           2H-pyrazol-3-yl)benzyl]-3-phenylpropionamide,       319.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-[3-(1-methyl-1H-pyrazol-3-yl)benzyl]propionamide,       320.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanoic acid 3-(1-methyl-1H-pyrazol-3-yl)benzyl amide,       321.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-[3-(1-methyl-           1H-pyrazol-3-yl)benzyl]-3-phenylpropionamide,       322.   (R)-2-{N′-[2-(4-chloro-2-fluorophenyl)acetyl]guanidino}-3-           cyclohexyl-N-(4-fluoro-3-methoxybenzyl)propionamide,       323.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-(3-thiazol-2-ylbenzyl)propionamide,       324.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanoic acid 3-thiazol-2-ylbenzyl amide,       325.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-3-phenyl-N-(3-           thiazol-2-ylbenzyl)propionamide,       326.   (R)-2-[N′-((1S,4R)-2-bicyclo[2.2.1]hept-2-ylacetyl)guanidino]-3-           cyclohexyl-N-(4-fluoro-3-methoxybenzyl)propionamide,       327.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethylphenyl)acetyl]guanidino}-N-           (4-fluoro-3-methoxybenzyl)propionamide,       328.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-[4-fluoro-3-(5-hydroxy-1,3,4-oxadiazol-2-yl)benzyl]propionamide,       329.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanoic acid 4-fluoro-3-(5-hydroxy-1,3,4-oxadiazol-2-yl)benzyl           amide,       330.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-[4-fluoro-3-           (5-hydroxy-1,3,4-oxadiazol-2-yl)benzyl]-3-phenylpropionamide,       331.   (R)-2-[N′-((1S,4R)-2-bicyclo[2.2.1]hept-2-ylacetyl)guanidino]-3-           cyclohexyl-N-[3-(1H-tetrazol-5-yl)benzyl]propionamide,       332.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethylphenyl)acetyl]guanidino}-N-           [3-(1H-tetrazol-5-yl)benzyl]propionamide,       333.   (R)-3-cyclohexyl-N-(4-fluoro-3-methoxybenzyl)-2-(N′-{2-[4-(2H-           tetrazol-5-yl)phenyl]acetyl}guanidino)propionamide,       334.   (R)-3-cyclohexyl-N-(4-fluoro-3-methoxybenzyl)-2-{N′-[2-(4-propyl-           cyclohexyl)acetyl]guanidino}propionamide,       335.   (R)-3-cyclohexyl-2-{N′-[2-(4-propylcyclohexyl)acetyl]guanidino}-N-           [3-(1H-tetrazol-5-yl)benzyl]propionamide,       336.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-[4-fluoro-3-           (2H-tetrazol-5-yl)benzyl]-3-phenylpropionamide,       337.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-[4-fluoro-3-(2H-tetrazol-5-yl)benzyl]propionamide,       338.   (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-4-methyl-           pentanoic acid 4-fluoro-3-(2H-tetrazol-5-yl)benzyl amide,       339.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-{(S)-1-[3-(1H-tetrazol-5-yl)phenyl]ethyl}propionamide,       340.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethylphenyl)acetyl]guanidino}-N-           {(S)-1-[3-(1H-tetrazol-5-yl)phenyl]ethyl}propionamide,       341.   (R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-           N-{(S)-1-[4-fluoro-3-(1H-tetrazol-5-yl)phenyl]ethyl}propionamide,       342.   (R)-N-[4-(bistrifluoromethylamino)benzyl]-3-cyclohexyl-2-{N′-[2-           (3,4-dimethoxyphenyl)acetyl]guanidino}propionamide,       343.   4-[((R)-3-cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]-           guanidino}propionylamino)methyl]benzoic acid,       344.   3-[((R)-2-{N′-[2-(4-chlorophenyl)acetyl]guanidino}-3-cyclohexyl-           propionylamino)methyl]benzoic acid methyl ester,       345.   3-[((R)-2-{N′-[2-(4-chlorophenyl)acetyl]guanidino}-4-methyl-           pentanoylamino)methyl]benzoic acid methyl ester,       346.   (R)-N-[3-(bistrifluoromethylamino)benzyl]-3-cyclohexyl-2-{N′-[2-           (3,4-dimethoxyphenyl)acetyl]guanidino}propionamide,       347.   (R)-3-cyclohexyl-N-(4-fluoro-3-methoxybenzyl)-2-(N′-{2-[3-(2H-           tetrazol-5-yl)phenyl]acetyl}guanidino)propionamide,       348.   (R)-N-{1-[4-(bistrifluoromethylamino)phenyl]cyclopropyl}-3-           cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}propion-           amide,       349.   (R)-3-cyclohexyl-N-((R)-2,3-dihydroxypropyl)-2-{N′-[2-(3,4-           dimethoxyphenyl)acetyl]guanidino}propionamide,       350.   (R)-3-cyclohexyl-N-((S)-2,3-dihydroxypropyl)-2-{N′-[2-(3,4-           dimethoxyphenyl)acetyl]guanidino}propionamide,                    
and physiologically acceptable salts, derivatives, solvates, prodrugs and stereoisomers thereof, including mixtures thereof in all ratios.
 
