MXPA01006613A

MXPA01006613A - Protease inhibitors

Info

Publication number: MXPA01006613A
Application number: MXPA/A/2001/006613A
Authority: MX
Inventors: Scott Kevin Thompson; Daniel Frank Veber; Robert Wells Marquis Jr; Yu Ru; Maxwell David Cummings; Dennis Yamashita
Original assignee: Smithkline Beecham Corporation
Priority date: 1998-12-23
Filing date: 2001-06-25
Publication date: 2002-03-26

Abstract

The present invention provides 4-amino-azepan-3-one protease inhibitors and pharmaceutically acceptable salts, hydrates and solvates thereof which inhibit proteases, including cathepsin K, pharmaceutical compositions of such compounds, novel intermediates of such compounds, and methods for treating diseases of excessive bone loss or cartilage or matrix degradation, including osteoporosis;gingival disease including gingivitis and periodontitis;arthritis,more specifically, osteoarthritis and rheumatoid arthritis;Paget's disease;hypercalcemia of malignancy;and metabolic bone disease, comprising inhibiting said bone loss or excessive cartilage or matrix degradation by administering to a patient in need thereof a compound of the present invention.

Description

PROTEASE INHIBITORS FIELD OF THE INVENTION In general, this invention relates to 4-amino-azepan-3-one protease inhibitors, particularly cysteine and serine protease inhibitors thereof; particularly, it refers to compounds that inhibit cysteine proteases, particularly compounds that inhibit cysteine proteases of the papain superfamily; very particularly it relates to compounds that inhibit cysteine proteases of the cathepsin family, particularly compounds that inhibit cathepsin K. These compounds are particularly useful for the treatment of diseases in which cysteine proteases are implicated, especially diseases of excessive bone loss or cartilage, for example osteoporosis, periodontitis and arthritis.

BACKGROUND OF THE INVENTION Cathepsins are a family of enzymes that are part of the papain cysteine protease superfamily. Cathepsins B, H, L, N and S have been described in the literature. Recently, the cathepsin K polypeptide and the cDNA encoding said polypeptide were described in the U.S. patent.

No. 5,501, 969 (called cathepsin O there). Cathepsin K has been recently expressed, purified and characterized. Bossard M.J. et al. (1996), J. Biol. Chem, 271, 12517-12524; Drake F.H. et al. (1996) J. Biol. Chem., 271, 12511-12516; Bromme D. et al. (1996) J. Biol. Chem. 271, 2126-2132. Cathepsin K has been variably denoted in the literature as cathepsin O or as cathepsin 02. The designation of cathepsin K is considered the most appropriate. Cathepsins function in the normal physiological processes of protein degradation in animals, including humans; for example, in the degradation of connective tissue. However, elevated levels of these enzymes in the body can cause pathological conditions that lead to disease. Thus, cathepsins have been implicated as causative agents of various disease states including, without limitation, infections by Pneumocystis carinii, Trypanosoma cruzi, Trypanosoma brucei brucei and Crithidia fusiculata; as well as schistosomiasis, malaria, tumor metastasis, metachromatic leukodystrophy, muscular dystrophy, amyotrophy and the like. See International Publication Number WO 94/04172, published March 3, 1994 and references cited therein. See also European patent application EP 0 603 873 A1 and references cited therein. Two bacterial cysteine proteases of P. gingivallis, called gingipains, have been implicated in the pathogenesis of gingivitis. Potempa J. et al. (1994) Perspectives in Drug Discovery and Design, 2, 445-458.

It is believed that cathepsin K has a causative role in diseases of excessive loss of bone and cartilage. The bone is composed of a protein matrix in which hydroxyapatite crystals in the form of a needle or plate are incorporated. Collagen type I represents the main structural protein of bone, comprising approximately 90% of the protein matrix. The remaining 10% of the matrix is composed of several non-collagenous proteins that include osteocalcin, proteoglycans, osteopontin, thrombospondin, fibronectin, and bone sialoprotein. The bone of the skeleton undergoes remodeling in discrete foci throughout life. These foci, or remodeling units, undergo a cycle consisting of a phase of bone resorption followed by a phase of bone replacement. The resorption of bone is carried out by osteoclasts, which are multinuclear cells of hematopoietic lineage. The osteoclasts adhere to the surface of the bone and form a hermetic sealing zone, followed by extensive ripple of the membrane on its apical surface (ie, resorption). This creates a closed extracellular compartment on the surface of the bone, which is acidified by proton pumps in the curled membrane, and in which the osteoclast secretes proteolytic enzymes. The low pH of the chamber dissolves the hydroxyapatite crystals on the surface of the bone, whereas proteolytic enzymes digest the protein matrix. In this way, a lagoon or resorption pit is formed. At the end of this phase of the cycle, the osteoblasts reserve a new protein matrix that is subsequently mineralized. In several pathological conditions such as osteoporosis and Paget's disease, the normal balance between resorption and bone formation is interrupted, and there is a net loss of bone in each cycle. Finally, this leads to weakening of the bone and can cause a greater risk of fracture with minimal trauma. Several published studies have shown that cysteine protease inhibitors are effective in inhibiting bone resorption mediated by osteoclast, and indicate an essential function of cysteine proteases in bone resorption. For example, Delaisse and others, Biochem. J., 1980, 192, 365, describe a series of protease inhibitors in a mouse bone organ culture system and suggest that cysteine protease inhibitors (e.g., leupeptin, Z-Phe-Ala-CHN2) prevent resorption of bone, whereas serine protease inhibitors are ineffective. Delaisse and others, Biochem. Biophys. Res. Commun., 1984, 125, 441, describe that E-64 and leupeptin are also effective in preventing bone resorption in vivo, as measured by acute calcium changes in the serum of rats in calcium-deficient diets. Lerner et al., J. Bone Min. Res., 1992, 7, 433, describe that cystatin, an endogenous cysteine protease inhibitor, inhibits bone resorption stimulated by PTH in the mouse skull. Other studies, such as Delaisse and others, Bone, 1987, 8, 305; Hill et al., J. Cell. Biochem., 1994, 56, 118; and Everts et al., J. Cell. Physiol., 1992, 150, 221, also report a correlation between the inhibition of cysteine protease activity and bone resorption. Tezuka et al., J. Biol. Chem. 1994, 269, 1106; Inaoka and others, Biochem. Biophys. Res. Commun., 1995, 206, 89; and Shi et al., FEBS Lett., 1995, 357, 129 describe that under normal conditions, cathepsin K, a cysteine protease, is abundantly expressed in osteoclasts and may be the main cysteine protease present in these cells. The abundant selective expression of cathepsin K in osteoclasts strongly suggests that this enzyme is essential for bone resorption. Thus, selective inhibition of cathepsin K can provide an effective treatment for diseases of excessive bone loss, including, without limitation, osteoporosis, gingival diseases such as gingivitis and periodontitis, Paget's disease, hypercalcemia of malignancy and metabolic disease of bone. It has also been shown that cathepsin K levels are elevated in osteoarthritic synovium chondroclastic. Thus, selective inhibition of cathepsin K may also be useful for treating diseases of excessive cartilage or matrix degradation, including, without limitation, osteoarthritis and rheumatoid arthritis. Metastatic neoplastic cells also typically express high levels of proteolytic enzymes that degrade the surrounding matrix. In this way, selective inhibition of cathepsin K may also be useful in treating certain neoplastic diseases. Several cysteine protease inhibitors are known. Palmer (1995), J. Med. Chem., 38, 3193, discloses certain vinylsulfones that irreversibly inhibit cysteine proteases, such as cathepsins B, L, S, 02 and cruzain. Other classes of compounds have also been reported such as aldehydes, nitriles, a-ketocarbonyl compounds, halomethylketones, diazomethylketones, (acyloxy) methylketones, cetomethylsulfonium salts and epoxysuccinyl compounds, which inhibit cysteine proteases. See Palmer, ibid., And the references cited therein. The patent of E.U.A. No. 4,518,528, describes peptidylfluoromethylketones as irreversible inhibitors of cysteine protease. The published International patent application No. WO 94/04172, and the European patent applications Nos. EP 0 525 420 A1, EP 0 603 873 A1 and EP 0 611 756 A2, describe alkoxymethyl- and mercaptomethyl-ketones which inhibit the cysteine proteases, cathepsins B, H and L. International patent application No. PCT / US94 / 08868 and European patent application No. EP 0 623 592 A1, describe alkoxymethyl- and mercaptomethyl-ketones that inhibit cysteine protease, IL -1 convertase. Alkoxymethyl and mercaptomethyl ketones have also been described as inhibitors of the serine protease kininogenase (International Patent Application No. PCT / GB91 / 01479). Azapeptides are described which are designed to release the azaamino acid at the active site of serine proteases, and which possess a good leaving group, in Elmore et al., Biochem. J., 1968, 107, 103; Garker and others, Biochem. J., 1974, 139, 555; Gray et al., Tetrahedron 1977, 33, 837; Gupton et al., J. Biol. Chem., 1984, 259, 4279; Powers et al., J. Biol. Chem., 1984, 259, 4288; and it is known that they inhibit serine proteases. In addition, J. Med. Chem., 1992, 35, 4279, discloses certain azapeptide esters as inhibitors of cysteine protease. Antipain and leupeptin are described as reversible inhibitors of cysteine protease in McConnell et al., J. Med. Chem., 33, 86; they have also been described as serine protease inhibitors in Umezawa et al., 45 Meth. Enzymol., 678. E64 and its synthetic analogs are also well-known cysteine protease inhibitors (Barret, Biochem J., 201, 189, and Grinde, Biochem Biophys. Acta, 701, 328). 1,3-diamido-propanones have been described as analgesic agents in the patents of E.U.A. Nos. 4, 749,792 and 4,638,010. In this way, a structurally diverse variety of protease inhibitors has been identified. However, these known inhibitors are not considered suitable for use as therapeutic agents in animals, especially in humans, because they have several drawbacks. These drawbacks include lack of selectivity, cytotoxicity, low solubility and elimination of plasma too fast. Therefore, there is a need for methods of treating diseases caused by pathological levels of proteases, particularly of cysteine proteases; particularly of cathepsins; very particular of cathepsin K; and of novel inhibitor compounds that are useful in such methods. The present inventors have now discovered a novel class of 4-amino-azepan-3-one compounds that are protease inhibitors, most particularly of cathepsin K.

BRIEF DESCRIPTION OF THE INVENTION An object of the present invention is to provide carbonyl-4-amino-azepan-3-one protease inhibitors, particularly cysteine and serine protease inhibitors thereof; particularly compounds of these which inhibit cysteine proteases; in particular compounds of these which inhibit cysteine proteases of the papain superfamily; in particular compounds of these which inhibit cysteine proteases of the cathepsin family; very particularly compounds of these which inhibit cathepsin K; and that are useful for treating diseases that can be therapeutically modified by altering the activity of said proteases. Therefore, in the first aspect, this invention provides a compound according to formula I. In another aspect, this invention provides a pharmaceutical composition comprising a compound according to formula I and a pharmaceutically acceptable carrier, diluent or excipient. In another aspect, this invention provides intermediates useful in the preparation of the compounds of formula I. In another aspect, this invention provides a method of treating diseases in which the pathology of the disease can be therapeutically modified by inhibiting proteases, particularly cysteine and serine proteases; particularly cysteine proteases; in particular cysteine proteases of the papain superfamily; in particular cysteine proteases of the cathepsin family; very particularly cathepsin K. In a particular aspect, the compounds of this invention are especially useful for treating diseases characterized by bone loss, such as osteoporosis, and gingival diseases such as gingivitis and periodontitis; or due to excessive degradation of cartilage or matrix, such as osteoarthritis and rheumatoid arthritis.

DETAILED DESCRIPTION OF THE INVENTION The present invention provides compounds of formula I: I where: R1 is selected from the group consisting of: R 2 is selected from the group consisting of: H, C 1-6 alkyl, (C 3-6) cycloalkyl-C 0-6 alkyl, Ar-C 6 alkyl. Het-C0-6 alkyl, R9C (O) -, R9C (S) -, R9SO2-, R9OC (O), R9R11NC (O) -, R9R11NC (S) -, R9 (R11) NSO2-, R3 is selected from the group consisting of: H, C-? -6 alkyl, C2-6 alkenyl, C2.6 alkynyl, Het-C0-6 alkyl and Ar-alkyl of Co-ßi R3 and R ' they can be joined to form a pyrrolidine (204), piperidine or morpholine ring; R4 is selected from the group consisting of H, C-? 6 alkyl, (C3.6) cycloalkyl-Co-6 alkyl, Co-6 alkyl aryl, C0-6 alkyl-Het, R5C (O ) -, R5C (S) -, R5SO2-, R5OC (O) -, R5R13NC (O) -, and R5R13NC (S) -; R5 is selected from the group consisting of: H, C-? 6 alkyl, C2_6 alkenyl, C2-6 alkynyl, C3_6 cycloalkyl-Co-β alkyl, Co-alkyl 6 and Het-alkyl of Co-β; R6 is selected from the group consisting of: H, C? -6 alkyl, Ar-C6 alkyl, and Het-alkyl of Co-β; R7 is selected from the group consisting of: H, C-? -6 alkyl, (C3-6) cycloalkyl-C0-6 alkyl, Ar-C0-6 alkyl, Het-alkyl of Co-6, R10C ( O) -, R10C (S) -, R10SO2-, R10OC (O) -, R10R14NC (O) -, and R10R14NC (S); R8 is selected from the group consisting of: H, C-? -6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Het-C0-6 alkyl and Ar-Co-βalkyl; R9 is selected from the group consisting of: C-? -6 alkyl, (C3-6) cycloalkyl-C0-6 alkyl, Ar-C06 alkyl and Het-C06 alkyl; R10 is selected from the group consisting of: C ^ e alkyl, (C3-6) cycloalkyl- C0-6 alkyl, Ar-C06 alkyl and Het-C06 alkyl; R1 is selected from the group consisting of: H, C-? -6 alkyl, Ar-alkyl of Co-β and Het-alkyl of Co-β; R12 is selected from the group consisting of: H, C? -6 alkyl, Ar-C06 alkyl and Het-alkyl of Co-β; R 13 is selected from the group consisting of: H, C 1-6 alkyl, Ar-C 1-6 alkyl and Het-C 1-6 alkyl; R14 is selected from the group consisting of: H, C? .6 alkyl, Ar-C alquilo-alkyl and Het-C de-alkyl, 'R' is selected from the group consisting of: H, C alquilo-alkyl -? - 6, Aralkyl of Co-6 and Het-alkyl of Co-β; R "is selected from the group consisting of: H, Ci-β alkyl, Ar-C0-6 alkyl or Het-alkyl of Co-β; R "'is selected from the group consisting of: H, C-? -6-alkyl, (C3-6) cycloalkyl-Co-6-alkyl, C0-T-alkyl and Het-alkyl of Co-β; X is selected from the group consisting of: CH2, S and O; Z is selected from the group consisting of: C (O) and CH2; and pharmaceutically acceptable salts, hydrates and solvates thereof. In the compounds of formula I, when R1 is R3 is selected from the group consisting of: H, C-i-β alkyl, C2-6 alkenyl, C2.6 alkynyl, Het-alkyl of co-β and Ar-alkyl of Co-β; R 3 is preferably selected from the group consisting of H, Ar-C 6 alkyl and C 1-6 alkyl; R3 is most preferably selected from the group consisting of: H, methyl, ethyl, n-propyl, 2-propyl, n-butyl, isobutyl, 2-butyl, cyclopropylmethyl, cyclohexylmethyl, 2-methanesulfonyl-ethyl, 1-hydroxyethyl, toluyl , naphthalene-2-yl-methyl, benzyloxymethyl and hydroxymethyl. R3 is preferably selected from the group consisting of: toluyl, isobutyl and cyclohexylmethyl. R3 is most preferably sobutyl. R4 is selected from the group consisting of H, C? .6 alkyl, (C3-6) cycloalkyl-Co-β alkyl, Ar-Co-β alkyl, Het-alkyl of Co-β, R5C (O) -, R5C (S) -, R5SO2-, R5OC (O) -, R5R13NC (O) -, and R5R13NC (S) -; R4 is preferably selected from the group consisting of: R5OC (O) -, R5C (O) - and R5SO2-. R4 is most preferably R5C (O) -.

In some embodiments, R4 is preferably methanesulfonyl. R5 is selected from the group consisting of: C1-6 alkyl, C2.6 alkenyl, C2-6 alkynyl, (C3-β) cycloalkyl-C0-β alkyl, Ar-6-alkyl and Het- C0-6 alkyl; R5 is preferably selected from the group consisting of: Ci-β alkyl, Ar-Co-β alkyl and Het-alkyl of Co-β- Most preferably, and especially when R 4 is R 5C (O) -, R 5 is selected of the group consisting of: methyl, especially halogenated methyl, especially trifluoromethyl; in particular methyl substituted by alkoxy, especially phenoxy-methyl, 4-fluoro-phenoxy-methyl; in particular methyl substituted with heterocycle, especially 2-thiophenyl-methyl; butyl, especially butyl substituted with aryl, especially 4- (4-methoxy) phenyl-butyl; isopentyl; cyclohexyl; pentanonyl, especially 4-pentanonyl; butenyl, especially butenyl substituted with aryl, especially 4,4-bis (4-methoxyphenyl) but-3-enyl; acetyl; phenyl, especially phenyl substituted with one or more halogens, especially 3,4-dichlorophenyl and 4-fluorophenyl, especially phenyl substituted with one or more alkoxy groups, especially 3,4-dimethoxy-phenyl, 3-benzyloxy-4-methoxy- phenyl, especially phenyl substituted with one or more sulfonyl groups, especially 4-methanesulfonyl-phenyl; benzyl; naphthalenyl, especially naphthylene-2-yl; benzo [1,3] dioxolyl, especially benzo [1,3] dioxol-5-yl; furanyl, especially furan-2-yl, especially substituted furanyl such as 5-n-tro-fu-2-yl, 5- (4-nitrophenyl) -furan-2-yl, 5- (3-trifluoromethyl-phenyl) ) -furan-2-ilo; in particular furanyl substituted with halogen, especially 5-bromo-furan-2-yl; especially furanyl substituted with aryl, especially 5- (4-chloro-phenyl) -furan-2-yl; tetrahydrofuran-2-yl; benzofuranyl, especially benzofuran-2-yl and substituted benzofuranyl, especially 5- (2-piperazine-4-carboxylic acid-ethoxy) -benzofuran-2-yl ter-butyl ester, 5- (2-morpholino-4-yl-ethoxy) ) benzofuran-2-yl, 5- (2-piperazin-1-yl-ethoxy) benzofuran-2-yl, 5- (2-cyclohexyl-ethoxy) benzofuran-2-yl; in particular benzofuranyl substituted with alkoxy, especially 7-methoxy-benzofuran-2-yl, 5-methoxy-benzofuran-2-yl, 5,6-dimethoxy-benzofuran-2-yl; in particular benzofuranyl substituted with halogen, especially 5-fluoro-benzofuran-2-yl (255), 5,6-difluoro-benzofuran-2-yl; especially benzofuranyl substituted with alkyl, especially 3-methyl-benzofuran-2-yl; benzo [b] thiophenyl, especially benzo [b] thiophen-2-yl; in particular benzo [b] thiophenyl substituted with alkoxy, especially 5,6-dimethoxy-benzo [b] thiophen-2-yl; quinolinyl, especially quinolin-2-yl, quinolin-3-yl, quinolin-4-yl, quinolin-6-yl and quinolin-8-yl; quinoxalinyl, especially quinoxalin-2-yl; 1,8-naphthyridinyl, especially 1,8-naphthyridin-2-yl; indolyl, especially indole-2-yl, especially indole-6-yl, indole-5-yl, especially indolyl substituted with alkyl, especially N-methyl-indol-2-yl; pyridinyl, especially pyridin-2-yl, pyridin-5-yl, especially 1-oxy-pyridin-2-yl; especially pyridinyl substituted with alkyl, especially 2-methyl-pyridin-5-yl; thiophenyl, especially thiophen-3-yl, especially thiophenyl substituted with alkyl, especially 5-methyl-thiophen-2-yl; especially thiophenyl substituted with halogen, especially 4,5-dibromo-thiophen-2-yl; thieno [3,2-D] thiophene, especially thieno [3,2-l)] thiophen-2-yl; in particular thieno [3,2-b] thiophen-2-yl substituted with alkyl, especially 5-tert-butyl-3-methyl-thieno [3,2-b] thiophen-2-yl; isoxazolyl, especially isoxazol-4-yl; especially isoxazolyl substituted with alkyl, especially 3,5-dimethyl-lsoxazol-4-yl; oxazolyl, especially oxazol-4-yl, in particular 5-methyl-2-phenyl-oxazol-4-yl, 2-phenyl-5-trifluoromethyl-oxazol-4-yl; When R4 is R5SO2, R5 is preferably pyridin-2-yl or 1-oxo-pyridin-2-yl.

R 'is selected from the group consisting of: H, C?-6 alkyl, Co-β-Aralkyl and H0-C alquilo-alkyl; Preferably R 'is selected from the group consisting of: H and naphthalen-2-yl-methyl. Most preferably, R 'is H. R "is selected from the group consisting of: H, Ct-β alkyl, Ar-C0-β alkyl and Het-Co-β alkyl; Most preferably, R" is H. R '"is selected from the group consisting of: H, C? _6 alkyl, (C3.6) cycloalkyl-CO-T alkyl and Het-alkyl of Co-β; R"' is preferably selected from the group consisting of of H and 6,6-dimethyl. Most preferably R '"is H. In the compounds of formula I, R 2 is selected from the group consisting of: H, C 1 .6 alkyl) cycloalkyl (C 3-6) -Cal-β alkyl, Ar- Co-e alkyl, Het-alkyl of Co-β. R9C (O) -, R9C (S) -, R9SO2-, R9OC (O) -, R9R11NC (O) -, R9R11NC (S) -, R9 (R11 ) NSO2-, Preferably, R is selected from the group consisting of: Co-eral aralkyl, R9C (O) -, R9SO2, R9R11NC (O) -, and R6 Most preferably, R 2 is selected from the group consisting of: Ar-alkyl of Co-β, R 9 C (O) - and R 9 SO 2. Preferably R2 is R9SO2. In these embodiments: R6 is selected from the group consisting of: H, Ci-β alkyl, Ar-alkyl of CO-T or Het-alkyl of C0-6, preferably H. R7 is selected from the group consisting of: H , Ci-β alkyl, (C3.β) cycloalkyl-Co-βalkyl, Ar-Co-βalkyl, Het-C0-βalkyl, R10C (O) -, R10C (S) -, R10SO2-, R10OC (O) -, R10R14NC (O) -, R10R14NC (S); preferably R7 is R10OC (O). R8 is selected from the group consisting of: H, C-i-β alkyl, C2-6 alkenyl, C2.6 alkynyl, Het-C06 alkyl and Ar-Co-β alkyl; preferably preferably isobutyl alkyl. R9 is selected from the group consisting of: Ci-β alkyl, (C3.β) cycloalkyl-Co-βalkyl, Ar-C06alkyl and Co-βHet-alkyl; R9 is preferably selected from the group consisting of: C-i-β alkyl, Ar-C06 alkyl and Het-alkyl of Co-β- Most preferably, R 9 is selected from the group consisting of: methyl; ethyl, especially ethyl substituted with C 1 -β alkyl, especially 2-cyclohexyl-ethyl; butyl, especially butyl substituted with d-β alkyl, especially 3-methylbutyl; tert-butyl, particularly when R2 is R9OC (O); isopentyl; phenyl, especially phenyl substituted with halogen, especially 3,4-dichlorophenyl, 4-bromophenyl, 2-fluorophenyl, 4-fluorophenyl, 3-chlorophenyl, 4-chlorophenyl; in particular C6 -6 alkoxyphenyl, especially 3-methoxyphenyl, 4-methoxyphenyl, 3,4-dimethoxyphenyl; in particular cyanophenyl, especially 2-cyanophenyl; toluyl, especially toluyl substituted with Het, especially 3- (pyridin-2-yl) toluyl; naphthylene, especially naphthyl-2-ene; benzoic acid, especially 2-benzoic acid; benzo [1,3] dioxolyl, especially benzo [1,3] dioxol-5-yl; benzo [1, 2,5] oxadiazolyl, especially benzo [1, 2,5] oxadiazol-4-yl; pyridinyl, especially pyridin-2-yl, pyridin-3-yl, in particular 1-oxy-pyridinyl, very especially 1-oxy-pyridin-2-yl, 1-oxy-pyridin-3-yl; in particular C alqu. β alkylpyridinyl, especially 3-methyl-pyridin-2-yl, 6-methyl-pyridin-2-yl, thiophene, especially thiophen-2-yl; thiazolyl, especially thiazol-2-yl; 1 H-imidazolyl, especially 1 H-imidazol-2-yl, 1 H-imidazol-4-yl, most especially imidazolyl substituted with C? -6 alkyl, especially 1-methyl-1 H-imidazol-2-yl , 1-methyl-1 H-imidazol-4-yl; 1 H- [1,4] triazolyl, especially 1 H- [1,4] triazol-3-yl; in particular 1 H- [1,4] triazolyl substituted with C 1 -β alkyl, especially 5-methyl-1 H- [1, 2,4] triazoi-3-yl. When R2 is R9SO2, R9 is preferably selected from the group consisting of: pyridin-2-yl and 1-oxy-pyridin-2-yl. R10 is selected from the group consisting of: C-i-β alkyl, (C3-6) cycloalkyl-C0-6 alkyl, Ar-C0-6 alkyl or Het-alkyl-Co-; preferably C 1 - β alkyl, C 0 - 6 Ar - alkyl and C 0 - 6 - Het alkyl - is selected from the group consisting of: C (O) and CH 2. R2 is also preferably: H; toluyl; ethyl substituted with aryl, especially 2-phenyl-ethyl, 2- [3- (pyridin-2-yl) phenyl] ethyl. Preferred are compounds of formula I wherein R "and R" 'are both H. Preferred are compounds of formula I wherein: R1 is R2 is selected from the group consisting of: Ar-Co-βalkyl. R9C (O) -, R9SO2, R9R11NC (O) -, and R6 R3 is selected from the group consisting of: H, C-i-β alkyl and Ar-C06 alkyl; R4 is selected from the group consisting of: R5OC (O) -, R5C (0) - and R5SO2-; R5 is selected from the group consisting of: C-? -6 alkyl, Co-ß-Aralkyl and H-C6-alkyl; R6 is H; R7 is R10OC (O); R8 is C6.6 alkyl; R9 is selected from the group consisting of: C? -6 alkyl, Co-6 Aralkyl and C0-β Het-alkyl; R10 is selected from the group consisting of C 1 -β alkyl, Co-6 Aralkyl and Het-C 1 -alkyl; R 'is H; R "is H; R, M is H; and Z is selected from the group consisting of: C (O) and CH2.

Of these, the compounds of formula I in which R2 is selected from the group consisting of: Ar-C0-6 alkyl, R9C (O) -, R9S02, are highly preferred. Most preferred are compounds of formula I wherein: R 1 is R2 is selected from the group consisting of: Ar-Co-6 alkyl. R9C (O) - and R9SO2; R3 is selected from the group consisting of: H, methyl, ethyl, n-propyl, prop-2-yl, n-butyl, isobutyl, but-2-yl, cyclopropylmethyl, cyclohexylmethyl, 2-methanesulfinyl-ethyl, 1-hydroxyethyl , toluyl, naphthalen-2-yl-methyl, benzyloxymethyl and hydroxymethyl; R4 is R5C (O) -; R5 is selected from the group consisting of: methyl, especially halogenated methyl, especially trifluoromethyl; in particular methyl substituted with alkoxy, especially phenoxy-methyl, 4-fluoro-phenoxy-methyl; in particular methyl substituted with heterocycle, especially 2-thiophenyl-methyl; butyl, especially butyl substituted with aryl, especially 4- (4-methoxy) phenyl-butyl; isopentyl; cyclohexyl; pentanonyl, especially 4-pentanonyl; butenyl, especially butenyl substituted with aryl, especially 4,4-bis (4-methoxyphenyl) -but-3-enyl; acetyl; phenyl, especially phenyl substituted with one or more halogens, especially 3,4-dichlorophenyl and 4-fluorophenyl; in particular phenyl substituted with one or more alkoxy groups, especially 3,4-dimethoxy-phenyl, 3-benzyloxy-4-methoxy-phenyl; especially phenyl substituted with one or more sulfonyl groups, very especially 4-methanesulfonyl-phenyl; benzyl; naphthylene-2-yl; benzo [1,3] dioxolyl, especially benzo [1,3] dioxol-5-yl; furanyl, especially furan-2-yl; especially substituted furanyl, such as 5-nitro-furan-2-yl, 5- (4-nitrophenyl) -furan-2-yl, 5- (3-trifluoromethyl-phenyl) -furan-2-yl; in particular furanyl substituted with halogen, especially 5-bromo-furan-2-yl; especially furanyl substituted with aryl, especially 5- (4-chloro-phenyl) -furan-2-yl; tetrahydrofuran-2-yl; benzofuranyl, especially benzofuran-2-yl and substituted benzofuranyl, especially 5- (2-piperazine-4-carboxylic acid-ethoxy) -benzofuran-2-yl tert-butyl ester, 5- (2-morpholino-4-yl) -ethoxy) -benzofuran-2-yl, 5- (2-piperazin-1-yl-ethoxy) -benzofuran-2-yl, 5- (2-cyclohexyl-ethoxy) -benzofuran-2-yl; in particular benzofuranyl substituted with alkoxy, especially 7-methoxy-benzofuran-2-yl, 5-methoxy-benzofuran-2-yl, 5,6-dimethoxy-benzofuran-2-yl; in particular benzofuranyl substituted with halogen, especially 5-fluoro-benzofuran-2-yl, 5,6-difluoro-benzofuran-2-yl; especially benzofuranyl substituted with alkyl, especially 3-methyl-benzofuran-2-yl. benzo [b] thiophenyl, especially benzo [b] thiophen-2-yl; in particular benzo [b] thiophenyl substituted with alkoxy, especially 5,6-dimethoxy-benzo [b] thiophen-2-yl; quinolinyl, especially quinolin-2-yl, quinolin-3-yl, quinolin-4-yl, quinolin-6-yl and quinolin-8-yl; quinoxalinyl, especially quinoxalin-2-yl; 1,8-naphthyridinyl, especially 1,8-naphthyridin-2-yl; indolyl, especially indole-2-yl, especially indole-6-yl, indole-5-yl, especially indolyl substituted with alkyl, especially N-methyl-yndol-2-yl; pyridinyl, especially pyridin-2-yl, pyridin-5-yl, especially 1 - . 1-oxy-pyridin-2-yl; especially pyridinyl substituted with alkyl, especially 2-methyl-pyridin-5-yl; thiophenyl, especially thiophen-3-yl, especially thiophenyl substituted with alkyl, especially 5-methyl-thiophen-2-yl; especially thiophenyl substituted with halogen, especially 4,5-dibromo-thiophen-2-yl; thieno [3,2-j] thiophene, especially thieno [3,2-b] thiophen-2-yl; in particular thieno [3,2-b] thiophen-2-yl substituted with alkyl, especially 5-tert-butyl-3-methyl-thieno [3,2-b] thiophen-2-yl; isoxazolyl, especially isoxazol-4-yl; especially isoxazolyl substituted with alkyl, especially 3,5-dimethyl-isoxazol-4-yl; oxazolyl, especially oxazol-4-yl, in particular 5-methyl-2-phenyl-oxazol-4-yl, 2-phenyl-5-trifluoromethyl-oxazol-4-yl; R9 is selected from the group consisting of: methyl; ethyl, especially ethyl substituted with Ci-β alkyl, especially 2-cyclohexyl-ethyl; butyl, especially butyl substituted with C? -6 alkyl, especially 3-methylbutyl; tert-butyl, particularly when R2 is R9OC (O); isopentyl; phenyl, especially phenyl substituted with halogen, especially 3,4-dichlorophenyl, 4-bromophenyl, 2-fluorophenyl, 4-fluorophenyl, 3-chlorophenyl, 4-chlorophenyl; in particular C6 -6 alkoxyphenyl, especially 3-methoxyphenyl, 4-methoxyphenyl, 3,4-dimethoxyphenyl; in particular cyanophenyl, especially 2-cyanophenyl; toluyl, especially toluyl substituted with Het, especially 3- (pyridin-2-yl) toluyl; naphthylene, especially naphthyl-2-ene; benzoic acid, especially 2-benzoic acid; benzo [1,3] dioxolyl, especially benzo [1,3] dioxol-5-yl; benzo [1, 2,5] oxadiazolyl, especially benzo [1, 2,5] oxadiazol-4-yl; pyridinyl, especially pyridin-2-yl, pyridin-3-yl, in particular 1-oxy-pyridinyl, very especially 1-oxy-pyridin-2-yl, 1-oxy-pyridin-3-yl; in particular C 1-6 alkylpyridinyl, especially 3-methyl-pyridin-2-yl, 6-methyl-pyridin-2-yl, thiophene, especially thiophen-2-yl; thiazolyl, especially thiazol-2-yl; 1 H-imidazolyl, especially 1 H-imidazol-2-yl (74), 1 H-imidazol-4-yl, most especially imidazolyl substituted with C? -6 alkyl, especially 1-methyl-1 H-imidazole- 2-yl, 1-methyl-1 H-imidazol-4-yl; 1 H- [1,4] triazolyl, especially 1 H- [1,4] triazol-3-yl; in particular 1 H- [1, 2,4] triazolyl substituted with C? -6 alkyl, especially 5-methyl-1 H- [1, 2,4] triazol-3-yl. R 'is H; R "is H; and R '" is H. More preferred are compounds of formula I wherein: R1 is R2 is R9SO2; R3 is isobutyl; R4 is R5C (O); R5 is selected from the group consisting of: 3-methyl-benzofuran-2-yl, thieno [3,2-b] thiophen-2-yl, 5-methoxybenzofuran-2-yl, quinoxalin-2-yl and quinolin-2 -yl, preferably 3-methyl-benzofuran-2-yl; R9 is selected from the group consisting of: pyridin-2-yl and 1-oxy-pyridin-2-yl, preferably 1-oxy-pyridin-2-yl. R 'is H; and R "'is H. The compounds of formula I selected from the following group are particularly preferred embodiments of the present invention: Example Chemical Name No. 1. Benzyl ester of acid. { (S) -1 - [1 - ((S) -2-benzyloxycarbonylamino-4-methyl-pentanoyl) -3-oxo-azepan-4-ylcarbamoyl} carbamic 2. [(S) -1 - (1-benzyl-3-oxo-azepan-4-ylcarbamoyl) -3-methyl-butyl] naphthylene-2-carboxylic acid amide 3. [(S) -1 - ( Benzo [1,3] dioxol-5-carboxylic acid 1-benzyl-3-oxo-azepan-4-ylcarbamoyl) -3-methyl-butyl] 4. [(S) -1 - (1-benzyl-3 benzofuran-2-carboxylic acid-oxo-azepan-4-ylcarbamoyl) -3-methyl-butyl] -amide 5. [(S) -1- (1-benzyl-3-oxo-azepan-4-ylcarbamoyl) -3 -methyl-butyl] benzo acid amide [b} thiophen-2-carboxylic acid 6. naphthylene-2-sulfonyl - [(S) -1 - (1-benzyl-3-oxo-azepan-4-ylcarbamoyl) -3-methyl-butyljamide 7. [(S) -1 - Quinolin-2-carboxylic acid (1-benzyl-3-oxo-azepan-4-ylcarbamoyl) -3-methyl-butyl] -amide 8. [(S) -1 - (1-benzyl-3-oxo-azepan 3,4-dichlorobenzoic acid-4-methyl-butyl] -4- [(S) -methyl-2 - [(quinoline-2-carbonyl) -amino] pentanoylamino] -3-oxo - 1- [2- (3-pyridin-2-yl-pheny] -acetyl] azepanium 10. 1 - ((S) -2-benzyloxycarbonylamino-4-methyl-pentyl) -4-. { (S) -4-methyl-2- [(2-quinoline-2-carbonyl) amino] -pentanoylamino) -3-oxo-azepanium 11. 1-benzoyl-4 - ((S) -2- (benzo [1,3] dioxol-carbonylamino) -4-methyl-pentanoylamino) -3-oxo-azepanium 12. 1-benzoyl-4 - ((S) - 2- (4-fluoro-benzoylamino) -4-methyl-pentanoylamino) 3-oxo-azepanium 13. 3-oxo-4 - ((S) -4-methyl-2- { [5- (2-morpholino -4-yl-ethoxy) -benzofuran-2-carbonyl] amino.}. -pentanoylamino) -1- (4-methyl-pentanoyl) -azepanium 14. [(S) -1- (1-benzenesulfonyl-3-oxo -azepan-4-ylcarbamoyl) -3-methyl- 5- (2-morpholin-4-yl-ethoxy) -benzofuran-2-carboxylic acid butyljamide 15. 4 - ((S) -4-methyl-2- { [5- (2- morpholin-4-yl-ethoxy) -benzofuran-2-carbonyl] amino.}. phenylamino) -3-oxo-azepane-1-carboxylic acid 16. ((S) -3-methyl-1 -. oxo-1 - [2- (3-pyridin-2-yl-phenyl) -acetyl] -azepan-4-ylcarbamoyl.} -butyl) 5- (2-morpholino-4-yl-ethoxy) -amide - benzofuran-2-carboxylic 17. [(S) -1 - (benzoyl-3-oxo-azepan-4-ylcarbamoyl) -3-methyl-butyl] 5- (2-morpholino-4-yl-ethoxy) acid amide ) -benzofuran-2-carboxylic acid 18. [(S) -1 - (1-benzenesulfonyl-3-oxo-azepan-4-ylcarbamoyl) -3-methyl-butyljamide of 5- (2-pyrrolidin-1-yl- ethoxy) -benzofuran-2-carboxylic acid 19. [(S) -1 - (1-benzenesulfonyl-3-oxo-azepan-4-ylcarbamoyl) -3-methyl-butyljamide of 5- (2-piperidin-1-yl) -ethoxy) -benzofuran-2-carboxylic acid 20. ((S) -3-methyl-1 -. {3-oxo-1 - [2- (3-pyridin-2-yl-phenyl) ethyl] -azepan- 4- (2-morpholino-4-yl-ethoxy) -benzofuran-2-carboxylic acid 5-carbamoyl.} -butyl) 21. ((S) -3-methyl-1- { 3-oxo-1- [2- (3-pyridin-2-yl-phenyl) ethyl] azepan-4-ylcarbamoyl} -butyl) naphthalene-2-carboxylic acid amide 22. ((S) -3-methyl-1 -. {3-oxo-1 - [2- (3-pyridin-2-yl-phenyl) ethyl ] -azepan-4-ylcarbamoyl.} -butyl) 1-H-indole-2-carboxylic acid amide 23. [(S) -1- (1-benzenesulfonyl-3-oxo-azepan-4-ylcarbamoyl) -3 1-H-Indole-2-carboxylic acid methyl-butyl-amide 24. [(S) -1 - (1-Benzenesulfonyl-3-oxo-azepan-4-ylcarbamoyl) -3-methyl-butyl-jimide benzofuran-2-acid carboxylic acid 25. [(S) -3-methyl-1 -. { 3-oxo-1 - [2- (3-pyridin-2-yl-phenyl) ethyl] -azepan-4-ylcarbamoyl} -butyl) benzofuran-2-carboxylic acid amide 26. [(S) -3-methyl-1- (3-0X0-1-phenethyl-azepan-4-ylcarbamoyl] -butyl} -amide of 5- ( 2-morpholino-4-yl-ethoxy) -benzofuran-2-carboxylic acid 27. [(S) -3-Methyl-1- (3-oxo-1-phenethyl-azepan-4-ylcarbamoyl] butyl} naphthylene-2-carboxylic acid amide 28. (. (S) -3-methyl) -1 - [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} -benzofuran-2-carboxylic acid amide 29. { (S) -3-methyl- 1 - [3-Oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl.} Naphthylene-2-carboxylic acid amide 30.. (S) -3-methyl-1 - [3-Oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl] -amide of 5- (2-morfoin-4-yl-ethoxy) -benzofuran-2-acid - carboxylic acid 31- ((S) -4-methyl-2- { [(5- (2-morpholino-4-yl-ethoxy) -benzofuran-2-carbonyl] -am butyl ester No.} - pentanolamine) -3-oxo-azepane-1-carboxylic acid 32. [(S) -3-methyl-1- (3-oxo-azepan-4-ylcarbamoyl] -butyl} acid amide 4 - ((S) -4-methyl-2- { [(5- (2-morpholino-4-yl-ethoxy) -benzofuran-2-carboxylic acid) {3-oxo-1 - [2 - (3-pyridin-2-yl-phenyl-acetyl] -azepan-4-yl.} - acid amide 4-methyl-pentanoic acid 34. ((S) -3-methyl-1-. {3-oxo-1- [2- (3-pyridin-2-yl-phenyl) -acetyl] tert-butyl ester -azepan-4-ylcarbamoyl.} - butyl) -naphthalene-2-methyl-carbamic acid 35. [3-oxo-1- [2- (3-pyridin-2-yl-phenyl) -acetyl-azepan-4-yl} -amino acid (S) -4-methyl-2 - [(naphthylene-2-ylmethyl) -amino] -pentenoic acid 36. 4- [2- (2 { (S) - tert -butyl ester] 3-Methyl-1- [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butylcarbamoyl.} - benzofuran-5-yloxy) -ethyl] -piperazine-1-carboxylic acid 37. [(S) -3-methyl-1 - [3-oxo-1 - (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -3-butyl-5-pyridin-1-yl acid amide -ethoxy) -benzofuran-2-carboxylic acid 38.. { (S) -3-methyl-1 - [3-oxo-1 - (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyljamide of 5- (2-cyclohexyl-ethoxy) benzofuran-2-carboxylic acid 39. ((S) -3-methyl-1 -. {3-oxo-1 - [2- (3-pyridin-2-yl-phenyl) ethyl] -azepan-4-ylcarbamoyl} -butyl) 5- (2-cyclohexyl-ethoxy) -benzofuran-2-carboxylic acid amide 40. 4- [2- (2- ({(S) -3-methyl-) -butyl-tert-butyl ester 1- [3-oxo-1- (3-pyridin-2-yl-phenyl) -ethyl- [azepan-4-ylcarbamoyl] -butylcarbamoyl} - benzofuran-5-yloxy) -ethyl] -piperazine- 1-carboxylic acid 41. ((S) -3-methyl-1 - { 3-oxo-1 - [2- (3-pyridin-2-yl-phenyl) ethyl] -azepan-4-ylcarbamoyl. -butyl) 5- (2-piperazin-1-yl-ethoxy) benzofuran-2-carboxylic acid amide 42. [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-yl] -amide (S) -4-Methylene-2- (methyl-naphthalen-2-ylmethyl-amino) pentanoic acid 43.. { 3-oxo-1 - [2- (3-pyridin-2-yl-phenyl) -acetyl] -azepan-4-yl} -amide of acid (S) -4-Methyl-2- (methyl-naphthalen-2-ylmethyl-amino] pentanoic acid 44. methyl - ((S) -3-methyl-1 -. {3-oxo-1 - [2- ( 5- (2-morpholino-4-yl-ethoxy) -benzofuran-2-carboxylic acid 3-pyridin-2-yl-phenyl) -acetyl] -azepan-4-ylcarbamoyl.] - butyl) -amide. methyl- { (S) -3-methyl-1 - [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl) -3-methyl-butyl] -amide of benzofu hydrocarbon ico 46. 2,2,2-trifluoro-N - ((S) -3-methyl-1 -. {3-oxo-1 - [2- (3-pyridin-2-yl-phenyl) -acetyl] -azepan-4-licarbamoyl.} - butyl) -N-naphthylene-2-methyl-acetamide 47. 4 - [(S) - (methanesulfonyl-naphthylene-2-ylmethyl-amino) -4-methyl-pentanoylamino] -3-oxo-azepane-1-carboxylic acid benzyl ester 48. . { (S) -3-methyl-1 - [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyljamide of quinoline-2-carboxylic acid 49.. { (S) -3-methyl-1 - [3-oxo-1 - (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} -quinoline-8-carboxylic acid amide 50.. { (S) -3-methyl-1- [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyljamide of quinoline-6-carboxylic acid 51.. { (S) -3-methyl-1 - [3-oxo-1 - (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} quinoline-4-carboxylic acid amide 52.. { (S) -3-methyl-1 - [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyljamide of quinoline-3-carboxylic acid 53.. { (S) -3-methyl-1 - [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyljamide of isoquinoline-3-carboxylic acid 54.. { (S) -3-methyl-1- [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} isoquinoline-1-carboxylic acid amide 55.. { (S) -3-methyl-1 - [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyljamide of quinoxaline-2-carboxylic acid 56.. { (S) -3-methyl-1 - [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyljamide of benzo [b] thiophene-2-carboxylic acid 57.. { (S) -3-methyl-1 - [3-oxo-1 - (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} acid amide 1, 8-naphthyridine-2-carboxylic 58.. { (S) -3-methyl-1 - [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyljamide of 1 H-indole-2-carboxylic acid 59.. { (S) -3-methyl-1 - [3-oxo-1 - (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 5-methoxy-benzofuran-2-carboxylic acid amide 60.. { (S) -3-methyl-1 - [3-oxo-1 - (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 5-bromo-furan-2-carboxylic acid amide 61.. { (S) -3-methyl-1 - [3-oxo-1 - (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} furan-2-carboxylic acid amide 62.. { (S) -3-methyl-1 - [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyljamide of 5-nitro-furan-2-carboxylic acid 63.. { (S) -3-Methyl-1 - [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyljamide of 5- (4-nitro-phenyl) -furan-2-carboxylic acid 64.. { (S) -3-methyl-1 - [3-oxo-1 - (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 5- (3-trifluoromethyl-phenyl) -furan-2-carboxylic acid amide 65.. { (S) -3-methyl-1 - [3-oxo-1 - (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} Tetrahydrofuran-2-carboxylic acid amide 66. [(3-oxo- (pyridin-2-sulfonyl) -azepan-4-yl] (S) -4-methyl-2- (2-phenoxy-acetylamino) -amide. ) Pentanoic 67. (S) -2- [2- (4-fluoro-phenoxy) -acetylamino] -4-methyl [3-oxo- (pyridin-2-sulfonyl) -azepan-4-yl] -amide. -pentanoic 68.. { (S) -3-methyl-1 - [3-oxo- (pyridine-2-carbonyl) -azepan-4-ylcarbamoyl) -3-butyl-2-benzofuran-2-carboxylic acid amide 69.. { (S) -3-methyl-1 - [3-oxo-1- (1-oxy-pyridine-2-carbonyl) -azepan-4-ylcarbamoyl-butyl-ammonia benzofuran-2-carboxylic acid 70. benzylester - ((S) -2-tert-Butylcarbonylamino-4-methyl-pentanoylamino) -3-oxo-azepane-1-carboxylic acid 71.. { (S) -3-methyl-1 - [3-oxo-1 - (1-methyl-1 H-imidazole-4-sulfonyl) -azepan-4-ylcarbamoyl] -butyl ester} 5,6-dimethoxy-benzofuran-2-carboxylic acid amide 72.. { (S) -3-methyl-1 - [1 - (5-methyM H- [1, 2,4] triazole-3-sulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -butyl ester} benzofuran-2-carboxylic acid amide 73.. { (S) -3-methyl-1 - [1 - (1-methyl-1 H-imidazol-3-sulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -butyl ester} benzofuran-2-carboxylic acid amide 74.. { (S) -3-methyl-1 - [1 - (1 H-imidazole-2-sulfonyl) -3-oxo-azepan-4-lcarbamoyl] -butyl} benzofuran-2-carboxylic acid amide 75.,. { (S) -3-methyl-1 - [3-oxo-1- (thiazole-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyljamide of benzofuran-2-carboxylic acid 76.. { (S) -3-methyl-1- [1- (1-methyl-1 H-imidazole-4-sulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -butyl ester} benzofuran-2-carboxylic acid amide 77.. { (S) -3-methyl-1 - [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyljamide of 5- (4-oxy-morpholino-4-yl-ethoxy) -benzofuran-2-carboxylic acid 78.. { (S) -3-methyl-1 - [3-oxo-1- (pyridin-3-sulfonyl) -azepan-4-ylcarbamoyl] -butyljamide of benzofuran-2-carboxylic acid 79.. { (S) -3-methyl-1 - [3-oxo-1- (1-oxy-pyridin-3-sulfonyl) -azepan-4-ylcarbamoyl] -butyl ester} benzofuran-2-carboxylic acid amide 80.. { (S) -1- (3,4-dichloro-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl)] - 3-methyl-butyl} -amine of quinoline-3-carboxylic acid 81.. { (S) -3-methyl-1- [1- (1-methyl-1 H-imidazole-4-sulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -butyl ester} amido acid 5-h id roxy-benzofuranic rboxilico ico 82.. { (S) -3-methyl-1 - [3-oxo-1 - (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl)] - 3-methyl-butyl} benzofuran-2-carboxylic acid amide 83. 2- (4-. {(S) -2-. {(benzofuran-2-carbonyl) -amino} -4-methyl-pentanoylamino} acid. -3-oxo-azepan-1-sulfonyl) -benzoic acid. 84. 3- (4-. {(S) -2-. {(Benzofuran-2-carbonyl) -amino] -4-methyl-pentanoylamino} -3-oxo-azepan-1-sulfonyl) -benzoic acid 85.. { (S) -3-methyl-1 - [3-oxo-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} benzo [b] thiophene-2-carboxylic acid amide 6.. { (S) -3-methyl-1 - [3-oxo-1 - (1-oxy-pyridin-2-sulfonyl) -azepan-4-lcarbamoyl] -butyl} 5-bromo-furan-2-carboxylic acid amide 87.. { (S) -3-methyl-1 - [3-oxo-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 5,6-dimethoxy-benzofuran-2-carboxylic acid amide 88.. { (S) -3-methyl-1 - [3-oxo-1 - (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 1-oxy-pyridine-2-carboxylic acid amide 89. [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-yl] -amide of (S) -4-methyl-2- ( pyridine-2-sulfonylamino) -pentanoic acid 90. [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-yl] -amide of (S) -2- (3-benzyl-ureido) -4 -methyl-pentanoic 91. [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-yl] -amide of (S) -4-methyl-2- (3-phenyl-ureido) -pentanoic acid 92.. { (S) -1 - [6, 6-dimethyl-3-oxo-1- (pyridine-sulfonyl) -azepan-4-ylcarbamoyl] -3-methyl-butyl} -benzofuran-2-carboxylic acid amide 93.. { (S) -3-methyl-1 - [3-oxo-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 5-methoxy-benzofuran-2-carboxylic acid amide 94.. { (S) -3-methyl-1 - [3-oxo-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} thieno [3,2-b] thiophene-2-carboxylic acid amide 95.. { (S) -3-methyl-1 - [3-oxo-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} Quinoxaline-2-carboxylic acid amide 96.. { (S) -3-methyl-1 - [3-oxo-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] butyl} Quinoline-2-carboxylic acid amide 97.. { (S) -3-methyl-1 - [3-oxo-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} thiophene-3-carboxylic acid amide 98.. { (S) -3-methyl-1 - [3-oxo-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 1 H-Indole-5-carboxylic acid amide 99.. { (S) -3-methyl-1 - [3-oxo-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} benzo [1, 3] dioxol-5-carboxylic acid amide 100. . { (S) -3-methyl-1 - [3-oxo-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} furan-2-carboxylic acid amide 101. [3-oxo-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-yl] -amide of (S) -4-methyl-2- ( 2-thiophen-2-yl-acetylamino) -pentanoic 102.. { (S) -3-methyl-1 - [3-oxo-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 1 H-indole-2-carboxylic acid amide 103. 4-fluoro-. { (S) -3-methyl-1 - [3-0X0-1 - (1-oxy-pyridin-2-sulfonyl) -azepan-4-carbamoyl] -butyl} -benzamide 104.. { (S) -3-methy1- [3-oxo- (1-oxy-pyridine-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 5- (2-morpholin-4-yl-ethoxy) -benzofuran-2-carboxylic acid amide 105. { (S) -3-methyl-1 - [3-oxo-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} thiophene-2-carboxylic acid amide 106.. { (S) -3-methy1- [3-oxo-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 3-methyl-benzofuran-2-carboxylic acid amide 107. 6-methyl-N-. { (S) -3-methyl-1 - [3-oxo-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} nicotinamide 108. [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-yl] -butyl} (S) -4-Methyl-2- (2-thiophen-yl-acetylamino) -pentanoic acid amide 109.. { (S) -3-methyl-1 - [3-oxo-1 - (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 1 H-indole-6-carboxylic acid amide 110.. { (S) -3-methyl-1 - [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyljamide of benzo [1,3] dioxol-5-carboxylic acid 111.. { (S) -3-methyl-1 - [3-oxo-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 3,4-dihydro-2H-benzo [b] [1,4] dioxepin-7-carboxylic acid amide 112. { (S) -3-methyl-1 - [3-oxo-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 5-methyl-thiophene-2-carboxylic acid amide 113.. { (S) -3-methyl-1 - [3-oxo-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 4,5-dibromo-thiophene-2-carboxylic acid amide 1 14.. { (S) -3-methyl-1 - [3-oxo-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 3,5-dimethyl-isoxazole-4-carboxylic acid amide 15- [1- (4-methoxy-benzenesulfonyl) -3-oxo-azepan-4-yl-] - (S) -2- ( 2-benzyloxy-acetylamino) -4-methyl-pentanoic 1 16.. { (S) -3-methyl-1 - [3-oxo-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] butyl} 5- (3-trifluoromethyl-phenyl) -furan-2-carboxylic acid amide 1 17.. { (S) -3-methyl-1 - [3-oxo-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 5-Methyl-2-phenyl-oxazole-4-carboxylic acid amide 118.. { (S) -1 - [1- (3,4-Dimethoxy-benzenesulfonyl) -3-oxo-azepane-4-ylcarbamoyl-butyl-amide of benzofuran-2-carboxylic acid 119.. { (S) -1 - [1 - (4-Bromo-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} -benzofuran-2-carboxylic acid amide 120.. { (S) -1 - [1 - (Benzo [1, 2,5] oxadiazole-4-sulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} benzofuran-2-carboxylic acid amide 121. . { (S) -1 - [1 - (3,5-dimethyl-oxazole-4-sulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} -benzofuran-2-carboxylic acid amide 122.. { (S) -3-methyl-1 - [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyljamide of 3-methyl-benzofuran-2-carboxylic acid 123. . { (S) -3-methyl-1 - [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyljamide of thieno [3,2-b] thiophene-2-carboxylic acid . { (S) -3-methyl-1 - [3-oxo-1 - (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 5-tert-Butyl-3-methyl-thieno [3,2-b] thiophen-2-carboxylic acid amide 125. { 5-Methyl-2-phenyl-oxazole-4-carboxylic acid (S) -3-methyl-1 - [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyljamide 126.. { (S) -3-Methyl-1 - [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyljamide of 2-phenyl-5-trifluoromethyl-oxazole-4-carboxylic acid 127. [(S) -1 - (1-methanesulfonyl-3-oxo-azepan-4-ylcarbamoyl) -3-methyl-butyl] -aminoquin-2-carboxylic acid amide 128. [(S) -1 - ( 1-Methyl-1 H-indole-2-carboxylic acid 1-methanesulfonyl-3-oxo-azepan-4-ylcarbamoyl) -3-methyl-butylj-amide 129.. { [(S) -1 - (1-methanesulfonyl-3-oxo-azepan-4-ylcarbamoyl) -3-methyl-butylcarbamoyl] -methyl} -furan-2-carboxylic acid amide 130. [(S) -1- (1-methanesulfonyl-3-oxo-azepan-4-ylcarbamoyl) -3-methyl-butyl-amide of 5-methoxy-benzofuran-2-carboxylic acid 131. [(S) -1- (1-methanesulfonyl-3-oxo-azepan-4-ylcarbamoyl) -3-methyl-butylj-amide of quinoxaline-2-carboxylic acid 132.. { (S) -3-Methyl-1- [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyljamide of 5- (4-chloro-phenyl) -furan-2-carboxylic acid 133. (S) -2- [2- (4-methoxy-phenyl) -acetylamino) -4-methyl-pentanoic acid (1-methanesulfonyl-3-oxo-azepan-4-yl) -amide. { [(S) -1 - [1 - (2-cyano-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} -quinoline-2-carboxylic acid amide 135.. { [(S) -1 - [1 - (2-cyano-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} 1-methyl-1H-indole-2-carboxylic acid amide 136. ( { (S) -1 - [1 - (2-cyano-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] - 3- methyl-butylcarbamoyl.} - methyl) -amide of furan-2-carboxylic acid 137. . { (S) -1 - [1 - (2-Cyano-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} 5-methoxy-benzofuran-2-carboxylic acid amide 138. . { (S) -1- [1 - (2-Cyano-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} -quinoxaline-2-carboxylic acid amide 139. [1- (2-cyano-benzenesulfonyl) -3-oxo-azepan-4-yl] -amide of (S) -2- [2- (4-methoxy) -amide. phenyl) -acetylamino) -4-methyl-pentanoic 140.. { [(S) -1 - [1 - (4-methoxy-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} -quinoline-2-carboxylic acid amide 141.. { [(S) -1- [1- (4-methoxy-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} 1-methyl-1 H-indole-2-carboxylic acid amide 142. ( { (S) -1- [1- (4-methoxy-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butylcarbamoyl.} - methyl) -amide of furan -2-carboxylic 143. . { [(S) -1- [1- (4-methoxy-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} 5-methoxy-benzofuran-2-carboxylic acid amide 144.. { [(S) -1- [1- (4-methoxy-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} -q-oxaline-2-carboxylic acid amide 145. [1- (4-methoxy-benzenesulfonyl) -3-oxo-azepan-4-yl] -amide of (S) -2- [2- (4-methoxy) -amide. phenyl) -acetylamino) -4-methyl-pentanoic 146.. { [(S) -1- [1- (4-Fluoro-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl-1-methyl-1H-indole-2-carboxylic acid 147. ( { (S) -1- [1- (4-Fluoro-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butylcarbamoyl.} - methyl) -amide of furan -2-carboxylic 148. . { [(S) -1- [1- (4-Fluoro-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} 5-methoxy-benzofuran-2-carboxylic acid amide 149.. { [(S) -1- [1- (4-Fluoro-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} -quinoxaline-2-carboxylic acid amide 150. [1- (4-fluoro-benzenesulfonyl) -3-oxo-azepan-4-yl] -amide acid (S) -2- [2- (4-methoxy-phenyl] -acetylamino) -4-methyl-pentanoic 151. . { [(S) -1 - [1 - (3-chloro-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} -benzofuran-2-carboxylic acid amide 152.. { (S) -1 - [1- (3-Chloro-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} 5-methoxy-benzofuran-2-carboxylic acid amide 153.. { (S) -1 - [1- (3-Chloro-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} 7-methoxy-benzofuran-2-carboxylic acid amide 154. . { (S) -1 - [1 - (3-chloro-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} 5,6-dimethoxy-benzofuran-2-carboxylic acid amide 155. . { (S) -1- [1 - (3-Chloro-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} 3-methyl-benzofuran-2-carboxylic acid amide 156. . { (S) -1 - [1 - (3-chloro-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} -benzo [b] thiophene-2-carboxylic acid amide 157.. { (S) -1- [1- (3-Chloro-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} 1-methyl-1 H-indole-2-carboxylic acid amide 158. { (S) -1 - [1 - (3-chloro-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} -quinoxaline-2-carboxylic acid amide 159.. { (S) -1- [1- (2-Fluoro-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} Benzofuran-2-carboxylic acid amide 160. { (S) -1 - [1- (2-Fluoro-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl-5-methoxy-benzofuran-2-carboxylic acid amide 161. ,. { (S) -1- [1- (2-Fluoro-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} 7-methoxy-benzofuran-2-carboxylic acid amide 162. . { (S) -1- [1- (2-Fluoro-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} 5,6-dimethoxy-benzofuran-2-carboxylic acid amide 163. . { (S) -1 - [1 - (2-Fluoro-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} 5-methyl-benzofuran-2-carboxylic acid amide 164. . { (S) -1 - [1 - (2-Fluoro-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} benzo [b] thiophene-2-carboxylic acid amide 165.. { (S) -1 - [1 - (2-Fluoro-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} 1-methyl-1 H-indole-2-carboxylic acid amide. 166. [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-yl] -amide acid (S) -4-methyl. -2- (1-oxy-pyridin-2-sulfonyl-amino) -pentanoic 167.. { (S) -1 - [1 - (2-Fluoro-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butylj-amide of quinoxaline-2-carboxylic acid 168.. { (S) -3-methyl-1 - [3-0X0-1 - (thiophen-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl-5-methoxy-benzofuran-2-carboxylic acid amide 169.. { (S) -3-methyl-1 - [3-oxo-1- (thiophene-2-sulfonyl] -azepan-4-ylcarbamoyl] -butyl} -amide of 7-methoxy-benzofuran-2-carboxylic acid { (S) -3-methyl-1 - [3-oxo-1- (thiophen-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} -amide, 6-dimethoxy-benzofuran-2-carboxylic acid 171. . { (S) -3-methyl-1 - [3-oxo-1 - (thiophen-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 3-methyl-benzofuran-2-carboxylic acid amide 172.. { (S) -3-methyl-1 - [3-oxo-1 - (thiophen-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} -benzo [b] thiophene-2-carboxylic acid amide 173.. { (S) -3-methyl-1 - [3-oxo-1 - (thiophen-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 1-methyl-1H-indole-2-carboxylic acid amide 174.. { (S) -3-methyl-1 - [3-oxo-1 - (thiophen-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} -quinoxaline-2-carboxylic acid amide 175.. { (S) -1- [1 - (4-Chloro-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} -benzofuran-2-carboxylic acid amide 176.. { (S) -1- [1- (4-Chloro-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} 5-methoxy-benzofuran-2-carboxylic acid amide 177. . { (S) -1 - [1 - (4-chloro-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} 7-methoxy-benzofuran-2-carboxylic acid amide 178. . { (S) -1 - [1 - (4-chloro-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} 5,6-dimethoxy-benzofuran-2-carboxylic acid amide 179. . { (S) -1 - [1 - (4-chloro-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} 3-methyl-benzofuran-2-carboxylic acid amide 180. . { (S) -1 - [1 - (4-chloro-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} -benzo [b] thiophene-2-carboxylic acid amide 181.. { (S) -1- [1- (4-Chloro-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} 1-methyl-1 H-indole-2-carboxylic acid amide 182.. { (S) -1 - [1 - (4-chloro-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} -quinoxaline-2-carboxylic acid amide 183.. { (S) -1 - [1 - (3-methoxy-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} -benzofuran-2-carboxylic acid amide 184.. { (S) -1 - [1 - (3-methoxy-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} 5-methoxy-benzofuran-2-carboxylic acid amide 185. . { (S) -1 - [1 - (3-methoxy-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} 7-methoxy-benzofuran-2-carboxylic acid amide 186.. { (S) -1 - [1 - (3-methoxy-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} 5,6-dimethoxy-benzofuran-2-carboxylic acid amide 187. { (S) -1- [1 - (3-methoxy-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} 3-methyl-benzofuran-2-carboxylic acid amide 188. . { (S) -1- [1- (3-methoxy-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} -benzo [b] thiophene-2-carboxylic acid amide 189.. { (S) -1 - [1 - (3-methoxy-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} 1-methyl-1 H-indole-2-carboxylic acid amide 190. . { (S) -1 - [1 - (3-methoxy-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} -quinoxaline-2-carboxylic acid amide 191.. { (S) -1- [3-oxo-1 - (thiophen-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} - benzofuran-2-carboxylic acid amide 192.. { (S) -3-methyl-1 - [(2,2 ', 4-trdedeterio) -3-oxo-1- (pyridin-2-sulfonyl)-azepan-4-ylcarbamoyl] -butyl} benzofuran-2-carboxylic acid amide 193.. { (S) -2-methyl-1 - [3-oxo-1 - (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} -benzofuran-2-carboxylic acid amide 194.. { (S) -1 - [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -propyl} - benzofuran-2-carboxylic acid amide 195.. { (S) -2-Cyclohexyl-1 - [3-oxo-1 - (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -ethyl} -amide of benzofuran-2-carboxylic acid 196.. { (S) -1- [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -ethyl} - benzofuran-2-carboxylic acid amide 197.. { (S) -3-methanesulfinyl-1 - [3-oxo-1 - (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -propyl} -benzofuran-2-carboxylic acid amide 198.. { [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -methyl} -benzofuran-2-carboxylic acid amide 199.. { (S) -1- [3-oxo-1 - (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -pentyl} - benzofuran-2-carboxylic acid amide 200.. { (S) -1 - [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} - benzofuran-2-carboxylic acid amide 201.. { (S) -2-methyl-1 - [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -propyl} benzofuran-2-carboxylic acid amide 202.. { (S) -2-hydroxy-1 - [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -propyl} -benzofuran-2-carboxylic acid amide 203.. { (S) -1 - [3-oxo-1 - (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -2-phenyl-ethyl} -benzofuran-2-carboxylic acid amide 204. [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-yl] -amide of 1- (benzofuran-2-carbonyl) -pyrrolidin-2- acid carboxylic 205. 3, 4-dimethoxy-N-. { (S) -1 - [1 - (4-methoxy-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} -benzamide 206.. { (S) -1 - [1 - (4-Imethoxy-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} benzo [b] thiophene-2-carboxylic acid amide 207. { (S) -1- [1- (4-Fluoro-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butylj-amide of benzo [1,3] dioxol-5-carboxylic acid 208. (S) -2- (2-benzyloxy-acetylamino) -4-methyl-pentanoic acid 1- (4-fluoro-benzenesulfonyl) -3-oxo-azepan-4-yl] -amide. { (S) -1 - [1 - (4-Fluoro-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} Benzo [b] thiophene-2-carboxylic acid amide 210. { (S) -1- [1-Benzoyl-3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} -benzofuran-2-carboxylic acid amide 211. [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-yl] -amide of (S) -4-methyl-2- (quinolin) -8-sulfonylamino) -pentanoic acid 212. [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-yl] -amide of (S) -4-methyl-2- (naphthylene-2) -sulfonylamino) -pentanoic acid 213.. { (S) -1- [1- (4-Fluoro-benzenesulfonyl) -3-oxo-azepan-4-yl-carbamoyl] -3-methyl-butyl} -amide of benzofuran-2-carboxylic acid 214. N-. { (S) -1- [1- (4-Fluoro-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl} - 3-methyl-butyl} -3,4-dimethoxy-benzamida 215.. { (S) -1- [1- (4-Fluoro-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl} -3- methyl-butyl} -cyclohexanecarboxylic acid amide 216. (S) -2- (2-benzyloxy-acetylamino) -4-methyl-pentanoic acid [1- (methanesulfonyl) -3-oxo-azepan-4-yl] -amide. { (S) -1- (1-methanesulfonyl-3-oxo-azepan-4-ylcarbamoyl) -3-methyl-butylj-benzo [b] thiophene-2-carboxylic acid amide 218.. { (S) -1, 3] dioxol-5-carboxylic acid (S) -1- (1-methanesulfonyl-3-oxo-azepan-4-ylcarbamoyl) -3-methyl-butylj-amide of benzo [1,3]. { (S) -1- (1-methanesulfonyl-3-oxo-azepan-4-ylcarbamoyl) -3-methyl-butylj-amide of benzofuran-2-carboxylic acid 220. N - [(S) -1 - (1- methanesulfonyl) -3-oxo-azepan-4-ylcarbamoyl} -3-methyl-butyl} -3,4-dimethoxy-benzamide 221. [1- (2-cyano-benzenesulfonyl) -3-oxo-azepan-4-yl] -amide acid (S) -2- (2-benzyloxy-acetylamino) -4-methyl-pentanoic 222. N-. { (S) -1- [1- (2-Cyano-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl} - 3-methyl-butyl} -4-methanesulfonyl-1-benzamide 223.. { (S) -1- [1- (2-Cyano-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl) -3-methyl-butyljamide of benzo [b] thiophene-2-carboxylic acid 224.. { (S) -1- [1 - 3] dioxol-5-carboxylic acid (S) -1- (2-cyano-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl) -3-methyl-butyl] -amide [3-oxo-1 - (pyridin-2-sufonyl) -azepan-4-yl] -amide of (S) -4-methyl-2- [4-oxo-4 - ((4-phenoxy)] phenyl) -butyrylamino.} - pentanoic acid 226. N- { (S) -1 - [(1 - (2-cyano-benzenesulfonyl) -3-oxo-azepane-4-ylcarbamoyl} -3-methyl -butyl) -3,4-dimethoxy-benzamide 227. { (S) -1 - [1- (4-methoxy-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl. methyI-butyl.} - cyclohexanecarboxylic acid amide 228. 4-methanesulfonyl-N- ({(S) -1- [4-methoxy-benzenesulfonyl) -3-oxo-azepane-4-carbamoyl] -3-methyl} -butyl-benzamide 229. 4-methanesulfonyl-N- { (S) -1- [4-fluoro-benzenesulfonyl] -3-oxo-azepan-4-carbamoyl] -3-methyl-butyl-benzamide 230. ester benzyl acid ( { (S) -3-methyl-1- [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butylcarbamoyl} -carbamic acid 231. [ 3-Oxo-1- (pyridin-2-sulfonyl) -azepan-4-yl] -amide of (S) -2- [5- (4-methoxy-phenyl) -pentanoylamino) no] -4-methyl-pentanoic 232. [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-yl] -amide of (S) -2- [2- (3-benzyloxy -4-methoxy-phenyl) -acetylamino] -4-methylpentanoic acid 233.. { (S) -3-methyl-1 - [1 - (pyridine-2-sulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -butyl} 5,6-difluoro-benzofuran-2-carboxylic acid amide 2. 34. [3-Oxo-1- (pyridin-2-sulfonyl) -azepan-4-yl] -amide of (S) -4-methyl-2- (5-oxo-hexanoylamino) -pentanoic acid 235.. { (S) -3-Methyl-1 - [1- (6-methyl-pyridine-2-sulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -butyl} benzofuran-2-carboxylic acid amide 236.. { (S) -3-Methyl-1 - [1- (6-methyl-pyridine-2-sulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -butyl} 5-methoxy-benzofuran-2-carboxylic acid amide 237.. { (S) -3-Methyl-1 - [1- (6-methyl-pyridine-2-sulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -butyl} 3-methyl-benzofuran-2-carboxylic acid amide 238. . { (S) -3-methyl-1 - [1- (pyridin-2-sulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -butyljamide of 7-methoxy-benzofuran-2-carboxylic acid 239.. { (S) -3-methyl-1 - [1- (pyridin-2-sulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -butyljamide of 5,6-dimethoxy-benzo [b] thiophene-2-carboxylic acid 240. . { (S) -3-methyl-1-. { 3-Oxo- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyljamide of (R) -1-benzyl-5-oxo-pyrrolidine-2-carboxylic acid 241. . { (S) -3-methyl-1-. { 3-Oxo- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} (S) -1-benzyl-5-oxo-pyrrolidine-2-carboxylic acid amide 242. . { (S) -2-Cyclopropyl-1 - [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl) -ethyl] -amide of benzofuran-2-carboxylic acid 243.. { (S) -3-methylsulfanyl-1- [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl) -propyl] -amide of benzofuran-2-carboxylic acid 244. . { (S) -2-naphthylene-2-yl-1 - [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl) -ethyl] -amide of benzofuran-2-carboxylic acid 245.. { (S) -3-methy1- [1- (6-methyl-pyridin-2-sulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -butyl} thieno [3,2-b] thiophene-2-carboxylic acid amide 246.. { (S) -3-methyl-1- [1- (3-methyl-pyridin-2-sulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -butyl} thieno [3,2-b] thiophene-2-carboxylic acid amide 247. . { (S) -3-methyl-1 - [1 - (3-methyl-pyridin-2-sulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -butyl} 3-methyl-benzofuran-2-carboxylic acid amide 248. . { (S) -3-methyl-1 - [1 - (3-methyl-pyridine-2-sulfonyl) -3-oxo-azepan-4-lcarbamoyl] -butyl} 5-methoxy-benzofuran-2-carboxylic acid amide 249.. { (S) -3-methyl-1 - [3-oxo-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 5,6-difluoro-benzofuran-2-carboxylic acid amide 250.. { (S) -2-cyclohexyl-1 -. { 3-Oxo-1 - (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -ethyl} 5- (3-trifluoromethyl-phenyl) -furan-2-carboxylic acid amide 251.. { (S) -2-cyclohexyl-1 -. { 3-Oxo-1 - (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -ethyl} 5- (4-Chloro-phenyl) -furan-2-carboxylic acid amide 252. { (S) -3-methyl-1 - [6-methyl-3-oxo-1 - (pyridine-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} -benzofuran-2-carboxylic acid amide 253.. { (S) -2-Cyclohexyl-1 - [3-oxo-1- (1-oxo-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -ethyl} -amido-5- (4-chloro-phenyl) -furan-2-carboxylic acid 254.. { (S) -2-Cyclohexyl-1 - [3-oxo-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -ethyl} 5- (3-trifluoromethyl-phenyl) -furan-2-carboxylic acid amide 255.. { (S) -3-methyl-1 - [3-oxo-1 - (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 5-Fluoro-benzofuran-2-carboxylic acid amide 256.. { (S) -2-cyclohexyl-1 - [3-oxo-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4- lcarbamoyl] -ethyl} -amide of acid 5, 6-dimethoxy-benzofuran-2-carboxylic acid 257.. { (S) -3-methyl-1 - [3-oxo-1 - (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl]} - Butyl } -5,5-bis- (4-methoxy-fenii) -pent-4-enoic acid amide 258. . { (S) -2-naphthylene-2-yl-1 - [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -ethyl] -aminoquin-8-carboxylic acid 259.. { (S) -2-naphthylene-2-yl-1 - [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-lcarbamoyl) -ethyl] -amide-1 -carboxylic acid amide 260. . { (S) -1 - [3-oxo-1 - (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -2-phenyl-ethyl} -quinoline-8-carboxylic acid amide 61.. { (S) -3-methyl-1 - [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butylj-naphthyridine-2-carboxylic acid 262.. { (S) -1- [3-oxo-1 - (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -2-phenyl-ethyl} Naphthylene-1-carboxylic acid amide 263.. { (S) -3-methyl-1 - [3-oxo-1 - (cyclohexyl-propionyl) -azepan-4-yl-carbamoyl] -butyl} 3-methylbenzofuran-2-carboxylic acid amide 264. . { (S) -3-methyl-1 - [3-oxo-1- (4-methyl-pentanoyl) -azepan-4-ylcarbamoyl] -butylj-3-methylbenzofuran-2-carboxylic acid amide 265.. { (S) -3-methyl-1 - [3-oxo-1- (1-oxy-pyridine-2-carbonyl) -azepan-4-yl-carbamoyl] -butyl} 3-methylbenzofuran-2-carboxylic acid amide 266. (S) -acetylamino-4-methyl-pentanoic acid [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-yl] -amide 267 . { 1 - [3-Oxo-1 - (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -pentyl} -quinoline-2-carboxylic acid amide 268.. { (S) -3-methyl-1 - [3-oxo-1 - (cyclohexyl-propionyl) -azepan-4-yl-carbamoyl] -butyl} -benzofuran-2-carboxylic acid amide 269. { (S) -3-methyl-1 - [3-oxo-1- (4-methyl-pentanoyl) -azepan-4-ylcarbamoyl] -butyljamide of benzofuran-2-carboxylic acid 270. { (S) -1 - [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -2-phenyl-ethyl-amide of quinoline-2-carboxylic acid 271. { (S) -2-benzyloxy-1 - [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -ethyl} benzofuran-2-carboxylic acid amide 272. { (S) -2-hydroxy-1 - [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -etl} -benzofuran-2-carboxylic acid amide 273. { (S) -3-methyl-1 - [3-oxo-1- (thiazol-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyljamide of 5-methoxybenzofuran-2-carboxylic acid 274. { (S) -3-methyl-1 - [3-oxo-1- (thiazol-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyljamide of 7-methoxybenzofuran-2-carboxylic acid 275. { (S) -3-methyl-1 - [3-oxo-1 - (thiazole-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 3-methylbenzofuran-2-carboxylic acid amide 276. { (S) -3-methyl-1 - [3-oxo-1 - (thiazole-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} benzo [b] thiophene-2-carboxylic acid amide 277. { (S) -3-methyl-1 - [3-oxo-1 - (thiazole-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 1-methyl-1 H-indole-2-carboxylic acid amide 278. { (S) -3-methyl-1 - [3-oxo-1 - (thiazole-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} quinoxaline-2-carboxylic acid amide 279. { [(S) -1 - [1 - [4-fluoro-benzenesulfonyl] -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} quinoline-2-carboxylic acid amide. Specific representative compounds of the present invention are described in Examples 1-279. In comparison with the corresponding 5 and 6-membered ring compounds, the 7-membered ring compounds of the present invention are configurationally more stable at the alpha carbon center with respect to the ketone. The present invention includes deuterated analogs of the compounds of the invention. A representative example of said deuterated compounds is described in example 192. In scheme 4, below, a representative synthetic route for the deuterated compounds of the present invention is described. The deuterated compounds of the present invention exhibit superior chiral stability as compared to the protonated isomer.

