Selective HDAC6 inhibitors

Abstract

The present invention relates to novel benzohydroxamic compounds of formula (I) and (II) and pharmaceutically acceptable salts, isomers and prodrugs thereof, exhibiting a high selective inhibitory activity against histone deacetylase 6 (HDAC6) enzyme.

Description

Field of the InventionThe present invention relates to novel selective benzohydroxamic inhibitors of histone deacetylase 6 (HDAC6) enzyme and pharmaceutical compositions thereof.Therefore, these compounds are useful in treating diseases associated with HDAC6 activity such as graft rejection, GVHD, myositis, diseases associated with abnormal lymphocyte function, multiple myeloma, non-Hodgkin lymphoma, peripheral neuropathy, autoimmune diseases, inflammatory diseases, cancer and neurodegenerative pathologies.State of the Art of the InventionThe genetic material of eukaryotic cells is organized in a complex and dynamic structure consisting of DNA and proteins, chromatin. The main protein components of chromatin are histones, basic proteins which interact with DNA forming the basic structural unit of chromatin, the nucleosome, the first level of chromosomal compaction within nucleus. The interaction between basic histone residues and DNA acid residues is crucial in determining the nucleosome compaction and the related DNA accessibility to molecular complexes regulating replication and transcription. This interaction is mainly influenced by histone degree of acetylation. Deacetylation of histone N-terminal lysine residues enables protonation of amine group, which carrying a positive charge, interacts with negative charges contained in DNA. Such interaction occurs in a more compact state of chromatin, involving the gene expression silencing. Conversely, acetylation of the same residues prevents ionic bonding formation, leading to a less compact form of chromatin which allows greater DNA exposure and the interaction with macromolecular complexes that activate gene transcription.The degree of histone acetylation is regulated by the activity balance of two classes of enzymes: histone acetyl transferases (histone acetyl-transferases HAT) and histone deacetylase (histone deacetylases HDAC). An alteration of this delicate balance can lead to a loss of cellular homeostasis, commonly found in various human diseases, including cancer, neurological disorders, inflammation, and autoimmune diseases.Histone deacetylases have been so classified as they reversibly catalyse the deacetylation of amine groups of histone N-terminus lysine residues. Subsequently, it has been found that there is a large number of substrates of these enzymes as their activity is also due to non-histone protein which are substrates of HAT enzymes containing N-acetyl-lysine, such as transcription factors, DNA repair enzymes and other nucleus and cytoplasmic proteins.The human HDAC class consists of 18 enzymes, divided into two groups: zinc-dependent HDACs and HDAC NAD-dependent, also known as sirtuins (class II I). Zinc-dependent HDACs are further distributed into four classes: 1 ) Class I, including HDAC1 , 2, 3 and 8, ubiquitous isoenzymes mainly located in the nucleus; 2) Class lla, including HDAC4, 5, 7 and 9, isoenzymes located both in the nucleus and the cytoplasm; 3) Class lib, including HDAC6 and HDAC10, mainly located in the cytoplasm and 4) Class IV, including only HDAC1 1 . Unlike Class I HDACs, Class lla and l ib have a tissue-specific expression.By regulating gene expression and acting on histones and transcription factors, it is clear that these enzymes are involved in a myriad of cellular functions. In addition, by acting on numerous other protein substrates, these enzymes, as well as phosphatases, are involved in many other processes such as signal transduction and cytoskeleton rearrangement.In the recent decades, HDACs have become a well-studied therapeutic target. Several HDAC inhibitors have been synthesized, some of which are currently in advanced clinical trials and four of them have been approved for different types of cancer: Vorinostat and Romidepsin for Cutaneous T-cell lymphoma (CTLC), Belinostat for Cell Peripheral T-cell lymphoma (PTLC) and Panobinostat for multiple myeloma. These last inhibitors can interact to a varying extent with different HDAC isoforms.Despite their clinical efficacy, the use of pan-inhibitors, thus non-selective for a particular isoform, is limited by their toxicity and side effects observed in both preclinical models and, most importantly, in clinical trials. Hence the need for developing HDAC inhibitors with a better pharmacological profile and therapeutic window (efficacy / toxicity ratio).The attention of the scientific community has thus focused on the synthesis and study of selective inhibitors for individual HDAC isoforms, aiming to develop molecules with better pharmacological capabilities.Therefore, the use of HDAC inhibitors can be an important therapeutic or diagnostic tool for pathologies caused by gene expression such as inflammatory disorders, diabetes, diabetes complications, homozygous thalassemia, fibrosis, cirrhosis, acute promyelocytic leukaemia (APL), organ transplant rejection, autoimmune pathologies, protozoal infections, cancers, etc. Selective inhibitors for a HDAC family or for a specific isoform, especially HDAC6, may be particularly useful for treating pathologies related to proliferative disorders and protein accumulation, immune system disorders and neurological and neurodegenerative disease, such as stroke, Huntington's disease, ALS and Alzheimer's disease.Particularly for HDAC6 isoform, different substrates have been identified, such as o tubulin, Hsp90 (Heat Shock Protein 90), cortactin, β-catenin. Modulation of these proteins acetylation by HDAC6 has been correlated with several important processes, such as immune response (Wang et al., Nat. Rev. Drug Disc. (2009), 8(12), 969-981 ; J. Med. Chem. (2012), 55, 639-651 ; Mol. Cell. Biol. (201 1 ), 31 (10), 2066-2078), regulation of microtubule dynamics, including cell migration and cell-cell interaction (Aldana-Masangkay et al., J. Biomed. Biotechnol. (201 1 ), 201 1 , 875824), and degradation of degenerated proteins.In addition, HDAC6 is involved in the process of catabolism of degraded proteins through the complex known as aggresome: HDAC6 is able to bind polyubiquitinated proteins and dynein, thus activating a kind of delivery of denatured proteins along the microtubules to the aggresome (Kawaguchi et al., Cell (2003) 1 15 (6), 727-738).Alteration of this HDAC6 cytoprotective activity has been correlated with various neurodegenerative pathologies such as Parkinson's disease (Outerio et al., Science (2007), 317 (5837), 516-519) and Huntington's disease (Dompierre et al., J. Neurosci. (2007), 27(13), 3571 -3583), wherein the accumulation of degraded proteins is a common pathological feature.Further HDAC6 is involved in regulating many oncological proteins, especially in hematologic tumours, such as various types of leukaemia (Fiskus et al., Blood (2008), 1 12(7), 2896-2905; Rodriguez-Gonzales, Blood (2008), 1 12(1 1 ), abstract 1923) and multiple myeloma (Hideshima et al., Proc. Natl. Acad. Sci. USA (2005), 102(24), 8567-8572). Regulation of a-tubulin acetylation by HDAC6 may be implicated in metastasis onset, wherein cellular motility plays an important role (Sakamoto et al., J. Biomed. Biotechnol. (201 1 ), 201 1 , 875824).International Patent Application WO 201 1 / 021209 discloses 1 ,2,3-triazole compounds having HDAC inhibitory activity.International Patent Application WO 2012 / 178208 discloses compounds with substituted heterocycles such as benzimidazole, benzimidazolone and benzotriazole having a selective HDAC6 inhibitory activity.International Patent Application WO 2015 / 102426 discloses new indole derivatives with HDAC inhibitory activity.International patent application WO 2015 / 087151 discloses new azaindole derivatives with HDAC inhibitory activity.International Patent Application WO 2012 / 106343 discloses HDAC inhibitors and compositions containing the same. Methods of treating diseases and conditions wherein inhibition of HDAC provides a benefit, like a cancer, a neurodegenerative disorder, a peripheral neuropathy, a neurological disease, traumatic brain injury, stroke, hypertension, malaria, an autoimmune disease, autism, autism spectrum disorders, and inflammation, also are disclosed.The paper "Valente et al., Journal of Medicinal Chemistry (2014), 57(14), 6259-6265" describes hydroxamates containing 1 ,3,4-oxadiazole (2) and 2-aminoanilides (3) as histone deacetylase inhibitors. Among these, compounds 2t, 2x, and 3i are described as being the most powerful and selective towards HDAC1 .DefinitionsUnless otherwise defined, all terms of art, notations and other scientific terminology used herein are intended to have the meanings commonly understood by those of skill in the art to which this disclosure pertains. In some cases, terms with commonly understood meanings are defined herein for clarity and / or for ready reference; thus, the inclusion of such definitions herein should not be construed to represent a substantial difference over what is generally understood in the art.The term "halogen" refers herein to fluorine (F), chlorine (CI), bromine (Br), or iodine (I). The term "C1 -C4 alkyl" refers herein to a branched or linear hydrocarbon containing 1 to 4 carbon atoms. Examples of C1 -C4 alkyl groups include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl.The term "aryl" refers herein to mono- and poly-carbocyclic aromatic ring systems (i), wherein individual carbocyclic rings in the poly-carbocyclic ring systems may be fused or attached to each other by a single bond. Suitable aryl groups include, but are not limited to, phenyl, naphthyl and biphenyl.The term "aryloxy" refers herein to O-aryl group, wherein "aryl" is as defined above. The term "alkoxy" refers herein to O-alkyl group, wherein "alkyl" is as defined above. The term "cycloalkyl" refers herein to a saturated or unsaturated hydrocarbon ring, preferably having 4 to 10 carbon atoms. Examples of cycloalkyl include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl.The term "arylalkyl" refers herein to an aryl radical as defined herein, attached to an alkyl radical as defined herein. An example of arylalkyl is benzyl.The term "heterocycle" refers herein to a 4-, 5-, 6-, 7- or 8-membered monocyclic ring which is saturated or unsaturated and consisting of carbon atoms and one or more heteroatoms selected from N, O and S, and wherein the nitrogen and sulphur heteroatoms may optionally be oxidized and the nitrogen heteroatom can be optionally quaternized. The heterocyclic ring may be attached to any heteroatom or carbon atom, provided that the attachment results in the creation of a stable structure. The term also includes any bicyclic system wherein any of the above heterocyclic rings is fused to an aryl or another heterocycle. When the heterocyclic ring is an aromatic heterocyclic ring, it can be defined as a "heteroaromatic ring".The term "unsaturated ring" refers herein to a partially or completely unsaturated ring. For example, an unsaturated C6 monocyclic ring refers to cyclohexene, cyclohexadiene and benzene.The term "substituted" refers herein to mono- or poly-substitution with a defined (or undefined) substituent provided that this single or multiple substitution is chemically allowed.The term "physiologically acceptable excipient" herein refers to a substance devoid of any pharmacological effect of its own and which does not produce adverse reactions when administered to a mammal, preferably a human. Physiologically acceptable excipients are well known in the art and are disclosed, for instance in the Handbook of Pharmaceutical Excipients, sixth edition 2009, herein incorporated by reference.The term "pharmaceutically acceptable salts or derivatives thereof" herein refers to those salts or derivatives which possess the biological effectiveness and properties of the salified or derivatized compound and which do not produce adverse reactions when administered to a mammal, preferably a human. The pharmaceutically acceptable salts may be inorganic or organic salts; examples of pharmaceutically acceptable salts include but are not limited to: carbonate, hydrochloride, hydrobromide, sulphate, hydrogen sulphate, citrate, maleate, fumarate, trifluoroacetate, 2-naphthalenesulphonate, and para-toluenesulphonate. Further information on pharmaceutically acceptable salts can be found in Handbook of pharmaceutical salts, P. Stahl, C. Wermuth, WILEY- VCH, 127-133, 2008, herein incorporated by reference. The pharmaceutically acceptable derivatives include the esters, the ethers and the N-oxides.The terms "comprising", "having", "including" and "containing" are to be understood as open terms (meaning "including, but not limited to") and are to be considered as a support also for terms such as "essentially consist of", "essentially consisting of", "consist of or "consisting of".The terms "essentially consists of", "essentially consisting of" are to be understood as semi-closed terms, meanings that no other ingredient affecting the novel characteristics of the invention is included (therefore optional excipients can be included).The terms "consists of", "consisting of" are to be understood as closed terms.The term "isomers" refers to stereoisomers (or spatial isomers), i.e. diastereoisomers and enantiomers.The term "prodrugs" refers to pharmacologically inactive derivatives, which can undergo in vivo metabolic transformation to afford an active compound included in the general formula of this invention. Many different prodrugs are known in the art (Prodrug approach: an effective solution to overcome side-effects, Patil S.J., Shirote P.J., International Journal of Medical and Pharmaceutical Sciences, 201 1 ,1 -13; Carbamate Prodrug Concept for Hydroxamate HDAC Inhibitors, Jung, Manfred et al., ChemMedChem, 201 1 , 1 193-1 198).The term "pathology" includes one or more of the following autoimmune diseases or disorders: diabetes mellitus, arthritis (including rheumatoid arthritis, juvenile rheumatoid arthritis, osteoarthritis, psoriatic arthritis), multiple sclerosis, severe myasthenia, systemic lupus erythematosus, autoimmune thyroiditis, dermatitis (including atopic dermatitis and eczematous dermatitis), psoriasis, Sjogren's syndrome, including dry keratoconjunctivitis secondary to Sjogren's syndrome, alopecia areata, allergic reactions due to arthropod bites, Chron's disease, stomach ulcer, iritis, conjunctivitis, keratoconjunctivitis, ulcerative colitis, asthma, allergic asthma, lupus erythematous cutaneous, scleroderma, vaginitis, proctitis, reaction to drug, leprosy, lupus erythema, autoimmune uveitis, allergic encephalomyelitis, acute necrotizing haemorrhagic encephalopathy, progressive bilateral idiopathic hearing loss, aplastic anaemia, anaemia, idiopathic thrombocytopenia, policondrite, Wegener's granulomatosis, chronic active hepatitis, Stevens-Jonhson syndrome, idiopathic sprues, lichen planus, Graves's ophthalmopathy, sarcoidosis, primary biliary cirrhosis, posterior uveitis, intestinal pulmonary fibrosis.The term "pathology" refers to one or more of the following neurological or neurodegenerative diseases: Wilson's disease, spinocerebellar ataxia, prion diseases, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis (ALS), amyloidosis, Alzheimer's disease, Alexander's disease, alcoholic liver disease, cystic fibrosis, Pick's disease, spinal muscular atrophy, and Lewy body dementia.The term "pathology" further includes one or more of the following diseases: rheumatoid spondylitis, post-ischemic reperfusion injury, intestinal inflammation, chronic inflammatory pulmonary disease, eczema, asthma, acute respiratory distress syndrome, infectious arthritis, chronic progressive arthritis, deforming arthritis, post-traumatic arthropathy, gouty arthritis, Reiter syndrome, acute sinovitis, acute spondylitis, glomerulonephritis, haemolytic anaemia, aplastic anaemia, neutropenia, graft-versus-host (GVHD), transplant rejection, chronic thyroiditis, Grave's disease, binary primary cirrhosis, contact dermatitis, sunburn, chronic renal failure, Guillain-Barre syndrome, uveitis, otitis media, periodontal disease, pulmonary intestinal fibrosis, bronchitis, sinusitis, pneumoconiosis, pulmonary