MXPA99009976A - Protease inhibitors - Google Patents

Abstract

The present invention provides compounds of formula (I) which inhibit proteases, including cathepsin K, pharmaceutical compositions 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 or malignancy;and metabolic bone disease therewith.

Description

PROTEASE INHIBITORS FIELD OF THE INVENTION This invention relates generally to inhibitors of heterocyclocetohydrazide protease, particularly, to inhibitors of cysteine and serine proteases, very particularly to compounds that inhibit cysteine proteases, still more particularly compounds that inhibit cysteine proteases of the papain superfamily, even more particularly compounds that inhibit cysteine proteases of the cathepsin family, most particularly compounds that inhibit cathepsin K. Said compounds are particularly useful for treating diseases in which cysteine proteases are implicated, especially diseases of excessive loss of bone or cartilage, eg, osteoporosis, periodontitis. and arthritis.

BACKGROUND OF THE INVENTION The bone is composed of a matrix of proteins in which hydroxyapatite crystals are incorporated in the form of cylinders or plates. Collagen type 1 represents the main structural protein of bone that comprises approximately 90% of the structural protein. The remaining 10% of the matrix is composed of a number of non-collagenous proteins, including osteocalcin, proteoglycans, osteopontin, osteonectin, thrombospondin, fibronectin and bone sialoprotein. Skeletal bone 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 bone resorption is carried out by osteoclasts, which are the multinuclear cells of hematopoietic lineage. The osteoclasts adhere to the surface of the bone and form a narrow sealing zone, followed by an extensive membrane undulation on its apical surface (i.e., resorption). This creates a closed extracellular compartment on the surface of the bone that is acidified by pumping protons in the corrugated membrane, and within which the osteoclast secretes proteolytic enzymes. The low pH of the compartment dissolves the hydroxyapatite crystals on the surface of the bone, while the proteolytic enzymes digest the protein matrix. In this way, a resorption or pitting lagoon is formed. At the end of this phase of the cycle, osteoblasts establish a new protein matrix that is subsequently mineralized. In several disease states, such as osteoporosis and Paget's disease, the normal balance between bone resorption and bone formation is altered, and there is a true actual bone loss in each cycle. Finally, this leads to weakening of the bone and can cause an increased risk of fracture with minimal trauma.

Several published studies have shown that cysteine protease inhibitors are effective in inhibiting bone resorption mediated by osteoclasts, and indicate an essential role for cysteine proteases in bone resorption. For example Delaisse, et al., Biochem J. 1980, 192,365, describe a series of protease inhibitors in a culture of mouse bone organs and suggest that cysteine protease inhibitors (e.g., leupeptin, Z-Phe-Ala- CHN2) prevent bone resorption, whereas serine protease inhibitors were not ineffective. Delaisse, and others, Biochem. Biofis Res. Commun., 1984, 125,441, describe that E-64 and leupeptin are also effective in preventing bone resorption in vivo, as measured by acute changes in serum calcium levels in rats with calcium-deficient diets. Lerner et al., J. Bone Min. Res., 1992,7,433, describe that cystatin, an endogenous inhibitor of cysteine protease, inhibits bone resorption stimulated by PTH in mouse calvaries. Other studies, such as by Delaisse, et al., Bone, 1987,8305, Hill, and others J. Cell. Biochem., 1994, 56, 18 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 and others, J. Biol. Chem. 1994, 269, 1 106, Inaoka et al., Biochem. Biophys. Res. Commun., 1995, 206, 89 and Shi et al., FEBS Lett, 1995, 357, 129 describe that under normal conditions cathepsin K (which has also been called cathepsin O), a cysteine protease, is expressed abundantly in osteoclasts. and it may be the largest 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, but not limited to, osteoporosis, Paget's disease, malignant hypercalcemia and metabolic bone disease. Cathepsin K levels have also been shown to be elevated in osteoarthritic synovium chondroclastics. In this way, selective inhibition of cathepsin K may also be useful for treating diseases of excessive cartilage or matrix degradation, including, but not limited to, 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. Palmer, et al., J. Med. Chem, 1995, 38, 3193, describe certain vinylsulfones that irreversibly inhibit cysteine proteases, such as cathepsins B, L, S, O2, and cruzain. Other classes of compounds, such as aldehydes, nitriles, α-ketocarbonyl compounds, halogenomethyl ketones, diazomethyl ketones, (acyloxy) methyl ketones, ketomethylsulfonium salts and epoxysuccinyl compounds have also been reported to inhibit cysteine proteases. The synthesis of azathides (polyacrylhydrazides) as peptide mimetics has been recently described by Han and Janda, J. Am. Chem. Soc. 1996, 118, 2539. The synthesis of N-phenyl-N '- (2-phenyloxazol-4) -carbonyl) hydrazide, as well as its N- (2,4-dinitrophenyl) derivative has been described in Afridi, A. et al., J. Chem. Soc, Perkin Trans. 1, 1976, 3, 315-20. Benko, A. and others, Justus Liebigs Ann. Chem. 1968, 717, 148-53 describes the preparation of N- (4-ethoxycarbonyltriazol-2-yl) -N '- [2- (4-pyrridinyl) triazol-4-ylcarbonyl] hydrazide. In this way, a structurally diverse variety of cysteine protease inhibitors has been identified. However, these known inhibitors are not considered suitable for use as therapeutic agents in animals, especially humans, because they suffer from several disadvantages. These disadvantages include lack of selectivity, cytotoxicity, poor solubility and too rapid plasma clearance. Therefore, there is a need for methods to treat diseases caused by pathological levels of proteases, especially cysteine proteases, including cathepsins, especially cathepsin K, and novel inhibitory compounds useful in such methods. We have now discovered a novel class of heterocyclocetohydrazide compounds which are protease inhibitors, most particularly of cathepsin K.

BRIEF DESCRIPTION OF THE INVENTION An object of the present invention is to provide inhibitors of heterocyclocetohydrazide protease, particularly inhibitors of cysteine and serine proteases, very particularly compounds that inhibit cysteine proteases, still more particularly compounds that inhibit cysteine proteases of the papain superfamily, still more particularly compounds that inhibit cysteine proteases of the cathepsin family, more particularly compounds that inhibit cathepsin K, and which are useful for treating diseases that can be therapeutically modified by altering the activity of said proteases. Accordingly, 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 still another aspect, this invention provides intermediates useful in the preparation of the compounds of formula I. In yet another aspect, this invention provides methods for treating diseases in which the disease pathology can be therapeutically modified by inhibiting proteases, particularly cysteine and serine proteases, very particularly cysteine protease, still more particularly cysteine proteases of the papain superfamily, even very particularly cysteine proteases of the cathepsin family, most 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 by excessive degradation of cartilage or matrix, such as osteoarthritis and rheumatoid arthritis.

DETAILED DESCRIPTION OF THE INVENTION The present invention provides compounds of the formula I: wherein: L is C2-6 alkyl. AR-C0-6 alkyl, Het-C0-6 alkyl, CH (R4) NR5R6, CH (R4) Ar, CH (R4) OAr1 or NR4R7; Ar is phenyl or naphthyl, independently substituted and optionally by one or more of Ph-C0-6 alkyl, Het-C0-6 alkyl, C? -6 alkyl, d-6 alkoxy, C0-Ph-alkoxy -6, Het-aicoxy of C0-6. OH, (CH2)? 6NR8R9, O (CH2)? - 6NR8R9, CO2R 'or halogen. Two Ci-β alkyl groups can be combined to form a 5-7 membered, saturated or unsaturated ring, fused to the Ar ring, Ph can optionally be substituted with one or more of C? -6 alkyl, alkoxy of, OH, (CH2)? - 6NR8R9, O (CH2)? - 6NR8R9, CO2R 'or halogen. Ar 'is phenyl or naphthyl, optionally substituted and independent by one or more of Ph-alkyl of CO-T. Het-C0-6alkyl, C-? -6alkyl, C-? -6alkoxy, Ph-C0-6alkoxy, Het-C0-6alkoxy, OH, (CH2)? - 6NR8R9, O (CH2)? - 6NR8R9 or halogen. Ph can be optionally substituted with one or more of C? -6 alkyl) C? -6 OH alkoxy, (CH2)? -6NR8R9, O (CH2)? -6NR8R9, CO2R 'or halogen. Two C -? - 6 alkyl groups can be combined to form a 5-7 membered ring, saturated or unsaturated, fused over the ring of Ar '. Het is a stable 5- to 7-membered monocyclic heterocyclic ring, or stable 7- to 10-membered bicyclic ring, which is either saturated or unsaturated and consisting of carbon atoms and one to four heterogeneous atoms selected from the group consisting of N, O and S, and wherein the heterogeneous nitrogen and sulfur atoms may optionally be oxidized, and the heterogeneous nitrogen atom may be optionally quaternized, and including any bicyclic group in which any of the heterocyclic rings mentioned above is fused to a benzene ring. The heterocyclic ring can be attached to any heterogeneous atom or carbon atom, which results in the creation of a stable structure, and can be optionally substituted with one or two portions selected from the group consisting of Ph-alkyl of Co-β , Het-alkyl of Co-6, alkyl of C -? - 6, alkoxy of C? -6, Ph-alkoxy of C0-6, Het-alkoxy of Co-6, OH (CH2)? 6NR8R9, O ( CH2)? - 6NR8R9, CO2R '. Two d-e alkyl groups can be combined to form a 5-7 membered, saturated or unsaturated ring, fused to the Het ring. Ph can optionally be substituted with one or more of d-6 alkyl, d6 alkoxy, OH, (CH2) ?. 6NR8R9, O (CH2)? - 6NR8R9, CO2 'or halogen. Preferably, said heterocycles are selected from the group consisting of the piperidinyl, piperazinyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, 2-oxoazepinyl, azepinyl, pyrrolyl, 4-piperidonyl, pyrrolidinyl, pyrazolyl, pyrazolidinyl, imidazolyl, triazolyl, tetrazolyl, pyridyl, pyridinyl, pyridazinyl, pyrimidinyl, triazinyl, tetrazinyl, oxazolidinyl, oxazolidinyl, oxazolnyl, oxazolyl, isothiazolyl, isoxazolyl, morpholinyl, thiazolidinyl, thiazolidyl, thiazolyl, quinuclidinyl, indolyl, quinolinyl, isoquinolinyl, benzimidazolyl, benzopyranyl, benzoxazolyl, furyl, pyranyl, tetrahydrofuryl, tetrahydropyranyl, thienyl, benzoxazolyl, thiamorpholinyl sulfoxide, thiamorpholinyl sulfone, thiadiazolyl and oxadiazolyl. W is C (O) or SO2; X, Y and Z are independently N, O, S or CR10, as long as at least two of X, Y and Z are heterogeneous atoms and at least one of X, Y and Z is N, or one of X, Y and Z is C = N, C = C or N = N and the other two are CR10 or N, as long as at least two of X, Y and Z are N: - indicates a single or double bond in the heterocycle of five members; R ', R1, R2, R5, R8, R9, R10 and R12 are independently H, alkyl of d-6, alkenyl of C2-6, Ar-alkyl of Co-6 or Het-alkyl of Co-ßl R3 is alkyl of C3-6, Ar, Het, CH (R11) Ar, CH (R11) OAr, NR11R12, CH (R11) NR12R13; or R4, R11 and R15 are independently H, C6-6alkyl, C2-6alkenyl, C3-6cycloalkyl-Co-6alkyl, Coal-Ar- alkyl or Het-alkyl- Co-6; R7 is d-6 alkyl, d-6 alkenyl > C3-6-cycloalkylCo-6alkyl, Ar-C0-6alkyl or Het-C06alkyl; R4 and R7 can be combined to form a 7- to 7-membered monocyclic or 7 to 10 membered monocyclic carbocyclic or heterocyclic ring optionally and independently substituted with 1-4 C-6 alkyl, C0-6 arylamino, Het- Co-6 alkyl, d6 alkoxy, C0-e alkoxy, C0-e-hydroxy, OH, (CH2)? - eNR8R9 or O (CH2)? - 6NR8R9; R6 and R13 are R14, R14 C (O), R14C (S), R1 OC (O) or R1 OC (O) NR9CH (R15) (CO), and R14 is C6.6 alkyl, C2- alkenyl 6, Ar-alkyl of C-0-6 or Het alkyl of C0-6- The compounds of the formula I wherein Z = N, X = S and Y = CH (thiazolo) are preferred. More preferred are compounds in which W is C (O). Still more preferred are compounds wherein R1 and R2 are H. Still more preferred are compounds wherein R3 is: wherein: R16 is H or alkyl of d-6, preferably H or Me; R17 is C6-6 alkyl, C2-6 alkenyl and C3-11 cycloalkyl-C1-6 alkyl, preferably n-propyl, / so-propyl, / so-pentyl-tert-butylmethyl, cyclopropylmethyl, -butyl, n-butyl or allyl; and R18 is C3-e alkyl, O-C3-6 alkyl, Ar, Het, O (CH2) or -3Ar or O (CH2) o-3Het, preferably 2-pyridinylmethoxy, 3-pyridinylmethoxy, 4-pyridinylmethoxy, 1-butoxy, 2-pyridinyl, 3-pyridinyl, 4-pyridinium, 2-pyrazinyl, 4-tert-butoxycarbonylbenzyloxy, 4-carboxybenzyloxy , 3-Ier-butoxycarbonylbenzyloxy, 3-carboxybenzyloxy, 2-methyl-3-pyridinylmethoxy, 6-methyl-3-pyridinylmethoxy, benzyloxy, 2-quinoline, 3-quinoline, 4-quinoline, 5-quinoline, 6-quinoline, -quinoline, 8-quinoline, 1-isoquinoline, 3-isoquinoline, piperidinyl, 4-methylpiperidinyl, 4-methylimidazol-5-yl, N-benzyl-pyrroiidinyl, N-methyl-pyrrolidinyl, 1-benzyl-5-methylimidazole-4 -yl, 1-piperazinyl; 3- (2-pyridyl) benzyl, 2-methyl-3-pyridinyl, 2-1 methyI-4-pyridinyl, 6-methyl-3-pyridinyl, 4-dimethylaminobenzyloxy, 4- (4-morpholinomethyl) phenyl, 5-hydroxymethylimidazol-4-yl, 5-butyl-2-pyridinyl, 4-flurophenyl, 3,4 -difluorophenyl, 2- (1,8-naphthyridinyl) or 3,4-dimethoxyphenyl. Also more preferred are compounds of formula I wherein Z = N, X = S and Y = CH (thiazolo), W is C (O), R1 and R2 are H, and where L is 4- (c) s-2,6-dimethyl) -4-morpholinyl, N-cyclopropylmethyl-N- (2-methylpropyl) amino, 4-methyl-1-naphthyl, N-methyl-N- (2-methylpropyl) amino, 1 -naphthyl , 5-acenaphthyl, N-cyclopropii-N-cyclopropylmethylamino, N, N-bis- (2-methylpropyl) amino, 1- (1, 2,3,4-tetrahydroquinolino, N-cyclopropylmethyl-N-propylamino, N- ( 2-methypropyl) -N-phenylamino, 2-methoxy-1-naphthyl, 2-benzyloxyphenyl, 2-benzyloxy-1-naphthyl, 9-phenanthrenyl, 9-anthracenyl, phenyl, 2- (4-tert-butoxycarbonyl) benzyl loxyphenyl, 2- (4-carboxybenzyloxy) phenyl, N-cyclopropylamino, 8-quinoline, N, N-bis- (cyclopropylmethyl) amino, 4- (2,2-dimethylaminoethoxy) -1-naphthyl or 1- (N -benzyloxycarboniamino) -3-methylbutyl The following compounds are particularly preferred embodiments of the present invention: N- [2- (cs-2,6-dimethyl-4-morpholino) triazol-4-ylcarbonyl] -N'- [N- (4-pyridinylmethoxycarbonyl) -L-leucinyl] hi drazide; N- [2- [N-cyclopropylmethyl-N- (2-methylpropyl) amino] tiazol-4-ylcarbonyl] -N '- [N- (4-pyridinolmethoxycarbonyl) - L-leucine] hydrazide; N- [2- (4-methyl-1-naphthyl) thiazole-4-alkylcarbonyl] -N '- [N- (4-pyrimidinylmethoxycarbonyl) -L-leucinyljhydrazide; N- [2- [N-methyl- (2-methylpropyl) amino] thiazol-4-ylcarbonyl] -N '- [N-methyl-N- (4-pyridinylmethoxycarbonyl) -L-leucinyl] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (3-pyridinylmethoxycarbonyl) -L-leucinyljhydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (2-pyridinylmethoxycarbonyl) -L-leucinylhydrazide; N- [2- (5-Acenaphthyl) thiazol-4-ylcarbonyl] -N '- [N- (4-pyridinylmethoxycarbonyl) -L-leucinylhydrazide; N- [2- [N-cyclopropylmethyl-N- (2-methylpropyl) amino] thiazol-4-ylcarbonyl] -N '- [N-methyl-N- (4-pyridinylmethoxycarbonyl) -L-leucinyl] hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- [N- (4-pyridinylmethoxycarbonyl) -L-leucinyl] hydrazide; N- [2- [N-cyclopropylmethyl-N- (2-methy1propyl) amino] thiazol-4-ylcarbonyl] -N '- [N- (3-pyridinylmethoxycarbonyl) -L-leucinyl] hydrazide; N- [2- [N-cyclopropylmethyl-N- (2-methylpropyl) amino] thiazol-4-ylcarbonyl] -N '- [N- (2-pyridinylmethoxycarbonyl) -L-leucinii] hydrazide; N- [2- [N-cyclopropylmethyl-N- (2-methylpropyl) amino] thiazol-4-ylcarbonyl] -N '- [N-methyl-N- (3-pyridinylmethoxycarbonyl) -L-leucinyl] hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino] thiazol-4-ylcarbonyl] -N '- [N- (3-pyridinylmethoxycarbonyl) -L-leucinyl] hydrazide; N- [2- (N-cyclopropyl-N -cyclopropylmethylamino] thiazol-4-ylcarbonyl] -N '- [N-methyl-N- (4-pyridinylmethoxycarbonyl) -L-leucinyl] hydrazide;N- [2- [N, N-bis- (2-methylpropyl) amino] thiazol-4-ylcarbonyl] -N '- [N- (2-pyridinylmethoxycarbonyl) -L-leucinii] hydrazide; N- [N- (4-pyridine-methoxycarbonyl) -L-leucinyl] -N '- [2- [1 - (1, 2,3,4-tetrahydroquinolino)] thiazol-4-ylcarbonyl] hydrazide: N - [2- [N-methyl-N- (2-methylpropyl) amino] thiazol-4-ylcarbonyl] -N '- [4-methyl-2- (3-phenyl) phenylpent-4-eneyl] hydrazide; N- [2- [N, N-bis- (2-methylpropyl) amino] thiazol-4-ylcarbonyl] -N '- [N -methyl-N- (3-pyridinylmethoxycarbonyl) -L-leucinii] hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- [N-methyl-N- (3-pyridinylmethoxycarbonyl) -L-leuciniI] hydrazide; N- [2- (N-cyclopropylmethyl-N-propylamino) thiazol-4-ylcarbonyl] -N '- [N- (3-pyridinylmethoxycarbonyl) -L-leucinyl] hydrazide; N- [2- [N-methyl-N- (2-methylpropyl) amino] thiazol-4-ylcarbonyl] -N '- [4-methyl-2- (3-phenyl) phenylpentanoyl] hydrazide; N- [N- (2-methylpropyl) -N- (3-phenylphenyl) carbamoyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonylhydrazide; N- [4-methyl-2- (3-phenyl) phenylpentanoyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- [4-methyl-2- (3-pheny] phenylentanoyl] -N '- [2- [N- (2-methylpropyl) -N-phenylamino] thiazol-4-ylcarbonyl] hydrazide; N- [2- (2-methoxy-1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (4-pyridinylmethoxycarbonyl) -L-leucinylhydrazide; N- [2- (2-benzyloxyphenyl) thiazol-4-ylcarbonyl] -N '- [4-methyl-2- (3-phenyl) phenylpentanoyl] hydrazide; N- [2- (2-benzyloxy-1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (4-pyridinylmethoxycarbonyl) -L-leucinylhydrazide; N- [2- [N, N-bis- (2-methylpropyl) amino] thiazol-4-ylcarbonyl] -N '- [N-methyl-N- (2-pyridinylmethoxycarbonyl) -L-leucine] l] hydrazide; N- [2- (9-Phenanthrenyl) thiazol-4-ylcarbonyl] -N '- [N- (4-pyridinylmethoxycarbonyl) -L-leucinylhydrazide; N- [2- (9-anthracenyl) thiazol-4-ylcarbonyl] -N '- [N- (4-pyridinylmethoxycarbonyl) -L-leucinylhydrazide; N- [2- [N, N-bis- (2-methylpropyl) amino] thiazol-4-ylcarbonyl] -N '- (eer-butoxycarbonyl-L-leucinylhydrazide; N- [2- [N, N-bis- (2-methylpropyl) amino] thiazol-4-ylcarbonyl] -N '- [N- (L-leucinyl)] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N' - [N -methyl-N- (3-pyridinylmethoxycarbonyl) -L-leucinylhydrazide; N- [2- [N, N-bis- (2-methylpropyl) amino] thiazole-4-alkylcarbonyl] -N '- (N-picol noyl-L-leucinyl) hydrazide; N- [2- [N, N-bis (2-methylpropyl) amino] thiazol-4-ylcarbonyl] -N '- [N- (2-pyrazinocarbonyl) -L-leucinyl] hydrazide; N- [N, N-bis (2-methylpropyl) carbamoyl] -N '- [2- [N- (2-methylpropyl) -N-phenylamino] thiazol-4-ylcarbonyl] hydrazide; N- (2-phenylthiazole; -4-ylcarbonyl] -N '- [N- (4-pyridinylmethoxycarbonyl) -L-leucinyl] hydanzate; N- [2- [2- (4-Ier-butoxycarbonyl) benzyloxyphenyl] thiazol-4-ylcarbonyl] -N '- [N- (4-pyridinylmethoxycarbonyl) -L-leucinyl] hydrazide; N- [2- [2- (4-carboxybenzyloxy) phenyl] thiazol-4-ylcarbonyl] -N '- [N- (4-pyridinylmethoxycarbonyl) -L-leucinyl] hydrazide; N- [N- (4-Ier-butoxycarbonylbenzyloxycarbonyl) -L-Ieucinyl] -N '- [2- [N- (methylpropyl) -N-phenylamino] thiazol-4-ylcarbonyl] hydrazide; N- [2- [N, N-bis- (2-methylpropyl) amino] thiazol-4-ylcarbonyl] -N '- [N- (4-yer-butoxycarbonylbenzyloxycarbonyl) -L-leucinyl] hydrazide; N- [N- (4-carboxybenzyloxycarbonyl) -L-Ieucinyl] -N '- [2- [N- (2-methylpropyl) -N-phenylamino] thiazol-4-ylcarbonyl] hydrazide; N- (N-benzyloxycarbphenyl-L-leucinyl) -N '- [2- [2- (4-ér-butoxycarbonyl) benzyloxyphenyl] itazol-4-ylcarbonyl] -hydrazide; N- (N-benzyloxycarbonyl-L-leucinyl) -N '- [2- [2- (4-carboxybenzyloxy) phenyl] thiazol-4-ylcarbonylhydrazide; N- [N- (6-methyl-3-pyridinylmethoxycarbonyl) -L-leucinyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonylhydrazide; N- (N-benzyloxycarbonyl-L-leucinyl) -N '- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- [N- (2-pyridinylmethoxycarbonyl) -L-leucinyl] hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamine) thiazol-4-ylcarbonyl] -N '- [N- (6-methyl-3-pyridinylmethoxycarbonyl) -L-leucinyl] hydrazide; N- (N-fer-butoxycarbonyl-L-leucinyl) -N '- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) tiazole-4-carbonyl] -N '- [N -methyl-N- (2-pyridinylmethoxycarbonyl) -L-leucyl] hydrazide; N- [2- (2-benzioxyphenyl) thiazol-4-ylcarbonyl] -N '- [N- (6-methyl-3-pyridinylmethoxycarbonyl) -L-leucinyl] hydrazide; N- [2- (2-benzyloxyphenyl] thiazol-4-ylcarbonyl] -N '- [N- (2-methyl-3-pyridinylmethoxycarbonyl) -L-leucinyl] hydrazide; N- [2- [N-methyl- N- (2-methylpropyl) amino] thiazol-4-ylcarbonyl] -N '- [N- (6-methyl-3-pyrridinylmethoxycarbonyl) -L-leucinyl] hydrazide; N- [2- [N-methyl-N- (2-methylpropyl) amino] thiazol-4-ylcarbonyl] -N '- [N - () - L-leucinyljhydrazide; N- [2- [N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] - N '- (N-picolinoyl-L-leucinyl) hydrazide; N- [2- [N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- [N- (2-methyl-3-pyridinylmethoxycarbonyl) -L-leucinyl] hydrazide; N- [N- (3-fer-butoxycarbonylbenzyloxycarbonyl) -L-leucinyl] -N '- [2- (N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (8-quinolinoyl) -L-leucinyl] hydrazide; N- [N- (2-methyl-3-pyridinylmethoxycarbonyl) -L-leucinyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonylhydrazide; N- [2- (1-naphthyl) thiazole-4-alkylcarbonyl] -N '- (N-picolinoyl-L-leucinyl) hydanzate; N- [N- (3-carboxybenzyloxycarbonyl) -L-leucinyl] -N '- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (2-quinolylnoyl) -L-leucinyl] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (3-quinolinoyl) -L-leucyl] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (4-methylpiperidinocarbonyl) -L-leucinylhydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (4-quinoxynol) -L-leucinyl] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (5-quinol-ynyl) -L-leucinyl] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (7-quinolinoyl) -L-leucinyl] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (6-quinolinoii) -L-leucinyl] hydrazide; N- [N- (1-Isoquinolylnoyl) -L-leucinyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- [2- (3-isoquinolinoyl) -L-leucinyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- [N- (4-methylimidazol-5-ylcarbonyl) -L-leucinyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonylhydrazide; N- (N-benzyl-L-prolinyl-L-leucinyl) -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- [N- (1-benzyl-5-methylimidazol-4-ylcarbonyl) -L-leucinyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonylhydrazide; N- [N- (3-methylisonicotinoyl) -L-leucinyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- [2- (N-cyclopropylamino) thiazol-4-ylcarbonyl] -N '- [N- (2-pyridinylmethoxycarbonyl) -L-leucinylhydrazide; N- [4-methyl-2- (3-phenoxy) phenylpentane] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- [N- (2-benzoxazolyl) -L-leucinyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- [N-benzyloxycarbonyl-L-leuciniI) -N '- [2- (N, N-bis- (2-methylpropyl) amino] oxazol-4-ylcarbonylhydrazide; N- [2- (N-cyclopropyl-N- (2-methylpropyl) amino] thiazol-4-ylcarbonyl] -N '- [N- (2-pyridinylmethoxycarbonyl) -L-leucinyl] hydrazide; N- [2- [N-cyclopropyl-N- (2-methylpropyl) amino] thiazol-4-ylcarbonyl] -N '- [N-methyl-N- (2-pyridinylmethoxycarbonyl) -L-leucinyl] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (1-piperazinocarbonyl) -L-leucinylhydrazide; N- [4-methyl-2- (4-phenoxy) phenylpentanoyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- [2- [N-bis- (cyclopropylmethyl) amino] thiazol-4-ylcarbonyl] -N '- [N- (2-pyridinylmethoxycarbonyl) -L-leucinyl] hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- [N- (2-quinolinoyl) -L-leucinyl] hydrazide; N- [N- (8-quinolinoyl) -L-leucinyl] -N '- [2- (8-quinoliniI) thiazol-4-ylcarbonyl] hydrazide; N- (N-benzyloxycarbonyl-L-leucinyl) -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- [N- (3-quinolinoyl) -L-leucinyl] hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylamethylamino) thiazol-4-ylcarbonyl] -N '- [N- (3-isoquinolinoyl) -L-leucinyl] hydrazide; N- [2- (N-cyclopropyI-N-cyclopropylmethylamino) thiazol-4-ylcarbonii] -N '- [N- (6-quinolinoyl) -L-leucinyl] hydrazide; N- [2- (N-bis- (cyclopropylmethyl) amino] thiazol-4-ylcarbonyl] -N '- [N- (2-methyl-3-pyridinylmethoxycarbonyl) -L-leucinyl] hydrazide; N- (N-benzyloxycarbonyl) -Lb-yer-butylalanyl) -N '- [2- (1-naphthyl) thiazol-4-ylcarbonylhydrazide; N- (N-benzyloxycarbonyl-Lb-cyclopropylalanyl) -N' - [2- (1-naphthyl); thiazol-4-ylcarbonyljhydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- [3- (2-pyridyl) phenylacetyl] -L-leucinylhydrazide; N- [2- [N-bis- (cyclopropylmethyl) amino] thiazol-4-ylcarbonyl] -N '- (N-picolinyl-L-leucinylhydrazide; N- (N-benzyloxycarbonyl-L-leuciniI) -N' - [ 2- [N-bis- (cyclopropiimethyl) amino] thiazol-4-ylcarbonylhydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- [N- (6- methylnicotinoyl) -L-leucinyl] hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- [N- (2-methylnicotinoyl) -L-leucinyl] hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- [N- (3-methyl-sonicotinoyl) -L-leucinyl] hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) ) thiazol-4-ylcarbonii] -N '- [N- (8-quinolinoyl) -L-leucinyl] hydrazide; N- [2- [N-bis- (c-chloropropylmethyl) amino] thiazol-4-ylcarbonii] - N '- [N- (8-quinolinoyl) -L-leucinylhydrazide; N- [2- (N-bis- (cyclopropylmethyl) amino] thiazol-4-ylcarbonyl] -N' - [N- (3-isoquinol-ynoyl ) -L-leucinylhydrazide; N- [2- [4- (2,2-dimethylaminoethoxy) -1-naphthyl] thiazole-4-ylcarbonyl] -N '- [N- (8-quinolinoyl) -L-leucinyl] hydrazide; N- [2- (N-cyclopropyl-N-cyclop ropilmethylamino) thiazol-4-ylcarbonyl] -N '- [N- (7-quinolinoii) -L-leucinyl] hydrazide; N- [2- [N-bis- (cyclopropylmethyl) amino] thiazol-4-ylcarbonyl] -N '- [N- (6-methylnicotinoyl) -L-leucinylhydrazide; N- [2- (N-bis- (cyclopropylmethyl) amino] thiazol-4-ylcarbonii] -N '- (N-methyl-L-prolylnyl-L-leucinylhydrazide; N- (N-benzyloxycarbonyl -L-norvalinyl) -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydanida; N- (N-benzyloxycarbonyl-L-isoleucinyl) -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- [N- (4-dimethylaminomethylbenzoyl) -L-leucinyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonylhydrazide; N- (N-benzyloxycarbonyl-L-norleucinyl) -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- [N- (4-dimethylaminomethylbenzyloxycarbonyl) -L-leucinyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonylhydrazide; N- (N-benzyloxycarbonyl-L-norvalinyl) -N '- [2- (2-benzyloxyphenyl) -thiazole-4-ylcarbonylhydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- [N- (4-methylimidazol-5-ylcarbonyl) -L-leucinyl] hydrazide; N- [N- [4- (4-morpholinomethyl) benzoyl] -L-leucinyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonylhydrazide; N- [N- (2-methylnicotinoyl) -L-leucinyl] N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- [N- (6-methylnicotinoyl) -L-leucinyl] N '- [2- (1-naphthyl) thiazole-4-ylcarbonyl] hydanida; N- (N-b-tert-butoxycarbonyl-L-tert-butylanyl) -N '- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] N '- [N- (8-quinolinoyl) -L-b-yer-butylalanyl] hydrazide; N- [N- (4-methylimidazol-5-ylcarbonyl) -L-allylglycinyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonylhydrazide; N- [N- (4-methylimidazol-5-ylcarbonyl) -L-b-yer-butylalanyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonylhydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- [N- (4-methylimidazoI-5-ylcarbonyl) -L-b-tert-butylalanyl] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- (N-picolinoyl-L-b-yer-butylalanyl) hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (8-quinolinoyl) -L-b-yer-butylalanyl) hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- (N-picolinoyl-L-allylglycinyl) hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- (N-picolinoii-L-b-cyclopropylalanyl) hydrazide; N- [N- (6-methynicotinoyl) -L-b-cyclopropylalanyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonylhydrazide; N- [N- (4-methylimidazol-5-ylcarbonyl) -L-b-cyclopropylalanyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonylhydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (8-quinolinoyl) -L-cyclopropylalanyl-hydrazide: N- [N- (6-methylnicotinoyl) -Lb-yer-butylalanyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyljhydrazide; N- [2- (N-cyclopropyl-cyclopropylmethyllamino-4-ylcarbonyl] -N '- (N-p-cholino-L-L-fer-butylalanyl) hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) ) thiazol-4-ylcarbonyl] -N '- [N- (3-isoquinolylnoyl) -Lb-tert-butylalanyl] hydrazide; N- (N-fer-butoxycarbonyl-L-b-cyclopropylalanyl) -N '- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] hydrazide; N- [2- (N-cyclopropylmethyl-N-propylamino) thiazol-4-ylcarbonyl] -N '- [N- (6-methyl-3-pyridinylmethoxycarbonyl) -L-leucine] hydrazide; N- [N- (6-methylnicotinoyl) -L-allyl] yl] - N '- [2- (1-naphthyl) thiazole) -4-ylcarbonyl] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (8-quinolinoyl) -L-allylglycinyl] hydanida; N- [2- (1-naphthylthiazol-4-ylcarbonyl] -N '- [N- (2-quinolinoyl) -L-cyclopropylalanyl-hydrazide; N- [N- (3-isoquinolinoyl) -L- cyclopropylalani] -N' [ - [2- (1-naphthyl) thiazol-4-ylcarbonylhydrazide; N- [N- (1-isoquinolylnoyl) -L-cyclopropylalanyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonylhydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (7-quinolinoyl) -L-cyclopropylalanyl-hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazole-4 -carbonyl] -N '- [N- (8-quinolinoyl) -L-cyclopropylalanyl] hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N' - [N- ( 4-methylimidazol-5-ylcarbonyl) -Lbcylclopropylalanyl] hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- [N- (3-isoquinolinoyl) -L- Cyclopropylalanyl] hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) tiazol-4-ylcarbonyl] -N '- [N- (6-methylnicotinoyl) -L-cyclopropylalanyl] hydrazide; N- [N- (4-methylimidazol-5-ylcarbonyl) -L-norleucinyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonylhydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- (N-picolinoyl-L-norleucinyl) hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (8-quinolinoyl) -L-norleucinyl) hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- [N- (2-quinolinoyl) -L-b-cyclopropylalanyl] hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- [N- (1-isoquinolinoyl) -L-b-cyclopropylalanyl] hydrazide; N- [2- [N-cyclopropyl-N- (2-methylpropyl) amino] thiazol-4-ylcarbonyl] -N '- [N- (6-methyl-3-pyridinylmethoxycarbonyl) -L-leucinyl] -hydrazide; N- (N-tert-butoxycarbonyl-L-leucinyl) -N '- [2- [N-cyclopropyl-N- (2-methylpropyl) amino] thiazol-4-ylcarbonyl] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (7-quinolino] l) -L-b-fer-butylalanyl-hydrazide; N- [2- (1-naphthyl) thiazoI-4-ylcarbonyl] -N '- [N- (2-quinolinoyl) -L-b-yer-butylalanyl-hydrazide; N- [N- (1-isoquinolinoyl) -L-b-tert-butylanyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonylhydrazide; N- [N- (3-isoquinolylnoyl) -L-b-yer-butylalanyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonylhydrazide; N- [N- (6-Methynylotinoyl) -L-norleucinyl] -N '- [2- (1-naphthyl) thiazole-4-ylcarbonyl] -hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (7-quinolinoyl) -L-norleucinyl] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (2-quinolinoyl) -L-norleucinyl] hydrazide; N- [N- (1-isoquinolinoyl) -L-norleucyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- [N- (3-isoquinolinoyl) -L-norleucinyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylammono) thiazol-4-ylcarbonyl] -N '- [N- (5-hydroxymethylimidazol-4-ylcarbonyl) -L-b-cyclopropylalanyl] hydrazide; N- [2- (N-cyclopropyl-N- (2-methylpropyl) amino] thiazol-4-ylcarbonyl] -N '- [N- (8-quinolinoyl) -L-cyclopropylalanyl] hydrazide; N- [2- ( N-cyclopropyl-N-cyclopropylmethylammono) thiazol-4-ylcarbonyl] -N '- [N- (6-methylnicotinoyl) -L-í -er-butylalanyl] hydrazide; N- [2- (N-cyclopropyl-N- (2- methylpropyl) amino] thiazole-4-ylcarbonyl] -N '- [N- (4-methyl-imidazol-5-ylcarbonyl) -L-cyclopropylalanyl] hydrazide; N- [2- (N-cyclopropyl-N- (2-methylpropyl) amino] thiazol-4-ylcarbonyl] -N '- [N- (2-quinolinoyl) -L-cyclopropylalanyl] hydrazide; N- [2- (N-cyclopropyI-N- (2-methylpropyl) amino] thiazole-4- ilcarboniI] -N '- [N- (6-methylnicotinoyl) -L-cyclopropylalanyl] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N' - [N- (8-quinolinoyl) ) glycinyl] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (8-quinolinoyl) -L-norvalinyl] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (2-quinolinoyl) -L-norvalinyl] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- (N-cholinoyl-L-norvalinyl] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] - N '- [N- (6-methynicotinoyl) -L-norvalinyl] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N' - [N- (4-methylimidazol-5-ylcarbonyl) -L-norvalinylhydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (1-isoquinolinoyl) -L-norvalentyl] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (3-isoquinolinoyl) -L-norvaiinyl] hydrazide; (1S, 1 'S) -N, N'-bis- [4- [1- (N-benzyloxycarbonylamino) -3-methylbutyl] thiazol-2-ylcarbonylhydrazide; N- [2- (N-cyclopropyl-N- (2-methylpropyl) amino] thiazol-4-ylcarbonyl] -N '- [N- (6-methynicotinyl) -Lb-fer-butylalanyl] h drazide; N- [2- (N-cyclopropyl-N- (2-methylpropyl) amino] thiazol-4-ylcarbonyl] -N '- [N- (4-methyl-imidazol-5-ylcarbonyl) -Lb-yer- butylalanyl] hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazole-4-ylcarbonyl] -N '- [N- (1-isoquinolinoyl) -Lb-yer-butylalanyl] hydrazide; N- [N- (5-butylopicolinoyl) -L-tert-butylanyl] -N '- [2- (N-cyclopropyl-N-cyclopropylmethyllamine) thiazole-4-ylcarbonyl] hydrazide; N- [2 - (N-cyclopropyl-N-cyclopropylmethyl amine) thiazol-4-ylcarbonyl] -N '- [N- (6-methylpicolinoyl) -Lb-yer-butylalanyl] hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino ) thiazol-4-ylcarbonyl] -N '- [N- (4-fluorobenzoyl) -L-leucinyl] hydrazide; N- [N- (4-fluorobenzoyl) -L-leucinyl] -N' - [2- (1 -naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (2-pyridinylmethoxycarbonyl) -L-b-yer-butylalanyl-hydrazide; N- [N- (2-methyl-3-pyridinylmethoxycarbonyl) -L-b-fer-butylalanyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (2-pyridinylmethoxycarbonyl) -L-b-cyclopropylalanylhydrazide; N- [N- (2-methyl-3-pyridinylmethoxycarbonyl) -L-b-cyclopropylalani] - N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- [N- (6-methyl-3-pyridine-methoxycarbonyl) -L-b-cyclopropylalanyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- [N- (6-methyl-3-pyridinylmethoxycarbonyl) -L-b-fer-butylalanyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonylhydrazide; N, N'-bis- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- [N- [2- (1, 8-naphthyridinoyl) -L-b-cyclopropylalanyl] hydrazide; N- [2- (N-cyclopropyl-N- (2-methylpropyl) amino] thiazol-4-ylcarbonyl] -N '- [N- (3,4-difluorobenzoyl) -L-cyclopropylalanyl] hydrazide; N- [2 - (N-cyclopropyl-N- (2-methylpropyl) amino] thiazol-4-ylcarbonyl] -N '- [N- (4-fluorobenzoyl) -L-leucinyl] hydrazide; N- [N- (5-butylpicolinoyl) -L-leucinyl] -N '- [2- (N-cyclopropyi-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] hydrazide; N- [2- (N-cyclopropyl-N- (2-methylpropy) amino] thiazole- 4-ylcarbonyl] -N '- [N- (3,4-dimethoxybenzoyl) -L-leucinyl] hydrazide; N- [2- (N-cyclopropyl-N- (2-methylpropyl) amino] thiazole-4-ylcarbonyl] -N '- [N- (3,4-difluorobenzoyl) -L-urea-butylalanyl] hydrazide; N- [2- (N-cyclopropyl-N- (2-methylpropii) amino] thiazol-4-ylcarbonyl] -N '- [N- (3,4-dimethoxybenzoyl) -L- β -er-butylalanyl] hydrazide; N- [N - (5-butylpicolinoyl) -Lb-yer-butylanyl] -N '- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] hydrazide and N- [2- [N-cyclopropyl-N- ( 2-methylpropyl) amino] thiazol-4-ylcarbonyl] -N '- [N- (6-methylpicolinoyl) -Lb-yer-buleylanyl] hydrazide; Compounds of the present invention which are very particularly preferred include: N- [2- [N-cyclopropylmethyl-N- (2-methylpropyl) amino] thiazol-4-ylcarbonyl] -N '- [N- (4 -pyridinylmethoxycarbonyl) -L-leucinyl] hydrazide; N- [2- (4-methyl-1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (4-pyridinylmethoxycarbonyl) -L-leucinylhydrazide; N- [2- [N-methyl- (2-methylpropyl) amino] thiazol-4-ylcarbonyl] -N '- [N-methyl-N- (4-pyridinylmethoxycarbonyl) -L-leucinyl] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (3-pyridinylmethoxycarbonyl) -L-leucinylhydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (2-pyridylmethoxycarbonyl) -L-leucinylhydrazide; N- [2- (5-Acenaphthyl) thiazol-4-ylcarbonyl] -N '- [N- (4-pyridinylmethoxycarbonyl) -L-leucinylhydrazide; N- [2- [N-cyclopropylmethyl-N- (2-methylpropyl) amino] thiazoi-4-alkylcarbonyl] -N '- [N-methyl-N- (4-pyridinylmethoxycarbonyl) -L-leucityl ] hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- [N- (4-pyridinylmethoxycarbonyl) -L-leucinyl] hydrazide; N- [2- [N-cyclopropylmethyl] - N- (2-methylpropyl) amino] thiazol-4-ylcarbonyl] -N '- [N- (3-pyridinylmethoxycarbonyl) -L-leucine] l] disidide; N- [2- [N-cyclopropylmethyl-N- (2-methylpropyl) amino] thiazol-4-ylcarbonyl] -N '- [N- (2-pyridinylmethoxycarbonyl) -L-leucine] l] hydrazide; N- [2- [N-Cyclopropylmethyl-N- (2-methylpropyl) amino] thiazole-4-ylcarbonyl] -N '- [N-methyl-N- (3-pyridinylmethoxycarbonyl) -L-leucine] ] hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino] thiazol-4-ylcarbonyl] -N '- [N- (3-pyridinylmethoxycarbonyl) -L-leucine] l] hydrazide; N- [2- (N-cyclopropyl -N-cyclopropylmethylamino] thiazol-4-ylcarbonyl] -N '- [N-methyl-N- (4-pyridinylmethoxycarbonyl) -L-leucyl] hydrazide; N- [2- [N) N-bis- (2 -methylpropyl) amino] thiazol-4-ylcarbonyl] -N '- [N- (2-pyridiniummethoxycarbonyl) -L-leucinii] hydrazide; N- [N- (4-pyridinylmethoxycarbonyl) -L-leucinyl] -N' - [ 2- [1 - (1, 2,3,4-tetrahydroquinolino)] thiazol-4-ylcarbonyl] hydrazide: N- [2- [N, N-bis- (2-methylpropyl) amino] thiazol-4-ylcarbonyl] -N '- [N-methyl-N- (3-pyridinylmethoxycarbonyl) -L-leucinyl] hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N' - [ N-methyl-N- (3-pyridinylmethoxycarbonyl) -L-leucinyl] hydrazide; N- [2- (N-cyclopropylmethyl-N-propylamino) thiazol-4-ylcarbonyl] -N '- [N - (3-pyridinylmethoxycarbonyl) -L-leucinyl] hydrazide; N- [2- (2-benzyloxy-1-naphthyl) thiazoi-4-ylcarbonyl] -N '- [N- (4-pyridinylmethoxycarbonyl) -L- leucinylhydrazide; N- [2- [N, N-bis (2-methylpropyl) amino] tia zol-4-ylcarbonyl] -N '- [N-methyl-N- (2-pyridinylmethoxycarbonyl) -L-leucyl] hydrazide; N- [2-9-phenanthrenyl) thiazol-4-ylcarbonyl] -N '- [N- (4-pyridinylmethoxycarbonyl) -L-leucinylhydrazide; N- [2- [N, N-bis- (2-methylpropyl) amino] thiazol-4-ylcarbonyl] -N '- (fer-butoxycarbonyl-L-leucinylhydrazide; N- [2- [N, N- bis- (2-methylpropyl) amino] thiazol-4-ylcarbonii] -N '- (N-picolinoyl-L-leucinyljhydrazide; N- [2- [N, N-bis- (2-methylpropyl) amino] thiazole-4 -carbonyl] -N '- [N- (2-pyrazinocarbonyl) -L-leucinyl] hydrazide; N- [2- [2- (4-fer-butoxycarbonyl) benzyloxyphenyl] thiazol-4-ylcarbonyl] -N' - [ N- (4-pyridinylmethoxycarbonyl) -L-leucinyl] hydrazide; N- [2- [2- (4-carboxybenzyloxy) phenyl] thiazol-4-ylcarbonyl] -N '- [N- (4-pyridinylmethoxycarbonyl) - L-leucinyl] hydrazide; N- [N- (4-yer-butoxycarbonylbenzyloxycarbonyl) -L-leucine] -N '- [2- [N- (2-methylpropyl) - N -phenylamino] thiazole-4 -carbonyl] hydrazide; N- [2- [N, N-bis- (2-methylpropyl) amino] thiazol-4-ylcarbonyl] -N '- [N- (4-yer-butoxycarbonylbenzyloxycarbonyl) -L-leucinii] hydrazide; N- [N- (4-carboxy-benzyloxycarbonyl) -L-leucinyl] -N '- [2- [N- (2-methylpropyl) -N-phenylamino] thiazol-4-ylcarbonyl] hydrazide; N- [N- ( 6-methyl-3-pyridinylmethoxycarbonyl) -L-leucine] -N '- [2- (1-naphthyl) thiazole-4-ylca rbonylhydrazide; N- (N-benzyloxycarbonyl-L-Ieucinyl) -N '- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) tiazol-4-ylcarbonyl] -N '- [N- (2-pyridinylmethoxycarbonyl) -L-leucinyl) hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- [N- (6-methyl-3-pyridinylmethoxycarbonyl) -L-leucine] hydrazide; N- (N-fer-butoxycarbonyl) -N '- [2- (N-cyclopropyi-N-cyclopropylmethylamino) thiazol-4-ylcarbonyljhydrazide; N- [2- (N-cyclopropy1-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- [N-methyl-N- (2-pyridiniummethoxycarbonyl) -L-leucinyl] hydrazide; N- [2- (2-benzyloxy) thiazol-4-ylcarbonyl] -N '- [N- (6-methyl-3-pyridinylmethoxycarbonyl) -L-leucinylhydrazide; N- [2- (2-benzyloxyphenyl) thiazol-4-ylcarbonyl] -N '- [N- (2-methyl-3-pyridinylmethoxycarbonyl) -L-leucinyl] hydrazide; N- [2- [N-methyl-N- (2-methylpropyl) amino] thiazol-4-ylcarbonyl] -N '- [N- (6-methyl-3-pyridinylmethoxycarbonyl) -L-leucinyl] hydrazide; N- [2- [N-methyl-N- (2-methylpropyl) amino] thiazol-4-ylcarbonyl] -N '- [N - () - L-leucinylhydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N- (N-picolinyl-L-leucinyl) hydrazide; N - ^ - N-cyclopropyl-N-cyclopropylmethylamino-thiazoM-ylcarbonyl-N'-CN ^ -methyl-S-pyridinylmethoxycarbonyl) -L-leucinyl] hydrazide; N- [N- (3-fer-butoxycarbonylbenzyloxycarbonyl) -L-leucinyl] -N '- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (8-quinolinoyl) -L-leucine] hydrazide; N- [N- (2-methy1-3-pyridinylmethoxycarbonyl) -L-leucinyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonylhydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- (N-picolinoyl-L-leucinyl) hydrazide; N- [N- (3-carboxybenzyloxycarbonyl) -L-leucinyl] -N '- [2- (N-cyclopropyl-N-cyclopropylmethyllamino) thiazol-4-ylcarbonyl] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (2-quinolinoyl) -L-leucinyl] h -drazida; N- [2- (1-naphthyl) thiazole-4-iicarbonyl] -N '- [N- (3-quinolinoyl) -L-leucine] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (4-methylpiperidinocarbonyl) -L-leucinylhydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (4-quinolinoyl) -L-leucinyl] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonii] -N '- [N- (5-quinolinoyl) -L-leucinyl] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (7-quinolinoyl) -L-leucinyl] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (6-quinolinoyl) -L-leucinyl] hydrazide; N- [N- (1-isoquinolinoyl) -L-leucinyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- [N- (3-isoquinolinoyl) -L-leucinyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- [N- (4-methylimidazol-5-ylcarbonyl) -L-leucinyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonylhydrazide; N- [N- (1-benzyl-5-methylimidazol-4-ylcarbonyl] -N '- [2- (1-naphthyl) thiazoI-4-ylcarbonylhydrazide; N- [N- (3-methylisonicotinoyl) -L-leucinyl; ] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- (N-benzyloxycarbonyl-L-leucinyl) -N '- [2- [N, N-bis- (2-methylpropyl) amino] oxazol-4-ylcarbonyljhydrazide; N- [2- [N-cyclopropyl-N- (2-methylpropyl) amino] thiazol-4-ylcarbonyl] -N '- [N- (2-pyridinylmethoxycarbonyl) -L-leucinyl] hydrazide; N- [2- [N-cyclopropyl-N- (2-methylpropyl!) Amino] thiazol-4-ylcarbonyl] -N '- [N-methyl-N- (2-pyridinylmethoxycarbonyl) -L-leucinyl] h Drazida; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (1-piperazinocarbonyl) -L-leucinylhydrazide; N- [2- [N-bis- (cyclopropylmethyl) amino] thiazol-4-ylcarbonyl] -N '- [N- (2-pyridinylmethoxycarbonyl) -L-leucinyl] hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- [N- (2-quinolinoyl) -L-leucinyl] hydrazide; N- [N- (8-quinolinoyl) -L-leucinyl] -N '- [2- (8-quinolinyl) thiazol-4-ylcarbonyl] hydrazide; N- (N-benzyloxycarbonyl-L-leucinyl) -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- [N- (3-quinolinoyl) -L-leucinyl] hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- [N- (3-isoquinolinoyl) -L-leucinyl] hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- [N- (6-quinolinoyl) -L-leucinyl] hydrazide; N- [2- [N-bis- (cyclopropylmethyl) amino] thiazoi-4-ylcarbonyl-N '- [N- (2-methyl-3-pyridiniummethoxycarbonyl) -L-leucyl] hydrazide; N- (N-benzyloxycarbonyl-L-b-yer-butylalanyl) -N '- [2- (1-naphthyl) thiazol-4-ylcarbonylhydrazide; N- (N-benzyloxycarbonyl-L-b-cyclopropylalanyl) -N '- [2- (1-naphthyl) thiazol-4-ylcarbonylhydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- [3- (2-pyridyl) phenyiacetyl] -L-leucinylhydrazide; N- [2- [N-bis- (cyclopropiimeti) amino] thiazol-4-ylcarbonyl-N '- (N-picolinyl-L-leucinylhydrazide; N- (N-benzyloxycarbonyl-L-leucinyl) -N' - [2 - [N-bis- (cyclopropylmethyl) amino] thiazol-4-ylcarbonyljhydrazide; N- [2- (N-cyclopropyl-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- [N- (6-methylnicotinoyl) - L-leucinyl] hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) t-azoi-4-ylcarbonyl] -N '- [N- (3- * methylson-phenyl-noyl) -L-leucinyl] hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- [N- (8-quinolinoyl) -L-leucinyl] hydrazide; N- [2- [N-bis - (cyclopropylmethyl) amino] tiazol-4-ylcarbonyl] -N '- [N- (8-quinolinoyl) -L-leucinylhydrazide; N- [2- [N-bis- (cyclopropylmethyl) amino] thiazole- 4-ylcarbonyl] -N '- [N- (3-isoquinolinoyl) -L-leucinylhydrazide; N- [2- [4- (2,2-dimethylaminoethoxy) -1-naphthyl] thiazol-4-ylcarbonyl] -N' - [N- (8-quinolinyl) - L-leucinyl] hydanzate; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- [N- ( 7-quinolinoyl) -L-leucinii] hydrazide; N- [2- [N-bis- (cyclopropi lmethyl) amino] tiazol-4-ylcarbonyl] -N '- [N- (6-methylnicotinoyl) -L-leucinylhydrazide; N- [2- [N-bis- (cyclopropylmethyl) amino] thiazole-4-ylcarbonyl] -N '- [N-methyl-L-prolinyl-L-leucinyljhydrazide; N- (N-benzyloxycarbonyl-L-norvalinyl) -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl) hydrazide; N- (N-benzyloxycarbonyl-L-isoleucinyl) -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- (N-benzyloxycarbonyl-L-norleucyl) -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- [N- (4-dimethylaminomethylbenzyloxycarbonyl) -L-leucinyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyhydrazide; N- (N-benzyloxycarbonyl-L-norvalinyl) -N '- [2- (2-benzyl-phenyl) -thiazol-4-ylcarbonyl-hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- [N- (4-methylimidazol-5-ylcarbonyl) -L-leucinyl] hydrazide; N- [N- [4- (4-morpholinomethyl) benzoyl] -L-leucinyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonylhydrazide; N- [N- (6-methylnicotinoyl) -L-leucinyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- (N-b-fer-butoxycarbonyl-L-yer-butylalanyl) -N '- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- [N- (8-quinolinoyl) -L-b-tert-butylalanyl] -hydrazide; N- [N- (4-methylimidazol-5-ylcarbonyl) -L-allylglynyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonylhydrazide; N- [N- (4-methylimidazol-5-ylcarbonyl) -L-b-tert-butylanyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonylhydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- [N- (4-methylimidazol-5-ylcarbonyl) -Lb-tert-butyllanyl] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- (N-picolinoyl-L-b-fer-butylalanyl) hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (8-quinolinoyl) -L-b-yer-butylalanyl) hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- (N-picolinoyl-L-allylglycinyl) hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- (N-picolinoyl-L-b-cyclopropylalanyl) hydrazide; N- [N- (6-Methynylotinoyl) -L-b-cyclopropylalanyl] -N '- [2- (1-naphthyl) thiazole-4-ylcarbonylhydrazide; N- [N- (4-methylimidazol-5-ylcarbonyl) -L-b-cisopropylalanyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonylhydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (8-quinolinoyl) -L-b-cyclopropylalanyljhydrazide; N- [N- (6-methylnicotinoyl) -L-b-yer-butylalanii] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonylhydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazole-4-ylcarbonyl] -N '- (N-picolinoyl-L-b-fer-butylalanyl) hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazole-4-ylcarbonyl] -N '- [N- (3-isoquinolinoyl) -L-b-yer-butylalanyl] hydrazide; N- (N-tert-butoxycarbonyl) -L-b-cyclopropyl-alanyl) -N '- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazole-4-ylcarbonyl] hydrazide; N- [2- (N-cyclopropylmethyl-N-propylamino) thiazol-4-ylcarbonyl] -N '- [N- (6-methyl-3-pyridinylmethoxycarbonyl) -L-leucinyl] hydrazide; N- [N- (6-methylnicotinnoyl) -L-allylgyl] nl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- [2- (1-naphthyl) thiazole-4-carbonyl] -N '- [N- (8-quinolinoyl) -L-allylglycinyl] -hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (2-quinolinoyl) -L-b-cyclopropylalanylhydrazide; N- [N- (3-isoquinolinoyl) -L-b-cyclopropylalanyl] -N '[- [2- (1-naphthyl) thiazol-4-ylcarbonylhydrazide; N- [N- (1-isoquinolinoyl) -L-b-cyclopropylanyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonylhydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (7-quinolino] l) -L-b-cyclopropylalanylhydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- [N- (8-quinolinoyl) -L-b-cyclopropylalanyl] hydrazide; N- [2- (N-cyclopropy1-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- [N- (4-methylimidazol-5-ylcarbonyl)) - L-b-cyclopropylalanyl] hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- [N- (3-isoquinolinoyl) -L-b-cyclopropylalanyl] hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- [N- (6-methylnicotinoyl) -L-b-cyclopropylalanyl] hydrazide; N- [N- (4-methylimidazol-5-ylcarbonyl) -L-norleucinyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonylhydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- (N-picolinoyl-L-norleucyl) hydrazide: N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] - N '- [N- (8-quinolinoyl) -L-norleucinyl) hydrazide: N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- [N- (2-quinolinoyl) -L-b-cyclopropylalanyl] hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethyllamino) thiazol-4-ylcarbonyl] -N '- [N- (1-isoquinolinoyl) -L-b-cyclopropylalanyl] hydrazide; N- [2- [N-cyclopropyl-N- (2-methylpropyl) amino) thiazol-4-ylcarbonyl] -N '- [N- (6-methyl-3-pyridinylmethoxycarbonyl) -L-leucinyl] hydrazide; N- (N-Ier-butoxycarbonyl-L-leucinyl) -N '- [2- [N-cyclopropyl-N- (2-methylpropyl) amino] thiazol-4-ylcarbonyl] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (7-quinolino] i) -L-b-fer-butylalanyl-hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (2-quinolinoyl) -L-b-fer-butylalanyl-hydrazide; N- [N- (1-isoquinolylnoyl) -L-b-tert-butyllanyl] -N '[- [2- (1-naphthyl) thiazole-4-ylcarbonylhydrazide; N- [N- (3-isoquinolinoyl) -L-b-tert-butylalanyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonylhydrazide; N- [N- (6-methylnicotinoyl) -L-norleucinyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (7-quinolinoyl) -L-norleucyl] h -drazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (2-quinolinoyl) -L-norleucinyl] hydrazide; N- [N- (1-isoquinolinoyl) -L-norleucyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- [N- (3-isoquinolinyl) -L-norleucinyl] -N '- [2- (1-naphthyl) thiazole-4-ylcarbonyl] hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- [N- (5-hydroxymethylimidazol-4-ylcarbonyl) -L-b-cyclopropylalanyl] hydrazide; N- [2- [N-cyclopropyl-N- (2-methylpropyl) amino] thiazol-4-ylcarbonyl] -N '- [N- (8-quinolinoyl) -L-b-cyclopropylalanyl] hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- (N- (6-methylnicotinoyl) -Lb-fer-butylalanyl] hydrazide; N- [2- [N-cyclopropyl] -N- (2-methylpropyl) amino] thiazol-4-ylcarbonyl] -N '- [N- (4-methylimidazol-5-ylcarbonyl)) - Lb-cyclopropylalanyl] hydrazide; N- [2- [N-cyclopropyl-N- (2-methylpropyl) amino] thiazol-4-ylcarbonyl] -N '- [N- (2-quinolinoyl) -L-b-cyclopropylalanyl] hydrazide; N- [2- [N-cyclopropyl-N- (2-methylpropyl) amino] thiazol-4-ylcarbonyl] -N '- [N- (6-methylnicotinoyl) -L-b-cyclopropylalanyl] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- [8-quinolinoyl] glycinyl] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- [8-quinolinyl] -L-norvalinyl] hydanzate; N- [2- (1 -naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (2-quinolinoii) -L-norvalinyl] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- (N-picolinoyl-norvalinyl] hydanzate; N- [2- (1-naphthyl) thiazole-4 -carbonylcarbonyl] -N '- [N- (6-methyl-p-cyano) -L-norvalentyl] -hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (4-methylimidazol-5-ylcarbonyl) -L-norvalinyl-hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (1-isoquinolinoyl) -L-norvalinyl] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (3-isoquinolinoyl) -L-norvalinyl] hydanida; (1S, 1 'S) -N, N'-bys- [4- [1- (N-benzyloxycarbonylamino) -3-methylbutyl] thiazol-2-ylcarbonylhydrazide; N- [2- [N-cyclopropyl-N- (2-methylpropyl) amino] thiazol-4-ylcarbonyl] -N '- [N- (6-methynicotinoyl) -L-b-yer-butylalanyl] -hydrazide; N- [2- [N-cyclopropyl-N- (2-methylpropyl] thiazol-4-ylcarbonyl] -N '- [N- (4-methyl-midazol-5-ylcarbonyl) -L-β-fer-butylalanyl] hydrazide; N- [2- [N-cyclopropyl-N- (2-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- [N- (1-isoquinolinoyl) -Lb-fer-butylalanyl] hydrazide; N- [N- (5-buty1-picolinnoyl) -Lb-yer-butylalanyl] -N '- [2- (N-cyclopropyl-cyclopropylmethyllamino) thiazol-4-ylcarbonyl] hydrazide; N- [2- (N -cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- [N- (6-methylpicolinnoyl) -L-tert-butylalanyl] hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- [N- (4-fluorobenzoyl) -L-leucinyl] hydrazide; N- [N- (4-fluorobenzoyl) -L-leucinyl] -N' - [2- (1- naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (2-pyridinylmethoxycarbonyl) -L-b-yer-butylalanyljhydrazide; N- [N- (2-methyl-3-pyridinylmethoxycarbonyl) -L-b-fer-butylalanyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonylhydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (2-pyridinylmethoxycarbonyl) -L-b-cyclopropylalanylhydrazide; N- [N- (2-methyl-3-pyridinylmethoxycarbonyl) -L-b-cyclopropylalanyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- [N- (6-methyl-3-pyridinylmethoxycarbonyl) -L-b-cyclopropylalanyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- [N- (6-methyl-3-pyridinylmethoxycarbonyl) -L-b-tert-butylanyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonylhydrazide; N, N-bis- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- [N- [2- (1,8-naphthyridinoyl)] - L-b-cyclopropylalanyl] hydrazide; N- [2- [N-cyclopropyl-N- (2-methylpropyl) amino] thiazol-4-ylcarbonyl] -N '- [N- (3,4-difluorobenzoyl) -L-b-cyclopropylalanyl] hydrazide; N- [2- [N-cyclopropyl-N- (2-methylpropyl) amino] thiazol-4-ylcarbonyl] -N '- [N- (4-fluorobenzoyl) -L-leucinyl] hydrazide; N- [N- (5-butylpicolinoyl) -L-leucinyl] -N '- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] hydrazide; N- [2- (N-cyclopropyl-N- (2-methylpropyl) amino] thiazol-4-ylcarbonyl] -N '- [N- (3,4-dimethoxybenzoyl) -L-leucinyl] hydrazide; N- [2- (N-cyclopropyl-N- (2-methylpropyl) amino] thiazol-4-ylcarbonyl] -N '- [N- (3,4-difluorobenzoyl) -Lb-fer-butyl-lalanyl] hydrazide; N- [2- [N-cyclopropyl-N- (2-methylpropyl) amino] tiazol-4-ylcarbonyl] -N '- [N- (3,4-dimethoxybenzoyl) -Lb-ter- butylalanyl] hydrazide; N- [Ñ] (5-butylpicolinoyl) -Lb-er-butylalanyl] -N '- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazole-4-alkylcarbonyl] hydanidate and N- [2- [N-cyclopropyl-N- (2-methylpropyl) amino] tiazol-4-ylcarbonyl] -N '- [N- (6-methylpicolinoyl) -Lb-fer-butylalanyl] -hydrazide.

