Azaspiroalkane derivatives metalloprotease inhibitors

FIELD: medicine.

SUBSTANCE: invention refers to compounds of formula I or formula II, to their pharmaceutically acceptable salts, enantiomers and diastereoisomers as metalloprotease inhibitors, and also to a pharmaceutical composition based thereon and to versions of application thereof. Said compounds can find application in treatment of the diseases mediated by activity of metalloproteases, Her-2 SHEDDASE, ADAM-10 and ADAM-17, such as arthritis, cancer, cardiovascular disorders, skin diseases, inflammatory and allergic conditions, etc. In general formula I or II: A represents CWNHOH; B represents CH2; G represents CH2; D represents oxygen; X represents CH2NRb; Y represents CH2; M represents C; U is absent or represents NRb; V is absent or represents phenyl, or 4-10-members heterocyclyl containing 1-2 heteroatoms chosen from N and S, substituted with 0-5 groups Re; U' is absent or represents C1-10alkylene, O or combinations thereof; V' represents H, C1-8alkyl, NRbRc, C6-10carbocyclyl substituted with 0-3 groups Re, or 5-14-members heterocyclyl containing 1-3 heteroatoms chosen from N, O and C substituted with 0-4 groups Re; Ra and Re, independently represents H, T, C1-8alkylene-T, C(O)NRa'(CRb'Rc')r-T, (CRb'Rc')r-O-(CRb'Rc')r-T, OH, Cl, F, CN, NO2, NRIRII, COORIV, ORIV, CONRIRII, C1-8halogenalkyl, C3-13carbocyclyl; Rb and Rc independently represents H, T, C1-6alkylene-T, C(O)O(CRb'Rc')r-T, C(O)(CRb'Rc')r-T, S(O)p(CRb'Rc')r-T; T represents H, C1-10alkyl substituted with 0-1 groups Rb'; C3-6carbocyclyl, 5-6-members heterocyclyl containing one oxygen atom; Ra' Rb' and Rc' independently represents H, ORIV or phenyl; R1 represents hydrogen; R2 represents hydrogen; R3 represents: (i) C1-10alkyl; (ii) 4-14-members heterocyclyl containing 1-3 nitrogen atoms optionally substituted with one or two substitutes chosen from C1-6alkyl, OR13, 5-10-members heterocyclyl containing 1-3 heteroatoms chosen from N O and C, or phenyl; (iii) NR16R17; R4 represents H; R4' represents H; R5' represents H; W represents oxygen; R13 represents C1-C6alkyl; R16 and R17 independently represents C1-C10alkyl or phenyl where each is optionally substituted with one C1-4alkyl; RI and RIIindependently represents H or C1-6alkyl; RIV represents C1-6alkyl; i is equal to 0; p is equal to 1 or 2 and r is equal to 0, 1 or 2; provided that a) a spiro ring represents a stable chemical base unit and b) NR8 and NRb do not contain neither N-N, nor N-O bonds.

EFFECT: higher efficiency of the composition and method of treatment.

54 cl, 1 tbl, 9 dwg, 284 ex

 

The scope of the invention

The present invention relates to Azospirillum compounds that are useful for the treatment of diseases, pathological conditions and disorders associated with the activity of metalloprotease, including the activity of sedds and agamaliev (ADAM).

Background of the invention

Most tissues exist in a highly regulated dynamic equilibrium, where the formation of new tissue and the destruction and elimination of the existing fabric. The destruction of the extracellular matrix (ECM), including connective tissue and basement membrane, is carried out under the action of metalloproteinases, which are released from the connective tissue and enviromix inflammatory cells. Excessive unregulated activity of these enzymes may lead to undesirable tissue destruction, and their activity is regulated at the transcription level by controlled activation of latent proferment and after the broadcast - specific intracellular factors, such as TIMP ("Tissue Inhibitors of Metalloproteinases), or more General proteinase inhibitors, such as α2-macroglobulin.

It is known that some structurally related metalloprotease (MP) play an important role in the cleavage of structural proteins. Such metalloprotease usually act on the extracellular matrix and, therefore clicks the zoom, participate in the destruction and remodeling of tissue. Such proteins are called metalloprotease, or MP. There are several different families of MP, which is classified according to the homology of the sequence. Some families are known MP, and the examples disclosed in the prior art.

Such MP include metalloprotease matrix [MMP], zinc-metalloprotease, many of membrane-bound metalloprotease, TNF-converting enzyme, angiotensin-converting enzymes (ACE), disintegrin, including ADAM (see Wolfsberg et al., 131 J. Cell Bio. 275-78 October, 25 1995) and enkephalinase. Examples include MP collagenase fibroblasts of human skin, gelatinase fibroblasts of human skin, collagenase, arakanese and gelatinase sputum from the human body, and stromelysin person. It is believed that the collagenase, stromelysin, arakanese and related enzymes play an important role in mediating the symptomatology of various diseases.

Zinc proteases are classified in accordance with the basic structure of their catalytic sites and include glycinin, Metzingen, innocency, carboxypeptidase and subgroups DD-carboxypeptidase (Hooper NM, 1994, FEBS Lett, 354:1-6). Subgroup Metzingen further subdivided by seralini, astatine, MatrixOne and Adamantine (Stocker W and Bode W, 1995, Curr Opin Struct Biol, 5:383-390).

MatrixOne include metalloprotease matrix, or MMP. MMP about atout family of structurally similar zinc-containing metalloprotease, involved in the remodeling and degradation of extracellular matrix proteins and as part of normal physiological processes and pathological conditions. Cm. Bode, W et al., 1996, Adv Exp Med Biol, 389:1-11. Connective tissue components of the extracellular matrix and the basement membrane are the biological material providing rigidity, differentiation, binding sites and, in some cases, the elasticity of biological systems. Components of connective tissue include, for example, collagen, elastin, proteoglycans, fibronectin and laminin, which form the framework for all human tissue. In normal conditions the processes of renewal and/or repair of connective tissue are monitored and are in balance. Loss of this balance for any reason leads to various painful conditions. Inhibition of enzymes responsible for the loss of balance, provides the control mechanism for the destruction of this tissue and, therefore, the treatment of such diseases. Uncontrolled destruction of the connective tissue under the action of metalloprotease is a characteristic feature of many pathological conditions.

In addition to their role in the regulation of extracellular matrix there is also information to suggest that MMP mediates the migration of inflammatory cells into the tissue (Moscatelli D and Rifkin DB, 188, Biochim Biophys Acta , 948: 67-85). In some reports it was shown that different MMP can activate various important amatrixia proteins, including cytokines, chemokines, integrins and antimicrobial peptides (see Parks WC, 2002, J Clin Invest, 110:613-4). Many of MMP person sverkhekspressiya in human tumors, and they are associated with precancer tissue destruction and formation of metastases. Another important function of the MMP is the activation of various enzymes, including other MMPs, by cleavage of the Pro-domains of their protease domains. So, some MMP show the effect on regulation of the activity of other MMPs, thus, overproduction one MMP can lead to excessive proteolysis of the extracellular matrix under the action of the other. It was also reported that MMP can cleave and thereby inactivate endogenous inhibitors of other proteases, such as elastase (Winyard PG, et al., 1991, FEBS Letts, 279: 91-94). The MMP inhibitors could, therefore, affect the activity of other destructive proteinases by changing the level of their endogenous inhibitors. In addition, increase or maintain levels of endogenous or injected inhibitor semipretioase contributes to the treatment and prevention of diseases such as emphysema, pulmonary diseases, inflammatory diseases and age-related diseases, such as loss of the ability to stretch and elastic cuff, full the particular skin or body. Thus, the MMP should not be seen only as proteases catabolism ECM, but rather as an extracellular processing enzyme involved in the regulation of cell-cell and cell-ECM signaling events.

Adamantine include reprolatina, metalloprotease the venom of the serpent and ADAM. ADAM (disintegrin and metalloprotease domain) are a family of transmembrane glycoproteins of type I, which play an important role in various biological processes such as cell adhesion and proteolytic shedding (“shedding”) of cell-surface receptors. Members of the ADAM family have been identified from sources related to mammals and memleketim, including Xenopus, Drosophila and Caenorhabditis elegans. Members of this family have a modular design, characterized by the presence of metalloprotease activity and the activity of binding to the integrin receptor and the cytoplasmic domain, which many members of this family defines the binding sites for various proteins of signal transduction. The family of ADAM is involved in the control of mergers membranes, shedding cytokines, growth factors and receptors of growth factors and cell migration, as well as in processes such as muscle growth, fertilization, neurogenesis, and the determination of cell death. Loss of regulation can lead to illness and disease. It was shown that clinicamente ADAM play a role in these pathologies, as infertility, inflammation and cancer. Cm. Wolfsberg TG and White JM, 1998, ADAM metalloproteinases. And Handbook of Proteolytic Enzymes (Barrett AJ, Rawlings ND and Woessner JF (eds), p.1310-1313, Academic Press, London; Seals DF and Courtneidge SA, 2003, Genes & Development, 17:7-30.

Some specific examples of importance of metalloprotease ADAM include TNFα-converting enzyme, TACE or ADAM17, which is currently an important target for anti-inflammatory drugs (Moss ML, et al., 2001, Drug Discov Today 6:417-426 and Black RA, 2002, Int J Biochem Cell Biol, 34:1-5). Other members of this family can also be a good therapeutic target. It was reported that ADAM8 almost exclusively ekspressiruetsya in the cells of the immune system, in particular in B-cells, monocytes, eosinophils and granulocytes. Therefore, ADAM8 is a therapeutic target of immune diseases. ADAM15 found in the smooth muscle cells of the aorta of man and the cultured cells of the umbilical vein endothelium. Although ADAM15 is not expressed in normal blood vessels, it has been found in developing atherosclerotic changes (Herren B, et al., 1997, FASEB J, 11:173-180), and has also been shown that it is activated in osteoarthritic cartilage person in contrast to normal cartilage (Bohm BB et al., 1999, Artritis Rheum, 42:1946-1950). Thus, ADAM15 may play a role in such diseases as atherosclerosis and degeneration of the cartilage is. The lymphocyte-specific expression of ADAM28 suggests that it may have important immunological function.

Believe that overproduction IgE is the main mediator of allergic reactions. CD23 is a low affinity receptor for IgE, is dependent metalloprotease type ADAM proteolytic release of soluble extracellular fragments, which have been shown to activate the production of IgE and induction of inflammatory cytokines (see Novak N, et al., 2001, Curr Opin Immunol, 13:721-726 and Mayer RJ, et al., 2002, Inflamm Res, 51:85-90). Elevated levels of soluble CD23 observed in allergic asthma, chronic B-linfocitos leukemia and rheumatoid arthritis. Inhibition of the enzyme(s)responsible for processing CD23, may offer a therapeutic approach to treat a variety of immune diseases. It turned out that metalloprotease ADAM is also responsible for the release or shedding (“shedding”) of soluble receptors (e.g., CD30 and receptors for TNF), adhesion molecules (e.g., L-selectin, SAM-1, fibronectin, growth factors and cytokines (for example, Fas ligand, TGF-α, EGF, HB-EGF, SCF, IL-6, IL-1, TSH and M-CSF) and receptor growth factors (for example, members of the EGFR family, such as Her-2 and Her-4, involved in the pathogenesis of various types of cancer (Yarden Y and Sliwkowski MX, 2001, Nature Reviews 2:127-137). For example, in 25-30%of breast cancer cases person is the overexpression of Her-2, and it is associated with an increased risk of recurrence and mortality (Slamon DJ et al, 1987, Science, 235:177-182). Recently it was shown that ADAM17 is critical for the regulated shedding Her-4 (Rio C, et al., 2000, Biol Chem, 275:10379-10387). The protease responsible for the cleavage of Her-2, also known as Her-2 sheddase is unknown MMP, which may also be a member of the family of ADAM (Codony-Servat J et al, 1999, Cancer Res 59:1196-1201). Therefore, modulation of the activity can play an important role in the modulation of human disease. Review sheddase activity of ADAM, see Moss ML and Lambert MH, 2002, Essays Biochem, 38:141-153.

ADA-TS protease were identified as members of the family of ADAM. These proteins are new, because they contain unique motifs thrombospondin (TS) type I in addition to some structurally conservative domains of other members of the family of ADAM. ADAMTS also differ from ADAM the absence of cysteine-rich, EGF-like, transmembrane and cytoplasmic domains. It was also shown that ADA-TS proteins are associated with various pathological conditions or diseases. For example, ADAMTS-1 is a selective against tumor gene expressed in tumor cells of the colon, and also is a protein that is associated with inflammation. It was recently shown that the human ortholog of ADAMTS-1, also known as METH-1, and related protein METH-2 possess antiangiogenic activity is d, and these or other members of the ADAMTS family can play an important role in regulating the growth of blood vessels. ADAMTS-2 is involved in the process of normal growth of the skin. This enzyme has long been known as N-procollagen proteinase - proteinase, which proteoliticeski removes aminopeptide in the processing of procollagen type I and type II collagens, and it was shown that there is a deficit in the skin of subjects with hereditary disease of connective tissue syndrome type VIIC Ehlers-Danros. ADAMTS-4 and ADAMTS-11 known as arakanese-1 and -2 due to their ability to cleavage of specific sites in arcane - proteoglycan that supports the mechanical properties of cartilage. Progressive degradation and depletion of Arcana associated with degenerative joint diseases such as osteoarthritis and inflammatory joint diseases such as rheumatoid arthritis. Review metalloprotease ADA-TS, see Tang BL, 2001, Int J Biochem Cell Biol, 33:33-44 and Kaushal GP and Shah SV, 2000, J Clin Invest 105:1335-1337.

Metalloprotease are one of the oldest classes of proteinases, and they are found in bacteria, fungi, and higher organisms. Many enzymes contain a sequence HEXXH, which provides two his-tag ligand for zinc, while the third ligand is either glutamic acid (thermolysin, neprilysin, alanylaminopeptidase) or histidine (astacin). Other Samast is and demonstrate another way of binding of Zn atoms. So metalloprotease were isolated from various prokaryotic and eukaryotic sources. Acid metalloprotease were isolated from the venom of broadband metrogroove Copperhead snake and a rattlesnake. Neutral metalloprotease, in particular those that have optimal activity at neutral pH, for example, were isolated from Aspergillus sojae. Alkaline metalloprotease, for example, were isolated from Pseudomonas aeruginosa, pathogenic insect Xenorhabdus luminescens. Inhibition of microbial metalloprotease can lead to growth inhibition, and is antibiotic strategy. Inhibition of metalloprotease associated with snake poison or toxic insects, also can lead to new therapeutic strategies.

Potential therapeutic indications for inhibitors MP discussed in the literature. See, for example, U.S. patent No. 6500847 (Bayer Corporation), U.S. patent No. 6268379 (DuPont Pharmaceuticals Company), U.S. patent No. 5968795 (Bayer Corporation), U.S. patent No. 5892112 (Glycomed Incorporated and The University of Florida and U.S. patent No. 5872152 (British Biotech Pharmaceuticals Limited). Some examples, where the inhibition activity of metalloprotease may be useful include: a) osteoarthritis b) rheumatic diseases and conditions, such as autoimmune disease, rheumatoid arthritis, c) septic arthritis, d) cancer, including tumor growth, tumor metastasis and angiogenesis, e diseases of the periodontium, f) peptic ulcer disease, corneal, epidermal or gastric (peptic ulcer condition may occur in the cornea resulting alkali burns or as a result of infection caused by Pseudomonas aeruginosa, Acanthamoeba spp., herpes simplex viruses and varicella), (g) proteinuria, (h) various cardiovascular and pulmonary diseases, such as atherosclerosis, thrombotic phenomena, atheroma, hemodynamic shock, unstable angina, restenosis, heart failure, i) aneurysmal disease, including aneurysmal aortic disease, heart or brain, j) the regulation of fertility, k) distribue true acantholytic the hand, foot, l) degenerative cartilage loss in the result of traumatic injuries of the knee joint, m) osteopenia and other diseases of abnormal bone loss, including osteoporosis, n) moderate mandibular joint disease, o) pulmonary diseases such as chronic obstructive pulmonary disease, p) demyelinating diseases of the nervous system such as multiple sclerosis, q) metabolic diseases, including diabetes (with increased breakdown of collagen) and obesity-mediated insulin resistance, macular degeneration and diabetic retinopathy-mediated angiogenesis, cachexia and premature aging of the skin, r) poor wound healing, vklyuchali, s) bedsores, t) acute and chronic neurodegenerative disorders including stroke, spinal cord injury and traumatic brain injury, amyotrophic lateral sclerosis, cerebral amyloid angiopathy, CNS lesions in AIDS, Parkinson's disease, Alzheimer's disease, Huntington's disease, pre-disease, malignant myathenia and Duchenne muscular dystrophy, u) pain, (v) autoimmune encephalomyelitis and w) diseases associated with the production and/or transmission of signals TNFα, such as a wide range of inflammatory and/or immunomodulatory diseases, including rheumatic attack, rheumatoid arthritis, multiple sclerosis, allergies, periodontal disease, hepatitis, bone resorption, sepsis, gram negative sepsis, septic shock, endotoxic shock, toxic shock syndrome, a syndrome of systemic inflammatory response, inflammatory bowel disease, including Crohn's disease and ulcerative colitis, reactions Jarisch-Herxheimer reaction, asthma, respiratory distress syndrome, adult acute fibrotic lung disease, pulmonary sarcoidosis, allergic respiratory disease, silicosis, pneumoconiosis workers of the coal industry, alveolar injury, hepatic failure, liver disease during acute inflammation, severe alcoholic hepatitis, malaria, on the tea Plasmodium falciparum malaria and cerebral malaria, congestive heart failure, disorders after heart disease, arteriosclerosis, including atherosclerosis, Alzheimer's disease, acute encephalitis, brain damage, pancreatitis, including systemic complications in acute pancreatitis, poor wound healing and immune response in infectious inflammation and cancer, myelodysplastic syndromes, systemic lupus erythematosus, biliary cirrhosis, insulin-independent diabetes, bowel necrosis, psoriasis, cachexia and anorexia, radiation damage and toxicity after administration of monoclonal antibodies, such as OKT3, response “host against the graft, including ischemic reperfusion injury and allograft rejection, including exclusion allograft kidney, liver, heart and skin, rejection of lung allograft, including chronic rejection of lung allograft (obliterative bronchitis), as well as complications in the setting of the femoral head, infectious diseases, including mycobacterial infection, meningitis, an infection caused by Helicobacter pylori, peptic ulcer disease Chaga as a result of infection caused by Trypanosoma cruzi, the action of Shiga-like toxin resulting from the infection caused by E. coli, action enterotoxin A result of infections caused by Staphylococcus, meningococcal infection and what Pecci, caused by Borrelia burgdorferi, Treponema pallidum, cytomegalovirus, influenza virus, Sendai virus, encephalomyelitis virus Theiler and human immunodeficiency virus (HIV). May have violated the healing process. This can lead to improper healing of wounds, leading to poor healing, spikes and scarring. These latter defects can lead to disability and/or permanent disability, as in the case of surgical adhesions.

Inhibitors metalloprotease matrix are useful for treating diseases caused, at least partially, by the destruction of structural proteins. Although there was obtained a number of inhibitors, there is still a need for strong inhibitors of metalloprotease matrix, useful for the treatment of such diseases. Applicants surprisingly found that the compounds of the present invention are powerful inhibitors of metalloprotease.

Brief description of the invention

The present invention provides a compound of formula I or II:

or its enantiomer, diastereoisomer, prodrug, MES, metabolite or pharmaceutically acceptable salt, where the constituent members described below.

The present invention also provides compositions containing a compound of formula I or II and pharmaceutically acceptable the initial carrier.

The present invention also provides a method of treating diseases associated with unwanted activity metalloprotease.

The present invention also provides a method of treating diseases modulated by metalloproteases, mammal, where the disease is selected from the group including arthritis, cancer, cardiovascular disorders, skin disorders, inflammatory or allergic condition.

The present invention also provides a method of treating cancer, including, but not limited to, breast cancer, in a mammal.

The present invention also provides a method of inhibiting pathological changes mediated by an increased level of metalloprotease matrix in mammals, including the introduction of a given mammal in need, a therapeutically effective amount of the compounds of the present invention.

The present invention also provides a method of treating diseases associated with undesired activity of TNF-α-converting enzyme.

The present invention also provides a method of treating diseases associated with unwanted activity metalloprotease matrix in a mammal, where the specified metalloprotease matrix selected from the group comprising MMP12, MMP14, MMP3, MMP2 and MMP9.

The present invention also provide the supports method for the treatment of disease, associated with the unwanted activity of Her-2 sheddase, seddas growth factor or seddas of cytokines in a mammal.

The present invention also provides a method of treating diseases associated with the activity of Her-2 sheddase the mammal.

The present invention also provides a method of treating diseases associated with undesirable activity of ADAM10, ADAM15, or ADAM17 in a mammal.

Detailed description of the invention

The present invention provides, inter alia, the compounds and pharmaceutical compositions for the treatment of pathological conditions that are associated with the activity of metalloprotease, such as the rapid and unregulated tissue destruction of the extracellular matrix under the action of MMP, including but not limited to, MMP 12, and MMP 13. Some of these conditions include rheumatoid arthritis, osteoarthritis, septic arthritis, ulcerative lesions of the cornea, the epidermis and the stomach; the periodontal disease, proteinuria, coronary thrombosis associated with the rupture of atherosclerotic plaques, a bone disease. Compounds of the present invention are also useful for treating cancer, including, for example, cancer metastasis and angiogenesis, which, as it turns out, is also associated with the activity of metalloprotease. Also, since the cycle of tissue damage and the response associated with the worsening of painful conditions, Ogre is ikenie induced metalloprotease tissue damage due to elevated levels of proteases using compounds of the present invention, as a rule, may be a useful therapeutic approach to many of these serious diseases, and also to others. Compounds of the present invention are also inhibitors of TNFα converting enzyme and seddas, including Her-2 sheddase and HB-EGF sheddase and other sheddase growth factors and cytokines.

The present invention provides a compound of formula I or II:

or its enantiomer, diastereoisomer, prodrug, MES, metabolite or pharmaceutically acceptable salt, where:

A represents the CWOH, CWNHOH, CWNHOR5N(OH)CHO, - N(OH)CWR6, SH, SR7or hydantoinyl;

B represents (CH2)n, (CH2)nC=W, (CRdRf)nNR8, NR8(CRdRf)n, (CRdRf)nO(CRdRf)r, (CRdRf)nS(CRdRf)r, O(C=W)NR8, O, N, NR8, S(O)m, S, C(O)NR8(CRdRf)nC(O)(CRdRf)nor combinations thereof;

G represents (CH2)n, (CH2)nC=W, (CRdRf)nNR8, NR8(CRdRf)n, (CRdRf)nO(CRdRf)r, (CRdRf)nS(CRdRf)r, O(C=W)NR8, O, N, NR8, S(O)m, S, C(O)NR8(CRdRf)nC(O)(CRdRf)n or combinations thereof;

D represents oxygen or sulfur;

X is absent or represents (CH2)jC1-10alkylene, substituted by 0 to 3 groups of RaC2-10albaniles, substituted 0-2 groups Ra, N, O, NRb, S(O)m, C=O, NRbC(O)NRbC(O)O, NRbC(O)NRbC(O)O, OC(O), S(O)mNRb, NRbS(O)m, NRbS(O)mNRb, (CRdRf)jNRb, NRb(CRdRf)jor combinations thereof;

Y is absent or represents (CH2)jC1-10alkylene, substituted by 0 to 3 groups of RaC2-ALKenilan, substituted 0-2 groups Ra, N, O, NRb, S(O)m, C=O, NRbC(O)NRbC(O)O, NRbC(O)NRbC(O)O, OC(O), S(O)mNRb, NRbS(O)m, NRbS(O)mNRb, (CRdRf)jNRb, NRb(CRdRf)jor combinations thereof;

M represents CO or S(O)i;

U is absent or represents a C1-10alkylene, substituted 0-5 groups RaC2-10albaniles, substituted 0-2 groups Ra, N, O, NRb, NRbC(O)NRbC(O)O, NRbC(O)NRb, NRbS(O)m, NRbS(O)NRbor combinations thereof;

V is absent or represents H, C3-13carbocyclic, substituted 0-5 groups Reor heterocyclyl, substituted 0-5 groups Re;

U' is absent or represents a C1-10alkylene, substituted 0-5 groups RaC2-10albaniles, substituted 0-2 groups Ra, N, O, NRbS(O)m, C=O, NRbC(O)NRbC(O)O, NRbC(O)NRbC(O)O, OC(O), S(O)mNRb, NRbS(O)m, NRbS(O)NRbor combinations thereof;

V' represents H, C1-8alkyl, NRbRcC3-13carbocyclic, substituted 0-5 groups Reor heterocyclyl, substituted 0-5 groups Re;

Raand Re, each independently, represents H, T, C1-8alkylen-T, C2-8albaniles-T, C2-6akinyan-T, C(O)NRa'(CRb'Rc')r-T, C(O)O(CRb'Rc')r-T, S(O)p(CRb'Rc')r-T, (CRb'Rc')r-O-(CRb'Rc')r-T, OH, Cl, F, Br, I, CN, NO2, NRIRII, CORIII, COORIV, ORIV, CONRIRII, NRICONRIRII, OCONRIRII, NRICORII, SO2NRIRII, NRISO2RII, NRISO2NRIRII, OSO2NRIRII, SOpRVC1-8halogenated, C3-13carbocyclic, heterocyclic, carbocyclic or geterotsiklicheskikh, where each of these carbonitrile, heterocyclyl, carbocyclization and heterocyclisation groups are optionally substituted one or ascoltami groups C 1-8alkyl, alkoxy, halogen, halogenated, halogenoalkane, cyano, nitro, amino, alkylamino, dialkylamino, carboxy, complex carboxyaniline ether complex carboxyaniline ether, aminocarbonyl, alkylaminocarbonyl, dialkylaminoalkyl, sulfonyl, aminosulfonyl, alkylaminocarbonyl, dialkylaminoalkyl, arylsulfonyl, arylsulfonyl, alkylsulfonyl or arylsulfonyl;

Rband Rc, each independently, represents H, T, C1-6alkylen-T, C2-8albaniles-T, C2-6akinyan-T, C(O)NRa'(CRc'Rb')r-T, C(O)O(CRb'Rc')r-T, C(O)(CRb'Rc')r-T, S(O)p(CRb'Rc')r-T, (CRc'Rb')r-O-(CRc'Rb')r-T, C(NRa'Ra')(=N-CN) or C(NRa'Ra')(=CHNO2);

Rdand Rf, each independently, represents H, C1-6alkyl, C2-6alkenyl, C2-6quinil, T, C1-6alkylen-T, C2-8albaniles-T, C2-6akinyan-T, C(O)NRa'(CRc'Rb')r-T, C(O)O(CRb'Rc')r-T, S(O)p(CRb'Rc')r-T or (CRc'Rb')r-O-(CRc'Rb')r-T, OH, Cl, F, Br, I, CN, NO2, NRIRII, CORIII, COORIV, ORIV, CONRIRII, RINCONRIRII, OCONRIRII, RINCORII, SO2NRIRII, NRI SO2RII, NRISO2NRIRII, OSO2NRIRII, SOpRVC1-8halogenated, carbocyclic, heterocyclic, carbocyclic, geterotsiklicheskikh, carbocyclic or heteroeroticism, where each of these carbonitrile, heterocyclyl, carbocyclization, heterocyclisation, carbocyclic or hemerocallidaceae optionally substituted by one or more groups C1-8alkyl, alkoxy, halogen, halogenated, halogenoalkane, cyano, nitro, amino, alkylamino, dialkylamino, carboxy, complex carboxyaniline ether complex carboxyaniline ether, aminocarbonyl, alkylaminocarbonyl, dialkylaminoalkyl, sulfonyl, aminosulfonyl, alkylaminocarbonyl, dialkylaminoalkyl, arylsulfonyl, arylsulfonyl, alkylsulfonyl or arylsulfonyl;

T represents H, C1-10alkyl, substituted 0-5 groups Rb'; C2-10alkenyl, substituted 0-5 groups Rb', C2-10quinil, substituted 0-5 groups Rb', C3-13carbocyclic, substituted by 0 to 3 groups of Rb', heterocyclyl, substituted 0-5 groups Rb';

Ra', Rb' and Rc'each independently represents H, C1-6alkyl, C2-6alkenyl,2-6quinil, HE, Cl, F, Br, I, CN, NO2, NRIRII, CORIII, COORIV, ORIV , CONRIRII, RINCONRIRII, OCONRIRII, RINCORII, SO2NRIRII, NRISO2RII, NRISO2NRIRII, OSO2NRIRII, SOPRVC1-8halogenated, carbocyclic, heterocyclic, carbocyclic, geterotsiklicheskikh, carbocyclic or heteroeroticism, where each of these carbonitrile, heterocyclyl, carbocyclization, heterocyclisation, carbocyclic or hemerocallidaceae optionally substituted by one or more groups C1-8alkyl, alkoxy, halogen, halogenated, halogenoalkane, cyano, nitro, amino, alkylamino, dialkylamino, carboxy, complex carboxyaniline ether complex carboxyaniline ether, aminocarbonyl, alkylaminocarbonyl, dialkylaminoalkyl, sulfonyl, aminosulfonyl, alkylaminocarbonyl, dialkylaminoalkyl, arylsulfonyl, arylsulfonyl, alkylsulfonyl or arylsulfonyl;

R1represents hydrogen, C1-6alkyl, SR10OR10or NR11R12;

R2hydrogen, C1-6alkyl, SR10OR10or NR11R12;

R3represents:

(i) C1-10alkyl, C2-8alkenyl or2-8quinil;

(ii) C3-13carbocycle optionally substituted by one or more of the substituents, selected from halogen, C1-6of alkyl, SR13, NR11R12OR13, heterocyclyl, aryl, =S, =O, CN, NO2, NRβRβ', CORγ, RγNC(O)NRγRγ', OC(O)NRγRγ', C(O)ORγC(O)NRγRγ' or RγNC(O)O;

(iii) aryl optionally substituted by one or more substituents selected from halogen, C1-6of alkyl, SR13, NR11R12OR13, heterocyclyl, aryl, =S, =O, CN, NO2, NRβRβ', CORγ, RγNC(O)NRγRγ', OC(O)NRγRγ', C(O)ORγC(O)NRγRγ' or RγNC(O)O;

(iv) heterocyclyl optionally substituted by one or more substituents selected from halogen, C1-6of alkyl, SR13, NR11R12OR13, heterocyclyl, aryl, =S, =O, CN, NO2, NRβRβ', CORγ, RγNC(O)NRγRγ', OC(O)NRγRγ', C(O)ORγC(O)NRγRγ' and RγNC(O)O;

(v) NR14(CH2)lNR14R15or

(vi) NR16R17;

R4and R5, each independently, represents H, halogen, T, C1-6alkylen-T2-6akinyan-T, C(O)NRa'(CRc'Rb')r-T, CO(CRb'Rc')r-T, C(O)O(CRb'Rc')r-T, S(O)p(CRb'Rc')r-T, (CRc'Rb')r-O-(CRc'Rb ')r-T, NR11R12, SR18or or18;

R4' represents H, halogen, T, C1-6alkylen-T, C2-6akinyan-T, C(O)NRa'(CRc'Rb')r-T, CO(CRb'Rc')r-T, C(O)O(CRb'Rc')r-T, S(O)p(CRb'Rc')r-T or (CRc'Rb')r-O-(CRc'Rb')r-T, NR11R12, SR18or or18;

R5' represents H, halogen, T, C1-6alkylen-T, C2-6akinyan-T, C(O)NRa'(CRc'Rb')r-T, CO(CRb'Rc')r-T, C(O)O(CRb'Rc')r-T, S(O)p(CRb'Rc')r-T or (CRc'Rb')r-O-(CRc'Rb')r-T, NR11R12, SR18or or18;

or R4' and R5'together with the atoms to which they are linked, form a ring selected from C3-13carbocycle and 3-14 membered heterocyclyl;

W represents oxygen or sulfur;

R6and R7each independently represents hydrogen, C1-6alkyl, C2-8alkenyl or C2-8quinil;

R8represents H, C1-10alkylen-T, C2-10albaniles-T and C2-10akinyan-T,

(CRb'Rc)rO(CRb'Rc')r-T

(CRb'Rc)rNRa'(CRb'Rc')r-T

(CRb'Rc)rC(O)(CRb'R c')r-T

(CRb'Rc)rC(O)O(CRb'Rc')r-T

(CRb'Rc)rOC(O)(CRb'Rc')r-T

(CRb'Rc)rC(O)NRa'(CRb'Rc')r-T

(CRb'Rc)rNRa'C(O)(CRb'Rc')r-T

(CRb'Rc)rOC(O)O(CRb'Rc')r-T

(CRb'Rc)rOC(O)NRa'(CRb'Rc')r-T

(CRb'Rc)rNRa'C(O)O(CRb'Rc')r-T

(CRb'Rc)rNRa'c(O)NRa'(CRb'Rc')r-T

(CRb'Rc)rS(O)p(CRb'Rc')r-T

(CRb'Rc)rSO2NRa'(CRb'Rc')r-T

(CRb'Rc)rNRa'SO2(CRb'Rc')r-T or

(CRb'Rc)rSO2NRa'SO2(CRb'Rc')r-T;

R10represents H or C1-C6alkyl;

R11and R12each independently represents hydrogen or C1-C8alkyl, or R11and R12together with the N atom to which they are bound, form a 3 to 14-membered heterocyclic ring;

R13represents a C1-C6alkyl, C1-C6halogenated, C3-13carbocyclic, carbocyclic, heterocyclic, hetaeras cyclically, each of which is optionally substituted by one or more groups selected from halogen, C1-4of alkyl, C1-4alkoxy, C1-4halogenoalkane, C1-4halogenoalkane, CN, NO2, OH, COOH, amino, alkylamino or dialkylamino;

R14and R15each independently represents hydrogen, C1-10alkyl, C3-13carbocyclic substituted by one or more heterocyclyl groups, or R14and R15together with the N atom to which they are bound, form a 3-14 membered heterocyclic system;

R16and R17each independently represents hydrogen, C1-C10alkyl, C3-C13carbocyclic, aryl, C3-C13carbocyclic or arylalkyl, where each of the specified C1-C10of alkyl, C3-C13carbocycle, aryl, C3-13carbocyclic or arylalkyl optionally substituted by one or more groups selected from halogen, C1-4of alkyl, C1-4halogenoalkane, OR17', SR17', COOR17', amino, alkylamino, dialkylamino or heterocyclyl;

or R16and R17together with the N atom to which they are bound, form a 3 to 14-membered heterocycle, substituted 0-5 groups Rαor substituted by one or more groups selected from heterocyclyl, geterotsiklicheskikh, C3-C13carbocycle or ka is ballinalee, where each of these heterocyclyl, geterotsiklicheskikh, C3-C13carbocycle or carbocyclic optionally substituted by one or more groups Rα;

R17' represents H, C1-4alkyl, C1-4halogenated, C3-13carbocyclic, carbocyclic, heterocyclic or geterotsiklicheskikh, where each of the specified C3-13carbocycle, carbocyclic, heterocyclic or geterotsiklicheskikh, optionally substituted with halogen or C1-4by alkyl;

R18represents a C1-6alkyl;

Rαrepresents halogen, C1-6alkyl, C2-8alkyloxyalkyl, C1-6halogenated, SR13, NR11R12, OH, OR13C3-13carbocyclic, heterocyclic, aryl, =S, =O, CN, NO2, NRβRβ', CORγ, NRβC(O)NRβRβ', OC(O)NRβRβ', C(O)NRβRβ', C(O)ORγ, NRβC(O)ORγor NRβC(O)Rγor two Rαtogether with the carbon atom to which they are both linked form a C3-13carbocycle;

Rβ, Rβ', Rγand Rγ'each independently represents H, C1-4alkyl, phenyl or benzyl;

RIand RII, each independently, represents H, C1-6alkyl or C3-13carbocyclic;

RIIIand RIV, each independently, represents H, C 1-6alkyl, halogenated, carbocyclic, heterocyclic, carbocyclic or geterotsiklicheskikh, where each of these carbocycle, heterocyclyl, carbocyclic or geterotsiklicheskikh optionally substituted by one or more groups selected from halogen, C1-4the alkyl or C1-4alkoxy;

RVrepresents a C1-6alkyl, halogenated, carbocyclic or heterocyclyl;

j is 1, 2, 3 or 4;

i is 0, 1 or 2;

l is 2, 3, 4, 5, 6, 7 or 8;

n is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12;

m is 0, 1 or 2;

p is 1 or 2 and

r is 0, 1, 2, 3, 4 or 5.

Spirocerca, preferably, is a stable chemical structural unit.

In some embodiments embodiment NR8and NRbcontain no N-N or N-O bonds.

In some embodiments, embodiment A represents CWNHOH, CWNHOR5N(OH)CHO or N(OH)CWR6.

In some embodiments, embodiment A represents CWNHOH or CWNHOR5.

In some embodiments, embodiment A represents C(O)NHOH.

In some embodiments, embodiment B represents (CH2)n, (CH2)nC=W, (CRdRf)nNR8, NR8(CRdRf)n, (CRdRf)nO(CRdRf)r, (CRdRf)nS(CRdRf)r, O(C=W)NR8, O, NR8, S(O)m, S,C(O)NR 8(CRdRf)nor C(O)(CRdRf)n.

In some embodiments, embodiment B represents (CH2)n, (CH2)nC=W, (CRdRf)nNR8, NR8(CRdRf)n, O(C=W)NR8, O, NR8, S(O)m, S, C(O)NR8(CRdRf)nor C(O)(CRdRf)n.

In some embodiments, embodiment B represents (CH2)n, (CH2)nC=W, (CRdRf)nNR8, NR8(CRdRf)n, O(C=W)NR8C(O)NR8(CRdRf)nor C(O)(CRdRf)n.

In some embodiments, embodiment B represents (CH2)n, (CH2)nC=W, (CRdRf)nNR8or NR8(CRdRf)n.

In some embodiments, embodiment B represents (CH2)n.

In some embodiments, embodiment B represents CH2.

In some embodiments of embodiment G is a (CH2)n, (CH2)nC=W, (CRdRf)nNR8, NR8(CRdRf)n, (CRdRf)nO(CRdRf)r, (CRdRf)nS(CRdRf)r, O(C=W)NR8, O, NR8, S(O)m, S, C(O)NR8(CRdRf)nor C(O)(CRdRf)n.

In some var is the preferable embodiment G is a (CH 2)n, (CH2)nC=W, (CRdRf)nNR8, NR8(CRdRf)n, O(C=W)NR8, O, NR8, S(O)m, S, C(O)NR8(CRdRf)nor C(O)(CRdRf)n.

In some embodiments of embodiment G is a (CH2)n, (CH2)nC=W, (CRdRf)nNR8, NR8(CRdRf)n, O(C=W)NR8C(O)NR8(CRdRf)nor C(O)(CRdRf)n.

In some embodiments of embodiment G is a (CH2)n, (CH2)nC=W, (CRdRf)nNR8, NR8(CRdRf)n.

In some embodiments of embodiment G is a (CH2)n.

In some embodiments of embodiment G is a CH2.

In some embodiments, embodiment B, and G both represent CH2.

In some embodiments, embodiment D represents oxygen.

In some embodiments embodiment X represents (CH2)jC1-10alkylene, substituted by 0 to 3 groups of Ra, NRb, S(O)m, C=O, NRbC(O)NRbC(O)O, NRbC(O)NRbC(O)O, OC(O), S(O)mNRb, NRbS(O)m, NRbS(O)NRbor (CRdRf)jNRb, NRb(CRdRf)j.

In some embodiments, the realization of X made the focus of a (CH 2)j, NRb, (CRdRf)jNRbor NRb(CRdRf)j.

In some embodiments embodiment X represents (CH2)j, (CRdRf)jNRbor NRb(CRdRf)j.

In some embodiments embodiment X represents CH2NRbCH2CH2or NRbCH2CH2.

In some embodiments embodiment X represents CH2NRb.

In some embodiments embodiment Y is absent or represents (CH2)jC1-10alkylene, substituted by 0 to 3 groups of Ra, NRb, S(O)m, C=O, NRbC(O)NRbC(O)O, NRbC(O)NRbC(O)O, OC(O), S(O)mNRb, NRbS(O)m, NRbS(O)NRbor (CRdRf)jNRb, NRb(CRdRf)j.

In some embodiments embodiment Y is absent or represents (CH2)j, NRb, (CRdRf)jNRbor NRb(CRdRf)j.

In some embodiments embodiment Y is absent or represents (CH2)j, (CRdRf)jNRbor NRb(CRdRf)j.

In some embodiments embodiment Y is absent or represents CH2CH2NRbCH2CH2or NRbCH2CH2.

p> In some embodiments embodiment Y is absent or represents CH2.

In some embodiments embodiment Y represents CH2.

In some embodiments embodiment R1represents H.

In some embodiments embodiment R2represents H.

In some embodiments embodiment R4represents H.

In some embodiments embodiment R4' represents H.

In some embodiments embodiment R5' represents H.

In some embodiments embodiment R3represents NR16R17.

In some embodiments of embodiment M is CO.

In some embodiments of embodiment U is missing.

In some embodiments of embodiment V is heterocyclyl, substituted 0-5 groups Re.

In some embodiments of embodiment V is azetidin-1-yl, 2,5-dihydro-1H-pyrrol-1-yl, piperidine-1-yl,

piperazine-1-yl, pyrrolidin-1-yl, ethanol-2-yl, pyridin-1-yl, 3,6-dihydropyridines-1-yl, 2,3-dihydroindol-1-yl,

1,3,4,9-tetrahydrocarboline-2-yl, thieno[2,3-c]pyridine-6-yl,

3,4,10,10a-tetrahydro-1H-pyrazino[1,2-a]indol-2-yl,

1,2,4,4a,5,6-hexahydropyrazino[1,2-a]quinoline-3-yl,

pyrazino[1,2-a]quinoline-3-yl, diazepan-1-yl,

1,4,5,6-tetrahydro-2H-benzo[f]isoquinoline-3-yl,

1,4,4a,5,6,10b-hexahydro-2H-benzo[f]isoquinoline-3-yl,

3,3a,8,8a-tet is ahydro-1H-2-azacyclopenta[a]inden-2-yl or

2,3,4,7-tetrahydro-1H-azepin-1-yl, azepin-1-yl.

In some embodiments of embodiment U' is absent or represents O or C1-10alkylene, substituted 0-5 groups Ra.

In some embodiments of embodiment U' is missing.

In some embodiments of embodiment V' represents a C3-13carbocyclic, substituted 0-5 groups Reor heterocyclyl, substituted 0-5 groups Re.

In some embodiments of embodiment V' represents a C3--13carbocyclic, substituted 0-5 groups Re.

In some embodiments of embodiment V' represents phenyl, substituted 0-5 groups Re.

In some embodiments of embodiment V' represents phenyl, substituted 0-5 T, C1-8alkylen-T, (CRb'Rc')r-O-(CRb'Rc')r-T, OH, Cl, F, Br, I, CN, NO2, ORIV, CONRIRIIor NRICORII.

In some embodiments of embodiment V' represents phenyl.

In some embodiments of embodiment V' represents heterocyclyl, substituted 0-5 groups Re.

In some embodiments of embodiment V' represents thiazolyl, benzothiazolyl, thienyl, chinoline, pyridinyl, pyrazinyl, benzimidazolyl, indazoles, 3,6-dihydropyridine, piperidinyl or 2,3-dihydrobenzofuran-5-yl.

In some embodiments of embodiment U' represents O or C1-10alkylen, and ' represents a C 3-13carbocyclic, substituted 0-5 groups Reor heterocyclyl, substituted 0-5 groups Re.

In some embodiments of embodiment M is CO, U is absent, V is heterocyclyl, substituted 0-5 groups ReU' is absent, and V' represents a C3-13carbocyclic, substituted 0-5 groups Reor heterocyclyl, substituted 0-5 groups Re.

In some embodiments of embodiment M is CO, U is absent, V is absent, U' is absent, and V' represents NRbRc.

In some embodiments embodiment Rband Rc, each independently, represents H, C1-6alkylen-T, C(O)NRa'(CRc'Rb')r-T, C(O)O(CRb'Rc')r-T, C(O)(CRb'Rc')r-T, S(O)p(CRb'Rc')r-T, (CRc'Rb')r-O-(CRc'Rb')r-T, C(NRa'Ra')(=N-CN) or C(NRa'Ra')(=CHNO2).

In some embodiments embodiment Rband Rc, each independently, represents H, C1-4alkyl, C(O)NRa'(CRc'Rb')r-T, C(O)O(CRb'Rc')r-T, S(O)p(CRb'Rc')r-T, (CRc'Rb')r-O-(CRc'Rb')r-T, C(NRa'Ra')(=N-CN) or C(NRa'Ra')(=CHNO2).

In some embodiments embodiment Rbthe submitted is a H, C1-4alkyl, C(O)(CRb'Rc')r-T, C(O)O(CRb'Rc')r-T, S(O)p(CRb'Rc')r-T or (CRc'Rb')r-O-(CRc'Rb')r-T.

In some embodiments embodiment Rbrepresents H.

In some embodiments embodiment Rbrepresents a C1-4alkyl.

In some embodiments embodiment Rbrepresents C(O)(CRb'Rc')r-T.

In some embodiments embodiment Rbrepresents C(O)O(CRb'Rc')r-T.

In some embodiments embodiment Rbrepresents S(O)p(CRb'Rc')r-T.

In some embodiments embodiment Rbrepresents (CRc'Rb')r-O-(CRc'Rb')r-T.

In some embodiments embodiment Rcrepresents H or C1-4alkyl.

In some embodiments embodiment Rerepresents H, T, C1-8alkylen-T, C(O)NRa'(CRb'Rc')r-T, (CRb'Rc')r-O-(CRb'Rc')r-T, OH, Cl, F, Br, I, CN, NO2, ORIV, NRIRII, CONRIRII, NRICORII, SO2NRIRIIC1-8halogenated, C3-13carbocyclic, heterocyclic, carbocyclic or geterotsiklicheskikh, where each of these carbonitrile, heterocyclyl, ka is ballinakill and heterocyclisation groups, optionally, substituted by one or more groups selected from C1-8of alkyl, alkoxy, halogen, halogenoalkane, halogenoalkane, cyano, nitro, amino, alkylamino, dialkylamino, carboxy, complex carboxycellulose ether complex carboxycellulose ether, aminocarbonyl, alkylaminocarbonyl, dialkylaminoalkyl, sulfonyl, aminosulfonyl, alkylaminocarbonyl, dialkylaminoalkyl, arylsulfonyl, arylsulfonyl, alkylsulfonyl or arylsulfonyl.

In some embodiments, embodiments, Rerepresents H, C1-6alkyl, OH, Cl, F, Br, I, CN, NO2, methoxy, ethoxy, n-propoxy, isopropoxy, phenoxy, benzyloxy, amino, (C1-4alkyl)amino, (C2-8)dialkylamino, C(O)O(C1-4alkyl), CONH2, CONH(C1-4alkyl), CON(C1-4alkyl)2C1-6halogenated, phenyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, benzyl or phenethyl.

In some embodiments embodiment R4' represents C(O)NRa'(CRc'Rb')r-T, C(O)O(CRb'Rc')r-T or S(O)p(CRb'Rc')r-T.

In some embodiments embodiment R5' represents C(O)NRa'(CRc'Rb')r-T, C(O)O(CRb'Rc')r-T or S(O)p(CRb'Rc')r-T.

In some embodiments embodiment r is 0, 1 or 2

In some embodiments embodiment n is 0, 1 or 2.