Definitions The present invention includes all hydrates, solvates, complexes and prodrugs of the compounds of the invention. Prodrugs are any covalently linked compound that releases the original active drug in vivo according to formula I. If a chiral center or other form of an isomeric center is present in a compound of the present invention, all forms of said isomer or isomers are covered in the present disclosure, including enantiomers and diastereomers. The compounds of the invention containing a chiral center can be used as a racemic mixture, an enantiomerically enriched mixture, or the racemic mixture can be separated using well known techniques and a single enantiomer alone can be used. In cases where the compounds have unsaturated carbon-carbon double bonds, both the cis (Z) and the trans (E) isomer are within the scope of this invention. In cases where the compounds can exist in tautomeric forms, such as keto-enol tautomers, it is contemplated that each tautomeric form is included within this invention, either in equilibrium or predominantly in one form.

The meaning of any substituent in any occurrence in formula I or any sub-formula thereof, is independent of its meaning or any other meaning of the substituent, in any other occurrence, unless otherwise specified. Abbreviations and symbols commonly used in the chemical and peptide techniques are used herein to describe the compounds of the present invention. In general, the abbreviations of amino acids follow the nomenclature of the Joint IUPAC-IUB Commission on Biochemical Nomenclature as described in Eur. J. Biochem., 158, 9 (1984). "Proteases" are enzymes that catalyze the cleavage of amide bonds of peptides and proteins by means of nucleophilic substitution at the amide bond, ultimately resulting in hydrolysis. These proteases include: cysteine proteases, serine proteases, aspartic proteases and metalloproteases. The compounds of the present invention are capable of binding to the enzyme more strongly than the substrate, and in general they are not subjected to shearing after the attack of the nucleophile catalyzed by the enzyme. Therefore, said compounds prevent the proteases from recognizing and hydrolyzing the natural substrates and therefore act as inhibitors. The term "amino acid" as used herein refers to the D- or L- isomers of alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine and valine.

"Ci-ß alkyl" as applied herein includes substituted and unsubstituted methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, t-butyl, pentyl, n-pentyl, isopentyl, neopentyl and hexyl, and the simple aliphatic isomers thereof. The Ci-β alkyl may be optionally substituted with a portion selected from the group consisting of: OR12, C (O) R12, SR12, S (O) R12, NR122, R12NC (O) OR5, CO2R12, CO2NR122, N ( C = NH) NH 2, Het, C 3-6 cycloalkyl and Ar; wherein R5 is selected from the group consisting of: H, C1-6 alkyl, C2.6 alkenyl, C2.sub.x alkynyl, (C3-6) cycloalkyl-Co-βalkyl. Ar-alkyl of Co-β and Het-alkyl of C0-β; and R 12 is selected from the group consisting of: H, C 1 -β alkyl, Ar-C 6 -alkyl and C 0-6 alkyl Het; "(C3-6) cycloalkyl" as applied herein includes substituted and unsubstituted cyclopropane, cyclobutane, cyclopentane and cyclohexane. "C2-β alkenyl" as used herein means an alkyl group of 2 to 6 carbons in which a single carbon-carbon bond is replaced with a carbon-carbon double bond. C2-6 alkenyl includes ethylene, 1-propene, 2-propene, 1-butene, 2-butene, sobutene, and the various isomeric pentenes and hexenes. Both cis and trans isomers are included. "C2-6 alkynyl" means an alkyl group of 2 to 6 carbons in which a single carbon-carbon bond is replaced with a carbon-carbon triple bond. C2-6 alkynyl includes acetylene, 1-propino, 2-propyne, 1-butene, 2-butyne, 2-butyne, 3-butyne and the simple isomers of pentino and hexino. "Halogen" means F, Cl, Br and I. "Ar" or "aryl" means phenyl or naphthyl, optionally substituted with one or more of Ph-alkyl of Co-β; Het-Co-βalkyl; C-i-β alkoxy; Ph-C06 alkoxy; Het-C0-β alkoxy; OH, (CH2) 1.6NR15R16; O (CH2) 1.6 NR15R16; C1-6 alkyl, OR17, N (R17) 2, SR17, CF3, NO2, CN, CO2R17, CON (R17), F, Cl, Br or I; wherein R15 and R16 are H, C? -6 alkyl, Ph-C06 alkyl, naphthyl-Co-ß alkyl or Het-C06 alkyl; and R17 is phenyl, naphthyl or C-? -6 alkyl. As used herein, "Het" or "heterocyclic" represents a stable monocyclic 5- to 7-membered heterocyclic ring, stable 7 to 10 membered bicyclic ring, or stable 11 to 18 membered tricyclic ring, which is saturated or unsaturated, and which consists of of carbon atoms and one to three heteroatoms selected from the group consisting of N, O and S, and wherein the nitrogen and sulfur heteroatoms may optionally be oxidized, and the nitrogen heteroatom may optionally be quaternized, and includes any bicyclic group in which any of the heterocyclic rings defined above is fused to a benzene ring. The heterocyclic ring can be attached at any heteroatom or carbon atom that originates a stable structure, and can be optionally substituted with one or more selected portions of Ar-C0-6, C 1-6 alkyl, OR 17, N (R 17) 2 , SR17, CF3, NO2, CN, CO2R17, CON (R17), F, Cl, Br and I, wherein R17 is phenyl, naphthyl or C1-6alkyl. Examples of these heterocycles include piperidinyl, piperazinyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, 2-oxoazepinyl, azepinyl, pyrrolyl, 4-piperidonyl, pyrrolidinyl, pyrazolyl, pyrazolidinyl, imidazolyl, pyridinyl, 1-oxo-pyridinyl, pyrazinyl. , oxazolidinyl, oxazolinyl, oxazolyl, isoxazolyl, morpholinyl, thiazolidinyl, thiazolidyl, thiazolyl, quinuclidinyl, indolyl, quinolinyl, quinoxalinyl, isoquinolinyl, benzimidazolyl, benzopyranyl, benzoxazolyl, furanyl, benzofuranyl, thiophenyl, benzo [b] thiophenyl, thieno [3,2 -b] thiophenyl, benzo [1,3] dioxolyl, 1,8-naphthyridinyl, pyranyl, tetrahydrofuranyl, tetrahydropyranyl, thienyl, benzoxazolyl, thiamorpholinyl sulfoxide, thiamorpholinyl sulfone and oxadiazolyl, as well as triazolyl, thiadiazolyl, oxadiazolyl, isothiazolyl, imidazolyl, pyridazinyl, pyrimidinyl, triazinyl and tetrazinyl, which are available by routine chemical synthesis and are stable. As used herein, the term "heteroatom" refers to oxygen, nitrogen and sulfur. Here and throughout this application, the term Co denotes the absence of the substituent group immediately following; for example, in the Ar-alkyl portion of Co-β, when C is 0, the substituent is Ar, for example, phenyl. Conversely, when the Ar-alkyl portion of Co-β is identified as a specific aromatic group such as for example phenyl, it is understood that the value of C is O. Certain radical groups are abbreviated here. t-Bu refers to the tertiary butyl radical, Boc refers to the t-butoxycarbonyl radical, Fmoc refers to the fluorenylmethoxycarbonyl radical, Ph refers to the phenyl radical, Cbz refers to the benzyloxycarbonyl radical.

Certain reagents are abbreviated here. m-CPBA refers to 3-chloroperoxybenzoic acid, EDC refers to N-ethyl-N '- (dimethylaminopropyl) -carbodiimide, DMF refers to dimethylformamide, DMSO refers to dimethyl sulfoxide, TEA refers to triethylamine, TFA is refers to trifluoroacetic acid, and THF refers to tetrahydrofuran.

Preparation methods The compounds of the general formula I can be prepared in a manner analogous to that described in schemes 1, 2 and 3. The alkylation of tert-butyl N-allylcarbamate (1) with a base such as hydroxide of sodium and 5-bromo-1-pentene, produces diene 2. Treatment of 2 with bis (tert-butoxide) of 2,6-diisopropylphenylimido-neofilidene of molybdenum or bis (tricyclohexylphosphine) benzylidene dichloride of ruthenium (IV) , olefin metathesis catalysts developed by Grubbs, produces azepine 3. Epoxidation of 3 with standard oxidizing agents common in the art, such as m-CPBA, produces epoxide 4. The nucleophilic opening of the epoxide ring can be carried out with a reagent such as sodium azide, to produce the azido alcohol (not shown), which can be reduced to the amino alcohol under conditions common in the art, such as 1,3-propanedithiol and triethylamine in methanol, or with hydrogen gas in presence of a c such as palladium on carbon. Acylation of 5 with an acid such as Cbz-leucine in the presence of a coupling agent such as EDC, followed by removal of the BOC protecting group under acidic conditions, yields the amine salt 6. The coupling of 6 with Cbz-leucine is it can be carried out with a coupling agent such as EDC, to produce the intermediate alcohol (not shown), which can be oxidized with an oxidant such as pyridine complex and sulfur trioxide in DMSO and triethylamine, to produce the ketone 7.

SCHEME 1 Reagents and conditions: a) NaH, 5-bromo-1-pentene, DMF; b) bis (tert-butoxide) of 2,6-diisopropylphenylimido-neofilidene of molybdenum or bis (tricyclohexylphosphine) benzylidene dichloride of ruthenium (IV); c) m-CPBA, CH2Cl2; d) NaN3, CH3OH, H2O, NH4CI; e) Pd / C 10%, H2; f) Cbz-leucine, EDC, CH2Cl2; g) HCl, EtOAc; h) Cbz-leucine, EDC, CH2Cl2; i) complex of sulfur trioxide and pyridine, DMSO, TEA. The compounds of general formula I wherein R1 and R2 are amides, can be prepared in the general manner described in scheme 2. The alkylation of N-Cbz-allylamine (8) with a base such as sodium hydride and 5-bromo-1-pentene produces diene 9. Treatment of 9 with ruthenium (IV) bis (tricyclohexylphosphine) benzylidene diene olefin metathesis catalyst, developed by Grubbs, produces azepine 10. Epoxidation of 10 with agents Standard oxidants common in the art, such as m-CPBA, produce epoxide 11. Nucleophilic opening of the epoxide ring can be performed with a reagent such as sodium azide, to give the azido alcohol (not shown), which can be reduced to amino alcohol 12 with a reducing agent such as propanedithiol, in the presence of triethylamine. Acylation of 12 with N-Boc-leucine and a coupling agent such as EDC, followed by removal of the Cbz protecting group under hydrogenolysis conditions, produces the amine 13. The coupling of 13 with a carboxylic acid is carried out with a coupling such as EDC, followed by removal of the acid-labile N-Boc protecting group, with an acid such as HCl or TFA, yielding intermediate 14. Acylation of 14 can be performed with a carboxylic acid in the presence of a coupling agent common in the art, such as EDC, to give the intermediate alcohol (not shown), which is oxidized with an oxidant such as sulfur trioxide complex and pyridine in DMSO and triethylamine, to produce the ketone 15.

SCHEME 2 12 13 14 15 Reagents and conditions: a) NaH, 5-bromo-1-pentene, DMF; b) bis (tricyclohexylphosphine) benzylidene dichloride catalyst of ruthenium (IV), CH2Cl2; c) m-CPBA, CH2Cl2; d) NaN3, CH3OH, H2O, NH4CI; e) propanedithiol, CH 3 OH, TEA; f) Boc-leucine, EDC, CH2Cl2; g) Pd / C 10%, H2; h) R? CO 2 H, EDC, CH 2 Cl 2 or RiCOCI, CH 2 Cl 2; i) HCl / EtOAc; j) R2CO2H, EDC, CH2Cl2; k) complex of sulfur trioxide and pyridine, DMSO, TEA. The compounds of the general formula I wherein R2 is an alkyl, urea or sulfonamide group and R1 is an amide, can be prepared in the general manner described in scheme 3. Reductive amination of 13 can be carried out by treatment with an aldehyde, followed by a reducing agent such as sodium triacetoxyborohydride. Subsequent deprotection of the N-Boc group under acidic conditions provides the amine salt 16. The coupling of 16 with an acid chloride or with a carboxylic acid in the presence of a coupling agent common in the art, such as EDC, followed by oxidation of the intermediate alcohol (not shown), with an oxidant such as sulfur trioxide complex and pyridine, produces the ketone 17. Alternatively, treatment of the amine 13 with an isocyanate, followed by deprotection of the N-Boc group, yields the amine salt 18. Acylation and oxidation produce the ketone 19. Additional derivatization of the amine 13 can be effected by treatment with a sulfonyl chloride, followed by deprotection of the N-Boc group to produce the amine salt 20. Acylation and oxidation yield the ketone 21.

SCHEME 3 13 20 Reagents and conditions: a) R ^ HO, NaBH (OAc) 3; b) HCl; c) R2CO2H, EDC, CH2Cl2; d) sulfur trioxide and pyridine complex, DMSO, TEA; e) R-iNCO, base; f) R? S02CI, TEA, CH2Cl2. The deuterated compound of example 192 can be conveniently prepared according to scheme 4. The skilled artisan will understand from example 192 and scheme 4 how to prepare any of the deuterated compounds of the present invention. The individual diastereomers of. { (S) -3-methyl-1 - [(2,2 ', 4-trideuterio) -3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] butyl} benzofuran-2-carboxylic acid amide 31 and 32 can be prepared as described in scheme 4. The alkylation of the benzyl ester of allylcarbamic acid 22 with 5-bromo-1-pentene in the presence of a base such as hydride sodium, produces the diene 23. The treatment of diene 23 with ruthenium (IV) bis (tricyclohexylphosphine) benzylidine dichloride, developed by Grubbs, produces the benzyl ester of 2,3,4,7-tetrahydro-azepin-1 - carboxylic acid 24. The epoxidation of azepine 24 can be carried out with standard oxidizing agents common in the art, such as m-CPBA, to produce epoxide 25. Nucleophilic opening of epoxide ring 25 can be carried out with a reagent such as sodium azide. , to produce the azido alcohol (not shown).

SCHEME 4 24 25 27 28 Reagents and conditions: a) NaH, 5-bromo-1-pentene, DMF; b) bis (tricyclohexylphosphine) benzylidene dichloride of ruthenium (IV), CH2Cl2; c) m-CPBA, CH2Cl2; d) NaN3, CH3OH, H2O, NH4CI; e) 1,3-propanedithiol, TEA, methanol; f) N-Boc-leucine, EDC, CH2Cl2; g) Pd / C 10%, H2; h) 2-pyridinesulfonyl chloride, TEA, CH2Cl2; i) 4N HCl / dioxane, methanol; j) benzofuran-2-carboxylic acid, EDC, CH2Cl2; k) sulfur trioxide and pyridine complex, DMSO, TEA; I) CD3OD: D2O (10: 1), TEA; m) CLAP separation. The intermediate azido alcohol can be reduced to the amino alcohol 26 under conditions common in the art, such as 1,3-propanedithiol and triethylamine in methanol, or with triphenylphosphine in tetrahydrofuran and water. Acylation of 26 can be carried out with an acid such as N-Boc-leucine in the presence of a coupling agent such as EDC. Removal of the benzyloxycarbonyl protecting group with hydrogen gas in the presence of 10% Pd / C yields the amine 27. Treatment of the amine 27 with 2-pyridinesulfonyl chloride in the presence of triethylamine or saturated solution of sodium bicarbonate and CH2Cl2, followed by removal of the tert-butoxycarbonyl protecting group under acidic conditions, it produces 28. Coupling of 28 with benzofuran-2-carboxylic acid can be effected with a coupling agent such as EDC, to produce the intermediate alcohol 29. The alcohol 29 can be oxidized with an oxidant such as pyridine complex and sulfur trioxide in DMSO and triethylamine, to produce the ketone 30 as a mixture of diastereomers. Treatment of the ketone 30 with triethylamine in CD3OD: D2O at reflux provides the deuterated analogue as a mixture of diastereomers which are separated by CLAP to produce the deuterated compounds 31 and 32. The compounds of general formula I can also be prepared as follows. described in scheme 5. The amine of compound 12 can be protected with di-tert-butyl dicarbonate to produce the N-Boc derivative 33 (scheme 2). Removal of the benzyloxycarbonyl protecting group can be effected by treatment of 33 with hydrogen gas in the presence of a catalyst such as 10% Pd / C, to produce the amine 34. Treatment of the amine 34 with a sulfonyl chloride such as 2-pyridinesulfonyl chloride in the presence of a base such as N-methylmorpholine or triethylamine, produces the sulphonamide derivative 35. Removal of the group can be carried out. tert-butoxycarbonyl protector with an acid such as hydrochloric acid, to produce intermediate 36. Coupling of 36 with an acid such as N-Boc-cyclohexylalanine, in the presence of a coupling agent common in the art such as HBTU or supported EDC in polymer, it produces the intermediate alcohol 37. Removal of the tert-butoxycarbonyl protecting group under acidic conditions produces the amine 38. The coupling of 38 with an acid such as benzofuran-2-carboxylic acid in the presence of a coupling agent such as HBTU or EDC supported on polymer, produces alcohol 39. Alcohol 39 can be oxidized with an oxidant common in the art, such as complex of sulfur trioxide and pyridine in DMSO, and triethylamine or Dess-Martin periodinane, to produce the ketone 40.

SCHEME 5 Reagents and conditions: (a) di-tert-butyl dicarbonate, THF; (b) H2, Pd / C 10%; (c) 2-pyridylsulfonyl chloride, TEA; (d) HCl, EtOAc; (e) N-Boc-cyclohexylalanine, P-EDC, CH2Cl2; (f) HCl, CH2Cl2; (g) benzofuran-2-carboxylic acid, P-EDC, CH2Cl2; (h) Dess-Martin periodinane, methylene chloride. The starting materials used herein are commercially available amino acids, or are prepared by routine methods well known to the person of ordinary skill in the art, which can be found in standard reference books, such as "Compendium of Organic Synthetic Methods. "Vol. I-VI (published by Wiley-lnterscience). Coupling methods for forming amide bonds are generally well known in the art. Peptide synthesis methods, generally described by Bodansky and others "The Practice of Peptide Synthesis", Springer-Verlag, Berlin, 1984; E. Gross and J. Meienhofer, "The Peptides", Vol. 1, 1-284 (1979); and J.M. Stewart and J.D. Young "Solid Phase Peptide Synthesis" 2nd. Edition, Pierce Chemical Co., Rockford Illinois, 1984, are generally illustrative of the art and are incorporated herein by reference. The synthetic methods for preparing the compounds of this invention often employ protecting groups to mask a reactive functionality or to reduce unwanted side reactions. These protecting groups are generally described in Green, T.W., "Protective Groups in Organic Synthesis," John Wiley & Sons, New York (1981). The term "amino protecting groups" generally refers to the Boc, acetyl, benzoyl, Fmoc and Cbz groups and derivatives thereof, as is known in the art. The methods for protection and deprotection, and for replacement of an amino protecting group with another portion, are well known. The acid addition salts of the compounds of formula I are prepared in a normal manner in a suitable solvent starting from the original compound and an excess of acid such as hydrochloric, hydrobromic, hydrofluoric, sulfuric, phosphoric, acetic, trifluoroacetic, maleic, succinic. or methanesulfonic. Some of the compounds form internal salts or zwitterions that may be acceptable. The cationic salts are prepared by treating the original compound with an excess of an alkaline reagent such as a hydroxide, carbonate or alkoxide, containing the appropriate cation; or with an appropriate organic amine. Cations such as L +, Na + K +, Ca ++, Mg ++ and NH4 +, are specific examples of cations present in pharmaceutically acceptable salts. Halides, sulfate, phosphate, alkanoates (such as acetate and trifluoroacetate), benzoates and sulfonates (such as mesylate), are examples of anions present in pharmaceutically acceptable salts. This invention also provides a pharmaceutical composition comprising a compound according to formula I and a pharmaceutically acceptable carrier, diluent or excipient. Therefore, the compounds of formula I can be used in the manufacture of a medicament. The pharmaceutical compositions of the compounds of formula I prepared as described hereinabove can be formulated as lyophilized solutions or powders for parenteral administration. The powders can be reconstituted before use by the addition of a suitable diluent or other pharmaceutically acceptable carrier. The liquid formulation can be an isotonic buffered aqueous solution. Examples of suitable diluents are normal isotonic saline solution, standard 5% dextrose solution in water or buffered solution of sodium or ammonium acetate. Said formulation is especially suitable for parenteral administration, but it can also be used for oral administration or dosages for insufflation can be packaged in an inhaler or nebulizer. It may be convenient to add excipients such as polyvinylpyrrolidone, gelatin, hydroxycellulose, acacia, polyethylene glycol, mannitol, sodium chloride or sodium citrate. Alternatively, these compounds can be encapsulated, tableted or prepared in an emulsion or syrup for oral administration. Pharmaceutically acceptable solid or liquid carriers can be added to improve or stabilize the composition, or to facilitate the preparation of the composition. Solid carriers include starch, lactose, calcium sulfate dihydrate, gypsum, magnesium stearate or stearic acid, talc, pectin, acacia, agar or gelatin. Liquid vehicles include syrup, peanut oil, olive oil, saline and water. The vehicle can also include a sustained release material such as glyceryl monostearate or glyceryl distearate, alone or with a wax. The amount of solid carrier varies, but will preferably be between about 20 mg to about 1 g per unit dose. The pharmaceutical preparations are made following conventional pharmacy techniques, which include grinding, mixing, granulation and compression, when necessary, for tablet forms; or grinding, mixing and filling for hard gelatin capsule forms. When a liquid carrier is used, the preparation will be in the form of a syrup, elixir, emulsion or an aqueous or non-aqueous suspension. Said liquid formulation can be administered directly orally or it can be supplied in a soft gelatin capsule. For rectal administration, the compounds of this invention can also be combined with excipients such as cocoa butter, glycerin, gelatin or polyethylene glycols, and molded into the form of a suppository.

Novel Intermediates Referring to the methods of preparation of the compounds of formula I described in schemes 1-4 above, the skilled artisan will appreciate that the present invention includes all novel intermediates required to make the compounds of formula I. In particular, the present invention provides the compounds of formula II: wherein: R1 is selected from the group consisting of: R2 is selected from the group consisting of: H, Ci-β alkyl, (C3-β) cycloalkyl-Co-βalkyl, Co-βalkyl, Co-β-Het alkyl, R9C ( OR)-, RaC (S) -, RaSO2-, ROC (O) -, R > 9aDR1p1NC (O) -, R 9aRo1p1 rNC (S) -, R > 9a (/ DR1"1A) NSO2- R6 R3 is selected from the group consisting of: H, C-? 6 alkyl, C2.6 alkenyl, C2.sub.x alkynyl, C0-6Het-alkyl and C0-6alkyl; R3 and R 'may be linked to form a pyrrolidine, piperidine or morpholine ring; R 4 is selected from the group consisting of H, C-α-6 alkyl, (C 3-6) cycloalkyl-Co-β alkyl, Co-β-Ar alkyl, Co-β-Het-aikyl, R 5C (O ) -, R5C (S) -, R5SO2-, R5OC (O) -, R5R13NC (O) -, and R5R13NC (S) -; R5 is selected from the group consisting of: H, d-β alkyl, C2-6 alkenyl, C2-β alkynyl, C3-6 cycloalkyl- Co-βalkyl, C0-6alkyl and Het-alkyl of CO-T; R6 is selected from the group consisting of: H, C-i-β alkyl, Ar-C0-6 alkyl or Het-C06 alkyl; R7 is selected from the group consisting of: H, Ci-β alkyl, (C3-6) cycloalkyl-C0-β alkyl, Ar-C0-β alkyl, Het-alkyl of Co-β, R10C (O) -, R10C (S) -, R10SO2-, R10OC (O) -, R10R14NC (O) -, and R10R14NC (S) -; R8 is selected from the group consisting of: H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Het-alkyl of Co-β and Ar-alkyl of C0-6; R9 is selected from the group consisting of: C-i-β alkyl, (C3-6) cycloalkyl-Co-β alkyl, Ar-C06 alkyl and Het-C06 alkyl; R10 is independently selected from the group consisting of: C1-6 alkyl, (C3-6) alkyl-C0-β alkyl. Ar-C0-β alkyl and Het-alkyl of Co-6; R11 is selected from the group consisting of: H, C-i-β alkyl, Ar-Co-β alkyl and Het-Co-β alkyl; R12 is selected from the group consisting of: H, C-i-β alkyl, Ar-Co-β alkyl and Het-Co-β alkyl; R13 is selected from the group consisting of: H, C-i-β alkyl, Ar-alkyl of Co-6 and Het-alkyl of Co-β; R 14 is selected from the group consisting of: H, C 1-6 alkyl, Ar-C 1 alkyl and Het-C 0 -β alkyl; R 'is selected from the group consisting of: H, C-i-β alkyl, Ar-C 0-6 alkyl and Het-alkyl of Co-6. R "is selected from the group consisting of: H, C? -6 alkyl, Ar-Co-ß alkyl or Het-Co-β alkyl; R "is selected from the group consisting of: H, C? -6 alkyl, (C3-6) cycloalkyl-Co-β alkyl, C0-6 Ar-alkyl and C0-? Het-alkyl; X is selected from the group consisting of: CH2, S and O; Z is selected from the group consisting of: C (O) and CH2; and pharmaceutically acceptable salts, hydrates and solvates thereof The following compounds are preferred novel intermediates: [(S) -1- (3-hydroxy-azepan-4-carbamoyl) -3-methyl-butyl-carbamic acid benzyl ester; (1-benzyl-3-hydroxy-azepane-4-yl) -am Of (S) -2-amino-4-methyl-pentanoic acid; .3-hydroxy-1 - [2- (3-pyridin-2-yl-phenyl) acetyl] azepane-4 -yl. -amide of (S) -2-amino-4-methyl-pentanoic acid; benzyl acid ester { (S) -1- [4 - ((S) -2-amino- 4-methyl-pentanoylamino) -3-hydroxy-azepan-1-ylmethyl] -3-methyl-butyl} -carbamic acid (1-benzoyl-3-hydroxy-azepan-4-yl) -amide (S) -2-amino-4-methyl-pentanoic; [3-hydroxy-1- (4-methyl-pentanoyl) -azepan-4-yl] -amide of (S) -2-amino-4 -amide methyl-pentanoic acid (S) -2-amino-4-methyl-pentanoic acid (1-benzenesulfonyl-3-hydroxy-azepan-4-yl) -amide; . { (S) -3-methyl-1- [3-hydroxy-1- (1-oxy-pyridine-2-sulfonyl) -azepan-4-yl-carbamoyl] -butyl} thieno [3,2-b] thiophene-2-carboxylic acid amide; . { (S) -3-methyl-1 - [3-hydroxy-1 - (1-oxy-pyridin-2-sulfonyl) -azepan-4-yl-carbamoyl] -butyl ester} 5-methoxybenzofuran-2-carboxylic acid amide; . { (S) -3-methyl-1 - [3-hydroxy-1- (pyridine-2-sulfonyl) -azepan-4-yl-carbamoyl] -butyl} thieno [3,2-b] thiophene-2-carboxylic acid amide; . { (S) -3-methyl-1- [3-hydroxy-1- (1-oxy-pyridine-2-sulfonyl) -azepan-4-yl-carbamoyl] -butyl ester} 3-methylbenzofuran-2-carboxylic acid amide; . { (S) -3-methyl-1 - [3-hydroxy-1 - (1-oxy-pyridin-2-sulfonyl) -azepan-4-yl-carbamoyl] -butyl ester} quinoline-2-carboxylic acid amide; Y . { (S) -3-methyl-1 - [3-hydroxy-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-yl-carbamoyl] -butyl ester} quinoxaline-2-carboxylic acid amide; Process for the synthesis of the compounds of the invention With reference to the schemes 1-5 above, the present invention provides a process for the synthesis of the compounds of formula (I), which comprises the step of oxidizing the appropriate compound of formula (II) with an oxidant, to provide the compound of formula (I) as a mixture of diastereomers. Preferably, the oxidant is a complex of sulfur trioxide and pyridine in DMSO and triethylamine. Referring to scheme 4, the present invention also provides a method for the synthesis of deuterated compounds of formula (I). Specifically, when a deuterated isomer is desired, an additional step of deuterating the protonated isomer after the oxidation step is added to the synthesis with a deuterating agent to produce the deuterated compound of formula (I) as a mixture of diastereomers. Preferably, the deuteterant is CD3OD: D2O (10: 1) in triethylamine. The process further comprises the step of separating the diastereomers of formula (I) by separation means, preferably high pressure liquid chromatography (CLAP).

Utility of the present invention The compounds of formula I are useful as protease inhibitors, particularly as inhibitors of cysteine and serine proteases, particularly as inhibitors of cysteine proteases; in particular as inhibitors of cysteine proteases of the papain superfamily, particularly as inhibitors of cysteine proteases of the cathepsin family; very particularly as inhibitors of cathepsin K. The present invention also provides useful compositions and formulations of said compounds, which include compositions and pharmaceutical formulations of said compounds. The present compounds are useful for treating diseases in which cysteine proteases are implicated, including infections by Pneumocystis carinii, Trypanosoma cruzi, Trypanosoma brucei and Crithidia fusiculata; as well as in schistosomiasis, malaria, tumor metastasis, metachromatic leukodystrophy, muscular dystrophy, amyotrophy; and especially diseases in which cathepsin K is involved, particularly diseases of excessive loss of bone or cartilage, including osteoporosis, gingival disease including gingivitis and periodontitis; arthritis, more specifically osteoarthritis and rheumatoid arthritis; Paget's disease; hypercalcemia of malignancy and metabolic bone disease. Regularly, metastatic neoplastic cells also express high levels of proteolytic enzymes that degrade the surrounding matrix, and certain tumors and metastatic neoplasms can be effectively treated with the compounds of the invention. The present invention also provides methods of treating diseases caused by pathological levels of proteases, particularly of cysteine and serine proteases, particularly cysteine proteases; particularly of cysteine proteases of the papain superfamily, particularly cysteine proteases of the cathepsin family; said methods comprise administering a compound of the present invention to an animal, in particular to a mammal, particularly a human in need thereof. Especially, the present invention provides methods of treating diseases caused by pathological levels of cathepsin K; said methods comprise administering a cathepsin K inhibitor that includes a compound of the present invention, to an animal, in particular to a mammal, particularly a human in need thereof. In particular, the present invention provides methods for treating diseases in which cysteine proteases are implicated, including infections by Pneumocystis carinii, Trypanosoma cruzi, Trypanosoma brucei and Crithidia fusiculata; as well as in schistosomiasis, malaria, tumor metastasis, metachromatic leukodystrophy, muscular dystrophy, amyotrophy, and especially diseases in which cathepsin K is implicated, particularly diseases of excessive loss of bone or cartilage, including osteoporosis, gingival disease including gingivitis and periodontitis; arthritis, more specifically osteoarthritis and rheumatoid arthritis; Paget's disease; hypercalcemia of malignancy and metabolic bone disease. This invention also provides a method for treating osteoporosis or inhibiting bone loss, comprising administering to a patient an effective amount of a compound of formula I, alone or in combination with other inhibitors of bone resorption, such as bisphosphonates (that is, alendronate), hormone replacement therapy, antiestrogens or calcitonin. In addition, treatment with a compound of this invention and an anabolic agent such as bone morphogenic protein, iproflavone, can be used to prevent bone loss or to increase bone mass. For acute therapy, parenteral administration of a compound of formula I is preferred. An intravenous infusion of the compound in 5% dextrose in water or normal saline, or a similar formulation with suitable excipients; however, an intramuscular bolus injection is also useful. Typically, the parenteral dose will be from about 0.01 to about 100 mg / kg, preferably between 0.1 and 20 mg / kg, so as to maintain the concentration of the drug in the plasma at an effective concentration to inhibit cathepsin K. The compounds are administer one to four times a day at a level sufficient to achieve a total daily dose of about 0.4 to about 400 mg / kg / day. The precise amount of the compound of the invention that is therapeutically effective, and the route by which said compound is best administered, can be readily determined by a person of average skill in the art by comparing the blood level of the agent with the concentration required for have a therapeutic effect The compounds of this invention can also be administered orally to the patient, such that the concentration of the drug is sufficient to inhibit bone resorption or to achieve any other therapeutic indication described herein. Typically, a pharmaceutical composition containing the compound is administered at an oral dose of between about 0.1 to about 50 mg / kg, consistent with the patient's condition. Preferably, the oral dose would be from about 0.5 to about 20 mg / kg. When the compounds of the present invention are administered in accordance with the present invention, unacceptable toxicological effects are not expected.

Biological Tests The compounds of this invention can be tested in one of several biological tests to determine the concentration of compound that is required to have a given pharmacological effect.

Determination of the proteolytic catalytic activity of cathepsin K All cathepsin K tests were carried out with recombinant human enzyme. Under the standard test conditions for the determination of kinetic constants, a fluorogenic peptide substrate, typically Cbz-Phe-Arg-AMC, was used and determined in 100 mM Na acetate at pH 5.5, containing 20 mM cysteine and EDTA 5 mM. Substrate supply solutions were prepared at concentrations of 10 or 20 mM in DMSO with a final substrate concentration in the 20 μM tests. All tests contained 10% DMSO. In independent experiments it was found that this level of DMSO had no effect on enzyme activity or on kinetic constants. All tests were performed at room temperature. The fluorescence of the product (excitation at 360 nM, emission at 460 nM) was monitored with a fluorescent plate reader Cytofluor II from Perceptiove Biosystems. Product advance curves were generated for 20 or 30 minutes following the formation of the AMC product.

Inhibition studies Potential inhibitors were evaluated using the forward curve method. The tests were carried out in the presence of varying concentrations of the test compound. The reactions were initiated by the addition of enzyme to buffered solutions of inhibitor and substre-:. Data analysis was carried out according to one of two procedures, C tending to the appearance of the advance curves in the presence of the • hybridizers. For those compounds whose forward curves were linear, apparent inhibition constants (Ki, ap) were calculated according to Nation 1 (Brandt et al., Biochemistry, 1989, 28, 140): • VnA / [Ka (1 + l / Ki, ap) + A] (1) where v is the 'Deity of the reaction with maximum velocity Vm, A is the concentration of ostrato with the Michaelis constant of Ka, and I is the concentration of ir j idor. For . . Those compounds whose forward curves showed downward characteristics of time-dependent inh? t tion, analyzed the c.os of individual groups -ira giving k0bs according to equation 2: [AMC] - Vs: (v0 - vss) [1-exp (-kobst)] / -s (2) where [AMC] is the concentration of product formed during time t, v0 is the initial velocity of the reaction and vss is the final steady state speed. The values for kobs were then analyzed as a linear function of inhibitor concentration to generate a second order apparent velocity constant (k0Ds / concentration of inhibitor or kobs / [I]) which describes the time-dependent inhibition. A complete discussion of this kinetic treatment has been fully described (Morrison et al., Adv. Enzymol, Relat.Areas Mol. Biol. 1988, 61, 201).

Resorption test of human osteoclasts Aliquots of cell suspensions derived from storage osteoclastoma were removed in liquid nitrogen; they were rapidly heated to 37 ° C and washed 1x in RPMI-1640 medium by centrifugation (1000 rpm, 5 minutes at 4 ° C). The medium was aspirated and replaced with murine anti-HLA-DR antibody; it was diluted 1: 3 in RPMI-1640 medium and incubated for 30 minutes on ice. The cell suspension was mixed frequently. The cells were washed x2 with cold RPMI-1640 by centrifugation (1000 rpm, 5 minutes at 4 ° C), and then transferred to a sterile 15 ml centrifuge tube. The number of mononuclear cells was counted in an improved Neubauer counting chamber. A few magnetic beads (5 / mononuclear cell), coated with goat anti-IgG, were removed from their supply container and placed in 5 ml of fresh medium (this washes the toxic azide preservative). The medium was removed by immobilizing the globules on a magnet and replaced with fresh medium. The beads were mixed with the cells and the suspension incubated for 30 minutes on ice. The suspension was mixed frequently. The cells that coated the globules were immobilized on a magnet, and the remaining cells (fraction rich in osteoclasts) were decanted in a 50 ml sterile centrifuge tube. New medium was added to the cells that coated the beads to dislodge any entrapped osteoclasts. This washing procedure was repeated x 10. The cells coating the beads were discarded. Viable osteoclasts were counted in a counting chamber using a large-bore disposable plastic Pasteur pipette to charge the chamber with the sample. The cells were pelleted by centrifugation, and the density of the osteoclasts was adjusted to 1.5 x 10 4 / ml in EMEM medium supplemented with 10% fetal calf serum and 1.7 g / liter of sodium bicarbonate. 3 ml aliquots of the cell suspension (by treatment) were decanted into 15 ml centrifuge tubes. The cells were pelleted by centrifugation. To each tube was added 3 ml of the appropriate treatment (diluted to 50 μM in the EMEM medium). Also included were appropriate vehicle controls, a positive control (87MEM1 diluted to 100 μg / ml) and an isotype control (IgG2a diluted to 100 μg / ml). The tubes were incubated at 37 ° C for 30 minutes. 0.5 ml aliquots of the cells were seeded onto pieces of sterile dentin in a 48-well plate and incubated at 37 ° C for 2 hours. Each treatment was screened in quadruplicate. The pieces were washed in six changes of hot PBS (10 ml / well in a 6-well plate) and then placed in new treatment or control and incubated at 37 ° C for 48 hours. The pieces were then washed in phosphate buffer saline and fixed in 2% glutaraldehyde (in 0.2 M sodium cacodylate) for 5 minutes, after which they were washed in water and incubated in buffer for 5 minutes at 37 ° C. C. The pieces were then washed in cold water and incubated in cold fast red garnet / acetate buffer for 5 minutes at 4 ° C. The excess cushion was sucked and the pieces were air dried after washing in water. TRAP positive osteoclasts were counted by bright field microscopy and then removed from the surface of the dentin by sonication. The pit volumes were determined using the Nikon / Lasertec ILM21W confocal microscope.

General Nuclear magnetic resonance spectra were recorded at 250 or 400 MHz using, respectively, a Bruker AM 250 spectrometer or Bruker AC 400. CDCI3 is deuteriochloroform, DMSO-dβ is hexadeuteriodimethyl sulfoxide and CD3OD is tetradeuteriomethanol. Chemical shifts are reported in parts per million (d) to the lower part of the internal tetramethylsilane standard. The abbreviations of the NMR data are as follows: s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet, dd = doublet of doublets, dt = doublet of triplets, ap = apparent, br = broad . J indicates the NMR coupling constant measured in Hertz. Continuous wave infrared (IR) spectra were recorded on a Perkin-Elmer 683 infrared spectrometer, and Fourier transform infrared (IRTF) spectra were recorded on a Nicolet Impact 400 D infrared spectrometer. The IR and I RTF spectra were recorded at transmission mode and band positions are reported in inverse wave numbers (cm "1). Mass spectra were obtained in instruments VG 70 FE, PE Syx API lll or VG ZAB HF, using fast atomic bombardment (FAB) techniques or Electrospray (ES) Elemental analyzes were obtained using a Perkin-Elmer 240C elemental analyzer, melting points were taken on a Thomas-Hoover melting point apparatus, and are not corrected, all temperatures are reported in degrees Celsius. Thin layer silica gel plates Analtech Silica Gel GF and E. Merck Silica Gel 60 F-254, to perform thin layer chromatography, flash and flash chromatography was carried out age on a Kieselgel 60 silica gel from E. Merck (230-400 mesh). Where indicated, some of the materials were purchased at Aldrich Chemical Co., Milwaukee, Wisconsin; Chemical Dynamics Corp., South Plainfield, New Jersey; and Advanced Chemtech, Lousville, Kentucky.

EXAMPLES In the following synthesis examples, the temperature is in degrees centigrade (° C). Unless otherwise indicated, all starting materials were obtained from commercial sources. Without further elaboration, it is considered that one skilled in the art can use the present invention to its fullest extent using the foregoing description. These examples are given to illustrate the invention, not to limit its scope. Reference is made to the claims which are reserved to the inventors by virtue of this.

EXAMPLE 1 Preparation of benzyl acid ester. { (S) -1 - | i - ((S) -2- benzyloxycarbonylamino-4-methyl-pentanoyl) -3-oxo-azepan-4-carbamoyl) -carbamic (a) Allyl-pent-4-enylcarbamic acid tert-butyl ester To a suspension of NaH (3.05 g, 76.33 mmol 60% NaH in oil, washed with hexane) in DMF (30 ml), added tert-butyl N-alylcarbamate (6.0 g, 38.2 mmol) in the form of drops. The mixture was stirred at room temperature for about 10 minutes, after which 5-bromo-1-pentene (6.78 ml, 57.24 mmol) was added as drops. The reaction was heated at 40 ° C for about 2 hours, after which the reaction was partitioned between ethyl acetate and water. The organic layer was washed with water (2 x) and brine; dried (MgSO4), filtered and concentrated to give 10 grams of the title compound as an oil: MS (EI) 226 (M + H +). (b) 2,3,4,7-Tetrahydro-azepine-1-carboxylic acid tert-butyl ester To a solution of the compound of example 1 to (4.5 g) in benzene was added bis (1-butoxide) 2,6-diisopropylphenylimidoneofilidene molybdenum (600 mg). The reaction was heated to reflux for 1.5 hours, after which the reaction was concentrated in vacuo. Chromatography of the residue (CH2Cl2 50%: hexane) gave 3.92 g of the product. (c) 8-Oxa-3-aza-bicyclo [5.1.0] octane-3-carboxylic acid tert-butyl ester To a solution of the compound of example 1b (3.0 g, 15.2 mmol) in CH2Cl2, it was added to -CPBA (7.8 g, 45.6 mmoles). The mixture was stirred overnight at room temperature, after which it was partitioned between CH2Cl2 and saturated K2CO3 solution. The organic layer was washed with saturated NaHCO3 solution, water and brine; dried (MgSO4), filtered and concentrated to give 3.11 g of the title compound as an oil: MS (EI) 214 (M + H +). (d) 4-Azido-3-hydroxy-azepan-1-carboxylic acid tert-butyl ester To a solution of the epoxide of example 1c (3.92 g, 20 mmol) in methanol (189 ml of an 8: 1 solution), NH CI (3.18 g, 60 mmol) and sodium azide (3.9 g, 60 mmol) were added. The reaction was heated to 40 ° C until full consumption of the starting epoxide was observed by CCD analysis. The majority of the solvent was removed in vacuo and the remaining solution was diluted with ethyl acetate, and washed with water and brine and dried (Na2SO), filtered and concentrated. Column chromatography of the residue (40% ethyl acetate: hexane) yielded 3.43 g of the title compound. (e) 4-amino-3-hydroxy-azepane-1-carboxylic acid tert-butyl ester To a solution of the azido alcohol of Example 1d (3.4 g) and 10% Pd / C (catalytic) in ethyl acetate: methanol (solution 2: 1), a hydrogen balloon was attached. The reaction was stirred until full consumption of the starting material was observed by CCD analysis. The reaction was filtered to remove the catalyst and the filtrate was concentrated in vacuo. Column chromatography of the residue (25% methanol: dichloromethane) yielded 2.57 g of the title compound: MS (EI) 231 (M + H +). (f) 4 - ((S) -2-Benzyloxycarbonylamino-4-methyl-pentanoylamino) -3-hydroxy-azepane-1-carboxylic acid tert-butyl ester To a solution of the amino alcohol of example 1e (160 mg, 0.70 mmoles) in CH2Cl2, EDC (134 mg), HOBt (94 mg) and Cbz-leucine (185 mg) were added. The reaction was maintained at room temperature until full consumption of the starting material was observed by CCD analysis. The reaction was diluted with ethyl acetate and washed with 1 N HCl, saturated K2CO3 solution, water and brine; dried (MgSO4), filtered and concentrated. Column chromatography of the residue (3% methanol: dichloromethane) gave 200 mg of the title compound: MS (El) 478 (M + H +), 500 (M + Na +). (g) [(S) -1- (3-hydroxy-azepan-4-ylcarbamoyl) -3-methyl-butyl] carbamic acid benzyl ester To a solution of the compound of example 1f (200 mg, 0.42 mmol) in methanol (5 ml) was added 4M HCl in dioxane (5 ml). The reaction was stirred at room temperature for about 2 hours, after which the solvent was removed under vacuum to give 168 mg of the title compound: MS (El) 378 (M + H +). (h) Benzyl ester of acid. { (S) -1- [4 - ((S) -2-benzyloxycarbonylamino-4-methyl-pentanoylamino) -3-hydroxy-azepan-1-carbonyl] -3-methyl-butyl} To a solution of the amine salt of example 1g (168 mg, 0.42 mmol) in CH2Cl2, EDC (81 mg), HOBt (57 mg), triethylamine (0.09 ml) and Cbz-leucine (111 mg) were added. . The reaction was stirred until complete, according to CCD analysis. Per treatment followed by column chromatography (CH3OH 5%: CH2Cl2) yielded 159 mg of the title compound. MS (El) 625 (M + H +). (i) Benzyl ester of acid. { (S) -1- [4 - ((S) -2-benzyloxycarbonylamino-4-methyl-pentanoylamino) -3-oxo-azepane-1-carbonyl] -3-methyl-butyl} carbonaceous To a solution of the alcohol of example 1 h (130 mg, 0.21 mmol) in DMSO, TEA (0.17 ml) and sulfur trioxide and pyridine complex (97 mg, 0.62 mmol) were added. The reaction was stirred at room temperature for about 2 hours, after which it was partitioned between ethyl acetate and water. The organic layer was washed with brine, dried (MgSO 4), filtered and concentrated. Column chromatography of the residue (CH3OH 5%: CH2Cl2) yielded 100 mg of the title compound as a mixture of diastereomers: 1 H NMR (CDCl 3): d 1.0 (m, 12 H), 1.5-2.1 (m, 8 H), 2.2 (m, 4H), 3.0 (m, 1H), 3.5 (d, 1 H), 3.6 (d, 1 H), 4.01 (m, 1 H), 4.5 (m, 2H), 4.7 (m, 1 H) ), 5.0 (m, 5H), 7.3 (m, 10H); MS (El) 623 (M + H +), 645 (M + Na +). Separation of the diastereomers by CLAP yielded diastereomer 1: MS (El) 623 (M + H +), 645 (M + Na +) and diastereomer 2: MS (ES) 623 (M + H +), 645 (M + Na + ).

EXAMPLE 2 Preparation of r S) -1- (1-benzyl-3-oxo-azepan-4-ylcarbamoyl) -3-methyl-butylamide of naphthylene-2-carboxylic acid (a) Benzyl ester of allyl-pent-4-enylcarbamic acid To a suspension of NaH (1.83 g, 76.33 mmoles of 90% NaH) in DMF, benzyl-allylcarbamic acid benzyl ester (7.3 g) was added. , 38.2 mmoles) in the form of drops. The mixture was stirred at room temperature for about 10 minutes, after which 5-bromo-1-pentene (6.78 ml, 57.24 mmol) was added as drops. The reaction was heated at 40 ° C for about 4 hours, after which the reaction was partitioned between dichloromethane and water. The organic layer was washed with water (2x) and brine; dried (MgSO), filtered and concentrated. By column chromatography of the residue (10% ethyl acetate: hexane) 10.3 grams of the title compound were obtained as an oil: MS (EI) 260 (M + H +). (b) 2, 3,4, 7-Tetrahydroazepin-1-carboxylic acid benzyl ester To a solution of the compound of Example 2a (50 g) in dichloromethane, ruthenium (IV) (5.0 g) dichloride (tricyclohexylphosphine) benzylidene dichloride was added. The reaction was heated to reflux until it was completed according to CCD analysis. The reaction was concentrated in vacuo. Column chromatography of the residue (dichloromethane 50%: hexane) yielded 35 g of the title compound: MS (EI) 232 (M + H +). (c) 8-Oxa-3-aza-bicyclo [5.1.0] octane-3-carboxylic acid benzyl ester The title compound was prepared following the general procedure of example 1c, but substituting the compound of example 2b: EM (EI) 248 (M + H +), 270 (M + Na +). (d) 4-Azido-3-hydroxy-azepan-1-carboxylic acid benzyl ester To a solution of the epoxide of example 2c (2.0 g, 8.1 mmol) in methanol: water (8: 1 solution), NH4Cl was added. (1.29 g, 24.3 mmol) and sodium azide (1.58 g, 24.30 mmol). The reaction was heated to 40 ° C until full consumption of the starting epoxide was observed according to CCD analysis. Most of the solvent was removed in vacuo and the remaining solution was partitioned between ethyl acetate and pH 4 buffer. The organic layer was washed with saturated NaHCO3 solution, water and brine; dried (MgSO4), filtered and concentrated. Column chromatography of the residue (20% ethyl acetate: hexane) yielded 1.3 g of the title compound: MS (EI) 291 (M + H +) plus 0.14 g of the trans-4-hydroxy-3-azidohexahydro- 1 H-azepine. (e) 4-Amino-3-hydroxy-azepane-1-carboxylic acid benzyl ester To a solution of the azido alcohol from Example 2d (1.1 g, 3.79 mmol) in methanol, triethylamine (1.5 mL, 11.37 mmol) was added. and 1,3-propanedithiol (1.1 ml, 11.37 ml). The reaction was stirred until complete consumption of the starting material was observed by CCD analysis, after which the reaction was concentrated in vacuo. Column chromatography of the residue (20% methanol: dichloromethane) afforded 0.72 g of the title compound: MS (EI) 265 (M + H +). (f) 4 - ((S) -2-tert-Butoxycarbonylamino-4-methyl-pentanoylamino) -3-hydroxy-azepane-1-carboxylic acid benzyl ester To a solution of the amino alcohol of example 2e (720 mg, 2.72 mmoles) in CH2Cl2, EDC (521 mg), HOBt (368 mg) and N-Boc-leucine (630 mg) were added. The reaction was maintained at room temperature until full consumption of the starting material was observed by CCD analysis. The reaction was diluted with ethyl acetate and washed with 1 N HCl, saturated K2CO3 solution, water and brine.; dried (MgSO), filtered and concentrated. Column chromatography of the residue (methanol 3%: dichloromethane) gave 1.0 g of the title compound: MS (EI) 478 (M + H +). (g) [(S) -1- (3-hydroxy-azepan-4-ylcarbamoyl) -3-methyl-butyl] carbamic acid tert-butyl ester To a solution of the compound of Example 2f (1.0 g) and Pd / C 10% (catalytic) in ethyl acetate: methanol (2: 1 solution), a hydrogen balloon was added. The reaction was stirred until full consumption of the starting material was observed by CCD analysis. The reaction was filtered to remove the catalyst and the filtrate was concentrated in vacuo to yield 0.82 g of the title compound: MS (EI) 344 (M + H +). (h) [(S) -1- (1-Benzyl-3-hydroxy-azepan-4-ylcarbamoyl) -3-methyl-butyl] carbamic acid tert-butyl ester To a solution of the compound of Example 2g (0.69 g , 2.01 mmol) in CH2Cl2, benzaldehyde (0.32 ml, 3.01 mmol) was added, followed by sodium triacetoxyborohydride (0.85 g, 4.02 mmol). The reaction was stirred until complete as determined by CCD analysis, after which several drops of water were added to the reaction to destroy the excess of sodium triacetoxyborohydride. The mixture was diluted with ethyl acetate, washed with saturated NaHCO3 solution, water and brine; dried (Na2SO4), filtered and concentrated. Column chromatography of the residue (5% methanol: dichloromethane) gave 800 mg of the title compound: MS (ES) 434 (M + H +). (i) (S) -2-amino-4-methyl-pentanoic acid (1-Benzyl-3-hydroxy-azepan-4-yl) amide To a solution of the compound of example 2h (800 mg) in methanol ( ml), 4M HCl in dioxane (15 ml) was added. The reaction was stirred at room temperature overnight, after which it was concentrated in vacuo to give 800 mg of the title compound: MS (ES) 334 (M + H +). (j) [(S) -1- (1-Benzyl-3-hydroxy-azepan-4-ylcarbamoyl) -3-methyl-butyljamide of naphthylene-2-carboxylic acid To a solution of the amine salt of example 2i ( 200 mg, 0.49 mmole) in CH2Cl2, triethylamine (0.17 ml, 1.22 mmol), EDC (103.5 mg, 0.54 mmol), HOBt (73 mg, 0.54 mmol) and 2-naphthoic acid (93 mg, 0.54 mmol) were added. . The reaction was stirred until complete by CCD analysis. The reaction was diluted with ethyl acetate and washed with saturated NaHCO3 solution, water and brine; dried (Na2SO4), filtered and concentrated. Column chromatography of the residue (5% methanol: dichloromethane) gave 0.14 g of the title compound: MS (EI) 488 (M + H +). (k) [(S) -1- (1-Benzyl-3-oxo-azepan-4-ylcarbamoyl) -3-methyl-butyl] naphthylene-2-carboxylic acid amide The title compound was prepared following the general procedure of example 1 i, but the compound of example 1 i was replaced with the compound of example 2i: 1 H NMR (CDCl 3): d 1.0 (m, 6H), 1.5-2.1 (m, 5H), 2.2 (m, 2H ), 2.9 (m, 1 H), 3.2 (dd, 1 H), 3.4 (m, 1 H), 3.7 (m, 2 H), 4.7 (m, 1 H), 5.2 (m, 1 H), 7.2 -8.4 (m, 12H); MS (EI): 486 (M + H +, 100%). Separation of the diastereomers by CLAP yielded diastereomer 1: MS (EI) 486.3 (M + H +), and diastereomer 2: MS (ES) 486.3 (M + H +).

EXAMPLE 3 Preparation of T (S) -1 - (1-benzyl-3-oxo-azepan-4-ylcarbamoyl) -3-methyl-butylamide of benzoM, 31-dioxol-5-carboxylic acid (a) [(S) -1- [3- (1-Benzyl-3-hydroxy-azepan-4-ylcarbamoyl) -3-methyl-butyljamide of benzo [1,3] -dioxol-5-carboxylic acid The title compound is prepared following the general procedure of Example 2j, but substituting 2-naphthoic acid with piperonyl acid: MS (ES) 482 (M + H +). (b) [(S) -1,3] -dioxol-5-carboxylic acid [(S) -1- (1-Benzyl-3-oxo-azepan-4-ylcarbamoyl) -3-methyl-butyl] -amide] The title was prepared following the general procedure of Example 11, but using the compound of Example 3a: 1 H NMR (CDCl 3): d 1.0 (m, 6H), 1.5-2.1 (m, 5H), 2.2 (m, 2H), 2.9 (m, 1 H), 3.0 (m, 1 H), 3.2 (d, 1 H), 3.2 (d, 1 H), 3.5 (q, 1 H), 3.7 (m, 2 H), 4.7 (m, 1 H), 5.2 (m, 1 H), 6.0 (s, 2H), 6.8 (m, 2H), 7.2 (m, 6H); MS (EI): 480 (M + H +, 100%). The diastereomers were separated by CLAP at the preparative scale. By lyophilization of the eluates, diastereomer 1 was obtained: MS (EI) 480.3 (M + H +), 959.6 2M + H +) and diastereomer 2: MS (EI) 480.3 (M + H +), 959.6 2M + H +).

EXAMPLE 4 Preparation of benzofuran-2-carboxylic acid T (S) -1H-benzyl-3-oxo-azepan-4-ylcarbamoyl) -3-methylene-butylamide (a) [(S) -1- (1-Benzyl-3-hydroxy-azepan-4-ylcarbamoyl) -3-methyl-butyl] -benzofuran-2-carboxylic acid amide The title compound was prepared following the general procedure of Example 2j, but substituting 2-naphthoic acid with benzofuran-2-carboxylic acid: MS (ES) 478 (M + H +). (b) [(S) -1- (1-Benzyl-3-oxo-azepan-4-ylcarbamoyl) -3-methyl-butyl] -benzofuran-2-carboxylic acid amide The title compound was prepared following the general procedure of Example 1, but using the compound of Example 4a: 476 EM (EI): 492 (M + H +, 100%). The diastereomers were separated by means of CLAP at the preparative scale. The lyophilization of the eluates produced diastereomer 1: MS (EI) 476.4 (M + H +), 951.6 (M + H +), and diastereomer 2: MS (EI) 476.4 (M + H +), 951.6 2M + H +).

EXAMPLE 5 Preparation of I? S) -1 - (1-benzyl-3-oxo-azepan-4-ylcarbamoyl) -3-methyl-butylamide of benzofiblothiophen-2-carboxylic acid (a) [(S) -1- (1-Benzyl-3-hydroxy-azepan-4-ylcarbamoyl) -3-methyl-butyljamide of benzo [b] thiophene-2-carboxylic acid The title compound was prepared following the General procedure of Example 2j, but substituting 2-naphthoic acid with benzothiophen-2-carboxylic acid: MS (ES) 494 (M + H +). (b) [(S) -1- (1-Benzyl-3-oxo-azepan-4-ylcarbamoyl) -3-methyl-butyl] benzo [b] thiophene-2-carboxylic acid amide The title compound was prepared following the general procedure of example 1 i, but using the compound of example 5a: 1H NMR (CDCl 3): d 1.0 (m, 6H), 1.5-2.1 (m, 5H), 2.2 (m, 2H), 2.9 (m, 1 H), 3.2 (dd, 1 H), 3.4 (m, 1 H ), 3.7 (m, 2H), 4.7 (m, 1H), 5.2 (m, 1H), 7.2-8.4 (m, 10H): MS (EI) 492 (M + H +, 100%). The diastereomers were separated by means of CLAP at the preparative scale. The lyophilization of the eluates yielded diastereomer 1: MS (EI) 492.4 (M + H +), 983.7 2M + H +) and diastereomer 2: MS (EI) 492.4 (M + H +), 983.7 2M + H +).

EXAMPLE 6 Preparation of naphthylene-2-sulfonyl-r (S) -1 - (1-benzyl-3-oxo-azepan-4-ylcarbamoyl) -3-methyl-butyl] amide (a) Naphthylene-2-sulfonyl - [(S) -1- (1-benzyl-3-hydroxy-azepan-4-lcarbamoyl) -3-methyl-butyl] amide To a solution of the amine salt of the example 2i (200 mg, 0.49 mmole) in CH2Cl2, triethylamine (0.24 ml, 1.72 mmol) and 2-naphthalenesulfonyl chloride (122 mg, 0.54 mmol) were added. The reaction was stirred at room temperature until complete as determined by CCD analysis. The reaction was treated, dried (Na2SO4), filtered and concentrated. Column chromatography of the residue (10% methanol: dichloromethane) yielded 52 mg of the title compound MS (EI) 524 (M + H +). (b) Naphthylene-2-sulfonyl - [(S) -1- (1-benzyl-3-oxo-azepan-4-ylcarbamoyl) -3-methyl-butyl] amide The title compound was prepared following the general procedure of example 1i, but using the compound of example 6a: 1 H NMR (CDCl 3): d 1.0 (m, 6H), 1.5-2.1 (m, 5H), 2.2 (m, 2H), 2.7 (m, 1 H), 3.0 (dd, 1 H), 3. 3 (m, 1 H), 3.6 (m, 2H), 3.7 (m, 1 H), 4.7 (m, 1 H), 5.3 (m, 1 H), 7.2-8.4 (m, 12H): MS ( EI): 522 (M + H +, 100%).

EXAMPLE 7 Preparation of f (S) -1 - (1-benzyl-3-oxo-azepan-4-ylcarbamoyl) -3-methyl-butylamide of quinoline-2-carboxylic acid (a) [(S) -1- (1-Benzyl-3-hydroxy-azepan-4-ylcarbamoyl) -3-methyl-butyljamide of quinoline-2-carboxylic acid The title compound was prepared following the general procedure of the example 2j, but substituting 2-naphthoic acid with 2-quinolinecarboxylic acid: MS (ES) 489 (M + H +). (b) [(S) -1- (1-Benzyl-3-oxo-azepan-4-ylcarbamoyl) -3-methyl-butyljamide of quinoline-2-carboxylic acid The title compound was prepared following the general procedure of the example 1i, but using the compound of example 7a: 1H NMR (CDCl 3): d 1.0 (m, 6H), 1.5-2.1 (m, 5H), 2.2 (m, 2H), 2.9 (m, 1H), 3.2 (dd, 1H), 3.4 (m, 1 H), 3.7 (m, 2H), 4.7 (m, 1H), 5.2 (m, 1 H), 7.2-8.4 (m, 11 H); EM (EI): 487 (M + H +, 100%). The diastereomers were separated by CLAP at the preparative scale. The lyophilization of the eluates produced diastereomer 1: MS (EI) 492. 4 (M + H +), 983.7 2M + H +) and diastereomer 2: MS (EI) 492.4 (M + H +), 983.7 2M + H +).

EXAMPLE 8 Preparation of 3,4-dichlorobenzoic acid IYSH -f 1 -benzyl-3-oxo-azepan-4-ylcarbamoyl) -3-methyl-butylamide (a) [(S) -1 - (1-Benzyl-3-hydroxy-azepan-4-ylcarbamoyl) -3-methyl-butyl-amide of 3,4-dichlorobenzoic acid The title compound was prepared following the general procedure of the example 2j, but substituting 2-naphthoic acid with 3,4-dichlorobenzoic acid: MS (ES) 506 (M + H +). (b) [(S) -1- (1-Benzyl-3-oxo-azepan-4-ylcarbamoyl) -3-methyl-butyl-amide of 3,4-dichlorobenzoic acid The title compound was prepared following the general procedure of the example 1 i, but using the compound of example 8a: 1H NMR (CDCI3): d 1.0 (m, 6H), 1.5-2.1 (m, 5H), 2.2 (m, 2H), 2.9 (m, 1 H), 3.2 (dd, 1 H), 3.4 (m, 1 H ), 3.7 (m, 2H), 4.7 (m, 2H), 5.2 (m, 1 H), 7.2-8.4 (m, 8H); MS (EI): 504 M +, 100%).

EXAMPLE 9 Preparation of 4-f S) -methyl-2-f (quinoline-2-carbonyl) -amino-1-pentane -lamino > -3-oxo-1-r2- (3-pyridin-2-yl-phenyl) acetinaneTpanium (a) 4 - ((S) -2-tert-Butoxycarbonylamino-4-methyl-pentanoylamino) -3-hydroxy-1- [2- (3-pyridin-2-yl-phenyl) -acetyl] azepane To one solution of the compound of example 2g (0.5 g, 1.46 mmol) in CH2Cl2, EDC (307 mg, 1.60 mmol), HOBt (216 mg, 1.60 mmol) and 3- (2-pyridyl) phenylacetic acid (341 mg, 1.60 mg) were added. mmoles). The reaction was stirred at room temperature until complete as determined by CCD analysis. By working-up and column chromatography (2% methanol: dichloromethane) the title compound was produced: MS (ES) 539 (M + H +). (b) 4 - ((S) -Amino-4-methyl-pentanoylamino.} - 3-hydroxy-1- [2- (3-pyridin-2-yl-phenyl) acetyl] azepane To a solution of the compound of Example 9a (1.3 g), dissolved in methanol (20 ml), was added 4M HCl in dioxane (20 ml) The reaction was stirred until complete by CCD analysis, after which it was concentrated in vacuo to give 1.1 g. of the title compound: MS (EI) 439 (M + H +). (c) 4-. {(S) -Methyl-2 - [(quinoline-2-carbonyl) -amino] pentanoylamino] -3- hydroxy-1 - [2- (3-pyridin-2-yl-phenyl) acetyl] azepanium The title compound was prepared following the procedure of example 7a, but using the compound of example 9b: MS (EI) 594 (M + H +). (D) 4-. {(S) -Methyl-2 - [(quinoline-2-carbonyl) -amino] pentanoylamino.} - 3-oxo-1 - [2- (3-pyridin-2 -yl-phenyl) acetyl] azepanium The title compound was prepared following the procedure of Example 1i, but using the compound of Example 9c: 1 H NMR (CDCl 3): d 1.0 (m, 6H), 1.5-2.1 (m, 5H ), 2.2 (m, 2H), 2.9 (m, 1H), 3.4 (dd, 1 H), 3.8 (m, 3H), 4.1 (m, 2H), 4.7 (m, 3H), 5.4 (m, 1 H), 7.2-8.4 (m, 14H); MS (EI): 592 ((M + H +, 100%).

EXAMPLE 10 Preparation of 1 - ((S) -2-benzyloxycarbonylamino-4-methyl-pentyl) -4-l (S) -4-methyl-2-r (2-quinoline-2-carbonyl) -amino-1-pentane lamino) -3-oxo-azepane (a) 1 - ((S) -2-Benzyloxycarbonylamino-4-methyl-pentyl) -4 - ((S) -2-tert-butoxycarbonyl-amino-4-methyl-pentanoylamino) -3-hydroxy-azepane The title compound was prepared following the procedure of Example 2h, but substituting the benzaldehyde with Cbz-leucinal: MS (EI) 577 (M + H +). (b) 4 - ((S) -2-Amino-4-methyl-pentanoylamino) -1 - ((S) -2-tert-benzyloxycarbonyl-amino-4-methyl-pentyl) -3-hydroxy-azepanium The title compound was prepared following the procedure of Example 2i, but using the compound of Example 10a: MS (EI) 477 (M + H +). (c) 1 - ((S) -2-Benzyloxycarbonylamino-4-methyl-pentyl) -4-. { (S) -4-methyl-2 - [(2-quinoline-2-carbonyl) -amino] -pentanoylamino) -3-hydroxy-azepanium The title compound was prepared following the procedure of example 7a, but using the compound of Example 10b: MS (EI) 632 (M + H +). (d) 1 - ((S) -2-Benzyloxycarbonyllamino-4-methyl-pentyl) -4-. { (S) -4-methyl-2 - [(2-quinoline-2-carbonyl) -amino] -pentanoylamino) -3-oxo-azepanium The title compound was prepared following the procedure of example 1 i, but using the compound of Example 10c: 1 H NMR (CDCl 3): d 1.0 (m, 12H), 1.5-2.1 (m, 10H), 2.2 (m, 4H), 2.9 (m, 1 H), 3.4 (M, 2H), 3.7 (m, 1 H), 4. 7 (m, 2H), 5.2 (m, 3H), 7.2 (m, 4H), 7.5 (m, 1 H), 7.6 (m, 1 H), 7.7 (m, 1 H), 8.1 (m, 1 H), 8.2 (m, 2H), 8.5 (m, 1 H); MS (EI) 630 (M + H +, 100%).

EXAMPLE 11 Preparation of 1-benzoyl-4 - ((S) -2- (benzori, 31-dioxol-carbonylamino) -4-methyl-pentanoylamino) -3-oxo-azepanium (a) 1-Benzoyl-4 - ((S) -2-tert-butoxycarbonylamino-4-methyl-pentanoylamino) -3-hydroxy-azepanium The title compound was prepared following the procedure of example 9a, but substituting the acid 3a. - (2-pyridyl) phenylacetic acid with benzoic acid: MS (EI) 448 (M + H +). (b) 4 - ((S) -2-Amino-4-methyl-pentanoylamino) -1-benzoyl-3-hydroxy-azepanium The title compound was prepared following the procedure of example 2i, but using the compound of example 11 a: MS (EI) 348 (M + H +). (c) 1-Benzoyl-4 - ((S) -2- (benzo [1,3] dioxol-carbonylamino) -4-methyl-pentanoyl-amino) -3-hydroxy-azepanium The title compound was prepared following the procedure of Example 2j, but substituting the compound of Example 2j with the compound of Example 11b, and 2-naphthoic acid with piperonyl acid: MS (EI) 496 (M + H +). (d) 1-Benzoyl-4 - ((S) -2- (benzo [1,3] dioxol-carbonylamino) -4-methyl-pentanoylamino) -3-oxo-azepanium The title compound was prepared following the procedure of example 1 i, but using the compound of example 11 c: 1 H NMR (CDCl 3): d 1.0 (m, 6 H), 1.5-2.1 (m, 5 H), 2.2 (m, 2 H), 2.9 (m, 1 H), 3.2 (dd, 1 H), 3.4 (m, 1 H), 3.7 (m, 2H), 4.7 (m, 1 H), 5.2 (m, 1 H), 6.0 (s, 2H), 7.2 -8.4 (m, 8H): MS (EI): 494 (M + H \ 70%).

EXAMPLE 12 Preparation of 1-benzoyl-4 - ((S) -2- (4-fluoro-benzoylamino) -4-methyl-pentanoylamino) -3-oxo-azepanium (a) 1-Benzoyl-4 - ((S) -2- (4-fluoro-benzoylamino) -4-methyl-pentanoylamino) -3-hydroxy-azepane The title compound was prepared following the procedure of the example 11c, but replacing piperonyl acid with 4-fluorobenzoic acid: MS (EI) 470 (M + H +). (b) 1-Benzoyl-4 - ((S) -2- (4-fluoro-benzoylamino) -4-methyl-pentanoylamino) -3-oxo-azepanium The title compound was prepared following the procedure of example 1 i, but using the compound of example 12a: 1 H NMR (CDCl 3): d 1.0 (m, 6H), 1.5-2.1 (m, 5H), 2.2 (m, 2H), 2.7 (m, 1H), 3.0 (dd, 1 H), 3.6 (m, 1 H), 4.0 (m, 2H), 4.7 (m, 1 H), 5.2 (m, 1 H), 7.2-8.4 (m, 9H); MS (EI): 468 (M + H +, 10%).