Definitions The present invention includes all hydrates, solvates, complexes and prodrugs of the compounds of this invention. The 2"prodrugs" are any covalently linked compound that releases the active source drug in vivo according to formula I. If a chelate or other form of an isomeric center is present in a compound of the present invention, it is intended that all forms of said isomer or isomers, including enantiomers and diastereomers, are covered herein. The compounds of the invention containing a chiral center can be used as a racemic mixture, 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 trans (E) isomers are within the scope of the invention. In cases where the compounds may exist in tautomeric forms, such as keto-enol tautomers, each tautomeric form is contemplated as being included within this invention, whether it exists in equilibrium or predominantly in one form. The meaning of any substituent in any occurrence in formula I or in any sub-formula thereof is independent of its meaning, or any other meaning of the substituent, in any other occurrence, unless otherwise specified. The abbreviations and symbols commonly used in the peptide and chemistry techniques are used herein to describe the compounds of the present invention. In general, the abbreviations of amino acids follow the nomenclature of the IUPAC-IUB Joint Commission on Biochemical Nomenclature as described in Eur. J. Biochem, 158.9 (1984). 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, soleucine, leucine, lysine, methionine , phenylalanine, proline, serine, threonine, tryptophan, tyrosine and valine. "Alkyl of C? -6" as applied herein is intended to include substituted and unsubstituted methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl and t-butyl, pentyl, n-pentyl, isopentyl, neopentyl and hexyl and the simple aliphatic isomers thereof. Any alkyl group of d-β can be optionally and independently substituted by one or two halogens SR ', OR', N (R ') 2, C (o) N (R') 2, carbamyl or C? - alkyl, wherein R 'is d-6 alkyl. Alkyl of Co means that an alkyl group is not present in the portion. In this way, Ar-alkyl of C0 is equivalent to Ar. "C3-11 cycloalkyl" as applied herein is intended to include cyclopropane, cyclobutane, cyclopentane, cyclohexane, cycloheptane, cyclooctane, cyclononane, cyclodecane, substituted or unsubstituted cycloundecane. When substituted, the substituents are defined as for "Crß alkyl" above. "C2-6 alkenyl" as used herein means an alkyl group of 2 to 6 carbons in which an individual carbon-carbon bond is replaced by a carbon-carbon double bond. C2-6 alkenyl includes ethylene, 1-propene, 2-propene, 1-butene, 2-butene, isobutene and the different 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 an individual carbon-carbon bond is replaced by a triple carbon-carbon bond. C2-6 alkynyl includes acetylene, 1-propin, 2-propin, 1-butin, 2-butin, 3-butin and the simple isomers of pentin and hexin. "Halogen" means F, Cl, Br and I. "Ar" or "aryl" or "Ar" 'or "aryl"' means phenyl or naphthyl, optionally and independently substituted by one or more of Ph-alkyl of Co-6 , Het-alkyl of C0-6, alkyl of d-6, alkoxy of d-6, Ph-alkoxy of C0-6, Het-alkoxy of Co-e, OH, (CH2)? - eNR8R9, O (CH2) ? -6NR8R9, CO2, R 'or halogen. Two C? -6 alkyl groups can be combined to form a 5-7 membered ring, saturated or unsaturated, fused over the ring of Ar. Ph can optionally be substituted with one or more of d-β alkyl, d-β alkoxy, OH, (CH 2)? - 6 NR 8 N 9, O (CH 2)? - e NR 8 R 9, CO 2 R 'or halogen. As used herein, "Het" or "heterocyclic" represents a 5- to 7-membered stable or bicyclic monocyclic heterocyclic ring of 7 to 10 stable members, which is either saturated or unsaturated, and which consists of carbon and from one to three heterogeneous atoms selected from the group consisting of N, O and S, and wherein the heterogeneous nitrogen and sulfur atoms may optionally be oxidized, and the heterogeneous atom of nitrogen may be optionally quaternized, and including any bicyclic group in which any of the heterocyclic rings mentioned above is fused to a benzene ring. The heterocyclic ring can be attached at any heterogeneous atom or carbon atom, which results in the creation of a stable structure, and can optionally be substituted with one or two portions selected from the group consisting of Ph-C6 alkyl, Het-C0-6alkyl, C? -6alkyl, C? -6alkoxy, Ph-C0-6alkoxy, Het-alkoxy of Co-e, OH, (CH2)? - 6NR8R9, O (CH2 )? - 6NR8R9, CO2, R '. Two alkyl groups of d-6 can be combined to form a 5-7 membered saturated or unsaturated ring, fused to the Het ring. Ph can optionally be substituted with one or more of C 1-6 alkyl, C? -6 alkoxy, OH, (CH 2)? - 6 NR 8 R 9, O (CH 2)? - 6 NR 8 R 9, CO 2, R 'or halogen. Examples of said heterocycles include the piperidinyl, piperazinyl, 2-oxopiperazinyl, 2-oxipiperinidyl, 2-oxypyrrolodinyl, 2-oxoazepinyl, azepinyl, pyrrolyl, 4-piperidonyl, pyrrolidinyl, pyrazolyl, pyrazolidinyl, imidazolyl, pyridyl, pyrazinyl, oxazolidinyl, oxazolinyl, oxazolyl, isoxazolyl, morpholinyl, thiazolidinyl, thiazolidyl, thiazolyl, quinuclidinyl, indolyl, quinolinyl, isoquinolinyl, benzimidazolyl, benzopyranyl, benzoxazolyl, furiio, pyranyl, tetrahydrofuryl, tetrahydropyranyl, thienyl, benzoxazolyl, thiamorpholinyl sulfoxide, thiamorpholinyl sulfone and oxadiazolyl. "HetAr" or "heteroaryl" means any heterocyclic moiety encompassed by the above definition of Het that is aromatic in character, eg, pyridine.

Certain radical groups are abbreviated in the present. t-Bu refers to the tertiary butyl radical, Boc refers to the t-butyloxycarbonyl radical, Fmoc refers to the fluorenylmethoxycarbonyl radical, Ph refers to the phenyl radical, Cbz refers to the benzyloxycarbonyl radical. Certain reagents were abbreviated in the present. EDC refers to N-ethyl-N '(dimethylaminopropyl) -carbodiimide. HOBT refers to 1-hydroxybenzotriazole, DMF refers to dimethylformamide, BOP refers to benzotriazole-1-yloxytris (dimethylamino) phosphonium hexafluorophosphate, Lawesson's reagent is 2,4-bis-2,4-disulfide (4). -methoxyphenyl) -1,3-dithia-2,4-diphosphtane, NMM is N-methylmorpholine, TFA refers to trifluoroacetic acid and THF refers to tetrahydrofuran.

Preparation methods The compounds of Formula I wherein X = S, Y = CH, Z = N and L = NR R7, are prepared by methods analogous to those described in scheme 1.

SCHEME 1 R1C0CI ^ -? 1CO HR4 - ^ -? - R7 HR4 £ - - * • R4N7NCSNH2 - 1 2 3 (R1CH2 = R7) 4 hoj R CHO Rt R7NHR4 \ ^ 4 3 (R1CH2 = R7) a) R 4 NH 2, Py, CH 2 Cl 2; b) LiAIH4, THF; c) i. CI2CS, Py, CH2Cl2; ii. NH3, MeOH or I. PhCONCS, CHCI3; ii. K2CO3, MeOH, H2O; d) EtO2CCOCH2Br, EtOH; e) H2NNH2"H2O, EtOH; f) R3CO2H, EDC »HCl, 1-HOBT, DMF or RnR12NCOCI, Et3N, CH2Cl2 wherein W is C (O) or R3SO2CI, NMM, CH2Cl2 wherein W is SO2; g) R 4 NH 2, CH 2 Cl 2; h) LiAIH4, Et2O; j) Na (OAc) 3BH, CH2Cl2.

An acid chloride (such as cyclopropanecarbonyl chloride or isobutyryl chloride) (1-Scheme 1) is treated with a primary amine (such as aniline, cyclopropylamine, isobutylamine or propylamine) and pyridine in an aprotic solvent (such as methylene chloride) for provide 2-scheme 1, which is treated with lithium-aluminum hydride in THF to give 3-scheme 1. Alternatively, 3-scheme 1 can be prepared by treating an aldehyde (such as cyclopropancarboxaldehyde or isobutyraldehyde) (8-scheme 1) with an amine (such as cyclopropylamine) in methylene chloride to provide 9-scheme 1, which it is treated with a reducing agent (such as lithium aluminum hydride in ether or sodium triacetoxyborohydride in methylene chloride). Treatment of 3-scheme 1 with thiophosgene and pyridine in methylene chloride, followed by treatment with ammonia in methanol provides 4-scheme 1. Alternatively, 4-scheme 1 can be prepared by treatment of 3-scheme 1 with benzoyl isothiocyanate, followed by the treatment of the intermediate benzoylthiourea with potassium carbonate in methanol / water. 4-scheme 1 is treated with hydrazine hydrated in ethanol to give 5-scheme 1. Treatment of 5-scheme 1 with a carboxylic acid (such as N- (2-pyridinylmethoxycarbonyl) -L-leucine, N- (3-pyridinylmethoxycarbonyl ) -L-leucine, N- (4-pyridinylmethoxycarbonyl) -L-leucine, N-methyl-N- (4-pyridinylmethoxycarbonyl) -L-Iucine, N-methyl-N- (3-pyrimidinethoxycarbonyl) ) -L-leucine, N-methyl-N- (2-pyridinylmethoxycarbonyl) -L-leucine, 4-methyl-2- (3-phenylphenyl) pent-4-enoic acid, 4-methyl-2 acid - (3-phenylphenyl) pentanoic acid, N-fer-butoxycarbonyl-L-leucine, N- (4-ér-butoxycarbonylbenzyloxycarbonyl) -L-leucine, N- (6-methyl-3-pyridinylmethoxycarbonyl) -L-leucine, N- (2-methyl-3-pyridinylmethoxycarbonyl) -L-leucine, N- (4-tert-butoxycarbonylbenzyloxycarbonyl) L-leucine, N-fer-butoxycarbonyl-Lb-tert-butylalanine and N-ér-butoxycarbonyl-L-cyclopropylalanine ) and a peptide coupling reagent (such as EDC * HC1 / 1-HOBT) in an aprotic solvent (such as DMF) or with a carbamoyl chloride (such as N-chloride). , N-diisobutylcarbomoyl) and triethylamine in methylene chloride gives 6-scheme 1.

SCHEME 2 Et02CCOCH2Br a) Thiourea, EtOH; b) i.NaNO2, HBr aqueous at 16%, ii. CuBR, Hbr aqueous at 16%, iii. HBr (cat.), EtOH; c) ArB (OH) 2 > Pd (PPh3) 4, NaHCO3, toluene, EtOH, H2O; d) H2NNH2"H2O,), EtOH; e) R3CO2H, EDCHCI, 1 -HOBT, DMF wherein W is C (O) or R3SO2CI, NMM, CH2CI2 wherein W is SO2. The compounds of the formula i wherein X = S, Y = CH, Z = N and L = Ar or Het, are prepared by methods analogous to those described in scheme 2. Ethyl bromopyruvate (1-scheme 2) is treated with thiourea in refluxing ethanol to provide 2-scheme 2, which is treated successively with sodium nitrite and copper (I) bromide in 16% aqueous HBr, and the product is heated in ethanol with a catalytic amount of HBr to give 3-scheme 2. The treatment of this material with an arylboronic acid (such as 2-benzyloxyphenylboronic acid, 1-naphthylboronic acid, 4-methyl-1-naphthylboronic acid, 5-acenaphylboronic acid, 2-methoxy-1-naphthylboronic acid, 2-methoxymethoxy-1-naphthylboronic acid, -antracenylboronic acid, 9-phenantenylboronic acid, 2- (4-tert-butoxycarbonylbenzyloxy) phenylboron, 4-methoxymethoxynaphthylboronic acid or 8-quinolinoboronic acid), tetrakis (triphenylphosphine) palladium (0) and sodium bicarbonate sodium in toluene / ethanoi / water at reflux provides 4-scheme 2. Treatment of 4-scheme 2 with hydrazine hydrated in ethanol provides 5-scheme 2, which is treated with a carboxylic acid (such as N- (2-pyridinylmethoxy) Carbonyl) -L-leucine, N- (3-pyridinylmethoxycarbonyl) -L-leucine, N- (4-pyridine ilmethoxycarbonyl) -L-leucine, N-methyl-N- (3-pyridinylmethoxycarbonyl) -L-leucine, N-benzyloxycarbonyl-L-Leucine, 4-methyl-2- (3-phenylphenyl) pentanoic acid, 4-methyl-2- (3-phenoxyphenyl) pentanoic acid, 4-methyl-2- (4-phenoxyphenyl) pentanoic acid, N-benzyloxycarbonyl-Ln-fer-butylalanine, N- (2-benzyloxycarbonyl) -L- cyclopropylalanine, N -benzyloxycarbonyl) -L-norvaline, N-benzyloxycarbonyl-L-norleucine, N-benzyloxycarbonyl-L-iso-isoacid, N- (4-dimethylaminomethyl-benzyloxycarbonyl-L-leucine), N-fer-butoxycarbonyl-L-leucine, N - (6-methyl-3-pyridinylmethoxycarbonii) -L-leucine, N- (2-methyl-3-pyridinylmethoxycarbonyl) -L-leucine, N- (8-quinolinoyl) -L-leucine, N- ( 8-quinolinoyl) glycine, N-fer-butoxycarbonyl-L-allylicine, N-ee / "-butoxycarbonyl-L-norleucine, N-fer-butoxycarbonyl-L-norvaline, N-yer-butoxycarbonyl-Lb-yer- butylalanine, N-yer-butoxycarbonyl-L-cyclopropylalanine) and a peptide coupling reagent (such as EDC "HC1 / 1-HOBT) in an aprotic solvent (such as DMF) or with a chlorine Carbamoyl urea (N-isobutyl-N-phenylcarbomoyl chloride) and triethylamine in methylene chloride to provide 6-scheme 2 wherein W is C (O). Where W = SO2, 5-scheme 2 is treated with a corresponding sulfonyl chloride, R3SO2C1, and n-methylmorpholine (NMM) in methylene chloride. The compounds of the formula I wherein X = S, Y = CH and Z = N are prepared by methods analogous to those described in scheme 1.

SCHEME 3 LC02H - - »- LCONH2 J? a) / -BUOCOCI, NMM, NH3, THF; b) Lawesson reagent, THF; c) i. EtO2CCOCH2Br; ii. TFAA, Py, CH2Cl2; d) H2NNH2"H2O, EtOH; e) R3CO2H, EDCHCI, 1-HOBT, DMF wherein W is C (O), or R3SO2C1, NMM, CH2 Cl2 wherein W is S02. A carboxylic acid (such as N-benzyloxycarbonyl-L-leucine) (1-scheme 3) is converted to 2-scheme 3 by treatment with isobutyl chloroformate, N-methylmorphurin and ammonia in THF. 2-scheme 3 is treated with Lawesson's reagent in THF to provide thioamide 3-scheme 3. This material is converted to thiazole by condensation with an α-keto ester followed by treatment with trifluoroacetic anhydride and pyridine in methylene chloride to give 4-scheme 3, which is converted to 5-scheme 3 by treatment with hydrazine monohydrate. This material is treated with a carboxylic acid (such as (1S) -1-benzyloxycarbonylamino-1- (4-carboxythiazol-2-yl) -3-methylbutane) and a peptide coupling reagent (such as EDC »HCI / l-HOBT) in an aprotic solvent (such as DMF) to provide 6-scheme 3, wherein W is C (O). Where W = SO2, 5-scheme 3 is treated with a corresponding sulfonyl chloride, R3SO2CI and n-methylmorpholine (NMM) in methylene chloride.

SCHEME 4 a) TFA; b) R14CO2H, EDCHCl, l-HOBT, DMF. The compounds of the formula I wherein X = S, Y = CH, Z = N, R 3 = CH (R 1) NR 12 R 13 wherein R 13 = R 14 CO are prepared by analogous methods to those described in scheme 4. 1-Scheme 4 treated with trifluoroacetic acid to give 2-scheme 4. This material is treated with carboxylic acid (such as pyrazinecarboxylic acid, picolinic acid, 2-quinolinecarboxylic acid, 3-quinolinecarboxylic acid, 4-quinolinecarboxylic acid, 5-quinolinecarboxylic acid, quinolinecarboxylic acid, 7- quinolinecarboxylic acid, 8-quinolinecarboxylic acid, 1-isoquinolinecarboxylic acid, 3-isoquinolinecarboxylic acid, N -methylpiperidinocarboxylic acid, 4-methylimidazole-5-carboxylic acid, N-benzylproline, N-methylproline, 1-benzylcarboxylic acid 5-Methylimidazole-4-carboxylic acid, 6-methylnicotinic acid, 2-methyl-nicotinic acid, 2-methylisonicotinic acid, 4-dimethylaminomethylbenzoic acid, 4- (4-morpholino) benzoic acid, 5-hydroxymethylimidazole-4-car boxyl, 5-butylpicolinic acid or 4-fluorobenzoic acid) and a coupling reagent to peptide (such as EDC »HCI / I-HOBT) in an aprotic solvent (such as DMF) to provide 3-scheme 4: The starting materials used herein are commercially available amino acids or are prepared by routine methods well known to those skilled in the art and can be found in standard reference books, such as COMPENDIUM OF ORGANIC SYNTHETIC METHODS, Vol. I-VI (published by Wiley- Interscience. Methods of coupling to form amide linkages herein are generally well known in the art. Methods of peptide synthesis are generally described by Bodansky et al., THE PRACTICE OF PEPTIDE SYNTHESIS, Springer-Verlag, Berlin, 1984; E. Gross and J. Meienhofer, THE PEPTIDES, Vol. I, I-284 (1979); and J.M. Stewart and J.D .: Young, SOLID PHASE PEPTIDE SYNTHESIS, 2nd Ed., Pierce Chemical Co., Rockford, Ill., 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 minimize unwanted side reactions. Said 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 which are known in the art. Methods for protection and deprotection, and the replacement of one amino protecting group with another portion are well known. The acid addition salts of the compounds of the formula I will be prepared in a standard manner in a suitable solvent from the compound of the origin and from an excess of an acid, such as hydrochloric, hydrobromic, hydrofluoric, sulfuric, phosphoric, acetic, trifluoroacetic, maleic, succinic or methansuiphoic acid. Certain of the compounds form internal salts or zwitterions that may be acceptable. The cationic salts are prepared by treating the parent compound with an excess of an alkaline reagent, such as a hydroxide, carbonate or alkoxide, containing the appropriate cation; or with a suitable organic amine. Cations such as L, +, Na +, K +, Ca ++, Mg ++ and NH + are specific examples of cations present in pharmaceutically acceptable salts. Halides, sulfate, phosphate, alkanoates (such as acetates 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. Accordingly, the compounds of the formula I can be used in the manufacture of a medicament. The pharmaceutical compositions of the compounds of the formula I prepared as described hereinabove can be formulated as lyophilized solutions or powders for parenteral administration. Powders can be reconstituted by the addition of a suitable diluent or other pharmaceutically acceptable vehicle before use. The liquid formulation can be an aqueous solution of regulated and isotonic pH. Examples of suitable diluents are normal saline solution, standard 5% dextrose in water, or sodium or ammonium acetate solution of regulated pH. Said formulation is especially suitable for parenteral administration, but can also be used for oral administration or be contained in a metered dose inhaler or nebulizer for insufflation. It may be desirable 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. The pharmaceutically acceptable solid or liquid carriers can be added to improve or stabilize the composition, or to facilitate the preparation thereof. Solid carriers include starch, lactose, calcium sulfate dihydrate, alba earth, magnesium stearate or stearic acid, talc, pectin, acacia, agar or gelatin. Liquid vehicles include syrup, peanut oil, olive oil, saline and water. The vehicle may also include a prolonged 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 the conventional techniques of the pharmacy including spraying, mixing, granulating and compressing, when necessary, for tablet forms; or spray, mix and fill 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 or filled into 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 to create a suppositoryUtility of the present invention The compounds of formula I are useful as protease inhibitors, particularly as inhibitors of cysteine and serine proteases, most particularly as inhibitors of cysteine proteases, still more particularly as inhibitors of cysteine proteases of the papain superfamily, still more particularly as inhibitors of cysteine proteases of the cathepsin family, most particularly as inhibitors of cathepsin K. The present invention also provides useful compositions and formulations of said compounds, including pharmaceutical compositions and formulations of said compounds. The present compounds are useful for treating diseases in which cysteine proteases are implicated, including infections by Pneumocystis carinii, Trypsanoma cruzi, Trípsanoma brucei and Críthidia fusiculata; as well as in schistosomiasis, malaria, tumor metastasis, metachromatic leukodystrophy, muscular dystrophy, amytrophy 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, very specifically osteoarthritis and rheumatoid arthritis, Paget's disease and malignant hypercalcemia, and metabolic loss of bone. Metastatic neoplastic cells also typically 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 cysteine and serine proteases, very particularly cysteine proteases, still more particularly cysteine proteases of the papain superfamily, even very particularly cysteine proteases of the cathepsin family, which comprise administering to an animal, particularly a mammal, most particularly a human in need thereof, an effective amount of a compound or combination of compounds of the present invention. The present invention especially provides methods of treating diseases caused by pathological levels of cathepsin K, methods comprising administering to an animal, particularly a mammal, most particularly a human requiring it, an effective amount of a cathepsin K inhibitor, including a compound or combination of compounds of the present invention. The person skilled in the art will understand that the term "effective amount" is intended to mean that amount of a compound or combination of compounds of the present invention that is sufficient to diminish or cure the clinically undesirable manifestations of the disease (e.g. brittle and weakened in osteoporosis) caused by such pathological levels of the target enzyme, eg, cathepsin K, by inhibiting the target enzyme. The present invention particularly provides methods for treating diseases in which cysteine proteases are implicated, including infections by Pneumocystis carinii, Trypsanoma cruzi, Tripsanoma brucei and Crithidia fusiculata; as well as in schistosomiasis, malaria, tumor metastasis, metachromatic leukodystrophy, muscular dystrophy, amitrophy 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, very specifically osteoarthritis and rheumatoid arthritis, Paget's disease, malignant hypercalcemia and metabolic bone loss. This invention further provides a method for treating osteoporosis or inhibiting bone loss, comprising administering internally to an animal, particularly a mammal, most particularly a human requiring it, of an effective amount of a compound or combination of compounds of the formula I, alone or in combination with other inhibitors of bone resorption, such as bisphosphonates (ie, alendronate), hormone replacement therapy, anti-estrogen or calcitonin. In addition, the treatment of this invention and an anabolic agent, such as morphogenic bone protein or proflavone 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 is very effective, although an injection is also useful. in intramuscular bolus. Typically, the parenteral dose will be from about 0.01 to about 100 mg / kg; preferably between 0.1 and 20 mg / kg, such that the concentration of the drug in the plasma is maintained at a concentration effective to inhibit cathepsin K. Compounds are administered one to four times a day at a level that achieves a dose total daily from about 0.4 to about 400 mg / kg / day. The precise amount of a compound of the invention that is therapeutically effective, and the route by which said compound is best administered, is readily determined by one skilled in the art by comparing the blood level of the agent with the concentration required to have a therapeutic effect. The compounds of this invention can also be administered orally to the patient, such that the concentration of drug is sufficient to inhibit bone resorption or to achieve any other therapeutic indication as described herein. Typically, a pharmaceutical composition containing the compound is administered at an oral dose between about 0.1 to about 50 mg / kg in a manner consistent with the patient's condition. Preferably, the oral dose will be from about 0.5 to about 20 mg / kg. No unacceptable toxicological effects are expected when the compounds of the present invention are administered in accordance therewith.