In some embodiments of embodiment j is set to 1 or 2.

In some embodiments, embodiments of the specified compound has the formula II.

In some embodiments embodiment the compound has formula II, where:

A represents CWNHOH,

B represents (CH2)n, (CH2)nC=W, (CRdRf)nNR8, NR8(CRdRf)n, (CRdRf)nO(CRdRf)r, (CRdRf)nS(CRdRf)r, OC(O)NR8, O, NR8, S(O)m, S, C(O)NR8(CRdRf)nor C(O)(CRdRf)n;

G represents (CH2)n, (CH2)nC=W, (CRdRf)nNR8, NR8(CRdRf)n, (CRdRf)nO(CRdRf)r, (CRdRf)nS(CRdRf)r, OC(O)NR8, O, NR8, S(O)m, S, C(O)NR8(CRdRf)nor C(O)(CRdRf)n;

X is absent or represents (CH2)jC1-10alkylene, substituted by 0 to 3 groups of Ra, O, NRb, S(O)m, C=O, NRbC(O)NRbC(O)O, NRbC(O)NRbC(O)O, OC(O), S(O)mNRb, NRbS(O)m, NRbS(O)NRb, (CRdRf)jNRbor NRb(CRdRf)j ;

Y is absent or represents (CH2)jC1-10alkylene, substituted by 0 to 3 groups of Ra, O, NRb, S(O)m, C=O, NRbC(O)NRbC(O)O, NRbC(O)NRbC(O)O, OC(O), S(O)mNRb, NRbS(O)m, NRbS(O)NRb, (CRdRf)jNRbor NRb(CRdRf)j;

M represents CO;

U is absent or represents a C1-10alkylene, substituted 0-5 groups Ra, O, NRb, S(O)m, C=O, NRbC(O)NRbC(O)O, NRbC(O)NRbC(O)O, OC(O), S(O)mNRb, NRbS(O)mor NRbS(O)NRb;

V is absent or represents a C3-13carbocyclic, substituted 0-5 groups Reor heterocyclyl, substituted 0-5 groups Re;

U' is absent or represents a C1-10alkylene, substituted 0-5 groups Ra, O, NRbS(O)m, C=O, NRbC(O)NRbC(O)O, NRbC(O)NRbC(O)O, OC(O), S(O)mNRb, NRbS(O)mor NRbS(O)NRb;

V' represents H, C1-8alkyl, NRbRcC3-13carbocyclic, substituted 0-5 groups Reor heterocyclyl, substituted 0-5 groups Re;

R1represents hydrogen;

R2represents hydrogen;

R3represents NR16R17;

R4' represents H, C(O)NRa '(CRc'Rb')r-T, C(O)O(CRb'Rc')r-T or S(O)p(CRb'Rc')r-T;

R5' represents H, C(O)NRa'(CRc'Rb')r-T, C(O)O(CRb'Rc')r-T or S(O)p(CRb'Rc')r-T; and

W represents oxygen.

In some embodiments embodiment the compound has formula II, where:

A represents C(O)NHOH;

B represents (CH2)n, (CH2)nC=W, (CRdRf)nNR8, NR8(CRdRf)n, (CRdRf)nO(CRdRf)r, (CRdRf)nS(CRdRf)r, OC(O)NR8, O, NR8, S(O)m, S, C(O)NR8(CRdRf)nor C(O)(CRdRf)n;

G represents (CH2)n, (CH2)nC=W, (CRdRf)nNR8, NR8(CRdRf)n, (CRdRf)nO(CRdRf)r, (CRdRf)nS(CRdRf)r, OC(O)NR8, O, NR8, S(O)m, S, C(O)NR8(CRdRf)nor C(O)(CRdRf)n;

X is absent or represents (CH2)j, NRb, (CRdRf)jNRbor NRb(CRdRf)j;

Y is absent or represents (CH2)j, NRb, (CRdR )jNRbor NRb(CRdRf)j;

M represents CO;

U is absent;

V is absent or represents a C3-13carbocyclic, substituted 0-5 groups Reor heterocyclyl, substituted 0-5 groups Re;

U' is absent or represents a C1-10alkylene, substituted 0-5 groups Ra, O, NRbS(O)m, C=O, NRbC(O)NRbC(O)O, NRbC(O)NRbC(O)O, OC(O), S(O)mNRb, NRbS(O)mor NRbS(O)NRb;

V' represents H, C1-8alkyl, NRbRcC3-13carbocyclic, substituted 0-5 groups Reor heterocyclyl, substituted 0-5 groups Re;

Rband Rc, each independently, represents H, C(O)O(CRb'Rc')r-T or S(O)p(CRb'Rc')r-T;

Rdand Rf, each independently, represents H or C1-6alkyl;

R1represents hydrogen;

R2represents hydrogen;

R3represents NR16R17;

R4' represents H, C(O)NRa'(CRc'Rb')r-T, C(O)O(CRb'Rc')r-T or S(O)p(CRb'Rc')r-T; and

R5' represents H, C(O)NRa'(CRc'Rb')r-T, C(O)O(CRb'Rc')r-T or S(O)p(CRb'Rc')r-T;

what some embodiments embodiment the compound has formula II, where:

A represents C(O)NHOH;

B represents (CH2)n, (CH2)nC=W, (CRdRf)nNR8, NR8(CRdRf)n, (CRdRf)nO(CRdRf)r, (CRdRf)nS(CRdRf)r, OC(O)NR8, O, NR8, S(O)m, S, C(O)NR8(CRdRf)nor C(O)(CRdRf)n;

G represents (CH2)n, (CH2)nC=W, (CRdRf)nNR8, NR8(CRdRf)n, (CRdRf)nO(CRdRf)r, (CRdRf)nS(CRdRf)r, OC(O)NR8, O, NR8, S(O)m, S, C(O)NR8(CRdRf)nor C(O)(CRdRf)n;

X is absent or represents (CH2)j, NRb, (CRdRf)jNRbor NRb(CRdRf)j;

Y is absent or represents (CH2)j, NRb, (CRdRf)jNRbor NRb(CRdRf)j;

M represents CO;

U is absent;

V is absent or represents a C3-13carbocyclic, substituted 0-5 groups Reor heterocyclyl, substituted 0-5 groups Re;

U' is absent or represents a C1-10alkylene, substituted 0-5 groups Ra, O, NRb S(O)m, C=O, NRbC(O)NRbC(O)O, NRbC(O)NRbC(O)O, OC(O), S(O)mNRb, NRbS(O)mor NRbS(O)NRb;

V' represents H, C1-8alkyl, NRbRcC3-13carbocyclic, substituted 0-5 groups Reor heterocyclyl, substituted 0-5 groups Re;

Rband Rc, each independently, represents H, C(O)O(CRb'Rc')r-T or S(O)p(CRb'Rc')r-T; C(O)(CRb'Rc')r-T, (CRc'Rb')r-O-(CRc'Rb')r-T, C(O)NRa'(CRc'Rb')r-T, C(NRa'Ra')(=N-CN) or C(NRa'Ra')(=CHNO2);

Rdand Rf, each independently, represents H or C1-6alkyl;

Ra' represents H or C1-6alkyl;

Rb' and Rc'each independently represents H, C1-6alkyl, OH, Cl, F, Br, I, CN, NO2, NRIRII, ORIVor halogenated;

R1represents hydrogen;

R2represents hydrogen;

R4' represents H, C(O)NRa'(CRc'Rb')r-T, C(O)O(CRb'Rc')r-T or S(O)p(CRb'Rc')r-T;

R5' represents H, C(O)NRa'(CRc'Rb')r-T, C(O)O(CRb'Rc')r-T or S(O)p(CRb'Rc')r-T;

j is 1 or 2;

l is 2, 3 or 4;

n is 0, 1, 2, 3 or 4 and

r is 0, 1 or 2.

In some embodiments embodiment the compound has formula II, where:

A represents CONHOH;

B represents (CH2)n, (CH2)nC=W, (CRdRf)nNR8, NR8(CRdRf)n, (CRdRf)nO(CRdRf)r, (CRdRf)nS(CRdRf)r, OC(O)NR8, O, NR8, S(O)m, S, C(O)NR8(CRdRf)nor C(O)(CRdRf)n;

G represents (CH2)n, (CH2)nC=W, (CRdRf)nNR8, NR8(CRdRf)n, (CRdRf)nO(CRdRf)r, (CRdRf)nS(CRdRf)r, OC(O)NR8, O, NR8, S(O)m, S, C(O)NR8(CRdRf)nor C(O)(CRdRf)n;

X is absent or represents (CH2)jCH2NRbor NRbCH2CH2;

Y is absent or represents (CH2)jCH2NRbor NRbCH2CH2;

M represents CO;

U is absent;

V represents heterocyclyl, substituted 0-5 groups Re;

U' is absent or represents a C1-10alkylene, substituted 0-5 groups Raor O;

V' is the battle H, C1-8alkyl, NRbRcC3-13carbocyclic, substituted 0-5 groups Reor heterocyclyl, substituted 0-5 groups Re;

Rbrepresents H, C(O)O(CRb'Rc')r-T or S(O)p(CRb'Rc')r-T; C(O)(CRb'Rc')r-T, (CRc'Rb')r-O-(CRc'Rb')r-T, C(O)NRa'(CRc'Rb')r-T, C(NRa'Ra')(=N-CN) or C(NRa'Ra')(=CHNO2);

Rcrepresents H, T, C1-6alkylen-T, C2-8albaniles-T or C2-6akinyan-T;

Rdand Rf, each independently, represents H or C1-6alkyl;

Ra' represents H or C1-6alkyl;

Rb' and Rc'each independently represents H, C1-6alkyl, OH, Cl, F, Br, I, CN, NO2, NRIRII, ORIVor halogenated;

R1represents hydrogen;

R2represents hydrogen;

R4' represents H;

R5' represents H;

j is 1 or 2;

l is 2, 3 or 4;

n is 0, 1, 2, 3 or 4 and

r is 0, 1 or 2.

In some embodiments embodiment the compound has formula II where:

A represents CONHOH;

B represents (CH2)n, (CH2)nC=W, (CRdRf)nNR8or NR8(CRdRf);

G represents the Oh (CH 2)n, (CH2)nC=W, (CRdRf)nNR8or NR8(CRdRf)n;

X is absent or represents (CH2)jCH2NRbor NRbCH2CH2;

Y is absent or represents (CH2)jCH2NRbor NRbCH2CH2;

M represents CO;

U is absent;

V represents heterocyclyl, substituted 0-5 groups Re;

U' is absent or represents a C1-10alkylene, substituted 0-5 groups Raor O;

V' represents H, C1-8alkyl, NRbRcC3-13carbocyclic, substituted 0-5 groups Reor heterocyclyl, substituted 0-5 groups Re;

Rbrepresents H, C(O)O(CRb'Rc')r-T or S(O)p(CRb'Rc')r-T; C(O)(CRb'Rc')r-T, (CRc'Rb')r-O-(CRc'Rb')r-T, C(O)NRa'(CRc'Rb')r-T, C(NRa'Ra')(=N-CN) or C(NRa'Ra')(=CHNO2);

Rcrepresents H, T, C1-6alkylen-T, C2-8albaniles-T or C2-6akinyan-T;

Rdand Rf, each independently, represents H or C1-6alkyl;

Ra' represents H or C1-6alkyl;

Rb' and Rc'each independently represents H, C 1-6alkyl, OH, Cl, F, Br, I, CN, NO2, NRIRII, ORIVor halogenated;

R1represents hydrogen;

R2represents hydrogen;

R4' represents H;

R5' represents H;

j is 1 or 2;

l is 2, 3 or 4;

n is 0, 1, 2, 3 or 4 and

r is 0, 1 or 2.

In some embodiments embodiment the compound has formula II, where:

A represents CONHOH;

B represents (CH2)n;

G represents (CH2)n;

X is absent or represents (CH2)jCH2NRbor NRbCH2CH2;

Y is absent or represents (CH2)jCH2NRbor NRbCH2CH2;

M represents CO;

U is absent;

V represents heterocyclyl, substituted 0-5 groups Re;

U' is absent or represents a C1-10alkylene, substituted 0-5 groups Raor O;

V' represents H, C1-8alkyl, NRbRcC3-13carbocyclic, substituted 0-5 groups Reor heterocyclyl, substituted 0-5 groups Re;

Rbrepresents H, C(O)O(CRb'Rc')r-T or S(O)p(CRb'Rc')r-T; C(O)(CRb'Rc')r-T, (CRc'Rb')r-O-(CRc'Rb')r-T, C(O)NRa'CR c'Rb')r-T, C(NRa'Ra')(=N-CN) or C(NRa'Ra')(=CHNO2);

Rcrepresents H, T, C1-6alkylen-T, C2-8albaniles-T or C2-6akinyan-T;

Ra' represents H or C1-6alkyl;

Rb' and Rc'each independently represents H, C1-6alkyl, OH, Cl, F, Br, I, CN, NO2, NRIRII, ORIVor halogenated;

R1represents hydrogen;

R2represents hydrogen;

R4' represents H;

R5' represents H;

j is 1 or 2;

l is 2, 3 or 4;

n is 0, 1, 2, 3 or 4 and

r is 0, 1 or 2.

In some embodiments embodiment the compound has formula II, where:

A represents CONHOH;

B represents CH2;

G represents CH2;

X represents CH2NRb;

Y is (CH2)j;

M represents CO;

U is absent;

V represents azetidin-1-yl,

2,5-dihydro-1H-pyrrol-1-yl, piperidine-1-yl, piperazine-1-yl,

pyrrolidin-1-yl, ethanol-2-yl, pyridin-1-yl,

3,6-dihydropyridines-1-yl, 2,3-dihydroindol-1-yl,

1,3,4,9-tetrahydrocarboline-2-yl, thieno[2,3-c]pyridine-6-yl,

3,4,10,10a-tetrahydro-1H-pyrazino[1,2-a]indol-2-yl,

1,2,4,4a,5,6-hexahydropyrazino[1,2-a]quinoline-3-yl,

pyrazino[1,2-a]quinoline-3-yl, diazepan-1-yl,

<> 1,4,5,6-tetrahydro-2H-benzo[f]isoquinoline-3-yl,

1,4,4a,5,6,10b-hexahydro-2H-benzo[f]isoquinoline-3-yl,

3,3a,8,8a-tetrahydro-1H-2-azacyclopenta[a]inden-2-yl or

2,3,4,7-tetrahydro-1H-azepin-1-yl, azepin-1-yl;

U' is missing;

V' represents a C3-13carbocyclic, substituted 0-5 groups Re;

Rbrepresents H, C(O)O(CRb'Rc')r-T or C(O)(CRb'Rc')r-T;

Ra' represents H or C1-6alkyl;

Rb' and Rc' both represent H;

R1represents hydrogen;

R2represents hydrogen;

R4' represents H;

R5' represents H;

j is 1 or 2 and

r is 0, 1 or 2.

In some embodiments embodiment the compound has formula II, where:

A represents CONHOH;

B represents CH2;

G represents CH2;

X represents CH2NRb;

Y is (CH2)j;

M represents CO;

U is absent;

V represents piperidine-1-yl, piperazine-1-yl, pyrrolidin-1-yl, pyridin-1-yl or 3,6-dihydropyridines-1-yl;

U' is missing;

V' represents a C3-13aryl, substituted 0-5 groups Re;

Rbrepresents H, C(O)O(CRb'Rc')r-T or C(O)(CRb'Rc')r-T;

Rb' and Rc' both represent H;

R1represents hydrogen;

R2represents hydrogen;

R4' represents H;

R5' represents H;

j is 1 or 2 and

r is 0, 1 or 2.

In some embodiments embodiment the compound has formula II, where:

A represents CONHOH;

B represents CH2;

G represents CH2;

X represents CH2NRb;

Y is (CH2)j;

M represents CO;

U is absent;

V represents piperidine-1-yl, piperazine-1-yl, pyrrolidin-1-yl, pyridin-1-yl or 3,6-dihydropyridines-1-yl;

U' is missing;

V' represents phenyl, substituted 0-3 Re;

Rbrepresents H, C(O)O(CRb'Rc')r-T or C(O)(CRb'Rc')r-T;

Rb' and Rc' both represent H;

R1represents hydrogen;

R2represents hydrogen;

R4' represents H;

R5' represents H;

j is 1 or 2 and

r is 0, 1 or 2.

In various sections of the present description, the substituents of the compounds of the present invention are disclosed, specifying groups or intervals. The present invention specifically presented so as to cover each of the different combinations of the members did the groups and intervals. For example, the term “C1-6alkyl” is specifically presented in a way that it covers every single group methyl, ethyl, C3alkyl, C4alkyl, C5alkyl and C6alkyl.

For compounds of the present invention, in which a variable occurs more than once, each variable can represent a different group selected from the Markush group (Markush), defining this variable. For example, if the description of the structure containing two groups of R1that are simultaneously present in the same connection, the two groups R may represent a different group selected from the Markush group defined for R.

It is also possible that some features of the present invention, which, for clarity, described in the context of the individual embodiment variants of the invention can also be provided in combination in a single embodiment. Therefore, various features of the invention, which, for brevity, described in the context of a single option may be presented separately or in any suitable combination.

As used herein, the term “alkyl” means a saturated hydrocarbon group which is linear or branched. Examples of alkyl groups include methyl (Me), ethyl (Et), propyl (e.g. n-propyl and isopropyl), butyl (n is an example, n-butyl, isobutyl, tert-butyl), pentyl (for example, n-pentyl, isopentyl, neopentyl) and the like, the Alkyl group may contain from 1 to about 20, from 2 to about 20, from 1 to about 10, from 1 to about 8, from 1 to about 6, from 1 to about 4, or from 1 to about 3 carbon atoms.

As used herein, “alkenyl” refers to an alkyl group that contains one or more carbon-carbon double bonds. Examples alkenyl groups include ethynyl, propenyl, cyclohexenyl etc.

As used in this description, “quinil” refers to an alkyl group that contains one or more carbon-carbon triple bonds. Examples etkinlik groups include ethinyl, PROPYNYL and the like

As used in this description, “halogenated” refers to an alkyl group that contains one or more halogen substituents. Examples halogenating groups include CF3C2F5, CHF2, CCl3, CHCl2C2Cl5and the other Alkyl group in which all hydrogen atoms are replaced by halogen atoms, may be specified as “perhalogenated.”

As used in this description, “alkylene” or “alkylene” refers to a divalent alkyl group. Example alkalinous group is methylene or ethylene.

As used in this description, “albaniles” or “alkenylacyl” apply is to divalent alkenylphenol group.

As used in this description, “carbocycle” groups are saturated (i.e. do not contain any double or triple bonds) or unsaturated (i.e. containing one or more double or triple bonds) cyclic hydrocarbon groups. Carbonitrile groups may be mono - or polycyclic (e.g., containing 2, 3 or 4 condensed rings) or spirocyclohexane. Examples carbocyclic groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclopentenyl, 1,3-cyclopentadienyl, cyclohexenyl, norbornyl, mobinil, nonkernel, substituted, phenyl, etc. Carbonitrile groups can be aromatic (e.g., “aryl”) or non-aromatic (e.g., “cycloalkyl”). In some embodiments embodiment carbonitrile groups can contain from about 3 to about 30 carbon atoms, from about 3 to about 20, from about 3 to about 10, or from about 3 to about 7 carbon atoms.

As used herein, “aryl” refers to aromatic carbocycles group includes monocyclic or polycyclic (e.g., containing 2, 3 or 4 condensed rings) aromatic hydrocarbons, such as, for example, phenyl, naphthyl, anthracene, phenanthrene, indanyl, indenyl, etc. In some embodiments the embodiment of the aryl groups contain from 6 to about 0 carbon atoms.

As used in this description, “cycloalkyl” refers to non-aromatic carbacyclin groups, including cyklinowanie alkyl, alkeline and alkyline group. Cycloalkyl group may include bi - or polycyclic (e.g., containing 2, 3 or 4 condensed rings) ring systems, as well as spirocycles system. Examples cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclopentenyl, cyclohexenyl, cyclohexadienyl, cycloheptatriene, norbornyl, mobinil, nonkernel, substituted etc. under the definition of “cycloalkyl” fall group containing one or more aromatic rings, condensed (i.e. have a common bond) with cycloalkyl ring, for example lansoprozole pentane, pentene, hexane, etc.

As used in this description, “heterocyclyl” or “heterocycle” refers to a saturated or unsaturated carbocycles group, where one or more forming ring carbon atoms carbonitrile group is replaced by a heteroatom such as O, S or N. Heterocyclyl groups can be aromatic (e.g., “heteroaryl”) or non-aromatic (e.g., “heteroseksualci”). Heterocyclyl group may also apply to gidrirovanny and partially gidrirovanny heteroaryl g is uppam. Heterocyclyl groups can be characterized as containing 3-14 forming ring atoms. In some embodiments embodiment heterocyclyl group may contain in addition to at least one heteroatom from about 1 to about 20, from about 2 to about 10, or from about 2 to about 7 carbon atoms and may be attached through a carbon atom or heteroatom. In the following variants of the embodiment of the heteroatom can be oxidized (for example, to contain oxo or sulfide Deputy), or the nitrogen atom may be stereoselectivity. Examples heterocyclyl groups include morpholino, thiomorpholine, piperazinil, tetrahydrofuranyl, tetrahydrofuranyl, 2,3-dihydrobenzofuran, 1,3-benzodioxole, benzo-1,4-dioxane, piperidinyl, pyrrolidinyl, isoxazolidine, isothiazolinones, pyrazolidine, oxazolidine, thiazolidine, imidazolidinyl and the like, as well as any of the groups listed below for heteroaryl” and “geterotsiklicheskie.” In addition, examples of the heterocycle include pyrimidinyl, phenanthridines, phenanthrolines, phenazines, phenothiazines, phenoxathiin, phenoxazines, phthalazine, piperazinil, piperidinyl, 3,6-dihydropyridin, 1,2,3,6-tetrahydropyridine, 1,2,5,6-tetrahydropyridine, piperidinyl, 4-piperidinyl, piperonyl, pteridinyl, purinol, pyranyl, pyrazinyl, pyrazolidine, pyrazoline, pyrazolyl, pyridazinyl, pyridoxal, PI is iodoimidazole, peridotite, pyridinyl, pyridyl, pyrimidinyl, pyrrolidinyl, pyrrolyl, 2H-pyrrolyl, pyrrolyl, tetrahydrofuranyl, tetrahydroisoquinoline, tetrahydroquinoline, tetrazolyl, 6H-1,2,5-thiadiazolyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl, thianthrene, thiazolyl, thienyl, theNational, cyanoacetyl, tenomodulin, thiophenyl, triazinyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,5-triazolyl, 1,3,4-triazolyl, xantener, octahydronaphthalene, oxadiazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, oxazolidinyl, oxazolyl, oxazolidinyl, hintline, chinoline, 4H-hemolysins, honokalani, hinokitiol, acridines, azocines, benzimidazolyl, benzofuranyl, benzothiophene, benzothiophene, benzoxazole, benzthiazole, benzotriazolyl, asterisell, benzisoxazole, benzisothiazole, benzimidazolinyl, methylenedioxyphenyl, morpholinyl, naphthyridine, decahydroquinoline, 2H,6H-1,5,2-detainer, dihydrofuro[2,3-b]tetrahydrofuran, furanyl, furutani, carbazolyl, 4aH-carbazolyl, carbolines, bromanil, bromanil, cinnoline, imidazolidinyl, imidazolyl, imidazolyl, 1H-indazole, indoline, indolinyl, indolizinyl, indolyl, 3H-indolyl, isobenzofuranyl, isopropanol, isoindolyl, isoindolines, isoindolyl, ethenolysis, isothiazole and isoxazole. The following examples of heterocycles include is azetidin-1-yl, 2,5-dihydro-1H-pyrrol-1-yl, piperidine-1-yl, piperazine-1-yl, pyrrolidin-1-yl, ethanol-2-yl, pyridin-1-yl, 3,6-dihydropyridines-1-yl, 2,3-dihydroindol-1-yl, 1,3,4,9-tetrahydrocarboline-2-yl, thieno[2,3-c]pyridine-6-yl, 3,4,10,10a-tetrahydro-1H-pyrazino[1,2-a]indol-2-yl, 1,2,4,4a,5,6-hexahydropyrazino[1,2-a]quinoline-3-yl, pyrazino[1,2-a]quinoline-3-yl, diazepan-1-yl, 1,4,5,6-tetrahydro-2H-benzo[f]isoquinoline-3-yl, 1,4,4a,5,6,10b-hexahydro-2H-benzo[f]isoquinoline-3-yl, 3,3a,8,8a-tetrahydro-1H-2-azacyclopenta[a]inden-2-yl and 2,3,4,7-tetrahydro-1H-azepin-1-yl, azepin-1-yl. Also included condensed cyclic and spiraeoideae containing, for example, the above heterocycles.

As used herein, “heteroaryl” groups are aromatic heterocyclyl groups include monocyclic and polycyclic (e.g., containing 2, 3 or 4 condensed rings) aromatic hydrocarbons that contain at least one heteroatom as a ring member such as sulfur, oxygen, or nitrogen. Heteroaryl groups include, without limitation, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, triazinyl, furyl, hinely, ethanolic, thienyl, imidazolyl, thiazolyl, indolyl, peril, oxazolyl, benzofuran, benzothiazyl, benzothiazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, indazoles, 1,2,4-thiadiazolyl, isothiazolin, benzothiazyl, purinol, carb is alil, benzimidazolyl, indolyl, etc. In some embodiments the embodiment of the heteroaryl group contains from 1 to about 20 carbon atoms, and in another variation of the embodiment from about 3 to about 20 carbon atoms. In some embodiments the embodiment of the heteroaryl group contains from 3 to about 14, from about 3 to about 7, or from 5 to 6 forming the ring atoms. In some embodiments the embodiment of the heteroaryl group contains from 1 to about 4, from 1 to about 3, or 1-2 heteroatoms.

As used in this description, “heteroseksualci” refers to non-aromatic heterocyclyl groups, including cyklinowanie alkyl, alkeline and alkyline group, where one or more forming the ring carbon atoms is replaced by a heteroatom, such as an atom of O, N, or S. Examples of “geterotsiklicheskikh” groups include morpholino, thiomorpholine, piperazinil, tetrahydrofuranyl, tetrahydrofuranyl, 2,3-dihydrobenzofuran, 1,3-benzodioxole, benzo-1,4-dioxane, piperidinyl, pyrrolidinyl, isoxazolidine, isothiazolinones, pyrazolidine, oxazolidine, thiazolidine, imidazolidine etc. under the definition of “heteroseksualci” fall group, containing one or more aromatic rings, condensed (i.e. have a common bond) with non-aromatic heterocyclic ring, such as phthalamide, naphthalimides, and benzoperylene hetaeras the cycles, such as indolinone and isoindoline group. In some embodiments embodiment heterocytolysine group contains from 1 to about 20 carbon atoms, and in another variation of the embodiment from about 3 to about 20 carbon atoms. In some embodiments embodiment heterocytolysine group contains from 3 to about 14, from about 3 to about 7, or 5-6 forming ring atoms. In some embodiments embodiment heterocytolysine group contains from 1 to about 4, from 1 to about 3, or 1-2 heteroatoms. In some embodiments embodiment heterocytolysine group contains from 0 to 3 double bonds. In some embodiments embodiment heterocytolysine group contains from 0 to 2 triple bonds.

As used herein, “halo” or “halogen” includes fluorine, chlorine, bromine and iodine.

As used herein, “alkoxy” refers to-O-alkyl groups. Examples of alkoxygroup include methoxy, ethoxy, propoxy (e.g., n-propoxy, isopropoxy), tert-butoxy etc.

As used in this description, “aryloxy” refers to-O-aryl groups. An example of alloctype is phenoxy.

As used in this description, “halogenoalkane” refers to-O-halogenosilanes groups. An example of halogenlampe is OCF3.

As used in this description, “carbocyclic” refers kalkile group, replaced by carbocyclic. Examples carbocyclization groups include aralkyl” (alkyl, substituted aryl (arylalkyl”)) and “cycloalkenyl” (alkyl, substituted cycloalkyl). In some embodiments embodiment carbocyclization groups contain from 4 to 24 carbon atoms.

As used in this description, “geterotsiklicheskikh” refers to an alkyl group substituted heteronormatively group. Examples heterotrophically groups include heteroaromatic” (alkyl, substituted heteroaryl) and geterotsiklicheskikh” (alkyl, substituted heterocyclization). In some embodiments embodiment heterocyclisation groups contain from 3 to 24 carbon atoms in addition to the at least one forming a ring heteroatom.

As used herein, “amino” refers to the group of NH2. “Alkylamino” refers to the amino group, substituted alkyl group, and dialkylamino” refers to an amino group substituted by two alkyl groups.

As used in this description, “aminocarbonyl” refers to CONH2.

As used in this description, “alkylaminocarbonyl” refers to CONH(alkyl).

As used in this description, “alkylaminocarbonyl” refers to CON(alkyl)2.

As used herein, “carboxy” or “Kar is oxyl” refers to COOH.

As used in this description, “carboxyaniline ester” refers to COO-alkyl.

As used in this description, “carboxypropyl ester” refers to COO-aryl.

As used in this description, “hydroxy” refers to-OH.

As used in this description, “mercapto” refers to SH.

As used in this description, “sulfinil” refers to SO.

As used in this description, “sulfonyl” refers to the SO2.

As used in this description, “aminosulfonyl” refers to the SO2NH2.

As used in this description, “alkylaminocarbonyl” refers to the SO2NH(alkyl).

As used in this description, “dialkylaminoalkyl” refers to the SO2N(alkyl)2.

As used in this description, “arylsulfonyl” refers to the SO2-aryl.

As used in this description, “arylsulfonyl” refers to SO-aryl.

As used in this description, “alkylsulfonyl” refers to the SO2-alkyl.

As used in this description, “alkylsulfonyl” refers to SO-alkyl.

As used herein, “combination” means a combination of two or more groups specified for this variable. For example, “CH2, NH, CO, and combinations thereof” include CH2NH, CH2CO, CONH, CH2NHCO other stable combination.

Unless otherwise indicated, the compounds represented by the above formula include pharmaceutically acceptable salts, prodrugs, enantiomers, diastereomers, racemic mixtures, crystalline forms, non-crystalline forms, amorphous form, hydrate and a solvate of these compounds.

The term “pharmaceutically acceptable salt” refers to salts of the active compounds obtained with relatively nontoxic acids or bases, depending on the particular substituents present in the compounds described in this application. When the compounds of the present invention contain relatively acidic functional group, can be obtained basically additive salts by contacting the neutral form of such compounds with a sufficient amount of the desired base, either without solvent or in a suitable inert solvent. Examples of pharmaceutically acceptable basic additive salts include salts of sodium, potassium, calcium, ammonium, organic amine or magnesium, or a similar salt. When the compounds of the present invention contain relatively basic functional group, it is possible to obtain an acid additive salt by contacting the neutral form of such compounds with a sufficient amount of the desired acid, either without solvent or in a suitable inert races is varicela. Examples of pharmaceutically acceptable acid additive salts include salts formed from inorganic acids such as hydrochloric, Hydrobromic, nitric, carbonic, phosphoric, partially neutralized phosphoric acid, sulfuric, partially neutralized sulfuric, itestosterone and phosphorous acid, etc. and salts formed from relatively nontoxic organic acids, such as acetic, propionic, somalina, maleic, malonic, benzoic, succinic, subernova, fumaric, almond, phthalic, benzolsulfonat, p-tolilsulfonil, citric, tartaric, methansulfonate etc. Also included are salts of amino acids such as arginate and the like, and salts of organic acids, such as glucuronic and galacturonic acids, etc. are Some of the specific compounds of the present invention may contain both basic and acidic functional groups, which allows you to convert such compounds either in primary or in an acid additive salt.

Compounds of the present invention can be restored to their neutral form by contacting the salt with a base or acid and the allocation of the parent compound in the traditional way. The original form of the compounds is different from the various forms of salts in certain physical properties, such as RAS is foremost in polar solvents, but otherwise for the purposes of the present invention the salt is equivalent to the original form of the compounds.

As indicated above, some of the compounds of the present invention contain chiral or asymmetric carbon atoms (optical centers) or double bonds; the racemates, diastereomers, geometric isomers and individual optical isomers - all included in the scope of the present invention.

Compounds of the present invention can also include all isotopes of atoms present in the intermediate compounds or end connections. Isotopes are atoms that have the same atomic number but different mass number. For example, isotopes of hydrogen include tritium and deuterium.

Compounds of the present invention can also include tautomeric forms, such as keto-enol tautomers. Tautomeric forms may be in equilibrium or can be spatially locked in one form by appropriate substitution.

Some compounds of the present invention may exist in resolutiony forms, as well as in solvated forms, including hydrated forms. As a rule, the solvated forms are equivalent nonsolvated forms and also included in the scope of the present invention. Some compounds of the present invention may being the AMB in various crystalline or amorphous forms. Generally, all physical forms are equivalent for the uses contemplated by this invention, and are included in the scope of the present invention.

In addition to the forms of salts present invention provides compounds that can be in the form of prodrugs. Prodrugs of the compounds described in this application are those compounds that readily undergo chemical changes under physiological conditions to form the compounds of the present invention. Additionally, prodrugs can be preobrazovany in connection with the present invention by chemical or biochemical methods in an ex vivo. For example, prodrugs can be slowly converted to the compounds of the present invention, being placed in the tank percutaneous patch, under the action of an enzyme or chemical reagent.

In some embodiments, embodiments of the present invention provides a compound selected from the group including:

N-hydroxy-5-methyl-6-{[4-(3-were)piperazine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-5-methyl-6-[(4-phenylpiperazin-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-5-methyl-6-({4-[3-(trifluoromethyl)phenyl]piperazine-1-yl}carbonyl)-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-5-methyl-6-{[4-(2-were)piperazine-1-yl]carbonyl}-5-azaspiro[2,Octan-7-carboxamide;

6-{[4-(4-chlorophenyl)piperazine-1-yl]carbonyl}-N-hydroxy-5-methyl-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-5-methyl-6-{[4-(2-methyl-4-nitrophenyl)piperazine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-5-methyl-6-[(4-phenylpiperazin-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-6-[(4-hydroxy-4-phenylpiperidine-1-yl)carbonyl]-5-methyl-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-5-methyl-6-[(4-phenyl-3,6-dihydropyridines-1(2H)-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-5-methyl-6-[(4-quinoline-2-reparation-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamide;

6-{[4-(2,3-dichlorophenyl)piperazine-1-yl]carbonyl}-N-hydroxy-5-methyl-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-5-methyl-6-[(4-quinoline-4-reparation-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-5-methyl-6-{[4-(2-methylinosine-4-yl)piperazine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-5-methyl-6-{[4-(2-phenylethyl)piperazine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-5-methyl-6-[(4-pyridin-4-reparacin-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-5-methyl-6-{[4-(4-nitrophenyl)piperazine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-6-{[4-(2-methoxyphenyl)piperazine-1-yl]carbonyl}-5-methyl-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-5-methyl-6-[(4-phenoxypyridine-1-yl)carbonyl]-5-azaspiro,5]Octan-7-carboxamide;

6-(3,4-dihydroisoquinoline-2(1H)-ylcarbonyl)-N-hydroxy-5-methyl-5-azaspiro[2,5]Octan-7-carboxamide;

6-(4,7-dihydrothieno[2,3-c]pyridine-6(5H)-ylcarbonyl)-N-hydroxy-5-methyl-5-azaspiro[2,5]Octan-7-carboxamide;

6-[(3-benzylpyrrolidine-1-yl)carbonyl]-N-hydroxy-5-methyl-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-5-methyl-6-[(4-pyridine-2-reparation-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-5-methyl-6-{[4-(2-pyridin-4-retil)piperidine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-5-methyl-6-({4-[5-(trifluoromethyl)pyridin-2-yl]piperazine-1-yl}carbonyl)-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-5-methyl-6-({4-[3-(trifluoromethyl)pyridin-2-yl]piperazine-1-yl}carbonyl)-5-azaspiro[2,5]Octan-7-carboxamide;

6-(1,4'-bipiperidine-1'-ylcarbonyl)-N-hydroxy-5-methyl-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-5-methyl-6-{[4-(pyridine-2-ylmethyl)piperazine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-5-methyl-6-{[4-(pyridine-4-ylmethyl)piperazine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-5-methyl-6-{[4-(pyridine-3-ylmethyl)piperazine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-5-methyl-6-{[4-(2-were)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-6-{[4-(3-were)piperazine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-5-methyl-6-(1,3,4,9-tetrahydro what-2H-β-carbolin-2-ylcarbonyl)-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-5-methyl-6-[(9-methyl-1,3,4,9-tetrahydro-2H-b-carbolin-2-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamide;

6-{[4-(2-forfinal)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-methyl-5-azaspiro[2,5]Octan-7-carboxamide;

6-{[4-(2-chlorophenyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-methyl-5-azaspiro[2,5]Octan-7-carboxamide;

6-{[4-(4-nitrophenyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-methyl-5-azaspiro[2,5]Octan-7-carboxamide;

6-{[4-phenyl-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-methyl-5-azaspiro[2,5]Octan-7-carboxamide;

6-{[4-(2-methyl-4-nitrophenyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-methyl-5-azaspiro[2,5]Octan-7-carboxamide;

N(7)-hydroxy-N(6),5-dimethyl-N(6)-(3-phenylpropyl)-5-azaspiro[2,5]octane-6,7-dicarboximide;

N(7)-hydroxy-N(6)-isobutyl-5-methyl-5-azaspiro[2,5]octane-6,7-dicarboximide;

N-hydroxy-5-methyl-6-{[4-(2-nitrophenyl)piperazine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;

N(7)-hydroxy-N(6)-isobutyl-N(6),5-dimethyl-5-azaspiro[2,5]octane-6,7-dicarboximide;

N(7)-hydroxy-5-methyl-N(6)-(2-phenoxyethyl)-5-azaspiro[2,5]octane-6,7-dicarboximide;

N(7)-hydroxy-N(6)-[2-(4-methoxyphenyl)ethyl]-5-methyl-5-azaspiro[2,5]octane-6,7-dicarboximide;

N(7)-hydroxy-5-methyl-N(6)-(4-phenylbutyl)-5-azaspiro[2,5]octane-6,7-dicarboximide;

N(7)-hydroxy-5-methyl-N(6)-[3-(2-oxopyrrolidin-1-yl)propyl]-5-azaspiro[2,5]octane-6,7-dicarboximide;

N-hydroxy-5-methyl-6-[(10)-3,4,10,10a-tetrahydropyrazino[1,2-a]indol-2(1H)-ylcarbonyl]-5-azaspiro[2,5]Octan-7-carboxamide;

(5,6-TRANS)-N-hydroxy-5-{[4-(2-methyl-4-nitrophenyl)piperazine-1-yl]carbonyl}Spiro[2,5]octane-6-carboxamide;

(5,6-TRANS)-N-hydroxy-6-{[4-(3-were)piperazine-1-yl]carbonyl}Spiro[2,5]octane-5-carboxamide;

(5,6-TRANS)-N-hydroxy-5-[(4-phenyl-3,6-dihydropyridines-1(2H)-yl)carbonyl]Spiro[2,5]octane-6-carboxamide;

(5,6-TRANS)-N-hydroxy-5-{[4-(3-were)piperazine-1-yl]carbonyl}Spiro[2,5]octane-6-carboxamide;

(5,6-TRANS)-N-hydroxy-6-[(4-phenyl-3,6-dihydropyridines-1(2H)-yl)carbonyl]Spiro[2,5]octane-5-carboxamide;

N-hydroxy-6-(3,4,10,10a-tetrahydropyrazino[1,2-a]indol-2(1H)-ylcarbonyl)-5-azaspiro[2,5]Octan-7-carboxamide;

6-(1,2,4,4a,5,6-hexahydro-3H-pyrazino[1,2-a]quinoline-3-ylcarbonyl)-N-hydroxy-5-methyl-5-azaspiro[2,5]Octan-7-carboxamide;

methyl-7-[(hydroxyamino)carbonyl]-6-[(4-phenyl-3,6-dihydropyridines-1(2H)-yl)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate;

benzyl-7-[(hydroxyamino)carbonyl]-6-[(4-phenyl-3,6-dihydropyridines-1(2H)-yl)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate;

N-hydroxy-5-(methylsulphonyl)-6-[(4-phenyl-3,6-dihydropyridines-1(2H)-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-6-{[3-(3-methoxyphenyl)piperidine-1-yl]carbonyl}-5-methyl-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-5-methyl-6-{[3-(2-phenylethyl)pyrrolidin-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-6-{[4-(3-methoxyphenyl)piperidine-1-yl]carbonyl}-5-methyl-5-azaspiro[2,5]Octan-7-carboxamide;

6-{[4-[3-(aminocarbonyl)phenyl]-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-6-{[4-(2-methoxyphenyl)piperidine-1-yl]carbonyl}-5-methyl-5-azaspiro[2,5]Octan-7-carboxamide;

6-{[4-(3-fluoro-2-were)piperazine-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-6-{[4-(2-methyl-3-nitrophenyl)piperazine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;

6-(3',6'-dihydro-3,4'-bipyridine-1'(2'H)-ylcarbonyl)-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;

N(7)-hydroxy-N(6)-(4-methoxyphenyl)-N(6)-methyl-5-azaspiro[2,5]octane-6,7-dicarboximide;

N-hydroxy-6-{[4-(3-methoxyphenyl)piperazine-1-yl]carbonyl}-5-methyl-5-azaspiro[2,5]Octan-7-carboxamide;

6-{[4-(3-chlorophenyl)piperazine-1-yl]carbonyl}-N-hydroxy-5-methyl-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-6-[(4-phenyl-1,4-diazepan-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-6-{[3-methyl-4-(3-were)piperazine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-6-{[4-(3-methoxyphenyl)piperidine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-6-[(3-phenylpyrrolidine-1-yl)carbonyl]Spiro[2,5]octane-5-carboxamide;

N-hydroxy-6-[(4-isobutylpyrazine-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamide;

6-{[4-(4-cyano-2-were)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;

N(7)-hydroxy-5-N(6)-{4-[(2-methylinosine-4-yl)methoxy]phenyl}-5-azaspiro[2,5]octane-6,7-dicarboximide;

N(7)-hydroxy-N(6)-{4-[(2-methylinosine-4-yl)methoxy]phenyl}-5-azaspiro[2,5]octane-6,7-dicarboximide;

6-{[4-(4-cyanophenyl)piperazine-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-7-[(4-phenylpiperazin-1-yl)carbonyl]-5-azaspiro[2,5]Octan-6-carboxamide;

N-hydroxy-6-[(4-phenylpiperazin-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamide;

N-Hydroxy-6-[(4-phenylpiperazin-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-6-({4-[3-(methoxymethyl)phenyl]piperidine-1-yl}carbonyl)-5-azaspiro[2,5]Octan-7-carboxamide;

methyl-3-[1-({7-[(hydroxyamino)carbonyl]-5-azaspiro[2,5]Oct-6-yl}carbonyl)piperidine-4-yl]benzoate;

6-[(3-cyclohexylpiperidine-1-yl)carbonyl]-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-6-{[4-(3-isopropylphenyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-6-{[4-(3-isopropylphenyl)piperidine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-6-{[4-(4-propylphenyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-6-{[4-(4-ethylphenyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-6-{[4-(4-ethylphenyl)piperidine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;

6-{[4-(4-cyano-2-were)piperazine-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-6-{[4-(3-isopropoxyphenyl)-36-dihydropyridines-1(2H)-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-6-{[4-(3-were)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-6-{[4-(3-were)piperidine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;

6-{[4-(4-tert-butylphenyl)piperazine-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-6-[(4-pyridin-4-reparation-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamide;

6-[(3-benzylpiperidine-1-yl)carbonyl]-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-6-[(5-methoxy-2,3-dihydro-1H-indol-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-6-({5-[(2-methylinosine-4-yl)methoxy]-2,3-dihydro-1H-indol-1-yl}carbonyl)-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-5-methyl-6-({5-[(2-methylinosine-4-yl)methoxy]-2,3-dihydro-1H-indol-1-yl}carbonyl)-5-azaspiro[2,5]Octan-7-carboxamide;

6-{[5-(benzyloxy)-2,3-dihydro-1H-indol-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;

6-(1,3-dihydro-1'H-Spiro[inden-2,4'-piperidine]-1'-ylcarbonyl)-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-6-{[4-(3-isopropoxyphenyl)piperidine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;

methyl-4-[1-({7-[(hydroxyamino)carbonyl]-5-azaspiro[2,5]Oct-6-yl}carbonyl)-1,2,3,6-tetrahydropyridine-4-yl]-3-methylbenzoate;

N-hydroxy-6-{[4-(2-methyl-4-nitrophenyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;

6-{[4-(2-ethylphenyl)piperidine-1-yl]arbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;

methyl-4-[1-({7-[(hydroxyamino)carbonyl]-5-azaspiro[2,5]Oct-6-yl}carbonyl)piperidine-4-yl]-3-methylbenzoate;

6-{[4-(2,3-dihydro-1-benzofuran-5-yl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-methyl-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-6-{[4-(3-isopropylphenyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-5-methyl-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-6-{[(3R)-3-phenylpyrrolidine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-6-{[(3S)-3-phenylpyrrolidine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-6-({3-[3-(trifluoromethyl)phenyl]pyrrolidin-1-yl}carbonyl)-5-azaspiro[2,5]Octan-7-carboxamide;

6-{[3-(3-chlorophenyl)pyrrolidin-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;

6-{[3-(3-forfinal)pyrrolidin-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;

6-{[3-(4-forfinal)pyrrolidin-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;

6-{[3-(4-chlorophenyl)pyrrolidin-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-6-({3-[4-(trifluoromethyl)phenyl]pyrrolidin-1-yl}carbonyl)-5-azaspiro[2,5]Octan-7-carboxamide;

6-{[3-(4-methoxyphenyl)pyrrolidin-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;

6-{[3-(4-phenoxyphenyl)pyrrolidin-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-6-{[4-(3-methoxyphenyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-5-azaspiro[2,5]OK the EN-7-carboxamide;

N-hydroxy-6-{[4-(4-cyano-3-were)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;

6-{[3-(3-methoxyphenyl)pyrrolidin-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-6-[(3-pyridin-4-iparralde-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-6-{[4-(3, 5dimethylphenyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-6-{[4-(3-trifloromethyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-6-{[5-(methoxymethyl)-4-phenyl-3,6-dihydropyridines-1(2H)-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-6-(1,4,5,6-tetrahydrobenzo[f]isoquinoline-3(2H)-ylcarbonyl)-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-6-{[4-(5-methoxy-2-were)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-6-{[4-(4-methoxy-2-were)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;

6-[(4-cyano-4-phenylpiperidine-1-yl)carbonyl]-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;

ethyl-7-[(hydroxyamino)carbonyl]-6-[(4-phenyl-3,6-dihydropyridines-1(2H)-yl)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate;

propyl-7-[(hydroxyamino)carbonyl]-6-[(4-phenyl-3,6-dihydropyridines-1(2H)-yl)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate;

isopropyl-7-[(hydroxyamino)carbonyl]-6-[(4-phenyl-3,6-dihydropyridines-1(2H)-yl)Carboni is]-5-azaspiro[2,5]octane-5-carboxylate;

isobutyl-7-[(hydroxyamino)carbonyl]-6-[(4-phenyl-3,6-dihydropyridines-1(2H)-yl)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate and

N-hydroxy-6-[(5-methyl-4-phenyl-3,6-dihydropyridines-1(2H)-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamide.