failure syndrome, pulmonary emphysema, pulmonary fibrosis, silicosis or pulmonary chronic inflammatory diseases.The term "pathology" further comprise one or more of the following diseases: cancer, tumour growth, colon, breast, bone, brain and other cancer (e.g. osteosarcoma, neuroblastoma, colon adenocarcinoma), chronic myeloid leukaemia (CML), acute myeloid leukaemia (AML), acute promyelocytic leukaemia (APL), cardiac cancer (sarcoma, myxoma, rhabdomyoma, fibroma, lipoma and teratoma), lung cancer (e.g. bronchogenic carcinoma, alveolar carcinoma, bronchial adenoma, sarcoma, lymphoma, chondromatous hamartoma, mesothelioma), gastrointestinal cancer (e.g. oesophagus, stomach, pancreas, small intestine, large intestine cancer), genitourinary tract cancer (e.g. kidney, bladder and urethra, prostate, testicular cancer), liver cancer (e.g. hepatocellular carcinoma, cholangiocarcinoma, hepatoblastoma, angiosarcoma, hepatocellular adenoma, haemangioma), bone cancer (e.g. osteogenic sarcoma, fibrosarcoma, fibrous histiocytomas malignant, chondrosarcoma, Ewing's Sarcoma, malignant lymphoma, multiple myeloma, malignant giant cell tumour, chordoma, chondrosteoma, benign chordoma, chondroblastoma, condromixofibroma, osteoid osteoma), nervous system tumours (e.g. skull, meningitis, brain, spinal cord), gynecological tumours (e.g. uterus, cervix, ovaries, vulva and vagina), hematologic cancer (e.g. blood tumours, Hodgkin's disease, non-Hodgkin's disease), skin cancer (e.g. malignant melanoma, basal cell carcinoma, malignant squamous cell tumour, Kaposi's sarcoma, dysplastic naevus, lipoma, angioma, dermatofibroma, cheloid, psoriasis) and adrenal gland tumors (e.g. neuroblastoma).Description of the FiguresFigure 1 : The inhibition of PD-L1 expression in iDC (GMCSF-IL-4 stimulated monocytes). Human monocytes were treated with HDAC6 inhibitors and stimulated with GMCSF-IL-4 for 5days. After incubation, cells were collected and labelled with an anti PD-L1 antibody. Cells were then washed and fluorescence data were acquired using a flow cyto meter (BD FACSVerse). Values on the graphs represent the mean of 3 experiment carried out on 3 different donors (n=3). The expression of PD-L1 is represented by the geometric mean of the fluorescence. * = P<0.05 determined by Student's t test.Figure 2: Compounds 8 and 10 reduce tumor growth in vivo and have comparable efficacy of an anti PD-1 antibody. The arrow indicates the treatment starting day.Figure 3: HDAC6 inhibitors reduces CT-26 tumor growth in vivo and their activity can be improved by combined treatment with anti PD-1 antibody. Statistics was evaluated at day 30 by Student's t test. *, PO.05; **, PO.01 ; ***, P<0.001 . See text for further details.Figure 4: In vivo Treatment with selective HDAC6 inhibitors induced specific T cell response. Splenocytes of animal treated with Compounds 8 and 10 and the combination with anti PD-1 Ab were stimulated with CT-26 derived tumor peptides and the production of IFN-y and TNF-a by CD4 Tcells was quantified by ELISPOT.Figure 5: In vivo Treatment with selective HDAC6 inhibitors induced specific T cell response. Splenocytes of animal treated with Compound 8 and 10 and the combination with anti PD-1 Ab were stimulated with CT-26 derived tumor peptides and the production of IFN-γ and TNF-a by CD8 Tcells was quantified by ELISPOT.Description of the InventionInventors have experimentally found that benzo-hydroxamic compounds, characterized by a pentaheterocyclic central core, exhibit a high and selective inhibitory activity against HDAC6 enzyme.These compounds also demonstrated a low cytotoxicity, thus allowing their chronic use. According to a first aspect, the present invention relates to compounds of formulas (I) and (II) and pharmaceutically acceptable salts, isomers and prodrugs thereof:whereinA = N, O, S in formula (I), while A = N in formula (II);B = C, N;C = N, O in formula (I), while C = N in formula (II);X = CH2, S, NH, O, CD2;n = 0, 1 ;when n = 1 , the carbon atom may be substituted with R 2 and R 3 being independently selected from the group comprising H, D, -Me, -phenyl, -F and -OH or together R 2 and R 3 can form a saturated cyclic moiety, preferably cyclopropane, cyclobutane, cyclopentane or cyclohexane;when n = 1 , R6 may be absent;R4 = R5 = H, F;R is absent or it is selected from the group comprising -H,-NH2, C1 -C4 alkyl, phenyl, phenyl substituted with one or more halogens, arylalkyl, cycloalkyl, methylfuran, cyclobutylmethyl, tetrahydrofuran-2-yl-methyl, 3- (diethylamino)propyl, 2-methoxyethyl, vinyl, 2-(methylsulfanyl)ethyl, 1 -cyclopropylethyl, pyridin-2-yl, (pyridin-3-yl)methyl, 2-(pyridi n-2-yl )ethyl , 2- (thiophen-2-yl)ethyl, 3,4-dimethoxyphenyl, 4-methoxyphenyl, methylpheny, 2-chloro-5- (morpholin-4-sulfonyl)phenyl, 4- [(difluoromethyl)sulfanyl]phenyl, 4- (morpholin-4-sulfonyl)phenyl, 5-(dimethylsulfamoyl)-2-methylphenyl, 3- (trifluoromethyl)phenyl, 4-(trifluoromethyl)phenyl, 2-(morpholin-4-yl) ethyl, 3-(morpholin-4-yl)propyl, 1 -naphthyl, 2,3-dihydro-1 ,4-benzodioxin-6-yl, benzhydryl, 5-indanyl, thiophene and methylthiophene;R2 is absent or it is selected from H, alkyl, cycloalkyl, cycloalkyl-methyl, heteroaryl, phenyl, phenyl substituted with one or more halogens, phenyl substituted with one or more alkoxy groups, phenyl substituted with one or more nitro groups, benzyl, alkyl-substituted benzyl, (2,2-difluorocyclopentyl)methyl, 2-bromo-3-fluorophenyl, (2,2-dimethylcyclopropyl)methyl, 4-hydroxyphenyl, 2-(benzyloxy)ethyl, 2-bromo-4-methoxyphenyl, 2-methyl-quinoline, 3-methylpyridin-4-yl, 4-methanesulfonyl-2-methylphenyl, 2-chloro-4,6-dinitrophenyl, 1 ,3-benzodioxol-5-ylmethyl, or 2-benzyloxyphenyl;R3 is absent or it is selected from H, alkoxyaryl, phenyl, phenyl substituted with CF3, benzyl, pyridyl, alkyl, cycloalkyl, cycloalkyl-methyl, heteroaryl, phenyl substituted with one or more halogens, phenyl substituted with one or more alkoxy groups, phenyl substituted with one or more nitro groups, benzyl, alkyl-substituted benzyl, (2,2-difluorocyclopentyl)methyl, 2-bromo-3-fluorophenyl, (2,2-dimethylcyclopropyl)methyl, 4-hydroxyphenyl, 2-(benzyloxy)ethyl, 2-bromo-4-methoxyphenyl, methyl-2-quinoline, 3-methylpyridin-4-yl, 4-methanesulfonyl-2-methylphenyl, 2-chloro-4,6-dinitrophenyl, 1 ,3-benzodioxol-5-ylmethyl, or 2-benzyloxyphenyl;R6 is a substituted or non-substituted mono or polycyclic residue, optionally partially or totally unsaturated, comprising carbon atoms and optionally one or more heteroatoms selected from N, S or O;or R6 can be selected from:with the proviso that in the compounds of formula (I), when the pentaheterocyclic core is 1 ,3,4-oxadiazole, R6 is not naphthyl.A further class of preferred compounds comprises compounds of formula (I) and (II) and pharmaceutically acceptable salts, isomers and pharmacologically acceptable esters thereof, wherein the pentaheterocyclic core is selected from the group consisting of tetrazole, 1 ,2,4-triazole, 1 ,3,4-oxadiazole, 1 ,2,4-oxadiazole, 1 ,3,4-thiadiazole.Another class of preferred compounds comprises compounds of formula (I) and (II) and pharmaceutically acceptable salts, isomers and pharmaceutically acceptable salts thereof, wherein:A = N, O, S in formula (I), while A = N in formula (II);B = C, N;C = N, O in formula (I), while C = N in formula (II);X— CH2, S;n = 0, 1 ;when n = 1 , the carbon atom may be substituted with R 2 and R 3 being independently selected from the group comprising H, -Me, -phenyl, -Fand -OH or together R 2 and R 3 can form a saturated cyclic moiety, preferably cyclopropane, cyclobutane, cyclopentane or cyclohexane;when n = 1 , R6 may be absent;R4 = R5 = H, F;R is absent or it is selected from the group comprising -H, -NH2, -CH3, -CH2CH3, phenyl, p-fluorophenyl, m-chlorophenyl, p-chlorophenyl, benzyl, methylfuran, cyclopropyl, isobutyl, methylphenyl, trifluorophenyl, thiophene and 2- (morpholin-4-yl) ethyl;R2 is absent or it is selected from H, phenyl, or p-dichlorophenyl;R3 is absent or it is selected from H, o-methoxyphenyl, p-trifluoromethylphenyl, benzyl, or pyridyl;R6 is selected from the roup comprising:wherein:R7 and R8 are independently selected from the group comprising H, D, -CI, -F, -Br, -CF3, -Me, -Et, -OMe, -OBenzyl, -SF5, -OCH2F, -CH2NH2, -NH2, -CH2NMe2, -NMe2, -N(CH2CH2OCH3)2, -COOH, -COOMe, -OH, -NHNH2, -N02, -OEt, -OCHF2, -OiPr, -CHF2, -NEt2,or R7 and R8 together can form a heteropentacyclic moiety (-OCH2O-);R9 = R 0 = -H, -Me, -Et;R is selected from the group comprising -H, -CI, -CH3, -NO2 and -Br.The following compounds of formulas (I) and (II) are particularly preferred:- (S)-N-(1 -(3-(4-(hydroxycarbamoyl)benzyl)-1 ,2,4-oxadiazol-5-yl)-2-(thiazol-4- yl)ethyl)-3,4-dimethoxybenzamide (comp. 1 );- 3,5-difluoro-N-hydroxy-4-((4-methyl-5-(naphthalen-1 -yl)-4H-1 ,2,4-triazol-3- yl)thio)benzamide (comp. 2);- 4-((5-(3-(N,N-dimethylsulfamoyl)phenyl)-1 ,3,4-oxadiazol-2-yl)methyl)-N- hydroxybenzamide (comp. 3);- 3,5-difluoro-N-hydroxy-4-((4-methyl-5-(2-phenylpropan-2-yl)-4H-1 ,2,4-triazol-3- yl)thio)benzamide (comp. 4);- 4-((5-(2,3-dihydrothieno[3,4-b][1 ,4]dioxin-5-yl)-1 H-tetrazol-1 -yl)methyl)-3,5- difluoro-N-hydroxybenzamide (comp. 5);- 3,5-difluoro-N-hydroxy-4-((5-(pyridin-2-yl)-2H-tetrazol-2-yl)methyl)benzamide (comp. 6);- difluoro-N-hydroxy-4-((5-(pyrimidin-2-yl)-2H-tetrazol-2-yl)methyl)benzamide (comp. 7);- N-hydroxy-4-((5-(thiophen-2-yl)-1 H-tetrazol-1 -yl)methyl)benzamide (comp. 8);- 3,5-difluoro-N-hydroxy-4-((4-methyl-5-(4-methyl-2-morpholinothiazol-5-yl)-4H- 1 ,2,4-triazol-3-yl)thio)benzamide (comp. 9);- N-hydroxy-4-((4-methyl-5-(thiophen-2-yl)-4H-1 ,2,4-triazol-3-yl)thio)benzamide (comp. 10);- 4-((5-(furan-2-yl)-2H-tetrazol-2-yl)methyl)-N-hydroxybenzamide (comp. 12);- 3,5-difluoro-N-hydroxy-4-((5-(pyridin-2-yl)-1 H-tetrazol-1 -yl)methyl)benzamide (comp. 13);- 3,5-difluoro-N-hydroxy-4-((4-methyl-5-(pyridin-2-yl)-4H-1 ,2,4-triazol-3- yl)thio)benzamide (comp. 14);- 3,5-difluoro-N-hydroxy-4-((5-(thiophen-2-yl)-1 H-tetrazol-1 -yl)methyl)benzamide (comp. 15);- 3,5-difluoro-N-hydroxy-4-((4-methyl-5-(4-(piperidin-1 -ylmethyl)phenyl)-4H-1 ,2,4- triazol-3-yl)thio)benzamide (comp. 16);- 3,5-difluoro-N-hydroxy-4-((4-methyl-5-(thiophen-2-yl)-4H-1 ,2,4-triazol-3- yl)thio)benzamide (comp. 17);- 3,5-difluoro-4-((5-(furan-2-yl)-2H-tetrazol-2-yl)methyl)-N-hydroxybenzamide (comp. 19);N-hydroxy-4-((5-(pyridin-2-yl)-1 H-tetrazol-1 -yl)methyl)benzamide (comp. 20); - 3-(3,4-dimethoxyphenyl)-N-[(1 S)-1 -[3-[[4-(hydroxycarbamoyl)phenyl]methyl]- 1 ,2,4-oxadiazol-5-yl]-2-thiazol-4-yl-ethyl]propanamide (comp. 21 );- 4-[[5-[4-(trifluoromethyl)phenyl]tetrazol-2-yl]methyl]benzenecarbohydroxamic acid (comp. 23);- 4-[(4,5-diphenyl-1 ,2,4-triazol-3-yl)sulfanyl]benzenecarbohydroxamic acid (comp.24);- 4-[[4-(2-furylmethyl)-5-(1 H-indol-3-yl)-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid;2,2,2-trifluoroacetic acid (comp. 25);- 4-[5-[(3,4-dimethoxyphenyl)methyl]-1 ,3,4-oxadiazol-2- yl]benzenecarbohydroxamic acid (comp. 26);- 4-[[5-benzyl-4-(4-fluorophenyl)-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid;2,2,2-trifluoroacetic acid (comp. 27);- 4-[[4-amino-5-[4-(difluoromethoxy)phenyl]-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 28);- 4-[[5-(4-fluorophenyl)-4H-1 ,2,4-triazol-3-yl]sulfanyl]benzenecarbohydroxamic acid (comp. 29);- 4-[[4-ethyl-5-(4-fluorophenyl)-1 ,2,4-triazol-3-yl]sulfanyl]benzenecarbohydroxamic acid (comp. 30);- 4-[[5-(4-chlorophenyl)tetrazol-2-yl]methyl]benzenecarbohydroxamic acid (comp.31 );- 4-[[5-(5-chloro-2-thienyl)tetrazol-2-yl]methyl]benzenecarbohydroxamic acid (comp. 32);- 4-[[5-(2-fluorophenyl)tetrazol-2-yl]methyl]benzenecarbohydroxamic acid (comp.33);- 4-[[5-(4-fluorophenyl)tetrazol-2-yl]methyl]benzenecarbohydroxamic acid (comp. 34);- 4-[[5-(4-methoxyphenyl)tetrazol-2-yl]methyl]benzenecarbohydroxamic acid (comp. 35);- 4-[(5-benzyltetrazol-2-yl)methyl]benzenecarbohydroxamic acid (comp. 36);- 4-[(5-benzyltetrazol-1 -yl)methyl]benzenecarbohydroxamic acid (comp. 37);- 4-[[5-(2,4-dichlorophenyl)tetrazol-2-yl]methyl]benzenecarbohydroxamic acid (comp. 38);- 4-[[5-(3-methyl-2-thienyl)tetrazol-2-yl]methyl]benzenecarbohydroxamic acid (comp. 39);- 4-[[5-(5-methyl-2-thienyl)tetrazol-2-yl]methyl]benzenecarbohydroxamic acid (comp. 41 );- 4-[[5-(benzothiophen-3-yl)tetrazol-2-yl]methyl]benzenecarbohydroxamic acid (comp. 42);- 4-[[5-(2,3-dihydrothieno[3,4-b][1 ,4]dioxin-5-yl)tetrazol-2- yl]methyl]benzenecarbohydroxamic acid (comp. 43);- 4-[[5-[(3,4-dimethoxyphenyl)methyl]-2-[4-(trifluoromethyl)phenyl]-1 ,2,4-triazol-3- yl]methyl]benzenecarbohydroxamic acid (comp. 44);- 4-[[5-[(3,4-dimethoxyphenyl)methyl]-1 ,3,4-oxadiazol-2- yl]methyl]benzenecarbohydroxamic acid (comp. 45);- 4-[[5-(2-fluorophenyl)tetrazol-2-yl]methyl]benzenecarbohydroxamic acid (comp.46);- 4-[[5-[(1 S)-1 -amino-2-thiazol-4-yl-ethyl]-1 ,2,4-oxadiazol-3- yl]methyl]benzenecarbohydroxamic acid;2,2,2-trifluoroacetic acid (comp. 48);- 4-[[5-(3,4-dimethoxyphenyl)-1 ,2,4-oxadiazol-3- yl]methyl]benzenecarbohydroxamic acid (comp. 49);- 4-[[5-(2-thienyl)tetrazol-2-yl]methyl]benzenecarbohydroxamic acid (comp. 50);- 4-[[2-benzyl-5-(4-chlorophenyl)-1 ,2,4-triazol-3- yl]methyl]benzenecarbohydroxamic acid (comp. 51 );- 4-[[2-(2-pyridyl)-5-(2-thienyl)-1 ,2,4-triazol-3-yl]methyl]benzenecarbohydroxamic acid (comp. 52);- 4-[[2-(2-methoxyphenyl)-5-(2-thienyl)-1 ,2,4-triazol-3- yl]methyl]benzenecarbohydroxamic acid (comp. 53);- 4-[[5-(6,6-dimethyl-3-methylsulfanyl-4-oxo-5,7-dihydro-2-benzothiophen-1 - yl)tetrazol-2-yl]methyl]benzenecarbohydroxamic acid (comp. 54);- 4-[[5-(benzothiophen-2-yl)tetrazol-2-yl]methyl]benzenecarbohydroxamic acid (comp. 55);- 4-[[5-(3,4-dimethoxyphenyl)-1 ,3,4-oxadiazol-2- yl]methyl]benzenecarbohydroxamic acid (comp. 57);- 4-[[5-(2,4-difluorophenyl)-1 ,3,4-oxadiazol-2-yl]methyl]benzenecarbohydroxamic acid (comp. 58);- 4-[[5-[3-(dimethylsulfamoyl)phenyl]tetrazol-2-yl]methyl]benzenecarbohydroxamic acid (comp. 59);- 4-[(5-phenyl-1 ,3,4-oxadiazol-2-yl)amino]benzenecarbohydroxamic acid (comp.60);- 4-[[4-amino-5-[3-(diethylsulfamoyl)phenyl]-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 61 );- 4-[[1 -(2,4-dichlorophenyl)-5-methyl-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 62);- 4-[[5-(3-pyrrolidin-1 -ylsulfonylphenyl)-1 ,3,4-oxadiazol-2- yl]amino]benzenecarbohydroxamic acid (comp. 63);- 4-[[5-(3-morpholinosulfonylphenyl)-1 ,3,4-oxadiazol-2- yl]methyl]benzenecarbohydroxamic acid (comp. 64);- 3,5-difluoro-4-[[5-(2-thienyl)tetrazol-2-yl]methyl]benzenecarbohydroxamic acid (comp. 65);- 4-[[5-[3-(diethylsulfamoyl)phenyl]-4-methyl-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 66);- 4-[[4-methyl-5-[2-(p-tolyl)-4-quinolyl]-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 67);- 4-[(5-phenyl-1 ,3,4-oxadiazol-2-yl)methyl]benzenecarbohydroxamic acid (comp.68);- 4-[[5-(4-pyrrolidin-1 -ylsulfonylphenyl)-1 ,3,4-oxadiazol-2- yl]methyl]benzenecarbohydroxamic acid (comp. 69);- 4-[[5-(3-benzyloxy-4-methoxy-phenyl)tetrazol-2- yl]methyl]benzenecarbohydroxamic acid (comp. 70);- 4-[[5-(3-benzyloxy-4-methoxy-phenyl)tetrazol-1 - yl]methyl]benzenecarbohydroxamic acid (comp. 71 );- 4-[(5-cyclopropyl-1 -phenyl-1 ,2,4-triazol-3-yl)sulfanyl]benzenecarbohydroxamic acid (comp. 72);- 4-[[5-[4-(dimethylamino)phenyl]-4-methyl-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 73);- 4-[[5-(4-methyl-2-morpholino-thiazol-5-yl)-1 ,3,4-oxadiazol-2- yl]methyl]benzenecarbohydroxamic acid (comp. 75);- 4-[[5-[3-(dimethylamino)phenyl]-4-methyl-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 77);- 4-[[5-(3-methoxyphenyl)-4-methyl-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 78);- 4-[[5-(2,3-dihydrothieno[3,4-b][1 ,4]dioxin-5-yl)tetrazol-2-yl]methyl]-3,5-difluoro- benzenecarbohydroxamic acid (comp. 79);- 4-[[5-[3-(dimethylamino)phenyl]-4-methyl-1 ,2,4-triazol-3-yl]sulfanyl]-3,5-difluoro- benzenecarbohydroxamic acid (comp. 80);- tert-butyl 4-[5-[4-(hydroxycarbamoyl)phenyl]sulfanyl-4-methyl-1 ,2,4-triazol-3- yl]piperidine-1 -carboxylate (comp. 82);- 4-[[5-(2,3-dihydro-1 ,4-benzodioxin-3-yl)-4-methyl-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 83);- 4-[[5-(1 ,3-benzodioxol-5-yl)-4-methyl-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 84);- 4-[[5-(1 ,5-dimethylpyrazol-3-yl)-4-methyl-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 85);- 4-[[5-(2-furyl)tetrazol-1 -yl]methyl]benzenecarbohydroxamic acid (comp. 86);- 4-[[5-(1 -isoquinolyl)tetrazol-2-yl]methyl]benzenecarbohydroxamic