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

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

Inhibition studies Potential inhibitors were evaluated using the progress 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 solutions with regulated pH of inhibitor and substrate. The analysis of the data was carried out according to one of two procedures depending on the appearance of the progress curves in the presence of inhibitors. For the compounds whose progression curves were linear, the constants of apparent inhibition (K, app) were calculated according to equation 1 (Brandt et al., Biochemitsry, 1989, 28, 140): v I [Ka (1 + 1 / K¡, app) + A] 0) where v is the velocity of the reaction with maximum velocity Vm, A is the substrate concentration with Michaelis constant of Ka ^ e / is the concentration of inhibitor. For the compounds whose progress curves showed a time-dependent decay curvature characteristic of inhibition, the data from individual sets was analyzed to give kobs according to equation 2: [AMC] = vsst + (vO - vss) [1- exp (-kobst)] / kobs (2) where [AMC] is the concentration of product formed during time t, vo is the initial reaction rate and vss is the final speed in a fixed state. The values for kobs were then analyzed as a linear function of the inhibitor concentration to generate an apparent rate constant of second order (k0bs / inhibitor concentration or k0bs / [I]) describing the time-dependent inhibition. A full description of this kinetic treatment has been given completely in Morrison et al., Adv. Enzymol. Relat. Areas Mol. Biol., 1988, 61, 201.

Human osteoclast resorption test Aliquots of suspensions of osteoclastoma-derived cells were removed from storage in liquid nitrogen, heated rapidly to 37 ° C and washed x1 in RPMI-1640 medium by centrifugation (1000 rpm, 5 min at 4 ° C ). The medium was aspirated and replaced with murine anti-HLA-DR antibody, 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 min 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. Enough magnetic spheres (5 / mononuclear cell), coated with goat anti-rabbit IgG, were removed from their storage bottle and placed in 5 mL of fresh medium (this eliminates the preservative of toxic azide). The medium was removed by immobilizing the spheres in a magnet and replaced with fresh medium. The spheres were mixed with the cells and the suspension was incubated for 30 minutes on ice. The suspension was mixed frequently. The cells coated with spheres were immobilized on a magnet and the remaining cells (fraction rich in osteoclasts) were decanted in a sterile 50 mL centrifuge tube. Fresh medium was added to the spider-coated cells to dislodge any entrapped osteoclasts. This washing procedure was repeated x10. The cells coated with spheres were discarded. The osteoclasts were enumerated in a counting chamber, using a large hole 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 1.5x104 / mL in EMEM medium, supplemented with 10% fetal calf serum and 1.7 g / liter of sodium bicarbonate. Aliquots of 3 mL of the cell suspension (by treatment) were decanted in centrifuge tubes of 15 mL. These cells were pelleted by centrifugation. To each tube was added 3 mL of the appropriate treatment (diluted to 50 uM in the EMEM medium). Also included were the appropriate vehicle controls, a positive control (87 MEM1 diluted at 100 ug / mL) and an isotype control (IgG2a diluted at 100 ug / mL). The tubes were incubated at 37 ° C for 30 minutes.

Aliquots of 0.5 mL of the cells were cultured on sterile dentin slides in a 48 cavity plate and incubated at 37 ° C for 2 hours. Each treatment was analyzed in quadruplicate. The slides were washed in six changes of warm PBS (10 mL / well in a 6-well plate) and then placed in fresh or control treatment and incubated at 37 ° C for 48 hours. The slides were then washed in phosphate-buffered saline solution and fixed in 2% glutaraldehyde (in 0.2 M sodium cacodylate) for 5 minutes, after which they were washed in water and incubated in pH regulator during 5 minutes at 37 ° C. The slides were then washed in cold water and incubated in pH regulator of cold acetate / fast red garnet for 5 minutes at 4 ° C. The excess pH regulator was aspirated and the slides were air-dried after washing in water. The positive TRAP osteoclasts were enumerated by bright field microscopy and then removed from the surface of the dentin by sonication. Sting volumes were determined using the Nikon / Lasertec ILM21W confocal microscope.

General Nuclear magnetic resonance spectra were recorded at either 250 or 400 MHz using, respectively, a Bruker AM spectrometer 250 or Bruker AC 400. CDCI3 is deuteriochloroform, DMSO-d6 is hexadeuterium dimethylsulfoxide and CD3OD is tetradeuteriomethanol. Chemical shifts are reported in parts per million (d) down from the internal standard tetramethylsilane. The abbreviations of the NMR data are as follows: s = single band, d = doublet, t = triplet, q = quartet, m = multiple band, dd = doublet of doublets, dt = doublet of triplets, app = apparent, br = broad. J indicates the NMR collection constant measured in Hertz (Hz). The continuous wave infrared (IR) spectra were recorded on a Perkin-Elmer 683 infrared spectrometer and the Fourier transform infrared spectra (FTIR) were recorded on a Nicolet Impact 400D infrared spectrometer. The IR and FTIR spectra were recorded in transmission mode, and the positions of the band are reported in inverse wave numbers (cm-1). The mass spectra are taken in instruments VG 70 PE, PE Syx Pl lll or VG ZAB HF, using ionization techniques of fast atom bombardment (FAB) or electroaspersion (ES). The elemental analyzes are obtained using a Perkin-Elmer 240C elemental analyzer. The melting points are taken in a Thomas-Hoover melting point apparatus and are not corrected. All temperatures report in degrees centigrade. Thin-film plates of Analtech Silica Gel GF and E. Merck Silica Gel 60 F-254 are used for thin layer chromatography. Both vaporization and gravity chromatographs are carried out on E. Merck Kieselgel 60 silica gel (230-400 mesh). When indicated, certain of the materials were purchased from Aldrich Chemical Co., Mylwaukee, Wisconsin, Chemical Dynamics Corp., South Plainfield, New Jersey and Advanced Chemtech, Louisville, Kentucky.

EXAMPLES In the following synthetic examples, the temperature is in degrees centigrade (° C). Unless otherwise stated; all starting materials were obtained from commercial sources. Without further elaboration, it is believed that one skilled in the art can, using the above description, utilize the present invention to its fullest extent. These examples are given to illustrate the invention and not to limit its scope. Reference is made to the claims for which it is reserved to the inventors.

EXAMPLE 1 Preparation of N-r2- (cis-2,6-dimethyl-4-morphol) thiazole-4-SlcaboniH-N'-rN- (4-pyridinylmethoxycarbonyl) -L-leucine-hydrazide a) cis-2, 6-dimethyl-4-morpholino-N-benzoylthiourea cis-2,6-dimethylmorpholine (1.40 g, 12.17 mmol, 1.5 mL) was dissolved in chloroform (20 mL) and benzoyl isothiocyanate (2.0 g, 12.17 mmoles, 1.75 mL). After stirring for 45 minutes at room temperature the solution was concentrated to give the title compound as a yellow solid (3.94 g, 100%). MS (ESI): 279.2 (M + H) +. b) cis-2, 6-dimethyl-4-morpholinothiourea The compound of example 1 (a) (3.38 g, 12.17 mmol) was dissolved in methanol (40 mL) and water (40 mL), potassium carbonate was added (8.4 g, 60.84 mmoles) and the solution was heated to reflux overnight. The reaction mixture was concentrated, redissolved in ethyl acetate, washed with sodium bicarbonate and water, then dried (MgSO), filtered and concentrated to give the title compound as a beige solid (1.7 g, 80%). %). MS (ESI): 174.9 (M + H) 7 c) Ethyl 2- (cis-2,6-dimethyl-l-4-morpholino) thiazole-4-carboxylate The compound of Example 1 (b) (1.7 g, 9.74 mmol) was dissolved in ethanol (25 mL) after to heat up The solution was cooled to room temperature and ethyl bromopyruvate (1.22 mL, 9.74 mmol) was added. The reaction mixture was heated to reflux for 10 minutes and then concentrated. The residue was partitioned between ethyl acetate and saturated aqueous sodium bicarbonate. The aqueous phase was extracted with ethyl acetate and the combined organic phases were washed with saturated brine, dried (MgSO4), filtered and concentrated to an orange oil. The crude product was passed through silica gel eluting with ethyl acetate / hexane (1: 8, then 1: 3) to give the title compound as a yellow solid (2.07 g, 79%). MS (ESI): 271.3 (M + H) 7 d) N-² 2 - (cιs-2,6-dimethyl-4-morpholino) thiazole-4-ylcarbonylnhydrazide The compound of example 1 (c) (2.07 g, 7.64 mmol) was dissolved in ethanol (25 mL) and hydrazine monohydrate (3.7 mL, 76.56 mmol) was added. The solution was refluxed for 2 hours and then concentrated to give the title compound as an orange solid (1.96 g, 100%). MS (ESI): 257.2 (M + H) 7 e) methyl ester of α-isocyanate-L-leucine L-leucine methyl ester hydrochloride (25 g, 0.14 mol) was dissolved in methylene chloride (450 mL), cooled to 0 ° C and pyridine was added (43.5 g, 0.55 mol, 44.5 mL), then a 1.93 M solution of phosgene in toluene (0.18 mol, 92.7 mL) was slowly added. After stirring at 0 ° C for 2 hours the mixture was poured into HCl at 0.5 N (1400 mL) and ice (900 mL). The organic layer was washed with HCl at 0.5 N (1400 mL) and ice (900 mL). The aqueous layers were extracted with methylene chloride (450 mL) and the combined organic layers were washed with saturated brine (1400 mL) and ice (900 mL), then dried (MgSO4), filtered and concentrated. The residue was distilled (56-58 ° C, 0.78 mmHg) to provide the title compound as a colorless liquid (20.4 g, 86%). 1 H NMR (250 MHz, CDCl 3) d 4.04 (dd, 1 H), 3.82 (s, 3 H), 1.92-1.72 (m, 1 H), 1.69-1.62 (m, 2 H), 0.96 (d, 3 H), 0.94 (d, 3H). f) N- (4-pyridinylmethoxycarbonyl) -L-leucine methyl ester A solution of the compound of Example 1 (e) (5.10 g, 29.8 mmol) and 4-pyridylcarbinol (3.25 g, 29.8 mmol) in toluene (30). mL) was heated to reflux for 24 hours. The solution was concentrated and the residue was purified by flash chromatography on 250 g of 230-400 mesh silica gel, eluting with 3: 1 ethyl acetate / hexane, to give the title compound (7.86 g, 94% ). 1 H NMR (250 MHz, CDCl 3) d 59 (d, 2 H), 7.24 (d, 2 H), 5.33 (d, 1 H), 5.13 (s, 3 H), 4.40 (d t, 1 H), 3.75 (s) , 3H), 1.81-1.51 (m, 3H), 0.96 (d, 3H), 0.95 (d, 3H). q) N- (4-pyridinylmethoxycarbonyl) -L-leucine To a stirred solution of the compound of Example 1 (f) (1.98 g), 7.06 mmol) in THF (7 mL) was added 7 mL of water followed by LiOH. H2? (325 mg, 7.76 mmol). The mixture was stirred for 30 minutes and then concentrated. The residue was dissolved in water (10 mL) and 3 N HCl (2.6 mL) was added. The solution was lyophilized to yield a white solid (2.015 g, 6.44 mmol). MS (ESI): 267.2 (M + H) 7 h) N-r2- (cis-2,6-dimethyl-4-morpholino) thiazol-4-ylcarbonin-N'-rN- (4-pyridinylmethoxycarbonyl) -L-leucinipihydrazide A stirred solution of the compound of example 1 (g) (104 mg, 0.39 mmoies) in DMF (2.5 mL) was added the compound of example 1 (d) (100 mg, 0.39 mmol), 1-hydroxybenzotriazole (9.5 mg, 0.07 mmol) and 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide (100 mg, 0.39 mmol). After stirring at room temperature for 16 hours, the solution was partitioned between ethyl acetate and water. The aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with saturated brine, dried (MgSO4), filtered and concentrated. The crude product was purified by column chromatography on silica gel (6% methanol in methylene chloride) to give the title compound as a white solid (125 mg, 51%), MS (ESI): 505.4 (M + H) +.

EXAMPLE 2 Preparation of N-f2-rN-cyclopropylmethi-N- (2-methylprop »i) amino] thiazol-4-ylcarbonyl-N '(4-pyridinylrnetoxycarbonyl) -L-eucinyl] hydrazide a) N-cyclopropylmethylisobutyramide Triethylamine (1.53 g, 15.09 mmoies, 2.1 mL) and isobutylamine (1.10 g, 15.09 mmol, 1.5 mL) were dissolved in methylene chloride (15 mL), cooled to 0 ° C and added by dripping cyclopropanecarbonyl chloride (1.58 g, 15.09 mmol, 1.4 mL). After stirring at 0 ° C for 1 hour the mixture was diluted with methylene chloride (60 mL) and washed with NaOH (1 M), then saturated brine, dried (MgSO 4), filtered and concentrated. The residue was washed with ether and dried to give the title compound as a beige solid (2.1 g, 100). MS (ESI): 141.9 (M + H) +. b) N-Cyclopropylmethylisobutylamine To a stirring solution of 1 M LiAIH in THF (1 1.3 mL, 1.3 mmol), cooled to 0 ° C, a solution of the compound of Example 2 (a) was added slowly over 20 minutes. (1.595 g, 1.3 mmol) in THF (20 mL). After the addition was complete, the ice bath was removed and the solution was heated at 55 ° C for 30 minutes. The mixture was cooled to 0 ° C and quenched with water (0.43 mL) and 15% aqueous NaOH (0.43 mL) and water (1.29 mL). The solid was removed by filtration and washed with ether, dried (MgSO4) and filtered. The filtrate was evaporated to dryness to give the title compound as a colorless liquid (1.15 g, 80%). MS (ESI): 128.0 (M + H) 7 c) N- [2-rN-cyclopropylmethyl-N- (2-methylpropyl) amino] thiazol-4-ylcarbonyl-N'-rN- (4-pyridinylmethoxycarbonyl) -L-leucine-hydrazide Following procedure of example 1 (a) -1 (h), but substituting cis-2,6-dimethylmofoline from step (a) for N-cyclopropylmethylisobutylamine, the title compound was prepared as a yellow solid (60 mg, 31%). MS (ESI): 517.3 (M + H) +.

EXAMPLE 3 Preparation of N-r2- (4-methyl-1-naphthiD-thiazole-4-Hcarbonip-N'-rN- (4-pyridinumemethoxycarboniD-L-leucinillhydrazide a) Ethyl 2-aminothiazole-4-carboxylate hydrochloride To a stirred solution of thiourea (46.7 g, 0.614 mol) in EtOH (640 mL) was slowly added ethyl bromopyruvate (120 g, 0.614 mol, 77.2 g). mL). After stirring at 45 ° C for 16 hours the solution was cooled to room temperature and placed in the refrigerator overnight. The mixture was filtered, the crystals were washed with cold ethane and air dried to give the product as light yellow crystals (132.74 g, 85%). MS (ESI): 172.9 (M + H) +. b) 2-bromothiazole-4-carboxylic acid To a stirred suspension of the compound of example 3 (a) (32.1 g, 0.127 mol) in 16% HBr (aq) (400 mL) at 0 ° C was added a solution of NaNO2 (9.1 1 g, 0.132 mol) in water (16 mL). After stirring for 35 minutes, 16% Hbr (aq) (150 mL) was added. The mixture was heated at 70 ° C for 1 hour and filtered immediately. The filtrate was saturated with NaCl and extracted with ethyl acetate (2 x 500 mL). The organic phases were combined, dried (MgSO4), filtered and concentrated to a brown solid. This was combined with the collected solid by filtration and used without further purification or characterization in the next step. c) ethyl 2-bromothiazole-4-carboxylate The compound of example 1 (b) was heated to reflux in EtOH (1 L) for 1 hour and then filtered. 64 drops of 48% HBr (ac) were added to the filtered material. After stirring at reflux for 24 hours, the solution was concentrated and redissolved in EtOAc (1 L). The solution was washed successively with saturated aqueous NaHC 3 (1 L) and brine (1 L), dried (MgSO 4), filtered, decolorized with charcoal, filtered through Celite and concentrated to a yellow solid. clear (16.95 g, 56%). 1 NMR (400 MHz, CDCl 3) d 8.14 (s, 1 H), 4.46 (q, 2H), 1.43 (t, 3H). d) 4-methyl-1-naphthaleboronic acid To a stirred solution of 1-bromo-4-methylnaphthalene (1.0 g, 4.52 mmol) in THF (5 mL) at -78 ° C was added N-butyllithium (1.8 mL). , 4.52 mmole, 2.5M in hexane) by trickling. After stirring at -78 ° C for 1 h, triisopropyl borate (4.52 g) was added., 22.6 mmol). After stirring at room temperature for 3 hours, the solution was partitioned between 3N HCl and ethyl acetate. The organic phase was washed successively with saturated aqueous NaHCO 3 and brine, then dried (MgSO), filtered and concentrated to a yellow solid which was washed with hexane to give the title compound as a light yellow solid (0.5 g). , 59%). 1 NMR (400 MHz, CDCl 3) d 9.35 (d, 1 H), 8.58 (d, 1 H), 8.14 (d, 1 H), 7.64 (m, 2 H), 7.54 (d, 1 H), 2.82, ( s, 3H). e) Ethyl 2- (4-methyl-1 -naphthyl) thiazole-4-carboxylate To a stirred mixture of the compound of example 1 (c) (0.30 g, 1.27 mmol), the compound of example 1 (d) ( 0.355 g, 1.91 mmoles) and Pd (Ph3P) 4 (0.059 g, 0.05 mmoles)) in EtOH (4 mL) was added NaHCO3 (4.42 mL, 1.0 M) in water. After stirring at reflux for 4 hours the mixture was cooled and separated between HCl at 1 N (25 mL) and ethyl acetate (25 mL). The organic layer was washed with brine, dried (MgSO), filtered and concentrated. The residue was purified by column chromatography (silica gel, ethyl acetate / hexane) to yield the title compound as a foamy solid. (0.257 g, 68%). MS (ESI): 298.2 (M + H) 7 f) N - ["2- (4-methyl-1-naphthyl) thiazole-4-ylcarbonyl] hydrazide Following the procedure of example Example 1 (d), but substituting 2- (4-methyl-1-naphthyl) thiazole Ethyl 4-carboxylate ethyl 2- (cis-2,6-dimethyl-4-morpholino) thiazole-4-carboxylate, the title compound was prepared as a light yellow solid (0.245 g, 100%). (ESI): 284.2 (M + H) 7 g) N-r2- (4-methyl-1-naphthyl) thiazol-4-ylcarbonin-N'-rN- (4-pyridinomethoxy-carbonyl) -L-leucine-diphydrazide The title compound was prepared following the procedure of the example 1 (e) -1- (h), but substituting N- [2- (4-methyl-1-naphthyl) thiazol-4-ylcarbonyl] hydrazide for N- [2- (cis-2,6-dimethyl) -4-morpholino) thiazol-4-ylcarbonyl] hydrazide from step (h), (0.122 g, 48%). MS (ESI): 532.1 (M + h) 7 EXAMPLE 4 Preparation of N 2 -I N -methyl-N- (2-methyl-propri-) α-ttino 1 t-azol-4-iicarbonip-N'-rN-methyl -N- (4-pyridylmethoxycarbonyl) -L-Ieuciniphidrazide a) N- (4-pyridinylmethoxycarbonyl) -L-leucine fer-butyl ester Following the procedure of Example 1 (e) -1 (f), but replacing the L-leucine methyl ester hydrochloride from step (e) ) with L-leucine fer-butyl ester hydrochloride, the title compound was prepared as a yellow solid (2945 g, 64%). MS (ESI): 323.4 (M + H) 7 b) N-methyl-N- (4-pyridinylmethoxycarbonyl) -L-leucine terbutoxycarbonyl ester The compound of example 3 (a) (2.9 g, 8.99 mmol) was dissolved in THF (40 mL) and methyl (2.24 mL, 35.98 mmol). The reaction mixture was cooled to 0 ° C in a flask protected from moisture. The sodium hydride dispersion (1, 214 mg, 13.49 mmol) was added cautiously and the suspension was stirred for 5 hours at room temperature. Then ethyl acetate (to consume the sodium hydroxide formed from the excess of sodium hydride) was added, followed by water, by dripping, to destroy the excess of sodium hydride. The solution was concentrated in vacuo and the oily residue was separated between ether and water. The ether layer was washed with saturated aqueous sodium bicarbonate. The product was extracted with ethyl acetate, the extract was washed with water, dried (MgSO4), filtered and concentrated. The crude product was purified by column chromatography on silica gel (ethyl acetate / hexane, 3: 1) to give a yellow oil (2.07 mg, 68% MS (ESI): 337.5 (M + H) +. c) N-methyl-N- (4-pyridinylmethoxycarbonyl) -L-leucine To the compound of Example 3 (b) (2.07 g, 6.15 mmol) in methylene chloride (20 mL) was added trifluoroacetic acid (3 mL). After stirring one hour at room temperature the solution was concentrated and the residue redissolved in methylene chloride, washed with saturated aqueous sodium bicarbonate, dried (MgSO) and concentrated to give the title compound as a white solid ( 1.72 g, 100%). MS (ESI): 281.3 (M + H) 7 d) N-r2-rN-methyl-N- (2-methylpropinamino-thiazol-4-ylcarbonip-N'-rN-methyl-N- (4-pyridinylmethoxycarbonyl) -L-leucinyl-1-hydrazide Following the procedure of example 1 (a) -1 (h), but substituting the cis-2,6-dimethylmorpholine from step (a) with N-methyl isobutylamine and N- (4-pyridinylmethoxycarbonyl) -L with N-methyl-N- (4-pyridinylmethoxycarbonyl) -L-leucine; -leucine from step (h), the title compound was prepared as a light yellow solid (91.8 mg, 43%) MS (ESI): 491.3 (M + H) +. 7 EXAMPLE 5 Preparation of N-r2- (1-naphthyl) thiazoI-4-ylcarbonin-N'-fN- (3-pyridinylmethoxycarbonyl) -L-leuciniphydan a) N- (3-pyridinylmethoxycarbonyl) -L-leucine Following the procedure of example 1 (f) -1 (g), but substituting the 4-pyridylcarbinol from step (f) with 3-pyridylcarbinol, the compound was prepared of the title as a white solid. MS (ESI): 267.2 (M + H) 7 b) N-F2- (1-naphthyl) thiazol-4-ylcarbonyl-1-NMN- (3-pyridinylmethoxycarbonyl) -L-leuciniphidrazide Following the procedure of examples 3 (a) -3 (c) and 3 ( e) -3 (g), but substituting the 4-methyl-1-naphthalenboronic acid from step (e) with 1-naphthylboronic acid and with N- (3-pyridinylmethoxycarbonyl) -L-leucine the N- (4-p) riridinolmethoxycarbonii) -L-leucine from step (g), the title compound was prepared as a white solid (0.029 g, 28%). MS (ESI): 518.2 (M + H) 7 EXAMPLE 6 Preparation of N-r2- (1-naphthantiazol-4-ylcarbonip-N'-rN- (2-pyridinylmethoxycarbonyl-L-leuciniphydrazide) Following the procedure of Example 5 (a) -5 (b), but substituting 3-pyridylcarbinol from step (a) with 2-pyridylcarbinol, the title compound was prepared as a white solid (0.084 g, 82%) MS (ESI): 518.2 (M + H) +.

EXAMPLE 7 Preparation of N-r2- (5-acenaphthyl) thiazol-4-ylcarbonip-N'-rN- (4-pyridinylmethoxycarbonyl) -L-leucinehydrazide Following the procedure of Example 3 (a) -3 (g), except substituting the 1-bromo-4-methylnaphthalene in step (d) with 5-bromoacenephthene, the title compound was prepared as a white solid (0.166 g, 74%). MS (ESI): 544.2 (M + H) 7 EXAMPLE 8 Preparation of N-r2-rN-cyclopropymethyl-N- (2-methyl-propylamino-thiazol-4-ylcarbonin-N'-rN-methyI-N- (4-pyridinyl-methoxycarbonyl) -L-leucine-hydrazide Following the procedure of example 2 (a) -2 (c), except substituting N- (4-pyridinylmethoxycarbonyl) -L-leucine in N- (4-pyridinylmethoxycarbonyl) -L-leucine with N-methyl-N- (4-pyridinylmethoxycarbonyl) -L-leucine in Step (c), the title compound was prepared as a yellow solid (50 mg, 25%). MS (ESI): 531.3 (M + H) +.

EXAMPLE 9 Preparation of N- [2-rN-cyclopropyl-N-cyclopropylmethylamino) thiazole-4-i! CarbQnii1-NWN- (4-pyridin-methoxycarboni-L-leuc-n-phidrazide a) N-Cyclopropylmethyl cyclopropylamine Cyclopropylamine (1.14 g, 20.0 mmol, 1.4 ml) and cyclopropanecarboxyaldehyde (1.40 g, 20.0 mmol, 1.5 ml) were dissolved in methylene chloride (10 ml), and stirred at room temperature. After two hours, the solution was dried (MgSO4), and concentrated to produce pure mine. The compound was dissolved in ether (10 ml), the solution was cooled to 0 ° C, and lithium aluminum hydride (30 ml, 30 mmol, 1 M in ether) was added slowly. The solution was stirred for 2 hours, and then warmed to 0 ° C with water (1.14 ml), 15% sodium hydroxide (1.14 ml) and water (3.42 ml). The solid was removed by filtration and washed with ether. The filtrate was dried (MgSO), filtered and concentrated to yield a colorless liquid (1.58 g, 71%). MS (ESI): 111.9 (M + H) 7 b) N-r2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazole-4-carbonyl-p-N'-rN- (4-pyridyl-methoxycarbonyl) -L-leuciniphydrazide Following the procedure of the example 1 (a) -1 (h), except substituting cis-2,6-dimethylmorpholine in step (a) with N-cyclopropylmethyl cyclopropylamine, the title compound was prepared as a white solid (165 mg, 88% yield). ). MS (ESI): 501.4 (M + H) +.

EXAMPLE 10 Preparation of N-r2-rN-cyclopropylmethyl-N- (2-methylpropyl) arnino-thiazole-4-lcarbonin-N'-rN- (3-pyridinylmethoxycarbonyl) -L-leucine-hydrazide Following the procedure of example 2 (a) -2 (c), except replacing N- (3-pyridinylmethoxycarbonyl) -L-leucine with N- (4-pyridinylmethoxycarbonyl) -L-leucine in step (c), was prepared the title compound as a yellow solid (154 mg, 89%). MS (ESI): 517.4 (M + H) +.

EXAMPLE 11 Preparation of N-2-fN-cyclopropylmethyl-N- (2-methylopropyl!) Amino] thiazole-4-ylcarbonin-N'-rN- (2-pyridinium-methoxycarbonyl) -L-leucine-diphydrazide Following the procedure of Example 2 (a) -2 (c), except substituting N- (2-pyridinylmethoxycarbonyl) -L-leucine for N- (4-pyridinylmethoxycarbonyl) -L-leucine in step (c), it was prepared the title compound as a yellow solid (100 mg, 65%). MS (ESI): 517.3 (M + H) +.

EXAMPLE 12 Preparation of N-r2-rN-cyclopropylmethyl-N- (2-methylpropyl) amino-1-thiazoI-4-ylcarbonin-N-rN-methyl-N- (3-pyridinylmethoxycarbonyl) -L-leucine-hydrazide Following the procedure of example 4 (a) -4 (d), except substituting 4-pyridylcarbinol with 3-pyridylcarbinol in step (a), and with N-cyclopropylmethyl isobutylamine the N-methyl isobutylamine in step (d), The title compound was prepared as a yellow solid (30 mg, 22%). MS (ESI): 531.4 (M + H) +.

EXAMPLE 13 Preparation of N-f2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazole-4-Hcarbonip-NVN- (3-pyridinylmethoxycarbonyl) -L-leuciniphydrazide Following the procedure of example 1 (a) -1 (h), except substituting cis-2,6-dimethylmorpholine for N-cyclopropylmethyl cyclopropylamine in step (a), and with 4-pyridylcarbinol 4-pyridylcarbinol in step ( f), the title compound was prepared as a white solid (85 mg, 43%). MS (ESI): 501.4 (M + H) 7 EXAMPLE 14 Preparation of N-r2-rN-cyclopropyl-N-cyclopropylammethylamino) thiazole-4-ylcarbonyl-N-rN-methyl-N- (4-pyridinylmethoxycarbonyl) -L-leucine-hydrazide Following the procedure of example 4 (a) -4 (d), except substituting N-cyclopropylmethyl cyclopropylamine for N-methyl isobutylamine in step (d), the title compound was prepared as a white solid (58 mg, 35% ). MS (ESI): 515.3 (M + H) 7 EXAMPLE 15 Preparation of N-r2-rN, N-bis- (2-methylpropii) amino-1-thiazol-4-ylcarbonyl-N'-rN- (2-pyridinylmethoxycarbonyl) -L-leucine-1-hydrazide Following the procedure of example 1 (a) -1 (h), except substituting cis-2,6-dimethylmorpholine with diisobutylamine in step (a), and with 2-pyridylcarbinol 4-pyridylcarbinol in step (f), The title compound was prepared as a yellow solid (140 mg, 77%). MS (ESI): 519.4 (M + H) +.

EXAMPLE 16 Preparation of N-rN- (4-pyridinylmethoxycarbonyl) -L-leucinip-N V2-I1 • (112.3A-tetrahydroquinolinoVitiazo-4-ylca-bon-l '| hydrazide Following the procedure of example 1 (a) -1 (h), except substituting cis, 2,6-dimetiimorpholine with 1, 2,3,4-tetrahydroquinoline in step (a), the title compound was prepared as a yellow solid (168 mg, 88%). MS (ESI): 523.4 (M + H) + EXAMPLE 17 Preparation of N-r4-methyl-2- (3-phenoxy) phenylpentanoyl-N'-r2- (1-naphthiD-thiazol-4-ylcarbonyhydrazide a) 2- (3-Phenoxyphenyl) -4-methylpent-4-enoic acid To a stirring solution of diisopropylamine (4.99 g, 49.3 mmol) in THF (50 ml) cooled to -78 ° C was added dropwise n-butyl lithium (19.4 ml, 48.5 mmol, 2.5M in hexane). After stirring for 15 minutes at -78 ° C, a solution of 3-phenoxyphenylacetic acid (5.0 g, 21.9 mmol) in THF (20 ml) was added dropwise. The mixture was heated to 0 ° C and then cooled to -78 ° C, and 3-bromo-2-methylpropene (4.4 g, 32.9 mmol) was added to the mixture. After stirring at -78 ° C for 2 hours, the reaction was warmed with 10 ml of water, and then concentrated. The residue was redissolved in water and extracted with ether (200 ml). The aqueous layer was acidified (3N HCl) and extracted with ether (2 X 200 ml). The organic layers were combined, dried (MgSO), filtered and concentrated to yield the title compound as a white solid (5.4 g, 87%). 1 H NMR (400 MHz, CDCl 3) d 7.36 (m, 3 H), 7.14 (m, 2 H), 7.01 (m, 4 H), 4.78 (d, 2 H), 3.82 (t, 1 H), 2.83 (dd, 1 H), 2.47 (dd, 1 H), 1.75 (s, 3H). b) 2- (3-Phenoxyphenyl) -4-methylpentanoic acid To a stirred solution of the compound of Example 17 (a) (5.4g, 19.1 mmol) in ethyl acetate (75 mL), palladium on carbon (2.0 g). After stirring under a balloon of hydrogen for 16 hours, the mixture was filtered through Celite. The filtrate was concentrated, and the residue was purified by column chromatography (silica gel, ethyl acetate / hexane) to yield the title compound as a white solid (2.1 g, 39%). MS (ESI): 283.2 (M-H). " c) (±) -N-4-methyl-2- (3-phenoxy) phenylpentanoyl-N'-r 2 - (1 -naphthyl) thiazol-4-ylcarbonin hydrazide Following the procedure of example 1 (h), except by substituting 2- (1-naphthyl) thiazol-4-ylcarbonylhydrazide for N- [2- (cis-2,6-dimethyl-4-morpholino) thiazol-4-ylcarbonyl] hydrazide, and with acid 2- (3-phenoxyphenyl) -4-methylpentanoic acid N- (4-pyridinylmethoxycarbonii) -L-leucine, the title compound was prepared as a white solid (0.246 g, 82%). MS (ESI): 536.2 (M + H) 7 EXAMPLE 18 Preparation of N-2-rN-methyl-N- (2-methyl-propyl) -nino-thiazoi-4-ylcarbonyl-N'-r4-methyl-2 - (3-phenophenylpent-4-enoiphydrazide a) 2- (3-Phenylphenyl) -4-methylpent-4-enoic acid Following the procedure of example 17 (a), except substituting 3-phenoxyacetic acid with 3-biphenylacetic acid, the title compound was prepared as a solid white. MS (ESI): 265.3 (M-H). " b) N-r2-rN-methyl-N- (2-methylpropyl) amino] tiazol-4-ylcarbonin-N'-f4-methyl-2- (3-phenol-phenylpent-4-enophidrazide Following procedure of Example 1 (a) -1 (h), except substituting cis-2,6-dimethylmorpholine in step-1 with N-methyl isobutylamine (a), and with N- (4-pyridinyl-methoxycarbonyl) -L-leucine in 2- (3-phenylphenyl) -4-methylpent-4-enoic acid in step (h), the title compound was prepared as a white solid. MS (ESI): 477.3 (M + H) 7 EXAMPLE 19 Preparation of N-r2-rN, N-bis- (2-methy1propyl) amino-1-thiazol-4-ylcarbonin-N'-rN-methyI-N- (3-pyridinylmethoxycarbonyl) -L-leucine-hydrazide Following the procedure of example 1 (a) -1 (h), except substituting cis-2,6-dimethylmorpholine with diisobutylamine in step (a), and with 3-pyridylcarbinol 4-pyridylcarbinol in step (f), The title compound was prepared as a yellow solid (110 mg, 30%). MS (ESI): 519.4 (M + H) +.

EXAMPLE 20 Preparation of N-r2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazole-4-ylcarbonin-N'-rN-methyI-N- (3-pyridinylmethoxycarbonyl) -L-leucinehydrazide Following the procedure of example 4 (a) -4 (d), except substituting 4-pyridylcarbinol with 3-pyridylcarbinol in step (a), and with N-cyclopropylmethylcyclopropylamine the N-methyl isobutylamine in step (d), The title compound was prepared as a yellow solid (33 mg, 25%). MS (ESI): 515.4 (M + H) +.

EXAMPLE 21 Preparation of N-f2- (N-cycloopropylmethyl-N-propylamino) thiazoS-4-ylcarbonip- N'-rN- (3-pyridiniummethoxycarbonyl) -L-leucine-p-hydrazide Following the procedure of example 1 (a) -1 (h), except replacing with N-cyclopropyl propylamine the cis-2,6-dimethylmorpholine in step (a), and with 3-pyridylcarbinol the 4-pyridylcarbinol in step ( f), the title compound was prepared as a yellow solid (40 mg, 25%). MS (ESI): 503.3 (M + H) +.

EXAMPLE 22 Preparation of N-r2-fN-methyl-N- (2-m? Ethylpropyl) amino-1-thiazole-1-carbylcarbonyl-N'-r4-methyl-2- (3-phenyl) phenylpentanohydrazide a) 2- (3-Phenylphenyl) -4-methyl pentanoic acid Following the procedure of Example 17 (a) -17 (b), except substituting 3-phenoxyacetic acid with 3-biphenylacetic acid, the title compound was prepared as a white solid. MS (ESI): 267.4 (M-H). " b) N-r2-rN-methyl-N- (2-methylpropyl) aminolthiazol-4-ylcarbon-p-N'-r4-methyl-2- (3-phenyl) -phenylpentanoyl hydrazide Following the procedure of example 1 (a) -1 (h), except replacing cis-2,6-dimethylmorpholine with step N-methyl isobutylamine in step (a), and with N- (4-pyridinyl-methoxycarbonyl) -L-leucine in 2- (3-phenylphenyl) -4-methylpentanoic acid in step (h), the title compound was prepared as a white solid ( 185 mg, 88%). MS (ESI): 479.4 (M + H) +.

EXAMPLE 23 Preparation of N-rN- (2-Methypropyl) -N- (3-phenylphenyl) carbamoyl-N'-r 2 - (1 • naphthyl) thiazol-4-ylcarbonyhydrazide a) 3-phenylaniline To a stirring solution of 3-nitrobiphenyl (1.2 g, 6.0 mmol) in ethyl acetate (25 ml), 10% palladium on carbon (500 mg, 40% w / w) was added. After stirring under a balloon of hydrogen for 24 hours, the mixture was filtered through Celite, and concentrated to yield the title compound as a white solid (0.956 g, 94%). MS (ESI): 170.0 (M + H) +. b) N- (3-phenyl) phenyl isobutylamine Following the procedure of example 2 (a) -2 (b), except substituting isobutylamine with 3-phenylaniline, and carbonyl cyclopropane chloride in step (with isobutyryl chloride) a), the title compound was prepared as a brown oil (1.1 g, 90%). MS (ESI): 226.1 (M + H) 7 c) N-r2- (1-naphththiazol-4-ylcarbonip-N'-r [N-isobutyl-N- (3-biphenin) amido] hydrazine To a solution of phosgene (0.289 ml, 1.93M in toluene), added dropwise a mixture of the compound of example 23 (b) (0.126 g, 0.558 mmol) and N-methylmorpholine (0.056 g)0.558 mmole) in dichloromethane (3 ml). After stirring for 20 minutes, 2- (1-naphthyl) thiazol-4-ylcarbonylhydrazide (0.150 g, 0.558 mmol) and N-methylmorpholine (0.056 g, 0.558 mmol) in dichloromethane (3 ml) were added, followed by DMF (3 ml). After stirring at 50 ° C for 16 hours, the solution was diluted with ethyl acetate and washed successively with water, saturated aqueous sodium bicarbonate and brine. The organic layer was dried (MgSO), filtered and concentrated. The residue was purified by column chromatography (silica gel, ethyl acetate / hexane) to give the title compound as a white solid (0.122 g, 42%). MS (ESI): 521.3 (M + H) +.