Compounds of the present invention, in addition, include:

6-(1,4,4a,5,6,10b-hexahydrobenzo[f]isoquinoline-3(2H)-ylcarbonyl)-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;

6-{[4-(4-forfinal)-3-hydroxypiperidine-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-6-(3,3a,8,8a-tetrahydroindene[1,2-c]pyrrole-2(1H)-ylcarbonyl)-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-6-{[4-(4-phenyl-1,3-thiazol-2-yl)piperidine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-6-{[4-(4-tert-butyl-1,3-thiazol-2-yl)piperidine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-6-[(4-methyl-4-phenylpiperidine-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-6-{[4-(4-ethyl-1,3-thiazol-2-yl)piperidine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-6-{[(TRANS)-3-methyl-4-phenylpyrrolidine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;

6-{[4-(2-forfinal)piperazine-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;

6-{[4-(3, 5dimethylphenyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-methyl-5-azaspiro[2,5]Octan-7-carboxamide;

tetrahydro-2H-Piran-4-yl-7-((hydroxyamino)carbonyl)-6-((4-penile perazin-1-yl)carbonyl)-5-azaspiro(2,5)octane-5-carboxylate;

ethyl-7-((hydroxyamino)carbonyl)-6-((4-phenylpiperazin-1-yl)carbonyl)-5-azaspiro(2,5)octane-5-carboxylate;

methyl-7-[(hydroxyamino)carbonyl]-6-[(4-phenylpiperazin-1-yl)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate;

N-hydroxy-6-[(4-pyrazin-2-reparation-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-6-[(4-quinoline-2-reparation-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-6-{[3-(5,6,7,8-tetrahydronaphthalen-2-yl)pyrrolidin-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-5-methyl-6-{[(3R)-3-phenylpyrrolidine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;

methyl-7-[(hydroxyamino)carbonyl]-6-{[(3R)-3-phenylpyrrolidine-1-yl]carbonyl}-5-azaspiro[2,5]octane-5-carboxylate;

N-hydroxy-6-[(3-pyridin-3-iparralde-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-6-[(3-pyridin-2-iparralde-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-6-[(3-methyl-3-phenylpyrrolidine-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-6-[(3-phenylaziridine-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-5-methyl-6-[(3-methyl-3-phenylpyrrolidine-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-5-methyl-6-[(3-phenylaziridine-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamide;

6-(1,3,3a,4,5,9b-hexahydro-2H-benzo[e]isoindole-2-ylcarbonyl)-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;

N-g is droxy-6-{[3-(2-naphthyl)pyrrolidin-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-6-{[4-(2-thienyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-6-{[3-(3-thienyl)pyrrolidin-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-6-{[3-(2-thienyl)pyrrolidin-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-6-{[4-(2-thienyl)piperidine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-6-{[3-(2-were)pyrrolidin-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-6-{[3-(4-were)pyrrolidin-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;

5-acetyl-N-hydroxy-6-[(4-phenyl-3,6-dihydropyridines-1(2H)-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-6-{[4-(3-thienyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-6-[(3-phenylpiperidine-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-6-{[4-(3-thienyl)piperidine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;

methyl-6-{[4-(3, 5dimethylphenyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-7-[(hydroxyamino)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate;

6-{[4-(3, 5dimethylphenyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-(methylsulphonyl)-5-azaspiro[2,5]Octan-7-carboxamide;

6-{[4-(3,5-differenl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;

6-{[4-(3,5-dichlorophenyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Oct the-7-carboxamide;

6-{[4-[3,5-bis(trifluoromethyl)phenyl]-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-5-(methylsulphonyl)-6-[(4-phenylpiperazin-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamide;

5-formyl-N-hydroxy-6-[(4-phenylpiperazin-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamide;

6-{[4-(3,5-differenl)piperidine-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;

6-{[4-(2,5-dimetilfenil)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;

6-{[4-(2,4,5-trimetilfenil)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;

6-[(4-biphenyl-3-reparacin-1-yl)carbonyl]-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;

6-[(4-dibenzo[b,d]furan-4-reparacin-1-yl)carbonyl]-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;

6-{[4-(2,5-dimetilfenil)piperidine-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;

6-{[4-(2,4,5-trimetilfenil)piperidine-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;

methyl-3-[1-({7-[(hydroxyamino)carbonyl]-5-azaspiro[2,5]Oct-6-yl}carbonyl)-1,2,3,6-tetrahydropyridine-4-yl]-4-methylbenzoate;

6-[(5-phenyl-2,3,4,7-tetrahydro-1H-azepin-1-yl)carbonyl]-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;

6-{[4-[3-(dimethylamino)phenyl]-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;

methyl-3-[1-({7-[(hydroxyamino)CT is of IMT]-5-azaspiro[2,5]Oct-6-yl}carbonyl)piperidine-4-yl]-4-methylbenzoate;

6-[(5-Penelitian-1-yl)carbonyl]-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;

6-({4-[3-(dimethylamino)phenyl]piperidine-1-yl}carbonyl)-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;

6-{[4-(2-were)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;

6-[(3-phenyl-2,5-dihydro-1H-pyrrol-1-yl)carbonyl]-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;

6-{[4-(4-cyano-2-were)piperidine-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;

6-[(3,3-dimethyl-4-phenyl-3,6-dihydropyridines-1(2H)-yl)carbonyl]-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;

6-[(3,3-dimethyl-4-phenylpiperidine-1-yl)carbonyl]-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-5-(methylsulphonyl)-6-[(3-phenyl-2,5-dihydro-1H-pyrrol-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamide;

methyl-7-[(hydroxyamino)carbonyl]-6-[(3-phenyl-2,5-dihydro-1H-pyrrol-1-yl)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate;

N-hydroxy-5-methyl-6-[(3-phenyl-2,5-dihydro-1H-pyrrol-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamide;

6-{[4-(4-cyano-3-were)piperidine-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;

6-{[4-[3-(benzyloxy)phenyl]-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;

6-{[4-[3-ethylphenyl]-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;

6-{[4-[3-(ethyloxy)phenyl]-3,6-dihydropyridines-1(2H)-the]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;

6-{[4-(3-ethylphenyl)piperidine-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;

6-{[4-(3-ethoxyphenyl)piperidine-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;

6-{[4-(3-cyclopropylmethyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;

6-{[4-(4-methoxy-3, 5dimethylphenyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;

6-{[4-(3,5-dimethyl-4-methoxyphenyl)piperidine-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;

6-{[4-(4-cyano-3-ethylphenyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;

6-{[4-(4-cyano-3-ethylphenyl)piperidine-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;

6-{[4-(4-cyano-3, 5dimethylphenyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;

6-{[4-(4-cyano-3, 5dimethylphenyl)piperidine-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;

6-{[4-(1,3-benzothiazol-6-yl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-6-{[4-(1-methyl-1H-benzimidazole-6-yl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-6-{[4-(1-methyl-1H-benzimidazole-6-yl)piperidine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;

6-{[4-(4-cyano-3-isopropylphenyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-carboxamide;

6-{[4-(4-cyano-3-isopropylphenyl)piperidine-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;

6-{[4-(4-cyano-3-ethylphenyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-methyl-5-azaspiro[2,5]Octan-7-carboxamide;

6-{[4-(4-cyano-3, 5dimethylphenyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-methyl-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-6-{[4-(1-ethyl-1H-benzimidazole-6-yl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-6-{[4-(1-methyl-1H-indazol-5-yl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-6-{[4-(1-ethyl-1H-benzimidazole-6-yl)piperidine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-6-{[4-(1-methyl-1H-indazol-5-yl)piperidine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-6-{[4-(1-ethyl-1H-indazol-5-yl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;

tetrahydro-2H-Piran-4-yl-6-{[4-(1-ethyl-1H-benzimidazole-6-yl)piperidine-1-yl]carbonyl}-7-[(hydroxyamino)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate;

methyl-6-{[4-(1-ethyl-1H-benzimidazole-6-yl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-7-[(hydroxyamino)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate;

6-{[4-(1-ethyl-1H-benzimidazole-6-yl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-(methylsulphonyl)-5-azaspiro[2,5]Octan-7-carboxamide;

methyl-6-{[4-(1-ethyl-1H-benzimidazole-6-yl)piperidine-1-yl]carbonyl-7-[(hydroxyamino)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate;

6-{[4-(1-ethyl-1H-benzimidazole-6-yl)piperidine-1-yl]carbonyl}-N-hydroxy-5-(methylsulphonyl)-5-azaspiro[2,5]Octan-7-carboxamide;

6-{[4-(4-cyano-2-were)piperidine-1-yl]carbonyl}-N-hydroxy-5-(methylsulphonyl)-5-azaspiro[2,5]Octan-7-carboxamide;

methyl-6-{[4-(4-cyano-2-were)piperazine-1-yl]carbonyl}-7-[(hydroxyamino)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate;

6-{[4-(1-ethyl-1H-benzimidazole-6-yl)piperazine-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;

methyl-6-{[4-(1-ethyl-1H-benzimidazole-6-yl)piperazine-1-yl]carbonyl}-7-[(hydroxyamino)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate;

6-{[4-(1-ethyl-1H-benzimidazole-6-yl)piperazine-1-yl]carbonyl}-N-hydroxy-5-(methylsulphonyl)-5-azaspiro[2,5]Octan-7-carboxamide;

tetrahydro-2H-Piran-4-yl-6-{[4-(4-cyano-2-were)piperazine-1-yl]carbonyl}-7-[(hydroxyamino)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate;

tetrahydro-2H-Piran-4-yl-6-{[4-(1-ethyl-1H-benzimidazole-6-yl)piperazine-1-yl]carbonyl}-7-[(hydroxyamino)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate;

N-hydroxy-6-[(3-methyl-4-phenylpiperidine-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamide;

6-{[5-(aminocarbonyl)-4-phenyl-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;

6-{[4-(4-cyanophenyl)-5-methyl-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;

6-{[4-(4-cyanophenyl)-3-methylpiperidin-1-yl]ka is bonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-6-{[5-methyl-4-(4-nitrophenyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;

N-hydroxy-6-{[5-methyl-4-(3-nitrophenyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;

6-[(4-dibenzo[b,d]furan-2-yl-3,6-dihydropyridines-1(2H)-yl)carbonyl]-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;

6-[(4-dibenzo[b,d]furan-2-reparacin-1-yl)carbonyl]-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;

6-{[4-(3,3-dimethyl-2,3-dihydro-1-benzofuran-5-yl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;

6-{[4-(3,3-dimethyl-2,3-dihydro-1-benzofuran-5-yl)piperidine-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;

isopropyl-7-[(hydroxyamino)carbonyl]-6-[(3-phenyl-2,5-dihydro-1H-pyrrol-1-yl)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate;

(3S)-tetrahydrofuran-3-yl-7-[(hydroxyamino)carbonyl]-6-[(3-phenyl-2,5-dihydro-1H-pyrrol-1-yl)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate;

cyclohexyl-7-[(hydroxyamino)carbonyl]-6-[(3-phenyl-2,5-dihydro-1H-pyrrol-1-yl)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate;

tetrahydro-2H-Piran-4-yl-7-[(hydroxyamino)carbonyl]-6-[(3-phenyl-2,5-dihydro-1H-pyrrol-1-yl)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate;

N-hydroxy-6-((4-phenylpiperazin-1-yl)carbonyl)Spiro(2,5)octane-5-carboxamide;

N-hydroxy-6-{[(3R)-3-phenylpyrrolidine-1-yl]carbonyl}Spiro[2,5]octane-5-carboxamide;

N-hydroxy-6-{[-(2-methyl-4-nitrophenyl)piperazine-1-yl]carbonyl}Spiro[2,5]octane-5-carboxamide;

N-hydroxy-6-[(4-phenyl-3,6-dihydropyridines-1(2H)-yl)carbonyl]Spiro[2,5]octane-5-carboxamide;

(3S)-tetrahydrofuran-3-yl-7-[(hydroxyamino)carbonyl]-6-[(4-phenylpiperazin-1-yl)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate;

(3R)-tetrahydrofuran-3-yl-7-[(hydroxyamino)carbonyl]-6-[(4-phenylpiperazin-1-yl)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate;

2-methoxyethyl-7-((hydroxyamino)carbonyl)-6-((4-phenylpiperazin-1-yl)carbonyl)-5-azaspiro(2,5)octane-5-carboxylate;

N-hydroxy-6-[(4-phenylpiperazin-1-yl)carbonyl]-5-(phenylsulfonyl)-5-azaspiro[2,5]Octan-7-carboxamide;

propyl-7-[(hydroxyamino)carbonyl)]-6-[(4-phenylpiperazin-1-yl)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate;

isopropyl-7-[(hydroxyamino)carbonyl]-6-[(4-phenylpiperazin-1-yl)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate;

methyl-6-{[4-(3,5-differenl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-7-[(hydroxyamino)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate;

methyl-6-{[4-(3,5-differenl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-7-[(hydroxyamino)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate;

N-hydroxy-6-{[4-(4-isopropylphenyl)piperazine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;

6-{[4-(3,5-differenl)piperidine-1-yl]carbonyl}-N-hydroxy-5-(methylsulphonyl)-5-azaspiro[2,5]Octan-7-carboxamide and

6-{[4-(4,5-dimethyl-1,3-thiazol-2-yl)piperidine-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide.

Some in the ways embodiment of the compounds of the present invention include:

hydroxyamide 5-methyl-6-(4-m-tailpipes-1-carbonyl)-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 5-methyl-6-(4-phenylpiperazin-1-carbonyl)-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 5-methyl-6-[4-(3-triptoreline)piperazine-1-carbonyl]-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 5-methyl-6-(4-o-tailpipes-1-carbonyl)-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 6-[4-(4-chlorophenyl)piperazine-1-carbonyl]-5-methyl-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 5-methyl-6-[4-(2-methyl-4-nitrophenyl)piperazine-1-carbonyl]-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 5-methyl-6-(4-phenylpiperidine-1-carbonyl)-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 6-(4-hydroxy-4-phenylpiperidine-1-carbonyl)-5-methyl-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 5-methyl-6-(4-phenyl-3,6-dihydro-2H-pyridine-1-carbonyl)-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 5-methyl-6-(4-(quinoline-2-reparation-1-carbonyl)-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 6-[4-(2,3-dichlorophenyl)piperazine-1-carbonyl]-5-methyl-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 5-methyl-6-(4-quinoline-4-reparation-1-carbonyl)-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 5-methyl-6-[4-(2-methylinosine-4-yl)piperazine-1-carbonyl]-5-azaspiro[2,5]Octan-7-carbon is th acid;

hydroxyamide 5-methyl-6-(4-penetentiary-1-carbonyl)-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 5-methyl-6-(3,4,5,6-tetrahydro-2H-[4,4']bipyridinyl-1-carbonyl)-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 5-methyl-6-[4-(4-nitrophenyl)piperazine-1-carbonyl]-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 6-[4-(2-methoxyphenyl)piperazine-1-carbonyl]-5-methyl-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 5-methyl-6-(4-phenoxypyridine-1-carbonyl)-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 6-(3,4-dihydro-1H-isoquinoline-2-carbonyl)-5-methyl-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 6-(4,7-dihydro-5H-thieno[2,3-c]pyridine-6-carbonyl)-5-methyl-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 6-(3-benzylpyrrolidine-1-carbonyl)-5-methyl-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 5-methyl-6-(4-pyridine-2-reparation-1-carbonyl)-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 5-methyl-6-[4-(2-pyridin-4-retil)piperidine-1-carbonyl]-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 5-methyl-6-[4-(5-triptorelin-2-yl)piperazine-1-carbonyl]-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 5-methyl-6-[4-(3-triptorelin-2-yl)piperazine-1-carbonyl]-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 6-([1,4']bipyridinyl-1'-carbonyl)-5-methyl-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 5-methyl-6-(4-pyridine-2-iletileri-1-carbonyl)-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 5-methyl-6-(4-pyridin-4-iletileri-1-carbonyl)-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 5-methyl-6-(4-pyridine-3-iletileri-1-carbonyl)-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 5-methyl-6-(4-o-tolyl-3,6-dihydro-2H-pyridine-1-carbonyl)-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 6-(4-m-tailpipes-1-carbonyl)-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 6-(1,3,4,9-tetrahydro-β-carbolin-2-carbonyl)-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 6-(9-methyl-1,3,4,9-tetrahydro-β-carbolin-2-carbonyl)-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 6-[4-(2-forfinal)-3,6-dihydro-2H-pyridine-1-carbonyl]-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 6-[4-(2-chlorophenyl)-3,6-dihydro-2H-pyridine-1-carbonyl]-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 6-[4-(4-nitrophenyl)-3,6-dihydro-2H-pyridine-1-carbonyl]-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 6-(4-phenyl-3,6-dihydro-2H-pyridine-1-carbonyl)-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 6-[4-(2-methyl-4-nitrophenyl)piperazine-1-carbonyl]-5-azaspiro[2,5]octane-7-carboxylic acid;

7-hydroxyamide 6-[methyl-(3-phenylpropyl)amide 5-methyl-5-azaspiro[2,5]octane-6,7-decarb the new acid;

7-hydroxyamide 6-(isobutylamino) 5-methyl-5-azaspiro[2,5]octane-6,7-dicarboxylic acid;

hydroxyamide 5-methyl-6-[4-(2-nitrophenyl)piperazine-1-carbonyl]-5-azaspiro[2,5]octane-7-carboxylic acid;

7-hydroxyamide 6-(isobutyramide) 5-methyl-5-azaspiro[2,5]octane-6,7-dicarboxylic acid;

7-hydroxyamide 6-[(2-phenoxyethyl)amide] 5-methyl-5-azaspiro[2,5]octane-6,7-dicarboxylic acid;

7-hydroxyamide 6-{[2-(4-methoxyphenyl)ethyl]amide} 5-methyl-5-azaspiro[2,5]octane-6,7-dicarboxylic acid;

7-hydroxyamide 6-[(4-phenylbutyl)amide] 5-methyl-5-azaspiro[2,5]octane-6,7-dicarboxylic acid;

7-hydroxyamide 6-{[3-(2-oxopyrrolidin-1-yl)propyl]amide} 5-methyl-5-azaspiro[2,5]octane-6,7-dicarboxylic acid;

hydroxyamide 6-(3,4,10,10a-tetrahydro-1H-pyrazino[1,2-a]indole-2-carbonyl)-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 5-[4-(2-methyl-4-nitrophenyl)piperazine-1-carbonyl]Spiro[2,5]octane-6-carboxylic acid;

hydroxyamide 6-(4-m-tailpipes-1-carbonyl)Spiro[2,5]octane-5-carboxylic acid;

hydroxyamide 5-(4-phenyl-3,6-dihydro-2H-pyridine-1-carbonyl)Spiro[2,5]octane-6-carboxylic acid;

hydroxyamide 5-(4-m-tailpipes-1-carbonyl)Spiro[2,5]octane-6-carboxylic acid;

hydroxyamide 6-(4-phenyl-3,6-dihydro-2H-pyridine-1-carbonyl)Spiro[2,5]octane-5-carboxylic acid;

hydroxyamide 6-(3,4,10,10a-tetrahydro-1H-pyrazino[1,2-a]indole-2-carbonyl)-5-azaspiro[2,5]is Chan-7-carboxylic acid;

hydroxyamide 6-(1,2,4,4a,5,6-hexahydropyrazino[1,2-a]quinoline-3-carbonyl)-5-methyl-5-azaspiro[2,5]octane-7-carboxylic acid;

methyl ether 7-hydroxycarbamoyl-6-(4-phenyl-3,6-dihydro-2H-pyridine-1-carbonyl)-5-azaspiro[2,5]octane-5-carboxylic acid;

benzyl ether of 7-hydroxycarbamoyl-6-(4-phenyl-3,6-dihydro-2H-pyridine-1-carbonyl)-5-azaspiro[2,5]octane-5-carboxylic acid;

hydroxyamide 5-methanesulfonyl-6-(4-phenyl-3,6-dihydro-2H-pyridine-1-carbonyl)-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 6-[3-(3-methoxyphenyl)piperidine-1-carbonyl]-5-methyl-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 5-methyl-6-(3-phenotypically-1-carbonyl)-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 6-[4-(3-methoxyphenyl)piperidine-1-carbonyl]-5-methyl-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 6-[4-(3-carbamoylmethyl)-3,6-dihydro-2H-pyridine-1-carbonyl]-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 6-[4-(2-methoxyphenyl)-3,6-dihydro-2H-pyridine-1-carbonyl]-5-methyl-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 6-[4-(3-fluoro-2-were)piperazine-1-carbonyl]-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 6-[4-(2-methyl-3-nitrophenyl)piperazine-1-carbonyl]-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 6-(3',6'-dihydro-2'H-[3,4']bipyridinyl-1'-carbonyl)-5-azaspiro[2,5]octane-7-carboxylic acid;

-hydroxyamide 6-[(4-methoxyphenyl)methylamide] 5-azaspiro[2,5]octane-6,7-dicarboxylic acid;

hydroxyamide 6-[4-(3-methoxyphenyl)piperazine-1-carbonyl]-5-methyl-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 6-[4-(3-chlorophenyl)piperazine-1-carbonyl]-5-methyl-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 6-(4-phenyl[1,4]diazepan-1-carbonyl)-5-azaspiro[2,5]octane-7-carboxylic acid

hydroxyamide 6-(3-methyl-4-m-tailpipes-1-carbonyl)-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 6-[4-(3-methoxyphenyl)piperidine-1-carbonyl]-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 6-(3-phenylpyrrolidine-1-carbonyl)-Spiro[2,5]octane-5-carboxylic acid;

hydroxyamide 6-(4-isobutylpyrazine-1-carbonyl)-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 6-[4-(4-cyano-2-were)-3,6-dihydro-2H-pyridine-1-carbonyl]-5-azaspiro[2,5]octane-7-carboxylic acid;

7-hydroxyamide 6-{[4-(2-methylinosine-4-ylethoxy)phenyl]amide} 5-methyl-5-azaspiro[2,5]octane-6,7-dicarboxylic acid;

7-hydroxyamide 6-{[4-(2-methylinosine-4-ylethoxy)phenyl]amide} 5-azaspiro[2,5]octane-6,7-dicarboxylic acid;

hydroxyamide 6-[4-(4-cyanophenyl)piperazine-1-carbonyl]-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 7-(4-phenylpiperazin-1-carbonyl)-5-azaspiro[2,5]Octan-6-carboxylic acid;

hydroxyamide 6-(4-phenylpiperidine-1-carbonyl)-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 6-(4-phenylpiperazin-1-carbonyl)5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 6-[4-(3-methoxymethyl)piperidine-1-carbonyl]-5-azaspiro[2,5]octane-7-carboxylic acid;

methyl ester of 3-[1-(7-hydroxycarbamoyl-5-azaspiro[2,5]octane-6-carbonyl)piperidine-4-yl]benzoic acid;

hydroxyamide 6-(3-cyclohexylpiperidine-1-carbonyl)-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 6-[4-(3-isopropylphenyl)-3,6-dihydro-2H-pyridine-1-carbonyl]-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 6-[4-(3-isopropylphenyl)piperidine-1-carbonyl]-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 6-[4-(4-propylphenyl)-3,6-dihydro-2H-pyridine-1-carbonyl]-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 6-[4-(4-ethylphenyl)-3,6-dihydro-2H-pyridine-1-carbonyl]-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 6-[4-(4-ethylphenyl)piperidine-1-carbonyl]-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 6-[4-(4-cyano-2-were)piperazine-1-carbonyl]-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 6-[4-(3-isopropoxyphenyl)-3,6-dihydro-2H-pyridine-1-carbonyl]-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 6-(4-m-tolyl-3,6-dihydro-2H-pyridine-1-carbonyl)-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 6-[4-(4-tert-butylphenyl)piperazine-1-carbonyl]-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 6-(4-pyridin-4-reparation-1-carbonyl)-5-azaspiro[2,5]Octan-7-carbon is howling acid;

hydroxyamide 6-(3-benzylpiperidine-1-carbonyl)-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 6-(5-methoxy-2,3-dihydroindol-1-carbonyl)-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 6-[5-(2-Methylinosine-4-ylethoxy)-2,3-dihydroindol-1-carbonyl]-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 5-methyl-6-[5-(2-methylinosine-4-ylethoxy)-2,3-dihydroindol-1-carbonyl]-5-azaspiro[2,5]octane-7-carboxylic acid hydroxyamide

hydroxyamide 6-(5-benzyloxy-2,3-dihydroindol-1-carbonyl)-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 6-[4-(2,2-serendipidy-1-carbonyl]-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 6-[4-(3-isopropoxyphenyl)piperidine-1-carbonyl]-5-azaspiro[2,5]octane-7-carboxylic acid;

methyl ester of 4-[1-(7-hydroxycarbamoyl-5-azaspiro[2,5]octane-6-carbonyl)-1,2,3,6-tetrahydropyridine-4-yl]-3-methylbenzoic acids;

hydroxyamide 6-[4-(2-methyl-4-nitrophenyl)-3,6-dihydro-2H-pyridine-1-carbonyl]-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 6-[4-(2-ethylphenyl)piperidine-1-carbonyl]-5-azaspiro[2,5]octane-7-carboxylic acid;

methyl ester of 4-[1-(7-hydroxycarbamoyl-5-azaspiro[2,5]octane-6-carbonyl)piperidine-4-yl]-3-methyl-benzoic acid;

hydroxyamide 6-[4-(2,3-dihydrobenzofuran-5-yl)-3,6-dihydro-2H-pyridine-1-carbonyl]-5-methyl-5-azaspiro[2,5]octane-7-carboxylic acid;

Hydra is xiemed 6-[4-(3-isopropylphenyl)-3,6-dihydro-2H-pyridine-1-carbonyl]-5-methyl-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 6-(3-phenylpyrrolidine-1-carbonyl)-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 6-(3-phenylpyrrolidine-1-carbonyl)-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 6-[3-(3-triptoreline)pyrrolidin-1-carbonyl]-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 6-[3-(3-chlorophenyl)pyrrolidin-1-carbonyl]-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 6-[3-(3-forfinal)pyrrolidin-1-carbonyl]-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 6-[3-(4-forfinal)pyrrolidin-1-carbonyl]-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 6-[3-(4-chlorophenyl)pyrrolidin-1-carbonyl]-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 6-[3-(4-triptoreline)pyrrolidin-1-carbonyl]-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 6-[3-(4-methoxyphenyl)pyrrolidin-1-carbonyl]-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 6-[3-(4-phenoxyphenyl)pyrrolidine-1-carbonyl]-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 6-[4-(3-methoxyphenyl)-3,6-dihydro-2H-pyridine-1-carbonyl]-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 6-[4-(4-cyano-3-were)-3,6-dihydro-2H-pyridine-1-carbonyl]-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 6-(3-pyridin-4-iparralde-1-carbonyl)-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 6-[4-(3,5-dimethylpent the l)-3,6-dihydro-2H-pyridine-1-carbonyl]-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 6-[4-(3-trifloromethyl)-3,6-dihydro-2H-pyridine-1-carbonyl]-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 6-(5-methoxymethyl-4-phenyl-3,6-dihydro-2H-pyridine-1-carbonyl)-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 6-(1,4,5,6-tetrahydro-2H-benzo[f]isoquinoline-3-carbonyl)-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 6-(4-m-tripeptides-1-carbonyl)-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 6-[4-(5-methoxy-2-were)-3,6-dihydro-2H-pyridine-1-carbonyl]-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 6-[4-(4-methoxy-2-were)-3,6-dihydro-2H-pyridine-1-carbonyl]-5-azaspiro[2,5]octane-7-carboxylic acid;

hydroxyamide 6-(4-cyano-4-phenylpiperidine-1-carbonyl)-5-azaspiro[2,5]octane-7-carboxylic acid;

ethyl ester of 7-hydroxycarbamoyl-6-(4-phenyl-3,6-dihydro-2H-pyridine-1-carbonyl)-5-azaspiro[2,5]octane-5-carboxylic acid;

propyl ether 7-hydroxycarbamoyl-6-(4-phenyl-3,6-dihydro-2H-pyridine-1-carbonyl)-5-azaspiro[2,5]octane-5-carboxylic acid;

isopropyl ether 7-hydroxycarbamoyl-6-(4-phenyl-3,6-dihydro-2H-pyridine-1-carbonyl)-5-azaspiro[2,5]octane-5-carboxylic acid;

isobutyl ether 7-hydroxycarbamoyl-6-(4-phenyl-3,6-dihydro-2H-pyridine-1-carbonyl)-5-azaspiro[2,5]octane-5-carboxylic acid and

hydroxyamide 6-(5-methyl-4-phenyl-3,6-dihydro-2H-pyridine-1-carbonyl)-5-azaspiro[25]octane-7-carboxylic acid.

Synthesis

The new compounds of the present invention can be obtained by various methods known to experts in the field of organic synthesis. Compounds of the present invention can be synthesized using the methods described below, in combination with the methods of synthesis known from the prior art that relate to the chemistry of organic synthesis, or their variants, as is known in the art.

Compounds of the present invention can be obtained from easily available starting materials using the following General methods and techniques. It should be clear that when the typical or preferred conditions of the method (i.e. the reaction temperature, reaction time, molar ratio of reactants, solvents, pressures, and so on), you can also use other terms means, unless otherwise specified. Optimum reaction conditions may vary depending on the specific reagents or solvents, but such conditions can be determined by a specialist using routine methods for optimization.

The described processes can be monitored using any known prior art method. For example, the formation of the product can be tracked with the help of spectroscopy, such as nuclear magnetic resonance (eg,1H or13C), infr the red spectroscopy, spectrophotometry (for example, in the UV visible spectrum) or mass spectrometry, or by chromatography such as high performance liquid chromatography (HPLC) or thin layer chromatography.

Upon receipt of the connection may need protection and the removal of protection from different chemical groups. The need to protect and remove protection and selection of suitable protective groups can be easily determined by the person skilled in the art. Chemistry of protective groups are described, for example, in Green et al., Protective Groups in Organic Synthesis, 2d. Ed., Wiley & Sons, 1991, included in this application in its entirety by reference.

The reaction processes described in this sauce can be carried out in suitable solvents which can easily choose a specialist in the field of organic synthesis. Suitable solvents may be essentially chemically inactive with respect to source substances (reactants), the intermediates, or products at the temperatures of the reactions performed, i.e. the temperature which can be between the freezing temperature of the solvent to the boiling point of the solvent. The above reaction can be performed in a single solvent or a mixture of more than one solvent. Depending on the particular reaction stage, you can choose the suitable solvents for the particular stage of the reaction.

New the compounds of the present invention can be obtained, using the ways and means of implementation of the reactions described below.

A series of compounds of formula 12 are ways, in the General form presented in scheme 1 (where R1 and R2 in formulas 10-12 and R3 and R4 in formulas 11-12 correspond to the appropriate Vice-providing compounds of the present invention). H-Asp(Otbutyl)-OH was treated with benzylbromide and DBU in toluene to obtain compound 2, which was subjected to interaction with the connection 3 connection 4. N-alkilirovanny product then was treated with NaI in acetone to obtain the corresponding iodide, which was subjected to cyclization using LiHMDS in THF to give the desired product 6. Benzyl protective group substituted Cbz to obtain compound 7. Cyclopropylamine compound 7 was carried out by treatment with diazomethane and Pd(OAc)2to give the desired product 8. Group Cbz and Bn compound 8 was removed by hydrogenation with obtaining acid 9. The resulting acid is combined with an amine using standard conditions for the formation of amide linkages, receiving of the connection 10. Reductive amination of compound 10 using an aldehyde or ketone gave compound 11. tert-Boutelou group was removed by treatment using TFA in methylene chloride, followed by direct combination with hydroxylamine to obtain the final compound 12.

Scheme 1

Further it is possible to carry out the synthesis of compounds of formula 7 using the approach in the General form presented in figure 2. And amino, and carboxyl group in H-Asp(OtButyl)-OH was protected by benzyl groups by obtaining Tris benzyl-protected amino acids 13. The compound obtained was then treated with KHMDS and then was subjected to allilirovanii with obtaining the product of the combination 14. Dihydroxypropane connection 14 gave 1,2-diol 15. The primary alcohol was then converted into the corresponding mesilate and then was first made to obtain the corresponding cyklinowanie product 17. Amino and carboxyl group of compound 17 again defended using Cbz and benzyl groups, respectively. The oxidation method Swarna connection 18 gave the ketone 19. Using the Wittig reaction, compound 19 was converted to the olefin 7.

Scheme 2

The synthesis of compounds of General formula 20 in the General form presented in figure 3 (where R1 and R2 in formulas 20 and 27 correspond to the appropriate Vice-providing compounds of the present invention). The reaction of the Diels-alder reaction of compound 21 compound 22 network connection 23. TMS ether is hydrolyzed to the corresponding ketone 24. The ketone was then converted into an olefin 25. Cyclopropylamine using a method similar to the described blashemy 1, gave the key intermediate compound 26. Ethyl ether was directly converted into an amide 27. tert-Boutelou group compound 27 was removed to obtain the acid. The resulting acid was converted into the final product 20 using standard synthesis conditions.

Scheme 3

Alternatively, as shown in figure 4 (where R1 and R2 in formulas 28 and 29 correspond to the appropriate Vice-providing compounds of the present invention), were first removed the tert-boutelou group of compounds 26 and then carried out the usual combination with obtaining the amide 28. Alkaline hydrolysis of compound 28 by boiling under reflux gave the acid, the acid was then converted into the target compound 29, using a standard method combination.

Scheme 4

Compounds of General formula 30 can be obtained using the procedure in the General form presented in figure 5 (where R1 and R2 in formulas 30 and 32 correspond to the appropriate Vice-providing compounds of the present invention). Ketone 24 were converted into the corresponding dithioketal 31. The group of the ethyl ester hydrolyzed to the acid with the subsequent combination with the amine to obtain amide 32. Following a methodology similar to that described for scheme 3, compound 32 was converted into the final joint is 30.

Scheme 5

A series of compounds of formulas 33 and 34 can be obtained by following the method of synthesis is presented in figure 6 (where R1 and R2 in formulas 33 and 34 correspond to the appropriate Vice-providing compounds of the present invention). Ketone 24 were treated with allyltrimethylsilane in the presence of TiCl4getting connection 35. Hydroporinae with subsequent oxidation gave the primary alcohol 36. Primary alcohol activated and subjected to cyclization to the corresponding tetrahydrofuran 37. The conversion of compound 37 in amide and in the final hydroxamic acid 33 or 34 was carried out in the same manner as described above.

Scheme 6

A series of compounds of formula 38 or 39 received, sequentially carrying out the reaction, in the General form presented in figure 7 (where R1 and R2 in formula 38 and 39 correspond to the appropriate Vice-providing compounds of the present invention). Primary alcohol 36 oxidized and converted to the olefin. Hydroporinae and oxidation gave diol 40. Cyclization sequentially performed as described above to give compound 38 or 39.

Scheme 7

A series of compounds of formula 41 received in accordance with the scheme, in the General form presented in figure 8 (where R1 and R2 in the formula 41 according to testout suitable substituents, providing compounds of the present invention). The olefin was treated with MCPBA getting epoxide 42. The epoxide was treated with the amine from the product 43 with the opening of the ring. Amerosport then subjected to cyclization to pyrocarbonate 44. The conversion of compound 44 in the amide and the final hydroxamic acid 41 was carried out in the same manner as described above.

Scheme 8

A series of compounds 4-aryl-1,2,3,6-tetrahydropyridine of formula 45 and 4-arylpiperazine formula 46 can be obtained according to Scheme 9. For example, catalyzed by palladium combination Suzuki tert-butyl ester 4-tripterocalyx-3,6-dihydro-2H-pyridine-1-carboxylic acid 47 with arylboronic acid can give the compounds of formula 48, using standard techniques (for example, Y. Deng, L. Gong, A Mi, H. Liu, Y. Jiang, Synthesis, 2003, 337-339). Protective Boc group was removed by treatment of the corresponding amine using TFA or HCl. Using the standard method of hydrogenation of 4-aryl-1,2,3,6-tetrahydropyridine can be converted to the corresponding 4-arylpiperazine.

Scheme 9

The invention is illustrated by the following examples which are not intended for any of its restrictions.

EXAMPLES

Reagents and solvents used, as described below, can be obtained from to the commercial sources, such as Aldrich Chemical Co. (Milwaukee, Wis., USA). The results of mass spectrometry are presented as the ratio of mass-to-charge with the subsequent indication of the relative amount of each ion (in parentheses). In tables separate the value of m/e is specified for M+H (or, as indicated, M-H) ion containing most common atomic isotopes. Patterns of isotopes in all cases correspond to the expected formula.

Example 1

(6S,7S)-N-hydroxy-5-methyl-6-{[4-(3-were)piperazine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamid

Stage 1a. Getting BnNH-L-Asp(Otbutyl)-OBn

To a mixture of H-L-Asp(OtButyl)-OH (22 g, 106 mmol) and benzylbromide (35 g, 205 mmol) in toluene (600 ml) was added DBU (33 g, 217 mmol). The mixture was stirred at room temperature overnight and filtered. The filtrate was concentrated. The residue was purified by Combiflash chromatography (hexane and ethyl acetate: gradient from 0% to 10% over 12 min) to give 12.1 g (30,9%) of the desired product BnNH-L-Asp(Otbutyl)-OBn. MS (ESI): 370,3 (M+H+).

Stage 1b. Obtain 1-benzyl-4-tert-butyl-(2S)-2-{benzyl[2-(chloromethyl)prop-2-EN-1-yl]amino}succinate

The mixture BnNH-L-Asp(Otbutyl)-Obn with stage 1a (12.1 g, a 32.6 mmol), K2CO3(14 g, 3 EQ.), NaI (3.0 g, 20 mmol) and 1-chloro-2-chloromethyl-1-propene (5,1 g and 40.8 mmol) in MeCN (150 ml) was stirred at 81°C for 16 hours. After cooling, the mixture was filtered. The filtrate was concentrated and cleaned the Lee Combiflash chromatography (hexane and ethyl acetate: gradient from 0 to 8% over 12 min) to obtain (8.7 g) 1-benzyl-4-tert-butyl-(2S)-2-{benzyl[2-(chloromethyl)prop-2-EN-1-yl]amino}succinate, MS (ESI): 458,3/460,3 (M+H+).

Stage 1c. Obtain 1-benzyl-4-tert-butyl-(2S)-2-{benzyl[2-(iodomethyl)prop-2-EN-1-yl]amino}succinate

A mixture of 1-benzyl-4-tert-butyl-(2S)-2-{benzyl[2-(chloromethyl)prop-2-EN-1-yl]amino}succinate with stage 1b (8.7 g) and NaI (8.0 g) in acetone (100 ml) was stirred at room temperature overnight. The solid was filtered and the filtrate was concentrated. The residue was treated with methylene chloride and filtered through a layer of silica gel to obtain 1-benzyl-4-tert-butyl-(2S)-2-{benzyl[2-(iodomethyl)prop-2-EN-1-yl]amino}succinate (9.2 grams). MS (ESI): 550,2 (M+H+).

Stage 1d. Getting 2-benzyl-3-tert-butyl-(2S,3S)-1-benzyl-5-methyleneimine-2,3-in primary forms

To a cooled (-78°C) solution of 1-benzyl-4-tert-butyl-(2S)-2-{benzyl[2-(iodomethyl)prop-2-EN-1-yl]amino}succinate with stage 1c (9.2 grams) in THF (50 ml) was added dropwise LiHMDS (1.0m in THF, 20.2 ml) at -78°C for 30 minutes. The mixture was stirred at -78°C for 1 hour and then allowed to warm to -30°C for 3 hours. The reaction mixture was extinguished 10% citric acid (10 ml) and diluted with saturated salt solution (100 ml). The mixture was extracted with ethyl acetate (4×75 ml). The combined organic layers were dried over MgSO4and concentrated under reduced pressure. The residue was purified by Combiflash chromatography (hexane and ethyl acetate: gradient from 0 to 5% over 12 min) to give the desired 2-benzyl-3-tert-butyl-(2S,3S)1-benzyl-5-methyleneimine-2,3-in primary forms (of 3.45 g). MS (ESI): 422,3 (M+H+).

Stage 1e. Obtaining 1,2-dibenzyl-3-tert-butyl-(2S,3S)-5-methyleneimine-1,2,3-tricarboxylate

A mixture of 2-benzyl-3-tert-butyl-(2S,3S)-1-benzyl-5-methyleneimine-2,3-in primary forms from step 1d (2.3 g) and benzylbromide (3 ml) was stirred at s within 28 hours. Excess benzylchloride was removed under reduced pressure. The residue was purified by Combiflash chromatography (hexane and ethyl acetate: gradient from 0% to 10% over 12 min) to give the desired 1,2-dibenzyl-3-tert-butyl-(2S,3S)-5-methyleneimine-1,2,3-tricarboxylate (1.40 g). MS (ESI): 488,1(M+Na+); 366,1(M+H+-COO(t-Bu)).

Stage 1f. Getting 5,6-dibenzyl-7-tert-butyl(6S,7S)-5-azaspiro[2,5]octane-5,6,7-tricarboxylate

A solution of Diazald (5.0 g) in ethyl ether (50 ml) was added dropwise to a mixture of KOH (2.65 g), di(ethylene)ethyl ether (5 ml), water (4 ml) and ethyl ether (5 ml) at 60°C. the Resulting diazomethane immediately drove into the reaction flask, which contained a mixture of 1,2-dibenzyl-3-tert-butyl-(2S,3S)-5-methyleneimine-1,2,3-tricarboxylate from step 1e (4.0 g) and palladium(II) acetate (50 mg) in ethyl ether (30 ml)at -20°C. the Reaction mixture was allowed to warm to room temperature and was stirred for 3 hours. The mixture was filtered and concentrated. The residue was purified by Combiflash chromatography to obtain 5,6-dibenzyl-7-tert-butyl(6S,7S)-5-azaspiro[2,5]octane-5,6,7-tricarboxylate (3,86 g). MS (ESI): 502,3 (M+Na ); 380,3 (M+H+-COO(t-Bu)).

Stage 1g. Receipt of (6S,7S)-7-(tert-butoxycarbonyl)-5-azaspiro[2,5]Octan-6-carboxylic acid

5,6-dibenzyl-7-tert-butyl(6S,7S)-5-azaspiro[2,5]octane-5,6,7-tricarboxylate (2.0 g) was first made in methanol (100 ml) with 5% Pd-BaSO4(750 mg) in an atmosphere of hydrogen (balloon with hydrogen) at room temperature. The catalyst was removed by filtration. The filtrate was concentrated. The residue was dried under reduced pressure to obtain (6S,7S)-7-(tert-butoxycarbonyl)-5-azaspiro[2,5]Octan-6-carboxylic acid (1.06 g). MS (ESI): 256,1 (M+H+); 200,1 (M+H+-tert-Bu).

Stage 1h. Obtaining Bn2N-L-Asp(OtButyl)-OBn

To a suspension of β-tert-butyl ester of L-aspartic acid (12.5 g, 66 mmol) in DMF(100 ml) and DMSO (25 ml) was added benzylbromide (39,5 ml, 236 mmol) and then K2CO3(27.5 g, 198 mmol). The mixture was stirred at 50oC during the night. After cooling to room temperature, the salts were filtered and the filtrate was reduced to a small volume by evaporation under reduced pressure. The residue was diluted with water (200 ml) and the resulting solution three times was extracted with EtOAc. The combined organic solution was washed three times with saturated salt solution, dried over MgSO4and concentrated. The residue was purified on silica gel, using as eluent 10% EtOAc/hexane, to obtain 25.1 g Bn2N-L-Asp(OtButyl)-OBn (83%). MS (ESI): 460,1 (M+H+).

To a solution of Bn2N-L-Asp(OtButyl)-Obn from step 1h (9.7 g, 21.1 mmol) in anhydrous THF (100 ml) at -78oC was added a 0.5m solution of KHMDS in toluene (50,7 mmol). After stirring at -78oC for one hour was added allride (2,9 ml, and 31.7 mmol). The temperature was raised to -30oC and stirring continued at this temperature for approximately 4 hours. The reaction was suppressed with 10% citric acid solution and then diluted with a small amount of saturated salt solution. The resulting solution three times was extracted with AcOEt. The combined solution was washed three times with saturated salt solution, dried over MgSO4and concentrated. The residue was purified on silica gel, using as eluent 20% EtOAc/hexane, mixture of CIS and anti-product 4-benzyl-1-tert-butyl-(3S)-2-allyl-3-(dibenzylamino)succinate (8,1 g, 77%). MS (ESI): 500,1 (M+H+).

Stage 1j: Obtain 1-benzyl-4-tert-butyl-(2S,3S)-2-(dibenzylamino)-3-(2,3-dihydroxypropyl)succinate

To a suspension of a mixture of CIS and anti-product 4-benzyl-1-tert-butyl-(3S)-2-allyl-3-(dibenzylamino)succinate from the stage 1i (3 g, 6,0 1 mmol) in acetone and water (10 ml, 1:1 vol./about.) at 0oC was added NMO (0,774 g of 6.61 mmol). The suspension was stirred at 0oC for one hour, then added to the solution OsO4(4%) in water (0.15 ml). The suspension was stirred at room temperature overnight. To reactionaryism added hydrosulfite sodium (90 mg) and was stirred for about 1 hour. The reaction suspension was filtered through celite. The filtrate three times was extracted with EtOAc and the combined organic solution was washed with saturated salt solution, dried over MgSO4and concentrated. The residue was purified on silica gel, using as eluent 50% EtOAc/hexane, to give the desired 1-benzyl-4-tert-butyl-(2S,3S)-2-(dibenzylamino)-3-(2,3-dihydroxypropyl)succinate (1.78 g, 56%). MS (ESI): 534,2 (M+H+).

Stage 1k: Obtain 1-benzyl-4-tert-butyl-(2S,3S)-2-(dibenzylamino)-3-{2-hydroxy-3-[(methylsulphonyl)oxy]propyl}succinate

1-benzyl-4-tert-butyl-(2S,3S)-2-(dibenzylamino)-3-(2,3-dihydroxypropyl)succinate from the stage 1j (2,917 g vs. 5.47 mmol) was dissolved in pyridine (10 ml), cooled to 0oC and was added MsCl (0,444 ml, 5,74 mmol). The solution was stirred at 0oC for 4 hours and diluted with 10% citric acid. The reaction mixture three times was extracted with EtOAc. The combined organic solution was washed three times with 10% citric acid, then with saturated salt solution, dried over MgSO4and concentrated, the residue was purified on silica gel, using as eluent 50% EtOAc/hexane, to obtain 1-benzyl-4-tert-butyl-(2S,3S)-2-(dibenzylamino)-3-{2-hydroxy-3-[(methylsulphonyl)oxy]propyl}succinate (2,696 g, 81%). MS (ESI): 612,1 (M+H+).

Stage 1l. Obtain (2S,3S)-3-(tert-butoxycarbonyl)-5-hydroxypiperidine-2-carboxylic acid

To a solution of 1-be the ZIL-4-tert-butyl-(2S,3S)-2-(dibenzylamino)-3-{2-hydroxy-3-[(methylsulphonyl)oxy]propyl}succinate with stage 1k (5,02 g, 8,2 mmol) in methanol (40 ml) was added Pd-Black and 1M aqueous HCl (4 ml). The mixture was first made in an atmosphere of H2at a pressure of 50 psi overnight. The catalyst was filtered and the solution concentrated to dryness. The residue was dissolved in ethanol was added triethylamine (2 ml). The solution was boiled under reflux for three hours and then concentrated to dryness to obtain the crude compound (2S,3S)-3-(tert-butoxycarbonyl)-5-hydroxypiperidine-2-carboxylic acid, this compound is directly used in the next stage. MS (ESI): 189,9 (M+H+-t-Bu); 246,0 (M+H+); 268,0 (M+Na+).

