VASOPRESSIN V1a RECEPTOR ANTAGONIST COMPOUNDS HAVING A 5,6-DIHYDRO-4H-[1,2,4]TRIAZOLO[4,3-A][1]BENZAZEPINE FRAMEWORK AND INTERMEDIATES THEREOF

Abstract

This document relates to derivatives of 5,6-dihydro-4H-[1,2,4]triazolo[4,3-a][1]benzazepine of general formula (1) and / or its salts and / or its geometric isomers and / or its stereoisomers and / or its enantiomers and / or its racemates and / or its diastereomers and / or its biologically active metabolites and / or its prodrugs and / or its solvates and / or its hydrates and / or its polymorphs, which are V1a receptor modulators acting centrally and / or peripherally, particularly V1a receptor antagonists. The process for preparing the compounds and intermediates for the preparation process are also covered. Pharmaceutical compositions containing the compounds, or in combination with one or more additional active ingredients, are also covered, as well as their use in the treatment and / or prophylaxis of a disease or condition associated with V1a receptor function.

Description

TRIAZOLOBENZAZEPINES AS ANTAGONISTS OF THE V1A RECEPTOR VASOPRESSIN FIELD OF INVENTION The present invention relates to 5,6-dihydro-4H-[1,2,4]triazolo[4,3a][1]benzazepine derivatives of general formula (I) and / or its salts and / or its geometric isomers and / or its stereoisomers and / or its enantiomers and / or its racemates and / or its diastereomers and / or its biologically active metabolites and / or its prodrugs and / or its solvates and / or its hydrates and / or its polymorphs, which are V1a receptor modulators that act centrally and / or peripherally, particularly V1a receptor antagonists. Another object of the present invention is the process for the preparation of the compounds, and also the intermediates for the preparation process. The invention also relates to pharmaceutical compositions containing the compounds, and the use thereof in the treatment and / or prophylaxis of a disease or condition associated with the function of the V1 a receptor. BACKGROUND OF THE INVENTION Vasopressin (antidiuretic hormone, ADH, CYIQNCPRG) is a 9-amino acid peptide hormone produced by magnocellular neurons of the paraventricular (PVN) and supraoptic nuclei (SON) of the hypothalamus and secreted directly into the posterior lobe of the pituitary gland, where the hormone is stored until it enters the bloodstream. In the periphery, the main role of vasopressin is observed in the contraction of blood vessels, as well as in glucose metabolism and the regulation of excretion. For this reason, conditions due to inadequate secretion of vasopressin, hence lack of vasopressin, can lead to pathological changes in the body, such as the central form of diabetes insipidus or abnormally low blood pressure (hypotension), while that in the case of elevated levels of vasopressin or exogenous administration, various forms of consolidation of aggressive behavior can be observed (Ferris et al., BMC Neuroscience 2008, 9: 111). Oxytocin (OXT, CYIQNCPLG) is a vasopressin-related peptide hormone, which differs from that of an amino acid, and its receptor is also related to vasopressin receptors. The effects of the compounds on the oxytocin receptor show species-specific differences, but the hormone oxytocin itself IF-2019-03 566964-APN-ANP#INPI Page 1 of 272 the same is identical in the different species of mammals. Similarly, the vasopressin peptide is the same in all mammals (except marsupials and pigs) and the effects exerted through its receptors may also show species-specific differences. The anxiolytic effect of oxytocin exerted on the central nervous system is well known (Neumann ID. J Neuroendocrinal 2008, 20(6): 858-65), therefore, inhibition of the oxytocin receptor in the central nervous system can trigger anxiety as an undesirable side effect. Three vasopressin receptors are distinguished; All of them are G protein-coupled receptors. The V1a receptor (V1aR) is expressed centrally in the cerebral cortex, hippocampus and pituitary gland, and peripherally in the liver, vascular smooth muscle, lungs, the uterus and the testes (Frank et al., Eur J Pharmacol 2008, 583: 226-42). V1b Receptors (V1b Receptors) can also be found in the cortex, hippocampus and pituitary gland, and in the periphery they play an important role in regulating the pancreas and adrenal glands. In contrast to this, the V2 receptor (V2R) is located mainly in the periphery, in the kidneys where it increases water reabsorption, thus exerting the antidiuretic effect of vasopressin (Robben et al., Am J Physiol Renal Physiol 2007, 292(1): F253-60). Therefore, due to changes in the regulation of! water balance, the effect on the V2 receptor may cause unwanted side effects. The secondary signaling pathway of V1a and V1b receptors includes changing the intracellular Ca2+ concentration through phosphatidylinositol, while V2 receptors activate the enzyme adenylate cyclase and influence cAMP levels (Gouzenes et al., J Physiol 1999, 517(Pt3):771-9; Tahara et al., Pflugers Arch 1999, 437(2):219-26). V1a receptors play an important role in regulating the circadian rhythm. One-third of the neurons in the suprachiasmatic nucleus (SCN) Suprachiasmatic Nucleus) express vasopressin and V1a receptor mRNA exhibits daily fluctuations in this brain region, of which the highest values ​​can be observed during nighttime hours (de Vries and Miller, Prog Brain Res 1998, 119:3- twenty). Vasopressin shows sexual dimorphism in inducing behavioral effects, despite the fact that the distribution and quantity of V1aR mRNAs do not differ in males and females (Szot et al., Brain Res Mol Brain Res 1994, 24(14 :1-10). Experiments in mice have shown that increased absorption of IF-2019-03 566964-APN-ANP#INPI Page 2 of 272 water before your sleep period was triggered by your internal clock and not your physiological needs (Gizowski et al., Nature 2016, 537(7622):685-8). Sleep disorder is a predominant symptom of autism (Glickman, Neurosci Biobehav Rev 2010, 34(5):755-68). Vasopressin acts as a neuromodulator in the brain; its elevated level can be detected in the amygdala under stress (Ebner et al., EurJ Neurosci 2002, 15(2):3848). It is widely known that these types of stressful life situations increase the likelihood of developing depression and anxiety (Kendler et al., Arch Gen Psychiatry 2003, 60(8)789-96; Simon et al., Recent Pat CNS Drug Discov, 2008, 3(2)7793; Egashira et al., J Pharmacol Sci 2009, 109(1):44-9; Bielsky et al., Neuropsychopharmacology 2004, 29(3):483-93). V1aR expression is high in the brain, especially in certain parts of the limbic system, such as the amygdala, lateral septum, and hippocampus, which play an important role in the development of anxiety. Male mice with the V1aR gene inactivated showed reduced anxiety in the maze, open field, and light-dark cage elevation tests, but these differences could not be detected in females (Bielsky et al., Behav Brain Res 2005, 164( 1):132-6). Male V1aR knockout mice did not show any phenotypic differences in motor performance. In normal light-dark cycle experiments, V1aR knockout mice showed no differences compared to their wild-type littermates; However, in experiments performed in continuous darkness, the diurnal rhythm of V1a knockout mice was significantly modified (Egashira et al., Behav Brain Res 2007, 178(1):123-7). V1aR knockout mice showed modified activity in the prepulse inhibition test, the test that is accepted as an animal model of sensory motor deficiency observed in the majority of schizophrenic patients. Egashira et al. have demonstrated decreased function in the social interaction test, which is suitable for measuring the socio-cognitive behavior of V1aR knockout mice in both sexes, but was not observed after treatment with the antagonist (Bleickard et al., Psychopharmacology ( Berl), 2009, 202:711-18). Two microsatellite polymorphisms associated with autism could be determined in the case of variants of the AVPR1A gene that encodes the V1a receptor (Kim et al., Mol Psychiatry 2002, 7:503-7; Yirmiya et al., Mol Psychiatry 2006, 11:488-94; Yang et al., Psychiatry Res, 2010, 178(1): 199-201; IF-2019-03 566964-APN-ANP#INPI Page 3 of 272 It also refers to a genetic connection that altered activation of the amygdala could detect in patients carrying two risk alleles in the V1aR gene. It has been shown that these modified receptors can alter the activation threshold of the amygdala during the emotional facial recognition process (Meyer-Lindenberg et al., Mol Psychiatry 2009, 14:968-75). Preclinical data also support the efficacy of V1aR antagonists in autism. A widely used and accepted animal model of autism is to study the behavior of rats exposed to valproate (VPA) treatment in utero. The reduction in social behavior of VPA-treated animals could be reversed by the V1aR antagonist compound to the normal level. In a functional magnetic resonance imaging study, it was also found that decreased perfusion values ​​were restored by V1aR antagonist in different brain regions of animals treated with VPA prenatally. Decreased function of the cortex, inferior colliculus, hippocampus, and hypothalamus increased with V1aR antagonist treatment, whereas in the ventral tegmentum, striatum, and superior colliculus, increased perfusion was normalized with the antagonist. of V1aR (Grundschober et al., Poster presented at Annual Meeting of the American College of Neuropsychopharmacology, 2014, Phoenix, USA). For this reason, V1aR antagonist compounds that show favorable penetration of the blood-brain barrier are expected to be advantageous. Influencing V1aR with small molecule antagonists is a promising strategy for the treatment of various pathological conditions of the female sexual organs (such as, but not limited to, dysmenorrhea, sexual dysfunction), long-standing pathological conditions in blood pressure control arterial (such as, but not limited to, hypertension and / or chronic heart failure), conditions resulting from inadequate secretion of vasopressin (such as, for example, diabetes insipidus, renal failure, nephrotic syndrome and cirrhosis). Another promising strategy can be considered in the treatment of anxiety, depression, aggression and central nervous system disorders where one of the symptoms and / or syndromes of the disease may be related to the last three diseases or show comorbidity with them. These include, but are not limited to, autism spectrum disorder (high-functioning autism, Asperger syndrome, Pervasive Developmental Disorder-Not Otherwise Specified (PDD-NOS), Pervasive Developmental Disorder-Not Otherwise Specified Autism Spectrum Disorder (ASD) and its various syndromic forms: Fragile X syndrome, Prader-Willi syndrome, Rett syndrome, IF-2019-03 566964-APN-ANP#INPI Page 4 of 272 tuberous sclerosis, obsessive compulsive disorder (OCD), various forms of Down syndrome, and post-traumatic stress disorder (PTSD). V1aR antagonists are also suitable for the treatment of disorders of aggressive behavior and / or irritability (such as, but not limited to, patients with ASD or those suffering from Huntington's Disease (HD) or various forms of schizophrenia ), behavioral hyperactivity disorders (such as, but not limited to, attention deficit hyperactivity disorder (ADHD), cognitive disorders (such as, but not limited to, dementia, mild cognitive disorders (MCI) Disorders), Cognitive Impairment Associated with Schizophrenia (CIAS) and Alzheimer's disease), and other neuropsychiatric disorders (such as, but not limited to, schizophrenia and associated diseases). Many patent applications deal with V1a receptor antagonists, for example, Otsuka describes benzoheterocyclic derivatives (WO 95 / 034540 A1, WO 2009 / 001968 A1, WO 2011 / 052519 A1), Astellas Pharma (Yamanouchi) describes condensed triazole and benzodiazepine derivatives (WO 95 / 03305 A1, WO 01 / 87855 A1, WO 02 / 44179 A1), AbbVie describes oxindole derivatives (WO 2006 / 072458 A2, WO 2006 / 100082 A2), Bayer Pharma describes aryl or heteroaryltriazole derivatives (WO 2017 / 191102 A1, WO 2017 / 191107 A1, WO 2017 / 191114 A1). Various derivatives containing benzoazulene nuclei (WO 2005 / 068466 A1, WO 2006 / 021213 A2, WO 2006 / 021882 A1, WO 2011 / 114109 A1, WO 2011 / 128265 A1, WO 2011 / 141396 A1, WO 2014 / 127350 A1) , spiroindolinone and indolylcarbonyl derivatives (WO 97 / 15556 A1, WO 2007 / 009906 A1, WO 2007 / 014851 A2) are also described as antagonists of the V1 a receptor. Early clinical developments considered the V1a receptor to be a peripheral target, so poor brain penetration was beneficial in compound development. Such was Sanofi's indoline core compound, relcovaptan (SR-49059, WO 93 / 03013 A1), which was developed into Phase 2 clinical trial. Among the indications studied were premature birth, pelvic pain observed during menstruation, dysmenorrhea (Brouard et al., Br J Obstetr Gynaecol 2000, 107: 614-9), heart failure, hypertension and coronary spasm, but it was also tested as an antineoplastic agent in small cell lung carcinoma until the last clinical trial was stopped in 2003 (Serradeil-Le Gal et al., Prog Brain Res 2002, 139:197-210; Adislnsight: Relcovaptan - Last information updated: 03 Oct 2006 IF-2019-03 566964-APN-ANP#INPI 5 Page 5 of 272 http: / / adisinsiqht.sprinqer.com / druas / 800Q04942). Relcovaptan has been in clinical development since 1993 and is the most widely used in vitro tool in V1aR research (Tahara et al., BrJ Pharmacol 2000, 129:131-9). Pfizer studied its triazole derivative PF 00738245 (WO 2005 / 063754 A1) and triazolobenzodiazepine core compound PF-184563 (WO 2004 / 074291 A1) in preclinical development for dysmenorrhea; According to the data measured, these are efficient V1aR antagonists (Russell et al., Eur. J Pharmacol, 2011, 670(2): 347-355; Johnson et al., Bloorg Med Chern Lett 2011,21:5684-7) but its development ended. By examining the effects exerted on the central nervous system, the treatment of depression and anxiety has also been proposed as a novel therapeutic area. Johnson & Johnson's spirobenzazepine core compound JNJ-17308616 was one of the first V1aR antagonist compounds acting on the central nervous system (Bleickard et al., Psychopharmacology (Berl.), 2009, 202:711-18; WO 02 / 02531 A1) which demonstrated efficacy in a variety of different animal models used for anxiety research: significantly reduced anxiety behavior in the maze elevation test, the defensive burying test and in ultrasonic vocalization of rat pups induced separation. Although it was shown to be effective in influencing the elevated O-maze and conditioned lick response, due to its poor metabolic stability measured in rodents, its efficacy was not good and could only be measured at high doses and was therefore difficult to evaluate. Azevan's V1aR antagonist azetidone derivatives, SRX246 and SRX251 (also known as API246 or API251, WO 03 / 031407 A2) also reached the clinical trial phase. Clinical trials of SRX246 are also currently ongoing for the treatment of intermittent explosive and aggressive disorder and irritability in Huntington's disease and post-traumatic stress disorder, as well as in behavioral models of anxiety and fear in humans ( Adislnsight: SRX 246 - Last information updated: 16 Feb 2017 http: / / adisinsiqht.sprinqer.com / druqs / 800023656) · A clinical trial was conducted with SRX251 to treat dysmenorrhea, but both Phase 1 studies were suspended in 2016 and , similarly to SRX246, was also investigated for aggression in preclinical development (Adislnsight: SRX 251 - Last information updated: 04 Nov 2017 http: / / adisinsiqht.sprinqer.com / druqs / 800025117). SRX-246 and SRX-251 are active on the human V1a receptor and, in rats, both compounds were detectable in the brain at IF-2019-03 566964-APN-ANP#INPI Page 6 of 272 approximately 100 times the effective concentrations detected in the binding assay (Guillon et al., Bioorg Med Chem 2007, 15:2054-80; Fabio et al., J Pharm Sci 2013, 102(6):2033- 43). The V1aR antagonist compound Vanti, VA 111913 from pyrazolobenzodiazepine core (WO 2010 / 097576 A1; Adislnsight: VA 111913 - Last information updated: 25 Aug 2015 http: / / adisinsiqht.sprinqer.com / druqs / 800028777) was evaluated in a phase 2 clinical trial for the treatment of dysmenorrhea, but there is no information on its development since 2015. Otsuka's V1aR antagonist, the quinolinone derivative OPC 21268 (EP0382185A2; Adislnsight: OPC 21268 - Last information updated: 06 Oct 2006 http: / / adisinsiqht.sprinqer.com / druqs / 800000284) was evaluated for the indication of damage to the gastric mucosa in the preclinical phase, while in Phase 2 clinical trials it was studied for heart failure and hypertension, but there is no information on its development since 2015 (Yamamura et al., Science 1991, 252:572 ; Serradeil-Le Gal et al., J Clin Invest 1993, 92(1):224). By examining the brainstem in postmortem human samples, selective localization of V1a receptors unrelated to oxytocin receptors in the prepositum nucleus, which plays a role in gaze stabilization, could be detected (Freeman et al., Soc Neurosci 2017, 12(2):113-123). A fundamental skill required for human social behavior is the recognition and eye tracking of biologically relevant information (Klin et al., Nature 2009, 459:257-63, Simion et al., PNAS 2008, 105(2):809- 13). The most active V1aR researcher, HoffmannLa Roche, reached the Phase 1 study with its indole derivative RO5028442 (RG-7713; WO 2007 / 006688 A1), where a positive effect on the orientation of the gaze