EXAMPLE 13 Preparation of 3-oxo-4 - ((S) -4-methyl-2- { R5- (2-morpholino-4-yl-ethoxy) -benzofuran-2-carbonyl-amino} -pentanoylamino) -1- (4-methyl-pentanoyl) - azepanium (a) 4 - ((S) -2-tert-Butoxycarbonylamino-4-methyl-pentanoylamino) -3-hydroxy-1- (4-methyl-pentanoyl) -azepanium The title compound was prepared following the procedure of example 9a , but substituting 3- (2-pyridyl) phenylacetic acid with iso-caproic acid: MS (EI) 442 (M + H +). (b) 4 - ((S) -2-Amino-4-methyl-pentanoylamino) -3-hydroxy-1- (4-methyl-pentanoyl) -azepanium The title compound was prepared following the procedure of Example 2i, but using the compound of example 13a: MS (EI) 342 (M + H +). (c) 3-Hydroxy-4 - ((S) -4-methyl-2- { [5- (2-morpholino-4-yl-ethoxy) -benzofuran-2-carbonyl] -amino.} - pentanoylamino) -1- (4-methyl-pentanoyl) -azepanium To a solution of the compound of Example 13b (200 mg, 0.53 mmol) in dichloromethane was added EDC (111 mg, 0.58 mmol), HOBt. (78 mg, 0.58 mmole), TEA (0.11 ml, 0.79 mmole) and 5- (2-morpholin-4-ylethyloxy) benzofuran-2-carboxylic acid. The reaction was stirred at room temperature until complete by CCD analysis. By treatment and column chromatography (5% methanol: dic! Oromethane), 160 mg of the title compound were obtained: MS (EI) 615 (M + H +). (d) 3-Oxo-4 - ((S) -4-methyl-2- { [5- (2-morpholino-4-yl-ethoxy) -benzofuran-2-carbonyl] amino.} - pentanoylamino ) -1- (4-methyl-pentanoyl) -azepanium The title compound was prepared following the procedure of Example 1, but using the compound of Example 13d: 1 H NMR (CDCl 3): d 1.0 (m, 12H), 1.5 -2.1 (m, 8H), 2.2 (m, 2H), 2.3 (m, 1 H), 2.4-2.5 (m, 2H), 2.6 (m, 5H), 2.7 (m, 2H), 2.9 (m, 1 H), 3.4 (m, 1 H), 3.7 (m, 4H), 4.1 (m, 2H), 4.5-4.6 (m, 2H), 5.2 (m, 1 H), 7.2-8.4 (m, 4H); MS (EI) 613 (M + H +, 100%) The diastereomers were separated by CLAP on a preparative scale, by lyophilization of the eluates, diastereomer 1 and diastereomer 2 were obtained.

EXAMPLE 14 Preparation of 3-oxo-4 - ((S) -4-methyl-2- { R5- (2-morpholino-4-yl-ethoxy) -benzofuran-2-carbonyl-amino) -pentanoylamino) -1- Benzenesulfonyl-azepanium (a) 1-Benzylsulfonyl-4 - ((S) -2-tert-butoxycarbonylamino-methyl-pentanoylamino) -3-hydroxy-azepane To a solution of the amine of example 2g (0.5 g, 1.46 mmol) in dichloromethane, he added triethylamine (0.4 ml, 2.92 mmol), followed by benzenesulfonyl chloride (0.28 ml, 2.18 mmol). The reaction was stirred at room temperature until complete as determined by CCD analysis. By treatment and column chromatography (10% methanol: dichloromethane), 450 mg of the title compound were obtained: MS (EI) 484 (M + H +). (b) 4 - ((S) -2-Amino-methyl-pentanoylamino) -1-benzenesulfonyl-3-hydroxy-azepanium The title compound was prepared following the procedure of example 2i, but using the compound of example 14a: MS (EI) 384 (M + H +). (c) 3-Hydroxy-4 - ((S) -4-methyl-2- { [5- (2-morpholino-4-yl-ethoxy) -benzofuran-2-carbonyl] amino.} - pentanoylamino ) -1-Benzenesulfonyl-azepanium The title compound was prepared following the procedure of Example 13c, but using the compound of Example 14b: MS (EI) 657 (M + H +). (d) 3-Oxo-4 - ((S) -4-methyl-2- { [5- (2-morpholino-4-yl-ethoxy) -benzofuran-2-carbonyl] amino.} - pentanoylamino ) -1-Benzenesulfonyl-azepane The title compound was prepared following the procedure of Example 1, but using the compound of Example 14c: 1 H NMR (CDCl 3): d 1.0 (m, 6H), 1.5-2.1 (m , 5H), 2.2 (m, 2H), 2.4 (m, 1H), 2.7 (m, 4H), 2.8 (m, 2H), 3.5 (m, 1 H), 3.8 (m, 4H), 4.0 ( m, 1 H), 4.1 (m, 2 H), 4.4 (m, 1 H), 4.4 (m, 1 H), 4.5 (m, 1 H), 4.7 (m, 1 H), 5.1 (m, 1 H), 7.0 (m, 3H), 7.3 (m, 2H), 7.5 (m, 3H), 7.7 (m, 2H): MS (EI): 655 (M + H +, 100%). An analysis of the mixture of diastereomers by means of analytical CLAP (gradient CH3CN: KHPO4 20 mM (buffer pH7) 40:60 to 45:55, 60 min, 1 ml / min; nertsil ODS-3, column 4.6 x 250 mm; UV detection at 215 nm), showed two peaks (Rt = 44.6 min, and 45.9 min). The diastereomers were separated by preparative CLAP (gradient CH3CN: KHPO mM (buffer pH7) 40:60 at 50:50, 60 min, 12 ml / min; nertsil ODS-3, column 250 x 20 mm; 215 nm). By lyophilization of the eluates, diastereomer 1 was obtained (anal Rt = 44.6 mins.) And diastereomer 2 (anal Rt = 45.9 mins.).

EXAMPLE 15 Preparation of 4 - ((S) -4-methyl-2-fr5- (2-morpholino-4-yl-ethoxy) -benzofuran-2-carbonamino) -pentanoylamino) -3-oxo- phenylamide azepane-1-carboxylic (a) [(S) -1- (3-Hydroxy-1-phenylcarbamoyl-azepan-4-ylcarbamoyl) -3-methyl-butyl] carbamic acid tert-butyl ester To a solution of the amine of Example 2g (0.5 g, 1.46 mmol) in dichloromethane (20 ml), phenyl isocyanate (0.24 ml, 2.18 mmol) was added. The reaction was stirred at room temperature until complete as determined by CCD analysis. By working-up and column chromatography (5% methanol: dichloromethane) 578 mg of the title compound were obtained: MS (EI) 463 (M + H +). (b) 4 - ((S) -2-amino-methyl-pentanoylamino) -3-hydroxy-azepane-1-carboxylic acid phenylamide The title compound was prepared following the procedure of Example 2i, but using the compound of the example 15a: MS (EI) 363 (M + H +). c) 3-hydroxy-4 - ((S) -4-methyl-2 { [5- (2-morpholino-4-yl-ethoxy) -benzofuran-2-carbonyl] amino acid phenylamide. pentanoylamino) -azepan-1-carboxylic acid The title compound was prepared following the procedure of example 13c, but using the compound of example 15b: MS (EI) 636 (M + H +). (d) 4 - ((S) -4-methyl-2- { [5- (2-morpholino-4-yl-ethoxy) -benzofuran-2-carbonyl] amino] -pentanoylamino acid phenylamide 3-oxo-azepane-1-carboxylic acid The title compound was prepared following the procedure of example 1 i, but using the compound of example 15c: H NMR (CDCl 3): d 1.0 (m, 6H), 1.5-2.1 ( m, 5H), 2.2 (m, 2H), 2.7 (m, 4H), 3.0 (m, 2H), 3.1 (m, 1H), 3.8 (m, 1 H), 3.9 (m, 4H), 4.2 ( m, 1H), 4.3 (m, 2H), 4.9 (m, 2H), 5.2 (m, 1H), 7.2-8.4 (m, 9H): MS (EI) 634 (M + H +, 100%). An analysis of the mixture of diastereomers by means of analytical CLAP (CH3CN: 20 mM KHPO4 (buffer pH7) 40:60, Socratic, 1 ml / min; Nertsil ODS-3, column 4.6 x 250 mm; UV detection at 215 nm), showed two peaks (Rt = 27.3 min and 30.1 min). The diastereomers were separated by preparative CLAP (gradient CH3CN: KHPO4 20mM (buffer pH7) 40:60 at 50:50, 60 min, 12 ml / min, inertsil ODS-3, column 250 x 20 mm, UV detection at 215 nm). By lyophilization and desalting the eluates by extraction with NaHCO 3: ethyl acetate, diastereomer 1 (Anal Rt = 27.3 mins) and diastereomer 2 (Anal Rt = 30.1 mins) were obtained.

EXAMPLE 16 Preparation of ((S) -3-methyl-1 -. {3-oxo-1-r2- (3-pyridin-2-l-phenyl) acetipapapan-4-ylcarbamoyl) -butyl) amide 5- (2-morpholin-4-yl-ethoxy) -benzofuran-2-carboxylic acid (a) ((S) -3-Methyl-1 - { 3-hydroxy-1 - [2- (3-pyridin-2-yl-phenyl) acetyl] azepan-4-ylcarbamoyl .) - butyl) 5- (2-morpholino-4-yl-ethoxy) -benzofuran-2-carboxylic acid amide The title compound was prepared following the procedure of example 13c, but using the compound of example 9b: MS (EI) 712 (M + H +). (b) ((S) -3-Methyl-1 -. {3-oxo-1 - [2- (3-pyridin-2-yl-phenyl) -acetyl]-azepan-4-ylcarbamoyl} -butyl) 5- (2-morpholino-4-yl-ethoxy) -benzofuran-2-carboxylic acid amide The title compound was prepared following the procedure of example 1 i, but using the compound of example 16a: 1 H NMR (CDCl 3): d 1.0 (m, 6H), 1.5-2.1 (m, 5H), 2.2 (m, 2H), 2.7 (m, 4H), 2.8 (m, 2H), 2.9 (m, 1H), 3.5 (m, 1 H) , 3.7 (m, 4H), 3.9 (m, 3H), 4.3 (m, 2H), 4.7 (m, 2H), 5.4 (m, 1 H), 7.2-8.0 (m, 13H), 8.5 (m, 1 H); MS (EI): 710 (M + H +, 100%) MS (EI). An analysis of the mixture of diastereomers by means of analytical CLAP (CH3CN: 20 mM KHPO4 (buffer pH7) 40:60, Socratic, 1 ml / min, inertsil ODS-3, column 4.6 x 250 mm, UV detection at 215 nm ), showed two peaks (Rt = 33.9 min and 37.9 min). The diastereomers were separated by preparative CLAP (gradient CH3CN: KHPO4 20mM (buffer pH7) 40:60 to 45:55, 60 min, 12 ml / min; nertsil ODS-3, column 250 x 20 mm; 215 nm). By lyophilization and desalting the eluates by extraction with NaHCO3: ethyl acetate, diastereomer 1 MS (EI) 710.3 (M + H +) (Anal Rt = 33.9 min) and diastereomer 2 MS (EI) 710.3 (M) were obtained. + H +) (Anal Rt = 37.9 min).

EXAMPLE 17 Preparation of f (S) -1 - (Benzoyl-3-oxo-azepan-4-ylcarbamoyl) -3-methyl-butylamide of 5- (2-morpholino-4-yl-ethoxy) - benzofuran-2-carboxylic (a) [(S) -1 - (Benzoyl-3-hydroxy-azepan-4-ylcarbamoyl) -3-methyl-butyljamide of 5- (2-morpholino-4-yl-ethoxy) -benzofuran-2- acid carboxyl The title compound was prepared following the procedure of Example 13c, but using the compound of Example 1 1 b: MS (EI) 621 (M + H +). (b) [(S) -1 - (Benzoyl-3-oxo-azepan-4-ylcarbamoyl) -3-methyl-butyl-buty-amide of 5- (2-morpholino-4-yl-ethoxy) -benzofuran -2-carboxylic acid The title compound was prepared following the procedure of example 1 i, but using the compound of example 17a: 1 H NMR (CDCl 3): d 1.0 (m, 6H), 1.5-2.1 (m, 5H), 2.2 (m, 2H), 2.7 (m, 4H), 2.9 (m, 2H), 3.0 (m, 1 H), 3.7 (m, 5H), 4.0 (m, 1 H), 4.1 (m, 2H), 4.7 (m, 2H), 5.4 (m, 1 H), 7.2-8.4 (m, 1 1 H); MS (EI): 619 (M + H +, 100%). An analysis of the mixture of diastereomers by means of analytical CLAP (gradient CH3CN: KHPO4 20 mM (buffer pH7) 40:60 to 55:45, 30 min, 1 ml / min, inertsil ODS-3, column 4.6 x 250 mm; UV detection at 215 nm), showed two peaks (Rt = 13.5 min and 17.6 min). The diastereomers were separated by preparative CLAP (gradient CH3CN: KHPO4 mM (buffer pH7) 40:60 to 45:55, 60 min, 15 ml / min, inertsil ODS-3, column 250 x 20 mm, UV detection at 215 nm). By lyophilization and desalting the eluates by extraction with NaHCO3: ethyl acetate, diastereomer 1 (anal Rt = 13.5 min) and diastereomer 2 (anal Rt = 17.6 min) were obtained.

EXAMPLE 18 Preparation of T (S) -1 - (1-benzenesulfonyl-3-oxo-azepan-4-ylcarbamoi-3-methyl-butylamide 5- (2-pyrrolidin-1-yl-ethoxy) -benzofuran-2-acid - carboxylic (a) [(S) -1- (1-Benzenesulfonyl-3-hydroxy-azepan-4-ylcarbamoyl) -3-methyl-butyl] -amide of 5- (2-pyrrolidin-1-yl-ethoxy) -benzofuran -2-carboxylic acid The title compound was prepared following the procedure of example 14c, but substituting 5- (2-morpholin-4-yl-ethyloxy) benzofuran-2-carboxylic acid with 5- (2-pyrrolidine) 1-yl-ethyloxy) -benzofuran-2-carboxylic acid: MS (EI) 641 (M + H +). (b) [(S) -1- (Benzoyl-3-oxo-azepan-4-ylcarbamoyl) -3-methyl-butyljamide of 5- (2-morpholino-1-yl-ethyloxy) -benzofuran-2-carboxylic acid The title compound was prepared following the procedure of Example 1 i, but using the compound of example 18a: 1 H NMR (CDCl 3): d 1.0 (m, 6H), 1.5-2.1 (m, 9H), 2.2 (m, 2H ), 2.5 (m, 1 H), 2.7 (m, 4H), 3.0 (m, 2H), 3.4 (m, 1 H), 4.0 (m, 1 H), 4.1 (m, 2H), 4.5 (m, 1 H), 4.6 (m, 1 H), 5.0 (m, 1 H), 7.2-8.4 (m, 11 H); MS (EI): 639 (M + H +, 100%).

EXAMPLE 19 Preparation of 5- (2-piperidin-1-yl-ethoxy) -benzofuran l "(S) -1 - (1-benzenesulfonyl-3-oxo-azepan-4-ylcarbamoyl) -3-methyl-butylamide of 5- (2-piperidin-1-yl-ethoxy) -benzofuran -2- carboxylic (a) [(S) -1- (1-Benzenesulfonyl-3-oxo-azepan-4-ylcarbamoyl) -3-methyl-butyljamide of 5- (2-piperidin-1-yl-ethoxy) -benzofuran-2 acid carboxylic The title compound was prepared following the procedure of example 14c, but substituting 5- (2-morpholin-4-yl-ethyloxy) benzofuran-2-carboxylic acid with 5- (2-piperidin-1-yl- ethyloxy) -benzofuran-2-carboxylic acid: MS (EI) 655 (M + H +). (b) [(S) -1- (1-Benzenesulfonyl-3-hydroxy-azepan-4-ylcarbamoyl) -3-methyl-butyljamide of 5- (2-piperidin-1-yl-ethoxy) -benzofuran-2 acid carboxylic The title compound was prepared following the procedure of example 1 i, but using the compound of example 18a: 1 H NMR (CDCl 3) d 1.0 (m, 6H), 1.5-2.1 (m, 11H), 2.2 (m, 2H), 2.5 (m, 5H), 2.7 (m, 2H), 3.5 (m, 1H), 4.0 (m, 1 H), 4.1 (m, 2H), 4.5 (m, 1 H), 4.6 (m , 1H), 5.0 (m, 1 H), 7.2-8.4 (m, 11H); MS (EI): 653 (M + H +, 100%).

EXAMPLE 20 Preparation of ((S) -3-Methyl-1-f3-oxo-1-f2- (3-pyridin-2-yl-phenyl) -etip-azepane-4-alkylcarbamoyl.) - butylamide acid 5- (2-morpholino-4-yl-ethoxy) -benzofuran-2-carboxylic acid (a) 5- (2-Morpholin-4-yl-ethyloxy) benzofuran-2-carboxylic acid methoxymethylamide To a solution of 3- (2-pyridyl) phenylacetic acid (1 g) in dichloromethane, N-hydrochloride was added. , O-dimethylhydroxylamine (0.92 g), triethylamine (1.3 ml), HOBt (0.96 g) and EDC (1.1 g). The reaction was stirred until complete. By treatment and column chromatography (ethyl acetate 40%: hexane) yielded 1.1 g of the title compound: MS (EI) 257 (M + H +). (b) 5- (2-Morpholin-4-yl-ethyloxy) benzofuran-2-carbaldehyde To a solution of methoxymethylamide of 5- (2-morpholin-4-yl-ethyloxy) benzofuran-2-carboxylic acid (0.2 g) of example 20a, in THF, LAH (2.0 ml of a 1 M solution in THF) was added. The reaction was stirred until complete consumption of the starting material. By treatment 160 mg of the title compound were obtained. (c) ((S) -. {3-hydroxy-1- [2- (3-pyridin-2-yl-phenyl) -ethyl] -azepan-4-ylcarbamoyl} tert-butyl ester. 3-methyl-butyl) carbamic acid The title compound was prepared following the general procedure of Example 2g, but substituting the benzaldehyde with 5- (2-morpholin-4-yl-ethyloxy) benzofuran-2-carbaldehyde: EM (EI) 525 (M + H +). (d). { 3-Hydroxy-1 - [2- (3-pyridin-2-yl-phenyl) -ethyl] -azepan-4-yl} - (S) -2-amino-4-methyl-pentanoic acid amide The title compound was prepared following the procedure of example 2i, but using the compound of example 20c. (e) ((S) -3-Methyl-1- { 3-hydroxy-1- [2- (3-pyridin-2-yl-pheny] ethyl] -azepan-4-ylcarbamoyl. -butyl) 5- (2-morpholino-4-yl-ethoxy) benzofuran-2-carboxylic acid amide The title compound was prepared following the procedure of Example 13c, but using the compound of Example 20d. (f) ((S) -3-Methyl-1 - { 3-oxy-1 - [2- (3-pyridin-2-yl-phenyl) ethyl] -azepan-4-ylcarbamoyl.} -butyl ) 5- (2-morpholino-4-yl-ethoxy) benzofuran-2-carboxylic acid amide The title compound was prepared following the procedure of example 1 i, but using the compound of Example 20e: 1 H NMR (CDCl 3): d 1.0 (m, 6H), 1.5-2.1 (m, 5H), 2.2 (m, 2H), 2.7 (m, 4H), 2.8 (m, 6H), 3.1 (m, 1 H), 3.3 (m, 1 H), 3.5 (m, 1 H), 3.7 (m, 4 H), 4.2 (m, 3 H), 4.6 (m, 1 H), 5.2 (m, 1 H), 7.2-8.4 (m, 13H), 8.6 (m, 1 H); MS (EI) 696 (M + H \ 80%).

The diastereomer mixture was separated by CLAP to give the fastest eluting diastereomer; MS (EI): 696 (M + H +, 100%), and the slowest eluting diastereomer; MS (EI) 696 (M + H +, 100%).

EXAMPLE 21 Preparation of naphthalene- (3-pyridn-2-yl-phenylethyl-1-azepane-4-ylcarbamoyl.) -butyl) -amide-1-r2- (3-pyridn-2-yl-phenylethyl-1-azepan-4-ylcarbamoyl. 2-carboxylic (a) ((S) -3-Methyl-1- { 3-hydroxy-1- [2- (3-pyridin-2-yl-phenyl) ethyl] -azepan-4-ylcarbamoyl.} -butyl ) Naphthalene-2-carboxylic acid amide The title compound was prepared following the procedure of Example 20f, but substituting 5- (2-morpholin-4-yl-etlloxy) benzofuran-2-carboxylic acid with 2-carboxylic acid. -naphthous: MS (EI) 579 (M + H +). (b) ((S) -3-Methyl-1 -. {3-oxo-1 - [2- (3-pyridin-2-yl-phenyl) ethyl] -azepan-4-ylcarbamoyl}. ) naphthalene-2-carboxylic acid amide The title compound was prepared following the procedure of example 1 i, but using the compound of example 21 a: 1 H NMR (CDCl 3): d 1.0 (m, 6H), 1.5-2.1 (m, 6H), 2.2 (m, 2H), 2.9 (m, 4H), 3.0 (m, 1 H), 3.4 (d, 1 H), 3.5 (m, 1 H), 4.7 (m, 1 H), 5.0 (m, 1 H), 6.8-7.2 (m, 6H), 7.3 (m, 1 H), 7.5 (m, 2H), 7.9 (m , 6H), 8.2 (m, 1 H), 8.7 (m, 1 H): MS (EI) 577 (M + H \ 100%).

EXAMPLE 22 Preparation of (1 S) -3-methyl-1- (3-oxo-1-r2- (3-pyridin-2-yl-phenyl) -etip-azepan-4-ylcarbamoyl) -butyl) -amide-1 -amide -indol-2 -carboxylic (a) ((S) -3-Methyl-1 -. {3-hydroxy-1 - [2- (3-pyridin-2-yl-phenyl) ethyl] -azepan-4-ylcarbamoyl}. ) amide The title compound was prepared following the procedure of Example 20f, but substituting 5- (2-morpholin-4-yl-ethyloxy) benzofuran-2-carboxylic acid with 1 H-indole-2-carboxylic acid: MS ( EI) 568 (M + H +). (b) ((S) -3-Methyl-1 - { 3-oxo-1 - [2- (3-pyridin-2-yl-phenyl) ethyl] -azepan-4-ylcarbamoyl.} -butyl ) amide The title compound was prepared following the procedure of Example 1 i, but using the compound of Example 22b: 1 H NMR (CDCl 3): d 1.0 (m, 6H), 1.5-2.1 (m, 5H), 2.2 (m, 2H), 2.9 (m, 4H), 3.0 (m, 1 H), 3.4 (d, 1 H), 3.5 (m, 1 H), 4.7 (m, 1 H), 5.0 (m, 1 H), 6.8-7.2 (m, 6H), 7.0-7.9 (m, 12H), 8.7 (m, 1 H), 9.5 (m, 1 H): MS (EI): 566 (M + H +, 100%).

EXAMPLE 23 Preparation of 1? S) -1 - (1-benzenesulfonyl-3-oxo-azepan-4-ylcarbamoyl.) - 3-methyl-butylamide of 1H-indole-2-carboxylic acid (a) [(S) -1- (1-Benzenesulfonyl-3-hydroxy-azepan-4-ylcarbamoyl.) - 3-methyl-butyl) amide of 1 H-indole-2-carboxylic acid The title was prepared following the procedure of Example 2j, but using the compound of Example 14b and substituting the naphthoic acid with 1 H-indole-2-carboxylic acid: MS (EI) 527 (M + H +). (b) [(S) -1- (1-Benzylsulfonyl-3-oxo-azepan-4-ylcarbamoyl.) - 3-methyl-butyl) 1-H-indole-2-carboxylic acid amide The title compound is prepared following the procedure of example 1 i, but using the compound of example 23b: 1 H NMR (CDCl 3): d 1.0 (m, 6H), 1.5-2.1 (m, 5H), 2.2 (m, 2H), 2.5 (m, 1 H), 3.5 (dd, 1 H), 3.9 (m, 1 H), 4. 5 (dd, 2H), 4.7 (m, 1H), 5.0 (m, 1H), 7.2-7.6 (m, 10H), 9.5 (b, 1H); MS (EI): 525 (M + H +, 10%) EXAMPLE 24 Preparation of T (S) -1 - (1-benzenesulfonyl-3-oxo-azepan-4-ylcarbamoyl > -3-methyl-butiPamide of benzofuran-2-carboxylic acid (a) [(S) -1- (1-Benzenesulfonyl-3-hydroxy-azepan-4-ylcarbamoyl.} - 3-methyl-butyl) benzofuran-2-carboxylic acid amide The title compound was prepared following the procedure of example 23a, but substituting the 1H-indole-2-carboxylic acid with benzofuran-2-carboxylic acid: MS (EI) 528 (M + H +). (b) [(S) -1- (1-Benzenesulfonyl-3-oxo-azepan-4-ylcarbamoyl.} - 3-methyl-butyl) benzofuran-2-carboxylic acid amide The title compound was prepared following the procedure of example 1 i, but using the compound of example 24b: 1 H NMR (CDCl 3): d 1.0 (m, 6 H), 1.5-2.1 (m, 5 H), 2.2 (m, 2 H), 2.6 (m, 1 H ), 3.5 (d, 1 H), 4.1 (m, 1 H), 4.7 (m, 2H), 5.0 (m, 1 H), 7.2-7.2 (m, 10H).

EXAMPLE 25 Preparation of 1- (S) -3-methyl-1- (3-oxo-1-r2- (3-pyridin-2-yl-phenyl) -ethyl-azepam-4-ylcarbamoyl) -butyl) -amide Benzofuran-2-carboxylic acid (a) [(S) -3-Methyl-1-. { 3-hydroxy-1- [2- (3-pyridin-2-yl-phenyl) ethyl] -azepan-4-ylcarbamoyl} -butyl) benzofuran-2-carboxylic acid amide The title compound was prepared following the procedure of example 20e, but substituting 5- (2-morpholin-4-yl-ethyloxy) benzofuran-2-carboxylic acid with benzofuran- 2-carboxylic: MS (EI) 569 (M + H +). (b) [(S) -3-Methyl-1 -. { 3-OXO-1 - [2- (3-pyridin-2-yl-phenyl) ethyl] -azepan-4-ylcarbamoyl} -butyl) benzofuran-2-carboxylic acid amide The title compound was prepared following the procedure of Example 1, but using the compound of Example 25a: 1 H NMR (CDCl 3): d 1.0 (m, 6H), 1.5-2.1 (m, 5H), 2.2 (m, 2H), 2.7 (m, 5H), 3.0 (m, 1 H), 3.3 (m, 1 H), 3.5 (m, 1 H), 4.7 (m, 1 H), 5.2 (m, 1 H), 7.2-7-7 (m, 14H), 8.7 (m, 1 H); EM (EI): 567 (M + H +, 100%).

The diastereomeric mixture was separated by CLAP to provide the fastest eluting diastereomer, MS (EI): 656 (M + H +, 100%), and the slowest eluting diastereomer, MS (EI) 656 (M + H +, 100 %).

EXAMPLE 26 r (S) -3-Methyl-1- (3-QXQ-1-phenethyl-azepan-4-ylcarbamoyl-butyl) -amide of 5- (2-morpholino-4-yl-ethoxy) -benzofuran-2 acid -carboxylic The title compound was prepared following the procedures of Examples 20 cf, but substituting the 5- (2-morpholin-4-yl-ethyloxy) benzofuran-2-carbaldehyde of Example 20c with phenylacetaldehyde: 1 H NMR (CDCl 3): d 1.0 (m, 6H), 1.5-2.1 (m, 5H), 2.2 (m, 2H), 2.4 (m, 1 H), 2.6 (m, 4H), 2.7 (m, 6H), 3.0 (m, 1 H) ), 3.3 (dd, 1 H), 3.5 (q, 1 H), 3.7 (m, 4H), 4.2 (m, 2H), 4.7 (m, 1 H), 5.0 (m, 1 H), 7.2- 7.2 (m, 11 H); MS (EI) 619 (M + H +, 80%). The diastereomeric mixture was separated by CLAP to provide the fastest eluting diastereomer, MS (EI): 619 (M + H \ 100%), and the slowest eluting diastereomer, MS (EI): 619 (M + H \ 100%).

EXAMPLE 27 Preparation of naphthylene-2-carboxylic acid r (S) -3-met l-1- (3-oxo-1-phenethyl-azepan-4-ylcarbamoyl-buti The title compound was prepared following the procedures of Examples 2 hk, but substituting the benzaldehyde of Example 2h with phenylacetaldehyde: 1 H NMR (CDCl 3): d 1.0 (m, 6H), 1.5-2.1 (m, 5H), 2.2 ( m, 2H), 2.4 (m, 1 H), 2.7 (m, 4H), 3.0 (m, 1 H), 3.7 (d, 1 H), 3.5 (q, 1 H), 4.7 (m, 1 H) ), 5.1 (m, 1 H), 6.9-7.2 (m, 7H), 7.5 (m, 2H), 7.9 (m, 4H), 8.4 (m, 1 H); MS (EI): 500 (M + H \ 100%).

EXAMPLE 28 Preparation of. { (S) -3-Methyl-1-r3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl-butyamide of benzofuran-2-carboxylic acid (a) [3-hydroxy-1- (pyridin-2-sulfonyl) -azepan-4-yl] -amide of (S) -2-amino-4-methyl-pentanoic acid The title compound was prepared following the procedures of Examples 14 ab, but substituting the benzenesulfonyl chloride of Example 14a with 2-pyridinesulfonyl chloride: MS (EI) 385 (M + H +). (b) { (S) -3-Methyl-1 - [3-hydroxy-1- (pyridine-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} benzofuran-2-carboxylic acid amide To a solution of (S) -2-amino-4-methyl-pentanoic acid [3-hydroxy-1- (pyridin-2-sulfonyl) -azepan-4-yl] -amide from example 28a (0.15 g) in dichloromethane, TEA (0.11 ml), HOBt (49 mg), EDC (69 mg) and benzofuran-2-carboxylic acid (58 mg) were added. The reaction was stirred until complete. By treatment and column chromatography (5% methanol: ethyl acetate) the title compound was obtained: MS (EI) 529 (M + H +). (c). { (S) -3-Methyl-1 - [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} benzofuran-2-carboxylic acid amide The title compound was prepared following the procedure of example 1, but using the compound of example 28b: 1 H NMR (CDCl 3): d 1.0 (m, 6H), 1.5-2.1 (m, 5H), 2.2 (m, 2H), 2.7 (m, 1 H), 3.7 (dd, 1 H), 4.0 (m, 1 H), 4. 7 (m, 2H), 5.0 (m, 1H), 7.2-7.3 (m, 3H), 7.4 (m, 4H), 7.6 (m, 1H), 8.0 (m, 2H), 8. 7 (m, 1 H); MS (EI): 527 (M + H 40%). The diastereomeric mixture was separated by CLAP to provide the fastest eluting diastereomer: 1 H NMR d 1.0 (m, 6H), 1.5-2.1 (m, 5H), 2. 2 (m, 2H), 2.7 (t, 1 H), 3.7 (d, 1 H), 4.0 (d, 1 H), 4.7 (m, 2H), 5.0 (m, 1 H), 7.2- 7.3 ( m, 3H), 7.4 (m, 4H), 7.6 (m, 1 H), 8.0 (m, 2H), 8.7 (m, 1 H); MS (EI): 527 (M + H \ 100%); and the slower eluting diastereomer: 1 H NMR d 1.0 (m, 6 H), 1.5-2.1 (m, 5 H), 2.2 (m, 2 H), 2.7 (t, 1 H), 3.7 (d, 1 H), 4.0 (d, 1 H), 4.7 (m, 2H), 5.0 (m, 1 H), 7.2-7.3 (m, 3H), 7.4 (m, 4H), 7.6 (m, 1 H), 8.0 (m , 2H), 8.7 (m, 1 H); MS (EI): 527 (M + H \ 100%); EXAMPLE 29 Preparation of. { (S) -3-methyl-1-y3-oxo-1 - (pyridin-2-sulfonih-azepan-4-ylcarbamoin-butyl &nt; naphthylene-2-carboxylic acid amide (to) . { (S) -3-Methyl-1- [3-hydroxy-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} Naphthylene-2-carboxylic acid amide The title compound was prepared following the procedure of example 28b, but substituting the benzofuran-2-carboxylic acid with 2-naphthoic acid: MS (EI) 539 (M + H +). (b) { (S) -3-Methyl-1 - [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} Naphthylene-2-carboxylic acid amide The title compound was prepared following the procedure of Example 1, but using the compound of Example 29a: 1 H NMR (CDCl 3): d 1.0 (m, 6H), 1.5-2.1 (m, 5H), 2.2 (m, 2H), 2.7 (m, 1 H), 3.7 (dd, 1 H), 4.0 (m, 1 H), 4.7 (m, 2H), 5.0 (m, 1 H), 7.2-7.3 (m, 2'H), 7.5 (m, 3H), 7.9 (m, 6H), 8.3 (m, 1 H), 8. 4 (m, 1 H); MS (EI): 537 (M + H +, 50%) The diastereomeric mixture was separated by CLAP to provide the fastest eluting diastereomer: MS (EI): 537 (M + H +, 100%), and the eluting diastereomer slower: MS (EI) 537 (M + H +, 100%).

EXAMPLE 30 Preparation of (f S) -3-methyl-1-l "3-oxo-1 - (pyridine-2-sulfoniD-azepan-4-ylcarbamoy-butyamide of 5- (2-morpholino-4-yl- ethoxy) -benzofuran-2-carboxylic acid (to) . { (S) -3-Methyl-1 - [3-hydroxy-1- (pyridine-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 5- (2-morpholino-4-yl-ethoxy) -benzofuran-2-carboxylic acid amide The title compound was prepared following the procedure of example 13c, but using the compound of example 28a: MS (EI) 658 ( M + H +). (b) { (S) -3-Methyl-1 - [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 5- (2-morpholino-4-yl-ethoxy) -benzofuran-2-carboxylic acid amide The title compound was prepared following the procedure of example 1 i, but using the compound of example 29a: ^ H NMR (CDCl 3) : d 1. 0 (m, 6H), 1.5-2.1 m, 5H), 2.2 (m, 2H), 2.7 (m, 1 H), 3.5 (m, 4H), 3.7 (m, 6H), 4. 1 (m, 1 H), 4.5 (m, 2H), 4.7 (m, 2H), 5.0 (m, 1H), 7.2-7.3 (m, 4H), 7.4 (m, 2H), 8. 0 (m, 2H), 8.7 (m, 1 H), 8.7 (m, 1 H); MS (EI): 656 (M + H +, 100%). The diastereomeric mixture was separated by CLAP to give the fastest diastereomer: MS (EI): 656 (M + H +, 100%), and the slowest diastereomer: MS (EI): 656 (M + H +, 100%).

EXAMPLE 31 Preparation of 4 - ((S) -4-methyl-2-IT (5- (2-morpholino-4-yl-ethoxy) -benzofuran-2-carbonyl-amino) -pentanoylamino) -butyl ester -3- oxo-azepane-1-carboxylic acid (a) 4 - ((S) -2-amino-4-methyl-pentanoylamino) -3-hydroxy-azepane-1-carboxylic acid tert-butyl ester To a solution of the compound of example 1f (0.89 g) in acetate of ethyl: methanol (30 ml of a 2: 1 mixture), 10% Pd / C was added and a balloon of hydrogen gas was added. The reaction was stirred until complete by CCD analysis, after which it was filtered and concentrated to give the title compound (0.57 g). (b) 4 - ((S) -4-methyl-2-. {[[5- (2-morpholino-4-yl-ethoxy) -benzofuran-2-carbonyl] -amino tert-butyl ester} -pentanoylamino) -3-hydroxy-azepane-1-carboxylic acid The title compound was prepared following the procedure of example 13c, but using the compound of example 31a. (c) 4-tert-butyl ester (- S) ) -4-methyl-2- { [(5- (2-morpholino-4-yl-ethoxy) -benzofuran-2-carbonyl] -amino}. -pentanoylamino) -3-oxo-azepan- 1-carboxylic acid The title compound was prepared following the procedure of Example 31b: H NMR (CDCl 3): d 1.0 (m, 6H), 1.5 (m, 9H), 1.7 (m, 5H), 2.2 (m, 2H) , 2.5 (m, 5H), 2.7 (m, 2H), 3.5 (m, 1H), 3.8 (m, 4H), 4.1 (m, 3H), 4.2 (m, 1 H), 4.7 (m, 2H) , 5.0 (m, 1 H), 7.2-7.3 (m, 5H); MS (EI): 615 (M + H +, 100%).

EXAMPLE 32 Preparation of r (S) -3-Methyl-1- (3-oxo-azepan-4-ylcarbamoy-butyl) 4 - ((S-methyl-2- (r (5- (2-morfoH) -4-yl-ethoxy) -benzofuran-2-carboxylic acid To a solution of the compound of Example 31c in THF (5 mL), 1 M HCl in ether (5 mL) was added. The reaction was stirred overnight, after which it was concentrated to give the title compound: "? NMR (CDCl 3): d 1.0 (m, 6H), 1.5-2.1 (m, 5H), 2.2 (m, 2H ), 2.7 (m, 4H), 3.2 (dd, 3H), 3. 7 (m, 6H), 4.0 (m, 3H), 4.5 (m, 2H), 5.0 (m, 1 H), 7.2-7.3 (m, 6H); EM (EI): 515 (M + H +, 100%).

EXAMPLE 33 Preparation of. { 3-Oxo-1-r2- (3-pyridin-2-yl-phenyl-acetyl-azepan-4-yl) -amide of 4-methyl-pentanoic acid (a) 3-Hydroxy-4- (4-methyl-pentanoylamino) -azepan-1-carboxylic acid tert-butyl ester The title compound was prepared following the procedure of Example 1f, but substituting Cbz-leucine with 4-carboxylic acid. methylpentanoic: MS (EI) 329 (M + H +). (b) (4-methyl-pentanoic acid (3-hydroxy-azepan-4-yl) -amide) To a solution of the compound of example 33a (200 mg) in methanol (5 ml), 4M dioxane in HCl ( 5 ml). The reaction was stirred until complete, after which it was concentrated to give the title compound (132 mg): MS (EI) 229 (M + H +). (c). { 3-Hydroxy-1- [2- (3-pyridin-2-yl-phenyl-acetyl] -zepan-4-yl}. -amide of 4-methyl-pentanoic acid The title compound was prepared following the procedure of Example 9a, but using the compound of Example 33b: MS (EI) 424 (M + H +). (d). {3-Oxo-l - [2- (3-pyridin-2-yl-phenyl-acetyl] 4-methyl-pentanoic acid amide 4-methyl-pentanoic acid The title compound was prepared following the procedure of example 1 i, but using the compound of example 33c: 1 H NMR (CDCl 3): d 1. 0 (m, 6H), 1.5-2.1 (m, 5H), 2.2 (m, 2H), 2.7 (m, 1 H), 2.9 (m, 1 H), 3.5 (m, 1 H), 3.7 (m) , 2H), 4.1 (m, 3H), 4.6 (m, 1 H), 5.3 (m, 1 H), 7.2-8.0 (m, 7H), 8.7 (m, 1 H); MS (EI): 422 (M + H +, 100%).

EXAMPLE 34 Preparation of ((S) -3-methyl-1- 3-oxo-1-r2- (3-pyridin-2-yl) -acetyl-azepan-4-ylcarbamoyl-butyl ester -naphthalen-2-methyl-carbamic (a) (S) -4-Methyl-2- [naphthalen-2-ylmethyl) -aminojpentanoic acid methyl ester To a solution of leucine methyl ester hydrochloride (0.5 g) in dichloromethane, triethylamine (0.9 ml) was added. ), 2-naphthaladehyde (0.43 g) and sodium triacetoxyborohydride (0.87 g). The mixture was stirred until the reaction was completed. By treatment and column chromatography (5% ethyl acetate: dichloromethane) 0.4 g of the title compound were obtained: MS (EI) 286 (M + H +). (b) (S) -2- (tert-Butoxycarbonyl-naphthalen-2-ylmethyl-amino) -4-methylpentanoic acid methyl ester To a solution of the compound of Example 34a (0.35 g) in dichloromethane was added dicarbonate of di-tert-butyl (0.29 g). After 2 hours at room temperature, triethylamine was added and the reaction was heated to reflux. After completion, the reaction was concentrated and the residue was purified by column chromatography (50% hexane: dichloromethane) to give 0.17 g of the title compound: MS (EI) 386 (M + H +). (c) (S) -2- (tert-Butoxycarbonyl-naphthalen-2-ylmethyl-amino) -4-methylpentanoic acid To a solution of the compound of example 34b (0.17 g) in THF: methanol (15 ml : 1), LiOH (0.019 g) was added. The reaction was stirred overnight, after which it was concentrated to give the title compound. (d) 4 - [(S) -ter-Butoxycarbonyl-naphthylene-2-ylmethyl-amino) -4-methylpentanoylamino] -3-hydroxy-azepane-1-carboxylic acid benzyl ester To a solution of the compound of example 2e ( 0.11 g) in dichloromethane, EDC (0.08 g), HOBt (0.06 g) and the acid of example 34c were added. After completion of the reaction, it was treated and subjected to chromatography (5% methanol: dichloromethane) to give the title compound (0.18 g): MS (EI) 618 (M + H +). (e) [(S) -1- (3-Hydroxy-azepoan-4-ylcarbamoyl) -3-methyl-butyl] -naphthylene-2-ylmethylcarbamic acid tert-butyl ester To a solution of the compound of Example 34d (0.17) g) in ethyl acetate: methanol (20:10 ml) was added Pd / C 10%. A hydrogen balloon was attached and the reaction was stirred until complete consumption of the starting material. The reaction was filtered and concentrated to give the title compound (0.10 g): MS (EI) 484 (M + H +). (f) ((S) -3-Methyl-1- {3-hydroxy-1- [2- (3-pyridin-2-yl-phenyl) -acetyl] -acetic acid tert-butyl ester 4-ylcarbamoyl] -butyl) -naphthylene-2-methyl-carbamic acid The title compound was prepared following the procedure of example 9a, but using the compound of example 34e: MS (EI) 679 (M + H + ). (g) ((S) -3-Methyl-1- {3-oxo-1- [2- (3-pyridin-2-yl-phenyl) -acetyl] -azepan-4-tert-butyl ester -ylcarbamoyl.} -butyl) -naphthylene-2-methyl-carbamic acid. The title compound was prepared following the procedure of example 1, but using the compound of Example 34f: "? NMR (CDCl 3): d 1.0 (m, 6H), 1.5-2.2 (m, 16H), 2.7 (m, 1 H), 3.2 (m, 1 H), 3.7 (m, 3H), 4.0 (m, 1 H), 4.7 (m, 2H), 5.2 (m, 1 H), 7.2-7.3 (m, 16H), 8.6 (m, 1 H), MS (EI): 677 (M + H +, 100%).

EXAMPLE 35 Preparation of P-oxo-l-r2- (3-pyridin-2-yl-phenyl) -acetH1-azepan-4-yl} (S) -4-methyl-2-r (naphthylene-2-ylmethyl) -amino-1-pentenoic acid amide To a solution of the compound of Example 34g (20 mg) in THF, 1 M HCl in ether was added. The reaction was stirred until complete consumption of the starting material, after which it was concentrated to give the title compound: 1 H NMR (CDCl 3): d 1.0 (m, 6H), 1.5-2.1 (m, 5H), 2.2 (m, 2H), 2.5 (m, 1 H), 3.5 (m, 5H), 4.0 (m, 1 H), 4.7 (m, 2H), 4.4 (m, 1 H), 7.2-8.0 (m, 16H), 8.7 (m, 1 H); MS (EI): 577 (M + H +, 100%).

EXAMPLE 36 Preparation of 4-l "2- (2. {(S) -3-methyl-1-r3-oxo-1- (pyridine-2-sulfonyl) -azepan-4-tert-butyl ester Icarbamoyl-butylcarbamoyl > -benzofuran-5-yloxy) -eti-piperazine-1-carboxylic acid (a) 4- [2- (2 { (S) -3-methyl-1- [3-hydroxy-1- (pyridine-2-sulfonyl) -azepan-4-ylcarbamoyl-tert-butyl ester ] -butylcarbamoyl] -benzofuran-5-yloxy) -ethyl] -piperazine-1-carboxylic acid To a solution of the compound of example 28a (0.15 g) in dichloromethane, EDC (0.07 g), HOBt, was added. (0.05 g), triethylamine (0.11 ml) and 4- [2- (2-carboxy-benzofuran-5-yloxy) -ethyl] -piperazine-1-carboxylic acid tert-butyl ester. The reaction was stirred until complete. By treatment and column chromatography (10% methanol: ethyl acetate) the title compound (0.10 g) was obtained: MS (EI) 757 (M + H +). (b) 4- [2- (2 { (S) -3-methyl-1- [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl-tert-butyl ester ] -butylcarbamoyl.} - benzofuran-5-yloxy) -ethyl] -piperazine-1-carboxylic acid The title compound was prepared following the procedure of Example 1, but using the compound of example 36a: H NMR (CDCl 3) : d 1.0 (m, 6H), 1.5-2.1 (m, 14H), 2.2 (m, 2H), 2.7 (m, 1 H), 3.0 (m, 2H), 3.5 (m, 4H), 3.7 (m , 6H), 4.1 (m, 1 H), 4.5 (m, 2H), 4.7 (m, 2H), 5.0 (m, 1 H), 7.0-7.6 (m, 6H), 8.0 (m, 2H), 8.7 (m, 1 H); MS (EI): 755 (M + H +, 100%).

EXAMPLE 37 Preparation of 5- (2-Piperazine-) S (3) -3-methyl-1-f3-oxo-1- (pyridine-2-sulfoniD-azepan-4-ylcarbamoyl) -3-but-n-amide 1-yl-ethoxy) -benzofuran-2-carboxylic acid The compound of example 36b (0.02 g) was dissolved in 4M HCl in dioxane. The reaction was stirred until complete, after which it was concentrated to yield the title compound: "? NMR (CDCl3): d 1.0 (m, 6H), 1.5-1.7 (m, 7H), 2.7 (m, 2H), 3.3 (M, 2H), 3.5 (m, 1 H), 3.8 (m, 5H), 4.1 (m, 3H), 4.7 ( m, 4H), 5.0 (m, 1 H), 7.0-7.3 (m, 2H), 7.4 (m, 6H), 8.0 (m, 2H), 8.7 (m, 1 H): MS (EI): 655 (M + H +, 100%).

EXAMPLE 38 Preparation of. { (S) -3-Methyl-1 -f3-oxo-1- (pyridin-2-sulfonyl) -azepan-4- (5-cyclohexyl-ethoxy) -benzofuran-2-carboxylic acid 5- (2-cyclohexyl-ethoxy) -carbamoy-buty-phenyl ester (to) . { (S) -3-methyl-1 - [3-hydroxy-1- (pyridine-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl ester} 5- (2-cyclohexyl-ethoxy) -benzofuran-2-carboxylic acid amide To a solution of the compound of example 28a (0.15 g) in dichloromethane, EDC (0.07 g), HOBt (0.05 g), triethylamine was added. (0.1 ml) and 5- (2-cyclohexyl-ethoxy) -benzofurancarboxylic acid (0.01 g). The reaction was stirred until complete by CCD analysis. By treatment and column chromatography (100% ethyl acetate) the title compound (0.15 g) was obtained: MS (EI) 655 (M + H +). (b) { (S) -3-Methyl-1- [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 5- (2-cyclohexyl-ethoxy) -benzofuran-2-carboxylic acid amide The title compound was prepared following the procedure of Example 1 i, but using the compound of Example 38b: MS (EI) 653 (M + H +).

EXAMPLE 39 Preparation of ((S) -3-methyl-1-f3-oxo-1-r2- (3-pyridin-2-yl-phenol) etH-azepan-4-ylcarbamoi-P-butyl) amide 5- (2-cyclohexyl-ethoxy) -benzofuran-2-carboxylic acid (a) ((S) -3-Methyl-1 -. {3-hydroxy-1 - [2- (3-pyridin-2-yl-phenyl) ethyl] -azepan-4-ylcarbamoyl}. butyl) 5- (2-cyclohexyl-ethoxy) -benzofuran-2-carboxylic acid amide To a solution of the compound of Example 20d (0.15 g) in dichloromethane was added EDC (0.06 g), HOBt (0.04 g), triethylamine (0.14 ml) and 5- (2-cyclohexyl-ethoxy) -benzofurancarboxylic acid (0.09 g). The reaction was stirred until complete by CCD analysis. By treatment and column chromatography (100% ethyl acetate) the title compound (0.10 g) was obtained: MS (EI) 695 (M + H +). (b) ((S) -3-Methyl-1 - {3-0X0-1 - [2- (3-pyridin-2-yl-phenyl) ethyl] -azepan-4-ylcarbamoyl}. ) 5- (2-cyclohexyl-ethoxy) -benzofuran-2-carboxylic acid amide The title compound was prepared following the procedure of Example 1, but using the compound of Example 39a: "? RMN (CDCl3): d 1. 0 (m, 6H), 1.5-2.1 (m, 18H), 2.2 (m, 2H), 2.7 (m, 3H), 3.2 (m, 1 H), 3.5 (m, 1 H), 3.9 (m, 4H), 4.7 (m, 2H), 5.0 (m, 1 H), 7.2-7.3 (m, 13H), 8.7 (m, 1 H): MS (EI): 693 (M + H +, 100%).

EXAMPLE 40 Preparation of 4-f2- (2. {(S) -3-methy1-r3-oxo-1- (3-pyridin-2-yl-phenyl) - tert-butyl ester etiirazepan-4-ylcarbamoin-butylcarbamoiP-benzofuran-5-yloxy) -eti-piperazine-1-carboxylic acid (a) 4- [2- (2 { (S) -3-methyl-1- [3-hydroxy] -1- (3-pyridin-2-yl-) ter-butyl ester phenyl) -eti [azepane-4-carbamoyl] -butylcarbamoyl] -benzofuran-5-yloxy) -ethyl] -piperazine-1-carboxylic acid To a solution of the compound of Example 20d (0.15 g) in dichloromethane, EDC (0.06 g), HOBt (0.04 g), triethylamine (0.14 ml) and 4- [2- (2-carboxy-benzofuran-5-yloxy) -ethyl] -piperazin-tert-butyl ester were added. -1-carboxylic acid (0.12 g). The reaction was stirred until complete by CCD analysis. By treatment and column chromatography (10% methanol: ethyl acetate) the title compound (0.09 g) was obtained: MS (EI) 797 (M + H +). (b) 4- [2- (2 { (S) -3-methyl-1- [3-oxo-1- (3-pyridin-2-yl-phenyl) -ethyl) tert-butyl ester [azepan-4-ylcarbamoyl] -butylcarbamoyl.]. benzofuran-5-yloxy) -ethyl] -piperazin-1-carboxylic acid The title compound was prepared following the procedure of example 1, but using the compound of example 40a: MS (EI) 795.9 (M + H +).

EXAMPLE 41 Preparation of 5- (2- (2-) -3-methyl-1-f3-oxo-1-f2- (3-pyridin-2-yl-phenyleptin-azepan-4-ylcarbamoiP-buti-P-phenyl acid piperazin-1-yl-ethoxy-benzofuran-2-carboxylic acid The title compound was prepared following the procedure of Example 37, but using the compound of Example 40b: 1 H NMR (CDCl 3): d 1. 0 (m, 6H), 1.5-2.1 (m, 5H), 2.2 (m, 2H), 3.4-3.6 (m, 19H), 4.5 (m, 1 H), 4.7 (m, 2H), 5.0 (m , 1 H), 7.2 (m, 1 H), 7.4 (m, 1 H), 7.5 (m, 2H), 7.7 (m, 2H), 7.8 (m, 1 H), 8.1 (m, 2H), 8.4 (m, 1 H), 8.7 (m, 1 H); MS (EI): 695 (M + H +, 70%).

EXAMPLE 42 Preparation of (S) -4-methyl-2- (methyl-naphthalen-2-ylmethyl-amino) pentanoic acid f3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-in-amide (a) 4 - [(S) -2- (tert-Butoxycarbonyl-methyl-amino) -4-methyl-pentanoylamino] -3-hydroxy-azepane-1-carboxylic acid benzyl ester To a solution of the compound of example 2e (0.35 g) in dichloromethane, was added N-methyl-N-Boc-leucine (0.36 g), HOBt (0.2 g) and EDC (0.28 g). The reaction was stirred until complete. By treatment and column chromatography (5% methanol: dichloromethane) 0.6 g of the title compound were obtained: MS (EI) 492 (M + H +). (b) [(S) -1- (3-Hydroxy-azepan-4-ylcarbamoyl) -3-methyl-butyl] -methyl-carbamic acid tert-butyl ester To a solution of the compound of example 42a (0.6 g) in methanol: ethyl acetate (10:20 ml), 10% Pd / C was added and a hydrogen balloon was added. The reaction was stirred overnight, after which it was filtered and concentrated to give 0.50 g of the title compound: MS (EI) 358 (M + H +). (c) Tert-butyl acid ester. { (S) -1- [3-hydroxy-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl) -3-methyl-butyl] -methylcarbamic acid To a solution of compound 42b (0.2 g) in dichloromethane, triethylamine (0.16 ml) and 2-pyridinesulfonyl chloride (0.15 g) were added. The reaction was stirred until complete. By treatment and column chromatography (5% methanol: ethyl acetate) the title compound (0.23 g) was obtained: MS (EI) 499 (M + H +). (d) [3-Hydroxy-1- (2-pyridin-2-sulfonyl) -azepan-4-yl] -amide acid (S) -4-methyl-2-methylamino-pentanoic To a solution of the compound of example 42c (0.23 g) in methanol (3.0 ml), 4M HCl in dioxane (3.0 ml) was added. The reaction was stirred until complete. Concentration was obtained by the title compound: MS (EI) 399 (M + H +). (e) [3-Hydroxy-1- (pyridin-2-sulfonyl) -azepan-4-yl] -amide of (S) -4-methyl-2- (methyl-naphthalen-2-ylmethyl-amino) - pentanoic To a solution of the compound of Example 42d (0.05 g) in dichloromethane, triethylamine (0.07 ml), 2-naphthaldehyde (0.05 g) and sodium triacetoxyborohydride (0.11 g) were added. the reaction was stirred until complete. By treatment and column chromatography (5% methanol: ethyl acetate) the title compound (0.03 g) was obtained: MS (EI) 539 (M + H +). (f) [3-Oxo-l - (pyridin-2-sulfonyl) -azepan-4-yl] -amide of (S) -4-methyl-2- (methyl-naphthalen-2-ylmethyl-amino) - pentanoic The title compound was prepared following the procedure of Example 1 i, but using the compound of example 42e: 1 H NMR (CDCl 3): d 1.0 (m, 6H), 1.5-2.1 (m, 5H), 2.2 (m , 5H), 2.6 (m, 1 H), 3.3 (m, 1 H), 3.7 (m, 2H), 4.1 (m, 1 H), 4.7 (m, 1 H), 5.2 (m, 1 H) , 7.2-8.0 (m, 10H), 8.7 (m, 1 H); EM (EI): 537 (M + H +, 100%).

EXAMPLE 43 Preparation of. { 3-Oxo-1-r2- (3-pyridin-2-yl-phen-P-acetyn-azepan-4-iP-amide of (S) -4-methyl-2- (methyl-naphthalene) -2-methylamino) pentanoic (a) (S) -1-. {3-Hydroxy-1- [2- (3-pyridin-2-yl-phenyl) -acetyl] -azepan-4-ylcarbamoyl} tert-butyl ester. -3-methyl-butyl) -methylcarbamic acid To a solution of the compound of example 42b (0.25 g), 3- (2-pyridyl) phenylacetic acid (0.16 g), HOBt (0.12 g) and EDC ( 0.15 g).

The reaction was stirred until complete. By treatment and column chromatography (5% methanol: ethyl acetate) the title compound (0.24 g) was obtained: MS (EI) 553 (M + H +). (b) { 3-Hydroxy-1- [2- (3-pyridin-2-yl-pheny] -acetyl] -azepan-4-yl} -amide of (S) -4-methyl-2-methylamino-pentanoic acid The title compound was prepared following the procedure of example 42d, but using the compound of example 43a: MS (EI) 453 (M + H +) . (c). { 3-Oxo-l - [2- (3-pyridin-2-yl-phenyl) -acetyl] -azepan-4-yl} - (S) -4-methyl-2- (methyl-naphthalen-2-ylmethylamino) pentanoic acid amide The title compound was prepared following the procedures of examples 42 ef, but using the compound of example 43b: ? NMR (CDCI3): d 1.0 (m, 6H), 1.5-2.1 (m, 5H), 2.2 (m, 5H), 3.0 (m, 1H), 3.5 (m, 1 H), 3. 7 (m, 4H), 4.1 (m, 1 H), 4.7 (m, 2H), 5.2 (m, 1 H), 7.2-8.0 (m, 15H), 8.7 (m, 1 HOUR); MS (EI): 591 (M + H +, 100%).

EXAMPLE 44 Preparation of Methyl-f (S? -3-Methyl-l3-oxo-l-r2- (3-pyridin-2-yl-phenylatin-azepan-4-ylcarbamoyl-p-butyl) -5- -morpholin-4-yl-ethoxy) -benzofuran-2-carboxylic acid (a) Methyl - ((S) -3-methyl-1-. {3-hydroxy-1- [2- (3-pyridin-2-yl-phenyl) -acetyl] -azepan-4-ylcarbamoyl} -butyl) 5- (2-morpholino-4-yl-ethoxy) -benzofuran-2-carboxylic acid amide To a solution of the compound of example 43b (0.1 g) in dichloromethane, 5- (2-hydroxy) acid was added. -morpholin-4-yl-ethyloxy) benzofuran-2-carboxylic acid (0.06 g), HOBt (0.026 g), TEA (0.07 ml) and EDC (0.04 g). The reaction was stirred until complete. By treatment and chromatography (20% methanol: ethyl acetate), the title compound (0.07 g) was obtained: MS (EI) 726 (M + H +). (b) Methyl - ((S) -3-methyl-1 -. {3-oxo-1 - [2- (3-pyridin-2-yl-phenyl) -acetyl] -azepan-4-yl-carbamoyl .) .butyl) 5- (2-morpholino-4-yl-ethoxy) -benzofuran-2-carboxylic acid amide The title compound was prepared following the procedure of example 1 i, but using the compound of example 44a: 1 H NMR (CDCl 3): d 1.0 (m, 6H), 1.5-2.1 (m, 5H), 2.2 (m, 5H), 2.7 (m, 4H), 2.8 (m, 2H), 2.9 (m, 1 H), 3.5 (m, 1 H), 3.7 (m, 4H), 3.9 (m, 3H), 4.3 (m, 2H), 4.7 (m, 2H), 5.4 (m, 1 H), 7. 2-8.0 (m, 12H), 8.5 (m, 1H); MS (EI): 724 (M + H +, 100%).

EXAMPLE 45 Preparation of methylf (S) -3-methyl-1-F3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoiP-3-methyl-butyl-benzofuran-2-carboxylic acid amide (a) Methyl-. { (S) -3-Methyl-1 - [3-hydroxy-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl) -3-methyl-butyl] -benzofuran-2-carboxylic acid amide To a solution of the Compound of example 42d (0.1 g) in dichloromethane was added benzofuran-2-carboxylic acid (0.04 g), TEA (excess), HOBt (0.03 g) and EDC (0.04 g). The reaction was stirred until complete. By working up and column chromatography (5% methanol, dichloromethane) the title compound (0.04 g) was obtained: MS (EI) 542.9 (M + H +). (b) Methyl-. { (S) -3-Methyl-1 - [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl) -3-methyl-butyl] -benzofuran-2-carboxylic acid amide The title compound was prepared following the procedure of example 1 i, but using the compound of example 45a: 1 H NMR (CDCl 3): d 1. 0 (m, 6H), 1.5-2.1 (m, 8H), 2.2 (m, 2H), 2.7 (m, 1 H), 3.0 r (m, 1 H), 3.7 (m, 2H), 4.1 (m , 1 H), 4.7 (m, 1H), 5.2 (m, 1 H), 7.2-8.0 (m, 8H), 8.7 (m, 1H); MS (EI): 541 (M + H +, 10%).

EXAMPLE 46 Preparation of 2,2,2-trifluoro-N - ((S) -3-methyl-1- (3-oxo-1-r2- (3-pyridin-2-yl-phenyp-acetin-azepan-4-ylcarbamoyl > -butyl) -N-naphthylene-2-ylmethyl-acetamide (a) (S) -4-Methyl-2- [naphthylene-2-ylmethyl- (2,2,2-trifluoro-acetyl) -amino] -pentanoic acid methyl ester To a solution of the compound of example 34a (0.5 g) in dichloromethane, potassium carbonate (catalytic amount), and trifluoroacetic acid (0.44 g) were added. The reaction was stirred at room temperature for 1 hour, after which it was concentrated and subjected to chromatography (20% ethyl acetate: hexane) to give the title compound. (b) Lithium salt of (S) -4-methyl-2- [naphthylene-2-ylmethyl- (2,2,2-trifluoroacetyl) -amino] -pentanoic acid To a solution of the compound of example 46a (0.49 g) ) in THF: water (3 ml of a 2: 1 solution), lithium hydroxide monohydrate (0.06 g) was added. The reaction was stirred overnight, after which it was concentrated to give the title compound (0.46 g): MS (EI) 366 (M + H +). (c) 3-Hydroxy-4-benzyl ester. { (S) -4-Methyl-2- [naphthylene-2-ylmethyl- (2,2,2-trifluoro-acetyl) -amino] -pentanoylamino} -azepan-1-carboxylic acid To a solution of the compound of example 2e (0.29 g) in dichloromethane was added EDC (0.24 g), HOBt (0.16 g) and the compound of example 46b (0.46 g). The reaction was stirred until complete. By treatment and column chromatography (5% methanol: ethyl acetate) the title compound (0.25 g) was obtained: MS (EI) 614 (M + H +). (d) 2,2,2-Trifluoro-N - [(S) -1- (3-hydroxy-azepan-ylcarbamoyl) -3-methyl-butyl] -N-naphthyleth-2-ylmethyl-acetamide The title compound was prepared following the procedure of Example 42b, but using the compound of Example 46c: MS (EI) 480 (M + H +). (e) 2,2,2-Trifluoro-N - ((S) -3-methyl-1-. {3-hydroxy-1- [2- (3-pyridin-2-yl-phenyl) -acetyl] azepan-4-ylcarbamoyl.} - butyl) - N -naphthylene-2-ylmethyl acetamide The title compound was prepared following the procedure of Example 43a, but using the compound of Example 46d: MS (EI) 675 (M + H +). (f) 2,2,2-Trifluoro-N - ((S) -3-methyl-1 -. {3-oxo-1 - [2- (3-pyridin-2-yl-phenyl) -acetyl] azepan-4-ylcarbamoyl.} -butyl) -N-naphthylene-2-ylmethyl acetamide The title compound was prepared following the procedure of example 1i, but using the compound of Example 46e: H NMR (CDCl 3): d 1.0 (m, 6H), 1.5-2.1 (m, 5H), 2.2 (m, 2H), 2.7 (m, 1 H), 3.2 (m, 1 H), 3.7 (m, 3H), 4.1 (m , 1 H), 4.5 (m, 2H), 4.7 (m, 2H), 5.2 (m, 1 H), 7.2-8.0 (m, 14H), 8.7 (m, 1H): MS (EI): 673 (M + H +, 100%).

EXAMPLE 47 Benzyl ester of 4-r (S) - (methanesulfonyl-naphthylene-2-ylmethyl-amino) -4-methyl-pentanoylamino-3-oxo-azepane-1-carboxylic acid (a) (S) -2- (Methanesulfonyl-naphthylene-2-ylmethyl-amino) -4-methyl-pentanoic acid methyl ester To a solution of the compound of Example 34a (0.5 g) in dichloromethane, triethylamine ( 0.36 ml) and methanesulfonyl chloride (0.16 ml). The reaction was stirred at room temperature until complete. By treatment and chromatography (20% ethyl acetate: hexane), the title compound (0.24 g) was obtained. (b) Lithium salt of (S) -2- (methanesulfonyl-naphthylene-2-ylmethyl-amino) -4-methyl-pentanoic acid The title compound was prepared following the procedure of example 46b, but using the compound of the example 47a: MS (EI) 348 (M + H +). (c) 4 - [(S) - (Methanesulfonyl-naphthylene-2-ylmethyl-amino) -4-methyl-pentanoylamino] -3-hydroxy-azepane-1-carboxylic acid benzyl ester The title compound was prepared following the procedure of Example 46c, but using the compound of Example 47b: MS (EI) 596 (M + H +). (d) 4 - [(S) - (Methanesulfonyl-naphthylene-2-methylmethyl) -4-methyl-pentanoylamino] -3-oxo-azepane-1-carboxylic acid benzyl ester The title compound was prepared following the procedure of example 1 i, but using the compound of example 47c: H H NMR (CDCl 3): d 1.0 (m, 6H), 1.5-2.1 (m, 5H), 2.2 (m, 5H), 3.0 (m, 1H), 3.5 (m, 1H), 4.1 (m, 1H), 4.5 (m, 3H), 4.7 (m, 1 H), 5.2- (m, 3H), 7.2-8.0 (m, 13H); MS (EI): 596 (M + H +, 100%).

EXAMPLE 48 Preparation of (S) -3-methyl-1-f3-oxo-1- (pyridine-2-sulfonyl) -azepan-4-ylcarbamoin-buti-pyrimidine quinoline-2-carboxylic acid (to) . { (S) -3-Methyl-1 - [3-hydroxy-1 - (pyridine-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} quinoline-2-carboxylic acid amide The title compound was prepared following the procedure of example 28b, but substituting the benzofuran-2-carboxylic acid with quinoline-2-carboxylic acid: MS (EI) 540 (M + H +). (b) { (S) -3-Methyl-1 - [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} quinoline-2-carboxylic acid amide The title compound was prepared following the procedure of example 1i, but using the compound of example 48a: 1 H NMR (CDCl 3): d 1. 0 (m, 6H), 1.5-2.1 (m, 5H), 2.2 (m, 2H), 2.7 (m, 1 H), 3.7 (d, 1 H), 4.1 (m, 1 H), 4.7 (m , 2H), 5.0 (m, 1 H), 7.0.7.2 (m, 1 H), 7.3 (m, 1 H), 7.5 (m, 1 H), 7.7 (m, 1 H), 7.8 (m, 3H), 8.1 (m, 1 H), 8.3 (m, 2H), 8.7 (m, 2H); MS (EI): 538 (M + H +, 100%). The diastereomeric mixture was separated by CLAP to produce the fastest eluting diastereomer: MS (EI) 538 (M + H 100%), and the slowest eluting diastereomer: MS (EI) 538 (M + H +, 100% ).

EXAMPLE 49 Preparation of. { (S) -3-Methyl-1 -f3-oxo-1- (pyridine-2-sulfonyl) -azepan-4-ylcarbamoin-buty-phenamide of quinoline-8-carboxylic acid (to) . { (S) -3-Methyl-1 - [3-hydroxy-1- (pyridine-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} -quinoline-8-carboxylic acid amide The title compound was prepared following the procedure of example 28b, but substituting benzofuran-2-carboxylic acid with quinoline-8-carboxylic acid: MS (EI) 540 (M + H +). (b) { (S) -3-Methyl-1 - [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} quinoline-8-carboxylic acid amide The title compound was prepared following the procedure of example 1 i, but using the compound of example 49a: H NMR (CDCl 3): d 1.0 (m, 6H), 1.5-2.1 (m, 5H), 2.2 (m, 2H), 2.7 (m, 1 H), 3.7 (d, 1 h), 4.0 (m, 1 H), 4.7 (m, 2H), 5.0 (m, 1H), 7.5 (m, 4H), 7.6 (m, 1 H), 7.7 (m, 3H), 8.2 (m, 1 H), 8.6 (m, 1 H), 8.7 (m, 1 H), 8.9 (m, 1 H); MS (EI): 538 (M + H +, 100%).

EXAMPLE 50 Preparation of l (S) -3-methyl-1 - [3-oxo-1- (pyridine-2-sulfonyl) -azepan-4- quinoline-6-carboxylic acid Icarbamoy-buty-phenamide (to) . { (S) -3-Methyl-1 - [3-hydroxy-1 - (pyridine-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl ester} quinoline-6-carboxylic acid amide The title compound was prepared following the procedure of example 28b, but substituting the benzofuran-2-carboxylic acid with quinoline-6-carboxylic acid: MS (EI) 540 (M + H +). (b) { (S) -3-Methyl-1 - [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} quinoline-6-carboxylic acid amide The title compound was prepared following the procedure of example 1 i, but using the compound of example 50a: 1 H NMR (CDCl 3): d 1. 0 (m, 6H), 1.5-2.1 (m, 5H), 2.2 (m, 2H), 2.7 (m, 1H), 3.7 (d, 1H), 4.0 (m, 1H), 4.7 (m, 2H) , 5.0 (m, 1 H), 7.0 (m, 2H), 7.5 (m, 2H), 7.9 (m, 2H), 8.0 (m, 3H), 8.2 (, 1 H), 8.7 (m, 1 H) ), 8.9 (m, 1 H); MS (EI): 538 (M + H +, 100%). The diastereomeric mixture was separated by CLAP to produce the fastest eluting diastereomer: MS (EI) 538 (M + H +, 100%), and the slowest eluting diastereomer: MS (EI) 538 (M + H +, 100% ).

EXAMPLE 51 Preparation of. { (S) -3-methyl-1-r3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoy-buty-pyrimidine quinoline-4-carboxylic acid (to) . { (S) -3-Methyl-1 - [3-hydroxy-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl ester} quinoline-4-carboxylic acid amide The title compound was prepared following the procedure of example 28b, but substituting the benzofuran-2-carboxylic acid with quinoline-4-carboxylic acid: MS (EI) 540 (M + H +). (b) { (S) -3-Methyl-1 - [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} quinoline-4-carboxylic acid amide The title compound was prepared following the procedure of example 1i, but using the compound of example 51a: "? NMR (CDCl 3): d 1.0 (m, 6H), 1.5-2.1 (m, 5H), 2.2 (m, 2H), 2.7 (m, 1 H), 3.7 (d, 1 H), 4.0 (m, 1 H), 4.7 (m, 2H), 5.0 (m, 1 H), 6.5 -7.2 (m, 2H), 7.4 (m, 2H), 7.5 (m, 1 H), 7.7 (m, 1 H), 7.9 (m, 2H), 8.0 (m, 1 H), 8.2 (m, 1H), 8.7 (m, 1H), 8.9 (m, 1H), MS (EI): 538 (M + H +, 100%). The diastereomeric mixture was separated by CLAP to produce the fastest eluting diastereomer: MS (EI) 538 (M + H +, 100%), and the slowest eluting diastereomer: MS (EI) 538 (M + H +, 100% ).

EXAMPLE 52 Preparation of (S) -3-methyl-1-f3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl-buti-pyrimidine quinoline-3-carboxylic acid (to) . { (S) -3-Methyl-1- [3-hydroxy-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} -quinoline-3-carboxylic acid amide The title compound was prepared following the procedure of example 28b, but substituting the benzofuran-2-carboxylic acid with quinoline-3-carboxylic acid: MS (EI) 540 (M + H +). (b) { (S) -3-Methyl-1 - [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} quinoline-3-carboxylic acid amide The title compound was prepared following the procedure of example 1, but using the compound of example 52a: "? NMR (CDCl 3): d 1. 0 (m, 6H), 1.5-2.1 (m, 5H), 2.2 (m, 2H), 2.7 (m, 1H), 3.7 (d, 1H), 4.0 (m, 1 H), 4.7 (m, 2H) ), 5.0 (m, 1 H), 7.2 (m, 2H), 7.5 (m, 1 H), 7.6 (m, 1 H), 7.7-7.9 (m, 4H), 8.1 (m, 1 H), 8.5 (m, 1 H), 8.6 (m, 1 H), 9.3 (m, 1 H); MS (EI): 538 (M + H +, 100%). The diastereomeric mixture was separated by CLAP to produce the fastest eluting diastereomer: MS (EI) 538 (M + H +, 100%), and the slowest eluting diastereomer: MS (EI) 538 (M + H +, 100% ).