acid (comp.87) ;- 4-[[5-(1 -isoquinolyl)tetrazol-1 -yl]methyl]benzenecarbohydroxamic acid (comp.88) ;- 4-[[5-(2-pyridyl)tetrazol-2-yl]methyl]benzenecarbohydroxamic acid (comp. 89);- 4-[[5-(2-quinolyl)tetrazol-2-yl]methyl]benzenecarbohydroxamic acid (comp. 90);- 4-[[5-(2-quinolyl)tetrazol-1 -yl]methyl]benzenecarbohydroxamic acid (comp. 91 ); - 3,5-difluoro-4-[[5-(2-furyl)tetrazol-1 -yl]methyl]benzenecarbohydroxamic acid (comp. 92);- 3,5-difluoro-4-[[5-(1 -isoquinolyl)tetrazol-2-yl]methyl]benzenecarbohydroxamic acid (comp. 93);- 3,5-difluoro-4-[[5-(1 -isoquinolyl)tetrazol-1 -yl]methyl]benzenecarbohydroxamic acid (comp. 94);- 3,5-difluoro-4-[[5-(2-quinolyl)tetrazol-2-yl]methyl]benzenecarbohydroxamic acid (comp. 95);- 3,5-difluoro-4-[[5-(2-quinolyl)tetrazol-1 -yl]methyl]benzenecarbohydroxamic acid (comp. 96);- 3,5-difluoro-4-[[5-(2-thienyl)-4H-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 97);- 4-[(5-benzhydryl-4-methyl-1 ,2,4-triazol-3-yl)sulfanyl]-3,5-difluoro- benzenecarbohydroxamic acid (comp. 98);- 4-[[5-(3-aminothieno[2,3-b]pyridin-2-yl)-4-methyl-1 ,2,4-triazol-3-yl]sulfanyl]-3,5- difluoro-benzenecarbohydroxamic acid (comp. 99);- 4-[[5-(1 ,5-dimethylpyrazol-3-yl)-4-methyl-1 ,2,4-triazol-3-yl]sulfanyl]-3,5-difluoro- benzenecarbohydroxamic acid (comp. 100);- 3,5-difluoro-4-[[4-methyl-5-(1 -phenylcyclobutyl)-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 101 );- 3,5-difluoro-4-[[5-[1 -(3-fluorophenyl)cyclopentyl]-4-methyl-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 102);- 3,5-difluoro-4-[[5-[1 -(4-methoxyphenyl)cyclohexyl]-4-methyl-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 103);- 3,5-difluoro-4-[[5-[1 -(4-methoxyphenyl)cyclopropyl]-4-methyl-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp 104);- 4-[[5-[3-(pentafluoro-lambda6-sulfanyl)phenyl]tetrazol-2- yl]methyl]benzenecarbohydroxamic acid (comp. 106);- 4-[[5-[3-(pentafluoro-lambda6-sulfanyl)phenyl]tetrazol-1 - yl]methyl]benzenecarbohydroxamic acid (comp. 107);- 3,5-difluoro- 4-[[5- [3-(pentafluoro- lambda6-sulfanyl)phenyl]tetrazol- 2- yl]methyl]benzenecarbohydroxamic acid (comp. 108);- 3,5-difluoro- 4-[[5- [3-(pentafluoro- lambda6-sulfanyl)phenyl]tetrazol- 1 - yl]methyl]benzenecarbohydroxamic acid (comp. 109);- 4-[[5-[4-(pentafluoro-lambda6-sulfanyl)phenyl]tetrazol- 2- yl]methyl]benzenecarbohydroxamic acid (comp. 1 10);- 4-[[5-[4-(pentafluoro-lambda6-sulfanyl)phenyl]tetrazol-1 - yl]methyl]benzenecarbohydroxamic acid (comp. 1 1 1 );- 3,5-difluoro-4-[[5-[4-(pentafluoro-lambda6-sulfanyl)phenyl]tetrazol-2- yl]methyl]benzenecarbohydroxamic acid (comp. 1 12);- 3,5-difluoro-4-[[5-[4-(pentafluoro-lambda6-sulfanyl)phenyl]tetrazol-1 - yl]methyl]benzenecarbohydroxamic acid (comp. 1 13);- 3,5-difluoro-4-[[4- methyl-5-[3-(4-methyl-4-oxido-piperazin-4-ium-1 -yl)phenyl]- 1 ,2,4-triazol-3-yl]sulfanyl]benzenecarbohydroxamic acid (comp. 1 14);- 3,5-difluoro-4-[[4-(4-fluorophenyl)-5-(1 -piperidylmethyl)-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 1 15);- 3,5-difluoro-4-[[4-(2-furylmethyl)-5-pyrrolidin-1 -yl-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 1 16);- 4-[(4- benzyl-5- morpholino-1 ,2,4-triazol-3-yl)sulfanyl]-3,5-difluoro- benzenecarbohydroxamic acid (comp. 1 17);- 4-[[5-(2,3-dihydrothieno[3,4-b][1 ,4]dioxin-5-yl)-4-methyl-1 ,2,4- triazol-3- yl]sulfanyl]-3,5-difluoro-benzenecarbohydroxamic acid (comp. 1 18);- 3,5-difluoro-4-[[5-(1 -isoquinolyl)-4-methyl-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 121 );- 3,5-difluoro-4-[[4-methyl-5-(2-quinolyl)-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 122);- 4-[(5-pyrimidin-2-yltetrazol-2-yl)methyl]benzenecarbohydroxamic acid (comp.123) ;- 4-[(5-pyrimidin-2-yltetrazol-1 -yl)methyl]benzenecarbohydroxamic acid (comp.124) ;- 3,5-difluoro-4-[(5-pyrimidin-2-yltetrazol-1 -yl)methyl]benzenecarbohydroxamic acid (comp. 125);- 4-[[5-[5-(trifluoromethyl)-2-pyridyl]tetrazol-2-yl]methyl]benzenecarbohydroxamic acid (comp. 126);- 4-[[5-[5-(trifluoromethyl)-2-pyridyl]tetrazol-1 -yl]methyl]benzenecarbohydroxamic acid (comp. 127);- 3,5-difluoro-4-[[5-[5-(trifluoromethyl)-2-pyridyl]tetrazol-2- yl]methyl]benzenecarbohydroxamic acid (comp. 128);- 3,5-difluoro-4-[[5-[5-(trifluoromethyl)-2-pyridyl]tetrazol-1 - yl]methyl]benzenecarbohydroxamic acid (comp. 129);- 4-[[5-[3-morpholino-5-(trifluoromethyl)-2-pyridyl]tetrazol-2- yl]methyl]benzenecarbohydroxamic acid (comp. 130);- 4-[[5-[3-morpholino-5-(trifluoromethyl)-2-pyndyl]tetrazol-1 - yl]methyl]benzenecarbohydroxamic acid (comp. 131 );- 4-[[5-(2-pyridylmethyl)tetrazol-2-yl]methyl]benzenecarbohydroxamic acid;2,2,2- trifluoroacetic acid (comp. 132);- 4-[[5- (2-pyridylmethyl)tetrazol- 1 -yl]methyl]benzenecarbohydroxamic acid;2,2,2- trifluoroacetic acid (comp. 133);- 3,5-difluoro-4-[[5-(2-pyridylmethyl)tetrazol-2-yl]methyl]benzenecarbohydroxamic acid;2,2,2-trifluoroacetic acid (comp. 134);- 3,5-difluoro-4-[[5-(2-pyridylmethyl)tetrazol-1 -yl]methyl]benzenecarbohydroxamic acid;2,2,2-trifluoroacetic acid (comp. 135);- 3,5-difluoro-4-[[4- methyl-5- [1 -phenyl- 5-(2- thienyl)pyrazol-3- yl]-1 ,2,4- triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 136);- 3,5-difluoro-4-[[5-(6-fluoro- 2-methyl-3-quinolyl)- 4-methyl-1 ,2,4-thazol- 3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 137);- 3,5-difluoro-4-[[5-(4-fluorophenyl)-4-(2-morpholinoethyl)-1 ,2,4- triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 138);- 3,5-difluoro-4-[[4-(2-furylmethyl)-5-pyrazin-2-yl-1 ,2,4-thazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 139);- 3,5-difluoro-4-[[4-(2-furylmethyl)-5-(2-pyhdyl)-1 ,2,4-thazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 140);- 4-[[4-benzyl-5-(pyrrolidin-1 -yl-methyl)-1 ,2,4-triazol-3-yl]sulfanyl]-3,5-difluoro- benzenecarbohydroxamic acid (comp. 141 );- 4-[[4-benzyl-5-(2-furyl)-1 ,2,4-thazol-3-yl]sulfanyl]-3,5-difluoro- benzenecarbohydroxamic acid (comp. 142);- 4-[[4-benzyl-5-(2-thienyl)-1 ,2,4-triazol-3-yl]sulfanyl]-3,5-difluoro- benzenecarbohydroxamic acid (comp. 143);- 3,5-difluoro-4-[[4-(2-furylmethyl)-5-(2-thienyl)-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 144);- 3,5-difluoro-4-[[5-(2-fluorophenyl)-4-(2-furylmethyl)-1 ,2,4- triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 145);- 3,5-difluoro-4-[[4-(2-furylmethyl)-5-(4-pyridyl)-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 146);- 3,5-difluoro-4-[[4-(2-furylmethyl)-5-(3-pyridyl)-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 147);- 3,5-difluoro-4-[[5-(3-isoquinolyl)-4-methyl-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 148);- 3,5-difluoro-4-[(5- imidazo[1 ,2-a]pyridin-3-yl-4-methyl-1 ,2,4-triazol- 3- yl)sulfanyl]benzenecarbohydroxamic acid (comp. 149);- 4-[[5-(1 -benzyl-4-phenyl-4-piperidyl)-4-methyl-1 ,2,4-triazol-3-yl]sulfanyl]- 3,5- difluoro-benzenecarbohydroxamic acid (comp. 150);- 3,5-difluoro-4-[[4-methyl-5-[3-(4-methylpiperazin-1 -yl)sulfonylphenyl]-1 ,2,4- triazol-3-yl]sulfanyl]benzenecarbohydroxamic acid (comp. 151 );- 4-[[5-[3-(4-benzylpiperazin-1 -yl)sulfonylphenyl]-4-methyl-1 ,2,4- triazol-3- yl]sulfanyl]-3,5-difluoro-benzenecarbohydroxamic acid (comp. 152);- 3,5-difluoro-4-[[4-methyl-5-(3-pyridyl)-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 153);- methyl 4-[[2-[[2,6-difluoro-4-(hydroxycarbamoyl)phenyl]methyl]tetrazol-5- yl]methyl]benzoate (comp. 154);- methyl 4-[[1 -[[2,6-difluoro-4-(hydroxycarbamoyl)phenyl]methyl]tetrazol-5- yl]methyl]benzoate (comp. 155);- methyl 6-[2-[[4-(hydroxycarbamoyl)phenyl]methyl]tetrazol-5-yl]pyridine-3- carboxylate (comp. 156);- methyl 6-[1 -[[4-(hydroxycarbamoyl)phenyl]methyl]tetrazol-5-yl]pyridine-3- carboxylate (comp. 157);- 4-[[2-[[4-(hydroxycarbamoyl)phenyl]methyl]tetrazol-5-yl]methyl]benzoic acid (comp. 158);- 4-[[1 -[[4-(hydroxycarbamoyl)phenyl]methyl]tetrazol-5-yl]methyl]benzoic acid (comp. 159);- 4-[[2-[[2,6-difluoro-4-(hydroxycarbamoyl)phenyl]methyl]tetrazol-5- yl]methyl]benzoic acid (comp. 160);- 4-[[1 -[[2,6-difluoro-4-(hydroxycarbamoyl)phenyl]methyl]tetrazol-5- yl]methyl]benzoic acid (comp. 161 );- 6-[2-[[4-(hydroxycarbamoyl)phenyl]methyl]tetrazol-5-yl]pyridine-3-carboxylic acid (comp. 162);- 3-[2-[[4-(hydroxycarbamoyl)phenyl]methyl]tetrazol-5-yl]benzoic acid (comp. 163);- 3,5-difluoro-4-[[4-methyl-5-(8-quinolylmethyl)-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 164);- 4-[[5-(2,6-difluorophenyl)-4-methyl-1 ,2,4-triazol-3-yl]sulfanyl]-3,5-difluoro- benzenecarbohydroxamic acid (comp. 165);- 3,5-difluoro-4-[[4-methyl-5-[3-(4-methylpiperazin-1 -yl)phenyl]-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 166);- 4-[[5-[3-(azepan-1 -ylmethyl)phenyl]-4-methyl-1 ,2,4-triazol-3-yl]sulfanyl]-3,5- difluoro-benzenecarbohydroxamic acid (comp. 167);- 4-[[5-[4-(azepan-1 -ylmethyl)phenyl]-4-methyl-1 ,2,4-triazol-3-yl]sulfanyl]-3,5- difluoro-benzenecarbohydroxamic acid (comp. 168);- 4-[[5-(4-aminophenyl)tetrazol-2-yl]methyl]benzenecarbohydroxamic acid (comp.169) ;- 4-[[5-(4-aminophenyl)tetrazol-1 -yl]methyl]benzenecarbohydroxamic acid (comp.170) ;- 4-[[5-(4-aminophenyl)tetrazol-2-yl]methyl]-3,5-difluoro-benzenecarbohydroxamic acid (comp. 171 );- 4-[[5-(4-aminophenyl)tetrazol-1 -yl]methyl]-3,5-difluoro-benzenecarbohydroxamic acid (comp. 172);- 4-[[5-[4-(aminomethyl)phenyl]tetrazol-2-yl]methyl]benzenecarbohydroxamic acid (comp. 173);- 4-[[5-[4-(aminomethyl)phenyl]tetrazol-1 -yl]methyl]benzenecarbohydroxamic acid (comp. 174);- 4-[[5-[4-(aminomethyl)phenyl]tetrazol-2-yl]methyl]-3,5-difluoro- benzenecarbohydroxamic acid (comp. 175);- 4-[[5-[4-(aminomethyl)phenyl]tetrazol-1 -yl]methyl]-3,5-difluoro- benzenecarbohydroxamic acid (comp. 176);- 3,5-difluoro-4-[[4-methyl-5-[1 -(2-pyridyl)cyclopropyl]-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 177);- 3,5-difluoro-4-[[4-methyl-5-[1 -(3-pyridyl)cyclopropyl]-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 178);- 3,5-difluoro-4-[(4-methyl-5-pyridazin-3-yl-1 ,2,4-triazol-3- yl)sulfanyl]benzenecarbohydroxamic acid (comp. 179);- 3,5-difluoro-4-[[5-(3-fluoro-2-pyridyl)-4-methyl-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 180);- 3,5-difluoro-4-[[4-methyl-5-[3-(1 -piperidylmethyl)phenyl]-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 181 );- 3,5-difluoro-4-[[4-methyl-5-[3-(morpholinomethyl)phenyl]-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 182);- 4-((3-((1 H-indol-3-yl)methyl)-5-(thiophen-2-yl)-4H-1 ,2,4-triazol-4-yl)methyl)-N- hydroxybenzamide (comp. 183);- 4-[[5-[3-[[benzyl(methyl)amino]methyl]phenyl]-4-methyl-1 ,2,4-triazol-3-yl]sulfanyl]- 3,5-difluoro-benzenecarbohydroxamic acid (comp. 184);- 4-[[3-[(3,4-dimethoxyphenyl)methyl]-5-(2-thienyl)-1 ,2,4-triazol-4- yl]methyl]benzenecarbohydroxamic acid (comp. 185);- 3,5-difluoro-4-[[4-methyl-5-[1 -methyl-1 -(3-pyridyl)ethyl]-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 186);- 3,5-difluoro-4-[[5-[4-[methyl(methylsulfonyl)amino]phenyl]-1 ,3,4-thiadiazol-2- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 187);- 4-[(5-phenyl-1 ,3,4-oxadiazol-2-yl)sulfanyl]benzenecarbohydroxamic acid (comp.188) ;- 4-[(5-phenyl-1 ,2,4-oxadiazol-3-yl)methyl]benzenecarbohydroxamic acid (comp.189) ;- 4-[(5-phenyl-1 ,3,4-thiadiazol-2-yl)methyl]benzenecarbohydroxamic acid (comp.190) ;- 3,5-difluoro-N-hydroxy-4-((5-(pyridin-3-yl)-1 ,3,4-thiadiazol-2-yl)thio)benzamide (comp. 191 );- 3,5-difluoro-4-[(5-phenyl-1 ,3,4-oxadiazol-2-yl)sulfanyl]benzenecarbohydroxamic acid (comp. 192);- 4-[[5-(2-morpholino-4-pyridyl)-1 ,2,4-oxadiazol-3- yl]methyl]benzenecarbohydroxamic acid (comp. 193);- 3,5-difluoro-N-hydroxy-4-((5-phenyl-1 ,2,4-oxadiazol-3-yl)methyl)benzamide(comp. 194);- 3,5-difluoro-4-[[5-(4-pyridyl)-1 ,3,4-thiadiazol-2- yl]methyl]benzenecarbohydroxamic acid (comp. 195);- 4-[[5-(5-bromo-3-pyridyl)-1 ,3,4-thiadiazol-2-yl]sulfanyl]-3,5-difluoro- benzenecarbohydroxamic acid (comp. 196);- 3,5-difluoro-4-[[5-(5-morpholino-3-pyridyl)-1 ,3,4-thiadiazol-2- yl]methyl]benzenecarbohydroxamic acid (comp. 197);- 3,5-difluoro-N-hydroxy-4-((5-phenyl-1 ,3,4-thiadiazol-2-yl)methyl)benzamide(comp. 198);- 3,5-difluoro-4-[[5-(2-furyl)-4-methyl-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 199);- 4-[[5-[5-[bis(2-methoxyethyl)amino]-3-pyridyl]-1 ,2,4-oxadiazol-3-yl]methyl]-3,5- difluoro-benzenecarbohydroxamic acid (comp. 200);- 3,5-difluoro-4-[[5-[5-(2-oxa-6-azaspiro[3.3]heptan-6-yl)-3-pyridyl]-1 ,2,4-oxadiazol- 3-yl]methyl]benzenecarbohydroxamic acid (comp. 201 );- 3,5-difluoro-4-[[5-[5-(pyrrolidin-1 -ylmethyl)-2-furyl]-1 ,2,4-oxadiazol-3- yl]methyl]benzenecarbohydroxamic acid (comp. 202);- 3,5-difluoro-4-[[4-methyl-5-[5-(morpholinomethyl)-3-furyl]-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 203);- 3,5-difluoro-4-[[4-methyl-5-[5-(morpholinomethyl)-2-furyl]-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 204);- 3,5-difluoro-4-[[4-methyl-5-[5-[(4-methylpiperazin-1 -yl)methyl]-2-furyl]-1 ,2,4- triazol-3-yl]sulfanyl]benzenecarbohydroxamic acid (comp. 205);- 4-[[5-[5-[(dimethylamino)methyl]-2-furyl]-4-methyl-1 ,2,4-triazol-3-yl]sulfanyl]-3,5- difluoro-benzenecarbohydroxamic acid (comp. 206);- 3,5-difluoro-4-[[4-methyl-5-[5-(pyrrolidin-1 -ylmethyl)-2-furyl]-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 207);- 4-[[5-[5-ethyl-4-(pyrrolidin-1 -ylmethyl)-2-furyl]-4-methyl-1 ,2,4-triazol-3-yl]sulfanyl]- 3,5-difluoro-benzenecarbohydroxamic acid (comp. 208);- 4-[[4-methyl-5-[5-[(4-methylpiperazin-1 -yl)methyl]-2-furyl]-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 209);- 3,5-difluoro-4-[[4-methyl-5-[6-(2-pyrrolidin-1 -ylethyl)-3-pyridyl]-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 210);- 4-[[5-[5-(diethylaminomethyl)-2-furyl]-4-methyl-1 ,2,4-triazol-3-yl]sulfanyl]-3,5- difluoro-benzenecarbohydroxamic acid (comp. 21 1 );- 3,5-difluoro-4-[[4-methyl-5-[5-(1 -piperidylmethyl)-2-furyl]-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 212);- 4-[[5-[5-(diethylaminomethyl)-2-methyl-3-furyl]-4-methyl-1 ,2,4-triazol-3- yl]sulfanyl]-3,5-difluoro-benzenecarbohydroxamic acid (comp. 213);- 4-[(5-phenyltetrazol-2-yl)methyl]benzenecarbohydroxamic acid (comp. 214);- 4-[(5-phenyltetrazol-1 -yl)methyl]benzenecarbohydroxamic acid (comp. 215);- 4-[(5-phenyl-4H-1 ,2,4-triazol-3-yl)methyl]benzenecarbohydroxamic acid (comp.216);- N-hydroxy-4-((4-methyl-5-phenyl-4H-1 ,2,4-triazol-3-yl)methyl)benzamide (comp. 217).The following compounds of formulas (I) and (II) are particularly preferred:Compounds of the present invention may contain one or more chiral centres (asymmetric carbon atoms), therefore they may exist in enantiomeric and / or diastereoisomeric forms.All possible optical isomers, alone or in a mixture with each other, fall within the scope of the present invention.Compounds according to the invention may be used alone or in combination with other drugs such as proteasome inhibitors, immunochemical inhibitors, steroids, bromodomain inhibitors and other epigenetic drugs, traditional chemotherapeutic agents, kinase inhibitors, such as, for example, but not limited to, JAK family, CTLA4, PD1 or PDL1 checkpoints inhibitors, such as nivolumab, pemprolizumab, pidilizumab or BMS-936559 (anti-PD1 ), atezolizumab or avelumab (anti-PDL1 ), ipilimumab or tremelimumab (anti-CTLA4).The compounds of the invention alone or in combination are preferably useful for the treatment of HDAC6-mediated diseases.The compounds of the invention alone or in combination are preferably useful for the treatment of graft rejection, GVHD, myositis, diseases associated with abnormal lymphocyte functions, multiple myeloma, non-Hodgkin lymphoma, peripheral neuropathy, autoimmune diseases, inflammatory diseases, cancer and neurodegenerative diseases, ocular diseases (e.g. uveitis).Therefore, the present invention also provides pharmaceutical compositions comprising a therapeutically effective amount of compounds of formula (I) or (II) or pharmaceutically acceptable salts, isomers and pharmacologically acceptable prodrugs thereof, together with at least one pharmaceutically acceptable excipient.Such compositions can be liquid, suitable for enteral or parenteral administration, or solid, for example, in the form of capsules, tablets, pills, powders or granules for oral administration, or in forms suitable for cutaneous administration such as creams or ointments, or for inhalation delivery.The pharmaceutical compositions of the present invention can be prepared by using known methods.General Synthetic PathwayThe compounds described in the present invention can be prepared by using methods