Title - PHARMACEUTICAL COMPOUND

Abstract

Claim 1: A compound of formula (1) and (2), and pharmaceutically acceptable salts, isomers, and prodrugs thereof, wherein A = N, O, S in formula (1), while A = N in formula (2); B = C, N; C = N, O in formula (1), while C = N in formula (2); X = CH₂, S, NH, O, CD₂; n = 0, 1; when n = 1, the carbon atom may be substituted with R¹² and R¹³ independently selected from each other comprising H, D, -Me, -phenyl, -F, and -OH, or together R¹² and R¹³ may form a saturated cyclic moiety, preferably cyclopropane, cyclobutane, cyclopentane, or cyclohexane; when n = 1, R⁶ may be absent; R⁴ = R⁵ = H, F;R¹ is absent or selected from the group that includes -H, -NH₂, alkyl C₁₋₄, phenyl, phenyl replaced with one or more halogens, arylalquil, cycloalkyl, methylfuran, cyclobutylmethyl, tetrahidrofuran-2-yl-methyl, 3-(diethylamino)propyl, 2-methoxyethyl, vinylyl, 2-(methylsulfanyl)ethyl, 1-cyclopropylethyl, pyridin-2-yl, (pyridin-3-yl)methyl, 2-(pyridin-2-yl)ethyl, 2-(thiophen-2-yl)ethyl, 3,4-dimethoxyphenyl, 4-methoxyphenyl, methylphenyl, 2-chloro-5-(morpholin-4-sulfonyl)phenylo, 4-[(difluoromethyl)sulfanyl]phenylo, 4-(morpholin-4-sulfonyl)phenylo, 5-(dimethylsulfamoyl)-2-methylphenylo, 3-(trifluoromethyl)phenylo, 4-(trifluoromethyl)phenylo, 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 selected from H, alkyl, cycloalkyl, cycloalkylmethyl, 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-methylquinoline, 3-methylpyridin-4-yl, 4-methansulfonyl-2-methylphenyl, 2-chloro-4,6-dinitrophenyl, 1,3-benzodioxol-5-ylmethyl, or 2-benzyloxyphenyl;R³ is absent or selected from H, alkoxyaryl, phenyl, CF₃-substituted phenyl, 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-methansulfonyl-2-methylphenyl, 2-chloro-4,6-dinitrophenyl, 1,3-benzodioxol-5-ylmethyl, or 2-benzyloxyphenyl; R⁶ is a substituted or unsubstituted, optionally partially and fully saturated mono- or polycyclic residue comprising carbon atoms and optionally one or more heteroatoms selected from N, S or O; or R⁶ is selected from: the compounds of the group of formulas (3);provided that in compounds of formula (1), when the pentaheterocyclic nucleus is 1,3,4-oxadiazole, R⁶ is not naphthyl.;

Description

V. PRIOR DISCLOSURE STATEMENT For the purposes of Article 5 of Law 24.481, it is stated that the present invention has been previously disclosed: NO | (YES / NO) If yes, on what date; VI. OBSERVATIONS_____________________________________________________________________ INVENTORS: VERGANI, Barbara; CAPRINI, Gianiuca; FOSSATI, Gianluca; LATTANZIO, Marta; MARCHINI Mattia; PAVICH, Gianfranco; PEZZUTO, Marcello; RIPAMONTI, Chiara; SANDRONE, Giovanni; STEINKÜHLER, Christian; STEVENAZZ1, Andrea. It is hereby stated that the data provided in this form constitutes a sworn declaration; any falsehood contained herein will have the corresponding legal consequences. NOTE: Payment of the corresponding fee must be made at the time of submission or within two business hours of the following business day. If payment is not received within this period, the submission will be considered invalid and will have no legal effect. the authorized representative or attorney or legal representative Firmanel DESCRIPTIVE MEMORANDUM OF THE PATENT OF INVENTION REFERRING TO: “NEW SELECTIVE HDAC6 INHIBITORS” REQUESTED BY: ITALFARMACO SPA RESIDING AT: VIALE FUL VIO TESTI, 330 1-20126 Milan - Italy FOR A TERM OF 20 YEARS __________ * NEW SELECTIVE HDAC6 INHIBITORS Field of invention The present invention relates to novel selective benzohydroxamic inhibitors of the histone deacetylase 6 (HDAC6) enzyme and pharmaceutical compositions thereof. Therefore, these compounds are useful in the treatment of 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 invention The genetic material of eukaryotic cells is organized into a dynamic and complex structure consisting of DNA and proteins: chromatin. The main protein components of chromatin are histones, basic proteins that interact with DNA and form the basic structural unit of chromatin, the nucleosome, the first level of chromosome compaction within the nucleus. The interaction between basic histone residues and acidic DNA residues is crucial for determining nucleosome compaction and DNA accessibility to the molecular complexes that regulate transcription. This interaction is primarily influenced by the degree of histone acetylation. Deacetylation of the N-terminal lysine residue of histones allows the protonation of the amino group, which carries a positive charge and interacts with the negative charges contained in the DNA.This interaction occurs in a more compact state of chromatin, which involves the silencing of gene expression. Conversely, acetylation of the same residues prevents the formation of ionic bonds, leading to a less compact form of chromatin that allows greater exposure to DNA and interaction with macromolecular complexes that activate gene transcription. The degree of histone acetylation is regulated by the balance of activity of two classes of enzymes: histone acetyltransferases (HATs) and histone deacetylase (HDACs). A disruption of this delicate balance can lead to a loss of cellular homeostasis, which is commonly found in various human diseases, including cancer, neurological disorders, inflammation, and autoimmune diseases. Histone deacetylases have been classified as such because they reversibly catalyze the deacetylation of amine groups from the N-terminal lysine residues of histones. Subsequently, it has been found that these enzymes have a wide range of substrates, as their activity also depends on non-histone proteins that are substrates of N-acetyllysine-containing HAT enzymes, such as transcription factors, DNA repair enzymes, and other nuclear and cytoplasmic proteins. The human HDAC class consists of 18 enzymes, divided into two groups: zinc-dependent HDACs and NAD-dependent HDACs, also known as sirtuins (class III). Zinc-dependent HDACs are further distributed into four classes: 1) Class I, which includes HDAC1, 2, 3, and 8, ubiquitous isoenzymes located primarily in the nucleus; 2) Class Ia, which includes the isoenzymes HDAC4, 5, 7, and 9, located in both the nucleus and cytoplasm; 3) Class IIb, which includes HDAC6 and HDAC10, located primarily in the cytoplasm; and 4) Class IV, which includes only HDAC11. Unlike Class I HDACs, Class Ia and IIb have tissue-specific expression. By regulating gene expression and acting on histones and transcription factors, these enzymes are clearly involved in a myriad of cellular functions. Furthermore, by acting on numerous other protein substrates, these enzymes, as well as phosphatases, are implicated in many other processes, such as signal transduction and cytoskeleton rearrangement. In 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 have been approved for different types of cancer: vorinostat and romidepsin for cutaneous T-cell lymphoma (CTLC), belinostat for peripheral T-cell lymphoma (PTLC), and panobinostat for multiple myeloma. These latter inhibitors can interact to varying degrees with different HDAC isoforms. Despite their clinical efficacy, the use of pan-inhibitors, which are therefore not selective for a particular isoform, is limited by their toxicity and side effects observed in both preclinical models and, especially, clinical trials. Consequently, there is a need to develop HDAC inhibitors with a better pharmacological profile and therapeutic window (efficacy / toxicity ratio). The attention of the scientific community has focused on the synthesis and study of selective inhibitors for individual HDAC isoforms, with the aim of developing 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, diabetic complications, homozygous thalassemia, fibrosis, cirrhosis, acute promyelocytic leukemia (APL), organ transplant rejection, autoimmune diseases, protozoal infections, cancers, and so on. Selective inhibitors for a specific HDAC family or isoform, especially HDAC6, can be particularly useful for treating pathologies related to proliferative disorders and protein accumulation, immune system disorders, and neurological and neurodegenerative diseases, such as stroke, Huntington's disease, ALS, and Alzheimer's disease. Particularly for the HDAC6 isoform, different substrates have been identified, such as α-tubulin, Hsp90 (heat shock protein 90), cortactin, β-catenin. The modulation of this protein acetylation by HDAC6 has been correlated with several important processes, such as the immune response (Wang et al., Nat. Rev. Drug Disc. (2009), 8(12), 969981; J. Med. Chem. (2012), 55, 639-651; Mol. Cell. Biol. (2011), 31(10), 2066-2078), regulation of microtubule dynamics, including cell migration and cell-cell interaction (Aldana-Masangkay et al., J. Biomed. Biotechnol. (2011), 2011, 875824), and degradation of degenerated proteins. In addition, HDAC6 is involved in the process of catabolism of degraded proteins through the complex known as the agresome: HDAC6 is able to bind polyubiquitinated proteins and dynein, thereby activating a type of delivery of denatured proteins along the microtubules to the agresome (Kawaguchi et al., Cell (2003) 115 (6), 727-738). Alteration of this cytoprotective activity of HDAC6 has been correlated with various neurodegenerative pathologies such as Parkinson's disease (Outerio et al., Science (2007), 317 (5837), 516519) and Huntington's disease (Dompierre et al., J. Neurosci. (2007), 27(13), 3571-3583), where the accumulation of degraded proteins is a common pathological feature. In addition, HDAC6 participates in the regulation of many oncological proteins, especially in hematological tumors, such as several types of leukemia (Fiskus et al., Blood (2008), 112 (7), 2896-2905; Rodríguez-Gonzales, Blood (2008), 112 (11), abstract 1923) and multiple myeloma (Hideshima et al., Proc. Nati. Acad. Sci. USA (2005), 102 (24), 8567-8572). The regulation of α-tubulin acetylation by HDAC6 may be involved in the initiation of metastasis, where cell motility plays an important role (Sakamoto et al., J. Biomed. Biotechnol. (2011), 2011, 875824). International patent application WO 2011 / 021209 describes 1,2,3-triazole compounds having HDAC inhibitory activity. International patent application WO 2012 / 178208 describes compounds with substituted heterocycles such as benzimidazole, benzimidazolone, and benzotriazole that have selective HDAC6 inhibitory activity. International patent application WO 2015 / 102426 describes novel indole derivatives with HDAC inhibitory activity. International patent application WO 2015 / 087151 describes novel azaindole derivatives with HDAC inhibitory activity. International patent application WO 2012 / 106343 describes HDAC inhibitors and compositions containing them. It also describes methods for treating diseases and conditions where HDAC inhibition provides a benefit, such as cancer, neurodegenerative disorders, peripheral neuropathy, neurological diseases, traumatic brain injury, stroke, hypertension, malaria, autoimmune diseases, autism, autism spectrum disorders, and inflammation. The document 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 the most potent and selective for HDAC1. Definitions Unless otherwise defined, all technical terms, annotations, and other scientific terminology used herein are understood to have the meanings commonly understood by those skilled in the art to which this description pertains. In some cases, terms with commonly understood meanings are defined herein for clarity and / or quick reference; the inclusion of such definitions herein should not be construed as representing a substantial difference from what is generally understood in the art. The term halogen refers hereto to fluorine (F), chlorine (Cl), bromine (Br), or iodine (I). The term C1-C4 alkyl refers hereto 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, and tert-butyl. The term aryl herein refers to mono- and polycarbocyclic aromatic ring systems (i), wherein the individual carbocyclic rings in the polycarbocyclic ring systems may be fused or joined together by a single bond. Suitable aryl groups include, but are not limited to, phenyl, naphthyl, and biphenyl. The term aryloxy refers hereto to an O-aryl group, where aryl is as defined above. The term alkoxy refers hereto to an O-alkyl group, where alkyl is as defined above. The term cycloalkyl herein refers to a saturated or unsaturated hydrocarbon ring, preferably one having 4 to 10 carbon atoms. Examples of cycloalkyl include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. The term arylalkyl refers hereto to an aryl radical as defined herein, bonded to an alkyl radical as defined herein. An example of an arylalkyl is benzyl. The term