EXAMPLE 24 Preparation of N-4-methyl-2- (3-phenyl) phenyl-pentanoyl-1-N'-r 2 - (1 -naphthyl) thiazo-4-ylcarboninhydrazide Following the procedure of Examples 3 (a) -3 (c) and 3 (e) -3 (g), except substituting 4-methyl-1-naphthaleneboronic acid in step (e) with 1-naphthyl boronic acid. , and with 2- (3-phenylphenyl) -4-methylpentanoic acid the N- (4-pyridinylmethoxycarbonyl) -L-leucine in step (g), the title compound was prepared as a white solid (0.1 19 g , 49%). MS (ESI): 520.3 (M + H) 7 EXAMPLE 25 Preparation of N-r4-methyI-2- (3-phenyl) phenylpentanoin-N'-r2-rN- (2-methiIpropip-N-phenylaminolothiazol-4-ylcarbonyhydrazide Following the procedure of Example 2 (a) -2 (c), except substituting isobutylamine and isobutyryl chloride with aniline, the carbonyl chloride-cyclopropane in step (a), and with 2- (3-phenylphenyl) acid -4-methylpentanoic N- (4-pyridinylmethoxycarbonyl) -L-leucine in step (c), the title compound was prepared as a white solid (72 mg, 52%). MS (ESI): 541.3 (M + H) 7 EXAMPLE 26 Preparation of N-r2- (2-methoxy-1-naphthyl) thiazole-1-carbonylcarbonyl-N'-rN - (- 4-pyridinylmethoxycarbonyl) -L-Iucine-hydrazide Following the procedure of example 3 (a) -3 (g), except substituting 1-bromo-4-methylnaphthalene with 1-bromo-2-methoxynaphthalene in step (d), the title compound was prepared as a white solid. (0.194 g, 85%). MS (ESI): 548.3 (M + H) 7 EXAMPLE 27 Preparation of N-r2- (2-benzyloxyphenyl) thiazole-4-iCarbonin-N'-r4-methyl-2-3-phenylPenylpentanoiphydrazide a) 2-benzyloxybromobenzene To a stirred solution of 2-bromophenol (10.0 g, 57.8 mmol) and benzyl bromide (9.9 g, 57.8 mmol) in acetone (150 ml), K2CO3 (12.0 g, 86.7 mmol) was added. After stirring at reflux for 4 hours, the mixture was separated between ethyl acetate and water. The organic layer was washed with brine, dried (MgSO), filtered and concentrated. The residue was purified by column chromatography (silica gel, ethyl acetate / hexane) to yield the title compound as a colorless oil (15.2 g, 57.8 mmol). 1 H NMR (400 MHz, CDCl 3) d 7.62 (m, 1 H), 7.54 (m, 2 H), 7.45 (m, 2 H), 7.37 (m, 1 H), 7.28 (m, 1 H), 6.98 (m , 1 H), 6.91 (m, 1 H), 5.17 (s, 2H). b) 2-Benzyloxy-phenylboronic acid To a stirred solution of the compound of example 27 (a) (15.2 g, 57.8 mmol) in THF (100 ml) at -78 ° C, n-BuLi (23.1 ml, 2.5 M in hexane, 57.8 mmol). The mixture was stirred at -78 ° C for 25 minutes when trisopropyl borate (54.4 g, 289 mmol) in THF (100 mL) was added via cannulation to -78 ° C under stirring solution. After warming to room temperature and stirring for 3 hours, the mixture was poured into 3N HCl (100 ml), and extracted with ethyl acetate (3 X 200 ml). The organic layers were combined, washed successively with water and brine, dried (MgSO4), filtered and concentrated. The residue was purified by column chromatography (silica gel, ethyl acetate / hexane) to give the title compound as a pale yellow solid (6.9 g, 30.3 mmol). 1 H NMR (400 MHz, CDCl 3) d 7.90 (d, 1 H), 7.42 (m, 6 H), 7.07 (t, 1 H), 7.02 (d, 1 H), 6.05 (s, 2 H), 5.16 (s) , 2H). c) N-r2- (2-benzyloxyphenyl) thiazol-4-ylcabonyl1-N'-r4-methyl-2- (3-phenyphenylpentanoyl) hydrazide Following the procedure of examples 3 (a) -3 (c) and 3 (e) ) -3 (g), except substituting 2-benzyloxyphenylboronic acid with 4-methyl-1-naphthalenboronic acid in step (e), and with 2- (3-phenylphenyl) -4-methylpentanoic acid N- (4-) pyridinylmethoxycarbonyl) -L-leucine in step (g), the title compound was prepared as a white solid (0.194 g, 85%) MS (ESI): 576.3 (M + H) +.

EXAMPLE 28 Preparation of N-r2- (2-benzyloxy-1-naphthyl-thiazole-4-ylcabon-p-N'-rN- (4-pyridine-S-methoxycarboniD-L-leucine-hydrazide a) 1-bromo-2-methoxymethoxynaphthalene To a stirred suspension of sodium hydride (1.6 g, 40.3 mmol, 60% dispersion in mineral oil) in DMF (150 ml) at 0 ° C, was added dropwise 1 - bromo-2-naphthol (5.0 g, 22.4 mmol). After stirring for 20 minutes, methyl bromomethyl ether (2.8 g, 22.4 mmol) was slowly added. After warming to room temperature and stirring for 4 hours, the mixture was poured into water and extracted with ethyl acetate. The organic phase was washed with saturated aqueous NaHC 3 and brine, and then dried (MgSO 4), filtered and concentrated to a red oil (5.98 g, 100%). 1 H NMR (400 MHz, CDCl 3), d 8.27 (d, 1 H), 7.79 (d, 2 H), 7.60 (t, 1 H), 7.46 (m, 2 H), 5.38 (s, 2 H), 3.61 (s) , 3H). b) Ethyl 2- (2-methoxymethoxy-1-naphthyothiazole-4-carboxylate) Following the procedure of Example 3 (a) -3 (e), except substituting 1-bromo-2-methoxymethoxynaphthalene for 1-bromine -4-methylnaphthalene in step (d), the title compound was prepared as an off-white solid (0.136 g, 15%) MS (ESI): 344.2 (M + H) 7 c) Ethyl 2- (2-hydroxy-1-naphthyl) thiazole-4-carboxylate To an agitated solution of the compound of example 28 (b) (0.136 g, 0.397 mmol) in EtOH (3 ml), acid was added Concentrated hydrochloric (5 drops). After stirring at reflux for 3 hours, the solution was concentrated, redissolved in ethyl acetate and washed successively with saturated aqueous NaHCO 3 and brine. The organic layer was dried (MgSO4), filtered and concentrated. The residue was purified by column chromatography (silica gel, ethyl acetate / hexane) to give the title compound as a white solid (0.080 g, 67%). MS (ESI): 300.2 (M + H) 7 d) Ethyl 2- (2-benzyloxy-1-naphthyl) thiazole-4-carboxylate To a stirred solution of the compound of Example 28 (c) (0.080 g, 0.268 mmol), benzyl alcohol (0.038 g, 0.348 mmol) and triphenylphosphine (0.091 g, 0.348 mmol) in THF (3 mL) at 0 ° C, diisopropyl azodicarboxylate (0.070 g, 0.348 mmol) was added dropwise. After stirring at room temperature for 16 h, the solution was concentrated and the residue was purified by column chromatography (silica gel, ethyl acetate / hexane) to yield the title compound as a white solid (0.060 g, 58% ) 1 H NMR (400 MHz, CDCl 3) d 8.41 (s, 1 H), 8.12 (d, 1 H), 7.91 (d, 1 H), 7.80 (d, 1 H), 7.52 (t, 1 H), 7.41 (t, 1 H), 7.34 (m, 6H), 5.24 (s, 2H), 4.49 (q, 2H), 1.44 (t, 3H). e) N-22- (2-benzyloxy-1-naphthyl) thiazol-4-ylcarbonin-N'-rN- (4-pyridinylmethoxycarbonyl-L-leucine-hydrazide Following the procedure of example 1 (d) -1 (h) except substituting 2- (2-benzyloxy-1-naphthyl) thiazole 4-carboxylate for 2- (cis-2,6-dimethyl-4-morpholino) thiazole-4-carboxylic acid ethyl ester (d), the compound of title as a white solid (0.050 g, 52%) MS (ESI): 624.2 (M + H) +.

EXAMPLE 29 Preparation of N-r2-rN, N-bis- (2-methyIpropH) amnolt-azole-4-ylcarbon-p-N'-rN-methyl-N- (2-pyridinylmethoxycarbonyl) -L-leucinehydrazide Following the procedure of Example 4 (a) -4 (b), except substituting 4-pyridylcarbinol with 2-pyridylcarbinol in step (a), and with N-methyl isobutylamine in diisobutylamine in step (d), the Compound the title as a yellow solid (40 mg, 20%). MS (ESI). 533.4 (M + H) +.

EXAMPLE 30 Preparation of N-r2- (9-Phenantreni-Tiazol-4-ylcarbonip-N'-rN- (4-pyridinylmethoxycarbonyl) -L-leucine-hydrazide Following the procedure of Example 3 (a) -3 (g), except substituting 1-bromo-4-methylnaphthalene with 9-bromophenanthrene in step (d), the title compound was prepared as an off-white solid (0.085 g, 48%). MS (ESI): 568.2 (M + H) 7 EXAMPLE 31 Preparation of N-r2- (9-anthracenyl) thiazole-4-ylcarbonyl-N'-rN- (4-pyridinylmethoxycarbonyl) -L-leucininhydrazide Following the procedure of Example 3 (a) -3 (g), except substituting 1-bromo-4-methylnaphthalene with 9-bromoanthracene in step (d), the title compound was prepared as a white solid (0.101 g, 67%). MS (ESI): 568.2 (M + H) 7 EXAMPLE 32 Preparation of N-f2-rN, N-bis-2-methylpropyl) amino-1-thiazol-4-ylcarbonin-N '- (tert-butoxycarbonyl-L-leucinyl) hydrazide Following the procedure of example 1 (a) -1 (d) and 1 (h), except substituting cis-2,6-dimethylmorpholine with diisobutyiamin in step (a), and with N-tert-butoxycarbonyl-L-leucine N- (4-pyridinylmethoxycarbonyl) -L-leucine in step (h), the title compound was prepared as a yellow solid (950 mg, 78% yield). MS (ESI): 484.3 (M + H) 7 EXAMPLE 33 Preparation of N-r2-rN, N-bis- (2-methylpropyl) amino-1-thiazo-4-ylcarbonyl-N'- [N- (L-leucinyl-1-hydrazide Following the procedure of example 4 (c), except substituting N- [2- [N, N-bis- (2-methylpropii) amino] thiazol-4-ylcarbonyl] N '- (- tert -butoxycarbonyl-L-leucinyl) ) hydrazide the terbutoxycarbonyl ester of N-methyl-N- (4-pyridinylmethoxycarbonyl) -L-leucine, the title compound was prepared as a yellow solid (370 mg, 85%). MS (ESI): 384.3 (M + H) 7 EXAMPLE 34 Preparation of N-f2- (1 -naphthyl) thiazol-4-ylcarbonip-N'-rN-methyI-N- (3-pyrridinylmethoxycarboniO-L-leucine-lhydrazide Following the procedure of Examples 3 (a) -3 (c) and 3 (e) -3 (g), except substituting 4-methyl-1-naphthaleneboronic acid in step (e) with 1-naphthyl boronic acid, and with N-methyl-N- (3-pyridinylmethoxycarbonyl) -L-leucine the N- (4-pyridinylmethoxycarbonyl) -L-leucine in step (g), the title compound was prepared as a white solid (0.100 g, 59%). MS (ESI): 532.2 (M + H) +.

EXAMPLE 35 Preparation of N-r2-rN, N-bis- (2-methylpropyl) amino-1-thiazol-4-ylcarbonin-N'- (N-picolinoyl-L-IeucinH) hydrazide Following the procedure of Example 1 (h), except substituting N- [2- [N, N-bis- (2-methylpropyl) amino] thiazole-4-ylcarbonyl] -N '- [N- (L-leucinyl )] hydrazide N- [2-cis-2,6-dimethyl-4-morpholino) thiazol-4-ylcarbonyl] -hydrazide, and with N-picolinic acid (4-pyridinylmethoxycarbonyl) -L Leucine, the title compound was prepared as a yellow solid (40 mg, 30%). MS (ESI): 489.3 (M + H) 7 EXAMPLE 36 Preparation of N-r2-rN, N-bis- (2-methylpropyl) amino-1-thiazol-4-ylcarbonin-N'-rN- (2-pyrazinocarbonyl) -L-Ieueiniphidrazide Following the procedure of example 1 (h), except substituting N- [2- [N, N-bis- (2-methylpropyl) amino] thiazol-4-ylcarbonyl] -N '- [N- (L-leucinyl) ] hydrazide N- [2- (cis-2,6-dimethyI-4-morpholino) thiazol-4-ylcarbonyl] -hydrazide, and with N-prazidinecarboxylic acid N- (4-pyridinylmethoxycarbonyl) -L-leucine, the Compound the title as a yellow solid (45 mg, 35%). MS (ESI): 490.3 (M + H) 7 EXAMPLE 37 Preparation of N-rN, N-bis- (2-methylpropyl) carbamoy-N'-r2-rN- (2-methylpropyl) -N-phenylamino-thiazole-4 icarbonhydrazide to N-isobutylaniline Following the procedure of Example 2 (a) -2 (d), except substituting the isobutylamine and isobutyryl chloride with aniline with the carbonyl chloride-cyclopropane in step (a), the title compound was prepared as an orange liquid (2.11 g, 83% yield). MS (ESI): 172.2 (M + Na) +. b) N-r 2 -I N- (2-methylpropyl) -N-phenytylazol-4-ylcarboniphidrazide Following the procedure of example 1 (a) -1 (d), except substituting cis-2,6-dimethylmorpholine with N-isobutylaniline. in step (a), the title compound was prepared as a white solid. MS (ESI): 291.3 (M + H) 7 c) N-rN, N-bis- (2-methylpropyl) carbamoyl-1-N'-r2-rN- (2-methylpropyl) -N-phenylaminol-thiazol-4-ylcarbonylhydrazide Following the procedure of example 23 (c) , except replacing N- [2- [N- (2-methylpropyl) -N-phenyl] thiazol-4-ylcarbonyl] hydrazide 2- (1-naphthyl) thiazol-4-ylcarbonylhydrazide, and with N-diisobutylamine ( 3-phenyl) phenyl isobutylamine, the title compound was prepared as a white solid (25 mg, 25%). MS (ESI): 446.3 (M + H) +.

EXAMPLE 38 Preparation of N- (2-phenylthiazol-4-ylcarbonyl) -N'-rN- (4-pyridinylmethoxycarbonyl-L-leucine-hydrazide Following the procedure of Examples 3 (a) -3 (c) and 3 (e) -3 (g), except substituting 4-methyl-1-naphthalenboronic acid in step (e) with phenylboronic acid, the compound of the title as a white solid (0.077 g, 27%). MS (ESI): 468.2 (M + H) +.

EXAMPLE 39 Preparation of N-r2-f2- (4-tert-butoxycarbonyl) benzyloxyphenitol-4-ylcarbonin-N'-rN- (4-pyridinylmethoxycarbonyl) -L-leucinehydrazide a) tert-butyl 4-bromomethyl benzoate To a stirred solution of 4-bromomethylbenzoic acid (4.0 g, 18.6 mmol) in cyclohexane (37 ml), dichloromethane (19 ml) and THF (2 ml), a solution was added of tert-butyl 2,2,2-trichloroacetimidate (8.1 g, 37. 2 mmole) in cyclohexane (12 ml), followed by a catalytic amount of boron trifluoride etherate. After stirring at room temperature for 18 hours, NaHCO3 (4 g) was added, and the mixture was filtered. The mixture was filtered through a short plug of silica gel, and concentrated to yield the title compound as a colorless oil which solidified on standing (3.6 g, 71%). 1 H NMR (400 MHz, CDCl 3) d 7.98 (d, 2 H), 7.44 (d, 2 H), 4.50 (s, 2 H), 1.59 (s, 9 H). b) Ethyl 2- (2-hydroxyphenyl) thiazole-4-carboxylate Following the procedure of example 28 (a) -28 (c), except substituting 1-bromo-2-naphthol in 2-bromophenol in step (a) ), the title compound was prepared as a white solid (0.560 g, 53%). MS (ESI): 250.1 (M + H) 7 c) Ethyl 2-r2- (4-tert-butoxycarbonylbenzyloxy) -phypythiazole-4-carboxylate To a stirred mixture of the compound of example 39 (b) (0.094 g, 0.379 mmol) and potassium carbonate (0.136 g, 0.985 mmol) ) in acetone (10 ml), the compound of example 39 (a) (0.133 g, 0.417 mmol) was added. After stirring at reflux for 16 hours, the mixture was separated between ethyl acetate and water. The organic layer was washed with brine, dried (MgSO), filtered and concentrated. The residue was purified by column chromatography (silica gel, ethyl acetate / hexane) to give the title compound as a white solid (0.160 g, 96%). MS (ESI): 440.2 (M + H) 7 d) N- [2-r2- (4-tert-butoxycarbonyl) benzyloxyphenylthiazole-4-ylcarboninN '- [N- (4-pyridinomethoxycarbonyl) -L- leucinyl-1-hydrazide Following the procedure of example 1 (d) -1 (h), except substituting with ethyl 2- [2- (4-tert-butoxycarbonylbenzyloxy) phene] thiazole-4-carboxylate 2- (cis-2,6- ethyl dimethyl-4-morpholino) thiazole-4-carboxylate in step (d), the title compound was prepared as a white solid (0.124 g, 47%).

MS (ESI): 674.2 (M + H) 7 EXAMPLE 40 Preparation of N-f2-r2- (4-carboxybenzyloxy) phenynthiazol-4-ylcarbonin-N'-rN- (4-pyridinylmethoxycarboniQ-L-leuciniphydrazide Following the procedure of Example 4 (c), except substituting N- [2- [2- (4-tert-butoxycarbonyl) benzioxyphenyl] thiazol-4-ylcarbonyl-N '- [N- (4-pyridinylmethoxycarbonyl) - L-leucinyl] hydrazide the terbutoxycarbonyl ester of N-methyl-N- (4-pyridinylmethoxycarbonyl) -L-leucine, the title compound was prepared as a pale yellow solid (0.130 g, 100%). MS (ESI): 618.2 (M + H) +.

EXAMPLE 41 Preparation of N-rN- (4-tert-butoxycarbonylbenzyloxycarbonyl) -L-leucine-N'-r2-rN- (2-methylpropyl) -N-phenylamino-thiazol-4-ylcarbonyhydrazide a) N-Isobutylaniline Following the procedure of Example 2 (a) -2 (b), except substituting the isobutylamine with isoyl amine and isobutyryl chloride with the carbonyl chloride-cyclopropane in step (a), the title compound was prepared as an orange liquid (2.1 1 g, 83%). MS (ESI): 335.3 (M + Na) 7 b) (4-tert-butoxycarbonyl) benzyl alcohol Water (5 ml) and potassium carbonate (710 mg, 5.15 mmol) were added to a solution of the compound of example 39 (a) (280 mg, 1.03 mmol) in dioxane ( 5 ml). The mixture was heated to reflux overnight, and then the dioxane was removed under reduced pressure. Methylene chloride was added followed by treatment with dilute HCl until all the solid remained dissolved. The organic phase was separated, washed with aqueous sodium bicarbonate, dried (MgSO4), filtered and concentrated to yield the title compound as a white solid (214 mg, 100%). 1 H NMR (400 MHz, CDCl 3) d 7.89 (d, 2 H), 7.33 (d, 2 H), 4.67 (s, 2 H), 3.08 (s, 1 H), 1.57 (s, 9 H). c) N-rN- (4-tert-butoxycarbonylbenzyloxycarbonyl) -L-leucinin-N'-r2-rN- (2-methyl-propyl) -N-phenylamino] thiazol-4-ylcarbonyl-1-didate Following the procedure of example 1 (a) -1 (h), except substituting cis-2,6-dimethylmorpholine in step (a) with N-isobutylaniline and 4-pyridylcarbinol in alcohol (4-ter) utoxycarbonyl) benzyl Step (f), the title compound was prepared as a white solid (15 mg, 17%). MS (ESI): 638.2 (M + H) 7 EXAMPLE 42 Preparation of N-r2-rN1N-bis (2-methi-propyl) amino-1-thiazol-4-ylcarbonyl-N'-rN- (4-tert-butoxycarbonyl-benzyloxycarbonyl) -L-Iucnin-hydrazide Following the procedure of example 1 (a) -1 (h), except substituting cis-2,6-dimethylmorpholine with diisobutylamine in step (a), and with 4-tert-butoxycarbonyl benzyl alcohol 4-pyridylcarbinol in step (f), the title compound was prepared as a white solid (35 mg, 16%). MS (ESI): 618.4 (M + H) 7 7 EXAMPLE 43 Preparation of N-rN- (4-carboxybenzyloxycarbonyl) -L-Iuccinyl-N'-i-2-rN-f2-methylpropyl) -N-phenylamino-4-ylcarbonylhydrazide Following the procedure of Example 4 (c), except substituting N- [N- (4-tert-butoxycarbonylbenzyloxycarbonyl) -L-leucinyl] -N '- [2- [N- (2-methylpropyl) -N-phenylamino] thiazol-4-ylcarbonyl] hydrazide the tert-butoxycarbonyl ester of N-methyl-N- (4-pyridinylmethoxycarbonyl) -L-leucine, the title compound was prepared as a yellow solid (10 mg, 85%) . MS (ESI): 582.2 (M + H) +.

EXAMPLE 44 Preparation of N- (N-benzyloxycarbonyl-L-leucinyl) -N'-r2-r2- (4-tert-butoxycarboniD-benzyloxyphenitol-4-ylcarbonipihydrazide) Following the procedure of example 1 (d) and 1 (h), except substituting ethyl 2- [2- (4-tert-butoxycarbonylbenzyloxy) phenyl] thiazole-4-carboxylate 2- (cis-2,6) ethyl-dimethyl-4-morpholino) thiazole-4-carboxylate in step (d), and with N-benzyloxycarbonyl-L-leucine the N- (4-pyridinimethoxycarbonyl) -L-leucine in step ( h), the title compound was prepared as a white solid (0.102 g, 68%). MS (ESI): 673.2 (M + H) +.

EXAMPLE 45 Preparation of N- (N-benzyloxycarbonyl-L-leucinyl) -N'-r2-r2- (4-carboxy-benzyloxy) -phenylazol-4-ylcarbonyl-hydrazide Following the procedure of Example 4 (c), except substituting N- (N-benzyloxycarbonyl-L-leucinyl) -N '- [2- [2- (4-tert-butoxycarbonyl) benzyloxyphenyl] thiazole-4-carbonyl ] hydrazide the terbutoxycarbonyl ester of N-methyl-N- (4-pyridinylmethoxycarbonyl) -L-leucine, the title compound was prepared as a pale yellow solid (0.103 mg, 100%). MS (ESI): 632.2 (M + H) +.

EXAMPLE 46 Preparation of N-rN- (6-methyI-3-pyridinylmethoxycarbonyl) -L-leucinin-N'-r2- (1-naphtH) thiazo-4-iCocarbonylhiderazide a) 6-Methyl-3-pyridylcarbinol Following the procedure of Example 2 (b), except substituting the N-cyclopropylmethyl isobutyramide with methyl 6-methylniconitate, the title compound was prepared as a yellow oil (4.32 g, 83%). . MS (ESI): 123.8 (M + H) 7 b) N-rN- (6-methy1-3-pyridylmethoxycarbonyl) -L-leucine-1'-N'-r2- (1-naphthyl) thiazol-4-yl-carbonylhydrazide Following the procedure of the example 5 (a) -5 (b), except substituting 3-pyridylcarbinol with 6-methyl-3-pyridylcarbinol in step (a), the title compound was prepared as a white solid (0.155 g, 63%). MS (ESI): 532.2 (M + H) +.

EXAMPLE 47 Preparation of N- (N-benzyloxycarbonyl-L-leucinyl-N'-r2- (N-cyclopropyl-N-cyclopropylmethyl) amino) thiazole-4-ylcarbonyhydrazide Following the procedure of example 1 (a) -1 (d) and 1 (h), except replacing cis-2,6-dimethylmorpholine with N-cyclopropylmethyl cyclopropylamine in step (a), and with N-benzyloxycarbonyl-L- leucine the N- (4-pyridinylmethoxycarbonyl) -L-leucine in step (h), the title compound was prepared as a solid, white (156 mg, 75%). MS (ESI): 500.3 (M + H) +.

EXAMPLE 48 Preparation of N-r2- (N-cyclopropyI-N-cyclopropylmethyl-arnino) thiazol-4-ylcarbonin-N'-rN- (2-pyridinylmethoxycarbonyl) -L-Ieucine-hydrazide Following the procedure of Example 1 (a) -1 (h), except substituting cis-2,6-dimethylmorpholine for N-cyclopropylmethyl cyclopropylamine in step (a), and with 2-pyridylcarbinol 4-pyridylcarbinol in step ( f), the title compound was prepared as a white solid (260 mg, 73%). MS (ESI): 501.1 (M + H) 7 EXAMPLE 49 Preparation of N-r2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazole-4-ylcarbonin-N'-rN- (6-methyI-3-pyridiniummethoxycarbonyl) -L-Ieuciniphidrazide Following the procedure of example 1 (a) -1 (h), except replacing with N-cyclopropylmethyl cyclopropylamine cis-2,6-dimethylmorpholine in step (a), and with 6-methyl-3-pyridylcarbinol 4-pyridylcarbinol in step (f), the title compound was prepared as a white solid (151 mg, 71%). MS (ESI): 515.3 (M + H) +.

EXAMPLE 50 Preparation of N- (N-tert-butoxycarbonyl-L-leucinyl) -N'-r2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazole-4-ylcarbonylhydrazide Following the procedure of example 1 (a) -1 (d) and 1 (h), except replacing cis-2,6-dimethylmorpholine with N-cyclopropylmethyl cyclopropylamine in step (a), and with N-tert-butoxycarbonyl- L-leucine the N- (4-pyridinylmethoxycarbonyl) -L-leucine in step (h), the title compound was prepared as a white solid (1.2 g, 72%). MS (ESI): 446.3 (M + H) 7 EXAMPLE 51 Preparation of N-r2- (N-cyclopropyl-N-cyclopropylammethylamino) thiazole-4-ylcarbonin-N'-rN-methyl-N- (2-pyrimidylmethoxycarbonyl) ) -L-leucinehydrazide Following the procedure of example 4 (a) -4 (d), except substituting 4-pyridylcarbinol with 2-pyridylcarbinol in step (a), and with cyclopropylmethyl cyclopropylamine the N-methyl isobutylamine in step (d), was prepared the title compound as a white solid (60 mg, 25%). MS (ESI): 515.3 (M + H) +.

EXAMPLE 52 Preparation of N-r2- (2-benzyloxypheni) thiazoI-4-ylcarbonin-N'-rN- (4-methyl-3-pyridiniummethoxycarbonyl) -L-leucinehydrazide a) N- (6-methy1-3-pyridinylmethoxycarbonyl) -L-leucine Following the procedure of example 1 (f) -1 (g), except substituting 6-methyl-3-pyridylcarbinol 4- pyridylcarbinol in step (f), the title compound was prepared as an off-white solid (5.8 g, 100%). 1 H NMR (400 MHz, CDCl 3) d 8.36 (s, 1 H), 7.61 (d, 1 H) , 7.15 (d, 1 H), 5.85 (d, 1 H), 5.01 (s, 2H), 4.20 (m, 1 H), 2.50 (s, 3H), 1.62 (m, 2H), 1.49 ( m, 1 H), 0.87 (t, 6H). b) N-r2- (2-benzloxyphenol) thiazol-4-ylcarbonip-N'-fN- (4-methyl-3-pyridinylmethoxycarbonyl) -L-leucinehydrazide Following the procedure of examples 3 (a ) -3 (c) and 3 (e) -3 (g), except substituting 2-benzyloxyphenylboronic acid with 4-methyl-1-naphthaleneboronic acid in step (e), and with N- (6-methyl-3) pyridinylmethoxycarbonyl-L-leucine the N- (4-pyridinylmethoxycarbonyl) -L-leucine in step (g), the title compound was prepared as a white solid (178 mg, 99%) .MS (ESI): 588.3 ( M + H) +.

EXAMPLE 53 Preparation of N-r2- (2-encyloxyphenyl) thiazoM-iCo-carbon-N 'N- (2-methyI-3-pyridinylmethoxycarbonyl) -L-leucine-hydrazide a) 2-methyl-3-pyridylcarbinol Following the procedure of Example 2 (b), except substituting N-cyclopropylmethyl isobutyramide with methyl 2-methylnicotinate, the title compound was prepared as a pale yellow oil (4.89 g "l 00 %). MS (ESI): 123.8 (M + H) +. b) N-3- (6-methyl) pyridylmethoxycarbonyl- (L) -leucine Following the procedure of example 1 (f) -1 (g), except substituting 4-pyridylcarbinol with 2-methyl-3-pyridylcarbinol in step (f), the title compound was prepared as a white solid (6.73 g, 100%). MS (ESI): 281.3 (M + H) 7 c) N-r2- (2-benzyloxyphenyl) thiazol-4-ylcarbonin-N'-rN- (2-methyl-3-pyridinylmethoxy-carbonyl!) - L-! euciniphidrazide Following the procedure of examples 3 (a) -3 (c) and 3 (e) -3 (g), except substituting 2-benzyloxyphenylboronic acid with 4-methyl-1-naphthalenboronic acid in step (e), and with N- (2-methyl-3-) pyridinylmethoxycarbonyl-L-leucine the N- (4-pyridinimethoxycarbonyl) -L-leucine in step (g), the title compound was prepared as a pale yellow solid (179.1 mg, 99%) .MS (ESI): 588.3 ( M + H) 7 EXAMPLE 54 Preparation of N-r2-fN-methyl-N- (2-methylpropyl) arnino-thiazol-4-ylcarbonin-N'-rN- (6-methyl-3-pyridinylmethoxycarbonyl) -L-leucinehydrazide Following the procedure of example 1 (a) -1 (h), except substituting cis-2,6-dimethylmorpholine in step (a) with N-methyl isobutylamine, and 4-pyridylcarbinol with 6-methyl-3-pyridylcarbinol in step (f), the title compound was prepared as a pale yellow solid (215 mg, 100%). MS (ESI): 491.3 (M + H) +.

EXAMPLE 55 Preparation of N-r2-fN-methyl-N- (2-methylpropyl) aminolthiazol-4-ylcarbonin-N'-rN-2-metit-3-pyridinylmethoxycarbonyl) -L-leucinehydrazide Following the procedure of Example 1 (a) -1 (h), except substituting cis-2,6-dimethylmorpholine with N-methyl isobutylamine in step (a), and with 2-methyl-3-pyridylcarbinol 4-pyridylcarbinol in step (f), the title compound was prepared as a pale yellow solid (215 mg, 100%). MS (ESI): 491.3 (M + H) 7 EXAMPLE 56 Preparation of N-r2- (N-cyclopropyl-N-cyclopropyltriamineamino) thiazole-4-ylcarbonyl-N '- (N-picolinoyl-L-leucinyl) hydrazide a) N-f2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazole-4-yl-carbonyl-N '- (L-leuciphenyl-hydrazide) Following the procedure of example 4 (c), except substituting N- ( N-iyer-butoxycarbonyl-L-leucinyl) -N '- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] hydrazide the terbutoxycarbonyl ester of N-methyl-N- (4-pyridinylmethoxycarbonyl) -L Leucine, the title compound was prepared as a white solid (668 mg, 81%) MS (ESI): 366.3 (M + H) +. b) N-r2- (N-cyclopropyl-N-cyclopropylmethylamine) thiazole-4-ylcarbonH-N '- (N-pico-linoyl-L-leucinyl) hydrazide Following the procedure of Example 1 (h), except substituting N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-yl-carbonyl] -N '- (L-leucinyl) hydrazide for N- [2- (cis-2,6- dimethyl-4-morpholino) thiazol-4-ylcarboniI] hydrazide, and with N-picolinic acid (4-pyridinylmethoxycarbonyl) -L-leucine, the title compound was prepared as a white solid (183 mg, 95%). MS (ESI): 471.2 (M + H) 7 EXAMPLE 57 Preparation of N-r2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazoI-4-ylcarbonin-N'-rN- (2-methyl-3-pyridinylmethoxycarbonyl) -L-Iucinyl hydrazide Following the procedure of Example 1 (a) -1 (h), except substituting cis-2,6-dimethylmorpholine in step (a) with N-cyclopropylmethyl cyclopropylamine, and 4-pyridylcarbinol with 2-methyl-3-pyridylcarbinol in step (f), the title compound was prepared as a white solid (310 mg, 84%). MS (ESI): 515.4 (M + H) 7 EXAMPLE 58 Preparation of N-rN- (3-tert-butoxycarbonylbenzyloxycarbonyl) -L-leucinin-N'-r2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazoI-4-ylcarboninhydrazide a) 3-Bromomethylbenzoic acid A mixture of Toluo (15.0 g, 10 mmol), N-bromosuccinimide (19.60 g, 110 mmol) and t-butyl peroxybenzoate (2.1 ml, 110 mmol) in carbon tetrachloride (50 ml) was heated to reflux overnight. The mixture was cooled and concentrated under reduced pressure. The residue obtained was washed with carbon tetrachloride and filtered under vacuum. The filtrate was evaporated to dryness to yield a white solid (12.57 g, 53%). 1 H NMR (400 MHz, CDCl 3) d 7.93 (m, 2 H), 7.43 (m, 2 H), 4.35 (s, 2 H). b) tert-butyl 3-bromomethyl benzoate Following the procedure of example 39 (a), except substituting 4-bromomethylbenzoic acid with 3-bromomethylbenzoic acid, the title compound was prepared as a yellow oil (7.9 g, 100%) . 1 H NMR (400 MHz, CDCl 3) d 7.93 (m, 2 H), 7.43 (m, 2 H), 4.55 (s, 2 H), 1.55 (s, 9 H). c) Alcohol (3-tert-butoxycarbonyl) benzyl Following the procedure of Example 41 (b), except substituting tert-butyl 3-bromomethylbenzoic acid with tert-butyl 4-bromomethylbenzoate, the title compound was prepared as an oil yellow (5.6 g, 92%). MS (ESI): 208.1 (M + H) 7 d) N-fN- (3-tert-butoxycarbonylbenzyloxycarbonyl) -L-leucine-N'-r2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazole-4- Iccarboniirhydrazide Following the procedure of Example 1 (a) -1 (h), except substituting the N-cyclopropylmethyl cyclopropylamine for cis-2,6-dimethylmorpholine in step (a), and with (3-terbutoxycarbonyl) benzyl alcohol 4-pyridylcarbinol in step (f), the title compound was prepared as a white solid (90 mg, 29%). MS (ESI): 600.4 (M + H) 7 EXAMPLE 59 Preparation of N-f2- (1 -nafil) thiazole- -lcarbonH] N -rN- (8-quinolinoid-L-leucine-hydrazide a) N- [2- (1-naphthyl) thiazole-4-ylcarboninhydrazide Following the procedure of Example 3 (a) -3 (f), except substituting 4-methyl-1-naphthalenboronic acid with 1-naphthaleneboronic acid in the Step (e), the title compound was prepared as a pale yellow solid. MS (ESI): 270.1 (M + H) +. b) N- (N-tert-butoxycarbonyl-L-leucinyl) -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl-1-hydrazide Following the procedure of example 1 (h), except by substituting N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide for N- [2- (cis-2,6-dimethyl-4-morpholino) thiazol-4-ylcarbonyl] hydrazide, and with N -ter-butoxycarbonyl-L-leucine, N- (4-pyridinylmethoxycarbonyl) -L-leucine, the title compound was prepared as a white solid (2.2 g, 96%). MS (ESI): 483.2 (M + H) +. c) N- (L-leucinyl) -N '- [2- (1-naphthi-Pthiazol-4-ylcarbonyl) -1-hydrazide Following the procedure of Example 4 (c), except substituting N- (N-tert-butoxycarbonyl) L-leucinyl) -N, - [2- (1-naphthyl) thiazoi-4-ylcarbonyljhydrazide the terbutoxycarbonyl ester of N-methyl-N- (4-pyridinimethoxycarbonyl) -L-leucine, the title compound was prepared as a whitish solid (1.7 g, 97%). MS (ESI): 383.3 (M + H) +. d) N-r2- (1-naphthyl) thiazole-4-alkylcarbonip-N '- [N- (8-quinolinoyl) -L-leuciniphydrazide Following the procedure of example 1 (h), except substituting N- (L -leucinyl) -N - [2- (1-naphthyl) thiazol-4-ylcarbonii] hydrazide N- [2- (cis-2,6-dimethyl-4-mofolino) thiazol-4-ylcarbonyl] hydrazide, and with 8-quinolinocarboxylic acid N- (4-pyridinylmethoxycarbonii) -L-leucine, the title compound was prepared as a white solid (18 mg, 84%). MS (ESI): 538.2 (M + H) 7 EXAMPLE 60 Preparation of N-rN- (2-methyl-3-pyridinylmethoxycarbonyl) -L-leucine-N'-r2-1-naphthyl) thiazole-4-carboxyl-hydrazide Following the procedure of Example 5 (a) -5 (b), except substituting 3-pyridylcarbinol with 2-methyl-3-pyridylcarbinol in step (a), the title compound was prepared as a white solid (0.160 g, 65%). MS (ESI): 532.2 (M + H) 7 EXAMPLE 61 Preparation of N-r2- (1-naphthyl, thiazol-4-ylcarbonip-N '- (n-picolnoyl-L-leucine O-hydrazide Following the procedure of example 59 (a) -59 (c), except substituting 8-quinolinocarboxylic acid with picolinic acid in step (d), the title compound was prepared as a white solid (0.086 g, 54%). MS (ESI): 488.3 (M + H) +.

EXAMPLE 62 Preparation of N-f- (3-carboxybenzyloxycarbonyl) -L-leucine-N'-r2- (N-cyclopropyI-N-cyclopropylamineamino) thiazoI-4-Icarbonylhydrazide Following the procedure of Example 4 (c), except substituting N-tN-IS-tert-butoxycarbonylbenzyloxycarbonyl-L-leucinyl-N'-P- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] hydrazide the terbutoxycarbonyl ester of N-methyl-N- (4-pyridinylmethoxycarbonyl) -L-leucine, the title compound was prepared as a white solid (21 mg, 93%). MS (ESI): 544.3 (M + H) 7 EXAMPLE 63 Preparation of N-r2- (1-naphthiD-thiazole-l -carbonyl H-N VN- (2-quinopnoiD-L-leucine-hydrazide Following the procedure of example 59 (a) -59 (d), except substituting 8-quinolinocarboxylic acid with 2-quinolinocarboxylic acid in step (d), the title compound was prepared as a white solid (0.123 g, 80% ). MS (ESI): 538.2 (M + H) +.

EXAMPLE 64 Preparation of N-f2- (1-naphthyl) thiazol-4-ylcarbon-p-N-rN- (3-quinozolino-L-leucine-hydrazide) Following the procedure of example 59 (a) -59 (d), except substituting 8-quinolinocarboxylic acid with 3-quinolinocarboxylic acid in step (d), the title compound was prepared as a white solid (0.109 g, 77% ). MS (ESI): 538.2 (M + H) +.

EXAMPLE 65 Preparation of N-r2- (1 -naphthyl) thiazol-4-ylcarbonip-N'-rN- (4-methylpiperidinocarbonyl) -L-leucinhydrazide Following the procedure of example 59 (a) -59 (d), except substituting 8-quinolinocarboxylic acid in step (d) with 1-methylpiperidine-4-carboxylic acid, the title compound was prepared as a white solid (0.059). g, 45%). MS (ESI): 508.2 (M + H) +.

EXAMPLE 66 Preparation of N-f2- (1-naphthyl) thiazol-4-ylcarbon-p-N-rN- (4-quinolinoyl) -L-leucinillhydrazide Following the procedure of example 59 (a) -59 (d), except substituting 8-quinolinocarboxylic acid with 4-quinolinocarboxylic acid in step (d), the title compound was prepared as a white solid (0.096 g, 68% ). MS (ESI): 538.3 (M + H) +.

EXAMPLE 67 Preparation of N-r2- (1 -naphthyl) thiazol-4-ylcarbonin-N'-rN- (5-quinolinoyl) -L-leucineHydrazide Following the procedure of example 59 (a) -59 (d), except substituting 8-quinolinecarboxylic acid with 5-quinolinocarboxylic acid in step (d), the title compound was prepared as a white solid (0.089 g, 63% ). MS (ESI): 538.3 (M + H) 7 EXAMPLE 68 Preparation of N-r2- (1-naphthyl) thiazol-4-ylcarbonip-N VN- (7-quinolinoyl) -L-leuciniphidrazide Following the procedure of example 59 (a) -59 (d), except substituting 8-quinolinocarboxylic acid with 7-quinolinocarboxylic acid in step (d), the title compound was prepared as a white solid (0.106 g, 75% ). MS (ESI): 538.2 (M + H) +.

EXAMPLE 69 Preparation of N-r2- (1-naphthyl) thiazol-4-ylcarbonip-N'-rN- (6-quinolinoyl-L-leuciniphidrazide Following the procedure of example 59 (a) -59 (d), except substituting the 8-quinolinocarboxylic acid with 8-quinolinocarboxylic acid in step (d), the title compound was prepared as a white solid (0.1 1 1 g, 79%). MS (ESI): 538.2 (M + H) 7 EXAMPLE 70 Preparation of N- | ~ N- (1-isoquinolinoyl) -L-leucinip-NW2- (1 -naphthyl) thiazoI-4-ylcarboniphidrazide Following the procedure of example 59 (a) -59 (d), except substituting 1-isoquinolinecarboxylic acid for 8-quinolinocarboxylic acid in step (d), the title compound was prepared as a white solid (0.076 g, 54% ). MS (ESI): 538.2 (M + H) +.