     For the avoidance of any doubt, the compound according to the invention is unambiguously defined by the depiction of the chemical structure in all cases where the chemical name of the compound and the depiction of the chemical structure of the compound for a compound according to the invention incorrectly do not agree. 
     The mass signals were determined on an Agilent 1200 instrument: Chromolith Speed Rod RP 18e 50-4.6 mm LCMS; polar. m, 2.4 ml/min, 220 nm, buffer A 0.05% of HCOOH/H2O, buffer B 0.04% of HCOOH/ACN, 0.0-2.8 min 4%-100% of buffer B; 2.8-3.3 min 100% of buffer B 3.3-3.4 min 100%-4% of buffer B 
     The retention times were determined on a Merck-Hitachi LaChrom instrument: 
     Chromolith Speed Rod RP18e-100-4.6 HPLC; 5 min 4 ml 215 nm; 4 ml/min, 215 nm, buffer A 0.05% of TFA/H2O, buffer B 0.04% of TFA/ACN, 0.0-0.2 min 5% of buffer B; 0.2-5.0 min 5%-100% of buffer B; 5.0-5.5 min 99%-5% of buffer B 
     EXAMPLE 2 
     Preparation of (R)-3-(2,4-dichlorophenyl)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]guanidino}-N-[2-(3,4-dimethoxyphenyl)ethyl]propionamide trifluoroacetate (compound No. 1) 
     
       
         
         
             
             
         
       
     
     197.4 μl of 4-methylmorpholine were added to the solution of 500 mg (1.5 mmol) of (R)-2-tert-butoxycarbonylamino-3-(2,4-dichlorophenyl)propionic acid in 10 ml of tetrahydrofuran under nitrogen, and the mixture was cooled to −50° C. After addition of 194.6 μl (1.5 mmol) of isobutyl chloroformate, the reaction solution was stirred at −50° C. for 15 min, 248.7 (1.5 mmol) of 2-(3,4-dimethoxyphenyl)ethylamine were then added, the mixture was subsequently stirred at −40° C. for a further 30 min and at room temperature for two hours. The reaction mixture was then evaporated in vacuo, the residue was taken up in 10 ml of 5% sodium hydrogencarbonate solution, and the aqueous mixture was extracted three times with 10 ml of ethyl acetate each time. Drying of the combined organic phases over sodium sulfate and stripping-off of the solvent gave 655 mg (88% yield) of tert-buty {(R)-2-(2,4-dichlorophenyl)-1-[2-(3,4-dimethoxyphenyl)ethylcarbamoyl]ethyl}carbamate as colourless crystals. LC/MS (M+Na):520. 
     
       
         
         
             
             
         
       
     
     655 mg (1.32 mmol) of tert-butyl {(R)-2-(2,4-dichlorophenyl)-1-[2-(3,4-dimethoxyphenyl)ethylcarbamoyl]ethyl}carbamate (1a)) were dissolved in 15 ml of dioxane, and 15 ml of 4N HCl/dioxane solution were added. Reaction mixture was subsequently stirred overnight at room temperature, then evaporated to dryness, and the residue was dried in vacuo at 60° C. for five hours, giving 571 mg (100%) of (R)-2-amino-3-(2,4-dichlorophenyl)-N-[2-(3,4-dimethoxyphenyl)ethyl]propionamide hydrochloride as pale-yellow solid. LC/MS (M+H) 397.  1 H NMR (500 MHz, DMSO-d 6 ) δ 8.53 (broad s, 4H; NH), 7.61 (d, J=2.0, 1H), 7.39 (dd, J=8.3, 2.0, 1 H), 7.34 (d, J=8.3, 1 H), 6.83 (d, J=8.2, 1 H), 6.78 (d, J=1.8, 1H), 6.63 (dd, J=8.1, 1.7, 1H), 3.94 (broad s, 1H), 3.74 (s, 3H), 3.71 (s, 3H), 3.32-3.26 (m, 1H), 3.18 (dq, J=12.5, 6.4, 2H), 3.09 (dd, J=13.8, 8.4, 1 H), 2.61-2.51 (m, 2H). 
     c) 2-(3,4-Dimethoxyphenyl)-N-(iminopyrazol-1-ylmethyl)acetamide 
     
       
         
         
             
             
         
       
     
     1.067 ml (1.2 mmol)) of ethyl chloroformate were added to the solution of 2 g (10.2 mmol) of 3,4-dimethoxyphenylacetic acid and 2.24 ml of 4-methylmorpholine in 50 ml of dichloromethane with ice-cooling and under an N 2  atmosphere, The reaction mixture was subsequently stirred with ice-cooling for one hour, 1.64 g (11.2 mmol) of pyrazole-1-carboxamidine hydrochloride were then added, and stirring was continued at room temperature for fifteen hours. The reaction solution was then washed with 10 ml of 5% sodium hydrogencarbonate solution and 10 ml of water and dried over sodium sulfate. After the desiccant had been filtered off and the solvent had been stripped off, the product was purified by column chromatography. Yield 1.85 g (62.1%) LC/MS (M+H) 289.  1 H NMR (400 MHz, DMSO-d 6 ) δ 9.30 (broad s, 2H), 8.46 (d, J=2.6, 1 H), 7.91 (d, J=1.6, 1H), 6.93 (d, J=1.7, 1H), 6.87 (d, J=8.2, 1H), 6.81 (dd, J=8.2, 1.7, 1H), 6.58 (dd, J=2.6, 1.6, 1H), 3.73 (s, 3H), 3.72 (s, 3H), 3.62 (s, 2H). 
     