heterocycle herein refers to a 4-, 5-, 6-, 7-, or 8-membered monocyclic ring that is either saturated or unsaturated and consists of carbon atoms and one or more heteroatoms selected from N, O, and S, where the nitrogen and sulfur heteroatoms may optionally be oxidized and the nitrogen heteroatom may optionally be quaternized. The heterocyclic ring may be attached to any heteroatom or carbon atom, provided that the attachment results in a stable structure. The term also includes any bicyclic system in which any of the above heterocyclic rings is fused to an aryl or another heterocycle. When the heterocyclic ring is an aromatic heterocyclic ring, it may be defined as a heteroaromatic ring. The term unsaturated ring herein refers to a partially or completely unsaturated ring. For example, an unsaturated C6 monocyclic ring refers to cyclohexene, cyclohexadiene, and benzene. The term substituted refers hereto to mono or polysubstitution with a defined (or undefined) substituent, provided that this single or multiple substitution is chemically permitted. The term physiologically acceptable excipient refers hereto 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 described, for example, in the Handbook of Pharmaceutical Excipients, sixth edition, 2009, incorporated herein by reference. The term "pharmaceutically acceptable salts or derivatives" herein refers to salts or derivatives that possess the effectiveness and biological properties of the salted or derived compound and that do not produce adverse reactions when administered to a mammal, preferably a human. Pharmaceutically acceptable salts may be inorganic or organic; examples of pharmaceutically acceptable salts include, but are not limited to: carbonate, hydrochloride, hydrobromide, sulfate, hydrogen sulfate, citrate, maleate, fumarate, trifluoroacetate, 2-naphthalenesulfonate, and para-toluenesulfonate. Additional information on pharmaceutically acceptable salts can be found in the Handbook of Pharmaceutical Salts, P. Stahl, C. Wermuth, WILEY-VCH, 127-133, 2008, incorporated herein by reference. Pharmaceutically acceptable derivatives include esters, ethers, and N-oxides. The terms that comprise, that have, that include, and that contain should be understood as open terms (i.e., that include, but without limitation) and should be considered as supporting terms such as essentially consist of, that essentially consists of, consists of, or that consists of. The terms "essentially" and "which essentially consists of" should be understood as semi-closed terms, meaning that no other ingredient affecting the novel features of the invention is included (therefore, optional excipients may be included). The terms "consists of" and "which consists of" should be understood as closed terms. The term isomers refers to stereoisomers (or spatial isomers), that is, diastereomers and enantiomers. The term prodrugs refers to pharmacologically inactive derivatives that can undergo in vivo metabolic transformation to yield an active compound included in the general formulation of this invention. Many different prodrugs are known in the art (Prodrug approach: an effective solution to overome side-effeets, Patil SJ, Shirote PJ, International Journal of Medical and Pharmaceutical Sciences, 2011,1-13; Carbamate Prodrug Conceptfor Hydroxamate HDAC Inhibitors, Jung, Manfred et al., ChemMedChem, 2011, 1193-1198). 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, myasthenia gravis, systemic lupus erythematosus, autoimmune thyroiditis, dermatitis (including atopic dermatitis and eczematous dermatitis), psoriasis, Sjogren's syndrome, including keratoconjunctivitis sicca secondary to Sjogren's syndrome, alopecia areata, allergic reactions to arthropod bites, Crohn's disease, stomach ulcer, iritis, conjunctivitis, keratoconjunctivitis, ulcerative colitis, asthma, allergic asthma, cutaneous lupus erythematosus, scleroderma, vaginitis, proctitis, drug reaction, leprosy, lupus erythematosus, autoimmune uveitis, allergic encephalomyelitis, acute necrotizing hemorrhagic encephalopathy, hearing loss progressive bilateral idiopathic, aplastic anemia, anemia, idiopathic thrombocytopenia, polychondrite,Wegener's granulomatosis, chronic active hepatitis, Stevens-Johnson syndrome, idiopathic celiac disease, lichen planus, Graves' 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 disease, alcoholic liver disease, cystic fibrosis, Pick's disease, spinal muscular atrophy, and Lewy body dementia. The term pathology also includes one or more of the following diseases: rheumatoid spondylitis, post-ischemic reperfusion injury, intestinal inflammation, chronic inflammatory lung disease, eczema, asthma, acute respiratory distress syndrome, infectious arthritis, chronic progressive arthritis, deforming arthritis, post-traumatic arthropathy, gouty arthritis, Reiter's syndrome, acute synovitis, acute spondylitis, glomerulonephritis, hemolytic anemia, aplastic anemia, neutropenia, graft-versus-host disease (GVHD), transplant rejection, chronic thyroiditis, Graves' disease, binary primary cirrhosis, contact dermatitis, sunburn, chronic renal failure, Guillain-Barré syndrome, uveitis, otitis media, periodontal disease, intestinal pulmonary fibrosis, bronchitis, sinusitis, pneumoconiosis, pulmonary failure syndrome, pulmonary emphysema, pulmonary fibrosis, silicosis, or chronic inflammatory lung diseases. The term pathology also includes one or more of the following diseases: cancer, tumor growth, colon, breast, bone, brain and other types of cancer (e.g., osteosarcoma, neuroblastoma, colon adenocarcinoma), chronic myeloid leukemia (CML), acute myeloid leukemia (AML), acute promyelocytic leukemia (APL), heart 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., cancer of the esophagus, stomach, pancreas, small intestine, large intestine), cancer of the genitourinary tract (e.g., cancer of the kidney, bladder and urethra, prostate, testicular), liver cancer (e.g., hepatocellular carcinoma, cholangiocarcinoma, hepatoblastoma, angiosarcoma, hepatocellular adenoma, hemangioma), bone cancer (e.g., osteogenic sarcoma, fibrosarcoma,malignant fibrous histiocytomas, chondrosarcoma, Ewing sarcoma, malignant lymphoma, multiple myeloma, malignant giant cell tumor, chordoma, chondrosteoma, benign chordoma, chondroblastoma, chondromyxofibroma, osteoid osteoma), tumors of the nervous system (e.g., skull, meningitis, brain, spinal cord), gynecological tumors (e.g., uterus, cervix, ovaries, vulva and vagina), hematological cancer (e.g., blood tumors, Hodgkin's disease, non-Hodgkin's disease), skin cancer (e.g., malignant melanoma, basal cell carcinoma, malignant squamous cell tumor, Kaposi's sarcoma, dysplastic nevus, lipoma, angioma, dermatofibroma, keloid, psoriasis) and adrenal gland tumors (e.g., neuroblastoma). Description of the Figures Figure 1: 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 5 days. After incubation, cells were harvested and labeled with an anti-PD-L1 antibody. The cells were then washed, and fluorescence data were acquired using a flow cytometer (BD FACSVerse). Values ​​in the graphs represent the mean of 3 experiments performed in 3 different donors (n = 3). PD-L1 expression 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 to an anti-PD-1 antibody. The arrow indicates the day of treatment initiation. Figure 3: HDAC6 inhibitors reduce CT26 tumor growth in vivo, and their activity can be enhanced by combination therapy with anti-PD-1 antibodies. Statistical data were assessed on day 30 using Student's t-test. *, P < 0.05; **, P < 0.01; ***, P < 0.001. See text for further details. Figure 4: In vivo treatment with selective HDAC6 inhibitors induced a specific T cell response. Splenocytes from animals treated with Compounds 8 and 10 and the combination with anti-PD-1 Ab were stimulated with CT-26-derived tumor peptides and IFN-γΠ TNF-κ production by CD4 cells was quantified by ELISPOT. Figure 5: In vivo treatment with selective HDAC6 inhibitors induced a specific T cell response. Splenocytes from animals treated with Compound 8 and 10 and the combination with anti-PD-1 Ab were stimulated with CT-26-derived tumor peptides, and IFN-γD TNF-LJ production by CD8 T cells was quantified by ELISPOT. Description of the invention The inventors have experimentally discovered that benzo-hydroxamic compounds, characterized by a central pentaheterocyclic core, exhibit high and selective inhibitory activity against the HDAC6 enzyme. These compounds also demonstrated low cytotoxicity, allowing for their chronic use. According to a first aspect, the present invention relates to the compounds of formulas (I) and (II) and their pharmaceutically acceptable salts, isomers and prodrugs: (YO) (II) where 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, NH, O, CD2; n = 0, 1; when η = 1, the carbon atom can be substituted with R12 and R13 that are independently selected from each other comprising H, D, -Me, phenyl, -F and -OH or together R12 and R13 can form a saturated cyclic residue, preferably cyclopropane, cyclobutane, cyclopentane or cyclohexane; when n = 1, R6 may be absent; R4 = R5 = H, F; R1 is absent or 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-(pyridin-2-yl)ethyl, 2-(thiophen- 2-1)ethyl, 3,4-dimethoxyphenyl, 4-methoxyphenyl, methylphenyl, 2-chloro-5-(morpholin- 4-sulfonyl)phenyl, 4-[(difluoromethyl)sulfanyl]phenyl, 4-(morpholin-4-sulfonyl)phenyl, 5-(dimethylsulfamoyl)-2-methylphenylo, 3-(trifluoromethyl)phenylo, 4-(trifluoromethyl)phenylo, 2-(morpholin-4-yl)ethyl, 3-(morpholin-4-yl)propyl, 1-naphthyl, 2,3-dihydro-1,4-benzodioxin-6-¡lo, benzhydryl, 5-¡ndanilo, thiophene and methylthiophene; R2 is absent or selected from H, alkyl, cycloalkyl, cycloalkylmethyl, 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-methylquinoline, 3-methylpyridin-4-yl, 4-methanesulfonyl-2,16-methylphenyl, 2-chloro-4,6-dinitrophenyl, 1,3-benzodioxol-5-ylmethyl, or 2-benzyloxyphenyl; R3 is absent or selected from H, alkoxyaryl, phenyl, CF3-substituted phenyl, 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-methansulfonyl-2-methylphenyl, 2-chloro-4,6-dinitrophenyl, 1,3-benzodioxol-5-ylmethyl, or 2-benzyloxyphenyl; R6 is a substituted or unsubstituted mono- or polycyclic residue, optionally partially and fully saturated, comprising carbon atoms and optionally one or more heteroatoms selected from N, S or O; or R6 can be selected from: with the condition that in compounds of formula (I), when the pentaheterocylic nucleus is 1,3,4-oxadiazole, R6 is not naphthyl. An additional class of preferred compounds comprises compounds of formula (I) and (II) and their salts, pharmaceutically acceptable isomers and pharmacologically acceptable esters, wherein the pentaheterocylic 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 their pharmaceutically acceptable salts, where: 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 can be substituted with R12 and R13 that are independently selected from each other comprising H, -Me,phenyl, -F and -OH or together R12 and R13 can form a saturated cyclic moiety, preferably cyclopropane, cyclobutane, cyclopentane or cyclohexane; when n = 1, R6 can be absent; R4 = R5 = H, F; R1 is absent or it is selected from the group comprising -H, -NH2, -CH31CH2CH3, phenyl, p-fluorophenyl, m-chlorophenyl, p-chlorophenyl, benzyl, methylfuran, cyclopropyl, isobutyl, methylphenyl, trifluorophenyl, thiophene and 2(morpholin-4-yl)ethyl; R2 is absent or selected from H, phenyl, or p-dichlorophenyl; R3 is absent or selected from H, o-methoxyphenyl, p-trifluoromethylphenyl, benzyl, or pyridyl; R6 is selected from the group comprising: R7 and R8 are selected independently of the group they include H, D, -CII-FI-Br,-CF3,-Me,-Et,-OMe,-OBencilo,-SF5I-OCH2FI-CH2NH2,- NH2>-CH2NMe2,-NMe2)-N(CH2CH2OCH3)2,-COOHI-COOMe,-OH,-NHNH2,NOs.-OEt.-OCHFz.-OiPr.-CHFz.