EXAMPLE 53 Preparation of (S) -3-methyl-1-oxo-l - (pyridine-2-sulfonyl) -azepan-4- H-carbamoyl-butyamidoquinoline-3-carboxylic acid (to) . { (S) -3-Methyl-1- [3-hydroxy-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} isoquinoline-3-carboxylic acid amide The title compound was prepared following the procedure of example 28b, but substituting the benzofuran-2-carboxylic acid with isoquinoline-3-carboxylic acid: MS (EI) 540 (M + H +). (b) { (S) -3-Methyl-1 - [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} isoquinoline-3-carboxylic acid amide The title compound was prepared following the procedure of example 1 i, but using the compound of example 53a: "? NMR (CDCl 3): d 1.0 (m, 6H), 1.5-2.1 (m , 5H), 2.2 (m, 2H), 2.7 (m, 1 H), 3.7 (d, 1 H), 4.0 (m, 1 H), 4.7 (m, 2H), 5.0 (m, 1 H), 7.0 (m, 1 H), 7.5 (m, 1 H), 7.7 (m, 2H), 7.9 (m, 4H), 8.7 (m, 3H), 9.2 (m, 1H), MS (EI): 538 (M + H +, 100%).

EXAMPLE 54 Preparation of f (S) -3-methyl-1-f3-oxo-1- (pyridine-2-sulfonyl) -azepan-4-ylcarbamoyl-buty-phenyl acid isoquinoline-1-carboxylic acid (to) . { (S) -3-Methyl-1 - [3-hydroxy-1- (pyridine-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} isoquinoline-1-carboxylic acid amide The title compound was prepared following the procedure of example 28b, but substituting the benzofuran-2-carboxylic acid with isoquinoline-1-carboxylic acid: MS (EI) 540 (M + H +). (b) { (S) -3-Methyl-1 - [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} isoquinolin-1-carboxylic acid amide The title compound was prepared following the procedure of Example 1, but using the compound of example 54a: 1 H NMR (CDCl 3): d 1. 0 (m, 6H), 1.5-2.1 (m, 5H), 2.2 (m, 2H), 2.7 (m, 1 H), 3.7 (d, 1 H), 4.0 (m, 1 H), 4.7 (m) , 2H), 5.0 (m, 1 H), 7.3 (m, 1 H), 7.5 (m, 1 H), 7.7-8.0 (m, 6H), 8.7 (m, 3H), 9. 5 (m, 1 H); MS (EI): 538 (M + H +, 100%). The diastereomeric mixture was separated by CLAP to produce the fastest eluting diastereomer: MS (EI) 537 (M +, 100%), and the slowest eluting diastereomer: MS (EI) 537 (M +, 100%).

EXAMPLE 55 Preparation of. { (S) -3-methyl-1 -f3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoill-b? TiPamide of quinoxaline-2-carboxylic acid (to) . { (S) -3-Methyl-1 - [3-hydroxy-1 - (pyridine-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} quinoxaline-2-carboxylic acid amide The title compound was prepared following the procedure of example 28b, but substituting the benzofuran-2-carboxylic acid with quinoxaline-2-carboxylic acid: MS (EI) 541 (M + H +). (b) { (S) -3-M ethyl-1 - [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} Quinoxaline-2-carboxylic acid amide The title compound was prepared following the procedure of Example 1 i, but using the compound of Example 55a: 1 H NMR (CDCl 3): d 1. 0 (m, 6H), 1 .5-2.1 (m, 5H), 2.2 (m, 2H), 2.7 (m, 1 H), 3.7 (d, 1 H), 4.0 (m, 1 H), 4.7 (m, 2H), 5.0 (m, 1 H), 7.0-7.2 (m, 2H), 7.5 (m, 1 H), 7.7 (m, 3H), 8.2 (m, 2H), 8. 3 (m, 1 H), 8.7 (m, 1 H), 9.5 (m, 1 H); MS (EI): 539 (M + H +, 30%).

EXAMPLE 56 Preparation of. { (S) -3-Methyl-1-r3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoin-buti-P-benzorbltiophen-2-carboxylic acid (to) . { (S) -3-Methyl-1 - [3-hydroxy-1 - (pyridine-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} benzo [b] thiophene-2-carboxylic acid amide The title compound was prepared following the procedure of example 28b, but substituting benzofuran-2-carboxylic acid with benzo [b] thiophene-2-carboxylic acid: MS (EI ) 545 (M + H +). (b) { (S) -3-Methyl-1 - [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} benzo [b] thiophene-2-carboxylic acid amide The title compound was prepared following the procedure of example 1i, but using the compound of Example 56a: H NMR (CDCl 3): d 1. 0 (m, 6H), 1.5-2.1 (m, 5H), 2.2 (m, 2H), 2.7 (m, 1 H), 3.7 (d, 1 H), 4.0 (m, 1 H), 4.7 (m) , 2H), 5.0 (m, 1 H), 6.8-7.2 (m.H1), 7.5 (m, 3H), 8.0 (m, 6H), 8.7 (m, 1H); MS (EI): 543 (M + H +, 60%). The diastereomeric mixture was separated by CLAP to produce the fastest eluting diastereomer: 1 H NMR (CDCl 3): d 1.0 (m, 6), 1.5-2.2 (m, 6H), 2.7 (m, 1 H), 3.8 (m, 1 H), 4.1 (m, 1 H), 4.7 (m, 2H), 5.1 (m, 1 H), 7.4-8.0 (m, 8H), 8.7 (m, 1 H); MS (EI): 543 (M + H +, 100%); and the slowest eluting diastereomer: 1.0 (m, 6H), 1.5-2.2 (m, 6H), 2.7 (m, 1 H), 3.8 (m, 1 H), 4.1 (m, 1 H), 4. 7 (m, 2H), 5.1 (m, 1 H), 7.4-8.0 (m, 8H), 8.7 (m, 1 H); EM (EI): 543 (M + H +, 100%).

EXAMPLE 57 Preparation of. { (S) -3-methyl-1-r3-oxo-1 - (pyridine-2-sulfonyl) -azepan-4- Icarbamoin-buti-p-pyridine of 1,8-naphthyridine-2-carboxylic acid (to) . { (S) -3-Methyl-1 - [3-hydroxy-1- (pyridine-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} - 1,8-naphthyridine-2-carboxylic acid amide The title compound was prepared following the procedure of example 28b, but substituting benzofuran-2-carboxylic acid with 1,8-naphthyridine-2-carboxylic acid: EM (EI) ) 541 (M + H +). (b) { (S) -3-Methyl-1 - [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 1,8-naphthyridine-2-carboxylic acid amide The title compound was prepared following the procedure of example 1 i, but using the compound of example 57a: 1 H NMR (CDCl 3): d 1. 0 (m, 6H), 1.5-2.1 (m, 5H), 2.2 (m, 2H), 2.7 (m, 1 H), 3.7 (d, 1 H), 4.0 (m, 1 H), 4.7 (m) , 2H), 5.0 (m, 1 H), 7.2 (m, 1 H), 7.6 (m, 2H), 7.9 (m, 2H), 8.3 (m, 1 H), 8.4 (m, 2H), 8.5 (m, 2H), 9.2 (m, 1 H); MS (EI): 539 (M + H +, 100%).

EXAMPLE 58 Preparation of 1 H-indole-2-carboxylic acid (S) -3-methyl-1-f3-oxo-1- (pyridine-2-sulfonyl) -azepan-4-ylcarbamoyl-buty-phenyl acid (to) . { (S) -3-Methyl-1 - [3-hydroxy-1- (pyridine-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 1-H-indole-2-carboxylic acid amide The title compound was prepared following the procedure of example 28b, but substituting benzofuran-2-carboxylic acid with 1H-indole-2-carboxylic acid: EM (EI) 528 (M + H +). (b) { (S) -3-Methyl-1 - [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 1 H-indole-2-carboxylic acid amide The title compound was prepared following the procedure of example 1 i, but using the compound of example 58a: "? RMN (CDCl 3): d 1. 0 (m, 6H), 1.5-2.1 (m, 5H), 2.2 (m, 2H), 2.7 (m, 1H), 3.7 (d, 1H), 4.0 (m, 1H), 4. 7 (m, 2H), 5.0 (m, 1H), 6.8 (m, 1 H), 7.1 (m, 1 H), 7.3 (m, 3H), 7.4 (m, 1H), 7.5 (m, 1 H) ), 7.6 (m, 1 H), 8.0 (m, 2H), 8.7 (m, 1 H), 9.4 (d, 1 H); EM (EI): 526 (M + H +, 80%).

EXAMPLE 59 Preparation of. { (S) -3-methyl-1-f3-oxo-1 - (pyridine-2-sulfonyl) -azepan-4- Icarbamoyl-buti-P-5-methoxybenzofuran-2-carboxylic acid (to) . { (S) -3-Methyl-1- [3-hydroxy-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 5-methoxybenzofuran-2-carboxylic acid amide The title compound was prepared following the procedure of example 28b, but substituting benzofuran-2-carboxylic acid with 5-methoxybenzofuran-2-carboxylic acid: MS (EI) 559 (M + H +). b) { (S) -3-Methyl-1 - [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 5-methoxybenzofuran-2-carboxylic acid amide The title compound was prepared following the procedure of example 1 i, but using the compound of example 59a: 1 H NMR (CDCl 3): d 1. 0 (m, 6H), 1.5-2.1 (m, 5H), 2.2 (m, 2H), 2.7 (m, 1 H), 3.7 (d, 4H), 4.0 (m, 1 H), 4.7 (m, 2H), 5.0 (m, 1 H), 7.0 (m, 4H), 7.6 (m, 3H), 8.0 (m, 2H), 8.7 (m, 1 H); MS (EI): 557 (M + H +, 70%). The diastereomeric mixture was separated by CLAP to produce the fastest eluting diastereomer: 1 H NMR (CDCl 3) d 1.0 (m, 6H), 1.5-2.1 (m, 5H), 2.2 (m, 2H), 2.7 (t, 1 H), 3.7 (m, 4H), 4.0 (d, 1 H), 4.7 (m, 2H), 5.0 (d, 1 H) 7.0 (m, 4H), 7.6 (m, 3H), 8.0 (m, 2H), 8.7 (d, 1 H), MS (EI): 557 (M + H +, 100%); and the slower eluting diastereomer: MS (EI): 557 (M + H +, 100%).

EXAMPLE 60 Preparation of. { (S) -3-methyl-1-f3-oxo-1 - (pyridine-2-sulfonyl) -azepan-4- Icarbamoip-butiPamide of 5-bromo-furan-2-carboxylic acid (to) . { (S) -3-Methyl-1 - [3-hydroxy-1- (pyridine-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 5-bromo-furan-2-carboxylic acid amide The title compound was prepared following the procedure of example 28b, but substituting benzofuran-2-carboxylic acid with 5-bromo-2-furoic acid: EM (EI) 558 (M + H +). (b) { (S) -3-Methyl-1 - [3-OXO-1 - (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 5-bromo-furan-2-carboxylic acid amide The title compound was prepared following the procedure of Example 1, but using the compound of Example 60a: 1 H NMR (CDCl 3): d 1. 0 (m, 6H), 1.5-2.1 (m, 5H), 2.2 (m, 2H), 2.7 (m, 1 H), 3.7 d, 1 H), 4.0 (m, 1 H), 4.7 (m, 2H), 5.0 (m, 1 H), 6.5 (m, 1 H), 6.7 (m, 1 H), 7.1 (m, 2H), 7.5 (m, 1 H), 8.0 (m, 2H), 8.7 (m, 1H); MS (EI): 555 (M + H +, 60%). The diastereomeric mixture was separated by CLAP to produce the fastest eluting diastereomer: MS (EI): 555 (M + H +, 100%), and the slowest eluting diastereomer: EM (EI) 555 (M + H +, 100 %).

EXAMPLE 61 Preparation of. { (S) -3-methyl-1 - [3-oxo-1 - (pyridine-2-sulfonyl) -azepan-4- Icarbamoip-buty-phenamide of furan-2-carboxylic acid (to) . { (S) -3-Methyl-1 - [3-hydroxy-1- (pyridine-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} Furan-2-carboxylic acid amide The title compound was prepared following the procedure of example 28b, but substituting the benzofuran-2-carboxylic acid with 2-furoic acid: MS (EI) 479 (M + H +). (b) { (S) -3-Methyl-1 - [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} furan-2-carboxylic acid amide The title compound was prepared following the procedure of example 1 i, but using the compound of Example 61a: 1 H NMR (CDCl 3): d 1. 0 (m, 6H), 1 .5-2.1 (m, 5H), 2.2 (m, 2H), 2.7 (m, 1 H), 3.7 (d, 1 H), 4.0 (m, 1 H), 4.7 (m, 2H), 5.0 (m, 1 H), 6.5 (m, 1 H), 7.2 (m, 3H), 7.5 (m, 2H), 8.0 (m, 2H), 8.7 (m, 1 H); MS (EI): 477 (M + H +, 50%).

EXAMPLE 62 Preparation of. { (S) -3-methyl-1 -f3-oxo-1 - (pyridine-2-sulfonyl-5-nitro-furan-2-carboxylic acid 5-nitro-furan-2-carboxylic acid Icarbamoyl-buty-phenyl (to) . { (S) -3-Methyl-1- [3-hydroxy-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 5-Nitro-furan-2-carboxylic acid amide The title compound was prepared following the procedure of example 28b, but substituting benzofuran-2-carboxylic acid with 5-nitro-2-furoic acid: EM (EI) 524 (M + H +). (b) { (S) -3-Methyl-1 - [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 5-Nitro-furan-2-carboxylic acid amide The title compound was prepared following the procedure of Example 1 i, but using the compound of Example 62a: 1 H NMR (CDCl 3): d 1. 0 (m, 6H), 1-5-2.1 (m, 5H), 2.2 (m, 2H). 2.7 (m, 1 H), 3.7 (d, 1 H), 4.0 (m, 1 H), 4.7 (m, 2 H), 5.0 (m, 1 H), 7.2 (m, 1 H), 7.3 (m, 1H), 7.5 (m, 1H), 7.9 (m, 2H), 8.7 (m, 1 H): MS (EI): 522 (M + H +, 80%).

EXAMPLE 63 Preparation of. { (S) -3-methyl-1 -f3-oxo-1-p-pyridin-2-s? Lphonl) -azepan-4- Icarbamoin-buti-P -amide of 5- (4-nitro-phenyl) -furan- 2-carboxylic (to) . { (S) -3-Methyl-1 - [3-hydroxy-1 - (pyridine-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 5- (4-nitro-phenyl) -furan-2-carboxylic acid amide The title compound was prepared following the procedure of example 28b, but substituting benzofuran-2-carboxylic acid with 5- (4-nitrophenyl) -2-furoic: MS (EI) 600 (M + H +). (b) { (S) -3-Methyl-1 - [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 5- (4-Nitro-phenyl) -furan-2-carboxylic acid amide The title compound was prepared following the procedure of Example 1, but using the compound of Example 63a: ^ H NMR (CDCl 3): d 1. 0 (m, 6H), 1.5-2.1 (m, 5H), 2.2 (m, 2H), 2.7 (m, 1 H), 3.7 (d, 1 H), 4.0 (m, 1 H), 4.7 (m) , 2H), 5.0 (m, 1 H), 6.9 (m, 1 H), 7.2 (m, 1 H), 7.5 (m, 2H), 7.9-8.0 (m, 4H), 8. 5 (m, 1 H), 8.6 (m, 1 H); MS (EI): 598 (M + H +, 80%).

EXAMPLE 64 Preparation of. { (S) -3-methyl-1 - [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoin-buty-p -amide of 5- (3-trifluoromethyl-phenyl) -furan-2-carboxylic acid (to) . { (S) -3-Methyl-1 - [3-hydroxy-1 - (pyridine-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 5- (3-trifluoromethyl-phenyl) -furan-2-carboxylic acid amide The title compound was prepared following the procedure of example 28b, but substituting benzofuran-2-carboxylic acid with 5- [3- (trifluoromethyl) ) phenyl] -2-furoic acid: MS (EI) 623 (M + H +). (b) { (S) -3-Methyl-1 - [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 5- (3-trifluoromethyl-phenyl) -furan-2-carboxylic acid amide The title compound was prepared following the procedure of Example 1i, but using the compound of example 64a: H-NMR (CDCl 3): d 1.0 (m , 6H), 1.5-2.1 (m, 5H), 2.2 (m, 2H), 2.7 (m, 1 H), 3.7 (d, 1 H), 4.0 (m, 1 H), 4.7 (m, 2H) , 5.0 (m, 1 H), 7.1 (m, 1 H), 7.5 (m, 3 H), 8.0 (m, 4 H), 8.7 (m, 1 H); MS (EI): 621 (M + H +, 80%). The diastereomeric mixture was separated by CLAP to produce the fastest eluting diastereomer: MS (EI) 621 (M + H +, 100%), and the slowest eluting diastereomer: MS (EI) 621 (M + H +, 100% ).

EXAMPLE 65 Preparation of Tetrahydro-furan-2-carboxylic acid ((S) -3-methyl-1-f3-oxo-1- (pyridine-2-sulfonyl) -azepan-4-ylcarbamoin-buti-pyrimidine (to) . { (S) -3-Methyl-1 - [3-hydroxy-1- (pyridine-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} Tetrahydrofuran-2-carboxylic acid amide The title compound was prepared following the procedure of example 28b, but substituting benzofuran-2-carboxylic acid with tetrahydrofuran-2-carboxylic acid: MS (EI) 483 (M + H + ). (b) { (S) -3-Methyl-1 - [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} Tetrahydrofuran-2-carboxylic acid amide The title compound was prepared following the procedure of Example 1, but using the compound of Example 65a: "NMR (CDCl 3): d 1. 0 (m, 6H), 1.5-2.2 (m, 12H), 2.7 (m, 1 H), 3.8 (m, 3H), 4.0 (m, 1 H), 4.5 (m, 2H), 4.8 (m, 1 H), 5.0 (m, 1 H), 7.0 (m, 1 H), 7.5 (m, 1 H), 7.9 (m, 2 H), 8.7 (m, 1 HOUR). MS (EI): 481 (M + H +, 80%).

EXAMPLE 66 Preparation of f3-oxo- (pyridine-2-sulfonyl) -azepan-4-n-amide of (S) -4-methyl-2- (2-phenoxy-acetylamino) -pentanoic acid (a) (S) -4-Methyl-2- (2-phenoxy-acetylamino) -pentanoic acid [3-hydroxy- (pyridin-2-sulfonyl) -azepan-4-yl] -amide The title compound is prepared following the procedure of example 28b, but substituting the benzofuran-2-carboxylic acid with phenoxyacetic acid: MS (EI) 519 (M + H +). (b) [3-Oxo- (pyridin-2-sulfonyl) -azepan-4-yl] -amide of (S) -4-methyl-2- (2-phenoxy-acetylamino) -pentanoic acid The title compound is prepared following the procedure of Example 1, but using the compound of Example 66a: H NMR (CDCl 3): d 1. 0 (m, 6H), 1.5-2.1 (m, 5), 2.2 (m, 2H), 2.7 (m, 1 H), 3.7 (d, 1 H), 4.0 (m, 1 H), 4.5 (m) , 3H), 4.7 (m, 1 H), 5.1 (m, 1 H), 7.0 (m, 3H), 7.3 (m, 2H), 7.5 (m, 1 H), 7.9 (m, 2H), 8.6 (m, 1 H); MS (EI): 517 (M + H +, 60%).

EXAMPLE 67 Preparation of (S) -2-r2- (4-Fluoro-phenoxy) -acetylamino-1-4-methyl-pentanoic acid r3-oxo-pyridine-2-sulfonyl) -zepan-4-yl-amide (a) [3-Hydroxy- (pyridin-2-sulfonyl) -azepan-4-yl] -amide of (S) -2- [2- (4-fluoro-phenoxy) -acetylamino] -4-methyl- pentanoic The title compound was prepared following the procedure of Example 28b, but substituting the benzofuran-2-carboxylic acid with 4-fluorophenoxyacetic acid: MS (EI) 537 (M + H +). (b) [3-O? o- (pyridin-2-sulfonyl) -azepan-4-yl] -amide of (S) -2- [2- (4-fluoro-phenoxy) -acetylamino) -4- methyl-pentanoic The title compound was prepared following the procedure of example 1 i, but using the compound of example 67a: "? NMR (CDCl 3): d 1. 0 (m, 6H), 1.5-2.1 (m, 5H), 2.2 (m, 2H), 2.7 (m, 1 H), 3.6 (d, 1 H), 4.0 (m, 1 H), 4.5 (, 3H), 4.8 (m, 1H), 5.1 (m, 1 H), 7.0 (m, 4H), 7.5 (m, 1H), 7.9 (m, 2H), 8.6 (m, 1H); MS (EI): 535 (M + H +, 50%).

EXAMPLE 68 Preparation of. { (S) -3-methyl-1-r3-oxo-1- (pyridine-2-carbonyl) -azepan-4-ylcarbamoiP-3-buty-benzofuran-2-carboxylic acid amide (a) Ter-butyl acid ester. { (S) -1- [3-hydroxy-1- (pyridine-2-carbonyl) -azepan-4-ylcarbamoyl) -3-methyl-butyl} -carbamic acid To a solution of the compound of example 2g (0.25 g) in dichloromethane, picolinic acid (0.09 g), EDC, (0.14 g) and HOBt were added. (0.10 g). The reaction was stirred until complete. By treatment and column chromatography (5% methanol: ethyl acetate) the title compound (0.35 g) was obtained. (b) [3-Hydroxy-1- (pyridine-2-carbonyl) -azepan-4-yl] -amide of (S) -2-amino-4-methylpentanoic acid To a solution of the compound of example 68a (0.34 g) ) in methanol (6 ml), 4M HCl in dioxane (6 ml) was added. The reaction was stirred until complete, after which it was concentrated to give the title compound (0.34 g): MS (EI) 349 (M + H +). (c). { (S) -3-Methyl-1- [3-hydroxy-1- (pyridin-2-carbonyl) -azepan-4-ylcarbamoyl) -3-butyl] -amide of benzofuran-2-carboxylic acid The compound of title was prepared following the procedure of example 28b, but using the compound of Example 68b: MS (EI) 493 (M + H +). (d). { (S) -3-Methyl-1 - [3-oxo-1- (pyridine-2-carbonyl) -azepan-4-lcarbamoyl) -3-butyl] -amide of benzofuran-2-carboxylic acid The title compound was prepared following the procedure of example 1i, but using the compound of example 68c: 1 H NMR (CDCl 3): d 1.0 (m, 6H), 1.5-2.1 (m, 5H), 2.2 (m, 2H), 2.5 ( m, 1 H), 3.7 (m, 1 H), 4.7 (m, 4H), 5.0 (m, 1 H), 7.0-7.5 (m, 8H), 8.2 (m, 1 H); MS (EI): 491 (M +, 100%).

EXAMPLE 69 Preparation of f (S) -3-methyl-1-r3-oxo-1- (1-oxy-pyridine-2-carbonyl) -azepan-4-ylcarbamoiD-butyromide of benzofuran-2-carboxylic acid The title compound was prepared following the procedures of examples 68 ad, but substituting the picolinic acid of example 68c with picolinic acid N-oxide: H NMR (CDCl 3): d 1.0 (m, 6H), 1.5-2.1 (m , 5H), 2.2 (m, 2H), 2.5 (m, 1 H), 3.5 (d, 1 H), 4.0 (m, 1 H), 4.7 (m, 3H), 5.5 (m, 1H), 7.0 ( m, 2H), 7.2-7.5 (m, 7H), 8.1 (m, 2H); MS (EI): 507 (M +, 20%).

EXAMPLE 70 Preparation of 4 - ((S) -2-tert-Butylcarbonylamino-4-methyl-pentanoylamino) -3-oxo-azepane-1-carboxylic acid benzyl ester The title compound was prepared following the procedure of Example 92j, but substituting. { (S) -1- [3-hydroxy-6,6-dimethyl-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -3-methyl-butyl} benzofuran-2-carboxylic acid amide with 4 - ((S) -2-tert-butoxycarbonylamino-4-methyl-pentanoylamino) -3-hydroxy-azepane-1-carboxylic acid benzyl ester. The residue was purified by CLAP. First eluted diastereomer MS (M + H +): 476.2; 1 H NMR (400 MHz, CDCl 3): d 7.40-6.95 (m, 7H), 5.25-4.60 (m, 4H), 4.40-4.06 (m, 2H), 3.70-3.58 (t, 1 H), 2.70-2.50 (m, 1 H), 2.25-1.30 (m, 16H); and the second diastereomer eluted: MS (M + H +) 476.2.

EXAMPLE 71 { (S) -3-Methyl-1 3-oxo-1- (1-methyl-1 H-imidazole-4-sulfonyl-5-dimethoxybenzofuran-2-carboxylic acid 5,6-dimethoxybenzofuran-2-carboxylic acid (a) Ter-butyl acid ester. { (S) -1- [3-hydroxy-1- (1-methyl-1 H-imidazole-2-sulfonyl) -azepan-4-ylcarbamoyl] -3-methyl-butyl} To a solution of the amine of Example 2g in methylene chloride (5 ml), pyridine (92 μl, 1.14 mmol) was added, followed by 1-methylimidazole-4-sulfonylchloride (0-112 g, 0.623 mmol). The reaction was allowed to stir for 16 hours at room temperature. The solution was then washed with saturated NaHC 3 solution, water and brine. The product was purified by column chromatography (silica gel; methanol / methylene chloride) to yield the title compound as a white solid (0.172 g, 68%): "? NMR (400MHz, CDCl 3) d 7.6 (d, 1 H), 7.5 (d, 1 H), 6.6 (d, 1 H), 3.8 (s, 3 H), 1.5 (s, 9H), 1 (d, 6H); MS (ESI): 488.2 (M + H) + (b) [3-Hydroxy-1- (1-methyl-1 H-imidazole-2-sulfonyl) -azepan-4-yl] -amide (S) -2-amino-4-methyl-pentanoic To a solution of the compound of example 71a (0.172 g, 0.353 mmol) in a minimum amount of methanol, 4M HCl in dioxane was added. (10 ml) and stirred at room temperature for 4 hours. The reaction mixture was concentrated and azeotropically distilled with toluene (2x) to give the title compound as an off white solid: MS (EI) 388.2 (M + H +). (c). { (S) -3-Methyl-1- [3-hydroxy-1- (1-methyl-1 H-imidazole-4-sulfonyl) -azepan-4-yl-carbamoyl] -butyl ester} 5,6-dimethoxybenzofuran-2-carboxylic acid amide To a stirred solution of the compound of example 71 b (0.137 g, 0.353 mmol), 5,6-dimethoxybenzofuran-2-carboxylic acid (0.86 g, 0.388 mmol), triethylamine ( 246 ml, 1.77 mmoles) and 1-hydroxybenzotriazole (0.01 g, 0.070 mmol) in DMF (5 ml), was added 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (0.074 g, 0.388 mmoles). After stirring at room temperature for 16 hours, the solution was diluted with EtOAc and washed successively with saturated aqueous sodium bicarbonate solution, water (2x) and brine. The organic layer was dried over Na2SO4, filtered and concentrated. The product was purified by column chromatography (silica gel; methanol / dichloromethane) to give the title compound as a white solid (0.088 g, 42%): MS (EI) 592.1 (M + H +). (d). { (S) -3-Methyl-1 - [3-oxo-1- (1-methyl-1 H-imidazole-4-sulfonyl) -azepan-4-yl-carbamoyl] -butyl ester} 5,6-dimethoxybenzofuran-2-carboxylic acid amide Oxalyl chloride (52 μl, 0.596 mmol) was cooled to -78 ° C. To this was added dropwise dimethyl sulfoxide (106 μL, 1.49 mmol) in methylene chloride. After stirring 15 minutes at -78 ° C, the alcohol was added slowly in methylene chloride and left stirring for 1 hour, after which Et3N (416 μL, 2.98 mmol) was added. The solution was then brought to room temperature and quenched with water; It was extracted into methylene chloride. The organic layer was separated and washed with brine, dried over MgSO 4, filtered and concentrated. The product was purified by column chromatography (silica gel; methanol / methylene chloride) to give the title compound as a white solid (0.068 g, 78%): 1 H NMR (400MHz, CDCl 3) d 6.8-7.6 ( m, 14H), 4 (d, 12H), 1 (d, 12H); MS (ESI): 590.1 (M + H) + EXAMPLE 72 Preparation of f (S) -3-methyl-1 -M- (5-methyl-1 HM, 2,41-triazole-3-sulfonyl) -3-oxo-azepan-4-ylcarbamoyl- benzofuran-2-carboxylic acid butiPamide (a) 4 - ((S) -2-amino-4-methyl-pentanoylamino) -3-hydroxy-azepane-1-carboxylic acid benzyl ester To a stirred solution of the compound of example 2f (3.5 g, 7.33 mmol) in EtOAc (0.5 ml), 4M HCl in dioxane (12.8 ml) was added. The mixture was stirred 1 hour at room temperature. The reaction mixture was then concentrated and azeotropically distilled with toluene (2 x 20 ml) to give the title compound as a light yellow oil (3.13 g, 100%); MS (ESI) 378.4 (M + H +). (b) 4- Benzyl ester of acid. { (S) -2 - [(benzofuran-2-carbonyl) -amino] -4-methyl-pentanoylamino} 3-hydroxy-azepane-1-carboxylic acid To a stirred solution of compound 72a (3.13 g, 7.57 mmol), benzofuran-2-carboxylic acid (1.35 g, 8.32 mmol), triethylamine (1.17 ml, 8.25 mmol) and 1- hydroxybenzotriazole (0.2 g, 1.48 mmol) in DMF (30 ml), 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (1.6 g, 8.33 mmol) was added. After stirring at room temperature for 16 hours, the solution was diluted with EtOAc and washed successively with saturated aqueous sodium bicarbonate solution, water (2x) and brine. The organic layer was dried over Na2SO4, filtered and concentrated. The product was purified by column chromatography (silica gel; ethyl acetate / dichloromethane) to give the title compound (3.7 g, 93%): "? NMR (400MHz, CDCl 3) d 6.8-7.7 (m, 12H), 5.35 (s, 2H), 1.0 (d, 6H): MS (ESI): 522 (M + H) + (c) [(S) -1 - (3-Hydroxy-azepan-4-ylcarbamoyl) -3-methyl-butyl} benzofuran-2-carboxylic acid amide To a solution of the compound of example 72b (2.6 g, 4.9 mmol) in EtOAc (150 ml), 10% palladium on carbon (1.3 g) was added and stirred at room temperature for 64 hours under a hydrogen atmosphere. The mixture was then filtered through celite and the filtrate was concentrated to give the title compound as a white solid (1.92 g, 100%): 1 H NMR (400MHZ, CDCl 3) d 6.8-7.7 (m, 7H), 1.02 (d, 6H); EM (ESI) 388 (M + H) + (d). { (S) -3-Methyl-1- [1- (5-methyl-1 H- [1, 2,4] triazole-3-sulfonyl) -3-hydroxy-azepan-4-yl-carbamoyl] -butyl ester} benzofuran-2-carboxylic acid amide To a stirred solution of the compound of example 72c (0.100 g, 0. 25 mmol) and triethylamine (35 μl, 0.25 mmol) in methylene chloride (2 ml), was added 5-methyl-1 H-1, 2,4-triazolesulfonyl chloride (0.043 g, 0.25 mmol). The reaction was allowed to stir for 10 minutes and then washed with saturated aqueous NaHCO 3 solution, water and brine. The organic layer was dried over Na2SO4, filtered and concentrated. The compound was purified by column chromatography (silica gel; ethyl acetate / hexane) to give the title compound as a light yellow oil (0.111, 84%); MS (ESI) 532.73 (M + H +). (e) { (S) -3-Methyl-1- [1- (5-methyl-1 H- [1,2,4] triazole-3-sulfonyl) -3-oxo-azepan-4-yl-carbamoyl] -butyl ester} benzofuran-2-carboxylic acid amide To a stirred solution of the compound of example 72d (0.108 g, 0.206 mmol) in dimethyl sulfoxide (2 ml), triethylamine (172 μl, 1.23 mmol) was added, followed by pyridine and trioxide. of sulfur (0.116 g, 0.718 mmol) and stirred for 16 hours at room temperature. The reaction mixture was diluted with EtOAc and washed with water (2x). The organic layer was dried over Na2SO4, filtered and concentrated. The crude product was purified by column chromatography (silica gel; methanol / methylene chloride) to give the title compound as a white solid (0.08 g, 81%): 1 H NMR (400MHz, CDCl 3) d 7.1-7.7 (m, 7H), 2.65 (s, 3H), 1.0 (d, 6H), MS (ESI): 552.71 (M + Na) + EXAMPLE 73 Preparation of (S) -3-methyl-1-f 1 -f 1 -methyl-1 H-imidazole-3-sulfoniP-3-oxo-azepan-4-ylcarbamoin-butyl benzofuran-2-carboxylic acid amide (to) . { (S) -3-Methyl-1 - [1- (1-methyl-1 H-imidazol-3-sulfonyl) -3-hydroxy-azepan-4-yl-carbamoyl] -butyl ester} benzofuran-2-carboxylic acid amide To a stirred solution of the compound of example 72c (0.100 g, 0. 25 mmol) and triethylamine (35 μl, 0.25 mmol), was added 1-methylimidazolesulfonyl chloride (0.046 g, 0.255 mmol). The reaction was allowed to stir for 10 minutes and was washed with saturated aqueous solution of NaHC 3, water and brine. The organic layer was dried over Na 2 SO 4, filtered and concentrated. The compound was purified by column chromatography (silica gel; ethyl acetate / hexane) to give the title compound as a light yellow oil (0.1 13 g, 82%): 1 H NMR (400MHz, CDCl 3) d 6.9-7.7 (m, 9H), 3.9 (2s, 3H), 1.0 (d, 6H); MS (ESI): 531.8 (M + H) + (b). { (S) -3-Methyl-1- [1- (1-methyl-1 H-imidazol-3-sulfonyl) -3-oxo-azepan-4-yl-carbamoyl] -butyl ester} benzofuran-2-carboxylic acid amide To a stirred solution of the compound of Example 73a (0.085 g, 0.159 mmol) in dimethyl sulfoxide, triethylamine (133 μl, 0.95 mmol) was added, followed by pyridine and sulfur trioxide (0.08 mmol). g, 0.5 mmol), and it was stirred for 16 hours at room temperature. The reaction mixture was diluted with EtOAc and washed with water (2x). The organic layer was dried over Na2SO4, filtered and concentrated. The crude product was purified by column chromatography (silica gel; methanol / methylene chloride) to give the title compound as a white solid (0.072 g, 83%); MS (ESI): 529.76 (M + H +).

EXAMPLE 74 Preparation of. { (S) -3-methyl-1-f1 - (1 H-imidazole-2-sulfoniP-3-oxo-azepane-4-ylcarbamoyl-buti-P-benzofuran-2-carboxylic acid) (to) . { (S) -3-Methyl-1 - [1 - (1 H-imidazole-2-sulfonyl) -3-oxo-azepan-4-yl-carbamoyl] -butyl ester} benzofuran-2-carboxylic acid amide To a stirred solution of the compound of Example 72c (0.100 g, 0.25 mmol) and triethylamine (35 μL, 0.25 mmol), 2-imidazolesulfonyl chloride (0.046 g, 0.255 mmol) was added. The reaction was allowed to stir for 10 minutes and was washed with saturated aqueous solution of NaHCO 3, water and brine. The organic layer was dried over Na2SO4, filtered and concentrated. The compound was purified by column chromatography (silica gel; ethyl acetate / hexane) to give the title compound as a light yellow oil (0.113 g, 82%): 1 H NMR (400MHz, CDCl 3) d 7.1 -7.7 (m, 9H), 4.8 (s, 1 H), d, 6H); MS (ESI): 517.76 (M + H) + (b). { (S) -3-Methyl-1- [1- (1 H-imidazole-2-sulfonyl) -3-oxo-azepan-4-yl-carbamoyl] -butyl ester} benzofuran-2-carboxylic acid amide To a stirred solution of the compound of example 74a (0.107 g, 0.206 mmol) in dimethyl sulfoxide (2 ml), triethylamine (172 μl, 1.23 mmol) was added, followed by pyridine and trioxide. of sulfur (0.115 g, 0.718 mmol), and it was stirred for 16 hours at room temperature. The reaction mixture was diluted with EtOAc and washed with water (2x). The organic layer was dried over Na2SO4, filtered and concentrated. The crude product was purified by column chromatography (silica gel; methanol / methylene chloride) to give the title compound as a white solid (0.09 g, 85%); MS (ESI): 515.84 (M + H +).

EXAMPLE 75 Preparation of. { (S) -3-methyl-1 -f3-oxo-1 - (thiazole-2-s? Lphon-P-azepan-4-ylcarbamoin-buti-P-benzofuran-2-carboxylic acid (a) Ter-butyl acid ester. { (S) -1- [3-hydroxy-1- (thiazole-2-sulfonyl) -azepan-4-ylcarbamoyl} -3-methyl-butyl} -carbamic To a solution of the compound of example 2g (2.50 g, 7.29 mmol) in DCE (100 ml) was added P-NMM (4.0 g) and thiazole-2-sulfonyl chloride (1.6 g, 8.75 mmol). After stirring at room temperature overnight, the solution was filtered. The filtrate was concentrated to give the title compound as a white solid (2.50 g, 5.10 mmol, 70%); MS: 490.91 (M + H +). (b) { (S) -3-Methyl-1 - [3-hydroxy-1 - (thiazole-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl ester} benzofuran-2-carboxylic acid amide To a solution of the compound of example 75b (0.15 g, 0.45 mmol) in CH 2 Cl 2 (20 ml), benzofuran-2-carboxylic acid (0.109 g, 0.172 mmol) was added, hydroxybenzotriazole (0.106 g, 0.762 mmol) and P-EDC (0.85 g, 1 mmol / g) in CH2Cl2 (10 mL). After stirring at room temperature overnight, the solution was treated with tisamine (0.589 g, 3.75 mmol / g). After stirring for another 2 hours, the solution was filtered and concentrated to yield the title compound as a white solid (166.7 mg, 70%); MS (ESI) 535.3 (M + H +). (c). { (S) -3-Methyl-1 - [3-oxo-l - (thiazole-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl ester} benzofuran-2-carboxylic acid amide To a stirred solution of the compound of example 75c (166.7 mg, 0.313 mmol) in dichloromethane (4 ml), Dess-Martin reagent (265.5 mg, 0.626 mmol) was added. After stirring at room temperature for 2 hours, sodium thiosulfate solution (2 ml of sol.10% in water) and saturated aqueous solution of bicarbonate (2 ml) were added to the solution simultaneously. The aqueous phase was extracted with dichloromethane (2x). The organic phases were combined and washed with brine; dried (MgSO4), filtered and concentrated. The residue was purified by CLAP (50:50 hexane ethane, 20 ml / min, WhelkO-1 column (R, R), 21 x 250 mm, UV detection at 280 nm and 305 nm) to give the first elution as a white solid (84.8 mg, 50.8%); MS (ESI): 533.2 (M + H +), and the second elution as a white solid (50.1 mg, 30.0%) MS: 533.2 (M + H +).

EXAMPLE 76 Preparation of. { (S) -3-Methyl-1 -M - (1-methyl-1 H-imidazole-4-sulfoniP-3-oxo-azepan-4-ylcarbamoin-buti-P-benzofuran-2-carboxylic acid) (a) Ter-butyl acid ester. { (S) -1- [3-hydroxy-1- (1-methyl-1 H-imidazole-2-sulfonyl) -azepan-4-ylcarbamoyl] -3-methyl-butyl} carbonate To a solution of the amine of example 2g in methylene chloride (5 ml), pyridine (92 μl, 1.14 mmol) was added, followed by 1-methylimidazole-4-sulfonylchloride (0.112 g, 0.623 mmol). The reaction was allowed to stir for 16 hours at room temperature. The solution was then washed with saturated aqueous NaHCO 3 solution, water and brine. The product was purified by column chromatography (silica gel: methanol / methylene chloride) to give the title compound as a white solid (0.172 g, 68%): 1 H NMR (400MHz, CDCI3) d 7.6 (d, 1 H), 7.5 (d, 1 H), 6.6 (d, 1 H), 3.8 (s, 3H), 1.5 (s, 9H), 1 (d, 6H); MS (ESI): 488.2 (M + H) + (b) [3-Hydroxy-1- (1-methyl-1 H-imidazole-2-sulfonyl) -azepan-4-yl] -amide (S) -2-amino-4-methyl-pentanoic To a solution of the compound of Example 76a (0.172 g, 0.353 mmol) in a minimum amount of MeOH, 4M HCl in dioxane (10 mL) was added and stirred at room temperature for 4 hours. The reaction mixture was concentrated and azeotropically distilled with toluene (2x) to give the title compound as an off white solid: MS (ESI) 388.2 (M + H +). (c). { (S) -3-Methyl-1- [1- (1-methyl-1 H-imidazole-4-sulfonyl) -3-hydroxy-azepan-4-yl-carbamoyl] -butyl ester} benzofuran-2-carboxylic acid amide To a stirred solution of the compound of Example 72c (0.2 g, 0.471 mmol), benzofuran-2-carboxylic acid (0.084 g, 0.388 mmol), triethylamine (72 μl, 0.517 mmol) and 1- hydroxybenzotriazole (0.012 g, 0.088 mmol) in DMF (5 ml), 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (0.099 g, 0.515 mmol) was added. After stirring at room temperature for 16 hours, the solution was diluted with EtOAc and washed successively with saturated aqueous sodium bicarbonate solution, water (2x) and brine. The organic layer was dried over Na2SO4, filtered and concentrated. The product was purified by column chromatography (silica gel; methanol / dichloromethane) to give the title compound as a white solid (0.226 g, 90%): 1 H NMR (400MHz, CDCl 3) d 6.9-8.1 ( m, 18H), 3.75 (2s, 6H), 1 (d, 12H); MS (ESI): 531.80 (M + H) + (d). { (S) -3-Methyl-1- [1- (1-methyl-1 H-imidazole-4-sulfonyl) -3-oxo-azepan-4-yl-carbamoyl] -butyl ester} benzofuran-2-carboxylic acid amide To a stirred solution of the compound of example 76a (0.226 g, 0.426 mmol) in dimethyl sulfoxide (2 ml), triethylamine (355 μl, 2.55 mmol) was added, followed by pyridine and trioxide of sulfur (0.238 g, 1.48 mmol), and stirred for 16 hours at room temperature. The reaction mixture was diluted with EtOAc and washed with water (2x). The organic layer was dried over Na2SO4, filtered and concentrated. The crude product was purified by column chromatography (silica gel; methanol / methylene chloride) to give the title compound as a white solid (0.168 g, 76%): 1 H NMR (400MHz, CDCI3) d 7.1-7.7 9m, 18H), 3.7 (2s, 6H), 0.9 (d, 12H); MS (ESI): 529.80 (M + H) + EXAMPLE 77 Preparation of f (S) -3-methyl-1-r3-oxo-1 - (pyridine-2-sulfonyl-P-azepane-4-yl-carbamoyl-buty-p -amide of 5- (4-oxy) morpholino-4-yl-ethoxy) -benzofuran-2-carboxylic acid To a solution of the compound of example 30b (0.01 g) in dichloromethane (2 ml), m-CPBA (0.008 g) was added. The reaction was stirred overnight. By treatment and column chromatography (methanol %: dichloromethane), the title compound was obtained: "? NMR (CDCl 3): d 1.0 (m, 6H), 1.5-2.1 (m, 5), 2.2 (m, 2H), 2.5 (m, 4H) , 2.7 (m, 1 H), 2.8 (m, 2H), 3.7 (m, 4H), 3.8 (q, 1 H), 4.0 (m, 3H), 4.7 (m, 1 H), 4.8 (m, 1 H), 5.0 (m, 1 H), 7.0 (m, 3 H), 7.4 (m, 2 H), 7.5 (m, 1 H), 7.9 (m, 2 H), 8.6 (m, 1 H): MS (EI): 671 (M +, 100%).

EXAMPLE 78 Preparation of benzofuran-2-carboxylic acid (S) -3-methyl-1-l "3-oxo-1- (pyridin-3-sulfonyl) -azepan-4-ylcarbamoyl-buti-p-phenyl acid (a) 4- (S) -2-amino-4-methyl-pentanoylamino) -3-hydroxy-azepane-1-carboxylic acid benzyl ester To a solution of 4 - ((S) -2- benzyl ester tert-butocarbonylamino-4-methyl-pentanoylamino) -3-hydroxy-azepan-1-carboxylic acid from Example 2f (4.0 grams) in methanol (20 mL), 4M HCl in dioxane (20 mL) was added. The reaction was stirred at room temperature for 2 hours until concentrated to provide the title compound (3.8 grams) MS: (El) 378 (M + H +). (b) 4- Benzyl ester of acid. { (S) -2 - [(benzofuran-2-carbonyl) -amino] -4-methyl-pentanoylamino) -3-hydroxy-azepane-1-carboxylic acid To a solution of 4 - ((S) -2) benzyl ester amino-4-methyl-pentanoylamino) -3-hydroxy-azepane-1-carboxylic acid from Example 78a (3.2 grams) in dichloromethane (200 mL), EDC (1.48 grams), HOBt (1.05 grams), TEA ( 1..29 mL) and benzofuran-2-carboxylic acid. The reaction was stirred at room temperature for 2 hours until complete. The title compound (3.78 grams) was obtained by treatment and column chromatography: MS (El) 521 (M + H +). (c) [(S) -1- (3-Hydroxy-azepan-4-ylcarbamoyl) -3-methyl-butyl] -amide of benzofuran-2-carboxylic acid To a solution of benzyl ester of 4-acid. { (S) -2 - [(benxofuran-2-carbonyl) -amino-4-methyl-pentanoylamino) -3-hydroxy-azepane-1-carboxylic acid of Example 78b (1.6 grams) in methanol: ethyl acetate (50 mL: 100 mL), 10% Pd / C was added. The reaction was stirred under a hydrogen balloon for 2 hours until it was filtered and concentrated to provide the title compound (1.16 grams): MS (El) 387 (M + H +). (d). { (S) -3-Methyl-1- [3-hydroxy-1- (pyridin-3-suphonyl) -azepan-4-ylcarbamoyl] -butyl} benzofuran-2-carboxylic acid amide To a solution of [(S) -1- (3-hydroxy-azepan-4-ylcarbomoyl] -3-methyl-butyl-benzofuran-2-carboxylic acid amide of Example 78c ( 0.3 grams) in dichloromethane, triethylamine (0.17 mL) was added followed by 3-pyridine sulfonyl chloride (0.25 grams) .The reaction was stirred at room temperature for 2 hours until it was complete as determined by CCD analysis. and column chromatography (5% methanol: ethyl acetate) gave the title compound (0.32 grams): MS (El) 528 (M + H +). (e) { (S) -3-Methyl- 1 - [3-Oxo-1- (pyridin-3-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} -amide of benzofuran-2-carboxylic acid The title compound was prepared following the procedure of Example 1 i, but using the. { (S) -3-methyl-1- [3-hydroxy-1- (pyridine-3-sulfonyl) -azepan-4-ylcarbamoyl] -butyl ester} benzofuran-2-carboxylic acid amide of Example 78d: 1 H NMR (CDCL 3): d 1.0 (m, 6H), 1.5-2.1 (m, 5H), 2.2 (m, 2H), 2.5 (m, 1 H), 3.5 (d, 1 H), 4.0 (m, 1 H), 4.7 (m, 1 H), 4.8 (m, 1 H), 5.0 (m, 1 H), 7.0 (m, 2 H), 7.2-7.5 (m, 6H), 8.1 (m, 1 H), 8.9-9.0 (m, 2H); MS (El): 526 (M +, 100%).

EXAMPLE 79 Preparation of i (S) -3-methyl-1-F3-oxo-1- (1-oxy-pyridine-3-sulfoniP-azepane-4-ylcarbamoyl-buty-phenamide of benzofuran-2-carboxylic acid (to) . { (S) -3-Methyl-1 - [3-hydroxy-1- (1-oxy-pyridin-3-sulfonyl) -azepan-4-ylcarbamoyl] -butyl ester} amide of benzofuran-2-carboxylic acid To a solution of. { (S) -3-Methyl-1- (3-hydroxy-1- (pyridin-3-sulfonyl) -azepan-4-ylcarbomoyl] -butyl} -amide of benzofuran-2-carboxylic acid of Example 78d (0.05 grams) in dichloromethane, m-CPBA (0.05 grams) was added. The reaction was stirred overnight. By treatment and column chromatography (10% methanol: dichloromethane) the title compound (0.03 grams) was obtained: MS (EI) 544 (M + H +). (b) { (S) -3-Methyl-1 - [3-oxo-1- (1-oxy-pyridin-3-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} benzofuran-2-carboxylic acid amide The title compound was prepared following the procedure of Example 1 i, but using the. { (S) -3-methyl-1- [3-hydroxy-1- (1-oxy-pyridin-3-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} benzofuran-2-carboxylic acid amide Example 79a: 1 H NMR (CDCL 3): d 1.0 (m, 6H), 1.5-2.1 (m, 5H), 2.2 (m, 2H), 2.5 (m, 1 H), 5.0 (m, 1 H), 7.2-7.5 (m, 7H), 8.1-8.2 (m, 2H); MS (El): 542 (M +, 50%).

EXAMPLE 80 Preparation of f (S) -1,4-dichloro-benzene-sulfonyl-3-oxo-azepan-4-ylcarbamoyl) -3-methyl-buty-phenamide of quinoline-3-carboxylic acid The title compound was prepared following the procedure of Example 75 ad, but using 3,4-dichlorosulfonyl chloride in place of thiazole-2-sulfonyl chloride from Example 75a and quinoline-3-carboxylic acid in place of benzofuran-2 acid -carboxylic acid: 1 H NMR (CDCl 3, 400 MHz): d 9.34 (s, 1 H), 8. 61 (s, 1 H), 8.14 (m, 1 H), 7.81 (m, 3 H), 7.6 (m, 3 H), 7.19 (m, 2 H), 5.09 (m, 1 H), 4.88 (m, 1 H), 4.50 (m, 1 H), 3.92 (m, 1 H), 3.51 (m, 1 H), 2.57 (m, 1 H), 2.23 (m, 2 H), 1.60 (m, 5 H), 1.01 ( m, 6H).

EXAMPLE 81 Preparation of. { (S) -3-methyl-1H - (1-methyl-1 H-imidazole-4-sulfonyl-3-oxo-azepan-4-ylcarbamoy-buty-phenamide 5-hydroxy-benzofuran-2-carboxylic acid (to) . { (S) -3-Methyl-1 - [1- (1-methyl-1 H-imidazoI-4-sulfonyl) -3-hydroxy-azepan-4-ylcarbamoyl] -butyl ester} 5-hydroxy-benzofuran-2-carboxylic acid amide To a stirred solution of the compound of Example 76b (0.1 grams, 0.235 mmol), 5-hydroxy-benzofuran-2-carboxylic acid (0.046 grams, 0.256 mmol), triethylamine (36 μL, 0.258 mmol) and 1-h id roxy benzotriazole (0.006 grams, 0.044 mmol) in DMF (5 mL), 1- (3-dimethylaminopropyl) 3-ethylcarbodiimide hydrochloride (0.05 grams, 0. 26 mmoles). After stirring at room temperature for 16 hours, the solution was diluted with EtOAc and successively washed with saturated aqueous sodium bicarbonate, water (2X) and saturated brine. The organic layer was dried over Na2SO4 ', filtered and concentrated. The product was purified by column chromatography (silica gel; methanol / dichloromethane) to give the title compound as a white solid (0.129 grams, 100%). 1H NMR (400 MHz, CDCL3): d 6.8-8 (m, 16H), 3.6 (2s, 6H), 0.85 (d, 12H). MS (El): 547.88 (M + H) +. (b) { (S) -3-Methyl-1 - [1- (1-methyl-1 H-imidazole-4-sulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -butyl ester} 5-hydroxy-benzofuran-2-carboxylic acid amide oxalyl chloride (13 μl, 0.149 mmol) was brought to -78 °. This mixture was added dropwise to dimethyl sulfoxide (28 μL, 0.394 mmol) in methylene chloride. After stirring for 15 minutes at -78 °, the alcohol of Example 81a was added slowly in methylene chloride and allowed to stir for 1 hour when EI3N (7 u (7 uL, 0.05 mmol) was added. The organic layer was separated and washed with brine, dried over MgSO4 ', filtered and concentrated, The product was purified by column chromatography (silica gel: methanol / methylene chloride) to give the title compound as a white solid (0.021 grams, 78%): MS (ESI) 545.9 (M + H) +.

EXAMPLE 82 Preparation of f (S) -3-methyl-1-f3-oxo-1- (1-oxy-pyridine-2-sulfoniP-azepane-4-ylcarbamoi-P-3-methyl-buti-p-pyrimide 5-benzofuran-2 -carboxylic (to) . { (S) -3-Methyl-1 - [3-hydroxy-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl)] - 3-methyl-butyl} 5-benzofuran-2-carboxylic acid amide To a solution of [(S) -1- [3-hydroxy-azepan-4-ylcarbamoyl)] - 3-methyl-butyl} benzofuran-2-carboxylic acid amide of Example 78c (0.10 grams) in dichloromethane, triethylamine (0-07 mL) was added followed by N-oxide of 2-piidinesulfonylchloride. The reaction was stirred at room temperature overnight. By treatment and column chromatography (10% methanol / dichloromethane) the title compound (0.01 grams) was obtained:: MS (EI) 544 (M + H +). ! ! (b) { (S) -3-Methyl-1- [3-oxo-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl)] - 3-methyl-butyl} amide i I The title compound was prepared following the procedure of ! Example 1 i, but using. { (S) -3-Methyl-1- [3-hydroxy-1- (1-oxy-pyridin-2-sulfonyl) -I-azepan-4-ylcarbamoyl)] - 3-methyl-butyl} benzofuran-2-carboxylic acid amide i of Example 82a: 1 H NMR (CDCl 3): d 1.0 (m, 6H), 1.5-2.1 (m, 5H), 2.2 (m, 2H), 2. 7 (m, 1 H), 3.8 (q, 1 H), 4.0 (m, 1 H), 4.7 (m, 1 H), 4.8 (m, 1 H), 5.0 (m, 1 H), 7.0- 7.5 (m, 9H), 8.1-8.2 (m, 2H). MS (EI) 542 (M +, 20%). ! The diastereomeric mixture was separated by CLAP to provide the fastest eluting diastereomer; 1 H NMR (CDCl 3): d 1 .0 (m, i 6 H), 1.5-2.1 (m, 5 H), 2.2 (m, 2 H), 2.7 (t, 1 H), 3.8 (d, 1 H), 4.0 (d, 1 H), 4.7 (m, 1 H), 4.8 (d, 1 H), 5.0 (m, 1 H), 7.0-7.5 (m, 9H), 8.1-8.2 (m, 2H). EM (EI) 542 (M \ 100%), and the slowest eluting diastereomer; MS (EI) 542 (M + H \ 100%).

EXAMPLE 83 Preparation of 2- (4-l (S) -2-f (benzofuran-2-carboniP-amino > -4-methyl-pentanoylamino) -3-oxo-azepane-1-sulfon-p-benzoic acid (a) 2- (4- (S) -2 - [(Benzofuran-2-carbonyl) -amino] -4-methyl-pentanoylamino] -3-hydroxy-azepan-1-sulfonyl methyl ester benzoic The title compound was prepared following the procedure of Example 75a-c, but using 2-carboxymethylsulfonyl chloride in place of the 2-thiazolesulfonyl chloride: MS (EI) (M + H +) = 585.56, M + Na + = 607.76, 2M + H + = 1170.48. (b) 2- (4- { (S) -2 - [(benzofuran-2-carbonyl) -amino] -4-methyl-pentanoylamino} -3-hydroxy-azepan-1-sulfonyl acid ) -benzoic acid 2- (4- (S) -2 - [(benzofu rnaca-rbonyl) -amino] -4-methyl-pentanoylamino} -3-hydroxy-azepane-1-sulfonyl) - methyl ester was dissolved benzoic acid (compound 83a, 180 mg, 0.309 mmol) in 5: 1 MeOH / water (6 ml), LiOH (14 mg, 0.34 mmol) was added and the reaction mixture was stirred and refluxed for 6 hours. The reaction mixture was then quenched with water and 6N HCl (adjusted to pH = 2); it was extracted with EtOAc (3 x 10 ml), dried with MgSO 4, filtered, concentrated and subjected to chromatography (silica gel, 1% acetic acid / 4% MeOH / CH 2 Cl 2) to give the title compound as a solid white (48 mg, 27%): M + H + = 572.2 (c) 2- (4- { (S) -2 - [(benzofuran-2-carbonyl) -amino] -4-methyl-pentanoylamino 3-Oxo-azepan-1-sulfonyl) -benzoic acid The title compound was prepared following the procedure of Example 75d, but using 2- (4- { (S) -2 - [(benzofuran- 2-carbonyl) -amino] -4-methyl-pentanoylamino.} - 3-hydroxy-azepan-1-sulfonyl) -benzoic acid instead of. { (S) -3-methyl-1 - [3-hydroxy-1 - (thiazole-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl ester} -benzofuran-2-carboxylic acid amide: Em (M + H +): 570.2 (M + H +). 1 H NMR (400Hz, CDCl 3 -CD 3 OD): d 8.05-7.95 (m, 1H), 7.70-7.15 (m, 8H), 5.15-5.00 (m, 1H), 4.95-4.75 (m, 2H), 4.15-4.00 (m, 1 H), 3.65 (d, 1 H), 2.85-2.70 (m, 1 H), 2.25-2.05 (m, 2H), 1.90-1.70 (m, 4H), 1.60-1.45 (m, 1 H), 0.95 (d, 6H).

EXAMPLE 84 Preparation of 3- (4- ({(S -2 - ((benzofuran-2-carboniP-amino-1-4-methyl-pentanoylamino) -3-oxo-azepane-1-sulfonyl-benzoic acid The title compound was prepared following the procedure of Example 83, but using 3-carboxymethylbenzenesulfonyl chloride in place of 2-carboxymethylbezenesulfonyl chloride: EM 570.2 (M + H +); 1 H NMR (400 Hz, CDCl 3 -CD 3 OD): d 8.46 (d, 1 H), 8.31-8.25 (m, 1 H), 8.00-7.97 (m, 1 H), 7.70-7.62 (m, 2 H), 7.55- 7.46 (m, 1 H), 7.45-7.35 (m, 1H), 7.30-7.25 (m, 1 H), 5.10-5.05 (m, 1H), 4.95-4.78 (m, 1H), 4.75-4.55 (q , 1H), 4.00 (d, 1H), 2.60-2.40 (m, 2H), 2.25-2.15 (m, 1 H), 1.95-1.70 (m, 4H), 1.55-1.40 (m, 1 H), 0.98 (t, 6H).

EXAMPLE 85 Preparation of. { (S) -3-Methyl-1-r3-oxo-1- (1-oxy-pyridin-2-sulfonyl) -zepane-4-ylcarbamoin-buty-phenoxybenzoyloxy-2-carboxylic acid (a) Ter-butyl acid ester. { (S) -1- [3-hydroxy-1- (1-oxy-pyridine-sulfonyl) -azepan-4-ylcarbamoyl] -3-methyl-butyl-carbamic acid To a solution of tert-butyl acid ester [(S ) -1- (3-hydroxy-azepan-4-ylcarbamoyl) -3-methyl-butyl] -carbamic acid from Example 2g (2.5 grams) in dichloromethane (100 mL) and saturated sodium bicarbonate, was added N-oxide freshly prepared 2-pyridinesulfonyl chloride (prepared by bubbling chlorine gas through a solution of 2-mercaptopyridine N-oxide in 9M HCl for about 90 minutes). Removal of the excess chlorine in vacuum produced the 2-pyridinesulfonyl chloride N-oxide). The reaction was stirred at room temperature for 1 hour. By treatment and column chromatography (10% methanol / dichloromethane) the title compound (2.0 grams) was obtained: MS (EI) 500 (M + H +). (b) [3-Hydroxy-1- (1-oxy-pyridine-sulfonyl) -azepan-4-yl] -amide of (S) -2-Amino-4-methyl-pentanoic acid To one solution of ter-butyl acid ester. { (S) -1- [3-hydroxy-1- (1-oxy-pyridine-sulfonyl) -azepan-4-ylcarbamoyl) -3-methyl-butyl] -carbamic acid Example 85a (2.0 g) in methanol (20 mL), 4M HCl in dioxane (20 mL) was added. The reaction was stirred at room temperature for 1.5 hours until it was concentrated to provide the title compound (1.8 grams): MS (EI) 400 (M + H +). (c). { (S) -3-Methyl-1 - [3-hydroxy-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl ester} benzo [b] thiophene-2-carboxylic acid amide To a solution of (S) -2-amino acid [3-hydroxy-1- (1-oxy-pyridine-sulfonyl) -azepan-4-yl] -amide -4-methyl-pentanoic of Example 85b (0.25 grams) in dichloromethane (12 mL), triethylamine (0.12 mL), EDC (0.11 grams), HOBt (0.077 grams) and benzo [b] thiophen-2-acid were added. carboxylic The reaction was stirred until complete. By treatment and column chromatography (10% methanol / dichloromethane) the title compound (0.26 grams) was obtained: MS: (EI) 560 (M + H +). (d). { (S) -3-Methyl-1 - [3-oxo-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl ester} benzo [b] thiophene-2-carboxylic acid amide The title compound was prepared following the procedure of Example 1, but using the. { (S) -3-methyl-1- [3-hydroxy-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl ester} benzo [b] thiophene-2-carboxylic acid amide of Example 85c: 1 H NMR (CDCl 3): d 1.0 (m, 6H), 1.5-2.1 (m, 5H), 2.2 (m, 2H), 2.7 (m, 1 H), 3.8 (q, 1 H), 4.0 (m, 1 H), 4.7 (m, 1 H), 4.8 (m, 1 H), 5.0 (m, 1 H), 7.5 (m, 4 H) , 7.8 (m, 3H), 8.1-8.2 (m, 2H); MS (El): 558 (M +, 100%). The diastereomeric mixture was separated by CLAP to provide the fastest eluting diastereomer; MS (EI): 558 (M +, 100%) and the slowest eluting diastereomer; MS (EI) 558 (M +, 100%).

EXAMPLE 86 Preparation of f (S) -3-Methyl-1-r3-oxo-1- (1-oxy-pyridine-2-sulfonyl-5-bromo-furan-2-azepan-4-ylcarbamoyl-buty-phenamide. carboxylic (to) . { (S) -3-Methyl-1- [3-hydroxy-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 5-bromo-furan-2-carboxylic acid amide The title compound was prepared following the procedure of Example 85c, but using 5-bromo-2-furoic acid instead of benzo [b] thiophene-2-carboxylic acid: (EI) 574 (M + H +). (b) { (S) -3-Methyl-1 - [3-oxo-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl ester} 5-bromo-furan-2-carboxylic acid amide The title compound was prepared following the procedure of Example 1 i, but using. { (S) -3-methyl-1- [3-hydroxy-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 5-bromo-2-furan-2-carboxylic acid amide of Example 86a: 1 H NMR (CDCl 3): d 1.0 (m, 6H), 1.5-2.1 (m, 5H), 2.2 (m, 2H), 2.7 ( m, 1 H), 3.8 (q, 1 H), 4.0 (m, 1 H), 4.7 (m, 1 H), 4.8 (m, 1 H), 5.0 (m, 1 H), 7.0 (m, 2H), 7.4 (m, 2H), 8.1-8.2 (m, 2H); MS (El): 570 (M +, 100%). The diastereomeric mixture was separated by CLAP to provide the fastest eluting diastereomer; MS (EI): 572 (M + H +, 100%) and the slowest eluting diastereomer; MS (EI) 572 (M + H +, 100%).

EXAMPLE 87 Preparation of f (S) -3-Methyl-1-r3-oxo-1- (1-oxy-pyridin-2-s-l-phonyl) -azepan-4-ylcarbamoin-buty-phenyl acid 5,6- dimethoxybenzofuran-2-carboxylic acid (to) . { (S) -3-Methyl-1- [3-hydroxy-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 5,6-dimethoxybenzofuran-2-carboxylic acid amide The title compound was prepared following the procedure of Example 85c, but using 5,6-dimethoxybenzofuran-2-carboxylic acid instead of benzo [b] thiophene-2-carboxylic acid : MS (EI) 604 (M + H +). (b) { (S) -3-Methyl-1 - [3-oxo-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 5,6-dimethoxybenzofuran-2-carboxylic acid amide The title compound was prepared following the procedure of Example 1, but using the. { (S) -3-methyl-1- [3-hydroxy-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoii] -butyl} 5,6-dimethoxybenzofuran-2-carboxylic acid amide of Example 87a: 1 H NMR (CDCL 3): d 1.0 (m, 6H), 1.5-2.1 (m, 5H), 2.2 (m, 2H), 2.7 (m, 1H), 3.8 (m, 7H), 4.0 (m, 1 H), 4.7 (m, 1H), 4.8 (m, 1H), 5.0 (m, 1 H), 7.0-7.5 (m, 5H), 8.1 -8.2 (m, 2H); MS (El): 602 (M +, 100%). The diastereomeric mixture was separated by CLAP to provide the fastest eluting diastereomer; MS (EI): 602 (M +, 100%) and the slowest eluting diastereomer; MS (EI) 602 (M +, 100%).

EXAMPLE 88 Preparation of. { (S) -3-methyl-1-r3-oxo-1 - (pyridin-2-suifoniP-azepane-4-ylcarbamoyl-buty-p-amide of 1-oxy-pyridine-2-carboxylic acid (to) . { (S) -3-Methyl-1 - [3-hydroxy-1- (pyridine-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 1-oxy-pyridine-2-carboxylic acid amide The title compound was prepared following the procedure of Example 28b, but using picolinic acid N-oxide in place of the benzofuran-2-carboxylic acid: MS (EI) 505 (M + H +). (b) { (S) -3-Methyl-1 - [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 1-Oxy-pyridin-2-carboxylic acid amide The title compound was prepared following the procedure of Example 1, but using the. { (S) -3-methyl-1- [3-hydroxy-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 1-oxy-pyridine-2-carboxylic acid amide of Example 88a: 1 H NMR (CDCL 3): d 1.0 (m, 6H), 1.5-2.1 (m, 5H), 2.2 (m, 2H), 2.7 (m, 1H), 3.8 (q, 7H), 4.1 (m, 1H), 4.7 (m, 2H), 5.0 (m, 1H), 7.5 (m, 3H), 7.9 (m, 2H), 8.3-8.4 (m , 2H), 8.6 (m, 1 H), 4.7 (m, 2H), 5.0 (m, 1 H), 7.5 (m, 3H), 7.9 (m, 2H), 8.3-8.4 (m, 2H) 8.6 (m, 1 H); MS (El): 503 (M +, 100%).

EXAMPLE 89 Preparation of r3-oxo-1- (pyridine-2-sulfoniP-azepan-4-ill-amide of S) -4-methyl-2- (pyridin-2-sulfonylamino) -pentanoic acid (a) [3-Hydroxy-1- (pyridin-2-sulfonyl) -azepan-4-yl] -amide acid (S) -4-Methyl-2- (pyridine-2-sulfonylamino) -pentanoic acid To a solution of [3-hydroxy-1- (pyridin-2-sulfonyl) -azepan-4-yl] -amide of acid (S) -2-amino-4-methyl-pentanoic of Example 28a (0.25 grams) in dichloromethane, triethylamine (0.27 mL9 and 2-pyridine sulfonyl chloride (0.15 grams) was added.The reaction was stirred until complete. By treatment and column chromatography (5% methanol: dichloromethane) the title compound (0.09 grams) was obtained: MS (El) 525 (M + H +). (B) [3-Hydroxy-1- (pyridine-2 sulfonyl) -azepan-4-yl] -amide of (S) -4-methyl-2- (pyridin-2-sulfonylamino) -pentanoic acid. The title compound was prepared following the procedure of Example 1 i, but using amide [3-hydroxy-1- (pyridin-2-sulfonyl) -azepan-4-yl] of (S) -4-methyl-2- (pyridin-2-sulfonylamino) pentanoic of Example 89a: 1 H NMR (CDCL 3): d 1.0 (m, 6H), 1.5-2.1 (m, 5H), 2.2 (m, 2H), 2.7 (m, 1 H), 3.8 (q, 1H) , 4.0 (m, 1 H), 4.7 (m, 1H), 5.0 (m, 1H), 5.5 (m, 1H), 7.0 (m, 1 H), 7.5 (m, 2H), 7.9 (m, 3H) ), 8.6 (m, 2H); MS (El): 523 (M +, 100%).

EXAMPLE 90 Preparation of r3-Oxo-1- ((S) -2- (3-benzyl-ureido) -4-methyl-pentanoic acid (pyridine-2-sulfoniP-azepan-4-yn-amide) (a) [3-Hydroxy-1- (pyridin-2-sulfonyl) -azepan-4-yl] -amide acid (S) -2- (3-benzyl-ureido) -4-methyl-pentanoic To a solution of [3-hydroxy-1- (pyridin-2-sulfonyl) -azepan-4-yl] -amide of acid (S) ) -2-amino-4-methyl-pentanecoic acid from Example 28a (0.25 grams) in dichloromethane, triethylamine (0.17 mL) and benzyl isocyanate (0.088 grams) were added. The reaction was stirred until complete. By treatment and column chromatography (5% methanol / dichloromethane) the title compound (0.12 grams) was obtained. (b) [3-Oxo-l- (pyridin-2-sulfonyl) -azepan-4-yl] -amide of (S) -2- (3-benzyl-ureido) -4-methyl-pentanoic acid. composed of the title following the procedure of Example 1 i, but using the amide [3-hydroxy-1- (pyridin-2-sulfonyl) -azepan-4-yl] of (S) -2- (3-benzyl-ureido) -4-methyl pentanoic of Example 89a: 1 H NMR (CDCL 3): d 1.0 (m, 6 H), 1.5-2.1 (m, 5 H), 2.2 (m, 2 H), 2.7 (m, 1 H), 3.8 (q, 1 H) ), 4.0 (m, 3H), 4.5 (t, 1 H), 4.7 (m, 1 H), 5.0 (m, 1 H), 7.2 (, 5H), 7.5 (m, 1 H), 7.9 (m , 2H), 8.6 (m, 1 H); MS (EI) 515 (M \ 60%). The diastereomeric mixture was separated by CLAP to provide the fastest eluting diastereomer; MS (EI) 516 (M + H +, 100%), and the slowest eluting diastereomer; MS (EI) 516 (M + H +, 100%).

EXAMPLE 91 Preparation of (S) -2- (3-phenyl-uriedo) -4-methyl-pentanoic acid r3-Oxo-1-fpyridin-2-sulfon-P-azepan-4-in-amide (a) [3-Hydroxy-1- (pyridin-2-sulfonyl) -azepan-4-yl] -amide of (S) -2- (3-phenyl-ureido) -4-methyl-pentanoic acid. composed of the title following the procedure of Example 90a, but using phenyl isocyanate instead of benzyl isocyanate: MS (El): 503 (M + H +) (b) [3-Oxo-l - (pyridin-2-sulfonyl) -azepan-4-yl] -amide (S) -2- (3-phenyl-ureido) -4-methyl-pentanoic acid The title compound was prepared following the procedure of Example 1 i, but using [3-hydroxy-1- (pyridine-2-sulfon L) -zepan-4-yl] (S) -2- (3-phenyl-ureido) -4-methyl-pentanoic acid amide of Example 91a: 1 H NMR (CDCL 3): d 1.0 (m, 6H), 1.5-2.1 (m, 5H), 2.2 (m, 2H), 2.7 (m, 1 H), 3.8 (q, 1 H), 4.0 (m, 1 H), 4.5 (t, 1 H), 4.7 ( m, 1 H), 5.0 (m, 1 H), 7.0-7.9 (m, 8H), 8.6 (m, 1 H); MS (EI) 501 (M +, 60%).