known to those skilled in the art.All starting materials, reagents, acids, bases, solvents and catalysts used in the synthesis of the described compounds are commercially available.Reaction progression was monitored by HPLC, UPLC or HPLC-MS analysis.The triazole-thiol core compounds were obtained by reaction of 1 ,2,4-triazole-thiols, optionally substituted with methyl-4-iodo-benzoate or methyl-3,4,5-trifluoro-benzoate, in the presence of potassium carbonate in DMF under heating overnight. The reaction with methyl 4-iodo-benzoate was catalysed with copper iodide and L-proline (Scheme 1 ) and was heated at 120°C (Liang-Feng et al., Tetrahedron (201 1 ), 67, 2878-2881 ). On the other hand, the reaction with methyl 3,4,5-trifluoro-benzoate proceeds even under mild conditions (55°C) and without catalysis (Scheme 2) (Dudutiene et al., Bioorg. Med. Chem. (2013), 27(7), 2093-2106; WO03 / 062225).The same conditions were used to synthesize 1 ,3,4-thiadiazole-2-thiol and 1 ,3,4-oxadiazole-2-thiol core compounds.The conversion of ester derivatives into the corresponding hydroxamic acids was achieved by treating with a large excess of aqueous hydroxylamine in a basic medium (NaOH), in methanol. Hydroxamic acid can also be synthesized by methyl ester hydrolysis with NaOH and subsequent condensation with hydroxylamine, upon activation with HATU or other coupling reagents.Scheme 1 - Synthesis of Benzohydroxamic Derivatives with Triazole, Thiadiazole and Oxadiazole CoreScheme 2 - Synthesis of 3,5-Difluorobenzohvdroxamic Derivatives with Triazole, Thiadiazole and Oxadiazole CoreMany of the starting 1 ,2,4-triazole-thiols are commercially available. In some cases they have been synthesized according to the two routes shown in Scheme 3. The open intermediate was prepared from carboxylic acid by activation with T3P and condensation with A / -substituted hydrazine carbothioamide in the presence of DIPEA in DMF (US2007 / 0232808). The same intermediate was obtained starting from hydrazide, which was treated with A / -substituted isothiocyanate in refluxing ethanol (Lei et al., ChemMedChem (2016), 1 1 , 822-826; Nadjet et al., Molecules (2015), 20, 16048-16067). Cyclization of the open intermediate was achieved by addition of aqueous NaOH to the reaction mixture.Scheme 3 - Synthesis of 1 ,2,4-Triazole-thiols1 ,3,4-thiadiazole-2-thiols not commercially available were synthesized by treating the corresponding hydrazide with KOH and CS2 at low temperature (0-5°C) for 1 hour and with H2SC in a second step, as described in Scheme 4.Scheme 4 - Synthesis of 1 ,3,4-Thiadiazole-thiolsCompounds with triazole core were prepared as described in Scheme 5a starting from 2-(4-(methoxycarbonyl)phenyl)acetic acid by reaction with a carboxyimidamide in the presence of HATU and DIPEA in DMF. Upon complete conversion of starting products into the intermediate, a substituted hydrazine and an excess of acetic acid were added to the reaction mixture. The formation of triazole cycle was achieved by heating the mixture overnight (Castanedo et al., J. Org. Chem. (201 1 ), 76(4), 1 177-1 179).Compounds with 1 ,3,4-thiadiazole and 1 ,3,4-oxadiazole scaffold were also obtained by cyclization of an open intermediate, prepared by condensation of 2-(4-(methoxycarbonyl)phenyl)acetic acid or 2-(2,6-difluoro-4- (methoxycarbonyl)phenyl)acetic acid with appropriate hydrazide by usual HATU, DIPEA activation. Hydrazides were either commercially available or could be easily prepared from the corresponding carboxylic acid (Scheme 5c). Lawesson's Reagent was used as cyclizing agent for 1 ,3,4-thiadiazole derivatives, while the same intermediate cyclized upon treatment with an excess of Burgess' Reagent in refluxing toluene or THF to provide 1 ,3,4-oxadiazoles (Scheme 5b). As 2-(2,6-difluoro-4-(methoxycarbonyl)phenyl)acetic acid is not commercially available, it was synthesized reacting methyl 3,4,5-trifluorobenzoate and di-ter-butyl malonate in presence of sodium hydride in anhydrous DMF. The resulting di-tert-butyl 2-(2,6-difluoro-4-(methoxycarbonyl)phenyl)malonate was then decarboxylated by treating with TFA under reflux (Scheme 5c).Due to the lower reactivity of 2-(2,6-difluoro-4-(methoxycarbonyl)phenyl)acetic acid, it was necessary to activate it with thionyl chloride to achieve the condensation (Scheme 5c).The conversion of ester derivatives into the corresponding hydroxamic acids was achieved by hydroxylaminolysis, as already described in the above cases.Scheme 5 - Synthesis of Benzohydroxamic Derivatives with Triazole, Thiadiazole andOxadiazole Core1 ,3,4-oxadiazol derivatives were used as starting material for the synthesis of compounds bearing triazole core. The conversion was obtained by heating the oxadiazole in THF in presence of MeNH2, as described in Scheme 6.Scheme 6 - Synthesis of 1 ,2,3-Triazole derivatives.Compounds bearing a 3,4,5-trisubstituted 1 ,2,4-triazole as a scaffold were prepared starting from methyl p-aminomethylbenzoate hydrochloride and the corresponding acylchloride in presence of trimethylamine. The amide thus obtained was refluxed in thionyl chloride to form an intermediate imidoyi chloride, which gave the desired product upon reaction with the corresponding hydrazide and subsequent cyclization in refluxing toluene (Scheme 7). (WO201 1 106650 (A2)— 201 1 -09-01 ; Begum et al Med. Chem. Commun. 2015, 6, 80-89; Aster et al. Bioorg. Med. Chem. Lett. 2008, 78, 2799-2804.)The compounds containing tetrazole moiety were obtained by reaction of Λ / -Η -tetrazole with methyl 4-(chloromethyl)benzoic acid or methyl 4-(chloromethyl)-3,5-difluoro benzoate in the presence of potassium carbonate in acetonitrile, under heating (Scheme 8) (WO2012 / 106995).2,5-sustituted1 ,5-substitutedScheme 8 - Synthesis of Benzo-hydroxamic and 3,5-DifluoroBenzo-Hydroxamic Derivatives with Tetrazole CoreRegioselectivity is dependent on the tetrazole substrate, usually being the 2,5-disubstituted product 2-10 fold favoured with respect to the 1 ,5-disubstituted product. The regioisomers, separated by chromatography on silica, were treated separately with an excess of hydroxylamine and aqueous sodium hydroxide to obtain the respective hydroxamic products.Some of the starting A / -H-tetrazoles are commercially available while others were synthesized by treating the respective nitrile with sodium azide and ammonium chloride in DMF under heating (Scheme 9).Scheme 9 - Synthesis of Λ / Η-TetrazolesCompounds containing the 2-amino-1 ,3,4-oxadiazole moiety were obtained by combining an acyl hydrazide with methyl 4-isocyanatobenzoate in THF at room temperature (rt) and refluxing the intermediate just formed in the presence of an excess of Burgess Reagent (Scheme 10) (Dolman et 71 (25), 9548).Scheme 10 - Synthesis of Benzo-Hydroxamic Derivatives with 2-Amino-1 ,3,4-Oxadiazole CoreConversion of ester compounds into hydroxamic acid has been achieved, as described in the above cases, by hydroxylaminolysis.The 1 ,2,4-oxadiazole core compounds were synthesized from 4-(cyanomethyl)benzoic acid, or from the corresponding methyl ester, by treatment with hydroxylamine hydrochloride in the presence of an excess of potassium hydroxide or sodium bicarbonate in refluxing ethanol (Scheme 1 1 ). The (Z)-4-(2-amino-2-(hydroxyimino)ethyl)benzoic acid thus obtained was then reacted with a suitable carboxylic acid previously activated with HATU and DIPEA or other activators to give an open intermediate, which undergoes cyclization by heating at 100°C and in the presence of molecular sieves or cyclizing agents, such as carbonildiimidazole.Scheme 1 1 - Synthesis of Benzohydroxamic Derivatives with 1 ,2,4-Oxadiazole CoreThe conversion of the carboxylic acid into hydroxamic acid can be accomplished with any method known in the art. Generally it is obtained by activation with HATU, DCC or acyl chloride and reaction of the activated compound with aqueous hydroxylamine. In some cases it has been necessary to condense the carboxylic acid with 0-(tetrahydro-2H-pyran-2-yl)hydroxylamine in order to obtain an hydroxamic acid protected form which can be released by treatment with TFA (Scheme 12).Scheme 12 - Conversion of the carboxylic acid into hydroxamic acid through a protected form thereofFor the synthesis of compounds with 1 ,3,4-oxadiazole core (Scheme 13) the appropriate hydrazide was prepared by reaction of the corresponding acid, activated by acyl chloride, with Boc-hydrazine and subsequent deprotection by TFA treatment. The hydrazide was then condensed with 2-(4-(methoxycarbonyl)phenyl)acetic acid, previously activated with HATU and DIPEA. The cyclisation of the open intermediate achieved by treatment with an excess of Burgess Reagent in toluene or THF under ux.Scheme 13 - Synthesis of Hydroxamic Derivatives with 1 ,3,4-Oxadiazole CoreAs previously shown, it is possible to obtain the final hydroxamic derivative by methyl ester hydroxylaminolysis reacting it with hydroxylamine, in the presence of a large excess of sodium hydroxide.The following examples are intended to further illustrate the invention but not limiting it.EXAMPLE 1 - Synthesis of (S)-N-(1 -(3-(4-(hydroxycarbamoyl)benzyl)-1 ,2,4-oxadiazol-5-yl)-2-(thiazol-4yl)ethyl-3,4-dimethoxybenzamide (comp. 1 )Step ATo a solution of 4-(cyanomethyl)benzoic acid (3.04 g, 1 eq) in EtOH (250 ml), KOH (3.17 g, 3 eq) and hydroxylamine hydrochloride (2.62 g, 2 eq) were added. The reaction mixture was refluxed 20 hours. The solution was then cooled, diluted with water (300 ml) and acidified to pH 6 with cone. HCI. The precipitated white solid was filtered and dried under vacuum at 50°C overnight. 2.6g of product were obtained, which was used for the next step without any further purification.Step B(S)-2-(A / -Fmoc-amino)-3-(thiazol-4-il)propanoic acid (2g, 1 eq) was activated by treatment with HATU (2.5 g, 1 .3 eq) and DIPEA (1 .4 ml) in DMA at room temperature for 1 hour. Additional DIPEA (1 .4 mL) and (Z)-4-(2-amino-2-(hydroxyimino)ethyl)benzoic acid (985 mg, 1 eq) were then added to the reaction mixture. After complete dissolution of the starting products, molecular sieves were added in order to remove the forming water and aid the cyclization of the open intermediate. After two hours, the molecular sieves were removed by filtration and the solvent evaporated under reduced pressure. The residue was taken up in methanol. The white solid separating was removed by filtration. The solvent was partially evaporated. An additional precipitation of a white solid was observed, which was filtered. The solution was evaporated to dryness and the residue was purified by reverse phase flash chromatography (C-is) in H2O / ACN / TFA gradient.Step CThe acid obtained in step B (82 mg, 1 eq) was activated by treatment with HATU (73 mg, 1 .3 eq) and DIPEA (41 μ1 .3 eq) in DMF at room temperature. 0-(tetrahydro-2H-pyran-2-yl)hydroxylamine (17 mg, 1 eq) was then added to the reaction mixture. After 2 hours stirring at room temperature, the solvent was evaporated in a vacuum centrifuge. The residue was used for the next step without any further purification.Step DThe product obtained in step C was diluted in 1 ml of THF and treated with DEA (70 μΙ, 4.5 eq). After 4h stirring at 40°C, the solvent and the excess of DEA were removed by evaporation under reduced pressure. The residue was taken up with 1 ml of DMF and 3,4-dimethoxybenzoic acid (27 mg, 1 eq), previously activated with HATU (74 mg, 1 .3 eq) and DIPEA (41 μ1 .3 eq) in DMF (1 ml), was added to the solution. The reaction mixture was stirred at room temperature 4 hours. Finally, 0.4 ml of TFA was added to deprotect the hydroxamic functionality. After 4 hours, the solvent and the excess of TFA were removed by evaporation and the residue was purified via semipreparative LC-MS (m / z 509.84 [MH+]).The following compound was synthesized using the same procedure:EXAMPLE 2- Synthesis of (S)-4 -((5-(1 -amino-2-(thiazol-4-yl)ethyl)-1 ,2,4-oxadiazol-3-yl)methyl)-N-hvdroxybenzamide 2,2,2-trifluoroacetate (comp, 48)(9H-Fluoren-9-yl)methyl((1 S)-1 -(3-(4-(((tetrahydro-2H-pyran-2-yl)oxy)carbamoyl)benzyl)-1 ,2,4-oxadiazol-5-yl)-2-(thiazol-4-yl)ethyl)carbamate (obtained in Step C of Synthesis of Compound 1 ) (222 mg, 1 eq) was treated with DEA (159 μΙ, 4.5 eq) in DMF (1 ml) overnight at RT. Then 0.520 ml of TFA (20 eq) were added to the reaction mixture. Solvent was removed by evaporation and the residue was purified in semipreparative LC-MS (m / z 346.04 [MH+]).Example 3 - Synthesis of 4-rr5-(3,4-dimethoxyphenyl)-1 ,2,4-oxadiazol-3-yllmethyllbenzenecarbohydroxamic acid (comp. 49)Step AA mixture of 4-(cyanomethyl)benzoic acid (3 g, 1 eq), hydroxylamine hydrochloride (2.6 g, 2 eq) and potassium hydroxide (3.2 g, 3 eq) in ethanol (250 ml) was heated overnight under reflux. After cooling to RT, 300 ml of water and 15 ml of 1 N HCI (pH ~ 5) were added to the reaction mixture. The desired product, obtained as a precipitate, wasfiltered off on a sintered septum and dried under vacuum overnight. 320 mg of clean product was recovered.Step B(Z)-4-(2-amino-2-(hydroxyimino)ethyl)benzoic acid (319 mg, 1 .1 eq) obtained in step A was dissolved in toluene (6 ml) and pyridine (3 ml) was added. 3,4-Dimethoxybenzoyl chloride (300 mg, 1 eq), previously prepared by reacting 3,4-dimethoxybenzoic acid with an excess of thionyl chloride, was added to the reaction mixture. The reaction mixture was refluxed 4 hours. Solvent was evaporated under reduced pressure and the product was purified by semipreparative LC-MS.Step C4-((5-(3,4-dimethoxyphenyl)-1 ,2,4-oxadiazol-3-yl)methyl)benzoic acid (71 mg, 1 eq) obtained in Step B was activated by treating with HATU (103 mg, 1 .3 eq) and DIPEA (47 μΙ, 1 .3 eq) in DMF (1 ml.) 30 minutes at room temperature. Hydroxylamine hydrochloride (14 mg, 1 eq) and additional DIPEA (47 μΙ, 1 .3 eq) were then added to the reaction mixture. After stirring at room temperature overnight, the solvent was removed evaporating under reduced pressure and the residue was purified by semipreparative LC-MS. 33 mg of clean product was recovered (m / z 356.08 [MH+]).Example 4. Synthesis of 4-((5-(2,4-difluorophenyl)-1 ,3,4-oxadiazol-2-yl)methyl)-N-hydroxybenzamide (comp. 58)Step AA solution of Boc-hydrazine (150 mg, 1 eq) in ACN (2 ml) and 95 mg of NaHCOs (1 eq) were added to a solution of 2,4-difluorobenzoyl chloride (200 mg, 1 eq) in ACN (3 ml). After three hours at RT, solvent was evaporated in air flow. Residue was treated with TFA for three hours. Acid was removed in air stream and the residue was taken up with EtOAc and washed with 2.5% NaHCOs solution. The combined organic phases were dried on Na2S04, filtered and evaporated to dryness. 159 mg of product was obtained, which was used for the next step without any further purification.Step BHATU (439 mg, 1 .3 eq) and DIPEA (0.4 mL, 2.6 eq) were added to a solution of 2-(4-(methoxycarbonyl)phenyl)acetic acid (224 mg, 1 .3 eq) in 5 ml of THF). The reaction mixture was stirred at room temperature for 1 h until complete dissolution of reagents. A solution of 2,4-difluorobenzohydrazide (153 mg, 1 eq) in THF (2 ml) was then added to the mixture. After 4 hours at RT, complete conversion of the starting reagents to the desired product was observed. Solvent was removed by evaporation in air stream. The residue was taken up in H2O and the formed precipitate was filtered on a sintered septum. The product (149 mg) was used in the subsequent step without any further purification.Step C175 mg of Burgess Reagent (1 .72 eq) was added to a suspension of compound obtained in Step B (149 mg, 1 eq) in 5 ml of dry toluene heated under reflux. After one hour, complete conversion of the starting compound into the cyclic product was observed. Solvent was removed evaporating under vacuum. The residue was taken up with DCM and washed with 1 N HCI and H2O. Organic phase was dried on Na2S04, filtered and evaporated to dryness. 132.3 mg of product was recovered, which was used in the following step without any further purification.Step D0.707 ml of aqueous hydroxylamine (60 eq) was added to a solution of compound obtained in step C (132 mg, 1 eq) in 4 ml of MeOH / THF. 1 ,998 ml of 1 N NaOH (5 eq) was slowly added dropwise. Approximately after one hour, the system was neutralized by addition of 1 N HCI (2 ml). The solvent was evaporated under vacuum and the residue was diluted with a 2.5% NaHC03 solution, filtered and washed with H2O. Solid was suspended in Et20 and filtered. 