       
         
         
             
             
         
       
     
     100 mg (0.35 mmol) of 2-(3,4-dimethoxyphenyl)-N-(iminopyrazol-1-yl-methyl)acetamide (1c)) and 150.45 mg (0.35 mmol) of (R)-2-amino-3-(2,4-dichlorophenyl)-N-[2-(3,4-dimethoxyphenyl)ethyl]propionamide hydrochloride (1 b)) are suspended in 2 ml of tetrahydrofuran. After addition of 58 μl of triethylamine, the suspension is heated at 90° C. for 2 hours and then cooled to room temperature. The reaction mixture is subsequently evaporated to dryness, and the residue is purified by column chromatography (RP-HPLC select B; 0.1% solution of trifluoroacetic acid in acetonitrile/water), giving 44 mg (16.5%) of the title compound in the form of the trifluoroacetate salt as white amorphous solid. LC/MS (M+H) 617.  1 H NMR (500 MHz, DMSO-d 6 ) δ 11.32 (s, 1H), 8.99 (d, J=8.3, 1H), 8.88 (broad s, 2H), 8.32 (t, J=5.2, 1H), 7.54 (s, 1H), 7.29 (dd, J=8.3, 2.0, 1H), 7.14 (d, J=8.3, 1H), 6.93 (d, J=8.2, 1 H), 6.89 (d, J=1.5, 1 H), 6.84 (d, J=8.2, 1 H), 6.79 (dd, J=8.0, 1.6, 2H), 6.67 (dd, J=8.1, 1.6, 1H), 4.62 (dd, J=13.0, 5.5, 1H), 3.75 (s, 6H), 3.73 (s, 3H), 3.70 (s, 3H), 3.67 (s, 2H), 3.40-3.27 (m, 3H), 3.04 (dd, J=14.3, 6.4, 1 H), 2.76-2.56 (m, 2H). 
     Compounds Nos. 4-14 were prepared analogously to the process from Example 2. 
     EXAMPLE 3 
     Preparation of (R)-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]-guanidino}-N-(4-methoxybenzyl)-3-phenylpropionamide trifluoroacetate 
     a) tert-Butyl[1-[2-(3,4-dimethoxyphenyl)acetylamino]-1-pyrazol-1-ylmeth-(Z)-ylidene]carbamate 
     
       
         
         
             
             
         
       
     
     1.17 g (29.38 mmol; 60% suspension in paraffin oil) of sodium hydride are added to the solution of 2.42 g (8.4 mmol) of 2-(3,4-dimethoxyphenyl)-N-(iminopyrazol-1-ylmethyl)acetamide (1c)) in 50 ml of tetrahydrofuran and 2 ml of dimethylformamide with ice-cooling and under a nitrogen atmosphere, and the mixture is stirred for 20 min. After addition of 11 g (50.36 mmol) of di-tert-butyl dicarbonate, the reaction mixture is stirred at room temperature for 48 hours, then evaporated to dryness, the residue is taken up in 10 ml of 5% sodium hydrogencarbonate solution, and the aqueous mixture is extracted three times with 10 ml of ethyl acetate each time. After the combined organic extracts have been dried over sodium sulfate and the solvent has been stripped off, the product is purified by column chromatography on silica gel (ethyl acetate/n-heptane), giving 1.86 g (52.5%) of tert-butyl[1-[2-(3,4-dimethoxyphenyl)acetylamino]-1-pyrazol-1-ylmeth-(Z)-ylidene]-carbamate as pale-yellow oil which gradually crystallises. LC/MS: 411 (M+Na).  1 H NMR (400 MHz, DMSO-d 6 ) δ 11.24 (s, 1H), 8.40 (s, 1H), 7.92 (s, 1H), 6.95 (s, 1H), 6.90 (d, J=8.2, 1 H), 6.84 (d, J=8.2, 1 H), 6.63 (s, 1H), 3.76 (s, 3H), 3.75 (s, 2H), 3.74 (s, 3H), 1.38 (s, 9H). 
     
       
         
         
             
             
         
       
     