EXAMPLE 92 Preparation of (S) -1-6,6-dimethyn-3-oxo-1 (pyridine-sulfonyl-p-azepan-4-yl-carbamoin-3-methyl-buty-p-benzofuran-2-carboxylic acid amide (a) Allyl- (2,2-dimethyl-pent-4-enylidene) -amine 2,2-Dimethyl-4-pentenal (2.8 grams, 25 mmol) was dissolved in 15 mL of benzene. Allylamine (2.85 grams, 50 mmol) was added to this solution. Few molecular sieves were used to absorb the water generated during the reaction. The mixture was stirred at room temperature overnight. Removal of the solvent and excess amount of allylamine in rotary vaporizer yielded 3.76 grams of the title compound as a clear liquid (100% yield). 1 H NMR (400 MHz, CDCl 3): • 7.52 (s, 1 H), 5.99-5.90 (m, 1 H), 5.80-5.70 (m, 1 H), 5.15-4.99 (m, 4H), 4.01-3.99 (m, 2H), 2.17 (d, 2H), 1.06 (s, 6H). (b) Allyl- (2,2-dimethyl-pent-4-enyl) -amine Allyl- (2,2-dimethyl-pent-4-enylidene) -amine was diluted from Example 92a (3.76 grams, 25 mmol) in 5ml of MeOH. To the solution was added NaBH4 (0.95 grams, 25 mmol) at 0 ° C. After the addition the mixture was stirred at room temperature for 5 hours. The methanol was removed by rotary evaporator and the residue was partitioned between EtOAc / 20% NaOH. The organic layer was dried over Na2SO4, filtered and evaporated to give 2.26 grams of the title compound: MS (M + H +): 154.0; 1 H NMR (400 MHz, CDCl 3): 5.93-5.76 (m, 2H), 5.29-4.99 (m, 4H), 3.22 (d, 2H), 2.34 (s, 2H), 2.01 (s, 2H), 0.94 ( s, 6H) (c) Allyl- (2,2-dimethyl-pent-4-enyl) -amide of pyridine-2-sulfonic acid. Allyl- (2,2-dimethyl-pent-4-enyl) -amine was mixed. (0.43 grams, 2.8 mmoles) and NMM (0.57 grams, 5.6 mmoles) in 30 mL CH2CI2. 2-Priridinesulfonyl hydrochloride was slowly added to the solution while cooling in an ice-water bath. After the addition, the reaction mixture was stirred at room temperature overnight. It was washed with 10% NaHC 3 and brine. Purification by column chromatography gave 0.6 grams of a colorless oil in a 73% yield. MS (M + H +): 295.2; 1 H NMR (400 MHz, CDCl 3): • 8.71-8.70 (d, 1 H), 7.98-7.86 (m, 2 H), 7.48-7.46 (m, 1 H), 5.88-5.77 (m, 1 H), 5.55- 5.45 (m, 1 H), 5.13-5.00 (m, 4H), 4.05-4.04 (d, 2H), 3.24 (s, 2H), 2.07-2.05 (d, 2H), 0.96 (s, 6H). (d) 3,3-Dimethyl-1- (pyridine-2-sulfonyl) -2,3,4,7-tetrahydro-1 H-azepine. Allyl- (2,2-dimethyl-pent-4-enyl) was diluted. pyridine-2-sulfonic acid amide (0.6 grams, 2 mmol) in CH2Cl2 (50 ml). After carefully degassing by Ar, Grubbs catalyst (0.17 grams, 0.2 mmol) was added under Ar protection. The mixture was then moistened for 2 hours before the solvent was removed by rotary evaporator. The crude product was purified by column chromatography (5% -20% E / H) to give 0.47 grams of the title compound in 87% yield. MS (M + H +): 567.0; 1 H NMR (400 MHz, CDCl 3): • 8.70-8.69 (d, 1 H), 7.96-7.88 (m, 2H), 7.49-7.46 (m, 1 H), 5.81-5.70 (m, 2H), 3.93- 3.92 (d, 2H), 3.26 (s, 2H), 2.13-2.12 (d, 2H), 1.00 (s, 6H). (e) 5,5-Dimethyl-3- (pyridine-2-sulfonyl) -8-oxa-3-aza-bicyclo [5.1.0] -octane To the solution of the compound of Example 92d (1.2 grams, 4.5 , mmoles) in 50 ml of CH2Cl2, NaHCO3 (2.4 grams, 13.5 mmol) and then MCPBA 81.2 grams, 13.5 mmol) was added in portions. The reaction was stirred at room temperature for 4 hours before it was treated by washing with 15% NaOH, saturated K2CO3, brine and dried (Na2SO4) to give 1.0 gram of crude product in 79% yield (good enough for the next reaction no further purification) MS (M + H +): 283.0; 1 H NMR (CDCL 3): • 8.68-8.67d1, 8.03-7.87 (m, 2H), 7.49-7.40 (m, 1 H), 4.44-3.89 (q, 1 H), 3.62-3.59 (d, 1 H) , 3.50 (m, 1 H), 3.00 (m, 1 H), 2.78-2.62 (m, 2H), 2.12-2.06 (m, 1 H), 1.52-1.46 (q, 1 H), 1.20 (s, 3H), 0.89 (s, 3H). (f) 4-Azido-6,6-dimethyl-1 - (pyridin-2-sulfonyl) -azepan-3-ol 5,5-Dimethyl-3- (pyridin-2-sulfonyl) -8- was dissolved oxa-3-aza-bicyclo [5.1.0] octane of Example 92e (1.2 grams, 4.3 mmol) in the mixture of 7 ml of MeOH and 1 ml of H2O. To the solution was added NaN3 (0.83 grams, 13 mmol) and NH4CI (0.7 grams, 13 mmol). The resulting mixture was inactive overnight. After removal of MeOH, the residue was diluted in EtOAc and washed with 10% NaHCO3 and brine. Purification by column chromatography gave 0.4 grams of 4-azido-6,6-dimethyl-1- (pyridin-2-sulfonyl) -azepan-3-ol (29% yield); MS (M + H +): 326.2; 1 H NMR (400 MHz, CDCl 3): • 8.68-8.67 (m, 1H), 8.05-7.90 (m, 2H), 7.53-7.50 (m, 1 H), 3.75-3.60 (m, 3H), 3.49-3.30 (m, 3H), 1.73-1.66 (m, 1 H), 1.56-1.52 (d, 1 H), 1.07 (s, 3H), 0.99 (s, 3H). (g) 4-Amino-6,6-dimethyl-1- (pyridin-2-sulfonyl) -azepan-3-ol 4-Azido-6,6-dimethyl-1- (pyridine-2-sulfonyl) - azepan-3-ol of Example 92f (0.4 grams, 1.23 mmol) in THF (50 ml) and H2O (0.2 ml). PPh3 (0.48 grams, 1.85 mmol) was added to this solution. The reaction mixture was stirred at 45 ° C overnight. The CCD did not show that there was no starting material left. The THF was evaporated and azeotropically distilled with toluene (2 times). The resulting thick oil was dissolved in MeOH, treated with HCl in ether to adjust the acidic pH. More ether was added and the solution became turbid. 0.22 grams of white precipitate of the title compound was collected. (45% yield); 1 H NMR (400 MHz, CD 3 OD): • 8.68 (m, 1 H), 8.10-7.93 (m, 2H), 7.62 (m, 1 H), 3.90 (m, 1 H), 3.68m1, 3.40-2.90 ( m, 4H), 1.82 (m, 1 H), 1.53 (d, 1 H), 1.05 (s, 6H). (h) Tert-butyl acid ester. { (S) -1- [3-hydroxy-6,6-dimethyl-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -3-methyl-butyl} 4-amino-6,6-dimethyl-1- (pyridine-2-sulfonyl) -azepan-3-ol carbamic acid salt of Example 92g (0.22 grams, 0.6 mmol) was dissolved in 6 ml of DMF. To this solution was added Boc-Leu-OH (0.22 grams, 0.9 mmoles) and HBTU (0.34 grams, 0.9 mmoles) and then NMM (0.24 grams, 2.4 mmoles). The mixture was stirred at room temperature overnight. The DMF was removed under high vacuum. The residue was diluted with EtOAc and washed with H2O, 10% NaHCO3 and brine. Purification by column chromatography gave 0.22 grams of the title compound (72% yield): MS (M + H +): 512.9; 1 H NMR (400 MHz, CDCL 3): • 8.68-8.67 (d, 1 H), 7.97-7.88 (m, 2 H), 7.69-7.64 (m, 1 H), 6.62-6.53 (m, 1 H), 5.06- 5.00 (m, 1H), 4.03-3.18 (m, 7H), 1.80-1.42 (m, 15H), 1.04-0.92 (m, 12H) (i). { (S) -1- [3-Hydroxy-6,6-dimethyl-1 - (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -3-methyl-butyl} -benzofuran-2-carboxylic acid amide to the ter-butyl acid ester. { (S) -1- [3-hydroxy-6,6-dimethyl-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -3-methyl-butyl} -carbamic from Example 92h (0.22 grams, 0.43 mmol) was added HCl / dioxane (4M, 20 mL, 80 mmol). The mixture was stirred at room temperature for 2 hours before the solvents and the excess amount of HCl were removed by rotary evaporator. The resulting white solid was dissolved in 5 ml of DMF. To the solution was added 2-benzofurancarboxylic acid (84 mg, 0.52 mmol), HBTU (0.2 grams, 0.52 mmol) and NMM (0.2 grams, 2 mmol). The mixture was stirred at room temperature overnight. DMF was then removed and the residue was dissolved in EtOAc (50 ml), washed with NaHC 3 (50 ml x 2) and brine (50 ml). Evaporation of the solvent gave the crude product, 0.26 grams. Purification by column chromatography gave the title compound, 0.15 grams in 63% total yield; MS (M + H +): 556.8; 1 H NMR (400 MHz, CDCl 3): • 8.66-8.63 (m, 1 H), 7.94-7.11 (m, 10H), 4.72 (m, 1H), 4.01-2.98 (m, 7H), 1.78-1.39 (m , 5H), 1.02-0.85 (m, 12H). (j) { (S) -1 - [3-Oxo-6,6-dimethyl-1 - (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -3-methyl-butyl} - benzofuran - 2 - carboxylic acid amide A solution of. { (S) -1- [3-hydroxy-6,6-dimethyl-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -3-methyl-butyl} Benzofuran-2-carboxylic acid amide of Example 92 (100 mg, 0.18 mmol) in 2 ml of CH 2 Cl 2, Dess-Martin agent (76 mg, 0.18 mmol) was added at room temperature. The solution was stirred for 2 hours when 20 ml of CH 2 Cl 2 was added and then washed with NaHCO 3 and brine. Purification by column chromatography (50% ethyl acetate in hexane) gave 70 mg of the title compound in 70% yield. MS (M + H +): 555.4; 1 H NMR (400 MHz, CDCl 3): • 8.68-8.67 (d, 1 H), 7.97-7.93 (m, 2H), 7.69-7.28 (m, 6H), 7.32-6.92 (m, 2H), 5.24 (m , 1 H), 4.79-4.69 (m, 2H), 3.80-3.71 (m, 2H), 2.54-2.50 (d, 1 H), 1.92-1.76 (m, 4H), 1.45-1.40 (m, 4H) , 1.01-0.91 (m, 9H). The diastereomeric mixture was separated by CLAP to provide the fastest eluting diastereomer; MS (EI) (M + H +) 555.2, and the slowest eluting diastereomer; MS (EI) (M + H +) 555.2.

EXAMPLE 93 Preparation of. { (S) -3-methyl-1-y3-oxo-1- (1-oxy-pyridin-2-sulfon-P-azepane-4-ylcarbamoyl-buty-phenamide of 5-methoxy-benzofuran-2-carboxylic acid (to) . { (S) -3-Met.l-1- [3-hydroxy-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 5-methoxybenzofuran-carboxylic acid amide The title compound was prepared following the procedure of Example 85c, but using 5-methoxybenzofuran-2-carboxylic acid instead of benzo [b] thiophene-2-carboxylic acid: MS (El): 574 (M + H +). (b) { (S) -3-Methyl-1 - [3-oxo-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl ester} 5-methoxybenzofuran-carboxylic acid amide The title compound was prepared following the procedure of Example 1 i, but using the. { (S) -3-methyl-1- [3-hydroxy-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl ester} 5-methoxybenzofuran-2-carboxylic acid amide of Example 93a: 1 H NMR (CDCl 3): d 1.0 (m, 6H), 1.5-2.1 (m, 5H), 2.2 (m, 2H), 2.7 (m, 1 H), 3.8 (m, 4H), 4.0 (m, 1 H), 4.5 (t, 1 H), 4.7 (m, 1 H), 5.0 (m, 1 H), 7.4-8.6 (m, 8H ), 8.0-8.2 (m, 2H); MS (El): 572 (M +, 30%). The diastereomeric mixture was separated by CLAP to provide the fastest eluting diastereomer; 1 H NMR (CDCL 3): d 1.0 (m, 6H), 1.5-2.1 (m, 5H), 2.2 (m, 2H), 2.7 (t, 1 H), 3.7 (s, 3H), 3.8 (d, 1 H), 4.0 (d, 1 H), 4.7 (m, 1 H), 5.0 (m, 1 H), 7.4-8.6 (m, 8H), 8.0-8.2 (m, 2H); EM (El): 573 (M + H \ 100%) and the slower eluting diastereomer; MS (EI) (M + H +) 573.

EXAMPLE 94 Preparation of. { (S) -3-Methyl-1-r3-oxo-1- (1-oxy-pyridine-2-sulfonyl-4-ylppane-4-ylcarbamoin-buty-phenamide of thienof3,2-biphenyl-2-carboxylic acid (to) . { (S) -3-Methyl-1- (3-hydroxy-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} - thienoamide [3,2-b] ] thiophene-2-carboxylic acid The title compound was prepared following the procedure of Example 85c, but using thieno [3,2-b] thiophene-2-carboxylic acid instead of benzo [b] thiophene-2-carboxylic acid: (El): 566 (M + H +). (B) { (S) -3-Methyl-1 - (3-0X0-1 - (1-oxy-pyridin-2-sulfonyl) -azepan- 4-ylcarbamoyl] -butyl} thieno [3,2-b] thiophene-2-carboxylic acid amide The title compound was prepared following the procedure of Example 1 i, but using the. {(S) -3 -methyl-1- [3-hydroxy-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} - thieno [3,2-b] thiophen-2-amide carboxylic acid from Example 94a: 1 H NMR (CDCL 3): d 1.0 (m, 6H), 1.5-2.1 (m, 5H), 2.2 (m, 2H) | 2.7 (m, 1 H), 3.8 (q, 1 H) , 4.0 (m, 1 H), 4.5 (t, 1 H), 4.7 (m, 1 H), 5.0 (m, 1 H), 7.4-7.5 (m, 6H), 7.7 (d, 1 H), 8.0-8.2 (m, 2H); MS (El): 564 (M \ 100%). The diastereomeric mixture was separated by CLAP to provide the fastest elution diastereomer; 1 H NMR (CDCL 3): d 1.0 (m, 6 H), 1.5-2.1 (m, 5 H), 2.2 (m, 2 H), 2.7 (t, 1 H), 3.8 (d, 1 H), 4.0 (d, 1 H), 4.5 (m, 1 H), 4.7 (d, 1 H), 5.0 (m, 1 H), 7.4-7.5 (m, 6H), 7.7 (d, 1 H), 8.0-8.2 (m 2H); MS (El): 565 (M + H +, 100%) and the slowest eluting diastereomer; MS (EI) (M + H +) 565 (M + H +, 100%).

EXAMPLE 95 Preparation of Quinoxaline-2-carboxylic acid ((S? -3-MetiM-r3-oxo-1- (1-oxy-pyridin-2-sulfoniP-azepan-4-ylcarbamoin-b? TiPamide) (to) . { (S) -3-Methyl-1- (3-hydroxy-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} - quinoxaline-2-carboxylic acid amide was prepared the title compound following the procedure of Example 85c, but using quinoxalino-2-carboxylic acid instead of benzo [b] thiophene-2-carboxylic acid: MS (El): 556 (M + H +). (b). { (S) -3-Methyl-1 - (3-oxo-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} - quinoxaline-2-carboxylic acid amide prepared the title compound following the procedure of Example 1i, but using the { (S) -3-methyl-1- [3-hydroxy-1- (1-oxy-pyridine-2-sulfonyl) -azepan-4 -carcarbonyl] -butyl.) quinoxaline-2-carboxylic acid amide of Example 95a: 1 H NMR (CDCL 3): d 1.0 (m, 6H), 1.5-2.1 (m, 5H), 2.2 (m, 2H), 2.7 (m, 1H), 3.8 (q, 1H), 4.0 (m, 1H), 4.5 (t, 1H), 4.7 (m, 1H), 5.0 (m, 1H), 7.4-7.5 (m, 2H) 7.9 (m, 1H), 8.0-8.4 (m, 4H), 9.6 (d, 1H), MS (El): 554 (M +, 100%). The diastereomeric mixture was separated by CLAP to provide er the fastest eluting diastereomer; MS (El): 555 (M + H \ 100%) and the slowest eluting diastereomer; MS (EI) (M + H +) 555 (M + H +, 100%).

EXAMPLE 96 Preparation of f (S) -3-Methyl-1-f3-oxo-1- (1-oxy-pyridine-2-sulfon-p-azepan-4-ylcarbamoyl-buty-phenamide quinoline-2-carboxylic acid (to) . { (S) -3-Methyl-1- [3-hydroxy-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} quinoline-2-carboxylic acid amide The title compound was prepared following the procedure of Example 85c, but using quinoline-2-carboxylic acid instead of benzo [b] thiophene-2-carboxylic acid: MS (El): 555 ( M + H +). (b) { (S) -3-Methyl-1 - [3-oxo-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl ester} quinoline-2-carboxylic acid amide The title compound was prepared following the procedure of Example 1 i, but using the. { (S) -3-methyl-1- [3-hydroxy-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl ester} quinoline-2-carboxylic acid amide of Example 94a: 1 H NMR (CDCL 3): d 1.0 (m, 6H), 1.5-2.1 (m, 5H), 2.2 (m, 2H), 2.7 (m, 1 H), 3.8 (q, 1H), 4.0 (m, 1H), 4.5 (t, 1 H), 4.7 (m, 1H), 5.0 (m, 1 H), 7.4-8.6 (m, 10H); MS (El): 553 (M \ 100%). The diastereomeric mixture was separated by CLAP to provide the fastest eluting diastereomer; MS (El): 554 (M + H +, 100%) and the slowest eluting diastereomer; MS (EI) (M + H +) 554 (M + H +, 100%).

EXAMPLE 97 Preparation of. { (S) -3-Methyl-1-r3-oxo-1- (1-oxy-pyridine-2-sulfoniP-azepan-4-ylcarbamoyl-buty-phenamide of thienophen-3-carboxylic acid (to) . { (S) -3-Methyl-1- (3-hydroxy-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} - thiophene-3-carboxylic acid amide was prepared the title compound following the procedure of Example 85c, but using thiophen-3-carboxylic acid instead of benzo [b] thiophene-2-carboxylic acid: MS (El): 510 (M + H +). (b). { (S) -3-Methyl-1 - (3-0X0-1 - (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} -amide of thiophene-3-carboxylic acid The title compound was prepared following the procedure of Example 1 i, but using the { (S) -3-methyl-1- [3-hydroxy-1- (1-oxy-pyridine-2-sulfonyl) -azepan -4-ylcarbamoyl] -butyl} thiophene-3-carboxylic acid amide of Example 97a: 1 H NMR (CDCL 3): d 1.0 (m, 6H), 1.5-2.1 (m, 5H), 2.2 (m, 2H ), 2.7 (m, 1 H), 3.8 (q, 1H), 4.0 (m, 1H), 4.5 (t, 1 H), 4.7 (m, 1H), 5.0 (m, 1H), 7.4-8.0 ( m, 4H), 7.8 (m, 1 H), 8.1-8.2 (m, 2H), MS (El): 508 (M +, 80%).

EXAMPLE 98 Preparation of. { (S) -3-Methyl-1 - | "3-oxo-1- (1-oxy-pyridine-2-sulfoniP-azepane-4-ylcarbamoyl-buty-phenamide of 1H-indole-5-carboxylic acid (to) . { (S) -3-Met l-1- (3-hydroxy-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} -amide of 1 H-indole 5-carboxylic acid The title compound was prepared following the procedure of Example 85c, but using 1 H-indole-5-carboxylic acid instead of benzo [b] thiophene-2-carboxylic acid: MS (El): 543 (M + H +). (B) { (S) -3-Methyl-1 - (3-OXO-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} -amide of 1 H-indole-5-carboxylic acid The title compound was prepared following the procedure of Example 1i, but using the. { (S) -3-methyl-1- [3-hydroxy-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl ester} 1 H-indole-5-carboxylic acid amide of Example 98a: 1 H NMR (CDCl 3): d 1.0 (m, 6H), 1.5-2.1 (m, 5H), 2.2 (m, 2H), 2.7 (m, 1 H), 3.8 (q, 1 H), 4.0 (m, 1 H), 4.5 (t, 1 H), 4.7 (m, 1 H), 5.0 (m, 1 H), 7.4-8.0 (m, 7H) ), 8.1-8.2 (m, 2H), 8.6 (b, 1 H); MS (El): 541 (M +, 100%). The diastereomeric mixture was separated by CLAP to provide the fastest eluting diastereomer; MS (El): 542 (M + H +, 80%) and the slowest eluting diastereomer; MS (EI) (M + H +) 542 (M + H +, 80%).

EXAMPLE 99 Preparation of C (S) -3-Methyl-1-r3-oxo-1- (1-oxy-pyridine-2-sulfoniP-azepan-4-ylcarbamoyl-butyamide of benzori, 31-dioxol-5-carboxylic acid (to) . { (S) -3-Methyl-1- (3-hydroxy-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} -amide of benzoic acid [1, 3 ] dioxol-5-carboxylic acid The title compound was prepared following the procedure of Example 85c, but using benzo [1, 3] dioxol-5-carboxylic acid in place of benzo [b] thiophene-2-carboxylic acid: ): 548 (M +). (B) { (S) -3-Methyl-1 - (3-oxo-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl .} benzo [1,3] dioxol-5-carboxylic acid amide The title compound was prepared following the procedure of Example 1 i, but using the { (S) -3-methyl-1- [ 3-Hydroxy-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} -benzo [1,3] dioxol-5-carboxylic acid amide of Example 99a: 1H NMR (CDCL3): d 1.0 (m, 6H), 1.5-2.1 (m, 5H), 2.2 (m, 2H), 2.7 (m, 1 H), 3.8 (q, 1 H), 4.0 (m, 1H) ), 4.5 (t, 1H), 4.7 (m, 1 H), 5.0 (m, 1 H), 6.0 (s, 2H), 7.4-8.0 (m, 5H), 8.1-8.2 (m, 2H); MS (El): 546 (M +, 100%). The diasteromeric mixture was separated before CLAP to provide the fastest elution diastereomer; MS (El): 547 (M + H +, 100%) and the slowest eluting diastereomer; MS (EI) (M + H +) 547 (M + H +, 100%).

EXAMPLE 100 Preparation of f (S) -3-Methyl-1-F3-oxo-1- (1-oxy-pyridin-2-sulfon-p-azepan-4-ylcarbamoy-buty-phenamide of furan-2-carboxylic acid (to) . { (S) -3-Methyl-1 - [3-hydroxy-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl ester} Furan-2-carboxylic acid amide The title compound was prepared following the procedure of Example 85c, but using furan-2-carboxylic acid instead of benzo [b] thiophene-2-carboxylic acid: MS (El): 494 ( M +). (b) { (S) -3-Methyl-1 - [3-oxo-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl ester} Furan-2-carboxylic acid amide The title compound was prepared following the procedure of Example 1i, but using the. { (S) -3-methyl-1- [3-hydroxy-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl ester} furan-2-carboxylic acid amide of Example 100a: 1 H NMR (CDCL 3): d 1.0 (m, 6H), 1.5-2.1 (m, 5H), 2.2 (m, 2H), 2.7 (m, 1 H), 3.8 (q, 1H), 4.0 (m, 1H), 4.5 (t, 1H), 4.7 (m, 1H), 5.0 (m, 1H), 7.4-8.0 (m, 5H), 8.1-8.2 (m, 2H); MS (El): 492 (M +, 100%). The diastereomeric mixture was separated by CLAP to provide the fastest eluting diastereomer; MS (El): 493 (M + H \ 100%) and the slowest eluting diastereomer; MS (EI) (M + H +) 493 (M + H \ 100%).

EXAMPLE 101 Preparation of r3-oxo-1- (1-oxy-pyridine-2-sulfoniP-azepan-4-ill-amide of (S) -4-methyl-2- (2-thiophen-2-yl-acetylamino ) -pentanoic (a) [3-Hydroxy-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-yl] -amide of acid. { (S) -4-methyl-2- (2-thiophen-2-yl-acetylamino) -pentanoic The title compound was prepared following the procedure of Example 85c, but using thiophen-2-acetic acid instead of benzoic acid [ b] thiophene-2-carboxylic acid. (b) [3-Oxo-l - (1-oxy-pyridin-2-sulfonyl) -azepan-4-yl] -amide of acid . { (S) -4-methyl-2- (2-thiophen-2-yl-acetylamino) -pentanoic The title compound was prepared following the procedure of Example 1 i, but using [3-oxo-1- (1- oxy-pyridin-2-sulfonyl) -azepan-4-yl] acid amide. { (S) -4-Methyl-2- (2-thiophen-2-yl-acetylamino) -pentanoic of Example 101a: 1 H NMR (CDCL 3): d 1.0 (m, 6H), 1.5-2.1 (m, 5H), 2.2 (m, 2H), 2.7 (m, 1 H), 3.8 (m, 3H), 4.0 (m, 1 H), 4.5 (t, 1 H), 4.7 (m, 1 H), 5.0 (m, 1 H), 7.4-8.0 (m, 5H), 8.1-8.2 (m, 2H); MS (El): 522 (M +, 20%).

EXAMPLE 102 Preparation of. { (S) -3-Methyl-1-r3-oxo-1- (1-oxy-pyridin-2-sulfonyl) -zepane-4-ylcarbamoin-buty-phenamide of 1H-indole-2-carboxylic acid (to) . { (S) -3-Methyl-1- (3-hydroxy-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} -amide of 1 H-indole-2- acid carboxylic acid The title compound was prepared following the procedure of Example 85c, but using 1 H-indole-2-carboxylic acid in place of benzo [b] thiophene-2-carboxylic acid: MS (El): 543 (M + H +). (b) { (S) -3-Methyl-1 - (3-oxo-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} - 1-H-indole-2-amide carboxylic acid The title compound was prepared following the procedure of Example 1i, but using the { (S) -3-methyl-1- [3-hydroxy-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl ester} 1 H-indole-2-carboxylic acid amide of Example 102a: 1 H NMR (CDC): d 1.0 (m, 6H), 1.5-2.1 (m, 5H), 2.2 (m, 2H), 2.7 (m, 1H), 3.8 (q, 1H), 4.0 (m, 1 H), 4.5 (t, 1H), 4.7 (m, 1H), 5.0 (m, 1H), 7.4-8.0 (m, 7H), 8.1-8.2 (m, 2H), 8.6 (b, 1 H); MS (El): 541 (M +, 100%). The diastereomeric mixture was separated by CLAP to provide the fastest eluting diastereomer; MS (El): 542 (M + H +, 100%) and the slowest eluting diastereomer; MS (EI) (M + H +) 542 (M + H +, 100%).

EXAMPLE 103 Preparation of 4-Fluoro-f (S) -3-methyl-1-r3-oxo-1- (1-oxy-pyridin-2-sulfonip-azepan-4-ylcarbamoy-but-P-benzamide (a) 4-Fluoro-. { (S) -3-Methyl-1 - (3-hydroxy-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} -benzamide The title compound was prepared following the procedure of Example 85c, but using fluorobenzoic acid in place of benzo [b] thiophene-2-carboxylic acid: MS (El): 522 (M +). (b) 4-Fluoro- {. (S) -3-methyl- 1 - (3-Oxo-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-yl-carbamoyl] -butyl} -benzamide The title compound was prepared following the procedure of Example 1i, but using 4-fluoro- ({(S) -3-methyl-1- [3-hydroxy-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} -benzamide Example 103a: 1 H NMR (CDCL 3): d 1.0 (m, 6 H), 1.5-2.1 (m, 5 H), 2.2 (m, 2 H), 2.7 (m, 1 H), 3.8 (q, 1 H), 4.0 (m, 1H), 4.5 (t, 1H), 4.7 (m, 1H), 5.0 (m, 1H), 7.4-8.0 (m, 6H), 8.1-8.2 (m, 2H), MS (El): 520 (M +, 100%) The diastereomeric mixture was separated by CLAP to provide the fastest eluting diastereomer, MS (El): 521 (M + H +, 100%) and the slowest eluting diastereomer; MS (EI) (M + H +) 521 (M + H +, 100%).

EXAMPLE 104 Preparation of. { (S) -3-Methyl-1-r3-oxo-1- (5- pyridin-2-sulfonyl-p-azepan-4-yl-carbamoyl-buty-p-phenyl acid) (2-morpholin-4-yl-ethoxy-benzofuran-2) - carboxylic (to) . { (S) -3-Methyl-1 - [3-hydroxy-1- (pyridine-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 5- (2-morpholin-4-yl-ethoxy) -benzofuran-2-carboxylic acid amide The title compound was prepared following the procedure of Example 85c, but using 5- (2-morpholin-4-yl-ethoxy) ) -benzofuran-2-carboxylic acid instead of benzo [b] thiophene-2-carboxylic acid: MS (El): 673 (M +). (b) { (S) -3-Methyl-1 - [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 5- (2-morpholin-4-yl-ethoxy) -benzofuran-2-carboxylic acid amide The title compound was prepared following the procedure of Example 1i, but using the { (S) -3-methyl-1- [3-hydroxy-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl ester} 5- (2-morpholin-4-yl-ethoxy) -benzofuran-2-carboxylic acid amide of Example 104a: H NMR (CDCL3): d 1.0 (m, 6H), 1.5-2.1 (m, 5H), 2.2 (m, 2H), 2.5 (m, 4H), 2.7 (m, 3H), 3.7 (m, 4H), 3.9 (m, 1 H), 4.5 (m, 3H), 4.7 (m, 1H), 5.0 (m, 1H), 7.4-8.0 (m, 6H), 8.1-8.2 (m, 2H); MS (El): 671 (M +, 100%).

The diastereomeric mixture was separated by CLAP to provide the fastest eluting diastereomer; MS (El): 672 (M + H +, 100%) and the slowest eluting diastereomer; MS (EI) (M + H +) 672 (M + H +, 100%). r \ EXAMPLE 105 Preparation of. { (S) -3-Methyl-1-y3-oxo-1- (1-oxo-pyridin-3-sulfonyl-p-azepane-t-ylcarbamoyl-buty-phenamide of thiophen-2-carboxylic acid (to) . { (S) -3-Methyl-1 - [3-hydroxy-1- (1-oxo-pyridin-3-sulfonyl) -azepan-4-10-ylcarbamoyl] -butyl ester} thiophene-2-carboxylic acid amide The title compound was prepared following the procedure of Example 85c, but using thiophen-2-carboxylic acid instead of benzo [b] thiophene-2-carboxylic acid: MS (El): 510 ( M +). (b) { (S) -3-Methyl-1- [3-oxo-1- (1-oxy-pyridin-3-sulfonyl) -azepan-4- 15 ylcarbamoyl] -butyl} thiophen-2-carboxylic acid amide The title compound was prepared following the procedure of Example 1i, but using the. { (S) -3-methyl-1- [3-hydroxy-1- (1-oxy-pyridin-2-sulfonyl)-azepan-4-ylcarbamoyl] -butyl} thiophene-2-carboxylic acid amide of Example 105a: 1 H NMR (CDCL 3): d 1.0 (m, 6H), 1.5-2.1 (m, 5H), 2.2 (m, 2H), 2.7 (m, 20 1H), 3.8 (q, 1H), 4.0 (m, 1H), 4.5 (t, 1H), 4.7 (m, 1H), 5.0 (m, 1H), 7.4-8.0 (m, 5H), 8.1-8.2 (m, 2H); MS (El): 508 (M +, 100%).

The diastereomeric mixture was separated by CLAP to provide the fastest eluting diastereomer; MS (El): 509 (M + H \ 100%) and the slowest eluting diastereomer; MS (EI) (M + H +) 509 (M + H +, 100%).

EXAMPLE 106 Preparation of. { (S) -3-Methyl-1 -f3-oxo-1- (3-methylbenzofuran-2-carboxylic acid (3-methyl-pyridin-3-sulfon-p-azepane-4-ylcarbamoip-butyamide) (to) . { (S) -3-Methyl-1 - [3-hydroxy-1- (1-oxy-pyridin-3-sulfonyl) -azepan-4-ylcarbamoyl] -butyl ester} 3-Methylbenzofuran-2-carboxylic acid amide The title compound was prepared following the procedure of Example 85c, but using 3-methylbenzofuran-2-carboxylic acid instead of benzo [b] thiophene-2-carboxylic acid: ): 558 (M +). (b) { (S) -3-Methyl-1- [3-oxo-1- (1-oxy-pyridin-3-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 3-methylbenzofuran-2-carboxylic acid amide The title compound was prepared following the procedure of Example 1, but using the. { (S) -3-methyl-1- [3-hydroxy-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl ester} 3-methylbenzofuran-2-carboxylic acid amide of Example 106a: 1 H NMR (CDCL 3): d 1.0 (m, 6H), 1.5-2.1 (m, 5H), 2.2 (m, 2H), 2.5 (d, 3H) , 2.7 (m, 1H), 3.8 (q, 1 H); 4.0 (m, 1H), 4.5 (t, 1H), 4.7 (m, 1H), 5.0 (m, 1H), 7.4-8.0 (m, 6H), 8.1-8.2 (m, 2H); MS (El): 556 (M \ 100%). The diastereomeric mixture was separated by CLAP to provide the fastest eluting diastereomer; 1 H NMR (CDCl 3): d 1.0 (m, 6H), 1.5-2.1 (m, 5H), 2.2 (m2, 2.6 (s, 3H), 2.7 (t, 1 H), 3.8 (d, 1 H); 4.1 (d, 1 H), 5.0 (m, 1 H), 7.0 (m, 2H), 7.3 (m, 2H), 7.4 (m, 4H), 8.1 (d, 1 H), 8.2 (d, 1) H); MS (El): 557 (M + H \ 100%) and the slowest eluting diastereomer, MS (EI) (M + H +) 557 (M + H \ 100%).

EXAMPLE 107 Preparation of 6-methyl-N-. { (S) -3-methyl-1-r3-oxo-1 - (1-oxy-pyridin-2-sulfonyl) - azepan-4-ylcarbamoyl-butiP-nicotinamide (a) 6-Methyl-N-. { (S) -3-methyl-1 - [3-hydroxy-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-yl-carbamoyl] -butyl ester} -nicotinamide The title compound was prepared following the procedure of Example 85c, but using 6-methylnicotinic acid instead of benzo [b] thiophene-2-carboxylic acid: MS (El): 519 (M +). (b) 6-Methyl-N-. { (S) -3-methyl-1 - [3-oxo-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-yl-carbamoyl] -butyl ester} -nicotinamide The title compound was prepared following the procedure of Example 1i, but using 6-methyl-N-. { (S) -3-methyl-1- [3-hydroxy-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} -nicotinamide of Example 107a: 1 H NMR (CDCL 3): d 1.0 (m, 6H), 1.5-2.1 (m, 5H), 2.2 (m, 2H), 2.6 (s, 3H), 2.7 (m, 1 H) , 3. 8 (q, 1 H); 4.0 (m, 1H), 4.5 (t, 1H), 4.7 (m, 1 H), 5.0 (m, 1 H), 7.4-8.0 (m, 3H), 9. 0 (m, 1H); MS (El): 517 (M +, 100%).

The diastereomeric mixture was separated by CLAP to provide the fastest eluting diastereomer; MS (El): 518 (M + H +, 100%) and the slowest eluting diastereomer; MS (EI) (M + H +) 518 (M + H \ 100%).

EXAMPLE 108 Preparation of r3-oxo-1- (pyridine-2-sulfon-p-azepan-4-iP-buti-p -amide of (S) -4-methyl-2- (2-thiophen-yl-acetylamino) -pentanoic acid (a) [3-Hydroxy-1 - (pyridine-2-sulfonyl) -azepan-4-yl] -butl} (S) -4-Methyl-2- (2-thiophene-yl-acetylamino) -pentanoic acid amide The title compound was prepared following the procedure of Example 28b, but using thiophen-2-acetic acid instead of benzofuran acid -2-carboxylic: MS (El): 508.8 (M + H +). (b) [3-Oxo-l - (pyridin-2-sulfonyl) -azepan-4-yl] -butyl} (S) -4-Methyl-2- (2-thiophene-yl-acetylamino) -pentanoic acid amide The title compound was prepared following the procedure of Example 1 i, but using [3-hydroxy-1- (pyridine -2-sulfonyl) -azepan-4-yl] -butyl} (S) -4-Methyl-2- (2-thiophen-yl-acetylamino) -pentanoic acid amide of Example 108a: MS (El): 506.8 (M + H +).

EXAMPLE 109 Preparation of. { (S) -3-Methyl-1-r3-oxo-1 - (pyridine-2-sulfonyl-1-indol-6-carboxylic acid 1-indol-6-carboxylic acid-butyl-p-azepane-4-ylcarbamoin-buty-phenyl ester (to) . { (S) -3-Methyl-1- (3-hydroxy-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} -amide of 1 H-indole-6-carboxylic acid was prepared the title compound following the procedure of Example 28b, but using 1 H-indole-6-carboxylic acid instead of benzofuran-2-carboxylic acid: MS (El): 527 (M + H +). (b) { (S) -3-Methyl-1- (3-OXO-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} -amide of 1H-indole-6-carboxylic acid The compound was prepared of the title following the procedure of Example 1i, but using the. {(S) -3-methyl-1- [3-hydroxy-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl}. 1 H-indole-6-carboxylic acid amide of Example 109a: MS (EI): 525 (M + H +) EXAMPLE 110 Preparation of. { (S) -3-Methyl-1 -f3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoin-buti-P-benzof 1,31-dioxol-5-carboxylic acid (to) . { (S) -3-Methyl-1- (3-hydroxy-1- (pyridin-2-sulfonyl) -azepan-4-lcarbamoyl] -butyl} -amido of benzo [1,3] dioxol-5-amide carboxylic The title compound was prepared following the procedure of Example 28b, but using piperonyl acid in place of the benzofuran-2-carboxylic acid: MS (El): 532.7 (M +). (b) { (S) -3 Methyl-1 - (3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} -benzo [1,3] dioxol-5-carboxylic acid amide. title following the procedure of Example 1i, but using the. {(S) -3-methyl-1- [3-hydroxy-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl}. benzo [1,3] dioxol-5-carboxylic acid amide of Example 110a: MS (El): 530.8 (M + H +).

EXAMPLE 111 Preparation of. { (S) -3-methyl-1-r3-oxo-1- (1-oxy-pyridine-2-sulfonyl-4-dihydro-2H-benzoyiphenyl, 4-dihydro-2H-benzoyiphenyl, 4-dihydro-2H-benzoyiphenyl, -carboxylic (to) . { (S) -3-Methyl-1 - [3-hydroxy-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl ester} 3,4-dihydro-2H-benzo [b] [1,4] dioxepino-7-carboxylic acid amide The title compound was prepared following the procedure of Example 85c, but using 3,4-dihydro-2H-benzoic acid [b] [1,4] dioxepino-7-carboxylic acid instead of benzo [b] thiophene-2-carboxylic acid: MS (El): 576 (M +). (b) { (S) -3-Methyl-1 - [3-0X0-1 - (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 3,4-dihydro-2H-benzo [b] [1,4] dioxepino-7-carboxylic acid amide The title compound was prepared following the procedure of Example 1i, but using. { (S) -3-methyl-1- [3-hydroxy-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl ester} 3,4-dihydro-2H-benzo [b] - [1,4] dioxepino-7-carboxylic acid amide of Example 111a: 1 H NMR (CDCL 3): d 1.0 (m, 6H), 1.5-2.1 (m, 5H), 2.2 (m, 4H), 2.5 (d, 3H), 2.7 (m, 1H), 3.8 (q, 1 H); 4.0 (m, 1 H), 4.2 (m, 4H), 4.5 (t, 1 H), 4.7 (m, 1 H), 5.0 (m, 1 H), 7.4-8.0 (m, 5H), 8.1- 8.2 (m, 2H); MS (El): 575 (M + H +, 100%). The diastereomeric mixture was separated by CLAP to provide the fastest eluting diastereomer; MS (El): 575 (M + H \ 100%) and the slowest eluting diastereomer; MS (EI) (M + H +) 575 (M + H +, 100%).

EXAMPLE 112 Preparation of 5- (methyl) -thio-thiophene-2-carboxylic acid ((S) -3-Methyl-1-f3-oxo-1- (1-oxy-pyridin-2-sulfoniP-azepan-4-ylcarbamoin-buty-phenamide) (to) . { (S) -3-Methyl-1 - [3-hydroxy-1 - (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl ester} 5-methyl-thiophene-2-carboxylic acid amide The title compound was prepared following the procedure of Example 85c, but using 5-methyl-thiophene-2-carboxylic acid instead of benzo [b] thiophene-2-carboxylic acid : MS (El): 524 (M +). (b) { (S) -3-Methyl-1 - [3-oxo-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl ester} 5-Methyl-thiophene-2-carboxylic acid amide The title compound was prepared following the procedure of Example 1i, but using the. { (S) -3-methyl-1- [3-hydroxy-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 5-Methyl-thiophene-2-carboxylic acid amide of Example 112a: 1 H NMR (CDCl 3): d 1.0 (m, 6H), 1.5-2.1 (m, 5H), 2.2 (m, 2H), 2.5 (d, 3H), 2.7 (m, 1H), 3.8 (q, 1 H); 4.0 (m, 1 H), 4.5 (m, 1 H), 4.7 (m, 1H), 5.0 (m, 1 H), 7..4-8.0 (m, 4H), 8.1-8.2 (m, 2H) ); MS (El): 523 (M + H \ 100%). The diastereomeric mixture was separated by CLAP to provide the fastest eluting diastereomer; MS (EI): 523 (M + H +, 100%) and the slowest eluting diastereomer; MS (EI) 523 (M + H +, 100%).

EXAMPLE 113 Preparation of. { (S) -3-Methyl-1-f3-oxo-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoy-buty-phenamide 4,5-dibromo-thiophene-2-carboxylic acid (to) . { (S) -3-Methyl-1 - [3-hydroxy-1 - (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl ester} 4,5-dibromo-thiophene-2-carboxylic acid amide The title compound was prepared following the procedure of Example 85c, but using 4,5-dibromo-thiophene-2-carboxylic acid instead of benzo [b] thiophene -2-carboxylic: MS (El): 668 (M +). (b) { (S) -3-Methyl-1 - [3-oxo-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl ester} 4,5-dibromo-thiophene-2-carboxylic acid amide ** The title compound was prepared following the procedure of Example 1i, but using the. { (S) -3-methyl-1- [3-hydroxy-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl ester} 4,5-dibromo-thiophene-2-carboxylic acid amide of Example 113a: 1 H NMR (CDCL 3): d 1.0 (m, 6H), 1.5-2.1 (m, 5H), 2.2 (m, 2H), 2.7 ( m, 1 H), 3.8 (q, 1 H); 4.0 (m, 1 H), 4.5 (t, 1 H), 4.7 (m, 1 H), 5.0 (m, 1 H), 7..4-8.0 (m, 3H), 8.1-8.2 (m, 2H); MS (El): 665 (M + H +, 100%).

EXAMPLE 114 Preparation of 3,5-dimethyl-isoxazole-4-methyl-1-r 3 -oxo-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl-buty-phenyl acid -carboxylic (to) . { (S) -3-Methyl-1 - [3-hydroxy-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl ester} 3,5-dimethyl-isoxazole-4-carboxylic acid amide The title compound was prepared following the procedure of Example 85c, but using 3,5-diimethyl-isoxazole-4-carboxylic acid instead of benzo [b] thiophene -2-carboxylic: MS (El): 524 (M + H +). (b) { (S) -3-Methyl-1 - [3-oxo-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl ester} 3,5-Dimethyl-isoxazole-4-carboxylic acid amide The title compound was prepared following the procedure of Example 1i, but using the. { (S) -3-methy1- [3-hydroxy-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 3,5-dimethyl-isoxazole-4-carboxylic acid amide of Example 114a: 1 H NMR (CDCL 3): d 1.0 (m, 6H), 1.5-2.1 (m, 5H), 2.2 (m, 2H), 2.4 (m, 3H), 2.6 (m, 3H), 2.7 (m, 1H), 3.8 (q, 1 H); 4.0 (m, 1 H), 4.5 (t, 1 H), 4.7 (m, 1H), 5.0 (m, 1H), 7.4-8.0 (m, 5H), 8.1-8.2 (m, 2H); MS (El): 521 (M + H \ 100%).

EXAMPLE 115 Preparation of (S) -2- (2-benzyloxy-acetylamino) -4-methyl-pentanoic acid 1- (4-methoxy-benzenesulfoniP-3-oxo-azepan-4-in-amide) (a) Ter-butyl acid ester. { (S) -1- [3-hydroxy-1- (4-methoxy-benzenesulfonyl) -azepan-4-ylcarbamoyl] -3-methyl-butyl} -carbamic [(S) -1- (3-hydroxy-azepan-4-ylcarbamoyl) -3-methyl-buty] carbamic acid tert-butyl ester (compound 2 grams, 0.8 grams, 2.33 mmol) was dissolved in 1, 2-dichloroethane (DCE, 20 ml). Then, morpholinomethylpolystyrene resin spheres (1.26 grams, 3.7 mmol / gram, Nov (a)) were added and the solution was stirred for 5 minutes, then p-methoxybenzenesulfonyl chloride (0.48 grams, 2.33 mmol) was dissolved in DCE ( 10 ml) and this solution was added to the reaction mixture, the reaction was stirred overnight, filtered, washed with DCE (2 x, 10 ml), then CH 2 Cl 2 (10 ml) The combined organic extracts were concentrated under vacuum and used in the next reaction without further purification: M + H + = 514.2 (b) HCl salt of [3-hydroxy-1- (4-methoxy-benzenesulfonyl) -azepan-4-yl] -amide of acid (S) -2-amino-4-methyl-pentanoic Tert-butyl acid ester { (S) -1- [3-hydroxy-1- (4-methoxy-benzenesulfonyl) -azepan-4-ylcarbamoyl was dissolved. ] -3-methyl-butyl.} - carbamic acid (compound 207a, 0.59 grams, 1.15 mmol) in CH2Cl2 (8 ml), then a solution of 4 M HCl in dioxane (8 ml) was added and the reaction was stirred at room temperature. room temperature for 4 hours The reaction mixture was concentrated in vacuo, azeotropically distilled from toluene twice 810 ml) in vacuo and used in the next reaction without further purification: M + H + = 413.8. (c) [3-Hydroxy-1- (4-methoxy-benzenesulfonyl) -azepan-4-yl] (S) -2- (2-benzyloxy-acetylamino) -4-methyl-pentanoic acid salt HCl of [ 3-Hydroxy-1- (4-methoxy-benzenesulfonyl) -azepan-4-yl] -amide of (S) -2-amino-4-methyl-pentanoic acid (crude product of the reaction mixture of 115b), dissolved in MeOH (10 ml) and treated with carbonate-polystyrene resin beads (1.75 grams, 2.63 mmoles / grams, 4.6 mmol) and stirred for 2 hours, filtered, washed with MeOH (10 ml) and the The combined organics were concentrated in vacuo. The product was then dissolved in DCE (2 ml) and morpholinomethylpolystyrene resin beads (0.25 grams, 3.77 mmoles / gram, 0.91 mmole, Nova) were added and the reaction was stirred for 5 minutes. Then, benzylacetyl chloride (0.081 grams, 0.44 mmol) was added and the reaction mixture was stirred overnight. Then, trisamine polystyrene spheres (0.1 gram, 3.66 mmole / gram, 0.366 mmole) were added and the reaction mixture was stirred for 1.5 hours. The reaction mixture was filtered, washed with DCE (2x10 ml) and CH2Cl2 (10 ml) and the organic extracts were concentrated in vacuo. The crude product was used in the following reaction without further purification: M + H + = 562.2. (d) [1- (4-methoxy-benzenesulfonyl) -3-oxo-azepan-4-yl] (S) -2- (2-benzyloxy-acetylamino) -4-methyl-pentanoic acid acid ester [1] (S) -2- (2-benzyloxy-acetylamino) -4-methyl-pentanoic acid ((compound 207c) - (4-methoxy-benzenesulfonyl) -3-oxo-azepan-4-yl] -amide., 0.24 grams, 0.44 mmol) in CH2Cl2 (5 ml), then Dess-Martin periodinane (0.3 grams, 0.7 mmol) was added and the reaction was stirred for 30 min. The reaction was diluted with CH2Cl2 (20 ml), then extracted with 10% aqueous Na2S2Os (10 ml), then 10% aqueous NaHCO3 (10 ml), water (10 ml), brine (10 ml). The combined organic extracts were concentrated in vacuo. The residue was purified by CLAP (50:50 Etanokhexane, 20 mL / min, 25 min, column WhelkO-1 (R, R) 21x250 mm, UV detection at 280 nm and 305 nm) to yield the first elution as a solid white (47 mg, 43%): MS 560.4 (M + H +). 1 H NMR (400 Hz, CDCl 3): d 7.73 (d, 2 H), 7.40-7.30 (m, 5 H), 7.05 (d, 2 H), 3.99 (s, 2 H), 3.88 (s, 3 H); 2.28-2.10 (m, 2H), 0.95 (t, 6H), and the second eluted diastereomer: MS 560.2 (M + H +).

EXAMPLE 116 Preparation of 5- (3-methyl-1-r3-oxo-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoin-buty-phenyl acid-3-trifluoromethyl-phenyl ester -furan-2-carboxylic acid (to) . { (S) -3-methyl-1 - [3-oxo-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl ester} 5- (3-trifluoromethyl-phenyl) -furan-2-carboxylic acid amide The title compound was prepared following the procedure of Example 85c, but using 5- (3-trifluoromethyl-phenyl) -furan-2-carboxylic acid. instead of benzo [b] thiophene-2-carboxylic acid: MS (El): 638 (M +). (b) { (S) -3-Methyl-1- (3-oxo-1- (1- (oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} -amide of 5- (3-trifluoromethyl- phenyl) -furan-2-carboxylic acid The title compound was prepared following the procedure of Example 1 i, but using the. {(S) -3-methyl-1- (3-hydroxy-1- (1-oxy) pyridine-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} -amide of 5- (3-trifluoromethyl-phenyl) -furan-2-carboxylic acid amide of Example 116a: 1 H NMR (CDCL3): d 1.0 (m , 6H), 1.5-2.1 (m, 5H), 2.2 (m, 2H), 2.6 (d, 3H), 2.7 (m, 1 H), 3.8 (q, 1 H), 4.1 (m, 1 H) , 4.7 (t, 1 H), 4.8 (m, 1 H), 5.0 (m, 1 H), 7.4-8.0 (m, 9H), 8.1 -8.2 (m, 2H), MS (El): 637 ( M + H +, 100%). The diastereomeric mixture was separated by CLAP to provide the fastest eluting diastereomer, MS (El): 637 (M + H +, 100%) and the slowest eluting diastereomer, MS (EI) 637 (M + H +, 100%).

EXAMPLE 117 Preparation of. { (S) -3-Methyl-1- (3-oxo-1- (1-oxy-pyridine-2-sulfonyl-5-methyl-2-phenyl-oxazole-4-carboxylic acid 5-methyl-2-phenyl-oxazole-4-carboxylic acid (to) . { (S) -3-Methyl-1- (3-hydroxy-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} - 5-methyl-2-amide phenyl-oxazole-4-carboxylic acid The title compound was prepared following the procedure of Example 85c, but using 5-methyl-2-phenyl-oxazole-4-carboxylic acid instead of benzo [b] thiophene-2-carboxylic acid : MS (El): 585 (M +). (B) { (S) -3-Methyl-1- (3-oxo-1- (1-oxy-pyridine-2-sulfonyl) -azepan-4- 5-methyl-2-phenyl-oxazole-4-carboxylic acid amide The title compound was prepared following the procedure of Example 1, but using the. {S (S) -3-methyl) 5- (3-hydroxy-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} -amide 5-methyl-2-phenyl-oxazole-4-carboxylic acid Example 117a: 1 H NMR (CDCL 3): d 1.0 (m, 6H), 1.5-2.1 (m, 5H), 2.2 (m, 2H), 2.6 (d, 3H), 2.7 (m, 1 H), 3.8 ( q, 1 H), 4.0 (m, 1 H), 4.5 (t, 1 H), 4.7 (m, 1 H), 5.0 (m, 1 H), 7.4-8.0 (m, 7H), 8.1-8.2 (m, 2H); MS (El): 584 (M + H +, 100%). thermerically using CLAP to provide the fastest eluting diastereomer; MS (El): 584 (M + H +, 100%) and the slowest eluting diastereomer; MS (EI) 584 (M + H \ 100%).

EXAMPLE 118 Preparation of f (S) -1-f 1 - (3,4-dimethoxy-benzenesulfonyl) -3-oxo-azepane-4-Icarbamoyl-butyamide of benzofuran-2-carboxylic acid (to) . { (S) -1- [1- (3,4-Dimethoxy-benzenesulfonyl) -3-hydroxy-azepan-4-ylcarbamoyl] -butyl ester} benzofuran-2-carboxylic acid amide To a solution of. { (S) -1- [1- (3,4-dimethoxy-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -butyl ester} benzofuran-2-carboxylic acid amide of Example 78c (0.175 grams) in dichloromethane, triethylamine (0.1 mL) and 3,4-dimethoxybenzenesulfonyl chloride (0.12 grams) were added. The reaction was stirred until complete. Treatment and column chromatography (5% methanol / dichloromethane) gave the title compound (0.21 grams): MS (EI) 587 (M +). (b) { (S) -1 - [1 - (3,4-dimethoxy-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -butyl ester} benzofuran-2-carboxylic acid amide The title compound was prepared following the procedure of Example 1i, but using the. { (S) -1- [1- (3,4-dimethoxy-benzenesulfonyl) -3-hydroxy-azepan-4-ylcarbamoyl] -butyl ester} benzofuran-2-carboxylic acid amide of Example 118a: 1 H NMR (CDCL 3): d 1.0 (m, 6H), 1.5-2.1 (m, 6H), 2.6 (m, 1 H), 3.5 (d, 1 H) 3.7 (t, 6H); 4.0 (m, 1 H), 4.5 (t, 1 H), 4.7 (m, 1 H), 5.0 (m, 1 H), 7.4-8.0 (m, 8H); MS (El): 586 (M + H \ 100%).

EXAMPLE 119 Preparation of. { (S) -1 -H - (4-bromo-benzenesulfonium-3-oxo-azepane-4-ylcarbamoin-buty-phenamide of benzofuran-2-carboxylic acid (to) . { (S) -1- [1- (4-Bromo-benzenesulfonyl) -3-hydroxy-azepan-4-ylcarbamoyl] -butyl ester} benzofuran-2-carboxylic acid amide The title compound was prepared following the procedure of Example 1i, but using 4-bromobenzenesulfonyl chloride in place of 3,4-dimethoxybenzenesulfonyl chloride: MS (El): 606 (M +, 100 %). (b) { (S) -1- [1- (4-Bromo-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -butyl ester} benzofuran-2-carboxylic acid amide The title compound was prepared following the procedure of Example 1 i, but using the. { (S) -1- [1- (4-Bromo-benzenesulfonyl) -3-hydroxy-azepan-4-ylcarbamoyl] -butyl ester} benzofuran-2-carboxylic acid amide of Example 119a: 1 H NMR (CDCL 3): d 1.0 (m, 6 H), 1.5-2.1 (m, 6 H), 2.6 (m, 1 H), 3.5 (d, 1 H); 4.0 (m, 1 H), 4.5 (t, 1 H), 4.7 (m, 1 H), 5.0 (m, 1 H), 7.4-8.0 (m, 9H); MS (El): 604 (M +, 100%).

EXAMPLE 120 Preparation of. { (S) -1-M- (benzoH .2.51-oxadiazole-4-sulfonyl) -3-oxo-azepan-4-ylcarbamoyl-3-methyl-buty-phenamide of benzofuran-2-carboxylic acid (to) . { (S) -1 - [1 - (Benzo [1, 2,5] oxadiazole-4-sulfonyl) -3-hydroxy-azepan-4-ylcarbamoyl] -3-methyl-butyl} benzofuran-2-carboxylic acid amide The title compound was prepared following the procedure of Example 118a, but using benzofurazan-4-sulfonyl chloride in place of 3,4-dimethoxybenzenesulfonyl chloride: MS (El): 569 (M +) . (b) { (S) -1 - [1 - (Benzo [1, 2,5] oxadiazole-4-sulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} benzofuran-2-carboxylic acid amide The title compound was prepared following the procedure of Example 1i, but using the. { (S) -1- [1- (Benzo [1, 2,5] oxadiazole-4-sulfonyl) -3-hydroxy-azepan-4-ylcarbamoyl] -3-methyl-butyl} benzofuran-2-carboxylic acid amide of Example 120a: 1 H NMR (CDCl 3): d 1.0 (m, 6H), 1.5-2.1 (m, 6H), 2.6 (m, 1H), 3.7 (m, 1H); 4.1 (m, 1 H), 4.7 (m, 2H), 5.2 (m, 1H), 7.4-8.0 (m, 8H); MS (El): 568 (M + H +, 100%).

EXAMPLE 121 Preparation of f (SM-H - (3,5-dimethyl-oxazole-4-sulfoniD-3-oxo-azepane-4-ylcarbamoin-3-methyl-buty-phenyl-benzofuran-2-carboxylic acid (to) . { (S) -1- [1- (3,5-dimethyl-oxazole-4-sulfonyl) -3-hydroxy-azepan-4-ylcarbamoyl] -3-methyl-butyl} benzofuran-2-carboxylic acid amide The title compound was prepared following the procedure of Example 118a, but using 3,5-dimethyloxazole-4-sulfonyl chloride in place of 3,4-dimethoxybenzenesulfonyl chloride: MS (El): 546 (M +). (b) { (S) -1 - [1 - (3,5-dimethyl-oxazole-4-sulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} benzofuran-2-carboxylic acid amide The title compound was prepared following the procedure of Example 1i, but using the { (S) -1- [1- (3,5-dimethyl-oxazole-4-sulfonyl) -3-hydroxy-azepan-4-ylcarbamoyl] -3-methyl-butyl} benzofuran-2-carboxylic acid amide of Example 121a: 1 H NMR (CDCL 3): d 1.0 (m, 6H), 1.5-2.2 (m, 6H), 2.2 (m, 2H), 2.4 (d, 3H), 2.7 (t, 3H), 3.6 (d, 1 H); 4.1 (m, 1 H), 4.4 (t, 1 H), 4.7 (m, 1 H), . 2 (m, 1 H), 7.4-8.0 (m, 5H); MS (El): 544 (M +, 100%).

EXAMPLE 122 Preparation of. { (S) -3-methyl-1-r3-oxo-1- (3-methylbenzofuran-2-carboxylic acid (pyridine-2-sulfoniP-azepan-4-ylcarbamoyl-buty-phenyl) (to) . { (S) -3-Methyl-1 - [3-hydroxy-1- (pyridine-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 3-methylbenzofuran-2-carboxylic acid amide The title compound was prepared following the procedure of Example 28b, but using 3-methylbenzofuran-2-carboxylic acid instead of benzofuran-2-carboxylic acid: MS (El): 542 (M +). (b) { (S) -3-Methyl-1 - [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 3-methylbenzofuran-2-carboxylic acid amide The title compound was prepared following the procedure of Example 1 i, but using the. { (S) -3-methyl-1- [3-hydroxy-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 3-methylbenzofuran-2-carboxylic acid amide of Example 122a: 1 H NMR (CDCl 3): d 1.0 (m, 6H), 1.5-2.2 (m, 6H), 2.2 (m, 2H), 2.6 (d, 3H) , 2.7 (m, 1 H), 3.8 (q, 1 H); 4.1 (m, 1 H), 4.7 (m, 2H), 5.2 (m, 1 H), 7.4-8.0 (m, 7H); 8.7 (m, 1H); MS (El): 540 (M +, 100%). The diastereomeric mixture was separated by CLAP to provide the fastest eluting diastereomer; H NMR (CDCL3): d 1.0 (m, 6H), 1.5-2.1 (m, 6H), 2.2 (m, 2H), 2.6 (s, 3H), 2.7 (m, 1 H), 3.8 (d, 1 H); 4.1 (d, 1H), 4.7 (m, 2H), 5.2 (m, 1 H), 7.4-8.0 (m, 7H); 8.7 (m, 1 H); MS (El): 541 (M + H +, 100%) and the slowest eluting diastereomer; MS (EI) (M + H +) 541 (M + H +, 100%).

EXAMPLE 123 Preparation of. { (S) -3-methyl-1 - [3-oxo-1- (pyridine-2-sulfoniP-azepane-4-ylcarbamoin-buty-phenamide of thienor-3,2-biphenyl-2-carboxylic acid (to) . { (S) -3-Methyl-1- (3-hydroxy-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} -amide of thieno [3,2-b] thiophene- 2-carboxylic The title compound was prepared following the procedure of Example 28b, but using thieno [3,2-b] thiophene-2-carboxylic acid instead of benzofuran-2-carboxylic acid: MS (El): 550 (M + (b). {S (S) -3-Methyl-1 - (3-OXO-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} - thienoamide [3] , 2-b] thiophene-2-carboxylic acid The title compound was prepared following the procedure of Example 1i, but using the. {(S) -3-Methyl-1- (3-hydroxy-1- (pyridin-2) -sulfonyl) -azepan-4-ylcarbamoyl] -butyl}. thieno [3,2-b] thiophene-2-carboxylic acid amide of Example 123a: 1 H NMR (CDCL3): d 1.0 (m, 6H) , 1.5-2.2 (m, 6H), 2.2 (m, 2H), 2.7 (m, 1 H), 3.8 (m, 1 H), 4.1 (m, 1 H), 4.7 (m, 2H), 5.2 ( m, 1 H), 7.4-8.0 (m, 8H), 8.7 (m, 1 H), MS (E): 548 (M +, 100%). The diastereomeric mixture was separated by CLAP to provide the elution diasteromer. n faster, 1H NMR (CDCL3): d 1.0 (m, 6H), 1.5-2.2 (m, 6H), 2.2 (m, 2H), 2.7 (t, 1 H), 3.8 (d, 1 H), 4.1 (d, 1 H), 4.7 (m, 2H), 5.2 (m, 1H), 7.4-8.0 (m, 8H); 8.7 (d, 1 H); MS (El): 549 (M + H +, 100%) and the slowest eluting diastereomer; MS (EI) (M + H +) 549 (M + H +, 100%).

EXAMPLE 124 Preparation of. { (S) -3-Methyl-1-r3-oxo-1- (pyridine-2-sulfonyl-5-tert-butyl-3-methyl-thienoyl-3,2-biphenyl-4-yl-carbamoyl-buty-phenyl acid 2- carboxylic (to) . { (S) -3-Methyl-1 - [3-hydroxy-1- (pyridine-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 5-tert-Butyl-3-methyl-thieno [3,2-b] thiophene-2-carboxylic acid amide The title compound was prepared following the procedure of Example 28b, but using 5-tert-butyl-3-acid -methyl-thieno [3,2-b] thiophene-2-carboxylic acid instead of benzofuran-2-carboxylic acid: MS (El): 620 (M +). (b) { (S) -3-Methyl-1 - [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 5-tert-Butyl-3-methyl-thieno [3,2-b] thiophene-2-carboxylic acid amide The title compound was prepared following the procedure of Example 1 i, but using the. { (S) -3-methyl-1- [3-hydroxy-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 5-tert-Butyl-3-methyl-thieno [3,2-b] thiophene-2-carboxylic acid amide of Example 124a: 1 H NMR (CDCL 3): d 1.0 (m, 6H), 1.45 (s, 9H) , 1.5-2.2 (m, 6H), 2.2 (m, 2H), 2.4 (d, 3H), 2.7 (m, 1H), 3.8 (m, 1H); 4.1 (m, 1H), 4.7 (m, 2H), 5.2 (m, 1 H), 7.4-8.0 (m, 4H); 8.7 (m, 1 H); MS (El): 618 (M \ 100%).

EXAMPLE 125 Preparation of (5-methyl-2-phenyl-oxazole-4-methyl-2-phenyl-oxazole-4 (3-methyl-1-r3-oxo-1- (pyridine-2-sulfoniD-azepane-4-yl-carbamoyl-buti-pyrimidine) -carboxylic (to) . { (S) -3-Methyl-1 - [3-hydroxy-1- (pyridine-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 5-Methyl-2-phenyl-oxazole-4-carboxylic acid amide The title compound was prepared following the procedure of Example 28b, but using 5-methyl-2-phenyl-oxazole-4-carboxylic acid instead of the acid benzofuran-2-carboxylic acid: MS (El): 569 (M +). (b) { (S) -3-Methyl-1 - [3-oxo-1 - (pyridine-2-sulfonyl) -azepan-4-lcarbamoyl] -butyl} 5-Methyl-2-phenyl-oxazole-4-carboxylic acid amide Prepared following the procedure of Example 1 i, but using the. { (S) -3-methyl-1 - [3-hydroxy-1- (pyridine-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl ester} 5-Methyl-2-phenyl-oxazole-4-carboxylic acid amide of Example 125a: 1 H NMR (CDCL 3): d 1.0 (m, 6H), 1.5-2.2 (m, 6H), 2.2 (m, 2H), 2.7 (m, 1 H), 2.6 (m, 3H), 3.8 (m, 1 H); 4.1 (m, 1 H), 4.7 (m, 2H), 5.2 (m, 1 H), 7.4-8.0 (m, 8H); 8.7 (m, 1H); MS (El): 567 (M \ 100%). The diastereomeric mixture was separated by CLAP to provide the fastest eluting diastereomer; MS (EI): 568 (M + H +, 100%) and the slowest eluting diastereomer; MS (EI) 568 (M + H +, 100%).

EXAMPLE 126 Preparation of. { (S) -3-methyl-1-f3-oxo-1- (2-phenyl-5-trifluoromethyl-oxazole-4-carboxylic acid (pyridine-2-sulfoniP-azepane-4-ylcarbamoin-buty-phenamide. (to) . { (S) -3-Methyl-1 - [3-hydroxy-1- (pyridine-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 2-Phenyl-5-trifluoromethyl-oxazole-4-carboxylic acid amide The title compound was prepared following the procedure of Example 28b, but using 2-phenyl-5-trifluoromethyl-oxazole-4-carboxylic acid instead of benzofuran-2-carboxylic acid: MS (El): 623 (M +). (b) { (S) -3-Methyl-1 - [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 2-Phenyl-5-trifluoromethyl-oxazole-4-carboxylic acid amide The title compound was prepared following the procedure of Example 1 i, but using the. { (S) -3-methyl-1- [3-hydroxy-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 2-phenyl-5-trifluoromethyl-oxazole-4-carboxylic acid amide of Example 126a: 1 H NMR (CDCl 3): d 1.0 (m, 6H), 1.5-2.2 (m, 6H), 2.2 (m, 2H), 2.7 (m, 1 H), 3.8 (m, 1 H); 4.1 (m, 1 H), 4.7 (m, 2H), 4.8 (m, 1H), 5.2 (m, 1 H), 7.4-8.0 (m, 8H); 8.7 (m, 1 H); MS (El): 621 (M +, 100%). The diastereomeric mixture was separated by CLAP to provide the fastest eluting diastereomer; MS (El): 622 (M + H \ 100%) and the slowest eluting diastereomer; MS (EI) 622 (M + H +, 100%).

EXAMPLE 127 Preparation of. { (SM - (1-methanesulfonyl-3-oxo-azepan-4-ylcarbamoyl) 13-methyl-buty-phenamide quinoline-2-carboxylic acid The title compound was prepared following the procedure of Example 75, but using methanesulfonyl chloride in place of thiazole-2-sulfonyl chloride and 2-quinoline-carboxylic acid in place of benzofuran-2-carboxylic acid. The residue was purified by CLAP. First diastereomer eluted with EM (M + H +): 475.2; 1 H NMR (400 MHz, CDCl 3,): • 8.65 (d, 1 H), 8.35-8.28 (q, 2 H), 8.20-8.18 (d, 1 H), 7.91-7.89 (d, 1 H), 7.80- 7.78 (t, 1 H), 7.67-7.65 (t, 1 H), 7.10 (d, 1 H), 5.08 (m, 1 H), 4.73 (m, 1 H), 4.56-4.51 (d, 1 H) ), 4.00 (m, 1 H), 3.67-3.62 (d, 1 H), 2.91 (s, 3H), 2.70 (m, 1 H), 2.32-2.10 (m, 2H), 1.95-1.40 (m, 5H), 1.02-1.00 (m, 6H); and the second diastereomer eluted: MS (M + H +): 475.2 EXAMPLE 128 Preparation of. { (S) -1 - (1-methanesulfonyl-3-oxo-azepan-4-ylcarbamoy-3-methyl-buty-phenylideamide of 1-methyl-1 H-indole-2-carboxylic acid The title compound was prepared following the procedure of Example 75, but using methanesulfonyl chloride and N-methylindole-2-carboxylic acid in place of benzofuran-2-carboxylic acid. The residue was purified by CLAP. First eluted diastereomer MS (M + H +): 477.2; 1 H NMR (400 MHz, CDCl 3,): • 7.65-7.63 (d, 1H), 7.39-7.33 (m, 2H), 7.17-7.14 (t, 1 H), 6.98-6.95 (m, 2H) 6.65 (d , 1 H), 5.08 (m, 1 H), 4.68 (m, 1H), 4.56-4.52 (d, 1 H), 4.03 (m, 4H), 3.67-3.63 (d, 1 H), 2.92 (s) , 3H), 2.71 (m, 1 H), 2.32-2.10 (m, 2H), 1.95-1.40 (m, 5H), 1.02-1.00 (d, 6H); and the second diastereomer eluted: .EM (M + H +): 477.2 EXAMPLE 129 Preparation of (f (S) -1 - (1-methanesulfonyl-3-oxo-azepan-4-ylcarbamop-3-methyl-butylcarbamoyl-methylamide of furan-2-carboxylic acid The title compound was prepared following the procedure of Example 75, but using methanesulfonyl chloride in place of thiazole-2-sulfonyl chloride, and N- (2-furan-carbonyl) -glycine acid in place of benzofuran-2-acid. carboxylic The residue was purified by CLAP. First diastereomer eluted with EM (M + H +): 471.2; 1 H NMR (400 MHz, CDCl 3,): • 7.50 (m, 1H), 7.15 (m, 1H), 7.05 (m, 1H), 6.90 (d, 1 H) 6.55 (m, 2H), 5.08 (m, 1 H), 4.55 (m, 2H), 4.12 (m, 2H), 4.05 (m, 1 H), 3.70 (d, 1 H), 2.92 (s, 3H), 2.75 (m, 1H), 2.20- 1.40 (m, 7H), 0.95 (m, 6H); and the second diastereomer eluted: MS (M + H +): 471.4 EXAMPLE 130 Preparation of 5-methoxybenzofuran-2-carboxylic acid ((5- (1-methanesulfonyl-3-oxo-azepan-4-ylcarbamoyl-3-methyl-b-tyl-amide 5-methoxybenzofuran-2-carboxylic acid The title compound was prepared following the procedure of Example 75, but using methanesulfonyl chloride in place of thiazole-2-sulfonyl chloride and 5-methoxybenzofuran-2-carboxylic acid in place of benzofuran-2-carboxylic acid. The residue was purified by CLAP. First eluted diastereomer MS (M + H +): 494.2; 1 H NMR (400 MHz, CDCl 3,): • 7.42-7.40 (d, 2H), 7.08-6.94 (m, 4H), 5.10 (m, 1 H), 4.71 (m, 1 H), 4.56-4.52 (d , 1 H), 4.02 (m, 1 H), 3.86 (s, 3H), 3.68-3.63 (d, 1 H), 2.92 (s, 3H), 2.72 (m, 1 H), 2.30-1.15 (m , 2H), 1.95-1.40 (m, 5H), 0.99 (d, 6H); and the second diastereomer eluted: .EM (M + H +): 494.2 EXAMPLE 131 Preparation of T (S) -1 - (1-methanesulfonyl-3-oxo-azepan-4-ylcarbamoyl) -3-methyl-butyl-amide of quinoxaline-2-carboxylic acid The title compound was prepared following the procedure of Example 75, but using methanesulfonyl chloride in place of thiazole-2-sulfonyl chloride and quinoxaline-2-carboxylic acid in place of benzofuran-2-carboxylic acid. The residue was purified by CLAP. First eluted diastereomer MS (M + H +): 476.2; 1 H NMR (400 MHz, CDCl 3,): • 9.66 (s, 1H), 8.38 (d, 1H), 8.20-8.18 (m, 2H), 7.88 (m, 2H), 7.01 (d, 1H), 5.10 ( m, 1 H), 4.77 (m, 1 H), 4.57-4.52 (d, 1H), 4.08-4.00 (m, 1 H), 3.69-3.64 (d, 1 H), 2.92 (s, 3H), 2.71 (m, 1 H), 2.42-2.15 (m, 2H), 1.95-1.42 (m, 5H), 1.02-1.01 (d, 6H); and the second diastereomer eluted: .EM (M + H +): 476.2 EXAMPLE 132 Preparation of f (S) -3-methyl-1-r3-oxo-1- (pyridine-2-sulfonyl) -azepan-4-ylcarbamoyl-buti-p -amide of 5- (4-chloro-phenyl) -furan- 2-carboxylic (to) . { (S) -3-Methyl-1 - [3-hydroxy-1 - (pyridine-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 5- (4-chloro-phenyl) -furan-2-carboxylic acid amide The title compound was prepared following the procedure of Example 28b, but using 5- (4-chlorophenyl) -2-furoic acid instead of the acid benzofuran-2-carboxylic acid: MS (EI) 590 (M + H +). (b) { (S) -3-Methyl-1 - [3-OXO-1 - (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 5- (4-chloro-phenyl) -furan-2-carboxylic acid amide The title compound was prepared following the procedure of Example 1, but using the. { (S) -3-methyl-1- [3-hydroxy-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 5- (4-chloro-phenyl) -furan-2-carboxylic acid amide of Example 132a: 1 H NMR (CDCl 3): d 1.0 (m, 6H), 1.5-2.1 (m, 5H), 2.2 (m, 2H ), 2.7 (m, 1H), 3.7 (d, 1H), 4.0 (m, 1H), 4.7 (m, 2H), 5.0 (m, 1 H), 6.7 (m, 1 H), 7.2 (m, 1 H), 7.3 (m, 2H), 7.5 (m, 1 H), 7.7 (m, 2H), 8.0 (m, 2H), 8.7 (m, 1 H); MS (El): 587 (M +, 80%).