EXAMPLE 71 Preparation of N-fN-Q-isoquinolinoiD-L-leucinip-N V2 - (- naphthyl) thiazole-4-ylcarbonyhydrazide Following the procedure of example 59 (a) -59 (d), except substituting 3-isoquinolinocarboxylic acid for 8-quinolinocarboxylic acid in step (d), the title compound was prepared as a white solid (0.055 g, 39% ). MS (ESI): 538.2 (M + H) 7 EXAMPLE 72 Preparation of N-rN- (4-methylimidazol-5-ylcarbonyl) -L-Iuccinyl-N -r2- (1 • naphthyl) thiazol-4-ylcarboninhydrazide a) 4-Methylimidazole-5-carboxylic acid Following the procedure of Example 1 (g), except substituting ethyl 4-methylimidazole-5-carboxylate for the N- (4-pyridinylmethoxycarbonyl) -L-leucine methyl ester, The title compound was prepared as a white solid (0.428 g, 52%). MS (ESI): 126.8 (M + H) 7 b) N-rN- (4-Methylimidazol-5-lcarbonyl-L-leucinyl-1-N'-r2- (1-naphthyl) thiazol-4-ylcarbonylhydrazide Following the procedure of Example 1 (h), except substituting N- (L-leucinyl) -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide N- [2- (cis-2,6-dimethyl-4-morpholino) thiazol-4-ylcarbonii ] hydrazide, and with 4-methylimidazole-5-carboxylic acid N- (4-pyridinimethoxycarbonii) -L-leucine, the title compound was prepared as a white solid (0.108 g, 84%) MS (ESI) : 491.3 (M + H) 7 EXAMPLE 73 Preparation of N- (N-benzyl-L-proinyl-L-leuciniI) -N'-r2- (1 -naphthyl) thiazole-4-ylcarbonyhydrazide Following the procedure of example 59 (a) -59 (d), except substituting the 8-quinolinocarboxylic acid with N-benzyl proline in step (d), the title compound was prepared as a white solid (0.075 g, 50% ). MS (ESI): 570.2 (M + H) 7 EXAMPLE 74 Preparation of N-rN- (1-benzyl-5-methylimidazol-4-ylcarbonyl) -L-Ieucinin-N'-r2- (1-naphthyl) thiazol-4-ylcarboniphydan Following the procedure of example 72 (a) -72 (b), except substituting 1-benzyl-5-methylimidazole-4-carboxylic acid with 4-methylimidazole-5-carboxylic acid in step (a), the compound was prepared of the title as a white solid (0.1 15 g, 75%). MS (ESI): 581.1 (M + H) +.

EXAMPLE 75 Preparation of N-rN- (3-methylisonicotinoyl) -L-Iuccinyl-N '-' 2- (1-naphthiD-thiazo-4-ylcarboninhydrazide a) 4-cyano-2-methyl pyridine A Pure picolinic N-oxide (10.0 g, 91.7 mmol) at room temperature, iodoethane (51.5 g, 330 mmol) was added dropwise. After standing for 24 hours, the salt was filtered and washed with ether. The solid was dissolved in ethanol / water (70 ml / 30 ml), and potassium cyanide (1.0 g, 172 mmol) in water (31 ml) at 48 to 50 ° C was added dropwise over 100 minutes. After the addition was complete, the solution was continued stirring at the same temperature for 30 min. The solution was then extracted with chloroform. The organic layer was washed with brine, dried (MgSO4), filtered and concentrated. The residue was purified by column chromatography (silica gel, ethyl acetate / hexane) to yield the title compound as a pale yellow oily solid (3.9 g, 36%). MS (ESI): 1 18.8 (M + H) +. b) 2-Methylpyridine-4-carboxylic acid - The compound of example 75 (a) (0.300 g, 2.5 mmol) was dissolved in concentrated hydrochloric acid (3 ml). After stirring at reflux for 18 hours, the solution was concentrated to give the title compound as a white solid (0.342 g, 100%). MS (ESI): 137.8 (M + H) 7 c) N-rN- (3-methylisonicotinoyl) -L-leucinin-N'-r 2 - (1 -naphthyl) thiazol-4-ylcarboniphidra-zide Following the procedure of the example 1 (h), except substituting N- (L-leucinyl) -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide for N- [2- (cis-2,6-dimethyl-4 -morpholino) thiazol-4-ylcarbonyl] hydrazide, and with 2-methylpyridine-4-carboxylic acid N- (4-pyridinylmethoxycarbonyl) -L-leucine, the title compound was prepared as a white solid (0.095 g, 72% ). MS (ESI): 502.2 (M + H) 7 EXAMPLE 76 Preparation of N-r2- (N-cyclopropylamine) thiazo-4-iCarbonip-N'-TN- (2-pyridinylmethoxycarbonyl) -L-leucine-phidrazide Following the procedure of example 1 (a) -1 (h), except substituting cyclopropylamine ia cis-2,6-dimethylmofoline in step (a), and with 2-pyridylcarbinol 4-pyridylcarbinol in step (f), The title compound was prepared as a white solid (140 mg, 50%). MS (ESI): 447.3 (M + H) 7 EXAMPLE 77 Preparation of N-rN- (2-benzoxazolyl) -L-leucine-N'-r2- (1-naphthyl) thiazol-4-ylcarbonylhydrazide A solution of the compound of example 59 (c) (100 mg, 0.26 mmol), 2-chlorobenzoxazole (40.2 mg, 0.26 mmol, 0.03 ml) and triethylamine (26.5 mg, 0.26 mmol, 0.365 ml) in THF / methanol 1: 1 (1 ml) was heated at 60 ° C for 48 hours. The solution was diluted with ethyl acetate, washed with saturated aqueous NaHCO, water (2 X) and saturated brine, and then dried (MgSO4), filtered and concentrated. The residue was purified by flash chromatography on 4 g of 230-400 mesh silica gel, eluting with 1: 1 ethyl acetate / hexanes to give the title compound as a pale yellow solid (50.2 mg, 38%). MS (ESI): 500.2 (M + H) +.

EXAMPLE 78 Preparation of N- (N-benzyloxycarbonyl-L-leucinyl) -N'-r2-rN, N-bis- (2-methylpropyl) amino-oxazol-4-ylcarbonipihydrazide a) N, N-diisobutylurea A solution of diisobutylamine (4.5 g, 34.8 mmol, 6.08 ml) and chlorosulfonyl isocyanate (4.93 g, 34.8 mmol, 3.03 ml) in THF (200 ml) was allowed to stir at room temperature for 20 min. and then water (10 ml) was added, and the solution was allowed to stir at room temperature for 17 hours.

The solution was concentrated, the residue redissolved in ethyl acetate, washed with water, saturated aqueous NaHCO 3 and saturated brine, and then dried (MgSO 4), filtered and concentrated to give the title compound as an oil. colorless which crystallized after standing (60 g, 100%). MS (ESI): 173.3 (M + H) 7 b) N- (N-benzyloxycarbonyl-L-leucinyl) -N'-r2- [N, N-bis- (2-methylpropyl) amino-oxazol-4-ylcarbonylhydrazide) Following the procedure of examples 1 (c) -1 (d) and 1 (h), except substituting cis-2,6-dimethyl-4-morpholinothiourea in step (c) with N, N-diisobutylurea, and N- (4) -N-benzyloxycarbonyl-L-leucine. pyridinylmethoxycarbonyl) -L-leucine in step (h), the title compound was prepared as a white solid (126 mg, 64%). MS (ESI): 502.3 (M + H) 7 EXAMPLE 79 Preparation of N-r 2 -RN-cyclopropyl-N- (2-methylpropyl) aminothiazole-4-ylcarbonip-N'-rN- (2-pyridinylmethoxycarbonyl) -L-leucinehydrazide a) N-cyclopropi isobutylamine Following the procedure of Example 9 (a), except substituting the cyclopropane carboxyaldehyde with isobutyraldehyde, the title compound was prepared as a colorless oil (1.9 g, 58%). MS (ESI): 1 13.9 (M + H) 7 b) N-r2-rN-cyclopropyl-N- (2-methylpropipamino-thiazol-4-ylcarbonyl-N '- [N- (2-pyridinomethoxycarbonyl) - L-Leucinillhydrazide Following the procedure of example 1 (a) -1 (h), except substituting cis-2,6-dimethylmorpholine in step (a) with N-cyclopropyl isobutylamine, and with 4-pyridylcarbinol in 2-pyridylcarbinol in Step (f), the title compound was prepared as a white solid (150 mg, 69% yield) MS (ESI): 503.2 (M + H) +.

EXAMPLE 80 Preparation of N-r2-rN-cyclopropyl-N- (2-methylpropyl) amino-1-thiazol-4-ylcarbonip-N'-rN-methyl-N- (2-pyridinyl-methoxycarbonyl) -L-leucine-hydrazide Following the procedure of Example 4 (a) -4 (d), except substituting 4-pyridylcarbinol with 2-pyridylcarbinol in step (a), and with N-cyclopropyl isobutylamine the N-methyl isobutylamine in step (d), The title compound was prepared as a white solid (85 mg, 32%). MS (ESI): 517.3 (M + H) +.

EXAMPLE 81 Preparation of N-r2- (1-naphthylHiazol-4-ylcarbonin-N'-rN- (1-piperazincarboniP-L-leuciniphidrazide a) N-r2- (1-naphthyl) thiazole-4-alkylcarbonyl-1-N'-rN- (4-tert-butoxycarbonyl-1-piperazinecarbonyl) -L-leucinehydrazide Following the procedure of example 23 (c), except by substituting N- (3-phenyl) phenyl isobutylamine with N-tert-butoxycarbonylpiperazine, the title compound was prepared as a white solid (131 mg, 85%). MS (ESI): 595.2 (M + H) 7 b) N-f2- (1-naftiptiazol-4-ylcarbonip-N'-IN- (1-piperazincarbonyl) -L-leucinyl hydrazide Following the procedure of example 4 (c), except substituting N- [2- ( 1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (4-tert-butoxycarbonyl-1-piperazincarbonyl) -L-leucinyl] hydrazide the terbutoxycarbonyl ester of N-methyl-N- (4-pyridinylmethoxycarbonyl) - L-leucine, the title compound was prepared as a white solid (47 mg, 54%) MS (ESI): 495.2 (M + H) + - EXAMPLE 82 Preparation of N-r4-metH-2- (4-phenoxyphenylpentane-p-N'-r2- (1-naphthiPetiazol-4-ylcarbonyhydrazide Following the procedure of example 17 (a) -17 (c), except substituting 4-phenoxyphenylacetic acid with 4-phenoxyphenylacetic acid in step (a), the title compound was prepared as a white solid (134 mg, 67% ). MS (ESI): 536.2 (M + H) + - EXAMPLE 83 Preparation of N-r2-fN-bis- (cyclopropylmethylP-amino-1-thiazol-4-ylcarbon-p-N'- fN- (2-pyridinylmethoxycarboniP-L-leucine-hydrazide a) bis (cyclopropylmethyl) amine Following the procedure of Example 9 (a), except substituting the cyclopropylamine with aminomethylcyclopropane, the title compound was prepared as a colorless liquid (2.5 g, 96%). MS (ESI): 125.8 (M + H) + - b) N-2-N-bis (cyclopropylmethyl) aminothiazole-4-ylcarbonin-N'-rN- (2-pyridinylmethoxycarbonyl) -L-leucinyl ] hydrazide Following the procedure of example 1 (a) -1 (h), except substituting bis- (cyclopropylmethyl) amine for cis-2,6-dimethylmorphoyl in step (a), and with 2-pyridylcarbinol 4- pyridylcarbinoi in step (f), the title compound was prepared as a yellow solid (15 mg, 30%). MS (ESI): 515.3 (M + H) + - EXAMPLE 84 Preparation of N-r2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonin-N'-rN- (2-quinolinoiP-L-leucinehydrazide Following the procedure of Example 56 (a) -56 (b), except substituting picolinic acid for 2-quinolinocarboxylic acid in step (b), the title compound was prepared as a white solid (125 mg, 59%). MS (ESI): 521.2 (M + H) + - EXAMPLE 85 Preparation of N-rN- (8-quinolinoiP-L-leucine-N'-r2- (8-quinoliniPtiazol-4-ylcarboninhydrazide a) N-f2- (8-quinolinyl) thiazol-4-ylcarboninhydrazide Following the procedure of "Example 3 (a) -3 (f), except substituting the 8-bromoquinoline with 1-bromo-4-methylnaphthalene in the step ( d), the title compound was prepared as a pale yellow solid (0.306 g, 100%) MS (ESI): 2.71 (M + H) + - b) N- [N- (8-quinolinoyl) -L- leucin-N '- [2- (8-quinolinyl) thiazol-4-ylcarbonyhydrazide Following the procedure of example 59 (b) -59 (d), except substituting N- [2- (8-quinolinyl) thiazole- 4-ylcarbonyl] hydrazide N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide in step (b), the title compound was prepared as a white solid (0.11 1 g, 66%). (ESI): 539.2 (M + H) + - EXAMPLE 86 Preparation of N- (N-benzyloxycarbonyl-L-leuciniP-N'-r2- (1-naphthiPetiazol-4-ylcarbonyhydrazide Following the procedure of Examples 3 (a) -3 (c) and 3 (e) -3 (g), except substituting 4-methyl-1-naphthalenboronic acid in step (e) with 1-naphthylboronic acid, and with N-benzyloxycarbonyl-L-leucine the N- (4-pyridinylmethoxycarbonyl) -L-leucine in step (g), the title compound was prepared as a white solid (0.145 g, 60%). MS (ESI): 517.3 (M + H) + - EXAMPLE 87 Preparation of N-r2-rN-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonip-N'-rN- (3-quinolinoiP-L-leucine-hydrazide Following the procedure of example 56 (a) -56 (b), except substituting the 3-quinolinocarboxylic acid for picolinic acid in step (b), the title compound was prepared as a white solid (0.150 mg, 75%). MS (ESI): 521.2 (M + H) + - EXAMPLE 88 Preparation of N-r2- (N-cyclopropyl-N-cyclopropylmethyl? T -no) thiazoi-4-ylcarbonin-N'-rN-Q-isoquinolinoiP-L-leuciniphidrazide Following the procedure of example 56 (a) -56 (b), except substituting the 3-isoquinolinecarboxylic acid for picolinic acid in step (b), the title compound was prepared as a white solid (187 mg, 82%). MS (ESI): 521.2 (M + H) + - EXAMPLE 89 Preparation of N-r2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazole-4-lcarbonin-N'-rN- (6-quinolinoip-L-leucinehydrazide) Following the procedure of Example 56 (a) -56 (b) ), except substituting 6-quinolinocarboxylic acid and picolinic acid in step (b), the title compound was prepared as a white solid (155 mg, 59%) MS (ESI): 521.3 (M + H) + - EXAMPLE 90 Preparation of N-2-rN-bis- (cyclopropylmethyl-P-aminothiazol-4-ylcarbonip-N'-rN- (2-methyl-3-pyridinylmethoxycarboniP-L-leucine-hydrazide Following the procedure of Example 83 (a) -83 (b), except substituting 2-methyl-3-pyridylcarbinol for 2-pyridylcarbinol in step (b), the title compound was prepared as a yellow solid (105 mg, 46%). MS (ESI): 529.3 (M + H) + - EXAMPLE 91 Preparation of N- (N-benzyloxycarbonyl-L-b-tert-butylalaniP-N'-r2- (1-naphthiPetiazol-4-ylcarbonipihydrazide a) N-Benzyloxycarbonyl-Lb-tert-butylalanine To a stirred solution of L-tert-butylalanine (1.0 g, 6.89 mmol) in water (2.1 ml) and 5 N NaOH (1.38 ml) at 0 ° C. slowly added benzyl chloroformate (1.3 g, 7.58 mmol) and 2 N NaOH (3.8 ml) in ten alternating portions, for 1.5 hours. After the additions were complete, the mixture was stirred for another 30 minutes at room temperature. The pH was then brought to 10, and the mixture was extracted with ether (50 ml). The aqueous layer was acidified to pH 3 with 3 N HCl and extracted with ether (3 x 50 mL). The organic layers were combined, dried (MgSO), filtered and concentrated to yield the title compound as a colorless oil (1.59 g, 83%). MS (ESI): 278.2 (M + H) "- b) N- (N-benzyloxycarbonyl-Lb-tert-butylanil) -N'-f2- (1 -naphthyl) thiazol-4-ylcarbonin-hydrazide Following the procedure of Examples 3 (a) -3 (c) and 3 (e) -3 (g), except substituting 4-methyl-1-naphthalenboronic acid in step (e) with 1-naphthylboronic acid, and with N-benzyloxycarbonyl-L-tert-butylalanine the N- (4-pyridinylmethoxycarbonyl) -L-leucine in step (g), the title compound was prepared as a white solid (0.214 g, 87%) MS (ESI) ): 531.3 (M + H) + - EXAMPLE 92 Preparation N- (N-benzyloxycarbonyl-L-cyclopropylalaniP-N'-T2- (1-naphthiPetiazol-4-ylcarboninhydrazide a) N-benzyloxycarbonyl-L-allyl-glycine Following the procedure of Example 91 (a), except replacing L-allylglycine with L-tert-butylalanine, the title compound was prepared. b) N-benzyloxycarbonyl-L-cyclopropylalanine methyl ester Diazomethane (4.8 mmoles in 18 ml of Et2O) was added to a solution of the compound of example 92 (a) (0.210 g, 0.48 mmole) in 1 ml of Et2O at room temperature , and stirred for 5 minutes. Then Pd (OAc) 2 (2 mg) was added, and the reaction was stirred overnight, filtered through silica gel, concentrated in vacuo, and used in the next reaction without further purification (205 mg, 95%). MS (ESI): 300.1 (M + Na) 7 c) N-benzyloxycarboni-L-cyclopropylalanine Following the procedure of Example 1 (g), except substituting N- (4-pyridinylmethoxycarbonyl) -L-leucine methyl ester with N-benzyloxycarbonyl-L-cyclopropylaminine methyl ester, prepared the title compound as a white solid (165 mg, 82%). MS (ESI): 264.2 (M + H) 7 d) N- (N-benzyloxycarbonyl-L-cyclopropylalanyl) -N'-r2- (1-naphthyl) thiazol-4-ylcarbonyl-hydrazide Following the procedure of examples 3 (a) -3 (c) and 3 (e) -3 (g), except substituting 4-methy1-1-naphthaleboronic acid in step (e) with 1-naphthylboronic acid, and N- (4-methy1-1-naphthylcarbonyl- (L) -ter-butylalanine) pyridinylmethoxycarbonyl) -L-leucine in step (g), the title compound was prepared as a white solid (0.054 g, 67%). MS (ESI): 515.2 (M + H) +.

EXAMPLE 93 Preparation of N-r2- (1-naphthiPthiazol-4-ylcarbonin-N'-rN-r3- (2-pyridiP-phenylacetyl-L-leuciniphidrazide a) Methyl 3-9-trifluoromethanesulfonyloxyphenylacetate To a flask dried in an oven under an argon atmosphere containing sodium hydride (2.54 g, dispersion at 60% in mineral oil), 63.5 mmoles), anhydrous pentane (20 ml) was added. The suspension was stirred for 5 minutes, allowed to settle, most of the pentane was removed, and anhydrous THF (40 ml) was added. To this suspension was added a solution of methyl 3-hydroxyphenylacetate (9.99 g, 60.1 mmol) in anhydrous THF (20 ml), and the reaction was stirred at room temperature for 20 minutes. To this mixture was then added a solution of N-phenyltrifluoromethanesulfonimide (22.53 g, 63.1 mmol) in anhydrous THF (40 ml), and the reaction was stirred at room temperature until the TLC analysis indicated complete consumption of the starting material (1.5 h). The reaction was quenched by the addition of H2O (10 mL), concentrated to half the original volume, then diluted with CHCl3 (200 mL), and washed with H2O. The aqueous layer was washed with fresh CHCl 3 (50 ml), the combined organic layers were washed with 10% Na 2 CO 3, H 2 O and brine, and then dried (MgSO 4), filtered and concentrated. Column chromatography of the residue (silica gel, 5:95 EtOAc: hexanes, then EtOAc: hexanes 10:90) gave 17.47 g of the title compound. 1 H NMR (400 MHz, CDCl 3) d 7.42 (m, 1 H), 7.31-7.19 (m, 3 H), 3.72 (s, 3 H), 3.68 (s, 2 H). b) 3- (2-pyridiPPeni! methyl acetate) To a solution of the compound of example 93 (a) (6.86 g, 23.0 mmol) in anhydrous dioxane (100 ml), 2-pyridylstannane (8.89 g, 24.1 mmol) was added. , LiCl (2.94 g, 69.3 mmol), 2,6-di-tert-butyl-4-methylphenol (a few crystals) and Pd (PPh3) (632.1 mg, 0.55 mmol) The reaction was protected from light with paper The reaction was allowed to cool to room temperature and concentrated, column chromatography of the residue (silica gel, EtOAc: hexanes, 1: 3, then EtOAc: hexanes). : 2) gave 3.85 g of the title compound: MS (ESI): 228.1 (M + H) 7 c) 3- (2-pyridylphenylacetic acid) Following the procedure of Example 1 (g), except substituting methyl 3- (2-pyridyl) phenylacetate and N- (4-pyridinylmethoxycarbonyl) -L-leucine methyl ester, The title compound was prepared MS (ESI): 214.3 (M + H) +. e) N- [2- (1-Naphthyl) thiazol-4-ylcarbonyl] -N '- [N- [3- (2-pyridyl) phenylacetyl] -L-Iuccinyl] -hydrazide Following the procedure of examples 3 ( a) -3 (c) and 3 (e) -3 (g), except substituting 4-methyl-1-naphthalenboronic acid in step (e) with 1-naphthylboronic acid, and with 3- (2-pyridyl) acid phenylacetic acid N- (4-pyridinylmethoxycarbonyl) -L-leucine in step (g), the title compound was prepared as a white solid (0.14 g, 79%). MS (ESI): 578.1 (M + H) 7 EXAMPLE 94 Preparation of N-r2-rN-bis (cyclopropylmethyl) p-amino-1-thiazoyl-4-ylcarbonyl-1N'- (N-picolinyl-L-leucine-P-hydrazide to} N-r2-rN-bis (cyclopropylmethylamino] thiazol-4-ylcarbonin-N '- (N-tert-butoxy-carbonii-L-leuciniPhidrazide) Following the procedure of example 1 (a) -1 (d) and 1 (h) except substituting the bis-2,6-dimethylmorpholine in step (a) with bis (cyclopropylmethyl) amino-cyclopropylamine and with N-tert-butoxycarbonyl-L-leucine the N- (4-pyridinylmethoxycarbonyl) -L-leucine in Step (h), the title compound was prepared as an orange oil MS (ESI): 480.3 (M + H) +. b) N-r2-rN-bis- (cyclopropylmethyl) amino] thiazol-4-ylcarbonin-N '- (N-picolinyl-L-leu-ciniPhydrazide) Following the procedure of example 56 (a) -56 (b) , except by substituting N- [2- [N-bis- (cyclopropylmethyl) amino] thiazol-4-ylcarbonyl] -N '- (N-tert-butoxycarbonyl-L-leucinyl) hydrazide for N- [2- ( N-cyclopropyl-N-cyclopropyl-methylamino) thiazol-4-ylcarbonyl] -N '- (N-tert-butoxycarbonyl-L-leucyl) -hydrazide in step (a), the compound of title as a yellow solid (74 mg, 41%) MS (ESI): 485.3 (M + H) 7 EXAMPLE 95 Preparation of N- (N-benzyloxycarbonyl-L-leuciniP-N'-r2-fN-bis- (ciciopropümetiPaminoltiazol-4-ylcarboniilhidrazida Following the procedure of example 1 (a) -1 (d) and 1 (h), except substituting bis- (cyclopropylmethyl) amine for cis-2,6-dimethylmorpholine in step (a), and with N-benzyloxycarbonyl- L-Leucine N- (4-pyridinylmethoxycarbonyl) -L-leucine in step (h), the title compound was prepared as a yellow solid (140 mg, 69%). MS (ESI): 514.3 (M + H) +.

EXAMPLE 96 Preparation of N-r2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarboniP-N'-rN- (6-methylnicotinoiP-L-leucinehydrazide a) Acid 6-meti! nicotin ico Following the procedure of Example 1 (g), except substituting methyl 6-methylnicotinate with N- (4-pyridinylmethoxycarbonyl) -L-leucine methyl ester, the title compound was prepared as a white solid (506 g). mg, 100%). MS (ESI): 137.9 (M + H) +. b) N-r2- (N-cyclopropyl-N-cyclopropylmethylamine) thiazole-4-ylcarbonyl-N'-fN- (4-methyl-nicotinoiP-L-leucine lhydrazide) Following the procedure of example 56 (a) -56 (b), except substituting the picolinic acid with 6-methylnicotinic acid in step (b), the title compound was prepared as a white solid (150 mg, 41%) MS (ESI): 485.4 (M + H) 7 EXAMPLE 97 Preparation of N-r2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazole-4-ylcarbonin-N'-rN-fS-methylnicotinoiP-L-leucinehydrazide a) 2-Methylnicotinic acid Following the procedure of example 1 (g), except substituting the methyl ester of N- (4-pyridinylmethoxycarbonyl) -L-leucine with methyl 2-methylnicotinate, the title compound was prepared as a white solid (1.6 g, 100%). MS (ESI): 138.2 (M + H) +. b) N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazole-4-ylcarbonyl-N'-rN- (2-methyl-nicotinoyl) -L-leucinehydrazide Following the procedure of example 56 (a) - 56 (b), except substituting picolinic acid with 2-methylnicotinic acid in step (b), the title compound was prepared as a white solid (170 mg, 71%). MS (ESI): 485.3 (M + H) 7 EXAMPLE 98 Preparation of N-α2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazole-4-ylcarbonin-N'-rN- (3-methylisonicotinoiP-L-leucinehydrazide Following the procedure of example 56 (a) -56 (b), except that picolinic acid was replaced by 2-methylpyridine-4-carboxylic acid in step (b), the title compound was prepared as a white solid ( 120 mg, 57%). MS (ESI): 485.2 (M + H) +.

EXAMPLE 99 Preparation of N-r2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazole-4-ylcarbon-p-N'-rN- (8-quinolino-P-L-leuciniphidrazide Following the procedure of example 56 (a) -56 (b), except that picoiinic acid was replaced with 8-quinolinecarboxylic acid in step (b), the title compound was prepared as a white solid (200 mg, 94%). %). MS (ESI): 521.2 (M + H) +.

EXAMPLE 100 Preparation of N-r2-rN-bis- (cyclopropylmethylP-amino-1-thiazol-4-ylcarbonin-N'- [N- (8-quinolinoiP-L-leucinii1-hydrazide Following the procedure of Example 56 (a) -56 (b), except that N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- (N-te? -butoxycarbonyl) is substituted. -L-leucinyl) hydrazide by N- [2- [N-bis- (cyclopropyimethi) amino] thiazol-4-ylcarbonyl] -N '- (N-tert-butoxycarbonyl-L-leucinyl) -hydrazide in step (a) and picolinic acid by 8-quinolinecarboxylic acid in step (b), the title compound was prepared as a yellow solid (25 mg, 12%). MS (ESI): 535.3 (M + H) +.

EXAMPLE 101 Preparation of N-r2-rN-bis- (cyclopropylmethyl) amino-thiazoyl-4-ylcarbonyl-N'- fN- (3-isoquinolinoiP-L-leucinehydrazide Following the procedure of Example 56 (a) -56 (b), except that N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- (N-tert-butoxycarbonyl-) is substituted. L-leucinyl) hydrazide by N- [2- [N-bis- (cyclopropylmethyl) amino] thiazol-4-ylcarbonyl] -N '- (N-tert-butoxycarbonyl-L-leucinyl) -hydrazide in step ( a), and picolinic acid by 3-isoquinolinecarboxylic acid in step (b), the title compound was prepared as a yellow solid (25 mg, 10%). MS (ESI): 535.3 (M + H) +.

EXAMPLE 102 Preparation of N-r2-r4- (2,2-Dimethylaminoethoxy-1-naphthylthiazol-4-ylcarbonip-N'-rN- (8-quininoy P-L-Iucininhydrazide a) 4-bromo-1-naphthol To a strongly stirred suspension of 1,4-dibromonaphthalene (15.3 g, 53.7 mmol) in hexane / THF (300 ml) at -78 ° C was added, dropwise, n-butyl -lithium (22.3 ml, 56.4 mmol, 2.5 M in hexane). After stirring for an additional 30 minutes at -78 ° C, bis (trimethylsilyl) peroxide (1.1 g, 61.8 mmol) was added slowly with the aid of a syringe [Taddei, M., Ricci, A., Synthesis, 1986, 633]. After warming to room temperature and stirring for an additional 3 hours, the mixture was diluted with ethyl acetate and washed with 1 N HCl and then with brine. The organic layer was dried (MgSO4), filtered and concentrated. The residue was purified by column chromatography (silica gel, ethyl acetate / hexane) to yield the title compound as an off-white solid (6.5 g, 54%). MS (ESI): 221.1 (M + H) +. b) 4-bromo-1-naphthyl tert-butyl ether Following the procedure of example 39 (a), except that 4-bromomethylbenzoic acid is replaced by 4-bromo-1-naphthol, the title compound was prepared as a colorless oil (2.34 g, 62%). 1 H NMR (400 MHz, CDCl 3) d 8.28 (d, 1 H), 8.18 (d, 1 H), 7.67 (d, 1 H), 7.60 (t, 1 H), 7.54 (t, 1 H), 7.01 (d, 1 H), 1.51 (s, 9H). c) Ethyl 2- (4-tert-butoxy-1-naphthyl) thiazole-4-carboxylate Following the procedure of Example 3 (a) -3 (e), except that 1-bromo-4-methyl naphthalene is replaced by the tert-butyl ether of 4-bromo-1-naphthyl in step (d), the title compound was prepared as a white solid (0.783 g, 67%). MS (ESI): 356.2 (M + H) 7 d) Ethyl 2- (4-hydroxy-1-naphthypiazole-4-carboxylate) Following the procedure of Example 4 (c), except that the tert-butoxycarbonyl ester of N-methyl-N- (4-pyridinylmethoxycarbonyl) is substituted. -L-leucine by ethyl 2- (4-tert-butoxy-1-naphthyl) thiazole-4-carboxylate, the title compound was prepared as a yellow solid (0.580 g, 88%) .MS (ESI) : 300.1 (M + H) 7 e) ethyl 2-r4- (2-N, N-dimethylaminoethoxy) -1-naphththiazole-4-carboxylate Following the procedure of example 28 (d), except that 2- (2-hydroxy-1-naphthyl) is substituted Ethyl thiazole-4-carboxylate by ethyl 2- (4-hydroxy-1-naphthyl) thiazole-4-carboxylate and benzyl alcohol by 2- (N, N-dimethylamino) ethanol, the title compound was prepared as a solid of white color (0.097 g, 52%). MS (ESI): 371.3 (M + H) 7 f) N- (8-quinolinoyl) -L-leucine methyl ester Following the procedure of Example 1 (h), except that N- [2- (c / is substituted s-2,6-d-methyl-4-morpholino) thiazol-4-ylcarbonyl] hydrazide by the methyl ester hydrochloride of L-leucine and N- (4-pyridylmethoxycarbonyl) -L-leucine by 8-quinolinecarboxylic acid, The title compound was prepared as a white solid (0.637 g, 41%). MS (ESI): 301.2 (M + H) +. q) N- (8-quinolinoyl) -L-leucine Following the procedure of example 1 (g), except that the methyl ester of N- (4-pyridylmethoxycarbonii) -L-Ieucine is replaced by the methyl ester of N- ( 8-quinolinoyl) -L-leucine, the title compound was prepared as a white solid (0.150 g, 25%). 1 H NMR (400MHz, CDCl 3) d 8.89 (t, 1 H), 8.78 (d, 1 H), 8.21 (d, 1 H), 7.90 (d, 1 H), 7.57 (t, 1 H), 7.43 ( t, 1 H), 4.88 (m, 1 H), 1, 92 (m, 3H), 1.03 (m, 6H). h) N- [2- [4- (2,2-dimethylaminoethoxy) -1-naphthylthiazol-4-ylcarbonanhydrazide Following the procedure of Example 1 (d), except that 2- (c / 'is substituted ethyl s-2,6-dimethyl-4-morpholino) thiazole-4-carboxylate by ethyl 2- [4- (2-N, N-dimethylaminoethoxy) -1-naphthyl] thiazole-4-carboxylate, the compound of title was prepared as a yellow solid (0.091 g, 100%). MS (ESI): 357.2 (M + H) 7 i) N-r2-f4- (2,2-dimethylaminoethoxy) -1-naphthiptiazol-4-ylcarbonan-N'-rN- (8-quinolinoyl) -L-leuciniphydrazide Following the procedure of example 1 (h), except that N- is replaced. { 2- (c / 's-2,6-dimethyl-4-morpholino) thiazol-4-ylcarbonyl] hydrazide by N- [2- [4- (2,2-dimethylaminoethoxy) -1-naphthyl] thiazole- 4-ylcarbonyl] hydrazide and N- (4-pyridymethoxycarbonyl) -L-leucine by N- (8-quinolinoyl) -L-leucine, and the title compound was prepared as a yellow solid (0.050 g, 31%). MS (ESI): 625.2 (M + H) 7 EXAMPLE 103 Preparation of N-r2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazoI-4-ylcarbonin-N'-rN- (7-quinolinoiP-L-leucinehydrazide Following the procedure of example 56 (a) -56 (b), except that picolinic acid is replaced by 7-quinolinecarboxylic acid in step (b), the title compound was prepared as a white solid (100 mg, 50 mg). %). MS (ESI): 521.2 (M + H) 7 EXAMPLE 104 Preparation of N-r2-rN-bis- (cyclopropylmethyl) amino-1-thiazol-4-ylcarbonip-N'-rN- (6-methylnicotinoiP-L-leucine-hydrazide Following the procedure of Example 56 (a) -56 (b), except that N-j2- (N-cyclopropyl-N-cyclopropylmethalamino) thiazol-4-ylcarbonyl] -N '- (N-ter) is substituted. -butoxycarbonyl-L-leucinyl) hydrazide by N- [2- [N-bis- (cyclopropylmethyl) amino] thiazol-4-ylcarbonyl] -N '- (N-tert-butoxycarbonyl-L-leucine] -hydrazide in step (a) and picolinic acid by 6-methylnicotinic acid in step (b), the title compound was prepared as a yellow solid (40 mg, 15%) MS (ESI): 499.3 (M + H ) + EXAMPLE 105 Preparation of N-2-rN-bis- (cyclopropylmethyl) -Pinoxy-thiazol-4-ylcarbonip-N'- (N-methyl-L-prolinyl-L-leucine-P-hydrazide Following the procedure of example 56 (a) -56 (b), except that picolinic acid was replaced by N-methyl-L-proline in step (b), the title compound was prepared as a white solid (62). mg, 48%). MS (ESI): 477.3 (M + H) +.

EXAMPLE 106 Preparation of N- (N-benzyloxycarbonyl-L-norvaliniP-N'-r2- (1 -na tl) thiazol-4-ylcarboniSlhydrazide Following the procedure of Examples 3 (a) -3 (c) and 3 (e) -3 (g), except that 4-methyl-1-naphthaleboronic acid is substituted for 1-naphthylboronic acid in step (e) and N- (4-pyridinylmethoxycarbonii) -L-leucine by N-benzyloxycarbonyl-L-norvaline in step (g), the title compound was prepared as a white solid (180 mg, 96%). MS (ESI): 503.2 (M + H) +.

EXAMPLE 107 Preparation of N- (N-benzyloxycarbonyl-L-isoleuciniP-N'-r2- (1-naphthiPetiazol-4-ylcarbonyhydrazide Following the procedure of Examples 3 (a) -3 (c) and 3 (e) -3 (g), except that 4-methyl-1-naphthalenboronic acid is substituted for 1-naphthylboronic acid in step (e) and N- (4-pyridinylmethoxycarbonyl) -L-leucine by N-benzyloxycarbonyl-L-isoleucine in step (g), the title compound was prepared as a white solid (167 mg, 87%). MS (ESI): 517.1 (M + H) 7 EXAMPLE 108 Preparation of N-rN- (4-dimethylaminomethylbenzoiP-L-leuciniH-N'-r2- (1-naphthiPthiazol-4-ylcarbonyhydrazide a) Methyl 4- (N, N-dimethylaminomethyl) benzoate Methyl 4- (bromomethyl) benzoate (2.0 g, 8.73 mmol) was added to a saturated solution of dimethylamino in methanol. After stirring for 25 minutes, the solution was concentrated and the residue was separated between 1 N NaOH and ethyl acetate. The organic layer was washed with saturated brine, dried (MgSO4), filtered and concentrated to provide the title compound as a colorless liquid (1.67 g, 99%). 1 H NMR (250 MHz, CDCl 3) d 8.00 (d, 2H), 7.39 (d, 2H), 3.91 (s, 3H), 3.47 (d, 2H), 2.25 (s, 6H). b) 4- (N, N-dimethylaminomethyl) benzoic acid Following the procedure of Example 1 (g), except that the N- (4-pyridinimethoxycarbonyl) -L-leucine methyl ester is replaced by 4- (N, N- methyl dimethylaminomethyl) benzoate, the title compound was prepared as a white solid (1.6 g, 100%). 1 H NMR (400 MHz, CD 3 OD) d 7. 94 (d, 2H), 7.36 (d, 2H), 3.64 (s, 2H), 2.35 (s, 6H). c) N-rN- (4-dimethylaminomethylbenzoyl) -L-leucine-p 'N' - [2- (1-naphthyl) -thiazol-4-ylcarbonylhydrazide Following the procedure example 59 (a) -59 (d), except that 8-quinolinecarboxylic acid is replaced by 4- (N, N-dimethylaminomethyl) benzoic acid in step (d), the title compound was prepared as a white solid (87 mg, 61%). MS (ESI): 544.2 (M + H) +.

EXAMPLE 109 Preparation of N- (N-benzyl) oxycarbonyl-L-norleucine P-N'-r 2 - (1 -naphthyl) thiazoyl-4-ylcarboniphidrazide Following the procedure of Examples 3 (a) -3 (c) and 3 (e) -3 (g), except that 4-methyl-1-naphthaleboronic acid is substituted for 1-naphthylboronic acid in step (e) and N- (4-pyridinylmethoxycarbonyl) -L-leucine by N-benzyloxycarbonyl-L-norleucine in step (g), the title compound was prepared as a white solid (184 mg, 96%). MS (ESI): 517.1 (M + H) 7 EXAMPLE 110 Preparation of N-rN- (4-dimethylaminomethyl) benzyloxycarboniP-L-leucinin-N'-r2- (1-naphthiPetiazol-4-ylcarbonyl-1-hydrazide a) 4- (N, N-dimethylamino) benzyl alcohol To a stirred solution of the compound of example 108 (a) (1.63 g, 8.4 mmoies) in 25 ml of ether, cooled to 0 ° C, was added dropwise a 1 M solution of lithium aluminum hydride (8.4 mmol, 8.4 ml). After 5 minutes, the reaction was quenched by the addition of water (0.33 ml), 15% aqueous NaOH solution (0.33 ml) and water (1.0 ml). The precipitate was removed by filtration, washed with ether twice and the The filtered material was concentrated to give the title compound as a colorless oil (1.36 g, 98%). 1 H NMR (250 MHz, CDCl 3) d 7.32 (d, 2 H), 7.28 (d, 2 H), 4.68 (s, 2 H), 3.41 (s, 2 H), 2.22 (s, 6 H). b) N-fN- (4-dimethylaminomethyl-benzylcarbonyl) -L-leucinyl-1-N '- [2- (1-naphthi-Pthiazol-4-ylcarboninhydrazide) Following the procedure of example 1 (e) -1 (h), except that 4-pyridylcarbinol is replaced by 4- (N, N-dimethylamino) benzyl alcohol in step (f) and N- [2- (c / s-2,6-dimethyl-4-morfoino) thiazole-4-ylcarbonyl] hydrazide by N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide, the title compound was prepared as a white solid (186 mg, 87%). MS (ESI): 574.3 (M + H ) + EXAMPLE 111 Preparation of N- (N-benzyloxycarbonyl-L-norvaliniP-N'-r2- (2-benzyloxy-phenyl-4-ylcarbonylhydrazide Following the procedure of Example 27 (a) -27 (c), except that 2- (3-phenylphenyl) -4-methylpentanoic acid is replaced by N-benzyloxycarbonyl-L-norvaline per in step (c), the compound of The title was prepared as a white solid. MS (ESI): 559.0 (M + H) +.

EXAMPLE 112 Preparation of N-r2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazole-4-iicarbonyl-1-N'-rN- (4-methylimidazoi-5-i! Carbon! P-L-le? Cini! Following the procedure of example 56 (a) -56 (b), except that picolinic acid was replaced by 4-methylimidazole-5-carboxylic acid in step (b), the title compound was prepared as a white solid ( 100 mg, 65%). MS (ESI): 474.3 (M + H) 7 EXAMPLE 113 Preparation of N-rN-r4- (4-morpholinomethyl-P-benzo-p-L-leucinin-N'-r2- (1-naphthi-Pthiazole-4-Hcarboniphidrazide Following the procedure of example 108 (a) -108 (c), except that dimethylamine was replaced by morpholine in step (a), the title compound was prepared as a white solid (0.097 g, 51%). MS (ESI): 586.2 (M + H) 7 EXAMPLE 114 Preparation of N-rN- (2-methylnicotinoiP-L-leucinin-N'-r2- (1-naphthiPthiazol-4-ylcarbonyhydrazide.

Following the procedure of example 59 (a) -59 (d), except that 8-quinolinecarboxylic acid is replaced by 2-methylnicotinic acid in step (d), the title compound was prepared as a white solid (0.103 g , 60%). MS (ESI): 502.2 (M + H) +.