     50 mg of N-ethyldiisopropylamine and 54.5 mg (0.17 mmol) of (R)-2-amino-N-(4-methoxybenzyl)-3-phenylpropionamide hydrochloride (prepared analogously to 1 b)) are added to the solution of 60 mg (0.15 mmol) of tert-butyl[1-[2-(3,4-dimethoxyphenyl)acetylamino]-1-pyrazol-1-ylmeth-(Z)-ylidene]carbamate (2a)) in 3 ml of tetrahydrofuran, the reaction mixture obtained in this way is stirred at room temperature for 18 hours and then evaporated to dryness. The residue is then dissolved in 3 ml of dichloromethane, 0.5 ml of trifluoroacetic acid is added to the solution, the reaction solution is stirred at room temperature for 15 hours and then evaporated in vacuo. After trituration of the residue with methanol, the product is filtered off with suction and dried at 60° C. in a vacuum drying cabinet for three hours, giving 42 mg (53.8%) the title compound as white powder. LC/MS (M+H) 505.  1 H NMR (500 MHz, DMSO-d 6 ) δ 11.31 (s, 1H), 8.94 (d, J=8.0, 1H), 8.84 (s, 2H), 8.69 (t, J=4.9, 1H), 7.28-7.19 (m, 3H), 7.17-7.11 (m, 2H), 7.10 (d, J=8.4, 2H), 6.92 (d, J=8.2, 1H), 6.89 (s, 1H), 6.86 (d, J=8.6, 2H), 6.79 (d, J=8.1, 1H), 4.65 (dd, J=12.8, 6.4, 1H), 4.22 (qd, J=14.7, 5.7, 2H), 3.74 (s, 6H), 3.73 (s, 3H), 3.68 (s, 2H), 3.16 (dd, J=13.9, 5.3, 1H), 3.03 (dd, J=13.9, 6.8, 1H). 
     Compounds Nos. 15-67 were prepared analogously to the process from Example 3. 
     EXAMPLE 4 
     (R)-3-Cyclohexyl-2-{N′-[2-(3,4-dimethoxyphenyl)acetyl]-guanidino}-N-(1-ethylpropyl)propionamide 
     a) BOC-guanidine 
     
       
         
         
             
             
         
       
     
     BOC-guanidine was synthesised in accordance with Ando et al., Tetrahedron (2010), 66(32), 6224-6237: 22.93 g (0.24 mol) of guanidinium chloride are added to the solution of 19.2 g (0.48 mol) of sodium hydroxide pellets in 50 ml of water at 0° C. The solution is left to stir for 10 min., a solution of 13.1 g (60 mmol) of di-tert-butyl dicarbonate in 150 ml of acetone is then added in one portion at 0° C., and the reaction mixture is then left to stir at room temperature for 15 hours. The acetone is subsequently stripped off in vacuo, and the aqueous mixture is extracted twice with 50 ml of ethyl acetate. The combined organic phases are washed with 50 ml of saturated sodium chloride solution and dried over sodium sulfate. After the solvent has been stripped off, the residue is recrystallised from ethyl acetate/n-heptane, giving 8.7 g (91%) of BOC-guanidine as white crystals. EI−MS (M+): 159. 
     b) (3,4-Dimethoxyphenyl)acetyl chloride 
     
       
         
         
             
             
         
       
     
     5 μl of dimethylformamide and then, dropwise, 10.93 ml (127.42 mmol) of oxalyl chloride are added to the solution of 5.00 g (25.48 mmol) of 3,4-dimethoxyphenylacetic acid in 100 ml of dichloromethane with ice-cooling and stirring, and, after removal of the cooling, the mixture is stirred at room temperature for two hours. The reaction mixture is subsequently evaporated to dryness in vacuo, the residue is taken up in 10 ml of toluene, the toluene is stripped off again, the residue is taken up again in 10 ml of toluene, and the toluene is stripped off again. The residue was finally taken up twice in 10 ml of diethyl ether each time, and the diethyl ether was stripped off again, giving 5.5 g (96%) of (3,4-dimethoxyphenyl)acetyl chloride, which is reacted further without additional purification. 
     c) N-[2-(3,4-Dimethoxyphenyl)acetyl]-N′-(tert-butyloxycarbonyl)guanidine 
     
       
         
         
             
             
         
       
     
     8.72 ml of N-ethyldiisopropylamine are added to the solution of 4.08 g (25.62 mmol) of BOC-guanidine (3a)) in 400 ml of dichloromethane, a solution of 5.50 g (25.62 mmol) of (3,4-dimethoxyphenyl)acetyl chloride (3b)) in 70 ml of dichloromethane is then slowly added dropwise under nitrogen at −10° C., the mixture is then left to stir with ice-cooling for one hour, and finally warmed to room temperature over the course of two hours. The reaction solution is then washed with 20 ml each of 5% sodium hydrogencarbonate solution and saturated sodium chloride solution and then dried over sodium sulfate. After the desiccant has been filtered off and the solvent has been stripped off, the product is purified by column chromatography on silica gel (ethyl acetate/n-heptane), giving 7.1 g (82.5%) of N-[2-(3,4-dimethoxyphenyl)acetyl]-N′-(tert-butyloxycarbonyl)-guanidine as yellow oil. LC/MS (M+H−BOC) 238. 
     d) tert-Butyl {[2-(3,4-dimethoxyphenyl)acetylamino]-[(Z)-trifluoromethanesulfonylimino]methyl}carbamate 
     
       
         
         
             
             
         
       
     