Stage 1m. Obtaining 1,2-dibenzyl-3-tert-butyl-(2S,3S)-5-hydroxypiperidine-1,2,3-tricarboxylate

To a solution of (2S,3S)-3-(tert-butoxycarbonyl)-5-hydroxypiperidine-2-carboxylic acid (2,02 g, crude product from the previous stage 1l) in DMF was added N-(benzyloxycarbonyloxy)succinimide (is 3.08 g, 12,36 mmol) and then NMM (2,71 ml of 24.7 mmol). The mixture was stirred at room temperature overnight. The solution was acidified to pH 1 with 1M HCl, and was extracted with EtOAc and the organic phase is washed three times with saturated salt solution, dried over MgSO4and concentrated. The residue was purified on silica gel using as eluting solvent a 10% MeOH/CH2Cl2, obtaining the crude mixture (2.17 g, 70%). MS (ESI): 280,0 (M+H+-COO(t-Bu)); 402,0 (M+Na+/sup> ).

To the above compound (1.28 g, to 3.38 mmol) in benzene (15 ml) was added benzylbromide (0.68 ml of 5.75 mmol) and then DBU (1,01 ml, 6,76 mmol). The mixture was stirred at room temperature overnight. Then added EtOAc. The solution was washed three times with 10% citric acid, then with saturated salt solution, dried over MgSO4and concentrated. The residue was purified on silica gel using as eluting solvent 40% EtOAc/hexane, to obtain 1,2-dibenzyl-3-tert-butyl-(2S,3S)-5-hydroxypiperidine-1,2,3-tricarboxylate (0.96 g, 61%). MS (ESI): 370,0 (M+H+-COO(t-Bu)); 492,0 (M+Na+).

Stage 1n. Obtaining 1,2-dibenzyl-3-tert-butyl-(2S,3S)-5-oxopiperidin-1,2,3-tricarboxylate

To a chilled solution of oxalicacid (315 mg) in methylene chloride (2.5 ml) was added dropwise a solution of DMSO (0,30 ml) in methylene chloride (3.0 ml) at -78°C. the Mixture was stirred at -78°C for 30 min, was added dropwise 1,2-dibenzyl-3-tert-butyl-(2S,3S)-5-hydroxypiperidine-1,2,3-tricarboxylate from the stage 1m (900 mg) in methylene chloride (4 ml). The mixture was stirred at -78°C to -60°C for 1 hour. Was added triethylamine (620 mg) in methylene chloride (2.5 ml). The mixture was allowed to warm to room temperature for 2 hours. The mixture was diluted with ethyl acetate (75 ml) and washed with saturated salt solution (2×25 ml). The organic layer was dried over Na2SO4and concentrated under reduced pressure, the NII. The residue was purified flash chromatography on a column of silica gel to obtain 1,2-dibenzyl-3-tert-butyl-(2S,3S)-5-oxopiperidin-1,2,3-tricarboxylate (570 mg). MS (ESI): 490,3 (M+Na+); 368,2 (M+H+-COO(t-Bu)).

Stage 1o. Obtaining 1,2-dibenzyl-3-tert-butyl-(2S,3S)-5-methyleneimine-1,2,3-tricarboxylate

To a solution of 1,2-dibenzyl-3-tert-butyl-(2S,3S)-5-oxopiperidin-1,2,3-tricarboxylate from the stage 1n (850 mg) in toluene (10 ml) was added dropwise a solution of Ph3P=CH2(0,25M in toluene/THF (3:1), and 9.1 ml) at -10°C. the Mixture was stirred and allowed to warm to room temperature for 2 hours. The mixture was diluted with ethyl acetate (75 ml) and washed with saturated salt solution (3×25 ml). The organic layer was dried over Na2SO4and concentrated under reduced pressure. The residue was purified flash chromatography on a column of silica gel to obtain 1,2-dibenzyl-3-tert-butyl-(2S,3S)-5-methyleneimine-1,2,3-tricarboxylate (546 mg). MS (ESI): 488,1 (M+Na+); 366,1 (M+H+-COO(t-Bu)).

Stage 1p. Obtain tert-butyl(6S,7S)-5-methyl-6-{[4-(3-were)piperazine-1-yl]carbonyl}-5-azaspiro[2,5]octane-7-carboxylate

A mixture of (6S,7S)-7-(tert-butoxycarbonyl)-5-azaspiro[2,5]Octan-6-carboxylic acid from step 1g (25 mg), BOP (45 mg), 1-(3-were)piperazine (176 mg) and diisopropylethylamine (70 μl) in DMF (500 μl) was stirred at room temperature overnight. To the mixture was added a solution of formaldehyde is (0.5m in THF/MeCN (1:1), 600 μl) and then NaBH(OAc)3(0,25M in THF/MeCN (1:1), 1000 ál). The resulting mixture was stirred over night. The solvents were removed under reduced pressure. The residue was dissolved in ethyl acetate (5 ml). The solution was washed with a solution of NaHCO3(7,5%, 3×1 ml). The organic phase was dried over MgSO4, filtered and concentrated. The residue was used directly in the next stage without additional purification.

Stage 1q. Receipt of (6S,7S)-N-hydroxy-5-methyl-6-{[4-(3-were)piperazine-1-yl]carbonyl}-5-azaspiro[2,5]octane-7-carboxamide

The crude product from step 1p was dissolved in methylene chloride (3 ml). To the resulting solution was added TFA (3 ml) and then water (0.15 ml). The mixture was stirred at room temperature overnight and concentrated under reduced pressure. The residue was dissolved in DMF (200 μl). To the solution was added BOP (45 mg) and hydroxylamine (21 mg). The mixture was brought to pH 9 using diisopropylethylamine (~80 ml)was stirred at room temperature overnight and then immediately subjected to the purification method RP-HPLC to obtain the final product - (6S,7S)-N-hydroxy-5-methyl-6-{[4-(3-were)piperazine-1-yl]carbonyl}-5-azaspiro[2,5]octane-7-carboxamide. MS(ESI): (M+H)+=387,1.

Example 2

(6S,7S)-N-hydroxy-5-methyl-6-[(4-phenylpiperazin-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained, using techniques obtained the ranks described in example 1. MS(ESI):(M+H)+=373,2.

Example 3

(6S,7S)-N-hydroxy-5-methyl-6-({4-[3-(trifluoromethyl)phenyl]piperazine-1-yl}carbonyl)-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=441.

Example 4

(6S,7S)-N-hydroxy-5-methyl-6-{[4-(2-were)piperazine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=387,1.

Example 5

(6S,7S)-6-{[4-(4-chlorophenyl)piperazine-1-yl]carbonyl}-N-hydroxy-5-methyl-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=407,1.

Example 6

(6S,7S)-N-hydroxy-5-methyl-6-{[4-(2-methyl-4-nitrophenyl)piperazine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=432,0.

Example 7

(6S,7S)-N-hydroxy-5-methyl-6-[(4-phenylpiperazin-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=372,2.

Example 8

(6S,7S)-N-hydroxy-6-[(4-hydroxy-4-phenylpiperidine-1-yl)carbonyl]-5-methyl-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to opeaning example 1. MS(ESI):(M+H)+=388.

Example 9

(6S,7S)-N-hydroxy-5-methyl-6-[(4-phenyl-3,6-dihydropyridines-1(2H)-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=370,0.

Example 11

(6S,7S)-N-hydroxy-5-methyl-6-[(4-quinoline-2-reparation-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=424,3.

Example 12

(6S,7S)-6-{[4-(2,3-dichlorophenyl)piperazine-1-yl]carbonyl}-N-hydroxy-5-methyl-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=441.

Example 13

(6S,7S)-N-hydroxy-5-methyl-6-[(4-quinoline-4-reparation-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=424,3.

Example 14

(6S,7S)-N-hydroxy-5-methyl-6-{[4-(2-methylinosine-4-yl)piperazine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=438,4.

Example 15

(6S,7S)-N-hydroxy-5-methyl-6-{[4-(2-phenylethyl)piperazine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was received, using the method of the Ki, similar to that described in example 1. MS(ESI):(M+H)+=401,3.

Example 16

(6S,7S)-N-hydroxy-5-methyl-6-[(4-pyridin-4-reparacin-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+.373,3.

Example 17

(6S,7S)-N-hydroxy-5-methyl-6-{[4-(4-nitrophenyl)piperazine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=418,3.

Example 18

(6S,7S)-N-hydroxy-6-{[4-(2-methoxyphenyl)piperazine-1-yl]carbonyl}-5-methyl-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=403.

Example 19

(6S,7S)-N-hydroxy-5-methyl-6-[(4-phenoxypyridine-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=388,3.

Example 20

(6S,7S)-6-(3,4-dihydroisoquinoline-2(1H)-ylcarbonyl)-N-hydroxy-5-methyl-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=344,3.

Example 21

(6S,7S)-6-(4,7-dihydrothieno[2,3-c]pyridine-6(5H)-ylcarbonyl)-N-hydroxy-5-methyl-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was received, using the Attiki, similar to that described in example 1. MS(ESI):(M+H)+=350,2.

Example 22

(6S,7S)-6-[(3-benzylpyrrolidine-1-yl)carbonyl]-N-hydroxy-5-methyl-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=372,3.

Example 23

(6S,7S)-N-hydroxy-5-methyl-6-[(4-pyridine-2-reparation-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=374,2.

Example 24

(6S,7S)-N-hydroxy-5-methyl-6-{[4-(2-pyridin-4-retil)piperidine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=401,3.

Example 25

(6S,7S)-N-hydroxy-5-methyl-6-({4-[5-(trifluoromethyl)pyridin-2-yl]piperazine-1-yl}carbonyl)-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=442,3.

Example 26

(6S,7S)-N-hydroxy-5-methyl-6-({4-[3-(trifluoromethyl)pyridin-2-yl]piperazine-1-yl}carbonyl)-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=442,3.

Example 27

(6S,7S)-6-(1,4'-bipiperidine-1'-ylcarbonyl)-N-hydroxy-5-methyl-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection recip is whether, using a technique similar to that described in example 1. MS(ESI):(M+H)+=379,3.

Example 28

(6S,7S)-N-hydroxy-5-methyl-6-{[4-(pyridine-2-ylmethyl)piperazine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=388,3.

Example 29

(6S,7S)-N-hydroxy-5-methyl-6-{[4-(pyridine-4-ylmethyl)piperazine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=388,3.

Example 30

(6S,7S)-N-hydroxy-5-methyl-6-{[4-(pyridine-3-ylmethyl)piperazine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=388,3.

Example 31

(6S,7S)-N-hydroxy-5-methyl-6-{[4-(2-were)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamid

Stage 1.

Getting 4-(2-were)-1,2,3,6-tetrahydropyridine

To a solution of tert-butyl 4-{[(trifluoromethyl)sulfonyl]oxy}-3,6-dihydropyridines-1(2H)-carboxylate (500 mg, is 1.51 mmol), Na2CO3(2.1 ml, 2.0m), LiCl (188 mg) and Pd(PPh3)412 mg) was added 2-methylphenylimino acid. The reaction mixture is boiled under reflux in a period of 2.0 hours and cooled to room temperature. The solution was extracted with ethyl acetate, washed with 2n. rest the rum Na 2CO3and NH4OH and a saturated solution of salt. The crude residue was purified column flash chromatography to obtain 370 mg of pure compound.

The above substance was dissolved in 4.5 ml of CH2Cl3and 0.5 ml of H2O and then added 5 ml of TFA. The mixture was stirred at room temperature for 50 minutes. The mixture was then concentrated to obtain the corresponding substance.

Stage 2. Receipt of (6S,7S)-N-hydroxy-5-methyl-6-{[4-(2-were)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-5-azaspiro[2,5]octane-7-carboxamide

1,4-(2-were)-1,2,3,6-tetrahydropyridine was subjected to reaction combination with (6S,7S)-7-(tert-butoxycarbonyl)-5-azaspiro[2,5]Octan-6-carboxylic acid using methods similar to those described in example 1 to give the desired (6S,7S)-N-hydroxy-5-methyl-6-{[4-(2-were)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide MS(ESI): (M+H)+=384,1.

Example 32

(6S,7S)-N-hydroxy-6-{[4-(3-were)piperazine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=373,1.

Example 33

(6S,7S)-N-hydroxy-5-methyl-6-(1,3,4,9-tetrahydro-2H-β-carbolin-2-ylcarbonyl)-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to the description of the figures in example 1. MS(ESI):(M+H)+=OF 383.0.

Example 34

(6S,7S)-N-hydroxy-5-methyl-6-[(9-methyl-1,3,4,9-tetrahydro-2H-β-carbolin-2-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=396,9.

Example 35

(6S,7S)-6-{[4-(2-forfinal)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-methyl-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 31. MS(ESI):(M+H)+=388,0.

Example 36

(6S,7S)-6-{[4-(2-chlorophenyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-methyl-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 31. MS(ESI):(M+H)+=404,0.

Example 37

(6S,7S)-6-{[4-(4-nitrophenyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-methyl-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 31. MS(ESI):(M+H)+=415,1.

Example 38

(6S,7S)-6-{[4-phenyl-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=356.

Example 39

(6S,7S)-6-{[4-(2-methyl-4-nitrophenyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamid

Decree is a great connection was received, using a technique similar to that described in example 31. MS(ESI):(M+H)+=418,0.

Example 40

(6S,7S)-N(7)-hydroxy-N(6),5-dimethyl-N(6)-(3-phenylpropyl)-5-azaspiro[2,5]octane-6,7-dicarboximide

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=360,1.

Example 41

(6S,7S)-N(7)-hydroxy-N(6)-isobutyl-5-methyl-5-azaspiro[2,5]octane-6,7-dicarboximide

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=284,0.

Example 42

(6S,7S)-N-hydroxy-5-methyl-6-{[4-(2-nitrophenyl)piperazine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=418,0.

Example 43

(6S,7S)-N(7)-hydroxy-N(6)-isobutyl-N(6),5-dimethyl-5-azaspiro[2,5]octane-6,7-dicarboximide

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=298,0.

Example 44

(6S,7S)-N(7)-hydroxy-5-methyl-N(6)-(2-phenoxyethyl)-5-azaspiro[2,5]octane-6,7-dicarboximide

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+.348,0

Example 45

(6S,7S)-N(7)-hydroxy-N(6)-[2-(4-methoxyphenyl)ethyl]-5-methyl-5-azaspiro[2,5]octane-6,7-dicarboximide

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=362,0.

When the EP 46

(6S,7S)-N(7)-hydroxy-5-methyl-N(6)-(4-phenylbutyl)-5-azaspiro[2,5]octane-6,7-dicarboximide

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=360,0.

Example 47

(6S,7S)-N(7)-hydroxy-5-methyl-N(6)-[3-(2-oxopyrrolidin-1-yl)propyl]-5-azaspiro[2,5]octane-6,7-dicarboximide

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=353,0.

Example 48

(6S,7S)-N-hydroxy-5-methyl-6-[(10aR)-3,4,10,10a-tetrahydropyrazino[1,2-a]indol-2(1H)-ylcarbonyl]-5-azaspiro[2,5]Octan-7-carboxamid

Stage 1. Obtaining methyl{[(2R)-2,3-dihydro-1H-indole-2-ylcarbonyl]amino}acetate

To a solution of (2R)-indolin-2-carboxylic acid (1 g, 5,64 mmol) and HCl-salt of methyl ester aminouksusnoy acid (710 mg, 5,64 mmol) and BOP (2,75 g, 1.1 EQ.) in 15 ml of DMF was added 2,95 ml base Janiga. The mixture was stirred over night. The mixture was dissolved in a saturated solution of NaHCO3, was extracted three times with EtOAc and washed with saturated solution of NaHCO3and a saturated solution of salt. The organic solution was dried over Na2SO4and concentrated to give the desired methyl{[(2R)-2,3-dihydro-1H-indole-2-ylcarbonyl]amino}acetate. This substance is used directly in the next stage without additional purification.

Stage 2.

Receiving (10aR)-1,2,3,4,10,10a-hexahydropyrazino what about[1,2-a]indole

Methyl{[(2R)-2,3-dihydro-1H-indole-2-ylcarbonyl]amino}acetate (390 mg) was mixed with 100 mg of NaOMe in 5 ml of ethanol. The mixture was boiled under reflux for 2 hours and cooled to room temperature. The crude substance was purified with flash chromatography to give the desired (10aR)-2,3,10,10a-tetrahydropyrazino[1,2-a]indole-1,4-dione.

To a solution of (10aR)-2,3,10,10a-tetrahydropyrazino[1,2-a]indole-1,4-dione (200 mg, 0,99 mmol) in 5 ml THF was added LAH. The reaction mixture is boiled under reflux for 1 hour. In the standard processing of the received 170 mg of pure (10aR)-1,2,3,4,10,10a-hexahydropyrazino[1,2-a]indole.

Stage 3.

Using the procedure described in example 1 (10aR)-1,2,3,4,10,10a-hexahydropyrazino[1,2-a]indole was converted into the desired (6S,7S)-N-hydroxy-5-methyl-6-[(10aR)-3,4,10,10a-tetrahydropyrazino[1,2-a]indol-2(1H)-ylcarbonyl]-5-azaspiro[2,5]Octan-7-carboxamid. MS(ESI): (M+H)+=385,0.

Example 49

(5,6-TRANS)-N-hydroxy-5-{[4-(2-methyl-4-nitrophenyl)piperazine-1-yl]carbonyl}Spiro[2,5]octane-6-carboxamide

Stage 1. Getting 2-tert-butyl-1-ethyl-(1,2-TRANS)-4-[(trimethylsilyl)oxy]cyclohex-4-ene-1,2-in primary forms

At -20oC 0,4M solution in toluene bis(2,6-di-tert-butyl-4-methylphenoxy)methylamine (MAD) (50 ml, 20 mmol) slowly with stirring was added to the solvent methylene chloride (15 ml). When attemperator to the MAD solution slowly with stirring was added a solution of tert-butylacrylate (of 3.60 g, 18 mmol) in methylene chloride (4 ml). At -20°C to the reaction mixture was slowly added a solution of 2-trimethylsilyloxy-1,3-butadiene (2,56 g, 18 mmol) in methylene chloride (4 ml). The reaction mixture was stirred at -20°C for 70 hours. The reaction mixture was extinguished with a saturated solution of citric acid and was diluted with methylene chloride. Deposited some amount of the insoluble substance was filtered. After separation the aqueous layer was extracted with methylene chloride (×2). The combined extracts were dried over Na2SO4. After filtration, the filtrate was concentrated. The obtained residue was purified flash chromatography, obtained 4.12 g of pure product. The filtrate was again purified column chromatography. Got another 0,56 pure product was isolated 0,78 g educt - tert-butylacrylate. Yield: 97%.

Stage 2. Getting 2-tert-butyl-1-ethyl-(1,2-TRANS)-4-oxocyclohexa-1,2-in primary forms

2-tert-Butyl-1-ethyl-(1,2-TRANS)-4-[(trimethylsilyl)oxy]cyclohex-4-ene-1,2 -, in primary forms with stage 1 (to 0.72 g, 2.1 mmol) was dissolved in methanol (10 ml). To the resulting solution was added a saturated solution of citric acid (1 ml). The mixture was stirred at room temperature for 4 hours. TLC showed that starting material had been consumed. The methanol was removed on a rotary evaporator. The obtained residue absorption is Ali in ethyl acetate and washed with water (×1), saturated salt solution (×1), dried over Na2SO4. After filtration, the filtrate was concentrated to obtain a product with a quantitative yield.

Stage 3. Getting 2-tert-butyl-1-ethyl-(1,2)-4-methyltriclosan-1,2-in primary forms

To a mixture of bromide methyltriphenylphosphonium (0.87 g, 2.4 mmol) in toluene (6 ml) and THF (2 ml) was added 1M solution of NaHMDS (2.4 ml, 2.4 mmol) in THF. The mixture was stirred at room temperature for 1.5 hours. The mixture slowly with stirring was added to pre-cooled (-10oC) solution of 2-tert-butyl-1-ethyl-(1,2-TRANS)-4-oxocyclohexa-1,2-in primary forms with a stage 2 (or 0.57 g, 2.1 mmol) in toluene (8 ml). Upon completion of addition the reaction mixture was stirred at -10oC for 10 minutes, then at room temperature for 1.5 hours. TLC showed that starting material had been consumed. The reaction mixture was diluted with ethyl acetate, washed with water (×1); saturated salt solution (×2), dried over Na2SO4. After filtration, the filtrate was concentrated. The obtained residue was purified flash chromatography. Was obtained 0.56 g of 2-tert-butyl-1-ethyl-(1,2)-4-methyltriclosan-1,2-in primary forms. Yield: 99%.

Stage 4. Getting 5-tert-butyl-6-ethyl-(5,6-TRANS)-Spiro[2,5]octane-5,6-in primary forms

To a solution of KOH (5 g) in the e (8 ml), di(ethylene glycol)ethyl ether (24 ml) and ethyl ether (25 ml) in A flask was added in three portions 3 g dieseld (diazald). After adding the first portion of dieseld the flask was placed on a preheated (60oC) oil bath for Stripping the formed CH2N2using a simple ester in another flask (B), pre-cooled to about -15oC and containing 2-tert-butyl-1-ethyl-(1,2)-4-methyltriclosan-1,2, in primary forms with stage 3 (500 mg) and Pd(OAc)2(80 mg) in ether (15 ml). After 5 minutes, the oil bath for A bulb was removed. Then add the second portion of dieseld and the above procedure was repeated twice. Upon completion of the distillation, CH2N2ether in the flask B cooling bath to flask B was removed. The reaction mixture was stirred at room temperature for 2 hours, then filtered through silica gel, washed with ethyl acetate and then with methylene chloride. The filtrate was concentrated. The obtained residue was treated three times using the above procedure. In the normal processing of received 5-tert-butyl-6-ethyl-(5,6-TRANS)Spiro[2,5]octane-5,6-in primary forms (yield 80%).

Stage 5.

Receiving (5,6-TRANS)-6-(etoxycarbonyl)Spiro[2,5]octane-5-carboxylic acid

5-tert-butyl-6-ethyl-(5,6-TRANS)-Spiro[2,5]octane-5,6-in primary forms (150 mg, of 0.53 mmol) was dissolved in races the thief methylene chloride (2 ml), TFA (2 ml) and water (0.1 ml). The mixture was stirred at room temperature for 3 hours. TLC showed that starting material had been consumed. The reaction mixture was concentrated to obtain the product (5,6-TRANS)-6-(etoxycarbonyl)Spiro[2,5]octane-5-carboxylic acid in quantitative yield.

Stage 6. Getting ethyl-(5,6-TRANS)-5-{[4-(2-methyl-4-nitrophenyl)piperazine-1-yl]carbonyl}Spiro[2,5]octane-6-carboxylate:

(5,6-TRANS)-6-(etoxycarbonyl)Spiro[2,5]octane-5-carboxylic acid from step 5 (27.4 mg, 0.12 mmol) and 1-(2-methyl-4-nitrophenyl)piperazine (of 29.4 mg, 0.13 mmol) was dissolved in DMF (1 ml). To the resulting solution was added BOP reagent (56,3 mg, to 0.127 mmol). After stirring for 10 minutes, to the mixture was added DIEA. The mixture was stirred at room temperature over night, then put a saturated solution of citric acid. The product was extracted with ethyl acetate. The extract was washed with water (×1), saturated salt solution (×1), dried over Na2SO4. After filtration, the filtrate was concentrated to obtain ethyl-(5,6-TRANS)-5-{[4-(2-methyl-4-nitrophenyl)piperazine-1-yl]carbonyl}Spiro[2,5]octane-6-carboxylate.

Stage 7. Receiving (5,6-TRANS)-5-{[4-(2-methyl-4-nitrophenyl)piperazine-1-yl]carbonyl}Spiro[2,5]octane-6-carboxylic acid

Ethyl-(5,6-TRANS)-5-{[4-(2-methyl-4-nitrophenyl)piperazine-1-yl]carbonyl}sleep is about[2,5]octane-6-carboxylate, received at stage 6, were mixed in a mixture of THF (2 ml)-water (0.4 ml) and LiOH·H2O (200 mg) and heated at boiling under reflux for 36 hours. After cooling, the reaction mixture was neutralized with a saturated solution of citric acid and was extracted with ethyl acetate (×3). The combined extracts were washed with citric acid (×1), saturated salt solution (×1) and dried over Na2SO4. After filtration, the filtrate was concentrated to obtain (5,6-TRANS)-5-{[4-(2-methyl-4-nitrophenyl)piperazine-1-yl]carbonyl}Spiro[2,5]octane-6-carboxylic acid.

Stage 8. Obtaining compounds (5,6-TRANS)-N-hydroxy-5-{[4-(2-methyl-4-nitrophenyl)piperazine-1-yl]carbonyl}Spiro[2,5]octane-6-carboxamide

To a solution of (5,6-TRANS)-5-{[4-(2-methyl-4-nitrophenyl)piperazine-1-yl]carbonyl}Spiro[2,5]octane-6-carboxylic acid, obtained in stage 7 and the HCl-salt of hydroxylamine (30 mg, 4.3 mmol) in 1 ml DMF was added agent combination BOP (56,3 mg, 0.13 mmol). After stirring for 10 minutes, to the mixture was added DIEA. The mixture was stirred at room temperature overnight and the reaction was monitored by HPLC. The final desired product was purified by the method OF HPLC with the receipt of 25.6 mg (5,6-TRANS)-N-hydroxy-5-{[4-(2-methyl-4-nitrophenyl)piperazine-1-yl]carbonyl}Spiro[2,5]octane-6-carboxamide with the release of 50%, from the three stages. MS(ESI): (M+H)+=417,2.

Example 50

(5,6-TRANS)-N-hydroxy-6-{[4-(3-were)piperazine-1-yl]carbonyl}Spiro[2,5]octane-5-carboxamid

The specified connection was obtained using a technique similar to that described in example 49. MS(ESI):(M+H)+=372,2.

Example 51

(5,6-TRANS)-N-hydroxy-5-[(4-phenyl-3,6-dihydropyridines-1(2H)-yl)carbonyl]Spiro[2,5]octane-6-carboxamide

The specified connection was obtained using a technique similar to that described in example 49. MS(ESI):(M+H)+=355.

Example 52

(5,6-TRANS)-N-hydroxy-5-{[4-(3-were)piperazine-1-yl]carbonyl}Spiro[2,5]octane-6-carboxamide

The specified connection was obtained using a technique similar to that described in example 49. MS(ESI):(M+H)+=372,0.

Example 53

(5,6-TRANS)-N-hydroxy-6-[(4-phenyl-3,6-dihydropyridines-1(2H)-yl)carbonyl]Spiro[2,5]octane-5-carboxamid

The specified connection was obtained using a technique similar to that described in example 49. MS(ESI):(M+H)+=355.

Example 54

(6S,7S)-N-hydroxy-6-(3,4,10,10a-tetrahydropyrazino[1,2-a]indol-2(1H)-ylcarbonyl)-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 48. MS(ESI):(M+H)+=371,2.

Example 55

(6S,7S)-6-(1,2,4,4a,5,6-hexahydro-3H-pyrazino[1,2-a]quinoline-3-ylcarbonyl)-N-hydroxy-5-methyl-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in the application is e 48. MS(ESI):(M+H)+=RUB 399.4.

Example 56

Methyl-(6S,7S)-7-[(hydroxyamino)carbonyl]-6-[(4-phenyl-3,6-dihydropyridines-1(2H)-yl)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=414,0.

Example 57

Benzyl(6S,7S)-7-[(hydroxyamino)carbonyl]-6-[(4-phenyl-3,6-dihydropyridines-1(2H)-yl)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=490,0.

Example 58

(6S,7S)-N-Hydroxy-5-(methylsulphonyl)-6-[(4-phenyl-3,6-dihydropyridines-1(2H)-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=434,0.

Example 59

(6S,7S)-N-hydroxy-6-{[3-(3-methoxyphenyl)piperidine-1-yl]carbonyl}-5-methyl-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=402,4.

Example 60

(6S,7S)-N-hydroxy-5-methyl-6-{[3-(2-phenylethyl)pyrrolidin-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=386,0.

Example 61

(6S,7S)-N-hydroxy-6-{[4-(3-methoxyphenyl)piperidine-1-yl]carbonyl}-5-methyl-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection is Uchali, using a technique similar to that described in example 1. MS(ESI):(M+H)+=402,4.

Example 62

(6S,7S)-6-{[4-[3-(aminocarbonyl)phenyl]-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 31. MS(ESI):(M+H)+=398,9.

Example 63

(6S,7S)-N-hydroxy-6-{[4-(2-methoxyphenyl)piperidine-1-yl]carbonyl}-5-methyl-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 31. MS(ESI):(M+H)+=402,4.

Example 64

(6S,7S)-6-{[4-(3-fluoro-2-were)piperazine-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=391,3.

Example 65

(6S,7S)-N-hydroxy-6-{[4-(2-methyl-3-nitrophenyl)piperazine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=418,3.

Example 66

(6S,7S)-6-(3',6'-dihydro-3,4'-bipyridine-1'(2'H)-ylcarbonyl)-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 31. MS(ESI):(M+H)+=357,4.

Example 67

(6S,7S)-N(7)-hydroxy-N(6)-(4-methoxyphenyl)-N(6)-methyl-5-azaspiro[2,5]octane-6,7-dicarboximide

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=334.

Example 68

(6S,7S)-N-hydroxy-6-{[4-(3-methoxyphenyl)piperazine-1-yl]carbonyl}-5-methyl-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=403,0.

Example 69

(6S,7S)-6-{[4-(3-chlorophenyl)piperazine-1-yl]carbonyl}-N-hydroxy-5-methyl-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=407,3.

Example 70

(6S,7S)-N-hydroxy-6-[(4-phenyl-1,4-diazepan-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=373.

Example 71

(6S,7S)-N-hydroxy-6-{[3-methyl-4-(3-were)piperazine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=387.

Example 72

(6S,7S)-N-hydroxy-6-{[4-(3-methoxyphenyl)piperidine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=OF 388.4.

Example 73

(5S,6S)-N-hydroxy-6-[(3-phenylpyrrolidine-1-yl)carbonyl]Spiro[2,5]octane-5-carboxamid

The specified connection was received, is using techniques similar to that described in example 1. MS(ESI):(M+H)+=343,3.

Example 74

(6S,7S)-N-hydroxy-6-[(4-isobutylpyrazine-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=353.

Example 75

(6S,7S)-6-{[4-(4-cyano-2-were)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 31. MS(ESI):(M+H)+=395.

Example 76

(6S,7S)-N(7)-Hydroxy-5-methyl-N(6)-{4-[(2-methylinosine-4-yl)methoxy]phenyl}-5-azaspiro[2,5]octane-6,7-dicarboximide

Stage 1.

Getting 4-(2-methylinosine-4-ylethoxy)phenylamine

To a mixture of 2-methylinosine (43,0 g, 0.3 mol), iron (5,04 g, 0.09 mol), FeSO4·7H2O (25,0 g, 0.09 mol) in methanol (400 ml) and water (200 ml) was added sulfuric acid (conc., 16.0 ml, 0.3 mol) at 0oC and then slowly added H2O2(160 ml) at 0oC. the Mixture then was heated to room temperature and was stirred overnight. The solution was diluted with water, podslushivaet with ammonium hydroxide and was extracted with ethyl acetate. The combined extract was washed with saturated salt solution, dried and concentrated. As a result of recrystallization from a mixture of ethyl ether/hexane was obtained (2-methylinosine-4-yl)methanol (12.0 g). ESI (M+H)+173,9.

(2-M is tinhinan-4-yl)methanol (7.0 g) was dissolved in chloroform (150 ml) and cooled to 0 oC, at this temperature, was slowly added thionyl chloride (15.0 ml) and then the reaction mixture was allowed to warm to room temperature with stirring overnight. The solvent was removed and the residue triturated in a mixture of ethyl acetate/ethyl ether to obtain compound 4-chloromethyl-2-methylinosine in the form of HCl salt (9.0 g). ESI (M+H)+191,9.

A mixture of 4-chloromethyl-2-methylinosine (6,84 g, 30.0 mmol), tert-butyl methyl ether (4-hydroxyphenyl)carbamino acid (6,24 g, 30.0 mmol), Cs2CO3(20,0 g, 60,0 mmol) and n-Bu4NI (11.1 g, 30.0 mmol) in DMSO (150 ml) was stirred at 80oC for 3 hours. The mixture was then cooled, immersed in cold water and was extracted with ethyl acetate. The combined extract was washed with water, saturated salt solution, dried and concentrated. The result chromatography using CH2Cl2/EtOAc was obtained tert-butyl ester [4-(2-methylinosine-4-ylethoxy)phenyl]carbamino acid (8.0 g). ESI (M+H)+365,3.

To a solution of tert-butyl, EPIRB [4-(2-methylinosine-4-ylethoxy)phenyl]carbamino acid (1.5 g) in ethyl acetate (5 ml) was added 4n. a solution of HCl in dioxane (20 ml) and the mixture was stirred at room temperature for 3 hours. Was added ethyl ether, the precipitate was filtered and washed with ethyl ether to obtain 4-(2-methylinosine-4-ylethoxy)phenylamine in the form of HCl salt (1.3 g). ESI (M+H)+ 265,0.

Stage 2. Obtain tert-butyl(6S,7S)-6-[({4-[(2-methylinosine-4-yl)methoxy]phenyl}amino)carbonyl]-5-azaspiro[2,5]octane-7-carboxylate

4-(2-Methylinosine-4-ylethoxy)phenylamine in the form of HCl salt (94,0 mg, 0.28 mmol) and (6S,7S)-7-(tert-butoxycarbonyl)-5-azaspiro[2,5]Octan-6-carboxylic acid (70.0 mg, 0.27 mmol) was dissolved in DMF (2.0 ml). To the resulting solution was added BOP (143,0 mg, 0.32 mmol) and then was cooled to 0oC. To the mixture was added diisopropylethylamine (0,175 ml, 1.0 mmol) at 0oC and then the reaction mixture was stirred at room temperature for 2 hours. The mixture was diluted with water, extracted with ethyl acetate, the combined extract was washed with saturated salt solution, dried and concentrated. The crude tert-butyl(6S,7S)-6-[({4-[(2-methylinosine-4-yl)methoxy]phenyl}amino)carbonyl]-5-azaspiro[2,5]octane-7-carboxylate (140 mg) was used in the next stage without purification. ESI (M+H)+502,4.

Stage 3. Obtain tert-butyl(6S,7S)-5-methyl-6-[({4-[(2-methylinosine-4-yl)methoxy]phenyl}amino)carbonyl]-5-azaspiro[2,5]octane-7-carboxylate

To a solution of tert-butyl(6S,7S)-6-[({4-[(2-methylinosine-4-yl)methoxy]phenyl}amino)carbonyl]-5-azaspiro[2,5]octane-7-carboxylate (140 mg, 0.27 mmol) in methanol (3.0 ml) was added formaldehyde (37% solution in water, 0.5 ml) and triacetoxyborohydride sodium (0.25 g, 1.2 mmol). The mixture was then stirred at room temperature T. the value of 2 hours. The reaction mixture was diluted with ethyl acetate, washed with saturated solution of NaHCO3, water and saturated salt solution. Was dried and concentrated. tert-butyl(6S,7S)-5-methyl-6-[({4-[(2-methylinosine-4-yl)methoxy]phenyl}amino)carbonyl]-5-azaspiro[2,5]octane-7-carboxylate (105,0 mg) was obtained by purification column chromatography using CH2Cl2/methanol (10%). ESI (M+H)+516,5.

Stage 4. Receipt of (6S,7S)-5-methyl-6-[({4-[(2-methylinosine-4-yl)methoxy]phenyl}amino)carbonyl]-5-azaspiro[2,5]octane-7-carboxylic acid

To a solution of tert-butyl(6S,7S)-5-methyl-6-[({4-[(2-methylinosine-4-yl)methoxy]phenyl}amino)carbonyl]-5-azaspiro[2,5]octane-7-carboxylate (105,0 mg) in CH2Cl2(1.0 ml) was added TFA (1.0 ml) and the mixture was stirred at room temperature for 5 hours. The solvent was removed to obtain (6S,7S)-5-methyl-6-[({4-[(2-methylinosine-4-yl)methoxy]phenyl}amino)carbonyl]-5-azaspiro[2,5]octane-7-carboxylic acid (140 mg) as a TFA salt. ESI (M+H)+460,3.

Stage 5. Receipt of (6S,7S)-N(7)-hydroxy-5-methyl-N(6)-{4-[(2-methylinosine-4-yl)methoxy]phenyl}-5-azaspiro[2,5]octane-6,7-dicarboximide

To a solution of (6S,7S)-5-methyl-6-[({4-[(2-methylinosine-4-yl)methoxy]phenyl}amino)carbonyl]-5-azaspiro[2,5]octane-7-carboxylic acid (140 mg, 0.20 mmol) in DMF (1.0 ml) at 0oC was added BOP (120,0 mg, 0.24 mmol) and then hydroxylamine hydrochloride (28,0 mg, 0.40 mmol). Then to the resulting mixture is at 0 oC was added 4-methylmorpholine (0,07 ml, 0.70 mmol) and was stirred at this temperature for 2 hours. The resulting product (70 mg) was purified preparative HPLC. ESI (M+H)+475,4.

Example 77

(6S,7S)-N(7)-Hydroxy-N(6)-{4-[(2-methylinosine-4-yl)methoxy]phenyl}-5-azaspiro[2,5]octane-6,7-dicarboximide

The specified connection was obtained using a technique similar to that described in example 77. MS(ESI):(M+H)+=461,0.

Example 78

(6S,7S)-6-{[4-(4-cyanophenyl)piperazine-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=384,0.

Example 79

(6S,7S)-N-hydroxy-7-[(4-phenylpiperazin-1-yl)carbonyl]-5-azaspiro[2,5]Octan-6-carboxamide

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=358,0.

Example 80

(6S,7S)-N-hydroxy-6-[(4-phenylpiperazin-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=358.

Example 81

(6S,7S)-N-Hydroxy-6-[(4-phenylpiperazin-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=359,4.

Example 82

(6S,7S)-N-hydroxy-6-({4-[3-(methoxymethyl)phenyl]piperidine-1-yl}carbonyl)-5-azaspiro[,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=402.

Example 83

Methyl-3-[1-({(6S,7S)-7-[(hydroxyamino)carbonyl]-5-azaspiro[2,5]Oct-6-yl}carbonyl)piperidine-4-yl]benzoate

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=416.

Example 84

(6S,7S)-6-[(3-Cyclohexylpiperidine-1-yl)carbonyl]-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=350,4.

Example 85

(6S,7S)-N-Hydroxy-6-{[4-(3-isopropylphenyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 31. MS(ESI):(M+H)+=398,4.

Example 86

(6S,7S)-N-hydroxy-6-{[4-(3-isopropylphenyl)piperidine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamid

(6S,7S)-N-hydroxy-6-{[4-(3-isopropylphenyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide (10 mg) was first made at a pressure of 1.0 ATM over BaSO4in MeOH for one hour to give the desired product, MS(ESI):(M+H)+=400,4.

Example 87

(6S,7S)-N-hydroxy-6-{[4-(4-propylphenyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=398.

Example 88

(6S,7S)-N-hydroxy-6-{[4-(4-ethylphenyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 31. MS(ESI):(M+H)+=384,4.

Example 89

(6S,7S)-N-Hydroxy-6-{[4-(4-ethylphenyl)piperidine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 86. MS(ESI):(M+H)+=386.

Example 90

(6S,7S)-6-{[4-(4-cyano-2-were)piperazine-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=398.

Example 91

(6S,7S)-N-Hydroxy-6-{[4-(3-isopropoxyphenyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 31. MS(ESI):(M+H)+=414,4.

Example 92

(6S,7S)-N-Hydroxy-6-{[4-(3-were)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 31. MS(ESI):(M+H)+=370,3.

Example 93

(6S,7S)-N-Hydroxy-6-{[4-(3-were)piperidine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in note the re 86. MS(ESI):(M+H)+=372,4.

Example 94

(6S,7S)-6-{[4-(4-tert-butylphenyl)piperazine-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=415,4.

Example 95

(6S,7S)-N-Hydroxy-6-[(4-pyridin-4-reparation-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=360.

Example 96

(6S,7S)-6-[(3-Benzylpiperidine-1-yl)carbonyl]-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=371,9.

Example 97

(6S,7S)-N-hydroxy-6-[(5-methoxy-2,3-dihydro-1H-indol-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 76. MS(ESI):(M+H)+=346,3.

Example 98

(6S,7S)-N-hydroxy-6-({5-[(2-methylinosine-4-yl)methoxy]-2,3-dihydro-1H-indol-1-yl}carbonyl)-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 76. MS(ESI):(M+H)+=487,4.

Example 99

(6S,7S)-N-hydroxy-5-methyl-6-({5-[(2-methylinosine-4-yl)methoxy]-2,3-dihydro-1H-indol-1-yl}carbonyl)-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to the description of the figures in example 76. MS(ESI):(M+H)+=501,4.

Example 100

(6S,7S)-6-{[5-(benzyloxy)-2,3-dihydro-1H-indol-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 76. MS(ESI):(M+H)+=422,3.

Example 101

(6S,7S)-6-(1,3-dihydro-1'H-Spiro[inden-2,4'-piperidine]-1'-ylcarbonyl)-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=384,4.

Example 102

(6S,7S)-N-hydroxy-6-{[4-(3-isopropoxyphenyl)piperidine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 86. MS(ESI):(M+H)+=416,4.

Example 103

Methyl-4-[1-({(6S,7S)-7-[(hydroxyamino)carbonyl]-5-azaspiro[2,5]Oct-6-yl}carbonyl)-1,2,3,6-tetrahydropyridine-4-yl]-3-methylbenzoate

The specified connection was obtained using a technique similar to that described in example 31. MS(ESI):(M+H)+=427,9.

Example 104

(6S,7S)-N-hydroxy-6-{[4-(2-methyl-4-nitrophenyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 31. MS(ESI):(M+H)+=414,8.

Example 105

(6S,7S)-6-{[4-(2-ethylphenyl)piperidine-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection is out received, using a technique similar to that described in example 86. MS(ESI):(M+H)+=385,9.

Example 106

Methyl-4-[1-({(6S,7S)-7-[(hydroxyamino)carbonyl]-5-azaspiro[2,5]Oct-6-yl}carbonyl)piperidine-4-yl]-3-methylbenzoate

The specified connection was obtained using a technique similar to that described in example 86. MS(ESI):(M+H)+=429,9.

Example 107

(6S,7S)-6-{[4-(2,3-dihydro-1-benzofuran-5-yl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-methyl-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 31. MS(ESI):(M+H)+=412,2.

Example 108

(6S,7S)-N-hydroxy-6-{[4-(3-isopropylphenyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-5-methyl-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 31. MS(ESI):(M+H)+=412,25.

Example 109

(6S,7S)-N-Hydroxy-6-{[(3R)-3-phenylpyrrolidine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=344,1.

Example 110

(6S,7S)-N-Hydroxy-6-{[(3S)-3-phenylpyrrolidine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=344,1.

Example 112

(6S,7S)-N-hydroxy-6-({3-[3-(trifluoromethyl)phenyl]pyrrolidin-1-yl}carbonyl)-5-azaspiro[2,5]Octan-7-carboxym is d

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=412,1.

Example 113

(6S,7S)-6-{[3-(3-chlorophenyl)pyrrolidin-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=378,1.

Example 114

(6S,7S)-6-{[3-(3-forfinal)pyrrolidin-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=362,1.

Example 115

(6S,7S)-6-{[3-(4-forfinal)pyrrolidin-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=362,1.

Example 116

(6S,7S)-6-{[3-(4-chlorophenyl)pyrrolidin-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=378,1.

Example 117

(6S,7S)-N-hydroxy-6-({3-[4-(trifluoromethyl)phenyl]pyrrolidin-1-yl}carbonyl)-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=412,1.

Example 118

(6S,7S)-6-{[3-(4-methoxyphenyl)pyrrolidin-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection is the received using a technique similar to that described in example 1. MS(ESI):(M+H)+=374,1.

Example 119

(6S,7S)-6-{[3-(4-phenoxyphenyl)pyrrolidin-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=436,2.

Example 120

(6S,7S)-N-hydroxy-6-{[4-(3-methoxyphenyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 31. MS(ESI):(M+H)+=386,1.

Example 121

(6S,7S)-N-hydroxy-6-{[4-(4-cyano-3-were)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 31. MS(ESI):(M+H)+=395,1.

Example 122

(6S,7S)-6-{[3-(3-methoxyphenyl)pyrrolidin-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=374,1.

Example 123

(6S,7S)-N-hydroxy-6-[(3-pyridin-4-iparralde-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=345,2.

Example 124

(6S,7S)-N-hydroxy-6-{[4-(3, 5dimethylphenyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamid

Specified soy is inania received, using a technique similar to that described in example 31. MS(ESI):(M+H)+=384,2.

Example 125

(6S,7S)-N-hydroxy-6-{[4-(3-trifloromethyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 31. MS(ESI):(M+H)+=440,1.

Example 126

(6S,7S)-N-hydroxy-6-{[5-(methoxymethyl)-4-phenyl-3,6-dihydropyridines-1(2H)-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=400.

Example 127

(6S,7S)-N-hydroxy-6-(1,4,5,6-tetrahydrobenzo[f]isoquinoline-3(2H)-ylcarbonyl)-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=381,9.

Example 129

(6S,7S)-N-hydroxy-6-{[4-(5-methoxy-2-were)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 31. MS(ESI):(M+H)+=400,2.

Example 130

(6S,7S)-N-hydroxy-6-{[4-(4-methoxy-2-were)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 31. MS(ESI):(M+H)+=400,2.

Example 131

(6S,7S)-6-[(4-cyano-4-phenylpiperidine-1-yl)shall arbonyl]-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=383,2.

Example 132

Ethyl-(6S,7S)-7-[(hydroxyamino)carbonyl]-6-[(4-phenyl-3,6-dihydropyridines-1(2H)-yl)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M-H)-=426,1.

Example 133

Propyl-(6S,7S)-7-[(hydroxyamino)carbonyl]-6-[(4-phenyl-3,6-dihydropyridines-1(2H)-yl)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M-H)-=440,2.

Example 134

Isopropyl-(6S,7S)-7-[(hydroxyamino)carbonyl]-6-[(4-phenyl-3,6-dihydropyridines-1(2H)-yl)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M-H)-=440,2.

Example 135

Isobutyl-(6S,7S)-7-[(hydroxyamino)carbonyl]-6-[(4-phenyl-3,6-dihydropyridines-1(2H)-yl)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M-H)-=454,2.

Example 136

(6S,7S)-N-hydroxy-6-[(5-methyl-4-phenyl-3,6-dihydropyridines-1(2H)-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=370.

Example 143

(6S,7)-6-(1,4,4a,5,6,10b-hexahydrobenzo[f]isoquinoline-3(2H)-ylcarbonyl)-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=384,2.

Example 144

(6S,7S)-6-{[4-(4-forfinal)-3-hydroxypiperidine-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=392,1.

Example 145

(6S,7S)-N-hydroxy-6-(3,3a,8,8a-tetrahydroindene[1,2-c]pyrrole-2(1H)-ylcarbonyl)-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=356,1.

Example 146

(6S,7S)-N-hydroxy-6-{[4-(4-phenyl-1,3-thiazol-2-yl)piperidine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=441,3.