EXAMPLE 115 Preparation of N-rN- (6-methylnicotino-P-L-leucinin-N'-r2- (1-naphthiD-thiazole-4-iicarbonylhydrazide Following the procedure of example 59 (a) -59 (d), except that 8-quinolinecarboxylic acid is replaced by 6-methylnicotinic acid in step (d), the title compound was prepared as a white solid (0.134 g , 79%). MS (ESI): 502.2 (M + H) 7 EXAMPLE 116 Preparation of N-rN- (4-methylimidazol-5-ylcarboniP-L-allyl-1,3-yl-N'-r2- (1-naphthi-Pthiazol-4-ylcarbonyhydrazide a) N-tert-butoxycarbonyl-L-allylcholine To a stirred solution of L-allylglycine (6.28 g, 54.5 mmol) in dioxane / water / 1 N NaOH (10 ml / 55 ml / 55 ml) at 0 ° C di-tert-butyium dicarbonate (12.5 g, 57.2 mmoies) was added. After stirring for 30 minutes, the solution was concentrated and redissolved in 60 ml of water. A layer of ethyl acetate was added and the aqueous layer was acidified to pH 3 with 0.3 N KHSO. The aqueous layer was extracted with ethyl acetate (2X). The organic layers were combined, washed with water (2X), dried (MgSO4), filtered and concentrated to yield the title compound as a white solid (10.1 g, 86%). MS (ESI): 453.2 (2M + Na) +. b) N-rN- (4-methylimidazol-5-ylcarbonyl) -L-allyl-chininip-N'-r2- (1-naphthiPatol-4-ylcarbonylhydrazide) Following the procedure of example 59 (a) -59 (d), except that N-tert-butoxycarbonyl-L-leucine is replaced by N-tert-butoxycarbonyl-L-aiylglycine in step (b) and 8-quinolinecarboxylic acid by 4-methylimidazole-5-carboxylic acid in step (d), The title compound was prepared as a white solid (0.112 g, 67%) MS (ESI): 475.1 (M + H) +.

EXAMPLE 117 Preparation of N- (N-b-fer-butoxycarbonyl-L-fer-butylalaniP-N'-r2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonipihydrazide a) N-tert-butoxycarbonyl-Lb-tert-butylalanine Following the procedure of Example 1 16 (a), except that L-allylglycine was substituted for L-tert-butylalanine, the title compound was prepared as a white solid (2.36 g, 70%). MS (ESI): 268.3 (M + Na) +. b) N- (Nb-tert-butoxycarbonyl-L-tert-butylalaniP-N'-r2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl-1-hydrazide Following the procedure of example 1 (a) -1 ( d) and 1 (h), except that c / s-2,6-dimethylmorpholine is replaced by N-cyclopropylmethylcyclopropylamine in step (a) and N- (4-pyridinylmethoxycarbonyl) -L-leucine by N-ter- butoxycarbonyl-Lb-tert-butylalanine in step (h), the title compound was prepared as a white solid (0.96 g, 100%) MS (ESI): 480.3 (M + H) 7 EXAMPLE 118 Preparation of N-r2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazole-4-ylcarbonip-N'-rN- (8-quinolino-P-L-b-tert-butylalaniphidrazide Following the procedure of Example 56 (a) -56 (b), except that N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- (N-tert-butoxycarbonyl-) is substituted. L-leucinyl) hydrazide by N- (Nb-tert-butoxycarbonyl-L-tert-butylalanyl) -N '- [2- (N-cyclopropyl-N-cyclopropylmethyl amine) -thiazol-4-ylcarbonyl] hydrazide in step (a ) and picolinic acid by 8-quinolinecarboxylic acid in step (b), the title compound was prepared as a white solid (160 mg, 82%). MS (ESI): 535.3 (M + H) +.

EXAMPLE 119 Preparation of N-rN- (4-Methylimidazol-5-ylcarboniP-L-b-tert-butylalan-N'-f2- (1-naphthiPetiazol-4-ylcarbonyhydrazide Following the procedure of example 59 (a) -59 (d), except that N-tert-butoxycarbonyl-L-leucine is replaced by N-tert-butoxycalbonyl-Lb-tert-butylalanine in step (b) and acid 8- 4-methylimidazole-5-carboxylic acid quinolinecarboxylic acid in step (d), the title compound was prepared as a white solid (0.096 g, 58%). MS (ESI): 505.2 (M + H) 7 EXAMPLE 120 Preparation of N-r2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonin-N'-rN- (4-methylimidazol-5-ylcarboniP-L-b-tert-butylalanine hydrazide Following the procedure of example 56 (a) -56 (b), except that N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonii] -N '- (N-tert-butoxycarbonyl-) is substituted. L-leucinyl) hydrazide by N- (Nb-tert-butoxycarbonyl-L-tert-butylalanyl) -N '- [2- (N-cyclopropyl-N-cyclopropylmethylamino) -thiazol-4-ylcarbonyl] hydrazide in step (a) and picolinic acid by 4-methylimidazole-5-carboxylic acid in step (b), the title compound was prepared as a white solid (180 mg, 78%). MS (ESI): 488.2 (M + H) 7 EXAMPLE 121 Preparation of N-f2- (1-naphthiPthiazol-4-ylcarboniH-N '- (N-picolinoyl-L-b-fer-butylalani-Hydrazide Following the procedure of example 59 (a) -59 (d), except that N-tert-butoxycarbonyl-L-leucine is replaced by N-tert-butoxycarbonyl-Lb-tert-butylalanine in step (b) and acid 8- quinolinecarboxylic acid by picolinic acid in step (d), the title compound was prepared as a white solid (0.098 g, 62%). MS (ESI): 502.3 (M + H) 7 EXAMPLE 122 Preparation of N-r2- (1-naphthiPathiazole A-ilcarbonip-N'-rN- (8-quinolinoiP-L-b-fer-butylalani-Hydrazide Following the procedure of Example 59 (a) -59 (d), except that N-tert-butoxycarbonyl-L-leucine is replaced by N-tert-butoxycarbonyl-Lb-tert-butylalanine in step (b), the compound of title was prepared as a white solid (0.083 g, 46%). MS (ESI): 552.2 (M + H) +.

EXAMPLE 123 Preparation of N-f2- (1-naphthyl) thiazoi-4-iicarbonyl-N '- (N-p-cholinoyl-L-allylquinini-Hydrazide Following the procedure of example 59 (a) -59 (d), except that N-tert-butoxycarbonyl-L-leucine is replaced by N-tert-butoxycarbonyl-L-allylglycine in step (b) and 8-quinolinecarboxylic acid by picolinic acid in step (d), the title compound was prepared as a white solid (0.141 g, 84%). MS (ESI): 472.2 (M + H) +.

EXAMPLE 124 Preparation of N-f2- (1-naphthiD-thiazol-4-ylcarbonyl-N '- (N-picolinoyl-L-b-cyclopropylalani-Hydrazide a) N-tert-butoxycarbonyl-Lb-cyclopropylalanine methyl ester To a stirred solution of the compound of example 16 (a) (7.81 g, 36.3 mmol) in ether (100 ml) at 0 ° C was added a solution of diazomethane (made from 10 equivalents of 1-methyl-3-nitro-1-nitrosoguanidine in ether (500 ml) and 40% NaOH (500 ml) at 0 ° C). After stirring for 10 minutes, Pd (OAc) 2 (0.300 g) was added to the solution. After 20 minutes, the solution was concentrated and the residue was filtered through a short plug of silica gel to remove the catalyst. not used. Concentrating the solution gave the title compound as a golden yellow oil (8.29 g, 99%). 1 H NMR (400 MHz, CDCl 3) d 5.17 (d, 1 H), 4.39 (m, 1 H), 3.73 (s, 3 H), 1.66 (t, 2 H), 1.44 (s, 9 H), 0.68 ( m, 1 H), 0.49 (m, 2H), 0.08 (m, 2H). b) N-tert-butoxycarbonyl-L-cyclopropylalanine Following the procedure of Example 1 (g), except that the N- (4-pyridinylmethoxycarbonyl) -L-leucine methyl ester is replaced by the N-methyl-methyl ester. butoxycarbonyl-Lb-cyclopropylalanine, the title compound was prepared as a golden yellow oil (6.37 g, 82%). EM (ESI): 252.3 (M + Na) +. c) N-r2- (1-naphthyl) thiazol-4-ylcarbonip-N '- (N-picolinoyl-L-cyclopropyl-alanyl) hydrazide Following the procedure of example 59 (a) -59 (d), except that N-tert-butoxycarbonyl-L-leucine is replaced by N-tert-butoxycarbonyl-L-cyclopropylalanine in step (b) and 8-quinolinecarboxylic acid by picolinic acid in step (d), the title compound was prepared as a white solid (0.1 14 g, 71%). MS (ESI): 486.1 (M + N) +.

EXAMPLE 125 Preparation of N-rN- (6-methylnicotino-P-L-b-cyclopropi-alanip-N'-r2- (1-naphthi-Pthiazol-4-ylcarboniphidrazide Following the procedure of example 59 (a) -59 (d), except that N-tert-butoxycarbonyl-L-leucine is replaced by N-tert-butoxycarbonyl-L-cyclopropylalanine in step (b) and 8-quinolinecarboxylic acid by 6-methylnicotinic acid in step (d), the title compound was prepared as a white solid (0.097 g, 59%). MS (ESI): 500.1 (M + H) +.

EXAMPLE 126 Preparation of N-rN- (4-methylimidazol-5-ylcarboniP-L-b-cyclopropylalanip-N'-r2- (1-naphthiPetiazol-4-ylcarbonyhydrazide Following the procedure of example 59 (a) -59 (d), except that N-tert-butoxycarbonyl-L-leucine is replaced by N-tert-butoxycarbonyl-L-cyclopropylalanine in step (b) and 8-quinolinecarboxylic acid by 4-Methylimidazole-5-carboxylic acid in step (d), the title compound was prepared as a white solid (0.095 g, 59%). MS (ESI): 489.1 (M + H) +.

EXAMPLE 127 Preparation of N-l ~ 2- (1-naphthiPthiazol-4-ylcarbonyl-N'-rN- (8-quinolinoiPL-b-cyclopropylalanine hydrazide Following the procedure of example 59 (a) -59 (d), except that N-tert-butoxycarbonyl-L-leucine is replaced by N-tert-butoxycarbonyl-L-cyclopropylalanine in step (b), the title compound is prepared as a white solid (0.138 g, 78%). MS (ESI): 536.2 (M + H) +.

EXAMPLE 128 Preparation of N-rN- (6-methylnicotinoiP-L-b-tert-butylalan-N'-r2- (1-naphthi-Pthiazol-4-ylcarbonipihydrazide Following the procedure of example 59 (a) -59 (d), except that N-tert-butoxycarbonyl-L-leucine is replaced by N-tert-butoxycarbonyl-Lb-tert-butylalanine in step (b) and acid 8- quinolinecarboxylic acid by 6-methynicotinic acid in step (d), the title compound was prepared as a white solid (0.124 g, 73%). MS (ESI): 516.1 (M + H) 7 EXAMPLE 129 Preparation of N-r2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazole-4-ylcarbonip-N '- (N-picolinoH-L-b-tert-butylalanyl) hydrazide Following the procedure of Example 56 (a) -56 (b), except that N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- (N-tert-butoxycarbonyl-) is substituted. L-leucinyl) hydrazide by N- (Nb-tert-butoxycarbonyl-L-tert-butylanilyl) -N '- [2- (N-cyclopropyl-N-cyclopropylmethylamino) -thiazol-4-ylcarbonyl] hydrazide in step (a), the title compound was prepared as a white solid (143 mg, 83%). MS (ESI): 485.1 (M + H) 7 EXAMPLE 130 Preparation of N-r2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazole-4-lcarbonyl-N'-rN- (3-isoquinolinoiP-L-b-tert-butylalaninehydrazide Following the procedure of example 56 (a) -56 (b), except that N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- (N-tert-butoxycarbonyl-) is substituted. L-leucinyl) hydrazide by N- (Nb-tert-butoxycarbonyl-L-tert-butylanyl) -N '- [2- (N-cyclopropyl-N-cyclopropylmethylamino) -thiazole-4-ylcarbonyl] hydrazide in step (a) and picolinic acid by 3-isoquinolinecarboxylic acid in step (b), the title compound was prepared as a white solid (138 mg, 85%). MS (ESI): 535.1 (M + H) 7 EXAMPLE 131 Preparation of N- (N-fer-butoxycarbonyl-L-b-cyclopropylalaniP-N'-r2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyhydrazide Following the procedure of example 1 (a) -1 (d) and 1 (h), except that cis-2,6-dimethylmorpholine is replaced by N-cpropylmethyl cpropylamine in step (a) and N- (4-pyridinylmethoxycarbonyl) -L -leucine by N-tert-butoxycarbonyl-L-cpropylalanine in step (h), the title compound was prepared as a white solid (1.375 g, 76%). MS (ESI): 464.2 (M + H) +.

EXAMPLE 132 Preparation of N-r2- (N-cpropylmethyl-N-propylamino) thiazol-4-ylcarbonin-N'-rN- (6-methyl-3-pyridinylmethoxycarboniP-L-leuciniphydrazide Following the procedure of example 1 (a) -1 (h), except that cis-2, 6-dimethylmorpholine is replaced by N-cpropyl-propylamine in step (a) and 4-pyridylcarbinol by 6-methyl-3-pyridiicarbinol in step (f), the title compound was prepared as an orange solid (84 mg, 33%). MS (ESI): 517.3 (M + H) 7 EXAMPLE 133 Preparation of N-rN- (6-methyl-p-cn) -P-L-allyl-Siphenyl-N'-r2- (1-naphthi-Pthiazol-4-ylcarbonyhydrazide Following the procedure of example 59 (a) -59 (d), except that N-tert-butoxycarbonyl-L-leucine is replaced by N-tert-butoxycarbonyl-L-aiylglycine in step (b) and 8-quinolinecarboxylic acid by 6-Methylnichotinic acid in step (d), the title compound was prepared as a white solid (0.097 g, 66%). MS (ESI): 486.1 (M + H) 7 EXAMPLE 134 Preparation of N-f2- (1-naphthi-Pthiazol-4-ylcarbonip-N'-rN- (8-quino! InoiP-L- alHqliciniphidrazide Following the procedure of example 59 (a) -59 (d), except that N-tert-butoxycarbonyl-L-leucine is replaced by N-tert-butoxycarbonyl-L-allylglycine in step (b), the title compound is prepared as a white solid (0.105 g, 74%). MS (ESI): 522.1 (M + H) +.

EXAMPLE 135 Preparation of N-f2- (1-naphthiPetiazol-4-ylcarbon-p-N'-rN- (2-quinoHnoiP-L-b-cpropylalanine hydrazide Following the procedure of example 59 (a) -59 (d), except that N-tert-butoxycarbonyl-L-leucine is replaced by N-tert-butoxycarbonyl-L-cpropylalanine in step (b) and 8-quinolinecarboxylic acid by 2-quinolinecarboxylic acid in step (d), the title compound was prepared as a white solid (0.151 g, 86%). MS (ESI): 536.3 (M + H) 7 17 EXAMPLE 136 Preparation of N-rN- (3-isoquinolinoiP-L-b-cpropylalanip-NT-f2- (1-naphthiPthiazol-4-ylcarboniphidrazide Following the procedure of example 59 (a) -59 (d), except that N-tert-butoxycarbonyl-L-leucine is replaced by N-tert-butoxycarbonyl-L-cpropylalanine in step (b) and 8-quinoxycarboxylic acid by 3-isoquinolinecarboxylic acid in step (d), the title compound was prepared as a white solid (0.145 g, 82%). MS (ESI): 536.1 (M + H) +.

EXAMPLE 137 Preparation of N-rN- (1-isoquinolylno-P-L-b-cpropylalan-p-N'-r2- (1-naphthi-Pthiazol-4-ylcarbonyhydrazide Following the procedure of example 59 (a) -59 (d), except that N-tert-butoxycarbonyl-L-leucine is replaced by N-tert-butoxycarbonyl-L-cpropylalanine in step (b) and 8-quinolinecarboxylic acid by 1-isoquinolinecarboxylic acid in step (d), the title compound was prepared as a white solid (0.143 g, 81%). MS (ESI): 536.1 (M + H) +.

EXAMPLE 138 Preparation of N-f2- (1-naphthiPetiazol-4-ylcarbonan-N'-rN- (7-quinolinoiP-L-b-cpropylalaniphidrazide Following the procedure of example 59 (a) -59 (d), except that N-tert-butoxycarbonyl-L-leucine is replaced by N-tert-butoxycarbonyl-L-cpropylalanine in step (b) and 8-quinolinecarboxylic acid by 7-quinolinecarboxylic acid in step (d), the title compound was prepared as a white solid (0.138 g, 78%). MS (ESI): 536.1 (M + H) 7 EXAMPLE 139 Preparation of N-f2- (N-cpropyl-N-cpropylmethylamino) thiazole-4-ylcarbonin-N'-rN- (8-quinolinoiP-L-b-cpropylalanine hydrazide Following the procedure of Example 56 (a) -56 (b), except that N- [2- (N-cpropyl-N-cpropylmethylamino) thiazol-4-ylcarbonyl] -N '- (N-tert-butoxycarbonyl-) is substituted. L-leucinyl) hydrazide by N- (N-tert-butoxycarbonyl-Lb-cpropylalalanyl) -N '- [2- (N-cpropyl-N-cpropylmethyl-amino) thiazol-4-ylcarbonyl] hydrazide in step ( a) and picolinic acid by 8-quinolinecarboxylic acid in step (b), the title compound was prepared as a white solid (120 mg, 73%). MS (ESI): 519.1 (M + H) 7 EXAMPLE 140 Preparation of N-r2- (N-cpropyl-N-c8-chloropropylmethylamino) thiazole-4-ylcarbonyl-N'-rN- (4-methylimidazol-5-ylcarboniP -Lb- cpropylalaninhydrazide Following the procedure of example 56 (a) -56 (b), except that N- [2- (N-cyclopropyl-N-cyclopropylmethyl amine) thiazol-4-ylcarbonyl] -N '- (N-tert-butoxycarbonyl-) is substituted. L-leucinyl) hydrazide by N- (N-tert-butoxycarbonyl-Lb-cyclopropylalanyl) -N '- [2- (N-cyclopropyl-N-cyclopropylmethyl-amino) thiazol-4-ylcarbonyl] hydrazide in step (a) and picolinic acid by 4-methylimidazole-5-carboxylic acid in step (b), the title compound was prepared as a white solid (120 mg, 81%). MS (ESI): 472.1 (M + H) 7 EXAMPLE 141 Preparation of N-r2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazole-4. ilcarbonill-N'-rN- (3-isoquinolinoiP-L-b-cyclopropylalaninhydrazide Following the procedure of Example 56 (a) -56 (b), except that N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- (N-tert-butoxycarbonyl-) is substituted. L-leucinyl) hydrazide by N- (N-tert-butoxycarbonyl-Lb-cyclopropylalanyl) -N '- [2- (N-cyclopropyl-N-cyclopropiimethyl-amino) thiazol-4-ylcarbonyl] hydrazide in step (a) and picolinic acid by 3-isoquinolinecarboxylic acid in step (b), the title compound was prepared and obtained as a white solid (140 mg, 82%). MS (ESI): 519.2 (M + H) 7 EXAMPLE 142 Preparation of N-r2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazole-4-ylcarbonin-N'-rN- (6-methyl-nicotino-P-L-b-cyclopropylalanyl) -razide Following the procedure of Example 56 (a) -56 (b), except that N- [2- (N-cyclopropyi-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- (N-tert-butoxycarbonyl-) is substituted. L-leucinyl) hydrazide by N- (N-tert-butoxycarbonyl-Lb-cyclopropylalanyl) -N '- [2- (N-cyclopropyl-N-cyclopropylo-N-cyclo-propylmethylamino) thiazol-4-ylcarbonyl] hydrazide in step (a) and picolinic acid by 6-methynicotinic acid in step (b), the title compound was prepared as a white solid (105 mg, 62%). MS (ESI): 483.2 (M + H) +.

EXAMPLE 143 Preparation of N-rN- (4-methylimidazol-5-ylcarboniP-L-norleucinip-N'-r2- (1-naphthyl, thiazol-4-ylcaboniphidrazide Following the procedure of example 59 (a) -59 (d), except that N-tert-butoxycarbonyl-L-leucine is replaced by N-tert-butoxycarbonyl-L-norleucine in step (b) and 8-quinolinecarboxylic acid by 4- methylimidazole-5-carboxylic acid in step (d), the title compound was prepared as a white solid (0.1 12 g, 70%). MS (ESI): 491.1 (M + H) +.

EXAMPLE 144 Preparation of N-f2- (1-naphthiPthiazol-4-ylcarbonip-N '- (N-picolinoyl-L-norleuciniPhidrazide Following the procedure of example 59 (a) -59 (d), except that N-tert-butoxycarbonyl-L-leucine is replaced by N-tert-butoxycarbonyl-L-norleucine in step (b) and 8-quinolinecarboxylic acid by picolinic acid in step (d), the title compound was prepared as a white solid (0.114 g, 72%). MS (ESI): 488.2 (M + H) +.

EXAMPLE 145 Preparation of N-f2- (1-naphthiPthiazol-4-ylcarbonin-N'-rN- (8-quinolino-P-L- norleuciniPhidrazide Following the procedure of example 59 (a) -59 (d), except that N-tert-butoxycarbonii-L-leucine is replaced by N-tert-butoxycarbonyl-L-norleucine in step (b), the title compound is prepared as a white solid (0.082 g, 47%). MS (ESI): 538.1 (M + H) +.

EXAMPLE 146 Preparation of N-r2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonip-N'-rN- (2-quinolinoiP-L-b-cyclopropylalanine hydrazide Following the procedure of Example 56 (a) -56 (b), except that N- [2- (N-cyclopropyl-cyclopropylmethylamino) thiazole-4-iicarbonyl] -N '- (N-tert-butoxycarbonyl-) is substituted. L-leucinyl) hydrazide by N- (N-tert-butoxycarbonyl-Lb-cyclopropylalanyl) -N '- [2- (N-cyclopropyl-N-cyclopropylmethyl-amino) thiazol-4-ylcarbonyl] hydrazide in step (a) and picolinic acid by 2-quinolinecarboxylic acid in step (b), the title compound was prepared as a white solid (150 mg, 81%). MS (ESI): 519.2 (M + H) 7 EXAMPLE 147 Preparation of N-r2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazole-4-ylcarbonin-N'-rN- (1-isoquinolinoiP-L-b-cyclopropylalaninhydrazide Following the procedure of example 56 (a) -56 (b), except that N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- (N-tert-butoxycarbonyl-L-leucinyl) hydrazide is replaced by N- (N-tert-butoxycarbonyl) -L-cyclopropylalanyl) -N '- [2- (N-cyclopropyl-N-cyclopropylmethyl-amino) thiazol-4-ylcarbonyl] hydrazide in step (a) and picolinic acid by 1-isoquinolinecarboxylic acid in step (b) , the title compound was prepared as a white solid (130 mg, 87%). MS (ESI): 519.2 (M + H) 7 EXAMPLE 148 Preparation of N-r2-rN-cyclopropyl-N- (2-methylpropiPamino-thiazol-4-ylcarbonip-N'-rN- (6-methyl-3-pyridinylmethoxycarboniP-L -leucininhidrazide Following the procedure of example 1 (a) -1 (h), except that cis-2, 6-dimethylmorpholine is replaced by N-isobutylcycropropylamine in step (a) and 4-pyridylcarbinol by 6-methyl-3-pyridylcarbinol in the Step (f), the title compound was prepared as a white solid (220 mg, 88%). MS (ESI): 517.2 (M + H) +.

EXAMPLE 149 Preparation of N- (N-fer-butoxycarbonyl-L-leuciniP-N'-r2-rN-cyclopropyl-N- (2-methy1propiPamino-thiazol-4-ylcarbonyhydrazide Following the procedure of example 1 (a) -1 (d) and 1 (h), except that cis-2, 6-dimethylmorpholine is replaced by N-cyclopropyl isobutylamine in step (a) and N- (4-pyridine) nylmethoxycarbonyl) -L-leucine by N-tert-butoxycarbonyl-L-leucine in step (h), the title compound was prepared as a white solid (1.01 g, 89%). MS (ESI): 466.3 (M + H) +.

EXAMPLE 150 Preparation of N- | ~ 2- (1-naphthiPetiazol-4-ylcarbon-p-N'-rN- (7-quinolinoiD-L-b-fer-butylalaniphidrazide Following the procedure of example 59 (a) -59 (d), except that N-tert-butoxycarbonyl-L-leucine is replaced by N-tert-butoxycarbonyl-Lb-tert-butylalanine in step (b) and acid 8- quinolinecarboxylic acid by 7-quinolinecarboxylic acid in step (d), the title compound was prepared as a white solid (0.139 g, 80%). MS (ESI): 552.2 (M + H) 7 EXAMPLE 151 Preparation of N-f2- (1-naphthiPthiazol-4-ylcarbonin-N'-rN- (2-quinolinoiP-L-b-fer-butylalaniphidrazide Following the procedure of example 59 (a) -59 (d), except that N-tert-butoxycarbonyl-L-leucine is replaced by N-tert-butoxycarbonii-Lb-tert-butylalanine in step (b) and acid 8- 2-quinolinecarboxylic acid in step (d), the title compound was prepared as a white solid (0.158 g, 91%). MS (ESI): 552.2 (M + H) 7 EXAMPLE 152 Preparation of NH.N- (1-IsoquinolinoiP-L-b-tert-butylanlanin-N'-r2- (1-naphthiPetiazol-4-ylcarbonyhydrazide Following the procedure of example 59 (a) -59 (d), except that N-tert-butoxycarbonyl-L-leucine is replaced by N-tert-butoxycarbonyl-Lb-tert-butylalanine in step (b) and acid 8- quinolinecarboxylic acid by 1-isoquinolinecarboxylic acid in step (d), the title compound was prepared as a white solid (0.143 g, 82%). MS (ESI): 552.2 (M + H) 7 EXAMPLE 153 Preparation of N-fN- (3-isoquinolinoiP-L-b-tert-butylanan-N-r2- (1-naphthiPthiazol-4-ylcarbonipihydrazide Following the procedure of example 59 (a) -59 (d), except that N-tert-butoxycarbonyl-L-leucine is replaced by N-tert-butoxycarbonyl-Lb-tert-butylalanine in step (b) and acid 8- quinolinecarboxylic acid by 3-isoquinolinecarboxylic acid in step (d), the title compound was prepared as a white solid (0.130 g, 75%). MS (ESI): 552.2 (M + H) 7 EXAMPLE 154 Preparation of N-rN- (6-methylnicotinoiP-L-norleucine-N'-r2- (1-naphthiD-thiazol-4-ylcarbonipihydrazide Following the procedure of example 59 (a) -59 (d), except that N-tert-butoxycarbonyl-L-leucine is replaced by N-tert-butoxycarbonyl-L-norleucine in step (b) and 8-quinolinecarboxylic acid by 6-Methylnicotinic acid in step (d), the title compound was prepared as a white solid (0.109 g, 67%). MS (ESI): 502.2 (M + H) +.

EXAMPLE 155 Preparation of N-f2- (1-naphtho-PthiazoI-4-iCarbonin-N'-rN- (7-quinolino-P-L-norleucine-hydrazide Following the procedure of example 59 (a) -59 (d), except that N-tert-butoxycarbonyl-L-leucine is replaced by N-tert-butoxycarbonyl-L-norleucine in step (b) and 8-quinoxycarboxylic acid by 7-quinolinecarboxylic acid in step (d), the title compound was prepared as a white solid (0.104 g, 59%). MS (ESI): 538.1 (M + H) +.

EXAMPLE 156 Preparation of N-r2- (1-naphthiPetiazol-4-ylcarbonan-N'-rN- (2-quinolinino-P-L-norleucininhydrazide Following the procedure of example 59 (a) -59 (d), except that N-tert-butoxycarbonyl-L-leucine is replaced by N-tert-butoxycarbonyl-L-norleucine in step (b) and 8-quinolinecarboxylic acid by 2-quinolinecarboxylic acid in step (d), the title compound was prepared as a white solid (0.153 g, 87%). MS (ESI): 538.1 (M + H) 7 EXAMPLE 157 Preparation of N- | ~ N- (1-IsoquinolinoiP-L-norleucinip-N'-r2- (1-naphthiPetiazol-4-ylcarboninhydrazide Following the procedure of example 59 (a) -59 (d), except that N-tert-butoxycarbonyl-L-leucine is replaced by N-tert-butoxycarbonyl-L-norleucine in step (b) and 8-quinolinecarboxylic acid by 1-isoquinolinecarboxylic acid in step (d), the title compound was prepared as a white solid (0.151 g, 86%). MS (ESI): 538.1 (M + H) 7 EXAMPLE 158 Preparation of N-rN- (3-isoquinolinoiP-L-norleucinip-N'-r2- (1-naphthiD-thiazol-4-ylcarboninhydrazide Following the procedure of example 59 (a) -59 (d), except that N-tert-butoxycarbonyl-L-leucine is replaced by N-tert-butoxycarbonyl-L-norleucine in step (b) and 8-quinolinecarboxylic acid by 3-isoquinolinecarboxylic acid in step (d), the title compound was prepared as a white solid (0.126 g, 72%). MS (ESI): 538.1 (M + H) +.

EXAMPLE 159 Preparation of N-r2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazole-4-ylcarbonin-N'-rN- (5-hydroxymethylimidazol-4-ylcarboniP-L-b-cyclopropylalanine hydrazide Following the procedure of Example 56 (a) -56 (b), except that N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- (N-tert-butoxycarbonyl-) is substituted. L-leucinyl) hydrazide by N- (N-tert-butoxycarbonyl-Lb-cyclopropylalanyl) -N '- [2- (N-cyclopropyl-N-cyclopropylmethyl-amino) thiazol-4-ylcarbonyl] hydrazide in step (a) and picolinic acid by 5-hydroxymethylimidazole-4-carboxylic acid in step (b), the title compound was prepared as a white solid (50 mg, 44%). MS (ESI): 488.2 (M + H) +.

EXAMPLE 160 Preparation of N-r2-rN-cyclopropyl-N- (2-methylpropiPaminolthiazol-4-ylcarbonin-N'-rN- (8-quinilinoiP-L-b-cyclopropylalaniphidrazide a) N- (N-tert-butoxycarbonyl-Lb-cyclopropylalanyl) -N'-r 2 - [N-cyclopropyl] - (2-methylpropyl) amino] thiazol-4-ylcarbonyhydrazide Following the procedure of Example 1 (a) - 1 (d) and 1 (h), except that cis-2, 6-dimethylmorpholine is replaced by N-cyclopropyl isobutylamine in step (a) and N- (4-pyridinylmethoxycarbonyl) -L-leucine by N-tert-butoxycarbonyl -Lb-cyclopropylalanine in step (h), the title compound was prepared as a white solid (1.01 g, 89%). MS (ESI): 466.3 (M + H) 7 b) N-r2-rN-cyclopropyl-N- (2-methylpropyl) amino] thiazol-4-ylcarbonin-N'-rN- (8-quinolinoiP-Lb-cyclopropylalaniphidrazide) Following the procedure of example 56 (a) -56 ( b), except that N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- (N-tert-butoxycarbonyl-L-leucinyl) hydrazide is replaced by N- (N-ter -butoxycarbonyl-Lb-cyclopropylalanyl) -N '- [2- [N-cyclopropyl-N- (2-methylpropyl) amino] -thiazole-4-alkylcarbonyl] hydanidate in step (a) and picolinic acid for acid 8-quinolinecarboxylic acid in step (b), the title compound was prepared as a white solid (135 mg, 100%), MS (ESI): 521.2 (M + H) +.

EXAMPLE 161 Preparation of N-α2- (N-cyclopropyl-N-cyclopropio-n-cyanamino) thiazoi-4-ylcarbonin-N'-rN- (6-methylnicotinoiP-L-b-fer-butylalanine hydrazide Following the procedure of Example 56 (a) -56 (b), except that N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- (N-tert-butoxycarbonyl-) is substituted. L-leucinii) hydrazide by N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- (N-tert-butoxycarbonyl-Lb-tert-butylalanyl) hydrazide in step (a) and picolinic acid by 6-methylnicotinic acid in step (b), the title compound was prepared as a white solid (85 mg, 79%). MS (ESI): 499.2 (M + H) 7 EXAMPLE 162 Preparation of N-r2-rN-cyclopropyl-N- (2-methylpropiPaminolthiazol-4-ylcarbonip-N'-rN-4-methylimidazol-5-ylcarbonyl-P-L-b-cyclopropylalanidehydrazide Following the procedure of example 56 (a) -56 (b), except that N- [2- (N-cyclopropyi-N-cyclopropylmethylamino) thiazol-4-ylcarbonii] -N '- (N-tert-butoxycarbonyl-) is substituted. L-leucinyl) hydrazide by N- (N-tert-butoxycarbonyl-Lb-cyclopropylalanyl) -N '- [2- [N-cyclopropyl-N- (2-methylpropyl) amino] -thiazol-4-ylcarbonyl] hydrazide in the Step (a) and picolinic acid for 4-methylimidazole-5-carboxylic acid in step (b), the title compound was prepared as a white solid (100 mg, 73%). MS (ESI): 474.2 (M + H) +.

EXAMPLE 163 Preparation of N-r2-rN-cyclopropyl-N- (2-methylpropiPamino-thiazol-4-ylcarbonin-N'-rN- (2-quinolinoiP-L-b-cyclopropylalaninhydrazide Following the procedure of Example 56 (a) -56 (b), except that N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- (N-tert-butoxycarbonyl-) is substituted. L-leucine I) hydrazide by N- (N-tert-butoxycarbonyl-L-cyclopropylalanyl) -N '- [2- [N-cyclopropyl-N- (2-methylpropyl) amino] -thiazol-4-ylcarbonyl] hydrazide in the Step (a) and picolinic acid by 2-quinolinecarboxylic acid in step (b), the title compound was prepared as a white solid (75 mg, 59%). MS (ESI): 521.2 (M + H) 7 EXAMPLE 164 Preparation of N-r2-rN-cyclopropyI-N- (2-methylpropiPamino-thiazol-4-ylcarbonin-N'-rN- (6-methyl-nicotino-P-L-b-cyclopropylalanine hydrazide Following the procedure of Example 56 (a) -56 (b), except that N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- (N-tert-butoxycarbonyl-) is substituted. L-leucinyl) hydrazide by N- (N-tert-butoxycarbonyl-L-cyclopropylalanyl) -N '- [2- [N-cyclopropyl-N- (2-methylpropyl) amino] -thiazol-4-ylcarbonyl] hydrazide in step (a) and picolinic acid by 6-methylnicotinic acid in step (b), the title compound was prepared as a white solid (12 mg, 65%). MS (ESI): 485.3 (M + H) 7 EXAMPLE 165 Preparation of N-r2- (1-naphthiPthiazol-4-ylcarbonin-N'-rN- (8-quinolinoiPqliciniphidrazide a) N- (8-quinolinoyl) qlicine Following the procedure of example 102 (f) -102 (g), except that the methyl ester of L-Ieucine is replaced by the glycine methyl ester hydrochloride in step (f) , the title compound was prepared as a pale yellow solid (0.207 g, 95%). MS (ESI): 231.1 (M + H) 7 b) N-r2- (1-naphthyl) thiazol-4-ylcarbonip-N '- [N- (8-quinolinoyl) qylinin-hydrazide Following the procedure of example 1 (h), except that N- [2- (cis-2,6-dimethy-4-morpholino) thiazoi-4-ylcarbonyl] hydrazide by N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide and N- (4-pyridylmethoxycarbonyl) -L-leucine , by N- (8-quinolinoyl) glycine, the title compound was prepared as a tan solid (0.028 g, 12%). MS (ESI): 482.1 (M + H) 7 EXAMPLE 166 Preparation of N- | ~ 2- (1-naphthiPetiazol-4-ylcarbon-p-N'-rN- (8-quinolinoiP-L- norva-iniphidrazide Following the procedure of example 59 (a) -59 (d), except that N-tert-butoxycarbonyl-L-leucine is replaced by N-tert-butoxycarbonyl-L-norvaline in step (b), the title compound is prepared as a white solid (0.131 g, 74%). MS (ESI): 524.1 (M + H) 7 EXAMPLE 167 Preparation of N-r2- (1-naphthiPthiazol-4-ylcarbonyl-N'-rN- (2-quinolinoiP-L-norvaliniphidrazide Following the procedure of example 59 (a) -59 (b), except that N-tert-butoxycarbonyl-L-leucine is replaced by N-tert-butoxycarbonyl-L-norvaline in step (b) and 8-quinolinecarboxylic acid by 2-Quinoxycarboxylic acid in step (d), the title compound was prepared as a white solid (0.135 g, 75%). MS (ESI): 524.1 (M + H) 7 EXAMPLE 168 Preparation of N-r2- (1-naphtol-Pthiazol-4-ylcarbonin-N '- (N-picolinoyl-L-norvalinuhydride) Following the procedure of example 59 (a) -59 (d), except that N-tert-butoxycarbonyl-L-leucine is replaced by N-tert-butoxycarbonyl-L-norvaline in step (b) and 8-quinoxycarboxylic acid by picolinic acid in step (d), the title compound was prepared as a white solid (0.126 g, 79%). MS (ESI): 474.2 (M + H) 7 EXAMPLE 169 Preparation of N-Í2- (1-naphthiPathiazol-4-ylcarbonan-N'-rN- (6-methyl-nicotino-P-L-norvalinylhydrazide Following the procedure of example 59 (a) -59 (d), except that N-tert-butoxycarbonii-L-leucine is replaced by N-tert-butoxycarbonyl-L-norvaline in step (b) and 8-quinolinecarboxylic acid by 6-Methylnicotinic acid in step (d), the title compound was prepared as a white solid (0.141 g, 85%). MS (ESI): 488.2 (M + H) +.

EXAMPLE 170 Preparation of N-f2- (1-naphthiPthiazol-4-ylcarbonin-N'-rN- (4-rnethylimidazol-5-ylcarboniP-L-norvaHninhydrazide Following the procedure of Example 59 (a) -59 (d), except that N-tert-butoxycarbonyl-L-leucine is replaced by N-tert-butoxycarbonyl-L-norvaline in step (b) and 8-quino-incarboxylic acid by 4-methyl imidazole-5-carboxylic acid in step (d), the title compound was prepared as a white solid (0.098 g, 51%). MS (ESI): 477.1 (M + H) +.

EXAMPLE 171 Preparation of N- | ~ 2- (1-naphthiPthiazol-4-ylcarbonip-N'-rN- (1-isoquinolinoiD-L- norvayinillhidrazide Following the procedure of example 59 (a) -59 (d), except that N-tert-butoxycarbonyl-L-leucine is replaced by N-tert-butoxycarbonyl-L-norvayine in step (b) and 8-quinoxycarboxylic acid by 1-Isoquinolinecarboxylic acid in step (d), the title compound was prepared as a white solid (0.146 g, 82%). MS (ESI): 524.2 (M + H) +.

EXAMPLE 172 Preparation of N- | ~ 2- (1-naphtol-Pthiazol-4-ylcarbonip-N'-fN- (3-isoquinolinoiP-L-norvalininhydrazide Following the procedure of example 59 (a) -59 (d), except that N-tert-butoxycarbonyl-L-leucine is replaced by N-tert-butoxycarbonyl-L-norvaline in step (b) and 8-quinolinecarboxylic acid by 3-isoquinolinecarboxylic acid in step (d), the title compound was prepared as a white solid (0.138 g, 78%). MS (ESI): 524.2 (M + H) +.

EXAMPLE 173 Preparation of (1 S, 1 'S) -N, N'-bis-r4-H - (N-benzyloxycarbonylamino) -3-methylbutyrtiazoi-2-ylcarbonipihydrazide a) N-benzyloxycarbonyl-L-leucinamide To a stirred solution of N-benzyloxycarbonyl-L-leucine (4.6 g, 17. 3 mmol) in THF, cooled to -40 ° C, N-methylmorpholine (3.68 g) was added. 36. 4 mmoies; 4.0 ml) and isobutyl chloroformate (2.37 g, 17.3 mmoies, 2.25 ml). After stirring for 15 min, ammonia was bubbled through the solution for 5 min. The solution was warmed to room temperature, evaporated, and the residue was dissolved in ethyl acetate, washed with 0.1 N HCl and saturated brine, then dried (MgSO), filtered and evaporated to dryness to yield the title compound. title as a white solid (4.58 g, 100%). b) N-benzyloxycarbonyl-L-leucithioamide The solution of the compound of Example 1 (a) (4.58 g, 17.3 mmol) and Lawesson's reagent (4.21 g, 10.4 mmol) in THF was allowed to stir at room temperature for 16 hours. The solution was concentrated and the residue was purified by flash chromatography on 230-400 mesh silica gel, eluted with 1: 3 EtOAc / hexanes, to give the title compound as a pale yellow solid (3.74 g. , 77%). c) (1 S) -1-benzyloxycarbonylamino-1- (4-carboethoxythiazol-2-yl) -3-methylbutane The compound of example 1 (b) (2.20 g, 7.83 mmol) was dissolved in acetone (35 ml), it was cooled to -10 ° C, and ethyl bromopyruvate (1.68 g, 8.62 mmol, 1.08 ml) was added. After stirring for one hour, the solution was poured into methylene chloride / water, then saturated aqueous NaHC 3. The aqueous layer was extracted with methylene chloride and the combined organic layers were washed with saturated brine, dried (MgSO), filtered and concentrated. The residue was dissolved in methylene chloride, cooled to -20 ° C and pyridine (1.36 g, 17.2 mmol, 1.39 ml) and trifluoroacetic anhydride (1.81 g, 8.62 mmol, 1.22 ml) was added. After stirring for one hour, the solution was washed with saturated aqueous NaHCO 3 and saturated brine, then dried (MgSO), filtered and concentrated. The residue was purified by flash chromatography on 90 g of 230-400 mesh silica gel, eluted with 1: 3 ethyl acetate / hexanes, to give the title compound as a pale yellow oil (2.36 g, 80%). 1 H NMR (400 MHz, CDCl 3) d 8.08 (s, 1 H), 7.38 (m, 5 H), 5.42 (s, 3 H), 5.23-5.07 (m, 3 H), 4.42 (q, 2 H), 2.01 -1.62. (m, 3H), 1.41 (t, 3H), 0.99 (d, 6H). d) (1 S) -1-benzyloxycarbonylamino-1- (4-hydrazinocarbonyl-thiazol-2-yl) -3-methylbutane Following the procedure of example 1 (d), except that 2- (cis-2,6-dimethyl) is substituted -4-morpholino) thiazole-4-carboxylic acid ethyl ester by (1S) -1-benzyloxycarbonylamino-1- (4-carboethoxythiazol-2-yl) -3-methylbutane, the title compound was prepared as a pale yellow foam (2.01 g, 97%). 1 H NMR (400 MHz, CDCl 3) d 8.35 (bs, 1 H), 8.03 (s, 1 H), 7.37 (m, 5 H), 5.29 (d, 1 H), 5.14-5.09 (m, 3 H), 4.07 (bs, 2H), 1 .92-1.82 (m, 1 H), 1.79-1.66 (m, 2H), 1.00 (d, 6H). e) (1 S) -1-benzyloxycarbonylamino-1- (4-carboxythiazol-2-yl) -3-methylbutane Following the procedure of example 1 (g), except that the N- (4-pyridinylmethoxycarbonyl) methyl ester is substituted. ) -L-Leucine by (1 S) -1-benzyloxycarbonylamino-1- (4-carboethoxythiazol-2-yl) -3-methylbutane, the title compound was prepared as an EM white solid (ESI): 349.2 ( M + H) 7 f) (1 S, 1 'S) -N.N'-bis-r 4 -l 1 - (N-benzyloxycarbonylamino) -3-methylbutyn-thiazol-2-yl-carbonyl] hydrazide Following the procedure of Example 1 (h), except that N- [2- (cs-2,6-dimethyl-4-morpholino) thiazol-4-ylcarbonyl] hydrazide is replaced by (1 S) -1-benzyloxycarbonylamino-1 - ( 4-hydrazinocarbonylthiazol-2-yl) -3-methylbutane and N- (4-pyridylmethoxycarbonyl) -L-leucine by (1 S) -1-benzioxycarbonylamino-1- (4-carboxythiazol-2-yl) -3-methylbutane, the title compound was prepared as a white solid (0.028 g, 59%). MS (ESI): 693.1 (M + H) +.