     (2010), 66(32), 6224-6237 
     Analogously to the literature (Feichtinger et al., J. Org. Chem., (1998), 63, 8432-8439), 5.1 g (15.12 mmol) of N-[2-(3,4-dimethoxyphenyl)acetyl]-N′-(tert-butyloxycarbonyl)guanidine (3c)); were dissolved in 50 ml of dichloromethane under an N 2  atmosphere. 5.24 ml of triethylamine were added to this solution, and the mixture was cooled to −78° C. 5.5 ml (33.26 mmol) of trifluoromethanesulfonic anhydride dissolved in 10 ml of dichloromethane were added dropwise to this solution at such a rate that the temperature did not rise above −65° C. The reaction mixture was then left to stir at −70° C. for a further 30 min. and then allowed to come to room temperature overnight. Reaction solution was then washed with 10 ml each of 1N sodium hydrogensulfate solution and water, dried over sodium sulfate, filtered and evaporated. The product was purified by column chromatography on silica gel (ethyl acetate/n-heptane), giving 4.4 g (58.1%) of tert-butyl {[2-(3,4-dimethoxyphenyl)acetylamino]-[(Z)-trifluoromethanesulfonylimino]methyl}carbamate LC/MS (M+H−BOC) 370. 
     
       
         
         
             
             
         
       
     