53 mg of pure product was obtained (m / z 332.01 [MH+]).The following compounds were synthesized using the same procedure:Example 5. Synthesis of 4-r(5-phenyl-1 ,3,4-oxadiazol-2-vDaminolbenzenecarbohydroxamic acid (comp. 60)Step A68 mg of benzohydrazide (1 eq) and methyl 4-isocyanobenzoate (88.5 mg, 1 eq) were mixed in THF (5 mL) at room temperature. The resulting solution was stirred for 3 hours. The intermediate formation was verified by HPLC and LC-MS. The solvent was removed by evaporation under reduced pressure. The residue was taken up with toluene. The mixture was refluxed and Burgess Reagent (298 mg, 2.5 eq) was added in small portions until complete conversion of the intermediate into cyclic product. After cooling down to room temperature, washing with water was carried out. The organic phase was dried, filtered and evaporated to dryness. The product was purified by crystallization from DCM. 172 mg of clean product was obtained (Dolman et al., J. Org. Chem. (2006), 77(25), 9548).Step BThe ester obtained in step A (172 mg, 1 eq) was suspended in 4 ml of methanol and the reaction mixture was cooled with ice bath at 0°C and magnetically stirred. After hydroxylamine (50%, aqueous solution, 1 .365 ml, 40 eq) addition, 1 M sodium hydroxide (6 ml, 10 eq) aqueous solution was slowly added dropwise. The ice bath was removed, allowing the solution to reach room temperature. The conversion of the starting product into hydroxamic acid was confirmed by HPLC after 1 hour. The methanolic portion was removed evaporating under reduced pressure, and the reaction was subsequently quenched by adding 6 ml of 1 M HCI aqueous solution and 6 ml of ethyl acetate. The phases were separated and the aqueous layer was re-extracted with additional ethyl acetate (3x). The organic phases were combined and washed with sodium bicarbonate saturated solution (2x), brine (2x), dried over sodium sulphate, filtered, and concentrated to dryness. 26 mg of pure product was recovered (m / z 297.09 [MH+]).The following compound was synthesized using the same procedure:Example 6. Synthesis of 3,5-difluoro-N-hvdroxy-4-((4-methyl-5-(pyridin-2-yl)-4H-1 ,2,4-triazol-3-yl)thio)benzamide (comp. 14)Step A2-Pyridylcarboxylic acid (123 mg, 1 eq) and 4-methyl-3-thiosemicarbazide (1 16 mg, 1 .1 eq) were suspended in 2 ml of DMF and the mixture was cooled to 0°C with an ice bath. T3P (50% DMF solution, 893 μΙ_, 1 .5 eq) and diisopropylethylamine (310 μΙ_, 1 .78 eq) were added slowly to the reaction mixture under stirring. The ice bath was removed and the mixture was reacted at room temperature for 16 hours. The complete conversion of the starting material was confirmed by HPLC. 2 ml of ethyl acetate, 2 ml of water and 2 ml of 4M NaOH aqueous solution were added to the reaction mixture. The phases were separated, and the organic layer was re-extracted with 4M NaOH aqueous solution. The combined aqueous phases were stirred 16 hours at 70°C. Conversion of the open intermediate into the desired product was confirmed by LC-MS. The reaction mixture pH was adjusted to 5 by dropwise addition of cone, hydrochloric acid under stirring. The precipitate was collected by filtration.157 mg of product was obtained, which was used in the following step without any further purification.Step B4-Methyl-5-(pyridin-2-yl)-4H-1 ,2,4-triazole-3-thiol (157 mg, 1 eq), methyl 3,4,5-trifluorobenzoate (156 mg, eq) and potassium carbonate (261 mg, 2.3 eq) were suspended in 2 ml of DMF under an argon atmosphere. The resulting mixture was warmed to 40°C and stirred overnight.The reaction mixture was diluted with 10 ml of ethyl acetate and 10 ml of water. The phases were separated and the aqueous layer was re-extracted with additional ethyl acetate (3x). The organic phases were combined and washed with brine (2x), dried over sodium sulphate, filtered and concentrated.The crude reaction was purified by flash chromatography (Grace Reveleris X2, hexane: ethyl acetate). 149 mg of clean product was obtained (Dudutiene et al., Bioorg. Med. Chem. (2013), 21(7), 2093-2106; International Patent Application WO03 / 062225).Step CThe ester obtained in step B (149 mg, 1 eq) was suspended in 5 ml of methanol and the reaction mixture was cooled with ice bath at 0°C and magnetically stirred. After hydroxylamine (50%, aqueous solution, 0.97 ml, 40 eq) addition, 1 M sodium hydroxide (4.1 ml, 10 eq) aqueous solution was added dropwise. The ice bath was removed, allowing the solution to reach room temperature. The conversion of the starting product into hydroxamic acid was confirmed by HPLC after 1 hour. The methanolic portion was removed by evaporation under reduced pressure, and the reaction was subsequently quenched by adding 4.1 ml of 1 M hydrochloric acid aqueous solution and 6 ml of ethyl acetate. The phases were separated and the aqueous layer was re-extracted with additional ethyl acetate (3x). The organic phases were combined and washed with sodium bicarbonate saturated solution (2x), brine (2x), dried over sodium sulphate, filtered, and concentrated to dryness. 1 1 3 mg of pure product was recovered (m / z 363.94 [MH+]).The following compounds were synthesized using this procedure:Comp. Structure m / z [MH+]2 412,894 405,019 468,9716 460,0117 368,9180 405,9297 354,9265 103 475,05114 477,08115 464,00116 422,01117 448,04118 426,91140 429,78141 445,94142 428,87143 444,82144 434,82145 447,00 146 430,10147 430,10148 414,00149 403,1150 536,1151 525,17071 184 496,3186 406,5199 353,12203 452,07204 452,09205 465,08206 410,1 207 433,8208 464,04210 461,05211 438,0212 449,76213 452,05 The following compound was synthesized using this procedure, starting from 2-mercapto-1 ,3,4-oxadiazole instead of 2-mercapto-1 ,3,4-triazole:Example 7. Synthesis of 4-rr5-r3-(diethylsulfamoyl)phenvn-4-methyl-1 ,2,4-triazol-3-yllsulfanyllbenzenecarbohvdroxamic acid (comp. 66)Step ATo a solution of copper iodide (10 mg, 0.05 eq), L-proline (1 1 mg, 0.1 eq) and potassium carbonate (152 mg, 1 .1 eq) in 1 ml. of DMF under argon atmosphere, methyl 4-iodobenzoate (288 mg, 1 .1 eq) and A / ,A / -diethyl-3-(5-mercapto-4-methyl-4H-1 ,3,4-triazol-3-yl)benzenesulfonamide (326 mg, 1 eq) were added sequentially. The reaction mixture was heated at 120°C and stirred overnight. The consumption of heteroaromatic thiol was observed by HPLC.The reaction mixture was diluted with 10 ml of ethyl acetate and 10 ml of water. The phases were separated and the aqueous layer was re-extracted with additional ethyl acetate (3x). The organic phases were combined and washed with brine (2x), dried over sodium sulphate, filtered and concentrated.The crude product was purified by flash chromatography (Grace Reveleris X2, hexane: ethyl acetate). 236 mg of product was obtained.Step BThe ester obtained in step A (236 mg, 1 eq) was suspended in 15 ml of methanol and the reaction mixture was cooled with ice bath at 0°C and magnetically stirred. After hydroxylamine (50%, aqueous solution, 1 .2 ml, 40 eq) addition, 1 M sodium hydroxide (4.1 ml, 10 eq) aqueous solution was added dropwise. The ice bath was removed, allowing the solution to reach room temperature. The conversion of the starting product into hydroxamic acid was confirmed by HPLC after 1 hour. The methanolic portion was removed by evaporation under reduced pressure, and the reaction was subsequently quenched by adding 4.1 ml of 1 M hydrochloric acid aqueous solution and 6 ml of ethyl acetate. The phases were separated and the aqueous layer was re-extracted with additional ethyl acetate (3x). The organic phases were combined and washed with sodium bicarbonate saturated solution (2x), brine (2x), dried over sodium sulphate, filtered, and concentrated to dryness. 207 mg of pure product was recovered (m / z 432.00 [MH+]).The following compounds were synthesized using this procedure:76 359,09463,12468,02353,07369,96370,03356,94The following compound was synthesized using this procedure, starting from 2-mercapto-1 ,3,4-oxadiazole instead of 2-mercapto-1 ,3,4-triazole:Example 8. Synthesis of 4-rri-(2,4-dichlorophenyl)-5-methyl-1 ,2,4-triazol-3-yllsulfanyllbenzenecarbohydroxamic acid (comp. 62)Step ATo a solution of potassium thiocyanate (194 mg, 1 eq) in dry acetonitrile (6 ml) acetyl chloride (143 μΙ_, 1 eq) was added slowly. The mixture was refluxed one hour, then the formed potassium chloride was removed by filtration. (2,4-dichlorophenyl)hydrazine (427 mg, 1 eq) was added to the solution and the reaction mixture was heated under reflux. After 1 .5 h, LC-MS analysis showed complete hydrazine consumption. The reaction mixture was abundantly diluted with cold water (50 mL) and the precipitated solid was recovered by filtration. The product was purified by crystallization from n-Hex / EtOAc 75:25. 60 mg of product was recovered.Step BTo a solution of copper iodide (2 mg, 0.05 eq), L-proline (3 mg, 0.1 eq) and potassium carbonate (35 mg, 1 .1 eq) in 2 ml of DMF under argon atmosphere, methyl 4-iodobenzoate (66.5 mg, 1 .1 eq) and 1 -(2,4-dichlorophenyl)-5-methyl-1 H-1 ,2,4-triazole-3-thiol (60 mg, eq) were added. The reaction mixture was heated at 120°C and stirred overnight. The consumption of heteroaromatic thiol was observed by HPLC.The reaction mixture was diluted with 6 ml of ethyl acetate and 6 ml of water. The phases were separated and the aqueous layer was re-extracted with additional ethyl acetate (3x). The organic phases were combined and washed with brine (2x), dried over sodium sulphate, filtered and concentrated. The obtained residue was used in the following step without any further purification.Step CThe ester obtained in step B (40 mg, 1 eq) was suspended in 6 ml of methanol and the reaction mixture was cooled with ice bath at 0°C and magnetically stirred. After hydroxylamine (50%, aqueous solution, 236 μΙ, 40 eq) addition, 1 M sodium hydroxide (1 ml, 10 eq) aqueous solution was added dropwise. The ice bath was removed, allowing the solution to reach room temperature. The conversion of the starting product into hydroxamic acid was confirmed by HPLC after 1 hour. The methanolic portion was removed by evaporation under reduced pressure, and the reaction was subsequently quenched by adding 1 ml of 1 M hydrochloric acid aqueous solution and 1 ml of ethyl acetate. The phases were separated and the aqueous layer was re-extracted with additional ethyl acetate (3x). The organic phases were combined and washed with sodium bicarbonate saturated solution (2x), brine (2x), dried over sodium sulphate, filtered, and concentrated to dryness. 30 mg of pure product was recovered (m / z 396.89 [MH+]).Example 9. Synthesis of 4-rr5-r(3,4-dimethoxyphenyl)methvn-2-r4-(trifluoromethyl¾phenyll-1 ,2,4-triazol-3-yllmethyllbenzenecarbohvdroxamic acid(comp. 44)Step AA vial with screw cap was charged with 2-(4-(methoxycarbonyl)phenyl)acetic acid (97 mg, 0.5 mmol), 1 -amino-2-(3,4-dimethoxyphenyl)ethan-1 -imino hydrochloride 200 mg, 1 .73 eq) and HATU (209 mg, 1 .1 eq). 2 ml of DMF and DIPEA (248 μΙ_, 3 eq) were added sequentially under argon atmosphere. The reaction mixture was stirred at room temperature and checked by HPLC for carboxylic acid consumption and acylamidine intermediate formation. The complete conversion into intermediate was observed within 2-3 hours.(4-(trifluoromethyl)phenyl)hydrazine hydrochloride (187 mg, 1 .76 eq) and acetic acid(286 μΙ_, 10 eq) were then added to the reaction mixture. The vial was sealed and the mixture was heated to 80°C and stirred overnight.Consumption of acylamidine intermediate was observed by HPLC.The mixture was allowed to reach room temperature before diluting it with ethyl acetate and sequentially washing with saturated sodium bicarbonate aqueous solution and brine. The organic layer was dried over sodium sulphate, filtered and concentrated to dryness.The product was purified by flash chromatography (hexane: ethyl acetate) (Castanedo et al., J. Org. Chem. (201 1 ), 76(4), 1 177-1 179).Step BThe ester obtained in step A (82 mg, 1 eq) was suspended in 5 ml of methanol and the resulting reaction mixture was cooled with ice bath at 0°C and magnetically stirred. After hydroxylamine (50%, aqueous solution, 189 μΙ, 20 eq) addition, 1 M sodium hydroxide (1 .6 ml, 10 eq) aqueous solution was added dropwise. The ice bath was removed, allowing the solution to reach room temperature. The conversion of the starting product into hydroxamic acid was confirmed by HPLC after 1 hour. The methanolic portion was removed by evaporation under reduced pressure, and the reaction was subsequently quenched by adding 1.6 ml of 1 M hydrochloric acid aqueous solution and 3 ml of ethyl acetate. The phases were separated and the aqueous layer was re-extracted with additional ethyl acetate (3x). The organic phases were combined and washed with sodium bicarbonate saturated solution (2x), brine (2x), dried over sodium sulphate, filtered, and concentrated to dryness. 27 mg of pure product was recovered (m / z 513.18 [MH+]).The following compounds were synthesized using this procedure:Comp. Structure m / z [MH+]51 419,0152 377,9953 407,04216 293,1Example 10. Synthesis of 4-((5-(furan-2-yl)-2H-tetrazol-2-yl)methyl)-N-hydroxybenzamide (comp. 12)Step AFuran-2-carbonitrile (500 mg, 1 eq) was dissolved in 10 ml of DMF. Sodium azide (770 mg, 2.2 eq) and ammonium chloride (631 mg, 2.2 eq) were added to the reaction mixture at room temperature under magnetic stirring. The suspension was heated at 120°C and stirred overnight. The complete conversion of the starting material was observed by LC-MS.The mixture was cooled to 0°C with ice bath, diluted with 10 ml of water and acidified with 1 M hydrochloric acid aqueous solution. The formed precipitate was collected by filtration and washed twice with water before drying under vacuum. 720 mg of product was obtained (International Patent Application WO2006 / 003096).Step BThe reaction vessel was charged with potassium carbonate (742 mg, 1 eq) and 5 ml of acetonitrile. The tetrazole obtained in step A (364 mg, 1 eq) was added as a solid under magnetic stirring at room temperature, while methyl 4-chloromethylbenzoate (1 .1 eq) was added as a solution in 5 ml of acetonitrile. The mixture was heated at 100°C and stirred overnight. The complete conversion of starting material into the two regioisomeric products was checked by LC-MS. Insoluble material was removed by filtration and the filtrate was evaporated under reduced pressure. The two regioisomers were isolated by column chromatography on silica gel (toluene : ethyl acetate). 384 mg of 2,5-disubstituted isomer and 234 mg of 1 ,5-disubstituted isomer were recovered (International Patent Application WO2012 / 106995).Step CThe ester obtained in step B (100 mg, 1 eq) was suspended in 10 ml of methanol and the resulting reaction mixture was cooled with ice bath at 0°C and magnetically stirred. After hydroxylamine (50%, aqueous solution, 700 μΙ, 30 eq) addition, 1 M sodium hydroxide (3.52 ml, 10 eq) aqueous solution was added dropwise. The ice bath was removed, allowing the solution to reach room temperature. The conversion of the starting product into hydroxamic acid was confirmed by HPLC after 1 hour. The methanolic portion was removed by evaporation under reduced pressure, and the reaction was subsequently quenched by adding 3.52 ml of 1 M hydrochloric acid aqueous solution and 6 ml of ethyl acetate. The phases were separated and the aqueous layer was re-extracted with additional ethyl acetate (3x). The organic phases were combined and washed with sodium bicarbonate saturated solution (2x), brine (2x), dried over sodium sulphate, filtered, and concentrated to dryness. 93.5 mg of clean product was recovered (m / z 286.02 [MH+]).The following compounds were synthesized using this procedure:71 431,9586 286,0287 347,0188 347,0289 297,0390 347,0291 133 311,03156 355,3157 355,5158 354,2159 354,4162 341,4 163 340,4169 311,5170 311,5173 325,3174 325,1214 296,08215 294,0 Example 11. Synthesis of 4-((5-(2,3-dihvdrothienor3,4-bin,41dioxin-5-yl)-1 H-tetrazol-1 -yl)methyl)-3,5-difluoro-N-hvdroxybenzamide (comp. 5)Step AThe reaction vessel was charged with potassium carbonate (85 mg, 1 eq) and 2 ml of acetonitrile. Tetrazole (105 mg, 1 eq) was added as a solid under magnetic stirring at room temperature, while methyl 3,5-difluoro-4-chloromethylbenzoate (122.3 mg, 1 .1 eq) was added as a solution in 2 ml of acetonitrile. The mixture was heated at 100°C and stirred overnight. The complete conversion of starting material into the two regioisomeric products was checked by LC-MS. Insoluble material was removed by filtration and the filtrate was evaporated under reduced pressure. The two regioisomers were isolated by column chromatography on silica gel (toluene : ethyl acetate). 