pattern in humans could be detected (Umbricht et al., Neuropsychopharmacology 2017, 42 (9):19141923; Adislnsight: RG 7713 - Latest information updated: 05 Nov 2015 http: / / adisinsiqht.sprinqer.com / druqs / 800043668) Phase 2 clinical trials for Autism treatment are currently ongoing with triazolobenzodiazepine core balovaptan (RG-7314, RO5285119; WO 2010 / 060836 A1; Adislnsight: RG 7314 - Last information updated: 10 Sep 2017 http: / / adisinsiqht.spnnqer.com / druqs / 8000351Q2). Despite numerous V1aR antagonist compounds and clinical studies, there remains an unmet medical need to develop a V1aR antagonist that is suitable for the treatment and / or prophylaxis of various conditions. IF-2019-03 566964-APN-ANP#INPI Page 7 of 272 pathologies of the female sexual organs, long-term conditions in the control of blood pressure, conditions generated by inadequate secretion of vasopressin, anxiety, depression, aggression, disorders of the central nervous system where one of the symptoms and / or or disease syndromes may be related to or show comorbidity with anxiety, depression, aggression (autism spectrum disorder, obsessive-compulsive disorder, various forms of Down syndrome, post-traumatic stress disorder), aggressive behavior disorders and / or irritability , behavioral hyperactivity disorders, cognitive disorders or other neuropsychiatnic disorders, SUMMARY OF THE INVENTION Our objective was to synthesize new structured V1a receptor antagonists whose physicochemical properties (e.g., kinetic or thermodynamic solubility, ionization, lipophilicity or permeability) or pharmaceutical properties (e.g., metabolic stability, inhibition of the CYP-450 enzyme) provide bioavailability. , favorable ADME (absorption, distribution, metabolism, excretion), membrane penetration or blood-brain barrier penetration. Surprisingly, such novel 5,6-dihydro-4H-[1,2,4]triazolo[4,3-aj[1]benzazepine derivatives of general formula (I) have been prepared, which show antagonistic activity profile. V1a receiver. The present invention refers to the compounds of general formula (I) where: ring A is a cycloalkyl or heterocyclyl group; Y is -O-, -C(O)-, -CH2-, -NH-, -Ci.4alqull-N(R18)- or bond if the B ring is present; or N(Ci-4alkyl)2, C(O)OCi-4alkyl, Ci-4alkyl optionally substituted with halogen, Ci-4alkoxy group or halogen if ring B is not present; IF-2019-03 566964-APN-ANPAINPI Page 8 of 272 ring B is an optionally substituted heteroaryl, aryl or heterocyclyl group; or B-Y-A- together represents 3 / - / -spiro[2-benzofuran-1,4'-piperidin-T-ílo]; either group or group — or group R1 is a hydrogen, halogen, Ci4alkyl, Ci. / .alkoxy, CF3 or CN; R2 is a hydrogen or Ci-4alkyl group; R3 is an NR4R5, OR6o halogen group; or R2 and R3 together represent -O-(CH2)m-O-, oxo or =N-OH group; R4 and R5 are independently hydrogen; Cy-4alkyl optionally substituted with OH, halogen, cycloalkyl, optionally substituted aryl or NR8R9 group; Cy1; C(O)R7; S(O2)R10o C2-4alkynyl group; or R4 and R5 taken together with the N to which they are attached form a heterocycle; R6 is a hydrogen; Ci.4alkyl optionally substituted with OH, halogen, Cy2, Ci.4alkoxy, Ci 4alkoxy-S(0)2o group NR11R12; C(O)R13; Si(CH3)2-butyl or C2-4alkynyl group; R7 is a Ci 4alkyl optionally substituted with OH group, CN, halogen, Cy3o NR11R12; Ci-4alkoxy group, C2¿alken¡lo;Cy3o N(Ci-4alkyl)2; R3 and R9 are independently a hydrogen, Ci-4alkyl or C(O)OR21 group; R10 is a ^alkyl group, OH or NR14R15; R11 and R12 are independently a hydrogen or alkyl group; or R11 and R12 taken together with the N to which they are attached form an optionally substituted heterocycle; R13 is a ^alkyl optionally substituted with CN or NR19R20 group; Cy3o NR16R17 group; R14 and R15 are independently a hydrogen or Ci_4alkyl group; R16 and R17 are independently a hydrogen, Ci^alkyl, or optionally substituted aryl group; or R16 and R17 taken together with the N to which they are attached form a heterocycle; R18 and R21 are a hydrogen or Ci.4alkyl group; IF-2019-03 566964-APN-ANP#INPI Page 9 of 272 R19 and R20 are independently a hydrogen or Ci-4alkyl group; Cy1 is an optionally substituted cycloaikyl, heterocyclyl or heteroaryl group; Cy2 is an optionally substituted aryl or cycloaikyl group; Cy3 is an optionally substituted aryl, cycloaikyl, heterocyclyl or heteroaryl group; X is a group (Realkyl, aryl or heteroaryl; Z is a group . alkyl: m is 2, 3, 4 or 5 and / or its salts and / or its geometric isomers and / or its stereoisomers and / or its enantiomers and / or its racemates and / or its diastereomers and / or its biologically active metabolites and / or their prodrugs and / or their solvates and / or their hydrates and / or their polymorphs. The present invention also relates to pharmaceutical compositions containing the compound of general formula (I) and / or its salt and / or its geometric isomer and / or its stereoisomer and / or its enantiomer and / or its racemate and / or its diastereomer. and / or its prodrug and / or its solvate and / or its hydrate and / or its polymorph as active ingredients. Likewise, the present invention also relates to the preparation of the compound of general formula (I) and / or its salt and / or its geometric isomer and / or its stereoisomer and / or its enantiomer and / or its racemate and / or its diastereomer. and / or its prodrug and / or its solvate and / or its hydrate and / or its polymorph, to the intermediates of the preparation process, and to the chemical and pharmaceutical preparation of the pharmaceutical compositions containing the compounds. The invention also relates to a method for treating a mammal, including humans, suffering from a central and / or peripheral disease, wherein modulation, preferably antagonism of the V1a receptor can have therapeutic benefits, wherein the compound of formula is administered general (I) and / or its salt and / or its geometric isomer and / or its stereoisomer and / or its enantiomer and / or its racemate and / or its diastereomer and / or its prodrug and / or its solvate and / or its hydrate and / or its polymorph, or a therapeutically effective amount thereof in a composition. The invention also relates to the use of the compound of general formula (I) and / or its salt and / or its geometric isomer and / or its stereoisomer and / or its enantiomer and / or its racemate and / or its diastereomer and / or its prodrug and / or its solvate and / or its hydrate and / or its polymorph, for the manufacture of a medicament for the treatment and / or prophylaxis of a disease or condition associated with the function of the V1 a receptor. IF-2019-03 566964-APN-ANP#INPI Page 10 of 272 DETAILED DESCRIPTION OF THE INVENTION The present invention relates to modulators of the V1a receptor, in particular, antagonists of the V1a receptor. It is another object of the invention to provide selective V1 receptor inhibitor compounds since selectivity is less likely to cause undesirable side effects. Another aspect of the invention is to provide compounds with favorable physicochemical properties since the favorable physicochemical properties are expected to generate beneficial bioavailability, ADME (absorption, distribution, metabolism, excretion), membrane penetration or blood-brain barrier penetration. . The compounds of general formula (I) of the present invention are, therefore, V1a receptor antagonists that are therapeutic agents that act centrally and / or peripherally in the treatment and / or prophylaxis of various pathological conditions of the female sexual organs, long-term conditions in the control of blood pressure, conditions generated by inadequate secretion of vasopressin, anxiety, depression, aggression, disorders of the central nervous system where one of the symptoms and / or syndromes of the disease may be related to anxiety, depression, aggression or showing comorbidity with them (autism spectrum disorder, obsessive-compulsive disorder, various forms of Down syndrome, post-traumatic stress disorder), aggressive behavior disorders and / or irritability, behavioral hyperactivity disorders, cognitive disorders or others neuropsychiatric disorders. The present invention refers to the compounds of general formula (I) where: ring A is a cycloalkyl or heterocyclyl group; yes-O-, -C(O)-, -CH2-, -NH-, -Ci-4alkyl-N(R18)- or bond if ring B is present; or N(Ci.4alkyl)2, C(0)OCi-4alkyl, Ci-4alkyl optionally substituted with halogen, Ci4alkoxy group or halogen if ring B is not present; IF-2019-03 566964-APN-ANP#INPI Page 11 of 272 ring B is an optionally substituted heteroaryl, aryl or heterocyclyl group; or B-Y-A- together represents 3H-spiro[2-benzofuran-1,4'-piperidin-1-yl]; either A \\ z° 2—N Z·—N \ group; or group; or group; R1 is a hydrogen, halogen, Ci-4alkyl, CmbIkoxy, CFs or CN; R2 is a hydrogen or Ci-4alkyl group; R3 is an NR4R5, OR6o halogen group; or R2 and R3 together represent -O-(CH2)m-O-, oxo or =N-OH group; R4 and R5 are independently hydrogen; Cy-4alkyl optionally substituted with OH, halogen, cycloalkyl, optionally substituted aryl or NR8R9 group; Cy1; C(O)R7; S(O2)R10o C2-4alkynyl group; or R4 and R5 taken together with the N to which they are attached form a heterocycle; R6 is a hydrogen; Cmalkyl optionally substituted with OH, halogen, Cy2, Ci-4alkoxy, Ci-4alkoxy-S(0)2 or NR11R12 group; C(O)R13; Si(CH3)2-t-butyl or C2.4alkynyl group; R7 is a Ci-4alkyl optionally substituted with OH group, CN, halogen, Cy3o NR11R12; Ci-4alkoxy, C2-4alkenyl, Cy3o N(Ci-4alkyl)2 group; R8 and R9 are independently a hydrogen group, Cmalkyl or C(O)OR21; R10 is a Ci-4alkyl group, OH or NR14R15; R11 and R12 are independently a hydrogen or Cmalkyl group; or R11 and R12 taken together with the N to which they are attached form an optionally substituted heterocycle; R13 is a Ci-4alkyl optionally substituted with CN group or NR19R20; Cy3o NR16R17 group; R14 and R15 are independently a hydrogen or Cmalkyl group; R16 and R17 are independently a hydrogen, Ci.alkyl, or optionally substituted aryl group; or R16 and R17 taken together with the N to which they are attached form a heterocycle; R18 and R21 are a hydrogen or Cmalkyl group; IF-2019-03 566964-APN-ANP#INPI Page 12 of 272 R19 and R20 are independently a hydrogen or Ci-4alkyl group; Cy1 is an optionally substituted cycloalkyl, heterocycyl or heteroaryl group; Cy2 is an optionally substituted aryl or cycloalkyl group; Cy3 is an optionally substituted aryl, cycloalkyl, heterocycyyl or heteroaryl group; X is a Ci^alkyl, aryl or heteroaryl group; Z is a Ci-4alkyl group; m is 2, 3, 4 or 5 and / or its salts and / or its geometric isomers and / or its stereoisomers and / or its enantiomers and / or its racemates and / or its diastereomers and / or its biologically active metabolites and / or their prodrugs and / or their solvates and / or their hydrates and / or their polymorphs. The definition of the general terms used herein, whether or not the terms in question are presented individually or in combination with other groups, are described below. The term cycloalkyl group refers, alone or in combination with other groups, to 3- to 8-membered, preferably 3- to 6-membered, saturated or unsaturated, preferably saturated, carbocyclic groups. Examples include cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl. In ring A, the term cycloalkyl group preferably refers to a 4- to 6-membered carbocyclic group, saturated or unsaturated, preferably saturated. Examples include cyclobutyl, cyclopentyl or cyclohexyl, more preferably cyclobutyl or cyclohexyl. Particularly preferred is the cyclohexyl group. The term substituted cycloalkyl group preferably refers to a cycloalkyl group having a geminal halogen substitution. The term "aryl group" refers, alone or in combination with other groups, to a 6- to 14-membered, preferably 6- to 10-membered, aromatic carbocyclic moiety comprising at least one aromatic ring or a fused ring system containing at least an aromatic ring. Examples include, but are not limited to, phenyl, benzyl, naphthyl, biphenyl, anthryl, azulenyl or indanyl. Particularly preferred is the phenyl group. The term "heterocycyl group" refers, alone or in combination with other groups, to a ring cycle of 3 to 8 members, preferably 4 to 7 members, saturated or unsaturated, preferably saturated, monocyclic, bicyclic, fused and / or bridged containing 1, 2 or 3 heteroatoms selected from O, S or N. Examples include, IF-2019-03 566964-APN-ANP#INPI 13 Page 13 of 272 but not limited to, oxirane, oxetane, tetrahydrofuran, tetrahydropyran, piperidine, pyrrolidine, morpholine, piperazine, 1,3-oxazolidine, 1,3-thiazolidine, thiomorpholine 1,1-dioxide, azepane, 1-azabicyclo[ 2.2.2]octane and the like. Preferably pyrrolidinyl, piperidinyl, piperazinyl or 1-azabicyclo[2.2.2] oct-3-yl. More preferably, piperidinyl or piperazinyl. When ring A is heterocyclyl, then "heterocyclyl" preferably refers to a 4- to 7-membered saturated heterocyclyl group containing 1 or 2 N, wherein ring A is linked through a ring nitrogen to Y or to the ring triazole from the 5,6-dihydro-4H-[1,2,4]triazolo[4,3-a][1]benzazepine nucleus. Examples include, but are not limited to, azetidinyl, 1,3-diazetidinyl, pyrrolidinyl, pyrazolidinyl, imidazolidinyl, piperidinyl, piperazinyl, azepanyl, 1,3- or 1,4-diazepanyl. Preferably azetidinyl, pyrrolidinyl, piperidinyl or piperazinyl. Particularly preferred is piperidinyl. In the case of Cy1o Cy3, the "heterocycle" preferably refers to a saturated 4 to 7 membered heterocyclyl group containing 1 O; more preferably, oxetane or tetrahydropyran. When R4 and R5 taken together with the N to which they are attached form a heterocycle, the heterocycle preferably refers to a saturated 4 to 7 membered ring containing 1, 2 or 3 heteroatoms selected from O, S or N; more preferably, pyrrolidine, 3-oxazolidine, 1,3-thiazolidine, piperidine, piperazine, morpholinyl or thiomorpholine-1,1-dioxide. When "R11 and R12", or "R16 and R17 taken together with the N to which they are attached form a heterocycle", the heterocycle is preferably selected from the group comprising morpholin-4-yl, 4-methylpiperazin-1-yl, pyrrolidinyl, piperidinyl , piperazinyl, 1,3oxazolidine, 1,3-thiazolidine or thiomorpholine-1,1-dioxide. The term heteroaryl group refers, alone or in combination with other groups, to a cyclic aromatic group containing a single 5- to 6-membered ring containing 1, 2 or 3 heteroatoms in which group at least one heterocyclic ring is aromatic. 6-membered monoheteroaryl refers to a monocyclic aromatic group that is a single 6-membered ring containing 1, 2 or 3 heteroatoms selected from O, S or N. Examples include, but are not limited to, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, thiazinyl, oxazinyl and the like. Preferred individual 6-membered mono-heteroaryl groups contain 1 or 2 N. A preferred 6-membered ring is pyridinyl; more preferably, pyridin-2-yl and pyridin-3-yl. Particularly preferred is pyridin-2-yl. The term 5-membered mono-heteroaryl refers to a monocyclic aromatic group that IF-2019-03 566964-APN-ANP#INPI 14 Page 14 of 272 is a single 5-membered ring containing 1, 2, or 3 heteroatoms selected from O, S, or N. Preferred 5-membered mono-heteroaryl groups contain 2 N and 1 O, 2 N and 1 S, 2 N. , 1 N or 1 S or 1 N and 1 O. Examples include, but are not limited to, thiophenyl, furanyl, pyrrolyl, imidazolyl, thiazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, thiadiazolyl, 1Hpyrazolyl, triazolyl and the like. A preferred 5-membered ring is isoxazol-3-yl and 1,3,4oxadiazol-5-yl. In the case of Cy1, heteroaryl preferably refers to a 6-membered monoheteroaryl group containing 1 or 2 N; more preferably, pyridine, pyrimidine or pyrazine, When ring B is an optionally substituted heteroaryl group, the heteroaryl group is preferably 3-chloropyridin-2-yl, 3-methylpyridin-2-yl or 5-methylisoxazol-3yl. The term bond refers to a single bond, in which a pair of electrons is shared between two atoms. The term C1-4 alkyl group refers, alone or in combination with other groups, to a linear or branched hydrocarbon radical, simple or multiple, and consists of 1 to 4 carbon atoms. Examples include, but are not limited to, methyl, ethyl, propyl, i-propyl (isopropyl), n-butyl, 2-butyl (sec-butyl), or t-butyl (tert-butyl) group. Preferred alkyl groups are those consisting of 1 to 3 carbon atoms. More preferred are methyl, ethyl and isopropyl groups. Particularly preferred is the methyl group. The term C2-4 alkenyl group refers, alone or in combination with other groups, to a linear or branched, single or multiple branched hydrocarbon radical, having a double bond and consisting of 2 to 4 carbon atoms. Examples include, but are not limited to, vinyl, propen-1-yl, propen-2-yl, butene-1-yl or butene-3-yl. Preferred alkenyl groups are those consisting of 2 to 3 carbon atoms. Particularly preferred is the vinyl group. The term C2-4 alkynyl group refers, alone or in combination with other groups, to a hydrocarbon radical that has a triple bond and consists of 2 to 4 carbon atoms. Examples include, but are not limited to, ethynyl, propynyl, propargyl, 1-butynyl, 2-butynyl and the like. Preferred alkynyl groups are those consisting of three carbon atoms. More preferred is the propargyl group. The term Cm alkoxy group refers, alone or in combination with other groups, to the O-C1.4 alkyl group, wherein the Cm alkyl group is as defined above. The IF-2019-03 566964-APN-ANP#INPI Page 15 of 272 examples include, but are not limited to, methoxy, ethoxy, propoxy, f-butoxy. Preferred