The diastereomeric mixture was separated by CLAP to provide the fastest eluting diastereomer; MS (El): 587 (M + H +, 100%) and the slowest eluting diastereomer; MS (EI) 587 (M + H +, 100%).

EXAMPLE 133 Preparation of (S) -2-r2- (4-methoxy-phenyl-acetylamino) -4-methyl-pentanoic acid (1-methanesulfonyl-3-oxo-azepan-4-ill-amide) The title compound was prepared following the procedure of Example 75, but using 4-methanesulfonyl chloride in place of thiazole-2-sulfonyl chloride and 2- (4-methoxyphenyl) -acetic acid in place of benzofuran-2-carboxylic acid . The residue was purified by CLAP. First diastereomer eluted with EM (M + H +): 468.2; 1 H NMR (400 MHz, CDCl 3 1): - 7.19-7.17 (d, 2H), 6.90-6.88 (d, 3H), 5.83-5.81 (d, 1H), 5.00 (m, 1 H), 4.53-4.40 (m , 2H), 4.03-3.99 (m, 1 H), 3.81 (s, 3H), 3.66-3.61 (d, 1H), 3.53 (s, 2H), 2.91 (s, 3H), 2.73 (t, 1 H) ), 2.22-2.10 (m, 2H), 1.99 (m, 1 H), 1.62-1.35 (m, 4H), 0.90-0.88 (d, 6H); and the second diastereomer eluted: .EM (M + H +): 468.2 EXAMPLE 134 Preparation of f (S -1 -M - (2-cyanobenzenesulfonyl) -3-oxo-azepan-4-ylcarbamoin-3-methyl-but-p-phenoxy-quinoline-2-carboxylic acid The title compound was prepared following the procedure of Example 75, but using 2-cyanobenzenesulfonyl chloride in place of thiazole-2-sulfonyl chloride and quinoline-2-carboxylic acid in place of benzofuran-2-carboxylic acid. The residue was purified by CLAP. First eluted diastereomer MS (M + H +): 562.2; 1 H NMR (400 MHz, CDCl 3,): • 8.65 (d, 1 H), 8.48-8.40 (q, 2H), 8.25-8.10 (q, 2H), 7.91-7.65 (m, 6H); and the second diastereomer eluted: 7.12 (d, 1 H), 5.10 (m, 1 H), 4.73 (m, 1 H), 4.61-4.56 (d, 1 H), 4.20 (m, 1 H), 3.73- 3.68 (d, 1 H), 2.80 (m, 1 H), 2.27 (m, 2H), 1.91-1.40 (m, 5H), 1.03-1.01 (m, 6H); and the second diastereomer eluted: MS (M + H +): 562.2 EXAMPLE 135 Preparation of (1-methyl-1 H-indole-2-carboxylic acid (f (S) -1 -f1 - (2-cyano-benzenesulfoniD-3-oxo-azepane-4-ylcarbamoin-3-methyl-buty-phenyl acid) The title compound was prepared following the procedure of Example 75, but using 2-cyanophenylsulfonyl chloride in place of thiazole-2-sulfonyl chloride and N-methylindole-2-carboxylic acid in place of benzofuran-2-carboxylic acid. The residue was purified by CLAP.

First diastereomer eluted with EM (M + H +): 564.2; 1 H NMR (400 MHz, CDCl 3,): • 8.13 (d, 1 H), 7.89 (d, 1 H), 7.77-7.67 (m, 3H), 7.38-7.16 (m, 4H), 6.97 (s, 1H) 6.70 (d, 1 H), 5.05 (m, 1H), 4.70-4.60 (m, 1 H), 4.55-4.50 (d, 1H), 4.07 (m, 1H), 4.05 (s, 3H), 3.76-3.71 (d, 1 H), 2.75 (m, 1 H), 2.30 (m, 2H), 2.00-1.45 (m, 5H), 1.00 (d, 6H); and the second diastereomer eluted: .EM (M + H +): 564.2 EXAMPLE 136 Preparation of. { [S S] -1-H- (2-cyano-benzenesulfoniP-3-oxo-azepan-4-ylcarbamoin-3-methyl-butylcarbamoiP-methylamide of furan-2-carboxylic acid The title compound was prepared following the procedure of Example 75, but using 2-cyanophenylsulfonyl chloride in place of thiazole-2-sulfonyl chloride and N- (2-furan-carbonyl) -glycine acid instead of benzofuran-2 acid. -carboxylic The residue was purified by CLAP.

First eluted diastereomer MS (M + H +): 558.2; 1 H NMR (400 MHz, CDCl 3,): • 8.14-8.12 (d, 1 H), 7.91-7.90 (d, 1 H), 7.80-7.72 (m, 2H), 7.48 (s, 1 H), 7.14 (d, 2H), 6.98 (d, 1) H) 6.80 (d, 1 H), 6.52-6.51 (t, 1 H), 5.03 (m, 1 H), 4.60-4.53 (m, 2H), 4.17-4.14 (m, 3H), 3.74-3.69 ( d, 1 H), 2.80 (m, 1 H), 2.25 (m, 2H), 2.00-1.40 (m, 5H), 1.03-1.01 (m, 6H); and the second diastereomer eluted: .EM (M + H +): 558.2 EXAMPLE 137 Preparation of. { (SM-M - (2-cyano-benzenesulfoniP-3-oxo-azepan-4-ylcarbamoyl-3-methyl-buty-p-5-methoxybenzofuran-2-carboxylic acid amide The title compound was prepared following the procedure of Example 75, but using 2-cyanophenylsulfonyl chloride in place of thiazole-2-sulfonyl chloride and 5-methoxybenzofuran-2-carboxylic acid in place of benzofuran-2-carboxylic acid. The residue was purified by CLAP. First eluted diastereomer MS (M + H +): 581.4; 1 H NMR (400 MHz, CDCl 3,): • 8.154-8.13 (d, 1 H), 7.92-7.90 (d, 1 H), 7.81-7.74 (m, 2H), 7.42-7.40 (m, 2H), 7.08 -7.03 (m, 3H), 6.96 (d, 1 H) 5.10 (m, 1 H), 4.72-4.60 (m, 2H), 4.17 (d, 1 H), 3.85 (s, 3H), 3.75-3.70 (d, 1 H), 2.83-276 (t, 1 H), 2.27 (m, 2H), 1.92-1.51 (m, 5H), 1.02-1.01 (m, 6H); and the second diastereomer eluted: .EM (M + H +): 581.2 EXAMPLE 138 Preparation of. { (SM-H - (2-cyano-benzenesulfonium-3-oxo-azepane-4-ylcarbamoy-3-methyl-buty-phenamine-2-carboxylic acid amide The title compound was prepared following the procedure of Example 75, but using 2-cyanophenylsulfonyl chloride in place of thiazole-2-sulfonyl chloride and quinoxaline-2-carboxylic acid in place of benzofuran-2-carboxylic acid. The residue was purified by CLAP. First eluted diastereomer MS (M + H +): 563.2; 1 H NMR (400 MHz, CDCl 3,): • 9.65 (s, 1 H), 8.40 (m, 1 H), 8.22-8.10 (m, 3 H), 7.90-7.22 (m, 5 H), 7.0 (d, 1 H ), 5.10 (m, 1 H), 4.75 (m, 1H), 4.65-4.60 (d, 1H), 4.20-4.10 (m, 1H), 3.72-3.70 (d, 1 H), 2.70 (m, 1) H), 2.38 (m, 2H), 1.95-1.40 (m, 5H), 1.02 (m, 6H); and the second diastereomer eluted: .EM (M + H +): 563.2 EXAMPLE 139 Preparation of (S) -2-r2- (4-methoxy-pheny-p-acetylamino) -4-methyl-pentanoic acid ri- (2-cyano-benzenesulfoniP-3-oxo-azepan-4-ill-amide) The title compound was prepared following the procedure of Example 75, but using 2-cyanophenylsulfonyl chloride in place of thiazole-2-sulfonyl chloride and 2- (methoxyphenyl) -acetic acid in place of benzofuran-2-carboxylic acid. The residue was purified by CLAP. First eluted diastereomer MS (M + H +): 555.2; 1 H NMR (400 MHz, CDCl 3,): "8.14-8.12 (d, 1 H), 7.91-7.89 (d, 1 H), 7.79-7.73 (m, 2H), 7.19-7.17 (d, 2H), 6.90 -6.88 (d, 3H) 5.80 (d, 1 H), 5.02 (m, 1 H), 4.59-4.55 (d, 1 H), 4.45-4.42 (m, 1 H), 4.18-4.15 (m, 1 H), 3.82 (s, 3H), 3.72-3.67 (d, 1 H), 3.53 (s, 2H), 2.82-2.79 (t, 1 H), 2.22 (m, 2H), 1.92 (m, 1 H) ), 1.60-1.30 (m, 4H), 0.91-0.89 (d, 6H); and the second diastereomer eluted: .EM (M + H +): 555.2 EXAMPLE 140 Preparation of. { f (SM -f-1 - (4-methoxy-benzenesulfoniD-3-oxo-azepane-4-Mcarbamoy-3-methyl-buty-phenamide of quinoxaline-2-carboxylic acid The title compound was prepared following the procedure of Example 75, but using 4-methoxybenzenesulfonyl chloride in place of thiazole-2-sulfonyl chloride, and 2-quinoline-carboxylic acid in place of benzofuran-2-carboxylic acid. The residue was purified by CLAP. First eluted diastereomer MS (M + H +): 567.2; 1 H NMR (400 MHz, CDCl 3,): • 8.72-8.61 (d, 1 H), 8.35-8.28 (q, 2H), 8.21-8.18 (d, 1 H), 7.91-7.60 (m, 5H), 7.10 -6.99 (m, 3H) 5.05 (m, 1 H), 4.73 (m, 1 H), 4.59-4.52 (d, 1 H), 4.00 (m, 1 H), 3.88 (s, 3H), 3.45- 3.38 (d, 1 H), 2.42 (m, 1 H), 2.30-1.35 (m, 7H), 1.03-1.01 (m, 6H); and the second diastereomer eluted: .EM (M + H +): 567.2.

EXAMPLE 141 Preparation of. { f (S) -1 -f1 - (4-methoxy-benzenesulfoniD-3-oxo-azepan-4-yl-carbamoin-3-methyl-buty-p-amide of 1.methyl-1 H-indole-2-carboxylic acid The title compound was prepared following the procedure of Example 75, but substituting thiazole-2-sulfonyl chloride with 4-methoxyphenylsulfonyl chloride and benzofuran-2-carboxylic acid with N-methyl-indole-2-carboxylic acid. The residue was purified by means of CLAP. First eluted diastereomer: MS (M + H +): 569.2; 1 H NMR (400 MHz, CDCl 3): d-7.78-7.72 (d, 2H), 7.70-7.65 (d, 1 H), 7.42-7.70 (m.2H), 7.17-7.14 (t, 1 H), 7.05-6.95 (m, 4H), 6.65 (d, 1 H), 5.05 (m, 1 H), 4.70-4.50 (m, 2H), 4.03 (s, 3H), 3.88 (s, 3H), 3.45- 3.40 (d, 1 H), 2.45 (m, 1 H), 2.30-2.10 (m, 2H), 1.90-1.35 (m, 6H); and the second diastereomer eluted: 1.00 (d, 6H); and the second diastereomer eluted: MS (M + H +) 569.2.

EXAMPLE 142 Preparation of (. {(SM (4- (Methoxy-benzenesulfon-P-3-oxo-azepan-4-H-carbamoin-3-methyl-butylcarbamoi-Pethyl) -amide of furan-2-acid carboxylic The title compound was prepared following the procedure of Example 75, but substituting the thiazole-2-sulfonyl chloride with 4-methoxyphenylsulfonyl chloride and the benzofuran-2-carboxylic acid with N- (2-furan-carbonyl) -glycine. The residue was purified by means of CLAP. First eluted diastereomer: MS (M + H +): 563.2; 1 H NMR (400 MHz, CDCI): d 7.74-7.72 (d, 2H), 7.47 (s, 1 H), 7.15-6.99 (m, 4H), 6.91 (d, 1 H), 6.70 (d, 1 H), 6.52-6.51 (m, 1 H), 5.01 (m, 1 H), 4.53-4.49 (m, 2H), 4.17-4.14 (m, 2H), (m, 2H), 4.00-3.90 (m , 1H), 3.88 (s, 3H), 3.45-3.41 (d, 1H), 2.47 (m, 1 H), 2.17 (m, 2H), 1.85-1.40 (m, 5H), 0.95 (m, 6H); and the second diastereomer eluted: MS (M + H +) 563.2.

EXAMPLE 143 Preparation of. { f (SM-H - (4-methoxy-benzenesulfoniD-3-oxo-azepan-4-H-carbamoin-3-methyl-butiP-amide of 5-methoxybenzofuran-2-carboxylic acid The title compound was prepared following the procedure of Example 75, but substituting thiazole-2-sulfonyl chloride with 4-methoxyphenylsulfonyl chloride, and benzofuran-2-carboxylic acid with 5-methoxybenzofuran-2-carboxylic acid. The residue was purified by means of CLAP. First eluted diastereomer: MS (M + H +): 586.2; 1 H NMR (400 MHz, CDCl 3): 7. 75-7.73 (d, 2H), 7.42-7.40 (m, 2H), 7.08-6.99 (m, 5H), 6.91 (d, 1 H), 5.05 (m, 1 H), 4.70-4.55 (m, 2H) ), 4.05-4.00 (m, 1 H), 3.89 (s, 3H), 3.86 (s, 3H), 3.45-3.40 (d, 1 H), 2.50-2.40 (m, 1 H), 2.30-2.10 ( m, 2H), 1.90-1.35 (m, 5H), 1.01 (m, 6H); and the second diastereomer eluted: MS (M + H +) 586.2.

EXAMPLE 144 Preparation of. { f (SM-H - (4-methoxy-benzenesulfonium-3-oxo-azepan-4-yl-carbamoyl-3-methyl-buty-phenamine-2-carboxylic acid amide The title compound was prepared following the procedure of Example 75, but substituting thiazole-2-sulfonyl chloride with 4-methoxyphenylsulfonyl chloride, and benzofuran-2-carboxylic acid with quinoxaline-2-carboxylic acid. The residue was purified by means of CLAP. First eluted diastereomer: MS (M + H +): 568.2; 1 H NMR (400 MHz, CDCl 3): d 9.66 (s, 1H), 8.40- 8.35 (m, 1H), 8.19 (m, 2H), 7.88 (m, 2H), 7.75-7.73 (d, 2H), 7.02-6.90 (m, 3H), 5.10-5.05 (m, 1H), 4.75 (m, 1 H), 4.60-4.55 (d, 1 H), 4.05-3.95 (m, 1 H), 3.89 ( s, 3H), 3.45-3.41 (d, 1 H), 2.45 (m, 1 H), 2.30.2.10 (m, 2H), 1.95-1.40 (m, 5H), 1.04-1.02 (d, 6H); and the second diastereomer eluted: MS (M + H +) 568.2.

EXAMPLE 145 Preparation of (S) -2-f2- (4-methoxy-pheny-p-acetylamino) -4-methyl-pentanoic acid f 1- (4-methoxy-benzenesulfoniP-3-oxo-azepan-4-yn-amide) The title compound was prepared following the procedure of Example 75, but substituting thiazole-2-sulfonyl chloride with 4-methoxyphenylsulfonyl chloride, and benzofuran-2-carboxylic acid with 2- (4-methoxyphenyl) -acetic acid. The residue was purified by means of CLAP. First eluted diastereomer: MS (M + H +): 560.4; 1 H NMR (400 MHz, CDCl 3): d 7.74- 7.71 (d, 2H), 7.19-7.17 (d, 2H), 7.01-6.99 (d, 2H), 6.90-6.88 (d, 2H), 6.85 (d , 1H), 5.81 (d, 1 H), 4.99 (m, 1H), 4.55-4.44 (m, 2H), 3.97 (m, 1H), 3.88 (s, 3H), 3.81 (s, 3H), 3.53 (s, 2H), 3.43-3.38 (d, 1H), 2.43 (t, 1H), 2.14 (m, 2H), 1.85-1.35 (m, 5H), 0.90-0.89 (d, 6H); and the second diastereomer eluted: MS (M + H +) 560.2.

EXAMPLE 146 Preparation of. { f (S) -1 -f1 - (4-Fluoro-benzenesulfon-8D-3-oxo-azepan-4-yl-carbamoin-3-methyl-buty-p-1-methyl-1H-indole-2-carboxylic acid amide) The title compound was prepared following the procedure of Example 75, but substituting thiazole-2-sulfonyl chloride with 4-fluorophenylsulfonyl chloride, and benzofuran-2-carboxylic acid with N-methyl-indole-2-carboxylic acid. The residue was purified by means of CLAP. First eluted diastereomer: MS (M + H +): 557.2; 1 H NMR (400 MHz, CDCl 3): 7.84-7.80 (m, 2H), 7.66-7.65 (d, 1 H), 7.40-7.14 (m, 5H), 6.95 (m, 2H), 6.65-6.63 (d , 1 H), 5.07 (m, 1H), 4.68-4.55 (m, 2H), 4.04 (s, 3H), 3.48-3.43 (d, 1 H), 2.49 (m, 1 H), 2.25 (m, 2H), 1.89-1.38 (m, 6H); and the second diastereomer eluted: 1.01 (d, 6H); and the second diastereomer eluted: MS (M + H +) 557.4.

EXAMPLE 147 Preparation of. { f (S) -1 -f1 - furan-2-carboxylic acid (4-fluoro-benzenesulfoniD-3-oxo-azepan-4-yl-carbamoyl-3-methyl-2-butylcarbamoyl-p-methyl) -amide The title compound was prepared following the procedure of Example 75, but substituting thiazole-2-sulfonyl chloride with 4-fluorophenylsulfonyl chloride, and benzofuran-2-carboxylic acid with N- (2-furan-carbonyl) -glycine . The residue was purified by means of CLAP. First eluted diastereomer: MS (M + H +): 551.4; 1 H NMR (400 MHz, CDCl 3): 7.81 (m, 2H), 7.48 (s, 1 H), 7.27-7.16 (m, 3H), 7.05 (m, 1 H), 6.90 (d, 1 H), 6.52 (m, 2H), 5.00 (m, 1 H) , 4.60-4.48 (m, 2H), 4.14 (m, 2H), 4.00-3.90 (d, 1 H), 3.48-3.44 (d, 1 H), 2.50 (m, 1 H), 2.20 (m, 2H ), 1.90-1.40 (m, 5H), 0.95 (m, 6H); and the second diastereomer eluted: MS (M + H +) 551.2.

EXAMPLE 148 Preparation of. { f (S) -1-f 1- (4-Fluoro-benzenesulfonyl-3-oxo-azepan-4-yl-carbamoin-3-methyl-buty-p-5-methoxybenzofuran-2-carboxylic acid) The title compound was prepared following the procedure of Example 75, but substituting thiazole-2-sulfonyl chloride with 4-fluorophenylsulfonyl chloride, and benzofuran-2-carboxylic acid with 5-methoxybenzofuran-2-carboxylic acid. The residue was purified by means of CLAP.

First eluted diastereomer: MS (M + H +): 574.2; "NMR (400 MHz, CDCl 3): d 7. 84-7.81 (m, 2H), 7.42-7.40 (m, 2H), 7.27-7.22 (m, 2H), 7.08-7.04 (m, 3H), 6.93 (d, 1 H), 5.10-5.02 (m, 1 H), 4.69-4.55 (m, 2H), 4.05-4.00 (m, 1 H), 3.86 (s, 3H), 3.47-3.43 (d, 1 H), 2.49 (m, 1 H), 2.24 ( m, 2H), 1.90-1.40 (m, 5H), 1.01 (m, 6H); and the second diastereomer eluted: MS (M + H +): 574.2.

EXAMPLE 149 Preparation of. { f (S) -1-1 1 - (4-fluoro-benzenesulfonyl) -3-oxo-azepan-4-yl-carbamoin-3-methyl-buty-phenamine-2-carboxylic acid amide The title compound was prepared following the procedure of Example 75, but substituting thiazole-2-sulfonyl chloride with 4-fluorophenylsulfonyl chloride, and benzofuran-2-carboxylic acid with quinoxaline-2-carboxylic acid. The residue was purified by means of CLAP. First eluted diastereomer: MS (M + H +): 556.2; 1 H NMR (400 MHz, CDCl 3): d 9.66 (s, 1 H), 8.40-8.35 (d, 1 H), 8.21-8.18 (m, 2 H), 7.90-7.81 (m, 4 H), 7.27-7.22. (m, 2H), 6.97 (d, 1 H), 5.10-5.02 (m, 1 H), 4.75 (m, 1 H), 4.59-4.55 (d, 1 H), 4.05-4.39 (m, 1 H) ), 3.48-3.44 (d, 1 H), 2.49 (m, 1 H), 2.32-2.10 (m, 2H), 1.90-1.40 (m, 5H), 1.03-1.02 (d, 6H); and the second diastereomer eluted: MS (M + H +) 556.2.

EXAMPLE 150 Preparation of (S) -2-f2- (4-methoxy-phenyl) -acetylamino) -4-methyl-pentanoic acid ri- (4-fluoro-benzenesulfoniP-3-oxo-azepan-4-in-amide) The title compound was prepared following the procedure of Example 75, but substituting thiazole-2-sulfonyl chloride with 4-fluorophenylsulfonyl chloride, and benzofuran-2-carboxylic acid with 2- (4-methoxyphenyl) -acetic acid. The residue was purified by means of CLAP. First eluted diastereomer: MS (M + H +): 548.2; 1 H NMR (400 MHz, CDCl 3): d 7.83- 7.80 (m, 2H), 7.27-7.17 (m, 4H), 6.90-6.8 (d, 3H), 5.85 (d, 1 H), 4.98 (m, 1 H), 4.55-4.43 (m, 2H), 4.00-3.97 (m, 1 H), 3.81 (s, 3H), 3.53 (s, 2H), 3.43-3.41 (d, 1H), 2.48 (t, 1 H), 2.17-2.14 (m, 2H), 1.90-1.30 (m, 5H), 0.90-0.88 (d, 6H); and the second diastereomer eluted: MS (M + H +): 548.4.

EXAMPLE 151 Preparation of. { (SH-H - (3-Chloro-benzenesulfonyl-3-oxo-azepane-4-yl-carbamoyl-3-methyl-butyl) -amide of benzofuran-2-carboxylic acid (a) Ter-butyl acid ester. { (S) -1- [1- (3-Chloro-benzenesulfonyl) -3-hydroxy-azepan-4-ylcarbamoyl] -3-methyl-butyl} -carbamic To a solution of the compound of example 2g (2.50 g, 7.29 mmoles) in DCE (100 ml), was added P-NMM (4.0 g) and 3-chlorobenzenesulfonyl chloride (1.85 g, 8.75 mmol). After stirring at room temperature overnight, the solution was filtered. The filtrate was concentrated to yield the title compound as a white solid (3.13 g, 83.3%); EM: 539. 78 (M + Na) +. (b) [1- (3-Chloro-benzenesulfonyl) -3-hydroxy-azepan-4-yl] -amide of (S) -2-amino-4-methyl-pentanoic acid To a stirred solution of the compound of the example 151a (1.0 g, 1. 93 mmol) in methanol (10 ml), HCl (4M in dioxane, 10 ml) was added.

After stirring at room temperature for 3 hours, the solution was concentrated to give a white solid. To a solution of the white solid (0.68 g, 1.50 mmol, 78%) in methanol (37 ml), P-CO3 (2.85 g, 2.63 mmol / g) was added. After stirring 2 hours, the solution was filtered and concentrated to yield the title compound as a white solid (0.59 g, 1.42 mmol, 95%); MS: 417.86 (M + H +). (c). { (S) -1- [1- (3-Chloro-benzenesulfonyl) -3-hydroxy-azepan-4-ylcarbamoyl] -3-methyl-butyl} benzofuran-2-carboxylic acid amide To a solution of the compound of example 151b (0.14 g, 0.33 mmol) in CH2Cl2 (20 ml), was added benzofuran-2-carboxylic acid (0.81, 0.50 mmol), 1-hydroxybenzotriazole ( 0.77 g, 0.57 mmol) and P-EDC (0.67 g, 1 mmol / g) in CH2Cl2 (10 mL). After stirring overnight at room temperature, the solution was treated with tisamine (0.45 g, 3.75 mmol / g). After stirring another 2 hours, the solution was filtered and concentrated to give the title compound as a white solid (122 mg, 65%); MS (ESI): 562.2 (M + H +). (d). { (S) -1- [1- (3-Chloro-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} benzofuran-2-carboxylic acid amide To a stirred solution of the compound of example 151c (122 mg, 0.22 mmol) in dichloromethane (4 ml), Dess-Martin reagent (185 mg, 0.44 mmol) was added. After stirring at room temperature for 2 hours, sodium thiosulfate solution (2 ml of 10% solution in water) and saturated aqueous sodium bicarbonate solution (2 ml) were added to the solution simultaneously. The aqueous layer was extracted with dichloromethane (2x). The organic phases were combined and washed with brine; dried (MgSO4), filtered and concentrated. The residue was purified by means of CLAP to produce the first diastereomer eluted as a white solid (62.7 mg, 51.6%), MS (ESI): 560.2 (M + H +), and the second diastereomer eluted as a white solid (40.2 mg , 33.1%); MS (ESI): 560.2 (M + H +).

EXAMPLE 152 Preparation of. { 5-methoxybenzofuran-2-carboxylic acid (3-chloro-benzenesulfonyl) -3-oxo-azepan-4-yl-carbamoin-3-methyl-buty-phenamide Following the procedure of example 151 cd, but replacing the benzofuran-2-carboxylic acid of example 151c with 5-methoxybenzofuran-2-carboxylic acid, the title compound was prepared, which was separated by means of CLAP to give the first diastereomer eluted as a white solid (64.4 mg, 50.3%); MS (ESI) 590.2 (M + H +), and the second diastereomer eluted as a white solid (44.4 mg, 34.7%); MS (ESI): 590.2 (M + H +).

EXAMPLE 153 Preparation of. { (7-Methoxybenzofuran-2-carboxylic acid 3-chloro-benzenesulfoniP-3-oxo-azepan-4-yl-carbamoyl-3-methyl-b? -phenylideamide) Following the procedure of example 151 cd, but replacing the benzofuran-2-carboxylic acid of example 151c with 7-methoxybenzofuran-2-carboxylic acid, the title compound was prepared, which was separated by means of CLAP to give the first diastereomer eluted as a white solid (51.1 mg, 39.9%); MS (ESI) 590.2 (M + H +), and the second diastereomer eluted as a white solid (36.7 mg, 28.7%); MS (ESI): 590.2 (M + H +).

EXAMPLE 154 Preparation of. { (S) -1-M- (3-Chloro-benzenesulfonyl-3-oxo-azepan-4-yl-carbamoin-3-methyl-buty-phenamide 5,6-dimethoxybenzofuran-2-carboxylic acid Following the procedure of example 151 c-d, but replacing the benzofuran-2-carboxylic acid of example 151c with acid ,6-dimethoxybenzofuran-2-carboxylic acid, was prepared. the title compound, which was separated by means of CLAP to give the first diastereomer eluted as a white solid (51.1 mg, 39.9%); MS (ESI) 622.2 (M + H +), and the second diastereomer eluted as a white solid (36.7 mg, 28.7%); MS (ESI): 622.2 (M + H +).

EXAMPLE 155 Preparation of. { (S) -1-H - (3-chloro-benzenesulfonyl) -3-oxo-azepan-4-yl-carbamoin-3-methyl-butyl-p-3-methylbenzofuran-2-carboxylic acid Following the procedure of example 151 cd, but substituting the benzofuran-2-carboxylic acid from step 151 c with 3-methylbenzofuran-2-carboxylic acid, the title compound was prepared, which was separated by means of CLAP to give the first diastereomer eluted as a white solid (78.6 mg, 63.1%); MS (ESI) 574.2 (M + H +), and the second diastereomer eluted as a white solid (40.7 mg, 32.6%); MS (ESI): 574.2 (M + H +).

EXAMPLE 156 Preparation of ((SH-H- (3-chloro-benzenesulfonyl-3-oxo-azepan-4-yl-carbamoyl-3-methyl-buti-p-amide of benzoyltiofen-S-carboxylic acid Following the procedure of example 151 cd, but replacing the benzofuran-2-carboxylic acid from step 151 c with benzo [b] thiophene-2-carboxylic acid, the title compound was prepared, which was separated by means of CLAP to give the first diastereomer eluted as a white solid (41.0 mg, 32.8%); MS (ESI) 576.2 (M + H +), and the second diastereomer eluted as a white solid (31.0 mg, 24.8%); MS (ESI): 576.4 (M + H +).

EXAMPLE 157 Preparation of. { (SH-H - (3-chloro-benzenesulfonium-3-oxo-azepan-4-yl-carbamoin-3-methyl-butyl-p-1-methyl-1H-indole-2-carboxylic acid Following the procedure of example 151 cd, but substituting the benzofuran-2-carboxylic acid from step 151c with 1-methylindol-2-carboxylic acid, the title compound was prepared, which was separated by means of CLAP to give the first diastereomer eluted as a white solid (28.5 mg, 22.9%); MS (ESI) 573.2 (M + H +), and the second diastereomer eluted as a white solid (28.5 mg, 22.9%); MS (ESI): 573.2 (M + H +).

EXAMPLE 158 Preparation of Quinoxaline-2-carboxylic acid ((SH -f1 - (3-chloro-benzenesulfoniP-3-oxo-azepan-4-yl-carbamoin-3-methyl-buty-phenamide Following the procedure of example 151 cd, but substituting the benzofuran-2-carboxylic acid from step 151 c with quinoxaline-2-carboxylic acid, the title compound was prepared, which was separated by means of CLAP to give the first diastereomer eluted as a white solid (63.1 mg, 50.8%); MS (ESI) 572.2 (M + H +), and the second diastereomer eluted as a white solid (43.2 mg, 34.8%); MS (ESI): 572.2 (M + H +).

EXAMPLE 159 Preparation of. { (SH -f 1 - benzofuran-2-carboxylic acid 2-fluoro-benzenesulfoniP-3-oxo-azepan-4-yl-carbamoin-3-methyl-buti-p-phenyl) (a) Ter-butyl acid ester. { (S) -1- [1- (2-Fluoro-benzenesulfonyl) -3-hydroxy-azepan-4-yl-carbamoyl] -3-methyl-butyl} To a solution of the compound of example 2g (1.03 g, 3.00 moles) in DCE (20 ml), P-NMM (1.65 g, 3.64 mmol / g) and 2-fluorobenzenesulfonyl chloride (0.70 g, 3.60 mmol) were added. ). After stirring at room temperature overnight, the solution was filtered. The filtrate was concentrated to yield the title compound as a white solid (1.13 g, 75.1%); MS: 523.88 (M + Na) +. (b) [1- (2-Fluoro-benzenesulfonyl) -3-hydroxy-azepan-4-yl] amide of (S) -2-amino-4-methyl-pentanoic acid To a stirred solution of the compound of the example 159a (1.13 g, 2.25 mmol) in methanol (15 ml), HCl (4M in dioxane, 15 ml) was added. After stirring at room temperature for 3 hours, the solution was concentrated to give a white solid. To a solution of the white solid (1.11 g, 2.60 mmol, 75%) in methanol (50 ml), P-CO3 (5.70 g, 2.63 mmol / g) was added. After stirring 2 hours, the solution was filtered and concentrated to yield the title compound as a white solid (0.868 g, 2.16 mmol, 96%); MS: 401.96 (M + H +). (c). { (S) -1 - [1 - (2-Fluoro-benzenesulfonyl) -3-hydroxy-azepan-4-ylcarbamoyl] -3-methyl-butyl} benzofuran-2-carboxylic acid amide To a solution of the compound of example 159b (0.11 g, 0.26 mmol) in CH 2 Cl 2 (10 mL), benzofuran-2-carboxylic acid (64.7 mg, 0.39 mmol), 1-hydroxybenzotriazole was added. (61.1 g, 0.45 mmol) and P-EDC (0.53 g, 1 mmol / g) in CH2Cl2 (10 mL). After stirring overnight at room temperature, the solution was treated with tisamine (0.35 g, 3.75 mmol / g). After stirring another 2 hours, the solution was filtered and concentrated to yield the title compound as a white solid (103.5 mg, 70%); MS (ESI) 546.2 (M + H +). (d). { (S) -1 - [1 - (2-Fluoro-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} benzofuran-2-carboxylic acid amide To a stirred solution of the compound of example 159c (103.5 mg, 0.19 mmol) in dichloromethane (4 ml), Dess-Martin reagent (164.7 mg, 0.39 mmol) was added. After stirring at room temperature for 2 hours, sodium thiosulfate solution (2 ml of 10% aqueous solution) and saturated aqueous sodium bicarbonate solution (2 ml) were added to the solution simultaneously. The aqueous phase was extracted with dichloromethane (2x). The organic phases were combined and washed with brine; dried (MgSO4), filtered and concentrated. The residue was purified by means of CLAP to produce the first diastereomer eluted as a white solid (76.2 mg, 73.6%); MS (ESI) 544.2 (M + H +), and the second diastereomer eluted as a white solid (20.7 mg, 20.0%); MS (ESI) 544.4 (M + H +).

EXAMPLE 160 Preparation of 5-methoxybenzofuran-2-carboxylic acid ((S) -1-H- (2-fluoro-benzenesulfonyl-D-3-oxo-azepan-4-ylcarbacillin-3-methyl-buty-phenamide) Following the procedure of example 159 cd, but substituting the benzofuran-2-carboxylic acid from step 159c with 5-methoxybenzofuran-2-carboxylic acid, the title compound was prepared, which was separated by means of CLAP to give the first diastereomer eluted as a white solid (48.3 mg, 59.2%); MS (ESI): 574.2 (M + H +), and the second diastereomer eluted as a white solid (24.2 mg, 29.6%); MS (ESI): 574.2 (M + H +).

EXAMPLE 161 Preparation of. { (SH -f1 - (2-fluoro-benzenesulfonyl) -3-oxo-azepan-4-yl-carbamoyl-3-methyl-buty-p -amide of 7-methoxybenzofuran-2-carboxylic acid Following the procedure of example 159 cd, but replacing the benzofuran-2-carboxylic acid from step 159c with 7- methoxybenzofuran-2-carboxylic acid, the title compound was prepared, which was separated by means of CLAP to give the first diastereomer eluted as a white solid (47.7 mg, 58.5%); MS (ESI): 574.2 (M + H +), and the second diastereomer eluted as a white solid (27.7 mg, 33.9%).

EXAMPLE 162 Preparation of. { (5-fluoro-benzenesulfoniP-3-oxo-azepan-4-yl-carbamoip-3-methyl-buti-p-p-5-dimethoxybenzofuran-2-carboxylic acid Following the procedure of example 159 cd, but substituting the benzofuran-2-carboxylic acid from step 159c with 5,6-dimethoxybenzofuran-2-carboxylic acid, the title compound was prepared, which was separated by means of CLAP to give the first diastereomer eluted as a white solid; MS (ESI): 606.4 (M + H +), and the second diastereomer eluted as a white solid MS (ESI): 606.4 (M + H +).

EXAMPLE 163 Preparation of. { (3-Methylbenzofuran-2-carboxylic acid 2-fluoro-benzenesulfoniP-3-oxo-azepan-4-yl-carbamoip-3-methyl-buty-phenyl acid) Following the procedure of example 159 cd, but substituting the benzofuran-2-carboxylic acid from step 159c with 3-methylbenzofuran-2-carboxylic acid, the title compound was prepared, which was separated by means of CLAP to give the first diastereomer eluted as a white solid (50.5 mg, 63.7%); MS (ESI): 558.2 (M + H +), and the second diastereomer eluted as a white solid (20.6 mg); MS: 558.2 (M + H +).

EXAMPLE 164 Preparation of. { (SH-2- (2-fluoro-benzenesulfonyl) -3-oxo-azepane-4-yl-carbamoyl-3-methyl-buty-phenamide of benzorbltiophen-2-carboxylic acid Following the procedure of example 159 cd, but replacing the benzofuran-2-carboxylic acid from step 159c with benzo [b] thiophene-2-carboxylic acid, the title compound was prepared, which was separated by means of CLAP to give the first diastereomer eluted as a white solid (52.5 mg, 65.9%); MS (ESI): 560.2 (M + H +), and the second diastereomer eluted as a white solid (20.7 mg, 26.0%); MS (ESI): 560.2 (M + H) +.

EXAMPLE 165 Preparation of. { (H-Indole-1 H-indole-2-carboxylic acid (H - H - (2-fluoro-benzenesulfonyl) -3-oxo-azepan-4-yl-carbamoip-3-methyl-buty-phenyl) Following the procedure of example 159 cd, but replacing the benzofuran-2-carboxylic acid from step 159c with 1-methylindol-2-carboxylic acid, the title compound was prepared, which was separated by means of CLAP to give the first diastereomer eluted as a white solid (51.4 mg, 64.9%); MS (ESI): 557.2 (M + H +), and the second diastereomer eluted as a white solid (21.0 mg, 26.5%); MS 557.2 (M + H +).

EXAMPLE 166 Preparation of 3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-yl-1-acid amide (S) -4-Methyl-2- (1-oxy-pyridin-2-sulfonylamino) -pentanoic acid (a) [3-Hydroxy-1- (pyridin-2-sulfonyl) -azepan-4-yl] (4) -methyl-2- (1-oxy-pyridin-2) -amide -sulfonylamino) pentanoic acid To a solution of the compound of example 28a (0.1 g) in dichloromethane (10 ml) and saturated NaHCO3 solution, 2-pyridine sulfonyl chloride (0.9 ml) was added dropwise over 3 minutes. ). The reaction was stirred at room temperature for 30 minutes. By treatment and column chromatography, 9.2 mg of the title compound were obtained; MS (ESI) 541 (M + H +). (b) [3-Oxo-l - (pyridin-2-sulfonyl) -azepan-4-yl] (S) -4-methyl-2- (1-oxy-pyridinyl) amide 2-sulfonylamino) pentane The title compound was prepared following the procedure of Example 1, but using the compound of Example 166a: MS (ESI) 539 (M + H +).

EXAMPLE 167 Preparation of. { (SH -f 1 - Quinoxaline-2-carboxylic acid 2-fluoro-benzenesulfoniD-3-oxo-azepan-4-yl-carbamoy-3-methyl-buty-phenamide Following the procedure of example 159 cd, but substituting the benzofuran-2-carboxylic acid from step 159c with quinoxaline-2-carboxylic acid, the title compound was prepared, which was separated by means of CLAP to give the first diastereomer eluted as a white solid (49.7 mg, 62.9%); MS (ESI): 556.2 (M + H +), and the second diastereomer eluted as a white solid (19.9 mg, 25.1%); MS 556.4 (M + H +).

EXAMPLE 168 Preparation of. { (S) -3-methyl-1 -f3-oxo-1- (5-methoxybenzofuran-2-carboxylic acid (5-methoxybenzofuran-2-carboxylic acid) -thiophene-2-sulfonyl-P-azepan-4-ylcarbamoyl-buty-phenyl Following the procedure of Example 75 ad, but substituting the 2-thiazolesulfonyl chloride of Example 75a with 2-thiophenesulfonyl chloride, and the benzofuran-2-carboxylic acid of step 75c with 5-methoxybenzofuran-2-carboxylic acid, the title compound, which was purified by means of CLAP to give the first diastereomer eluted as a white solid (71 mg, 65%): MS (ESI) 562.2 (M + H +), and the second diastereomer eluted as a white solid (21.6 mg, 20.0%): MS (ESI): 562.2 (M + H +).

EXAMPLE 169 Preparation of. { (S) -3-methyl-1 - | "3-oxo-1 - (thiophen-2-sulfonyl-7-methoxybenzofuran-2-carboxylic acid 7-methoxybenzofuran-2-carboxylic acid thiophene-4-ylcarbamoyl-buty-phenyl Following the procedure of example 168, but substituting 5-methoxy-benzofuran-2-carboxylic acid with 7-methoxybenzofuran-2-carboxylic acid, the title compound was prepared, which was purified by means of CLAP to give the first diastereomer eluted as a white solid (88 mg, 80%): MS (ESI) 562.2 (M + H +), and the second diastereomer eluted as a white solid (18 mg, 16%), MS (ESI): 562.2 (M + H +).

EXAMPLE 170 Preparation of. { (S) -3-Methyl-1-r3-oxo-1 - (thiophen-2-sulfon-p-azepan-4-yl-carbamoin-buty-phenamide 5,6-D-methoxybenzofuran-2-carboxylic acid Following the procedure of example 168, but substituting 5-methoxy-benzofuran-2-carboxylic acid with 5,6-dimethoxybenzofuran-2-carboxylic acid, the title compound was prepared, which was purified by means of CLAP to give the first eluted diastereomer: MS (ESI) 594.2 (M + H +), and the second diastereomer eluted.

EXAMPLE 171 Preparation of. { (S) -3-methyl-1 -f3-oxo-1- (3-methylbenzofuran-2-carboxylic acid 3-methylbenzofuran-2-carboxylic acid thiophene-2-sulfoniD-azepan-4-yl-carbamoin-buty-phenyl Following the procedure of example 168, but substituting 5-methoxy-benzofuran-2-carboxylic acid with 3-methylbenzofuran-2-carboxylic acid, the title compound was prepared, which was purified by means of CLAP to give the first diastereomer eluted as a white solid (88 mg, 83%): MS (ESI) 546.2 (M + H +), and the second diastereomer eluted as a white solid (16 mg, 15%), MS (ESI): 546.2 (M + H +).

EXAMPLE 172 Preparation of. { (S) -3-Methyl-1-r3-oxo-1 - (thiophene-2-sulfonyl) -azepan-4-yl-carbamoyl-butyamidobenzylbothiophen-2-carboxylic acid Following the procedure of Example 168, but substituting 5-methoxybenzofuran-2-carboxylic acid with benzo [b] thiophene-2-carboxylic acid, the title compound was prepared, which was purified by means of CLAP to give the first diastereomer eluted as a white solid (43.4 mg, 41%): MS (ESI) 548.4 (M + H +), and the second diastereomer eluted as a white solid (33.4 mg, 31.5%), MS (ESI): 548.2 (M + H +).

EXAMPLE 173 Preparation of. { (S) -3-methyl-1 - | "3-oxo-1- (thiophene-2-sulfonyl) -azepan-4-yl-carbamoyl-buty-phenylideamide of 1-methyl-1 H-indole-2-carboxylic acid Following the procedure of example 168, but substituting 5-methoxybenzofuran-2-carboxylic acid with 1-methylindol-2-carboxylic acid, the title compound was prepared, which was separated by means of CLAP to give the first diastereomer eluted as a white solid (35.8 mg, 34.0%): MS (ESI) 545.2 (M + H +), and the second diastereomer eluted as a white solid (45.8 mg, 43%), MS (ESI): 545.2 (M + H +) .

EXAMPLE 174 Preparation of. { (S) -3-methyl-1 -f3-oxo-1- (thiophene-2-sulfonyl) -azepan-4-yl-carbamoin-buty-phenamide of quinoxaline-2-carboxylic acid Following the procedure of example 168, but substituting 5-methoxybenzofuran-2-carboxylic acid with quinoxaline-2-carboxylic acid, the title compound was prepared, which was separated by means of CLAP to give the first diastereomer eluted as a solid white (60 mg, 56%): MS (ESI) 544.4 (M + H +), and the second diastereomer eluted as a white solid (38.7 mg, 37%), MS (ESI): 544.4 (M + H +).

EXAMPLE 175 Preparation of ((SH-H- (4-chloro-benzenesulfoniD-3-oxo-azepan-4-yl-carbamoin-3-methyl-buti-p-phenylbenzofuran-2-carboxylic acid (a) Ter-butyl acid ester. { (S) -1- [1- (3-Chloro-benzenesulfonyl) -3-hydroxy-azepan-4-ylcarbamoyl] -3-methyl-butyl} To a solution of the compound of example 2g (2.50 g, 7.29 mmol) in DCE (100 mL) was added P-NMM (4.0 g) and 4-chlorobenzenesulfonyl chloride (1.85 g, 8.75 mmol). After stirring at room temperature overnight, the solution was filtered. The filtrate was concentrated to give the title compound as a white solid (3.13 g, 83.3%): MS: 539. 78 (M + Na) +. (b) [1- (3-Chloro-benzenesulfonyl) -3-hydroxy-azepan-4-yl] -amide of (S) -2-amino-4-methyl-pentanoic acid To a stirred solution of the compound of the example 175a (1.0 g, 1. 93 mmol) in methanol (10 ml), HCl (4M in dioxane, 10 ml) was added.

After stirring at room temperature for 3 hours, the solution was concentrated to give a white solid. To a solution of the white solid (0.68 g, 1. 50 mmol, 78%) in methanol (37%), P-CO3 (2.85 g, 2.63 mmol / g) was added. After stirring for 2 hours, the solution was filtered and concentrated to yield the title compound as a white solid (0.59 g, 1. 42 mmol, 95%); MS: 417.86 (M + H +). (c). { (S) -1 - [1 - (4-Chloro-benzenesulfonyl) -3-hydroxy-azepan-4-ylcarbamoyl] -3-methyl-butyl} benzofuran-2-carboxylic acid amide To a solution of the compound of example 175b (0.14 g, 0.335 mmol) in CH2Cl2 (20 ml), was added benzofuran-2-carboxylic acid (0.81, 0.50 mmol), 1-hydroxybenzotriazole ( 0.77 g, 0.569 mmol) and P-EDC (0.67 g, 1 mmol / g) in CH2Cl2 (10 mL). After stirring at room temperature overnight, the solution was treated with tisamine (0.446 g, 3.75 mmol / g). After stirring for another 2 hours, the solution was filtered and concentrated to yield the title compound as a white solid (122.2 mg, 65%); MS (ESI): 562.2 (M + H +). (d). { (S) -1- [1- (4-Chloro-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} benzofuran-2-carboxylic acid amide To a stirred solution of the compound of example 175c (122.2 mg, 0.217 mmol) in dichloromethane (4 ml), Dess-Martin reagent (184.8 mg, 0.436 mmol) was added. After stirring at room temperature for 2 hours, sodium thiosulfate solution (2 ml of a 10% solution in water) and saturated aqueous sodium bicarbonate solution (2 ml) were added to the solution simultaneously. The aqueous phase was extracted with dichloromethane (2x). The organic phases were combined and washed with brine: dried (MgSO4), filtered and concentrated. The residue was purified by means of CLAP to produce the first diastereomer eluted as a white solid (62.7 mg, 51.6%); MS (ESI) 560.2 (M + H +); and the second diastereomer eluted as a white solid (32.7 mg, 26.9%); MS (ESI) 560.2 (M + H +). 2 EXAMPLE 176 Preparation of 5-methoxybenzofuran-2-carboxylic acid ((SH-H- (4-chloro-benzenesulfoni-3-oxo-azepane-4-yl-carbamoin-3-methyl-buti-p-pyrimide) Following the procedure of example 175 cd, but replacing the benzofuran-2-carboxylic acid from step 175c with 5-methoxybenzofuran-2-carboxylic acid, the title compound was prepared, which was separated by means of CLAP to give the first diastereomer eluted as a white solid (64.4 mg, 50%); MS (ESI) 590.2 (M + H +), and the second diastereomer eluted as a white solid (32.2 mg, 25.2%); MS (ESI) 590.0 (M + H +).

EXAMPLE 177 Preparation of 7-methoxybenzofuran-2-carboxylic acid ((SH-H- (4-chloro-benzenesulfoni-3-oxo-azepane-4-yl-carbamoip-3-methyl-buti-p-p-amide) Following the procedure of example 175 cd, but replacing the benzofuran-2-carboxylic acid from step 175c with 7-methoxybenzofuran-2-carboxylic acid, the title compound was prepared, which was separated by means of CLAP to give the first diastereomer eluted as a white solid (51.1 mg, 40%); MS (ESI) 590.2 (M + H +), and the second diastereomer eluted as a white solid (41 mg, 32%); MS (ESI) 590.2 (M + H +).

EXAMPLE 178 Preparation of. { (SH -f 1 - (4-Chloro-benzenesulfonyl) -3-oxo-azepan-4-yl-carbamoyl-3-methyl-buty-didamide of 5,6-dimethoxybenzofuran-2-carboxylic acid Following the procedure of example 175 cd, but replacing the benzofuran-2-carboxylic acid from step 175c with 5,6-dimethoxybenzofuran-2-carboxylic acid, the title compound was prepared, which was separated by means of CLAP to give the first eluted diastereomer; MS (ESI) 622.2 (M + H +), and the second diastereomer eluted; MS (ESI) 622.2 (M + H +).

EXAMPLE 179 Preparation of 3-methylbenzofuran-2-carboxylic acid ((3H-methyl- (4-chloro-benzenesulfonyl) -3-oxo-azepane-4-yl-carbamoin-3-methyl-buty-phenamide) Following the procedure of example 175 cd, but replacing the benzofuran-2-carboxylic acid from step 175c with 3-methylbenzofuran-2-carboxylic acid, the title compound was prepared, which was separated by means of CLAP to give the first diastereomer eluted as a white solid (78.6 mg, 63%); MS (ESI) 574.2 (M + H +), and the second diastereomer eluted as a white solid (27.6 mg, 22%); MS (ESI) 574.2 (M + H +).

EXAMPLE 180 Preparation of ((SH-1 - (4-chloro-benzenesulfonyl) -3-oxo-azepan-4-yl-carbamoin-3-methyl-buty-phenamide of benzorbltiophen-2-carboxylic acid Following the procedure of example 175 cd, but substituting the benzofuran-2-carboxylic acid from step 175c with benzo [b] thiophene-2-carboxylic acid, the title compound was prepared, which was separated by means of CLAP to give the first diastereomer eluted as a white solid (41 mg, 33%); MS (ESI) 576.2 (M + H +), and the second diastereomer eluted as a white solid (32.6 mg, 26%); MS (ESI) 576.2 (M + H +).

EXAMPLE 181 Preparation of. { (SH-M - (4-chloro-benzenesulfon-P-3-oxo-azepan-4-yl-carbamoin-3-methyl-butylamide of 1-methyl-1 H-indole-2-carboxylic acid Following the procedure of example 175 cd, but substituting the benzofuran-2-carboxylic acid from step 175c with 1-methylindol-2-carboxylic acid, the title compound was prepared, which was separated by means of CLAP to give the first diastereomer eluted as a white solid (28.5 mg, 23%); MS (ESI) 573.2 (M + H +), and the second diastereomer eluted as a white solid (38.5 mg, 31%); MS (ESI) 573.2 (M + H +).

EXAMPLE 182 Preparation of ((SH-H- (4-chloro-benzenesulfoniP-3-oxo-azepan-4-yl-carbamoin-3-methyl-buty-phenamide of quinoxaline-2-carboxylic acid Following the procedure of example 175 cd, but substituting the benzofuran-2-carboxylic acid from step 175c with quinoxaline-2-carboxylic acid, the title compound was prepared, which was separated by means of CLAP to give the first diastereomer eluted as a white solid (63 mg, 51%); MS (ESI) 572.2 (M + H +), and the second diastereomer eluted as a white solid (44.5 mg, 36%); MS (ESI) 572.2 (M + H +).

EXAMPLE 183 Preparation of benzofuran-2-carboxylic acid ((SH-11 - (3-methoxy-benzenesulfoniD-3-oxo-azepane-4-yl-carbamoin-3-methyl-buty-phenyl) (a) Ter-butyl acid ester. { (S) -1- [1- (3-methoxy-benzenesulfonyl) -3-hydroxy-azepan-4-ylcarbamoyl] -3-methyl-butyl} To a solution of the compound of example 2g (1.60 g, 4.66 mmol) in DCE (50 ml), P-NMM (2.56 g, 3.64 mmol / g) and 3-methoxy-benzenesulfonyl chloride (1.15 g, 5.59 mmoles). After stirring at room temperature overnight, the solution was filtered. The filtrate was concentrated to give the title compound as a white solid (1.70 g, 71.1%); MS: 535.8 (M + Na) +. (b) (S) -2-amino-4-methyl-pentanoic acid [1- (3-methoxy-benzenesulfonyl) -3-hydroxy-azepan-4-yl] -amide. To a stirred solution of the compound of example 183a ( 1.70 g, 3.31 mmol) in methanol (22 ml), HCl (4M in dioxane, 22 ml) was added. After stirring at room temperature for 3 hours, the solution was concentrated to give a white solid. To the solution of the white solid (1.19 g, 2.64 mmol, 80%) in methanol (50 ml), P-CO3 (5.02 g, 2.63 mmol / g) was added. After stirring the solution for 2 hours, it was filtered and concentrated to yield the title compound as a white solid (1.03 g, 2.49 mmol, 96%).; MS 413.90 (M + H +). (c). { (S) -1- [1- (3-Methoxy-benzenesulfonyl) -3-hydroxy-azepan-4-ylcarbamoyl] -3-methyl-butyl} benzofuran-2-carboxylic acid amide To a solution of the compound of Example 183b (0.11 g, 0.26 mmol) in CH2Cl2 (10 mL), benzofuran-2-carboxylic acid (64.69 mg, 0.399 mmol), 1- was added. hydroxybenzotriazole (61.1 g, 0.452 mmol) and P-EDC (0.532 g, 1 mmol / g) in CH2Cl2 (10 mL). After stirring at room temperature overnight, the solution was treated with tisamine (0.355 g, 3.75 mmol / g). After stirring another 2 hours, the solution was filtered and concentrated to yield the title compound as a white solid (103.5 mg, 70%); MS (ESI) 558.2 (M + H +). (d). { (S) -1- [1- (3-Methoxy-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} benzofuran-2-carboxylic acid amide To a stirred solution of the compound of example 183c (103 mg, 0.19 mmol) in dichloromethane (4 ml), Dess-Martin reagent (157 mg, 0.37 mmol) was added. After stirring at room temperature for 2 hours, sodium thiosulfate solution (2 ml of sol.10% in water) and saturated aqueous solution of bicarbonate (2 ml) were added to the solution simultaneously. The aqueous phase was extracted with dichloromethane (2x). The organic phases were combined and washed with brine; dried (MgSO), filtered and concentrated. The residue was purified by CLAP to produce the first diastereomer eluted as a white solid (76.2 mg, 73.6%); MS (ESI): 556.2 (M + H +), and the second diastereomer eluted as a white solid (24.1 mg, 23.3%) MS (ESI) 556.2 (M + H +).

EXAMPLE 184 Preparation of 5-methoxybenzofuran-2-carboxylic acid ((5-methoxybenzofuran-2-carboxylic acid ((5-methoxybenzofuran-2-carboxylic acid (5-7-methoxybenzofuran-2-carboxylic acid (5- (methoxybenzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl-3-methyl-buti-pyrimide Following the procedure of example 183 cd, but substituting the benzofuran-2-carboxylic acid from step 183c with 5-methoxybenzofuran-2-carboxylic acid, the title compound was prepared, which was separated by means of CLAP to give the first diastereomer eluted as a white solid (33 mg, 31%); MS (ESI) 586.2 (M + H +), and the second diastereomer eluted as a white solid (35.2 mg, 32%); MS (ESI) 586.2 (M + H +).

EXAMPLE 185 Preparation of. { (7-Methoxybenzofuran-2-carboxylic acid 3- (3-methoxy-benzenesulfoniD-3-oxo-azepan-4-yl-carbamoin-3-methyl-butiPamide) Following the procedure of example 183 cd, but replacing the benzofuran-2-carboxylic acid from step 183c with 7-methoxybenzofuran-2-carboxylic acid, the title compound was prepared, which was separated by means of CLAP to give the first diastereomer eluted as a white solid (41 mg, 38%); MS (ESI) 586.4 (M + H +), and the second diastereomer eluted as a white solid (39.5 mg, 36%); MS (ESI) 586.2 (M + H +).

EXAMPLE 186 Preparation of ((SH-ri- (3-methoxy-benzenesulfonyl) -3-oxo-azepan-4-yl-carbamoin-3-methyl-butyl > 4,5-dimethoxybenzofuran-2-carboxylic acid amide Following the procedure of example 183 cd, but substituting the benzofuran-2-carboxylic acid from step 183c with 5,6-dimethoxybenzofuran-2-carboxylic acid, the title compound was prepared, which was separated by means of CLAP to give the first eluted diastereomer; MS (ESI) 618.4 (M + H +), and the second diastereomer eluted.

EXAMPLE 187 Preparation of. { 5-Methylbenzofuran-2-carboxylic acid (H - (3-methoxy-benzenesulfonyl) -3-oxo-azepan-4-yl-carbamoyl-3-methyl-buty-diamide) Following the procedure of example 183 cd, but substituting the benzofuran-2-carboxylic acid from step 183c with 3-methylbenzofuran-2-carboxylic acid, the title compound was prepared, which was separated by means of CLAP to give the first diastereomer eluted as a white solid (76 mg, 72%); MS (ESI) 570.2 (M + H +), and the second diastereomer eluted as a white solid (23.2 mg, 22%); MS (ESI) 570.2 (M + H) +.

EXAMPLE 188 Preparation of. { (S) -1-H - (3-methoxy-benzenesulfonyl) -3-oxo-azepan-4-yl-carbamoin-3-methyl-buty-phenylidene of benzorbltiophen-2-carboxylic acid Following the procedure of example 183 cd, but replacing the benzofuran-2-carboxylic acid from step 183c with benzo [b] thiophene-2-carboxylic acid, the title compound was prepared, which was separated by means of CLAP to give the first diastereomer eluted as a white solid (37 mg, 35%); MS (ESI) 572.2 (M + H +), and the second diastereomer eluted as a white solid (31 mg, 29%); MS (ESI) 572.2 (M + H) +.

EXAMPLE 189 Preparation of. { (1-Methyl-1 H-indole-2-carboxylic acid (H - H - (3-methoxy-benzenesulfonyl) -3-oxo-azepan-4-yl-carbamoin-3-methyl-buty-phenyl) Following the procedure of example 183 cd, but substituting the benzofuran-2-carboxylic acid from step 183c with 1-methylindol-2-carboxylic acid, the title compound was prepared, which was separated by means of CLAP to give the first diastereomer eluted as a white solid (34 mg, 32%); MS (ESI) 569.2 (M + H) +, and the second diastereomer eluted as a white solid (38 mg, 38%); MS (ESI) 569.4 (M + H) +.

EXAMPLE 190 Preparation of quinoxalin - ((SH -f1- (3-methoxy-benzenesulfoniP-3-oxo-azepan-4-yl-carbamoyl-1-3-methyl-buti-p-amide Following the procedure of example 183 cd, but substituting the benzofuran-2-carboxylic acid from step 183c with quinoxaline-2-carboxylic acid, the title compound was prepared, which was separated by means of CLAP to give the first diastereomer eluted as a white solid (71 mg, 67%); MS (ESI) 568.2 (M + H) \ and the second diastereomer eluted as a white solid (27 mg, 24%); MS (ESI) 568.2 (M + H) +.

EXAMPLE 191 Preparation of. { (S) -3-Methyl-1-r3-oxo-1 - (thiophen-2-sulfoniP-azepan-4-yl-carbamoyl-buty-phenylbenzofuran-2-carboxylic acid Following the procedure of Example 168, but substituting 5-methoxybenzofuran-2-carboxylic acid with benzofuran-2-carboxylic acid, the title compound was prepared, which was purified by means of CLAP to give the first diastereomer eluted as a solid. white (76 mg, 73%); MS (ESI) 532.2 (M + H) \ and the second diastereomer eluted as a white solid (25 mg, 23%); MS (ESI) 532.2 (M + H) +.

EXAMPLE 192 Preparation of. { (S) -3-methyl-1-r (2,2 ', 4-trideuterio) -3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl-1-buty-phenylmethyl benzofuran-2 - carboxylic To a solution of. { (S) -3-methyl-1- [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl ester} benzofuran-2-carboxylic acid amide of example 28c (0.03 g) in D20: CD3OD (0.4: 4 ml), triethylamine (0.04 ml) was added. The reaction was heated to reflux for 2 hours, after which it was concentrated and dried under vacuum. The residue was redissolved in the same mixture and heated to reflux overnight. The reaction was concentrated and the residue was purified by column chromatography (5% methanol: dichloromethane) to give the title compound (0.02 g); 1 H NMR: d 1.0 (m, 6H), 1.5-2.2 (m, 6H), 2.7 (m, 1H), 4.1 (m, 1H), 4.7 (m, 2H), 7.4-8.0 (m, 8H), 8.7 (m, 1H); MS (ESI): 529 M +, 45%). The diastereomeric mixture was separated by CLAP to provide the fastest eluting diastereomer, MS (EI): 530 (M + H +, 100%), and the slowest eluting diastereomer, MS (EI) 530 (M + H +, 100 %).

EXAMPLE 193 Preparation of. { (S) -2-methyl-1 -f3-oxo-1 - (pyridin-2-sulfonyl) -azepan-4-yl-carbamoyl-buty-phenylbenzofuran-2-carboxylic acid (a) 4-tert-Butoxycarbonylamino-3-hydroxy-azepane-1-carboxylic acid benzyl ester To a stirred solution of the compound of example 2e (1.04 g, 3.92 mmol) in THF, di-terbicarbonate was added to it. butyl (0.864 g). After stirring at room temperature for 30 minutes, the reaction mixture was diluted with diethyl ether and extracted with saturated NaHCO 3 solution. The organic layer was dried over anhydrous Na2SO, filtered and concentrated; was purified by means of a column of silica gel to give the title compound as a yellow oil (0.963 g, 2.64 mmol, 67%); MS (ESI): 365.03 (M + H) +. (b) (3-Hydroxy-azepan-4-yl) carbamic acid tert-butyl ester To a solution of the compound of example 193a (0.963 g, 2.64 mmol) in ethyl acetate (16 ml), palladium was added 10% carbon (500 mg). After stirring the solution at room temperature for 48 hours, the mixture was filtered through celite. The filtrate was concentrated to yield the title compound (0.529 g, 2.29 mmol, 87%); MS (ESI): 231.92 (M + H +). (c) [3-Hydroxy-1- (pyridin-2-sulfonyl) -azepan-4-yl] carbamic acid tert-butyl ester To a solution of the compound of example 193b (0.53, 2.29 mmol) in dichloromethane (20 ml. ), triethylamine (232 mg) and pyridine-2-sulfonyl chloride (410 mg, 2.32 mmol) were added. After stirring at room temperature for 30 minutes, the mixture was washed with saturated NaHC 3 solution. The organic layer was dried, filtered, concentrated and purified on a column of silica gel, to give the title compound as a solid (0.58 g, 1.57 mmol, 68%); MS (ESI): 372.95 (M + H +). (d) 4-Amino-1 - (pyridine-2-sulfonyl) -azepan-3-ol To a stirred solution of the compound of example 193c (0.583 g, 1.57 mmol) in ethyl acetate (0.5 ml) was added HCl (4M in dioxane, 3.9 ml). After stirring the reaction mixture for 30 minutes at room temperature, the mixture was concentrated to yield a white solid. The solid was treated with NaOH and then extracted with ethyl acetate. The organic layer was dried, filtered and concentrated to yield a yellow solid (0.35 g, 1.28 mmol, 81%); MS (ESI) 272.93 (M + H +). (e) Tert-butyl acid ester. { (S) -1- [3-hydroxy-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -2-methyl-butyl} To a solution of the compound of Example 193d (19 mg, 0.070 mmol) in CH2Cl2, N-Boc-isoleucine (24.5 mg) was added., 0.10 mmol), 1-hydroxybenzotriazole (16.1 mg, 0.12 mmol) and P-EDC (140 mg, 0.14 mmol) in CH2Cl2. After stirring at room temperature overnight, the mixture was treated with PS-Trisamine. After stirring another 2 hours, the mixture was filtered and concentrated to yield the title compound as a solid. MS (ESI) 484.97 (M + H +). (f) [3-Hydroxy-1- (pyridin-2-sulfonyl) -azepan-4-yl] (S) -2-amino-3-methyl-pentanoic acid amide To a stirred solution of the compound of the example 193e (34 mg, 0. 07 mmol) in CH2CI2 (0.50 ml), HCl (4M in dioxane, 0.165 ml) was added. After stirring at room temperature for 30 minutes, the mixture was concentrated, giving a white solid. The white solid was azeotropically distilled with toluene and then treated with MP-carbonate (0.35 mmol) in methanol. After four hours of stirring, the mixture was filtered and concentrated to give the title compound as a solid: MS (ESI) 384.9 (M + H +). (g) { (S) -2-Methyl-1 - [3-hydroxy-1- (pyridin-2-sulfonyl) -azepan-4-yl-carbamoyl] butyl} benzofuran-2-carboxylic acid amide To a solution of the compound of example 193f (27 mg, 0.070 mmol) in CH2Cl2, was added 2-benzofurancarboxylic acid (17.0 mg, 0.106 mmol), 1-hydroxy benzotriazole (16.1 mg, 0.12 mmole), and P-EDC (140 mg, 0.14 mmole) in CH2Cl2. After stirring at room temperature overnight, the mixture was treated with PS-trisamine. After stirring another 2 hours, the mixture was filtered and concentrated to yield the title compound as a solid: MS (ESI) 528.9 (M + H +). (h). { (S) -2-Methyl-1 - [3-oxo-1 - (pyridin-2-sulfonyl) -azepan-4-yl-carbamoyl] butyl} benzofuran-2-carboxylic acid amide To a stirred solution of the compound of example 193g (37 mg, 0.07 mmol) in CH2Cl2 (0.5 ml), Dess-Martin reagent (45 mg, 0.105 mmol) was added. After stirring for 30 minutes, sodium thiosulfate solution (10% in water, 0.50 ml) and saturated aqueous sodium bicarbonate solution (0.50 ml) were added to the reaction simultaneously. The mixture was then extracted with dichloromethane (2 times). The organic layer was dried, filtered and concentrated. The residue was purified by means of CLAP to produce the two diastereomers of the title compound as solids (first eluate: 7 mg, second eluate: 5.5 mg); MS (ESI) 526.91 (M + H +).

EXAMPLE 194 Preparation of. { (SH-r3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-yl-carbamoillpropiP-benzofuran-2-carboxylic acid amide Following the procedure of Example 193 e-h, but using N-Boc-alpha-aminobutyric acid in step 193e, the title compound was purified to yield two diastereomers as solids (first eluate: 5 mg, second eluate: 5 mg); MS (ESI) 543.8 (M + H +).

EXAMPLE 195 Preparation of benzofuran-2-carboxylic acid ((S) -2-cyclohexyl-1 -P-oxo-1- (pyridine-2-sulfonyl) -azepan-4-yl-carbamoylletiP-amide Following the procedure of Example 193 e-h, but using N-Boc-cyclohexylalanine in step 193e, the title compound was purified to produce two diastereomers as solids (first eluate: 4.5 mg, second eluate: 4.5 mg); MS (ESI) 566.87 (M + H +).

EXAMPLE 196 Preparation of benzofuran-2-carboxylic acid ((SH-r3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-yl-carbamoylletiP-amide Following the procedure of Example 193 e-h, but using N-Boc-alanine for step 193e, the title compound was purified to yield two diastereomers as solids (first eluate: 5.5 mg, second eluate: 5 mg).

EXAMPLE 197 Preparation of. { (S) -3-methanesulfinyl-1-f3-oxo-1- (pyridin-2-sulfonyl) -acetyl-4-yl-carbamoinpropiP-benzofuran-2-carboxylic acid amide Following the procedure of Example 193 eh, but using N-Boc-L-methionine for step 1 (f), the title compound was purified to produce two diastereomers as solids (first eluate: 3 mg, second eluate: 3 mg); MS (ESI) 560.7 (M + H +).

EXAMPLE 198 Preparation of benzofuran-2-carboxylic acid (r3-oxo-1- (pyridine-2-sulfoniP-azepane-4-yl-carbamo-n-phenyl-amide) Following the procedure of Example 193 e-h, but using N-Boc-glycine for step 193e, the title compound was purified to produce two diastereomers as solids (first eluate: 3 mg, second eluate: 3 mg); MS (ESI) 470.81 (M + H +).

EXAMPLE 199 Preparation of. { (SH-r3-oxo-1 - (pyridin-2-sulfonyl) -azepan-4-yl-carbamoillpentiP-benzofuran-2-carboxylic acid amide Following the procedure of Example 193 e-h, but using N-Boc-norleucine for step 193e, the title compound was purified to produce two diastereomers as solids (first eluate: 4 mg, second eluate: 5 mg); MS (ESI) 526.85 (M + H +).

EXAMPLE 200 Preparation of. { (SH-r3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-yl-carbamoyl-buty-p-benzofuran-2-carboxylic acid amide Following the procedure of example 193 e-h, but using N-Boc-norvaline for step 193e, the title compound was purified to produce two diastereomers as solids (first eluate: 7.5 mg, second eluate: 3.5 mg); MS (ESI) 512.8 (M + H +).

EXAMPLE 201 Preparation of benzofuran-2-carboxylic acid ((S) -2-methyl-1-r3-oxo-1- (pyridine-2-sulfonyl) -azepan-4-yl-carbamoillpropiP-amide Following the procedure of Example 193 e-h, but using N-Boc-valine for step 193e, the title compound was purified to produce two diastereomers as solids (first eluate: 6 mg, second eluate: 4.5 mg); MS (ESI) 512.8 (M + H +).

EXAMPLE 202 Preparation of. { (S) -2-hydroxy-1- [3-oxo-1- (pyridyl-2-sulfonyl) -azepan-4-yl-carbamoylpropyl-benzofuran-2-carboxylic acid Following the procedure of Example 193 e-h, but using N-Boc-L-threonine for step 193e, the title compound was purified to produce two diastereomers as solids (first eluate: 3 mg, second eluate: 3 mg).

EXAMPLE 203 Preparation of benzofuran-2-carboxylic acid ((SH-r3-oxo-1- (pyridine-2-sulfonyl-D-azepan-4-yl-carbamoyl-2-phenyl-ethy-d-amide) Following the procedure of Example 193 e-h, but using N-Boc-phenylalanine for step 193e, the title compound was purified to yield two diastereomers as solids (first eluate: 5 mg, second eluate: 5 mg); MS (ESI) 560.8 (M + H +).

EXAMPLE 204 Preparation of r3-oxo-1- (pyridine-2-sulfoniP-azepan-4-ylamide of 1- (benzofuran-2-carbonyl) -pyrrolidine-2-carboxylic acid Following the procedure of Example 193 e-h, but using N-Boc-L-proline for step 193e, the title compound was purified to produce two diastereomers as solids (first eluate: 4 mg, second eluate: 5 mg); MS (ESI) (M + H +).

EXAMPLE 205 Preparation of 3,4-dimethoxy-N - ((SH -H - (4-imethoxy-benzenesulfonyl) -3-oxo-azepan-4-yl-carbamoin-3-methyl-buti-P-benzamide The title compound was prepared following the procedure of Example 115, but substituting the benzyloxy acetyl chloride with 3,4-dimethoxybenzoyl chloride. The residue was purified by CLAP. First eluted diastereomer: EM 576.4 (M + H +); 1 H NMR (500 MHz, CDCl 3): d 7.68 (d, 2 H), 7.00 (d, 1 H), 6.89 (s, 2 H), 3.84 (s, 3 H), 3.77 (s, 6 H), 2.38 (t, 1 H), 0.94 (d, 6H); MS 576.4 (M + H +).

EXAMPLE 206 Preparation of. { (S) -1-I1- (4-imethoxy-benzenesulfonyl) -3-oxo-azepane-4-yl-carbamoip-3-methyl-buty-phenamide of benzorbltiophen-2-carboxylic acid The title compound was prepared following the procedure of Example 115, but substituting the benzyloxy acetyl chloride with 2-thiophenecarbonyl chloride. The residue was purified by CLAP. First eluted diastereomer: EM 572.2 (M + H +); H NMR (500 MHz, CDCl 3): d 7.80-7.68 (m, 5H), 7.38-7.34 (m, 2H), 7.01-6.93 (m, 4H), 3.83 (s, 3H), 2.38 (t, 1 H ), 0.97 (d, 6H); second diastereomer eluted EM 572.2 (M + H +).