Example 147

(6S,7S)-N-hydroxy-6-{[4-(4-tert-butyl-1,3-thiazol-2-yl)piperidine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=421,1.

Example 148

(6S,7S)-N-hydroxy-6-[(4-methyl-4-phenylpiperidine-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=372,2.

Por the measures 149

(6S,7S)-N-hydroxy-6-{[4-(4-ethyl-1,3-thiazol-2-yl)piperidine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=393,1.

Example 150

(6S,7S)-N-hydroxy-6-{[(TRANS)-3-methyl-4-phenylpyrrolidine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=358,2.

Example 151

(6S,7S)-6-{[4-(2-forfinal)piperazine-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=377,2.

Example 152

(6S,7S)-6-{[4-(3, 5dimethylphenyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-methyl-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=398,1.

Example 153

Tetrahydro-2H-Piran-4-yl-(6S,7S)-7-((hydroxyamino)carbonyl)-6-((4-phenylpiperazin-1-yl)carbonyl)-5-azaspiro(2,5)octane-5-carboxylate

Stage 1. Obtain tert-butyl(6S,7S)-6-((4-phenylpiperazin-1-yl)carbonyl)-5-azaspiro(2,5)octane-7-carboxylate

To a solution of (6S,7S)-7-(tert-butoxycarbonyl)-5-azaspiro[2,5]Octan-6-carboxylic acid (160 mg, to 0.63 mmol) in DMF (1.5 ml) was added 1-finalpaper is in (112 mg, 0.69 mmol) and then was added BOP (292 mg, 0.66 mmol). After stirring for 10 minutes was added DIEA (204 mg, 1.57 mmol). The mixture was stirred at room temperature for 3 hours, reduce saturated solution KH2PO4and were extracted with ethyl acetate. The extract was washed with water, saturated salt solution and dried over MgSO4. After filtration, the filtrate was concentrated. The crude substance was purified column flash chromatography. Was obtained tert-butyl(6S,7S)-6-((4-phenylpiperazin-1-yl)carbonyl)-5-azaspiro(2,5)octane-7-carboxylate in quantitative yield. LC-MS: m/z 400,1 (M+H)+.

Stage 2. Receipt of (6S,7S)-6-((4-phenylpiperazin-1-yl)carbonyl)-5-azaspiro(2,5)octane-7-carboxylic acid

The above-mentioned product tert-butyl(6S,7S)-6-((4-phenylpiperazin-1-yl)carbonyl)-5-azaspiro(2,5)octane-7-carboxylate was stirred in 8 ml of 50% solution of TFA in methylene chloride (about./about.) within 4 hours. After removal of solvent the residue was dried under high vacuum overnight to obtain (6S,7S)-6-((4-phenylpiperazin-1-yl)carbonyl)-5-azaspiro(2,5)octane-7-carboxylic acid. LC-MS: m/z 344,1 (M+H)+.

Stage 3. Receipt of (6S,7S)-N-(benzyloxy)-6-((4-phenylpiperazin-1-yl)carbonyl)-5-azaspiro(2,5)octane-7-carboxamide

Obtained in the previous phase of the substance - (6S,7S)-6-((4-phenylpiperazin-1-yl)carbonyl)-5-azaspiro(2,5)octane-7-carboxylic acid (330 mg, 0.96 mmol) was dissolved in DMF (2 m is). To the resulting solution were added hydrochloride O-benzylhydroxylamine (307 mg, 1.92 mmol) and then BOP (510 mg, 1.15 mmol). After stirring for 5 minutes at 0°C was added DIEA (437 mg, to 3.36 mmol). The mixture was stirred at room temperature for 3 hours and then extinguished with a saturated solution KH2PO4. The product was extracted with ethyl acetate. The extract was washed with water, saturated salt solution and dried over MgSO4. After filtration, the filtrate was concentrated to give the desired product in quantitative yield.

Stage 4.

Tetrahydro-2H-Piran-4-yl-(6S,7S)-7-(((benzyloxy)amino)carbonyl)-6-((4-phenylpiperazin-1-yl)carbonyl)-5-azaspiro(2,5)octane-5-carboxylate

(6S,7S)-N-(benzyloxy)-6-((4-phenylpiperazin-1-yl)carbonyl)-5-azaspiro(2,5)octane-7-carboxamide (18.6 mg, 0,041 mmol) was mixed with 4-nitrophenylhydrazine-4-ylcarbamate (13.3 mg, 0,050 mmol) and DIEA (11.0 mg, 0,083 mmol) in THF and stirred at room temperature for 24 hours. After concentration the crude substance was purified column flash chromatography to give the desired product (6.0 mg) in quantitative yield.

Stage 5.

Tetrahydro-2H-Piran-4-yl-(6S,7S)-7-((hydroxyamino)carbonyl)-6-((4-phenylpiperazin-1-yl)carbonyl)-5-azaspiro(2,5)octane-5-carboxylate

Tetrahydro-2H-Piran-4-yl-(6S,7S)-7-(((benzyloxy)amino)carbonyl)-6-((4-phenylpiperazin-1-yl)ka is bonyl)-5-azaspiro(2,5)octane-5-carboxylate (6.0 mg, 0,0104 mmol) was dissolved in methanol (0.3 ml) and was added to the obtained reaction mixture of 2 mg of 5% Pd/BaSO4. The mixture was stirred in hydrogen atmosphere (1 ATM) for 1.5 hours. After filtration the product was purified preparative RP-HPLC. The desired fractions were collected and freeze dried to obtain 3.8 mg solids. LC-MS: m/z 487,1 (M+H)+; 509,0 (M+Na)+.

Example 154

Ethyl-(6S,7S)-7-((hydroxyamino)carbonyl)-6-((4-phenylpiperazin-1-yl)carbonyl)-5-azaspiro(2,5)octane-5-carboxylate

Stage 1.

7-tert-butyl-5-ethyl-(6S,7S)-6-((4-phenylpiperazin-1-yl)carbonyl)-5-azaspiro(2,5)octane-5,7-in primary forms

A mixture of tert-butyl(6S,7S)-6-((4-phenylpiperazin-1-yl)carbonyl)-5-azaspiro(2,5)octane-7-carboxylate obtained in example 153 (40 mg, 0.10 mmol), ethylchloride (13 mg, 0.12 mmol) and DIEA (26 mg, 0.2 mmol) in acetonitrile (0,20 ml) was stirred at room temperature for 1 hour. After concentration the residue was purified column flash chromatography. Received 29 mg of 7-tert-butyl-5-ethyl-(6S,7S)-6-((4-phenylpiperazin-1-yl)carbonyl)-5-azaspiro(2,5)octane-5,7-in primary forms. Yield: 61%. MS: m/z 472,3 (M+H)+.

Stage 2.

(6S,7S)-5-(etoxycarbonyl))-6-((4-phenylpiperazin-1-yl)carbonyl)-5-azaspiro(2,5)octane-7-dicarboxylic acid

Obtained in the previous phase of matter - 7-tert-butyl-5-ethyl-(6S,7S)-6-((4-phenylpiperazin-1-yl)carbonyl)-5-azaspiro(2,5)octane-5,7-in primary forms was stirred in 2 ml of 50% solution of the TFA in DCM solution (about./about.) within 1.5 hours. After removal of solvent the residue was dried under high vacuum overnight to give the desired product in quantitative yield. LC-MS: m/z 416,2 (M+H)+; 853,4 (2M+Na)+.

Stage 3. Ethyl-(6S,7S)-7-((hydroxyamino)carbonyl))-6-((4-phenylpiperazin-1-yl)carbonyl)-5-azaspiro(2,5)octane-5-carboxylate

To a solution of (6S,7S)-5-(etoxycarbonyl)-6-((4-phenylpiperazin-1-yl)carbonyl)-5-azaspiro(2,5)octane-7-dicarboxylic acid (30 mg, 0,072 mmol), hydroxylamine hydrochloride (15 mg, 0,217 mmol) and BOP (34 mg, 0,076 mmol) in DMF (0,30 ml) was added DIEA (33 mg, 0,253 mmol). The mixture was stirred at room temperature for 2 hours. The final product was purified preparative HPLC to obtain solids (14,5 mg). Yield: 37%. MS: m/z 431,2 (M+H)+; 883,5 (2M+Na)+.

Example 155

Methyl-(6S,7S)-7-[(hydroxyamino)carbonyl]-6-[(4-phenylpiperazin-1-yl)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate

Stage 1.

tert-Butyl(6S,7S)-6-[(4-phenylpiperazin-1-yl)carbonyl]-5-azaspiro[2,5]octane-7-carboxylate

1-Phenylpiperazine (124 mg, from 0.76 mmol) was added to a mixture of (6S,7S)-7-(tert-butoxycarbonyl)-5-azaspiro[2,5]Octan-6-carboxylic acid (180 mg, 0.70 mmol) and BOP (320 mg, 0.75 mmol) in DMF (4 ml) at 0°C. the Mixture was stirred at 0°C for 10 minutes, then was added N-methylmorpholine (300 ml). The resulting mixture was stirred at room temperature overnight, diluted to 5% solution of NaHCO3and were extracted with ethyl acetate (3 the 10 ml). The combined organic layers were washed with saturated salt solution and dried over Na2SO4. The solution was filtered and concentrated to obtain 248,4 mg of tert-butyl(6S,7S)-6-[(4-phenylpiperazin-1-yl)carbonyl]-5-azaspiro[2,5]octane-7-carboxylate.

Stage 2.

7-tert-Butyl-5-methyl-(6S,7S)-6-[(4-phenylpiperazin-1-yl)carbonyl]-5-azaspiro[2,5]octane-5,7-in primary forms

Methylchloroform (55 ml, 700 ml) was added to a solution of tert-butyl(6S,7S)-6-[(4-phenylpiperazin-1-yl)carbonyl]-5-azaspiro[2,5]octane-7-carboxylate (248,4 mg of 0.62 mmol) and diisopropylethylamine (0.70 mmol, 0,125 ml) in 5 ml of acetonitrile. The mixture was stirred at room temperature for 3 hours. The solvent was removed to obtain a residue, which was dissolved in ethyl ether (15 ml), washed with water (3×2 ml) and dried over Na2SO4. The solution was filtered and concentrated to obtain 281 mg of 7-tert-butyl-5-methyl-(6S,7S)-6-[(4-phenylpiperazin-1-yl)carbonyl]-5-azaspiro[2,5]octane-5,7-in primary forms.

Stage 3

Methyl-(6S,7S)-7-[(hydroxyamino)carbonyl]-6-[(4-phenylpiperazin-1-yl)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate

7-tert-Butyl-5-methyl-(6S,7S)-6-[(4-phenylpiperazin-1-yl)carbonyl]-5-azaspiro[2,5]octane-5,7-in primary forms (281 mg) was treated with 5 ml TFA in 5 ml of dichloromethane and 1.0 ml of water. The mixture was stirred at room temperature overnight. The solvents were removed under reduced pressure. OST the current was subjected to co-evaporation with methanol (2×3 ml) and dried under high vacuum.

The above residue was dissolved in DMF (4.0 ml) and cooled in a bath of ice-water. To the resulting solution was added PyBOP (320 mg), hydroxylamine hydrochloride (125 mg) and N-methylmorpholin (320 ml). After 15 minutes the ice bath, the water was removed and stirred at room temperature for 2 hours. The mixture was brought to pH 2 using TFA. The resulting solution was purified by HPLC to obtain 126 mg of the desired product: methyl-(6S,7S)-7-[(hydroxyamino)carbonyl]-6-[(4-phenylpiperazin-1-yl)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate. MS(ESI): (M+H)+=417,1.

Example 156

(6S,7S)-N-hydroxy-6-[(4-pyrazin-2-reparation-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=361,2.

Example 157

(6S,7S)-N-hydroxy-6-[(4-quinoline-2-reparation-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=410,1.

Example 158

(6S,7S)-N-hydroxy-6-{[3-(5,6,7,8-tetrahydronaphthalen-2-yl)pyrrolidin-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=398,2.

Example 159

(6S,7S)-N-hydroxy-5-methyl-6-{[(3R)-3-phenylpyrrolidine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was received, ISOE is isua techniques similar to that described in example 1. MS(ESI):(M+H)+=358,1.

Example 160

Methyl-(6S,7S)-7-[(hydroxyamino)carbonyl]-6-{[(3R)-3-phenylpyrrolidine-1-yl]carbonyl}-5-azaspiro[2,5]octane-5-carboxylate

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=402,1.

Example 161

(6S,7S)-N-hydroxy-6-[(3-pyridin-3-iparralde-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=345,1.

Example 162

(6S,7S)-N-hydroxy-6-[(3-pyridin-2-iparralde-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=345,1.

Example 163

(6S,7S)-N-hydroxy-6-[(3-methyl-3-phenylpyrrolidine-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=358,2.

Example 164

(6S,7S)-N-hydroxy-6-[(3-phenylaziridine-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=330,3.

Example 165

(6S,7S)-N-hydroxy-5-methyl-6-[(3-methyl-3-phenylpyrrolidine-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to OPI the data in example 1. MS(ESI):(M+H)+=372,4.

Example 166

(6S,7S)-N-hydroxy-5-methyl-6-[(3-phenylaziridine-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=TO 344.4.

Example 168

(6S,7S)-6-(1,3,3a,4,5,9b-hexahydro-2H-benzo[e]isoindole-2-ylcarbonyl)-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=370,4.

Example 169

(6S,7S)-N-hydroxy-6-{[3-(2-naphthyl)pyrrolidin-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=394,4.

Example 170

(6S,7S)-N-hydroxy-6-{[4-(2-thienyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=362,1.

Example 171

(6S,7S)-N-hydroxy-6-{[3-(3-thienyl)pyrrolidin-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=350,1.

Example 172

(6S,7S)-N-hydroxy-6-{[3-(2-thienyl)pyrrolidin-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in the note is re 1. MS(ESI):(M+H)+=350,2.

Example 173

(6S,7S)-N-hydroxy-6-{[4-(2-thienyl)piperidine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI): (M+H)+=364,1.

Example 174

(6S,7S)-N-hydroxy-6-{[3-(2-were)pyrrolidin-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=358,2.

Example 175

(6S,7S)-N-hydroxy-6-{[3-(4-were)pyrrolidin-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=358,2.

Example 176

(6S,7S)-5-acetyl-N-hydroxy-6-[(4-phenyl-3,6-dihydropyridines-1(2H)-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 154. MS(ESI):(M-H)+=396,2.

Example 177

(6S,7S)-N-hydroxy-6-{[4-(3-thienyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=362,1.

Example 178

(6S,7S)-N-hydroxy-6-[(3-phenylpiperidine-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in point is the iMER 1. MS(ESI):(M+H)+=358,2.

Example 179

(6S,7S)-N-hydroxy-6-{[4-(3-thienyl)piperidine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=364,1.

Example 180

Methyl-(6S,7S)-6-{[4-(3, 5dimethylphenyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-7-[(hydroxyamino)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate

The specified connection was obtained using a technique similar to that described in example 154. MS(ESI):(M+H)+=442,2.

Example 181

(6S,7S)-6-{[4-(3, 5dimethylphenyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-(methylsulphonyl)-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 154. MS(ESI):(M+H)+=462,1.

Example 182

(6S,7S)-6-{[4-(3,5-differenl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=392,2.

Example 183

(6S,7S)-6-{[4-(3,5-dichlorophenyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=424,1.

Example 184

(6S,7S)-6-{[4-[3,5-bis(trifluoromethyl)phenyl]-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamid

The decree is the authorized connection is received, using a technique similar to that described in example 1. MS(ESI):(M+H)+=492,1.

Example 185

(6S,7S)-N-hydroxy-5-(methylsulphonyl)-6-[(4-phenylpiperazin-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 154. MS(ESI):(M+H)+=437,2.

Example 186

(6S,7S)-5-formyl-N-hydroxy-6-[(4-phenylpiperazin-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 154. MS(ESI):(M+H)+=387,2.

Example 187

(6S,7S)-6-{[4-(3,5-differenl)piperidine-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=394,2.

Example 188

(6S,7S)-6-{[4-(2,5-dimetilfenil)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=384,1.

Example 189

(6S,7S)-6-{[4-(2,4,5-trimetilfenil)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=398,2.

Example 190

(6S,7S)-6-[(4-biphenyl-3-reparacin-1-yl)carbonyl]-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamid

Specify the first connection is received, using a technique similar to that described in example 1. MS(ESI):(M+H)+=434,2.

Example 191

(6S,7S)-6-[(4-dibenzo[b,d]furan-4-reparacin-1-yl)carbonyl]-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=USD 448,2.

Example 192

(6S,7S)-6-{[4-(2,5-dimetilfenil)piperidine-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=386,2.

Example 193

(6S,7S)-6-{[4-(2,4,5-trimetilfenil)piperidine-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=400,2.

Example 194

Methyl-3-[1-({(6S,7S)-7-[(hydroxyamino)carbonyl]-5-azaspiro[2,5]Oct-6-yl}carbonyl)-1,2,3,6-tetrahydropyridine-4-yl]-4-methylbenzoate

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=428,2.

Example 195

(6S,7S)-6-[(5-phenyl-2,3,4,7-tetrahydro-1H-azepin-1-yl)carbonyl]-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=370,2.

Example 196

(6S,7S)-6-{[4-[3-(dimethylamino)phenyl]-3,6-hydropyridine-1(2H)-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=399,2.

Example 197

Methyl-3-[1-({(6S,7S)-7-[(hydroxyamino)carbonyl]-5-azaspiro[2,5]Oct-6-yl}carbonyl)piperidine-4-yl]-4-methylbenzoate

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=430,2.

Example 198

(6S,7S)-6-[(5-Penelitian-1-yl)carbonyl]-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=372,2.

Example 199

(6S,7S)-6-({4-[3-(dimethylamino)phenyl]piperidine-1-yl}carbonyl)-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=401,2.

Example 200

(6S,7S)-6-{[4-(2-were)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=370,2.

Example 201

(6S,7S)-6-[(3-phenyl-2,5-dihydro-1H-pyrrol-1-yl)carbonyl]-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=342,1.

Example 202

(6S,7S)-6-{[4-(4-cyano-2-were)piperidine-1-yl]carbonyl}-N-guide the hydroxy-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=397,2.

Example 203

(6S,7S)-6-[(3,3-dimethyl-4-phenyl-3,6-dihydropyridines-1(2H)-yl)carbonyl]-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=384,1.

Example 204

(6S,7S)-6-[(3,3-dimethyl-4-phenylpiperidine-1-yl)carbonyl]-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=386,2.

Example 205

(6S,7S)-N-hydroxy-5-(methylsulphonyl)-6-[(3-phenyl-2,5-dihydro-1H-pyrrol-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 154. MS(ESI):(M+H)+=420,2.

Example 206

Methyl-(6S,7S)-7-[(hydroxyamino)carbonyl]-6-[(3-phenyl-2,5-dihydro-1H-pyrrol-1-yl)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate

The specified connection was obtained using a technique similar to that described in example 154. MS(ESI):(M+H)+=400,2.

Example 207

(6S,7S)-N-hydroxy-5-methyl-6-[(3-phenyl-2,5-dihydro-1H-pyrrol-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=356,2.

Example 208

(6S,7S)-6-{[4-(cyano-3-were)piperidine-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=397,2.

Example 209

(6S,7S)-6-{[4-[3-(benzyloxy)phenyl]-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamid

To a mixture of tert-butyl 5,6-dihydro-4-(3-hydroxyphenyl)pyridine-1(2H)-carboxylate (crude, 100 mg) and potassium carbonate (300 mg) in DMF was added benzylbromide (60 μl) at room temperature. The resulting mixture was stirred at 80oC for 16 hours. The mixture was cooled, diluted with ethyl acetate, washed with water, saturated salt solution, dried and concentrated. The product (60 mg) was purified by Combiflash chromatography using hexane/ethyl acetate (Max. EtOAc 10%) to give tert-butyl 4-(3-(benzyloxy)phenyl)-5,6-dihydropyridines-1(2H)-carboxylate, which was then converted into the target compound, using a technique similar to that described in example 1. MS(ESI):(M+H)+=462,2.

Example 210

(6S,7S)-6-{[4-[3-ethylphenyl]-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=384,1.

Example 211

(6S,7S)-6-{[4-[3-(ethyloxy)phenyl]-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that of sunnym in example 1, MS(ESI):(M+H)+=400,1.

Example 212

(6S,7S)-6-{[4-(3-ethylphenyl)piperidine-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=386,1.

Example 213

(6S,7S)-6-{[4-(3-ethoxyphenyl)piperidine-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=402,1.

Example 214

(6S,7S)-6-{[4-(3-cyclopropylmethyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=396,2.

Example 215

(6S,7S)-6-{[4-(4-methoxy-3, 5dimethylphenyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=level of 414.2.

Example 216

(6S,7S)-6-{[4-(3,5-dimethyl-4-methoxyphenyl)piperidine-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=416,2.

Example 217

(6S,7S)-6-{[4-(4-cyano-3-ethylphenyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamid

Stage 1 4-Bromo-2-ethylbenzonitrile

To a solution of 4-bromo-2-methylbenzonitrile (0.4 g, 2.0 mmol) in anhydrous THF (10 ml) was slowly added LDA (1.3 ml, 1.8m in THF) at -78oC and stirred at this temperature for another 30 minutes. To the resulting dark pink solution at -78oC was added methyliodide (0.15 ml, 2.4 mmol) and the mixture was heated to room temperature within 3 hours. The reaction is extinguished with water, was extracted with simple ether, then washed with saturated salt solution, dried and concentrated. 4-Bromo-2-ethylbenzonitrile (0.34 g) was purified by Combiflash chromatography.

Stage 2.

2-ethyl-4-(1,2,3,6-tetrahydropyridine-4-yl)benzonitrile

4-Bromo-2-ethylbenzonitrile was converted to 2-ethyl-4-(1,2,3,6-tetrahydropyridine-4-yl)benzonitrile using a standard method combination Suzuki.

Stage 3.

(6S,7S)-6-{[4-(4-cyano-3-ethylphenyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamid

Using a technique similar to that described in example 1, 2-ethyl-4-(1,2,3,6-tetrahydropyridine-4-yl)benzonitrile were converted into the target compound (6S,7S)-6-{[4-(4-cyano-3-ethylphenyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide, MS(ESI):(M+H)+=409,2.

Example 218

(6S,7S)-6-{[4-(4-cyano-3-ethylphenyl)piperidine-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in the ore 1, MS(ESI):(M+H)+=411,2.

Example 219

(6S,7S)-6-{[4-(4-cyano-3, 5dimethylphenyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=409,2.

Example 220

(6S,7S)-6-{[4-(4-cyano-3, 5dimethylphenyl)piperidine-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=411,4.

Example 221

(6S,7S)-6-{[4-(1,3-benzothiazol-6-yl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamid

A solution of sodium nitrite (0,147 g, 2.1 mmol) in water (1.0 ml) was slowly added to a suspension of 6-aminobenzothiazole (0,30 g, 2.0 mmol) in HBr (48% in water, 3 ml) at 0oC and then the mixture was stirred at room temperature for 30 minutes. The resulting solution was then slowly added to a solution of copper bromide (I) (0,435 g, 3.0 mmol) in HCl (conc., 5 ml) at 0oC. After addition the mixture was stirred at 60oC for 1.5 hours. The reaction mixture was cooled, podslushivaet excessive amounts of ammonia and was extracted with diethyl ether. The combined extract was washed with water, saturated salt solution, dried and concentrated. 6-Bromobenzimidazole (0.26 g) was obtained by Combiflash chromatography and then conversions is provided in the target compound, using a technique similar to that described in example 1. MS(ESI):(M+H)+=413,1.

Example 222

(6S,7S)-N-hydroxy-6-{[4-(1-methyl-1H-benzimidazole-6-yl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamid

Stage 1. Tetrafluoroborate 5-bromo-2-methylphenidate

To a mixture of 2-methyl-5-bromoaniline (1.50 g) in terraforming acid (6.0 ml) and water (4.0 ml) at 0-5oC was slowly added sodium nitrite (0.56 g) in water (2.0 ml). After the addition the reaction mixture was stirred at room temperature for 30 minutes. The mixture was cooled to 0oC, was filtered, washed with cold water, cold methanol and ether. The mixture was then dried to obtain a product of tetrafluoroborate 5-bromo-2-methylphenidate (1,90 g).

Stage 2. 6-brominated

Tetrafluoroborate 5-bromo-2-methylphenidate (1.50 g) portions was added to a mixture of potassium acetate (1.0 g) and 18-crown-6 (70 mg) in chloroform (50 ml) at room temperature and then the reaction mixture was stirred for 2 hours. The resulting mixture was filtered and washed with chloroform. The filtrate was concentrated and the residue was dissolved in diethyl ether, then washed with water, saturated salt solution, dried and the solvent was removed to obtain the product 6-brominate (0.9 g). The product was used in the next stage without additional purification.

Stage 3. 6-bromo-1-methylindol

6-Brominated 400 mg) was dissolved in methanol (10 ml). To the resulting solution was added potassium hydroxide (450 mg), then methyliodide (0,50 ml) and the mixture is boiled under reflux for 2.5 hours. The reaction mixture was cooled, diluted with diethyl ether, washed with water, saturated salt solution, dried and concentrated. The product 6-bromo-1-methylindole (160 mg) was separated from its isomer by Combiflash chromatography.

Stage 4.

(6S,7S)-N-hydroxy-6-{[4-(1-methyl-1H-benzimidazole-6-yl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamid

6-Bromo-1-methylindol then converted to the target compound using a technique similar to that described in example 1. MS(ESI):(M+H)+=410,2.

Example 223

(6S,7S)-N-hydroxy-6-{[4-(1-methyl-1H-benzimidazole-6-yl)piperidine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=412,3.

Example 224

(6S,7S)-6-{[4-(4-cyano-3-isopropylphenyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamid

Stage 1. 4-bromo-2-isopropylphenol

To a stirred solution of 2-isopropylphenol (2.0 g) in acetic acid (20 ml) was added Hydrobromic acid (48%, 10 ml) and then was added dropwise DMSO (10 ml). The mixture was stirred for another 20 minutes, diluted with water and was extracted with diethyl ether. The combined extract was washed asystem solution of NaHCO 3, water, saturated salt solution, dried and concentrated to obtain the product 4-bromo-2-isopropylphenol (2.2 g, purity by HPLC 95%).

Stage 2. tert-butyl 4-(4-hydroxy-3-isopropylphenyl)-3,6-dihydropyridines-1(2H)-carboxylate

To a solution of tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydropyridines-1(2H)-carboxylate (0.36 g), 4-bromo-2-isopropylphenol (0.3 g) in DMF (8.0 ml) under nitrogen atmosphere was added potassium carbonate (0.5 g) and PdCl2dppf (60 mg). The mixture was stirred at 80oC for 16 hours. The reaction mixture was cooled, diluted with ethyl acetate, washed with water, saturated salt solution, dried and concentrated. The product tert-butyl 4-(4-hydroxy-3-isopropylphenyl)-3,6-dihydropyridines-1(2H)-carboxylate (0.12 g) was obtained using a Combiflash chromatography.

Stage 3.

tert-butyl 4-(3-isopropyl-4-{[(trifluoromethyl)sulfonyl]oxy}phenyl)-3,6-dihydropyridines-1(2H)-carboxylate

To a solution of tert-butyl 4-(4-hydroxy-3-isopropylphenyl)-3,6-dihydropyridines-1(2H)-carboxylate (0.10 g) in toluene (3.0 ml) at 0oC was added triethylamine (85 ml) and then triperoxonane anhydride (60 ml). The reaction mixture was heated to room temperature and was stirred for 2 hours. The mixture was immersed in a saturated solution of NaHCO3and was extracted with diethyl ether. The combined extract was washed with water, saturated salt solution, dried and conc the Vali with the product tert-butyl 4-(3-isopropyl-4-{[(trifluoromethyl)sulfonyl]oxy}phenyl)-3,6-dihydropyridines-1(2H)-carboxylate (0.14 g, purity according to HPLC 95%).

Stage 4.

Hydrochloride of 2-isopropyl-4-(1,2,3,6-tetrahydropyridine-4-yl)benzonitrile

A mixture of tert-butyl 4-(3-isopropyl-4-{[(trifluoromethyl)sulfonyl]oxy}phenyl)-3,6-dihydropyridines-1(2H)-carboxylate (0.14 g), cyanide zinc (65 mg) and tetrakis(triphenylphosphine)palladium(0) (25.0 mg) in DMF (3.0 ml) was stirred at 100oC in nitrogen atmosphere for 4 hours. The reaction mixture was cooled, diluted with water, was extracted with diethyl ether. The combined extract was washed with water, saturated salt solution, dried and concentrated. Tert-butyl 4-(4-cyano-3-isopropylphenyl)-3,6-dihydropyridines-1(2H)-carboxylate (85 mg) were isolated by Combiflash chromatography. The isolated product was dissolved in minimum amount of ethyl acetate was added 4n. a solution of HCl in dioxane (3.0 ml) and was stirred for 1 hour. Added diethyl ether (10 ml), the solid was filtered and washed with simple ether to obtain the product of the hydrochloride of 2-isopropyl-4-(1,2,3,6-tetrahydropyridine-4-yl)benzonitrile (65 mg).

Stage 5.

(6S,7S)-6-{[4-(4-cyano-3-isopropylphenyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamid

Hydrochloride of 2-isopropyl-4-(1,2,3,6-tetrahydropyridine-4-yl)benzonitrile then converted to the target compound using a technique similar to that described in example 1. MS(ESI):(M+H)+=423,2.

Example 225

6S,7S)-6-{[4-(4-cyano-3-isopropylphenyl)piperidine-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI): (M+H)+=425,2.

Example 236

(6S,7S)-6-{[4-(4-cyano-3-ethylphenyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-methyl-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=423,2.

Example 237

(6S,7S)-6-{[4-(4-cyano-3, 5dimethylphenyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-methyl-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=423,2.

Example 238

(6S,7S)-N-hydroxy-6-{[4-(1-ethyl-1H-benzimidazole-6-yl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=424,3.

Example 239

(6S,7S)-N-hydroxy-6-{[4-(1-methyl-1H-indazol-5-yl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=410,2.

Example 240

(6S,7S)-N-hydroxy-6-{[4-(1-ethyl-1H-benzimidazole-6-yl)p is peridin-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=to 426.2.

Example 241

(6S,7S)-N-hydroxy-6-{[4-(1-methyl-1H-indazol-5-yl)piperidine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=412,2.

Example 242

(6S,7S)-N-hydroxy-6-{[4-(1-ethyl-1H-indazol-5-yl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=424,2.

Example 243

Tetrahydro-2H-Piran-4-yl-(6S,7S)-6-{[4-(1-ethyl-1H-benzimidazole-6-yl)piperidine-1-yl]carbonyl}-7-[(hydroxyamino)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate

The specified connection was obtained using a technique similar to that described in example 154, MS(ESI):(M+H)+=554,3.

Example 244

Methyl-(6S,7S)-6-{[4-(1-ethyl-1H-benzimidazole-6-yl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-7-[(hydroxyamino)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate

The specified connection was obtained using a technique similar to that described in example 154, MS(ESI):(M+H)+=RUB 482.2.

Example 245

(6S,7S)-6-{[4-(1-ethyl-1H-benzimidazole-6-yl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-(methylsulphonyl)-5-azaspiro[2,5]about the tan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 154, MS(ESI):(M+H)+=502,2.

Example 246

Methyl-(6S,7S)-6-{[4-(1-ethyl-1H-benzimidazole-6-yl)piperidine-1-yl]carbonyl}-7-[(hydroxyamino)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate

The specified connection was obtained using a technique similar to that described in example 154, MS(ESI):(M+H)+=484,2.

Example 247

(6S,7S)-6-{[4-(1-ethyl-1H-benzimidazole-6-yl)piperidine-1-yl]carbonyl}-N-hydroxy-5-(methylsulphonyl)-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 154, MS(ESI):(M+H)+=504,2.

Example 248

(6S,7S)-6-{[4-(4-cyano-2-were)piperidine-1-yl]carbonyl}-N-hydroxy-5-(methylsulphonyl)-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 154, MS(ESI):(M+H)+=476,2.

Example 249

Methyl-(6S,7S)-6-{[4-(4-cyano-2-were)piperazine-1-yl]carbonyl}-7-[(hydroxyamino)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate

The specified connection was obtained using a technique similar to that described in example 154, MS(ESI):(M+H)+=456,2.

Example 250

(6S,7S)-6-{[4-(1-ethyl-1H-benzimidazole-6-yl)piperazine-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar description is authorized in example 1, MS(ESI):(M+H)+=427,5.

Example 251

Methyl-(6S,7S)-6-{[4-(1-ethyl-1H-benzimidazole-6-yl)piperazine-1-yl]carbonyl}-7-[(hydroxyamino)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate

The specified connection was obtained using a technique similar to that described in example 154, MS(ESI):(M+H)+=485,3.

Example 252

(6S,7S)-6-{[4-(1-ethyl-1H-benzimidazole-6-yl)piperazine-1-yl]carbonyl}-N-hydroxy-5-(methylsulphonyl)-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 154, MS(ESI):(M+H)+=505,2.

Example 253

Tetrahydro-2H-Piran-4-yl-(6S,7S)-6-{[4-(4-cyano-2-were)piperazine-1-yl]carbonyl}-7-[(hydroxyamino)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate

The specified connection was obtained using a technique similar to that described in example 154, MS(ESI):(M+H)+=526,3.

Example 254

Tetrahydro-2H-Piran-4-yl-(6S,7S)-6-{[4-(1-ethyl-1H-benzimidazole-6-yl)piperazine-1-yl]carbonyl}-7-[(hydroxyamino)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate

The specified connection was obtained using a technique similar to that described in example 154, MS(ESI):(M+H)+=455,3.

Example 255

(6S,7S)-N-hydroxy-6-[(3-methyl-4-phenylpiperidine-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 86. MS(ESI):(M+H)+=372,1.

Example 256

(6S,7S)-6-{[5(aminocarbonyl)-4-phenyl-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 31. MS(ESI):(M+H)+=386,1.

Example 257

(6S,7S)-6-{[4-(4-cyanophenyl)-5-methyl-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 31. MS(ESI):(M+H)+=395,2.

Example 258

(6S,7S)-6-{[4-(4-cyanophenyl)-3-methylpiperidin-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 86. MS(ESI): (M+H)+=397,1.

Example 259

(6S,7S)-N-hydroxy-6-{[5-methyl-4-(4-nitrophenyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 31. MS(ESI):(M+H)+=415,2.

Example 260

(6S,7S)-N-hydroxy-6-{[5-methyl-4-(3-nitrophenyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 31. MS(ESI):(M+H)+=415,1.

Example 262

(6S,7S)-6-[(4-dibenzo[b,d]furan-2-yl-3,6-dihydropyridines-1(2H)-yl)carbonyl]-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 31. MS(ESI):(M+H)+=446,1.

Example 263

(6S,7S)-6-[(4-dibenzo[b,d]furan-2-reparacin-1-yl)shall arbonyl]-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 86. MS(ESI):(M+H)+=448,1.

Example 264

(6S,7S)-6-{[4-(3,3-dimethyl-2,3-dihydro-1-benzofuran-5-yl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 31. MS(ESI):(M+H)+=426,1.

Example 265

(6S,7S)-6-{[4-(3,3-dimethyl-2,3-dihydro-1-benzofuran-5-yl)piperidine-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 86. MS(ESI):(M+H)+=428,1.

Example 266

Isopropyl-(6S,7S)-7-[(hydroxyamino)carbonyl]-6-[(3-phenyl-2,5-dihydro-1H-pyrrol-1-yl)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate

The specified connection was obtained using a technique similar to that described in example 56. MS(ESI):(M+H)+=428,1.

Example 267

(3S)-tetrahydrofuran-3-yl-(6S,7S)-7-[(hydroxyamino)carbonyl]-6-[(3-phenyl-2,5-dihydro-1H-pyrrol-1-yl)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate

The specified connection was obtained using a technique similar to that described in example 56. MS(ESI):(M+H)+=456,1.

Example 268

Cyclohexyl-(6S,7S)-7-[(hydroxyamino)carbonyl]-6-[(3-phenyl-2,5-dihydro-1H-pyrrol-1-yl)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate

The specified connection was obtained using a technique similar to that described in the ore 56. MS(ESI):(M+H)+=468,2.

Example 269

Tetrahydro-2H-Piran-4-yl-(6S,7S)-7-[(hydroxyamino)carbonyl]-6-[(3-phenyl-2,5-dihydro-1H-pyrrol-1-yl)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate

The specified connection was obtained using a technique similar to that described in example 56. MS(ESI):(M+H)+=470,2.

Example 270

(5S,6S)-N-hydroxy-6-((4-phenylpiperazin-1-yl)carbonyl)Spiro(2,5)octane-5-carboxamid

Stage 1. Obtain (1S,2S,5S)-2-(tert-butoxycarbonyl)-5-oxocyclohexanecarboxylic acid

Tert-butyl(1S,2S,5S)-7-oxo-6-oxabicyclo(3,2,1)octane-2-carboxylate was dissolved in THF-H2O. was Added at 0oWith LiOH (3 EQ.) and the resulting mixture was stirred at 0oC for 2 hours. TLC showed that starting material had been consumed. The mixture was then acidified to pH~2. The product was extracted with EtOAc (×3). The combined extracts were washed with saturated salt solution (×1), dried over MgSO4. After filtration, the filtrate was concentrated to obtain (1S,2S,5S)-2-(tert-butoxycarbonyl)-5-oxocyclohexanecarboxylic acid (quantitative yield).

Stage 2. Getting 2-benzyl-1-tert-butyl-(1S,2S,4S)-4-hydroxycyclohexane-1,2-in primary forms

(1S,2S,5S)-2-(tert-butoxycarbonyl)-5-oxocyclohexanecarboxylic acid (1.07 g, of 4.38 mmol) was dissolved in benzene (20 ml). To the solution at room temperature was added benzylbromide and then DBU. The mixture was stirred at room temperature is f for 3 hours. The resulting mixture was extinguished 1H. HCl solution and was extracted with EtOAc (×2). The combined extracts were washed with 10% citric acid solution (×1); saturated salt solution (×1) and dried over MgSO4. After filtration, the filtrate was concentrated to obtain 2-Benzyl-1-tert-butyl(1S,2S,4S)-4-hydroxycyclohexane-1,2-in primary forms.

Stage 3. Getting 2-benzyl-1-tert-butyl(1S,2S)-4-oxocyclohexa-1,2-in primary forms

(1S,2S,4S)-1-tert-Butyl-2-benzyl-4-hydroxycyclohexane-1,2, in primary forms (1.47 g, 4.40 mmol) was dissolved in DCM (30 ml). To the solution at room temperature with stirring was added a reagent Dess-Martin. After 2 hours, TLC showed that starting material had been consumed. The mixture was suppressed with saturated solution of Na2S2O3and then was extracted with EtOAc (×2). The combined extracts were washed with water (×1), saturated salt solution (×1) and dried over MgSO4. After filtration, the filtrate was concentrated. The obtained residue was purified by Combiflash chromatography and suirable EtOAc/hexane to obtain 2-benzyl-1-tert-butyl(1S,2S)-4-oxocyclohexa-1,2-in primary forms.

Stage 5. Getting 2-benzyl-1-tert-butyl-(1S,2S)-4-methyltriclosan-1,2-in primary forms

The solution methyltriphenylphosphonium (1.9 grams, 5,32 mmol) and bis(trimethylsilyl)amide, sodium (1.0m in THF, 5,32 ml, 5,32 mmol) in a mixture of toluene (15 ml)/THF (5 ml) was combined with a solution of (1S,2S)-1-tert-butyl-2-gasoline is-4-oxocyclohexa-1,2-in primary forms (1.0 g, 4.09 to mmol) in toluene (15 ml) at -10oC. the resulting mixture was stirred at room temperature for 2 hours at -10oC and at room temperature for 2 hours. TLC showed that starting material had been consumed. The mixture was diluted with EtOAc and the resulting solution washed with water (×1), saturated salt solution (×2) and dried over MgSO4. After filtration, the filtrate was concentrated. The crude product was purified by Combiflash chromatography to obtain (1S,2S)-1-tert-butyl-2-benzyl-4-methyltriclosan-1,2-in primary forms (0.65 g; 1.97 mmol).

Stage 6. Getting 5-benzyl-6-tert-butyl(5S,6S)-Spiro(2,5)octane-5,6-in primary forms

To a solution of KOH (1.9 g) in water (3 ml), di(ethylene glycol)ethyl ether (9 ml) and ethyl ether (10 ml) in A flask was added in three portions to 1.0 g dieseld. After adding the first portion of the flask was placed on a preheated (60oC) oil bath for Stripping the formed CH2N2which led to another flask (B), pre-cooled to about -15oC and containing (1S,2S)-1-tert-butyl-2-benzyl-4-methyltriclosan-1,2, in primary forms (200 mg) and Pd(OAc)2(80 mg) in a simple ether (10 ml). After 5 minutes, the oil bath for A bulb was removed. Then add the second portion of dieseld and the above procedure was repeated twice. Upon completion of the distillation, CH2N2in flask B by means of ether on ladusaw bath to flask B was removed. The reaction mixture was stirred at room temperature for 2 hours, then filtered through silica gel, washed with ethyl acetate and methylene chloride. The filtrate was concentrated. The remainder consisted of the desired product 5-benzyl-6-tert-butyl(5S,6S)-Spiro(2,5)octane-5,6-in primary forms, which was confirmed by the method of1H NMR. The product is directly used in the reaction in the next stage without additional purification.

Stage 7.

Receipt of (5S,6S)-5-((benzyloxy)carbonyl)Spiro(2,5)octane-6-carboxylic acid

The product obtained in the previous phase 6, was stirred in DCM/TFA (1:1) overnight and then concentrated to obtain (5S,6S)-5-((benzyloxy)carbonyl)Spiro(2,5)octane-6-carboxylic acid.

Step 8.

Obtain benzyl(5S,6S)-6-((4-phenylpiperazin-1-yl)carbonyl)Spiro(2,5)octane-5-carboxylate

(5S,6S)-5-((Benzyloxy)carbonyl)Spiro(2,5)octane-6-carboxylic acid from step 7 (47 mg, 0.16 mmol) was dissolved in DMF (0.7 ml). To the solution was added 1-phenylpiperazine (29 mg, 0.18 mmol) and then BOP (76 mg, 0,17 mmol). After stirring the mixture at room temperature for 10 minutes was added DIEA (53 mg, 0.41 mmol). The mixture was then stirred at room temperature over night, extinguished a saturated solution of NaHCO3and was extracted with EtOAc. The extract was washed with saturated solution of NaHCO3, a saturated solution with the and, dried over MgSO4. After filtration, the filtrate was concentrated. The obtained residue was purified column chromatography to obtain benzyl(5S,6S)-6-((4-phenylpiperazin-1-yl)carbonyl)Spiro(2,5)octane-5-carboxylate.

Stage 9.

Receipt of (5S,6S)-6-((4-phenylpiperazin-1-yl)carbonyl)Spiro(2,5)octane-5-carboxylic acid

The product obtained in the previous stage 8, was dissolved in methanol. To the solution was added 5% Pd-BaSO4. The mixture was stirred in hydrogen atmosphere at room temperature for 2 hours. After removal of the solids, the solution was concentrated to dryness (yield: 30%) to give (5S,6S)-6-((4-phenylpiperazin-1-yl)carbonyl)Spiro(2,5)octane-5-carboxylic acid.

Stage 10.

Receipt of (5S,6S)-N-hydroxy-6-((4-phenylpiperazin-1-yl)carbonyl)Spiro(2,5)octane-5-carboxamide

The product from step 9 (36 mg, 0,105 mmol) and hydroxylamine hydrochloride (22 mg, 0,315 mmol) was dissolved in DMF (0,70 ml). To the solution under stirring at room temperature for 10 minutes was added BOP (49 mg, 0.11 mmol). Added DIEA (61 mg, 0.47 mmol). The mixture was stirred at room temperature for 2 hours. The product was purified preparative HPLC to obtain 22 mg of (5S,6S)-N-hydroxy-6-((4-phenylpiperazin-1-yl)carbonyl)Spiro(2,5)octane-5-carboxamide. Yield: 44%. MS: M/Z 358,2 (M+H)+; 380,2 (M+Na)+; 737,2 (2M+Na)+.

Example 271

(6S)-N-hydroxy-6-{[(3R)-3-phenylpyrrolidine-1-yl]carbonyl}Speer is[2,5]Octan-5-carboxamid

The specified connection was obtained using a technique similar to that described in example 270. MS:M/Z 343,3 (M+H)+; 365,2 (M+Na)+; 707,3 (2M+Na)+.

Example 272

(5S,6S)-N-hydroxy-6-{[4-(2-methyl-4-nitrophenyl)piperazine-1-yl]carbonyl}Spiro[2,5]octane-5-carboxamid

The specified connection was obtained using a technique similar to that described in example 270. MS:M/Z 417,2 (M+H)+.

Example 273

(5S,6S)-N-hydroxy-6-[(4-phenyl-3,6-dihydropyridines-1(2H)-yl)carbonyl]Spiro[2,5]octane-5-carboxamid

The specified connection was obtained using a technique similar to that described in example 270. MS: M/Z 355,2 (M+H)+; 377,2 (M+Na)+; 731,4 (2M+Na)+.

Example 274

(3S)-tetrahydrofuran-3-yl-(6S,7S)-7-[(hydroxyamino)carbonyl]-6-[(4-phenylpiperazin-1-yl)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate

The specified connection was obtained using a technique similar to that described in example 154. MS: m/z 473,2 (M+H)+; 495,0 (M+Na)+.

Example 275

(3R)-tetrahydrofuran-3-yl-(6S,7S)-7-[(hydroxyamino)carbonyl]-6-[(4-phenylpiperazin-1-yl)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate

The specified connection was obtained using a technique similar to that described in example 154. MS: m/z 473,2 (M+H)+; 495,2 (M+Na)+.

Example 276

2-Methoxyethyl-(6S,7S)-7-((hydroxyamino)carbonyl)-6-((4-phenylpiperazin-1-yl)carbonyl)-5-azaspiro(2,5)octane-5-carboxylate

The specified connection was obtained using a technique similar to that described in example 154. MS: m/z 461,1 (M+H)+; 483 (M+Na)+.

Example 277

(6S,7S)-N-hydroxy-6-[(4-phenylpiperazin-1-yl)carbonyl]-5-(phenylsulfonyl)-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 154. MS: m/z 499,1 (M+H)+.

Example 278

Propyl-(6S,7S)-7-[(hydroxyamino)carbonyl)]-6-[(4-phenylpiperazin-1-yl)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate

The specified connection was obtained using a technique similar to that described in example 154. MS: m/z 445,2 (M+H)+.

Example 279

Isopropyl-(6S,7S)-7-[(hydroxyamino)carbonyl]-6-[(4-phenylpiperazin-1-yl)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate

The specified connection was obtained using a technique similar to that described in example 154. MS: m/z 445,2 (M+H)+; 467,2 (M+Na)+.

Example 280

Methyl-(6S,7S)-6-{[4-(3,5-differenl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-7-[(hydroxyamino)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI):(M+H)+=450,2.

Example 281

Methyl-(6S,7S)-6-{[4-(3,5-differenl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-7-[(hydroxyamino)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate

The specified connection was obtained using a technique similar to that described in example 154. MS(ESI):(M+H)+=470,2.

Example 282

(6S,7S)-N-hydroxy-6-{[4-(4-isopropylphenyl)piperazine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamid

the data connection is received, using a technique similar to that described in example 1. MS(ESI):(M+H)+=400,2.