     35.43 μl of triethylamine were added to the solution of 60 mg (0.13 mmol) of tert-butyl {[2-(3,4-dimethoxyphenyl)acetylamino]-[(Z)-trifluoromethanesulfonylimino]methyl}carbamate (3d)) and 35.4 mg (0.13 mmol) of (R)-2-amino-3-cyclohexyl-N-(1-ethylpropyl)propionamide hydrochloride (prepared from (R)-2-tert-butoxycarbonylamino-3-cyclohexylpropionic acid and 1-ethyl-propylamine analogously to Example 1 b)) in 2 ml of dichloromethane, and the reaction mixture was stirred at room temperature for 18 hours. 1 ml of trifluoroacetic acid was subsequently added to the reaction mixture, the mixture was stirred at room temperature for a further two hours, then evaporated to dryness in vacuo, and the product was purified by column chromatography (RP-HPLC select B; 0.1% solution of trifluoroacetic acid in acetonitrile/water), giving 21 mg (28.4%) of the title compound as amorphous white powder. LC/MS (M+H) 461.  1 H NMR (500 MHz, DMSO-d 6 ) δ 11.08 (s, 1H), 8.89 (d, J=7.9, 1 H), 8.80 (broad s, 2H), 6.92 (d, J=8.2, 1 H), 6.90 (d, J=1.6, 1 H), 6.81 (dd, J=8.2, 1.5, 1 H), 1.74-1.53 (m, 6H), 1.53-1.41 (m, 2H), 1.34 (dt, J=13.5, 7.5, 2H), 1.25 (m, 2H), 1.20-1.06 (m, 3H), 1.00-0.84 (m, 2H), 0.81 (td, J=7.4, 4.0, 6H). 
     Compounds Nos. 68-350 were prepared analogously to the process from Example 4. 
     Abbreviations 
     DCM=dichloromethane 
     DMA=dimethylacetamide 
     DMF=dimethylformamide 
     EA=ethyl acetate 
     MTBE=methyl tert-butyl ether 
     PE=petroleum ether 
     RT=room temperature 
     TFA=trifluoroacetic acid 
     EXAMPLE 5 
     In-Vitro Fluorescence Assay for the Identification of Cathepsin D Inhibitors 
     In order to identify modulators of cathepsin D activity, a continuous enzymatic test was carried out with a synthetic peptide which carries a fluorescent group (MCA=(7-methoxycoumarin-4-yl)acetyl) which is quenched by energy transfer from a Dpn (2,4 dinitrophenyl) group on the same molecule, in Greiner 384-well nb microtitre plates. Cleavage of the peptidic substrate by cathepsin D causes an increase in the fluorescence intensity. In order to determine the efficacy of substances, the time-dependent increase in the fluorescence intensity in the presence of the substance was compared with the time-dependent increase in fluorescence in the absence of substances. The reference substance used was pepstatin A (Sigma-Aldrich). The substrate used was MCA-GKPILFFRLK(Dnp)d-R—NH 2  (Enzo Life Sciences, Lörrach). The enzyme employed was cathepsin D isolated from the human liver (Sigma-Aldrich) in a final concentration of 1.4 nM. The test was carried out in 100 mM sodium acetate buffer, 1.25% (v/v) of DMSO, 0.25% (w/v) of Chaps, pH 5.5. 2 μl of each substance solution with serially diluted substance concentration were added to in each case 4 μl of cathepsin D solution and incubated at room temperature for 10 min. The reaction was started by addition of 2 μl of substrate solution (final concentration 5 μM). After carrying out a starting-point fluorescence measurement (excitation wavelength 340 nm/emission wavelength 450 nm) using an Envision multilabel reader (Perkin Elmer), the reaction was incubated at room temperature for 60 min. The amount of peptide fragment cleaved off during the reaction time was subsequently measured by determination of the increase in the fluorescence intensity at 450 nm (excitation wavelength 340 nm). 
     The IC 50  values of the compounds according to the invention are shown in Table 2 from Example 1. 
     EXAMPLE 6 
     Cartilage Explant Assay 
     In order to investigate the effect of potential cathepsin D inhibitors on cartilage degradation, a pH-induced model based on bovine explants is used. The pH of the medium in which the explants are cultivated is matched here to the pathophysiological pH of an arthrotic knee. This pH is pH 5.5. In this ex vivo model, potential cathepsin D inhibitors are subsequently investigated for their action with respect to stopping of the cartilage degradation process. If the cartilage is destroyed, glycosaminoglycans (GAGs) are released into the cell culture supernatant. The amount of GAGs liberated can be determined quantitatively with the aid of DMMB (dimethylmethylene blue hydrochloride). If sulfated GAGs are detected using dimethylmethylene blue hydrochloride, the decrease in the absorption at 633 nm is utilised. Since work can also be carried out at very low GAG concentrations, a dye/GAG complex does not precipitate out even after extended incubation of DMMB with GAG, which sometimes happens after only a short time in other measurement methods. In order to determine the concentration, a calibration line is also recorded using chondroitin sulfate. The GAG values can be used to calculate an IC 50  value, i.e. a concentration at which a substance exhibits 50% of its action. 
     Solutions: 
     Incubation Medium, pH 7.4: 
     DMEM without FBS, addition of 1% of Pen/Strep and 30 μg/ml of ascorbic acid, the medium is not stored. 
     Incubation Medium, pH 5.5: 
     DMEM without FBS, the pH is adjusted by addition of MES and monitored using a pH meter, addition of 1% of Pen/Strep and 30 μg/ml of ascorbic acid. 
     Solutions for the GAG Measurement: 
     DMMB colouring solution (V=500 ml): 
     Dissolve 8 mg of DMMB (dimethylmethylene blue) in 2.5 ml of ethanol+1 g of sodium formate+1 ml of formic acid, make up to 500 ml with bidistilled water. 
     Incubation Medium: FBS (Medium without FBS) 
     Chondroitin Sulfate Solutions (Standard Curve) 
     Preparation of standard solutions with the following concentrations: 50 μg/ml; 25 μg/ml; 12.5 μg/ml; 6.25 μg/ml; 3.125 μg/ml; 1.56 μg/ml; 0.78 μg/ml and a blank control of the medium. The preparation of the standard solution is carried out in the medium with which the experiment was also carried out. 
     1.) Procedure: pH-Induced Cartilage Degradation of Bovine Explants 
     The bovine explants are firstly prepared. The induction of the cartilage degradation is carried out in 96-multiwell plates. One explant is cultivated per well. In each case, 200 μl of DMEM (incubation medium pH 5.5) without FBS+30 μg/ml of ascorbic acid are added. Thus negative control, explants (n=4) are incubated at pH 7.4 (without FBS). This control is not included in the calculation of the data, but instead ensures that the pH change has the desired effect on the liberation of GAG. At this point, the substances to be tested are added. No pre-incubation of the explants is carried out. The explants are cultivated with the corresponding substances for 3 days in the incubator at 37° C. and 7.5% CO 2 . 
     2.) Incubation Procedure 
     In order to investigate the effect of cathepsin D inhibitors on the liberation of GAG (glycosaminoglycan), the substances are employed in the desired concentration and cultivated for 3 days. The compounds to be tested are tested in a first experiment in a concentration of 1 μM and 1% of DMSO. Substances which have an effect of &gt;50% on the liberation of GAG (this corresponds to &lt;50% of the control in the Assay Explorer) are tested in the next experiment at 100 nM and 1% of DMSO. Substances which have an effect of &gt;50% on the liberation of GAG under these conditions (this corresponds to &lt;50% of the control in the Assay Explorer) are tested in a concentration/effect relationship. The compounds here are investigated in the following concentrations: 30 μM, 10 μM, 3 μM, 1 μM, 0.3 μM, 0.1 μM, 0.03 μM, 0.01 μM. 
     The positive control used is pepstatin A with a concentration of 0.01 μM. 
     The assay window is defined by the control (pH 5.5), defined as 0% effect, and the control pH 5.5+0.01 μM pepstatin A, defined as 100% effect. After incubation for 3 days, the cell culture supernatants are collected and stored at −20° C. or measured directly. The amount of liberated GAG is measured photometrically. 
     The effect (1 value) of the respective substance in % based on the positive control (pH 5.5+0.01 μM pepstatin A) and the negative control (pH 5.5) is reported for concentrations of 1 μM and 100 nM. The value represents the average of 4 replicants. In the determination of a concentration/effect relationship, an IC 50  value is reported to the database (Assay Explorer). 