EXAMPLE 207 Preparation of. { (SH -f 1- (4-fluoro-benzenesulfonyl) -3-oxo-azepan-4-yl-carbamoin-3-methyl-buty-phenamide of benzoyl, 31-dioxol-5-carboxylic acid The title compound was prepared following the procedure of Example 115, but substituting 4-methoxybenzenesulfonyl chloride with 4-fluorobenzenesulfonyl chloride, and benzyloxyacetyl chloride with 3,4-methylenedioxybenzoyl chloride. The residue was purified by CLAP. First eluted diastereomer: EM 548.2 (M + H +); 1 H NMR (400 MHz, CDCl 3): d 7.85-7.78 (m, 2H), 7.38-7.20 (m, 4H), 7.05 (d, 1 H), 2.52-2.40 (m, 1 H), 1.00 (d, 6H); second diastereomer eluted EM 548.2 (M + H +).

EXAMPLE 208 Preparation of (S) -2- (2-benzyloxy-acetylamino) -4-methyl-pentanoic acid p- (4-fluoro-benzenesulfonyl) -3-oxo-azepan-4-yl-1-yl-amide The title compound was prepared following the procedure of Example 115, but substituting 4-methoxybenzenesulfonyl chloride with 4-fluorobenzenesulfonyl chloride. The residue was purified by CLAP. First eluted diastereomer: EM 548.2 (M + H +). 1 | H NMR (400Hz, CDCl3-CD3? D) d - 7.88-7.80 (m, 2H), 7.45-7.30 (m, 5H), 7.30-7.20 (m, 2), 4.00 (s, 2h), 2.60-2.48 (m, 1 H), 0.96 (t, 6H): MS 548.2 (M + H +).

EXAMPLE 209 Preparation of ((H-H - (4-fluoro-benzenesulfonyl) -3-oxo-azepan-4-yl-carbamoyl-3-methyl-buty-phenylbenzyl-bromo-2-carboxylic acid The title compound was prepared following the procedure of Example 115, but substituting 4-methoxybenzenesulfonyl chloride with 4-fluorobenzenesulfonyl chloride, and benzyloxy acetyl chloride with benzo [b] thiophenecarbonyl chloride. The residue was purified by CLAP. First eluted diastereomer: MS 560.2 (M + H +); 1 H NMR (500 MHz, CDCl 3): d 7.80-7.72 (m, 5H), 7.37-7.34 (m, 2H), 7.33-7.15 (m, 4), 2.43 (t, 1H), 0.96 (d, 6H ). Second eluted diastereomer: MS 560.2 (M + H +).

EXAMPLE 210 Preparation of benzofuran-2-carboxylic acid ((SH -f 1 -benzoyl-3-oxo-azepan-4-ylcarbamop-3-methyl-butiPamide) (to) . { (S) -1- [1-benzoyl-3-hydroxy-azepan-4-ylcarbamoyl] -3-methyl-butyljamide of benzofuran-2-carboxylic acid To a solution of. { (S) -1- (3-hydroxy-azepan-4-ylcarbamoyl) -3-methyl-butyl] benzofuran-2-carboxylic acid amide of example 78c (0.2 g) in dichloromethane, benzoic acid (0.12 g) was added. ), HOBt (0.07 g) and EDC (0.99 g). The reaction was stirred until complete. By treatment and column chromatography (5% methanol: dichloromethane) the title compound (0.2 g) was obtained: 1 H NMR (CDCl 3): d 1.0 (m, 6H), 1.5-2.2 (m, 6H), 2.7 ( m, 1 H), 3.8 (m, 1 H), 4.1 (m, 1 H), 4.7 (m, 2 H), 5.1 (m, 1 H), 7.0-7.7 (m, 10H), 8.7 8m, 1 H); MS (EI): 492 (M + H +, 100%). (b) { (S) -1- [1-benzoyl-3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyljamide of benzofuran-2-carboxylic acid The title compound was prepared following the procedure of Example 1, but using . { (S) -1- [1-benzoyl-3-hydroxy-azepan-4-ylcarbamoyl] -3-methyl-butyljamide of benzofuran-2-carboxylic acid of example 210a: '? NMR (CDCl 3): d 1.0 (m, 6H), 1.5-2.2 (m, 6H), 2.7 (m, 1H), 3.7 (m, 1H), 4.0 (m, 1 H), 4.7 (m, 2H), 5.1 (m, 1H), 7.4-8.0 (m, 8H); MS (EI): 490 (M + H +, 100%).

EXAMPLE 211 Preparation of r3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-yl-amide of (S) -4-methyl-2- (quinoline-8-sulfonylamino) pentanoic acid (a) (S) -4-methyl-2- (quinolin-8-sulfonylamino) pentanoic acid [3-hydroxy-1- (pyridin-2-sulfonyl) -azepan-4-yl] -amide The title compound is prepared following the procedure of example 89a, but substituting the 2-pyridinesulfonyl chloride with 8-quinolinesulfonyl chloride: EM (El) 576 (M + H +). (b) [3-Oxo-l- (pyridin-2-sulfonyl) -azepan-4-yl] (S) -4-methyl-2- (quinolin-8-sulfonylamino) pentanoic acid The title was prepared following the procedure of Example 1 i, but using [3-hydroxy-1- (pyridin-2-sulfonyl) -azepan-4-yl] (S) -4-methyl-2- (quinoline- 8-sulfonylamino) pentanoic of example 211 a: *? NMR { CDCI3): d 0.5-0.8 (m, 6H), 1.4-1.8 (m, 7H), 2.5 (m, 1 H), 3.5-3.9 (m, 3H), 4. 4 (m, 1 H), 4.6 (m, 1 H), 5.5 (m, 1 H), 6.7-7.0 (m, 2H), 7.5 (m, 3H), 8.0 (m, 2H), 8.3 (m , 2H), 8.6 (m, 1 H), 9.0 (m, 1 H); MS (EI): 674 (M + H +, 100%).

EXAMPLE 212 Preparation of (S) -4-methyl-2- (naphthylene-2-sulfonylamino) pentanoic acid T3-oxo-1- (pyridine-2-sulfonyl) -azepan-4-ylamide (a) [3-Hydroxy-1- (pyridin-2-sulfonyl) -azepan-4-yl] -amide of (S) -4-methyl-2- (naphthylene-2-sulfonylamino) pentanoic acid The title compound was prepared following the procedure of example 89a, but substituting the 2-pyridinesulfonyl chloride with 2-naphthylenesulfonyl chloride: MS (EI) 575 (M + H +). (b) [3-Oxo-l - (pyridin-2-sulfonyl) -azepan-4-yl] (S) -4-methyl-2- (naphthylene-2-sulfonylamino) pentanoic acid The title compound was prepared following the procedure of Example 1 i, but using [3-hydroxy-1- (pyridin-2-sulfonyl) -azepan-4-yl] -amide acid (S) -4-methyl-2 - (naphthylene-2-sulfonylamino) pentanoic acid from Example 212a: 1 H NMR (CDCl 3): d 0.5-0.8 (m, 6H), 1.4-1.8 (m, 7H), 2.5 (m, 1H), 3.5-3.9 (m, 3H), 4. 5 (m, 1 H), 4.6 (m, 1H), 5.5 (m, 1H), 6.7 (m, 1H), 7.5-8.0 (m, 9H), 8.5-8.6 (m, 2H); MS (EI): 673 (M + H +, 100%).

EXAMPLE 213 Preparation of ((SH-H- (4-fluoro-benzenesulfonyl) -3-oxo-azepan-4-yl-carbamo-p-3-methyl-buti-D-benzofuran-2-carboxylic acid The title compound was prepared following the procedure of Example 115, but substituting 4-methoxybenzenesulfonyl chloride with 4-fluorobenzenesulfonyl chloride, and benzyloxy acetyl chloride with 2-benzofurancarbonyl chloride. The residue was purified by CLAP. First eluted diastereomer: EM 544.2 (M + H +); H NMR (500 MHz, CDCl 3): d 7.79-7.77 (m, 2H), 7.61 (d, 1 H), 7.46-7.38 (m, 3H), 7.25-7.06 (m, 5H), 2.43 (t, 1 H), 0.95 (d, 6H). Second eluted diastereomer: EM 544.4 (M + H +).

EXAMPLE 214 Preparation of N-. { (S) -1 - | i - (4-fluoro-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl-3-methyl-buty-3,4-dimethoxy-benzamide The title compound was prepared following the procedure of Example 115, but substituting 4-methoxybenzenesulfonyl chloride with 4-fluorobenzenesulfonyl chloride, and benzyloxy acetyl chloride with 3,4-dimethoxybenzoyl chloride. The residue was purified by CLAP. First eluted diastereomer: EM 564.2 (M + H +); 1 H NMR (500 MHz, CDCl 3): d 7.80-7.76 (m, 2H), 7.19 (t, 2H), 7.05 (d, 1 H), 6.88 (s, 2H), 6.78 (d, 1 H), 6.53 (s, 1 H), 3. 77 (s, 6H), 2.43 (t, 1H), 0.94 (d, 6H). Second eluted diastereomer: EM 546.2 (M + H +).

EXAMPLE 215 Preparation of. { (SH -f 1 - (4-fluoro-benzenesulfonyl) -3-oxo-azepane-4-ylcarbamoyl-3-methyl-buty-phenamide of cyclohexanecarboxylic acid The title compound was prepared following the procedure of Example 115, but substituting 4-methoxybenzenesulfonyl chloride with 4-fluorobenzenesulfonyl chloride, and benzyloxy acetyl chloride with cyclohexylcarbonyl chloride. The residue was purified by CLAP. First eluted diastereomer: MS 510.4 (M + H +); 1 H NMR (400Hz, CDCl 3): d 7.83-7.80 (m, 2H), 7.27-7.20 (m, 2H), 6.92 (d, 1H), 6.95 (d, 1H), 2.50 (t, 1H), 1.90 -1.20 (m, 15H), 0.94 (t, 6H). Second eluted diastereomer: MS 510.2 (M + H +).

EXAMPLE 216 Preparation of f1- (S) -2- (2-benzyloxy-acetylamino) -4-methyl-pentanoic acid methanesulfonium-3-oxo-azepan-4-amide acid The title compound was prepared following the procedure of Example 115, but substituting 4-methoxybenzenesulfonyl chloride with methanesulfonyl chloride. The residue was purified by CLAP. First eluted diastereomer: EM 468.2 (M + H +); «? NMR (500 MHz, CDCl 3): d 7.37- 7.24 (m, 4H), 6.93-6.91 (m, 2H), 5.02-5.00 (m, 1 H), 2.88 (s, 3H), 2.70 (t, 1 H ), 0.92 (t, 6H). Second eluted diastereomer: EM 468.2 (M + H +).

EXAMPLE 217 Preparation of ((SH - (1-methanesulfonyl-3-oxo-azepan-4-ylcarbamoyl-3-methyl-buty-phenyl-benzorbltiophen-2-carboxylic acid The title compound was prepared following the procedure of Example 115, but substituting 4-methoxybenzenesulfonyl chloride with methanesulfonyl chloride, and benzyloxy acetyl chloride with benzo [b] thiophenecarbonyl chloride. The residue was purified by CLAP. First eluted diastereomer: EM 480.2 (M + H +); 1 H NMR (500 MHz, CDCl 3): d 7.83-7.78 (m, 3H), 7.42-7.37 (m, 2H), 6.94 (d, 1 H), 6.75 (d, 1 H), 2.89 (s, 3H ), 2.68 (t, 1 H), 0.97 (d, 6H). Second eluted diastereomer: MS 480.2 (M + H +).

EXAMPLE 218 Preparation of. { (SH - (1-methanesulfonyl-3-oxo-azepan-4-ylcarbamoyl) -3-methyl-butylamide of benzori, 31-dioxol-5-carboxylic acid The title compound was prepared following the procedure of Example 1, but substituting 4-methoxybenzenesulfonyl chloride with methanesulfonyl chloride, and benzyloxy acetyl chloride with piperonylcarbonyl chloride. The residue was purified by CLAP. First eluted diastereomer: EM 468.2 (M + H +); 1 H NMR (500 MHz, CDCl 3): d 7.31-7.24 (m, 2H), 6. 91 (d, 1 H), 6.00 (s, 2H), 2.89 (s, 3H), 2.67 (t, 1 H), 0.95 (d, 6H). Second eluted diastereomer: EM 468.2 (M + H +).

EXAMPLE 219 Preparation of. { (SH - (1-methanesulfonyl-3-oxo-azepan-4-ylcarbamoyl) -3-methyl-butipamide of benzofuran-2-carboxylic acid The title compound was prepared following the procedure of Example 115, but substituting 4-methoxybenzenesulfonyl chloride with methanesulfonyl chloride, and benzyloxy acetyl chloride with 2-benzofurancarbonyl chloride. The residue was purified by CLAP. First eluted diastereomer: EM 464.2 (M + H +); H NMR (500 MHz, CDCl 3): d 7.64 (d, 1 H), 7.51- 7.37 (m, 3 H), 7.29-7.28 (m, 1 H), 2.89 (s, 3 H), 2.67 (t, 1 H ), 0.97 (d, 6H). Second eluted diastereomer: EM 464.2 (M + H +).

EXAMPLE 220 Preparation of N-MSM - (1-methanesulfonyl) -3-oxo-azepan-4-ylcarbamoiP-3-methyl-butyl-3,4-dimethoxy-benzamide The title compound was prepared following the procedure of Example 115, but substituting 4-methoxybenzenesulfonyl chloride with methanesulfonyl chloride, and benzyloxy acetyl chloride with 3,4-dimethoxybenzoyl chloride. The residue was purified by CLAP. First eluted diastereomer: EM 484.2 (M + H +); ^ H NMR (500 MHz, CDCl 3): d 6.94-6.88 (m, 3H), 6. 58-6.55 (m, 2H), 3.80 (s, 6H), 2.89 (s, 3H), 0.95 (d, 6H). Second eluted diastereomer: EM 484.2 (M + H +).

EXAMPLE 221 Preparation of (S) -2- (2-benzyloxy-acetylamino) -4-methyl-pentanoic acid ri- (cyano-benzenesulfonyl) -3-oxo-azepane-4-panamide The title compound was prepared following the procedure of Example 1, but substituting 4-methoxybenzenesulfonyl chloride with 2-cyanophenylsulfonyl chloride. The residue was purified by CLAP. First eluted diastereomer: EM 555.2 (M + H +); 1 H NMR (500 MHz, CDCl 3). d 8.10 (d, 1 H), 7.86 (d, 1 H), 7.76-7.70 (m, 2H), 7.35-7.31 (m, 5H), 6.93 (d, 2H), 4.61 -4.47 (m, 4H), 2.77 (t, 1 H), 0.92 (t, 6H). Second eluted diastereomer: EM 555.2 (M + H +).

EXAMPLE 222 Preparation of N - ((S) -1 -H - (2-cyano-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyP-3-methyl-butiP-4-methanesulfonyl-1-benzamide The title compound was prepared following the procedure of Example 1, but substituting 4-methoxybenzenesulfonyl chloride with 2-cyanophenylsulfonyl chloride, and benzyloxy acetyl chloride with 4-methanesulfonylbenzoyl chloride. The residue was purified by CLAP. First eluted diastereomer: EM 589.2 (M + H +); H NMR (500 MHz, CDCl 3): d 8.10 (d, 1 H), 7.96 (s, 4H), 7.88 (d, 1 H), 7.78-7.71 (m, 2H), 3.05 (s, 3H), 2.79 (t, 1 H), 0.97 (t, 6H). Second eluted diastereomer: EM 589.2 (M + H +).

EXAMPLE 223 Preparation of ((2-cyano-benzenesulfonyl) -3-oxo-azepan-4-yl-carbamoiP-3-methyl-butiDamide of benzorbltiophen-2-carboxylic acid The title compound was prepared following the procedure of Example 115, but substituting 4-methoxybenzenesulfonyl chloride with 2-cyanophenylsulfonyl chloride, and benzyloxy acetyl chloride with benzo [b] thiophene-2-carbonyl chloride. The residue was purified by CLAP. First eluted diastereomer: EM 567.2 (M + H +); H NMR (500 MHz, CDCl 3): d 8.10 (d, 1 H), 7.86-7.70 (m, 6h), 7.37-7.30 (m, 2H), 2.76 (t, 1 H), 0.98 (d, 6H). Second eluted diastereomer: EM 567.2 (M + H +).

EXAMPLE 224 Preparation of benzofl, 3] dioxol-5-carboxylic acid ((SH-M- (2-cyano-benzenesulfonyl) -3-oxo-azepan-4-yl-carbamoyl) -3-methyl-buty-phenyl acid) The title compound was prepared following the procedure of Example 115, but substituting 4-methoxybenzenesulfonyl chloride with 2-cyanophenylsulfonyl chloride, and benzyloxy acetyl chloride with piperoniloyl chloride. The residue was purified by CLAP. First eluted diastereomer: EM 555.2 (M + H +); 1 H NMR (500 MHz, CDCl 3): d 8.11 (d, 1H), 7.87 (d, 1H), 7.76-7.71 (m, 2H), 7.31-7.24 (m, 2H), 6.00 (s, 2H), 2.77 (t, 1 H), 0.97 (d, 6H). Second eluted diastereomer: EM 555.4 (M + H +).

EXAMPLE 225 Preparation of r3-oxo-1- (pyridine-2-sulfonyl) -azepan-4-ipamida of (S) -4-methyl-2-f4-oxo-4 - ((4-phenoxy) acid phenyl) -butyrylamino) pentanoic The title compound was prepared following the procedure of Example 75, but substituting tiaxol-2-sulfonyl chloride with 2-pyridylsulfonyl chloride, and benzofuran-2-carboxylic acid with 4-phenoxyphenyl-carboxylic acid. The residue was purified by CLAP. First eluted diastereomer: EM 635. 4 (M + H +); 1 H NMR (400 MHz, CdCl 3): 8.69 (d, 1H), 7.99-7.94 (m, 4H), 7. 53-7.39 (m, 3H), 7.23-6.95 (m, 7H), 6.20 (d, 1 H), 5.07 (m, 1 H), 4.77-4.72 (d, 1H), 4.46 (m, 1 H) , 4.13-4.09 (m, 1 H), 3.85-3.80 (d, 1 H), 3.33 (m, 2H), 2.70- 2.64 (m, 3H), 2.20-1.40 (m, 6H); and the second diastereomer eluted: 0.96-9.92 (m, 6H), and the second diastereomer eluted EM (M + H +) 635.4.

EXAMPLE 226 Preparation of N - ((S) -1-i (1 - (2-cyano-benzenesulfoniP-3-oxo-azepan-4-ylcarbamoyl) -3-methyl-butiD-3,4-dimethoxy-benzamide The title compound was prepared following the procedure of Example 115, but substituting 4-methoxybenzenesulfonyl chloride with 2-cyanophenylsulfonyl chloride, and benzyloxy acetyl chloride with 3,4-dimethoxybenzoyl. The residue was purified by CLAP. First eluted diastereomer: EM 571.4 (M + H +); 1 H NMR (500 MHz, CDCl 3): d 8.10 (d, 1 H), 7.87 (d, 1 H), 7.76-7.70 (m, 2H), 6.98 (s, 2H), 6.89 (s, 2H), 3.79 (s, 6H), 2.76 (t, 1 H), 0.96 (d, 6H). Second eluted diastereomer: EM 571.4 (M + H +).

EXAMPLE 227 Preparation of. { (SH-M - (4-methoxy-benzenesulfonyl) -3-oxo-azepan-4-yl-carbamoy-3-methyl-buty-phenamide of cyclohexanecarboxylic acid The title compound was prepared following the procedure of Example 115, but substituting the benzyloxy acetyl chloride with cyclohexylcarbonyl chloride. The residue was purified by CLAP. First eluted diastereomer: EM 522.4 (M + H +); H NMR (500 MHz CDCl 3): d 7.70 (d, 2H), 6.97 (d, 2H), 2.40 (t, 1 H), 1.90-1.20 (m, 16H), 0.92 (d, 6H). Second eluted diastereomer: EM 522.4 (M + H +).

EXAMPLE 228 Preparation of 4-methanesulfonyl-N - ((SH - [4-methoxy-benzenesulfonyl) -3-oxo-azepane-4-carbamoyl-P-3-methyl-butylbenzamide The title compound was prepared following the procedure of Example 115, but substituting the benzyloxy acetyl chloride with 4-methanesulfonylbenzoyl chloride. The residue was purified by CLAP. First eluted diastereomer: MS 594.2 (M + H +); "NMR (500 MHz, CDCl 3): d 7.94 (s, 4H), 7.80-7.77 (m, 2H), 7.25-7.19 (m, 3H), 7.00 (d, 1 H), 3.04 (s, 3H) 0.96 (d, 6H) Second diastereomer eluted: MS 594.2 (M + H +).

EXAMPLE 229 Preparation of 4-methanesulfonyl-N-. { (SH-r4-fluoro-benzenesulfonyl) -3-oxo-azepan-4-carbamoin-3-methyl-butyl-benzamide The title compound was prepared following the procedure of Example 115, but substituting 4-methoxybenzenesulfonyl chloride with 4-fluorophenylsulfonyl chloride, and benzyloxyacetyl chloride with sodium chloride. 4-methanesulfonylbenzoyl. The residue was purified by CLAP. First eluted diastereomer: EM 582.2 (M + H +); "NMR (500 MHz, CDCl 3): d 7.94 (s, 4H), 7.80-7.77 (m, 2H), 7.25-7.19 (m, 3H), 7.00 (d, 1 H), 3.04 (s, 3H) 0.96 (d, 6H) Second eluted diastereomer: EM 582.2 (M + H +).

EXAMPLE 230 Preparation of benzylic acid ester ( { (S) -3-methyl-1-y3-oxo-1- (pyridine-2-sulfonyl) -azepan-4-ylcarbamoyl-butylcarbamoylcarbamic acid The title compound was prepared following the procedure of Example 75, but substituting the benzenesulfonyl chloride with 2-pyridylsulfonyl chloride, and the benzofuran-2-carboxylic acid with N-carbobenzyloxycarbonyl-glycine. The residue was purified by CLAP. First eluted diastereomer, MS (M + H +): 574.2: 1 H NMR (400 MHz, CDCl 3): d 8.60 (d, 1 H), 7.97-7.90 (m, 2H), 7.50 (m, 1 H), 7.42 -7.25 (m, 5H), 6.90 (m, 1 H), 6.42 (m, 1 H), 5.38 (m, 1 H), 5.18-5.10 (m, 4H), 4.78-4.72 (d, 1 H) , 4.50 (m, 1 H), 4.12-4.05 (m, 1 H), 3.95-3.85 (m, 2H), 2.72 (m, 1 H), 2.25-2.10 (m, 2H), 1.90-1.40 (m , 5H), 0.92 (m, 6H); and second diastereomer eluted EM (M + H +) 574.2.

EXAMPLE 231 Preparation of r3-oxo-1- (pyridine-2-sulfonyl) -azepan-4-amide of (S) -2-f5- (4-methoxy-phenyl) -pentanoylamino-1-4-methyl-pentanoic acid The title compound was prepared following the procedure of Example 75, but substituting the benzenesulfonyl chloride with 2-pyridiisulfonyl chloride, and the benzofuran-2-carboxylic acid with 5- (4-methoxyphenyl) pentanoic acid. The residue was purified by CLAP. First eluted diastereomer, MS (M + H +): 573.4: 1 H NMR (400 MHz, CDCl 3): 8.59 (d, 1 H), 7.97-7.94 (m, 2H), 7.53 (m, 1 H), 7.09-7.07 (d, 2H), 6.89-6.81 (m, 3H), 5.90 (m, 1 H), 5.12 (m, 1 H), 4.79- 4.74 (d, 1 H), 4.48 (m, 1 H), 4.12 (m, 1 H), 3.86-3.81 (d, 1H), 3.79 (s, 3H), 2.69 (m, 1 H), 2.59- 2.57 (m, 2H), 2.23-2.10 (m, 3H), 1.75-1 ¡45 (m, 10H), 0.96-0.95 (m, 6H); and the second diastereomer eluted with EM (M + H +) 573.4.

EXAMPLE 232 Preparation of r3-oxo-1- (pyridine-2-sulfonyl) -azepan-4-amide of (S) -2-r2- (3-benzyloxy-4-methoxy-phenyl) -acetylamino-4-amide methylpentanoic The title compound was prepared following the procedure of Example 75, but substituting the benzenesulfonyl chloride with 2-pyridiisulfonyl chloride, and the benzofuran-2-carboxylic acid with (3-benzyloxy-4-methoxy-phenyl) acetic acid. The residue was purified by CLAP. First eluted diastereomer, MS (M + H +): 637.4: H NMR (400 MHz, CDCl 3): d 8.69 (d, 1 H), 7.98-79.91 (m, 2H), 7.53-7.30 (m, 6H); and the second diastereomer eluted: 6.89-6.82 (m, 4H), 5.82 (m, 1 H), 5.14-5.07 (m, 3H), 4.78-4.73 (d, 1 H), 4.43 (m, 1 H ), 4.09 (m, 1H), 3.89 (s, 3H), 3.82 (d, 1 H), 3.49 (s, 2H), 2.69 (m, 1 H), 2.14 (m, 2H), 1.82-1.40 ( m, 5H), 0.89 (d, 6H); and the second diastereomer eluted EM (M + H +) 637.4.

EXAMPLE 233 Preparation of 5- (6-difluoro-benzofuran ((S) -3-methyl-1-ri- (pyridin-2-sulfon-p-3-oxo-azepane-4-yl-carbamoyl-buti-p-pivamide) -2-carboxylic (to) . { (S) -3-Methyl-1- [1- (pyridin-2-sulfonyl) -3-hydroxy-azepan-4-ylcarbamoyl] -butyl ester} 5,6-difluoro-benzofuran-2-carboxylic acid amide The title compound was prepared following the procedure of example 28b, but substituting benzofuran-2-carboxylic acid with 5,6-d? -fluorobenzofuran-2-carboxylic acid: MS (M + H +): 564. (b). { (S) -3-Methyl-1- [1- (pyridin-2-sulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -butyl ester} 5,6-difluoro-benzofuran-2-carboxylic acid amide The title compound was prepared following the procedure of example 1i, but using the compound of example 233a. The residue was purified by CLAP. First eluted diastereomer: MS (M + H +): 562; and the second diastereomer eluted: MS (M + H +) 562.

EXAMPLE 234 Preparation of r3-oxo-1- (pyridine-2-sulfoniP-azepan-4-ylamide of (S) -4-methyl-2- (5-oxo-hexanoylamino) pentanoic acid The title compound was prepared following the procedure of Example 115, but substituting 4-methoxybenzenesulfonyl chloride with 2-pyridinesulfonyl chloride, and benzyloxy acetyl chloride with 5-oxo-hexanoyl chloride. The residue was purified by CLAP. First eluted diastereomer: MS 495.4 (M + H +); second eluted diastereomer: MS 495.4 (M + H +).

EXAMPLE 235 Preparation of. { (S) -3-methyl-1 -M - (6-methyl-pyridin-2-sulfoniD-3-oxo-azepan-4-ylcarbamoin-buty-phenyl) -benzofuran-2-carboxylic acid (a) 6-Methyl-pyridine-2-sulfonyl chloride The title compound was prepared in a manner similar to that described in Example 85a for the preparation of 2-pyridinesulfonyl chloride N-oxide. (b) Tert-butyl acid ester. { (S) -1- [3-hydroxy-1- (6-methyl-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -3-methyl-butyl} To a solution of [(S) -1- (3-hydroxy-azepan-4-ylcarbamoyl) -3-methyl-butyl] carbamic acid tert-butyl ester of example 2g (1.0 g) in dichloromethane (20 g). ml), saturated bicarbonate solution (50 ml) was added.

To this solution was added 6-methyl-pyridine-2-sulfonyl chloride (6.44 ml of a 0.13 g / ml solution in 9M HCl). The reaction was stirred until complete.

By treatment and column chromatography (5% methanol: diclpromethane) the title compound (1.2 g) was obtained. (c) [3-Hydroxy-1- (6-methyl-pyridin-2-sulfonyl) -azepan-J4-yl] (S) -2-amino-4-methyl-pentanoic acid amide To a solution of [3-Hydroxy-1- (6-methyl-pyridin-2-sulfonyl) -azepan-4-yl] (S) -2-amino-4-methyl-pentanoic acid amide of Example 235a (1.2 g) in methanol (20 ml), 4M HCl in dioxane (20 ml) was added. The reaction was stirred until complete, after which it was concentrated to give the title compound (1 g). (d). { (S) -3-Methyl-1 - [1- (6-methyl-pyridin-2-sulfonyl) -3-hydroxy-azepan-4-ylcarbamoyl] -butyl ester} benzofuran-2-carboxylic acid amide The title compound was prepared following the procedure of example 28b, but using [3-hydroxy-1- (6-methyl-pyridin-2-sulfonyl) -azepan-4-yl-amide acid ( S) -2-amino-4-methyl-pentanoic of Example 235c: MS (El) 542 (M +). (e) { (S) -3-Methyl-1 - [1- (6-methyl-pyridine-2-sulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -butyl ester} benzofuran-2-carboxylic acid amide The title compound was prepared following the procedure of example 1, but using the. { (S) -3-methyl-1- [1- (6-methyl-pyridin-2-sulfonyl) -3-hydroxy-azepan-4-ylcarbamoyl] -butyl ester} benzofuran-2-carboxylic acid amide of example 235d: 1 H NMR (CDCl 3) d 1.0 (m, 6H), 1.5-2.2 (m, 6H), 2.6 (m, 3H), 2. 7 (m, 1 H), 4.1 (m, 1 H), 4.7 (m, 2H), 5.3 (m, 1 H), 7.4-8.0 (m, 8H); MS (EI); 540 (M +, 100%).

EXAMPLE 236 Preparation of. { (S) -3-methyl-1 -M - (6-methyl-pyridin-2-sulfoniD-3-oxo-azepan-4-ylcarbamoin-buti-P-5-methoxybenzofuran-2-carboxylic acid (to) . { (S) -3-Methyl-1 - [1- (6-methyl-pyridin-2-sulfonyl) -3-hydroxy-azepan-4-ylcarbamoyl] -butyl ester} 5-methoxybenzofuran-2-carboxylic acid amide The title compound was prepared following the procedure of example 28b, but substituting benzofuran-2-carboxylic acid with 5-methoxybenzofuran-2-carboxylic acid, and substituting [3-hydroxy] 1- (pyridin-2-sulfonyl) -azepan-4-yl] (S) -2-amino-4-methyl-pentanoic acid amide of example 28b with [3-hydroxy-1- (6-methyl-pyridine- 2-sulfonyl) -azepan-4-yl] amide of (S) -2-amino-4-methyl-pentanoic acid of Example 235c: MS (El) 572 (M +). (b) { (S) -3-Methyl-1 - [1- (6-methyl-pyridine-2-sulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -butyl ester} 5-methoxybenzofuran-2-carboxylic acid amide The title compound was prepared following the procedure of example 1 i, but using the. { (S) -3-methyl-1- [1- (6-methyl-pyridin-2-sulfonyl) -3-hydroxy-azepan-4-ylcarbamoyl] -butyl ester} 5-methoxybenzofuran-2-carboxylic acid amide of example 236a: 1 H NMR (CDCl 3) d 1.0 (m, 6H), 1.5-2.2 (m, 6H), 2.6 (m, 3H), 2.7 (m, 1 H ), 3.8 (s, 3H), 4.1 (m, 1 H), 4.7 (m, 2H), 5.3 (m, 1 H), 7.4-8.0 (m, 7H); MS (EI): 570 (M +, 100%).

EXAMPLE 237 Preparation of. { (S) -3-methyl-1H - (6-methyl-pyridin-2-sulfonyl) -3-oxo-azepan-4-ylcarbamoin-buti-P-3-methylbenzofuran-2-carboxylic acid (to) . { (S) -3-Methyl-1 - [1- (6-methyl-pyridin-2-sulfonyl) -3-hydroxy-azepan-4-ylcarbamoyl] -butyl ester} 3-methylbenzofuran-2-carboxylic acid amide The title compound was prepared following the procedure of example 236a, but substituting 5-methoxybenzofuran-2-carboxylic acid with 3-methylbenzofuran-2-carboxylic acid: EM (El) 556 ( M +). (b) { (S) -3-Methyl-1- [1- (6-methyl-pyridine-2-sulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -butyl ester} 3-methylbenzofuran-2-carboxylic acid amide The title compound was prepared following the procedure of example 1i, but using the. { (S) -3-methyl-1- [1- (6-methyl-pyridin-2-sulfonyl) -3-hydroxy-azepan-4-ylcarbamoyl] -butyl ester} 3-methylbenzofuran-2-carboxylic acid amide of Example 237a: 1 H NMR (CDCl 3) d 1.0 (m, 6H), 1.5-2.2 (m, 6H), 2.6 (m, 3H), 2. 7 (m, 1 H), 3.8 (s, 1 H), 4.1 (m, 1 H), 4.7 (m, 2H), 5.3 (m, 1H), 7.4-8.0 (m, 6H); MS (EI): 564 (M +, 100%).

EXAMPLE 238 Preparation of. { (S) -3-Methyl-1H- (pyridin-2-sulfonyl) -3-oxo-azepan-4-yl-carbamoin-buty-phenyl acid of 7-methoxybenzofuran-2-carboxylic acid I 5 (a). { (S) -3-Methyl-1 - [1- (6-methyl-pyridine-2-sulfonyl) -3-hydroxy-azepan-4-ylcarbamoyl] -butyl} 7-methoxybenzofuran-2-carboxylic acid amide The title compound was prepared following the procedure of example 28b, but substituting benzofuran-2-carboxylic acid with 7- methoxybenzofuran-2-carboxylic acid: EM (El) 559 (M +) . 0 (b). { (S) -3-Methyl-1- [1- (6-methyl-pyridine-2-sulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -butyl} 7-methoxybenzofuran-2-carboxylic acid amide The title compound was prepared following the procedure of example 1 i, but using the. { (S) -3-methyl-1- [1- (6-methyl-pyridin-2-sulfonyl) -3-hydroxy-azepan-4-ylcarbamoyl] -butyl ester} 7-methoxybenzofuran-2-carboxylic acid amide 5 of Example 238a: MS (El) 557 (M + H +). 1 EXAMPLE 239 Preparation of 5,6-dimethoxybenzofiblofen-2- (1- S) -3-methyl-1-f 1 - (pyridin-2-sulfonyl) -3-oxo-azepane-4-yl-carbamoin-buty-phenamide carboxylic acid 0 (a) { (S) -3-Methyl-1- [1- (6-methyl-pyridin-2-sulfonyl) -3-hydroxy-azepan-4-ylcarbamoyl] -butyl}. 5,6-dimethoxy-benzo [b] thiophene-2-carboxylic acid amide The title compound was prepared following the procedure of example 28b, but substituting benzofuran-2-carboxylic acid with 5,6-dimethoxy-benzo [ b] thiophene-2-carboxylic acid: EM (El) 604 (M +). (b) { (S) -3-Methyl-1- [1- (6-methyl-pyridine-2-sulfonyl) -3- oxo-azepan-4-ylcarbamoyl] -butyl} - 5,6-dimethoxy-benzo [b] thiophene-2-carboxylic acid amide The title compound was prepared following the procedure of example 1i, but using the. (S) -3-methyl-1- [1- (6-methyl-pyridin-2-sulfonyl) -3-hydroxy-azepan-4-ylcarbamoyl] -butyl} -amide of 5,6-dimethoxybenzo [b] acid ] thiophen-2-carboxylic acid from Example 239a: MS (El) 602.9 (M + H +).

EXAMPLE 240 Preparation of. { (S) -3-methyl-1 -. { 3-Oxo- (pyridin-2-sulfonyl) -azepan-4-yl-carbamoin-buty-phenyl acid (R) -1-benzyl-5-oxo-pyrrolidin-2-carboxylic acid The title compound was prepared following the procedure of Example 75, but substituting thiazole-2-sulfonyl chloride with 2-pyridylsulfonyl chloride, and benzofuran-2-carboxylic acid with (R) -1-benzyl-5- acid oxo-pyrrolidine-2-carboxylic acid. The residue was purified by CLAP. First eluted diastereomer, MS (M + H +): 584.4: 1 H NMR (400 MHz, CDCl 3): d 8.69 (d, 1 H), 7.99-7.92 (m, 2H), 7.52 (m, 1 H), 7.32-7.22 (m, 5H), 6.92 (d, 1 H), 6.38 (d, 1h), 5.15-5.08 (m , 2H), 4.80-4.75 (d, 1 H), 4.47-4.44 (m, 1H), 4.14-4.10 (m, 1 H), 3.89-3.80 (m, 3H), 2.75-2.63 (m, 2H) , 2.46-1.44 (m, 10H), 0.95 (d, 6H); and the second diastereomer eluted EM (M + H +) 584.4.

EXAMPLE 241 Preparation of ((S) -3-methyl-1-f3-oxo- (pyridin-2-sulfonyl) -azepan-4-yl-carbamoH-butyamide (SH-benzyl-5-oxo-pyrrolidin-2) - carboxylic The title compound was prepared following the procedure of Example 75, but substituting benzenesulfonyl chloride with 2-pyridylsulfonyl chloride, and benzofuran-2-carboxylic acid with (S) -1-benzyl-5-oxo-pyrrolidin- 2-carboxylic acid The residue was purified by CLAP. First eluted diastereomer, MS (M + H +): 584.4: "NMR (400 MHz, CDCl 3): d 8.69 (d, 1H), 7.98-7.92 (m, 2H), 7.52 (m, 1H), 7.32-7.22 (m, 5H), 6.92 (d, 1H), 6.38 (d, 1 H), 5.22-5.18 (d, 1 H), 5.10 (m, 1 H), 4.80-4.75 (d, 1 H), 4.51 (m, 1 H), 4.12-4.08 (m, 1 H), 3.91-3.79 (m, 3H), 2.71- 1.38 (m, 12H), 0.97 (d, 6H); and the second diastereomer eluted EM (M + H +) 584.4.

EXAMPLE 242 Preparation of. { (S) -2-cyclopropyl-1 -. { 3-oxo-1 - (pyridin-2-sulfonyl) -azepan-4-ylcarbamoiP-benzofuran-2-carboxylic acid ethinamide Following the procedure of Example 193 e-h, but using N-Boc-cyclopropylalanine for step 193e, the title compound was purified to produce two diastereomers as solids (first eluate: 8 mg, second eluate: 8 mg); MS (ESI) 525 (M + H +).

EXAMPLE 243 Preparation of ((S) -3-methylsulfanyl-1-r3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl) -propipamide of benzofuran-2-carboxylic acid The procedures of examples 193 e-g were followed, but using N-Boc-L-methionine in step 193e. Oxidation of step 193g was performed by adding sulfur trioxide-pyridine complex (34 mg, 0.211 mmol) and triethylamine (0.077 ml) to the intermediate alcohol in DMSO solvent (0.200 ml). After stirring at room temperature for two hours, the mixture was diluted with water and extracted with ethyl acetate. The organic layer was dried, filtered, concentrated and purified by CLAP to yield two diastereomers of the title compound as solids (first eluate: 8 mg, second eluate: 5 mg); MS (ESI) 545 (M + H +).

EXAMPLE 244 Preparation of. { (S) -2-naphthylene-2-yl-1-oxo-l- (pyrid? N-2-sulfonyl) -azepan-4-ylcarbamoi-P-etipamide of benzofuran-2-carboxylic acid Following the procedure of Example 193 eh, but using N- (t-butoxycarbonyl) -3- (2-naphthyl) -L-alanine, the title compound was purified to produce two diastereomers as solids (first eluate: 5.3 mg; eluate: 3.3 mg); MS (ESI) 610.8 (M + H +).

EXAMPLE 245 Preparation of (3 S) -3-methyl-1 - [1- (6-methyl-pyridine-2-sulfonyl) -3-oxo-azepane-4-carbamoin-buty-phenamide of thienor-3-1,2-thiophene 2-carboxylic (to) . { (S) -3-Methyl-1 - [1- (6-methyl-pyridin-2-sulfonyl) -3-hydroxy-azepan-4-ylcarbamoyl] -butyl ester} thieno [3,2-b] thiophene-2-carboxylic acid amide The title compound was prepared following the procedure of example 236a, but substituting 5-methoxybenzofuran-2-carboxylic acid with thieno acid [3,2-b] thiophen-2-carboxylic acid: MS (El) 564 (M +). (b) { (S) -3-Methyl-1 - [1- (6-methyl-pyridine-2-sulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -butyl ester} thieno [3,2-b] thiophene-2-carboxylic acid amide The title compound was prepared following the procedure of example 1i, but using the. { (S) -3-methyl-1- [1- (6-methyl-pyridin-2-sulfonyl) -3-hydroxy-azepan-4-ylcarbamoyl] -butyl ester} thieno [3,2-b] thiophene-2-carboxylic acid amide of example 245a: 1 H NMR (CDCl 3): d 1.0 (m, 6H), 1.5-2.2 (m, 6H), 2.6 (m, 3H) , 2.7 (m, 1 H), 3.8 (s, 1H); 4.1 (m, 1 H), 4.7 (m, 2H), 5.3 (m, 1 H), 7.4-8.0 (m, 6H); MS (EI): 562 (M +, 100%).

EXAMPLE 246 Preparation of ((S) -3-methyl-1H - (3-methyl-pyridin-2-sulfonyl) -3-oxo-azepan-4-ylcarbamoyl-butyamide of thienor-3,2-b] thiofTn- 2 -carboxylic (a) [3-H -droxy-1- (3-methyl-pyridin-2-sulfonyl) -azepan-4-yl] (S) -2-amino-4-methyl-pentanoic acid amide The compound of the title was prepared following the procedure of Examples 235 bc, but substituting the 6-methyl-pyridine-2-sulfonyl chloride with 3-methyl-pyridine-2-sulfonyl chloride; MS (El) 399 (M +). (b) { (S) -3-Met l-1- [1- (3-methyl-pyridin-2-sulfonyl) -3-hydroxy-azepan-4-ylcarbamoyl] -butyl ester} thieno [3,2-b] thiophene-2-carboxylic acid amide To a solution of [3-hydroxy-1- (3-methyl-pyridin-2-sulfonyl) -azepan-4-yl] acid (S) 2-amino-4-methyl-pentanoic acid from example 246a (0.25 g) in dichloromethane, was added thieno [3,2-b] thiophene (0.10 g), triethylamine (0.12 ml), HOBt (0.085 g) and EDC (0.12 g). The reaction was stirred until complete. By treatment and column chromatography (5% methanol: dichloromethane) the title compound (0.18 g) was obtained: MS (El) 564 (M +). (c). { (S) -3-Methyl-1- [1- (3-methyl-pyridin-2-sulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -butyl ester} thieno [3,2-b] thiophene-2-carboxylic acid amide The title compound was prepared following the procedure of example 1 i, but using the. { (S) -3-methyl-1- [1- (3-methyl-pyridin-2-sulfonyl) -3-hydroxy-azepan-4-ylcarbamoyl] -butyl ester} thieno [3,2-b] thiophene-2-carboxylic acid amide of example 246b: 1 H NMR (CDCl 3): d 1.0 (m, 6H), 1.5-2.2 (m, 6H), 2.6 (m, 3H) , 3.0 (m, 1 H), 3.8 (s, 3H), 4.1 (m, 2H), 4.7 (m, 2H), 5.3 (m, 1H), 7.4-8.0 (m, 5), 8. 4 (m, 1 H); MS (EI): 562 (M +, 100%).

EXAMPLE 247 Preparation of. { (S) -3-Methyl-1H- (3-methyl-pyridin-2-sulfonyl) -3-oxo-azepan-4-ylcarbamoy-buty-phenamide 3-methylbenzofuran-2-carboxylic acid (to) . { (S) -3-Methyl-1 - [1- (3-methyl-pyridin-2-sulfonyl) -3-hydroxy-azepan-4-ylcarbamoyl] -butyl} 3-methylbenzofuran-2-carboxylic acid amide The title compound was prepared following the procedure of example 246c, but replacing thieno [3,2-b] thiophene with 3-methylbenzofuran-2-carboxylic acid: EM (El) 556 (M +). (b) { (S) -3-Methyl-1 - [1- (3-methyl-pyridine-2-sulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -butyl ester} 3-methylbenzofuran-2-carboxylic acid amide The title compound was prepared following the procedure of example 1i, but using the. { (S) -3-methyl-1- [1- (3-methyl-pyridin-2-sulfonyl) -3-hydroxy-azepan-4-ylcarbamoyl] -butyl ester} 3-methylbenzofuran-2-carboxylic acid amide of Example 247a: 1 H NMR (CDCl 3): d 1.0 (m, 6H), 1.5-2.2 (m, 6H), 2.6 (d, 3H), 2.6 (m, 3H) ), 3.0 (m, 1 H), 4.1 (m, 2H), 4.7 (m, 2H), 5.3 (m, 1 H), 7.4-8.0 (m, 6H), 8.4 (m, 1H); MS (EI): 554 (M +, 100%).

EXAMPLE 248 Preparation of. { (S) -3-methyl-1H - (3-methyl-pyridin-2-sulfonyl) -3-oxo-azepan-4-ylcarbamoin-buty-5-methoxybenzofuran-2-carboxylic acid amide (to) . { (S) -3-Methyl-1 - [1- (3-methyl-pyridin-2-sulfonyl) -3-hydroxy-azepan-4-ylcarbamoyl] -butyl} 5-methoxybenzofuran-2-carboxylic acid amide The title compound was prepared following the procedure of example 246c, but replacing thieno [3,2-b] thiophene with 5-methoxybenzofuran-2-carboxylic acid: EM (El) 572 ( M +). (b) { (S) -3-Methyl-1 - [1- (3-methyl-pyridine-2-sulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -butyl ester} 5-methoxybenzofuran-2-carboxylic acid amide The title compound was prepared following the procedure of example 1i, but using. { (S) -3-methyl-1- [1- (3-methyl-pyridin-2-sulfonyl) -3-hydroxy-azepan-4-ylcarbamoyl] -butyl ester} 5-methoxybenzofuran-2-carboxylic acid amide of example 248a: 1 H NMR (CDCl 3): d 1.0 (m, 6H), 1.5-2.2 (m, 6H), 2.6 (d, 3H), 3.0 (m, 1H ), 3.8 (s, 3H); 4.1 (m, 2H), 4.7 (m, 2H), 5.3 (m, 1H), 7.4-8.0 (m, 6H), 8.4 (m, 1 H); MS (EI): 570 (M +, 100%).

EXAMPLE 249 Preparation of 5,6-difluoro-benzofuran- ((S) -3-methyl-1-r3-oxo-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoin-buti-p-pyrimidine 2-carboxylic (to) . { (S) -3-Methyl-1 - [3-hydroxy-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl ester} 5,6-difluoro-benzofuran-2-carboxylic acid amide The title compound was prepared following the procedure of Example 85c, but substituting benzo [b] thiophene-2-carboxylic acid with 5,6-difluorobenzofuran-2-carboxylic acid: MS (ESI) 580.9 (M + H +). (b) { (S) -3-Methyl-1 - [3-oxo-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl ester} 5,6-difluoro-benzofuran-2-carboxylic acid amide The title compound was prepared following the procedure of Example 1i, but using the compound of Example 249a: MS (ESI) 578.87 (M + H +).

EXAMPLE 250 Preparation of 5- (3-trifluoromethyl-phenyl) -furan- ((S) -2-cyclohexyl-1-r3-oxo-1- (pyridine-2-sulfonyl) -azepan-4-ylcarbamoyl-etiPamide 2- carboxylic (a) 4 - ((S) -2-tert-Butoxycarbonylamino-3-cyclohexyl-propionylamino) -3-hydroxy-azepane-1-carboxylic acid benzyl ester To a solution of the compound ^ of Example 2e (3.2 g, 12.2 mmoles) in DMF (35 ml), was added N-Boc-cyclohexylalanine (3.3 g), HOBt (1.8 g) and EDC (2.56 g). The reaction was stirred until complete. By treatment and column chromatography of the residue (65% hexane: ethyl acetate) 5.5 g of the title compound were obtained. (b) [(S) -cyclohexyl-1- (3-hydroxy-azepan-4-ylcarbamoyl) -ethyl] -carbamic acid tert-butyl ester To a solution of the compound of example 250a (5.5 g) in ethyl acetate: methanol (185 ml: 40 ml), 10% Pd / C was added. This mixture was stirred under a hydrogen atmosphere until complete consumption of the starting material was observed. The reaction was filtered and concentrated to provide 3.75 g of the title compound. (c) Tert-butyl acid ester. { (S) -2-Cyclohexyl-1- [3-hydroxy-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] ethyl} To a solution of the compound of example 250b (1.0 g, 1.91 mmol) in dichloromethane (5 ml), water (10 ml) and sodium bicarbonate (1 g) were added. To this mixture was added 2-pyridinesulfonyl chloride (0.55 g in 5 ml of dichloromethane) in the form of drops. The mixture was stirred 20 minutes, after which the organic layer was separated and washed with water and brine; it was filtered and concentrated. Column chromatography (2% methanol: dichloromethane) of the residue gave 1.0 g of the title compound: MS (ESI) 525 (M + H +). (d) (S) -2-Amino-3-cyclohexyl-N- [3-hydroxy- (pyridin-2-sulfonyl) -azepan-4-yl] -propionamide To a solution of the compound of example 250c (1.0 g) in methanol (10 ml), HCl (10 ml of 4M HCl in dioxane) was added. The reaction was stirred until complete consumption of the starting material, after which it was concentrated. The residue was azeotropically distilled with toluene and then washed with ether to give 0.95 g of the title compound. (e) { (S) -2-Cyclohexyl-1 - [3-hydroxy-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -ethyl} 5- (3-trifluoromethyl-phenyl) -furan-2-carboxylic acid amide To a solution of the compound of example 250d (0.20 g, 0.4 mmol) in DMF (0.5 ml), diisopropylethylamine (0.16 ml), HOBt, was added. (0.06 g), EDC (0.084 g) and 5- [3- (trifluoromethyl) phenyl] -2-furoic acid (0.11 g). The reaction was stirred until complete consumption of the starting material. By treatment and column chromatography (4% methanol: dichloromethane) 0.23 g of the title compound were obtained. (f) { (S) -2-Cyclohexyl-1 - [3-oxo-1 - (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -ethyl} 5- (3-trifluoromethyl-phenyl) -furan-2-carboxylic acid amide The title compound was prepared following the procedure of Example 75d, but using the compound of Example 250e. Separation of the diastereomers by CLAP gave the first eluted diastereomer (52 mg): MS (ESI) 661.4, and the second diastereomer eluted (45.8 mg): MS (ESI) 661. 6 EXAMPLE 251 Preparation of. { (S) -2-cyclohexyl-1 - (3-oxo-1 - (pyridine-2-sulfonyl) -azepan-4-ylcarbamoin-etiPamide of 5- (4-chloro-phenyl) -furan-2-acid carboxylic The title compound was prepared following the procedure of Example 250 e-f, but substituting the 5- [3- (trifluoromethyl) phenyl] -2-furoic acid of Example 250e with 5- [4-chlorophenyl) -2-furoic acid. Separation of the diastereomers by CLAP gave the first eluted diastereomer (57 mg): MS (ESI) 627.4, and the second diastereomer eluted (53 mg): MS (ESI) 627.4.

EXAMPLE 252 Preparation of benzofuran-2-carboxylic acid ((S) -3-methyl-1-r6-methyl-3-oxo-1- (pyridine-sulfonyl) -azepan-4-ylcarbamoy-buty-phenyl acid The title compound was prepared following the procedure of Example 92, but substituting 2,2-dimethyl-4-pentenal with 2-methyl-4-pentenal. The residue was purified by CLAP. First eluted diastereomer, MS (M + H +) 541. 2, 1 H NMR (400 MHz, CDCl 3): d 8.71-8.66 (m, 1 H), 7.98-7.93 (m, 2 H), 7.91 (d, 1 H), 7.67-7.29 (m, 5 H), 7.15-6.92 (m, 2H), 5.28-5.20 (m, 1H), 4.82-4.47 (m, 2H), 3.97-3.78 (m, 1H), 3.65-2.98 (m, 1 H), 2.37-2.34 (m, 1H) ), 2.20-1.55 (m, 3H), 1.22-1.19 (m, 3H), 1.00-0.86 (m, 9H).

EXAMPLE 253 Preparation of. { (S) -2-cyclohexyl-1-f3-oxo-1- (1-oxy-pyridin-2-sulfonyl)-azepan-4-ylcarbamoin-etiPamide of 5- (4-chloro-phenyl) -furan-2 acid - carboxylic The title compound was prepared following the procedure of Example 250 cf, but substituting the 2-pyridinesulfonyl chloride of Example 250c with 2-pyridinesulfonyl chloride N-oxide, and substituting 5- [3- (trifluoromethyl) phenyl] -2-furoic of example 252e with 5- (4-chlorophenyl) -2-furoic acid. By separation of the diastereomers by CLAP, the first eluted diastereomer was obtained: MS (ESI) 643.4, and the second diastereomer eluted: MS (ESI) 643.2.

EXAMPLE 254 Preparation of 5- (3-trifluoromethyl-phenyl) - ((S) -2-cyclohexyl-1-r3-oxo-1- (1- (oxy-pyridin-2-sulfonyl)-azepan-4-ylcarbamoin-etiPamide) ) -furan- 2 -carboxylic The title compound was prepared following the procedure of example 250 c-f, but substituting the 2-pyridinesulfonyl chloride of the example 250c with 2-pyridinesulfonyl chloride N-oxide. The first diastereomer eluted was obtained by separating the diastereomers by means of CLAP: (ESI) 677.2, and the second diastereomer eluted: MS (ESI) 677.4.

EXAMPLE 255 Preparation of. { (S) -3-rnetl-1-r3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-yl-carbamoyl-buty-p -amide of 5-fluoro-benzofuran-2-carboxylic acid (to) . { (S) -3-Methyl-1- [3-hydroxy-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 5-Fluoro-benzofuran-2-carboxylic acid amide The title compound was prepared following the procedure of example 28b, but substituting benzofuran-2-carboxylic acid with 5-fluorobenzofuran-2-carboxylic acid: MS (ESI) 547 (M + H +). (b) { (S) -3-Methyl-1 - [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 5-Fluoro-benzofuran-2-carboxylic acid amide The title compound was prepared following the procedure of example 1i, but using the compound of example 255a: MS (ESI) 544.9 (M + H +).

EXAMPLE 256 Preparation of ((S) -2-cyclohexyl-1-r3-oxo-1- (1-oxy-pyridin-2-sulfonyl)-azepan-4-ylcarbamoy-ethi-5,6-dimethoxybenzofuran-2-acid carboxylic The title compound was prepared following the procedure of Example 250 cf, but substituting the 2-pyridinesulfonyl chloride of Example 250c with 2-pyridinesulfonyl chloride N-oxide, and substituting 5- [3- (trifluoromethyl) phenyl] -2-furoic acid with 5,6-dimethoxybenzofuran-2-carboxylic acid. By separation of the diastereomers by CLAP, the first eluted diastereomer was obtained: MS (ESI) 643.4, and the second diastereomer eluted: MS (ESI) 643.2.

EXAMPLE 257 Preparation of 5,5-bis- (4-methoxy-phenyl) ((S) -3-methyl-1-r3-oxo-1- (pyridine-2-sulfonyl) -azepan-4-yl-carbamoilllbutiPamide ) -pent-4-enoic The title compound was prepared following the procedure of Example 75, but substituting thiazole-2-sulfonyl chloride with 2-pyridylsulfonyl chloride and benzofuran-2-carboxylic acid with 5,5-bis- (4-methoxy) phenyl) -pent-4-enoic. The residue was purified by CLAP. First eluted diastereomer, MS (M + H +) 677.4; 1 H NMR (400 MHz, CDCl 3): d 8.69 (d, 1 H), 7.98-7.92 (m, 2H), 7.53-7.50 (m, 1 H), 7.27-6.77 (m, 10H), 6.00-5.87 (m, 2H), 5.08 (m, 1 H), 4.76-4.72 (d, 1 H), 4.48 (m, 1 H), 4.08 (m, 1H), 3.83 (s, 3H), 3.78 (s, 3H), 2.70-1.35 (m, 12H), 0.91 (d, 6H); and the second diastereomer eluted EM (M + H +) 677.4 EXAMPLE 258 Preparation of ((S) -2-naphthylene-2-yl-1 - [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl-ethylamide of quinoline-8-carboxylic acid (a) 4-Amino-1- (pyridin-2-sulfonyl) -azepan-3-ol To a solution of the compound of example 193c (1.5 g) in methanol (10 ml), HCl ( 10 ml 4M HCl in dioxane). The reaction was stirred until complete by CCD analysis, after which it was concentrated to give 1.2 g of the title compound as a white solid. (b) Tert-butyl acid ester. { (S) -1- [3-hydroxy-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -2-naphthylene-2-yl-etl} to a solution of the compound of example 258a (225 mg) in dichloromethane, TEA (0.15 ml), HOBt (99 mg), EDC (140 mg) and N-Boc-L-2-naphthylalanine (230 mg) were added. The reaction was stirred until complete. By treatment and column chromatography of the residue (3% methanol: dichloromethane) 0.35 g of the title compound were obtained: MS (ESI) 569 (M + H +). (c) (S) -2-Amino-N- [3-hydroxy-1- (pyridin-2-sulfonyl) -azepan-4-yl] -3-naphthylene-2-yl-propionamide To a solution of the compound of Example 258b (0.35 g) in methanol (5 ml), HCl (5 ml 4M HCl in dioxane) was added. The reaction was stirred until complete by CCD analysis, after which it was concentrated to give 0.31 g of the title compound as a white solid. (d). { (S) -2-Naphthylene-2-yl-1- [3-hydroxy-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl) -ethyl] quinoline-8-carboxylic acid amide A solution of the Compound of example 258c (131 mg) in dichloromethane was added TEA, HOBt (39 mg), EDC (55 mg) and quinoline-8-carboxylic acid (51 mg). The reaction was stirred until complete. By treatment and column chromatography of the residue (5% methanol: dichloromethane), 0.35 g of the title compound was obtained: MS (ESI) 574 (M + H +). (e) { (S) -2-Naphthylene-2-yl-1 - [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl) -ethyl] quinoline-8-carboxylic acid amide The title compound was prepared following the procedure of example 1 i, but using the compound of example 258d.

EXAMPLE 259 Preparation of. { (S) -2-naphthylene-2-yl-1-oxo-l- (pyridine-2-sulfonyl) -azepan-4-ylcarbamoiP-naphthylene-1-carboxylic acid naphthylamide The title compound was prepared following the procedures of examples 258 d-e, but substituting the quinoline-8-carboxylic acid with 1-naphthoic acid.

EXAMPLE 260 Preparation of ((SH-r3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl) -2-phenyl-etiPamide of quinoline-8-carboxylic acid The title compound was prepared following the procedures of Examples 258 a-e, but substituting N-Boc-L-2-naphthylalanine with N-Boc-phenylalanine.

EXAMPLE 261 Preparation of naphthyridin-2-carboxylic acid ((S) -3-methyl-1-r3-oxo-1- (pyridine-2-sulfonyl) -azepan-4-ylcarbamoiP-butiPamide The title compound was prepared following the procedure of example 28 b-c, but substituting benzofuran-2-carboxylic acid with 1,6-naphthyridine-2-carboxylic acid.

EXAMPLE 262 Preparation of naphthylene-1-carboxylic acid ((SH-r3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl) -2-phenyl-etiPamide . The title compound was prepared following the procedure of Example 260, but substituting quinoline-8-carboxylic acid with 1-naphthoic acid.

EXAMPLE 263 Preparation of. { (S) -3-methyl-1-y3-oxo-1 - (cyclohexyl-propionyl) -azepan-4- 3-methylbenzofuran-2-carboxylic acid IcarbamoiP-butiPamide (a) Benzyl ester of 4- acid. { (S) -2 - [(3-methylbenzofuran-2-carbonyl) -amino] -4-methyl-pentanoylamino} -3-hydroxy-azepane-1-carboxylic acid To a solution of the compound of Example 72a (1.2 g, 2.67 mmol), EDC (0.56 g), HOBt (0.36 g), TEA (0.67 g) and acid 3- were added. methylbenzofuran-2-carboxylic acid (0.47 g). The reaction was stirred until full consumption of the starting material was observed. By treatment and column chromatography (hexane: ethyl acetate 4: 1) 1.05 g of the title compound were obtained: MS (ESI) 536 (M + H +). (b) [(S) -1- (3-Hydroxy-azepan-4-ylcarbamoyl) -3-methyl-butyl] -3-methylbenzofuran-2-carboxylic acid amide The title compound was prepared following the procedure of Example 2g, but using the compound of Example 263a: MS (ESI) 402 (M + H +). (c). { (S) -3-Methyl-1- [3-hydroxy-1- (cyclohexyl-propionyl) -azepan-4-ylcarbamoyl] -butyl} 3-methylbenzofuran-2-carboxylic acid amide The title compound was prepared following the procedure of example 263a, but substituting 3-methylbenzofuran-2-carboxylic acid with the compound of example 263b and 3-cyclohexylpropionic acid: MS (ESI) 540 (M + H +). (d). { (S) -3-Methyl-1 - [3-oxo-1 - (cyclohexyl-propionyl) -azepan-4-ylcarbamoyl] -butl} 3-methylbenzofuran-2-carboxylic acid amide The title compound was prepared following the procedure of Example 1i, but using the compound of Example 263c: MS (ESI) 538 (M + H +).

EXAMPLE 264 Preparation of. { (S) -3-methyl-1 - | "3-oxo-1- (4-methyl-pentanoyl) -azepan-4-yl-carbamoin-buty-phenylideamide 3-methylbenzof? Ran-2-carboxylic acid The title compound was prepared following the procedures of Examples 263 c-d, but substituting 3-cyclohexylpropionic acid with 4-methylpentanoic acid: MS (ESI) 498 (M + H +).

EXAMPLE 265 Preparation of ((S) -3-methyl-1-l "3-oxo-1- (1-oxy-pyridine-2-carbonyl) -azepan-4-l-carbamoyl-buti-P-3-methylbenzofuran acid -2-carboxylic The title compound was prepared following the procedures of Examples 263 c-d, but substituting 3-cyclohexylpropionic acid with picolinic acid N-oxide: MS (ESI) 498 (M + H +).

EXAMPLE 266 Preparation of f3-oxo-1- (pyridine-2-sulfonyl) -azepan-4-amide of (S) -acetylamino-4-methyl-pentanoic acid Following the procedure of example 75 cd, but substituting the benzofuran-2-carboxylic acid from step 75c with acetic acid, the title compound was prepared, which was separated by CLAP to give the first diastereomer eluted: MS (M + H +) 425.2: 1 H NMR (400 Hz, CDCl 3): 8.69 (d, 1 H), 7. 96-7.94 (m, 2H), 7.53-7.52 (m, 1 H), 7.05 (m, 1 H), 5.92 (m, 1 H), 5.08 (m, 1 H), 4.69-4.53 (m, 2H) ), 4.05-3.90 (m, 2H), 2.80 (m, 1 H), 2.25-2.12 (m, 2H), 1.64 (s, 3H), 1.90-1.40 (m, 5H), 0.95 (m, 6H); and the second diastereomer eluted: MS (M + H +) 425.2.

EXAMPLE 267 Preparation of. { (SH-r3-oxo-1 - (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl-pentiPamide of quinoline-2-carboxylic acid (a) 4 - ((S) -2-tert-Butoxycarbonylamino-hexanoylamino) -3-hydroxy-azepane-1-carboxylic acid benzyl ester To a stirred solution of the amino alcohol compound of example 2e (200 mg, 0.74 mmoles) in DMF (4 ml), was added N-Boc-norleucine (175 mg, 0.76 mmol), EDC-HCI (145 mg, 0.76 mmol) and 1-hydroxybenzotriazole (21 mg, 0.16 mmol). The reaction was allowed to proceed overnight at room temperature. The next morning the mixture was diluted with ethyl acetate, washed with saturated NaHCO3 solution, H2O and brine. Dry over MgSO 4, filter and purify by column chromatography to give 300 mg of the title compound: MS (ESI) 478.11 (M + H +). (b) [(S) -1- (3-hydroxy-azepan-4-ylcarbamoyl) -pentyl] carbamic acid tert-butyl ester To a solution of the compound of example 267a (300 mg, 0.63 mmol) in ethyl acetate (5 ml), palladium on carbon 10% (160 mg) and H2 of a filled balloon were added. After stirring the solution at room temperature for 48 hours, the mixture was filtered through celite. The filtrate was concentrated to yield the title compound (crude, 161 mg, 0.47 mmol): MS (ESI) 344.19 (M + H +). (c) Tert-butyl acid ester. { (S) -1- [3-hydroxy-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -pentyl} To a solution of the compound of example 267b (161 mg, 0.47 mmol) in dichloromethane (6 ml), triethylamine (0.065 ml, 0.47 mmol) and pyridine-2-sulfonyl chloride (83 mg, 0.47 mmol) were added. After stirring at room temperature for 1 hour, the mixture was washed with saturated NaHCO3 solution. The organic layer was dried, filtered and concentrated; was purified on a column of silica gel to give the title compound (142 mg, 0.29 mmol): MS (ESI): 485.10 (M + H +). (d) [3-Hydroxy-1- (pyridin-2-sulfonyl) -azepan-4-yl] (S) -2-amino-hexanoic acid amide To a stirred solution of the compound of example 267c (142 mg, 0.29 mmoles) in ethyl acetate, HCl (4M in dioxane) (0.760 ml, 3.0 mmol) was added. After stirring the reaction mixture for 1 hour at room temperature, the mixture was concentrated to yield a white solid. The solid was azeotropically distilled with toluene in a rotary evaporator twice, and then treated with a resin-bound carbonate (1.47 mmol) in methanol and placed on a stirrer. After 4 hours, the suspension was filtered and concentrated to yield 104 mg of crude product: MS (ESI) 385.08 (M + H +). (e) { (S) -1- [3-Hydroxy-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -pentyl} quinoline-2-carboxylic acid amide To a solution of the compound of example 267d (104 mg, 0.27 mmol) in CH2Cl2, quinaldic acid (47 mg, 0.27 mmol), 1-hydroxybenzotriazole (7.4, 0.055 mmol) was added thereto, and EDC-HCl (52 mg, 0.27 mmol) in DMF (2 ml). After stirring at room temperature overnight, the mixture was diluted with ethyl acetate, washed with saturated NaHCO3 solution and H2O, and dried over MgSO4; it was filtered to obtain 172 mg of crude product: MS (ESI) 539.90 (M + H +). (f) { (S) -1- [3-Oxo-l - (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -pentyl} quinoline-2-carboxylic acid amide To a stirred solution of the compound of example 267e (172 mg, crude, 0.32 mmol) in 1 ml of DMSO, sulfur trioxide-pyridine complex (260 mg, 1.6 mmol) was added thereto and triethylamine (0.88 ml, 3.2 mmol). 2 After stirring at room temperature for 2 hours, the mixture was diluted with water and extracted with ethyl acetate. The organic layer was dried, filtered and concentrated; was purified by CLAP to produce two diastereomers of the title compound as solids (first: 40 mg, second: 43 mg): MS (ESI) 537.86 (M + H +).

EXAMPLE 268 Preparation of. { (S) -3-methyl-1-f3-oxo-1 - (cyclohexyl-propionyl) -azepan-4-ylcarbamoyl-buti-P-benzofuran-2-carboxylic acid The title compound was prepared following the procedures of Examples 263 a-d, but substituting the 3-methylbenzofuran-2-carboxylic acid of Example 263a with benzofuran-2-carboxylic acid: MS (ESI) 524 (M + H +).

EXAMPLE 269 Preparation of benzofuran-2-carboxylic acid ((S) -3-methyl-1-f3-oxo-1- (4-methyl-pentanoyl) -azepan-4-ylcarbamoin-buty-phenyl acid The title compound was prepared following the procedures of Examples 263 ad, but substituting 3-methylbenzofuran-2-carboxylic acid from Example 263a with benzofuran-2-carboxylic acid, and cyclohexylpropionic acid with 5-methylpentanoic acid: MS (ESI) ) 484 (M + H +).

EXAMPLE 270 Preparation of ((SH-r3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoin-2-phenyl-ethi-quinoline-2-carboxylic acid The title compound was prepared following the procedure of example 267 a-f, but substituting N-Boc-norleucine from step 267a with N-Boc-phenylalanine. Separation of the mixture by means of CLAP produced two diastereomers as solids (first eluent: 20.5 mg, second eluent 27 mg): MS (ESI) 571.95 (M + H +).

EXAMPLE 271 Preparation of. { (S) -2-benzyloxy-1 -P-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoin-eti-benzofuran-2-carboxylic acid The title compound was prepared as a mixture of diastereomers following the procedure of Example 193 e-h, but using N-Boc-O-benzyl-L-serine in step 193e. To a solution of. { (S) -2-Benzyloxy-1 - [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -ethyl} Benzofuran-2-carboxylic acid amide (90 mg) in ethyl acetate (2 ml), 10% Pd / C (50 mg) was added. After hydrogenolysis of about 50% of the starting benzylic ether, the reaction was filtered and concentrated. Purification of this 4 component mixture by CLAP gave the first eluted diastereomer of the title compound (1 mg) and the second diastereomer eluted from the title compound (0.3 mg): MS (ESI): 590.94 (M + H +). Additionally, the two individual diastereomers of. { (S) -2-hydroxy-1 - [3-oxo-1 - (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -ethyl} benzofuran-2-carboxylic acid amide as described below in Example 272.

EXAMPLE 272 Preparation of benzofuran-2-carboxylic acid ((S) -2-hydroxy-1-f3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoip-etiPamide The title compound was obtained as described above in example 271. By purification of the mixture by CLAP, the two diastereomers were obtained in solid form (first eluate: 1.6 mg, second eluate 2.1 mg): MS (ESI) 500.9 (M + H +).

EXAMPLE 273 Preparation of 5-methoxybenzofuran-2-carboxylic acid ((S) -3-methyl-1-r3-oxo-1- (thiazole-2-sulfonyl) -azepan-4-yl-carbamoyl-buty-phenyl acid Following the procedure of example 75 cd, but substituting the benzofuran-2-carboxylic acid from step 75c with 5-methoxybenzofuran-2-carboxylic acid, the title compound was prepared, which was separated by CLAP to give the first diastereomer eluted as a white solid (144.3 mg, 85.1%): MS (ESI) 563.2 (M + H +), and the second diastereomer eluted as a white solid (16.9 mg, 10.0%): MS (ESI) 563.0 (M + H +).

EXAMPLE 274 Preparation of. { (S) -3-methyl-1-r3-oxo-1- (7-methoxybenzofuran-2-carboxylic acid 7-methoxybenzofuran-2-carboxylic acid thiazole-2-sulfonyl-p-azepane-4-ylcarbamoyl-buty-phenamide Following the procedure of example 75 cd, but replacing the benzofuran-2-carboxylic acid from step 75c with 7-methoxybenzofuran-2-carboxylic acid, the title compound was prepared, which was separated by CLAP to give the first diastereomer eluted as a white solid (75 mg, 47%): MS (ESI) 563.2 (M + H +), and the second diastereomer eluted as a white solid (57 mg, 35%): MS (ESI) 563.0 (M + H +).

EXAMPLE 275 Preparation of 3-methylbenzofuran-2-carboxylic acid ((S) -3-methyl-1-r3-oxo-1- (thiazole-2-sulfonyl) -azepan-4-yl-carbamoyl-buty-phenyl acid.

Following the procedure of example 75 cd, but replacing the benzofuran-2-carboxylic acid from step 75c with 3-methylbenzofuran-2-carboxylic acid, the title compound was prepared, which was separated by CLAP to give the first diastereomer eluted as a white solid (69.5 mg, 42%): MS (ESI) 547.2 (M + H +), and the second diastereomer eluted as a white solid (65 mg, 40%): MS (ESI) 547.2 (M + H +).

EXAMPLE 276 Preparation of. { (S) -3-Methyl-1-Q-oxo-l - (thiazole-2-sulfonyl) -zepane-4-yl-carbamoyl-buti-P-benzofibenophen-2-carboxylic acid Following the procedure of example 75 cd, but replacing the benzofuran-2-carboxylic acid of step 75c with benzo [b] thiophene-2-carboxylic acid, the title compound was prepared, which was separated by CLAP to give the first diastereomer eluted as a white solid (79.5 mg, 48%): MS (ESI) 549.3 (M + H +), and the second diastereomer eluted as a white solid (50.5 mg, 31%): MS (ESI) 549.2 (M + H + ).