Example 283

(6S,7S)-6-{[4-(3,5-differenl)piperidine-1-yl]carbonyl}-N-hydroxy-5-(methylsulphonyl)-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 154. MS(ESI):(M+H)+=472,1.

Example 284

(6S,7S)-6-{[4-(4,5-dimethyl-1,3-thiazol-2-yl)piperidine-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamid

The specified connection was obtained using a technique similar to that described in example 1. MS(ESI): (M+H)+=393,1.

Connection examples are listed below in Table 1.

Table 1
Ave. 1-48, 54-78, 80-136, 143-225, 236-269, 271-284Ave. 50, 53, 270-273Ave. 79Ave. 49,
51, 52

td align="justify"> H
Approx.CoreNR"R"'R'MS: M+H
1A4-(3-were)piperazine-1-IlMe 387,1
2A4-phenylpiperazin-1-ylMe373,2
3A4-[3-(trifluoromethyl)phenyl]piperazine-1-IlMe441
4A4-(2-were)piperazine-1-IlMe387,1
5A4-(4-chlorophenyl)piperazine-1-IlMe407,1
6A4-(2-methyl-4-nitrophenyl)piperazine-1-IlMe432
7A4-phenylpiperidine-1-ylMe372,2
8A4-hydroxy-4-phenylpiperidine-1-ylMe388
9A/td> 4-phenyl-3,6-dihydropyridines-1(2H)-ylMe370
11A4-quinoline-2-reparation-1-ylMe424,3
12A4-(2,3-dichlorophenyl)piperazine-1-IlMe441
13A4-quinoline-4-reparation-1-ylMe424,3
14A4-(2-methylinosine-4-yl)piperazine-1-IlMe438,4
15A4-(2-phenylethyl)piperazine-1-IlMe401,3
16A4-pyridin-4-reparacin-1-ylMe373,3
17A4-(4-nitrophenyl)piperazine-1-Il Me418,3
18A4-(2-methoxyphenyl)piperazine-1-IlMe403
19A4-phenoxypyridine-1-ylMe388,3
20A3,4-dihydroisoquinoline-2(1H)-ylMe344,3
21A4,7-dihydrothieno[2,3-c]pyridine-6(5H)-ylMe350,2
22A3-benzylpyrrolidine-1-ylMe372,3
23A4-pyridine-2-reparation-1-ylMe374,2
24A4-(2-pyridin-4-retil)piperidine-1-ylMe401,3
25A4-[5-(trifluoromethyl)pyridin-2-yl]piperazine-1-IlMe442,3
26A4-[3-(trifluoromethyl)pyridin-2-yl]piperazine-1-IlMe442,3
27A1,4'-bipiperidine-1'-ylMe379,3
28A4-(pyridine-2-ylmethyl)piperazine-1-IlMe388,3
29A4-(pyridine-4-ylmethyl)piperazine-1-IlMe388,3
30A4-(pyridine-3-ylmethyl)piperazine-1-IlMe388,3
31A4-(2-were)-3,6-dihydropyridines-1(2H)-ylMe384,1
32 A4-(3-were)piperazine-1-IlH373,1
33A1,3,4,9-tetrahydro-2H-β-carbolin-2-ylMe383
34A9-methyl-1,3,4,9-tetrahydro-2H-β-carbolin-2-ylMe396,9
35A4-(2-forfinal)-3,6-dihydropyridines-1(2H)-ylMe388
36A4-(2-chlorophenyl)-3,6-dihydropyridines-1(2H)-ylMe404
37A4-(4-nitrophenyl)-3,6-dihydropyridines-1(2H)-ylMe415,1
38A4-phenyl-3,6-dihydropyridines-1(2H)-ylH356
39A 4-(2-methyl-4-nitrophenyl)piperazine-1-IlH418
40AN-methyl-N'-(3-phenylpropyl)aminoMe360,1
41AisobutylaminoMe284
42A4-(2-nitrophenyl)piperazine-1-IlMe418
43AN-methyl-N'-(isobutyl)aminoMe298
44A(2-phenoxyethyl)aminoMe348
45A2-(4-methoxyphenyl)ethylaminoMe362
46A4 phenylethylamineMe360
47A3-(2-oxopyrrolidin-1-yl)propylaminoMe353
48A3,4,10,10a-tetrahydropyrazino[1,2-a]indol-2(1H)-ylH385
49D4-(2-methyl-4-nitrophenyl)piperazine-1-Il417,2
50B4-(3-were)piperazine-1-Il372,2
51D4-phenyl-3,6-dihydropyridines-1(2H)-yl355
52D4-(3-were)piperazine-1-Il372
53B4-phenyl-3,6-dihydropyridines-1(2H)-yl355
54A 3,4,10,10a-tetrahydropyrazino[1,2-a]indol-2(1H)-ylH371,2
55A1,2,4,4a,5,6-hexahydro-3H-pyrazino[1,2a]quinoline-3-ylMeRUB 399.4
56A4-phenyl-3,6-dihydropyridines-1(2H)-ylMeloxicam-
boil
414
57A4-phenyl-3,6-dihydropyridines-1(2H)-ylBenzyloxy-
carbonyl
490
58A4-phenyl-3,6-dihydropyridines-1(2H)-ylMatilal-
were radioactive
434
59A3-(3-methoxyphenyl)piperidine-1-ylMe402,4
60A3-(2-phenylethyl)pyrrolidin-1-ylMe386
61 A4-(3-methoxyphenyl)piperidine-1-ylMe402,4
62A4-[3-(aminocarbonyl)phenyl]-3,6-dihydropyridines-1(2H)-ylH398,9
63A4-(2-methoxyphenyl)piperidine-1-ylMe402,4
64A4-(3-fluoro-2-were)piperazine-1-IlH391,3
65A4-(2-methyl-3-nitrophenyl)piperazine-1-IlH418,3
66A3',6'-dihydro-3,4'-bipyridine-1'(2'H)-ylH357,4
67AN-(4-methoxyphenyl)-N'-methylaminoH334
68A 4-(3-methoxyphenyl)piperazine-1-IlMe403
69A4-(3-Chlorophenyl)piperazine-1-IlMe407,3
70A4-phenyl[1,4]diazepan-1-ylH373
71A3-methyl-4-(3-were)piperazine-1-IlH387
72A4-(3-methoxyphenyl)piperidine-1-ylHof 388.4
73B3-phenylpyrrolidine-1-yl343,3
74A4-isobutylpyrazine-1-ylH353
75A4-(4-cyano-2-were)-3,6-dihydropyridines-1(2H)-ylH 395
76A4-[(2-methylinosine-4-yl)methoxy]phenylaminoMe475,4
77A4-[(2-methylinosine-4-yl)methoxy]phenylaminoH461
78A4-(4-cyanophenyl)piperazine-1-IlH384
79C4-phenylpiperidine-1-ylH358
80A4-phenylpiperidine-1-ylH358
81A4-phenylpiperazin-1-ylH359
82A4-[3-(methoxymethyl)phenyl]piperidine-1-ylH402
3 A4-(3-methoxycarbonylbenzyl)piperidine-1-ylH416
84A3-cyclohexylpiperidine-1-ylH350,4
85A4-(3-isopropylphenyl)-3,6-dihydropyridines-1(2H)-ylH398,4
86A4-(3-isopropylphenyl)piperidine-1-ylH400,4
87A4-(4-propylphenyl)-3,6-dihydropyridines-1(2H)-ylH398
88A4-(4-ethylphenyl)-3,6-dihydropyridines-1(2H)-ylH384,4
89A4-(4-ethylphenyl)piperidine-1-ylH386
90 A4-(4-cyano-2-were)piperazine-1-IlH398
91A4-(3-isopropoxyphenyl)-3,6-dihydropyridines-1(2H)-ylH414,4
92A4-(3-were)-3,6-dihydropyridines-1(2H)-ylH370,3
93A4-(3-were)piperazine-1-IlH372,4
94A4-(4-tert-butylphenyl)piperazine-1-IlH415,4
95A4-pyridin-4-reparation-1-ylH360
96A3-benzylpiperidine-1-ylH371,9
97A5-labels and-2,3-dihydro-1H-indol-1-yl H346,3
98A5-[(2-methylinosine-4-yl)methoxy]-2,3-dihydro-1H-indol-1-ylH487,4
99A5-[(2-methylinosine-4-yl)methoxy]-2,3-dihydro-1H-indol-1-ylMe501,4
100A5-(benzyloxy)-2,3-dihydro-1H-indol-1-ylH422,3
101A1,3-dihydro-1'H-Spiro[inden-2,4'-piperidine]-1'-ylH384,4
102A4-(3-isopropoxyphenyl)piperidine-1-ylH416,4
103A4-(2-methyl-4-ethoxycarbonylphenyl)-3,6-dihydropyridines-1(2H)-ylH427,9
104A 4-(2-methyl-4-nitrophenyl)-3,6-dihydropyridines-1(2H)-ylH414,8
105A4-(2-ethylphenyl)piperidine-1-ylH385,9
106A4-(2-methyl-4-methoxycarbonylbenzyl)piperidine-1-ylH429,9
107A4-(2,3-dihydro-1-benzofuran-5-yl)-3,6-dihydropyridines-1(2H)-ylMe412,2
108A4-(3-isopropylphenyl)-3,6-dihydropyridines-1(2H)-ylMe412,2
109A(3R)-3-phenylpyrrolidine-1-ylH344,1
110A(3S)-3-phenylpyrrolidine-1-ylH344,1
112A 3-[3-(trifluoromethyl)phenyl]pyrrolidin-1-ylH412,1
113A3-(3-chlorophenyl)pyrrolidin-1-ylH378,1
114A3-(3-forfinal)pyrrolidin-1-ylH362,1
115A3-(4-forfinal)pyrrolidin-1-ylH362,1
116A3-(4-chlorophenyl)pyrrolidin-1-ylH378,1
117A3-[4-(trifluoromethyl)phenyl]pyrrolidin-1-ylH412,1
118A3-(4-methoxyphenyl)pyrrolidin-1-ylH374,1
119A3-(4-phenoxyphenyl)pyrrolidin-1-yl H436,2
120A4-(3-methoxyphenyl)-3,6-dihydropyridines-1(2H)-ylH386,1
121A4-(4-cyano-3-were)-3,6-dihydropyridines-1(2H)-ylH395,1
122A3-(3-methoxyphenyl)pyrrolidin-1-ylH374,1
123A3-pyridin-4-iparralde-1-ylH345,2
124A4-(3, 5dimethylphenyl)-3,6-dihydropyridines-1(2H)-ylH384,2
125A4-(3-trifloromethyl)-3,6-dihydropyridines-1(2H)-ylH440,1
126A5-(methoxymethyl)-4-phenyl-3,6-dihydropyridines-1(2H)-yl400
127A1,4,5,6-tetrahydrobenzo[f]isoquinoline-3(2H)-ylH381,9
129A4-(5-methoxy-2-were)-3,6-dihydropyridines-1(2H)-ylH400,2
130A4-(4-methoxy-2-were)-3,6-dihydropyridines-1(2H)-ylH400,2
131A4-cyano-4-phenylpiperidine-1-ylH383,2
132A4-phenyl-3,6-dihydropyridines-1(2H)-ylTaxicar-
boil
426,1*
133A4-phenyl-3,6-dihydropyridines-1(2H)-ylPropionic-
dicarbonyl
440,2*
134A4-phenyl-3,6-digitop ridin-1(2H)-yl Isopropano-
xianbei
440,2*
135A4-phenyl-3,6-dihydropyridines-1(2H)-ylIsobutoxy-
carbonyl
454,2*
136A5-methyl-4-phenyl-3,6-dihydropyridines-1(2H)-ylH370
143A1,4,4a,5,6,10b-hexahydrobenzo[f]isoquinoline-3(2H)-ylH384,2
144A4-(4-forfinal)-3-hydroxypiperidine-1-ylH392,1
145A3,3a,8,8a-tetrahydroindene[1,2-c]pyrrole-2(1H)-ylH356,1
146A4-(4-phenyl-1,3-thiazol-2-yl)piperidine-1-ylH441,3
147A 4-(4-tert-butyl-1,3-thiazol-2-yl)piperidine-1-ylH421,1
148A4-methyl-4-phenylpiperidine-1-ylH372,2
149A4-(4-ethyl-1,3-thiazol-2-yl)piperidine-1-ylH393,1
150A3-methyl-4-phenylpyrrolidine-1-ylH358,2
151A4-(2-forfinal)piperazine-1-IlH377,2
152A4-(3, 5dimethylphenyl)-3,6-dihydropyridines-1(2H)-ylMe398,1
153A4-phenylpiperazin-1-yltetrahydro-2H-Piran-4-oxycarpa-
Neil
487,1
154A4-phenylpiperazin-1-yl taxicar-
boil
431,2
155A4-phenylpiperazin-1-ylmeloxicam-
boil
417,1
156A4-pyrazin-2-reparation-1-ylH361,2
157A4-quinoline-2-reparation-1-ylH410,1
158A3-(5,6,7,8-tetrahydronaphthalen-2-yl)pyrrolidin-1-ylH398,2
159A(3R)-3-phenylpyrrolidine-1-ylMe358,1
160A(3R)-3-phenylpyrrolidine-1-ylmeloxicam-bonil402,1
161A3-pyridin-3-iparralde-1-yl H345,1
162A3-pyridin-2-iparralde-1-ylH345,1
163A3-methyl-3-phenylpyrrolidine-1-ylH358,2
164A3-phenylaziridine-1-ylH330,3
165A3-methyl-3-phenylpyrrolidine-1-ylMe372,4
166A3-phenylaziridine-1-ylMeto 344.4
168A1,3,3a,4,5,9b-hexahydro-2H-benzo[e]isoindole-2-ylH370,4
169A3-(2-naphthyl)pyrrolidin-1-ylH394,4
170 A4-(2-thienyl)-3,6-dihydropyridines-1(2H)-ylH362,1
171A3-(3-thienyl)pyrrolidin-1-ylH350,1
172A3-(2-thienyl)pyrrolidin-1-ylH350,2
173A4-(2-thienyl)piperidine-1-ylH364,1
174A3-(2-were)pyrrolidin-1-ylH358,2
175A3-(4-were)pyrrolidin-1-ylH358,2
176A4-phenyl-3,6-dihydropyridines-1(2H)-ylAc396,2
177A4-(3-Tien is l)-3,6-dihydropyridines-1(2H)-yl H362,1
178A3-phenylpiperidine-1-ylH358,2
179A4-(3-thienyl)piperidine-1-ylH364,1
180A4-(3, 5dimethylphenyl)-3,6-dihydropyridines-1(2H)-ylMeloxicam-
boil
442,2
181A4-(3, 5dimethylphenyl)-3,6-dihydropyridines-1(2H)-ylMethanol-
were radioactive
462,1
182A4-(3,5-differenl)-3,6-dihydropyridines-1(2H)-ylH392,2
183A4-(3,5-dichlorophenyl)-3,6-dihydropyridines-1(2H)-ylH424,1
184A4-[3,5-bis(trif ormetal)phenyl]-3,6-dihydropyridines-1(2H)-yl H492,1
185A4-phenylpiperazin-1-ylMethanol-
were radioactive
437,2
186A4-phenylpiperazin-1-ylformyl387,2
187A4-(3,5-differenl)piperidine-1-ylH394,2
188A4-(2,5-dimetilfenil)-3,6-dihydropyridines-1(2H)-ylH384,1
189A4-(2,4,5-trimetilfenil)-3,6-dihydropyridines-1(2H)-ylH398,2
190A4-biphenyl-3-reparacin-1-ylH434,2
191A4-dibenzo[b,d]furan-4-reparacin-1-yl HUSD 448,2
192A4-(2,5-dimetilfenil)piperidine-1-ylH386,2
193A4-(2,4,5-trimetilfenil)piperidine-1-ylH400,2
194A4-(3-methoxycarbonyl-6-were)-3,6-dihydropyridines-1(2H)-ylH428,2
195A5-phenyl-2,3,4,7-tetrahydro-1H-azepin-1-ylH370,2
196A4-[3-(dimethylamino)phenyl]-3,6-dihydropyridines-1(2H)-ylH399,2
197A4-(3-methoxycarbonyl-6-were)piperidine-1-ylH430,2
198A5-Penelitian-1-yl H372,2
199A4-[3-(dimethylamino)phenyl]piperidine-1-ylH401,2
200A4-(2-were)-3,6-dihydropyridines-1(2H)-ylH370,2
201A3-phenyl-2,5-dihydro-1H-pyrrol-1-ylH342,1
202A4-(4-cyano-2-were)piperidine-1-ylH397,2
203A3,3-dimethyl-4-phenyl-3,6-dihydropyridines-1(2H)-ylH384,1
204A3,3-dimethyl-4-phenylpiperidine-1-ylH386,2
205A3-phenyl-2,5-dihydro-1H-pyrrol-1-ylMethanol-
F. the Nile
420,2
206A3-phenyl-2,5-dihydro-1H-pyrrol-1-ylMethoxy-
carbonyl
400,2
207A3-phenyl-2,5-dihydro-1H-pyrrol-1-ylMe356,2
208A4-(4-cyano-3-were)piperidine-1-ylH397,2
209A4-[3-(benzyloxy)phenyl]-3,6-dihydropyridines-1(2H)-ylH462,2
210A4-[3-ethylphenyl]-3,6-dihydropyridines-1(2H)-ylH384,1
211A4-[3-(ethyloxy)phenyl]-3,6-dihydropyridines-1(2H)-ylH400,1
212A4-(3-ethylphenyl)piperidine-1-yl H386,1
213A4-(3-ethoxyphenyl)piperidine-1-ylH402,1
214A4-(3-cyclopropylmethyl)-3,6-dihydropyridines-1(2H)-ylH396,2
215A4-(4-methoxy-3, 5dimethylphenyl)-3,6-dihydropyridines-1(2H)-ylHlevel of 414.2
216A4-(3,5-dimethyl-4-methoxyphenyl)piperidine-1-ylH416,2
217A4-(4-cyano-3-ethylphenyl)-3,6-dihydropyridines-1(2H)-ylH409,2
218A4-(4-cyano-3-ethylphenyl)piperidine-1-ylH411,2
219A4-(4-cyano-3, 5dimethylphenyl)-3,6-dihydropyridin is n-1(2H)-yl H409,2
220A4-(4-cyano-3, 5dimethylphenyl)piperidine-1-ylH411,4
221A4-(1,3-benzothiazol-6-yl)-3,6-dihydropyridines-1(2H)-ylH413,1
222A4-(1-methyl-1H-benzimidazole-6-yl)-3,6-dihydropyridines-1(2H)-ylH410,2
223A4-(1-methyl-1H-benzimidazole-6-yl)piperidine-1-ylH412,3
224A4-(4-cyano-3-isopropylphenyl)-3,6-dihydropyridines-1(2H)-ylH423,2
225A4-(4-cyano-3-isopropylphenyl)piperidine-1-ylH425,2
236A 4-(4-cyano-3-ethylphenyl)-3,6-dihydropyridines-1(2H)-ylMe423,2
237A4-(4-cyano-3, 5dimethylphenyl)-3,6-dihydropyridines-1(2H)-ylMe423,2
238A4-(1-ethyl-1H-benzimidazole-6-yl)-3,6-dihydropyridines-1(2H)-ylH424,3
239A4-(1-methyl-1H-indazol-5-yl)-3,6-dihydropyridines-1(2H)-ylH410,2
240A4-(1-ethyl-1H-benzimidazole-6-yl)piperidine-1-ylHto 426.2
241A4-(1-methyl-1H-indazol-5-yl)piperidine-1-ylH412,2
242A4-(1-ethyl-1H-indazol-5-yl)-3,6-dihydropyridines-1(2H)-ylH424,2
23 A4-(1-ethyl-1H-benzimidazole-6-yl)piperidine-1-yltetrahydro-2H-Piran-4-oxycarpa-
Neil
554,3
244A4-(1-ethyl-1H-benzimidazole-6-yl)-3,6-dihydropyridines-1(2H)-ylMethoxy-
carbonyl
RUB 482.2
245A4-(1-ethyl-1H-benzimidazole-6-yl)-3,6-dihydropyridines-1(2H)-ylMethanol-
were radioactive
502,2
246A4-(1-ethyl-1H-benzimidazole-6-yl)piperidine-1-ylMeloxicam-
boil
484,2
247A4-(1-ethyl-1H-benzimidazole-6-yl)piperidine-1-ylMethanol-
were radioactive
504,2
248A4-(4-cyano-2-were)piperidine-1-ylMethanol-
were radioactive
476,2
2494-(4-cyano-2-were)piperazine-1-IlMethoxy-
carbonyl
456,2
250A4-(1-ethyl-1H-benzimidazole-6-yl)piperazine-1-IlH427,5
251A4-(1-ethyl-1H-benzimidazole-6-yl)piperazine-1-IlMethoxy-
carbonyl
485,3
252A4-(1-ethyl-1H-benzimidazole-6-yl)piperazine-1-IlMethanol-
were radioactive
505,2
253A4-(4-cyano-2-were)piperazine-1-Iltetrahydro-2H-Piran-4-oxycarpa-
Neil
526,3
254A4-(1-ethyl-1H-benzimidazole-6-yl)piperazine-1-Iltetrahydro-2H-Piran-4-oxycarpa-
Neil
455,3
255A3-methyl-4-fenil is peridin-1-yl H372,1
256A5-(aminocarbonyl)-4-phenyl-3,6-dihydropyridines-1(2H)-ylH386,1
257A4-(4-cyanophenyl)-5-methyl-3,6-dihydropyridines-1(2H)-ylH395,2
258A4-(4-cyanophenyl)-3-methylpiperidin-1-ylH397,1
259A5-methyl-4-(4-nitrophenyl)-3,6-dihydropyridines-1(2H)-ylH415,2
260A5-methyl-4-(3-nitrophenyl)-3,6-dihydropyridines-1(2H)-ylH415,1
262A4-dibenzo[b,d]furan-2-yl-3,6-dihydropyridines-1(2H)-ylH446,1
263A 4-dibenzo[b,d]furan-2-reparacin-1-ylH448,1
264A4-(3,3-dimethyl-2,3-dihydro-1-benzofuran-5-yl)-3,6-dihydropyridines-1(2H)-ylH426,1
265A4-(3,3-dimethyl-2,3-dihydro-1-benzofuran-5-yl)piperidine-1-ylH428,1
266A3-phenyl-2,5-dihydro-1H-pyrrol-1-ylIsopropano-
xianbei
428,1
267A3-phenyl-2,5-dihydro-1H-pyrrol-1-yl(3S)-tetrahydro-furan-3-oxycarpa-
Neil
456,1
268A3-phenyl-2,5-dihydro-1H-pyrrol-1-ylCyclohexa-
xianbei
468,2
269A3-phenyl-2,5-dihydro-1H-pyrrol-1-yltetrahydro-2H-Piran-oxycarpa-
Neil
470,2
270B4-phenylpiperazin-1-yl358,2
271B(3R)-3-phenylpyrrolidine-1-yl343,3
272B4-(2-methyl-4-nitrophenyl)piperazine-1-Il417,2
273B4-phenyl-3,6-dihydropyridines-1(2H)-yl355,2
274A4-phenylpiperazin-1-yl(3S)-tetrahydro-
furan-3-oxycarpa-
Neil
473,2
275A4-phenylpiperazin-1-yl(3R)-tetrahydro-
furan-3-oxycarpa-
Neil
473,2
276A4-phenylpiperazin-1-ylThe 2nd is toxico-
xianbei
461,1
277A4-phenylpiperazin-1-ylPeninsul-
were radioactive
499,1
278A4-phenylpiperazin-1-ylPropiona-
xianbei
445,2
279A4-phenylpiperazin-1-ylIsopropy-
oxycarbonyl
445,2
280A4-(3,5-differenl)-3,6-dihydropyridines-1(2H)-ylMeloxicam-
boil
450,2
281A4-(3,5-differenl)-3,6-dihydropyridines-1(2H)-ylMethanol-
were radioactive
470,2
282A4-(4-isopropylphenyl)piperazine-1-IlH400,2
283A 4-(3,5-differenl)piperidine-1-ylMethanol-
were radioactive
472,1
284A4-(4,5-dimethyl-1,3-thiazol-2-yl)piperidine-1-ylH393,1
*M-H

The ability of new compounds of the present invention to inhibit metalloprotease can be determined using the appropriate test methods, such as high-performance test methods. For example, the tool can be tested by using analysis of extracellular acidification, analysis of the inflow of calcium, analysis of binding with the ligand or analysis of chemotaxis. Below are examples of tests.

Analysis of TNFα

In some embodiments, embodiments of the ability of the compounds of the present invention to act as inhibitors of the production of TNFα can be determined using the following procedure. a 100 μm solution of the test inhibitor or its dilution were incubated at 37° C in an atmosphere of 5% CO2cells THP-1 (human monocytes), suspended in medium RPM1 1640 and 20 μm β-mercaptoethanol, at a density of cells 1×106/ml and stimulated with the help of LPS. After 18 hours the supernatant was analyzed to determine the level of TNFα using a commercial the ski available ELISA kit. Activity in the presence of 0.1 mm inhibitor or dilutions was compared to activity in a control sample containing no inhibitor, and the results were reported as the concentration of inhibitor that provides 50% inhibition of TNFα production.

Analysis of PBMC for measuring the activity of TNFα

Leucophores received from (Biological Specialties, Colmar PA) normal, not treated with drugs (without aspirin, ibuprofen, NSAID), etc.) donors. In a 50 ml conical tube (VWR, NJ) was added to 20 ml of blood and 20 ml of sterile 0,9% saline (Baxter Healthcare, Dearfield, IL) and thoroughly mixed. Used sublayer 10 ml containing no endotoxin plaques in the solution picola (Pharmacia, Uppsala, Sweden) and spin at 3000 rpm for 30 minutes. Remove the layer of leukocytes and washed with 50 ml of 0.9% saline solution. Cells were counted and added 0,250 ml to 96-well plate (Costar/Corning VWR, NJ) with 2×106cells/ml in RPMI medium 1640 (Gibco BRL). Added connection and pre-incubated with cells for 10 min before the addition of LPS (Calbiochem, CA) at 1 µg/ml for 5 hours. Collected supernatant and analyzed for the production of TNFα standard sandwich ELISA method (R&D Systems, Minneapolis, MN). Inhibitory activity of compounds was determined relative to cells cultured only with LPS.

Analysis of the activity of Her-2 sheddase

Cell l is of breast cancer human BT474 (ATCC, Manassas, Va) were sown at 2×104cells/well in 100 ml in 96-well plate (Costar/Corning VWR, NJ) in RPMI medium 1640 (In Vitrogen, Carlsbad, CA)containing 10% fetal calf serum (Hyclone, Lenexa, KS)and incubated over night at 37°C, 5% CO2. The next morning, the medium was removed and again was added to fresh medium with 100 ml/well. Compounds were added at appropriate concentrations and cells were incubated for 72 hours at 37°C, 5% CO2. The supernatant was then removed and either analyzed immediately or stored at -20°C until its use in the analysis. Supernatant analyzed at a dilution of 1/20 for inhibition of Her-2 sheddase using a commercial ELISA (Oncogene Research, San Diego, CA). Inhibitory activity of compounds was determined relative to cells cultured without adding connections.

In Vitro analyses of ADAM and MMP

With the exception of ADAM17 and MT1-MMP, all of recombinant human MMP and ADAM were obtained from R&D Systems (Minneapolis, MN). Their numbers in the following directory: MMR (901-MP), MMR (902-MP), MMR (513-MP), MMR (907-MP), MMR (908-MP), MMR (911-MP), MMR (910-MP), MMR (919-MP), MMR (511 MM), ADAM9 (939-AD) and ADAM10 (936 AD). MT1-MMP was obtained from US Biological (SwaMPcott, MA), catalog number M2429. ADAM17 pigs were obtained from the spleen of a pig and was purified in the laboratory.

Fluorogenic peptide substrate, (7-methoxycoumarin-4-yl)acetyl-Pro-Leu-Gly-Leu-(3-[2,4-dinitrophenyl]-L-2,3-diaminopropionic)-Ala-Arg-NH2received from R&D Systems, room ES001. It was used as a substrate for MMR, MMR, MR, MMR, MR, MMR, MMR and MT1-MMP analyses. Fluorogenic peptide substrate, (7-methoxycoumarin-4-yl)acetyl-Arg-Pro-Lys-Pro-Val-Glu-Nva-Trp-Arg-Lys(2,4-dinitrophenyl)-NH2received from R&D Systems, catalog number ES002. It was used as a substrate for MMR and NMR analyses. Fluorogenic peptide substrate, (7-methoxycoumarin-4-yl)-acetyl-Pro-Leu-Ala-Gln-Ala-Val-(3-[2,4-dinitrophenyl]-L-2,3-diaminopropionic)-Arg-Ser-Ser-Ser-Arg-NH2received from R&D Systems, catalog number ES003. It was used as a substrate for ADAM9, ADAM10 and ADAM17 tests.

Buffer conditions for analysis: usually the buffer conditions for the analysis is chosen on the basis of enzyme activity. Specific buffer conditions for analysis in General consisted of the following. For MMR, MMR, MR, MMR and MMR buffer for analysis contained 50 mm Tricine, 10 mm NaCl, 10 mm CaCl2, 1.0 mm ZnCl2, a pH of 7.4. For MMR and MMR buffer for analysis contained 50 mm Tricine, 10 mm NaCl, 10 mm CaCl2, 1.0 mm ZnCl2, 0,001% Brij35, pH of 7.4. For MMR and MMR buffer for analysis contained 50 mm Tris-HCl, 150 mm NaCl, 10 mm CaCl2, 0,001% Brij35, pH 7.5. For MT1-MMP buffer for analysis contained 100 mm Tris-HCl, 100 mm NaCl, 10 mm CaCl2, 0,001 Brij35, pH 7.5. For ADAM9 buffer for analysis contained 25 mm Tris, 2.5 μm ZnCl2and 0.001% Brij35, 0.1 mg/ml BSA, pH of 9.0. For ADAM10 buffer for analysis contained 25 mm Tris, 2.5 μm ZnCl2and 0.005% Brij35, pH of 9.0. For ADAM17 Boo the EP for the analysis contained 25 mm Tris, 2.5 μm ZnCl20.001 Brij35, pH 9,0.

To activate the enzymes MMP 10 or 20 µg of lyophilized Pro-MMP was dissolved in 100 μl water. To Pro-MMP was added 100 mm initial solution of acetate p-aminophenylacetate (APMA) in DMSO with a final concentration of 1.0 mm. Pro-MMP were incubated with APMA at 37°C for the time specified below. For MMR, MMR and MMR the incubation time was 1 hour. For MMR and MMR the incubation time was 2 hours. For MMR and MMR the incubation time was 24 hours.

Mostly 5 mm of the original solution of the compounds were obtained in DMSO. Was carried out by 2-fold serial dilution from a certain concentration with getting a tablet with the connection. 1,0 μl of compound in DMSO was transferred from the tablet containing compound, analytical tablet. The enzyme solution was received in the buffer for analysis with a concentration specified below. The substrate solution was received in the buffer for analysis with a concentration of 20 μm. 50 μl of an enzyme solution was added to the analytical tablet. Analytical tablet incubated for 5 minutes. Then in analytical tablet was added 50 μl of the substrate solution. The tablet was protected from light and incubated at room temperature or 37°C for the time specified below. The reaction was stopped by adding 10 μl of 500 mm EDTA solution. The tablet read on planetrenders upon excitation at 320 nm and emission at 405 nm. About the UNT inhibition was calculated for each concentration and IC50 value was obtained by curve. The specific conditions for each analysis were as follows: concentration of enzyme MMR 1000 ng/ml, room temperature, 1 hour incubation; the concentration of the enzyme MR 200 ng/ml, room temperature, 1 hour incubative; the concentration of the enzyme MMR 1000 ng/ml, room temperature, 1 hour incubation; the concentration of the enzyme MMR 100 ng/ml, room temperature, 1 hour incubation; the concentration of the enzyme MMR 500 ng/ml, room temperature, 2 hours of incubation; the concentration of the enzyme MMR 100 ng/ml, room temperature, 1 hour incubation; the concentration of the enzyme MMR 1000 ng/ml, room temperature, 2 hours of incubation; the concentration of the enzyme MR 200 ng/ml, room temperature, 1 hour incubation; the concentration of the enzyme MR 200 ng/ml, room temperature, 1.5 hours of incubation; the concentration of the enzyme MT1-MMP 200 ng/ml, room temperature, 1 hour incubation; the concentration of the enzyme ADAM9 4000 ng/ml, incubation at 37°C for 6 hours; the concentration of the enzyme ADAM10 700 ng/ml, incubation at 37°C for 6 hours; the concentration of the enzyme ADAM17 600 ng/ml, incubation at 37°C for 1 hour.

Analysis MMR

5 mm of the original solution of the compounds were obtained in DMSO. Tablet compound was obtained by 2-fold dilution for the 11-point curve with the highest concentration of 500 μm. 1 μl of a solution of the compound in DMSO was transferred from the tablet containing compound, analytical tablet. RA is a creation of the enzyme was obtained in the buffer for analysis with a concentration of 10 ng/50 μl. The substrate solution was received in the buffer for analysis with a concentration of 20 μm. 50 μl of an enzyme solution was added to the analytical tablet. Analytical tablet incubated for 5 minutes. Then in analytical tablet was added 50 μl of the substrate solution. The tablet was protected from light and incubated at room temperature for 1 hour. The reaction was stopped by adding 10 μl of 500 mm EDTA solution. The tablet read on planetrenders upon excitation at 320 nm and emission at 405 nm.

Analysis MMR

5 mm of the original solution of the compounds were obtained in DMSO. Tablet compound was obtained by 2-fold dilution for the 11-point curve with the highest concentration of 500 μm. 1 μl of a solution of the compound in DMSO was transferred from the tablet with the compound in the analytical tablet. The enzyme solution was received in the buffer for analysis with a concentration of 50 ng/50 μl. The substrate solution was received in the buffer for analysis with a concentration of 20 μm. In analytical tablet was added 50 μl of an enzyme solution. Analytical tablet incubated for 5 minutes. The wells used to obtain background values for comparison, was added 10 μl of 500 mm EDTA solution. Then in analytical tablet was added 50 μl of the substrate solution. The tablet was protected from light and incubated at room temperature for 1 hour. The reaction was stopped by adding 10 μl of 500 mm Rast is ora EDTA. The tablet read on planetrenders upon excitation at 320 nm and emission at 405 nm.

Analysis MMR

5 mm of the original solution of the compounds were obtained in DMSO. Tablet compound was obtained by 2-fold dilution for the 11-point curve with the highest concentration of 500 μm. 1 μl of a solution of the compound in DMSO was transferred from the tablet with the compound in the analytical tablet. The enzyme solution was received in the buffer for analysis with a concentration of 10 ng/50 μl. The substrate solution ((7-methoxycoumarin-4-yl)acetyl-Pro-Leu-Gly-Leu-(3-[2,4-dinitrophenyl]-L-2,3-diaminopropionic)-Ala-Arg-NH2), received in the buffer for analysis with a concentration of 20 μm. In analytical tablet was added 50 μl of an enzyme solution. Analytical tablet incubated for 5 minutes. The wells used to obtain background values for comparison, was added 10 μl of 500 mm EDTA solution. Then in analytical tablet was added 50 μl of the substrate solution. The tablet was protected from light and incubated at room temperature for 1 hour. The reaction was stopped by adding 10 μl of 500 mm EDTA solution. The tablet read on planetrenders upon excitation at 320 nm and emission at 405 nm.

Analysis of ADAM10

5 mm of the Original solution of the compounds were obtained in DMSO. Tablet compound was obtained by 2-fold dilution for the 11-point curve with the highest concentration of 500 μm. 1 μl of a solution of the compound DMSO plumage is osili of the tablet with the compound in the analytical tablet. The enzyme solution was received in the buffer for analysis with a concentration of 100 ng/50 μl. The substrate solution ((7-methoxycoumarin-4-yl)acetyl-Pro-Leu-Ala-Gln-Ala-Val-(3-[2,4-dinitrophenyl]-L-2,3-diaminopropionic)-Arg-Ser-Ser-Ser-Arg-NH2), received in the buffer for analysis with a concentration of 20 μm. 50 μl of an enzyme solution was added to the analytical tablet. Analytical tablet incubated for 5 minutes. Then in analytical tablet was added 50 μl of the substrate solution. The tablet was protected from light and incubated at 37°C for 4 hours. The reaction was stopped by adding 10 μl of 500 mm EDTA solution. The tablet read on planetrenders upon excitation at 320 nm and emission at 405 nm.

Analysis of ADAM15

ADAM15 can be analyzed in the same way as ADAM10 (see, for example, Fourie et al., J Biol Chem. 2003, 278(33), 30469-77). Briefly, the peptide substrate containing fluorescently dye and a quencher of fluorescence, was obtained by marking one end fluorescent dye, and the other end of the quenching dye. Cleavage of the peptide under the action of ADAM15 can be measured by the increase in fluorescence intensity due to the decrease in spatial proximity quenching of the dye by a fluorescent dye.

Active connections

Compounds of the present invention are set IR50in the range from about 5 nm to about 10 microns, a specific target for ingebyra the project when tested using at least one of the above in vitro tests.

Analysis of In Vivo

For measurement of antitumor activity of inhibitors of metalloprotease used as estrogenzawisimy (MCF-7 and BT-474)and independent (MDA-MB-435 cell line breast cancer human experiments using xenograft in immunocompromised mice (BALB/c nude and SCID/bg). Tumor BT-474 were obtained from subclone parent cells BT-474 from ATCC (BT-474-SC1), which were chosen on the basis of their increased ability to opukholeobrazovanie and growth rate, and for simplicity they are shown as BT-474. In models of tumor BT-474 and MCF-7 granules delayed release of estrogen (Innovative Research of America) were injected subcutaneously (s.c.) in the side of each mouse 24 hours before inoculation of tumor cells. For all models specified number of cells were combined with BD Matrigel™ in the ratio of 1:1 immediately before implantation. One day after implantation of estrogen pellets 2×107BT-474 cells were injected by subcutaneous injection in the upper lateral part of each mouse. MCF-7 were established by subcutaneous implantation of 5×106cells, administered by injection in a similar way. For tumor cells MDA-MB-435 cells 2×106was administered by subcutaneous injection in the flank of mice BALB/c nude. For all models of the tumors were measured weekly, and their volume was calculated by the formula is [volume=(length×width 2):2]. Once the mean tumor volume at the required number of mice reached the desired value (typically>150 mm3), mice were randomly divided into groups of processing, including, typically, from 6 to 10 mice. Animals were then treated with the test compound or the carrier by intraperitoneal or subcutaneous implantation of osmotic Minnesota for 7-28 days to achieve control of the desired effect of the compound by changing the flow rate provided by the pump, and/or concentration of the compound inside the pump. The size of the tumor and body weight (an indicator of the health of the animal) was monitored weekly. Also took blood samples in the period of functioning of osmotic pumps and plasma was separated (by centrifugation) and kept at-s for subsequent pharmacokinetic analysis.

Methods of treatment, the dose and composition

Compounds of the present invention it is possible to enter a mammal, such as man, but they can also be entered and other mammals, such as animals in need of veterinary care, such as domestic animals (e.g. dogs, cats and the like), farm animals (e.g. cows, sheep, pigs, horses and the like) and laboratory animals (e.g., rats, mice, Guinea pigs and the like). Mammals that are subject to treatment by the methods of the present the invention, can be mammals, male or female, have the desired modulation of the activity of metalloprotease matrix. The term “modulation” refers to the antagonism, agonism, partial antagonism and/or partial agonism.

In the present description, the term “therapeutically effective amount” means the number of pending connections, which causes the biological or medical response of a tissue, system, animal or human that is being hunted by a researcher, veterinarian, doctor or other Clinician.

Compounds of the present invention is administered in therapeutically effective amounts for the treatment of diseases, such as rheumatoid arthritis. A therapeutically effective amount of the compound represents a quantity that provides the inhibition of one or more processes mediated by metalloproteases, the subject suffering from a disease associated with aberrant activity of metalloprotease. Alternatively, a therapeutically effective amount of a compound is the amount necessary to achieve the desired therapeutic and/or prophylactic effect, such as the number, which ensures the prevention or reduction of symptoms associated with the disease, which is associated with aberrant AK is ewnetu of metalloprotease.

The present invention provides a method of treating diseases associated with unwanted activity metalloprotease the mammal. In some embodiments, embodiments of unwanted activity metalloprotease associated with arthritis, cancer (such as breast cancer, ovarian cancer, prostate cancer, non-small cell lung cancer, colon cancer, stomach cancer, pancreatic cancer, glioma, and the like), cardiovascular diseases, skin diseases, inflammatory or allergic conditions. In other embodiments, the embodiment of the present invention provides a method of inhibiting pathological changes mediated by an increased level of metalloprotease in mammals.

The compounds disclosed in this application, useful for the treatment of diseases, pathological conditions and disorders associated with the activity of metalloprotease, for example, by modulation (e.g., such as the inhibition or antagonism) metalloprotease, including metalloprotease matrix (MMP), ADAM ADA-TS and sheddase that in pathological cases can cause the destruction of the matrix, shedding (“shedding”) of the surface-cell protein ectodomain and/or the synthesis of TNF. In the following variants of the embodiment of the compounds of the present invention modulate metalloprotease matrix (for example, MMR, MR, THE MP3 MMR or MMR), members of the family of enzymes ADAM, including TNF α-Mac, ADAM10, ADAM15, ADAM17, and cheddadi, such as Her-2 sheddase binding to heparin, EGF sheddase. Compounds of the present invention can modulate the activity of enzymes ADAM, who, it is believed, are responsible for the release and shedding (“shedding”) of soluble receptors (e.g., CD30, and receptors for TNF), adhesion molecules (e.g., L-selectin, SAM-1, fibronectin, growth factors and cytokines (such as Fas ligand, TGF-α, EGF, HB-EGF, SCF, IL-6, IL-1, TSH and M-CSF) and receptor growth factors (for example, members of the EGFR family, such as Her-2 and Her-4), which are involved in the pathogenesis of various types of cancer, including breast cancer, ovarian cancer, prostate cancer, non-small cell lung cancer, colon cancer, stomach cancer, pancreatic cancer, glioma. Accordingly, the compounds of the present invention may be useful for treating diseases and disorders associated with the activity of any of the above targets.

Diseases or conditions of humans or other species which can be treated with modulators of metalloprotease of the present invention, include, but are not limited to: inflammatory or allergic diseases and conditions, including respiratory allergic diseases such as asthma, allergic rhinitis, al is ergicheskie pulmonary disease, allergic pneumonitis, eosinophilic cellulitis (for example, the syndrome Well), eosinophilic pneumonias (e.g., Loeffler's syndrome, chronic eosinophilic pneumonia), eosinophilic fasciitis (e.g., Shulman syndrome), allergic reaction of the delayed type, interstitial lung diseases (ILD) (e.g., idiopathic pulmonary fibrosis, or ILD associated with rheumatoid arthritis, systemic lupus erythematosus, Ankylosaurus spondylitis, systemic sclerosis, Sjogren's syndrome, polymyositis or dermatomyositis); systemic anaphylaxis or allergic reactions, allergic to medicines (e.g., to penicillin, cephalosporins), syndrome eosinophilia-myalgia caused by injection of the crude tryptophan, allergies to insect bites; autoimmune diseases such as rheumatoid arthritis, psoriatic arthritis, multiple sclerosis, systemic lupus erythematosus, severe myasthenia gravis, juvenile diabetes; glomerulonephritis, autoimmune thyroiditis, Behcet's disease; graft rejection (e.g., in transplantation), including allograft rejection or disease graft-versus-host; inflammatory bowel disease such as Crohn's disease and ulcerative colitis; spondyloarthropathies; scleroderma; psoriasis (including T-cell-mediated psoriasis) and inflammatory dermatoses, such as the dermis is it eczema, atopic dermatitis, allergic contact dermatitis, urticaria; vasculitis (e.g., necrotizing, cutaneous and allergic vasculitis); eosinophilic myositis, eosinophilic fasciitis; neoplastic diseases such as breast cancer and types of cancer with infiltration of leukocytes into the skin or organs. It is possible to treat other diseases or conditions where it is necessary to inhibit unwanted inflammatory reactions, including but not limited to, reperfusion injury, atherosclerosis, some malignant hematological diseases induced by cytokines toxicity (e.g., septic shock, endotoxic shock), polymyositis and dermatomyositis.

The compounds presented in this invention, it is possible to enter in such oral dosage forms as tablets, capsules (each of which includes a song with a slow or timed release), pills, powders, granules, elixirs, tinctures, suspensions, syrups and emulsions. They can also be entered in the form for intravenous (bolus or infusion), intraperitoneal, subcutaneous or intramuscular injection, and all such use of dosage forms well known to experts in the field of pharmaceutics. You can enter them separately, but is usually administered with a pharmaceutical carrier which is chosen in dependence the value from the selected route of administration and standard pharmaceutical practice.

Input dose of the compounds of the present invention, of course, vary depending upon known factors such as the pharmacodynamic characteristics of the particular means and method of its introduction; the metabolic stability, rate of excretion, combination with other drugs and duration of action of such compounds; the species, age, gender, health status, conditions of treatment and weight of the recipient; the nature and severity of symptoms; kind of concurrent treatment; the frequency of administration of the medicine; the specific route of administration, the renal function and liver of the patient and the desired effect. The attending physician or veterinarian can determine and prescribe the effective amount of the drug required to prevent, slow or stop the development of a specific disorder that should be treated.

As a rule, the daily oral dosage of each active ingredient when used for obtaining the above effects is from about 0.0001 to about 1000 mg/kg body weight, preferably from about 0.001 to about 100 mg/kg of body weight per day and most preferably from about 0.1 to about 20 mg/kg/day. For intravenous administration, the most preferred dose is from about 0.1 to about 10 mg/kg/minute during a constant rate infusion. For oral in which edenia composition is preferably supplied in the form of tablets, containing 1.0 to 1000 mg of active ingredient, in particular, 1,0, 5,0, 10,0, 15,0, 20,0, 25,0, 50,0, 75,0, 100,0, 150,0, 200,0, 250,0, 300,0, 400,0, 500,0, 600,0, 750,0, 800,0, 900,0 and 1000,0 mg of the active ingredient for the symptomatic adjustment dose for a patient to be treated. The compounds can be administered in scheme 1-4 times a day, preferably once or twice a day.

Compounds of the present invention can also be entered in the form for intranasal administration by topical use of suitable intranasal carriers or percutaneous, by using plasters for percutaneous introduction. With the introduction in the form of a percutaneous delivery systems diagram of a dose of drug, of course, assumes a continuous, rather than intermittent introduction.

Compounds of the present invention are typically administered in a mixture with suitable pharmaceutical diluents, excipients or carriers (collectively indicated in the present description as pharmaceutical carriers), appropriately selected depending on the intended form of administration, i.e. oral tablets, capsules, elixirs, syrups and the like, and consistent with conventional pharmaceutical practices.

For example, for oral administration in the form of tablets or capsules, the active ingredient of medicines can be combined with oral non-toxic pharmaceutically p is memlimit inert carrier, such as lactose, starch, sucrose, glucose, methylcellulose, magnesium stearate, dicalcium phosphate, calcium sulfate, mannitol, sorbitol and the like, For oral administration in liquid form components of oral medicines can be combined with an oral, non-toxic, pharmaceutically acceptable inert carrier such as ethanol, glycerol, water, etc. in Addition, when it is desirable or necessary, you can also include a mixture of suitable binders, lubricants, disintegrant and dyes. Suitable binders include starch, gelatin, natural sugars such as glucose or β-lactose, sweeteners, natural and synthetic resins, such as the Arabian gum, tragakant or sodium alginate, carboxymethylcellulose, polyethylene glycol, waxes and other Lubricants used in these dosage forms include sodium oleate, sodium stearate, magnesium stearate, sodium benzoate, sodium acetate, sodium chloride, etc. Disintegrant include, without limitation, starch, methylcellulose, agar, bentonite, xanthan resin, etc.