     4.) Measurement 
     The cell culture supernatants (200 μl) are either measured directly or stored at −20° C. In order to ensure an accurate determination of the concentration (μg/ml of GAG in the supernatant) of GAG, the measurement values must be located in the linear region of the standard curve. In order to ensure this, various dilutions are routinely introduced (1/5, 1/10, 1/20, 1/40). The dilutions are prepared with medium and introduced automatically (Hamilton) into a 384-well plate (15 μl). 60 μl of DMMB solution are likewise added automatically (or using a multichannel pipette). A rapid colour reaction occurs, which is subsequently measured at 633 nm using a plate reader (for example Envision). 
     Depending on the amount of sample present, at least one double determination is carried out. 
     The data are provided by the MTP reader as csv or xls files and stored as raw data based on this format (xls) or used for the calculation of the percentage effect of the particular compound. 
     5.) Quality Controls 
     As control for the induction of the pH-induced cartilage degradation, 4 explants are incubated at pH 7.4. This corresponds to the physiological pH of the cartilage, and no effect on the liberation of GAG is thus expected here. These GAG values (μg/ml of supernatant) are thus always significantly lower than the GAG values for incucation at pH 5.5. 
     A further control, which both serves for checking of the experiment, but is also important for the definition of the assay window, is the pepstatin control (pH 5.5+0.01 μM pepstatin A). This substance non-specifically blocks the activity of most proteases and thus determines the maximum possible effect of a compound. 
     6.) Results 
     All compounds measured exhibited an IC 50  value of 10 −8  to 10 −10  M in the GAG assay. 
     (1) Klompmakers, A. &amp; Hendriks, T. (1986) Anal. Biochem. 153, 80-84, Spectrophotometric Determination of Sulfated Glycosaminoglycans. 
     (2) Groves, P. J. et al. (1997) Anal. Biochem. 245, 247-248 Polyvinyl alcohol-stabilised binding of sulfated GAGs to dimethylmethylene blue. 
     EXAMPLE 7 
     Investigation of Anti-Hyperalgesic Effect in Animals 
     In order to induce an inflammation reaction, a carrageenan solution (CAR, 1%, 50 μl) was injected intra-articularly on one side into a rat knee joint. The uninjected side was used for control purposes. Six animals per group were used. The threshold was determined by means of a micrometer screw (medial-lateral on the knee joint), and the thermal hyperalgesia was determined by means of a directed infrared light source by the Hargreaves method (Hargreaves et al., 1988) on the sole of the foot. Since the site of inflammation (knee joint) is different from the site of measurement (paw sole), use is made here of the term secondary thermal hyperalgesia, the mechanism of which is of importance for the discovery of effective analgesics. 
     Experimental description of thermal hyperalgesia (Hargreaves test): the experimental animal is placed in a plastic chamber on a quartz sheet. Before testing, the experimental animal is firstly given about 5-15 minutes time to familiarise itself with the environment. As soon as the experimental animal no longer moves so frequently after the familiarisation phase (end of the exploration phase), the infrared light source, whose focus is in the plane of the glass bottom, is positioned directly beneath the rear paw to be stimulated. An experiment run is then started by pressing the button: infrared light results in an increase in the skin temperature of the rear paw. The experiment is terminated either by the experimental animal raising the rear paw (as an expression of the pain threshold being reached) or by automatic switching-off of the infrared light source when a prespecified maximum temperature has been reached. Light reflected by the paw is recorded as long as the experimental animal sits still. Withdrawal of the paw interrupts this reflection, after which the infrared light source is switched off and the time from switching on to switching off is recorded. The instrument is calibrated in such a way that the infrared light source increases the skin temperature to about 45 degrees Celsius in 10 s (Hargreaves et al. 1988). An instrument produced by Ugo Basile for this purpose is used for the testing. 
     CAR was purchased from Sigma-Aldrich. The specific cathepsin D inhibitors according to the invention were administered out intra-articularly 30 minutes before the CAR. Triamcinolone (TAC) in an amount of 10 μg/joint was used as positive control, and the solvent (vehicle) was used as negative control. The hyperalgesia is quoted as the difference in the withdrawal times between the inflamed and non-inflamed paw. 
     Result: TAC was capable of reducing the CAR-induced swelling, but the specific cathepsin D inhibitors according to the invention were not. In contrast, the specific cathepsin D inhibitors according to the invention were able to reduce the extent of thermal hyperalgesia as a function of the dose. 
     Assessment: it has been shown that the compounds of the present invention exert an anti-hyperalgesic action. This can be postulated, since the compounds exhibited no influence on inflammatory swelling and thus on the hyperalgesia trigger. It can thus be assumed that the compounds develop a pain-reducing action in humans. 
     EXAMPLE 8 
     Stability of the Compounds According to the Invention in Bovine Synovial Fluid 
     1.) Extraction of Bovine Synovial Fluid 
     In the preparation of bovine explants (for the diffusion chamber or other assays), either cow hoof (metacarpal joints) or cow knee is used. The synovial fluid can be obtained from both joints. To this end, the synovial fluid is carefully removed from the open joint using a 10 ml syringe and a cannula and transferred into prepared 2 ml Eppendorf vessels. The Eppendorf vessels are labelled depending on the animal (cow passport is available). It must be ensured here that blood does not enter the joint gap during preparation of the joints. If this is the case, the synovial fluid will become a reddish colour and must consequently be discarded. The synovial fluid is basically highly viscous and clear to yellowish in colour. The removal together with a macroscopic analysis of the synovial fluid is documented. 
     2.) Batch for Stability Testing of Substances in SF 
     In order to check the stability of individual compounds, a pool of four different bovine synovial fluids is mixed. To this end, about 1 ml per SF is used. The mixture is prepared directly in a 5 ml glass vessel. The SFs are mixed thoroughly, but carefully. No air bubbles or foam should form. To this end, a vortex unit is used at the lowest speed. The compounds to be tested are tested in an initial concentration (unless required otherwise) of 1 μM. After addition of the substance, the batch is again mixed thoroughly and carefully. For visual monitoring, all SF batches are photographed, and the pictures are filed in the eLabBio file for the corresponding experiment. FIG. 1 shows photo documentation of this type by way of example. The batches are incubated in the incubator for 48 h at 37° C. and 7.5% CO 2 . 
     3.) Sampling 
     The sampling is carried out after the pre-agreed times (unless required otherwise, see below). 200 μl of the SF are removed from the mixture per time and transferred directly into a 0.5 ml “low-binding” Eppendorf vessel. “Low-binding” Eppendorf vessels are used in order to minimise interaction of the substances with the plastic of the vessels. 200 μl of acetonitrile have already been introduced into the Eppendorf vessel, so that a 1+1 mixture of the SF forms thereafter. This simplifies the subsequent analysis, but precipitation of protein may occur immediately after addition of the SF. This should be noted on the protocol. The 0 h sample is taken immediately after addition of the substance. This corresponds to the 100% value in the stability calculation. Ideally, the concentration employed should be retrieved here. The samples can be frozen at −20° C.
         0 h   6 h   24 h   48 h       