23 mg of 2,5-disubstituted isomer and 52 mg of 1 ,5-disubstituted isomer was recovered (International Patent Application WO2012 / 106995).Step BThe ester obtained in step A (52 mg, 1 eq) was suspended in 2 ml of methanol and the resulting reaction mixture was cooled with ice bath at 0°C and magnetically stirred. After hydroxyl amine (50%, aqueous solution, 31 1 μΙ, 40 eq) addition, 1 M sodium hydroxide (1 .3 ml, 10 eq) aqueous solution was added dropwise. The ice bath was removed, allowing the solution to reach room temperature. The conversion of the starting product into hydroxamic acid was confirmed by HPLC after 1 hour. The methanolic portion was removed by evaporation under reduced pressure, and the reaction was subsequently quenched by adding 1.3 ml of 1 M hydrochloric acid aqueous solution and 2 ml of ethyl acetate. The phases were separated and the aqueous layer was re-extracted with additional ethyl acetate (3x). The organic phases were combined and washed with sodium bicarbonate saturated solution (2x), brine (2x), dried over sodium sulphate, filtered, and concentrated to dryness. 32 mg of clean product was recovered (m / z 395.91 [MH+]).The following compounds were synthesized using this procedure:96382,97382,98382,97457,91979899 0171 347,50172 347,3175 361,4176 361,1Example 12 - Synthesis of 3,5-difluoro-N-hvdroxy-4-((5-(pyridin-3-yl)-1 ,3,4-thiadiazol-2-yl)thio)benzamide (comp, 191 )Step AKOH (1 .48g, 26.47 mmol, 1 .1 equiv) was dissolved in 45 mL of anhydrous ethanol. The hydrazide (3.30g, 24.06 mmol, 1 equiv) was added and the reaction mixture was cooled to 0-5°C. CS2 (1 .66 mL, 27.67 mmol, 1 .15 equiv) was added dropwise and the reaction mixture was stirred at 0-5°C for 1 h. The resulted precipitate was collected, rinsed with cold acetone and dried affording 5.50g of yellow solid. The obtained intermediate was added in small portions to 25 mL of sulfuric acid cooled to 0-5°C. After 1 h at 0-5°C the reaction mixture was poured into ice water and the resulted precipitate was collected, rinsed with water and dried.Step BA mixture of 5-(pyridin-3-yl)-1 ,3,4-thiadiazole-2-thiol obtained in step A (0.8g, 4.1 mmol, 1 equiv), 4-iodobenzoic acid (1 .22g, 4.92 mmol, 1 .2 equiv), L-proline (0.047g, 0.4 mmol, O.l equiv) and K2CO3 (2.26g, 16.4 mmol, 4 equiv) in 20 mL of anhydrous DMF was degassed and Cul (0.039g, 0.2 mmol, 0.05 equiv) was added. The reaction vessel was sealed and the reaction mixture was stirred at 120°C for 48h. Complete conversion of the starting thiole was monitored by LC-MS. The reaction mixture was poured into 150 mL of water and filtered through a pad of Celite. The filtrate was acidified with HCI. The formed precipitate was filtered and rinsed successively with water, acetonitrile and diethyl ether.Step CHATU (0.181 mg, 0.476 mmol, 1 .5 equiv) was added to a solution of the carboxylic acid obtained in step B (0.1 g, 0.317 mmol, 1 equiv) and DIPEA (0.333 mL, 1 .902 mmol, 6 equiv) in 2 mL of anhydrous DMF. The reaction mixture was stirred at room temperatureand monitored by LC-MS for full conversion of the acid into the HATU-intermediate: after 1 h conversion was complete. NH2OH-HCI (0.066g, 0.951 mmol, 3 equiv) was added and the reaction mixture was stirred for 2h more. The reaction was monitored by LC-MS. The reaction mixture was diluted with water to 50 mL of total volume and extracted with EtOAc (225 mL). After evaporation, 101 mg of very viscous orange oil was obtained. Trituration with acetonitrile (~15min sonication) led to formation of a precipitate which was collected by filtration, rinsed with acetonitrile and diethyl ether and dried. 40mg of pure product were obtained (m / z 366.99 [MH+]). LCMS: 94.5%. NMR: OK.The following compounds were synthesized using this procedure:Example 13 - Synthesis 3,5-difluoro-N-hvdroxy-4-((5-phenyl-1 ,3,4-thiadiazol-2-vDmethvDbenzamide (comp. 198)Step ABu tert-Butyl malonate (1 1 .4g, 52.73 mmol, 2 equiv) was added dropwise to a suspension of NaH (1 .5 equiv) in 70 mL of anhydrous DMF. After 5 min of stirring at rt, methyl 3,4,5-trifluorobenzoate (5g, 26.3 mmol, 1 equiv) was added. The reaction mixture was stirred for 3h at rt (formation of a white precipitate was observed), diluted with water and extracted with EtOAc. After concentration, the residue was purified by column chromatography. 1 1 .0gof inseparable mixture of the product and tert-Butyl malonate in 1 :3 ratio (by NMR) was obtained. This mixture was used in the next step without further purification.Step BThe mixture obtained in step A (8.6g, 22 mmol, 1 equiv) and TFA (17 mL, 10 equiv) were dissolved in 10 mL of anhydrous DCE and refluxed o / n. After cooling, the solvent was evaporated and the residue was treated with hexane and the formed precipitate was collected. NMR analysis of the precipitate and of the filtrate revealed that a mixture of the product and malonic acid (in approx. the same 2:1 ratio in favor of the product) was obtained. The crops were combined and used in the next step.Step CThe mixture obtained in step B (0.5g, 2.17 mmol, 1 equiv) was dissolved in 5 mL of SOCI2, refluxed for 1 h and concentrated. The obtained crude chloroanhydride was mixed with benzoylhydrazine (0.643g, 4.72 mmol, 2 equiv) in 10 mL of anhydrous DMF followed by addition of DIPEA (1 .99 mL, 1 1 .45 mmol, 5 equiv). After being stirred overnight, the reaction mixture was quenched with water, extracted with EtOAc and concentrated. The residue was treated with DCM and filtered.Step DA mixture of the compound obtained in step C (0.277g, 0.88 mmol, 1 equiv) and Lawesson Reagent (0.35g, 0.86 mmol, 0.98 equiv) in 5 mL of toluene was stirred in the sealed vessel at 120°C for 15 min. Full conversion of the starting material was monitored by UPLC. The solvent was evaporated and the residue was purified by column chromatography first using EtOAc in hexane (gradient 20% to 100%) then 5% MeOH in DCM.Step EKOH (0.021 g, 0.37mmol, 2 equiv) was added to a solution of the cyclic compound obtained in step D (0.06g, 0.18 mmol, 1 equiv) in 14 mL of THF / water = 4 / 1 mixture. The reaction mixture was stirred at rt overnight and acidified with 1 M HCI. The obtained precipitate was collected and dried in vacuo. This solid was then dissolved in THF together with DIPEA (0.333 mL, 1 .902 mmol, 6 equiv). HATU (0.181 mg, 0.476 mmol, 1 .5 equiv) was added and the reaction mixture was stirred at rt and the full conversion of the acid to the HATU-intermediate was monitored by LC-MS. NH2OH-HCI (0.066g, 0.951 mmol, 3 equiv) was added and the reaction mixture was stirred for 2h more. The reaction mixture was diluted with water to 50 mL of total volume and extracted with EtOAc (225 mL). After evaporation 101 mg of very viscous oil was obtained. Trituration with acetonitrile (~15min sonication) led to formation of a precipitate which was collected by filtration, rinsed with acetonitrile and ether and dried. 33 mg of pure product were obtained (m / z 348.09 [MH+].The following compounds were synthesized using this procedure:Example 14 - Synthesis of 3,5-difluoro-N-hvdroxy-4-((5-phenyl-1 ,2,4-oxadiazol-3-vDmethvDbenzamide (comp. 194)Step Atert-Butyl cyanoacetate (1 1 .4g, 52.73 mmol, 2 equiv) was added dropwise to a suspension of NaH (1.5 equiv) in 70 mL of anhydrous DMF. After 5 min of stirring at rt, methyl 3,4,5-trifluorobenzoate (5g, 26.3 mmol, 1 equiv) was added. The reaction mixture was stirred for 3h at rt, diluted with water and extracted with EtOAc. After concentration the residue was purified by column chromatography, then diluted in 20 mL of anhydrous DCE and treated with TFA (8.6 mL, 10 equiv) under reflux o / n. The solvent was evaporated, the residue was dissolved in DCM, washed with NaHC03 saturated solution, dried over Na2S04 and concentrated. The crude product was purified by column chromatography.Step BA mixture of the nitrile derivative obtained in step A (2g, 1 1 mmol, 1 equiv), NH2OH hydrochloride (1 .5g, 22 mmol, 2 equiv) and NaHC03 (1 .81 , 22 mmol, 2 equiv) in 40 mL of methanol was refluxed overnight. After filtration and concentration the obtained crude product was purified by column chromatography (10% of EtOAc in DCM).Step CBenzoyl chloride (0.243g, 1 .73 mmol, 1 .2 equiv) was added to a solution of methyl (Z)-4-(2-amino-2-(hydroxyimino)ethyl)-3,5-difluorobenzoate obtained in step B (0.3g, 1 .44 mmol, 1 equiv) and DIPEA (0.75 mL, 4.32 mmol, 3 equiv) in 2 mL of anhydrous DMF. After being stirred overnight the reaction mixture was quenched with water and extracted with EtOAc. Column chromatography purification (neat DCM) gave 41 mg of product.Step DKOH (0.014 g, 0.24 mmol, 2 equiv) was added to a solution of the methyl ester obtained in step C (0.04 g, 0.12 mmol, 1 equiv) in 14 mL of THF / water = 4 / 1 mixture. The reaction mixture was stirred at rt overnight and acidified with 1 M HCI. The obtained precipitate was collected and dried in vacuo. The obtained carboxylic acid was dissolved in 2 mL of anhydrous THF. DIPEA (0.72 mmol, 6 equiv) and HATU (0.18 mmol, 1 .5 equiv) were added. The reaction mixture was stirred at rt and monitored by LC-MS for full conversion of the acid to the HATU-intermediate. NH2OH hydrochloride (0.025 g, 0.36 mmol, 3 equiv) was added and the reaction mixture was stirred for 2h more, then diluted with water to 50 mL of total volume and extracted with EtOAc (225 mL). After evaporation 101 mg of very viscous oil was obtained. Trituration with acetonitrile (~15min sonication) led to formation of a precipitate which was collected by filtration, rinsed with acetonitrile and ether and dried. 20mg of pure product were obtained (m / z 332.13 [MH+]).The following compounds were synthesized using this procedure:Example 15 - Synthesis of N-hvdroxy-4-((4-methyl-5-phenyl-4H-1 ,2,4-triazol-3-vDmethvDbenzamide (comp. 217)Step AAcetic acid (0.3 mL) was added dropwise to a solution of crude methyl 4-((5-phenyl-1 ,3,4-oxadiazol-2-yl)methyl)benzoate (0.38g, 1 .29 mmol, 1 equiv) in 2M solution of MeNH2 in THF (15 mL). The reaction vessel was sealed and the reaction mixture was allowed to stir at 150°C overnight. After cooling, the solvent was evaporated; the residue was treated with water and extracted with EtOAc. The organic phase was dried and evaporated yielding 258 mg of orange oil which was used in the next step without further purification.Step BThe methyl ester obtained in step A (0.041 g, 0.139 mmol, 1 equiv) was suspended in 8 mL of methanol and the resulted solution was cooled with ice bath. 50% solution of NH2OH in water (0.34 mL, 40 equiv) was added followed by slow addition of 1 M NaOH solution (1 .4 mL, 10 equiv). The reaction mixture was stirred allowing to reach rt (about 1 h) and acidified with 1 M HCI. The white precipitate was collected by filtration. Prep. HPLC purification gave 24 mg of pure product (m / z 309.12 [MH+]).Example 16 - Synthesis of 4-((3-((1 H-indol-3-yl)methvn-5-(thiophen-2-vn-4H-1.2.4-triazol-4-yl)methyl)-N-hvdroxybenzamide (comp. 183)Step AMethyl 4-(aminomethyl)benzoate hydrochloride (402 mg, 2 mmol, 1 eq.) was dissolved in dichloromethane (8 ml) in presence of trimethylamine (616 uL, 4.4 mmol, 2.2 eq.). 2-Thiophenecarbonyl chloride (236 uL, 2.2 mmol, 1 .1 eq.) was then added and the mixture was stirred at r.t. overnight.Upon completion, reaction mixture was diluted with dichloromethane and washed with water. Organic layer was dried over Na2S04, filtered and concentrated affording a crude product which was used for the subsequent step without any further purification.Step BMethyl 4-((thiophene-2-carboxamido)methyl)benzoate (1 mmol, 1 eq.) was suspended in tionyl chloride (4 ml, 5.5 eq) under argon, and stirred at reflux temperature overnight. The mixture was concentrated at reduced pressure to remove the excess of SOCI2. The crude imidoyl chloride thus obtained was suspended in dry toluene, and indole-3-acetic acid hydrazide (189 mg, 1 mmol, 1 eq) was added as a solid. The resulting mixture was heated up to 120°C and agitated over weekend. The mixture was concentrated by rotary evaporation. Product was precipitated from EtOAc / MeOH 1 % and collected by filtration. 1 13 mg of product were obtained.Step CThe methyl ester obtained in step B (0.041 g, 0.139 mmol, 1 equiv) was suspended in 8 mL of methanol and the resulted solution was cooled with ice bath. 50% solution of NH2OH in water (0.34 mL, 40 equiv) was added followed by slow addition of 1 M NaOH solution (1 .4 mL, 10 equiv). The reaction mixture was stirred allowing to reach rt (about 1 h) and acidified with 1 M HCI. The white precipitate was collected by filtration. Prep. HPLC purification gave pure product (m / z 430.3 [MH+]).The following compound was synthesized using this procedureExample 17 - Enzymatic screeningEnzymatic activity on recombinant human HDAC6 and HDAC3 was evaluated (Table 2) for each synthesized compound. Compounds that showed good HDAC6 selectivity,defined as log of the IC50 ratio between HDAC6 and another isoform less than -2, were also screened on all other isoforms in order to obtain the full profile (Table 3).For each test compound, solutions at five different concentrations (usually in the range 3-30000 nM) 5X concentrated in the reaction buffer (25 mM Tris-HCI, pH 8, 130 mM NaCI, 0.05% Tween-20, 10% Glycerol) plus DMSO normalized to the amount present in the more concentrated inhibitor solution, usually 0.75% equivalent to the final 0.15% in the plate were prepared. 10 μΙ_ of triplicate solution for each test compound concentration were placed on a 96-well plate and 15 μΙ_ of 3,33X concentrated enzyme solution in the reaction buffer (25 mM Tris-HCI, pH 8, 130 mM NaCI 0.05% Tween-20 10% glycerol, 1 mg / ml BSA or 2 mg / ml for HDAC4, HDAC5 and HDAC9 - note: for HDAC7, 50mM TRIS-HCI, pH 8, 137mM NaCI, 2.7mM KCI, and 1 mM MgCI2 were used) were added to each well. After a period of incubation at 30°C (incubation times vary for different isoforms and are shown in table 1 ) 25 μΙ_ of solution containing the substrate were added. As substrate, FLUOR DE LYS® deacetylase substrate (Enzo Life Sciences, cat# BML-KI104, FdL), FLUOR DE LYS®-Green substrate (Enzo Life Sciences, cat# BML-KI572 FdL_G) and trifluoroacetyl-L-lysine (Tfal)- 2X concentrated solution in 25 mM Tris-HCI, pH 8, 130 mM NaCI 0,05% Tween-20 10% glycerol) were used. Following a reaction period at 30°C (reaction times vary for different isoforms and are reported in Table 1 ), 50 μί of the development solution consisting of concentrate FLUOR DE LYS® developer I (Enzo Life Sciences, cat# BML-KI105), diluted 200 times in HAB plus 2 μΜ TSA was added and, after 25 minutes at room temperature in the dark, using the Victor 1420 Multilabel Counter Perkin Elmer Wallac instrument, the fluorescence reading was carried out.Table 1 - Operational details for the enzymatic test of each individual isoformmethodIsoform Source Concentration λ ex / λ em(0.1 s)BPS cat 150 μΜ 30 minutes at 30 minutesHDAC1 1.6 nM 355 / 460 nm50051 FdL 30°C at 30°CBPS cat 150 μΜ 30 minutes at 30 minutesHDAC2 3 nM 355 / 460 nm50002 FdL 30°C at 30°CBPS cat 30 minutes at 30 minutesHDAC3 400 pM 60 μΜ FdL 355 / 460 nm50003 30°C at 30°CBPS cat 30 minutes at 80 minutesHDAC4 32 pM 20 μΜ Tfal 355 / 460 nm50004 30°C at 30°CBPS cat 30 minutes at 60 minutesHDAC5 700 pM 20 μΜ Tfal 355 / 460 nm50005 30°C at 30°CBPS cat 30 minutes at 30 minutesHDAC6 1.5 nM 60 μΜ FdL 355 / 460 nm50006 30°C at 30°CBPS cat 30 minutes at 30 minutesHDAC7 14 pM 20 μΜ Tfal 355 / 460 nm50007 30°C at 30°CBPS cat 25 μΜ 55 minutes at 25 minutesHDAC8 3.9 nM 485 / 535 nm50008 FdL G RT at 30°CBPS cat 30 minutes at 80 minutesHDAC9 900 pM 20 μΜ Tfal 355 / 460 nm50009 30°C at 30°CBPS cat 150 μΜ 30 minutes at 180 minutesHDAC10 13 nM 355 / 460 nm50010 FdL 30°C at 30°CBML cat 150 μΜ 30 minutes at 240 minutesHDAC1 1 25 nM 355 / 460 nmSE560 FdL 30°C at 30°CData on HDAC6 and HDAC3 enzymatic inhibition of synthesized compounds are shown in Table 2. Complete inhibition profiles on all isoforms for selected compounds are shown in Table 3. Molecules showed good HDAC6 activity and marked selectivity against other isoforms.