EXAMPLE 174 Preparation of N-r2-rN-cyclopropyl-N- (2-methylpropiPamino-thiazole-4-iCocarbonip-N'-rN- (6-methylnicotino-P-L-b-tert-butylalanyl-hydrazide a) N- (N-tert-butoxycarbonyl-Lb-tert-butylalanyl) -N'-r2-rN-cyclopropyl-N- (2-methyl-propyl) aminolthiazol-4-ylcarbonipyridine Following the procedure of example 1 ( a) -1 (d) and 1 (h), except that cis-2, 6-dimethylmorpholine is replaced by N- (4-cyclopropyl isobutylamine) in step (a) and N- (4-pyridinylmethoxycarbonyl) - L-Leucine by N-tert-butoxycarbonii-Lb-tert-butylanine in step (h), the title compound was prepared as a white solid (0.44 g, 100%). MS (ESI): 482.3 (M + H) +. b) N-r2-rN-cyclopropyl-N- (2-methylpropyl) amino-1-azazol-4-ylcarbonip-N'-rN- (6-methylnicotinoyl) -Lb-tert-butylalanidphidrazide Following the procedure of example 56 ( a) -56 (b), except that N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazole-4-ylcarbonyl] N '- (N-tert-butoxycarbonyl-L-leucinyl) hydrazide is replaced by N- (N-tert-butoxycarbonyl-Lb-tert-butylalanyl) -N '- [2- [N-cyclopropyl-N- (2-methylpropyl) amino] -thiazoi-4-ylcarbonyl] hydrazide in step (a) and picolinic acid by 6-methylnicptinic acid in step (b), the title compound was prepared as a white solid (70 mg, 66%). MS (ESI): 501.2 (M + H) 7 EXAMPLE 175 Preparation of N-r2-rN-cyclopropyl-N- (2-methylpropiPamino-1-thiazole-4-8-carbonyl-N'-rN- (4-methyl-imidazol-5-ylcarboniP-L-b-tert-butylalanidphidrazide Following the procedure of Example 56 (a) -56 (b), except that N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- (N-tert-butoxycarbon) is substituted. L-leucinyl) hydrazide by N- (N-tert-butoxycarbonyl-Lb-tert-butylanyl) -N '- [2- [N-cyclopropyl-N- (2-methylpropyl) amino] -thiazol-4-ylcarbonyl] hydrazide in step (a) and picolinic acid by 4-methylimidazole-5-carboxylic acid in step (b), the title compound was prepared as a white solid (70 mg, 39%). MS (ESI): 490.2 (M + H) 7 EXAMPLE 176 Preparation of N-r2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazole-4-ylcarbonin-N'-rN- (1-isoquinolinoip-Lb-tert-butylan Nhydrazide Following the procedure of Example 56 (a) -56 (b), except that N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- (N-tert-butoxycarbonyl) is substituted. L-leucinyl) hydrazide by N- (N-tert-butoxycarbonyl-Lb-tert-butylanyl) -N '- [2- [N-cyclopropyl-N- (2-methylpropyl) amino] -thiazol-4-ylcarbonyl] hydrazide in step (a) and picolinic acid by 1-isoquinolinecarboxylic acid in step (b), the title compound was prepared as a white solid (123 mg, 88%). MS (ESI): 535.3 (M + H) 7 EXAMPLE 177 Preparation of N N- (5-butylpicolinoiP-L-b-fer-butylalan-p-N'-r2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonhydrazide Following the procedure of example 56 (a) -56 (b), except that N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- (N-tert-butoxycarbonyl-) is substituted. L-leucinyl) hydrazide by N- (N-tert-butoxycarbonyl-Lb-tert-butylalanyl) -N '- [2- [N-cyclopropyl-N- (2-methylpropyl) amino] -thiazole-4-ylcarbonyl ] hydrazide in step (a) and picolinic acid by 5-butylpicolinic acid in step (b), the title compound was prepared as a white solid (90 mg, 85%). MS (ESI): 541.3 (M + H) +.

EXAMPLE 178 Preparation of N-r2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazole-4-ylcarbonin-N'-fN- (6-methylpicolinoiP-L-b-fer-butylalanidphidrazide Following the procedure of Example 56 (a) -56 (b), except that N- [2- (N-cyclopropyl-cyclopropylmethyl amine) thiazol-4-ylcarbonyl] -N '- (N-tert-butoxycarbonyl-) is substituted. L-leucinyl) hydrazide by N- (N-tert-butoxycarbonyl-Lb-tert-butylanyl) -N '- [2- [N-cyclopropyl-N- (2-methylpropyl) amino] -thiazol-4-ylcarbonyl] hydrazide in step (a) and picolinic acid for 6-methylpicolinic acid in step (b), the title compound was prepared as a white solid (170 mg, 86%). MS (ESI): 499.2 (M + H) 7 EXAMPLE 179 Preparation of N-r2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazole-4-ylcarbonyl-N'-rN- (4-fluorobenzoiP-L-leucinehydrazide Following the procedure of example 56 (a) -56 (b), except that picolinic acid is replaced with 4-fluorobenzoic acid in step (b), the title compound was prepared as a white solid (88 mg, 97 mg). %). MS (ESI): 488.2 (M + H) +.

EXAMPLE 180 Preparation of N-rN- (4-fluorobenzoiP-L-leucinip-N'-r2- (1-naphthiPetiazol-4-ylcarbonyhydrazide Following the procedure of example 59 (a) -59 (d), except that 8-quinolinecarboxylic acid was replaced by 4-fluorobenzoic acid in step (d), the title compound was prepared as a white solid (0.1%). g, 69%). MS (ESI): 505.1 (M + H) 7 EXAMPLE 181 Preparation of N-r2- (1-naphthiPthiazof-4-ylcarbonyl-N'-rN- (2-pyridinylmethoxycarboniP-L-b-fer-butylalanine hydrazide a) L-b-tert-butylalanine methyl ester hydrochloride To a suspension of L-b-tert-butylalanine (2.0 g, 13.8 mmol) in 2,2-dimethoxypropane (75 ml) was added concentrated hydrochloric acid (12 ml). After standing at room temperature for 16 hours, the solution was concentrated, redissolved in ethyl acetate and washed with 7.5% Na2CO3 (2X). The organic layer was dried (MgSO), filtered and concentrated to yield the free base (1.3 g, 8.2 mmol). This was dissolved in ether and HCl (8.2 ml, 1.0 M in ether) was added. The white precipitate was collected by filtration and yielded the title compound as a white solid (1.32 g, 49%). MS (ESI): 159.7 (M + H) +. b) N- (2-pyridinylmethoxycarbonyl) -Lb-tert-butylanine Following the procedure of example 1 (e) -5 (g), except that L-leucine methyl ester hydrochloride is replaced by methyl ester hydrochloride Lb-tert-butylalanine in step (e) and 4-pyridylcarbinol by 2-pyridylcarbinol in step (f), the title compound was prepared as a white solid (0.55 g, 100%). MS (ESI): 281.3 (M + H) +. c) N-α2- (1-naphthyl) thiazol-4-ylcarbonin-N '- [N- (2-pyridylmethoxycarbonyl) -Lb-tert-butylalanine hydrazide Following the procedure of example 1 (h), except that N- [2- (cis-2,6-dimethyl-4-morpholino) thiazol-4-ylcarbonyl] hydrazide is replaced by N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide and N- (4-pyridylmethoxycarbonyl) -L-leucine by N- (2-pyridinylmethoxycarbonyl) -Lb-tert-butylanine, the title compound was prepared as a white solid (0.155 g, 47%). MS (ESI): 532.2 (M + H) +.

EXAMPLE 182 Preparation of N-rN- (2-methyl-3-pyridinylmethoxycarboniP-L-b-tert-butylalanip-N'-r2- (1-naphthi-Pithiazol-4-ylcarboni | - | hydrazide Following the procedure of example 181 (a) -181 (c), except that 2-pyridylcarbinol was substituted for 2-methyl-3-pyridinylcarbinol in step (b), the title compound was prepared as a white solid ( 0.169 g, 67%). MS (ESI): 546.2 (M + Hf.

EXAMPLE 183 Preparation of N-r2- (1-naphthiPthiazoi-4-ylcarbonyl-N'-rN- (2-pyridinylmethoxycarboniP-L-b-cycloprophalaniphidrazide a) Lb-cyclopropylalanine methyl ester hydrochloride Following the procedure of Example 181 (a), except that Lb-tert-butylalanine is substituted for the N-tert-butoxycarbonyl-L-cyclopropylalanine methyl ester, the title compound was prepared as a white solid (2.2 g, 30%). MS (ESI): 144.0 (M + H) 7 b) N-f2- (1-naphthyl) thiazol-4-ylcarbonin-N'-rN- (2-pyridinylmethoxy-carbonyl) -L-b-cyclopropylalanine hydrazide Following the procedure of example 181 (b) -181 (c), except that the methyl ester hydrochloride of Lb-tert-butylalanine is replaced by the methyl ester hydrochloride of Lb-cyclopropylalanine in step (b), the compound of the title was prepared as a white solid (0.147 g, 61%). MS (ESI): 516.1 (M + H) 7 EXAMPLE 184 Preparation of N-fN- (2-methyl-3-pyridinylmethoxycarboniP-L-b-cyclopropylalanin-N'-r2- (1-naphthiPetiazol-4-ylcarboni-P-hydrazide Following the procedure of Example 181 (a) -181 (c), except that Lb-tert-butylalanine is substituted for the N-tert-butoxycarbonyl-L-cyclopropylalanine methyl ester in step (a) and 2-pyridylcarbinol for 2-pyridylcarbinol. -methyl-3-pyridylcarbinol in step (b), the title compound was prepared as a white solid (0.159 g, 65%). MS (ESI): 530.2 (M + H) +.

EXAMPLE 185 Preparation of N-rN- (6-methyl-3-pyridinylmethoxycarboniP-L-b-cyclopropylalanip-N'-r2- (1-naphthiPetiazol-4-ylcarbonnhydrazide Following the procedure of Example 181 (a) -181 (c), except that Lb-tert-butylalanine is replaced by the methyl ester N-tert-butoxycarbonii-L-cyclopropylalanine in step (a) and 2-pyridylcarbinol by methyl-3-pyridylcarbinol in step (b), the title compound was prepared as a white solid (0.169 g, 69%). MS (ESI): 530.2 (M + H) +.

EXAMPLE 186 Preparation of N-rN- (6-methyl-3-pyridinylmethoxycarboniP-L-b-fer-butyialanyl-N'-22- (1 -naphthyl) thiazole-4-alkylcarbonylhydrazide Following the procedure of example 181 (a) -181 (c), except that 2-pyridylcarbinol was substituted for 6-methyl-3-pyridylcarbinol in step (b), the title compound was prepared as a white solid ( 0.194 g, 77%). MS (ESI): 546.2 (M + H) 7 EXAMPLE 187 Preparation of N, Nl-bis- [2- (1-naphthi-Pthiazol-4-ylcarboniphidrazide a) Ethyl 2- (1-naphthyl) thiazole-4-carbohydrazide Following the procedure of example 3 (a) -3 (c), except that 4-methyl-1-naphthylboronic acid is substituted for 1-naphthylboronic acid in step (e), the title compound was prepared as a pale yellow solid EM (ESI): 270.1 (M + H) +. a) Ethyl 2- (1-naphthiaPetiazole-4-carbohydrazide) Following the procedure of example 1 (g), except that the N- (4-pyridinylmethoxycarbonyl) -L-leucine methyl ester is replaced by 2 (1-) Naphthyl) thiazole-4-ethyl carbohydrazide, the title compound was prepared as an EM white solid (ESI): 256.0 (M + H) +.

EXAMPLE 188 Preparation of N-r2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazole-4-88carbonin-N'-rN-r2- (1, 8-naphthyridinoiP1-L-b-cyclopropylalaninhydrazide Following the procedure of Example 56 (a) -56 (b), except that N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- (N-tert-butoxycarbonyl-) is substituted. L-leucinyl) hydrazide by N- (N-tert-butoxycarbonyl-Lb-cyclopropylalanyl) -N '- [2- (N-cyclopropyl-N-cyclopropymethyl-amino) thiazol-4-ylcarbonyl] hydrazide in step (a) and piconilic acid by 1,8-naphthyridine-2-carboxylic acid in step (b), the title compound was prepared as a white solid (100 mg, 59%). MS (ESI): 520.2 (M + H) 7 EXAMPLE 189 Preparation of N-r2-rN-cyclopropyl-N- (2-methylprop.Pamino-thiazol-4-ylcarbonin-N'-rN- (3,4-difluorobenzoiP-L-b-cyclopropylalanine hydrazide Following the procedure of Example 56 (a) -56 (b), except that N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- (N-tert-butoxycarbonyl-) is substituted. L-leucinyl) hydrazide by N- (N-tert-butoxycarbonyl-Lb-cyclopropylalanyl) -N '- [2- [N-cyclopropyl-N- (2-methylpropyl) amino] -thiazol-4-ylcarbonyl] hydrazide in the Step (a) and picolinic acid by 3,4-difluorobenzoic acid in step (b), the title compound was prepared as a white solid (208 mg, 100%). MS (ESI): 506.1 (M + H) +.

EXAMPLE 190 Preparation of N-r2-fN-cyclopropyl-N- (2-methylpropiPaminolthiazol-4-ylcarbonyl-N'-rN- (4-fluorobenzoiP-L-leucinehydrazide Following the procedure of Example 56 (a) -56 (b), except that N- [2- (N-cyclopropyi-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- (N-tert-butoxycarbonyl-) is substituted. L-leucinyl) hydrazide by N- (N-tert-butoxycarbonyl-L-leucinyl) -N '- [2- [N-cyclopropyl-N- (2-methylpropyl) amino] tiazol-4-ylcarbonyl] hydrazide in Step (a) and picolinic acid by 4-fluorobenzoic acid in step (b), the title compound was prepared as a white solid (130 mg, 70%). MS (ESI): 490.2 (M + H) +.

EXAMPLE 191 Preparation of N-rN- (5-butylpicolinoyl-L-leucinin-N'-r2- (N-cyclopropyl-N-c8-chloropropylmethylamino) thiazol-4-ylcarbonyhydrazide Following the procedure of example 56 (a) -56 (b), except that N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- (N-tert-butoxycarbon) is substituted. L-leucinyl) hydanidase by N- (N-tert-butoxycarbonyl-L-leucinyl) -N '- [2- [N-cyclopropyl-N- (2-methylpropyl) amino] thiazole-4-l-carbonyl] hydrazide in step (a) and picolinic acid for 5-butylpicolinic acid in step (b), the title compound was prepared as a white solid (100 mg, 63%). MS (ESI): 529.3 (M + H) +.

EXAMPLE 192 Preparation of N-r2-rN-cyclopropyl-N- (2-methyl-1-propiopazol-4-ylcarbonin-N'-fN- (3,4-dimethoxybenzoiP-L-leucine-hydrazide Following the procedure of Example 56 (a) -56 (b), except that N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazoi-4-ylcarbonyl] -N '- (N-tert-butoxycarbonyl-) is substituted. L-leucinyl) hydrazide by N- (N-tert-butoxycarbonyl-L-leucinyl) -N '- [2- [N-chloropropyl-N- (2-methylpropyl) amino] thiazol-4-ylcarbonyl] hydrazide in Step (a) and picolinic acid by 3,4-dimethoxybenzoic acid in step (b), the title compound was prepared as a white solid (130 mg, 84%). MS (ESI): 532.2 (M + H) +.

EXAMPLE 193 Preparation of N-r2-rN-cyclopropyl-N- (2-methylpropipamino-thiazol-4-ylcarbonin-N'-rN- (3,4-difluorobenzoiP-L-b-tert-butylalaniphidrazide Following the procedure of Example 56 (a) -56 (b), except that N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- (N-tert-butoxycarbonyl-) is substituted. L-leucine) hydrazide by N- (N-tert-butoxycarbonyl-Lb-tert-butylalanyl) -N '- [2- [N-cyclopropyI-N- (2-methylpropyl) amino] -thiazole-4-ylcarbonyl ] hydrazide in step (a) and picolinic acid for 3,4-difluorobenzoic acid in step (b), the title compound was prepared as a white solid (120 mg, 78%). MS (ESI): 522.2 (M + H) +.

EXAMPLE 194 Preparation of N-r2-rN-cyclopropyl-N- (2-methylpropiPamino-1-thiazole-4-i-carbon-p-N'-rN- (3,4-D-methoxy-benzo-P-L-b-fer-butylalanyl-hydrazide Following the procedure of Example 56 (a) -56 (b), except that N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- (N-ter-N-) is substituted. butoxycarbonyl-L-leucyl) hydrazide by N- (N-tert-butoxycarbonyl-L-tert-butylalanyl) -N '- [2- [N-cyclopropyl-N- (2-methylpropyl) amino] -thiazole-4 -carbonyl] hydrazide in step (a) and picolinic acid by 3,4-dimethoxybenzoic acid in step (b), the title compound was prepared as a white solid (73 mg, 51%). MS (ESI): 546.3 (M + H) +.

EXAMPLE 195 Preparation of N-rN- (5-butylphenyl) -P-L-b-fer-butylalanip-N'-r2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonylphidrazide Following the procedure of Example 56 (a) -56 (b), except that N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- (N-tert-butoxycarbonyl-) is substituted. L-leucinyl) hydrazide by N- (N-tert-butoxycarbonyl-Lb-tert-butylalanyl) -N '- [2- [N-cyclopropyl-N- (2-methyIpropyl) amino] -thiazol-4-ylcarbonyl] hydrazide in step (a) and picolinic acid by 5-butylpicolinic acid in step (b), the title compound was prepared as a white solid (120 mg, 77%). MS (ESI): 543.2 (M + H) +.

EXAMPLE 196 Preparation of N-r2-rN-cyclopropyl-N- (2-rnetiipropiPamino-thiazol-4-ylcarbonyl-N'-rN- (6-methylpicolinoiP-L-b-tert-butylalanidphidrazide Following the procedure of Example 56 (a) -56 (b), except that N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- (N-tert-butoxycarbonyl) is substituted. L-leucinyl) hydrazide by N- (N-tert-butoxycarbonyl-Lb-tert-butylalanii) -N '- [2- [N-Chlopropyl-N- (2-methylpropyl) amino] -thiazol-4-ylcarbonyl] hydrazide in step (a) and picolinic acid for 6-methylpicolinic acid in step (b), the title compound was prepared as a white solid (104 mg, 72%). MS (ESI): 501.3 (M + H) +. The above specification and the examples completely describe how to make and use the compounds of the present invention. However, the present invention is not limited to the particular embodiments described hereinabove, but includes all modifications thereof within the scope of the following claims. The various references to periodicals, patents and other publications, which are cited herein, comprise the most advanced technique and are incorporated herein for reference as to whether they are indicated completely for the same.

Claims (2)