alkoxy groups are methoxy, propoxy or f-butoxy. Particularly preferred are methoxy and f-butoxy groups. The term Boc refers, alone or in combination with other groups, to the fbutoxycarbonyl group. The term halogen refers, alone or in combination with other groups, to fluorine, chlorine, bromine or iodine; preferably fluorine, chlorine or bromine; more preferably chlorine or bromine. Particularly preferred is chlorine. The term 'Optionally substituted on any atom of the relevant group refers to substitution by one or more Cm alkyl groups, Cm alkoxy groups, oxo groups or halogens. Here, one or more means “from one to the largest possible number of substitutions”, that is, from replacing one hydrogen to replacing all hydrogens. One, two or three substituents on a given atom are preferred. Even more preferred are one or two, or a substitution. Particularly preferred is a substitution for a substituted aryl or heteroanyl group. The term "Cm alkyl optionally substituted with halogen" preferably refers to a Cm alkyl group having one, two or three halogen substituents on any atom of the Cm alkyl group; more preferably, to a methyl group having three halogen substituents. Particularly preferred is the CF3 group. The term salt refers to pharmaceutically acceptable and / or pharmaceutically unacceptable salts. The pharmaceutically acceptable salt refers to conventional acid addition salts and base addition salts that retain the biological efficacy and properties of the compounds of general formula (I) and which can be formed with organic or inorganic bases or organic or inorganic acids. suitable non-toxic. Examples of acid addition salts include salts derived from inorganic acids, such as, but not limited to, hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, sulfamic acid, phosphoric acid, nitric acid and perchloric acid and derivatives of various organic acids, such as, but not limited to, acetic acid, propionic acid, benzoic acid, glycolic acid, phenylacetic acid, salicylic acid, malonic acid, maleic acid, oleic acid, pamoic acid, palmitic acid, benzenesulfonic acid, toluenesulfonic acid, methanesulfonic acid, oxalic acid, tartaric acid, succinic acid, citric acid, malic acid, lactic acid, glutamic acid, fumaric acid and the like. Examples of base addition salts are salts derived from ammonium, potassium, sodium and quaternary ammonium hydroxides, such as hydroxide. IF-2019-03 566964-APN-ANP#INPI Page 16 of 272 tetramethylammonium. These salts often exhibit more favorable solubility properties than the compounds used for their preparation and are therefore more suitable for use in the preparation of, for example, liquid or emulsion formulations. Pharmaceutically non-acceptable salts may be preferred for the purification and isolation of compounds of general formula (I) and therefore also fall within the scope of the invention. The term prodrug refers to derivatives of the compounds of general formula (I) according to the invention which, by themselves, have no therapeutic effect but which contain said groups which, after chemical or metabolic degradation in vivo ( biotransformation) are converted into biologically active metabolites that are responsible for the therapeutic effect. Such decomposition groups associated with the compounds of general formula (I) of the present invention, particularly those suitable for prodrugs, are known in the art and may also be applied to the compounds of the present invention (Rautio et al., Nat Rev Drug Discov 2008, 7:255-270). Compounds of general formula (I) can exist in various geometric isomeric forms. Furthermore, certain compounds of general formula (I) may contain one or more asymmetric centers; therefore, they exist in the form of stereoisomers and diastereomers. All these compounds, such as cis isomers, trans isomers, diastereomeric mixtures, racemates, non-racemic mixtures of enantiomers, substantially pure and pure enantiomers also fall within the scope of the invention. Substantially pure enantiomers contain up to 5% by weight, preferably 2% by weight, more preferably 1% by weight, of the corresponding opposite enantiomer. Optical isomers can be prepared by resolving racemic mixtures by known methods, for example, using an optically active base or acid to form diastereoisomeric salts or by forming covalent diastereomers. Suitable acids include, for example, tartaric acid, diacetyltartaric acid, dibenzoyltartaric acid, ditoltartaric acid and camphorsulfonic acid. Diastereoisomeric mixtures can be separated into individual diastereomers on the basis of their physical and / or chemical differences, through methods known to those skilled in the art, such as chromatography or fractional crystallization. Subsequently, the optically active bases or acids are released from the separated diastereoisomeric salts. Several methods to separate optical isomers include chiral chromatography (e.g. IF-2019-03 566964-APN-ANP#INPI Page 17 of 272 example, chiral HPLC columns) optionally used for derivatization with the aim of maximizing the separation of the enantiomers. Suitable chiral HPLC columns are Diacel columns, such as CHIRALPAK or CHIRALCEL columns, which can be routinely chosen as desired. Where applicable, enzymatic separations carried out by derivatization may also be used. Optically active compounds of general formula (I) can also be prepared using optically active starting materials using chiral synthesis without racemization reaction conditions. The absolute configuration of the chiral compounds was determined by the vibrational circular dichroism (VCD) spectroscopy method described in the literature (Freedman et al., Chirality 2003, 75(9)743-58; Stephens et al. , Chirality 2008, 20:643-663) and / or by 1H NMR spectroscopic assays of the diastereomeric pair of compounds synthesized from chiral compounds (Seco et al., J Org Chem 1999, 64:4669-4675; Seco et al. , Tetrahedron Asymmetry 2001, 72:2915-2925; Latypov et al., J.Am.Chem.Soc. 1998, 720, 4741-4751). Compounds of general formula (I) can exist in various polymorphic forms. As is known in the art, polymorphism is the ability of a compound to crystallize in more than one crystalline form, that is, in polymorphic form. Polymorphic forms of a particular compound may be defined by an identical chemical formula or composition and differ in their chemical structure like the crystal structures of two different chemical compounds. Compounds of general formula (I) and salts thereof may also be present as solvates or hydrates, which also fall within the scope of the invention. The term "solvate" refers to non-covalent combinations of solvent and solute. The term "hydrate" refers to non-covalent combinations of water and solute. The present invention further relates to pharmaceutical compositions containing the compound of general formula (I) and / or its salt and / or its geometric isomer and / or its stereoisomer and / or its enantiomer and / or its racemate and / or its diastereomer. and / or its prodrug and / or its solvate and / or its hydrate and / or its polymorph. The present invention also relates to the chemical and pharmaceutical preparation of pharmaceutical compositions containing the compound of general formula (I) and / or its salt and / or its geometric isomer and / or its stereoisomer and / or its enantiomer and / or its racemate and / or its diastereomer and / or its solvate and / or its hydrate and / or its polymorph. IF-2019-03 566964-APN-ANP#INPI Page 18 of 272 The pharmaceutical compositions of the present invention can be formulated in various pharmaceutical formulations, such as, but not limited to, solid oral dosage forms such as tablets (e.g., for buccal administration, sublingual, effervescent, chewable, orally dispersible), capsules, pills. , tablets, orally dispersed films, granules, powders; liquid formulations such as solutions, emulsions, suspensions, syrups, elixirs, drops; parenteral dosage forms such as intravenous injections, intramuscular injections, subcutaneous injections; other forms of medicines such as eye drops, semi-solid ophthalmic preparations, semi-solid dermal preparations (such as ointments, creams, pastes), transdermal therapeutic systems, suppositories, rectal capsules, rectal solutions, emulsions and suspensions, etc. One embodiment of the invention relates to pharmaceutical compositions for pediatric use, such as, but not limited to, solutions, syrups, elixirs, suspensions, powders for the preparation of suspensions, dispersible or effervescent tablets, chewable tablets, orodispersible tablets, tablets or coated tablets, effervescent powders or granules for oral administration, capsules. The pharmaceutical compositions of the present invention can be prepared by methods known per se, such as conventional mixing, dissolution, emulsification, suspension, microencapsulation, lyophilization, extrusion and spheronization, lamination, film coating, granulation, encapsulation, coating or pressing. The pharmaceutical compositions of the present invention may be formulated in the usual manner using one or more physiologically acceptable excipients, including binders, which promote the incorporation of the active ingredient into pharmaceutically acceptable dosage forms. The appropriate formulation depends on the mode of administration chosen. Any of the techniques and excipients widely known in the art can be used. The excipients applicable in the preparation can be selected from the following categories, such as, but not limited to, tablet and capsule fillers, tablet and capsule binders, modified drug binding agents, disintegrants, glidants, lubricants, sweeteners, flavor masking, flavoring agents, coating materials, surfactants, stalyzing agents, preservatives or antioxidants, buffering agents, complexing agents, wetting or emulsifying agents, salts for adjusting the IF-2019-03 566964-APN-ANP#INPI Page 19 of 272 osmotic pressure, lyophilization excipients, microencapsulation agents, ointment materials, penetration enhancers, solubilizers, solvents, suppository materials, suspending agents. Suitable pharmaceutical excipients may be, for example: starch, microcrystalline cellulose, talc, glucose, lactose, gelatin, silica, talc, magnesium stearate, sodium stearate, glycerol monostearate, cellulose derivatives, sodium chloride, glycerol, propylene glycol , water, ethanol and the like. Another embodiment of the present invention refers to the use of special binders that can improve the solubility, dissolution, penetration, absorption or bioavailability of the active ingredient(s), such as, but not limited to, hydrophilic polymers, extrusion excipients of hot melt, surfactants, buffering agents, complexing agents, emulsifying agents, lyophilization excipients, disintegrants, microencapsulation agents, penetration promoters, solubilizers, cosolvents, suspending agents. The excipients described above and the various preparation methods are only representative examples. Other materials and processing techniques known in the art may also be used. The terms "disease or condition associated with V1a receptor function" or "disease or condition associated with central and / or peripheral modulation, preferably V1a receptor antagonism" refer to a disease or condition selected from the group consisting of various pathological conditions of the female sexual organs, long-term conditions in the control of blood pressure, conditions generated by inadequate secretion of vasopressin, anxiety, depression, aggression, disorders of the central nervous system where one of the symptoms and / or syndromes of The disease may be related to anxiety, depression, aggression or show comorbidity with them (autism spectrum disorder, obsessive-compulsive disorder, various forms of Down syndrome, post-traumatic stress disorder), aggressive behavior disorders and / or irritability, mood disorders. behavioral hyperactivity, cognitive disorders or other neuropsychiatric disorders. Various pathological conditions of the female sexual organs include, but are not limited to, dysmenorrhea (primary and / or secondary) or sexual dysfunction. Long-standing conditions in blood pressure control include, but are not limited to, hypertension and / or chronic heart failure. IF-2019-03 566964-APN-ANP#INPI Page 20 of 272 Conditions caused by inappropriate vasopressin secretion include, but are not limited to, diabetes insipidus, kidney failure, nephrotic syndrome, or cirrhosis. Disorders of the central nervous system where one of the symptoms and / or syndromes of the disease may be related to or comorbid with anxiety, depression, aggression include, but are not limited to, autism spectrum disorder (full-term autism). functioning, Asperger syndrome, pervasive developmental disorder, not otherwise specified (PDD-NOS), autism spectrum disorder (ASD) and its various syndromic forms: fragile X syndrome, Prader-Willi syndrome, Reti syndrome, sclerosis tuberose, obsessive compulsive disorder (OCD), various forms of Down syndrome and post-traumatic stress disorder (PTSD). Disorders of aggressive behavior and / or irritability include, but are not limited to, ASD, Huntington's disease, or different forms of schizophrenia. Behavioral hyperactivity disorders include, but are not limited to, attention deficit hyperactivity disorder. Cognitive disorders include, but are not limited to, dementia, mild cognitive disorders, cognitive impairment associated with schizophrenia or Alzheimer's disease. Other neuropsychiatric disorders include, but are not limited to, schizophrenia and associated diseases. In one embodiment, the disease or condition associated with V1a receptor function or disease or condition associated with central and / or peripheral modulation; preferably, V1a receptor antagonism refers to autism spectrum disorder. The present invention relates to a method for treating and / or preventing a disease or condition associated with the function of the V1a receptor, comprising administration to a subject in need of treatment and / or prophylaxis, preferably a mammal, more preferably a human. , of a therapeutically effective amount of a compound of general formula (I) and / or salt thereof and / or geometric isomer thereof and / or stereoisomer thereof and / or enantiomer thereof and / or racemate thereof and / or diastereomer of the same and / or prodrug thereof and / or solvate thereof and / or hydrate thereof and / or polymorph thereof, alone or with at least one pharmaceutically acceptable excipient in the form of a pharmaceutical formulation. IF-2019-03 566964-APN-ANP#INPI Page 21 of 272 The present invention relates to a method for the treatment of a subject, preferably a mammal, more preferably a human being, suffering from a disease or condition selected from the group consisting of various pathological conditions of the female sexual organs, long-term conditions duration of blood pressure control, conditions generated by inadequate secretion of vasopressin, anxiety, depression, aggression, disorders of the central nervous system where one of the symptoms and / or syndromes of the disease may be related to anxiety, depression, aggression or show comorbidity with them (autism spectrum disorder, obsessive-compulsive disorder, various forms of Down syndrome, post-traumatic stress disorder), aggressive behavior disorders and / or irritability, behavioral hyperactivity disorders, cognitive disorders or other neuropsychiatric disorders, or combination of these diseases. This method of treatment comprises administering to a subject in need of said treatment, preferably a mammal, more preferably a human being, the therapeutically effective amount of the compound of general formula (I) and / or its salt and / or its geometric isomer and / or or its stereoisomer and / or its enantiomer and / or its racemate and / or its diastereomer and / or its prodrug and / or its solvate and / or its hydrate and / or its polymorph. The treatment method may include administration to a subject in need of said treatment, preferably a mammal, more preferably a human, of a therapeutically effective amount of a pharmaceutical composition comprising the compound of general formula (I) and / or its salt. and / or its geometric isomer and / or its stereoisomer and / or its enantiomer and / or its racemate and / or its diastereomer and / or its prodrug and / or its solvate and / or its hydrate and / or its polymorph. The present invention relates to the use of the compound of general formula (I) and / or its salt and / or its geometric isomer and / or its stereoisomer and / or its enantiomer and / or its racemate and / or its diastereomer and / or its prodrug and / or its solvate and / or its hydrate and / or its polymorph, for the manufacture of a medicament for the treatment and / or prophylaxis of a disease or condition associated with the function of the V1 a receptor. The term treatment refers to the alleviation of a specific pathological condition, the elimination or reduction of one or more of the symptoms of the condition, the slowing or elimination of the progression of the disease state, and the prevention or delay of recurrence of the condition. pathology of a patient or subject who already suffers from or is diagnosed with the disease. Prevention (or prophylaxis or delay of the onset of the disease) is typically carried out by administering the drug of the same IF-2019-03 566964-APN-ANP#INPI Page 22 of 272 manner or in a similar manner as if it were administered to a patient with an already developed disease or