Claims

ClaimsA compound of the formula (I) and (II), and pharmaceutically acceptable salts, isomers and prodrugs thereof:whereinA = N, O, S in formula (I), while A = N in formula (II);B = C, N;C = N, O in formula (I), while C = N in formula (II);X = CH2, S, NH, O, CD2;n = 0, 1 ;when n = 1 , the carbon atom may be substituted with R 2 and R 3 being independently selected from the group comprising H, D, -Me, -phenyl, -F and -OH or together R 2 and R 3 can form a saturated cyclic moiety, preferably cyclopropane, cyclobutane, cyclopentane or cyclohexane;when n = 1 , R6 may be absent;R4 = R5 = H, F;R is absent or it is selected from the group comprising -H,-NH2, C1 -C4 alkyl, phenyl, phenyl substituted with one or more halogens, arylalkyl, cycloalkyl, methylfuran, cyclobutylmethyl, tetrahydrofuran-2-yl-methyl, 3- (diethylamino)propyl, 2-methoxyethyl, vinyl, 2-(methylsulfanyl)ethyl, 1 -cyclopropylethyl, pyridin-2-yl, (pyridin-3-yl)methyl, 2-(pyridi n-2-yl )ethyl , 2- (thiophen-2-yl)ethyl, 3,4-dimethoxyphenyl, 4-methoxyphenyl, methylpheny, 2-chloro-5- (morpholin-4-sulfonyl)phenyl, 4- [(difluoromethyl)sulfanyl]phenyl, 4-(morpholin-4-sulfonyl)phenyl, 5-(dimethylsulfamoyl)-2-methylphenyl, 3- (trifluoromethyl)phenyl, 4-(trifluoromethyl)phenyl, 2-(morpholin-4-yl) ethyl, 3-(morpholin-4-yl)propyl, 1 -naphthyl, 2,3-dihydro-1 ,4-benzodioxin-6-yl, benzhydryl, 5-indanyl, thiophene and methylthiophene;R2 is absent or it is selected from H, alkyl, cycloalkyl, cycloalkyl-methyl, heteroaryl, phenyl, phenyl substituted with one or more halogens, phenyl substituted with one or more alkoxy groups, phenyl substituted with one or more nitro groups, benzyl, alkyl-substituted benzyl, (2,2-difluorocyclopentyl)methyl, 2-bromo-3-fluorophenyl, (2,2-dimethylcyclopropyl)methyl, 4-hydroxyphenyl, 2-(benzyloxy)ethyl, 2-bromo-4-methoxyphenyl, 2-methyl-quinoline, 3-methylpyridin-4-yl, 4-methanesulfonyl-2-methylphenyl, 2-chloro-4,6-dinitrophenyl, 1 ,3-benzodioxol-5-ylmethyl, or 2-benzyloxyphenyl;R3 is absent or it is selected from H, alkoxyaryl, phenyl, phenyl substituted with CF3, benzyl, pyridyl, alkyl, cycloalkyl, cycloalkyl-methyl, heteroaryl, phenyl substituted with one or more halogens, phenyl substituted with one or more alkoxy groups, phenylsubstituted with one or more nitro groups, benzyl, alkyl-substituted benzyl, (2,2- difluorocyclopentyl)methyl, 2-bromo-3-fluorophenyl, (2,2-dimethylcyclopropyl)methyl, 4- hydroxyphenyl, 2-(benzyloxy)ethyl, 2-bromo-4-methoxyphenyl, methyl-2-quinoline, 3- methylpyridin-4-yl, 4-methanesulfonyl-2-methylphenyl, 2-chloro-4,6-dinitrophenyl, 1 ,3- benzodioxol-5-ylmethyl, or 2-benzyloxyphenyl;R6 is a substituted or non-substituted mono or polycyclic residue, optionally partially or totally unsaturated, comprising carbon atoms and optionally one or more heteroatoms selected from N, S or O;or R6 is selected from:with the proviso that in the compounds of formula (I), when the pentaheterocyclic core is 1 ,3,4-oxadiazole, R6 is not naphthyl.

2. A compound according to claim 1 , wherein:X = CH2, S;when n = 1 , the carbon atom may be substituted with R 2 and R 3 being independently selected from the group comprising H, -Me, -phenyl, -F and -OH or together R 2 and R 3 can form a saturated cyclic moiety, preferably cyclopropane, cyclobutane, cyclopentane or cyclohexane;R is absent or it is selected from the group comprising -H, -NH2, -CH3, -CH2CH3, phenyl, p-fluorophenyl, m-chlorophenyl, p-chlorophenyl, benzyl, methylfuran, cyclopropyl, isobutyl, methylphenyl, trifluorophenyl, thiophene and 2- (morpholin-4-yl) ethyl;R2 is absent or it is selected from H, phenyl, or p-dichlorophenyl;R3 is absent or it is selected from H, o-methoxyphenyl, p-trifluoromethylphenyl, benzyl, or pyridyl;R6 is selected from the group comprising:148R7 and R8 are independently selected from the group comprising H, D, -CI, -F, -Br, -CF3, -Me, -Et, -OMe, -OMe, -OBenzyl, -SF5, -OCH2F, -CH2NH2, -CH2NMe2, -NH2, -NMe2, -N (CH2CH2OCH3)2, -COOH, -COOMe, -OH, -NHNH2, -N02, -OEt, -OCHF2, -OiPr, -CHF2, -NEt2,or R7 and R8 together can form a heteropentacyclic moiety (-OCH2O-);R9 = R 0 = -H, -Me, -Et;R is selected from the group comprising -H, -CI, -CH3, -NO2 and -Br.

3. A compound according to claim 1 or 2, selected from:- (S)-N-(1 -(3-(4-(hydroxycarbamoyl)benzyl)-1 ,2,4-oxadiazol-5-yl)-2-(thiazol-4- yl)ethyl)-3,4-dimethoxybenzamide (comp. 1 );- 3,5-difluoro-N-hydroxy-4-((4-methyl-5-(naphthalen-1 -yl)-4H-1 ,2,4-triazol-3- yl)thio)benzamide (comp. 2);- 4-((5-(3-(N,N-dimethylsulfamoyl)phenyl)-1 ,3,4-oxadiazol-2-yl)methyl)-N- hydroxybenzamide (comp. 3);- 3,5-difluoro-N-hydroxy-4-((4-methyl-5-(2-phenylpropan-2-yl)-4H-1 ,2,4-triazol-3- yl)thio)benzamide (comp. 4);- 4-((5-(2,3-dihydrothieno[3,4-b][1 ,4]dioxin-5-yl)-1 H-tetrazol-1 -yl)methyl)-3,5- difluoro-N-hydroxybenzamide (comp. 5);- 3,5-difluoro-N-hydroxy-4-((5-(pyridin-2-yl)-2H-tetrazol-2-yl)methyl)benzamide (comp. 6);- difluoro-N-hydroxy-4-((5-(pyrimidin-2-yl)-2H-tetrazol-2-yl)methyl)benzamide (comp. 7);- N-hydroxy-4-((5-(thiophen-2-yl)-1 H-tetrazol-1 -yl)methyl)benzamide (comp. 8);- 3,5-difluoro-N-hydroxy-4-((4-methyl-5-(4-methyl-2-morpholinothiazol-5-yl)-4H- 1 ,2,4-triazol-3-yl)thio)benzamide (comp. 9);- N-hydroxy-4-((4-methyl-5-(thiophen-2-yl)-4H-1 ,2,4-triazol-3-yl)thio)benzamide (comp. 10);- 4-((5-(furan-2-yl)-2H-tetrazol-2-yl)methyl)-N-hydroxybenzamide (comp. 12);- 3,5-difluoro-N-hydroxy-4-((5-(pyridin-2-yl)-1 H-tetrazol-1 -yl)methyl)benzamide (comp. 13);- 3,5-difluoro-N-hydroxy-4-((4-methyl-5-(pyridin-2-yl)-4H-1 ,2,4-triazol-3- yl)thio)benzamide (comp. 14);- 3,5-difluoro-N-hydroxy-4-((5-(thiophen-2-yl)-1 H-tetrazol-1 -yl)methyl)benzamide (comp. 15);- 3,5-difluoro-N-hydroxy-4-((4-methyl-5-(4-(piperidin-1 -ylmethyl)phenyl)-4H-1 ,2,4- triazol-3-yl)thio)benzamide (comp. 16);- 3,5-difluoro-N-hydroxy-4-((4-methyl-5-(thiophen-2-yl)-4H-1 ,2,4-triazol-3- yl)thio)benzamide (comp. 17);- 3,5-difluoro-4-((5-(furan-2-yl)-2H-tetrazol-2-yl)methyl)-N-hydroxybenzamide (comp. 19);N-hydroxy-4-((5-(pyridin-2-yl)-1 H-tetrazol-1 -yl)methyl)benzamide (comp. 20); - 3-(3,4-dimethoxyphenyl)-N-[(1 S)-1 -[3-[[4-(hydroxycarbamoyl)phenyl]methyl]- 1 ,2,4-oxadiazol-5-yl]-2-thiazol-4-yl-ethyl]propanamide (comp. 21 );- 4-[[5-[4-(trifluoromethyl)phenyl]tetrazol-2-yl]methyl]benzenecarbohydroxamic acid (comp. 23);- 4-[(4,5-diphenyl-1 ,2,4-triazol-3-yl)sulfanyl]benzenecarbohydroxamic acid (comp.24);- 4-[[4-(2-furylmethyl)-5-(1 H-indol-3-yl)-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid;2,2,2-trifluoroacetic acid (comp. 25);- 4-[5-[(3,4-dimethoxyphenyl)methyl]-1 ,3,4-oxadiazol-2- yl]benzenecarbohydroxamic acid (comp. 26);- 4-[[5-benzyl-4-(4-fluorophenyl)-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 27);- 4-[[4-amino-5-[4-(difluoromethoxy)phenyl]-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 28);- 4-[[5-(4-fluorophenyl)-4H-1 ,2,4-triazol-3-yl]sulfanyl]benzenecarbohydroxamic acid (comp. 29);- 4-[[4-ethyl-5-(4-fluorophenyl)-1 ,2,4-triazol-3-yl]sulfanyl]benzenecarbohydroxamic acid (comp. 30);- 4-[[5-(4-chlorophenyl)tetrazol-2-yl]methyl]benzenecarbohydroxamic acid (comp.31 );- 4-[[5-(5-chloro-2-thienyl)tetrazol-2-yl]methyl]benzenecarbohydroxamic acid (comp. 32);- 4-[[5-(2-fluorophenyl)tetrazol-2-yl]methyl]benzenecarbohydroxamic acid (comp.33);- 4-[[5-(4-fluorophenyl)tetrazol-2-yl]methyl]benzenecarbohydroxamic acid (comp. 34);- 4-[[5-(4-methoxyphenyl)tetrazol-2-yl]methyl]benzenecarbohydroxamic acid (comp. 35);- 4-[(5-benzyltetrazol-2-yl)methyl]benzenecarbohydroxamic acid (comp. 36);- 4-[(5-benzyltetrazol-1 -yl)methyl]benzenecarbohydroxamic acid (comp. 37);- 4-[[5-(2,4-dichlorophenyl)tetrazol-2-yl]methyl]benzenecarbohydroxamic acid (comp. 38);- 4-[[5-(3-methyl-2-thienyl)tetrazol-2-yl]methyl]benzenecarbohydroxamic acid (comp. 39);- 4-[[5-(5-methyl-2-thienyl)tetrazol-2-yl]methyl]benzenecarbohydroxamic acid (comp. 41 );- 4-[[5-(benzothiophen-3-yl)tetrazol-2-yl]methyl]benzenecarbohydroxamic acid (comp. 42);- 4-[[5-(2,3-dihydrothieno[3,4-b][1 ,4]dioxin-5-yl)tetrazol-2- yl]methyl]benzenecarbohydroxamic acid (comp. 43);- 4-[[5-[(3,4-dimethoxyphenyl)methyl]-2-[4-(trifluoromethyl)phenyl]-1 ,2,4-triazol-3- yl]methyl]benzenecarbohydroxamic acid (comp. 44);- 4-[[5-[(3,4-dimethoxyphenyl)methyl]-1 ,3,4-oxadiazol-2- yl]methyl]benzenecarbohydroxamic acid (comp. 45);46);- 4-[[5-[(1 S)-1 -amino-2-thiazol-4-yl-ethyl]-1 ,2,4-oxadiazol-3- yl]methyl]benzenecarbohydroxamic acid;2,2,2-trifluoroacetic acid (comp. 48);- 4-[[5-(3,4-dimethoxyphenyl)-1 ,2,4-oxadiazol-3- yl]methyl]benzenecarbohydroxamic acid (comp. 49);- 4-[[5-(2-thienyl)tetrazol-2-yl]methyl]benzenecarbohydroxamic acid (comp. 50);- 4-[[2-benzyl-5-(4-chlorophenyl)-1 ,2,4-triazol-3- yl]methyl]benzenecarbohydroxamic acid (comp. 51 );- 4-[[2-(2-pyridyl)-5-(2-thienyl)-1 ,2,4-triazol-3-yl]methyl]benzenecarbohydroxamic acid (comp. 52);- 4-[[2-(2-methoxyphenyl)-5-(2-thienyl)-1 ,2,4-triazol-3- yl]methyl]benzenecarbohydroxamic acid (comp. 53);- 4-[[5-(6,6-dimethyl-3-methylsulfanyl-4-oxo-5,7-dihydro-2-benzothiophen-1 - yl)tetrazol-2-yl]methyl]benzenecarbohydroxamic acid (comp. 54);- 4-[[5-(benzothiophen-2-yl)tetrazol-2-yl]methyl]benzenecarbohydroxamic acid (comp. 55);- 4-[[5-(3,4-dimethoxyphenyl)-1 ,3,4-oxadiazol-2- yl]methyl]benzenecarbohydroxamic acid (comp. 57);- 4-[[5-(2,4-difluorophenyl)-1 ,3,4-oxadiazol-2-yl]methyl]benzenecarbohydroxamic acid (comp. 58);- 4-[[5-[3-(dimethylsulfamoyl)phenyl]tetrazol-2-yl]methyl]benzenecarbohydroxamic acid (comp. 59);- 4-[(5-phenyl-1 ,3,4-oxadiazol-2-yl)amino]benzenecarbohydroxamic acid (comp.60);- 4-[[4-amino-5-[3-(diethylsulfamoyl)phenyl]-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 61 );- 4-[[1 -(2,4-dichlorophenyl)-5-methyl-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 62);- 4-[[5-(3-pyrrolidin-1 -ylsulfonylphenyl)-1 ,3,4-oxadiazol-2- yl]amino]benzenecarbohydroxamic acid (comp. 63);- 4-[[5-(3-morpholinosulfonylphenyl)-1 ,3,4-oxadiazol-2- yl]methyl]benzenecarbohydroxamic acid (comp. 64);- 3,5-difluoro-4-[[5-(2-thienyl)tetrazol-2-yl]methyl]benzenecarbohydroxamic acid (comp. 65);- 4-[[5-[3-(diethylsulfamoyl)phenyl]-4-methyl-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 66);- 4-[[4-methyl-5-[2-(p-tolyl)-4-quinolyl]-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 67);- 4-[(5-phenyl-1 ,3,4-oxadiazol-2-yl)methyl]benzenecarbohydroxamic acid (comp.68);- 4-[[5-(4-pyrrolidin-1 -ylsulfonylphenyl)-1 ,3,4-oxadiazol-2- yl]methyl]benzenecarbohydroxamic acid (comp. 69);- 4-[[5-(3-benzyloxy-4-methoxy-phenyl)tetrazol-2- yl]methyl]benzenecarbohydroxamic acid (comp. 70);- 4-[[5-(3-benzyloxy-4-methoxy-phenyl)tetrazol-1 - yl]methyl]benzenecarbohydroxamic acid (comp. 71 );- 4-[(5-cyclopropyl-1 -phenyl-1 ,2,4-triazol-3-yl)sulfanyl]benzenecarbohydroxamic acid (comp. 72);- 4-[[5-[4-(dimethylamino)phenyl]-4-methyl-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 73);- 4-[[5-(4-methyl-2-morpholino-thiazol-5-yl)-1 ,3,4-oxadiazol-2- yl]methyl]benzenecarbohydroxamic acid (comp. 75);- 4-[[5-[3-(dimethylamino)phenyl]-4-methyl-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 77);- 4-[[5-(3-methoxyphenyl)-4-methyl-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 78);- 4-[[5-(2,3-dihydrothieno[3,4-b][1 ,4]dioxin-5-yl)tetrazol-2-yl]methyl]-3,5-difluoro- benzenecarbohydroxamic acid (comp. 79);- 4-[[5-[3-(dimethylamino)phenyl]-4-methyl-1 ,2,4-triazol-3-yl]sulfanyl]-3,5-difluoro- benzenecarbohydroxamic acid (comp. 80);- tert-butyl 4-[5-[4-(hydroxycarbamoyl)phenyl]sulfanyl-4-methyl-1 ,2,4-triazol-3- yl]piperidine-1 -carboxylate (comp. 82);- 4-[[5-(2,3-dihydro-1 ,4-benzodioxin-3-yl)-4-methyl-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 83);- 4-[[5-(1 ,3-benzodioxol-5-yl)-4-methyl-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 84);- 4-[[5-(1 ,5-dimethylpyrazol-3-yl)-4-methyl-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 85);- 4-[[5-(2-furyl)tetrazol-1 -yl]methyl]benzenecarbohydroxamic acid (comp. 86);- 4-[[5-(1 -isoquinolyl)tetrazol-2-yl]methyl]benzenecarbohydroxamic acid (comp.87) ;- 4-[[5-(1 -isoquinolyl)tetrazol-1 -yl]methyl]benzenecarbohydroxamic acid (comp.88) ;- 4-[[5-(2-pyridyl)tetrazol-2-yl]methyl]benzenecarbohydroxamic acid (comp. 89);- 4-[[5-(2-quinolyl)tetrazol-2-yl]methyl]benzenecarbohydroxamic acid (comp. 90);- 4-[[5-(2-quinolyl)tetrazol-1 -yl]methyl]benzenecarbohydroxamic acid (comp. 91 ); - 3,5-difluoro-4-[[5-(2-furyl)tetrazol-1 -yl]methyl]benzenecarbohydroxamic acid (comp. 92);- 3,5-difluoro-4-[[5-(1 -isoquinolyl)tetrazol-2-yl]methyl]benzenecarbohydroxamic acid (comp. 93);- 3,5-difluoro-4-[[5-(1 -isoquinolyl)tetrazol-1 -yl]methyl]benzenecarbohydroxamic acid (comp. 94);- 3,5-difluoro-4-[[5-(2-quinolyl)tetrazol-2-yl]methyl]benzenecarbohydroxamic acid (comp. 95);- 3,5-difluoro-4-[[5-(2-quinolyl)tetrazol-1 -yl]methyl]benzenecarbohydroxamic acid (comp. 96);- 3,5-difluoro-4-[[5-(2-thienyl)-4H-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 97);- 4-[(5-benzhydryl-4-methyl-1 ,2,4-triazol-3-yl)sulfanyl]-3,5-difluoro- benzenecarbohydroxamic acid (comp. 98);- 4-[[5-(3-aminothieno[2,3-b]pyridin-2-yl)-4-methyl-1 ,2,4-triazol-3-yl]sulfanyl]-3,5- difluoro-benzenecarbohydroxamic acid (comp. 99);- 4-[[5-(1 ,5-dimethylpyrazol-3-yl)-4-methyl-1 ,2,4-triazol-3-yl]sulfanyl]-3,5-difluoro- benzenecarbohydroxamic acid (comp. 100);- 3,5-difluoro-4-[[4-methyl-5-(1 -phenylcyclobutyl)-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 101 );- 3,5-difluoro-4-[[5-[1 -(3-fluorophenyl)cyclopentyl]-4-methyl-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 102);- 3,5-difluoro-4-[[5-[1 -(4-methoxyphenyl)cyclohexyl]-4-methyl-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 103);- 3,5-difluoro-4-[[5-[1 -(4-methoxyphenyl)cyclopropyl]-4-methyl-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp 104);- 4-[[5-[3-(pentafluoro-lambda6-sulfanyl)phenyl]tetrazol-2- yl]methyl]benzenecarbohydroxamic acid (comp. 106);- 4-[[5- [3-(pentafluoro-lambda6-sulfanyl)phenyl]tetrazol-1 - yl]methyl]benzenecarbohydroxamic acid (comp. 107);- 3,5-difluoro- 