1. NOVELTY OF THE INVENTION CLAIMS 1 .- A compound of the formula I: wherein: L is C2.e alkyl, Ar-C06 alkyl, Het-C0-6 alkyl, CH (R4) NR5R6, CH (R4) Ar, CH (R4) OAr1 or NR4R7; Ar is phenyl or naphthyl; Ar 'is phenyl or naphthyl; Het is a stable 5- to 7-membered monocyclic heterocyclic ring, or stable 7- to 10-membered bicyclic ring, which is either saturated or unsaturated and consisting of carbon atoms and one to four heterogeneous atoms selected from the group consisting of N, O and S, the heterocyclic ring being attached to any heterogeneous atom or carbon atom which results in a stable structure, or any bicyclic group in which any of said heterocyclic monocyclic rings is fused to a benzene ring; W is C (O) or SO2; X, Y and Z are independently N, O, S or CR10, provided that at least two of X, Y and Z are heterogeneous atoms and at least one of X, Y and Z is N, or one of X, Y and Z are C = N, C = C or N = N and the other two are CR10 or N, as long as at least two of X, Y and Z are N; ~ indicates a single or double bond in the five-member heterocycle; R ', R1, R2, R5, R8, R9, R10 and R12 are independently H, C1-6 alkyl, C2-6 alkenyl, Ar-Co-alkyl or Het-alkyl of C0-e; R3 is C3-e alkyl, Ar, Het, CH (R11) Ar, CH (R11) OAr, NR11R12, CH (R11) NR12R13; or R4, R11 and R15 are independently H, C-? -6 alkyl, C2-6 alkeniio, C3-6 cycloalkyl-Co-6-alkyl, Co-6-alkyl or Het-alkyl of Co-β ! R7 is d6 alkyl, C6-6 alkenyl, C3-6 cycloalkyl- C0-6alkyl, C6-6alkyl or Het-C0-6alkyl; R6 and R13 are R14, R14C (O), R14C (S), R14OC (O) or R14OC (O) NR9CH (R15) (CO), and R14 is alkyl, C2-6 alkenyl, Arkylamino Co-6 or Het C0-6 alkyl and pharmaceutically acceptable salts, hydrates and solvates thereof.
2. 2. A compound according to claim 1, further characterized in that Ar is independently substituted by one or more portions that are selected from the group consisting of: Ph-alkyl of Co-6, Het-alkyl of CO-6, Ct-6 alkyl, C-? 6 alkoxy, C0-6 Ph-alkoxy, C0-e-Het-alkoxy, OH, (CH ^ -eNR ^ 9, OCH2 ^ -eNR ^ 9, CO2R 'or Halogen 3. A compound according to claim 2, further characterized in that Ph is independently substituted by one or more portions that are selected from the group consisting of: Ci. 6 alkyl) C? -6 alkoxy, OH, (CH2)? ^ NR? R9, O (CH2) 1-6 NR8R9, CO2R 'or halogen. 4. A compound according to claim 2, further characterized in that two C? -6 alkyl groups combine to form a 5-7 membered, saturated or unsaturated ring fused on the Ar ring. 5. A compound according to claim 1, further characterized in that Ar 'is independently substituted by one or more portions that are selected from the group consisting of: Ph-alkyl of Co-6, Het-alkyl of Co-6, alkyl of d-6, alkoxy of C? -6, Ph-alkoxy of Co-β, Het-alkoxy of C0-6, OH, (CH2)? -6NR8R9, O (CH2) 1-6NR8R9, CO2R 'or halogen . 6. A compound according to claim 5, further characterized in that Ph is independently substituted by one or more portions that are selected from the group consisting of: alkyl of, alkoxy of, OH, (CH2)? - 6NR8R9, O (CH2)? - 6NR8R9, CO2R 'or halogen. 7. A compound according to claim 5, further characterized in that two alkyl groups of d-6 combine to form a ring of 5-7 members, saturated or unsaturated, fused on the ring Ar *. 8. A compound according to claim 1, further characterized in that Het is independently substituted by one or more portions that are selected from the group consisting of: Ph-alkyl of Co-6, Het-alkyl of CO-6, alkyl from d.6, C-.Q alkoxy, Ph-C0-6 alkoxy, C0-6 Het-alkoxy, OH, (CH2)? -eNR8R9, O (CH2) 1-6NR8R9 or CO2R '. 9. A compound according to claim 8, further characterized in that Ph is independently substituted by one or more portions that are selected from the group consisting of: C? _ alquiloalkyl, d-6alkoxy, OH, (CH 2) - -NR 8 R 9, O (CH 2) 1.6NR 8R 9 , CO2R 'or halogen. 10. A compound according to claim 8, further characterized in that two alkyl groups of d-β combine to form a 5-7 membered, saturated or unsaturated ring, fused to the Het ring. 1. A compound according to claim 1, further characterized in that Het is selected from the group consisting of the piperidinyl, piperazinyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, 2-oxoazepinyl, azepinyl, and pyrrolyl rings. , 4-piperidoniio, pyrrolidinyl, pyrazolyl, pyrazolidinyl, imidazolyl, triazolyl, tetrazolyl, pyridyl, pyrazinyl, pyridazinyl, pyrimidinyl, triazinyl, tetrazinyl, oxazolidinyl, oxazolinyl, oxazolyl, isothiazolyl, isoxazolyl, morpholinyl, thiazolidinyl, thiazolinyl, thiazolyl, quinuclidinyl, indolyl , quinolinyl, isoquinolinyl, benzimidazolyl, benzopyranyl, benzoxazolyl, furyl, pyranyl, tetrahydrofuryl, tetrahydropyranyl, thienyl, benzoxazolyl, thiamorpholinyl sulfoxide, thiamorpholinyl sulfone, thiadiazolyl and oxadiazolyl. 12. A compound according to claim 1, further characterized in that R4 and R7 can be combined to form a carbocyclic or heterocyclic 3-7 membered monocyclic or 7-10 membered bicyclic ring. 13. A compound according to claim 12, further characterized in that said carbocyclic or heterocyclic 3-7 membered monocyclic or 7-10 membered bicyclic ring is independently substituted with 1-4 portions which are selected from the group consisting of: C6-6alkyl, C6-6alkylamino, C6-6alkynyl, C0-6alkoxy, C0-ealkyloxy, C0-e-Het-alkoxy, OH, (CH2)? - 6NR8R9 and O (CH2) 1-6NR8R9. 14. A compound according to claim 1, further characterized in that Z = N, X = S and Y = CH. 15. A compound according to claim 14, further characterized in that R3 is further defined as: wherein: R16 is H or C1-6 alkyl; R17 is alkyl of d-6, alkenyl of C2-6 or cycloalkyl of C3-11 and R18 is alkyl of C3-6, O-alkyl of C3.6, Ar, Het, O (CH2) or -3Ar or O (CH2) o-3Het. 16. A compound according to claim 15, further characterized in that R16 is H or Me. 17. - A compound according to claim 15, further characterized in that R17 is n-propyl, / so-propyl, / so-pentyl, tert-butylmethyl, cyclopropylmethyl, / so-butyl, n-butyl or allyl 18.- A compound according to claim 15, further characterized in that R18 is selected from the group consisting of: 2-pyridinylmethoxy, 3-pyridinylmethoxy, 4-pyridinylmethoxy, tert-butoxy, 2-pyridinyl, 3-pyridinyl, 4-pyridinyl, 2-pyrazinyl , 4-tert-butoxycarbonylbenzyloxy, 4-carboxybenzyloxy, 3-tert-butoxycarbonylbenzyloxy, 3-carboxybenzyloxy, 2-methyl-3-pyridinylmethoxy, 6-methyl-3-pyridinylmethoxy, benzyloxy, 2-quinoxy, 3-quinoline, 4- quinoline, 5-quinoline, 6-quinoline, 7-quinoline, 8-quinoline, 1-isoquinoline, 3-isoquinoline, piperidinyl, 4-methylpiperidinyl, 4-methylimidazol-5-yl, N-benzyl-pyrrolidinyl, N-methyl- pyrrolidinyl, 1-benzyl-5-methylimidazoi-4-yl, 1-piperazinyl; 3- (2-pyridyl) benzyl, 2-methyl-3-pyridinyl, 2-methyl-4-pyridinyl, 6-methyl-3-pyridinyl, 4-dimethylaminobenzyloxy, 4- (4-morpholinomethyl) phenyl, 5-hydroxymethylimidazole- 4-yl, 5-butyl-2-pyridinyl, 4-fluorophenyl, 3,4-difluorophenyl, 2- (1,8-naphthyridinyl) or 3,4-dimethoxyphenyl. 19. A compound according to claim 14, further characterized in that L is selected from the group consisting of: 4- (cis-2,6-dimethyl) -4-morpholinyl, N-cyclopropymethyl-N- (2) -methylpropyl) amino, 4-methyl-1-naphthyl, N-methyl-N- (2-methylpropyl) amino, 1-naphthyl, 5-acenaphthyl, N-cyclopropyl-N-cyclopropylmethylamino, N, N-bis- (2 -methylpropyl) amino, 1- (1, 2,3,4-tetrahydroquinolino, N-cyclopropylmethyl-N-propylamino, N- (2-methylpropyl) -N-phenylamino, 2-methoxy-1-naphthyl, 2-benzyloxyphenyl, 2-benzyloxy-1-naphthyl, 9-phenanthrenyl, 9-anthracenyl, phenyl, 2- (4-tert-butoxycarbonyl) benzyloxyphenyl, 2- (4-carboxybenzyloxy) phenyl, N-cyclopropylamino, 8-quinoline, N, N -bis- (cyclopropylmethyl) amino, 4- (2,2-dimethylaminoethoxy) -1 -naphthyl or 1- (N-benzyloxycarboniamino) -3-methylbutyl 20.- A compound according to claim 1 which is selected from the group which consists of: N- [2- (cis-2,6-dimethyl-4-morpholino) thiazol-4-ylcarbonyl] -N '[N- (4-pyridinylmethoxycarbonyl) -L-leucinyl] hydrazide; N- [2 - [N-cyclo-propylmethyl-N- (2-methylpropyl) amino] thiazol-4-ylcarbonyl] -N '- [N- (4-pyridinylmethoxycarbonyl) -L-leucinyl] hydrazide; N- [2- (4-methyl-1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (4-pyridinylmethoxycarbonyl) -L-leucinyl] hydrazide; N- [2- [N-methyl- (2-methyIpropyl) amino] -thiazol-4-ylcarbonyl] -N '- [N-methyl-N- (4-pyridinylmethoxycarbonyl) -L-leucinyl] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (3-pyridinylmethoxycarbonyl) -L-leucinyl] -hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (2-pyridinylmethoxycarbonyl) -L-leucinyl] hydrazide; N- [2- (5-Acenaphthyl) thiazol-4-ylcarbonyl] -N '- [N- (4-pyridinylmethoxycarbonyl) -L-leucinyl] hydrazide; N- [2- [N-cyclopropylmethyl-N- (2-methylpropyl) amino] -thiazoi-4-ylcarbonyl] -N '- [N-methyl-N- (4-pyridinylmethoxycarbonyl) -L-leucinyl] hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- [N- (4-pyridinyl-methoxycarbonyl) -L-leucinyl] hydrazide; N- [2- [N-cyclopropylmethyl-N- (2-methylpropyl) -amino] thiazol-4-ylcarbonyl] -N '- [N- (3-pyridinylmethoxycarbonyl) -L-leucine] hydrazide; N- [2- [N-cyclopropylmethi-N- (2-methylpropyl) amino] thiazol-4-ylcarbonyl] -N '- [N- (2-pyridinylmethoxycarbonyl) -L-leuciniI] hydrazide; N- [2- [N-cyclopropylmethyl-N- (2-methyl-propyl) amino] thiazol-4-ylcarbonyl] -N '- [N-methyl-N- (3-pyridinylmethoxycarbonyl) -L-Iuccinyl] hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino] thiazol-4-ylcarbonyl] -N '- [N- (3-pyridinylmethoxycarbonyl) -L-leucinyl] hydrazide; N- [2- (N-cyclopropyl) -N-cyclopropylmethylamino] tiazol-4-ylcarbonyl] -N '- [N-methyl-N- (4-pyridinyl-methoxycarbonyl) -L-leucinyl] hydrazide; N- [2- [N, N- Bis- (2-methylpropyl) amino] thiazol-4-ylcarbonyl] -N '- [N- (2-pyridinylmethoxycarbonyl) -L-leucine] hydrazide; N- [N- (4-pyridinyl-methoxycarbonyl) -L-leucinyl] -N '- [2- [1 - (1, 2,3,4-tetrahydroquinolino)] thiazol-4-ylcarbo-niljhydrazide; N- [2- [N-methyI-N- (2-methy1propyl) amino] thiazol-4-ylcarbonyl] -N '- [4-methyl-2- (3-phenyl) phenylpent-4-enoyl] hydrazide; N- [2- [N, N-bis- (2-methylpropyl) amino] -thiazol-4-ylcarbonyl] -N '- [N -methyl-N- (3-pyridinylmethoxycarbonyl) -L-leucinyl] hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- [N -methyl-N- (3-pyridinylmethoxycarbonyl) -L-leucinyl] hydrazide; N- [2- (N-cyclopropylmethyl-N-propyl-amino) thiazol-4-ylcarbonyl] -N '- [N- (3-pyridinimethoxycarbonyl) -L-leucinyl] hydrazide; N- [2- [N-methyl-N- (2-methylpropyl) amino] thiazol-4-ylcarbonyl] -N '- [4-methyl-2- (3-phenyl) -phenylpentanoyl] hydrazide; N- [N- (2-methylpropyl) -N- (3-phenylphenyl) carbamoyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- [4-methyl-2- (3-phenyl) phenylpentanoyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- [4-methyl-2- (3-phenyl) phenylpentanoyl] -N '- [2- [N- (2-methylpropyl) -N-phenylamino] thiazol-4-ylcarbonyl] hydrazide; N- [2- (2-methoxy-1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (4-pyridinimethoxycarbonyl) -L-eucinyl] hydrazide; N- [2- (2-benzyloxyphenyl) thiazol-4-ylcarbonyl] -N '- [4-methyl-2- (3-phenyl) phenylpentanoyl] -hydrazide; N- [2- (2-benzyloxy-1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (4-pyridinylmethoxycarbonyl) -L-leucinyl] hydrazide; N- [2- [N, N-bis- (2-methy1propyl) amino] thiazol-4-ylcarbonyl] -N '- [N-methyl-N- (2-pyridinylmethoxycarbonyl) -L- leucinyl] hydrazide; N- [2- (9-Phenanthrenyl) thiazol-4-ylcarbonyl] -N '- [N- (4-pyridinylmethoxycarbonyl) -L-leucinyl] -hydrazide; N- [2- (9-anthracenyl) thiazole-4-carbonyl] -N '- [N- (4-pyridinylmethoxycarbonyl) -L-leucinyl] hydrazide; N- [2- [N, N-bis- (2-methylpropyl) amino] thiazol-4-ylcarbonyl] -N '- (tert-butoxycarbonyl-L-leucinyl] hydanzate; N- [2- [N, N-bis- (2-methylpropyl) amino] -thiazol-4-ylcarbonyl] -N '- [N- (L-leucinyl)] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] - N '- [N-methyl-N- (3-pyridinylmethoxycarbonyl) -L-leucinii] hydrazide; N- [2- [N, N-bis- (2-methylpropyl) amino] thiazol-4-ylcarbonyl] - N '- (N-picoiinoyl-L-leucinyl) hydrazide; N- [2- [N, N-bis (2-methylpropyl) amino] thiazol-4-ylcarbonyl] -N' - [N- (2-p) razinocarbonyl) -L-leucinyljhydrazide; N- [N, N-bis (2-methylpropyl) carbamoyl] -N '- [2- [N- (2-methylpropyl) -N-phenylamino] thiazol-4-ylcarbonyl] hydrazide; N- (2-phenylthiazol-4-ylcarbonyl] -N '- [N- (4-pyridinylmethoxycarbonyl) -L-leucinyl] hydrazide; N- [2- [2- (4-tert-butoxycarbonyl) benzyl] -oxophenyl] thiazole-4-alkylcarbonyl] -N '- [N- (4-pyridinylmethoxycarbonyl) -L-leucinyl] hydrazide; N- [2- [2- (4-carboxybenzyloxy) phenyl] thiazole- 4-ylcarbonyl] -N '- [N- (4-pyridinylmethoxycarbonyl) -L-leucinyl] hydrazide; N- [N- (4-tert-butoxycarboniibenzyloxycarbonyl) -L-leucinyl] -N' - [2- [ N- (2-methyl) propyl) -N-phenylamino] thiazol-4-ylcarbonyl] hydrazide; N- [2- [N, N-bis- (2-methylpropyl) amino] thiazol-4-ylcarbonyl] -N '- [N- (4-tert-butoxycarbonyl-benzyloxycarbonyl) -L-leucinyl] hydrazide; N- [N- (4-carboxybenzyloxycarbonyl) -L-leucinyl] -N '- [2- [N- (2-methylpropyl) -N-phenylamino] thiazol-4-ylcarbonii] hydrazide; N- (N-benzyloxycarbonyl-L-leucinyl) -N '- [2- [2- (4-tert-butoxycarbonyl) benzyloxyphenyl] thiazole-4-ylcarbonyl] hydrazide; N- (N-benzyloxycarbonyl-L-leucinyl) -N '- [2- [2- (4-carboxy-benzyloxy) phenyl] thiazol-4-ylcarbonii] hydrazide; N- [N- (6-methyl-3-pyridinimethoxy-carbonyl) -L-leucinyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- (N-benzyloxycarbonyl-L-leucinyl) -N '- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbo-nyl] hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- [N- (2-pyridinylmethoxycarbonyl) -L-leucinyl] hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- [N- (6-methyl-3-pyridinylmethoxycarbonyl) -L-leucinyl] hydrazide; N- (N-tert-butoxycarbonyl-L-leucinyl) -N '- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] hydrazide; N- [2- (N-cyclopropyl-N-cyclo-propylmethylamino) thiazol-4-ylcarbonyl] -N '- [N -methyl-N- (2-pyridinylmethoxycarbonyl) -L-leucinyl] hydrazide; N- [2- (2-benzyloxyphenyl) thiazol-4-ylcarbonyl] -N '- [N- (6-methyl-3-pyridinylmethoxycarbonyl) -L-leucinyl] hydrazide; N- [2- (2-benzyloxyphenyl] thiazol-4-ylcarbonyl] -N '- [N- (2-methyl-3-pyridinylmethoxycarbonyl) -L-leucinyl] hydrazide; N- [2- [N-methyl-N- (2-methylpropyl) amino] thiazol-4-ylcarbonyl] -N '- [N- (6-methyl-3-pyridinylmethoxycarbonyl) -L-leucinyl] hydrazide; N- [2- [N-methyl-N- (2-methylpropyl) amino] thiazoI-4-ylcarbonyl] -N '- [N - () - L-leucinyl] hydrazide; N- [2- [N-cyclopropyl-N-cyclopropylmethyl-amino) thiazol-4-ylcarbonyl] -N '- (N-picolinoyl-L-leucinyl) hydrazide; N- [2- [N-cyclo-propyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- [N- (2-methyl-3-pyridyl-methoxycarbonyl) -L-leucinyl] ] hydrazide; N- [N- (3-tert-butoxycarbonylbenzyloxycarbonyl) -L-leucinyl] -N '- [2- (N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] hydrazide; N- [2- (1-naphthyl) thiazole-4-carbonyl] -N '- [N- (8-quinolinoyl) -L-leucinyl] -hydrazide; N- [N- (2-methyl-3-pyridinylmethoxycarbonyl) -L-leucinyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- (N-picolinoyl-L-leucinii) hydrazide; N- [N- (3-carboxybenzioxycarbonyl) -L-leucinyl] -N '- [2- (N-cyclopropyl-N-cyclopropyl-methylamino) thiazol-4-ylcarbonyl] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (2-quinolinoii) -L-leucinyl] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (3-quinolinoyl) -L-leuciniI] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (4-methylpiperidinocarbonii) -L-leucinyl] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (4-quinoiinoyl) -L-leucinyl] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (5-quinolinoyl) -L-leucinyl] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (7-quino-linoyl) -L-leucinyl] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (6-quinoIinoyl) -L-leucinyl] hydrazide; N- [N- (1-isoquinolinoyl) -L-leucinyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- [N- (3-isoquinolinoyl) -L-leucine] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- [N- (4-methylimidazoi-5-ylcarbonyl) -L-leucinyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- (N-benzyi-L-prolinyl-L-leucinyl) -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- [N- (1-benzyl-5-methylimidazol-4-ylcarbonyl) -L-leucinyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- [N- (3-methylisonicotinoyl) -L-leucinyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- [2- (N-cyclopropylamino) -thiazol-4-ylcarbonyl] -N '- [N- (2-pyridinylmethoxycarbonyl) -L-leucyl] hydrazide; N- [4-methyl-2- (3-phenoxy) phenylentanol] -N '- [2- (1-naphthyl) thiazoi-4-ylcarbonyl] hydrazide; N- [N- (2-benzoxazolyl) -L-leucine] -N '- [2- (1-naphthyl) thiazole-4-ylcarbonyl] hydrazide; N- [N-benzyloxycarbonyl-L-leucinyl) -N '- [2- (N, Nb.sup.- (2-methylpropyl) amino] oxazoi-4-ylcarbonyl] hydrazide; N- [2 - (N-cyclopropyl-N- (2-methylpropii) amino] thiazol-4-ylcarbonyl] -N '- [N- (2-pyridinylmethoxycarbonyl) -L-leucinyl] hydrazide; N- [2- [N-cyclopropyl- N- (2-methy1propyl) amino] thiazol-4-ylcarbonyl] -N '- [N-methyl-N- (2-pyridinylmethoxycarbonyl) -L-leucinyl] hydrazide; N- [2- (1 - Naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (1-piperazinocarbonyl) -L-leucinyl] hydrazide; N- [4-methyl-2- (4-phenoxy) phenylpentanoyl] -N' - [2 - (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- [2- [N-bis- (cyclopropylmethyl) amino] thiazole-4-ylcarbonyl] -N '- [N- (2-pyridinylmethoxycarbonyl) -L- leucinyl] hydrazide; N- [2- (N-cyclopropyl-N-cyclo-propylmethylamino) thiazol-4-ylcarbonyl] -N '- [N- (2-quinolinoyl) -L-leucinyl] hydrazide; N- [ N- (8-quinolinoyl) -L-leucinyl] -N '- [2- (8-quinolinyl) thiazol-4-ylcarbonyl] hydrazide; N- (N-benzloxycarbonyl-leucinyl) -N' - [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- [N- ( 3-quinolylnoyl) -L-leucinylhydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbo-nyl] -N '- [N- (3-isoquinolinoyl) -L-leucinyl] hydrazide; N- [2- (N-cyclopropyl-N-cyclopropyl-methylamino) thiazol-4-ylcarbonyl] -N '- [N- (6-quinoylnoyl) -L-leucinyl] -hydrazide; N- [2- (N-bis- (cyclopropylmethyl) amino] thiazol-4-ylcarbonyl] -N '- [N- (2-methyl-3-pyridinylmethoxycarbonyl) -L-leucinyl] hydrazide; N- (N-benzyloxycarbonii-Lb-tert-butylalanyl) -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- (N-benzyloxycarbonyl-L-cyclopropylalanyl) -N' - [2- ( 1-naphthyl) thiazoi-4-ylcarbonyl] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- [3- (2-pyridyl) phenylacetyl] -L-leucinyl] hydrazide; N- [2- [N-bis- (cyclopropylmethyl) -amino] thiazol-4-ylcarbonyl] -N '- (N-picolinyl-L-leucinyl) hydrazide; N- (N-benzyloxycarbonyl-L-leucinyl) -N '- [2- [N-bis- (cyclopropylmethyl) amino] tiazol-4-ylcarbonyl] -hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- [N- (6-methylnicotinoyl) -L-leucinyl] hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethyl-amino) thiazol-4-ylcarbonyl] -N '- [N- (2-methylnicotinoyl) -L-leucinyl] -hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- [N- (3-methylisonicotinoyl) -L-leucinyl] hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonii] -N '- [N- (8-quinolinoyl) -L-leucinyl] hydrazide; N- [2- [N-bis- (cyclopropyl-methyl) amino] thiazol-4-ylcarbonyl] -N '- [N- (8-quinoylnoyl) -L-leucyl] hydrazide; N- [2- (N-bis- (cyclopropylmethyl) amino] thiazol-4-ylcarbonyl] -N '- [N- (3-isoquinolylnoyl) -L-leucyl-nyl] hydrazide; N- [2- [4- (2,2-dimethylaminoethoxy) -1-naphthyl] thiazol-4-ylcarbonyl] -N '- [N- (8-quinolinoyl) -L-leucinyl] hydrazide; N- [2- (N-cyclopropyl- N-cyclopropylmethylamino) -thiazol-4-ylcarbonyl] -N '- [N- (7-quinolinoyl) -L-leucinyl] hydrazide; N- [2- [N-bis- (cyclo-propylmethyl) amino] thiazole-4 -carbonyl] -N '- [N- (6-methyl-nicotinoyl) -L-leucinii] hydrazide; N- [2- (N-bis- (cyclopropylmethyl) amino] thiazol-4-ylcarbonyl] -N' - ( N-methyl-L-prolinyl-L-leucinyl] hydrazide; N- (N-benzyloxycarbonyl-L-norvalinyl) -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- (N-) benzyloxycarbonyl-L-isoleucinyl) -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -hydrazide; N- [N- (4-dimethylaminomethylbenzoyl) -L-leucinyl] -N' - [ 2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- (N-benzyloxycarbonyl-L-norleucinyl) -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- [N - (4-dimethylaminomethylbenzyl-oxycarbonyl) -L-leucinyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- (N-benzyl) L-oxycarbonyl-L-norvalinyl) -N '- [2- (2-benzyloxyfenii) thiazol-4-ylcarbonyl] hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethyllamino) thiazol-4-ylcarbonyl] -N '- [N- (4-methylim- dazol-5-ylcarbonyl) -L-leucinyl] hydrazide; N- [N- [4- (4-morpholinomethyl) benzoyl] -L-leucinyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- [N- (2-methylnicotinoyl) -L-leucinyl] N '- [2- (1-naphthyl) thiazol-4-ylcarbonii] hydrazide; N- [N- (6-methylnicotinoyl) -L-leucinyl] N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- (N-b-tert-butoxycarbonyl-L-tert-butylanyl) -N '- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- [N- (8-quinolinoyl) -L-b-tert-butylalanyl] hydrazide; N- [N- (4-methylimidazol-5-ylcarbonyl) -L-allylglynyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- [N- (4-methylimidazol-5-ylcarbonyl) -L-b-tert-butylanyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- [N- (4-methylimidazol-5-ylcarbonyl) -L-b-tert-butylalanyl] hydrazide; N- [2- (1-naphthyl) thiazoi-4-ylcarbonii] -N '- (N-picolinoyl-L-b-tert-butylalanyl) hydanida; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (8-quinolinoyl) -L-b-tert-butylalanyl) hydrazide; N- [2- (1-naphthyl) thiazoi-4-ylcarbonii] -N '- (N-picolinoyl-L-allylglycinyl) hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonii] -N '- (N-picolinoyl-L-b ~ cyclopropylalani!) Hydrazide; N- [N- (6-methylnicotinoyl) -L-b-cyclopropylalan] I] - N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- [N- (4-methylimidazol-5-ylcarbonyl) -L-b-cyclopropylalanyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (8-quinolinoyl) -L-cyclopropylalanyl] hydrazide: N- [N- (6-methyl-nicotinoyl) -L- tert-butylalanyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonii] hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino-4-ylcarbonyl] -N '- (N-picolinoiI-Lb-tert-butyl-alanyl) hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino ) thiazol-4-ylcarbonyl] -N '- [N- (3-isoquinolinoyl) -Lb-tert-butylalanyl] hydrazide; N- (N-tert-butoxycarbonyl-Lb-cyclopropylalanyl) -N' - [2- (N -cyclopropyl-N-cyclopropiimethylamino) thiazol-4-ylcarbonyl] -hydrazide; N- [2- (N-cyclopropylmethyl-N-propylamino) thiazol-4-ylcarbonyl] -N '- [N- (6-methyl-3-) pyridinylmethoxycarbonyl) -L-leucinyl] hydrazide; N- [N- (6-methylnicotinoyl) -L-allylglycinyl] -N '- [2- (1-naphthyl) thiazole) -4-ylcarbonyl] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (8-quinolinoyl) -L-allyl] yl] hydrazide; N- [2- (1-naphthylthiazol-4-ylcarbonyl] -N '- [N- (2-quinolinoyl) -L-cyclopropylalanyl] hydrazide; N- [N- (3-isoquinolinoyl) -L-cyclopropylalani] -N '[- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- [N- (1-isoquinolinoii) -L-cyclopropylalanyl] -N' - [2- (1-naphthyl) thiazole- 4-ylcarbonyl] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (7-quinolinoyl) -L-cyclopropylalanyl] -hydrazide; N- [2- (N -cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- [N- (8-quinolinoyl) -L-cyclopropylalanii] hydrazide; N- [2- (N-cyclopropyl-N-cyclopropyl- methylamino) thiazol-4-ylcarbonyl] -N '- [N- (4-methylimidazol-5-ylcarbonyl) -Lbc] -clopro-pillalanyl-hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazole-4-) ilcarbonyl] -N '- [N- (3-isoquinolinoyl) -Lb-cyclopropylalanyl] hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N' - [N- (6 -methylnicotinoyl) - Lb-cyclopropylalanyl] hydrazide; N- [N- (4-methylimidazol-5-ylcarbonyl) -L-norleucinyl] -N '- [2- (1-naphthyl) thiazole-4-ylcarbonyl] ] hydazole; N- [2- (1 -naft il) thiazol-4-ylcarbonyl] -N '- (N-picolinoyl-L-norleucinyl) hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (8-quinolinoyl) -L-norleucinyl) hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethyl-amino) thiazol-4-ylcarbonyl] -N '- [N- (2-quinolinoyl) -L-b-cyclopropylalanyl] hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) tiazol-4-ylcarbonyl] -N '- [N- (1-isoquinolinoyl) -L-b-cyclopropylalanii] hydrazide; N- [2- [N-cyclopropyl-N- (2-methylpropyl) -amino] thiazol-4-ylcarbonyl] -N '- [N- (6-methyl-3-pyridinylmethoxycarbonyl) -L-leucinyl] -hydrazide; N- (N-tert-butoxycarbonyl-L-leucinii) -N '- [2- [N-cyclopropyl-N- (2-methylpropyl) amino] thiazol-4-ylcarbonyl] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (7-quinolinoyl) -L-b-tert-butylalanii] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (2-quinolinoyl) -L-b-tert-butylalanyl] hydrazide; N- [N- (1-isoquinolinoyl) -L-b-tert-butylanyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- [N- (3-isoquinolinoyl) -L-b-tert-butylanyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- [N- (6-methylnicotinoyl) -L-norleucyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydanzate; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (7-quinolinoyl) -L-norleuccinyl] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (2-quinolinoyl) -L-norleucinyl] h -drazide; N- [N- (1-isoquinolinoyl) -L-norleucyl] -N '- [2- (1-naphthyl) thiazole-4-carbonyl] hydrazide; N- [N- (3-isoquinolinoyl) -L-norleucinyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- [2- (N-cyclopropyl-N-cyclopropiimethylamono) thiazol-4-ylcarbonyl] -N '- [N- (5-hydroxymethyl-imidazol-4-ylcarbonyl) -L-b-cyclopropylalanyl] hydrazide; N- [2- (N-cyclopropyl-N- (2-methylpropyl) amino] thiazol-4-ylcarbonii] -N '- [N- (8-quinolinoyl) -L-cyclopropylalanyl] -hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylammono) thiazol-4-ylcarbonyl] -N '- [N- (6-methynicotinoyl) -L-tert-butylalanyl] hydrazide; N- [2- (N-cyclopropyl-N- (2 -methyl-propyl) amino] thiazol-4-ylcarbonyl] -N '- [N- (4-methylimidazol-5-ylcarbonyl) -L-cyclopropylalanyl] hydrazide; N- [2- (N-cyclopropyl-N- (2-methylpropyl) amino] thiazol-4-ylcarbonyl] -N '- [N- (2-quinol-ynyl) -L-cyclopropyl-lanyl] -hydrazide; N- [2- (N-cyclo- propyl-N- (2-methylpropyl) amino] thiazol-4-ylcarbonyl] -N '- [N- (6-methylnicotinoyl) -L- cyclopropylalanylhydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (8-quino-linoyl) glycinyl] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N' - [N- (8-quinolinoyl) -L-norvalinyl] ] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (2-quinolinoyl) -L-norvalinyl] hydrazide; N- [2- (1-naphthyl) thiazole- 4-ylcarbonyl] -N '- (N-picolinoyl-L-norvalinyl] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N' - [N- (6-methyl) cotinoyl) -L-norvalinii] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (4-methylimidazol-5-ylcarbonyl) -L-norvalinyl] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (1-isoquinolinoyl) -L-norvalinyl] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (3-isoquinolinoyl) -L-norvalinyl] hydrazide; (1S, 1 'S) -N, N'-bis- [4- [1- (N-benzyloxycarbonylamino) -3-methylbutyl] thiazol-2-ylcarbonyl] hydrazide; N- [2- (N-cyclopropyl-N- (2-methylpropyl) amino] thiazol-4-ylcarbonii] -N '- [N- (6-methylnicotinoyl) -L-b-tert-butylalanii] -hydrazide; N- [2- (N-cyclopropyl-N- (2-methylpropyl) amino] thiazol-4-ylcarbonyl] -N '- [N- (4-methylimidazol-5-ylcarbonyl) -L-tert-butylalanyl] hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazole-4-ylcarbonyl] -N '- [N- (1-isoquinolinoyl) -Lb-tert-butyl-alanyl] hydrazide; N- [N- ( 5-butylpicolinoyl) -Lb-tert-butylalanyl] -N '- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] hydrazide; N- [2- (N-cyclopropyl-N-cyclo-propylmethylamino ) thiazol-4-ylcarbonyl] -N '- [N- (6-methylpicolinoyl) -Lb-tert-butylanyl] -hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] - N '- [N- (4-fluorobenzoii) -L-leucinyl] hydrazide; N- [N- (4-fluorobenzoyl) -L-leucinyl] -N' - [2- (1-naphthyl) thiazole-4-iicarbonyl ] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (2-pyridinimethoxycarbonyl) -Lb-tert-butylalanyl] hydrazide; N- [N- (2- methyl-3-pyridinyl-methoxycarbonyl) -L-tert-butylalanyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- [2- (1-naphthyl) thiazole-4-; lcarbonyl] -N '- [N- (2-pyridinylmethoxycarbonyl) -L- cyclopropyl-al aniljhidrazide; N- [N- (2-methy1-3-pyridinylmethoxycarbonyl) -L-b-cyclopropylalanyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- [N- (6-methyl-3-pyridinylmethoxycarbonyl) -L-b-cyclopropylalanyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- [N- (6-methyl-3-pyridinylmethoxycarbonyl) -L-b-tert-butylalanii] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -hydrazide; N, N'-bis- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- [2- (N-cyclopropyI-N-cyclopropylmethylammonyl) thiazole-4-carbonyl] -N '- [N- [2- (1, 8-naphthyridinoyl) -L-b-cyclopropylalanyl] hydrazide; N- [2- (N-cyclopropyl-N- (2-methylpropyl) amino] thiazol-4-ylcarbonyl] -N '- [N- (3,4-difluorobenzoyl) -L-cyclopropylalanyl] hydrazide; N- [2 - (N-cyclopropyl-N- (2-methylpropyl) amino] thiazol-4-ylcarbonyl] -N '- [N- (4-fluorobenzoyl) -L-leucinyl] hydrazide; N- [N- (5-butylpicolinoyl) -L-leucinyl] -N '- [2- (N-cyclopropyl-N-cyclo-propylmethylamino) thiazol-4-ylcarbonyl] hydrazide; N- [2- (N-cyclopropyl-N- (2-methyl-propyl) amino] thiazol-4-ylcarbonyl] -N '- [N- (3,4-dimethoxybenzoii) -L-leucinyl] hydrazide; N- [2- (N-cyclopropyl-N- (2-methylpropyl) amino] thiazol-4-ylcarbonyl] -N '- [N- (3,4-difluo-robenzoyl) -L-tert-butylalanyl] hydrazide; N- [2- (N-cyclopropyl-N- (2-methylpropyl) -amino] ] thiazol-4-ylcarbonyl] -N '- [N- (3,4-dimethoxybenzoyl) -Lb-tert-butylanyl] -hydrazide; N- [N- (5-butylpicolinoii) -Lb-tert-butylanyl] -N '- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] hydrazide and N- [2- [N-cyclopropyl-N- (2-methylpropyl) amino] thiazol-4-ylcarbonyl] -N' - [N- (6-methylpicolinoyl) -Lb-tert-butylanyl] -hydrazide; 21 .- A compound in accordance with to claim 20 which is selected from the group consisting of: N- [2- [N-cyclopropylmethyl-N- (2-methylpropyl) amino] thiazole-4-ylcarbonyl] -N '- [N- ( 4-pyridinylmethoxycarbonyl) -L-leucinyl] -hydrazide; N- [2- (4-methyl-1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (4-pyridinylmethoxycarbonyl) -L-leucinyl] hydrazide; N- [2- [N-methyl- (2-methylpropyl) amino] thiazole-4-iicarbonyl] -N '- [N-methyl-N- (4-pyridinylmethoxycarbonyl) -L-leucinyl] hydrazide; N- [2- (1-naphthyl) thiazoi-4-ylcarbonyl] -N '- [N- (3-pyridinylmethoxycarbonyl) -L-leucinyl] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (2-pyridinylmethoxycarbonyl) -L-leucyl] -hydrazide; N- [2- (5-Acenaphthyl) thiazol-4-ylcarbonyl] -N '- [N- (4-pyridinylmethoxycarbonyl) -L-leucinyl] hydrazide; N- [2- [N-cyclopropylmethyl-N- (2-methylpropyl) amino] thiazole-4-lcarbonyl] -N '- [N -methyl-N- (4-pyridinylmethoxycarbonyl) -L-leucinyl] hydrazide; N- [2- (N-cyclopropyi-N-cyclopropiimethylamino) thiazol-4-ylcarbonyl] -N '- [N- (4-pyridinylmethoxycarbonyl) -L-leucinyl] hydrazide; N- [2- [N-cyclopropylmethyl-N- (2-methylpropyl) amino] -thiazole-4-ylcarbonyl] -N '- [N- (3-pyridinylmethoxycarbonyl) -L-leucinyl] hydrazide; N- [2- [N -cyclopropylmethyl-N- (2-methylpropyl) amino] thiazol-4-ylcarbonyl] -N '- [N- (2-pyridinyl-methoxycarbonyl) -L-leucinyl] hydrazide; N- [2- [N-cyclopropylmethyl-N- (2-methylpropyl) -amino] thiazol-4-ylcarbonyl] -N '- [N-methyl-N- (3-pyridinylmethoxycarbonyl) -L-leucinyl] -hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino] thiazol-4-ylcarbonyl] -N '- [N- (3-pyridinylmethoxycarbonyl) -L-leucinyl] hydrazide; N- [2- (N-cyclopropyl -N-cyclo-propylmethylamino] thiazol-4-ylcarbonyl] -N '- [N-methyl-N- (4-pyridinylmethoxycarbonyl) -L-Ieucinyl] hydrazide; N- [2- [N, N-bis- (2-methylpropyl) amino] thiazol-4-ylcarbonyl] -N '- [N- (2-pyridinylmethoxycarbonyl) -L-leucine] hydrazide; N- [N- (4-pyridinylmethoxycarbonyl) -L-leucinyl] -N '- [2- [1 - (1, 2,3,4-tetrahydroquinolino)] thiazol-4-ylcarbonyl] hydrazide: N- [ 2- [N, N-bis- (2-methylpropyl) amino] thiazol-4-ylcarbonyl] -N '- [N-methyl-N- (3-pyridinyl-methoxycarbonyl) -L-leucinyl] hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethyl-amino) thiazol-4-ylcarbonyl] -N '- [N-methyl-N- (3-pyridinylmethoxycarbonyl) -L-leucinyl] -hydrazide; N- [2- (N-cyclopropylmethyl-N-propylamino) thiazol-4-ylcarbonyl] -N '- [N- (3-pyridinylmethoxycarbonyl) -L-leucinyl] hydrazide; N- [2- (2-benzyloxy-1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (4-pyridinylmethoxycarbonyl) -L-leucinyl] hydrazide; N- [2- [N, N-bis (2-methylpropyl) amino] thiazole-4-iicarbonyl] -N '- [N -methyl-N- (2-pyridinylmethoxycarbonyl) -L-leucinyl] hydrazide; N- [2-9-phenanthrenyl) thiazol-4-ylcarbonyl] -N '- [N- (4-pyridinylmethoxycarbonyl) -L-leucinyl] hydrazide; N- [2- [N, N-bis- (2-methylpropyl) amino] thiazol-4-ylcarbonyl] -N '- (tert-butoxycarbonyl-L-leucinyl] hydrazide; N- [2- [N, N- bis- (2-methyl-propyl) amino] thiazol-4-ylcarbonii] -N '- (N-picolinoyl-L-leucinyl] hydanidate; N- [2- [N, N-bis- (2-methylpropyl ) amino] thiazol-4-ylcarbonyl] -N '- [N- (2-pyrazinocarbonyl) -L-leucinyl] -hydrazide; N- [2- [2- (4-tert-butoxycarbonyl) benzyloxyphenyl] thiazole-4- ilcarbonyl] -N '- [N- (4-pyridinylmethoxycarbonyl) -L-leucinyl] hydrazide; N- [2- [2- (4-carboxybenzyl-oxy) phenyl] thiazol-4-ylcarbonyl] -N'- [N- (4-pyridinylmethoxycarbonyl) -L-leucinyl] hydrazide; N- [N- (4-tert-butoxycarbonylbenzyloxycarbonyl) -L-leucinii] -N '- [2- [N- (2-methylpropyl ) -N-phenylamino] thiazol-4-ylcarbonyl] hydanzate; N- [2- [N, N-bis- (2-methylpropyl) amino] -thiazol-4-ylcarbonyl] -N '- [N - (4-tert-butoxycarbonylbenzyloxycarbonyl) -L-leucinyl] -hydrazide; N- [N- (4-carboxybenzyloxycarbonyl) -L-leucine] -N '- [2- [N- (2-methypropyl) -N phenylamino] thiazol-4-ylcarbonyl] hydrazide; N- [N- (6-methyl-3-pyridinylmethoxycarbonyl) -L-leuciniI] -N '- [2- (1-naphthyl) thiazole- 4-ilcarbo nil] hydrazide; N- (N-benzyl-oxalic-rbonyl-L-leucinyl) -N '- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonylhydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- [N- (2-pyridinimethoxycarbonyl) -L-leucinyl) hydanzate; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- [N- (6-methyl-3-pyridinylmethoxycarbonyl) -L-leucinyl] hydrazide; N- (N-tert-butoxycarbonyl) -N '- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] hydanzate; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- [N-methyl-N- (2-pyridinylmethoxycarbonyl) -L-leucinylhydrazide; N- [2- (2-benzyloxy) thiazol-4-ylcarbonyl] -N '- [N- (6-methyl-3-pyridinyl-methoxycarbonyl) -L-leucinyl] hydrazide; N- [2- (2-benzyloxyphenyl) thiazol-4-ylcarbonyl] -N '- [N- (2-methyl-3-pyridinylmethoxycarbonyl) -L-leucinyl] hydanzate; N- [2- [N-methyl-N- (2-methylpropyl) amino] thiazol-4-ylcarbonii] -N '- [N- (6-methyl-3-pyridinylmethoxycarbonyl) -L-leucinyl] hydrazide; N- [2- [N-methyl-N- (2-methylpropyl) amino] thiazol-4-ylcarbonyl] -N '- [N - () - L-leucinyl] hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethyllamino) thiazol-4-ylcarbonyl] -N- (N-picolinoyl-L-leucinyl) hydrazide; N- [2- (N-cyclopropyl-N-cyclopropyl-methylamino) thiazol-4-ylcarbonyl] -N '- [N- (2-methyl-3-pyridinylmethoxycarbonyl) -L-leu-cinyl] hydrazide; N- [N- (3-tert-butoxycarbonylbenzyloxycarbonyl) -L-leucinyl] -N '- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] hydrazide; N- [2- (1-naphthyl) -thiazol-4-ylcarbonyl] -N '- [N- (8-quinolinoyl) -L-leucinyl] hydrazide; N- [N- (2-methyl-3-pyridinylmethoxycarbonyl) -L-leucinii] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- (N-p-butyl-L-leucinyl) hydanida; N- [N- (3-carb-oxy-benzyloxycarbonyl) -L-leucinyl] -N '- [2- (N-cyclopropyl-N-cyclopropylmethylamino) -thiazol-4-ylcarbonyl] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (2-quinolinoyl) -L-leucinyl] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (3-quinolinoyl) -L-leucinyl] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (4-methylpiperidinocarbonyl) -L-leucinyl] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (4-quinolinoyl) -L-leucinyl] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (5-quinolinoyl) -L-leucinyl] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (7-quinolinoyl) -L-leucinyl] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (6-quinolinoyl) -L-leucinyl] hydrazide; N- [N- (1-isoquinolinoyl) -L-leucinyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- [N- (3-isoquinolinoyl) -L-leucinyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- [N- (4-methylimidazol-5-ylcarbonii) -L-leucinyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- [N- (1-benzyl-5-methylimidazoi-4-ylcarbonyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- [N- (3-methylisonicotinoyl) -L -leucinyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- (N-benzyloxycarbonyl-L-leucinyl) -N' - [2- [N, N-bis- (2 -methylpropyl) amino] oxazol-4-ylcarbonyl] hydrazide; N- [2- [N-cyclopropyl-N- (2-methylpropyl) amino] thiazole-4-ylcarbonyl] -N '- [N- (2- pyridinylmethoxycarbonyl) -L-leucinyl] hydrazide; N- [2- [N-cyclopropyl-N- (2-methylpropyl) amino] thiazol-4-ylcarbonyl] -N '- [N-methyl-N- (2- pyridinylmethoxycarbonyl) -L-leucinyl] hydrazide; N- [2- (1-naphthyl) thiazole-4-ylcarbonyl] -N '- [N- (1-piperazinocarbonyl) -L-leucinyl] hydrazide; N- [2- [N-bis- (cyclopropylmethyl) amino] thiazol-4-ylcarbonyl] -N '- [N- (2-pyridinylmethoxycarbonyl) -L-leucinyl] hydrazide; N- [2- (N-cyclopropyl-N -cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- [N- (2-quinolinoyl) -L-leucine] -hydrazide; N- [N- (8-quinolinoyl) -L-leucinyl] -N' - [2- (8-quinolinyl) thiazol-4-ylcarbonii] hydrazide; N- (N-benzyloxycarbonyl-L-leucinyl) -N '- [2- (1-naphthyl) thiazole-4-ylca rbonii] hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) tiazol-4-ylcarbonyl] -N '- [N- (3-quinolinoii) -L-leucine] -hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- [N- (3-isoquininoyl) -L-leucinyl] hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethyl-amino) thiazole-4-ylcarbonyl] -N '- [N- (6-quinolinyl) -L-leucinyl] hydroquinone gives; N- [2- [N-bis- (cyclopropylmethyl) amino] thiazol-4-ylcarbonyl-N '- [N- (2-methyl-3-pyridinylmethoxy-carbonyl) -L-leucinyl] hydrazide; N- (N-benzyloxycarbonyl-L-b-tert-butylanyl) -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- (N-benzyloxycarbonyl-L-b-cyclopropyl-alanyl) -N '- [2- (1-naphthyl) thiazol-4-ylcarbonii] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- [3- (2-pyridyl) phenylacetyl] -L-leucinyl] hydrazide; N- [2- [N-bis- (cyclo-propylmethyl) amino] thiazol-4-ylcarbonyl-N '- (N-picolinyl-L-leucinyl] hydrazide; N- (N-benzyloxycarbonyl-L-leucine) -N '- [2- [N-bis- (cyclopropylmethyl) amino] thiazol-4-ylcarbonyl] hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N' - [ N- (6-methylnicotinoyl) -L-leucinyl] hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- [N- (3-methylsonicotinoyl) -L-leucine] L] -hydrazide; N- [2- (N-cyclopropyl-N-cyclopropimethylamino) thiazol-4-ylcarbonyl] -N '- [N- (8-quinolinoii) -L-leucinyl] hydrazide; N- [ 2- [N-bis- (cyclopropylmethyl) amino] thiazol-4-ylcarbonii] -N '- [N- (8-quinolinoyl) -L-leucinyl] hydrazide; N- [2- [N-bis- (cyclopropyl- methyl) amino] thiazol-4-ylcarbonyl] -N '- [N- (3-isoquinolylnoyl) -L-leucinyl] hydrazide; N- [2- [4- (2,2-dimethylaminoethoxy) -1-naphthyl ] thiazol-4-ylcarbonyl] -N '- [N- (8-quinolinoyl) -L-leucinylhydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) tiazol-4-ylcarbo-nyl] -N '- [N- (7-quinolinoyl) -L-leucinyl] hydrazide; N- [2- [N-bis- (cyclopropylmethyl) -am] no] thiazol-4-ylcarbonii] -N '- [N- (6-methylnicotinoyl) -L-leucinii] hydanida; N- [2- [N-bis- (c-chloropropylmethyl) amino] thiazol-4-ylcarbonyl] -N '- [N-methyl-L-prolinyl-L-leucinyl] -hydrazide; N- (N-benzyloxycarbonyl-L-norvalinyl) -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -hydrazide; N- (N-benzyloxycarbonyl-L-isoleucinyl) -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -hydrazide; N- (N-benzyloxycarbonyl-L-norleucinyl) -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- [N- (4-dimethylaminomethylbenzyloxycarbonyl) -L-leucinyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- (N-benzyloxycarbonyl-L-norvalinyl) -N '- [2- (2-benzylphenyl) thiazol-4-ylcarbonyl] hydrazide; N- [2- (N-cyclopropyl-N-cyclopropyl-methylamino) thiazol-4-ylcarbonyl] -N '- [N- (4-methylimidazol-5-ylcarbonyl) -L-leucinyl] -hydrazide; N- [N- [4- (4-morpholinomethyl) benzoyl] -L-leucinyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- [N- (6-methylnicotinoyl) -L-leucinyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- (N-b-tert-butoxycarbonyl-L-tert-butylanyl) -N '- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazole-4-ylcarbonyl] -N '- [N- (8-quinolino] l) -L-b-tert-butylalanyl] hydrazide; N- [N- (4-methylimidazol-5-ylcarbonyl) -L-allylglycinyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- [N- (4-methylimidazol-5-ylcarbonyl) -L-b-tert-butylalanyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- [N- (4-methylimidazol-5-ylcarbonyl) -L-b-tert-butylalanyl] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonii] -N '- (N-picolinoyl-L-b-tert-butylalanii) hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonii] -N '- [N- (8-quino-linoyl) -L-b-tert-butylalanyl) hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- (N-picolinoyl-L-allylglycinyl) hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- (N-picolinoyl-L-b-cyclopropylalanyl) hydrazide; N- [N- (6-methylnicotinoyl) -L-b-cyclopropylalanyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- [N- (4-methylimidazol-5-ylcarbonyl) -L-b-cyclopropylalanyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (8-quinolinoyl) -L-b-c-chloropylalanii] hydrazide; N- [N- (6-methynicotinoyl) -L-b-tert-butylanyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- (N-picolinoyl-L-b-tert-butylalanyl) hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- [N- (3-isoquinolinoii) -L-b-tert-butylalanyl] hydrazide; N- (N-tert-butoxy-carbonyl) -L-b-cyclopropylalanyl) -N '- [2- (N-cyclopropyl-N-cyclopropylmethylamino) -thiazol-4-ylcarbonyl] hydrazide; N- [2- (N-cyclopropylmethyl-N-propylamino) thiazol-4-ylcarbonyl] -N '- [N- (6-methyl-3-pyridinylmethoxycarbonyl) -L-leucinyl] -hydrazide; N- [N- (6-methylnicotinoyl) -L-allyiglicinyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (8-quinolinoyl) -L-allylglicinii] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (2-quinolinoyl) -L-b-cyclopropylalanyl] hydrazide; N- [N- (3-isoquinolinoyl) -L-b-cyclopropylalanyl] -N '[- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -hydrazide; N- [N- (1-isoquinolinoyl) -L-b-cyclopropylalanyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (7-quinolinoyl) -L-b-cyclopropylalanyl-hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- [N- (8-quinolinoyl) -L-b-cyclopropylalanyl] hydrazide; N- [2- (N-cyclo-propyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- [N- (4-methylimidazol-5-ylcar-bonyl)) - L-b-cyclopropylalanyl] hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethyl-amino) thiazol-4-ylcarbonyl] -N '- [N- (3-isoquinolylnoyl) -L-b-cyclopropyl-lanyl] -hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- [N- (6-methyl-nicotinoyl) -L-b-cyclopropylalanyl] hydrazide; N- [N- (4-methylimidazoi-5-ylcarbonyl) -L-norleuccini] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- [2- (1-naphthyl) thiazole-4-ylcarbonyl] -N '- (N-picolinoyl-L-norleucinyl) hydrazide: N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (8-quinolinoyl) -L-norleucinyl) hydrazide: N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N' - [N- (2-quinolinoyl) - Lb-cyclopropyl-aianylhydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- [N- (1-isoquinolinoyl) -L-b-cyclopropyllalanyl] hydrazide; N- [2- [N-cyclopropyl-N- (2-methylpropyl) amino) thiazol-4-ylcarbonii] -N '- [N- (6-methyl-3-pyridinylmethoxycarbonyl) -L-leucinylhydrazide; N- (N-tert-butoxycarbonyl-L-leucinyl) -N '- [2- [N-cyclopropyl-N- (2-methylpropyl) amino] thiazol-4-ylcarbonyl] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (7-quinolinoyl) -L-b-tert-butylalanyl] hydrazide; N- [2- (1-naphthyl) thiazole-4-ylcarbonyl] -N '- [N- (2-quinoiinoyl) -L-b-tert-butylalanyl] hydrazide; N- [N- (1-isoquinolinoyl) -L-b-tert-butylanyl] -N '[- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- [N- (3-isoquinolinoyl) -L-b-tert-butylalanii] -N '- [2- (1-naphthyl) thiazole-4-alkylcarbonyl] hydrazide; N- [N- (6-methylnicotinoyl) -L-norleucinyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonii] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (7-quinolinoyl) -L-norleucinyl] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (2-quinolinoyl) -L-norleucyl] hydanza; N- [N- (1 -soquinolinoyl) -L-norleucinyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- [N- (3-isoquinolinoyl) -L-norleucinyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- [N- (5-hydroxymethyl-4-ylcarbonyl) -L-b-cyclopropylalanyl] hydrazide; N- [2- [N-cyclopropyl-N- (2-methylpropyl) amino] thiazol-4-ylcarbonyl] -N '- [N- (8-quinoxy) -L-cyclopropylalani] -hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- (N- (6-methylnicotinoyl) -L-tert-butylalanyl] hydrazide; N- [2- [N-cyclopropyl] -N- (2-methyl-propyl) amino] thiazole-4-ylcarbonyl] -N '- [N- (4-methylimidazol-5-ylcarbonyl)) - Lb-cyclopropylalanyl] hydrazide; N- [2- [N-cyclopropyl-N- (2-methylpropyl) amino] thiazol-4-ylcarbonyl] -N '- [N- (2-quinolinoyl) -L-b-cyclopropylalanyl] hydrazide; N- [2- [N-cyclopropyl-N- (2-methylpropyl) amino] thiazol-4-ylcarbonyl] -N '- [N- (6-methylnicotinoyl) -L- b -cyclopropylalanyl] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarboni] - N '- [N- [8-quino-ynyl] glycinyl] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- [8-quinolinoyl] -L-norvalinylhydrazide; N- [2- (1-naphthyl) thiazoi-4-ylcarbonyl] -N '- [N- (2-quinolylnoyl) -L-norvalinii] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- (N-picolinoyl-L-norvaiinyl] hydrazide; N- [2- (1-naphthyl) thiazole-4-ylcarbonyl] - N '- [N- (6-methylnicotinoyl) -L-norvaylinylhydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N' - [N- (4-methyl-midazol-5-ylcarbonii) -L-norvalinyl] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (1-isoquinolinoyl) -L-norvalinyl] hydrazide; N- [2- (1 - Naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (3-isoquinolinoyl) -L-norvalinyl] hydrazide; (1 S, S) -N, N'-bis- [4- [1 - ( N-benzyloxycarbonylamino) -3-methylbutyl] thiazol-2-ylcarbonyl] hydrazide; N- [2- [N-cyclopropyl-N- (2-methylpropii) amino] thiazol-4-ylcarbonyl] -N '- [N - (6-methylnicotinoi) -Lb-tert-butyl-alanyl] hydrazide; N- [2- [N-cyclopropyl-N- (2-methylpropyl] thiazol-4-ylcarbonyl] -N '- [N- ( 4-methylimidazol-5-ylcarbonyl) -Lb-tert-butyllane] hydrazide; N- [2- [N-cyclopropyl-N- (2-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N'- [N- (1-isoquinolinoyl) -L-tert-butyl-alanyl] hydrazide; N- [N- (5-butylpicolinoyl) -Lb-tert-butylalanyl] -N '- [2- (N-cyclopropyl-N- cyclopropylmethylam ino) thiazol-4-ylcarbonyl] hydrazide; N- [2- (N-cyclopropyl-N-cyclo-propylmethylamino) thiazol-4-ylcarbonyl] -N '- [N- (6-methylpicolinoyl) -L-b-tert-butylalanyl] -hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- [N- (4-fluorobenzoyl) -L-leucinyl] hydrazide; N- [N- (4-fIuorobenzoyl) -L-leucinyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonii] -N '- [N- (2-pyridinylmethoxycarbonyl) -L-b-tert-butylalanyl] hydrazide; N- [N- (2-methyl-3-pyridinyl-methoxycarbonyl) -L-b-tert-butylanyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -N '- [N- (2-pyridinimethoxycarbonyl) -L-b-cyclopropyl-alanyl] hydrazide; N- [N- (2-methyl-3-pyridinylmethoxycarbonyl) -L-b-cyclopropylalanyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] hydrazide; N- [N- (6-methyl-3-pyridinylmethoxycarbonyl) -L-b-cyclopropylalanyl] -N '- [2- (1-naphthyl) thiazoi-4-ylcarbonyl] hydrazide; N- [N- (6-methyl-3-pyridinylmethoxycarbonii) -L-b-tert-butylanyl] -N '- [2- (1-naphthyl) thiazol-4-ylcarbonyl] -hydrazide; N, N-bis- [2- (1-naphthyl) thiazoi-4-ylcarbonii] hydrazide; N- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] -N '- [N- [2- (1, 8-naphthyridinoyl)] - L-b-cyclopropylalanyl] hydrazide; N- [2- [N-cyclopropyl-N- (2-methylpropyl) amino] thiazole-4-ylcarbonii] -N '- [N- (3,4-difluorobenzoyl) -L-b-cyclopropylalanyl] hydrazide; N- [2- [N-cyclopropii-N- (2-methylpropyl) amino] thiazol-4-ylcarbonyl] -N '- [N- (4-fluorobenzoii) -L-leucinyl] hydrazide; N- [N- (5-butylpicolinoyl) -L-leucinyl] -N '- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] hydrazide; N- [2- (N-cyclopropyl-N- (2-methylpropyl) amino] thiazol-4-ylcarbonyl] -N '- [N- (3,4-dimethoxybenzoyl) -L-leucinyl] -hydrazide; N- [2- (N-cyclopropyl-N- (2-methylpropyl) amino] thiazol-4-ylcarbonyl] -N '- [N- (3,4-difluorobenzoyl) -Lb-tert-butylalanii] hydrazide; N- [2- [N-cyclopropyl-N- (2-methyl-propyl) amino] thiazole-4-ylcarbonyl] -N '- [N- (3,4-d- methoxybenzoyl) -L- tert-butylalanyl] -hydrazide; N- [N- (5-butylpicolinoyl) -Lb-tert-butylanyl] -N '- [2- (N-cyclopropyl-N-cyclopropylmethylamino) thiazol-4-ylcarbonyl] hydrazide and N- [2- [N-cyclopropyl-N- (2-methylpropyl) amino] thiazol-4-ylcarbonii] -N '- [N- (6-methylpicolinoi) -Lb-tert-butylalanyl] -hydrazide. A pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable carrier, diluent or excipient.23. - A pharmaceutical composition comprising a compound according to claim 21 and a pharmaceutically acceptable carrier, diluent or excipient. 24. The use of a compound according to claim 1 for the manufacture of a medicament for inhibiting a protease in a patient, wherein the protease is selected from the group consisting of a cysteine protease and a serine protease. 25. The use according to claim 21, wherein said cysteine protease is cathepsin K. 26.- The use according to claim 24, wherein said protease is a cysteine protease. 27. The use according to claim 25, wherein said protease is a cysteine protease. 28. The use according to claim 26, wherein said cysteine protease is cathepsin K. 29. The use according to claim 27, wherein said cysteine protease is cathepsin K. 30.- The use of a compound according to claim 1 for the manufacture of a medicament for the treatment of a disease characterized by bone loss in a patient. 31. The use according to claim 30, wherein said disease is osteoporosis. 32. - The use according to claim 30, wherein said disease is periodontitis. 33. The use according to claim 30, wherein said disease is gingivitis. 34. The "use of a compound according to claim 1 for the manufacture of a medicament for the treatment of a disease characterized by excessive degradation of the cartilage or matrix in a patient." 35.- Use in accordance with the claim 34, wherein said disease is osteoarthritis 36. The use according to claim 34, wherein said disease is rheumatoid arthritis 37. The use of a compound according to claim 21 for the manufacture of a medicament for 38. The use according to claim 37, wherein said disease is osteoporosis 39. The use according to claim 37, wherein said disease is periodontitis. 40. The use according to claim 37, wherein said disease is gingivitis 41. The use of a compound according to claim 21 for to the manufacture of a medicament for the treatment of a disease characterized by excessive degradation of the cartilage or matrix in a patient. 42. The use according to claim 41, wherein said disease is osteoarthritis. j with a carbamoyl chloride, R3COCI and triethylamine in methylene chloride. 48. A method for preparing compounds according to claim 1, comprising the step of reacting an intermediate: -CONHNH2 Y- X with a sulfonium chloride, R3SO2CI and NMM in CH2Cl2. 49. The use of a compound according to any of claims 1 to 21 for making a medicament for use in the inhibition of a protease that is selected from the group consisting of a cysteine protease and a serine protease. 50.- A use according to claim 49, wherein said protease is cysteine protease. 51. A use according to claim 50, wherein said cysteine protease is cathepsin K. 52. The use of a compound according to any of claims 1 to 21 for the manufacture of a medicament for use in the treatment of a disease characterized by bone loss. 53. A use according to claim 52, wherein said disease is osteoporosis. 54.- A use according to claim 52, wherein said disease is periodontitis. said disease is gingivitis. 56.- The use of a compound according to any of claims 1 to 21 in the manufacture of a medicament for use in the treatment of a disease characterized by excessive degradation of the cartilage or matrix. 57. A use according to claim 56, wherein said disease is osteoarthritis. 58. A use according to claim 56, wherein said disease is rheumatoid arthritis.