condition. The term therapeutically effective amount refers to the amount of active ingredient that produces the treatment, cure, prevention or improvement of the disease or pathological condition or side effect, and reduces the progression of the disease or pathological condition in comparison to the corresponding subject that did not receive such an amount. The term also includes amounts effective to improve normal physiological functioning. For use in therapy, the compound of general formula (I) and / or its geometric isomer and / or its stereoisomer and / or its enantiomer and / or its racemate and / or its diastereomer and / or its prodrug and / or its solvate and / or its hydrate and / or its polymorph, as well as any pharmaceutically acceptable salt thereof, can be administered in a therapeutically effective amount as a crude chemical. Furthermore, the active ingredient may be available as a pharmaceutical formulation. The exact therapeutically effective amount of the compound of general formula (I) and / or salt thereof and / or geometric isomer thereof and / or stereoisomer thereof and / or enantiomer thereof and / or racemate thereof and / or diastereomer thereof and / or prodrug thereof and / or solvate thereof and / or hydrate thereof and / or polymorph thereof depends on a number of factors including, but not limited to, the age and body weight of the subject (patient) treated. , the exact type of disease requiring treatment and its severity, the nature of the medicinal product and the route of administration. The term mammal refers to any member of the class Mammalia, including, but not limited to, humans. The present invention also relates to pharmaceutical compositions comprising the compound of general formula (I) and / or its salt and / or its geometric isomer and / or its stereoisomer and / or its enantiomer and / or its racemate and / or its diastereomer and / or its prodrug and / or its solvate and / or its hydrate and / or its polymorph, suitable for the treatment of a disease or condition associated with central and / or peripheral modulation; preferably, V1 a receptor antagonism. The compound of the invention can also be used in combination with one or more of the compounds of the invention or with one or more different active ingredients (for example, psycholeptics, psychoanaleptics, antihypertensives, spasmolytics, antiepileptics or other agents) in a mammal, including, but not limited to, humans, suffering from a central and / or peripheral disease, where central and / or peripheral modulation, preferably antagonism of the V1 a receptor, has therapeutic benefits. IF-2019-03 566964-APN-ANP#INPI Page 23 of 272 Psycholeptics include, but are not limited to, antipsychotics, anxiolytics, and sedatohypnotics or narcotics. Antipsychotics include, but are not limited to, typical and atypical antipsychotics, such as phenothiazines with aliphatic side chains (chlorpromazine, promazine, levomepromazine, acepromazine, triflu proazine, cyamemazine, chlorproetazine, protipendyl), phenothiazines derived from piperazine (dixyrazine, fluphenazine , perazine, perphenazine, prochlorperazine, thiopropazate, trifluoperazine, acetophenazine, thioproperazine, butaperazine, perazine), phenothiazines derived from piperidine (periciazine, thioridazine, mesoridazine, pipotiazine), thioxanthenes (chlorprothixene, clopentixol, flupentixol, zuclopentix, ol), derived from butyrophenone (haloperidol, triflupidol, melperone, moperone, pipamperone, bromperidol, benperidol, droperidol, thymiperone, fluanisone), diphenylbutylpiperidine derivatives (fluspirilene, penfluridol, plmozide), diazepine, oxazepine or tiazepine derivatives (clozapine, olanzapine , clothiapine, quetiapine, loxapine, azenapine), indole derivatives (sertindole, ziprasidone, lurazidone, molindone, oxypertin), benzamide derivatives (sulpiride, sultropride, tiapride, remoxipride, amisulpride, veralipride, nemonapride, verasulpiride) or other agents ( risperidone, aripiprazole, cariprazine, brexpiprazole, metoclopramide, mosapramine, iloperidone, paliperidone, amoxapine, amperoside, perospirone, carpipramine, clocapramine, tetrabenazine, lithium). Ansiolithic include, in a non -taxative way, benzodiazepines (diazepam, chlorodiazepoxide, medazepam, oxazepam, potassium chlorine Iazepam, Ethil Loflazepato, etizolam, clothiazepam, coxazolam, tofizopam), diphenylmethane derivatives (hydroxyzine, captodiamine), carbamates (meprobamate, emilcamate, mebutamate), dibenzobicyclooctadiene derivatives (benzoquinone), azaspirode-diones (buspirone), other agents (mefenoxalone, gedocarnil, etifoxine, fabomotizoi, trimetosine), derivatives that act by increasing GABAa-mediated inhibition or compounds that act on serotonin receptors and other GABAergic agents (such as GABAa ct5 NAMs, for example, basmisanil, GABAa a5 PAMs, for example RG7816). Sedative or narcotic hypnotics include, but are not limited to, barbiturates (pentobarbital, amobarbital, butobarbital, barbital, approvebital, secabarbital, talbutal, vinylbital, vinbarbital, cyclobarbital, heptabarbital, reposal, methohexitol, hexobarbital, thiopental, etalobarbital, allobarbital, proxibarbital) , aldehydes (doral hydrate, chloralodol, acetylglycinamide doral hydrate, dichloralphenazone, paraldehyde), benzodiazepines IF-2019-03 566964-APN-ANPAINPI Page 24 of 272 (flurazepam, nitrazepam, flunitrazepam, estazolam, triazolam, lormetazepam, temazepam, midazolam, brotizolam, quazepam, loprazolam, doxefazepam, cinolazepam), piperidinedione derivatives (glutethimide, methylprilon, pyrildildione), benzodiazepine cyclopyrrolone derivatives (zopiclone , zolpidem, zaleplon, eszopiclone), melatonin receptor agonists (melatonin, ramelteon) or other hypnotics and sedatives (methaqualone, clomethiazole, bromisoval, carbromal, scopolamine, propiomazine, triclophos, etichlorvinol, Valerianae Radix, hexapropylamate, bromides, apronal, valnoctamide, methylpentynol, niaprazine, dexmedetomidine). Psychoanaleptics include, but are not limited to, psychostimulants or antidepressants. Psychostimulants include, but are not limited to, centrally acting sympathomimetics (amphetamine, dexamphetamine, methamphetamine, methylphenidate, pemoline, fencamfamine, modafinil, phenazolone, atomoxetine, phenethylline, dexmethylphenidate, lisdexfetamine), nootropics or other psychostimulants (caffeine, propentofylline, meclofenoxate, pyritinol, piracetam, deanol, fipexide, cytocholine, oxiracetam, pyrisudanol, linopyridine, nizofenone, aniracetam, acetylcarnitine, idebenone, prolintane, pipradrol, pramiracetam, adrafinil, vinpocetine, tacrine, donepezil, rivastigmine, galantamine, ipidacrine, memantlna, mebica r, phenibut). Antidepressants include, but are not limited to, non-selective monoamine reuptake inhibitors (desipramine, imipramine, imipramine oxide, clomipramine, opipramol, trimipramine, lofepramine, dibenzepine, amitriptyline, nortriptyline, protriptyline, doxepin, iprindole, melitracene, butriptyline , dosulepin, amoxapine, dimethacrine, amineptine, maprotiline, quinupramine), serotonin modulators and stimulators (vilazodone, vortioxetine), selective serotonin reuptake inhibitors (zimeldine, fluoxetine, paroxetine, sertraline, alaproclate, fluvoxamine, etoperidone, citalopram , escitalopram), non-selective monoamine oxidase inhibitors derived from hydrazide (isocarboxazid, nlalamide, phenelzine, tranylcypromine, iproniazide, iprocloside), monoamine oxidase inhibitors not derived from hydrazide (moclobemide, toloxatone) or other agents (oxitriptan, tryptophan, mianserine, nomifensin, trazodone, nefazodone, mineprine, bifemelana, viloxazine, oxaflozana, mirtazapine, medifoxamine, thianeptin, pivagabine, venlafaxine, milnacipran, reboxetine, pyrazidol, duloxetin, agomelatin Ropion, Gepirone, hyperic grass extract). Antihypertensives include, but are not limited to, β-receptor blockers, thiazide diuretics, angiotensin-converting enzyme inhibitors, IF-2019-03 566964-APN-ANP#INPI Page 25 of 272 calcium antagonists, angiotensin receptor antagonists (losartan), Rauwolfia alkaloids (rescinamine, reserpine, deserpidine, metoserpidine, bietaserpine), methyldopa, imidazoline receptor agonists (clonidine, guanfacine, tolonidine, moxonidine, rilmenidine), ganglion-blocking antiadrenergic agents (sulfonium-derived trimetapane, secondary and tertiary amine mecamylamine), peripherally acting antiadrenergic agents, alpha-adrenoreceptor blockers (prazosin, indoramine, trimazosin, doxazosin, urapidil), guanidine derivatives (betanidine, guanethidine, guanoxane, debrisoquine, guanoclor, guanocidine, guanoxabenz), agents acting on arteriolar smooth muscle, the thiazide derivative diazoxide, the hydrazinophthalazine derivatives (dihydralazine, hydralazine, endralazine, cadralazine), the pyrimidine derivative minoxidil, the nitroferricyanide nitroprusside derivative, the guanidine derivative pinacidil, the non-Rauwolfia alkaloid veratrum, the tyrosine hydroxylase inhibitor metyrosine, the MAO inhibitor pargyline, the serotonin antagonist ketanserin or other antihypertensives (bosentan, ampbrisentan, sitaxentan, macitentan, riociguat) and a combination of these substances with a diuretic. Spasmolytics or antispasmodics include, but are not limited to, peripheral muscle relaxants, curare alkaloids, choline derivatives, other quaternary ammonium muscle relaxants (pancuronium, gallamine, vecuronium, atracurium, hexafluronium, pipecuronium bromide, doxacurium chloride, fazadinium, rocuronium bromide, mlvacurium bromide, cisatracurium, botulinum toxin), central nervous system muscle relaxants, carbamic acid esters (fenprobamate, carisoprodol, methocarbamol, styramate, febarbamate), oxazole, thiazine and triazine derivatives (chlormezanone, chlorzoxazone ), antihistamine-related ethers (orphenadrine, guaifenesin) and other histaminergic agents (such as histamine H3 receptor antagonists / inverse agonists, e.g., ciproxifan, thioperamide, pitolisant, clobenpropit, ABT-239, conessine, A-349,821, betahistine ), other centrally acting agents (baclofen, arbaclofen, tizanidine, pridinol, tolperisone, thiocolchicoside, mephenesin, tertazepam, cyclobenzaprine, pheniramidol), the direct-acting muscle relaxant dantrolene and its derivatives, compounds that act by increasing GABAa-mediated inhibition or decreasing Na+ conduction (phenytoin, carbamazepine, lamotrigine, VPA), gamma-aminobutyric acid derivatives (vigabatrin, gabapentin), other GABAergic agents (such as GABAb PAMs, e.g. ADX71441), esters with a tertiary amino group (oxyphencyclimine , camilofin, mebeverine, trimebutine, rocaverine, dicycloverine, dlhexyverine, diemerin, piperidolat), quaternary ammonium compounds (benzylone, glycopyrronium, oxyphenium, penthienate, propantheline, otilonium bromide, IF-2019-03 566964-APN-ANP#INPI Page 26 of 272 methantheline, tridihexetil, isopropamide, hexocyclyl, poldine, mepenzolate, bevonium, pipenzolate, dipemanil, emethonium iodide, thiemonium iodide, priphinium bromide, thiepidio and fenpiverinium bromide), amides with tertiary amines (astra 1397, nicofetamide , tíropramide), papaverine and its derivatives (drotaverine, moxaverine, etaverine), agents that act on serotonin receptors (alosetron, tegaserod, cilansteron, prucalopride), other agents of functional gastrointestinal disorders (fenpiprane, diisopromine, chlorbenzoxamine, pinaverium, fenoverine, idanpramine, proxazole, alverine, trepibutone, isometheptene, caroverine, phloroglucinol, silicones, trimethyldiphenylpropylamine), succinimide derivatives (ethosuximide, fensuximide, mesuximide) or Belladonna alkaloids and their derivatives (atropine, hyoscyamine, butylscopolamine, methyltropine, methylscopolamine, fentonium, cimetropium bromide). Antiepileptics include, but are not limited to, barbiturates and their derivatives (methylphenobarbital, phenobarbital, primidone, barbexaclone, metarbital), hydantoin derivatives (etothion, phenytoin, amino valeric acid (diphenylhydantoin), mephenyltoin, fosphenytoin), oxazolidine (paramethadione, trimethadione, etadione), succinimide derivatives (ethosuximide, fensuximide, mesuximide), benzodiazepine derivative clonazepam, carboxamide derivatives (carbamazepine, oxcarbazepine, rufinamide), fatty acid derivatives (valproic acid, valpromide, aminobutyric acid , vigabatrin, progabide, tiagabine) and other antiepileptics (sultiame, phenacemide, lamotrigine, felbamate, topiramate, gabapentin, feneturide, levetiracetam, zonisamide, pregabalin, stiripentol, lacosamide, carisbamate, retigabine, brivaracetam, beclamide), Other agents include, but are not limited to, medicinal products (probiotics, digestion / digestive aids, herbal extracts), vitamins (both water and fat soluble, such as, but not limited to, vitamin A, D3, E, K, B1, B5, B6, B12, C or their derivatives) and nutritional supplements (coenzymes, e.g. Q10, flavonoids, e.g. resveratrol, lecithin, unsaturated fatty acids, including ω-3 and ω- fatty acids 6). The compounds of the invention can also be used in combination with Phosphodiesterase 5 Isoenzyme Inhibitors (PDE5), nitric oxide donors, cyclooxygenase inhibitors, other V1a receptor antagonists (such as balovaptan) or L-arginine for the treatment and / or prophylaxis of a disease or condition associated with V1 a receptor function. IF-2019-03 566964-APN-ANP#INPI Page 27 of 272 The combinatorial composition may comprise the compound of the invention together with some other active ingredient in a single pharmaceutical form or separately. The combinatorial composition may be administered simultaneously, separately or sequentially. Suitable dosage forms include forms for oral, rectal, mucosal, transdermal or intestinal administration; parenteral administration that includes intramuscular, subcutaneous, intravenous, intramedullary injections as well as intra-articular, intrathecal, direct intraventricular, intraperitoneal, intranasal or intraocular injections and eye drops. Alternatively, the compounds may be administered locally and not systemically, for example by direct injection of the compound to the kidney or heart, usually in modified release formulation. Likewise, the drug can be administered in a targeted delivery system, for example, in a tissue-specific antibody-encapsulated liposome. Liposomes transfer the active ingredient selectively to the target organ, which absorbs it. The pharmaceutical composition can be administered in various ways and in various dosage forms. The compound of the invention can be administered alone or in combination with pharmaceutically acceptable excipients, in single or multiple doses. The dose required to achieve the appropriate therapeutic effect can vary widely and should always be adapted to individual needs in relation to the state of the disease, the condition and weight of the patient to be treated, and the sensitivity to the active ingredient, as in the dosage regimen, and the number of daily treatments. For simple administration, it is preferred that the pharmaceutical compositions consist of dosage units containing the amount of drug to be administered once, or a small number of its multiple, or half, one third, one quarter. Such dosage units are, for example, tablets which may be provided with a score in the middle or quarters to facilitate halving or quartering the tablet in order to measure the required amount of the drug. Pharmaceutical compositions containing the active ingredient according to the invention generally contain 0.01 to 500 mg of active ingredient per dose unit. Of course, it is also possible that the amount of active ingredient in each formulation exceeds the limit mentioned above or below. IF-2019-03 566964-APN-ANP#INPI Page 28 of 272 Other groups of preferred compounds of general formula (I) are those in which each of the embodiments of ring A, ring B, X, Y, Z, R1-R21, Cy1-Cy3y m described below are optionally combined . Any of the combinations of the preferred, more preferred or even more preferred embodiments of ring A, ring B, X, Y, Z, R1-R21, Cy1-Cy3o m as defined below are also the preferred groups, plus preferred or even more preferred of the compounds of formula (l). In certain embodiments of the invention, ring A in the compounds of general formula (I) is a 4- to 6-membered saturated carbocycle. In certain preferred embodiments of the invention, ring A in the compounds of general formula (I) is cyclobutyl or cyclohexyl. In certain more preferred embodiments of the invention, ring A in compounds of general formula (I) is cyclohexyl. In certain embodiments of the invention, ring A in the compounds of general formula (I) is a saturated 4- to 7-membered heterocyclyl group containing 1 or 2 N, wherein ring A is attached via a nitrogen from the ring to Y. In certain embodiments of the invention, ring A in the compounds of general formula (I) is a saturated 4- to 7-membered heterocyclyl group containing 1 or 2 N, wherein ring A is attached via a nitrogen from the ring to the triazole ring of the nucleus of 5,6-dlhydro-4H-[1,2,4]triazolo[4,3-a][1]benzazepine. In certain embodiments of the invention, ring A in the compounds of general formula (I) is azetidinyl, 1,3-diazetidinyl, pyrrolidinyl, pyrazolidinyl, imidazolidinyl, piperidinyl, piperazinyl, azepanyl, 1,3- or 1,4 -diazepanyl, wherein ring A is linked via a ring nitrogen to Y. In certain embodiments of the invention, ring A in the compounds of general formula (I) is azetidinyl, 1,3-diazetidinyl, pyrrolidinyl, pyrazolidinyl, imidazolidinyl, piperidinyl, piperazinyl, azepanyl, 1,3- or 1,4 -diazepanyl, wherein the