     The negative control used is SF without substance. The positive control used is SF with 1 μM of substance. This corresponds to the 0 h value and thus 100% stability. 
     The samples are stored in “low-binding” Eppendorf vessels at −20° C. The samples are subsequently measured quantitatively. 
     4.) Data Processing 
     The concentrations measured (ng/ml) are plotted against the time in a graph (GraphPad Prism®). The percentage stability of the substance is determined here. The 100% value used is the initial value in the SF at time 0 h. The data are stored in eLabBio under the respective experiment number and reported in the MSR database (as percent stability after the corresponding incubation times). 
     5.) Results 
     All compounds measured remained stable. 
     EXAMPLE 9 
     In-Vitro Fluorescence Assay for Identification of Renin-Inhibitory Activity 
     In order to identify modulators of renin activity, a continuous enzymatic test was carried out with a synthetic peptide which carries a fluorescent group Edans (=(5-(aminoethyl)aminonaphthalenesulfonate) which is quenched by energy transfer from a Dabcyl (4′-dimethylaminoazobenzene-4-carboxylate) group on the same molecule, in Greiner 384-well microtitre plates. Cleavage of the peptidic substrate by renin causes an increase in the fluorescence intensity. In order to determine the efficacy of substances, the time-dependent increase in the fluorescence intensity in the presence of the substance was compared with the time-dependent increase in fluorescence in the absence of substances. The reference substance used was renin inhibitor 2 (Z-Arg-Arg-Pro-Phe-His-Sta-Ile-His N-Boc-Lys methyl ester Z) (Sigma-Aldrich). The substrate used was renin FRET substrate I (DABCYL-g-Abu-Ile-His-Pro-Phe-His-Leu-Val-Ile-His-Thr-EDANS) (Anaspec, Fremont Calif.). The enzyme employed was recombinant human renin (Proteos, Kalamazoo, Mich.) in a final concentration of 10 nM. The test was carried out in 50 mM Mops buffer, 1.5% (v/v) of DMSO, 0.1% (w/v) of Igepal®, pH 7.2, 0.5% (w/v) of BSA. 2 μl of each substance solution with serially diluted substance concentration were added to in each case 4 μl of renin solution and incubated at room temperature for 15 min. The reaction was started by addition of 4 μl of substrate solution (final concentration 5 μM). After carrying out a starting-point fluorescence measurement (excitation wavelength 340 nm/emission wavelength 495 nm) using an Envision multilabel reader (Perkin Elmer), the reaction was incubated at 37° C. for 60 min. The amount of peptide fragment cleaved off during the reaction time was subsequently measured by determination of the increase in the fluorescence intensity at 495 nm (excitation wavelength 340 nm). 
     Result: all compounds measured have an IC 50  of the renin selectivity of &gt;30 μM. 
     EXAMPLE 10 
     Injection Vials 
     A solution of 100 g of a compound of the formula I and 5 g of disodium hydrogenphosphate in 3 I of bidistilled water is adjusted to pH 6.5 using 2N hydrochloric acid, filtered under sterile conditions, transferred into injection vials, lyophilised under sterile conditions and sealed under sterile conditions. Each injection vial contains 5 mg of a compound of the formula I. 
     EXAMPLE 11 
     Solution 
     A solution is prepared from 1 g of a compound of the formula I, 9.38 g of NaH 2 PO 4  2H 2 O, 28.48 g of Na 2 HPO 4 . 12 H 2 O and 0.1 g of benzalkonium chloride in 940 ml of bidistilled water. The pH is adjusted to 6.8, and the solution is made up to 1 I and sterilised by irradiation. This solution can be used in the form of eye drops. 
     EXAMPLE 12 
     Ointment 
     500 mg of a compound of the formula I are mixed with 99.5 g of Vaseline under aseptic conditions. 
     EXAMPLE 13 
     Ampoules 
     A solution of 1 kg of a compound of the formula I in 60 I of bidistilled water is filtered under sterile conditions, transferred into ampoules, lyophilised under sterile conditions and sealed under sterile conditions. Each ampoule contains 10 mg of a compound of the formula I.