-NEtz, ί ΛΑ •S---Ν O a VV ίΐ ΛΑ s—ν r ϊ V7 o Ο / ° yΝ \ or R7 and R8 joints can form a heteropentacyclic remainder (-OCH2O-); r9 = r1° =-H,-Me,-Et; R11 is selected from the group that includes-H,-CI,-CH3,-NO2 and-Br. The following components of forms (I) and (II) are particularly preferable: - ((S)-N-(1-(3-(4-(hidroxicarbamoyl)bencyl)-1,2,4-oxad¡azol-5-yl)-2(thiazol-4-yl)ethyl)-3,4-dimethoxybenzam¡da (comp. 1); - 3,5-difluoro-N-hydroxy-4-((4-methyl-5-(naphthalene-1-¡l)-4H-1,2,4-triazol-3- yl)thio)benzamide (comp. 2); - 4-((5-(3-(N,Nd¡met¡lsulfamo¡l)phenyl)-1I3)4-oxad¡azol-2-yl)methyl)-Nhydroxybenzamide (comp. 3); - 3,5-difluoro-N-hydroxy-4-((4-methyl-5-(2-phenylpropan-2-yl)-4H-1,2,4triazol-3-yl)thio)benzamide (comp. 4); - 4-((5-(2,3-d ih id rotieno[3,4-b][1,4]d ioxin-5-yl)-1 H-tetrazol-1 -yl)methyl)21 3,5-difluoro-N-hydroxybenzamide (comp. 5); - 3,5-difluoro-N-hydroxy-4-((5-(p¡ridin-2-yl)-2H-tetrazol-2- ¡l)methyl)benzamide (comp. 6); - difluoro-Nh¡droxi-4-((5-(p¡r¡midin-2-¡l)-2H-tetrazol-2- 11) methyl)benzamide (comp. 7); - N-hydroxy-4-((5-(thiophen-2-yl)-1 H-tetrazol-1 -yl)methyl)benzam¡da (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); - Nh¡droxy-4-((4-met¡l-5-(t¡ophen-2-yl)-4H-1,2,4-triazol-3¡l)thio)benzamide (comp. 10); - 4-((5-(furan-2-yl)-2H-tetrazol-2-yl)methyl)-N-hydrox¡benzam¡da (comp. 12) ; - 3,5-d ¡f luoro-Nh id roxi-4-((5-(pi rid i η-2-i I)-1 H-tetrazol-1 yl)methyl)benzamide (comp. 13); - 3,5-difluoro-N-hydroxy-4-((4-methyl-5-(pyridin-2-¡l)-4H-1,2,4-triazol-3yl)thio)benzamide (comp. 14); - 3,5-difluoro-N-hydrox¡-4-((5-(t¡ophen-2-yl)-1 H-tetrazol-1yl)methyl)benzamide (comp. 15); - 3,5-d¡fluoro-Nh¡drox¡-4-((4-met¡l-5-(4-(piperid¡n-1-ilmet¡l)phen¡lo)-4H- 1.2.4- triazol-3-yl)thio)benzam¡da (comp. 16); - 3,5-difluoro-N-hydroxy-4-((4-methyl-5-(thiophen-2-yl)-4H-1,2,4-tr¡azol-3yl)thio)benzamide (comp. 17); - 3,5-difluoro-4-((5-(furan-2-¡l)-2H-tetrazol-2-¡l)methyl)-Nhydroxybenzamide (comp. 19); - N-hydroxy-4-((5-(pyridin-2-¡l)-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-íl-ethyl]propanamide (comp. 21); - 4-[[5-[4-(trifluoromethyl)phenyl]tetrazol-2-IJmethylJbenzenecarbohydiOxamic acid (comp. 23); - 4-[(4,5-diphenyl-1,2,4-triazol-3-yl)sulfanyl]benzencarbohydroxamic acid (comp. 24); - 4-[[4-(2-furylmethyl)-5-(1H-indol-3-yl)-1,2,4-triazol-3-1]sulfanyl]benzencarbohydroxamic acid; 2,2,2-trifluoroacetic acid (comp. 25); - 4-[5-[(3,4-dimethoxyphenyl)methyl]-1,3,4-oxadiazol-2-ylbenzenecarbohydroxamic 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]benzencarbohydroxamic 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]benzencarbohydroxamic acid (comp. 30); - 4-[[5-(4-chlorophenyl)tetrazol-2-yl]methyl]benzencarbohydroxamic acid (comp. 31); - 4-[[5-(5-chloro-2-thienyl)tetrazol-2-yl]methyl]benzencarbohydroxamic acid (comp. 32); - 4-[[5-(2-fluorophenyl)tetrazol-2-yl]methyl]benzencarbohydroxamic acid (comp. 33); - 4-[[5-(4-fluorophenyl)tetrazol-2-yl]methyl]benzencarbohydroxamic acid (comp. 34); - 4-[[5-(4-methoxyphenyl)tetrazol-2-yl]methyl]benzencarbohydroxamic acid (comp. 35); - 4-[(5-benzyltetrazol-2-yl)methyl]benzencarbohydroxamic acid (comp. 36) ; - 4-[(5-benzyltetrazol-1-yl)methyl]benzencarbohydroxamic acid (comp. 37) ; - 4-[[5-(2,4-dichlorophenyl)tetrazol-2-yl]methyl]benzencarbohydroxamic acid (comp. 38); - 4-[[5-(3-methyl-2-thienyl)tetrazol-2-yl]methyl]benzencarbohydroxamic acid (comp. 39); - 4-[[5-(5-methyl-2-thienyl)tetrazol-2-yl]methyl]benzencarbohydroxamic acid (comp. 41); - 4-[[5-(benzothiophen-3-yl)tetrazol-2-yl]methyl]benzencarbohydroxamic acid (comp. 42); - 4-[[5-(2,3-dihydrothieno[3,4-b][1,4]dioxin-5-yl)tetrazol-2-yl]methyl]benzencarbohydroxamic acid (comp. 43); - 4-[[5-[(3,4-dimethoxyphenyl)methyl]-2-[4-(trifluoromethyl)phenyl]-1,2,4triazol-3-yl]methyl]benzenecarbohydroxamic acid (comp. 44); - 4-[[5-[(3,4-dimethoxyphenyl)methyl]-1,3,4-oxadiazol-2yl]methyl]benzencarbohydroxamic acid (comp. 45); - 4-[[5-(2-fluorophenyl)tetrazol-2-yl]methyl]benzencarbohydroxamic acid (comp. 46); - 4-[[5-[(1 S)-1 -amino-2-thiazol-4-yl-ethyl]-1,2,4-oxadiazol-3-yl]methyl]benzencarbohydroxamic acid; 2,2,2-trifluoroacetic acid (comp. 48); - 4-[[5-(3,4-dimethoxyphenyl)-1,2,4-oxadiazol-3-yl]methyl]benzencarbohydroxamic acid (comp. 49); - 4-[[5-(2-thienyl)tetrazol-2-yl]methyl]benzencarbohydroxamic acid (comp. 50); - 4-[[2-benzyl-5-(4-chlorophenyl)-1,2,4-triazol-3-yl]methyl]benzencarbohydroxamic acid (comp. 51); - 4-[[2-(2-pyridyl)-5-(2-thienyl)-1,2,4-triazol-3-yl]methyl]benzencarbohydroxamic acid (comp. 52); - 4-[[2-(2-methoxyphenyl)-5-(2-thienyl)-1,2,4-triazol-3-1Methylbenzenecarbohydroxamic acid (comp. 53); - 4-[[5-(6,6-dimethyl-3-methylsulfanyl-4-oxo-5,7-dihydro-2-benzothiophen-1-1)tetrazol-2-1]methyl]benzencarbohydroxamic 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]benzencarbohydroxamic acid (comp. 57); - 4-[[5-(2,4-difluorophenyl)-1,3,4-oxadiazol-2-yl]methyl]benzencarbohydroxamic acid (comp. 58); acid 4-[[5-[3-(dimethylsulfamoyl)phenyl]tetrazol-2-yl]methyl]benzenecarbohydroxamic (comp. 59); - 4-[(5-phenyl-1,3,4-oxadiazol-2-yl)amino]benzencarbohydroxamic 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]benzencarbohydroxamic acid (comp. 62); - 4-[[5-(3-pyrrolidine-1-ylsulfonylphenyl)-1,3,4-oxadiazol-2-yl]amino]benzencarbohydroxamic acid (comp. 63); - 4-[[5-(3-morpholinosulfonylphenyl)-1,3,4-oxadiazol-2-yl]methyl]benzencarbohydroxamic acid (comp. 64); - 3,5-difluoro-4-[[5-(2-thienyl)tetrazol-2-yl]methyl]benzencarbohydroxamic 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]benzencarbohydroxamic acid (comp. 67); - 4-[(5-phenyl-1,3,4-oxadiazol-2-yl)methyl]benzencarbohydroxamic acid (comp. 68); - 4-[[5-(4-pyrrolidine-1-ylsulfonylphenyl)-1,3,4-oxadiazol-2-yl]methyl]benzencarbohydroxamic acid (comp. 69); - 4-[[5-(3-benzyloxy-4-methoxyphenyl)tetrazol-2-yl]methyl]benzencarbohydroxamic acid (comp. 70); acid 4-[[5-(3-benzyloxy-4-methoxyphenyl)tetrazol-1-1]methyl]benzencarbohydroxamic 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-sulfanylbenzencarbohydioxamic acid (comp. 73); - 4-[[5-(4-methyl-2-morpholino-thiazol-5-yl)-1,3,4-oxadiazol-2-yl]methyl]benzencarbohydroxamic acid (comp. 75); - 4-[[5-[3-(dimethylamino)phenyl]-4-methyl-1,2,4-triazol-3-yl]sulfanyl]benzencarbohydroxamic acid (comp. 77); - 4-[[5-(3-methoxyphenyl)-4-methyl-1,2,4-triazol-3-yl]sulfanyl]benzencarbohydroxamic acid (comp. 78); - 4-[[5-(2,3-dihydrothiene[3,4-b][1,4]dioxin-5-1l)tetrazol-2-1l]methyl]-3,5-difluorobenzencarbohydroxamic acid (comp. 79); - 4-[[5-[3-(dimethylamino)phenyl]-4-methyl-1,2,4-triazol-3-¡l]sulfanyl] acid 3,5-difluorobenzencarbohydroxamic acid (comp. 80); - 4-[5-[4-(hydroxycarbamoyl)phenyl]sulfanyl-4-methyl-1,2,4-triazol-3-yl]piperidine-1-carboxylate tert-butyl (comp. 82); - 4-[[5-(2,3-dihydro-1,4-benzodioxin-3-yl)-4-methyl-1,2,4-triazol-3yl]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]benzencarbohydroxamic acid (comp. 85); 4-[[5-(2-furyl)tetrazol-1-yl]methyl]benzencarbohydroxamic acid (comp. 86); - 4-[[5-(1-isoquinolyl)tetrazol-2-yl]methyl]benzencarbohydroxamic acid (comp. 87); - 4-[[5-(1-isoquinolyl)tetrazol-1-yl]methyl]benzencarbohydroxamic acid (comp. 88); - 4-[[5-(2-pyridyl)tetrazol-2-yl]methyl]benzencarbohydroxamic acid (comp. 89); - 4-[[5-(2-quinolyl)tetrazol-2-yl]methyl]benzencarbohydroxamic acid (comp. 90); - 4-[[5-(2-quinolyl)tetrazol-1-ylmethylbenzenecarbohydroxamic acid (comp. 91); - 3,5-difluoro-4-[[5-(2-furyl)tetrazol-1-yl]methyl]benzencarbohydroxamic acid (comp. 92); - 3,5-difluoro-4-[[5-(1-isoquinolyl)tetrazol-2-yl]methyl]benzencarbohydroxamic acid (comp. 93); - 3,5-difluoro-4-[[5-(1-isoquinolyl)tetrazol-1-yl]methyl]benzencarbohydroxamic acid (comp. 94); - 3,5-difluoro-4-[[5-(2-quinolyl)tetrazol-2-yl]methyl]benzencarbohydroxamic acid (comp. 95); - 3,5-difluoro-4-[[5-(2-quinolyl)tetrazol-1-yl]methyl]benzencarbohydroxamic acid (comp. 96); - 3,5-difluoro-4-[[5-(2-thienyl)-4H-1,2,4-triazol-3yl]sulfanyl]benzenecarbohydroxamic acid (comp. 97); - 4-[(5-benzhydryl-4-methyl-1,2,4-triazol-3-yl)sulfanyl]-3,5-difluorobenzenecarbohydroxamic acid (comp. 98); - 4-[[5-(3-aminothione[2,3-b]pyridin-2-yl)-4-methyl-1,2,4-triazol-3yl]sulfan¡l]-3,5-d¡fluoro-benzenecarbohydroxamic acid (comp. 99); - acid 4-[[5-(1,5-dimethylpyrazol-3-yl)-4-methyl-1,2,4-triazol-3-yl]sulfanyl]- 3,5-difluoro-benzenecarbohydroxamic acid (comp. 100); - acid 3,5-difiuoro-4-[[4-methyl-5-(1 -phenylcyclobutyl)-1,2,4-triazol-3¡l]sulfan¡l]benzenecarboh¡droxam¡co (comp. 101); - acid 3,5-difluoro-4-[[5-[1 -(3-fluorophenyl)cyclopentyl]-4-methyl-1,2,4- triazol-3-¡l]sulfan¡l]benzenecarboh¡droxamic (comp. 102); - 3,5-d¡fluoro-4-[[5-[1-(4-methoxyphenyl)cyclohexyl]-4-methyl-1,2,4- triazol-3-yl]sulfanyl]benzenecarbohydroxamic acid (comp. 103); - ácido 3,5-difluoro-4-[[5-[1-(4-methoxyphenyl)cyclopropyl]-4-methyl-1,2,4-triazol-3-yl]sulfan¡l]benzenecarb¡droxám¡co (comp 104); - ácido 4-[[5-[3-(pentafluoro-lambda-6-sulfanyl)phenyl]tetrazol-2-¡l]methyl]benzenecarbohydroxámico (comp. 106); - 4-[[5-[3-(pentafluoro-lambda6-sulfanyl)phenyl]tetrazol-1-methylbenzenecarbohydroxamic acid (comp. 107); - 3,5-difluoro-4-[[5-[3-(pentafluoro-lambda6-sulfanyl)phenyl]tetrazolium acid 2-yl]methyl]benzenecarbohydroxamic (comp. 108); - 3,5-difluoro-4-[[5-[3-(pentafluoro-lambda6-sulfanyl)phenyl]tetrazolium acid 1-¡l]methyl]benzenecarbohydroxamic (comp. 109); - 4-[[5-[4-(pentafluoro-lambda6-sulfanyl)phenyl]tetrazol-2yl]methyl]benzenecarbohydroxamic acid (comp. 110); acid 4-[[5-[4-(pentafluoro-lambda6-sulfanyl)phenyl]tetrazol-1yl]methyl]benzenecarbodihydroxamic acid (comp. 111); - 3,5-difluoro-4-[[5-[4-(pentafluoro-lambda6-sulfanyl)phenyl]tetrazolium acid 2-¡l]methyl]benzenecarbohydroxámico (comp. 112); - ácido 3,5-difluoro-4-[[5-[4-(pentafluoro-lambda6-sulfanyl)phen¡l]tetrazol- 1-¡l]methyl]benzenecarbohydroxamic (comp. 113); - ácido 3,5-difluoro-4-[[4-methyl-5-[3-(4-methyl-4-oxido-piperazin-4-io-1 yl)phenyl]-1,2,4-triazol-3-¡l]sulfan¡l]benzenecarbohydroxámico (comp. 114); - ácido 3,5-difluoro-4-[[4-(4-fluorophenyl)-5-(1-piperidylmethyl)-1,2,4-triazole- 3-¡l]sulfanyl]benzenecarbohydroxámico (comp. 115); - ácido 3,5-d¡fluoro-4-[[4-(2-furylmethyl)-5-pyrrolid¡n-1-yl-1,2,4-triazol-3-yl]sulfanyl]benzenecarbohydroxámico (comp. 116); - 4-[(4-benzyl-5-morpholino-1,2,4-triazol-3-yl)sulfanyl]-3,5-difluorobenzenecarbohydroxamic acid (comp. 117); - 4-[[5-(2,3-dihydrothieno[3,4-b][1,4]dioxin-5-yl)-4-methyl-1,2,4triazol-3-yl]sulfanyl]-3,5-difluoro-benzenecarbohydroxamic acid (comp. 118); - 3,5-difluoro-4-[[5-(1-isoquinolyl)-4-methyl-1,2,4-triazol-3-ylsulfanylbenzencarbohydroxamic acid (comp. 121); - 3,5-difluoro-4-[[4-methyl-5-(2-quinolyl)-1,2,4-triazol-3-ylsulfanylbenzencarbohydroxamic acid (comp. 122); - 4-[(5-pyrimidin-2-yltetrazol-2-yl)methyl]benzencarbohydroxamic acid (comp. 123); - 4-[(5-pyrimidin-2-yltetrazol-1-yl)methyl]benzencarbohydroxamic acid (comp. 124); - 3,5-difluoro-4-[(5-pyrimidine-2-yltetrazol-1-yl)methyl]benzencarbohydroxamic acid (comp. 125); - 4-[[5-[5-(trifluoromethyl)-2-pyridyl]tetrazol-2-methylbenzenecarbohydroxamic 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]benzencarbohydroxamic acid (comp. 128); - 3,5-difluoro-4-[[5-[5-(trifluoromethyl)-2-pyridyl]tetrazol-1-yl]methyl]benzencarbohydroxamic acid (comp. 129); - 4-[[5-[3-morpholino-5-(trifluoromethyl)-2-pyridyl]tetrazol-2-11Methylbenzenecarbohydroxamic acid (comp. 130); - 4-[[5-[3-morpholino-5-(trifluoromethyl)-2-pyridyl]tetrazol-1-yl]methyl]benzencarbohydroxamic acid (comp. 131); - 4-[[5-(2-pyridylmethyl)tetrazol-2-yl]methyl]benzencarbohydroxamic acid; 2,2,2-trifluoroacetic acid (comp. 132); - 4-[[5-(2-pyridylmethyl)tetrazol-1-yl]methyl]benzencarbohydroxamic acid; 2,2,2-trifluoroacetic acid (comp. 133); - 3,5-difluoro-4-[[5-(2-pyridylmethyl)tetrazol-2-yl]methyl]benzencarbohydroxamic acid; 2,2,2-trifluoroacetic acid (comp. 134); - ácido 3,5-difluoro-4-[[5-(2-pyridylmethyl)tetrazol-1-¡IJmethylJbenzenecarbohidiOxámico; 2,2,2-trifluoroacetic acid (comp. 135); - ácido 3,5-difluoro-4-[[4-methyl-5-[1-phenyl-5-(2-thienyl)pyrazol-3-yl]-1,2,4triazol-3-yl]sulfanyl]benzenecarbohydroxámico (comp. 136); - ácido 3,5-difluoro-4-[[5-(6-fluoro-2-methyl-3-quinolyl)-4-methyl-1,2,4triazol-3-yl]sulfanyl]benzenecarbohydroxámico (comp. 137); - ácido 3,5-difluoro-4-[[5-(4-fluorophenyl)-4-(2-morpholinoethyl)-1,2,4-triazol- 3-yl]sulfanyl]benzenecarbohydroxamic (comp. 138); - 3,5-difluoro-4-[[4-(2-furylmethyl)-5-pyrazin-2-yl-1,2,4-triazol-3-yl]sulfanyl]benzenecarbohydroxamic acid (comp. 139); - ácido 3,5-difluoro-4-[[4-(2-furylmethyl)-5-(2-pyridyl)-1,2,4-triazol-3yl]sulfan¡l]benzenecarboh¡droxámico (comp. 140); - ácido 4-[[4-benzyl-5-(pyrrolidin-1-ylmethyl)-1,2,4-triazol-3-yl]sulfanyl]-3,5difluoro-benzenecarbohydroxámico (comp. 141); - 4-[[4-benzyl-5-(2-furyl)-1,2,4-triazol-3-yl]sulfanyl]-3,5-difluorobenzenecarbohydroxamic acid (comp. 142); - 4-[[4-benzyl-5-(2-thienyl)-1,2,4-triazol-3-yl]sulfanyl]-3,5-difluorobenzencarbohydroxamic 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]benzencarbohydroxamic acid (comp. 145); - 3,5-difluoro-4-[[4-(2-furylmethyl)-5-(4-pyridyl)-1,2,4-triazol-3yl]sulfanyl]benzenecarbohydroxamic acid (comp. 146); acid 3,5-difluoro-4-[[4-(2-furylmethyl)-5-(3-pyridyl)-1,2,4-triazol-3-yl]sulfanyl]benzenecarbohydroxamic (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 (comp. 149); - 4-[[5-(1-benzyl-4-phenyl-4-pyridyl)-4-methyl-1,2,4-triazol-3-1]sulfanyl]-3,5-difluorobenzencarbohydroxamic acid (comp. 150); - 3,5-difluoro-4-[[4-methyl-5-[3-(4-methylpiperazin-1 -yl)su Ifon i lien i I]- acid 1,2,4-triazol-3-yl]sulfanyl]benzenecarbohydroxamic (comp. 151); - 4-[[5-[3-(4-benzylpiperazin-1 -yl)sulfonylphenyl]-4-methyl-1,2,4-triazole acid 3-yl]sulfanyl]-3,5-difluoro-benzenecarbohydroxamic (comp. 152); - 3,5-difluoro-4-[[4-methyl-5-(3-pyridyl)-1,2,4-triazol-3-yl]sulfanyl]benzencarbohydroxamic acid (comp. 153); - methyl 4-[[2-[[2,6-difluoro-4-(hydroxycarbamoyl)phenyl]methyl]tetrazol-5-yl]methyl]benzoate (comp. 154); ~ 4-[[1-[[2,6-difluoro-4-(hydroxycarbamol)phenyl]methyl]tetrazol-5-yl]methyl]benzoate methyl (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-l]methyl]benzoic (comp. 159); - 4-[[2-[[2,6-difluoro-4-(hydroxycarbamoyl)phenyl]methyl]tetrazol-5yl]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]pridine-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-difluorobenzencarbohydroxamic acid (comp. 165); - 3,5-difluoro-4-[[4-methyl-5-[3-(4-methylpiperazin-1-¡l)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]su lyan i I]- acid 3,5-difluorobenzencarbohydroxamic acid (comp. 167); - 4-[[5-[4-(azepan-1-iImethyl)pheníl]-4-methiI-1,2,4-triazol-3-yl]su Ifanyl]-3,5difluoro-benzenecarbohydroxamic acid (comp. 168); - 4-[[5-(4-aminophenyl)tetrazol-2-yl]methyl]benzencarbohydroxamic acid (comp. 169); - 4-[[5-(4-aminophenyl)tetrazol-1-yl]methyl]benzencarbohydroxamic acid (comp. 170); - 4-[[5-(4-aminophenyl)tetrazol-2-yl]methyl]-3,5-difluorobenzenecarbohydroxamic acid (comp. 171); - 4-[[5-(4-aminophenyl)tetrazol-1-yl]methyl]-3,5-difluorobenzenecarbohydroxamic acid (comp. 172); - 4-[[5-[4-(aminomethyl)phenyl]tetrazol-2-11methylbenzenecarbohydroxamic acid (comp. 173); - 4-[[5-[4-(aminomethyl)phenyl]tetrazol-1-methylbenzenecarbohydroxamic acid (comp. 174); - 4-[[5-[4-(aminomethyl)phenyl]tetrazol-2-yl]methyl]-3,5-difluorobenzenecarbohydroxamic acid (comp. 175); - 4-[[5-[4-(aminomethyl)phenyl]tetrazol-1-1]methyl]-3,5-difluorobenzencarbohydroxamic acid (comp. 176); - 3,5-difluoro-4-[[4-methyl-5-[1-(2-pyridyl)cyclopropyl]-1,2,4-triazol-3-yl]sulfanyl]benzencarbohydroxamic acid (comp. 177); - 3,5-difluoro-4-[[4-methyl-5-[1-(3-pyridyl)cyclopropyl]-1,2,4-triazol-3-yl]sulfanyl]benzencarbohydroxamic 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]benzencarbohydroxamic acid (comp. 180); - ácido 3,5-difluoro-4-[[4-methyl-5-[3-(1-piperidylmethyl)phenyl]-1,2,4-triazole- 3-yl]sulfanyl]benzenecarbohydroxamic (comp. 181); - 3,5-difluoro-4-[[4-methyl-5-[3-(morpholinomethyl)phenyl]-1,2,4-triazolo- acid 3-yl]sulfanyl]benzenecarbohydroxamic (comp. 182); - ácido 4-((3-((1H-indol-3-yl)methyl)-5-(thiophen-2-yl)-4H-1,2,4-triazol-4yl)methyl)-N-hydroxybenzamide (comp. 183); - ácido 4-[[5-[3-[[benzyl(methyl)amino]methyl]phenyl]-4-methyl-1,2,4-triazol-3yl]sulfanyl]-3,5-difluorobenzenecarbohydroxámico (comp. 184); - ácido 4-[[3-[(3,4-dimethoxyphenyl)methyl]-5-(2-thienyl)-1,2,4-triazol-4yl]methyl]benzenecarbohydroxámico (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); - ácido 3,5-difluoro-4-[[5-[4-[methyl(methylsulfonyl)amino]phenyl]-1,3,4thiadiazol-2-yl]sulfanyl]benzenecarbohydroxámico (comp. 187); - 4-[(5-phenyl-1,3,4-oxadiazol-2-yl)sulfanyl]benzencarbohydroxamic acid (comp. 188); - 4-[(5-phenyl-1,2,4-oxadiazol-3-yl)methyl]benzencarbohydroxamic acid (comp. 189); - 4-[(5-phenyl-1.S^-thiadiazol^-1Omethylbenzenecarbohydroxamic acid (comp. 190); - 3,5-difluoro-N-hydroxy-4-((5-(pyridin-3-yl)-1,3,4-thiadiazol-2-yl)thio)benzamide acid (comp. 191); - 3,5-difluoro-4-[(5-phenyl-1,3,4-oxadiazol-2-yl)sulfanyl]benzencarbohydroxamic acid (comp. 192); - 4-[[5-(2-morpholino-4-pyridyl)-1,2,4-oxadiazol-3-yl]methyl]benzencarbohydroxamic acid (comp. 193); - 3,5-difluoro-N-hydroxy-4-((5-phenyl-1,2,4-oxadiazol-3-yl)methyl)benzamide acid (comp. 194); acid 3,5-d if luoro-4-[[5-(4-pyridyl)-1,3,4-thiad iazol-2-yl]methyl]benzenecarbohydroxamic (comp. 195); - 4-[[5-(5-bromo-3-pyridyl)-1,3,4-thiadiazol-2-yl]sulfanyl]-3,5-difluorobenzencarbohydroxamic acid (comp. 196); - 3,5-difluoro-4-[[5-(5-morpholino-3-pyridyl)-1,3,4-thiadiazol-2-yl]methyl]benzencarbohydroxamic 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]benzencarbohydroxamic 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] acid 1.2.4- oxadiazol-3-yl]methyl]benzencarbohydroxamic acid (comp. 201); - 3,5-difluoro-4-[[5-[5-(pyrrolidine-1-ylmethyl)-2-furyl]-1,2,4-oxadiazol- 3-yl]methyl]benzenecarbohydroxamic (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]- acid 1.2.4-triazol-3-yl]sulfanyl]benzenecarbohydroxamic (comp. 205); - 4-[[5-[5-[(dimethylamino)methyl]-2-furyl]-4-methyl-1,2,4-triazol-3-yl]sulfanyl]-3,5-difluorobenzencarbohydroxamic acid(comp. 206); - 3,5-difluoro-4-[[4-methyl-5-[5-(pyrrolidine-1-ylmethyl)-2-furyl]-1,2,4-triazol-3-yl]sulfanyl]benzencarbohydroxamic acid (comp. 207); - 4-[[5-[5-ethyl-4-(pyrrolidine-1-ylmethyl)-2-furyl]-4-methyl-1,2,4-triazol-3-1]sulfanyl]-3,5-difluorobenzencarbohydroxamic acid (comp. 208); - 4-[[4-methyl-5-[5-[(4-methylpiperazin-1 -yl)methyl]-2-furyl]-1,2,4-triazole acid 3-yl]sulfanyl]benzenecarbohydroxamic (comp. 209); - ácido 3,5-difluoro-4-[[4-methyl-5-[6-(2-pyrrolidin-1-ylethyl)-3-pyridyl]-1,2,4triazol-3-yl]sulfanyl]benzenecarbohydroxám¡co (comp. 210); - ácido 4-[[5-[5-(diethylaminomethyl)-2-furyl]-4-methyl-1,2,4-triazol-3-yl]sulfanyl]-3,5-difluorobenzenecarbohydroxamic acid (comp. 211); - ácido 3,5-difluoro-4-[[4-methyl-5-[5-(1-piperidylmethyl)-2-furyl]-1,2,4triazol-3-yl]sulfanyl]benzenecarbohydroxamic acid (comp. 212); - ácido 4-[[5-[5-(diethylaminomethyl)-2-methyl-3-furyl]-4-methyl-1,2,4-triazol-3yl]sulfanyl]-3,5-difluorobenzenecarbohydroxámico (comp. 213); - ácido 4-[(5-phenyltetrazol-2-yl)methyl]benzenecarbohydroxámico (comp. 214) ; - ácido 4-[(5-phenyltetrazol-1-yl)methyl]benzenecarbohydroxámico (comp. 215) ; - ácido 4-[(5-phenyl-4H-1,2,4-triazol-3-yl)methyl]benzenecarbohydroxámico (comp. 216); - N-hydroxy-4-((4-methyl-5-phenyl-4H-1,2,4-triazol-3-1)methyl)benzamide (comp.217). The following compounds of formulas (I) and (II) are particularly preferred: The compounds of the present invention may contain one or more chiral centers (asymmetric carbon atoms), therefore, they may exist in enantiomeric and / or diastereomeric forms. All possible optical isomers, alone or in combination with each other, are within the scope of the present invention. The compounds according to the invention can be used alone or in combination with other drugs such as proteasome inhibitors, immunochemical inhibitors, spheroids, bromodomain inhibitors and other epigenetic drugs, traditional chemotherapeutic agents, kinase inhibitors such as, for example, but without limitation, JAK family, CTLA4, PD1 or PDL1 checkpoint 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 preferably in combination, are useful for the treatment of HDAC-mediated diseases. The compounds of the invention, alone or preferably in combination, are 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, and eye diseases (e.g., uveitis). Accordingly, the present invention also provides pharmaceutical compositions comprising a therapeutically effective amount of compounds of formula (I) or (II) or salts, pharmaceutically acceptable isomers and pharmacologically acceptable prodrugs thereof, together with at least one pharmaceutically acceptable excipient. These compositions may be liquid, suitable for enteral or parenteral administration, or solid, for example, in the form of capsules, tablets, lozenges, powders, or granules for oral administration, or in forms suitable for cutaneous administration such as creams or ointments, or for inhalation administration. The pharmaceutical compositions of the present invention may be prepared using known methods. General synthesis method The compounds described in the present invention can be prepared 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. The progression of the reaction was monitored by HPLC, UPLC or HPLCMS analysis. The triazol-thiol core compounds were obtained by reaction of 1,2,4-triazol-tioles, opcionalmente sustituido con metil-4-yodo-benzoato o metil-3,4,5-trifluoro-benzoato, en presencia de carbonato de potasio en DMF bajo calentamiento durante la noche. La reacción con 4-yodobenzoato de metilo se catalizó con yoduro de cobre y L-prolina (Esquema 1) y se calentó a 120 °C (Liang-Feng y col., Tetrahedron (2011), 67, 28782881). Por otro lado, la reacción con 3,4,5-trifluoro-benzoato de metilo procede incluso en condiciones suaves (55 °C) y sin catálisis (Esquema 2) (Dudutiene et al., Bioorg. Med. Chem. (2013) , 21 (7), 2093-2106; WO03 / 062225). The same conditions were used to synthesize core compounds of 1,3,4-thiadiazol-2-thiol and 1,3,4-oxadiazol-2-thiol. The conversion of ester derivatives to the corresponding hydroxamic acids was achieved by treatment with a large excess of aqueous hydroxylamine in a basic medium (NaOH) in methanol. Hydroxamic acid can also be synthesized by hydrolysis of methyl ester with NaOH and subsequent condensation with hydroxylamine, after activation with HATU or other coupling reagents. Scheme 1-Synthesis of benzohydroxamic derivatives with Triazole, Thiadiazole and Oxadiazole core Scheme 2-Synthesis of 3,5-Difluorobenzohydroxamic derivatives with triazole, thiadiazole and oxadiazole core Many of the starting 1,2,4-triazol-thiols are commercially available. In some cases, they have been synthesized according to the two routes shown in Scheme 3. The open-chain intermediate was prepared from carboxylic acid by activation with T3P and condensation with N-substituted hydrazinecarbothiamide in the presence of DIPEA in DMF (US2007 / 0232808). The same intermediate was obtained from hydrazide, which was treated with N-substituted isothiocyanate in refluxing ethanol (Lei et al., ChemMedChem (2016), 11, 822-826; Nadjet et al., Molecules (2015), 20, 16048-16067). Cyclization of the open-chain intermediate was achieved by adding aqueous NaOH to the reaction mixture. vAoh * s h2n^ JL >-R1 NN Η H T3P, DIPEA DMF 0°C -> rt, 2h O 'hS'' H • V EtOH, reflux 2M NaOH 70°C, 16h Scheme 3-Synthesis of 1,2,4-Triazol-thiols Commercially unavailable 1,3,4-thiadiazol-2-thiols were synthesized by treating the corresponding hydrazide with KOH and CS2 at low temperature (0-5 °C) for 1 hour and with H2SO4 in a second step, as described in Scheme 4. R6< vCONHNHo 1. KOH, CS2 2. H2SO4 -----► NN rVíÁs>~SH Scheme 4-Synthesis of 1,3,4-Thiadiazol-thiols The triazole core compounds were prepared as described in Scheme 5a from 2-(4-(methoxycarbonyl)phenyl)acetic acid by reaction with a carboxyimidamide in the presence of HATU and DIPEA in DMF. After complete conversion of the starting materials into the intermediate, a substituted hydrazine and an excess of acetic acid were added to the reaction mixture. The formation of the triazole cycle was achieved by heating the mixture overnight (Castañedo et al., J. Org. Chem. (2011), 76(4), 1177-1179). The 1,3,4-thiadiazole and 1,3,4-oxadiazole backbone compounds were also obtained by cyclization of an open-chain intermediate prepared by condensation of 2-(4-(methoxycarbonyl)phenyl)acetic acid or 2-(2,6-difluoro-4-(methoxycarbonyl)phenyl)acetic acid with an appropriate hydrazide by standard HATU DIPEA activation. The hydrazides were commercially available or could be readily prepared from the corresponding carboxylic acid (Scheme 5c). Lawesson's reagent was used as the cyclizing agent for 1,3,4-thiadiazole derivatives, while the same intermediate was cyclized after treatment with an excess of Burgess's reagent in refluxing toluene or THF to give 1,3,4-oxadiazoles (Scheme 5b). Since 2-(2,6-difluoro-4(methoxycarbonyl)phenyl)acetic acid is not commercially available, it was synthesized by the reaction of methyl 3,4,5-trifluorobenzoate and di-tert-butyl malonate in the presence of sodium hydride in anhydrous DMF.The resulting di-tert-butyl 2-(2,6-difluoro-4-(methoxycarbonyl)phenyl)malonate was then decarboxylated by reflux TFA treatment (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 condensation (Scheme 5c). The conversion of ester derivatives to the corresponding hydroxamic acids was achieved by hydroxylaminolysis, as already described in the previous cases. _ HATU O H flF* |dcl *·= Aχ\ν| I1· FOJ i.soca ÍMQMOoc, LL 3TFA.DCW Laweson Totaer» Laweson Tofo»» or W™ reagent My <Z Reagent M or **Laweson Scheme 5-Synthesis of benzohydroxamic derivatives with triazole, thiadiazole and oxadiazole core 1,3,4-Oxadiazole derivatives were used as starting materials for the synthesis of triazole-core compounds. The conversion was achieved by heating oxadiazole in THF in the 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 scaffold were prepared from methyl p-aminomethylbenzoate hydrochloride and the corresponding acyl chloride in the presence of trimethylamine. The amide thus obtained was refluxed in thionyl chloride to form an imidoyl chloride intermediate, which gave the desired product after reaction with the corresponding hydrazide and subsequent cyclization in refluxing toluene. Scheme 7). (WO2011106650 (A2) — 2011-09-01; Begum et al. Med. Chem. Commun. 