Compounds of the present invention can also be supplied for use by the patient in the form of liposomal delivery systems, such as small single-layer vesicles, large single-layer and multi-layered vesicles vesicles. Liposomes can be obtained from a variety of phospholipids, so is x as cholesterin, stearylamine or phosphatidylcholine.

Compounds of the present invention can also be associated with soluble polymers are used as carriers to deliver the drug to the target. Such polymers can include polyvinylpyrrolidone, a copolymer of Piran, polyhydroxyethylmethacrylate, polyhydroxyethylmethacrylate or polyethylenepolyamine, substituted palmitoleate remains. In addition, the compounds of the present invention can be associated with a class of biodegradable polymers, which are used for controlled release of a drug, for example polylactic acid, polyglycolic acid, copolymers of polylactic and polyglycolic acid, polietilentireftalat, polyhydroxyalkanoic acid, polyarteritis, polyacetylene, policyidreference and sewn or amphipatic block copolymers of hydrogels.

Suitable for injection dosage forms for the compounds of the present invention can contain from about 0.1 to about 100 mg of active ingredient per unit dosage form. In these pharmaceutical compositions the active ingredient is typically present in an amount of about 0.5 to 95 wt.% calculated on the total weight of the composition.

Gelatin capsules can also be used as dozirovanno the th form and they may contain the active ingredient and powdered carriers, such as lactose, starch, cellulose derivatives, magnesium stearate, stearic acid, etc. Such diluents can be used to obtain the compressed tablets. And tablets, and capsules can be manufactured in the form of slow release products that provide a continuous release of the drug within a few hours. Compressed tablets can be sugar coating or film coating, mask any unpleasant taste and protect the tablet from atmospheric effects, or may have intersolubility floor for selective degradation in the gastrointestinal tract.

When using liquid dosage forms for oral administration they may contain a dye or perfume, to be more attractive for the patient.

Generally, suitable carriers for parenteral solutions are water, a suitable oil, saline, aqueous dextrose (glucose) and the corresponding solutions of sugars and glycols, such as propylene glycol or polyethylene glycol. Solutions for parenteral administration preferably contain a water-soluble salt of the active ingredient, suitable stabilizers and, if necessary, buffer substances. The approach is relevant stabilizers are antioxidants, such as sodium bisulfite, sodium sulfite, or ascorbic acid, used separately or in combination. Also use citric acid and its salts and sodium salt of EDTA. In addition, parenteral solutions can contain preservatives, such as benzylaniline, methyl - or propyl-paraben and chlorbutanol. Suitable pharmaceutical carriers are described in Remington's Pharmaceutical Sciences, Mack Publishing Company, a standard reference in the field of pharmacology.

The pharmaceutical compositions of the present invention can also be in the form of emulsions of oil-in-water. The oil phase may be a vegetable oil, such as olive oil or peanut oil, or mineral oil, for example liquid paraffin or mixtures of these substances. Suitable emulsifiers may be a natural resin, such as resin acacia or resin tragakant, natural phosphatides, for example soy bean, lecithin, esters or partial esters derived from fatty acids and mexicanvalium, for example, servicemanual, and condensation products of these partial esters with ethylene oxide, for example polyoxyethylene sorbitan monooleate. The emulsions may also contain sweetening and flavouring agents.

Compounds of the present invention can also be entered in the form of suppositories for rectal administration of medicinal what about the tools. Such compositions can be obtained by mixing the drug with a suitable non-irritating by excipients, which is a solid at ordinary temperature, but when the rectal temperature is liquid and therefore melt in the rectum, releasing the drug. Such substances are cocoa butter and polyethylene glycols.

For local use of creams, ointments, jellies, solutions or suspensions, etc. containing compounds of the present invention. As used in this description, the application often involves a solution or liquid for rinsing the mouth.

Pharmaceutical compositions and methods of the present invention may also include other therapeutically active compounds usually applied for the treatment of the above-mentioned pathological conditions.

Illustrative examples of pharmaceutical dosage forms that can be used for administration of the compounds of the present invention are as follows.

Capsules

A large number of individual capsules can be obtained by filling two-part hard gelatin capsules so that each contained 50 mg of powdered active ingredient, 100 mg of lactose, 25 mg of cellulose and 3 mg of magnesium stearate.

Soft gelatin ka is Sula

You can get a mixture of the active ingredient in the edible oil such as soybean oil, cottonseed oil or olive oil, and to introduce it by means of the delivery piston pump into gelatin with the formation of soft gelatin capsules containing 75 mg of active ingredient. Capsules should be washed and dried.

Tablets

Tablets can be obtained using conventional procedures so that the dosage unit contains 75 mg of the active ingredient, 0.15 mg of colloidal silicon dioxide 4 mg stearate 250 mg microcrystalline cellulose, 9 mg of starch and 75 mg of lactose. You can apply suitable coatings are well known to specialists in this field, to improve the taste and delay absorption.

Forms for injection

A parenteral composition suitable for administration by injection, can be obtained by mixing 1.0 wt.% the active ingredient in the 8% solution (by volume) of propylene glycol and water. The solution should be made isotonic with sodium chloride and sterilized.

Suspension

Aqueous suspension for oral administration can be obtained so that each 5 ml suspension contains 75 mg of finely powdered active ingredient, 150 mg of sodium salt of carboxymethyl cellulose, 3.75 mg sodium benzoate, 0.75 g of sorbitol solution, U.S.P. and 0.015 ml of vanillin.

All PA the coefficients, patent applications and publications referenced in this application, incorporated by reference in their entirety for all purposes and to the same extent as if each individual patent, patent application or publication were separately specified.

Despite the fact that many disclosed in this application form of the present invention are preferred at the moment, ways of its embodiment, it is possible and many other forms and other details preferred options of the incarnation, and other possible embodiments should not be construed as a limitation. It should be clear that in the present description, the terms are merely descriptive, and not restrictive, and there may be various changes and many of equivalents without departure from the essence and scope of the claimed invention.

1. The compound of formula I or II


its enantiomer, diastereoisomer, or a pharmaceutically acceptable salt, where
But a CWNHOH;
Represents a CH2;
G represents CH2;
D represents oxygen;
X represents CH2NRb;
Y represents CH2;
M represents CO;
U is absent or represents NRb;
V is absent or represents from the battle phenyl, or 4-10-membered heterocyclyl containing 1-2 heteroatoms selected from N and S, substituted 0-5 groups Re;
U' is absent or represents a C1-10alkylen, or their combination;
V' represents H, C1-8alkyl, NRbRcWith6-10carbocyclic, substituted by 0 to 3 groups of Reor 5-14 membered heterocyclyl containing 1-3 heteroatoms selected from N, O and S, substituted 0-4 groups Re;
Raand Re, each independently, represents H, T1-8alkylen-T, C(O)NRa'(CRb'Rc')r-T, (CRb'Rc')r-O-(CRb'Rc')r-T, HE, Cl, F, CN, NO2, NRIRII, COORIV, ORIV, CONRIRIIWith1-8halogenated,3-13carbocyclic;
Rband Rc, each independently, represents H, T, C1-6alkylen-T, C(O)O(CRb'Rc')r-T, C(O)(CRb'Rc')r-T, S(O)p(CRb'Rc')r-T;
T represents H, C1-10alkyl, substituted 0-1 groups Rb'; C3-6carbocyclic, 5-6-membered heterocyclyl containing one oxygen atom;
Ra', Rb' and Rc'each independently represents H, ORIVor phenyl;
R1represents hydrogen;
R2represents hydrogen;
R3is:
(1) C1-10alkyl;
(ii) 4-14-membered hetero is iklil, containing 1-3 nitrogen atom optionally substituted by one or two substituents selected from C1-6the alkyl, OR13, 5-10-membered heterocyclyl containing 1-3 heteroatoms selected from N, O and S, or phenyl;
(iii) NR16R17;
R4represents H;
R4'represents H;
R5'represents H;
W represents oxygen;
R13represents a C1-C6alkyl;
R16and R17each independently represents a C1-C10alkyl or phenyl, where each optionally substituted With one1-4by alkyl;
RIand RIIeach, independently, represents H or C1-6alkyl;
RIVrepresents a C1-6alkyl;
i is 0;
p is 1 or 2 and
r is 0, 1 or 2;
provided that
a) spirocerca is a stable chemical structural unit and
b) NR8and NRbcontain no N-N or N-O bonds.

2. The compound according to claim 1 or its pharmaceutically acceptable salt, where a represents C(O)NHOH.

3. The compound according to claim 1 or its pharmaceutically acceptable salt, where R3represents NR16R17.

4. The compound according to claim 1 or its pharmaceutically acceptable salt, where U is missing.

5. The compound according to claim 1 or its pharmaceutically acceptable salt, where V is a 4-10-membered g is eroticly with 1-2 heteroatoms, selected from N and S, substituted 0-5 groups Re.

6. The compound according to claim 1 or its pharmaceutically acceptable salt, where V represents azetidin-1-yl, 2,5-dihydro-1H-pyrrol-1-yl, piperidine-1-yl, piperazine-1-yl, pyrrolidin-1-yl, ethanol-2-yl, pyridin-1-yl, 3,6-dihydropyridines-1-yl, 2,3-dihydroindol-1-yl, 1,3,4,9-tetrahydrocarboline-2-yl, thieno[2,3-C]pyridine-6-yl, 3,4,10,10A-tetrahydro-1H-pyrazino[1,2-a]indol-2-yl, 1,2,4,4A,5,6-hexahydropyrazino[1,2-a]quinoline-3-yl, pyrazino[1,2-a]quinoline-3-yl, diazepan-1-yl, 1,4,5,6-tetrahydro-2H-benzo[f]isoquinoline-3-yl, 1,4,4A,5,6,10b-hexahydro-2H-benzo[f]isoquinoline-3-yl, 3,3A,8,8A-tetrahydro-1H-2-azacyclopenta[a]inden-2-yl or 2,3,4,7-tetrahydro-1H-azepin-1-yl, azepin-1-yl.

7. The compound according to claim 1 or its pharmaceutically acceptable salt, where U' is absent or represents O or C1-10alkylen.

8. The compound according to claim 1 or its pharmaceutically acceptable salt, where U' is missing.

9. The compound according to claim 1 or its pharmaceutically acceptable salt, where V' represents a C6-10carbocyclic, substituted by 0 to 3 groups of Reor 5-14 membered heterocyclyl containing 1-3 heteroatoms selected from N, O and S, substituted 0-4 groups Re.

10. The compound according to claim 1 or its pharmaceutically acceptable salt, where V' represents a C6-10carbocyclic, substituted by 0 to 3 groups of Re.

11. The compound according to claim 1 or its pharmaceutically PR is acceptable salt, where V' represents phenyl, substituted by 0 to 3 groups of Re.

12. The compound according to claim 1 or its pharmaceutically acceptable salt, where V' represents phenyl, substituted 0-2 T1-8alkylen-T, (CRb'Rc')r-O-(CRb'Rc')r-T, Cl, F, CN, NO2, ORIVor CONRIRII.

13. The compound according to claim 1 or its pharmaceutically acceptable salt, where V' represents phenyl.

14. The compound according to claim 1 or its pharmaceutically acceptable salt, where V' is a 5-14-membered heterocyclyl containing 1-3 heteroatoms selected from N, O and S, substituted 0-4 groups Re.

15. The compound according to claim 1 or its pharmaceutically acceptable salt, where V' is thiazolyl, benzothiazolyl, thienyl, chinoline, pyridinyl, pyrazinyl, benzimidazolyl, indazoles, 3,6-dihydropyridine, piperidinyl or 2,3-dihydrobenzofuran-5-yl.

16. The compound according to claim 1 or its pharmaceutically acceptable salt, where U' represents O or C1-10alkylen, and V' represents a C6-10carbocyclic, substituted by 0 to 3 groups of Reor 5-14 membered heterocyclyl containing 1-3 heteroatoms selected from N, O and S, substituted 0-4 groups Re.

17. The compound according to claim 1 or its pharmaceutically acceptable salt, where M represents CO, U is absent, V is a 4-10-membered heterocyclyl, substituted 0-5 GRU the groups of R eU' is absent, and V' represents a C6-10carbocyclic, substituted by 0 to 3 groups of Reor 5-14 membered heterocyclyl containing 1-3 heteroatoms selected from N, O and S, substituted 0-4 groups Re.

18. The compound according to claim 1 or its pharmaceutically acceptable salt, where M represents CO, U is absent, V is absent, U' is absent, and V' represents NRbRc.

19. The compound according to claim 1 or its pharmaceutically acceptable salt, where Rband Rceach, independently, represents H, C1-6alkylen-T, C(O)O(CRb'Rc')r-T, C(O)(CRb'Rc')r-T or S(O)p(CRb'Rc')r-T.

20. The compound according to claim 1 or its pharmaceutically acceptable salt, where Rband Rceach, independently, represents H, C1-4alkyl, C(O)O(CRb'Rc')r-T or S(O)p(CRb'Rc')r-T.

21. The compound according to claim 1 or its pharmaceutically acceptable salt, where Rbrepresents H, C1-4alkyl, C(O)(CRb'Rc')r-T, C(O)O(CRb'Rc')r-T or S(O)p(CRb'Rc')r-T.

22. The compound according to claim 1 or its pharmaceutically acceptable salt, where Rbrepresents N.

23. The compound according to claim 1 or its pharmaceutically acceptable salt, where Rbrepresents a C1-4alkyl.

24. The connection p of the claim 1 or its pharmaceutically acceptable salt, where Rbrepresents C(O)(CRb'Rc')r-T.

25. The compound according to claim 1 or its pharmaceutically acceptable salt, where Rbrepresents C(O)O(CRb'Rc')r-T.

26. The compound according to claim 1 or its pharmaceutically acceptable salt, where Rbrepresents S(O)p(CRb'Rc')r-T.

27. The compound according to claim 1, where Rcrepresents N or C1-4alkyl.

28. The compound according to claim 1 or its pharmaceutically acceptable salt, where Rerepresents H, T1-8alkylen-T, C(O)NRa'(CRb'Rc')r-T, (CRb'Rc')r-O-(CRb'Rc')r-T, HE, Cl, F, CN, NO2, ORIV, NRIRII, CONRIRIIWith1-8halogenated,3-6carbocyclic.

29. The compound according to claim 1 or its pharmaceutically acceptable salt, where Rerepresents H, C1-6alkyl, HE, Cl, F, CN, NO2, methoxy, ethoxy, n-propoxy, isopropoxy, phenoxy, benzyloxy, amino, (C1-4alkyl)amino, (C2-8)dialkylamino, CONH2, CONH(C1-4alkyl), CON(C1-4alkyl)2C1-6halogenated, phenyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, benzyl or phenethyl.

30. The compound according to claim 1 or its pharmaceutically acceptable salt having the formula II.

31. The compound according to claim 1 or its pharmaceutically acceptable salt, imouse the formula II, where
But a CWNHOH,
Represents a CH2;
G represents CH2;
X represents CH2NRb;
Y represents CH2;
M represents CO;
U is absent or represents NRb;
V is absent or represents phenyl, or a 4-10-membered heterocyclyl containing 1-2 heteroatoms selected from N and S, substituted 0-5 groups Re;
U' is absent or represents a C1-10alkylen or;
V' represents H, C1-8alkyl, NRbRcWith6-10carbocyclic, substituted by 0 to 3 groups of Reor 5-14 membered heterocyclyl containing 1-3 heteroatoms selected from N, O and S, substituted 0-4 groups Re;
R1represents hydrogen;
R2represents hydrogen;
R3represents NR16R17;
R4' represents H;
R5' represents H; and
W represents oxygen.

32. The compound according to claim 1 or its pharmaceutically acceptable salt having the formula II, where
And represents C(O)NHOH;
Represents a CH2;
G represents CH2;
X represents CH2NRb;
M represents CO;
U is absent;
V is absent or represents phenyl, or a 4-10-membered heterocyclyl containing 1-2 heteroatoms, selected the s from N and S, substituted by 0-5 groups Re;
U' is absent or represents a C1-10alkylen or;
V' represents H, C1-8alkyl, NRbRcWith6-10carbocyclic, substituted by 0 to 3 groups of Reor 5-14 membered heterocyclyl containing 1-3 heteroatoms selected from N, O and S, substituted 0-4 groups Re;
Rband Rc, each independently, represents H, C(O)O(CRb'Rc')r-T or S(O)p(CRb'Rc')r-T;
R1represents hydrogen;
R2represents hydrogen;
R3represents NR16R17;
R4' represents H; and
R5' represents N.

33. The compound according to claim 1 or its pharmaceutically acceptable salt having the formula II, where
And represents C(O)NHOH;
Represents a CH2;
G represents CH2;
X represents CH2NRb;
Y represents CH2;
M represents CO;
U is absent;
V is absent or represents phenyl, or a 4-10-membered heterocyclyl containing 1-2 heteroatoms selected from N and S, substituted 0-5 groups Re;
U' is absent or represents a C1-10alkylen or;
V' represents H, C1-8alkyl, NRbRcWith6-10carbocyclic, substituted by 0 to 3 groups of Reor 5-14 membered heterocyclyl, containing 1-3 heteroatoms selected from N, O and S, substituted 0-4 groups Re;
Rband Rceach independently represents H, C(O)O(CRb'Rc')r-T or S(O)p(CRb'Rc')r-T;
Ra' represents H;
Rb' and Rc'each independently represents H;
R1represents hydrogen;
R2represents hydrogen;
R4' represents H;
R5' represents H; and
r is 0, 1 or 2.

34. The compound according to claim 1 or its pharmaceutically acceptable salt having the formula II, where
But a CONHOH;
Represents a CH2;
G represents CH2;
X represents CH2NRb;
Y represents CH2;
M represents CO;
U is absent;
V is a 4-10-membered heterocyclyl containing 1-2 heteroatoms selected from N and S, substituted 0-5 groups Re;
U' is absent or represents a C1-10alkylen or;
V' represents H, C1-8alkyl, NRbRcWith6-10carbocyclic, substituted by 0 to 3 groups of Reor 5-14 membered heterocyclyl containing 1-3 heteroatoms selected from N, O and S, substituted 0-4 groups Re;
Rbrepresents H, C(O)O(CRb'Rc')r-T or S(O)p(CRb'Rc')r-T;
R crepresents H, T or C1-6alkylen-T;
Ra' represents H;
Rb' and Rc'each independently represents H;
R1represents hydrogen;
R2represents hydrogen;
R4' represents H;
R5' represents H; and
r is 0, 1 or 2.

35. The compound according to claim 1 or its pharmaceutically acceptable salt having the formula II, where
But a CONHOH;
Represents a CH2;
G represents CH2;
X represents CH2NRb;
Y represents CH2;
M represents CO;
U is absent;
V represents azetidin-1-yl, 2,5-dihydro-1H-pyrrol-1-yl, piperidine-1-yl, piperazine-1-yl, pyrrolidin-1-yl, ethanol-2-yl, pyridin-1-yl, 3,6-dihydropyridines-1-yl, 2,3-dihydroindol-1-yl, 1,3,4,9-tetrahydrocarboline-2-yl,thieno[2,3-C]pyridine-6-yl, 3,4,10,10A-tetrahydro-1H-pyrazino[1,2-a]indol-2-yl, 1,2,4,4A,5,6-hexahydropyrazino[1,2-a]quinoline-3-yl, pyrazino [1,2-a]quinoline-3-yl, diazepan-1-yl, 1,4,5,6-tetrahydro-2H-benzo[f]isoquinoline-3-yl, 1,4,4A,5,6,10b-hexahydro-2H-benzo[f]isoquinoline-3-yl, 3,3A,8,8A-tetrahydro-1H-2-azacyclopenta[a]inden-2-yl or 2,3,4,7-tetrahydro-1H-azepin-1-yl, azepin-1-yl;
U' is absent;
V' represents a C6-10carbocyclic, substituted by 0 to 3 groups of Re;
Rbrepresents H, C(O)O(CRb'Rc')r -T or C(O)(CRb'Rc')r-T;
Ra' represents H;
Rb' and Rc' both represent H;
R1represents hydrogen;
R2represents hydrogen;
R4' represents H;
R5' represents H; and
r is 0, 1 or 2.

36. The compound according to claim 1 or its pharmaceutically acceptable salt having the formula II, where
But a CONHOH;
Represents a CH2;
G represents CH2;
X represents CHaNRb;
Y represents CH2;
M represents CO;
U is absent;
V represents piperidine-1-yl, piperazine-1-yl, pyrrolidin-1-yl, pyridin-1-yl or 3,6-dihydropyridines-1-yl;
U' is absent;
V' represents a C6-10aryl, substituted 0-3 groups Re;
Rbrepresents H, C(O)O(CRb'Rc')r-T or C(O)(CRb'Rc')r-T;
Rb' and Rc' both represent H;
R1represents hydrogen;
R2represents hydrogen;
R4' represents H;
R5' represents H; and
r is 0, 1 or 2.

37. The compound according to claim 1 or its pharmaceutically acceptable salt having the formula II, where
But a CONHOH;
Represents a CH2;
G represents CH2;
X t is made by a CH 2NRb;
Y represents CH2;
M represents CO;
U is absent;
V represents piperidine-1-yl, piperazine-1-yl, pyrrolidin-1-yl, pyridin-1-yl or 3,6-dihydropyridines-1-yl;
U' is absent;
V' represents phenyl, substituted 0-3 Re;
Rbrepresents H, C(O)O(CRb'Rc')r-T or C(O)(CRb'Rc')r-T;
Rb' and Rc' both represent H;
R1represents hydrogen;
R2represents hydrogen;
R4' represents H;
R5' represents H; and
r is 0, 1 or 2.

38. The compound according to claim 1, selected from the group including:
N-hydroxy-5-methyl-6-{[4-(3-were)piperazine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-5-methyl-6-[(4-phenylpiperazin-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-5-methyl-6-({4-[3-(trifluoromethyl)phenyl]piperazine-1-yl}carbonyl)-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-5-methyl-6-{[4-(2-were)piperazine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;
6-{[4-(4-chlorophenyl)piperazine-1-yl]carbonyl}-N-hydroxy-5-methyl-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-5-methyl-6-{[4-(2-methyl-4-nitrophenyl)piperazine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-5-methyl-6-[(4-phenylpiperazin-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamide;
N-g is droxy-6-[(4-hydroxy-4-phenylpiperidine-1-yl)carbonyl]-5-methyl-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-5-methyl-6-[(4-phenyl-3,6-dihydropyridines-1(2H)-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-5-methyl-6-[(4-quinoline-2-reparation-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamide;
6-{[4-(2,3-dichlorophenyl)piperazine-1-yl]carbonyl}-N-hydroxy-5-methyl-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-5-methyl-6-[(4-quinoline-4-reparation-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-6-methyl-6-{[4-(2-methylinosine-4-yl)piperazine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-5-methyl-6-{[4-(2-phenylethyl)piperazine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-5-methyl-6-[(4-pyridin-4-reparacin-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-5-methyl-6-{[4-(4-nitrophenyl)piperazine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-6-{[4-(2-methoxyphenyl)piperazine-1-yl]carbonyl}-5-methyl-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-5-methyl-6-[(4-phenoxypyridine-l-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamide;
6-(3,4-dihydroisoquinoline-2(1H)-ylcarbonyl)-N-hydroxy-5-methyl-5-azaspiro[2,5]Octan-7-carboxamide;
6-(4,7-dihydrothieno[2,3-C]pyridine-6(5H)-ylcarbonyl)-N-hydroxy-5-methyl-5-azaspiro[2,5]Octan-7-carboxamide;
6-[(3-benzylpyrrolidine-1-yl)carbonyl]-N-hydroxy-5-methyl-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-5-methyl-6-[(4-pyridine-2-reparation-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamide;
N-is hydroxy-5-methyl-6-{[4-(2-pyridin-4-retil)piperidine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-5-methyl-6-({4-[5-(trifluoromethyl)pyridin-2-yl]piperazine-1-yl}carbonyl)-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-5-methyl-6-({4-[3-(trifluoromethyl)pyridin-2-yl]piperazine-1-yl}carbonyl)-5-azaspiro[2,5]Octan-7-carboxamide;
6-(1,4'-bipiperidine-1'-ylcarbonyl)-N-hydroxy-5-methyl-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-5-methyl-6-{[4-(pyridine-2-ylmethyl)piperazine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-5-methyl-6-{[4-(pyridine-4-ylmethyl)piperazine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-5-methyl-6-{[4-(pyridine-3-ylmethyl)piperazine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-5-methyl-6-{[4-(2-were)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-6-{[4-(3-were)piperazine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-5-methyl-6-(1,3,4,9-tetrahydro-2H-β-carbolin-2-ylcarbonyl)-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-5-methyl-6-[(9-methyl-1,3,4,9-tetrahydro-2H-β-carbolin-2-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamide;
6-{[4-(2-forfinal)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-methyl-5-azaspiro[2,5]Octan-7-carboxamide;
6-{[4-(2-chlorophenyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-methyl-5-azaspiro[2,5]Octan-7-carboxamide;
6-{[4-(4-nitrophenyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-methyl-5-azaspiro[2,5]Octan-7-carboxamide;
6-{[4-phenyl-36-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-methyl-5-azaspiro[2,5]Octan-7-carboxamide;
6-{[4-(2-methyl-4-nitrophenyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-methyl-5-azaspiro[2,5]Octan-7-carboxamide;
N(7)-hydroxy-N(6),5-dimethyl-N(6)-(3-phenylpropyl)-5-azaspiro[2,5]octane-6,7-dicarboximide;
N(7)-hydroxy-N(6)-isobutyl-5-methyl-5-azaspiro[2,5]octane-6,7-dicarboximide;
N-hydroxy-5-methyl-6-{[4-(2-nitrophenyl)piperazine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;
N(7)-hydroxy-N(6)-isobutyl-N(6),5-dimethyl-5-azaspiro[2,5]octane-6,7-
dicarboxamide;
N(7)-hydroxy-5-methyl-N(6)-(2-phenoxyethyl)-5-azaspiro[2,5]octane-6,7-dicarboximide;
N(7)-hydroxy-N(6)-[2-(4-methoxyphenyl)ethyl]-5-methyl-5-azaspiro[2,5]octane-6,7-dicarboximide;
N(7)-hydroxy-5-methyl-N(6)-(4-phenylbutyl)-5-azaspiro[2,5]octane-6,7-dicarboximide;
N(7)-hydroxy-5-methyl-N(6)-[3-(2-oxopyrrolidin-1-yl)propyl]-5-azaspiro[2,5]octane-6,7-dicarboximide;
N-hydroxy-5-methyl-6-[(10A)-3,4,10,10A-tetrahydropyrazino[1,2-a]indol-2(1H)-ylcarbonyl]-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-6-(3,4,10,10A-tetrahydropyrazino[1,2-a]indol-2(1H)-ylcarbonyl)-5-azaspiro[2,5]Octan-7-carboxamide;
6-(1,2,4,4A,5,6-hexahydro-3H-pyrazino[1,2-a]quinoline-3-ylcarbonyl)-N-hydroxy-5-methyl-5-azaspiro[2,5]Octan-7-carboxamide;
methyl-7-[(hydroxyamino)carbonyl]-6-[(4-phenyl-3,6-dihydropyridines-1(2H)-yl)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate;
benzyl-7-[(hydroxyamino)carbonyl]-6-[(4-phenyl-3,6-dihydropyridines-1(2H)-yl)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate;
N guide the hydroxy-5-(methylsulphonyl)-6-[(4-phenyl-3,6-dihydropyridines-1(2H)-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-6-{[3-(3-methoxyphenyl)piperidine-1-yl]carbonyl}-5-methyl-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-5-methyl-6-{[3-(2-phenylethyl)pyrrolidin-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-6-{[4-(3-methoxyphenyl)piperidine-1-yl]carbonyl}-5-methyl-5-azaspiro[2,5]Octan-7-carboxamide;
6-{[4-[3-(aminocarbonyl)phenyl]-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-6-{[4-(2-methoxyphenyl)piperidine-1-yl]carbonyl}-5-methyl-5-azaspiro[2,5]Octan-7-carboxamide;
6-{[4-(3-fluoro-2-were)piperazine-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-6-{[4-(2-methyl-3-nitrophenyl)piperazine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;
6-(3',6'-dihydro-3,4'-bipyridine-1'(2 N)-ylcarbonyl)-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;
N(7)-hydroxy-N(6)-(4-methoxyphenyl)-N(6)-methyl-5-azaspiro[2,5]octane-6,7-dicarboximide;
N-hydroxy-6-{[4-(3-methoxyphenyl)piperazine-1-yl]carbonyl}-5-methyl-5-azaspiro[2,5]Octan-7-carboxamide;
6-{[4-(3-chlorophenyl)piperazine-1-yl]carbonyl}-N-hydroxy-5-methyl-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-6-[(4-phenyl-1,4-diazepan-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-6-{[3-methyl-4-(3-were)piperazine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-6-{[4-(3-methoxyphenyl)piperidine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-6-[(4-ISO is utillitariansim-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamide;
6-{[4-(4-cyano-2-were)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;
N(7)-hydroxy-5-methyl-N(6)-{4-[(2-methylinosine-4-yl)methoxy]phenyl}-5-azaspiro[2,5]octane-6,7-dicarboximide;
N(7)-hydroxy-N(6)-{4-[(2-methylinosine-4-yl)methoxy]phenyl}-5-azaspiro[2,5]octane-6,7-dicarboximide;
6-{[4-(4-cyanophenyl)piperazine-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-6-[(4-phenylpiperazin-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-6-[(4-phenylpiperazin-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-6-({4-[3-(methoxymethyl)phenyl]piperidine-1-yl}carbonyl)-5-azaspiro[2,5]Octan-7-carboxamide;
methyl-3-[1-({7-[(hydroxyamino)carbonyl]-5-azaspiro[2,5]Oct-6-yl}carbonyl)piperidine-4-yl]benzoate;
6-[(3-cyclohexylpiperidine-1-yl)carbonyl]-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-6-{[4-(3-isopropylphenyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-6-{[4-(3-isopropylphenyl)piperidine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-6-{[4-(4-propylphenyl)-3,b-dihydropyridines-1(2H)-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-6-{[4-(4-ethylphenyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-6-{[4-(4-ethylphenyl)piperidine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;
6-{[4-(4-cyano-2-were)Pipa is Azin-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-6-{[4-(3-isopropoxyphenyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-6-{[4-(3-were)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-6-{[4-(3-were)piperidine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;
6-{[4-(4-tert-butylphenyl)piperazine-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-6-[(4-pyridin-4-reparation-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamide;
6-[(3-benzylpiperidine-1-yl)carbonyl]-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-6-[(5-methoxy-2,3-dihydro-1H-indol-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-6-({5-[(2-methylinosine-4-yl)methoxy]-2,3-dihydro-1H-indol-1-yl}carbonyl)-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-5-methyl-6-({5-[(2-methylinosine-4-yl)methoxy]-2,3-dihydro-1H-indol-1-yl}carbonyl)-5-azaspiro[2,5]Octan-7-carboxamide;
6-{[5-(benzyloxy)-2,3-dihydro-1H-indol-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;
6-(1,3-dihydro-1 N-Spiro[inden-2,4'-piperidine]-1'-ylcarbonyl)-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-6-{[4-(3-isopropoxyphenyl)piperidine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;
methyl-4-[1-({7-[(hydroxyamino)carbonyl]-5-azaspiro[2,5]Oct-6-yl}carbonyl)-1,2,3,6-tetrahydropyridine-4-yl]-3-methylbenzoate;
N-hydroxy-6-{[4-(2-methyl-4-nitrophenyl)-3,6-dihydropyridin is n-1(2H)-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;
6-{[4-(2-ethylphenyl)piperidine-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;
methyl-4-[1-({7-[(hydroxyamino)carbonyl]-5-azaspiro[2,5]Oct-6-yl}carbonyl)piperidine-4-yl]-3-methylbenzoate;
6-{[4-(2,3-dihydro-1-benzofuran-5-yl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-methyl-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-6-{[4-(3-isopropylphenyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-5-methyl-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-6-{[(3R)-3-phenylpyrrolidine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-6-{[(3S)-3-phenylpyrrolidine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-6-({3-[3-(trifluoromethyl)phenyl]pyrrolidin-1-yl}carbonyl)-5-azaspiro[2,5]Octan-7-carboxamide;
6-{[3-(3-chlorophenyl)pyrrolidin-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;
6-{[3-(3-forfinal)pyrrolidin-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;
6-{[3-(4-forfinal)pyrrolidin-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;
6-{[3-(4-chlorophenyl)pyrrolidin-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-6-({3-[4-(trifluoromethyl)phenyl]pyrrolidin-1-yl}carbonyl)-5-azaspiro[2,5]Octan-7-carboxamide;
6-{[3-(4-methoxyphenyl)pyrrolidin-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;
6-{[3-(4-phenoxyphenyl)pyrrolidin-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-6-{[4-(methoxyphenyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-6-{[4-(4-cyano-3-were)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;
6-{[3-(3-methoxyphenyl)pyrrolidin-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-6-[(3-pyridin-4-iparralde-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-6-{[4-(3, 5dimethylphenyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-6-{[4-(3-trifloromethyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-6-{[5-(methoxymethyl)-4-phenyl-3,6-dihydropyridines-1(2H)-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-6-(1,4,5,6-tetrahydrobenzo[f]isoquinoline-3(2H)-ylcarbonyl)-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-6-{[4-(5-methoxy-2-were)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-6-{[4-(4-methoxy-2-were)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;
6-[(4-cyano-4-phenylpiperidine-1-yl)carbonyl]-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;
ethyl-7-[(hydroxyamino)carbonyl]-6-[(4-phenyl-3,6-dihydropyridines-1(2H)-yl)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate;
propyl-7-[(hydroxyamino)carbonyl]-6-[(4-phenyl-3,6-dihydropyridines-1(2H)-yl)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate;
isopropyl-7-[(hydroxyamino)carbonyl]-6-[(4-phenyl-3,6-dihydropyridines-1(2H)-yl)carbonyl]-5-azaspiro[2,5]about the tan-5-carboxylate;
isobutyl-7-[(hydroxyamino)carbonyl]-6-[(4-phenyl-3,6-dihydropyridines-1(2H)-yl)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate;
N-hydroxy-6-[(5-methyl-4-phenyl-3,6-dihydropyridines-1(2H)-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamid,
or its pharmaceutically acceptable salt.

39. The compound according to claim 1, selected from the group including
6-(1,4,4A,5,6,10b-hexahydrobenzo[f]isoquinoline-3(2H)-ylcarbonyl)-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;
6-{[4-(4-forfinal)-3-hydroxypiperidine-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-6-(3,3A,8,8A-tetrahydroindene[1,2-C]pyrrol-2(1H)-ylcarbonyl)-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-6-{[4-(4-phenyl-1,3-thiazol-2-yl)piperidine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-6-{[4-(4-tert-butyl-1,3-thiazol-2-yl)piperidine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-6-[(4-methyl-4-phenylpiperidine-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-6-{[4-(4-ethyl-1,3-thiazol-2-yl)piperidine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-6-{[(TRANS)-3-methyl-4-phenylpyrrolidine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;
6-{[4-(2-forfinal)piperazine-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;
6-{[4-(3, 5dimethylphenyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-methyl-5-azaspiro[2,5]Octan-7-carboxamide;
tetrahydro-2H-Piran-4-yl-7-((hydroxyamino)is arbonyl)-6-((4-phenylpiperazin-1-yl)carbonyl)-5-azaspiro(2,5)octane-5-carboxylate;
ethyl-7-((hydroxyamino)carbonyl)-6-((4-phenylpiperazin-1-yl)carbonyl)-5-azaspiro(2,5)octane-5-carboxylate;
methyl-7-[(hydroxyamino)carbonyl]-6-[(4-phenylpiperazin-1-yl)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate;
N-hydroxy-6-[(4-pyrazin-2-reparation-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-6-[(4-quinoline-2-reparation-l-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-6-{[3-(5,6,7,8-tetrahydronaphthalen-2-yl)pyrrolidin-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-5-methyl-6-{[(3R)-3-phenylpyrrolidine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;
methyl-7-[(hydroxyamino)carbonyl]-6-{[(3R)-3-phenylpyrrolidine-1-yl]carbonyl}-5-azaspiro[2,5]octane-5-carboxylate;
N-hydroxy-6-[(3-pyridin-3-iparralde-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-6-[(3-pyridin-2-iparralde-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-6-[(3-methyl-3-phenylpyrrolidine-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-6-[(3-phenylaziridine-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-5-methyl-6-[(3-methyl-3-phenylpyrrolidine-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-5-methyl-6-[(3-phenylaziridine-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamide;
6-(1,3,3A,4,5,9b-hexahydro-2H-benzo[e]isoindole-2-ylcarbonyl)-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-6-{[3-(2-naphthyl)the feast of ridin-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-6-{[4-(2-thienyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-6-{[3-(3-thienyl)pyrrolidin-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-6-{[3-(2-thienyl)pyrrolidin-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-6-{[4-(2-thienyl)piperidine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-6-{[3-(2-were)pyrrolidin-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-6-{[3-(4-were)pyrrolidin-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;
5-acetyl-N-hydroxy-6-[(4-phenyl-3,6-dihydropyridines-1(2H)-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-6-{[4-(3-thienyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-6-[(3-phenylpiperidine-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-6-{[4-(3-thienyl)piperidine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;
methyl-6-{[4-(3, 5dimethylphenyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-7-[(hydroxyamino)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate;
6-{[4-(3, 5dimethylphenyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-(methylsulphonyl)-5-azaspiro[2,5]Octan-7-carboxamide;
6-{[4-(3,5-differenl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;
6-{[4-(3,5-dichlorophenyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;
6{[4-[3,5-bis(trifluoromethyl)phenyl]-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-5-(methylsulphonyl)-6-[(4-phenylpiperazin-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamide;
5-formyl-N-hydroxy-6-[(4-phenylpiperazin-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamide;
6-{[4-(3,5-differenl)piperidine-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;
6-{[4-(2,5-dimetilfenil)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;
6-{[4-(2,4,5-trimetilfenil)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;
6-[(4-biphenyl-3-reparacin-1-yl)carbonyl]-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;
6-[(4-dibenzo[b,d]furan-4-reparacin-1-yl)carbonyl]-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;
6-{[4-(2,5-dimetilfenil)piperidine-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;
6-{[4-(2,4,5-trimetilfenil)piperidine-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;
methyl-3-[1-({7-[(hydroxyamino)carbonyl]-5-azaspiro[2,5]Oct-6-yl}carbonyl)-1,2,3,6-tetrahydropyridine-4-yl]-4-methylbenzoate;
6-[(5-phenyl-2,3,4,7-tetrahydro-1H-azepin-1-yl)carbonyl]-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;
6-{[4-[3-(dimethylamino)phenyl]-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;
methyl-3-[1-({7-[(hydroxyamino)carbonyl]-5-azaspiro[2,5]Oct-6-yl}carbonyl)piperidine-4-yl]-4-methylbenzoate;
6-[(5-Penelitian-1-yl)carbonyl]-N-hydroxy-5-azaspiro[2,5]Octan-7-ka is backslid;
6-({4-[3-(dimethylamino)phenyl]piperidine-1-yl}carbonyl)-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;
6-{[4-(2-were)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;
6-[(3-phenyl-2,5-dihydro-1H-pyrrol-1-yl)carbonyl]-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;
6-{[4-(4-cyano-2-were)piperidine-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;
6-[(3,3-dimethyl-4-phenyl-3,6-dihydropyridines-1(2H)-yl)carbonyl]-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;
6-[(3,3-dimethyl-4-phenylpiperidine-1-yl)carbonyl]-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-5-(methylsulphonyl)-6-[(3-phenyl-2,5-dihydro-1H-pyrrol-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamide;
methyl-7-[(hydroxyamino)carbonyl]-6-[(3-phenyl-2,5-dihydro-1H-pyrrol-1-yl)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate;
N-hydroxy-5-methyl-6-[(3-phenyl-2,5-dihydro-1H-pyrrol-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamide;
6-{[4-(4-cyano-3-were)piperidine-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;
6-{[4-[3-(benzyloxy)phenyl]-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;
6-{[4-[3-ethylphenyl]-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;
6-{[4-[3-(ethyloxy)phenyl]-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;
6-{[4-(3-ethylphenyl)piperidine-1-yl]carbon is l}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;
6-{[4-(3-ethoxyphenyl)piperidine-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;
6-{[4-(3-cyclopropylmethyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;
6-{[4-(4-methoxy-3, 5dimethylphenyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;
6-{[4-(3,5-dimethyl-4-methoxyphenyl)piperidine-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;
6-{[4-(4-cyano-3-ethylphenyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;
6-{[4-(4-cyano-3-ethylphenyl)piperidine-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;
6-{[4-(4-cyano-3, 5dimethylphenyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;
6-{[4-(4-cyano-3, 5dimethylphenyl)piperidine-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;
6-{[4-(1,3-benzothiazol-6-yl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-6-{[4-(1-methyl-1H-benzimidazole-6-yl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-6-{[4-(1-methyl-1H-benzimidazole-6-yl)piperidine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;
6-{[4-(4-cyano-3-isopropylphenyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;
6-{[4-(4-cyano-3-isopropylphenyl)piperidine-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-ka is backslid;
6-{[4-(4-cyano-3-ethylphenyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-methyl-5-azaspiro[2,5]Octan-7-carboxamide;
6-{[4-(4-cyano-3, 5dimethylphenyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-methyl-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-6-{[4-(1-ethyl-1H-benzimidazole-6-yl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-6-{[4-(1-methyl-1H-indazol-5-yl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-6-{[4-(1-ethyl-1H-benzimidazole-6-yl)piperidine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-6-{[4-(1-methyl-1H-indazol-5-yl)piperidine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-6-{[4-(1-ethyl-1H-indazol-5-yl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;
tetrahydro-2H-Piran-4-yl-6-{[4-(1-ethyl-1H-benzimidazole-6-yl)piperidine-1-yl]carbonyl}-7-[(hydroxyamino)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate;
methyl-6-{[4-(1-ethyl-1H-benzimidazole-6-yl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-7-[(hydroxyamino)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate;
6-{[4-(1-ethyl-1H-benzimidazole-6-yl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-(methylsulphonyl)-5-azaspiro[2,5]Octan-7-carboxamide;
methyl-6-{[4-(1-ethyl-1H-benzimidazole-6-yl)piperidine-1-yl]carbonyl}-7-[(hydroxyamino)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate;
6-{[4-(1-ethyl-1H-benzimidazole-6-yl)piperidine-1-yl]rbony}-N-hydroxy-5-(methylsulphonyl)-5-azaspiro[2,5]Octan-7-carboxamide;
6-{[4-(4-cyano-2-were)piperidine-1-yl]carbonyl}-N-hydroxy-5-(methylsulphonyl)-5-azaspiro[2,5]Octan-7-carboxamide;
methyl-6-{[4-(4-cyano-2-were)piperazine-1-yl]carbonyl}-7-[(hydroxyamino)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate;
6-{[4-(1-ethyl-1H-benzimidazole-6-yl)piperazine-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;
methyl-6-{[4-(1-ethyl-1H-benzimidazole-6-yl)piperazine-1-yl]carbonyl}-7-[(hydroxyamino)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate;
6-{[4-(1-ethyl-1H-benzimidazole-6-yl)piperazine-1-yl]carbonyl}-N-hydroxy-5-(methylsulphonyl)-5-azaspiro[2,5]Octan-7-carboxamide;
tetrahydro-2H-Piran-4-yl-6-{[4-(4-cyano-2-were)piperazine-1-yl]carbonyl}-7-[(hydroxyamino)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate;
tetrahydro-2H-Piran-4-yl-6-{[4-(1-ethyl-1H-benzimidazole-6-yl)piperazine-1-yl]carbonyl}-7-[(hydroxyamino)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate;
N-hydroxy-6-[(3-methyl-4-phenylpiperidine-1-yl)carbonyl]-5-azaspiro[2,5]Octan-7-carboxamide;
6-{[5-(aminocarbonyl)-4-phenyl-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;
6-{[4-(4-cyanophenyl)-5-methyl-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;
6-{[4-(4-cyanophenyl)-3-methylpiperidin-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;
N-hydroxy-6-{[5-methyl-4-(4-nitrophenyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-5-azaspiro[,5]Octan-7-carboxamide;
N-hydroxy-6-{[5-methyl-4-(3-nitrophenyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;
6-[(4-dibenzo[b,d]furan-2-yl-3,6-dihydropyridines-1(2H)-yl)carbonyl]-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;
6-[(4-dibenzo[b,d]furan-2-reparacin-1-yl)carbonyl]-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;
6-{[4-(3,3-dimethyl-2,3-dihydro-1-benzofuran-5-yl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;
6-{[4-(3,3-dimethyl-2,3-dihydro-1-benzofuran-5-yl)piperidine-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamide;
isopropyl-7-[(hydroxyamino)carbonyl]-6-[(3-phenyl-2,5-dihydro-1H-pyrrol-1-yl)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate;
(3S)-tetrahydrofuran-3-yl-7-[(hydroxyamino)carbonyl]-6-[(3-phenyl-2,5-dihydro-1H-pyrrol-1-yl)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate;
cyclohexyl-7-[(hydroxyamino)carbonyl]-6-[(3-phenyl-2,5-dihydro-1H-pyrrol-1-yl)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate;
tetrahydro-2H-Piran-4-yl-7-[(hydroxyamino)carbonyl]-6-[(3-phenyl-2,5-dihydro-1H-pyrrol-1-yl)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate;
(3S)-tetrahydrofuran-3-yl-7-[(hydroxyamino)carbonyl]-6-[(4-phenylpiperazin-1-yl)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate;
(3R)-tetrahydrofuran-3-yl-7-[(hydroxyamino)carbonyl]-6-[(4-phenylpiperazin-1-yl)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate;
2-methoxyethyl-7-((hydroxyamino)carbonyl)-6-((4-Hairdryer is piperazin-1-yl)carbonyl)-5-azaspiro(2,5)octane-5-carboxylate;
N-hydroxy-6-[(4-phenylpiperazin-1-yl)carbonyl]-5-(phenylsulfonyl)-5-azaspiro[2,5]Octan-7-carboxamide;
propyl-7-[(hydroxyamino)carbonyl)]-6-[(4-phenylpiperazin-1-yl)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate;
isopropyl-7-[(hydroxyamino)carbonyl]-6-[(4-phenylpiperazin-1-yl)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate;
methyl-6-{[4-(3,5-differenl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-7-[(hydroxyamino)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate;
methyl-6-{[4-(3,5-differenl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-7-[(hydroxyamino)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate;
N-hydroxy-6-{[4-(4-isopropylphenyl)piperazine-1-yl]carbonyl}-5-azaspiro[2,5]Octan-7-carboxamide;
6-{[4-(3,5-differenl)piperidine-1-yl]carbonyl}-N-hydroxy-5-(methylsulphonyl)-5-azaspiro[2,5]Octan-7-carboxamide;
6-{[4-(4,5-dimethyl-1,3-thiazol-2-yl)piperidine-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2,5]Octan-7-carboxamid,
or its pharmaceutically acceptable salt.