A ring is linked via a ring nitrogen to the triazole ring of the 5,6-dihydro-4H[1,2,4]triazolo[4,3-a][1]benzazepine nucleus . In certain preferred embodiments of the invention, ring A in the compounds of general formula (I) is azetidin-1,3-diyl, piperidin-1,4-diyl or piperazin-1,4-diyl, wherein ring A It is linked via a ring nitrogen to Y or to the triazole ring of the 5,6-dihydro-4H-[1,2,4]triazolo[4,3-a][1]benzazepine nucleus. IF-2019-03 566964-APN-ANP#INPI Page 29 of 272 In certain embodiments of the invention, ring B in compounds of general formula (I) is optionally substituted aryl group. In certain preferred embodiments of the invention, ring B in compounds of general formula (I) is optionally substituted phenyl. In certain embodiments of the invention, ring B in compounds of general formula (I) is optionally substituted heterocyclyl group. In certain preferred embodiments of the invention, ring B in the compounds of general formula (I) is optionally substituted tetrahydrofuranyl, tetrahydropyranyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl or azabicyclo[2,2,2]octyl. . In certain more preferred embodiments of the invention, ring B in the compounds of general formula (I) is tetrahydrofuran-3-yl, tetrahydropyran-4-yl, pyrrolidin1-yl, pyrrolidin-1-yl-2-one, piperidin-1-yl, 4-methyl-piperazin-1-yl, morpholin-4-yl or 1azabicyclo[2,2,2]oct-3-yl. In certain embodiments of the invention, ring B in compounds of general formula (I) is optionally substituted heteroaryl group. In certain embodiments of the invention, ring B in compounds of general formula (I) is optionally substituted single 6- or 5-membered mono-heteroaryl group. In certain preferred embodiments of the invention, ring B in compounds of general formula (I) is optionally substituted pyridinyl, pyrimidinyl or isoxazolyl. In certain more preferred embodiments of the invention, ring B in the compounds of general formula (I) is pyridin-2-yl, pyridin-3-yl, 3-chloropyridin-2-yl, 3-methylpyridin-2- yl, pyrimidin-2-yl or 5-methyl-isoxazol-3-yl. In certain even more preferred embodiments of the invention, ring B in compounds of general formula (I) is pyridin-2-yl. In certain embodiments of the invention, Y in compounds of general formula (I) is -O-, if the B ring is present. In certain embodiments of the invention, Y in compounds of general formula (I) is -C(O)-, if the B ring is present. In certain embodiments of the invention, Y in compounds of general formula (I) is -CH2-, if ring B is present. IF-2019-03 566964-APN-ANP#INPI Page 30 of 272 In certain embodiments of the invention, Y in compounds of general formula (I) is -NH-, if the B ring is present. In certain embodiments of the invention, Y in compounds of general formula (I) is -Ci-4alkyl-N(R18)-, if ring B is present. In certain preferred embodiments of the invention, Y in compounds of general formula (I) is a single bond, if ring B is present, In certain embodiments of the invention, Y in the compounds of general formula (I) is -N(Ci^alkyl)2, C(O)OCMalkyl, Ci-4alkyl optionally substituted with halogen, Ci+alkoxy group or halogen, if ring B is not present. In certain embodiments of the invention, Y in compounds of general formula (I) is Ci-4alkyl optionally substituted with halogen or O.4alkoxy group; if ring B is not present. In certain preferred embodiments of the invention, Y in compounds of general formula (I) is C-i-salkyl group, if ring B is not present. In certain more preferred embodiments of the invention, Y in compounds of general formula (I) is methyl, ethyl, or propyl group, if ring B is not present. In certain preferred embodiments of the invention, Y in the compounds of general formula (I) is Ci.galkoxy group, if ring B is not present. In certain more preferred embodiments of the invention, Y in the compounds of general formula (I) is a methoxy or ethoxy group, if ring B is not present. In certain preferred embodiments of the invention, Y in compounds of general formula (I) is CF3 group, if ring B is not present. In certain embodiments of the invention, Y in compounds of general formula (I), if ring B is not present, refers to a group selected from the group consisting of -N(Ci-4alkyl)2, C (0)OC+4alkyl, Ci-4alkyl optionally substituted with halogen, Ci-4alkoxy group and halogen. In certain preferred embodiments of the invention, Y in the compounds of general formula (I), if ring B is not present, refers to a group selected from the group consisting of dimethylamine group, C(O)OCi- 4alkyl and CF3. In certain embodiments of the invention, Y in the compounds of general formula (I), if ring B is not present, refers to two groups selected from IF-2019-03 566964-APN-ANP#INPI 31 Page 31 of 272 group consisting of Ci^alkyl optionally substituted with halogen, CmsIkoxy group and halogen. In certain preferred embodiments of the invention, Y in the compounds of general formula (I), if ring B is not present, refers to two groups selected from the group consisting of Ci.3alkyl, Ci-salkoxy, group CF3y fluorine. In certain more preferred embodiments of the invention, Y in the compounds of general formula (I), if ring B is not present, refers to two groups selected from the group consisting of methyl, ethyl, propyl, methoxy, ethoxy, CF3 group and fluorine. In certain even more preferred embodiments of the invention, Y in the compounds of general formula (I), if ring B is not present, refers to two groups selected from the group consisting of methyl, ethyl, propyl, methoxy and ethoxy. In certain preferred embodiments of the invention, in the compounds of general formula (I), ring A is cyclobutyl or cyclohexyl, Y refers to a group selected from the group consisting of -N(Ci-4alkyl)2, -C(0)OCi-4alkyl, CF3y halogen and the B ring is not present. In certain preferred embodiments of the invention, in the compounds of general formula (I), ring A is cyclobutyl or cyclohexyl, Y refers to two groups selected from the group consisting of Cmalkyl optionally substituted with halogen, group C^ alcoxl and halogen and the B ring is not present. In certain preferred embodiments of the invention, in the compounds of general formula (I), ring A is cyclobutyl or cyclohexium, Y is -O- or bond and ring B is optionally substituted phenyl, piperidin-1-yl, morpholin-4-yl, 1-azabicyclo[2,2,2]oct-3-yl, pyridin-2-yl, pyridin-3-yl, 3-chloro-pyridin-2-yl, 3-methylpyridin-2- yl, pyrimidin-2-yl or 5methylisoxazol-3-yl. In certain more preferred embodiments of the invention, in the compounds of general formula! (I), ring A is cyclohexyl, Y is -O- and ring B is pyridin-2-yl, pyridin3-yl, 3-chloro-pyridin-2-yl, 3-methylpyridin-2-yl, pyrimidin-2-yl or 5-methylisoxazol-3-yl. In certain even more preferred embodiments of the invention, in the compounds of general formula (I), ring A is cyclohexyl, Y is -O- and ring B is pyridin-2-yl. In certain preferred embodiments of the invention, in the compounds of general formula (I), ring A is azetidin-1,3-diyl, piperidin-1,4-diyl or plperazin-1,4-diyl, IF- 2019-03 566964-APN-ANP#INPI 32 Page 32 of 272 I·: ί: wherein ring A is linked via a ring nitrogen to Y or to the triazole ring of the 5,6-dihydro-4H-[1,2,4]triazolo[4,3-a][1] nucleus benzazepine, Y is -O- or bond and ring B is optionally substituted phenyl, piperidin-1 -lio, morpholin-4-yl, 1azabicyclo[2,2,2]oct-3-yl, pyridin-2-yl, pyridin-3-yl, 3-chloro-pyridin-2-yl, 3-methylpyridin-2-yl, pyrimidin-2-yl or 5-methylisoxazol-3-yl. , In certain more preferred embodiments of the invention, in compounds I of general formula (I), ring A is piperidin-1,4-diyl or piperazin-1,4-diyl, where ring A is linked by means of a ring nitrogen to Y or to the triazole ring of the core of 5,6-dihydro-4H-[1,2,4]triazolo[4,3-a][1]benzazepine, Y is -O- or bond and ring B is pyridin-2-yl or pyridin-3-yl.। In certain embodiments of the invention, in compounds of general formula (I), ring A is cyclobutyl, cyclohexyl or pyrrolidinyl, Y is -C(O)- and ring B is pyrrolidin-1-yl, piperidin -1-yl, morpholin-4-yl, 4-methyl-piperazinyl or pyridine-3-yl. In certain embodiments of the invention, B-Y-A- in the compounds of general formula (I) together represent 3H-spiro[2-benzofuran-1,4'-piperidin-1J-íl],i 1-oxa-3-azaspiro[4,5]decan-2-on-8-yl substituted in the 3-position by Ci-4alkyl or 2azaspiro[4,5]decan-1-on-8-yl substituted in the 2 for Ci-4alkyl, aryl or heteroaryl.. In certain preferred embodiments of the invention, B-Y-A- in the compounds of general formula (I) together represent 3H-spiro[2-benzofuran-1,4'piperidin-1 '-yl], (5S,8S)-3 -methyl-1-oxa-3-azaspiro[4,5]decan-2-on-8-yl, (5R,8R)-3-methyl-1- i oxa-3-azaspiro[4,5]decan- 2-on-8-yl, (5R,8R)-2-(propan-2-yl)-2-azaspiro[4,5]decan-1one or (5S,8S)- 2-(propan-2-yl )-2-azaspiro[4,5]decan-1-one. In certain embodiments of the invention, R1 in the compounds of general formula (I) is hydrogen. In certain embodiments of the invention, R1 in the compounds of general formula (I) is halogen. In certain preferred embodiments of the invention, R1 in the compounds of general formula (I) is chlorine, bromine or fluorine. In certain more preferred embodiments of the invention, R1 in the compounds of general formula (I) is chlorine. In certain embodiments of the invention, R1 in the compounds of formula (I) is Ci^alkyl. IF-2019-03 566964-APN-ANP#INPI Page 33 of 272 In certain preferred embodiments of the invention, R1 in the compounds of general formula (I) is methyl. In certain embodiments of the invention, R1 in the compounds of general formula (I) is Ci-4alkoxy. In certain preferred embodiments of the invention, R1 in the compounds of general formula (I) is methoxy. In certain embodiments of the invention, R1 in the compounds of general formula (I) is CF3. In certain embodiments of the invention, R1 in the compounds of general formula (I) is CN. In certain embodiments of the invention, in the compounds of general formula (I), R2 is hydrogen or Ci-4alkyl, R3 is NR4R5, OR6or halogen group. In certain embodiments of the invention, in the compounds of general formula (I), R2 is Ci-4alkyl, R3 is NR4R5, OR6o halogen group. In certain embodiments of the invention, in the compounds of general formula (I), R2 is hydrogen, R3 is NR4R5, OR6 group or halogen. In certain preferred embodiments of the invention, in the compounds of general formula (I), R2 is hydrogen, R3 is NR4R5or group OR6 and the absolute configuration of the carbon in the 5 position in the nucleus of 5,6-dihydro-4H-[1 ,2,4]triazolo[4,3a](1)benzazepine is (R). In certain embodiments of the invention, in compounds of general formula (I), R2 is hydrogen, R3 is NR4R5 or OR6 group, and the absolute configuration of the carbon in the 5 position in the nucleus of 5,6-dihydro-4H-[1, 2,4]triazolo[4,3a][1]benzazepine is (S). In certain embodiments of the invention, in the compounds of general formula (I), R2 is hydrogen, R3 is NR4R5or OR6 group. In certain embodiments of the invention, in the compounds of general formula (I), R2 is hydrogen, R3 is NR4R5 group. In certain embodiments of the invention, in the compounds of general formula (I), R2 is a hydrogen or Ci-4alkyl group, R3 is an NR4R5 group, where R4 and R6 are hydrogen. IF-2019-03 566964-APN-ANP#INPI Page 34 of 272 In certain embodiments of the invention, in the compounds of general formula (I), R2 is hydrogen, R3 is NR4R5 group, where R4 is hydrogen, R5 is Ci-4alkyl group. In certain preferred embodiments of the invention, in the compounds of general formula (I), R2 is hydrogen, R3 is NR4R5 group, where R4 is hydrogen R5 is isopropyl group. In certain embodiments of the invention, in the compounds of general formula (I), R2 is hydrogen, R3 is NR4R5 group, where R4 and R5 are CV4alkyl groups. In certain preferred embodiments of the invention, in the compounds of general formula (I), R2 is hydrogen, R3 is NR4R5 group, where R4 and R5 are independently methyl, ethyl or isopropyl group. In certain more preferred embodiments of the invention, in the compounds of general formula (I), R2 is hydrogen, R3 is NR4R5 group, where R4 and R5 are methyl groups. In certain embodiments of the invention, in the compounds of general formula (I), R2 is hydrogen, R3 is NR4R5 group, where R4 is hydrogen, R5 is Ci-4alkyl group substituted with OH. In certain preferred embodiments of the invention, in the compounds of general formula (I), R2 is hydrogen, R3 is NR4R5 group, where R4 is hydrogen, R5 is hydroxymethyl or hydroxyethyl group. In certain embodiments of the invention, in the compounds of general formula (I), R2 is hydrogen, R3 is NR4R5 group, where R4 is hydrogen, R5 is Cv4alkyl group substituted with halo. In certain preferred embodiments of the invention, in the compounds of general formula (I), R2 is hydrogen, R3 is NR4R5 group, where R4 is hydrogen, R5 is trifluoro-substituted Ci-2alkyl group. In certain preferred embodiments of the invention, in the compounds of general formula (I), R2 is hydrogen, R3 is NR4R5 group, where R4 is hydrogen, R5 is methyl-cyclopropyl group. In certain embodiments of the invention, in the compounds of general formula | r2eshydrogen, R3is NR4R5 group, where R4is hydrogen, R5is methyl or ethyl group substituted with 4-fluorophenyl. IF-2019-03 566964-APN-ANP#INPI Page 35 of 272 In certain embodiments of the invention, in the compounds of general formula (I), R2 is hydrogen, R3 is NR4R5 group, where R4 is hydrogen, R5 is Ci4alkyl substituted with NR8R9 group, where R8 and R9 are independently hydrogen, Ci-4alkyl group or group C(O)OR21. In certain preferred embodiments of the invention, in the compounds of general formula (I), R2 is hydrogen, R3 is NR4R5 group, where R4 is hydrogen, R5 is Ci-4alkyl substituted with NR8R9 group, where R8 is hydrogen, R9 is C( O)OR21. In certain embodiments of the invention, in the compounds of general formula (I), R2 is hydrogen, R3 is NR4R5 group, where R4 is hydrogen, R5 is Ci4alkyl substituted with NR8R9 group, where R8 and R9 are independently hydrogen or Ci-4alkyl group. In certain preferred embodiments of the invention, in the compounds of general formula (I), R2 is hydrogen, R3 is NR4R5 group, where R4 is hydrogen, R5 is aminomethyl or ethyl group. In certain preferred embodiments of the invention, in the compounds of general formula (I), R2 is hydrogen, R3 is NR4R5 group, where R4 is hydrogen, R5 is dimethylamino-methyl or -ethyl group. In certain embodiments of the invention, in compounds of general formula (1), R2 is hydrogen, R3 is NR4R5 group, where R4 is hydrogen, R5 is Cy1. In certain preferred embodiments of the invention, in the compounds of general formula (I), R2 is hydrogen, R3 is NR4R5 group, wherein R4 is hydrogen, R5 is cyclobutyl, cyclopentyl, cyclohexyl, 4,4-difluoro-cyclohexyl, oxetan-2 -yl or tetrahydropyranyl. In certain preferred embodiments of the invention, in the compounds of general formula (I), R2 is hydrogen, R3 is NR4R5 group, where R4 is hydrogen, R5 is pyridin-2-yl, pyrimidin-2-yl or pyrazin-2-yl . In certain embodiments of the invention, in the compounds of general formula (I), R2 is hydrogen, R3 is NR4R5 group, where R4 is hydrogen, R5 is C(O)R7 group, where R7 is methyl, ethyl or isopropyl group. In certain embodiments of the invention, in the compounds of general formula (I), R2 is hydrogen, R3 is NR4R5 group, where R4 is hydrogen, R5 is C(O)R7 group, where R7 is CMalkyl substituted with OH, CN, halogen, Cy3o group NR11R12 IF-2019-03 566964-APN-ANP#INPI Page 36 of 272 In certain preferred embodiments of the invention, in the compounds of general formula (I), R2 is hydrogen, R3 is NR4R5 group, where R4 is hydrogen, R5 is C(O)R7 group, where R7 is methyl, ethyl or substituted isopropyl group with OH, CN or trifluoro. In certain embodiments of the invention, in the compounds of general formula (I), R2 is hydrogen, R3 is NR4R5 group, where R4 is hydrogen, R5 is C(O)R7 group, where R7 is methyl or ethyl substituted with NR11R12 group, in where R11 and R12 are independently hydrogen or methyl or R11 and R12 taken together with the N to which they are attached form morpholin-4-yl or 4-methyl-piperazin-1-yl. In certain preferred embodiments of the invention, in the compounds of general formula (I), R2 is hydrogen, R3 is NR4R5 group, where R4 is hydrogen, R5 is C(O)R7 group, where R7 is aminomethyl group. In certain preferred embodiments of the invention, in the compounds of general formula (I), R2 is hydrogen, R3 is NR4R5 group, where R4 is hydrogen, R5 is C(O)R7 group, where R7 is dimethylaminomethyl group. In certain preferred embodiments of the invention, in the compounds of general formula (I), R2 is hydrogen, R3 is NR4R5 group, where R4 is hydrogen, R5 is C(O)R7 group, where R7 is phenyl and / or methyl substituted with NH2. In certain embodiments of the invention, in the compounds of general formula (I), R2 is hydrogen, R3 is NR4R5 group, where R4 is hydrogen, R5 is C(O)R7 group, where R7 is Nbutoxy group. In certain embodiments of the invention, in the compounds of general formula (I), R2 is hydrogen, R3 is NR4R5 group, where R4 is hydrogen, R5 is C(O)R7 group, where R7 is vinyl group. In certain embodiments of the invention, in the compounds of general formula (I), R2 is hydrogen, R3 is NR4R5 group, where R4 is hydrogen, R5 is C(O)R7 group, where R7 is Cy3 group. In certain preferred embodiments of the invention, in the compounds of general formula (I), R2 is hydrogen, R3 is NR4R6 group, where R4 is hydrogen, R5 is C(O)R7 group, where R7 is 4-fluorophenyl, cyclopropyl, cyclobutyl , dihalo-cyclobutyl or cyclohexyl, oxetanyl, tetrahydropyran-4iio, 4-methyl-piperidinyl, or 5-methyl-1,3,4-oxadiazol-2yl. IF-2019-03 