2015, 6, 80–89; Aster et al. Bioorg. Med. Chem. Lett. 2008, 18, 2799–2804.) either Scheme 7-Synthesis of benzohydroxamic derivatives with a triazole core 3,4,5-trisubstituted Compounds containing tetrazole residue were obtained by the reaction of / VH-tetrazol with methyl-4-(chloromethyl)benzoic acid or methyl 4-(chloromethyl)-3,5-difluorobenzoate in the presence of potassium carbonate in acetonitrile, under heating (Scheme 8) (WO2012 / 106995). either Scheme 8-Synthesis of Benzohydroxamic derivatives v 3,5DifluoroBenzohydroxamic with tetrazole core Regioselectivity depends on the tetrazole substrate, which is usually the 2,5-disubstituted product, favored 2-10 times over the other product. 1,5-disubstituted. 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 NH-tetrazoles are commercially available, while others were synthesized by the respective nitrile treatment with sodium azide and ammonium chloride in DMF under heating (Scheme 9). NaN3, NH4Cl DMF, 100°C, 16h Scheme 9-Synthesis of / VH-Tetrazoles Compounds containing the 2-amino-1,3,4-oxadiazole moiety were obtained by combining an acyl hydrazide with methyl isocyanatobenzoate in THF at room temperature (rt) and refluxing the newly formed intermediate in the presence of an excess of Burgess reagent (Scheme 10) (Dolman et al., J. Org. Chem. (2006), 71(25), 9548). OH Burgess reagent THF, refhgo Scheme 10-Synthesis of Benzo-Hydroxamic derivatives with a 2Amino-1,3,4-Oxadiazole core The conversion of ester compounds into hydroxamic acid has been achieved, as described in the previous cases, by hydroxylaminolysis. Los compuestos del núcleo de 1,2,4-oxadiazol se sintetizaron a partir de ácido 4-(cianometil)benzoico, o del correspondiente metil éster, mediante tratamiento con clorhidrato de hidroxilamina en presencia de un exceso de hidróxido de potasio o bicarbonato de sodio en etanol a reflujo (Esquema 11). El ácido (Z)-4-(2-amino-2-(hidroxiimino) etil) benzoico así obtenido se hizo reaccionar después con un ácido carboxílico adecuado activado previamente con HATU y DIPEA u otros activadores para dar un intermediario abierto, que se somete a ciclación por calentamiento a 100 °C y en presencia de tamices moleculares o agentes de ciclación, tales como carbonildiimidazol. 1,2,4-Qxadiazole The conversion of carboxylic acid to hydroxamic acid can be carried out using any method known in the art. It is generally 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 O-(tetrahydro-2H-pyran-2-yl)hydroxylamine in order to obtain a hydroxamic acid-protected form that can be released by treatment with TFA (Scheme 12). through a protected form of this For the synthesis of compounds with a 1,3,4-oxadiazole core (Scheme 13), the appropriate hydrazide was prepared by reacting the corresponding acid, activated by acyl chloride, with Boc-hydrazine and subsequent deprotection by treatment with TFA. The hydrazide was then condensed with 2-(4-(methoxycarbonyl)phenyl)acetic acid, previously activated with HATU and DIPEA. Deletion of the open intermediate was achieved by treatment with an excess of Burgess reagent in toluene or THF under reflux. either Burgess reagent toluene Scheme 13-Synthesis of hydroxamic derivatives with a 1,3,4Qxadiazole core As shown previously, it is possible to obtain the final hydroxamic derivative by hydroxylaminolysis of the methyl ester by reaction with hydroxylamine, in the presence of a large excess of sodium hydroxide. The following examples are intended to further illustrate the invention, but not to limit it. EXAMPLE 1-Synthesis of (S)-N-(1-(3-(4-(hydroxycarbamoyl)benzyl)-1,2,4-oxadiazol-5-yl)-2-(thiazol-4-yl)ethyl-3,4-dimethoxybenzamide (comp. 1) Stage A NH,OH To 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 for 20 hours. The solution was then cooled, diluted with water (300 mL), and acidified to pH 6 with concentrated HCl. The white precipitated solid was filtered and dried under vacuum at 50 °C overnight. 2.6 g of product were obtained, which was used for the next step without further purification. Stage B (S)-2-( / V-Fmoc-amino)-3-(thiazol-4-yl)propanoic acid (2 g, 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 materials, molecular sieves were added to remove water of formation and aid cyclization of the open intermediate. After two hours, the molecular sieves were removed by filtration, and the solvent was evaporated under reduced pressure. The residue was taken in methanol. The white solid was removed by filtration. The solvent was partially evaporated. A further precipitation of a white solid was observed, which was filtered out. The solution was evaporated to dryness and the residue was purified by reversed-phase flash chromatography (RPC) in an H2O / ACN / TFA gradient. The acid obtained in step B (82 mg, 1 eq) was activated by treatment with HATU (73 mg, 1.3 eq) and DIPEA (41 μg, 1.3 eq) in DMF at room temperature. O-(tetrahydro-2H-pyran-2-yl)hydroxylamine (17 mg, 1 eq) was then added to the reaction mixture. After 2 hours of stirring at room temperature, the solvent was evaporated in a vacuum centrifuge. The residue was used for the next step without further purification. Stage D The product obtained in step C was diluted in 1 mL of THF and treated with DEA ​​(70 g, 4.5 eq). After 4 h of stirring at 40 °C, the solvent and excess DEA were removed by evaporation under reduced pressure. The residue was taken with 1 mL of DMF and 3,4-dimethoxybenzoic acid (27 mg, 1.3 eq), previously activated with HATU (74 mg, 1.3 eq) and DIPEA (41 g, 1.3 eq) in DMF (1 mL), and added to the solution. The reaction mixture was stirred at room temperature for 4 hours. Finally, 0.4 ml of TFA to unprotect the hydroxamic function. After hours, the solvent and excess TFA were removed by evaporation and the residue was purified by semi-preparative LC-MS (m / z 509.84 [MH +]). The following compound was synthesized using the same procedure: Structure 537.97 EXAMPLE 2-Synthesis of 2,2,2-trifluoroacetate of (S)-4-((5-(1-amino-2(thiazol-4-yl)ethyl)-1,2,4-oxadiazol-3-yl)methyl)-N-hydroxybenzamide (comp. 48) 1,2,4-oxadiazol-5-1,2-(thiazol-4-1)ethylcarbamate (obtained in Step C of Synthesis of Compound 1) (222 mg, 1 eq) was treated with DEA ​​(159 μL, 4.5 eq) in DMF (1 ml) overnight at RT. Then 0.520 ml of TFA (20 eq) were added to the reaction mixture. The solvent was removed by evaporation and the residue was purified by semipreparative LC-MS (m / z 346.04 [MH+]). Example 3-Synthesis of 4-[[5-(3,4-dimethoxyphenyl)-1,2,4-oxadiazol-3-1-1-methylbenzenecarbohydroxamic acid compound 49) Stage A A 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 HCl (pH ≥ 5) were added to the reaction mixture. The desired product, obtained as a precipitate, was filtered through a sintered septum and dried under vacuum overnight. The 320 mg of clean product. Stage 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 the reaction of 3,4-dimethoxybenzoic acid with an excess of thionyl chloride, was added to the reaction mixture. The reaction mixture was refluxed for 4 hours. The solvent was evaporated under reduced pressure and the product was purified by semipreparative LC-MS. Stage C 4-((5-(3,4-dimethoxyphenyl)-1,2,4-oxadiazol-3-yl)methyl)benzoic acid (71 mg, 1 eq) obtained in Step B was activated by treatment with HATU (103 mg, 1.3 eq) and DIPEA (47 g / ml, 1.3 eq) in DMF (1 ml) for 30 minutes at room temperature. Hydroxylamine hydrochloride (14 mg, 1 eq) and additional DIPEA (47 g / ml, 1.3 eq) were then added to the reaction mixture. After stirring at room temperature overnight, the solvent was removed by evaporation under reduced pressure, and the residue was purified by semipreparative LC-MS. 33 mg of clean product (m / z 356.08 [MH+]) was recovered. Example 4. Synthesis of 4-((5-(2,4-difluorophenyl)-1,3,4-oxadiazol-2¡l)methyl)-Nh¡droxybenzamide (comp. 58) Stage A A solution of boc-hydrazine (150 mg, 1 eq) in ACN (2 mL) and 95 mg of NaHCO3 (1 eq) were added to a solution of 2,4-difluorobenzoyl chloride (200 mg, 1 eq) in ACN (3 mL). After three hours at room temperature, the solvent was evaporated in an air stream. The residue was treated with TFA for three hours. The acid was removed in an air stream, and the residue was taken with EtOAc and washed with 2.5% NaHCO3 solution. The combined organic phases were dried over Na2SO4, filtered, and evaporated to dryness. 159 mg of product were obtained, which was used for the next step without any further purification. Stage B HATU (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 the reagents. A solution of 2,4-difluorobenzohydrazide (153 mg, 1 eq) in THF (2 mL) was then added to the mixture. After 4 h at room temperature, complete conversion of the starting reagents to the desired product was observed. The solvent was removed by evaporation in a stream of air. The residue was collected in water, and the resulting precipitate was filtered through a sintered septum. The product (149 mg) was used in the subsequent step without further purification. Stage C Burgess Reagent F EITHER 175 mg of Burgess reagent (1.72 eq) were added to a suspension of the compound obtained in Step B (149 mg, 1 eq) in 5 mL of refluxed dry toluene. After one hour, complete conversion of the starting compound to the cyclic product was observed. The solvent was removed by vacuum evaporation. The residue was collected with DCM and washed with 1N HCl and H2O. The organic phase was dried over Na2SO4, filtered, and evaporated to dryness. 132.3 mg of product was recovered and used in the next stage without further purification. Stage D 0.707 mL of aqueous hydroxylamine (60 eq) was added to a solution of the compound obtained in step C (132 mg, 1 eq) in 4 mL of MeOH / THF. 1.988 mL of 1 N NaOH (5 eq) was slowly added dropwise. After approximately one hour, the system was neutralized by adding 2 mL of 1 N HCl. The solvent was evaporated under vacuum, and the residue was diluted with a 2.5% NaHCO3 solution, filtered, and washed with H2O. The solid was resuspended in Et2O and filtered. 53 mg of pure product (m / z 332.01 [MH+]) was obtained. The following compounds were synthesized using the same procedure: Εαπρ. m / z [MH] Structure 40BJCE 445JB 356JH 370JB KM 428^94 401.96 Example 5. Synthesis of 4-[(5-phenyl-1,3,4-oxadiazol-2-Daminobenzenecarbohydroxamic acid (comp. 60) Stage A 1 mg of benzohydrazide (1 eq) and methyl 4-isosiacianobenzoate (88.5 mg, 1 eq) were mixed in THF (5 mL) at room temperature. The resulting solution was stirred for 3 hours. Intermediate formation was verified by HPLC and LC-MS. The solvent was removed by evaporation under reduced pressure. The residue was collected with toluene. The mixture was heated under reflux, and Burgess reagent (298 mg, 2.5 eq) was added in small portions until complete conversion of the intermediate to the cyclic product. After cooling to room temperature, the mixture was washed with water. The organic phase was dried, filtered, and evaporated to dryness. The product was purified by crystallization on DCM. 172 mg of clean product were obtained (Dolman et al., J. Org. Chem. (2006), 71 (25), 9548). Stage B or either .OH The ester obtained in Step A (172 mg, 1 eq) was suspended in 4 mL of methanol, and the reaction mixture was cooled to 0 °C in an ice bath and magnetically stirred. After the addition of hydroxylamine (50% aqueous solution, 1.365 mL, 40 eq), 1 M aqueous sodium hydroxide solution (6 mL, 10 eq) was slowly added dropwise. The ice bath was removed, allowing the solution to reach room temperature. The conversion of the starting material to hydroxamic acid was confirmed by HPLC after 1 hour. The methanolic portion was removed by evaporation under reduced pressure, and the reaction was subsequently inactivated by the addition of 6 mL of 1 M aqueous HCl 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 saturated sodium bicarbonate solution (2x), brine (2x), dried over sodium sulfate, filtered, and concentrated to dryness. 26 mg of pure product (m / z 297.09 [MH+]) was recovered. The following compound was synthesized using the same procedure: 43000 Example 6. Synthesis of 3,5-diflupro-N-hydroxy-4-((4-methyl-5-(pyridin-2-yl)4H-1,2,4-triazol-3-yl)thio)benzamide (comp. 14) Stage A 2M NaOH 70°C, 16hr 2-Pyridylcarboxylic acid (123 mg, 1 eq) and 4-methyl-3-thiosemicarbazide (116 mg, 1.1 eq) were suspended in 2 mL of DMF, and the mixture was cooled to 0 °C in an ice bath. T3P (50% DMF solution, 893 µL, 1.5 eq) and diisopropylethylamine (310 µL, 1.78 eq) were slowly added to the reaction mixture under stirring. The ice bath was removed, and the mixture was reacted at room temperature for 16 hours. Complete conversion of the starting material was confirmed by HPLC. 2 mL of ethyl acetate, 2 mL of water, and 2 mL of 4 M aqueous NaOH solution were added to the reaction mixture. The phases were separated, and the organic layer was re-extracted with a 4M aqueous NaOH solution. The combined aqueous phases were stirred for 16 hours at 70 °C. The conversion of the open intermediate to the desired product was confirmed by LC-MS. The pH of the reaction mixture was adjusted to 5 by dropwise addition of concentrated hydrochloric acid under stirring.The precipitate was collected by filtration. 