40. The compound according to claim 1, selected from the group including
(6S,7S)-N-hydroxy-5-methyl-6-{[4-(3-were)piperazine-1-yl]carbonyl}-5-azaspiro[2.5]octane-7-carboxamide;
(6S,7S)-N-hydroxy-5-methyl-6-[(4-phenylpiperazin-1-yl)carbonyl]-5-azaspiro[2.5]octane-7-carboxamide;
(6S,7S)-N-hydroxy-5-methyl-6-({4-[3-(trifluoromethyl)phenyl]piperazine-1-yl}carbonyl)-5-azaspiro[2.5]octane-7-carboxamide;
(6S,7S)-N-hydroxy-5-methyl-6-{[4-(2-were)piperazine-1-yl]carbonyl}-5-asase what about[2.5]octane-7-carboxamide;
(6S,7S)-6-{[4-(4-chlorophenyl)piperazine-1-yl]carbonyl}-N-hydroxy-5-methyl-5-azaspiro[2.5]octane-7-carboxamide;
(6S,7S)-N-hydroxy-5-methyl-6-{[4-(2-methyl-4-nitrophenyl)piperazine-1-yl]carbonyl}-5-azaspiro[2.5]octane-7-carboxamide;
(6S,7S)-N-hydroxy-5-methyl-6-[(4-phenylpiperazin-1-yl)carbonyl]-5-azaspiro[2.5]octane-7-carboxamide;
(6S,7S)-N-hydroxy-6-[(4-hydroxy-4-phenylpiperidine-1-yl)carbonyl]-5-methyl-5-azaspiro[2.5]octane-7-carboxamide;
(6S,7S)-N-hydroxy-5-methyl-6-[(4-phenyl-3,6-dihydropyridines-1(2H)-yl)carbonyl]-5-azaspiro[2.5]octane-7-carboxamide;
(6S,7S)-N-hydroxy-5-methyl-6-[(4-quinoline-2-reparation-1-yl)carbonyl]-5-azaspiro[2.5]octane-7-carboxamide;
(6S,7S)-6-{[4-(2,3-Dichlorophenyl)piperazine-1-yl]carbonyl}-N-hydroxy-5-methyl-5-azaspiro[2.5]octane-7-carboxamide;
(6S,7S)-N-hydroxy-5-methyl-6-[(4-quinoline-4-reparation-1-yl)carbonyl]-5-azaspiro[2.5]octane-7-carboxamide;
(6S,7S)-N-hydroxy-5-methyl-6-{[4-(2-methylinosine-4-yl)piperazine-1-yl]carbonyl}-5-azaspiro[2.5]octane-7-carboxamide;
(6S,7S)-N-hydroxy-5-methyl-6-{[4-(2-phenylethyl)piperazine-1-yl]carbonyl}-5-azaspiro[2.5]octane-7-carboxamide;
(6S,7S)-N-hydroxy-5-methyl-6-[(4-pyridin-4-reparacin-1-yl)carbonyl]-5-azaspiro[2.5]octane-7-carboxamide;
(6S,7S)-N-hydroxy-5-methyl-6-{[4-(4-nitrophenyl)piperazine-1-yl]carbonyl}-5-azaspiro[2.5]octane-7-carboxamide;
(6S,7S)-N-hydroxy-6-{[4-(2-methoxyphenyl)piperazine-1-yl]carbonyl}-5-methyl-5-azaspiro[2.5]octane-7-carboxamide;
(6S,7S)-N-hydroxy-5-methyl-6-[(4-Fe is oxopiperidin-1-yl)carbonyl]-5-azaspiro[2.5]octane-7-carboxamide;
(6S,7S)-6-(3,4-dihydroisoquinoline-2(1H)-ylcarbonyl)-N-hydroxy-5-methyl-5-azaspiro[2.5]octane-7-carboxamide and
(6S,7S)-6-(4,7-dihydrothieno[2,3-C]pyridine-6(5H)-ylcarbonyl)-N-hydroxy-5-methyl-5-azaspiro[2.5]octane-7-carboxamide,
or its pharmaceutically acceptable salt.

41. The compound according to claim 1, selected from the group including
(6S,7S)-6-[(3-benzylpyrrolidine-1-yl)carbonyl]-N-hydroxy-5-methyl-5-azaspiro[2.5]octane-7-carboxamide;
(6S,7S)-N-hydroxy-5-methyl-6-[(4-pyridine-2-reparation-1-yl)carbonyl]-5-azaspiro[2.5]octane-7-carboxamide;
(6S,7S)-N-hydroxy-5-methyl-6-{[4-(2-pyridin-4-retil)piperidine-1-yl]carbonyl}-5-azaspiro[2.5]octane-7-carboxamide;
(6S,7S)-N-hydroxy-5-methyl-6-({4-[5-(trifluoromethyl)pyridin-2-yl]piperazine-1-yl}carbonyl)-5-azaspiro[2.5]octane-7-carboxamide;
(6S,7S)-N-hydroxy-5-methyl-6-({4-[3-(trifluoromethyl)pyridin-2-yl]piperazine-1-yl}carbonyl)-5-azaspiro[2.5]octane-7-carboxamide;
(6S,7S)-6-(1,4'-bipiperidine-1'-ylcarbonyl)-N-hydroxy-5-methyl-5-azaspiro[2.5]octane-7-carboxamide;
(6S,7S)-N-hydroxy-5-methyl-6-{[4-(pyridine-2-ylmethyl)piperazine-1-yl]carbonyl}-5-azaspiro[2.5]octane-7-carboxamide;
(6S,7S)-N-hydroxy-5-methyl-6-{[4-(pyridine-4-ylmethyl)piperazine-1-yl]carbonyl}-5-azaspiro[2.5]octane-7-carboxamide;
(6S,7S)-N-hydroxy-5-methyl-6-{[4-(pyridine-3-ylmethyl)piperazine-1-yl]carbonyl}-5-azaspiro[2.5]octane-7-carboxamide;
(6S,7S)-N-hydroxy-5-methyl-6-{[4-(2-were)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-5-azaspiro[2.5]octane-7-ka is backslid;
(6S,7S)-N-hydroxy-6-{[4-(3-were)piperazine-1-yl]carbonyl}-5-azaspiro[2.5]octane-7-carboxamide;
(6S,7S)-N-hydroxy-5-methyl-6-(1,3,4,9-tetrahydro-2H-(3-carbolin-2-ylcarbonyl)-5-azaspiro[2.5]octane-7-carboxamide;
(6S,7S)-N-hydroxy-5-methyl-6-[(9-methyl-1,3,4,9-tetrahydro-2H-(3-carbolin-2-yl)carbonyl]-5-azaspiro[2.5]octane-7-carboxamide;
(6S,7S)-6-{[4-(2-forfinal)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-methyl-5-azaspiro[2.5]octane-7-carboxamide;
(6S,7S)-6-{[4-(2-chlorophenyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-methyl-5-azaspiro[2.5]octane-7-carboxamide;
(6S,7S)-6-{[4-(4-nitrophenyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-methyl-5-azaspiro[2.5]octane-7-carboxamide;
(6S,7S)-6-{[4-phenyl-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-methyl-5-azaspiro[2.5]octane-7-carboxamide;
(6S,7S)-6-{[4-(2-methyl-4-nitrophenyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-methyl-5-azaspiro[2.5]octane-7-carboxamide;
(6S,7S)-N(7)-hydroxy-N(6),5-dimethyl-N(6)-(3-phenylpropyl)-5-azaspiro[2.5]octane-6,7-dicarboximide;
(6S,7S)-N(7)-hydroxy-N(6)-isobutyl-5-methyl-5-azaspiro[2.5]octane-6,7-dicarboximide,
or its pharmaceutically acceptable salt.

42. The compound according to claim 1, selected from the group including
(6S,7S)-6-(1,4,4A,5,6,10b-hexahydrobenzo[1]isoquinoline-3(2H)-ylcarbonyl)-N-hydroxy-5-azaspiro[2.5]octane-7-carboxamide;
(6S,7S)-6-{[4-(4-forfinal)-3-hydroxypiperidine-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2.5]octane-7-carboxamide;
(S,7S)-N-hydroxy-6-(3,3A,8,8A-tetrahydroindene[1,2-C]pyrrol-2(1H)-ylcarbonyl)-5-azaspiro[2.5]octane-7-carboxamide;
(6S,7S)-N-hydroxy-6-{[4-(4-phenyl-1,3-thiazol-2-yl)piperidine-1-yl]carbonyl}-5-azaspiro[2.5]octane-7-carboxamide;
(6S,7S)-N-hydroxy-6-{[4-(4-tert-butyl-1,3-thiazol-2-yl)piperidine-1-yl]carbonyl}-5-azaspiro[2.5]octane-7-carboxamide;
(6S,7S)-N-hydroxy-6-[(4-methyl-4-phenylpiperidine-1-yl)carbonyl]-5-azaspiro[2.5]octane-7-carboxamide;
(6S,7S)-N-hydroxy-6-{[4-(4-ethyl-1,3-thiazol-2-yl)piperidine-1-yl]carbonyl}-5-azaspiro[2.5]octane-7-carboxamide;
(6S,7S)-N-hydroxy-6-{[(TRANS)-3-methyl-4-phenylpyrrolidine-1-yl]carbonyl}-5-azaspiro[2.5]octane-7-carboxamide;
(6S,7S)-6-{[4-(2-forfinal)piperazine-1-yl]carbonyl}-N-hydroxy-5-azaspiro[2.5]octane-7-carboxamide;
(6S,7S)-6-{[4-(3, 5dimethylphenyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-methyl-5-azaspiro[2.5]octane-7-carboxamide;
tetrahydro-2H-Piran-4-yl-(6S,7S)-7-((hydroxyamino)carbonyl)-6-((4-phenylpiperazin-1-yl)carbonyl)-5-azaspiro(2,5)octane-5-carboxylate;
ethyl-(6S,7S)-7-((hydroxyamino)carbonyl)-6-((4-phenylpiperazin-1-yl)carbonyl)-5-azaspiro(2,5)octane-5-carboxylate;
methyl-(6S,7S)-7-[(hydroxyamino)carbonyl]-6-[(4-phenylpiperazin-1-yl)carbonyl]-5-azaspiro[2.5]octane-5-carboxylate;
(6S,7S)-N-hydroxy-6-[(4-pyrazin-2-reparation-1-yl)carbonyl]-5-azaspiro[2.5]octane-7-carboxamide;
(6S,7S)-N-hydroxy-6-[(4-quinoline-2-reparation-1-yl)carbonyl]-5-azaspiro[2.5]octane-7-carboxamide;
(6S,7S)-N-hydroxy-6-{[3-(5,6,7,8-tetrahydronaphthalen-2-yl)pyrrolidin-1-yl]carbonyl}-5-azaspiro[2.5]octane-7-carboxamide;
(S,7S)-N-hydroxy-5-methyl-6-{[(3R)-3-phenylpyrrolidine-1-yl]carbonyl}-5-azaspiro[2.5]octane-7-carboxamide;
methyl-(6S,7S)-7-[(hydroxyamino)carbonyl]-6-{[(3R)-3-phenylpyrrolidine-1-yl]carbonyl}-5-azaspiro[2.5]octane-5-carboxylate;
(6S,7S)-N-hydroxy-6-[(3-pyridin-3-iparralde-1-yl)carbonyl]-5-azaspiro[2.5]octane-7-carboxamide;
(6S,7S)-N-hydroxy-6-[(3-pyridin-2-iparralde-1-yl)carbonyl]-5-azaspiro[2.5]octane-7-carboxamide,
or its pharmaceutically acceptable salt.

43. The compound according to claim 1, selected from the group including
(6S,7S)-N-hydroxy-6-[(3-methyl-3-phenylpyrrolidine-1-yl)carbonyl]-5-azaspiro[2.5]octane-7-carboxamide;
(6S,7S)-N-hydroxy-6-[(3-phenylaziridine-1-yl)carbonyl]-5-azaspiro[2.5]octane-7-carboxamide;
(6S,7S)-N-hydroxy-5-methyl-6-[(3-methyl-3-phenylpyrrolidine-1-yl)carbonyl]-5-azaspiro[2.5]octane-7-carboxamide;
(6S,7S)-N-hydroxy-5-methyl-6-[(3-phenylaziridine-1-yl)carbonyl]-5-azaspiro[2.5]octane-7-carboxamide;
(6S,7S)-6-(1,3,3A,4,5,9b-hexahydro-2H-benzo[e]isoindole-2-ylcarbonyl)-N-hydroxy-5-azaspiro[2.5]octane-7-carboxamide;
(6S,7S)-N-hydroxy-6-{[3-(2-naphthyl)pyrrolidin-1-yl]carbonyl}-5-azaspiro[2.5]octane-7-carboxamide;
(6S,7S)-N-hydroxy-6-{[4-(2-thienyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-5-azaspiro[2.5]octane-7-carboxamide;
(6S,7S)-N-hydroxy-6-{[3-(3-thienyl)pyrrolidin-1-yl]carbonyl}-5-azaspiro[2.5]octane-7-carboxamide;
(6S,7S)-N-hydroxy-6-{[3-(2-thienyl)pyrrolidin-1-yl]carbonyl}-5-azaspiro[2.5]octane-7-carboxamide;
(6S,7S)-N-hydroxy-6-{[4-(2-thienyl)piperidine-1-yl]carbonyl}-5-azaspiro[2.5]octane-7-carboxamide;
(6S,7S)-N-Ki-the Roxy-6-{[3-(2-were)pyrrolidin-1-yl]carbonyl}-5-azaspiro[2.5]octane-7-carboxamide;
(6S,7S)-N-hydroxy-6-{[3-(4-were)pyrrolidin-1-yl]carbonyl}-5-azaspiro[2.5]octane-7-carboxamide;
(6S,7S)-5-acetyl-N-hydroxy-6-[(4-phenyl-3,6-dihydropyridines-1(2H)-yl)carbonyl]-5-azaspiro[2.5]octane-7-carboxamide;
(6S,7S)-N-hydroxy-6-{[4-(3-thienyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-5-azaspiro[2.5]octane-7-carboxamide;
(6S,7S)-N-hydroxy-6-[(3-phenylpiperidine-1-yl)carbonyl]-5-azaspiro[2.5]octane-7-carboxamide;
(6S,7S)-N-hydroxy-6-{[4-(3-thienyl)piperidine-1-yl]carbonyl}-5-azaspiro[2.5]octane-7-carboxamide;
methyl-(6S,7S)-6-{[4-(3, 5dimethylphenyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-7-[(hydroxyamino)carbonyl]-5-azaspiro[2.5]octane-5-carboxylate;
(6S,7S)-6-{[4-(3, 5dimethylphenyl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-(methylsulphonyl)-5-azaspiro[2.5]octane-7-carboxamide;
(6S,7S)-6-{[4-(3,5-differenl)-3,6-dihydropyridines-1(2H)-yl]carbonyl}-N-hydroxy-5-azaspiro[2.5]octane-7-carboxamide,
or its pharmaceutically acceptable salt.

44. The compound according to claim 1, where the compound is a methyl-(6S,7S)-7-[(hydroxyamino)carbonyl]-6-[(4-phenylpiperazin-1-yl)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate, or its pharmaceutically acceptable salt.

45. The compound according to claim 1, where the compound is a methyl-(6S,7S)-7-[(hydroxyamino)carbonyl]-6-[(4-phenylpiperazin-1-yl)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate.

46. Pharmaceutical composition having the property of inhibitor metalloprotease, tereasa compound according to any one of claims 1 to 45, or its pharmaceutically acceptable salt, and pharmaceutically acceptable carrier.

47. The use of compounds according to any one of claims 1 to 45, or its pharmaceutically acceptable salt for the manufacture of a medicinal product for the treatment of diseases associated with unwanted activity metalloprotease.

48. The use of compounds according to any one of claims 1 to 45, or its pharmaceutically acceptable salt for the manufacture of a medicinal product for the treatment of diseases modulated by metalloproteases.

49. The use of compounds according to any one of claims 1 to 45, or its pharmaceutically acceptable salt for the manufacture of a medicinal product for the treatment of breast cancer.

50. The use of compounds according to any one of claims 1 to 45, or its pharmaceutically acceptable salt for the manufacture of a medicinal product for the treatment of diseases associated with undesirable activity of Her-2 sheddase.

51. The use of compounds according to any one of § § 11-45 or its pharmaceutically acceptable salt for the manufacture of a medicinal product for the treatment of diseases associated with the activity of Her-2 sheddase.

52. The application of § 51, where the disease is a cancer.

53. The application of paragraph 52, where the cancer is a cancer of the breast.

54. The use of compounds according to any one of claims 1 to 45, or its pharmaceutically acceptable salt for the manufacture of a medicinal product for the treatment of diseases linked to the CSO with undesirable activity of ADAM10 or ADAM17.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing new 3,4-dithienyl-substituted maleic anhydrides or maleimides of general formula I: , where X=O, or NR1; R1 and R2=alkyl C1-C4; R3=alkyl C1-C4, or nitrogen- and/or sulphur-containing heterocyclic substitute. The method involves reacting the corresponding 2,5-disubstituted 3-thienyl-acetic acid with the corresponding 2,5-disubstituted 3-halogen acetythiophenes while heating in the presence of a base in a medium of inert organic solvent in atmospheric oxygen with subsequent separation of the end product of general formula I, where X=O, or, if necessary, the latter is converted to a compound of general formula I, where X=NR1, where R1 assumes values given above, by treating it with the corresponding amine. These compounds can be used as photochromes, which are widely used as optical switches in high-capacity data carriers used for recording, processing and storing data.

EFFECT: versatility of the method, ie possibility of obtaining compounds with and without equivalent heterocyclic substitutes using readily available thienyl-acetic acid and halogen ketones of the thiophene family, which considerably widens the assortment of organic photochromic dithienylethenes.

4 cl, 5 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to a quinazoline compound of formula or its pharmaceutically acceptable salts, used as inhibitors of potential-dependant sodium and calcium channels, where R1, R2, R3, R5a, R5, y and x are defined in the formula of invention. The invention also relates to a pharmaceutical composition containing the disclosed compound and to methods of inhibiting one or more of NaV1.2, NaV1.3, NaV1.8, or CaV2.2.

EFFECT: 4-aminoquinazoline antagonists of selective sodium and calcium ion channels.

17 cl, 3 tbl, 1 ex

FIELD: medicine.

SUBSTANCE: invention is related to compounds with common formulae I , III , IV and V , value of radicals such as given in formula of invention. Also suggested invention is related to pharmaceutical composition in the basis of above-mentioned compounds, to their use, and also to method of frequent urination treatment, enuresis and increased activity of urinary bladder.

EFFECT: increased efficiency of diseases treatment, in particular for treatment of frequent urination and enuresis, increased activity of urinary bladder and pain.

16 cl, 406 ex, 73 tbl

V:

FIELD: chemistry.

SUBSTANCE: invention relates to derivatives of 1,3-diiminoisoindoline, and more specifically to N1,N3-bis(5-amino-3-pentyl-1,3,4-thiadiazol-2-ylidene)-2H-isoindole-1,3-diamine. This compound is soluble in organic solvents and can be used for colouring hydrocarbons, synthetic fibre, fats, wax, alcohols, polymers of plastics, rubber.

EFFECT: wider assortment of fat-soluble light tone dyes.

1 cl, 2 dwg, 1 dwg

FIELD: chemistry.

SUBSTANCE: invention relates to inhibitors of leukotriene A4-hydrolase (LTA4H) of formula (II), their enatiomers, racemates and pharmaceutically acceptable salts, as well as a pharmaceutical composition based on said inhibitors and method of treating, preventing or suppressing inflammation and other conditions which are mediated by activity of leukotriene A4-hydrolase. In general formula (II) , X is chosen from a group which consists of NR5, O and S, where R5 is one of H and CH3; Y is O; Z is chosen from a group which consists of O and a bond; W is chosen from a group which consists of CH2 and CHR1-CH2, where R1 is H or OH, and where the carbon group bonded to R1 in the said CHR1-CH2 is not directly bonded to the nitrogen atom which is bonded to the said W; R4 is chosen from a group which consists of H, OCH3 and Cl; R6 is H or F; and R2' and R3' are each independently chosen from a group which consists of: A) H, C1-7alkyl, C3-7cycloalkyl, C3-7cycloalkyl-C1-7alkyl, where each of substitutes (A) is independently substituted with 0 or 1 RQ, where each of said RQ is a carbon atom substitute, which is at least one carbon atom, separate from nitrogen atom; B) HetRa substitute; C) -C1-7alkyl-C(O)Rx; H) -C0-4alkyl-Ar5, where Ar5 is a 5-member heteroaryl, which has one heteroatom, chosen from a group >NRY, and 0 or 1 additional heteroatom -N=, and optionally contains two carbonyl groups, and optionally benzo-condensed; I) -C0-4alkyl-Ar5' , where Ar5' is a 5-member heteroaryl, which contains 3 or 4 nitrogen atoms; M) SO2C1-4alkyl; alternatively, R2' and R3', taken together with a nitrogen atom with which they are bonded, form a heterocyclic ring which contains at least one heteroatom, which is the said bonded nitrogen atom, where the said heterocyclic ring is chosen from a group which consists of i) 4-7-member heterocyclic ring HetRb, where the said 4-7-member heterocyclic ring HetRb has one heteroatom, which is the said bonded nitrogen atom, and is substituted with 0, 1 or 2 identical or different substitutes, where the said substitutes are chosen from a group which consists of -RY, -CN, -C(O)RY, -C0-4alkyl-CO2RY, -C0-4alkyl-C(O)CO2RY, -C0-4alkyl-ORY, -C0-4alkyl-C(O)NRYRZ-, -C0-4alkyl-NRYC(O)RZ-, -C(O)NRZORY, -C0-4alkyl-NRYCO2RY, -C0-4alkyl-NRYC(O)NRYRY, -C0-4alkyl-NRYC(S)NRYRZ, -NRYC(O)CO2RY, -C0-4alkyl-NRWSO2RY, 1,3-dihydrobenzoimidazol-2-on-1-yl, 1-RY-1H-tetrazol-5-yl, RY-triazolyl, 2-RY-2H-tetrazol- 5-yl, -C0-4alkyl-C(O)N(RY)(SO2RY), -C0-4alkyl-N(RY)(SO2)NRYRY, -C0-4alkyl-N(RY)(SO2)NRYCO2RY, halogen, , ,; ii) 5-7-member heterocyclic ring HetRC which has one additional heteroatom separated from the said bonded nitrogen atom by at least one carbon atom, where the said additional heteroatom is chosen from a group which consists of O, S(=O)2 and >NRM, where the said 5-7-member heterocyclic ring HetRC has 0 or 1 carbonyl group and is substituted with 0, 1 or 2 substitutes at identical or different substituted carbon atoms, where the said substitutes are chosen from a group which consists of -C(O)RY and RZ; iii) one of 1H-tetrazol-1-yl, where 1H-tetrazol-1-yl is substituted at the carbon atom by 0 or 1 substitute such as -C0-4alkyl-RZ, -C0-4alkyl-CO2RY; and iv) one of benzimidazol-1-yl, 2,8-diazospiro[4.5]decan-1-on-8-yl, 4-{[(2-tert-butoxycarbonylaminocyclobutanecarbonyl)amino]methyl}piperidin-1-yl, 4-{[(2-aminocyclobutanecarbonyl)amino]methyl}piperidin-1-yl, 9-yl-tert-butyl ether 3,9-diazaspiro[5.5]undecane-3-carboxylic acid, 4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]dec-8-yl, and where substitute HetRa is a 6-member heterocyclic ring, with a carbon atom at the bonding site and contains a >NRM group as a heteroatom, where the said heteroatom is separated from the said carbon atom at the bonding site with at least 1 additional carbon atom; Rk is chosen from a group which consists of H and -C1-4alkyl; RL is chosen from a group which consists of -CO2RS; RS is hydrogen; RM is chosen from a group which consists of RZ, -C(O)RY; RN is chosen from a group which consists of OCH3, CI, F, Br, I, OH, NH2, CN, CF3, CH3 and NO2; RQ is chosen from a group which consists of -CN, -C0-4alkyl-ORY, -C0-4alkyl-CO2RY, -C0-4alkyl-NRYRY, -C0-4alkyl-NRYCORY, -C0-4alkyl-NRYCONRYRZ, -C0-4alkyl-NRYSO2RY; RW is chosen from a group which consists of RY; RX is chosen from a group which consists of -ORY, -NRYRZ, -C1-4alkyl and -C1-4alkyl-RAr; RY is chosen from a group which consists of H, C1-4alkyl, -C0-4alkyl-RAr and -C0-4alkyl-RAr', each of which is substituted with 1 or 2 RN substitutes; RZ is chosen from a group which consists of RY, -C1-2alkyl-CO2RY ; RAr is a radical with a carbon atom at the bonding position, where the said radical is chosen from a group which consists of phenyl, pyridyl and pyrazinyl, where each carbon atom with permissible valence in each of the said groups is independently substituted with at least 0, 1 or 2 RN or 0 or 1 RL; RAr' is a 5-6-member ring which has 1 or 2 heteroatoms, chosen from a group which consists of O, S, N and >NRY, and has 0 or 2 unsaturated bonds and 0 or 1 carbonyl group, where each member with permissible valence in each of the said rings is independently substituted with 0 or 1 or 2 RK; Description is given of inhibitors of leukotriene A4-hydrolase (LTA4H) of formula (II), a composition which contains these inhibitions, and their use for inhibiting activity of the LTA4H enzyme, as well as for treating, preventing or suppressing inflammation and/or conditions which are associated with such inflammation. In the said formula (I): X is chosen from a group which consists of NR5, O and S, where R5 is one of H and CH3; Y is chosen from a group which consists of CH2 and O, W is chosen from a group which consists of CH2 and CHR1-CH2, where R1 is H or OH, and where the carbon group bonded to R1 in the said CHR1-CH2 is not directly bonded to a nitrogen atom; R4 is chosen from a group which consist of H, OCH3, CI, F, Br, OH, NH2, CN, CF3 and CH3; R6 is H or F; and R2 and R3 are each independently chosen from different groups.

EFFECT: new compounds have useful biological activity.

43 cl, 8 tbl, 12 dwg, 484 ex

FIELD: chemistry.

SUBSTANCE: in new compounds with formula (I): (I) A is absent or represents (CH2)2; L is CH or N; M is NR1, O, S, S(O) or S(O)2; R1 is C1-6alkyl, substituted with phenyl {which itself is possibly substituted with halogen, C1-4alkyl, C1-4alkoxy, CF3}; phenyl {which is possibly substituted with halogen, C1-4alkyl, C1-4alkoxy, CF3, C1-4alkylthio}, S(O)2R, S(O)2NR6R7, C(O)R8; R2 is phenyl (which is possibly substituted with halogen, CN or C1-4halogenalkyl), thienyl or halogenthienyl; R3 is hydrogen or methyl; Rb is hydrogen or C1-3alkyl; R4 is a five- or six-member heterocycle, containing at least one carbon atom, one to four nitrogen atoms and, possibly, one oxygen or sulphur atom, where the carbon atom in the said heterocycle R4 is possibly substituted with oxo, C1-6alkyl [which is possibly substituted with halogen, OH, C1-4alkoxy, S(C1-4alkyl) group or piperidinyl {which it self is possibly substituted with benzene [which is possibly substituted with a S(O)2(C1-4alkyl) group], C(O)(C1-4alkoxy) group, C(O)NH2, C(O)NH(C1-4alkyl), C(O)N(C1-4alkyl)2 or S(O)2(C1-4alkyl) [where alkyl is possibly substituted with fluoro]}], C3-6cycloalkyl, CN, C(O)NH2, C(O)NH(phenylC1-2alkyl) group, phenyl [which is possibly substituted with a S(O)2(C1-4alkyl) group] or benzyl [which is possibly substituted with a S(O)2(C1-4alkyl) group]; if possible, the nitrogen atom in the said heterocycle R4 is substituted with C1-6alkyl [which is possibly substituted with C1-4alkoxy, S(O)(C1-4alkyl) group, S(O)2(C1-4alkyl), C(O)(C1-4alkoxy), CONH2, CONH(C1-4alkyl), CON(C1-4alkyl)2, phenyl{which is possibly substituted with C1-4alkyl, C1-4alkoxy, S(O)(C1-4alkyl) group or S(O)2(C1-4alkyl)}, piperidinyl {which is possibly substituted with a S(O)(C1-4alkyl) group or S(O)2(C1-4alkyl)}], C3-6cycloalkyl, CO(C1-4alkyl) group [which is possibly substituted with a halogen], S(O)2(C1-4alkyl) group [which is possibly substituted with fluorine], COO(C1-6alkyl) group, phenyl [which is possibly substituted with a S(O)(C1-4alkyl) or S(O)2(C1-4alkyl) group]; - under the condition that the nitrogen atom in the said heterocycle R4 is substituted with an alky group, the said alkyl does not have C1-4alkoxy, S(O)(C1-4alkyl) or S(O)2(C1-4alkyl) substitute on the carbon atom, bonded to the nitrogen atom in the said heterocycle R4; - five- or six-member heterocyle R4 is possibly condensed with cyclohexane, piperadine, benzole, pyridine, pyridazine, pyrimidine or pyrazine ring; ring carbon atoms in the said condensed cyclohexane, piperadine, benzole, pyridine, pyridazine, pyrimidine or pyrazine ring are possibly substituted with a halogen, C1-4alkyl, C1-4alkoxy, CF3, S(C1-4alkyl), S(O)(C1-4alkyl) or S(O)2(C1-4alkyl) group; and the nitrogen atom of the condensed piperidine ring is possibly substituted with C1-4alkyl [which is possibly substituted with oxo, halogen, OH, C1-4alkoxy, C(O)(C1-4alkoxy), C(O)NH2, C(O)NH(C1-4alkyl) group, C(O)N(C1-4alkyl)2 group, C(O)(C1-4alkyl)group [where alkyl is possibly substituted with C1-4alkoxy or halogen], benzene [which is possibly substituted with S(O)(C1-4alkyl) or S(O)2(C1-4alkyl)], C(O)(C1-4alkoxy), C(O)NH2, C(O)NH(C1-4alkyl), C(O)N(C1-4alkyl)2 or S(O)2(C1-4alkyl) group [where alkyl is possibly substituted with fluoro]; R5 is C1-6alkyl [which is possibly substituted with a halogen (for example fluoro), C1-4alkoxy, phenyl {which itself is possibly substituted with a halogen, C1-4alkyl, C1-4alkoxy}], C3-7cycloalkyl (which is possibly substituted with a halogen or C1-6alkyl), piranyl, phenyl {which is possibly substituted with halogen, C1-4alkyl, C1-4alkoxy}, or a 5- or 6-member saturated nitrogen-containing heterocyclic ring {which is possibly substituted with a S(O)2(C1-4alkyl) or C(O)(C1-4alkyl) group}; R8 is hydrogen, C1-4alkyl [which is possibly substituted with halogen (for example fluro), C1-4alkoxy, phenyl{which itself is possibly substituted with halogen, C1-4alkyl, C1-4alkoxy}], C3-7cycloalkyl (which is possibly substituted with halogen or C1-4alkyl), piranyl, phenyl {which is possibly substituted with halogen, C1-4alkyl, C1-4alkoxy}, or a 5- or 6-member saturated nitrogen-containing heterocyclic ring {which is possibly substituted with S(O)2(C1-4alkyl) or C(O)(C1-4alkyl) group}; R6 and R7 are bonded, forming a 5- or 6-member ring which is possibly substituted with C1-4alkyl; R9 and R10 independently represent hydrogen or C1-6alkyl; or to its pharmaceutically acceptable salts. The invention also relates to a method of obtaining compounds in paragraph 1, to a method of modulating activity of CCR5 receptor, as well as to a pharmaceutical composition.

EFFECT: obtaining new biologically active compounds with modulating effect towards CCR5 receptor.

15 cl, 29 ex, 12 tbl

FIELD: chemistry.

SUBSTANCE: invented compounds have inhibitory activity towards protein kinase. In formula 1a m lies between 0 and 1, R1 is chosen from a group which includes hydrogen, methyl, isopropyl, imidazolylpropyl, piperazinylpropyl, pyridinyl, diethylaminopropyl, hydroxyethyl, pyrimidinyl, morpholinopropyl, phenyl, cyclopropyl, morpholinoethyl, benzyl and morpholino, where any of pyridinyl, imidazolyl, piperazinyl or pyrimidinyl in R1 are optionally substituted with 1-3 radicals, independently chosen from a group, which includes methyl, methylamine, dimethylaminomethyl, cycloproylamine, hydroxyethylamine, diethylaminopropylamine, pyrrolydinylmethyl, morpholino, morpholinomethyl, piperazinylmethyl and piperazinyl, where any of morpholino and piperazinyl in R1 are optionally further substituted with a radical, chosen from a group which includes methyl, hydroxyethyl and ethyl, R2, R3 and R5 each represents hydrogen, R4 represents methyl, L is chosen from a group which includes -NR5C(O)- and -C(O)NR5-, R10 represents trifluoromethyl, and R11 is chosen from a group which includes halogen, morpholinomethyl, piperazinyl, optionally substituted with a methyl, ethyl or hydroxyethyl group; piperazinylmethyl, optionally substituted with a methyl or ethyl group, imidazolyl, optionally substituted with methyl, pyrrolidinylmethoxy and piperidinyl, optionally substituted with a hydroxy group.

EFFECT: more effective treatment.

4 cl, 1 tbl, 3 ex

FIELD: medicine.

SUBSTANCE: invention covers thaizole derivatives of formula (I) and to their pharmaceutically acceptable salts. In formula I: X1 and X2 differ from each other and represent sulphur atom or carbon atom; R1 represents phenyl group; phenyl group substituted by 1-2 members chosen from the group including halogen atoms, alkoxygroup with 1-6 carbon atoms, hydroxygroup, phenylalkoxygroup with 7-12 carbon atoms; phenyl group fused with 5-7-membered heteroaromatic or nonaromatic ring with at least one heteroatom consisting of N, O and S; pyridyl group; R2 represents hydrogen atom, halogen atom, alkyl group with 1-6 carbon atoms, alkyl group with 1-6 carbon atoms substituted by 1-5 halogen atoms, alkoxygroup with 1-6 carbon atoms, or hydroxyalkyl group with 1-5 carbon atoms; A represents group which is presented by formula or . Also, the invention concerns ALK5 inhibitor containing compound of the invention as an active component, stimulators of hair follicles proliferation and hair growth, and also to thiazole derivative of formula where A1 represents .

EFFECT: higher efficiency.

12 cl, 2 tbl, 50 ex, 1 dwg

FIELD: chemistry.

SUBSTANCE: present invention refers to the aminopyridin compound of general formula (I) or its salt wherein X1, X2, X3, Z, Y1, Y2 are carbon or nitrogen atom, R, R1, R5, R6 are hydrogen atom, alkyl group, further see formula of the invention, and R7 is hydrogen or halogen atom, nitro or cyano group, -CpH2(p-1)(Ra1)(Ra2)-O-Ra3, -C(=O)-Rd1, 5-or 6-membered saturated heterocycle group, aromatic heterocycle group, -N(Rh1)(Rh2), further see formula of the invention. The invention refers also to the pharmaceutic composition thereof intended for treatment or prevention of allergic diseases, autoimmune diseases caused by malignant tumour, to the Syk inhibitor containing the compound of formula I and to the therapeutic and/or preventive agent.

EFFECT: compounds which not only possess high Syk inhibition activity but are selective Syk inhibitors are obtained and described.

24 cl, 24 ex, 2 tbl

Cynnamide compound // 2361872

FIELD: chemistry.

SUBSTANCE: invention relates to a compound with formula (I) , where Ar1 is an imidazolyl group, which can be substituted with 1-3 substitutes; Ar2 is a pyridinyl group, pyrimidinyl group or phenyl group, which can be substituted with 1-2 substitutes; X1 is (1) -C≡C- or (2) double bond etc., which can be substituted, R1 and R2 are, for example, C1-6-alkyl group or C3-8-cycloalkyl group, which can be substituted; or to a pharmacologically acceptable salt of the said compound and pharmaceutical drugs for lowering production of Aβ42, containing formula (I) compound as an active ingredient.

EFFECT: wider field of use of the compounds.

26 cl, 1119 ex, 31 tbl

FIELD: medicine.

SUBSTANCE: invention is related to new derivatives (indole-3-yl)heterocyclic compounds of formula 1: , where: A represents 5-member aromatic heterocyclic ring, where X1, X2 and X3 are independently selected from N, O, S, CR; R means H, (C1-4)alkyl; or R, when it is available in X2 or X3, may form 5-8-member ring together with R3; R1 means 5-8-member saturated carbocyclic ring, which unnecessarily contains heteroatom O; R2 means H; or R2 is connected to R7 with creation of 6-member ring, which unnecessarily contains heteroatom O, or where mentioned heteroatom is connected to position 7 of indole ring; R3 and R4 independently mean H, (C1-6)alkyl, which is unnecessarily substituted with OH, (C1-4)alkyloxy; or R3 together with R4 and N, with which they are connected, creates 4-8-member ring, which unnecessarily contains additional heteroatom, selected from O and S, and unnecessarily substituted with OH, (C1-4)alkyl, (C1-4)alkyloxy or (C1-4)alkyloxy-(C1-4)alkyl; or R3 together with R5 creates 4-8-member ring, unnecessarily substituted with OH, (C1-4)alkyl, (C1-4)alkyloxy; or R3 together with R, when present in X2 or X3, creates 5-8-member ring; R5 means H; or R5 together with R3 creates 4-8-member ring, unnecessarily substituted with OH, (C1-4)alkyl, (C1-4)alkyloxy; R5' means H; R6 means one substituent selected from H, (C1-4)alkyl, (C1-4)alkyloxy, halogen; R7 means H, (C1-4)alkyl, (C1-4)alkyloxy, halogen; or R7 is connected to R2 with creation of 6-member ring, which unnecessarily contains additional heteroatom O, and where heteroatom is connected to position 7 of indole ring; or its pharmaceutically acceptable salt. Compounds of formula I display activity of agonists to cannabinoid receptor CB1.

EFFECT: possibility to use them for treatment of pains of various nature.

10 cl, 1 tbl, 42 ex

FIELD: medicine.

SUBSTANCE: invention is related to compounds with common formulae I , III , IV and V , value of radicals such as given in formula of invention. Also suggested invention is related to pharmaceutical composition in the basis of above-mentioned compounds, to their use, and also to method of frequent urination treatment, enuresis and increased activity of urinary bladder.

EFFECT: increased efficiency of diseases treatment, in particular for treatment of frequent urination and enuresis, increased activity of urinary bladder and pain.

16 cl, 406 ex, 73 tbl

V:

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (ZP) , in which U is a CH group, V is an oxygen atom, W is a hydroxyl-substituted heterocycloalkylene group which contains 5 to 7 atoms in the ring, including an N atom as a heteroatom, X is an oxygen atom, Y is , Z is C1-C6-alkylene group. Invention also relates to use of invented compounds to produce compounds of formula (I) , in which A is a nitrogen atom or CH group.

EFFECT: wider field of use of compounds.

6 cl, 2 ex

FIELD: chemistry.

SUBSTANCE: invention relates to formula (I), compounds, , their pharmacologically acceptable salt, solvate and hydrate, where A is an alkylene group, alkenyl group, alkynyl group, heteroalkylene group, cycloalkylene group, heterocylcoalkylene group, arylene group or heteroarylene group, where each of the said groups can be substituted, Q is CR4, X is CR7 or N, Y is CR6 or N, n equals 1, 2 or 3, m equals 1, 2 or 3, R1 is H, F, Cl, Br, I, OH, NH2, alkyl group or heteroalkyl group, R is H, F or Cl, R3 is H, alkyl group, alkenyl group, alkynyl group, heteroalkyl group, cycloalkyl group, heterocycloalkyl group, aryl group, heteroaryl group, alkylaryl group or heteroarylalkyl group, where each of the said groups can be substituted with one, two or more halogen atoms or amino groups, R4 is hydroxy, a group with formula OPO3R92 or OSO3R10 or a heteroalkyl group, containing at least one OH, NH2, SO3R10, PO3R92 or COOH group or ester group of natural amino acid or its derivative, where R9 groups independently represent H, alkyl, cycloalkyl, aryl or aralkyl, and R10 is H, alkyl, cycloalkyl, aryl or aralkyl, and further values of R5, R6, R7 and R8 are given in the formula of invention. The invention also relates to pharmaceutical compositions with antibacterial activity, containing compounds described above, as well as to use of formula (I) compounds and a pharmaceutical composition for treating bacterial infection.

EFFECT: new compounds are obtained and described, which can be used as antibacterial agents and which are effective against multi-drug resistant bacteria.

18 cl, 32 ex

FIELD: pharmacology.

SUBSTANCE: invention concerns compounds of the formula and other compounds listed in cl. 1 of invention claim, and pharmaceutical composition based on them, as well as method of mGluR5 receptor activity inhibition involving claimed compounds.

EFFECT: application in treatment and prevention of diseases mediated by mGluR5 receptor activity.

4 cl, 18 dwg, 1009 ex

FIELD: medicine.

SUBSTANCE: invention refers to the compound of the formula (I) , where R1 is a group of the formula and, in which R2, R3, R4, R5, R6, R7 and R8, each one independently represents a hydrogen atom or C1-6alkyl or its salt, to the method of its producing, to the method of antagonist effect on angiotensin II in the mammal, to the application of compounds of formula (I) as well as to methods of diseases prevention or treatment.

EFFECT: there are produced and provided new compounds that can be applied for prevention or treatment of disturbed circulation.

16 cl, 2 tbl, 9 ex

FIELD: medicine.

SUBSTANCE: invention refers to salt N,2-dimetyl-6-[7-(2-morpholinoethoxy)chinoline-4-iloxy]benzofuran-3-carboxamide, particularly bismaleate N,2-dimetyl-6-[7-(2-morpholinoethoxy)chinoline-4-iloxy]benzofuran-3-carboxamide with antitumor activity.

EFFECT: cancer treatment availability.

11 cl, 35 dwg, 9 tbl, 12 ex

FIELD: chemistry.

SUBSTANCE: present invention refers to compounds of general formula (I) in the state of base salt or acid-addition salt, to method of their preparation and to the pharmaceutical composition thereof In the said formula R1 is (C1-C6)alkyl; (C3-C7)cycloalkyl unsubstituted or substituted once or more than once; (C3-C7)cycloalkylmethyl unsubstituted or substituted once or more than once; phenyl unsubstituted or substituted ; benzyl unsubstituted or substituted once or twice ; thienyl unsubstituted or substituted ; R2 is atom hydrogen or (C1-C3)alkyl; R3 is (C1-C5)alkyl; R4, R5, R6, R7, each R8 and R9 independently represents the atom of hydrogen, atom of halogen, (C1-C7)alkyl, (C1-C5)alkoxy or trifluoromethyl radical; n is 0, 1 or 2; Alk is (C1-C4)alkyl.

EFFECT: new compounds possess useful biological activity.

5 cl, 5 tbl, 4 ex

FIELD: chemistry.

SUBSTANCE: present invention refers to the aminopyridin compound of general formula (I) or its salt wherein X1, X2, X3, Z, Y1, Y2 are carbon or nitrogen atom, R, R1, R5, R6 are hydrogen atom, alkyl group, further see formula of the invention, and R7 is hydrogen or halogen atom, nitro or cyano group, -CpH2(p-1)(Ra1)(Ra2)-O-Ra3, -C(=O)-Rd1, 5-or 6-membered saturated heterocycle group, aromatic heterocycle group, -N(Rh1)(Rh2), further see formula of the invention. The invention refers also to the pharmaceutic composition thereof intended for treatment or prevention of allergic diseases, autoimmune diseases caused by malignant tumour, to the Syk inhibitor containing the compound of formula I and to the therapeutic and/or preventive agent.

EFFECT: compounds which not only possess high Syk inhibition activity but are selective Syk inhibitors are obtained and described.

24 cl, 24 ex, 2 tbl

Cynnamide compound // 2361872

FIELD: chemistry.

SUBSTANCE: invention relates to a compound with formula (I) , where Ar1 is an imidazolyl group, which can be substituted with 1-3 substitutes; Ar2 is a pyridinyl group, pyrimidinyl group or phenyl group, which can be substituted with 1-2 substitutes; X1 is (1) -C≡C- or (2) double bond etc., which can be substituted, R1 and R2 are, for example, C1-6-alkyl group or C3-8-cycloalkyl group, which can be substituted; or to a pharmacologically acceptable salt of the said compound and pharmaceutical drugs for lowering production of Aβ42, containing formula (I) compound as an active ingredient.

EFFECT: wider field of use of the compounds.

26 cl, 1119 ex, 31 tbl

FIELD: chemistry.

SUBSTANCE: present invention relates to novel derivatives of aminobenzimidazole and benzimidazole of general formula (I-b-1), additive salt or stereochemically isomeric form thereof, where G is a single bond or C1-10alkanediyl; R1 is halogenphenyl, pyridyl, pyrazinyl, quinolinyl, benzimidazoly or a radical of formula (c-4), where each of the said monocyclic or bicyclic heterorings can be optionally substituted with 1, 2 or 3 substitutes, independently selected from a group consisting of halogen, hydroxy, C1-6alkyl, C1-6alkyloxy, Ar1C1-6alkyloxy, C1-6alkyloxy-CH2-CH2-O-; m equals 2; Q is hydrogen, amino or mono(C1-4alkyl)amino; R3b is hydrogen or C1-6alkyl; R4a is selected from a group of substitutes consisting of hydrogen, Ar2C1-6alkyl, Het- C1-6alkyl, hydroxy C1-6alkyl, (hydroxyC1-6alkyl)oxy C1-6alkyl, C1-6alkyl, (Ar1C1-6alkyloxy)(hydroxy)C1-6alkyl, aminoC1-6alkyl, mono- and di(C1-6alkyl)amino-C1-6alkyl, carboxyl-C1-6alkyl, C1-6alkyloxycarbonyl C1-6alkyl, aminocarbonylC1-6alkyl, (C1-4alkyloxy)2-P(=O)-C1-6alkyl, aminosulphonylC1-6alkyl; R6a is hydrogen or C1-6alkyl; R6b is hydrogen, C1-6alkyl, Ar1 or Ar1C1-6alkyl; R6c is C1-6alkyl; Alk is C1-6alkanediyl; R9, R10, R11 are each independently selected from halogen, cyano, C1-6alkyl, Het-C1-6alkyl, Ar1C1-6alkyl, cyano C1-6alkyl, C2-6alkenyl, R6b-O-C3-6alkenyl, C2-6alkynyl, Ar1, R6b-O-, R6b-S-, R6b-O- C1-6alkyl-SO2-, polyhalo-C1-6alkyl, polyhaloC1-6alkyloxy, polyhaloC1-6alkylthio, R6c-C(=O)-, R6b-O-C(=O)-, N(R6aR6b)-C(=O)-, R6b-O-C1-6alkyl, R6b-O-C(=O)-C1-6alkyl, N(R6aR6b)-C(=O)-C1-6alkyl, R6c-C(=O)-NR6b-, N(R6aR6b)-S(=O)2-, H2N-C(=NH)-, and R10 and/or R11 can also be hydrogen; Ar1 is phenyl; Ar2 is phenyl; Het is a heteroring selected from imidazolyl or morpholinyl. The invention also relates to a pharmaceutical composition based on formula (I-b-1) compound, use of formula (I-b-1) compound to prepare a medicinal agent and a method of producing formula (I-b-1) compound.

EFFECT: novel aminobenzimidazole and benzimidazole derivatives with antiviral activity are obtained.

15 cl, 8 tbl, 31 ex

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