566964-APN-ANP#INPI Page 37 of 272 In certain preferred embodiments of the invention, in the compounds of general formula (I), R2 is hydrogen, R3 is NR4R5 group, where R4 is hydrogen, R5 is C(O)R7 group, where R7 is dimethylamino group. In certain preferred embodiments of the invention, in the compounds of general formula (I), R2 is hydrogen, R3 is NR4R5 group, where R4 is hydrogen or methyl, R5 is -S(O2)R10, where R10 is methyl group, OH, NH2, NH-t-butyl or dimethylamino. In certain embodiments of the invention, in the compounds of general formula (ΐχ R2 is hydrogen, R3 is NR4R5 group, where R4 is hydrogen or Ci4alkyl group, R5 is C2-4alkynyl group. In certain preferred embodiments of the invention, in the compounds of general formula (I), R2 is hydrogen, R3 is NR4R5 group, where R4 is methyl group, R5 is propargyl group. In certain embodiments of the invention, in the compounds of general formula (I), R2 is hydrogen, R3 is NR4R5 group, wherein R4 and R5 taken together with the N to which they are attached form a 4 to 7 membered heterocycle optionally containing one or more heteroatoms selected from O, S or N. In certain preferred embodiments of the invention, in the compounds of general formula (I), R2 is hydrogen, R3 is NR4R5, wherein R4 and R5 taken together with the N to which they are attached form pyrrolidine, piperidine, piperazine, morpholine, 1,3 -oxazolidine, 1,3-thiazolidine or thiomorpholine-1,1-oxide. In certain preferred embodiments of the invention, in the compounds of general formula (I), R2 is hydrogen, R3 is OR6 group, where R6 is hydrogen. In certain preferred embodiments of the invention, in the compounds of general formula (I), R2 is hydrogen, R3 is OR6 group, where R6 is methyl, ethyl or isopropyl group. In certain more preferred embodiments of the invention, in the compounds of general formula (I), R2 is hydrogen, R3 is OR6 group, where R6 is methyl group. In certain embodiments of the invention, in the compounds of general formula (I), R2 is hydrogen, R3 is OR6 group, where R6 is Ci-4alkyl group substituted with OH or halogen. IF-2019-03 566964-APN-ANP#INPI Page 38 of 272 In certain preferred embodiments of the invention, in the compounds of general formula (I), R2 is hydrogen, R3 is OR6 group, where R6 is methyl or ethyl group substituted with chlorine or fluorine. In certain embodiments of the invention, in the compounds of general formula (I), R2 is hydrogen, R3 is OR6 group, where R6 is cyclopropyl-methyl group. In certain embodiments of the invention, in the compounds of general formula (I), R2 is hydrogen, R3 is OR6 group, where R6 is Ci4alkyl substituted with Ci-4alkoxy group. In certain preferred embodiments of the invention, in the compounds of general formula (I), R2 is hydrogen, R3 is OR6 group, where R6 is methoxy-ethyl group. In certain embodiments of the invention, in the compounds of general formula (I), R2 is hydrogen, R3 is ORS group, where R6 is Ci.zalkyl substituted with Ci-4alkyl-S(O)2 group. In certain preferred embodiments of the invention, in the compounds of general formula (I), R2 is hydrogen, R3 is OR6 group, where R6 is methylsulfonylethyl group. In certain embodiments of the invention, in the compounds of general formula (I), R2 is hydrogen, R3 is OR6 group, where R6 is methyl or ethyl substituted with NR11R12 group, where R11 and R12 are independently hydrogen or methyl. In certain embodiments of the invention, in the compounds of general formula (I), R2 is hydrogen, R3 is OR6 group, where R6 is methyl or ethyl substituted with NR11R12, where R11 and R12 taken together with the N to which they are attached form a morpholin-4-yl. In certain preferred embodiments of the invention, in the compounds of general formula (I), R2 is hydrogen, R3 is OR6 group, where R6 is dimethylaminoethyl group. In certain embodiments of the invention, in the compounds of general formula (I), R2 is hydrogen, R3 is OR6 group, where R6 is C(O)R13, ​​where R13 is Ci.4alkyl group. In certain preferred embodiments of the invention, in the compounds of general formula (I), R2 is hydrogen, R3 is OR6 group, where R6 is C(O)R13, ​​where R13 is methyl, ethyl or f-butyl. IF-2019-03 566964-APN-ANP#INPI Page 39 of 272 In certain embodiments of the invention, in the compounds of general formula (I), R2 is hydrogen, R3 is OR6 group, where R6 is C(O)R13, ​​where R13 is Ci-4alkyl group substituted with CN. In certain preferred embodiments of the invention, in the compounds of general formula (I), R2 is hydrogen, R3 is OR6 group, where R6 is C(O)R13, ​​where R13 is cyanomethyl group. In certain embodiments of the invention, in the compounds of general formula (I), R2 is hydrogen, R3 is OR6 group, where R6 is C(O)R13, ​​where R13 is ^alkyl group substituted with NR19R20 group. In certain preferred embodiments of the invention, in the compounds of general formula (I), R2 is hydrogen, R3 is OR6 group, where R6 is C(O)R13, ​​where R13 is dimethylamino-methyl group. In certain embodiments of the invention, in the compounds of general formula (I), R2 is hydrogen, R3 is OR6 group, where R6 is C(O)R13, ​​where R13 is Cy3 group. In certain preferred embodiments of the invention, in the compounds of general formula (I), R2 is hydrogen, R3 is OR6 group, where R6 is C(O)R13, ​​where R13 is dihalo-substituted cycloalkyl group. In certain embodiments of the invention, in the compounds of general formula (I), R2 is hydrogen, R3 is OR6 group, where R6 is C(O)R13, ​​where R13 is NR16R17, where R16 and R17 are independently hydrogen, Ci-4alkyl or optionally substituted aryl. In certain embodiments of the invention, in the compounds of general formula (I), R2 is hydrogen, R3 is OR6 group, where R6 is C(O)R13, ​​where R13 is NR16R17, where R16 and R17 taken together with the N to which They are linked to piperidine or pyrrolidine. In certain embodiments of the invention, in the compounds of general formula (I), R2 is hydrogen, R3 is OR6 group, where R6 is Si(CH3)2-f-butyl. In certain embodiments of the invention, in the compounds of general formula (I), R2 is hydrogen, R3 is OR6 group, where R6 is C24alkynyl group. In certain preferred embodiments of the invention, in the compounds of general formula (I), R2 is hydrogen, R3 is OR6 group, where R6 is propargyl group. IF-2019-03 566964-APN-ANP#INPI Page 40 of 272 In certain embodiments of the invention, in the compounds of general formula (I), R2 is Ci-4alkyl, R3 is NR4R5or OR6 group. In certain embodiments of the invention, in the compounds of general formula! (I), R2is Ci^alkyl, R3is OR6 group. In certain embodiments of the invention, in the compounds of general formula (I), one of R2 and R3 is methyl or isopropyl and the other is OR6, where R6 is hydrogen. In certain embodiments of the invention, in the compounds of general formula (I), R2 is hydrogen and R3 is halogen. In certain preferred embodiments of the invention, in the compounds of general formula (I), R2 is hydrogen and R3 is fluorine. In certain embodiments of the invention, in the compounds of general formula (I), R2 is Ci^alkyl group and R3 is halogen. In certain preferred embodiments of the invention, in the compounds of general formula (I), R2 and R3 together represent -O-(CH2)m-O and m = 2, 3 or 4. In certain more preferred embodiments of the invention, in the compounds of general formula (I), R2 and R3 together represent -O-(CH2)nrO- and m = 2. In certain preferred embodiments of the invention, in the compounds of general formula (I), R2 and R3 together represent an oxo-group. In certain embodiments of the invention, in compounds of general formula (I), R2 and R3 together represent a =N-OH group. While the invention has been described in relation to certain embodiments, certain preferred, more preferred or even more preferred embodiments, it is not intended to limit the scope of the invention to the particular form set forth, but rather, to the contrary, It is intended to cover such alternatives, modifications, and equivalents as may be included within the spirit and scope of the invention as defined in the statements of invention. Examples of alternative claims directed to the compounds of the present invention may include: (1) Compounds of general formula (I) as described above, or in any other embodiment. IF-2019-03 566964-APN-ANP#INPI Page 41 of 272 (2) The compound as described in (1), or in any other embodiment, wherein R1 is a hydrogen, fluorine, chlorine, bromine, methyl, methoxy, CF3 or CN group. (3) The compound as described in any of (1) to (2), or in any other embodiment, wherein: ring A is a 3- to 6-membered saturated carbocyclic or a 4- to 7-membered saturated heterocycle containing 1 or 2 N; ring B is an optionally substituted 5- or 6-membered mono-heteroaryl group, 6- to 10-membered aromatic carbocycle, or 4- to 7-membered monocylic, bicyclyl, saturated, fused, and / or bridged heterocycle containing 1, 2 or 3 heteroatoms selected from O, So N; or B-Y-A- together represent a 3 / - / -spiro[2-benzofuran-1,4'-piper¡din-T-yl]; o o o Ao Ao group or group or group X is isopropyl group; Z is methyl group. (4) The compound as described in any of (1) to (3), or in any other embodiment, wherein ring B is an optionally substituted 6-membered mono-heteroaryl group, phenyl, or monocyclic heterocycle of 5 to 6 members containing 1 or 2 heteroatoms selected from O, S or N. (5) The compound as described in any of (1) to (4), or in any other embodiment, wherein Y is -O-, -C(O)-, -CFh-, -NH-, -Ci4alkyl-N(R18)- or a single bond if ring B is present and R18 is a hydrogen or methyl group. (6) The compound as described in any of (1) to (5), or in any other embodiment, wherein ring A is a 4- to 6-membered saturated carbocyclic group or a 4- to 7-membered saturated heterocycle members containing 1 or 2 N linked via a ring nitrogen to Y or to the triazole ring of the 5,6-dihydro-4H[1,2,4]triazolo[4,3-a][1] nucleus benzazepine. (7) The compound as described in any of (1) to (6), or in any other embodiment, wherein ring A is a cyclohexyl group, Y is -O-, ring B is a pyridin- 2-yl and R1 is chloro. IF-2019-03 566964-APN-ANP#INPI Page 42 of 272 (8) The compound as described in any of (1) to (6), or in any other embodiment, wherein ring A is a piperidine, piperazine, or pyrrolidine, AND is O-, -C(O)-, -CH2-, or a single bond, the B ring is a pyridine, piperidine, tetrahydrofuran, or tetrahydropyran, and R1 is chloro. (9) The compound as described in any of (1) to (3), or in any other embodiment, wherein Y is -N(Ci-4alkyl)2, C(O)OCi-4alkyl, Cmalkyl optionally substituted with halogen, Ci group, alkoxy or halogen and the B ring is not present. (10) The compound as described in (9), or in any other embodiment, wherein ring A is a 4- to 6-membered saturated carbocyclic group. (11) The compound as described in (10), or in any other embodiment, wherein Y is a group selected from the group consisting of -N(Ci4alkyl)2, C(0)OCi-4alkyl, Cmalkyl optionally substituted with halogen, Ci4alkoxy group and halogen. (12) The compound as described in (10), or in any other embodiment, wherein Y is two groups selected from the group consisting of Ci4alkyl optionally substituted with halogen, Ci-4alkoxy group and halogen. (13) The compound as described in any of (1) to (12), or in any other embodiment, wherein R2 is a hydrogen or Cv4alkyl group and R3 is an NR4R5 group. (14) The compound as described in (13), or in any other embodiment, wherein R2 is a hydrogen. (15) The compound as described in (14), or in any other embodiment, wherein R4 and R5 are independently a hydrogen; C(O)R7; Cmalkyl optionally substituted with OH, halogen, cycloalkyl, optionally substituted aryl or NR8R9 group. (16) The compound as described in (15), or in any other embodiment, wherein R4 and R5 are hydrogens. (17) The compound as described in (15), or in any other embodiment, wherein R4 is a hydrogen, R5 is a Ci-4alkyl group. (18) The compound as described in (15), or in any other embodiment, wherein R4 and R5 are Ci-4alkyl groups. IF-2019-03 566964-APN-ANP#INPI Page 43 of 272 (19) The compound as described in (15), or in any other embodiment, wherein R4 is a hydrogen, R5 is a C(O)R7 group. (20) The compound as described in (14), or in any other embodiment, wherein R4 is a hydrogen, R5 is Cy1. (21) The compound as described in (14), or in any other embodiment, wherein R4 is a hydrogen or Ci^alkyl, R5 is an S(O2)R10 group. (22) The compound as described in (14), or in any other embodiment, wherein R4 and R5 taken together with the N to which they are attached form a 4 to 7 membered heterocycle optionally containing 1, 2 or 3 heteroatoms selected from O, S or N. (23) The compound as described in any of (1) to (12), or in any other embodiment, wherein R2 is a hydrogen or Ci-4alkyl group; R3 is an OR6 group. (24) The compound as described in (23), or in any other embodiment, wherein R2 is a hydrogen. (25) The compound as described in (24), or in any other embodiment, wherein R6 is a hydrogen. (26) The compound as described in (24), or in any other embodiment, wherein R6 is a Ci-4alkyl group. (27) The compound as described in (24), or in any other embodiment, wherein R6 is a C(O)R13 group. (28) The compound as described in any of (13) to (27), or in any other embodiment, wherein the absolute configuration of the carbon in the 5 position in the nucleus of 5,6-dihydro-4H- [1,2,4]triazolo[4,3-a][1]benzazepine is (R). (29) The compound as described in any of (13) to (27), or in any other embodiment, wherein the absolute configuration of the carbon in the 5 position in the nucleus of 5,6-dihydro-4H- [1,2,4]triazolo[4t3-a][1]benzazepine is (S). (30) The compound as described in any of (1) to (12), or in any other embodiment, wherein R2 and R3 together represent group -O-(CH2)mO-, oxo or =N-OH, m is 2, 3, 4 or 5. (31) The compound as described in (30), or in any other embodiment, wherein R2 and R3 together represent group -0-(CH2)m-0- and m is 2. IF-2019-03 566964-APN-ANP#INPI Page 44 of 272 A preferred group of compounds of general formula (I) of the present invention are, for example, the following compounds and / or salts and / or solvates and / or hydrates and / or polymorphs and / or biologically active metabolites and / or prodrugs of the same: 1. fer-butyl [8-chloro-1 -[ 1 -(pirtdin-2-yl)piperidin-4-yl]-5,6-dihydro-4W-[1,2,4]trlazolo[4,3- a][1]benzazepin-5-yl] carbamate, 2. 8-chloro-1-[1-(pindin-2-yl)piperidin-4-yl]-5,6-dihydro-4H-[1,2,4]trlazolo[4,3- a][1]benzazepin-5-amine, 3. A / -[8-chloro-[1-(pyridin-2-¡l)piperidin-4-yl]-5,6-dihydro-4 / 7-[1,2,4]triazolo[4,3 - a] [ 1 ]benzazepin-5-yl]acetamide, 4. N-(8-chloro-[1 -(pyridin-2-yl)piperidin-4-yl]-5,6-dihydro-4 / - / -[1,2,4]triazolo[4,3- a][1]benzazepin-5-yl)-2-methylpropanamide, 5. tert-butiI {8-chloro-1 -[ / rans-4-(pyridin-2-yloxy)cyclohexyl]-5,6-dihydro-4H- [1,2,4]triazolo[4,3-a][1]benzazepin-5-yl}carbamate, 6. 8-chloro-1-[frans-4-(pyridin-2-yloxy)cyclohexyl]-5,6-dihydro-4H-[1,2,4]triazolo[4,3- a][1]benzazepin-5-amine, 7. (5S)-8-chloro-1 ¿frans-4-(pyridine n-2-i loxy)cyclohexyl]-5,6-d i h idro-4H-[1,2,4]tri azo lo[4, 3- a][1]benzazepin-5-amine, 8. (5R)-8-chloro-1-[frans-4-(pyridin“2-yloxy)cyclohexyl]-5,6-dihydro-4H-[1,2,4]triazolo[4,3- a][ 1 ]benzazepin-5-amine, 9. N-{8-chloro-1-[frans-4-(pindin-2-yloxy)cyclohexyl]-5,6-dihydro-4 / 7-[1,2,4]triazolo[4,3- a][1]benzazepin-5-yl}acetamide, 10. / V~{8-chloro-1-[frans-4-(pyridin-2-yloxy)cyclohexyl]-5,6-dihydro-4 / - / -[1,2,4]triazolo[4,3a ][1]benzazepin-5-yl}glycinamide, 11. Λ / -{(5 S)-8-clo ro-1 -[fra / 7S-4-(py rid i n-2-yl oxy)cyclo hexi l]-5,6-di h id ΓΟ- 4 / -7- [1,2,4]triazolo[4,3-a][1]benzazepin-5-yl}glycinamide, 12. A / -{(5R)-8-chloro-1 -[frans-4-(pyridin-2-yloxy)cyclohexyl]-5,6-dihydro-4H- [1,2,4]triazolo[4,3-a][1]benzazepin-5-yl}glycinamide, 13. (2S)-2-amino- / V-{(5R)-8-chloro-1 -[frans-4-(pyridin-2-yloxy)cyclohexyl]-5,6-dihydro-4 / - / ~ [1,2,4]triazolo[4,3-a][1]benzazepin-5-yl}-2-phenylacetamide, 14. (2R)-2-amino- / V-{(5R)-8-chloro-1-[frans-4-(pyridin-2-yloxy)cyclohexyl]-5,6-dihydro-4 / - / - [1,2,4]triazolo[4,3-a][1]benzazepin-5-yl}-2-phenylacetamide, 15. A / -{8-chloro-1 -[ / rans-4-(pyridin-2-yloxy)cyclohexyl]-5,6-dihydro-4H-[1,2,4]triazolo[4,3a][ 1]benzazepin-5-yl}-2-hydroxyacetamide, 16. 3-{8-chloro-1-[frans-4-(pyridin-2-yloxy¡)cyclohexyl]-5,6-dihydro-4H-[1,2,4]triazolo[4,3a] [1]benzazepin-5-yl}-1,1-dimethylurea, IF-2019-03 566964-APN-ANP#INPI Page 45 of 272 17, / \ / -{8-chloro-1 -[frans-4-(pyridin-2-yloxy)cyclohexyl]-5,6-dihydro-4 / - / -[1,2,4]triazolo[4, 3a][1 jbenzazepin-S-ilj-A / ^A^-dimethylglycinamide. 18. / V-{8-chloro-1-[irans-4-(pindin-2-yloxy)cyclohexyl]-5,6-dihydro-4 / - / -[1,2,4]triazolo[4,3a ][1]benzazepin“5-yl}methanesulfonamide, 19. / V-{8“C!oro-1-[frans-4-(pyridin-2-yloxy)cyclohexyl]-5,6-dihydrO4H-[1f2,4]triazolo[4;3a][1]benzazepin -54l}- / V-methylmethanonsulfonarnide, 20. A / '-{8-clofO-1-[írans-4-(pyridin-2-yloxy¡)cyclohexyl]-5:6-dihydro-4H-[1,2,4]triazolo[ 4,3a][1 ]benzazepin-5-yl}- / V, / V-dimethylsulfamide, 21. 8-chloro- / \ / -nnetyl-1-[irans-4-(pyridin-2-yloxy)cyclohexyl]-5,6-dihydro-4H-[1,2,4]triazolo[4,3a] [1]benzazepin-5-amine, 22. 8-chloro- / V, / V-dimethyl-1 -[trans-4-(pyridin-2-yloxy)cyclohexyl]-5,6-dihydro-4H- [1,2,4]triazolo[4,3-a][1]benzazepin-5-amine, 23. 8-chloro-A / -ethyl-1 -[irans-4-(pyridin-2-yloxy)cyclohexyl]-5,6-dihydro-4H-[1,2,4]triazolo[4,3a][ 1 ]benzazepin-5-amine, 24. 