157 mg of product were obtained, which were used in the next stage without any further purification. Stage B oo 4-methyl-5-(pyridin-2-yl)-4H-1,2,4-triazol-3-thiol (157 mg, 1 eq), methyl 3,4,5trifluorobenzoate (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 heated 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 sulfate, filtered, and concentrated. The crude reaction was purified by flash chromatography (Grace Reveleris X2, hexane:ethyl acetate). 149 mg of clean product were obtained (Dudutiene et al., Bioorg. Med. Chem. (2013), 21 (7), 2093-2106; international patent application WO03 / 062225). Stage C either The ester obtained in step B (149 mg, 1 eq) was suspended in 5 mL of methanol, and the reaction mixture was cooled to 0 °C in an ice bath and magnetically stirred. After the addition of hydroxylamine (50% aqueous solution, 0.97 mL, 40 eq), 1 M aqueous sodium hydroxide solution (4.1 mL, 10 eq) was added dropwise. The ice bath was removed, allowing the solution to reach room temperature. The conversion of the starting material to hydroxamic acid was confirmed by HPLC after 1 hour. The methanolic portion was removed by evaporation under reduced pressure, and the reaction was subsequently inactivated by the addition of 4.1 mL of 1 M aqueous hydrochloric acid solution and 6 mL of ethyl acetate were added. The phases were separated, and the aqueous layer was re-extracted with additional ethyl acetate (3x). The organic phases were combined and washed with saturated sodium bicarbonate solution (2x) and brine (2x), dried over sodium sulfate, filtered, and concentrated to dryness. 113 mg of pure product (m / z 363.94 [MH+]) was recovered. The following compounds were synthesized using this procedure: Comp. Structure «L2JB · «®uq¡w?4b > 405.01 Wíl- OMrttpccíbS 468.97 osanfors-ib 1lf¡ 46OJQ1 :W¡ · mirfpB-lb 11 / 368^91 W 405.92 ÍW3 452.94 104 101 102 434,89 380,94 432,93 417,04 449,02 y X JL a 103 475,05 114 477,08 115 464,00 116 117 118 422,01 448,04 426,91 121 413,89 136 137 138 139 F 413,96 510,89 445,87 479,88 430,9 140 429,78 141 142 143 144 145 445,94 428,87 444,82 434,82 447,00 146 430,10 147 149 151 430,10 414,00 403,1 536,1 525,1 601,2 364,1 428,3 399,5 461,3 474,4 168 474,5 177 178 180 182 404,8 404,8 365,1 382,1 460,7 462,2 184 496,3 199 204 205 206 406,5 353,12 452,07 452,09 465,08 410,1 433,8 208 464,04 210 211 213 461.05 438.0 449.76 452.05 The following compound was synthesized using this procedure, starting from 2-mercapto-1,3,4-oxadiazole instead of 2-mercapto-1,3,4-triazole: Comp. m / z [MH+] 192 350.03 Example 7. Synthesis of 4-[[5-[3-(diethylsulfamoyl)phenyl]-4-methyl-1,2,4-triazol-3-yl]sulfanyl]benzencarbohydroxamic acid (comp. 66) To a solution of copper iodide (10 mg, 0.05 eq), L-proline (11 mg, 0.1 eq), and potassium carbonate (152 mg, 1.1 eq) in 1 mL of DMF under an argon atmosphere, methyl 4-iodobenzoate (288 mg, 1.1 eq) and N,N-diethyl-3-(5-mercapto-4-methyl-4H-1,3,4-triazol-3-11)benzenesulfonamide (326 mg, 1 eq) were sequentially added. The reaction mixture was heated to 120 °C and stirred overnight. Heteroaromatic thiol consumption 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 sulfate, filtered, and concentrated. The crude product was purified by flash chromatography (Grace Reveleris X2, hexane:ethyl acetate). 236 mg of the product were obtained. Stage B .OH The ester obtained in step A (236 mg, 1 eq) was suspended in 15 mL of methanol, and the reaction mixture was cooled to 0 °C in an ice bath and magnetically stirred. After the addition of hydroxylamine (50% aqueous solution, 1.2 mL, 40 eq), 1 M aqueous sodium hydroxide solution (4.1 mL, 10 eq) was added dropwise. The ice bath was removed, allowing the solution to reach room temperature. The conversion of the starting material to hydroxamic acid was confirmed by HPLC after 1 hour. The methanolic portion was removed by evaporation under reduced pressure, and the reaction was subsequently inactivated by the addition of 4.1 mL of 1 M aqueous hydrochloric acid solution and 6 mL of ethyl acetate were added. The phases were separated, and the aqueous layer was re-extracted with additional ethyl acetate (3x). The organic phases were combined and washed with saturated sodium bicarbonate solution (2x) and brine (2x), dried over sodium sulfate, filtered, and concentrated to dryness. 207 mg of pure product (m / z 432.00 [MH+]) was recovered. The following compounds were synthesized using this procedure: Eps. Structure 4Χξ1Β 3HGU1 BJJB 359.09 463.12 468.02 353.07 369.96 370.03 356.94 434.05 384.93 370.94 344.98 209 429.07 The following compound was synthesized using this procedure, starting from 2-mercapto-1,3,4-oxadiazole instead of 2-mercapto-1,3,4-triazole: Comp. m / z [MH+] 188 314.3 Example 8. Synthesis of 4-[[1-(2,4-dichlorophenyl)-5-methyl-1,2,4 triazol-3-yl]sulfanyl]benzencarbohydroxamic acid (comp. 62) Stage A .Cl Cl To a solution of potassium thiocyanate (194 mg, 1 eq) in dry acetonitrile (6 L, 1 eq).pml, acetyl chloride (143) was slowly added. The mixture was heated under reflux for one hour, and the potassium chloride formed was then 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 consumption of the hydrazine. The reaction mixture was diluted abundantly 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 were recovered. Stage B To 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 an argon atmosphere, methyl 4-iodobenzoate (66.5 mg, 1.1 eq) and 1-(2,4-dichloropheniO-S-methyl-1H-1^^-triazol-S-thiol) (60 mg, eq) were added. The reaction mixture was heated to 120°C and stirred overnight. The consumption of the 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 extracted again with additional ethyl acetate (3x). The organic phases were combined and washed with brine (2x), dried over sodium sulfate, filtered, and concentrated. The resulting residue was used in the next stage without further purification. Stage C ci. ci .OH The ester obtained in step B (40 mg, 1 eq) was suspended in 6 mL of methanol, and the reaction mixture was cooled to 0 °C in an ice bath and magnetically stirred. After the addition of hydroxylamine (50% aqueous solution, 236 mL, 40 eq), 1 M aqueous sodium hydroxide solution (1 mL, 10 eq) was added dropwise. The ice bath was removed, allowing the solution to reach room temperature. The conversion of the starting material to hydroxamic acid was confirmed by HPLC after 1 hour. The methanolic portion was removed by evaporation under reduced pressure, and the reaction was subsequently inactivated by the addition of 1 mL of 1 M aqueous hydrochloric acid solution and 1 mL of ethyl acetate. The phases were separated, and the aqueous layer was further extracted with additional ethyl acetate (3x). The organic phases were combined and washed with saturated sodium bicarbonate solution (2x), brine (2x), were dried over sodium sulfate, filtered and concentrated to dryness. 30 mg of pure product (m / z 396.89 [MH +]) was recovered. Example 9. Synthesis of 4-[[5-[(3,4-dimethoxyphenyl)methyl]-2-[4-(trifluoromethyl)phenyl]-1,2,4-triazol-3-yl]methyl]benzencarbohydroxamic acid (comp. 44) Stage A A screw-cap vial was loaded with 2-(4-(methoxycarbonyl)phenyl)acetic acid (97 mg, 0.5 mmol), 1-amino-2-(3,4-dimethoxyphenyl)ethan- hydrochloride 1-imino (200 mg, 1.73 eq) and HATU (209 mg, 1.1 eq). 2 mL of DMF and DIPEA (248 μL, 3 eq) were added sequentially under an argon atmosphere. The reaction mixture was stirred at room temperature and monitored by HPLC for carboxylic acid consumption and acylamine intermediate formation. Complete conversion to the intermediate was observed at 2-3 hours. Then 4-(trifluoromethyl)phenyl)hydrazine hydrochloride (187 mg, 1.76 eq) and acetic acid (286 μL, 10 eq) to the reaction mixture. The vial was sealed and the mixture was heated to 80 °C and stirred overnight. The consumption of the intermediate acylamidine was observed by HPLC. The mixture was allowed to reach room temperature before being diluted with ethyl acetate and sequentially washed with saturated aqueous sodium bicarbonate solution and brine. The organic layer was dried on sodium sulfate, filtered, and concentrated to dryness. The product was purified by flash chromatography (hexane: ethyl acetate) (Castañedo et al., J. Org. Chem. (2011), 76(4), 1177-1179). Stage B The ester obtained in step A (82 mg, 1 eq) was suspended in 5 mL of methanol, and the resulting reaction mixture was cooled to 0 °C in an ice bath and magnetically stirred. After the addition of hydroxylamine (50% aqueous solution, 189 µL, 20 eq), 1 M aqueous sodium hydroxide solution (1.6 mL, 10 eq) was added dropwise. The ice bath was removed, allowing the solution to reach room temperature. The conversion of the starting material to hydroxamic acid was confirmed by HPLC after 1 hour. The methanolic portion was removed by evaporation under reduced pressure, and the reaction was subsequently inactivated by the addition of 1.6 mL of 1 M aqueous hydrochloric acid solution and 3 mL of ethyl acetate. The phases were separated, and the aqueous layer was further extracted with additional ethyl acetate (3x).The organic phases were combined and washed with saturated sodium bicarbonate solution (2x), brine (2x), dried over sodium sulfate, filtered, and concentrated to dryness. 27 mg of pure product (m / z) was recovered. 513.18 [MH +]). The following compounds were synthesized using this procedure: Qxi¥L XAH 41301 216 37Z99 407JM 2SV1 Example 10. Synthesis of 4-((5-(furan-2-yl)-2H-tetrazol-2-yl)methyl)-Nhydroxybenzamide (comp. 12) Stage A NaN3, NH4Cl DMF, 100°C, 16h Furan-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 to 120 °C and stirred overnight. Complete conversion of the starting material was observed by LC-MS. The mixture was cooled to 0°C in an ice bath, diluted with 10 mL of water, and acidified with a 1 M aqueous hydrochloric acid solution. The precipitate formed was collected by filtration and washed twice with water before vacuum drying. 720 mg of product were obtained (International Patent Application W02006 / 003096). Stage B The 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 to 100 °C and stirred overnight. Complete conversion of the starting material into the two regioisomeric products was verified 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). Stage C or either The ester obtained in step B (100 mg, 1 eq) was suspended in 10 mL of methanol, and the resulting reaction mixture was cooled to 0 °C in an ice bath and magnetically stirred. After the addition of hydroxylamine (50% aqueous solution, 700 mL, 30 eq), 1 M aqueous sodium hydroxide solution (3.52 mL, 10 eq) was added dropwise. The ice bath was removed, allowing the solution to reach room temperature. The conversion of the starting material to hydroxamic acid was confirmed by HPLC after 1 hour. The methanolic portion was removed by evaporation under reduced pressure, and the reaction was subsequently inactivated by the addition of 3.52 mL of 1 M aqueous hydrochloric acid 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 saturated sodium bicarbonate solution (2x), brine (2x), dried over sodium sulfate, filtered, and concentrated to dryness. 