EXAMPLE 277 Preparation of (1-methyl-1-r3-oxo-1- (thiazole-2-sulfonyl) -azepan-4-yl-carbamoy-buty-phenylidene-1-methyl-1 H-indol-2 -carboxylic Following the procedure of example 75 cd, but substituting the benzofuran-2-carboxylic acid from step 75c with 1-methylindol-2-carboxylic acid, the title compound was prepared, which was separated by CLAP to give the first diastereomer eluted as a white solid (75 mg, 47%): MS (ESI) 563.2 (M + H +), and the second diastereomer eluted as a white solid (57 mg, 35%): MS (ESI) 563.0 (M + H +).

EXAMPLE 278 Preparation of. { (S) -3-methyl-1-r3-oxo-1- (thiazole-2-sulfonyl) -azepan-4-yl-carbamoyl-buty-phenamide of quinoxaline-2-carboxylic acid Following the procedure of example 75 cd, but substituting the benzofuran-2-carboxylic acid from step 75c with quinoxaline-2-carboxylic acid, the title compound was prepared, which was separated by CLAP to give the first diastereomer eluted as a solid White (126 mg, 77%): MS (ESI) 545.2 (M + H +), and the second diastereomer eluted as a white solid (25 mg, 15%): MS (ESI) 545.2 (M + H +).

EXAMPLE 279 Preparation of ((SH -f 1 - (4-fluoro-benzenesulfonyl) -3-oxo-azepan-4-yl-carbamoyl-3-methyl-buty-phenamide of quinoline-2-carboxylic acid The title compound was prepared following the procedure of Example 75, but substituting the benzenesulfonyl chloride with 4-fluorophenylsulfonyl chloride, and the benzofuran-2-carboxylic acid with 2-quinoline-carboxylic acid. The residue was purified by CLAP. First eluted diastereomer: EM (M + H +) 555.2; "? NMR (400Hz, CDCI3): d 8.62 (d, 1 H), 8.34-8.23 (q, 2H) 8.19- 8.17 (d, 1 H), 7.90-7.88 (d.1 H), 7.88-7.80 ( m, 3H), 7.66-7.64 (t, H), 7.25-7.07 (m, 3H), 5.08 (m, 1 H), 4.72 (m, 1 H), 4.58-4.53 (d, 1H), 4.00 ( m, 1 H), 3.46-3.42 (d, 1 H), 2.47 (m, 1H), 2.27-2.12 (m, 2H), 1.90-1.40 (m, 5H), 1.03-1.01 (m, 6H); and the second diastereomer eluted EM (M + H +) 555.4 The specification and the above examples fully describe how to prepare and use the compounds of the present invention, however, this invention is not limited to the particular embodiments described above, but includes all modifications thereof which are within the scope of the following claims The various references to journals, patents and other publications cited herein, comprise the state of the art and are hereby incorporated by reference as if they were fully described. .

Claims

NOVELTY OF THE INVENTION CLAIMS 1. - A compound of formula wherein: R1 is selected from the group consisting of R2 is selected from the group consisting of: H, d-β alkyl, (C3.6) cycloalkyl-Co-β alkyl, Ar-Co-β alkyl, Het-C0-β alkyl, R9C (O) -, R9C (S) -, R9SO2-, R9OC (O) -, R9R11NC (O) -, R9R11NC (S) -, R9 (R11) NSO2-, is selected from the group consisting of: H, C? _6 alkyl, C2 alkenyl. 6, C2.6 alkynyl, Het-C0-β alkyl and Ar-C06 alkyl; R3 and R 'may be linked to form a pyrrolidine, piperidine or morpholine ring; R4 is selected from the group consisting of H, C-? 6 alkyl, C3-6 cycloalkyl-Co-e alkyl, C0-ß alkyl, C0-Het alkyl -e, R5C (O) -, R5C (S) -, R5SO2-, R5OC (O) -, R5R13NC (O) -, and R5R13NC (S) -; R5 is selected from the group consisting of: H, C? 6 alkyl, C2.6 alkenyl, C2-6 alkynyl, (C3-6) cycloalkyl-Co-6 alkyl, Ar-Co-b alkyl and Het-alkyl of Co-β; R6 is selected from the group consisting of: H, C-? -6 alkyl, Ar-Co-ß alkyl or Het-Co-β alkyl; R7 is selected from the group consisting of: H, Ci-β alkyl, (C 3-6) cycloalkyl-C 0-6 alkyl, Ar-Co-β alkyl, Het-alkyl of Co-β, R 10 C (O) -, R10C (S) -, R10SO2-, R10OC (O) -, R10R14NC (O) -, and R10R14NC (S); R8 is selected from the group consisting of: H, C6.6 alkyl, C2.6 alkenyl, C2-6 alkynyl, Het-alkyl of Co-β and Ar-alkyl of Co-β; R9 is selected from the group consisting of: C6-6alkyl) C3-6cycloalkyl-Co-βalkyl, Co-βalkaryl and Het-Co-βalkyl; R10 is selected from the group consisting of: C6_6 alkyl, C3.6 cycloalkyl, C0_3 alkyl, C0_3 Ar alkyl, and Co-β alkyl Het; R11 is selected from the group consisting of: H, Ci alkyl. β, Ar-alkyl of Co-β and Het-alkyl of Co-β; R 12 is selected from the group consisting of: H, C 1 .6 alkyl, Ar-Co-β alkyl and Het-Co-β alkyl; R 13 is selected from the group consisting of: H, C 1-6 alkyl-Ar alkyl and Co-β Het-alkyl; R14 is selected from the group consisting of: H, C-? -6 alkyl, Ar-C06 alkyl and Het-alkyl of Co-β; R * is selected from the group consisting of: H, C- | 6 alkyl, Ar-C06 alkyl and Het-Co-β alkyl; R "is selected from the group consisting of: H, C?. Β alkyl, Ar-C alquilo-alkyl or Het-alkyl of Co-β; R '" is selected from the group consisting of: H, alkyl d-6, (C3-β) cycloalkyl-Co-β alkyl, Ar-C0-β alkyl and Het-alkyl of Co-β; X is selected from the group consisting of: CH2, S and O; and Z is selected from the group consisting of: C (O) and CH2; and pharmaceutically acceptable salts, hydrates and solvates thereof.
2. The compound according to claim 1, further characterized in that 3. The compound according to claim 1, further characterized in that R3 is selected from the group consisting of: H, methyl, ethyl, n-propyl, prop-2-yl, n-butyl, isobutyl, but-2-yl, cyclopropylmethyl, cyclohexylmethyl, 2-methanesulfinyl-ethyl, 1-hydroxyethyl, toluyl, naphthalen-2-yl-methyl, benzyloxymethyl and hydroxymethyl. 4. The compound according to claim 3, further characterized in that R3 is selected from the group consisting of: toluyl, isobutyl and cyclohexylmethyl. 5. The compound according to claim 4, further characterized in that R3 is isobutyl. 6. The compound according to claim 1, further characterized in that R4 is selected from the group consisting of: R5OC (O) -, R5C (O) - or R5SO2 ~. 7. The compound according to claim 6, further characterized in that R4 is R5C (O) -. 8. - The compound according to claim 7, further characterized in that R5 is selected from the group consisting of β-alkyl, Ar-Co-β alkyl and Het-alkyl of Co-β- 9. The compound in accordance with claim 8, further characterized in that R5 is selected from the group consisting of: methyl, halogenated methyl, methyl substituted with alkoxy, methyl substituted with heterocycle; butyl, butyl substituted with aryl; isopentyl; cyclohexyl; butenyl, butenyl substituted with aryl; acetyl; phenyl, phenyl substituted with one or more halogens, phenyl substituted with one or more alkoxy groups, phenyl substituted with one or more sulfonyl groups; benzyl; naphthylenyl; benzo [1,3] dioxolyl; furanyl, furanyl substituted with halogen, furanyl substituted with aryl; tetrahydrofuran-2-yl; benzofuranyl, benzofuranyl substituted by alkoxy, benzofuranyl substituted by halogen, benzofuranyl substituted by alkyl; benzo [b] thiophenyl, benzo [b] thiophenyl substituted with alkoxy; quinolinyl; Quinoxalinyl; 1,8-naphthyridinyl; indolyl, indolyl substituted with alkyl; pyridinyl, pyridinyl substituted with alkyl, 1-oxy-pyridinyl; thiophenyl, thiophenyl substituted with alkyl, thiophenyl substituted with halogen; thieno [3,2-b] thiophenyl; isoxazolyl, isoxazolyl substituted with alkyl, and oxazolyl. 10. The compound according to claim 8, further characterized in that R5 is selected from the group consisting of: pentanonyl; naphthylene-2-yl; benzo [1,3] dioxol-5-yl, furan-2-yl; benzofuran-2-yl; benzo [b] thiophen-2-yl; quinolin-2-yl, quinolin-3-yl, quinolin-4-yl, quinolin-6-yl and quinolin-8-yl; quinoxalin-2-Ilo; 1,8-naphthyridin-2-yl; indol-3-yl, indol-5-yl, pyridin-2-yl, pyridin-5-yl, thiophen-3-yl; thieno [3,2-b] thiophen-2-yl; isoxazol-4-yl; and oxazol-4-yl. 11. The compound according to claim 8, further characterized in that R5 is selected from the group consisting of: trifluoromethyl, phenoxy-methyl, 4-fluoro-phenoxy-methyl, 2-thiophenyl-methyl; 4- (4-methoxy) phenyl-butyl; 4-pentanonyl; 4,4-bis (4-methoxyphenyl) -but-3-enyl; 3,4-dichlorophenyl, 4-fluorophenyl, 3,4-dimethoxy-phenyl, 3-benzyloxy-4-methoxy-phenyl, 4-methanesulfonyl-phenyl; 5-Nitro-furan-2-yl, 5- (4-nitrophenyl) -furan-2-yl, 5- (3-trifluoromethyl-phenyl) -furan-2-yl, 5-bromo-furan-2-yl, 5- (4-chloro-phenyl) -furan-2-yl; 5- (2-piperazine-4-carboxylic acid-ethoxy) benzofuran-2-yl, 5- (2-morpholino-4-yl-ethoxy) benzofuran-2-yl, 5- (2-piperazine) tert-butyl ester -1-yl-ethoxy) benzofuran-2-yl, 5- (2-cyclohexyl-ethoxy) benzofuran-2-yl, 7-methoxy-benzofuran-2-yl, 5-methoxy-benzofuran-2-yl, , 6-dimethoxy-benzofuran-2-yl, 5-fluoro-benzofuran-2-yl, 5,6-difluoro-benzofuran-2-yl, 3-methyl-benzofuran-2-yl; 5,6-dimethoxy-benzo [b] thiophen-2-yl; N-methyl-indol-2-yl; 1-oxy-pyridin-2-yl, 2-methyl-pyridin-5-yl; 5-methyl-thiophen-2-yl, 4,5-dibromo-thiophen-2-yl; 5-tert-butyl-3-methyl-thieno [3,2-b] thiophen-2-yl; 3,5-dimethyl-isoxazol-4-yl; and 5-methyl-2-phenyl-oxazol-4-yl and 2-phenyl-5-trifluoromethyl-oxazol-4-yl. 12. The compound according to claim 8, further characterized in that R5 is selected from the group consisting of: 3-methyl-benzofuran-2-yl, thieno [3,2-b] thiophen-2-yl, 5- methoxybenzofuran-2-yl, quinoxalin-2-yl and quinolin-2-yl. 13. The compound according to claim 1, further characterized in that R 'is selected from the group consisting of H and naphthalen-2-yl-methyl. 14. The compound according to claim 13, further characterized in that R 'is H. 15. The compound according to claim 1, further characterized in that R "is H. 16. The compound according to claim 1, further characterized in that R '"is selected from the group consisting of H and 6,6-dimethyl. 17. The compound according to claim 16, further characterized in that R "'is H. 18. The compound according to claim 1, further characterized in that R" and R "' are both H. 19.- compound according to claim 1, further characterized in that R2 is selected from the group consisting of: H, C? -6 alkyl, (C3.6) cycloalkyl-C0-b alkyl, C0-b-alkyl, Het-alkyl of Co-β, R9C (O) -, R9C (S) -, R9SO2-, R9OC (O) -, R9R11NC (O) -, R9R11NC (S) -, R6 FT - y2 R6 is selected from the group consisting of: H, alkyl of d-β, Ar-alkyl of Co-β and Het-alkyl of CO-β; R7 is selected from the group consisting of: H, d-β alkyl, (C3.6) cycloalkyl-Co-β alkyl, Ar-Co-β alkyl, Het-Co-β alkyl, R10C (O) -, R10C (S) -, R10SO2-, R10OC (O) -, R10R14NC (O) - and R10R14NC (S); R8 is selected from the group consisting of: H, C? -6 alkyl, C2-? Alkenyl, C2-6 alkynyl, Het-alkyl of Co-β and Ar-alkyl of C0-?; R9 is selected from the group consisting of: d-β alkyl, (C3-6) cycloalkyl-Co-βalkyl, Co-βalkaryl, and C0.βHet-alkyl, 'R10 is selected from the group consisting of alkyl of d-β, (C3_6) cycloalkyl-Co-β alkyl, Ar-Co-β alkyl or Het-Co-βalkyl; and Z is selected from the group consisting of C (O) and CH2. 20. The compound according to claim 19, further characterized in that R2 is selected from the group consisting of: Co-eral aralkyl, R9C (O) -, R9SO2, RR11NC (O) -, and 21. The compound according to claim 20, further characterized in that R 2 is selected from the group consisting of: Co-β-Aralkyl, R 9 C (O) -, and R 9 SO 2. 22. The compound according to claim 21, further characterized in that R2 is R9SO2. 23. The compound according to claim 19, , further characterized in that R6 is H. The compound according to claim 19, further characterized in that R7 is R10OC (O). 25. - The compound according to claim 19, further characterized in that R8 is C? _6 alkyl. 26. The compound according to claim 25, further characterized in that R8 is isobutyl. 27. The compound according to claim 19, further characterized in that R9 is selected from the group consisting of: alkyl of d-β, Ar-alkyl of Co-β and Het-alkyl of Co-β- 28.- compound according to claim 27, further characterized in that R9 is selected from the group consisting of: methyl; ethyl, and ethyl substituted with C 1 -β alkyl; butyl, butyl substituted with d-β alkyl; tert-butyl; isopentyl; phenyl, phenyl substituted by halogen, C? -6 alkoxyphenyl, cyanophenyl; toluyl, toluyl substituted with Het; benzoic acid; naphthylenyl; benzo [1,3] dioxolyl; benzo [1, 2,5] oxadiazolyl; pyridinyl, 1-oxy-pyridinyl, alkyl pyridinyl of d_6; thiophene; thiazolyl; 1 H-imidazolyl, imidazolyl substituted with C? -6 alkyl; 1 H- [1, 2,4] triazolyl, 1 H- [1, 2,4] triazolyl substituted with d-β alkyl, and quinolinyl. 29. The compound according to claim 27, further characterized in that R9 is selected from the group consisting of: 2-cyclohexyl-ethyl; 3-methylbutyl; 3,4-dichlorophenyl, 4-bromophenyl, 2-fluorophenyl, 4-fluorophenyl, 3-chlorophenyl, 4-chlorophenyl, 3-methoxyphenyl, 4-methoxyphenyl, 3,4-dimethoxyphenyl, 2-cyanophenyl; 2-benzoic acid; naphthylene-2-yl; benzo [1,3] -dioxol-5-yl; benzo [1, 2,5] oxadiazol-4-yl; pyridin-2-yl, pyridin-3-yl, 1-oxy-pyridin-2-yl, 1-oxy-pyridin-3-yl, 3-methyl-pyridin-2-yl, 6-methyl-pyridin-2- ilo; thiophen-2-yl; 3 thiazol-2-yl; 1 H-imidazol-2-yl, 1 H-imidazol-4-yl, 1-methyl-1 H-imidazol-2-yl, 1-methyl-1H-imodazol-4-yl; 1 H- [1, 2,4] triazol-3-yl, 5-methyl-1 H [1, 2,4] triazol-3-yl and quinolin-2-yl. 30. The compound according to claim 1, further characterized in that: R2 is selected from the group consisting of: Ar-alkyl of Co-β, R C (O) -, R3 is selected from the group consisting of: H, Ci-β alkyl and Ar-alkyl Co-ß; R4 is selected from the group consisting of: R5OC (O) -, R5C (0) - and R5SO2-; R5 is selected from the group consisting of: d-β alkyl, Ar-Co-e alkyl and Het-alkyl of C0-e; R6 is H; R7 is R10OC (O); R8 is alkyl of d.6; R9 is selected from the group consisting of: d-β alkyl, Ar-Co-β alkyl and Het-Co-β alkyl; R10 is selected from the group consisting of alkyl of. β, Ar-C0-β alkyl and Het-C0-β alkyl; R "is H; R" is H; and R '"is H. The compound according to claim 30, further characterized in that: R 2 is selected from the group consisting of: Ar-alkyl of Co-β, R 9 C (O) - and R 9 SO 2; selected from the group consisting of: H, methyl, ethyl, n-propyl, prop-2-yl, n-butyl, isobutyl, but-2-yl, cyclopropylmethyl, cyclohexylmethyl, 2-methanesulfinyl-ethyl, 1-hydroxyethyl, toluyl , naphthalene-2-ylmethyl, benzyloxymethyl and hydroxymethyl, R4 is R5C (O) -; R5 is selected from the group consisting of: methyl, halogenated methyl, methyl substituted by alkoxy, methyl substituted by heterocycle, butyl, butyl substituted by aryl; isopentyl, cyclohexyl, butenyl, butenyl substituted with aryl, acetyl, phenyl, phenyl substituted with one or more halogens, phenyl substituted with one or more alkoxy groups, phenyl substituted with one or more sulfonyl groups, benzyl, naphthylenyl, benzo [1, 3] ] dioxolyl, furanyl, furanyl substituted with halogen, furanyl substituted with aryl, tetrahydrofuran-2-yl benzofuranyl, benzofuranyl substituted by alkoxy, benzofuranyl substituted by halogen, benzofuranyl substituted by alkyl; benzo [b] thiophenyl, benzo [b] thiophenyl substituted with alkoxy; quinolinyl; Quinoxalinyl; 1,8-naphthyridinyl; indolyl (22), indolyl substituted with alkyl; pyridinyl, pyridinyl substituted with alkyl, 1-oxy-pyridinyl; thiophenyl, thiophenyl substituted with alkyl, thiophenyl substituted with halogen; thieno [3,2-] thiophene; Soxazolyl, isoxazolyl substituted with alkyl; and oxazolyl; R9 is selected from the group consisting of: methyl; ethyl, ethyl substituted with C-t-β alkyl; butyl, butyl substituted with alkyl of d6; tert-butyl; isopentyl; phenyl, phenyl substituted by halogen, C? -6 alkoxyphenyl, cyanophenyl; toluyl, toluyl substituted with Het; benzoic acid; naphthylenyl; benzo [1,3] dioxolyl; benzo [1, 2,5] oxadiazolyl; pyridinyl, 1-oxy-pyridinyl, d-β-alkylpyridinyl; thiophene; thiazolyl; 1 H-imidazolyl, midazolyl substituted with alkyl of d.6; 1 H- [1, 2,4] triazolyl, 1 H- [1, 2,4] triazolyl substituted with d-β alkyl, and quinolinyl. 32. The compound according to claim 30, further characterized in that R5 is selected from the group consisting of: pentanonyl; naphthylene-2-yl; benzo [1,3] dioxol-5-yl, furan-2-yl; benzofuran-2-yl; benzo [b] thiophen-2-yl; quinolin-2-yl, quinolin-3-yl, quinolin-4-yl, quinolin-6-yl and quinolin-8-yl; quinoxalin-2-yl; 1,8-naphthyridin-2-yl; indol-3-yl, indol-5-yl, pyridin-2-yl, pyridin-5-yl, thiophen-3-yl; thieno [3,2-b] thiophen-2-yl; isoxazol-4-yl; and oxazol-4-yl. 33. The compound according to claim 30, further characterized in that R5 is selected from the group consisting of: trifluoromethyl, phenoxy-methyl, 4-fluoro-phenoxy-methyl, 2-thiophenyl-methyl; 4- (4-methoxy) phenyl-butyl; 4-pentanonyl; 4,4-bis (4-methoxyphenyl) -but-3-enyl; 3,4-dichlorophenyl, 4-fluorophenyl, 3,4-dimethoxy-phenyl, 3-benzyloxy-4-methoxy-phenyl, 4-methanesulfonyl-phenyl; 5-Nitro-furan-2-yl, 5- (4-nitrophenyl) -furan-2-yl, 5- (3-trifluoromethyl-phenyl) -furan-2-yl, 5-bromo-furan-2-yl, 5- (4-chloro-phenyl) -furan-2-yl; 5- (tert-butyl ester of 2-piperazine-4-carboxylic acid-ethoxy) benzofuran-2-yl, 5- (2-morpholino-4-yl-ethoxy) benzofuran-2-yl (44), 5- (2-piperazin-1-yl-ethoxy) -benzofuran-2-yl, 5- (2-cyclohexyl-ethoxy) benzofuran-2-yl, 7-methoxy-benzofuran-2-yl, 5-methoxy-benzofuran- 2-yl, 5,6-dimethoxy-benzofuran-2-yl, 5-fluoro-benzofuran-2-yl, 5,6-difluoro-benzofuran-2-yl, 3-methyl-benzofuran-2-yl; 5,6-dimethoxy-benzo [b] thiophen-2-yl; N-methyl-indol-2-yl; 1-oxy-pyridin-2-yl, 2-methyl-pyridin-5-yl; 5-methyl-thiophen-2-yl, 4,5-dibromo-thiophen-2-yl; 5-tert-butyl-3-methyl-thieno [3,2- £)] thiophen-2-yl; 3,5-dimethyl-isoxazol-4-yl; and 5-methyl-2-phenyl-oxazol-4-yl and 2-phenyl-5-trifluoromethyl-oxazol-4-yl. 34. The compound according to claim 30, further characterized in that R9 is selected from the group consisting of: 2-cyclohexyl-ethyl; 3-methylbutyl; 3,4-dichlorophenyl, 4-bromophenyl, 2-fluorophenyl, 4-fluorophenyl, 3-chlorophenyl, 4-chlorophenyl, 3-methoxyphenyl, 4-methoxyphenyl, 3,4-dimethoxyphenyl, 2-cyanophenyl; 2-benzoic acid; naphthylene-2-yl; benzo [1,3] -dioxol-5-yl; benzo [1, 2,5] oxadiazol-4-yl; pyridin-2-yl, pyridin-3-yl, 1-oxy-pyridin-2-yl, 1-oxy-pyridin-3-yl, 3-methyl-pyridin-2-yl, 6-methyl-pyridin-2- ilo; thiophen-2-yl; thiazol-2-yl; 1 H-imidazol-2-yl, 1 H-imidazol-4-yl, 1-methyl-1 H-imidazol-2-yl, 1-methyl-1 H-imodazol-4-yl; 1 H- [1,4] triazol-3-yl, 5-methyl-1 H [1, 2,4] triazol-3-yl and quinolin-2-yl. The compound according to claim 30, further characterized in that: R2 is R9SO2; R3 is isobutyl; R4 is R5C (0); R5 is selected from the group consisting of 3-methyl-benzofuran-2-yl, thieno [3,2-b] thiophen-2-yl, 5-methoxybenzofuran-2-yl, quinoxalin-2-yl or quinolin-2 ilo; and R9 is selected from the group consisting of pyridin-2-yl and 1-oxy-pyridin-2-yl. 36. The compound according to claim 35, further characterized in that R5 is 3-methyl-benzofuran-2-yl. 37. The compound according to claim 35, further characterized in that R9 is 1-oxy-pyridin-2-yl. 38.- The compound according to claim 1, further characterized in that it is selected from the group consisting of: benzyl ester of acid. { (S) -1- [1 - ((S) -2-benzyloxycarbonylamino-4-methyl-pentanoyl) -3-oxo-azepan-4-ylcarbamoyl} carbamic [(S) -1-naphthylene-2-carboxylic acid (1-benzyl-3-oxo-azepan-4-ylcarbamoyl) -3-methyl-butyl] -amide; [(S) -1- [3] dioxol-5-carboxylic acid [(S) -1- (1-benzyl-3-oxo-azepan-4-ylcarbamoyl) -3-methyl-butyl] -benzo [1,3] acid; [(S) -1- (1-benzyl-3-oxo-azepan-4-ylcarbamoyl) -3-methyl-butyl] -amide of benzofuran-2-carboxylic acid; [(S) -1- (1- Benzo [b] thiophene-2-carboxylic acid benzyl-3-oxo-azepan-4-ylcarbamoyl) -3-methyl-butyl] -amide; Naphthylene-2-sulfonyl - [(S) -1 - (1-benzyl-3-oxo-azepan-4-ylcarbamoyl) -3-methyl-butyl] amide [(S) -1 - (1 -benzyl-3- oxo-azepan-4-ylcarbamoyl) -3-methyl-butyl] -amide of quinoline-2-carboxylic acid; [(S) -1- (1-benzyl-3-oxo-azepan-4-ylcarbamoyl) -3-methyl-butyl] -3,4-dichlorobenzoic acid amide; 4 - [(S) -methyl-2 - [(quinoline-2-carbonyl) -amino] pentanoylamino] -3-oxo-1 - [2- (3-pyridin-2-yl-phenyl) -acetyl] azepanium 1 - ((S) -2-mencyloxycarbonylamino-4-methyl-pentyl) -4-. { (S) -4-methyl-2 - [(2-quinoline-2-carbonyl) amino] -pentanoylamino) -3-oxo-azepanium 1-benzoyl-4 - ((S) -2- (benzo [1, 3 ] dioxol-carbonylamino) -4-methyl-pentanoylamino) -3-oxo-azepanium 1-benzoyl-4 - ((S) -2- (4-fluoro-benzoylamino) -4-methyl-pentanoylamino) 3-oxo-azepanium 3-oxo-4 - ((S) -4-methyl-2- { [5- (2-morpholino-4-yl-ethoxy) -benzofuran-2-carbonyl] amino.} - pentanoylamino) -1 - (4-Methyl-pentanoyl) -azepanium [(S) -1- (1-benzenesulfonyl-3-oxo-azepan-4-ylcarbamoyl) -3-methyl-butyljamide of 5- (2-morpholin-4-yl) -ethoxy) -benzofuran-2-carboxylic acid; 4 - ((S) -4-methyl-2- {[5- (2-morpholin-4-yl-ethoxy) -benzofuran-2-carbonyl] amino} -pentanoylamino) phenylamide) -3- oxo-azepane-1-carboxylic acid; ((S) -3-methyl-1 - { 3-oxo-1 - [2- (3-pyridin-2-yl-phenyl) -acetyl] -azepan-4-ylcarbamoyl.} - butyl) -amide 5- (2-morpholino-4-yl-ethoxy) -benzofuran-2-carboxylic acid; 5- (2-morpholino-4-yl-ethoxy) -benzofuran-2-carboxylic acid [(S) -1- (benzoyl-3-oxo-azepan-4-ylcarbamoyl) -3-methyl-butyl] -amide.; [(S) -1- (1-benzenesulfonyl-3-oxo-azepan-4-ylcarbamoyl) -3-methyl-butyl] -amide of 5- (2-pyrrolidin-1-yl-ethoxy) -benzofuran-2- acid carboxylic; [(S) -1- (1-Benzenesulfonyl-3-oxo-azepan-4-ylcarbamoyl) -3-methyl-butyl] -amide of 5- (2-piperidin-1-yl-ethoxy) -benzofuran-2 acid -carboxylic; ((S) -3-methyl-1 - { 3-oxo-1 - [2- (3-pyridin-2-yl-phenyl) ethyl] -azepan-4-ylcarbamoyl.} - butyl) ami 5- (2-morpholino-4-yl-ethoxy) -benzofuran-2-carboxylic acid; ((S) -3-methyl-1 - { 3-oxo-1- [2- (3-pyridin-2-yl-phenyl) ethyl] azepan-4-ylcarbamoyl.} - butyl) amide Naphthalene-2-carboxylic acid; ((S) -3-methyl-1 - { 3-oxo-1 - [2- (3-pyridin-2-yl-phenyl) ethyl] -azepan-4-ylcarbamoyl.} - butyl) amide of 1 H-indole-2-carboxylic acid; [(S) -1 H -indole-2-carboxylic acid (1-benzenesulfonyl-3-oxo-azepan-4-ylcarbamoyl) -3-methyl-butyl] -amide; [(S) -1- (1-Benzenesulfonyl-3-oxo-azepan-4-ylcarbamoyl) -3-methyl-butyl] -benzofuran-2-carboxylic acid amide; [(S) -3-methyl-1-. { 3-oxo-1- [2- (3-pyridin-2-yl-phenyl) ethyl] -azepan-4-carbamoyl} -butyl) benzofuran-2-carboxylic acid amide; [(S) -3-methyl-1- (3-oxo-1-phenethyl-azepan-4-ylcarbamoyl] -butyl} -amide of 5- (2-morpholino-4-yl-ethoxy) -benzofuran- 2-carboxylic, [(S) -3-methyl-1- (3-oxo-1-phenethyl-azepan-4-ylcarbamoyl] butyl} naphthylene-2-carboxylic acid amide; 3-Methyl-1 - [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} -benzofuran-2-carboxylic acid amide: { (S) -3- methyl-1- [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} - naphthylene-2-carboxylic acid amide;. (S) -3-met? l-1 - [3-Oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} -amide of 5- (2-morpholino-4-yl-ethoxy) - benzofuran-2-carboxylic acid, 4 - ((S) -4-methyl-2-. {[[(5- (2-morpholino-4-yl-ethoxy)) -benzofuran-2-carbonyl tert-butyl ester ] -amino.}. phenylamino) -3-oxo-azepane-1-carboxylic acid [(S) -3-methyl-1- (3-oxo-azepan-4-ylcarbamoyl] -butyl} acid amide 4 - ((S) -4-methyl-2- { [(5- (2-morpholino-4-yl-ethoxy) -benzofuran-2-carboxylic acid;. {3-oxo-1- [2t (3-pyridin-2-yl-phenyl-acetyl) ] -azepan-4-yl.} 4-methyl-pentanoic acid amide; ((S) -3-methyl-1- {3-oxo-1 - [2- (3-pyridin-2-yl-phenyl) -acetyl] -azepam-tert-butyl ester 4-ylcarbamoyl.} - butyl) -naphthalene-2-methyl-carbamic; [3-oxo-1 - [2- (3-pyridin-2-yl-phenyl) -acetyl-azepan-4-yl} - (S) -4-Methylene-2 - [(naphthylene-2-ylmethyl) -amino] -pentenoic acid amide; 4- [2- (2 { (S) -3-methyl-1 - [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butylcarbamoyl-tert-butyl ester .} - benzofuran-5-yloxy) -ethyl] -piperazin-1-carboxylic acid; [(S) -3-methyl-1- [3-oxo-1 - (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -3-butyl} 5- (2-piperazin-1-yl-ethoxy) -benzofuran-2-carboxylic acid amide; . { (S) -3-methyl-1- [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl ester} 5- (2-cyclohexyl-ethoxy) benzofuran-2-carboxylic acid amide; ((S) -3-methyl-1 - { 3-oxo-1 - [2- (3-pyridin-2-yl-phenyl) ethyl] -azepan-4-ylcarbamoyl.} - butyl) amide 5- (2-cyclohexyl-ethoxy) -benzofuran-2-carboxylic acid; 4- [2- (2 { (S) -3-methyl-1- [3-oxo-1 - (3-pyridin-2-yl-phenyl) -ethyl- [azepane] -butyl ester. -4-ylcarbamoyl] -butylcarbamoyl.} - benzofuran-5-yloxy) -ethyl] -piperazin-1-carboxylic acid; ((S) -3-methyl-1 - { 3-oxo-1 - [2- (3-pyridin-2-yl-phenyl) ethyl] -azepan-4-ylcarbamoyl.} - butyl) amide 5- (2-piperazin-1-yl-ethoxy) benzofuran-2-carboxylic acid; [3-Oxo-1 - (pyridin-2-sulfonyl) -azepan-4-yl] -amide of (S) -4-methyl-2- (methyl-naphthalen-2-ylmethyl-amino) pentanoic acid; . { 3-oxo-1 - [2- (3-pyridin-2-yl-phenyl) -acetyl] -azepan-4-yl} - (S) -4-methyl-2- (methyl-naphthalen-2-ylmethyl-amino] pentanoic acid amide: methyl - ((S) -3-methyl-1 -. {3-oxo-1 - [ 5- (2-morpholino-4-yl-ethoxy) -benzofuran-2-carboxylic acid 2- (3-pyridin-2-yl-phenyl) -acetyl] -azepan-4-ylcarbamoyl} -butyl) -amide; methyl- { (S) -3-methyl-1 - [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl) -3-methyl-butyl] -amide of benzofuran-2 -carboxylic; 2,2,2-trifluoro-N - ((S) -3-methyl-1 -. {3-oxo-1 - [2- (3-pyridin-2-yl-phenyl) -acetyl] -azepan -4 - [(S) - (methanesulfonyl-naphthylene-2-ylmethyl-amino) -4-methyl-pentanoylamino] -4-ylcarbamoyl.} - butyl) -N-naphthylene-2-ylmethyl-acetamidase ester] -3-oxo-azepane-1-carboxylic acid; . { (S) -3-methyl-1- [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl ester} quinoline-2-carboxylic acid amide; . { (S) -3-methyl-1 - [3-oxo-1 - (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} -quinoline-8-carboxylic acid amide; . { (S) -3-methyl-1 - [3-oxo-1 - (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} quinoline-6-carboxylic acid amide; . { (S) -3-methyl-1- [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl ester} quinoline-4-carboxylic acid amide; . { (S) -3-methy1- [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} quinoline-3-carboxylic acid amide; . { (S) -3-methyl-1- [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl] -isoquinoline-3-carboxylic acid amide; . { (S) -3-methyl-1 - [3-oxo-1 - (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} isoquinoline-1-carboxylic acid amide; . { (S) -3-methyl-1 - [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl] -aminoxaline-2-carboxylic acid amide; . { (S) -3-methyl-1 - [3-oxo-1 - (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} benzo [b] thiophene-2-carboxylic acid amide; . { (S) -3-methyl-1 - [3-oxo-1 - (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 1,8-naphthyridine-2-carboxylic acid amide; . { (S) -3-methyl-1- [3-oxo-1 - (pyridin-2-sulfonyl) .azepan-4-ylcarbamoyl] -butyl} 1H-indole-2-carboxylic acid amide; . { (S) -3-methyl-1 - [3-oxo-1 - (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 5-methoxy-benzofuran-2-carboxylic acid amide; . { (S) -3-methyl-1 - [3-oxo-1 - (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 5-bromo-furan-2-carboxylic acid amide; . { (S) -3-methyl-1 - [3-oxo-1 - (pyridin-2-sulfonyl) -azepan-4-carbamoyl] -butyl} furan-2-carboxylic acid amide; . { (S) -3-methyl-1- [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl] 5-n-tro-fu-2-carboxylic acid amide; . { (S) -3-methyl-1- [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyljamide of 5- (4-nitro-phenyl) -furan-2 acid -carboxylic; . { (S) -3-methyl-1- [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl ester} 5- (3-Trifluoromethyl-phenyl) -furan-2-carboxylic acid amide; . { (S) -3-methyl-1- [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl ester} tetrahydrofuran-2-carboxylic acid amide; [3-Oxo- (pyridin-2-sulfonyl) -azepan-4-yl] (S) -4-methyl-2- (2-phenoxy-acetylamino) pentanoic acid amide; [3-Oxo- (pyridin-2-sulfonyl) -azepan-4-yl] -amide of (S) -2- [2- (4-fluoro-phenoxy) -acetylamino] -4-methyl-pentanoic acid; . { (S) -3-methyl-1 - [3-oxo- (pyridine-2-carbonyl) -azepan-4-ylcarbamoyl) -3-butyl] -amide of benzofuran-2-carboxylic acid; . { (S) -3-methyl-1 - [3-oxo-1- (1-oxy-pyridine-2-carbonyl) -azepan-4-ylcarbamoyl] -butyl} benzofuran-2-carboxylic acid amide; benzyl ester of 4 - ((S) -2-tert-butylcarbonylamino-4-methyl-pentanoylamino) -3-oxo-azepane-1-carboxylic acid; . { (S) -3-methyl-1 - [3-oxo-1- (1-methyl-1 H-imidazole-4-sulfonyl) -azepan-4-ylcarbamoyl] -butyl ester} 5,6-dimethoxy-benzofuran-2-carboxylic acid amide; . { (S) -3-methyl-1- [1- (5-methyl-1 H- [1, 2,4] triazole-3-sulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -butyl ester} benzofuran-2-carboxylic acid amide; . { (S) -3-methyl-1- [1- (1-methyl-1 H-imidazoI-3-sulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -butyl ester} benzofuran-2-carboxylic acid amide; . { (S) -3-methyl-1- [1- (1 H-imidazole-2-sulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -butyl ester} benzofuran-2-carboxylic acid amide; . { (S) -3-methyl-1 - [3-0X0-1 - (thiazole-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} benzofuran-2-carboxylic acid amide; . { (S) -3-methyl-1- [1- (1-methyl-1 H-imidazole-4-sulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -butyl ester} benzofuran-2-carboxylic acid amide; . { (S) -3-methyl-1 - [3-oxo-1 - (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 5- (4-oxy-morpholino-4-yl-ethoxy) -benzofuran-2-carboxylic acid amide; . { (S) -3-methyl-1 - [3-oxo-1- (pyridine-3-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} benzofuran-2-carboxylic acid amide; . { (S) -3-methy1- [3-oxo-1- (1-oxy-pyridin-3-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} benzofuran-2-carboxylic acid amide; . { (S) -1- (3,4-dichloro-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl)] - 3-methyl-butyl} quinoline-3-carboxylic acid amide; . { (S) -3-methyl-1- [1- (1-methyl-1 H-imidazole-4-sulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -butyl ester} 5-hydroxy-benzofuran-2-carboxylic acid amide; . { (S) -3-methyl-1- [3-oxo-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl)] - 3-methyl-butyl} - benzofuran-2-carboxylic acid amide; 2- (4-. {(S) -2-. {(benzofuran-2-carbonyl) -amino} -4-methyl-pentanoylamino} -3-oxo-azepan-1-sulfonyl) -benzoic; 3- (4- { (S) -2-. {(Benzofuran-2-carbonyl) -amino] -4-methyl-pentanoylamino} -3-oxo-azepan-1-sulfonyl) -benzoic acid; . { (S) -3-methyl-1 - [3-oxo-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} benzo [b] thiophene-2-carboxylic acid amide; . { (S) -3-methyl-1 - [3-oxo-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl ester} 5-bromo-furan-2-carboxylic acid amide; . { (S) -3-methyl-1 - [3-oxo-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl ester} 5,6-dimethoxy-benzofuran-2-carboxylic acid amide; . { (S) -3-methyl-1 - [3-oxo-1 - (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 1-oxy-pyridine-2-carboxylic acid amide; [3-Oxo-1- (pyridin-2-sulfonyl) -azepan-4-yl] -amide of (S) -4-methyl-2- (pyridin-2-sulfonylamino) -pentanoic acid; [3-Oxo-1- (pyridin-2-sulfonyl) -azepan-4-yl] -amide of (S) -2- (3-benzyl-ureido) -4-methyl-pentanoic acid; [3-Oxo-1- (pyridin-2-sulfonyl) -azepan-4-yl] -amide of (S) -4-methyl-2- (3-phenyl-ureido) -pentanoic acid; . { (S) -1- [6,6-Dimethyl-3-oxo-1- (pyridine-sulfonyl) -azepan-4-ylcarbamoyl] -3-methyl-butyl} - benzofuran-2-carboxylic acid amide; . { (S) -3-methyl-1 - [3-oxo-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl ammonide of 5-methoxy-benzofuran-2-carboxylic acid; . { (S) -3-methyl-1- [3-oxo-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} thieno [3,2-b] thiophene-2-carboxylic acid amide; . { (S) -3-methyl-1- [3-oxo-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} quinoxaline-2-carboxylic acid amide; . { (S) -3-methyl-1- [3-oxo-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] butyl} quinoline-2-carboxylic acid amide; . { (S) -3-methyl-1- [3-oxo-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} thiophene-3-carboxylic acid amide; . { (S) -3-methyl-1- [3-oxo-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-carbamoyl] -butyl} amide of 1 H-indole-5-carboxylic acid; . { (S) -3-methyl-1- [3-oxo-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} benzo [1,3] dioxol-5-carboxylic acid amide; . { (S) -3-methyl-1- [3-oxo-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl ester} furan-2-carboxylic acid amide; [3-Oxo-1- (2-thiophene-2-yl-acetylamino) -3-methyl-2- (2-thiophene-2-yl-acetylamino) -3-oxo-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-yl] -amide. -pentanoic; . { (S) -3-methyl-1- [3-oxo-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 1 H-indole-2-carboxylic acid amide; 4-fluoro- { (S) -3-methyl-1- [3-oxo-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-carbamoyl] -butyl} -benzamide. { (S) -3-methyl-1- [3-oxo- (1-oxy-pyridine-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 5- (2-morpholin-4-yl-ethoxy) -benzofuran-2-carboxylic acid amide; . { (S) -3-methyl-1 - [3-oxo-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl ester} thiophene-2-carboxylic acid amide; . { (S) -3-methyl-1- [3-oxo-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 3-methyl-benzofuran-2-carboxylic acid amide; 6-methyl-N-. { (S) -3-methyl-1- [3-oxo-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} nicotinamide [3-oxo-1- (pyridin-2-sulfonyl)-azepan-4-yl] -butyl} amide of (S) -4-methyl-2- (2-thiophen-yl-acetylamino) -pentanoic acid; . { (S) -3-methyl-1 - [3-oxo-1 - (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 1 H-indole-6-carboxylic acid amide; . { (S) -3-methyl-1- [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl ester} benzo [1,3] dioxol-5-carboxylic acid amide; . { (S) -3-methyl-1 - [3-oxo-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl ester} 3,4-dihydro-2H-benzo [b] [1,4] dioxepin-7-carboxylic acid amide; . { (S) -3-methyl-1 - [3-oxo-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl ester} 5-methyl-thiophene-2-carboxylic acid amide; . { (S) -3-methyl-1- [3-oxo-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 4,5-dibromo-thiophene-2-carboxylic acid amide; . { (S) -3-methyl-1 - [3-oxo-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl ester} 3,5-dimethyl-isoxazoyl-4-carboxylic acid amide; (S) -2- (2-benzyloxy-acetylamino) -4-methyl-pentanoic acid [1- (4-methoxy-benzenesulfonyl) -3-oxo-azepan-4-yl -] - amide; . { (S) -3-methyl-1 - [3-oxo-1 - (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] butyl} 5- (3-trifluoromethyl-phenyl) -furan-2-carboxylic acid amide; . { (S) -3-methyl-1- [3-oxo-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 5-methyl-2-phenyl-oxazole-4-carboxylic acid amide; . { (S) -1- [1- (3,4-dimethoxy-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -butl} benzofuran-2-carboxylic acid amide; . { (S) -1 - [1 - (4-Bromo-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} - benzofuran-2-carboxylic acid amide; . { (S) -1- [1- (Benzo [1, 2,5] oxadiazol-4-sulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyljamide of benzofuran-2-carboxylic acid; . { (S) -1- [1- (3,5-dimethyl-oxazole-4-sulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} - benzofuran-2-carboxylic acid amide; . { (S) -3-Methyl-1- [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyljamide of 3-methyl-benzofuran-2-carboxylic acid; . { (S) -3-methyl-1- [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl ester} thieno [3,2-b] thiophene-2-carboxylic acid amide; . { (S) -3-methyl-1 - [3-oxo-1 - (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 5-tert-butyl-3-methyl-thieno [3,2-b] thiophene-2-carboxylic acid amide; . { (S) -3-methyl-1 - [3-oxo-1 - (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 5-methyl-2-phenyl-oxazole-4-carboxylic acid amide; . { (S) -3-methyl-1 - [3-oxo-1 - (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 2-phenyl-5-trifluoromethyl-oxazole-4-carboxylic acid amide; [(S) -1- (1-methanesulfonyl-3-oxo-azepan-4-ylcarbamoyl) -3-methyl-butyl] -amide of quinoline-2-carboxylic acid; [(S) -1- (1-methanesulfonyl-3-oxo-azepan-4-ylcarbamoyl) -3-methyl-butyl] -amide of 1-methyl-1 H-indole-2-carboxylic acid; . { [(S) -1- (1-methanesulfonyl-3-oxo-azepan-4-ylcarbamoyl) -3-methyl-butylcarbamoyl] -methyl-amide of furan-2-carboxylic acid; [(S) -1- (1-methanesulfonyl-3-oxo-azepan-4-ylcarbamoyl) -3-methyl-butyl] -amide of 5-methoxy-benzofuran-2-carboxylic acid; [(S) -1- (1-methanesulfonyl-3-oxo-azepan-4-ylcarbamoyl) -3-methyl-butyl] -amino-quinoxalin-2-carboxylic acid; . { (S) -3-methyl-1- [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 5- (4-chloro-phenyl) -furan-2-carboxylic acid amide; (S) -2- [2- (4-methoxy-phenyl) -acetylamino) -4-methyl-pentane-1-methanesulfonyl-3-oxo-azepan-4-yl) -amide; . { [(S) -1 - [1 - (2-cyano-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} -quinoline-2-carboxylic acid amide; . { [(S) -1- [1- (2-Cyano-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} 1-methyl-1 H-indole-2-carboxylic acid amide; ( { (S) -1- [1- (2-cyano-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butylcarbamoyl.} - methyl) -amide of furan-2 -carboxylic; . { (S) -1- [1- (2-Cyanobenzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} 5-methoxy-benzofuran-2-carboxylic acid amide; . { (S) -1 - [1 - (2-Cyano-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} quinoxaline-2-carboxylic acid amide; [1- (2-cyano-benzenesulfonyl) -3-oxo-azepan-4-yl] -amide of (S) -2- [2- (4-methoxy-phenyl) -acetylamino) -4-methyl-pentanoic acid; . { [(S) -1 - [1 - (4-methoxy-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} -quinoline-2-carboxylic acid amide; . { [(S) -1- [1 - (4-methoxy-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} 1-methyl-1 H-indole-2-carboxylic acid amide; ( { (S) -1- [1- (4-methoxy-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butylcarbamoyl.} - methyl) -amide of furan-2 -carboxylic; . { [(S) -1- [1- (4-methoxy-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} 5-methoxy-benzofuran-2-carboxylic acid amide; . { [(S) -1 - [1 - (4-methoxy-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} quinoxaline-2-carboxylic acid amide; [1- (4-methoxy-benzenesulfonyl) -3-oxo-azepan-4-yl] -amide of (S) -2- [2- (4-methoxy-phenyl) -acetylamino) -4-methyl-pentanoic acid; . { [(S) -1- [1- (4-Fluoro-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} 1-methyl-1 H-indole-2-carboxylic acid amide; ( { (S) -1- [1- (4-Fluoro-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butylcarbamoyl.} - methyl) -amide of furan-2 -carboxylic; . { [(S) -1- [1- (4-Fluoro-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} 5-methoxy-benzofuran-2-carboxylic acid amide; . { [(S) -1- [1- (4-Fluoro-benzenesulfonyl) 3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} quinoxaline-2-carboxylic acid amide; [1- (4-methyl-pentanoic) -2- [2- (4-methoxy-phenyl] -acetylamino) -4-methyl-pentanoic acid [1- (4-fluoro-benzenesulfonyl) -3-oxo-azepan-4-yl] -amide.; . { [(S) -1- [1- (3-chloro-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} - benzofuran-2-carboxylic acid amide; . { (S) -1 - [1 - (3-chloro-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} 5-methoxy-benzofuran-2-carboxylic acid amide; . { (S) -1- [1- (3-Chloro-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} 7-methoxy-benzofuran-2-carboxylic acid amide; . { (S) -1- [1- (3-Chloro-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} 5,6-dimethoxy-benzofuran-2-carboxylic acid amide; . { (S) -1- [1- (3-Chloro-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} 3-methyl-benzofuran-2-carboxylic acid amide; . { (S) -1- [1- (3-Chloro-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} benzo [b] thiophene-2-carboxylic acid amide; . { (S) -1- [1- (3-Chloro-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} 1-methyl-1 H-indole-2-carboxylic acid amide; . { (S) -1 - [1 - (3-chloro-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} quinoxaline-2-carboxylic acid amide; . { (S) -1- [1- (2-Fluoro-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} - benzofuran-2-carboxylic acid amide; . { (S) -1- [1- (2-Fluoro-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} 5-methoxy-benzofuran-2-carboxylic acid amide; . { (S) -1 - [1 - (2-Fluoro-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} 7-methoxy-benzofuran-2-carboxylic acid amide; . { (S) -1- [1- (2-Fluoro-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} 5,6-dimethoxy-benzofuran-2-carboxylic acid amide; . { (S) -1- [1- (2-Fluoro-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} 5-methyl-benzofuran-2-carboxylic acid amide; . { (S) -1 - [1 - (2-Fluoro-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} benzo [b] thiophene-2-carboxylic acid amide; . { (S) -1 - [1 - (2-Fluoro-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} 1-methyl-1 H-indole-2-carboxylic acid amide; [3-Oxo-1- (pyridin-2-sulfonyl) -azepan-4-yl] -amide of (S) -4-methyl-2- (1-oxy-pyridin-2-sulfonylamino) -pentanoic acid; . { (S) -1 - [1 - (2-Fluoro-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} quinoxaline-2-carboxylic acid amide; . { (S) -3-methyl-1 - [3-oxo-1 - (thiophen-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 5-methoxy-benzofuran-2-carboxylic acid amide; . { (S) -3-methyl-1 - [3-oxo-1- (thiophene-2-sulfonyl] -azepan-4-ylcarbamoyl] -butyl} -amide of 7-methoxy-benzofuran-2-carboxylic acid; { (S) -3-methyl-1 - [3-0X0-1 - (thiophene-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} -amide of acid 5.6 -dimethoxy-benzofuran-2-carboxylic acid; {. (S) -3-methyl-1- [3-oxo-1- (thiophene-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} -amide of 3-methyl-benzofuran-2-carboxylic acid; {. (S) -3-methyl-1 - [3-oxo-1 - (thiophen-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} .-benzo [b] thiophene-2-carboxylic acid amide; {. (S) -3-methyl-1- [3-oxo-1- (thiophene-2-sulfonyl) -azepan-4-lcarbamoyl] - butyl.) - 1-methyl-1H-indole-2-carboxylic acid amide; {. (S) -3-methyl-1 - [3-oxo-1 - (thiophene-2-sulfonyl) - azepan-4-ylcarbamoyl] -butyl} -amido-quinoxaline-2-carboxylic acid; {. (S) -1- [1- (4-chloro-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl ] -3-methyl-butyl.} - benzofuran-2-carboxylic acid amide; {. (S) -1- [1- (4-chloro-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-buti l.} - 5-methoxy-benzofuran-2-carboxylic acid amide; . { (S) -1 - [1 - (4-chloro-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} 7-methoxy-benzofuran-2-carboxylic acid amide; . { (S) -1- [1- (4-Chloro-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} 5,6-dimethoxy-benzofuran-2-carboxylic acid amide; . { (S) -1 - [1 - (4-chloro-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} 3-methyl-benzofuran-2-carboxylic acid amide; . { (S) -1 - [1 - (4-chloro-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} benzo [b] thiophene-2-carboxylic acid amide; . { (S) -1- [1- (4-Chlorobenzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} 1- methyl-1 H-indole-2-carboxylic acid amide; . { (S) -1- [1- (4-Chloro-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} quinoxaline-2-carboxylic acid amide; . { (S) -1- [1- (3-methoxy-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} - benzofuran-2-carboxylic acid amide; . { (S) -1 - [1 - (3-methoxy-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} 5-methoxy-benzofuran-2-carboxylic acid amide; . { (S) -1- [1- (3-methoxy-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl-7-methoxy-benzofuran-2-carboxylic acid; . { (S) -1- [1- (3-methoxy-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} 5,6-dimethoxy-benzofuran-2-carboxylic acid amide; . { (S) -1- [1- (3-methoxy-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} 3-methyl-benzofuran-2-carboxylic acid amide; . { (S) -1- [1- (3-methoxy-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} benzo [b] thiophene-2-carboxylic acid amide; . { (S) -1- [1- (3-methoxy-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} 1-methyl-1 H-indole-2-carboxylic acid amide; . { (S) -1- [1- (3-methoxy-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} quinoxaline-2-carboxylic acid amide; . { (S) -1- [3-oxo-1 - (thiophen-2-sulfonyl) -azepan-4-, lcarbamoyl] -butyl} - benzofuran-2-carboxylic acid amide; . { (S) -3-methyl-1 - [(2,2 ', 4-trideuterio) -3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} benzofuran-2-carboxylic acid amide; . { (S) -2-methyl-1- [3-oxo-1 - (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} - benzofuran-2-carboxylic acid amide; . { (S) -1 - [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -propyl} - benzofuran-2-carboxylic acid amide; . { (S) -2-cyclohexyl-1- [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -ethyl} - benzofuran-2-carboxylic acid amide; . { (S) -1 - [3-0X0-1 - (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -ethyl} - benzofuran-2-carboxylic acid amide; . { (S) -3-methanesulfinyl-1 - [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -propyl} - benzofuran-2-carboxylic acid amide; . { [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -methyl} -amid benzofuran-2-carboxylic acid; . { (S) -1 - [3-oxo-1 - (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -pentyl} - benzofuran-2-carboxylic acid amide; . { (S) -1- [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} - benzofuran-2-carboxylic acid amide; . { (S) -2-methyl-1 - [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -propyl} - benzofuran-2-carboxylic acid amide; . { (S) -2-hydroxy-1- [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -propyl} - benzofuran-2-carboxylic acid amide; . { (S) -1- [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -2-phenylethyl} - benzofuran-2-carboxylic acid amide; [3-Oxo-1- (pyridin-2-sulfonyl) -azepan-4-yl] -amide of 1- (benzofuran-2-carbonyl) -pyrrolidine-2-carboxylic acid; 3,4-dimethoxy-N-. { (S) -1- [1- (4-methoxy-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} -benzamide. { (S) -1 - [1 - (4-imethoxy-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} benzo [b] thiophene-2-carboxylic acid amide; . { (S) -1 - [1 - (4-Fluoro-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-, methyl-butyl} benzo [1,3] dioxol-5-carboxylic acid amide; [1- (4-fluoro-benzenesulfonyl) -3-oxo-azepan-4-yl] -amide of (S) -2- (2-benzyloxy-acetylamino) -4-methyl-pentanoic acid; . { (S) -1- [1- (4-Fluoro-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} benzo [b] thiophene-2-carboxylic acid amide; . { (S) -1 - [1-benzoyl-3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} - benzofuran-2-carboxylic acid amide; [3-Oxo-1- (pyridin-2-sulfonyl) -azepan-4-yl] -amide of (S) -4-methyl-2- (quinolin-8-sulfonylamino) -pentanoic acid; [3-Oxo-1- (pyridin-2-sulfonyl) -azepan-4-yl] -amide of (S) -4-methyl-2- (naphthylene-2-sulfonylamino) -pentanoic acid; . { (S) -1- [1- (4-Fluoro-benzenesulfonyl) -3-oxo-azepan-4-yl-carbamoyl] -3-methyl-butyl} - benzofuran-2-carboxylic acid amide; N-. { (S) -1- [1- (4-Fluoro-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl} -3-methyl-butyl} -3,4-dimethoxy-benzamide. { (S) -1- [1- (4-Fluoro-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl} -3-methyl-butyl} cyclohexanecarboxylic acid amide; (S) -2- (2-benzyloxy-acetylamino) -4-methyl-pentanoic acid [1- (methanesulfonyl) -3-oxo-azepan-4-yl] -amide; . { (S) -1- (1-methanesulfonyl-3-oxo-azepan-4-ylcarbamoyl) -3-methyl-butyl] -amide of benzo [b] thiophene-2-carboxylic acid; . { (S) -1- [3] dioxol-5-carboxylic acid (S) -1- (1-methanesulfonyl-3-oxo-azepan-4-ylcarbamoyl) -3-methyl-butyl] -amide; . { (S) -1- (1-methanesulfonyl-3-oxo-azepan-4-ylcarbamoyl) -3-methyl-butyl] -amide of benzofuran-2-carboxylic acid; N - [(S) -1- (1-methanesulfonyl) -3-oxo-azepan-4-ylcarbamoyl} -3-methyl-butyl} -3,4-Dimethoxy-benzamide [1- (2-cyano-benzenesulfonyl) -3-oxo-azepan-4-yl] -amide of (S) -2- (2-benzyloxy-acetylamino) -4-methyl -pentanoic; N-. { (S) -1 - [1 - (2-cyano-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl} -3-methyl-butyl} -4-methanesulfonyl-1-benzamide. { (S) -1- [1- (2-Cyano-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl) -3-methyl-butyl] benzo [b] thiophene-2-carboxylic acid amide; . { (S) -1- [3- (2-Cyanobenzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl) -3-methyl-butyl] -amino [1,3] dioxol-5-carboxylic acid amide; [3-Oxo-1- (pyridin-2-sufonyl) -azepan-4-yl] -amide of (S) -4-methyl-2- [4-oxo-4 - ((4-phenoxy-phenyl)] -butyrylamino.}. -pentanoic acid; N-. { (S) -1 - [(1- (2-cyano-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl} - 3-methyl-butyl] -3,4-dimethoxy-benzamide. .... (S) -1 - [1 - (4-methoxy-benzenesulfonyl) -3-oxo-azepan-4-ylcarbamoyl} -3-methyl-butyl} -amide cyclohexanecarboxylic acid; 4-methanesulfonyl-N- . {S (S) -1- [4-methoxy-benzenesulfonyl) -3-oxo-azepan-4-carbamoyl] -3-methyl-butyl-benzamide-4-methanesulfonyl-N-. { (S) -1- [4-fluoro-benzenesulfonyl] -3-oxo-azepan-4-carbamoyl] -3-methyl-butyl-benzamide benzyl ester of (. {(S) -3-methyl-1 - [3-oxo-1 - (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] carbamic -butilcarbamoilj; [3-oxo-1 - (pyridin-2-sulfonyl) -azepan-4-yl] -amide (S) -2- [5- (4-methoxy-phenyl) -pentanoylamino] -4-methyl-pentanoic acid; [3-oxo-1 - (pyridine-2-sulfonyl) -azepan-4-yl] -amido (S) -2- [2- (3-benzyloxy-4-methoxy-phenyl) -acetylamino] -4-methylpentanoic acid;. {S (S) -3-methyl-1 - [1 - ( pyridin-2-sulfon¡l) -3-oxo-azepan-4-ylcarbamoyl] -butyl} -amide 5,6-difluoro-benzofuran-2-carboxylic acid.. [3-oxo-1- (pyridine- 2-Sulfonyl) -azepan-4-yl] -amide of (S) -4-methyl-2- (5-oxo-hexanoylamino) -pentanoic acid;. (S) -3-methyl-1 - [1 .. - (6-methyl-pyridin-2-sulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -butyl} amide benzofuran-2-carboxylic acid; {(S) -3-methyl-1 -.. [1 - (6-methyl-pyridin-2-sulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -butyl} amide 5-metox¡-benzofuran-2-carboxylic acid {(S).... 3-methyl-1 - [1- (6-methyl-pyridine-2-sulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -butyl ester} 3-methyl-benzofuran-2-carboxylic acid amide; . { (S) -3-methyl-1 - [1 - (pyridin-2-sulfonyl) -3-oxo-azepan-4-ylcarbamoll] -butyl} 7-methoxy-benzofuran-2-carboxylic acid amide; . { (S) -3-methyl-1 - [1- (pyridine-2-sulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -butyl ammonium acid 5,6-dimethoxy-benzo [b] thiophen-2- carboxylic; . { (S) -3-methyl-1-. { 3-Oxo- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} (R) -1-Benzyl-5-oxo-pyrrolidine-2-carboxylic acid amide; . { (S) -3-methyl-1-. { 3-Oxo- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} amide of (S) -1-benzyl-5-oxo-pyrrolidine-2-carboxylic acid; . { (S) -2-Cyclopropyl-1- [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl) -ethyl] -amide of benzofuran-2-carboxylic acid; . { (S) -3-methylsulfanyl-1 - [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl) -propyl] -amide of benzofuran-2-carboxylic acid; . { (S) -2-naphthylen-2-yl-1 - [3-oxo-1 - (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl) -ethyl] benzofuran-2-carboxylic acid; . { (S) -3-methyl-1 - [1- (6-methyl-pyridine-2-sulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -butyl} thieno [3,2-b] thiophene-2-carboxylic acid amide; . { (S) -3-methyl-1 - [1- (3-methyl-pyridine-2-sulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -butyl ester} thieno [3,2-b] thiophene-2-carboxylic acid amide; . { (S) -3-methyl-1 - [1- (3-methyl-pyridine-2-sulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -butyl ester} 3-methyl-benzofuran-2-carboxylic acid amide; . { (S) -3-methyl-1 - [1- (3-methyl-pyridine-2-sulfonyl) -3-oxo-azepan-4-ylcarbamoyl] -butyl ester} 5-methoxy-benzofuran-2-carboxylic acid amide; . { (S) -3-methyl-1- [3-oxo-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} 5,6-difluoro-benzofuran-2-carboxylic acid amide; . { (S) -2-cyclohexyl-1-. { 3-Oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -ethyl} 5- (3-trifluoromethyl-phenyl) -furan-2-carboxylic acid amide; . { (S) -2-cyclohexyl-1 -. { 3-Oxo-1 - (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -ethyl} - 5- (4-Chloro-phenyl) -furan-2-carboxylic acid amide; . { (S) -3-methyl-1- [6-methyl-3-oxo-1- (pyridine-sulfonyl) -azepan-4-ylcarbamoyl] -butyl ester} benzofuran-2-carboxylic acid amide; . { (S) -2-Cyclohexyl-1 - [3-oxo-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -ethyl} 5- (4-chloro-phenyl) -furan-2-carboxylicamide; . { (S) -2-Cyclohexyl-1 - [3-oxo-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -ethyl} 5- (3-trifluoromethyl-phenyl) -furan-2-carboxylic acid amide; . { (S) -3-methyl-1- [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl ester} 5-fluoro-benzofuran-2-carboxylic acid amide; . { (S) -2-Cyclohexyl-1- [3-oxo-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -ethyl} 5,6-dimethoxy-benzofuran-2-carboxylic acid amide; . { (S) -3-methyl-1 - [3-oxo-1 - (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl]} -butil} -5,5-bis- (4-methoxy-phenyl) -pent-4-enoic acid amide; . { (S) -2-naphthylene-2-yl-1 - [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -ethyl] -amide of quinoline-8-carboxylic acid; . { (S) -2-naphthylene-2-yl-1- [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl) -ethyl] -amhtilene-1-carboxylic acid amide; . { (S) -1- [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -2-phenyl-ethyl} -quinoline-8-carboxylic acid amide; . { (S) -3-methyl-1 - [3-oxo-1 - (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl} Naphthyridine-2-carboxylic acid amide; . { (S) -1- [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -2-phenyl-etl} Naphthylene-1-carboxylic acid amide; . { (S) -3-methyl-1 - [3-oxo-1 - (cyclohexyl-propionyl) -azepan-4-ylcarbamoyl] -butyl} 3-methylbenzofuran-2-carboxylic acid amide; . { (S) -3-methyl-1 - [3-oxo-1- (4-methyl-pentanoyl) -azepan-4-ylcarbamoyl] -butyl} 3-methylbenzofuran-2-carboxylic acid amide; . { (S) -3-methyl-1- [3-oxo-1- (1-oxy-pyridine-2-carbonyl) -azepan-4-ylcarbamoyl] -butyl ester} 3-methylbenzofuran-2-carboxylic acid amide; [3-Oxo-1- (pyridin-2-sulfonyl) -azepan-4-yl] -amide of (S) -acetylamino-4-methyl-pentanoic acid; . { 1- [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -pentyl} -amide 69 of quinoline-2-carboxylic acid; . { (S) -3-methyl-1 - [3-oxo-1- (cyclohexyl-propionyl) -azepan-4-ylcarbamoyl] -butyl} - benzofuran-2-carboxylic acid amide; . { (S) -3-methyl-1 - [3-oxo-1- (4-methyl-pentanoyl) -azepan-4-ylcarbamoyl] -butyl} benzofuran-2-carboxylic acid amide; { (S) -1 - [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -2-phenyl-ethyl} quinoline-2-carboxylic acid amide; . { (S) -2-Benzyloxy-1 - [3-oxo-1- (pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -ethyl} benzofuran-2-carboxylic acid amide; . { (S) -2-hydroxy-1 - [3-oxo-1 - (pyridine-2-sulfonyl) -azepan-4-carbamoyl] -ethyl} - benzofuran-2-carboxylic acid amide; . { (S) -3-methyl-1- [3-oxo-1 - (thiazole-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl ester} 5-methoxybenzofuran-2-carboxylic acid amide; . { (S) -3-methyl-1 - [3-oxo-1 - (thiazole-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl ester} 7-methoxybenzofuran-2-carboxylic acid amide; . { (S) -3-methyl-1 - [3-oxo-1 - (thiazole-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl ester} 3-methylbenzofuran-2-carboxylic acid amide; . { (S) -3-methyl-1 - [3-oxo-1 - (thiazole-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl ester} benzo [b] thiophene-2-carboxylic acid amide; . { (S) -3-methyl-1 - [3-oxo-1- (thiazole-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl-1-methyl-1H-indole-2-carboxylic acid methyl ester; . { (S) -3-methyl-1- [3-oxo-1- (thiazole-2-sulfonyl) -azepan-4-ylcarbamoyl] -butl} quinoxaline-2-carboxylic acid amide; Y . { [(S) -1- [1- [4-fluoro-benzenesulfonyl] -3-oxo-azepan-4-ylcarbamoyl] -3-methyl-butyl} amide of quinoline-2-carboxylic acid. 39.- A pharmaceutical composition comprising a compound as claimed in claims 1 to 38, and a pharmaceutically acceptable carrier, diluent or excipient. 40.- A compound of formula II: wherein: R1 is selected from the group consisting of: R2 is selected from the group consisting of: H, d6 alkyl, C3-6 cycloalkyl-C0-β alkyl, Ar-Co-β alkyl, Het-C0-β alkyl, R9C ( O) -, R9C (S) -, R9SO2-, R9OC (O) -, R9R11NC (O) -, R9R11NC (S) -, R9 (R11) NSO2-, R6 R3 is selected from the group consisting of: H, d-β alkyl, C2- al alkenyl, C2-6 alkynyl, Het-alkyl of Co-β and Ar-alkyl of C0- ß; R3 and R 'may be linked to form a pyrrolidine, piperidine or morpholine ring; R 4 is selected from the group consisting of H, C 1-6 alkyl, (C 3-6) cycloalkyl-Co-e alkyl, C 0 -C 0 alkyl, C 0-6 Het-alkyl, R 5C (0) - , R5C (S) -, R5S02-, R5OC (O) -, R5R13NC (O) -, and R5R13NC (S) -; R5 is selected from the group consisting of: H, alkyl of d-6, alkenyl of C2-β, alkynyl of C2-6, cycloalkyl (C3-6) -alkyl of Co-β, Ar-alkyl of Co-β and Het-Co-βalkyl; Rd is selected from the group consisting of: H, alkyl of d.6, Ar-alkyl of Co-β or Het-alkyl of Co-6¡R7 is selected from the group consisting of: H, alkyl of d-6, (C3-β) cycloalkyl-C0-β alkyl, Ar-Co-β alkyl, Het-alkyl of Co-β, R10C (O) -, R10C (S) -, R10SO2-, R10OC (O) -, R10R14NC (O) -, and R10R14NC (S) -; R8 is selected from the group consisting of: H, C-j-β alkyl, C2-β alkenyl, C2-6 alkynyl, Het-alkyl of Co-β and Ar-alkyl of Co-β; R9 is selected from the group consisting of: C1-6alkyl, (C3.6) cycloalkyl-Co-βalkyl, Co-βalkaryl and Het-Co-βalkyl; R10 is independently selected from the group consisting of: Ci-β alkyl, C3-6 cycloalkyl-Co-β alkyl, Co-6 Aralkyl, and Het-Co-β alkyl; R11 is selected from the group consisting of: H, alkyl of d-β, Ar-alkyl of C0-β and Het-alkyl of Co-β; R 12 is selected from the group consisting of: H, C 1 .6 alkyl, Ar-Co-β alkyl and Het-C 0 -β alkyl; R13 is selected from the group consisting of: H, alkyl of -6, Ar-alkyl of C0-β and Het-alkyl of Co-β; R 14 is selected from the group consisting of: H, C 1 .6 alkyl, Ar-C 0-6 alkyl and Het-C 0 -β alkyl; R 'is selected from the group consisting of: H, alkyl of d-β, Ar-alkyl of Co-β and Het-alkyl of Co-β; R "is selected from the group consisting of: H, C1-6alkyl, Ar-C0-βalkyl or Het-alkyl of Co-β; R '" is selected from the group consisting of: H, Ci alkyl -β, (C3.6) cycloalkyl-Co-6 alkyl, Ar-Co-β alkyl and Het-Co-β alkyl; X is selected from the group consisting of: CH2, S and O; Z is selected from the group consisting of: C (O) and CH2; and pharmaceutically acceptable salts, hydrates and solvates thereof. 41. The compound according to claim 40, further characterized in that it is selected from the group consisting of: [(S) -1- (3-hydroxy-azepan-4-ylcarbamoyl) -3-methyl- benzyl ester] butyl] -carbamic; (S) -2-amino-4-methyl-pentanoic acid (1-benzyl-3-hydroxy-azepan-4-yl) -amide; . { 3-hydroxy-1 - [2- (3-pyridin-2-yl-phenyl) acetyl] azepan-4-yl} - (S) -2-amino-4-methyl-pentanoic acid amide; benzyl ester of acid. { (S) -1- [4 - ((S) -2-amino-4-methyl-pentanoylamino) -3-hydroxy-azepan-1-ylmethyl] -3-methyl-butyl} -carbamic; (S) -2-amino-4-methyl-pentanoic acid (1-benzoyl-3-hydroxy-azepan-4-yl) -amide; [3-hydroxy-1- (4-methyl-pentanoyl) -azepan-4-yl] -amide of (S) -2-amino-4-methyl-pentanoic acid; (S) -2-amino-4-methyl-pentanoic acid (1-benzenesulfonyl-3-hydroxy-azepan-4-yl) -amide; . { (S) -3-methyl-1- [3-hydroxy-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl ester} thieno [3,2-b] thiophene-2-carboxylic acid amide; . { (S) -3-methyl-1- [3-hydroxy-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl ester} 5-methoxybenzofuran-2-carboxylic acid amide; . { (S) -3-methyl-1 - [3-hydroxy-1- (pyridine-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl ester} thieno [3,2-b] thiophene-2-carboxylic acid amide; . { (S) -3-methyl-1- [3-hydroxy-1- (1-oxy-pyridine-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl ester} 3-methylbenzofuran-2-carboxylic acid amide; . { (S) -3-methyl-1- [3-hydroxy-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-ylcarbamoyl] -butyl ester} quinoline-2-carboxylic acid amide; Y . { (S) -3-methyl-1- [3-hydroxy-1- (1-oxy-pyridin-2-sulfonyl) -azepan-4-carbamoyl] -butyl} Quinoxaline-2-carboxylic acid amide. 42. - A method for the synthesis of a compound as claimed in claim 1, comprising the step of oxidizing a corresponding compound of those claimed in claim 40, with an oxidant, to give the compound of formula (I) as a mixture of diastereomers. 43.- The method according to claim 42, further characterized in that the oxidant is a complex of sulfur trioxide and pyridine in DMSO and triethylamine. 44. The method according to claim 43, further characterized in that it comprises the step of separating the diastereomers by separation means. 45.- The method according to claim 44, further characterized in that said separation means consist of high pressure liquid chromatography (CLAP). 46. The method according to claim 42, further characterized in that it comprises the step of deuterating said diastereomers with a deuterating agent. 47. The method according to claim 46, further characterized in that said deuterant agent is CD3OD: D2O (10: 1) in triethylamine. 48. The use of a compound as claimed in any of claims 1 to 38, in the manufacture of a medicament for use in the inhibition of a protease selected from the group consisting of a cysteine protease and a serine protease. 49. The use according to claim 48, wherein said protease is a cysteine protease. 50.- The use according to claim 49, wherein said cysteine protease is cathepsin K. 51.- The use of a compound as claimed in any of claims 1 to 38, in the manufacture of a medicament for use in the treatment of a disease characterized by bone loss. 52. The use according to claim 51, wherein said disease is osteoporosis. 53. The use according to claim 51, wherein said disease is periodontitis. 54.- The use according to claim 51, wherein said disease is gingivitis. The use of a compound as claimed in any of claims 1 to 38, in the manufacture of a medicament for use in the treatment of a disease characterized by excessive degradation of cartilage or matrix. 56.- The use according to claim 55, wherein said disease is osteoarthritis. 57. - The use according to claim 55, wherein said disease is rheumatoid arthritis.