8-chloro-A / -(propan-2-yl)-1 -[frans-4-(pyridin-2-yloxy)cyclohexyl]-5,6-dihydro-4H[1,2,4]triazolo[ 4,3-a][1]benzazepin-5-amine, 25. (5S)-8-chloro-A / -(propan-2-yl)-1-[tra / 7s-4-(pyridin-2-yloxy)cyclohexyl]-5,6-dihydro«-4H[1 ,2,4]triazolo[4,3-a][1]benzazepin-5-amine, 26. (5R)-8-chloro- / V-(propan-24l)-1-[frans-4-(pyridin-24loxy)cyclohexyl]-5,6-dihydro-4H- [1,2,4]tr iazolo[4,3-a][1 ]benzazepin-5-amine, 27. 8-chloro-A / -cyclobutyl-1 -[trans-4-(pyridin-2-yloxy)cyclohexyl]-5,6-dihydro-4H- [1,2,4]tr iazolo[4,3-a] [ 1 ]benzazepin-5-amine, 28. 8-chloro- / \ / -(oxetan-3-yl)-1-[irans-4-(pyridin-2-yloxy)cyclohexyl]“5,6-dihydro-4H- [1,2,4]triazolo[4;3-a][1]benzazepin-5-amine, 29. 8-chloro-1-[frans-4-(pyrldin-2-yloxy)cyclohexyl]- / V-(tetrahydro-2 / 7-pyran-4-yl)-5,6-dihydro4H-[1,2 ,4]triazolo[4,3-a][1]benzazepin-5-amine, 30. 8-chloro- / V-(4,4-difluorcyclohexyl)-1-[frans-4-(pyridin-2-yloxy)cyclohexll]-5,6-dihydro-4H[1,2,4]triazolo[ 4,3-a][1]benzazepin-5-amine, 31. 8-methoxy-1 -[frans-4-(pyridin-2-yloxy)cyclohexyl]-5,6-dihydro-4H-[1,2,4]triazole or[4,3- a][1]benzazepin-5-amine hydrochloride, 32. 8-methoxy~ / \ / -(propan-2-yl)-1-[trans-4-(pyridin-2-yloxy)cic]ohexyl]-5,6-dihydro-4H- [1,2,4]triazolo[4,3-a][1]benzazepin-5-amine, 33. tert-butiI {1 -[ira / 7S-4-(pyridin-2-yloxy)cyclohexyl]-8-(trifluoromethyl)-5,6-dihydro-4H- [1,2,4]triazolo[4,3-a][1]benzazepln-5-yl}carbamate, IF-2019-03 566964-APN-ANP#INPI Page 46 of 272 34. 1 -[frans-4-(pyridin-2-yloxy)cyciohexyl]-8-(trifluoromethyl)-5,6-dihydro-4H- [1,2,4]tnazolo[4,3-a][1]benzazepin-5-amine hydrochloride, 35. A / , / V-dimethyl-1 -[frans-4-(plridin-2-yloxy)cyclohexyl]-8-(trifluoromethyl)-5,6-dihydro-4H- [1,2,4]t riazolo[4,3-a] [ 1 ]benzazepin-5-amine, 36. / V-(propan-2-yl)-1-(trans-4-(pyridin-2-yloxy)cyclohexyl]-8-(trifluoromethyl)-5,6-dihydro-4H[1,2,4] triazolo[4,3-a][1]benzazepin-5-amine, 37. 8-methi I-1 -[irans-4-(pyridi n-2-i loxy) cyclohexyl]-5,6-d i hydro-4H-[ 1,2,4]tnazolo[4,3- a][1 ]benzazepin-5-amine, 38. 8-methyl- / V-(propan-2-yl)-1 -[irans-4-(pyridin-2-yloxy)cyclohexyl]-5,6-dihydro-4H- [1,2,4]triazolo[4;3-a][1]benzazepin-5-amine, 39. 8-bromo-1 -[frans-4-(pyridin-2-yloxy)cyclohexyl]-5;6-dihydro-4H-['1;2,4]triazolo[4,3- a][1 ]benzazepin-5-amine, 40. 8-bromo- / V-(propan-2-yl)-1-[frans-4-(pyridin-2-yloxy)cyclohexyl]-5,6-dihydro-4H- [1,2,4]triazolo[4,3-a][1]benzazepin-5-amine, 41. 8-chloro-4 -(3,3-d if I uorocyclobutyl)-A / -(propan-2-yl )-5,6-d ih idro-4H-[1,2,4]triazolo[ 4.3- a][1lbenzazepin-5-amine, 42. 8-chloro-1-(4,4-difluorocyclohexyl)- / \ / -(propan-2-yl)-5,6-dihydro-4H-[1,2,4]triazolo(4,3a][ 1]benzazepin-5-amine, 43. 8-chloro-1-[Mans-4-(trifluoromethyl)cyclohexyl]-5,6-dihydro-4H-[1,2,4]triazolo[4,3a][1]benzazepin-5-amine, 44. 8-chloro-A / -(propan-2-yl)-1-(irans-4-(trifluoromethyl)cyclohexyl]-5,6-dihydro-4H- [1,2,4]triazolo[4,3-a][1]benzazepin-5-amine, 45. 8-bromo-1-[frans-4-(trifluoromethyl)cyclohexyl]-5,6-dihydro-4H“[1,2,4]tnazolo[4,3- a][1 ]benzazepin-5-amine, 46. ​​8-bromo- / V-(propan-2-yl)-1-[frans-4-(trifuoromethyl)cyclohexyl]-5,6-dihydro-4H- [1,2,4]triazolo[4,3-a][1]benzazepin-5-amine, 47. 1,-[frans-4-(pyridin-2-yloxy)cyclohexyl]-8,-(trifiuoromethyl)-4, / 7,6' / - / -spiro[1,3-dioxolane- 2,5-(1,2,4]triazolo[4,3-a][1]benzazepine], 48. 1-[frans-4-(pyridin-2-yloxy)cyclohexyl]-8-(tnfluoromethyl)-4 / 7-[1,2,4]triazoloE4,3“ a] [ 1 ]benzazepin-5(6 / 7)-one, 49. 1-[tranS“4-(pyridin-2-yloxy)cyclohexyl]-8-(trifluoromethyl)-5,6“dihydro-4 / - / [1,2,4]triazolo[4,3-a] [1]benzazepin-5-ol, 50. 5-methoxy-1-[irar?s-4-(pyridin-2-yloxy)cyclohexyl]8-(trifluoromethyl)-5,6-dihydro-4H- [1,2,4]triazolo[4,3-a][1]benzazepine, IF-2019-03 566964-APN-ANP#INPI Page 47 of 272 J. .A ···- .....— ......:|· 51. 5-(cyclopropylmethoxy)-1-[írans-4-(pyridin-2-yloxy)cyclohexii]-8-(trifluoromethyl)-5,6dihydro-4H-[1,2,4]triazolo[4,3- a][1 Jbenzazepine, 52. 5-{[fer-butyl(dimethyl)silyl]oxy}-8-chloro-1 -[trans-4-(pyridin-2-yloxy)cyclohexylJ-5,6-dihydro4H-[1,2]4] tnazolo[4,3-a][1]benzazepine, 53. 8'-chloro-T-[irans-4-(pyridin-2-yloxy)cyclohexyl]-4' / 7,6' / 7-spiro[1,3-dioxolane-2,5'- [1,2,4Jtriazolo[4,3-aJ[1 Jbenzazepine], 54. 8-chloro-1-[irans-4-(pyridin-2-yloxy)cyclohexyl]-4 / - / -[1,2,4]triazolo[4,3-a][1Jbenzazepin5(6H)-one , 55. 8-chloro-1-[frans-4-(pyridin-2-yloxy)cyclohexyl]-5,6-dihydro-4 / - / -[1,2,4]triazolo[4,3a][1] benzazepin-5-ol, 56. (5S)-8-chloro-1-[irans-4-(pyridin-2-yloxy)cyclohexyl]-5;6-dihydro-4 / 7-[1,2.4]triazolo[4,3~ a] [1]benzazepin-5-ol, 57. (5F?)-8-chloro-1-[trans-4-(pyridin-2-i!oxy)cyclohexyl]-5,6-dihydro-4 / 7-[1,2,4]triazolo[4 ,3- a][ 1 ]benzazepin-5-ol, 58. 8-cioro-5-methoxy-1-[irans-4-(pindin-2-yloxy)cyclohexylJ-5,6-dihydro-4H- [1,2,4]triazolo[4,3-aJ[1 Jbenzazepine, 59. 5-(cyclopropy!methoxy)-8-chloro-1-[frans-4-(pyridin-2-yloxy)cyclohexylJ-5,6-dihydro-4H- [1,2,4]triazolo[4,3-a][1 Jbenza^epina, 60. 2-({8-chloro-1-[frans-4-(pyridin-2-yloxy)cyclohexyl]-5,6-dihydro-4H-[1,2,4]triazolo[4,3a][1 ]benzazepin-5-yl}oxy)-A / .A / -dimethylethanaiTiina, 61. 8,-chloro-T“[t / 'ans-4-(tπfluoromethyl)cyclohexíl]“4Ή,6l / 7-spiro[1,3-dioxolanO2,5,[1,2,4] triazolo[413-a] [ 1 JbenzazepinaJ, 62. 8'-bromo-T-[traas-4-(pyridin-2-yloxy)cyclohexylJ-4'H,6'H-spiro[1,3-dioxolane-2,5'[1,2,4] triazolo[4,3-a][1 Jbenzazepine], 63. 14trans-4-(pyridin-2-yloxy)cyclohexyl]-4'H,6' / - / -spiro[1,3dioxolane-2,5'[1,2,4]triazolo[4,3-a ][1 Jbenzazepine], 64. 8-bromo-1¿frans-4-(pyridin-2-yloxy)cyclohexyl]“4 / - / -[1,2,4]tnazolo[4,3-a][1]benzazepin5(6H)- ona, 65. 8-bromo-1-[frans-4-(pyridin2-yloxy)cyclohexyl]-5,6-dihydrO“4H-[1,2,4]triazolo[4,3a][ 1 ]benzazepin-5-oi , 66. 1'-[irans-4-(pl rid ίη-2-yloxy)cyciohexyl]-4'H, 6'H-spiro[ 1,3-dioxolane-2,5'- [1,2,4]triazolo[4,3-a][1 ]benzazepin]-8'-carbonitrile, 67. (5S)-8-chloro-A / , / \ / -dimethyl-1-[irans-4-(pyridin-2“yloxy)cyclohexii]-5,6-dihydro-4H“ [1,2,4]triazolo[4,3“a][1 ]benzazepin-5-amine, IF-2019-03 566964-APN-ANPAINPI Page 48 of 272 68. (5S)- / V-{8-chloro-1-[frans-4-(pyridin-2-yloxy)cyclohexyl]-5t6-dihydro-4 / - / [1,2,4]triazolo[4, 3-a][1]benzazepin-5-yl}acetamide, 69. 8'-chloro-14^a^s-4¿pyridin-2-¡lmet¡l)cyclohexyl]-4' / 7.6' / 7-spiro[1.3-dioxolane-2 ,5'[1,2,4]triazolo[4,3-a][1]benzazepine], 70. -1 -i I) meta nona, 71. 8-chloro-1-[irans-4-(trifluoromethyl)cyclohexyl]-4H-[1,2,4]triazo!o[4,3-a][1]benzazepin5(6H)-one, 72. 8-chloro-1-[frans-4-(trifluoromethyl)cyclohexyl]-5,6-dihydro-4H¿1,2,4]tnazolo[4,3a][1]benzazepin-5-ol, 73. (c / s)-8-(8' “0ΐ0Γ0-4Ή,6Ή-θ5ρΪΓΌ[1,3-dioxolane-2,5'-[1,2,4]triazolo[4,3~ a][ 1 ]benzazepin]-1 '-yl)-3-methyl-1 -oxa-3-azaspiro[4,5]decan-2-one, 74. 8-chloro-5-methoxy-1-[bans-4-(trifluoromethi!)cyclohexyl]-5,6-dihydro-4H- [1,2,4]triazolo[4,3-a][1]benzazepine, 75. (frcins)-8-(8l-chloro-4, / -A6'H-spiro[1,3-dioxolane-2,5'-[1.2;4]triazolo[4,3a][1]benzazepin] “1'yl)-3-methyl-1-oxa-3-azaspiro[4,5]decan“2-one, 76. A / -{(5S)-8“Chloro-1-[irans-4-(pyridin-2-yloxy)cyclohexyl]-5,6-dihydro-4H“ [1:2:4]triazolo[4, 3-a][1]benzazepin-5-yl}-A / -methylmethanesulfonamide, 77. (5S)-8-cioro-N-ethyl-1-[irans-4-(pindin-2-yloxy)cyclohexyl]-5,6-dihldro-4H[1,2,4]triazolo[4,3 -a][1]benzazepin-5-amine( 78. (5S)-8-chloro- / V-methyl-1-[frans-4-(pyridin-2-yloxy)cyclohexyl]-5,6-dihydro-4H[1,2,4]tnazolo[4, 3-a][1]benzazepin-5-amine, 79. 8l-chloro-1'-[1-(pyrimidin-2-yl)azetidin-3-yl]-4' / 7:6, / - / -spiro[1,3-dioxolane-2,5'[ 1,2,4]triazolo[4,3-a][1]benzazepine], 80. / V-{(5S)-8-chloro-1-[frans-4-(pyridin-2-yloxy)cyclohexyl]-5,6-dihydro-4H- [1,2,4]tr iazolo[4,3-a][1 ]benzazepin-5-yl}-4-fluorobenzamide; 81. 8'-bΓomo-1,-[^ans-4-(tΓifluoromethyl)cyclohexyl]-4Ή,6Ή-spiro[1l3-dioxolane-2,5,[1,2,4]triazolo[4,3-a ][1]benzazepine], 82. 5-(propan-2-ylamino)-1-[Ma / 7s-4-(pyridin-2-yloxy)cyclohexyl]-5,6-dihydro-4H- [1,2,4]tr iazolo[4,3-a][1 ]benzazepin-8-carbonitrile trifluoroacetate, 83. (5S)-8-chloro-W-(4-f!uorobenzyl)-1-[trans-4-(pindin-2-iioxy)cyclohexyl]-5,6-dihydro-4H[1:2;4 ]tnazolo[4:3-a][1]benzazepin-5-amine: 84. 1,-[trans-4-(trifluoromethyl)cyciohexyl]-4>H,6' / 7-spiro[1,3-dioxolane-2,5'“ [1,2,4]triazolo[4,3-a][1]benzazepine]-8:-carbonitrile, IF-2019-03 566964-APN-ANP#INPI Page 49 of 272 85. [kans-4-(8'-bromo-4,H,6' / 7-spiro[1,3-dioxolane-2.5,-[1,2,4]triazolo[4,3- a][1]benzazepin]-T-yl)cyclohexyl](pipendin-1-yl)methanone, 86. methyl irans-4-(8-bromo-5-oxo-5,6-dihydro-4H-[1,2,4]triazolo[4,3-a][1]benzazepin-1yl)cyclohexanecarboxylate, 87. 8-bromo-1-[kaDS~4-(piperidin-1-ylcarbonyl)cyclohexyl]-4H-[1:2.4]triazolo[4:3a][1]benzazepin-5(6H)-one, 88. 8'-chloro-14frans-4-(trif luoromethyl) hexy Ι]-4Ή cycle, 6'H-spiro[ 1,3-d ioxane-2,5'- [1,2,4]triazolo[4,3-a][1]benzazepine], 89. T-[irans-4-(piperidin-1-ylcarbonyl)cyclohexyl]-4' / 7J6'H-spiro[1,3-dioxolane-2,5'[1,2,4]triazolo[4,3 -a][1]benzazepin]-8'-carbonitol, 90. 8'“Chloro-1'-[trans-4-(pyridin-2-yloxy)cyclohexyl]-4' / - / ,6' / - / -spiro[1,3-dioxane-2,5'“ [1,2.4]triazolo[4,3-a][1]benzazepine]; 91. S-bromo-l^rans^-itrifluoromethiOcyclohexylHH-Il^^triazoloKjS-aniJbenzazepin5(6H)-one, 92. [trans-4-(8-bromo-5-hydroxy-5,6-dihydro-4H-[1,2,4]triazolo[4,3-a][1]benzazepin-1yl)cyclohexyl](piperidin -1-yl)methanone, 93. 8-bromo-1-[trans-4-(trifluoromethyl)cyclohexyl]-5,6-dihydro-4H-[1,2,4]triazolo[4,3 a] [ 1 ]benzazepin-5-ol, 94. 1 '-(1,4'-bipi perid in-1 '-yl)-8'-chloro-4, / 7,6, / - / -spiro[1,3-dioxolane-2,541,2,4 ]tnazolo[4,3- a][1]benzazepine], 95. tert-butyl [1-(1,4,-bipiperidin-T-yl)-8-chloro-5,6-dihydro-4 / -7-[1,2,4]triazolo[4,3a] [ 1 ]benzazepin-5-yl]carbamate, 96. 8,-fluoro-r-[trans-4-(pyridin-2-yloxy)cyclohexyl]-4' / - / ,6' / 7-spiro[1J3-dioxolane-2)5'[1,2, 4]triazolo[4,3-a][1]benzazepine], 97. (5S)-8-chloro- / \ / -(4-fluorobenzyl)- / \ / -methyl-1-[frans-4-(pindin-2-yloxy)cyclohexyl]-5,6dihydro-4 / - / -[1,2,4]iriazolo[4;3-a][1]benzazepin-5-amine, 98. / V-{(5S)-8-chloro-1-[trans-4-(pyridin-2-yloxy)cyclohexyl]-5,6-dihydro-4 / 7[1,2,4]triazolo[4 ,3-a][1]benzazepin-5-yl}prop-2-enamide, 99. (5 / ?)-8-chloro- / V-ethyl-1 -[trans-4-(pyridin-2-yloxy)cyclohexyl]-5,6-dihydro-4 / - / [1,2,4 ]triazolo[4,3-a][1]benzazepin-5-amine, 100. (5R)-8-chloro- / V-methyl-1-[frans-4-(pyridin-2-yloxy)cyclohexyl]-5,6-dihydro-4H- [1,2,4]triazolo[4,3-a][1]benzazepin-5-amine, 101. (5R)-8-chloro- / V,A / -dimethyl-1 -[frans-4-(pyridin-2-yloxy)cyclohexyl]-5,6-dihydro-4H- [1,2,4]triazolo[4,3-a][1]benzazepin-5-amine, IF-2019-03 566964-APN-ANP#INPI Page 50 of 272 102. 1-[trans-4-(pyridin-2-yloxy)cyclohexyl]-4H-[1,2,4]triazolo[4,3-a][1]benzazepin-5(6H)-one, 103. (5S)-8-chloro-5-methoxy-1 -[fra / ?s-4-(pyridIn-2-yloxy)cyclohexyl]-5,6-dihydro-4H- [1,2,4]tnazolo[4,3-a][1 jbenzazepine, 104. (5R)-8-chloro-5-methoxy-1-[frans-4-(pyridin-2-yloxy)cyclohexyl]-5,6-dihydro-4H- [1,2,4]triazolo[4,3-a][1]benzazepine, 105. 8-chloro-5-(propan-2-yloxy)-1 -[fra / 7S-4-(pyridin-2-yloxy)cyclohexyl]-5,6-dihydro-4H- [1,2,4]triazolo[4,3-a][1]benzazepine, 106. S'-chloro-IHfrans^-ipyridin^-yloxyjcyclohexin-^H.e'H-spiroIl.S-dioxepane-a.S'[1,2,4]triazolo[4,3-a][1] benzazepine], 107. 1-[frans-4-(pyridin-2-yloxy)cyclohexyl]-5,6-dihydro-4 / - / -[1,2,4]triazolo[4,3a][1]benzazepin-5- ol, 108. [irans-4-(8'-cioro-4' / - / ,6'H-spiro[1,3-dioxolane-2,5I-[1,2,4]triazolo[4,3- a][1 ]benzazepin]-1 '-yl)cyclohexyl](morpholin-4-yl)methanone 109. 5-methoxy-1 -[frans-4-(pyridin-2-yloxy)cyclohexyl]-5,6-dihydro-4H-[1,2,4]triazolo[4,3a][1]benzazepine, 110. 8-fluoro-1-[frans-4-(pyridin-2-iIoxy)cyclohexyl]-4H-[1,2,4]triazolo[4,3-a][1]benzazepin5(6H)-one; 111. 8-fIuoro-1 -[trans-4-(pyridin-2-yloxy)cyclohexyl]-5,6-dihydro-4 / - / -[ 1,2,4]triazolo[4,3a][1] benzazepin-5-ol, 112. tert-butyl {8-chloro-1-[^a / 7S-4-(morpholin-4-yl)cyclohexyl]-5;6-dihydro-4 / - / -[1;2!4]triazolo[ 4,3a][1 ]benzazepin-5-yl}carbamate, 113. 8-chloro-1 -[Aa / ^s^amorpholine-é-iDcicIohexylj-S^-dihydro-éH-fl,2,4]tnazolo[4,3a][1]benzazepin-5-amine, 114. 8-chloro-1-[frans-4-(morpholin-4-yl)cyclohexyl]- / V-(propan-2-yl)-5,6-dihydro-4 / - / - [1,2,4]triazolo[4,3-a][1]benzazepin-5-amine, 115. (5r,8r)-8-(8'-chloro-4' / - / ,6' / 7-spiro[1,3-dioxolane-2,5,-[1,2,4]triazolo[4 ,3- a][1 ]benzazepin]-1 '-yl)-2-(propan-2-ii)-2-azaspiro[4,5]decan-1 -one, 116. (5r,8r)-8-(8-chloro-5-hydroxy-5,6-dihydro-4H-[1,2,4]triazolo[4,3-a][1]benzazepin-1-yl )-2(propan-2-yl)-2-azaspiro[4,5]decan-1-one, 117. (5S)-8-chloro-1 -[ira / 7S-4-(pyridin-2-yloxy)cyclohexyl]-5-(pyrrolidin-1 -yl)-5,6-dihydro-4H[1,2 ,4]triazolo[4,3-a][1]benzazepine, 118. / V-{(5S)-8-chloro-1-[ira / 7S-4-(pyridin-2-yloxy)cyclohexyl]-5,6-dihydro-4H[1;2:4]tnazolo[4 ,3-a][1]benzazepin-5-yl}-2,2-dimethylpropanamide, IF-2019-03 566964-APN-ANP#INPI Page 51 of 272 119. A / -{(5 S)-8-chloro-1 -[íra / 7S~4-(pyrid i n-2-i I oxy) cyclohex i l]-5,6-d i h id γο-4 / - / ~ [1,2,4]triazolo[4,3-a][1]benzazepin-5-yl}cyclopropanecarboxamide, 120. / V-{(5S)-8-chloro-1-[trans-4-(pyridin-2-yloxy)cyclohexyl]-5,6-dihydro-4H- [1,2,4]triazolo[4,3-a][1 ]benzazepin-5-yl}-2-methylpropanamide, 121. A / -{(5S)-8-chloro-1-[hans-4-(pyridin-2-yloxy)cyclohexyl]-5;6-dihydro-4H- [1,2,4]triazolo[4,3-a][1]benzazepin-5yl}cyc!obutanecarboxamide, 122. (5S)-8-chloro-5-(morpholin-4-i[)-1 -[frans-4-(pyridin-2-yloxy)cyclohexyl]-5,6-dihydro-4H[1,2, 4]triazolo[4,3-a][1]benzazepine, 123. / V-{(5R)-8-chloro-1 -[trans-4-(pyridin-2-yloxy)cyc!ohexll]-5,6-dihydro-4 / 7[1,2,4]triazo [o[4,3-a][1]benzazepin-5-yl}-2,2-dimethylprOpanamlda, 124. N-{(5R)-8-chloro-1-[trans-4-(pyridin-2-yloxy)cyclohexyl]-5,6-dihydro-4H- [1,2,4]triazolo[4,3-a][1]benzazepin-5-yl}-2-methylpropannide, 125. A / -{(5 / ?)-8-chloro-1-[irans-4-(pyridin-2-yloxy)cyclohexyl]-5,6-dihydro-4 / 7- [1,2,4]triazolo[4,3-a][1]benzazepin-5-yl}cyclobutanecarboxannide, 126. W-{(5R)-8-chloro-1-[irans-4-(pyrldin-2-yloxy)cyclohexyl]-5,6-dihydro-4H[I^Xltnazoium^S-aHIjbenzazepin-S-HJcyclopropanecarboxamide, 127. (5S)-8-c[oro-5-(piperidin-1 -i!)-1 -[irans-4-(pyridin-2-yloxy)cyclohexyl]-5!6-dihydro-4H- [1,2,4]triazolo[4,3-a][1]benzazepine, 128. (5S)- / V-(butan-2-yl)-8-chloro-1 -[trans-4-(pyridin-2-yloxy)cyclohexyl]-5,6-dihydro-4H- [1,2,4]triazo!o[4:3-a][1]benzazepin-5-amine, 129. (5s;8s)-8-(8'-chloro-4' / 7.6'H-spiro[1,3-dioxolane-2,5'-[1,2,4]triazolo[4,3a][ 1 ]benzazepin]-1 '-yl)-2-(propan-2-yl)-2-azaspiro[4,5]decan-1 -one, 130. 8-chloro-5-methoxy-1 -[frans-4-(morpholin-4-ll)cyclohexyl]-5,6-dihydro-4H- [1,2,4]triazolo[4,3-a][1]benzazepinaf 131. 8-cyoro-5-ethoxy-1-[írans-4-(pyridin-2-yloxy)cyclohexyl]-5,6-dihydro-4H-[1,2,4]triazolo[4, 3a][1]benzazepine, 132. (5R)-8-chloro-5-methoxy-1-[frans-4-(tnf!uoromethyl)cyclohexyl]-5,6-dihydrO“4H- [1,2,4]triazolo[4,3-a][1]benzazepinat 133. (5S)-8-chloro-5-methoxy-1 -[frans-4-(trifluoromethyl)cic]ohexy[]-5,6-dihydro-4H- [1,2,4]triazolo[4,3-a][1 Jbenzazepine, 134. 8-fluoro-5-methoxy-1-[trar?s-4-(pyridin“2-i[oxy)cyclohexyl]-5,6-dihydro-4H- [1,2,4]triazolo[4,3-a][1]benzazepine, 135. 8-chloro-A / -(propan-2-yl)-1 -[1 -(pyridin-2-yl)piperidin-4-yl]-5,6-dihydro-4 / - / - [1,2,4]triazolo[4,3-a][1]benzazepin-5-amine, IF-2019-03 566964-APN-ANP#INPI Page 52 of 272 136. 2-({8-chloro-1 -[frans-4-(pyridin-2-yloxy)cyclohexyl]-5,6-dihydro-4H-[1,2,4]triazolo[4,3a][1 ]benzazepin-5-yl}oxy)ethanol, 137. (5S)-8-chloro- / V, / V-dietiI-1 -[irans-4-(pyridin-2-yloxy)cyc!ohexyl]-5,6-dihydro-4H[1,2,4 ]triazolo[4,3-a][1]benzazepin-5-amine, 138. 8-chloro- / V-methyl-N-(propan-2-yl)-1 -[ira / 7S-4-(pyridin-2-yloxy)cyclohexyl]-5,6-dihydro-4H[1, 2,4]triazolo[4,3-a][1]benzazepin-5-amine, 139. fer-butyl {8-chloro-1-[4-(3-chloropyridin-2-yl)piperazin-1-yl]-5,6-dihydro-4H- [1,2,4]triazolo[4,3-a][1]benzazepin-5-yl}carbamate, 140. fer-butyl 4-(8-chloro-5-methoxy-5,6-dihydro-4H-[1,2,4]triazolo[4,3-a](1]benzazepin-1- i I) piperid ina-1 -carboxy lato, 141. A / -{(5R)-8-chloro-1 -[frans-4-(pyridin-2-yloxy)cyclohexyl]-5,6-dihydro-4 / - / - [1,2;4]triazolo[4,3-a][1]benzazepin-5-yl}-D-valinamide, 142. fer-butyl {1 -[frans-4-(pyridin-2-yloxy)cyclohexyl]-5,6-dihydro-4 / - / -[1,2,4]triazolo[4,3a][1] benzazepin-5-yl}carbamate, 143. fer-butyl {8-fluoro-1-[frans-4-(pyridin-2-yloxy)cyclohexyl]-5,6-dihydro-4H- [1,2,4]triazolo[4,3-a][1 ]benzazepin-5-yl}carbamate, 144, 1-[frans-4-(pyridin-2-yloxy)cyclohexyl]-5,6-dihydro-4H-[1,2,4]triazolo[4,3a][1]benzazepin-5-amine, 145. 8-fluoro-1-[frans-4-(pyridin-2-yloxy)cyclohexyl]-5,6-dihydro-4 / - / -[1,2,4]triazolo[4,3a][1 ] benzazepin-5-amine, 146. 8-fluoro- / V-(propan-2-yl)-1Etrans-4-(pyridin-2-yloxy)cyclohexyl]-5,6-dihydrO4H- [1,2,4]triazolo[4,3-a][1]benzazepin-5-amine, 147. 8-fluoro- / V, / V-dimethyl-1-[frans-4-(pyridin-2-yloxy)cyclohexyl]-5,6-dihydro-4 / 7- [1,2,4]triazolo[4,3-a][1]benzazepin-5-amine, 148. Λ / ,ΛΛ-dimethyl-l -[írans-4-(pyridin-2-íloxy)cyclohexíl]-5,6-dihydro-4H-[1,2,4]triazolo[4,3a] (1 Jbenzazepin-5-amine, 149. 8'-fluoro-T-[írans-4-(trifluoΓometίl)cyclohexΐl]-4Ή,6' / 7-spiro[1,3-dioxolane-2,5,[1,2,4]triazolo[ 4,3-a][1]benzazepine], 150. / V-(propan-2-yl)-1 -[trans-4-(pyridin-2-ylox!)cyclohexyl]-5,6-dihydro-4H-(1,2,4]triazolo[4, 3a][1]benzazepin-5-amine, 151. / V-{(5S)-8-chloro-1-[frans-4-(pyridin-2-yloxy)cyclohexyl]-5,6-dihydro-4H- [1,2,4]triazolo[4,3-a][1]benzazepin-5-yl}tetrahydro-2H-pyran-4-carboxamide, 152. A / -{(5S)-8-chloro-1-[irans-4-(pyridin-2-yloxy)cyclohexyl]-5,6-dihydro-4H- [1,2,4]triazolo[4,3-a][1 ]benzazepin-5-yl}-2-methylbutanamide, IF-2019-03 566964-APN-ANP#INPI Page 53 of 272 153. Λ / -{(5S)-8-chloro-1 -[trans-4-(pyridin-2-yloxyJcyclohexylJ-5,6-dihydro-4H[1.2,4]tnazolo[4,3-a][1 ]benzazepin-5-yl}- / \ / 3:A / 3-dimethyl-p-alaninamide. 154. (5S)-8-chloro- / V-cyclopentyl-1~[Mans-4-(pyridin-2-yloxy)cyclohexyl]-5:6-dihydro-4H- [1,2,4]tr iazolo[4,3-a][1 ]benzazepin-5-amine, 155. 8'-chloro-1'-(1'H,3 / 7-spiro[2-benzofuran-1,4'-piperidin]-1'-yl)-4' / - / ,6,H-spiro [1,3dioxolane-2:5'-[L2:4]triazolo[4;3-a][1]benzazepine], 156. 8-chloro-1-(r / 7,3H-spiro[2-benzofuran-1;4'-piperidin]-r-yl)-4 / 7-[1;2,4]triazolo[4,3a ][1]benzazepin-5(6H)-one, 157. 