93.5 mg of clean product (m / z 286.02 [MH+]) was recovered. The following compounds were synthesized using this procedure: m / z [MH+1 Comp. Structure 301.92 297.01 364.06 330.12 336.07 314.1 314.1 326.13 310.18 310.18 365.95 316.12 316.05 352.09 360.00 314.03 301.99 444.00 352.03 403.12 431.92 431.95 286.02 347.01 347.02 297.03 347.02 347.01 106 107 110 111 123 OR 421.94 421.94 421.94 421.94 297.98 124 297.99 126 127 364.99 364.99 449.99 450.00 132 311.03 133 311.03 156 157 158 159 355.3 355.5 354.2 354.4 162 341.4 163 169 170 173 174 214 340.4 311.5 311.5 325.3 325.1 296.08 215 294.0 Example 11. Synthesis of 4-((5-(2,3-dihydrothiene[3,4-b][1,4]dioxin-5-yl)- H-tetrazol-1-yl)methyl)-3,5-difluoro-N-hydroxybenzamide (comp. 5) The reaction vessel was charged with potassium carbonate (85 mg, 1 eq) and 2 mL of acetonitrile. Tetrazol (105 mg, 1 eq) was added as a solid under magnetic stirring at room temperature, while adding Methyl 3,5-difluoro-4-chloromethylbenzoate (122.3 mg, 1.1 eq) was prepared as a solution in 2 mL of acetonitrile. The mixture was heated to 100 °C and stirred overnight. Complete conversion of the starting material to the two regioisomeric products was verified 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 the 2,5-disubstituted isomer and 52 mg of the 1,5-disubstituted isomer were recovered (International Patent Application WO2012 / 106995). Stage B 0 0 V / ° íYv nh2oh NaOH jQ-vC l / ° nV YF MeOH 1h, rt YF The ester obtained in step A (52 mg, 1 eq) was suspended in 2 mL of methanol, and the resulting reaction mixture was cooled to 0 °C in an ice bath and magnetically stirred. After the addition of hydroxylamine (50% aqueous solution, 311 mL, 40 eq), 1 M aqueous sodium hydroxide solution (1.3 mL, 10 eq) was added dropwise. The ice bath was removed, allowing the solution to reach room temperature. The conversion of the starting material to hydroxamic acid was confirmed by HPLC after 1 hour. The methanolic portion was removed by evaporation under reduced pressure, and the reaction was subsequently inactivated by the addition of 1.3 mL of 1 M aqueous hydrochloric acid 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 saturated sodium bicarbonate solution (2x), brine (2x), dried over sodium sulfate, filtered, and concentrated to dryness. 32 mg of clean product were recovered (m / z). 395.91 [MH +]). The following compounds were synthesized using this procedure: 100 Coqi. Structure nrfzP*^] ?19í< · laettueΛ< M 33^02 33336 ]3 -M«φί*Α<1» 33^02 Yes¿-,sa.Ti<-oe«R«iiíi 33736 32197 Master! 33736 39531 101 321.97 108 382.97 382.97 382.98 382.97 457.91 102 109 457.91 112 113 125 128 129 457.91 457.91 333.95 400.94 400.94 103 F 347.00 346.99 404.4 404.5 390.3 390.4 104 the 171 347.5 172 347.3 175 361.4 176 361.1 Example 12 - Synthesis of 3,5-difluoro-N-hydroxy-4-((5-(pyridin-3-yl)-1,3,4 thiadiazol-2-yl)thio)benzamide (comp. 191) Stage A KOH (1.48 g, 26.47 mmol, 1.1 equiv) was dissolved in 45 mL of anhydrous ethanol. Hydrazide (3.30 g, 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 resulting precipitate was collected, rinsed with cold acetone, and dried. 105 yielding 5.50 g of a yellow solid. The intermediate obtained was added in small portions to 25 ml of sulfuric acid cooled to 0-5°C. After 1 hour at 0-5°C, the reaction mixture was poured into ice water and the resulting precipitate was collected, rinsed with water and dried. Stage B either OH A mixture of 5-(pyridin-3-yl)-1,3,4-thiadiazol-2-thiol obtained in step A (0.8 g, 4.1 mmol, 1 equiv), 4-iodobenzoic acid (1.22 g, 4.92 mmol, 1.2 equiv), L-proline (0.047 g, 0.4 mmol, 0.1 equiv) and K2CO3 (2.26 g, 16.4 mmol, 4 equiv) in 20 mL of anhydrous DMF was degassed and Cul (0.039 g, 0.2 mmol, 0.05 equiv) was added. The reaction vessel was sealed and the reaction mixture was stirred at 120 °C for 48 h. Complete conversion of the starting thiol was monitored by LC-MS. The reaction mixture was poured into 150 ml of water and filtered through a Celite bed. The filtrate was acidified with HCl. The precipitate formed was filtered and rinsed successively with water, acetonitrile, and diethyl ether. Stage C OH nh2oh-hci HATU DIPEA NHOH 106 HATU (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 temperature and monitored by LC-MS for complete conversion of the acid to the HATU intermediate; conversion was complete after 1 hour. NH₂OH-HCl (0.066 g, 0.951 mmol, 3 equiv) was added, and the reaction mixture was stirred for a further 2 hours. The reaction was monitored by LC-MS. The reaction mixture was diluted with water to a total volume of 50 mL and extracted with EtOAc (225 mL). After evaporation, 101 mg of highly viscous orange oil were obtained. Triggering with acetonitrile (~15 min sonication) led to the formation of a precipitate, which was collected by filtration, rinsed with acetonitrile and diethyl ether, and dried. 40 mg of pure product were obtained (m / z 366.99 [MH Λ {+}]). LC-MS: 94.5%. NMR: OK. The following compounds were synthesized using this procedure: Comp. m / z [MH+] Structure 443.7 187 473.4 107 Example 13 - Synthesis of 3,5-difluoro-N-hydroxy-4-((5-phenyl-1,3,4-thiadiazol-2-yl)methyl)benzamide (comp. 198) Stage A tert-Butyl malonate (11.4 g, 52.73 mmol, 2 equiv) was added dropwise to a suspension of NaH (1.5 equiv) in 70 mL of anhydrous DMF. After 5 minutes of stirring at room temperature, methyl 3,4,5-trifluorobenzoate (5 g, 26.3 mmol, 1 equiv) was added. The reaction mixture was stirred for 3 h at room temperature (the formation of a white precipitate was observed), diluted with water, and extracted with EtOAc. After concentration, the residue was purified by column chromatography. A 1:3 concentration of the inseparable mixture of the product and tert-butyl malonate (11.0 g) was determined by NMR. This mixture was used in the next step without further purification. Stage B TFA The mixture obtained in step A (8.6 g, 22 mmol, 1 equiv) and TFA (17 ml, equiv) were dissolved in 10 ml of anhydrous DCE and refluxed a / a. 108 After cooling, the solvent was evaporated, and the residue was treated with hexane. The resulting precipitate was collected. NMR analysis of the precipitate and filtrate revealed a mixture of the product and malonic acid (in approximately the same 2:1 ratio, favoring the product). The cultures were combined and used in the next stage. Stage C COOME COOME | A 1. soci2 / A 2. PhCONHNH2 [í 1 DIPEA II J ----- FAA 0 Luí ΌΟΟΗ YH Ph 0 The mixture obtained in step B (0.5 g, 2.17 mmol, 1 equiv) was dissolved in 5 ml of SOCl2, heated under reflux for 1 h, and concentrated. The crude chloroanhydride obtained was mixed with benzoylhydrazine (0.643 g, 4.72 mmol, 2 equiv) in 10 ml of anhydrous DMF followed by the addition of DIPEA (1.99 ml, 11.45 mmol, 5 equivalents). After stirring overnight, the reaction mixture was inactivated with water, extracted with EtOAc, and concentrated. The residue was treated with DCM and filtered. Stage D A mixture of the compound obtained in Step C (0.277 g, 0.88 mmol, 1 equiv) and Lawesson's reagent (0.35 g, 0.86 mmol, 0.98 equiv) in 5 mL of toluene was stirred in a sealed container at 120 °C for 15 min. Complete conversion of the starting material was monitored by UPLC. The solvent was evaporated and the residue was purified by column chromatography, using first µg EtOAc in hexane (gradient 20% to 100%) then MeOH 5% in DCM. It was added KOH (0.021 2.NH2OH-HCI, T3P, DIPEA 1.KOH NHOH F g, 0.37 mmol, 2 equiv) to a solution of the cyclic compound obtained in step D (0.06 g, 0.18 mmol, 1 equiv) in mL of a 4 / 1 THF / water mixture. The reaction mixture was stirred at room temperature overnight and acidified with 1 M HCl. The resulting precipitate was collected and dried under vacuum. This solid was then dissolved in THF along 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 room temperature. Complete conversion of the acid to the HATU intermediate was monitored by LC-MS. NH₂OH-HCl (0.066 g, 0.951 mmol, 3 equiv) was added, and the reaction mixture was stirred for an additional 2 hours. The reaction mixture was diluted with water to a total volume of 50 mL and extracted with EtOAc (225 mL). After evaporation, 101 mg of a highly viscous oil was obtained.Trimming with acetonitrile (~15 min sonication) led to the 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: 110 Comp. Structure m / z [MH+] 190 195 197 Example - Summary of 312.12 349.11 433.8 3,5-difluoro-N-hydroxy-4-((5-phenyl-1,2,4oxadiazol-3-yl)methyl)benzamide (comp. 194) Stage A COoMe COoMe 6 tBu-cyanoacetate. NaH [| F^ FIFF t-BuOOC' oN tert-Butyl cyanoacetate (11.4 g, 52.73 mmol, 2 equiv) was added dropwise to a suspension of NaH (1.5 equiv) in 70 mL of anhydrous DMF. After 5 minutes of stirring at room temperature, methyl 3,4,5-trifluorobenzoate (5 g, 26.3 mmol, 1 equiv) was added. The reaction mixture was stirred for 3 hours at room temperature, diluted with water, and extracted with EtOAc. After concentration, the residue was purified by 111 The sample was then diluted in 20 mL of anhydrous DCE and treated with TFA (8.6 mL, 10 equivalents) under reflux. The solvent was evaporated, the residue was dissolved in DCM, washed with a saturated NaHCO3 solution, dried over Na2SO4, and concentrated. The crude product was purified by column chromatography. Stage B 1. soci2 2. PhCONHNH2 DIPEA -----► A mixture of the nitrile derivative obtained in Step A (2 g, 11 mmol, 1 equiv), NH2OH hydrochloride (1.5 g, 22 mmol, 2 equiv) was refluxed overnight. After filtration and concentration, the crude product obtained was purified by column chromatography (10% EtOAc in DCM). Stage C benzotyl chloride DIPEA

Claims

1. A pharmaceutical compound, its sales and foreign isomeros pharmaceutically acceptable, characterized by being selected from: - (S)-N-(1-(3-(4-(hidroxicarbamoyl)bencyl)-1,2,4-oxadiazol-5-yl)-2-(thiazol-4-yl)ethyl)-3,4-dimethoxybenzamida (comp. 1); - 3,5-difluoro-N-hidroxi-4-((4-methyl-5-(naphthalene-1-yl)-4H-1,2,4-triazol-3-yl)thio)benzamida (comp. 2); - 4-((5-(3-(N,N-dimethylsulfamoyl)phenylo)-1,3,4-oxadiazol-2-yl)methyl)-N-hidroxibenzamida (comp. 3); - 3,5-difluoro-N-hidroxi-4-((4-methyl-5-(2-phenylpropan-2-yl)-4H-1,2,4-triazol-3-yl)thio)benzamida (comp. 4); - 4-((5-(2,3-dihidrotieno[3,4-b][1,4]dioxin-5-yl)-1H-tetrazol-1-yl)methyl)-3,5-difluoro-N-hidroxibenzamida (comp. 5); - 3,5-difluoro-N-hidroxi-4-((5-(pyridin-2-yl)-2H-tetrazol-2-yl)methyl)benzamida (comp. 6); - difluoro-N-hidroxi-4-((5-(pyrimidin-2-yl)-2H-tetrazol-2-yl)methyl)benzamida (comp. 7); - N-hidroxi-4-((5-(thiophen-2-yl)-1H-tetrazol-1-yl)methyl)benzamida (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)-1H-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)-1H-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)-1H-tetrazol-1-yl)methyl)benzamide (comp.20); - 3-(3,4-dimethoxyphenyl)-N-[(1S)-1-[3-[[4-(hydroxycarbamoyl)phenyl]methyl]-1,2,4-oxadiazol-5-yl]-2-thiazol-4-ylethyl]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-(1H-indol-3-yl)-1,2,4-triazol-3-yl]sulfanyl]benzenecarbohydroxamic acid; 2,2,2-trifluoroacetic acid (comp. 25); - ácido 4-[5-[(3,4-dimethoxyphenyl)methyl]-1,3,4-oxadiazol-2-yl]benzenecarbohydroxámico (comp. 26); - ácido 4-[[5-benzyl-4-(4-fluorophenyl)-1,2,4-triazol-3-yl]sulfanyl]benzenecarbohydroxámico (comp. 27); - ácido 4-[[4-amino-5-[4-(difluoromethoxy)phenyl]-1,2,4-triazol-3-yl]sulfanyl]benzenecarbohydroxámico (comp. 28); - ácido 4-[[5-(4-fluorophenyl)-4H-1,2,4-triazol-3-yl]sulfanyl]benzenecarbohydroxámico (comp. 29); - ácido 4-[[4-ethyl-5-(4-fluorophenyl)-1,2,4-triazol-3-yl]sulfanyl]benzenecarbohydroxámico (comp.30); - 4-[[5-(4-chlorophenyl)tetrazol-2-yl]methyl]benzencarbohydroxamic acid (comp. 31); - 4-[[5-(5-chloro-2-thienyl)tetrazol-2-yl]methyl]benzencarbohydroxamic acid (comp. 32); - 4-[[5-(2-fluorophenyl)tetrazol-2-yl]methyl]benzencarbohydroxamic acid (comp. 33); - 4-[[5-(4-fluorophenyl)tetrazol-2-yl]methyl]benzencarbohydroxamic acid (comp. 34); - 4-[[5-(4-methoxyphenyl)tetrazol-2-yl]methyl]benzencarbohydroxamic acid (comp. 35); - 4-[(5-benzyltetrazol-2-yl)methyl]benzencarbohydroxamic acid (comp. 36); - 4-[(5-benzyltetrazol-1-yl)methyl]benzencarbohydroxamic acid (comp. 37); - 4-[[5-(2,4-dichlorophenyl)tetrazol-2-yl]methyl]benzencarbohydroxamic acid (comp. 38); - 4-[[5-(3-methyl-2-thienyl)tetrazol-2-yl]methyl]benzencarbohydroxamic acid (comp. 39); - 4-[[5-(5-methyl-2-thienyl)tetrazol-2-yl]methyl]benzencarbohydroxamic acid (comp. 41); - 4-[[5-(benzothiophen-3-yl)tetrazol-2-yl]methyl]benzencarbohydroxamic acid (comp.42); - 4-[[5-(2,3-dihydrothieno[3,4-b][1,4]dioxin-5-yl)tetrazol-2-yl]methyl]benzencarbohydroxamic acid (comp. 43); - 4-[[5-[(3,4-dimethoxyphenyl)methyl]-2-[4-(trifluoromethyl)phenyl]-1,2,4-triazol-3-yl]methyl]benzencarbohydroxamic acid (comp. 44); - 4-[[5-[(3,4-dimethoxyphenyl)methyl]-1,3,4-oxadiazol-2-yl]methyl]benzencarbohydroxamic acid (comp. 45); - 4-[[5-(2-fluorophenyl)tetrazol-2-yl]methyl]benzencarbohydroxamic acid (comp. 46); - 4-[[5-[(1S)-1-amino-2-thiazol-4-yl-ethyl]-1,2,4-oxadiazol-3-yl]methyl]benzencarbohydroxamic acid; - 2,2,2-trifluoroacetic acid (comp. 48); - 4-[[5-(3,4-dimethoxyphenyl)-1,2,4-oxadiazol-3-yl]methyl]benzencarbohydroxamic acid (comp. 49); - 4-[[5-(2-thienyl)tetrazol-2-yl]methyl]benzencarbohydroxamic acid (comp. 50); - 4-[[2-benzyl-5-(4-chlorophenyl)-1,2,4-triazol-3-yl]methyl]benzencarbohydroxamic acid (comp. 51); - 4-[[2-(2-pyridyl)-5-(2-thienyl)-1,2,4-triazol-3-yl]methyl]benzencarbohydroxamic acid (comp.52); - 4-[[2-(2-methoxyphenyl)-5-(2-thienyl)-1,2,4-triazol-3-yl]methyl]benzencarbohydroxamic acid (comp. 53); - 4-[[5-(6,6-dimethyl-3-methylsulfanyl-4-oxo-5,7-dihydro-2-benzothiophen-1-yl)tetrazol-2-yl]methyl]benzencarbohydroxamic acid (comp. 54); - 4-[[5-(benzothiophen-2-yl)tetrazol-2-yl]methyl]benzencarbohydroxamic acid (comp. 55); - 