4-[[5- [3-(pentafluoro- lambda6-sulfanyl)phenyl]tetrazol- 2- yl]methyl]benzenecarbohydroxamic acid (comp. 108);- 3,5-difluoro- 4-[[5- [3-(pentafluoro- lambda6-sulfanyl)phenyl]tetrazol- 1 - yl]methyl]benzenecarbohydroxamic acid (comp. 109);- 4-[[5- [4-(pentafluoro- lambda6-sulfanyl)phenyl]tetrazol- 2- yl]methyl]benzenecarbohydroxamic acid (comp. 1 10);- 4-[[5- [4-(pentafluoro- lambda6-sulfanyl)phenyl]tetrazol- 1 - yl]methyl]benzenecarbohydroxamic acid (comp. 1 1 1 );- 3,5-difluoro- 4-[[5- [4-(pentafluoro- lambda6-sulfanyl)phenyl]tetrazol- 2- yl]methyl]benzenecarbohydroxamic acid (comp. 1 12);- 3,5-difluoro- 4-[[5- [4-(pentafluoro- lambda6-sulfanyl)phenyl]tetrazol- 1 - yl]methyl]benzenecarbohydroxamic acid (comp. 1 13);- 3,5-difluoro- 4-[[4- methyl-5- [3-(4- methyl-4- oxido-piperazin- 4-ium- 1 -yl)phenyl]- 1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 1 14);- 3,5-difluoro- 4-[[4-(4-fluorophenyl)-5-(1 - piperidylmethyl)-1 ,2,4- triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 1 15);- 3,5-difluoro- 4-[[4- (2-furylmethyl)- 5-pyrrolidin- 1 -yl- 1 ,2,4-triazol- 3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 1 16);- 4-[(4- benzyl-5- morpholino-1 ,2,4- triazol-3- yl)sulfanyl]-3,5- difluoro- benzenecarbohydroxamic acid (comp. 1 17);- 4-[[5- (2,3-dihydrothieno[3,4-b][1 ,4]dioxin-5- yl)-4-methyl-1 ,2,4- triazol-3- yl]sulfanyl]-3,5-difluoro- benzenecarbohydroxamic acid (comp. 1 18);- 3,5-difluoro- 4-[[5-(1 -isoquinolyl)-4-methyl-1 ,2,4-triazol- 3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 121 );- 3,5-difluoro- 4-[[4-methyl-5-(2-quinolyl)-1 ,2,4-triazol- 3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 122);- 4-[(5-pyrimidin-2-yltetrazol-2-yl)methyl]benzenecarbohydroxamic acid (comp.123) ;- 4-[(5-pyrimidin-2-yltetrazol-1 -yl)methyl]benzenecarbohydroxamic acid (comp.124) ;- 3,5-difluoro-4-[(5-pyrimidin-2-yltetrazol-1 - yl)methyl]benzenecarbohydroxamic acid (comp. 125);- 4-[[5-[5-(trifluoromethyl)-2-pyridyl]tetrazol-2-yl]methyl]benzenecarbohydroxamic acid (comp. 126);- 4-[[5-[5-(trifluoromethyl)-2-pyridyl]tetrazol-1 -yl]methyl]benzenecarbohydroxamic acid (comp. 127);- 3,5-difluoro-4-[[5-[5-(trifluoromethyl)-2-pyridyl]tetrazol-2- yl]methyl]benzenecarbohydroxamic acid (comp. 128);- 3,5-difluoro-4-[[5-[5-(trifluoromethyl)-2-pyridyl]tetrazol-1 - yl]methyl]benzenecarbohydroxamic acid (comp. 129);- 4-[[5-[3-morpholino-5-(trifluoromethyl)-2-pyridyl]tetrazol-2- yl]methyl]benzenecarbohydroxamic acid (comp. 130);- 4-[[5-[3-morpholino-5-(trifluoromethyl)-2-pyndyl]tetrazol-1 - yl]methyl]benzenecarbohydroxamic acid (comp. 131 );- 4-[[5-(2-pyridylmethyl)tetrazol-2-yl]methyl]benzenecarbohydroxamic acid;2,2,2- trifluoroacetic acid (comp. 132);- 4-[[5- (2-pyridylmethyl)tetrazol- 1 -yl]methyl]benzenecarbohydroxamic acid;2,2,2- trifluoroacetic acid (comp. 133);- 3,5-difluoro-4-[[5-(2-pyridylmethyl)tetrazol-2-yl]methyl]benzenecarbohydroxamic acid;2,2,2-trifluoroacetic acid (comp. 134);- 3,5-difluoro-4-[[5-(2-pyridylmethyl)tetrazol-1 -yl]methyl]benzenecarbohydroxamic acid;2,2,2-trifluoroacetic acid (comp. 135);- 3,5-difluoro- 4-[[4- methyl-5- [1 -phenyl- 5-(2- thienyl)pyrazol-3- yl]-1 ,2,4- triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 136);- 3,5-difluoro- 4-[[5- (6-fluoro- 2-methyl- 3-quinolyl)- 4-methyl- 1 ,2,4-triazol- 3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 137);- 3,5-difluoro- 4-[[5- (4-fluorophenyl)- 4-(2- morpholinoethyl)-1 ,2,4- triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 138);- 3,5-difluoro- 4-[[4-(2-furylmethyl)- 5-pyrazin- 2-yl- 1 ,2,4-triazol- 3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 139);- 3,5-difluoro-4-[[4-(2-furylmethyl)- 5-(2-pyridyl)-1 ,2,4- triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 140);- 4-[[4- benzyl-5- (pyrrolidin-1 - ylmethyl)-1 ,2,4- triazol-3- yl]sulfanyl]-3,5- difluoro- benzenecarbohydroxamic acid (comp. 141 );- 4-[[4- benzyl-5- (2-furyl)- 1 ,2,4-triazol- 3-yl]sulfanyl]- 3,5-difluoro- benzenecarbohydroxamic acid (comp. 142);- 4-[[4- benzyl-5- (2-thienyl)- 1 ,2,4-triazol- 3-yl]sulfanyl]- 3,5-difluoro- benzenecarbohydroxamic acid (comp. 143);- 3,5-difluoro- 4-[[4-(2-furylmethyl)-5-(2- thienyl)-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 144);- 3,5-difluoro- 4-[[5- (2-fluorophenyl)- 4-(2- furylmethyl)-1 ,2,4- triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 145);- 3,5-difluoro-4-[[4-(2-furylmethyl)-5-(4-pyridyl)-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 146);- 3,5-difluoro-4-[[4-(2-furylmethyl)-5-(3-pyridyl)-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 147);- 3,5-difluoro-4-[[5-(3-isoquinolyl)-4-methyl-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 148);- 3,5-difluoro- 4-[(5- imidazo[1 ,2-a]pyridin- 3-yl- 4-methyl- 1 ,2,4-triazol- 3- yl)sulfanyl]benzenecarbohydroxamic acid (comp. 149);- 4-[[5-(1 -benzyl- 4-phenyl- 4-piperidyl)-4-methyl- 1 ,2,4-triazol- 3-yl]sulfanyl]- 3,5- difluoro-benzenecarbohydroxamic acid (comp. 150);- 3,5-difluoro-4-[[4-methyl-5-[3-(4-methylpiperazin-1 -yl)sulfonylphenyl]-1 ,2,4- triazol-3-yl]sulfanyl]benzenecarbohydroxamic acid (comp. 151 );- 4-[[5-[3-(4-benzylpiperazin-1 -yl)sulfonylphenyl]-4-methyl-1 ,2,4- triazol-3- yl]sulfanyl]-3,5-difluoro-benzenecarbohydroxamic acid (comp. 152);- 3,5-difluoro-4-[[4-methyl-5-(3-pyridyl)-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 153);- methyl 4-[[2-[[2,6-difluoro-4-(hydroxycarbamoyl)phenyl]methyl]tetrazol-5- yl]methyl]benzoate (comp. 154);- methyl 4-[[1 -[[2,6-difluoro-4-(hydroxycarbamoyl)phenyl]methyl]tetrazol-5- yl]methyl]benzoate (comp. 155);- methyl 6-[2-[[4-(hydroxycarbamoyl)phenyl]methyl]tetrazol-5-yl]pyridine-3- carboxylate (comp. 156);- methyl 6-[1 -[[4-(hydroxycarbamoyl)phenyl]methyl]tetrazol-5-yl]pyridine-3- carboxylate (comp. 157);- 4-[[2-[[4-(hydroxycarbamoyl)phenyl]methyl]tetrazol-5-yl]methyl]benzoic acid (comp. 158);- 4-[[1 -[[4-(hydroxycarbamoyl)phenyl]methyl]tetrazol-5-yl]methyl]benzoic acid (comp. 159);- 4-[[2-[[2,6-difluoro-4-(hydroxycarbamoyl)phenyl]methyl]tetrazol-5- yl]methyl]benzoic acid (comp. 160);- 4-[[1 -[[2,6-difluoro-4-(hydroxycarbamoyl)phenyl]methyl]tetrazol-5- yl]methyl]benzoic acid (comp. 161 );- 6-[2-[[4-(hydroxycarbamoyl)phenyl]methyl]tetrazol-5-yl]pyridine-3-carboxylic acid (comp. 162);- 3-[2-[[4-(hydroxycarbamoyl)phenyl]methyl]tetrazol-5-yl]benzoic acid (comp. 163);- 3,5-difluoro-4-[[4-methyl-5-(8-quinolylmethyl)-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 164);- 4-[[5-(2,6-difluorophenyl)-4-methyl-1 ,2,4-triazol-3-yl]sulfanyl]-3,5-difluoro- benzenecarbohydroxamic acid (comp. 165);- 3,5-difluoro-4-[[4-methyl-5-[3-(4-methylpiperazin-1 -yl)phenyl]-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 166);- 4-[[5-[3-(azepan-1 -ylmethyl)phenyl]-4-methyl-1 ,2,4-triazol-3-yl]sulfanyl]-3,5- difluoro-benzenecarbohydroxamic acid (comp. 167);- 4-[[5-[4-(azepan-1 -ylmethyl)phenyl]-4-methyl-1 ,2,4-triazol-3-yl]sulfanyl]-3,5- difluoro-benzenecarbohydroxamic acid (comp. 168);- 4-[[5-(4-aminophenyl)tetrazol-2-yl]methyl]benzenecarbohydroxamic acid (comp.169) ;- 4-[[5-(4-aminophenyl)tetrazol-1 -yl]methyl]benzenecarbohydroxamic acid (comp.170) ;- 4-[[5-(4-aminophenyl)tetrazol-2-yl]methyl]-3,5-difluoro-benzenecarbohydroxamic acid (comp. 171 );- 4-[[5-(4-aminophenyl)tetrazol-1 -yl]methyl]-3,5-difluoro-benzenecarbohydroxamic acid (comp. 172);- 4-[[5-[4-(aminomethyl)phenyl]tetrazol-2-yl]methyl]benzenecarbohydroxamic acid (comp. 173);- 4-[[5-[4-(aminomethyl)phenyl]tetrazol-1 -yl]methyl]benzenecarbohydroxamic acid (comp. 174);- 4-[[5-[4-(aminomethyl)phenyl]tetrazol-2-yl]methyl]-3,5-difluoro- benzenecarbohydroxamic acid (comp. 175);- 4-[[5-[4-(aminomethyl)phenyl]tetrazol-1 -yl]methyl]-3,5-difluoro- benzenecarbohydroxamic acid (comp. 176);- 3,5-difluoro-4-[[4-methyl-5-[1 -(2-pyridyl)cyclopropyl]-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 177);- 3,5-difluoro-4-[[4-methyl-5-[1 -(3-pyridyl)cyclopropyl]-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 178);- 3,5-difluoro-4-[(4-methyl-5-pyridazin-3-yl-1 ,2,4-triazol-3- yl)sulfanyl]benzenecarbohydroxamic acid (comp. 179);- 3,5-difluoro-4-[[5-(3-fluoro-2-pyridyl)-4-methyl-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 180);- 3,5-difluoro-4-[[4-methyl-5-[3-(1 -piperidylmethyl)phenyl]-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 181 );- 3,5-difluoro-4-[[4-methyl-5-[3-(morpholinomethyl)phenyl]-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 182);- 4-((3-((1 H-indol-3-yl)methyl)-5-(thiophen-2-yl)-4H-1 ,2,4-triazol-4-yl)methyl)-N- hydroxybenzamide (comp. 183);- 4-[[5-[3-[[benzyl(methyl)amino]methyl]phenyl]-4-methyl-1 ,2,4-triazol-3-yl]sulfanyl]- 3,5-difluoro-benzenecarbohydroxamic acid (comp. 184);- 4-[[3-[(3,4-dimethoxyphenyl)methyl]-5-(2-thienyl)-1 ,2,4-triazol-4- yl]methyl]benzenecarbohydroxamic acid (comp. 185);- 3,5-difluoro-4-[[4-methyl-5-[1 -methyl-1 -(3-pyridyl)ethyl]-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 186);- 3,5-difluoro-4-[[5-[4-[methyl(methylsulfonyl)amino]phenyl]-1 ,3,4-thiadiazol-2- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 187);- 4-[(5-phenyl-1 ,3,4-oxadiazol-2-yl)sulfanyl]benzenecarbohydroxamic acid (comp.188) ;- 4-[(5-phenyl-1 ,2,4-oxadiazol-3-yl)methyl]benzenecarbohydroxamic acid (comp.189) ;- 4-[(5-phenyl-1 ,3,4-thiadiazol-2-yl)methyl]benzenecarbohydroxamic acid (comp.190) ;- 3,5-difluoro-N-hydroxy-4-((5-(pyridin-3-yl)-1 ,3,4-thiadiazol-2-yl)thio)benzamide (comp. 191 );- 3,5-difluoro-4-[(5-phenyl-1 ,3,4-oxadiazol-2-yl)sulfanyl]benzenecarbohydroxamic acid (comp. 192);- 4-[[5-(2-morpholino-4-pyridyl)-1 ,2,4-oxadiazol-3- yl]methyl]benzenecarbohydroxamic acid (comp. 193);- 3,5-difluoro-N-hydroxy-4-((5-phenyl-1 ,2,4-oxadiazol-3-yl)methyl)benzamide(comp. 194);- 3,5-difluoro-4-[[5-(4-pyridyl)-1 ,3,4-thiadiazol-2- yl]methyl]benzenecarbohydroxamic acid (comp. 195);- 4-[[5-(5-bromo-3-pyridyl)-1 ,3,4-thiadiazol-2-yl]sulfanyl]-3,5-difluoro- benzenecarbohydroxamic acid (comp. 196);- 3,5-difluoro-4-[[5-(5-morpholino-3-pyridyl)-1 ,3,4-thiadiazol-2- yl]methyl]benzenecarbohydroxamic acid (comp. 197);- 3,5-difluoro-N-hydroxy-4-((5-phenyl-1 ,3,4-thiadiazol-2-yl)methyl)benzamide(comp. 198);- 3,5-difluoro-4-[[5-(2-furyl)-4-methyl-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 199);- 4-[[5-[5-[bis(2-methoxyethyl)amino]-3-pyridyl]-1 ,2,4-oxadiazol-3-yl]methyl]-3,5- difluoro-benzenecarbohydroxamic acid (comp. 200);- 3,5-difluoro-4-[[5-[5-(2-oxa-6-azaspiro[3.3]heptan-6-yl)-3-pyridyl]-1 ,2,4-oxadiazol- 3-yl]methyl]benzenecarbohydroxamic acid (comp. 201 );- 3,5-difluoro-4-[[5-[5-(pyrrolidin-1 -ylmethyl)-2-furyl]-1 ,2,4-oxadiazol-3- yl]methyl]benzenecarbohydroxamic acid (comp. 202);- 3,5-difluoro-4-[[4-methyl-5-[5-(morpholinomethyl)-3-furyl]-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 203);- 3,5-difluoro-4-[[4-methyl-5-[5-(morpholinomethyl)-2-furyl]-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 204);- 3,5-difluoro-4-[[4-methyl-5-[5-[(4-methylpiperazin-1 -yl)methyl]-2-furyl]-1 ,2,4- triazol-3-yl]sulfanyl]benzenecarbohydroxamic acid (comp. 205);- 4-[[5-[5-[(dimethylamino)methyl]-2-furyl]-4-methyl-1 ,2,4-triazol-3-yl]sulfanyl]-3,5 difluoro-benzenecarbohydroxamic acid (comp. 206);- 3,5-difluoro-4-[[4-methyl-5-[5-(pyrrolidin-1 -ylmethyl)-2-furyl]-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 207);- 4-[[5-[5-ethyl-4-(pyrrolidin-1 -ylmethyl)-2-furyl]-4-methyl-1 ,2,4-triazol-3-yl]sulfanyl]- 3,5-difluoro-benzenecarbohydroxamic acid (comp. 208);- 4-[[4-methyl-5-[5-[(4-methylpiperazin-1 -yl)methyl]-2-furyl]-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 209);- 3,5-difluoro-4-[[4-methyl-5-[6-(2-pyrrolidin-1 -ylethyl)-3-pyridyl]-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 210);- 4-[[5-[5-(diethylaminomethyl)-2-furyl]-4-methyl-1 ,2,4-triazol-3-yl]sulfanyl]-3,5- difluoro-benzenecarbohydroxamic acid (comp. 21 1 );- 3,5-difluoro-4-[[4-methyl-5-[5-(1 -piperidylmethyl)-2-furyl]-1 ,2,4-triazol-3- yl]sulfanyl]benzenecarbohydroxamic acid (comp. 212);- 4-[[5-[5-(diethylaminomethyl)-2-methyl-3-furyl]-4-methyl-1 ,2,4-triazol-3- yl]sulfanyl]-3,5-difluoro-benzenecarbohydroxamic acid (comp. 213);- 4-[(5-phenyltetrazol-2-yl)methyl]benzenecarbohydroxamic acid (comp. 214);- 4-[(5-phenyltetrazol-1 -yl)methyl]benzenecarbohydroxamic acid (comp. 215);- 4-[(5-phenyl-4H-1 ,2,4-triazol-3-yl)methyl]benzenecarbohydroxamic acid (comp.216);- N-hydroxy-4-((4-methyl-5-phenyl-4H-1 ,2,4-triazol-3-yl)methyl)benzamide (comp.217).

4. A compound according to claim 3, selected from:1 1412 1453 1464 1475 1496 1507 1518 1529 1535. A compound according to any one of claims 1 to 4, in combination with a drug selected from the group comprising proteasome inhibitors, immune checkpoint inhibitors,steroids, bromodomain inhibitors, epigenetic drugs, traditional chemotherapy, kinase inhibitors, preferably JAK family and CTLA4, PD1 or PDL1 checkpoints inhibitors.

6. A compound according to any one of claims 1 to 5, for use as a medicament.

7. A compound for use according to claim 6, in the treatment of one or more diseases HDAC6-mediated selected from the group comprising organ transplant rejection, myositis, diseases associated with abnormal functions of lymphocytes, multiple myeloma, non-Hodgkin's lymphoma, peripheral neuropathy, autoimmune diseases, inflammatory diseases, cancer and neurodegenerative diseases, ocular diseases, and GVHD.

8. A pharmaceutical composition comprising a therapeutically effective quantity of at least one of the compounds of the formula (I) or (II) or pharmaceutically acceptable salts, isomers and prodrugs thereof according to any one of claims 1 to 5 together with at least one pharmaceutically acceptable excipient.

9. A pharmaceutical composition according to claim 8, suitable to be administered by enteral route, parenteral route, oral route, topical route, or inhalatory route.

10. A pharmaceutical composition according to claim 8 or 9, in the form of a liquid or a solid, preferably in the form of capsules, tablets, coated tablets, powders, granules, creams or ointments.