4-[[5-(3,4-dimethoxyphenyl)-1,3,4-oxadiazol-2-yl]methyl]benzencarbohydroxamic acid (comp. 57); - 4-[[5-(2,4-difluorophenyl)-1,3,4-oxadiazol-2-yl]methyl]benzencarbohydroxamic acid (comp. 58); - 4-[[5-[3-(dimethylsulfamoyl)phenyl]tetrazol-2-yl]methyl]benzencarbohydroxamic acid (comp. 59); - 4-[(5-phenyl-1,3,4-oxadiazol-2-yl)amino]benzencarbohydroxamic acid (comp. 60); - 4-[[4-amino-5-[3-(diethylsulfamoyl)phenyl]-1,2,4-triazol-3-yl]sulfanyl]benzencarbohydroxamic acid (comp. 61); - 4-[[5-(3-pyrrolidine-1-ylsulfonylphenyl)-1,3,4-oxadiazol-2-yl]amino]benzencarbohydroxamic acid (comp.63); - 4-[[5-(3-morpholinosulfonylphenyl)-1,3,4-oxadiazol-2-yl]methyl]benzencarbohydroxamic acid (comp. 64); - 3,5-difluoro-4-[[5-(2-thienyl)tetrazol-2-yl]methyl]benzencarbohydroxamic acid (comp. 65); - 4-[[5-[3-(diethylsulfamoyl)phenyl]-4-methyl-1,2,4-triazol-3-yl]sulfanyl]benzencarbohydroxamic acid (comp. 66); - 4-[[4-methyl-5-[2-(p-tolyl)-4-quinolyl]-1,2,4-triazol-3-yl]sulfanyl]benzencarbohydroxamic acid (comp. 67); - 4-[(5-phenyl-1,3,4-oxadiazol-2-yl)methyl]benzencarbohydroxamic acid (comp. 68); - 4-[[5-(4-pyrrolidine-1-ylsulfonylphenyl)-1,3,4-oxadiazol-2-yl]methyl]benzencarbohydroxamic acid (comp. 69); - 4-[[5-(3-benzyloxy-4-methoxyphenyl)tetrazol-2-yl]methyl]benzencarbohydroxamic acid (comp. 70); - 4-[[5-(3-benzyloxy-4-methoxyphenyl)tetrazol-1-yl]methyl]benzencarbohydroxamic acid (comp. 71); - 4-[(5-cyclopropyl-1-phenyl-1,2,4-triazol-3-yl)sulfanyl]benzencarbohydroxamic acid (comp.72); - 4-[[5-[4-(dimethylamino)phenyl]-4-methyl-1,2,4-triazol-3-yl]sulfanyl]benzencarbohydroxamic acid (comp. 73); - 4-[[5-(4-methyl-2-morpholino-thiazol-5-yl)-1,3,4-oxadiazol-2-yl]methyl]benzencarbohydroxamic acid (comp. 75); - 4-[[5-[3-(dimethylamino)phenyl]-4-methyl-1,2,4-triazol-3-yl]sulfanyl]benzencarbohydroxamic acid (comp. 77); - 4-[[5-(3-methoxyphenyl)-4-methyl-1,2,4-triazol-3-yl]sulfanyl]benzencarbohydroxamic acid (comp. 78); - 4-[[5-(2,3-dihydrothieno[3,4-b][1,4]dioxin-5-yl)tetrazol-2-yl]methyl]-3,5-difluorobenzencarbohydroxamic acid (comp. 79); - 4-[[5-[3-(dimethylamino)phenyl]-4-methyl-1,2,4-triazol-3-yl]sulfanyl]-3,5-difluorobenzencarbohydroxamic acid (comp. 80); - 4-[5-[4-(hydroxycarbamoyl)phenyl]sulfanyl-4-methyl-1,2,4-triazol-3-yl]piperidine-1-carboxylate tert-butyl (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]benzencarbohydroxamic acid (comp. 84); - 4-[[5-(1,5-dimethylpyrazol-3-yl)-4-methyl-1,2,4-triazol-3-yl]sulfanyl]benzencarbohydroxamic acid (comp. 85); - 4-[[5-(2-furyl)tetrazol-1-yl]methyl]benzencarbohydroxamic acid (comp. 86); - 4-[[5-(1-isoquinolyl)tetrazol-2-yl]methyl]benzencarbohydroxamic acid (comp. 87); - 4-[[5-(1-isoquinolyl)tetrazol-1-yl]methyl]benzencarbohydroxamic acid (comp. 88); - 4-[[5-(2-pyridyl)tetrazol-2-yl]methyl]benzencarbohydroxamic acid (comp. 89); - 4-[[5-(2-quinolyl)tetrazol-2-yl]methyl]benzencarbohydroxamic acid (comp. 90); - 4-[[5-(2-quinolyl)tetrazol-1-yl]methyl]benzencarbohydroxamic acid (comp. 91); - 3,5-difluoro-4-[[5-(2-furyl)tetrazol-1-yl]methyl]benzencarbohydroxamic acid (comp. 92); - 3,5-difluoro-4-[[5-(1-isoquinolyl)tetrazol-2-yl]methyl]benzencarbohydroxamic acid (comp. 93); - 3,5-difluoro-4-[[5-(1-isoquinolyl)tetrazol-1-yl]methyl]benzencarbohydroxamic acid (comp.94); - 3,5-difluoro-4-[[5-(2-quinolyl)tetrazol-2-yl]methyl]benzencarbohydroxamic acid (comp. 95); - 3,5-difluoro-4-[[5-(2-quinolyl)tetrazol-1-yl]methyl]benzencarbohydroxamic acid (comp. 96); - 3,5-difluoro-4-[[5-(2-thienyl)-4H-1,2,4-triazol-3-yl]sulfanyl]benzencarbohydroxamic acid (comp. 97); - 4-[(5-benzhydryl-4-methyl-1,2,4-triazol-3-yl)sulfanyl]-3,5-difluorobenzencarbohydroxamic 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]benzencarbohydroxamic 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-6-sulfanyl)phenyl]tetrazol-2-yl]methyl]benzenecarbohydroxamic acid (comp. 106); - 4-[[5-[3-(pentafluoro-6-sulfanyl)phenyl]tetrazol-1-yl]methyl]benzenecarbohydroxamic acid (comp. 107); - 3,5-difluoro-4-[[5-[3-(pentafluoro-6-sulfanyl)phenyl]tetrazol-2-yl]methyl]benzenecarbohydroxamic acid (comp. 108); - 3,5-difluoro-4-[[5-[3-(pentafluoro-6-sulfanyl)phenyl]tetrazol-1-yl]methyl]benzenecarbohydroxamic acid (comp. 109); - 4-[[5-[4-(pentafluoro-6-sulfanyl)phenyl]tetrazol-2-yl]methyl]benzenecarbohydroxamic acid (comp. 110); - 4-[[5-[4-(pentafluoro-6-sulfanyl)phenyl]tetrazol-1-yl]methyl]benzenecarbohydroxamic acid (comp.111); - 3,5-difluoro-4-[[5-[4-(pentafluoro-6-sulfanyl)phenyl]tetrazol-2-yl]methyl]benzenecarbohydroxamic acid (comp. 112); - 3,5-difluoro-4-[[5-[4-(pentafluoro-6-sulfanyl)phenyl]tetrazol-1-yl]methyl]benzenecarbohydroxamic acid (comp. 113); - 3,5-difluoro-4-[[4-methyl-5-[3-(4-methyl-4-oxido-piperazin-4-io-1-yl)phenyl]-1,2,4-triazol-3-yl]sulfanyl]benzenecarbohydroxamic acid (comp.114); - 3,5-difluoro-4-[[4-(4-fluorophenyl)-5-(1-piperidylmethyl)-1,2,4-triazol-3-yl]sulfanyl]benzenecarbohydroxamic acid (comp. 115); - 3,5-difluoro-4-[[4-(2-furylmethyl)-5-pyrrolidin-1-yl-1,2,4-triazol-3-yl]sulfanyl]benzenecarbohydroxamic acid (comp. 116); - 4-[(4-benzyl-5-morpholino-1,2,4-triazol-3-yl)sulfanyl]-3,5-difluorobenzenecarbohydroxamic acid (comp. 117); - ácido 4-[[5-(2,3-dihydrothieno[3,4-b][1,4]dioxin-5-yl)-4-methyl-1,2,4-triazol-3-yl]sulfanyl]-3,5-difluorobenzenecarbohydroxámico (comp.118); - ácido 3,5-difluoro-4-[[5-(1-isoquinolyl)-4-methyl-1,2,4-triazol-3-yl]sulfanyl]benzenecarbohydroxámico (comp.121); - 3,5-difluoro-4-[[4-methyl-5-(2-quinolyl)-1,2,4-triazol-3-yl]sulfanyl]benzencarbohydroxamic acid (comp. 122); - 4-[(5-pyrimidin-2-yltetrazol-2-yl)methyl]benzencarbohydroxamic acid (comp. 123); - 4-[(5-pyrimidin-2-yltetrazol-1-yl)methyl]benzencarbohydroxamic acid (comp. 124); - 3,5-difluoro-4-[(5-pyrimidin-2-yltetrazol-1-yl)methyl]benzencarbohydroxamic acid (comp. 125); - 4-[[5-[5-(trifluoromethyl)-2-pyridyl]tetrazol-2-yl]methyl]benzencarbohydroxamic acid (comp. 126); - 4-[[5-[5-(trifluoromethyl)-2-pyridyl]tetrazol-1-yl]methyl]benzencarbohydroxamic acid (comp. 127); - 3,5-difluoro-4-[[5-[5-(trifluoromethyl)-2-pyridyl]tetrazol-2-yl]methyl]benzencarbohydroxamic acid (comp. 128); - 3,5-difluoro-4-[[5-[5-(trifluoromethyl)-2-pyridyl]tetrazol-1-yl]methyl]benzencarbohydroxamic acid (comp. 129); - 4-[[5-[3-morpholino-5-(trifluoromethyl)-2-pyridyl]tetrazol-2-yl]methyl]benzencarbohydroxamic acid (comp.130); - 4-[[5-[3-morpholino-5-(trifluoromethyl)-2-pyridyl]tetrazol-1-yl]methyl]benzencarbohydroxamic acid (comp. 131); - 4-[[5-(2-pyridylmethyl)tetrazol-2-yl]methyl]benzencarbohydroxamic acid; 2,2,2-trifluoroacetic acid (comp. 132); - 4-[[5-(2-pyridylmethyl)tetrazol-1-yl]methyl]benzencarbohydroxamic acid; 2,2,2-trifluoroacetic acid (comp. 133); - 3,5-difluoro-4-[[5-(2-pyridylmethyl)tetrazol-2-yl]methyl]benzencarbohydroxamic acid; 2,2,2-trifluoroacetic acid (comp. 134); - 3,5-difluoro-4-[[5-(2-pyridylmethyl)tetrazol-1-yl]methyl]benzencarbohydroxamic 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]benzencarbohydroxamic acid (comp. 136); - 3,5-difluoro-4-[[5-(6-fluoro-2-methyl-3-quinolyl)-4-methyl-1,2,4-triazol-3-yl]sulfanyl]benzencarbohydroxamic 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]benzencarbohydroxamic acid (comp. 139); - 3,5-difluoro-4-[[4-(2-furylmethyl)-5-(2-pyridyl)-1,2,4-triazol-3-yl]sulfanyl]benzencarbohydroxamic acid (comp. 140); - 4-[[4-benzyl-5-(pyrrolididin-1-ylmethyl)-1,2,4-triazol-3-yl]sulfanyl]-3,5-difluorobenzencarbohydroxamic acid (comp. 141); - 4-[[4-benzyl-5-(2-furyl)-1,2,4-triazol-3-yl]sulfanyl]-3,5-difluorobenzenecarbohydroxamic acid (comp. 142); - 4-[[4-benzyl-5-(2-thienyl)-1,2,4-triazol-3-yl]sulfanyl]-3,5-difluorobenzenecarbohydroxamic 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]benzencarbohydroxamic acid (comp. 145); - 3,5-difluoro-4-[[4-(2-furylmethyl)-5-(4-pyridyl)-1,2,4-triazol-3-yl]sulfanyl]benzencarbohydroxamic acid (comp.146); - 3,5-difluoro-4-[[4-(2-furylmethyl)-5-(3-pyridyl)-1,2,4-triazol-3-yl]sulfanyl]benzencarbohydroxamic acid (comp. 147); - 3,5-difluoro-4-[[5-(3-isoquinolyl)-4-methyl-1,2,4-triazol-3-yl]sulfanyl]benzencarbohydroxamic acid (comp. 148); - 3,5-difluoro-4-[(5-imidazo[1,2-a]pyridin-3-yl-4-methyl-1,2,4-triazol-3-yl)sulfanyl]benzencarbohydroxamic 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]benzencarbohydroxamic acid (comp. 153); - 4-[[2-[[2,6-difluoro-4-(hydroxycarbamoyl)phenyl]methyl]tetrazol-5-yl]methyl]methylbenzoate (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]benzencarbohydroxamic 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-difluorobenzencarbohydroxamic acid (comp. 168); - 4-[[5-(4-aminophenyl)tetrazol-2-yl]methyl]benzencarbohydroxamic acid (comp. 169); - 4-[[5-(4-aminophenyl)tetrazol-1-yl]methyl]benzencarbohydroxamic acid (comp. 170); - 4-[[5-(4-aminophenyl)tetrazol-2-yl]methyl]-3,5-difluorobenzencarbohydroxamic acid (comp. 171); - 4-[[5-(4-aminophenyl)tetrazol-1-yl]methyl]-3,5-difluorobenzencarbohydroxamic acid (comp. 172); - 4-[[5-[4-(aminomethyl)phenyl]tetrazol-2-yl]methyl]benzencarbohydroxamic acid (comp.173); - 4-[[5-[4-(aminomethyl)phenyl]tetrazol-1-yl]methyl]benzencarbohydroxamic acid (comp. 174); - 4-[[5-[4-(aminomethyl)phenyl]tetrazol-2-yl]methyl]-3,5-difluorobenzencarbohydroxamic acid (comp. 175); - 4-[[5-[4-(aminomethyl)phenyl]tetrazol-1-yl]methyl]-3,5-difluorobenzencarbohydroxamic acid (comp. 176); - 3,5-difluoro-4-[[4-methyl-5-[1-(2-pyridyl)cyclopropyl]-1,2,4-triazol-3-yl]sulfanyl]benzencarbohydroxamic acid (comp. 177); - 3,5-difluoro-4-[[4-methyl-5-[1-(3-pyridyl)cyclopropyl]-1,2,4-triazol-3-yl]sulfanyl]benzencarbohydroxamic acid (comp. 178); - 3,5-difluoro-4-[[5-(3-fluoro-2-pyridyl)-4-methyl-1,2,4-triazol-3-yl]sulfanyl]benzencarbohydroxamic acid (comp. 180); - 3,5-difluoro-4-[[4-methyl-5-[3-(1-piperidylmethyl)phenyl]-1,2,4-triazol-3-yl]sulfanyl]benzencarbohydroxamic 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-((1H-indol-3-yl)methyl)-5-(thiophen-2-yl)-4H-1,2,4-triazol-4-yl)methyl)-N-hydroxybenzamide acid (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); - ácido 3,5-difluoro-4-[[4-methyl-5-[1-methyl-1-(3-pyridyl)ethyl]-1,2,4-triazol-3-yl]sulfanyl]benzenecarbohydroxámico (comp. 186); - ácido 3,5-difluoro-4-[[5-[4-[methyl(methylsulfonyl)amino]phenyl]-1,3,4-thiadiazol-2-yl]sulfanyl]benzenecarbohydroxámico (comp. 187); - ácido 4-[(5-phenyl-1,3,4-oxadiazol-2-yl)sulfanyl]benzenecarbohydroxámico (comp. 188); - ácido 4-[(5-phenyl-1,2,4-oxadiazol-3-yl)methyl]benzenecarbohydroxámico (comp. 189); - ácido 4-[(5-phenyl-1,3,4-thiadiazol-2-yl)methyl]benzenecarbohydroxámico (comp. 190); - ácido 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]benzencarbohydroxamic acid (comp. 192); - 4-[[5-(2-morpholino-4-pyridyl)-1,2,4-oxadiazol-3-yl]methyl]benzencarbohydroxamic 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]benzencarbohydroxamic acid (comp. 195); - 4-[[5-(5-bromo-3-pyridyl)-1,3,4-thiadiazol-2-yl]sulfanyl]-3,5-difluorobenzenecarbohydroxamic 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-difluorobenzencarbohydroxamic 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]benzencarbohydroxamic acid (comp. 201); - 3,5-difluoro-4-[[5-[5-(pyrrolidine-1-ylmethyl)-2-furyl]-1,2,4-oxadiazol-3-yl]methyl]benzencarbohydroxamic acid (comp. 202); - 3,5-difluoro-4-[[4-methyl-5-[5-(morpholinomethyl)-3-furyl]-1,2,4-triazol-3-yl]sulfanyl]benzencarbohydroxamic acid (comp. 203); - 3,5-difluoro-4-[[4-methyl-5-[5-(morpholinomethyl)-2-furyl]-1,2,4-triazol-3-yl]sulfanyl]benzencarbohydroxamic 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]benzencarbohydroxamic acid (comp. 205); - 4-[[5-[5-[(dimethylamino)methyl]-2-furyl]-4-methyl-1,2,4-triazol-3-yl]sulfanyl]-3,5-difluorobenzencarbohydroxamic acid (comp. 206); - 3,5-difluoro-4-[[4-methyl-5-[5-(pyrrolidine-1-ylmethyl)-2-furyl]-1,2,4-triazol-3-yl]sulfanyl]benzencarbohydroxamic acid (comp.207); - ácido 4-[[5-[5-ethyl-4-(pyrrolidin-1-ylmethyl)-2-furyl]-4-methyl-1,2,4-triazol-3-yl]sulfanyl]-3,5-difluorobenzenecarbohydroxámico (comp. 208); - ácido 4-[[4-methyl-5-[5-[(4-methylpiperazin-1-yl)methyl]-2-furyl]-1,2,4-triazol-3-yl]sulfanyl]benzenecarbohydroxámico (comp. 209); - ácido 3,5-difluoro-4-[[4-methyl-5-[6-(2-pyrrolidin-1-ylethyl)-3-pyridyl]-1,2,4-triazol-3-yl]sulfanyl]benzenecarbohydroxámico (comp. 210); - ácido 4-[[5-[5-(diethylaminomethyl)-2-furyl]-4-methyl-1,2,4-triazol-3-yl]sulfanyl]-3,5-difluorobenzenecarbohydroxámico (comp. 211); - ácido 3,5-difluoro-4-[[4-methyl-5-[5-(1-piperidylmethyl)-2-furyl]-1,2,4-triazol-3-yl]sulfanyl]benzenecarbohydroxámico (comp. 212); - ácido 4-[(5-phenyltetrazol-2-yl)methyl]benzenecarbohydroxámico (comp. 214); - ácido 4-[(5-phenyltetrazol-1-yl)methyl]benzenecarbohydroxámico (comp. 215); - acido 4-[(5-phenyl-4H-1,2,4-triazol-3-yl)methyl]benzenecarbohydroxámico (comp. 216); - N-hydroxy-4-((4-methyl-5-phenyl-4H-1,2,4-triazol-3-yl)methyl)benzamide (comp. 217).Four more claims follow.