8'-chloro-1 '-[4-(pyridin-2-yloxy)piperidin-1 -yl]-4' / - / J6i / - / -spiro[1,3-dioxolane-2,5'[ 1,2,4]triazolo[4,3-a][1]benzazepine], 158. A / -{(5S)-8-chloro-1-[irans-4-(pyridin-2-yloxy)cyclohexyl]-5;6-dihydro-4H[1:2;4]triazolo[4.3-a ][1]benzazepin-5-yl}-2;2-dimethylbutanamide, 159. A / -{(5S)-8-chloro-1 -[frans-4-(pyridin-2-yloxy)cyclohexyl]-5,6-dihydro-4 / - / [1l2;4]triazolo[4, 3-a][1]benzazepin-5-yl}-2-hydroxy-2-methylpropanamide, 160. (5S)-8-chloro-A / -ethyl-A / -methyl-1-[fra / 7s-4(pyridin-2-yloxy)cyclohexyl]-5,6-dihydro-4 / - / - [1,2,4]triazolo[4,3-a][1]benzazepin-5-amine. 161. (5S)-8-chloro- / V-(2-methylpropyl)-1 -[frans-4-(pindin-2-yloxy)cyclohexyl]-5,6-dihydro-4 / - / - [1,2,4]tr iazolo[4,3-a] [ 1 ]benzazepin-5-amine, 162. 8,-chloro-r-[Ma / 7S-4-(morpholin-4-yl)cyclohexyl]-4,H;6' / - / -spiro[1;3-dioxolane-2;5'[1 ,2,4]triazolo[4,3-a][1]benzazepine] hydrochloride, 163. 8-chloro- / V, / V-dimethyl-1 -(1 W,3H-spiro[2-benzofuran-1,4'-piperidin]-141)-5,6-dihydro4 / 7-[1, 2,4]triazolo[4,3-a][1]benzazepin-5-amine, 164. 8'-chloro-T-[4-(3-chloropyridin-2-yl)piperazin-1-yl]-4, / - / ,6lH-spiro[1,3-dioxolane-2,5'[1 ,2,4]triazolo[4,3-a][1]benzazepine], 165. (5S)-8-chlorO“ / V-(2,2-dimethylpropyl)-1-[irans-4-(pyridin-2-yloxy)cyclohexyl]-5,6-dihydro-4 / - / [1 ,2,4]triazolo[4,3-a][1 ]benzazepin-5-amine, 166. [irans-4-(8-chloro-5-methoxy-5,6-dihydro-4H-[1,2,4]triazolo[4,3-a][1]benzazepin-1“yl)cyclohexyl] (4-methylpiperazin-1-yl)methanone, 167. (5R)-8-chloro-5-(morpholin-4-yl)-1-[frans-4-(pyridin-2-yloxy)cyclohexyl]-5,6-dihydro-4H[1,2,4 ]triazolo[4,3-a][1]benzazepine, 168. A / -{(5R)-8-chloro-1-[Mans-4-(pyridin-2-yloxy)cyclohexyl]-5,6-dihydro-4H[1,2,4]triazolo[4,3 -a][1]benzazepin-5-yl}acetamide, 169. A / -{(5R)-8-chloro-1-[irans-4-(pyridin-2-yloxy)cyclohexyl]-5,6-dihydro-4H[1,2,4]triazolo[4,3 -a][1]benzazepin-5-yl}-2-hydroxy-2-methylpropanamide, IF-2019-03 566964-APN-ANP#INPI Page 54 of 272 170. 8-chloro-5-methoxy-1 -[ 1 -(tetrahydΓ0“2Λ7~ρίraη-4-iI)piperidin-4-yl]-5,6-dihydro-4H- [1,2,4]triazolo[4,3-a][1 Jbenzazepine, 171. 8'-clo ro-1 '-[4-( pi rid i n-2-¡ I) piperazi η-1 -i l]-4' Λ / , 6' / -7-spira ro [ 1,3 -dioxolane-2,5'- [1,2,4Jtriazolo[4,3-aJ[1 Jbenzazepine], 172. 8-chloro-1-(rH,3H-spiro[2-benzofuran-1 A'-piperidinJ-l'-iO-S.e-dihydro^H- [1,24Jtriazolo[4;3-a][1Jbenzazepin-5-ol, 173. 8-chloro-1 -[4-(3-chloropyridin-2-iI)piperidin-1 -yl]-5,6-dihydγο-4Λ7-[1 ,2,4]triazolo[4,3a][ 1 ]benzazepin-5-ol, 174. (5R)-8-chloro-1 -[¿rans-4-(pyridi n-2-yl oxy i )cyclohexyl]-5-(pyrrole id i n-1 -i l)-5,6 -d i h idro-4H- [1,2,4]tr iazolo[4,3-a][1 Jbenzazepine, 175. 8-chloro-5-methoxy-1-{1-[(3S)-tetrahydrofuran-3-yl]piperidin-4-iI}-5,6-dihydro-4H- [1,2,4]triazolo[4,3-aJ[1 Jbenzazepine, 176. (5Rj-8-fluoro-5-methoxM -[Ma / ?s-4-(pyridin-2-yloxy)cyclohexyl]-5;6-dihydro-4H- [1,2,4]triazolo[4,3-a][1 Jbenzazepine, 177. (5S)-8-fluoro-5-methoxy-1 -[f / 'ans-4-(pyridin-2-yloxy)cyclohexyl]-5;6-dihydro-4H- [1,2,4Jtriazolo[4,3-aJ[1 Jbenzazepine, 178. 8-chloro-5-methoxy-1 -{1 -[(3F?)-tetrahydrofuran-3-yl]piperidin-4-yl}-5,6-dihydro-4H- [1,2,4]triazolo[4,3-a][1 Jbenzazepine, 179. A / -{(5R)-8-chloro-1-[írans-4-(pyridin-2-yloxy)cyclohexyl]-5,6-dihydro-4H- [1,2J4]triazoio[4,3-a][1]benzazepin-5-yl}- / \ / 3, / \ / 3-dimethyl-p-alaninamide, 180. A / “{(5R)-8-chloro-1 -[írans-4-(pyridin-2-yloxy)cyclohexylJ-5,6-dihydro-4H[1,2,4Jtriazolo[4,3-a] [1]benzazepin-5-yl}tetrahydro-2H-pyran-4-carboxamide, 181. 8-chloro-1 -[4-(pyridin-2-yloxy)piperidin-1-yl]-5,6-dihydro-4H-[ 1,2,4]triazolo[4,3a][1]benzazepin -5-ol, 182. 8-chloro-5-methoxy-1-[frans-4-(4-methylpiperazin-1-yl)cyclohexyl]-5,6-dihydro-4H- [1,2,4]triazolo[4,3-aJ[1 Jbenzazepine, 183. 8-chloro-5-methoxy-1-[c / s-4-(4-methylpiperazin-1-yl)cyclohexyl]-5.6-dihydro-4H- [1,2,4]triazolo[4,3-a][1 Jbenzazepine, 184. 8-chloro-5-methoxy¡-1 -[ 1 -(pyrid i n-3-i I metí I) pyrrol id in-3-yl]-5,6-d i hydro-4 H- [1,2,4Jt riazolo [4,3-a] [1 Jbenzazepine, 185. 8-chloro-5-methoxy-1 -[ 1 -(pyridin-2-ΐΙmethyl)pyrrolidin-3“yl]-5,6~dihydΓΟ-4Η- [1,2,4]triazolo[4,3-a][1 Jbenzazepine, 186. / V-{(5R)-8-chloro-1¿tranS4-(pyridin-2-lloxy)cyclohexyl]-5,6-dihydro-4H[1;2:4Jtriazolo[4:3-a] [1]benzazepin-5-yl}-2-cyanoacetamide, IF-2019-03 566964-APN-ANP#INPI Page 55 of 272 187. [3-(8-chloro-5-methoxy-5;6-dihydro-4 / - / -[1;2,4]tnazolo[4;3-a][1]benzazepin-1-yl)pyrrolidine - -yl](pyridin-3-yl)methanone, 188. 8'-chloro-1H1-[(3R)-tetrahydrofuran-3-yl]piperidin-4-yl}-4'H,6' / - / -spiro(1,3-dioxolane- 2,5-(1,2,4Jtriazolo[4,3-aJ[1 Jbenzazepine], 189. [3-(8-chloro-5-methoxy-5,6-dihydro-4H-(1,2,4]tnazolo[4,3-a](1]benzazepin-1-yl)pyrrolidin- -yl](pyridin-2-yl)methanone, 190. hans-4-(8'-chloro-4' / - / ,6' / 7-spiro[L3-dioxolane-2!5'-[1,2,4]triazolo[4,3a][1] benzazepin]-1'-yl)- / V,N-dirnetylcytohexanamine, 191. 8-cioro-5-methoxy-1 -(1 W,3H-spiro[2-benzofuran-1,4'-piperidin]-1 -yl)-5,6-dihydro-4H[1,2,4 ]triazolo(4,3-a][1 Jbenzazepine, 192. 8-chloro-1 -[4-(3-chloropyridin-2-iI)piperazin-1 -yl]-5-methoxy-5,6-dihydro-4H- [1,2,4]triazolo[4,3-a](1 Jbenzazepine, 193. A / -[frans-4-(8,-chloro-4'H,6'H-spiro[1,3-dioxolane-2,5'-[1,2,4]triazolo(4,3a) [1]benzazepin]-T-yl)cyclohexyl]pyridin-2-amine 194. / V-{(5R)-8-chloro-1-[irans-4-(pyridin-2-yloxy)cyclohexylJ-5,6-dihydro-4 / 7- [1,2,4]triazolo[4,3-a][1]benzazepin-5-yl}- / V, / \ / -dimethylethane-1,2-diamine, 195. 8-chloro-1 -[fra / 7S-4-(pyridin-2-iioxy)cyclohexylJ-5,6-dihydro-4 / - / -[1,2,4]triazolo[4,3a][1 ]benzazepin-5-yl acetate, 196. 2-({(5R)-8-cioro-1 -(frans-4-(pyridin-2-yloxy)cyclohexyl]-5,6-dihydro-4H- [1,2,4]tr iazo!o[4,3-aJ[1 ]benzazepin-5-yl}amino)ethanol, 197. 8-chloro-5-methoxy-1 -[4-(pyridin-2-yloxy)piperidin-1 -yl]-5,6-dihydro-4H-(1,2,4]triazolo(4,3a) [1]benzazepine, 198. 8'-chloro-r-(tra / 7S-4-methox(-4-methylcyclohexyl)-4' / - / ,6' / - / -spiro[1,3-dioxolane-2,51- [1,2,4]triazoium[4,3-a][1 Jbenzazepine], 199. (5S)-8-chloro-A / -(cyclopropylmethyl)-1-(irans-4-(pyridin-2-yloxy)cyclohexyl]-5,6-dihydro-4H-(1,2,4]triazolo (4,3-a][1]benzazepin-5-amine, 200. / V-{(5S)-8-chloro-1-[frans-4-(pindin-2-yloxy)cyclohexyl]-5,6-dihydro-4 / 7- [1,2,4]tr iazolo[4,3-a][1 ]benzazepin-5-yl}-1 -methylpiperidine-4-carboxamide, 201. A / -{(5S)-8-chloro-1-[frans-4-(pyridin-2-i!oxy)cyclohexyl]-5,6-dihydro-4 / - / - [1,2,4]triazolo[4,3-a][1]benzazepin-5-yl}-2,2,2-trifluoroacetamide, 202. 8-chloro-5-(2-methoxyethoxy)-1-[irans-4-(pyridin-2-yloxy)cyclohexyl]-5,6-dihydro-4H- [1,2,4]triazolo(4,3-a][1 Jbenzazepine, 203. 8-chloro-1-(4-methoxy-4-methylcyclohexy!)- / \ / -(propan-2-yl)-5,6“dihydro-4H- [1,2,4]triazolo[4,3-aJ[1]benzazepin-5-amine, IF-2019-03 566964-APN-ANP#INPI Page 56 of 272 204. 8'-chloroM'^Aa / ?s-4-methoxy-4-methylcyclohexyl)-4, / 7,6' / 7-spiro[1,3-dioxane-2,5'[1,2,4 ]triazolo[4,3-a][1]benzazepine], 205. 8'-chloro-1 '-(c / s-4-nnethoxy-4-methylcyclohexyl)-4' / 7.6l / 7-spiro[1,3“dioxane-2,5'[1,2, 4]triazolo[4,3-a][1]benzazepine], 206. 8-chloro-5-fluoro-1-[Aans-4-(pyridin-2-yloxy)cyclohexyl]-5,6-dihydro-4H- [1,2,4]triazolo[4,3-a][1]benzazepine, 207. 8-chloro-5-[2-(methylsulfonyl)ethoxy]-1 -[¿rans-4-(pyridin-2-yloxy)cyclohexyl]“5,6-dihydro-4H- [1,2,4]triazolo[4,3-a][1]benzazepine, 208. 8-chloro- / V-hydroxy“ 1 -[irans-4-(pyridin-2-yloxy)cyclohexyl]-4 / 7-[1,2,4]triazolo[4,3- a][1 ]benzazepin-5(6 / 7)-imine, 209. (5S)-8-chloro- / V-methyl- / \ / -(prop-2-yn-1-yl)-1-[irans-4-(pyridin-2-yloxy)cyclohexyl]-5, 6- d ih id ro-4 / 7-[ 1,2,4]triazolo[4,3-a][1 ]benzazepin-5-amine, 210. A / -{(5S)-8-chloro-1 -[frans-4-(pyridin-2-yloxy)cyclohexyl]-5,6-dihydro-4H- [1,2,4]triazolo[4,3-a][1]benzazepin-5-yl}-3,3-difluorocyclobutanecarboxamide, 211. 8-chloro-5-(prop-2-yn-1-yloxy)“1-[frans-4-(pyridin-2-yloxy)cyclohexyl]-5,6-dihydro-4H [1 ^AJtriazoloKS-ajiljbenzazepine, 212. 8-chloro-1“[trans-4-(pyridin-2-yloxy)cyclohexyl]-5,6dihydro-4 / 7-[1,2,4]triazolo[4,3a][1 ]benzazepin-5 -yl 4,4-difluorociciohexanecarboxylate, 213. 8-chloro-1 -[irans-4-(pyridin-2-yloxy)cyclohexyl]-5,6-dihydro-4 / - / -[ 1,2,4]triazolo[4,3a][1] benzazepin-5-yl 3,3-difluorocyclobutanecarboxylate, 214. / V-{(5S)-8-chloro-1-[frans-4-(pyridin-2-yloxy)cyclohexyl]-5,6-dihydro-4H- [1,2,4]triazolo[4,3-a][1]benzazepin-5-yl}-4,4-difluorocyclohexanecarboxamide, 215. 8-chloro-1 [irans-4-(pyridin-2-yloxy)cyclohexyl]-5,6-dihydro-4 / - / -[ 1,2,4]triazolo[4,3a][ 1 ]benzazepin -5“yl cyanoacetate, 216. 8-chloro-1 -[irans-4-(pyridin-2-yloxy)cyclohexii]-5,6-dihydro-4H-[1,2,4]triazolo[4,3~ a][1]benzazepin -5-yl W. / V-dimethylglycinate, 217. / V-{(5R)-8-chloro-1-[frans-4“(pyridin-2-yloxy)cyclohexii]-5,6-dihydro-4H[1,2:4]triazolo[4,3 -a][1]benzazepin-5-yl}-2:2;2-trifluoroacetamide. 218. 1 -[c / s-4-(8-chloro-5methoxy-5,6-dihydro-4 / - / -[1,2,4]triazolo[4;3-a][1 ]benzazepin-1 il)cyclohexyl]pyrrolidin-2-one, 219. l-fira / JS^-ie-chloro-S-’methoxy-S^-dihydrcM / - / ·]·! ,2,4]triazoium[4,3-a][1]benzazepin-1 yl)cyclohexyl]pyrrolidin-2-one, 220. / \ / -{(5R)-8-chloro-1-[trans-4“(pyridin“2-yloxy)cyclohexyl]-5,6-dihydrO“4H[1,2,4]triazolo[4, 3-a][1]benzazepin-5-yl}-3,3-difluorocyclobutanecarboxamide, IF-2019-03 566964-APN-ANP#INPI Page 57-of 272 221. A / -{(5R)-8-chloro-1-[írans-4-(pyridin-2-yloxy)cyclohexy[]-5,6-dihydro-4H- [1,2,4]triazolo[4,3-a][1]benzazepin-5-yl}-4,4-difluorocyclohexanecarboxamide, 222. 8-chloro-5-methoxy-1-[c / s-4-methoxy-4-(trifluoromethyl)cyclohexyl]-5,6-dihydro-4H- [1,2,4]triazolo[4;3-a][1]benzazepine, 223. 8-chloro-5-methoxy-1-[ira / 7S-4-methoxy-4-(trifluoromethyl)cyclohexyl]-5:6-dihydro-4H- [1,2,4]triazolo[4,3-a][1]benzazepine, 224. (5S)-8-chloro-1-[frans-4-(pfridin-2-yloxy)cyclohexyl]“A / -(2,2,2-tnfluoroethyl)-5,6-dihydrO“4 / - / [1,2t4]triazolo[4,3-a][1]benzazepin-5~amine, 225. A / -{(5S)-8-chloro-1-[irans-4-(pyridin-2“yloxy)cyclohexii]-5,6-dihydro-4H[1,2,4]triazolo[4,3 -a][1]benzazepin-5-ii)-3-methyloxetane-3-carboxamide, 226. / V-{(5F?)-8-chloro-1 -[ / rar?s-4-(pyridin-2-yloxy)cyclohexyl]-5>6-dihydro-4 / 7- [1,2,4]triazolo[4,3-a][1]benzazepin-5-yl}-3-methyloxetane-3-carboxamide, 227. AaA?s-4-(8'-chloro-4'H,6' / - / -spiro[1 ^-dioxolane^^'-fl ,2,4]triazolo[4,3- a][1 ]benzazepin]-1 '-yl)- / V-(4-methoxybenzyl)cyclohexanamine, 228. tert-butyl [2-({(5R)-8-chloro-1-[frans-4-(pyridin-2-yloxy)cyclohexyl]-5,6-dihydro-4H- [1,2,4]triazolo[4,3-a][1]benzazepin-5~yl}amino)ethyl]carbamate, 229. 8'-chloro-T-(frans-4-ethoxy-4-ethylcyclohexyl)-4' / 7,6' / 7-spiro[1,3-dioxolane-2,5'“ [1,2,4]triazolo[4t3-a][1]benzazepine], 230. frans-4-(8,“Chloro-4'H,6' / 7-spiro[1,3-dioxolane-2;5'-[1,2,4]triazolo[4,3a][1] benzazepin]-r-yl)-A / -(4-methoxybenzyl)- / V-methylcyclohexanamine, 231. 8'-chloro-1 *-[ 1 -(pi ridi n-3-yl metí I) pyrrol idi n-3-i l]-4' / 7,6' / 7-spiro[ 1,3- dioxolane-2,5'[1]2,4]triazolo[4,3-a][1]benzazepine], 232. 8“ChlorO-5-methoxy-1 -[4-(pyridin-2~yl)piperazin-1 -i!]-5,6-dihydro-4H-[1,2,4]triazolo[4,3a ][1]benzazepine, 233. 8-chloro-1-(trans-4-ethyl-4-methoxycyclohexyl)-A / , / V-dimethyl-5,6-dihydro-4H- [1,2,4]triazolo[4,3-a][1]benzazepin-5-amine, 234. 8-chloro-1-(frans-4-ethoxy-4-methylcyclohexyl)-A / ,A / -dimethyl-5,6-dihydrO-4H- [1,2,4]triazolo[4,3--a][1]benzazepin-5-amine, 235. 8'-chloro-1 '-[irans^-methoxy^trifluorometiDciciohexiO^'H^’H-spiroyl ,3-dioxolane- 2,5'-[1,2,4]triazolo[4,3-a][1]benzazepine], 236. 8,-chloro-T-[c / s-4-methoxy-4-(trifluoromethyl)cyclohexyl]-4' / - / :6'H-spiro[L3-dioxolane-2,5'[1,2 ,4]triazolo[4,3-a][1lbenzazepine], 237. S'-chloro-IXírans^-ethoxy^-methylcicIohexiQ^'H^'H-spiroíTS-dioxolane^S'- [1,2,4]triazolo[4,3-a][1]benzazepine], IF-2019-03 566964-APN-ANP#INPI Page 58 of 272 238. 8'-chloro~1 '-(7ra / 7S-4-ethoxy-4-propylcyclohexíl)-4, / -7,6' / -7-spiro[1,3-dioxolane-2, 5'- [1,2,4]triazolo(4,3-a][1 Jbenzazepine], 239. 8'-chloro-1'-[ 1 -(pyrid η-2-ylmeti I) pyrrol id i n-3-yl]“4'H, 6' / - / -spiro( 1,3- dioxolane-2,5'- [1,2,4]triazolo[4,3-a][1]benzazepine], 240. 8'-chloro-r-(c / s-4-ethyl-4-methoxy¡cyclohex¡l)~4',H,6l / 7-spiro[1,3-dioxolane-2,5'- [1,2,4]triazolo[4,3-a][1 Jbenzazepine], 241. 8'-chloro-r-( / rans-4-ethyl-4-methoxycyclohexyl)-4' / - / ,6'H-spiro[1,3-dioxolane-2,5'[1,2,4 ]triazolo[4,3-a][1]benzazepine], 242. 8'-chloro-1 '-(ifa / ?s-4-methoxy-4-propylcyclohexyl)-4' / 7,6' / - / -spiro[1,3-dioxolane-2,5'[1 ,2,4]tnazolo[4,3-a][1 Jbenzazepine], 243. 8'-chloro-1'-(c / s-4-methoxy-4-propylcyclohexyl)-4' / 7,6'H-spiro[1,3-dioxolane-2,5'(1,2,4] triazolo[4,3-a](1 Jbenzazepine), 244. 8-chloro-1-(irans-4-ethoxy-4-ethylcyclohexyl)- / V-(propan-2-yl)-5,6-dihydro-4H- [1,2,4]triazolo[4,3-aH1]benzazepin-5-amine, 245. 8-chloro-1-(fra / ?s-4-ethoxy-4-ethylcyclohexyl)- / V,A / -dimethyl-5,6-dihydro-4H- [1,2,4]triazo[o[4,3-a](1)benzazepin-5-amine, 246. 8'-chloro-1 '-[(3R)-1 -(pyridin-2-ylmethyl)pyrrolidin-3-yl]-4' / - / ,6'H-spiro[1,3-dioxolane-2 ,5'[1,2,4]triazolo(4,3-a][1 Jbenzazepine], 247. 8-chloro-5-methoxy-1 -[(3F?)-1 -(pindln-3-ylmethiI)pyrrolidin-3-ii]-5,6-dihydro-4H- [1,2,4]tnazolo[4,3-a][1 Jbenzazepine, 248. 8-chloro-5~methoxy-1 -[(3R)-1 -(pyridi n-2-i I m etll) pyrrole idin-3-i l]-5,6-dihyd ro-4 H- [1,2,4]tnazolo[4,3-a](1)benzazepine, 249. 8'-chloro-1r~[(3S)-1 -(py ridi n-3~yl m eti I) pyrrole id in-3-yl]-4' / - / , 6' / - / -espi ro[ 1,3-dioxolane-2,5'“ [1,2,4]triazolo[4,3-a][1 Jbenzazepine], 250. 8'-chloro-1 '-[(3 A?)-1 -(pyrid i n-3-yl methyl I) pyrrole id i n-3-yl J-4' AY, 6' / -7- spi ro[ 1,3-dioxolane-2,5'- [1,2,4]triazolo(4,3-a][1 Jbenzazepine], 251. 8-chloro-5-methoxy-1 -[(3S)-1 -(py rid i n-3-ii metí I) pyrrol id i n-3-yl]-5,6-d ih hydro- 4H- [1,2,4]triazolo[4,3-a](1 Jbenzazepine, 252. 8'-chloro-r-[(3S)-1-(pyridin-2-ylmethyl)pyrrolidin-3-yl]-4, / 7,6'H-spiro[1,3-dioxolane-2 ,5'(1,2,4]triazolo(4,3-a][1]benzazepineJ and 253. 8-cyoro-5-methoxy-1 -[(3S)-1 -(pyridin-2-ylmethyl)pyrrolidin-3-yl]-5,6-dihydro-4H[1,2t4]triazolo[4,3 -a][1 Jbenzazepine. IF-2019-03 566964-APN-ANP#INPI Page 59 of 272 The present invention also relates to the synthesis of compounds of general formula (I). Accordingly, the compounds of formula (I) of the present invention can be prepared by one of the following methods: Provided that, in the compound of formula (I), R2 is hydrogen, R3 is -NHBoc or -OSi(CH3)2-f-butyl group and ring A is a cycloalkyl or a 4- to 7-membered saturated heterocycle containing 1 N , wherein ring A is bonded via the ring nitrogen to Y, compounds of general formula (I) of the present invention are prepared by reacting compounds of general formula (II) / —X / NH—NH2(ΒΔ_γ O(H) - wherein ring B and Y are as defined above for general formula (I) and ring A is a saturated 4- to 7-membered cycloalkyl or heterocycle containing 1 N, wherein ring A is bonded by ring nitrogen medium to Y - and compounds of general formula III - where R1 is as defined above for the general formula (I), R2 is hydrogen, R3 is -NHBoc or -OSi(CH3)2-f-butyl- group or the compounds of general formula (IV) (IV) - where R1 is as defined above for formula (I), R2 is hydrogen, R3 is -NHBoc or -OSi(CH3)2-bbutyl group. The procedure is illustrated in detail in Figure 1: IF-2019-03 566964-APN-ANP#INPI Page 60 of 272 Figure 1 In step a) of Figure 1 the acid hydrazide of general formula (II) is subjected to reaction with the benzazepine thione of general formula (III) or the methylsulfanylbenzazepine derivatives of general formula (IV), The reaction is carried out carried out preferably in a suitable solvent, at the boiling point of the solvent, with a required reaction time of 4 to 150 hours. Suitable solvents include xylene, n-butanol, 1,4dioxane. Preferred embodiments are, for example, the following: i) reaction of (II) and (III) in xylene at 140 °C for 20 to 150 hours, or i) reaction of (II) and (III) in n-butanol at 110 °C for 20 to 50 hours, or iii) reaction of (II) and (III) in 1,4-dioxane at 110 °C for 4 to 20 hours, or iv) reaction of (II) and (IV) in xylene in the presence of catalytic hydrogen chloride at 140°C for 4 to 20 hours, or v) reaction of (II) and (IV) in 1,4-dioxane in the presence of catalytic hydrogen chloride at 110 °C for 4 to 20 hours, The synthesis of the hydrazide of acids of general formula (II) can be carried out in various ways (Figure 2): (V) to) (Vli) Figure 2 In step a) of Figure 2, carboxylic acid esters of general formula (V) are reacted with hydrazine hydrate in a suitable alcohol at the boiling point of the solvent to obtain the acid hydrazide of general formula ( II) or, in step c), the carboxylic acids of general formula (VI) are subjected to reaction with terIF-2019-03 566964-APN-ANP#INPI 61 Page 61 of 272 butylcarbazate and the protecting group of the hydrazide derivative of the protected carboxylic acid obtained with general formula (Vil) is removed with acid (step d)). Preferred embodiments are, for example, the following: step a) methanol or ethanol, hydrazine hydrate, reflux temperature, 4 to 50 hours; step b) methanol, thionyl chloride, 0 to 25 °C, 4 to 24 hours; step c) tert-butyl carbazate, Λ / , / V-dimethylformamide, A / , / V-diisopropylethylamine, A / -(3dimethylaminopropyl)- / \ / -ethylcarbodiimide hydrochloride, 1-hydroxybenzotriazole hydrate, room temperature, 4 to 20 hours; step d) hydrogen chloride in ethyl acetate, room temperature, 4 to 20 hours. Esters of carboxylic acids of general formula (V) and carboxylic acids of general formula (VI) are commercially available or can be prepared according to the methods described in the Examples. Provided that, in the compounds of general formula (I), R1 is as defined above for general formula (I), R2 is hydrogen, R3 is -NHBoc, the benzazepine-thione derivatives of general formula (III) and the methylsulfanyl derivatives Benzazepine of general formula (IV) can be prepared according to the following procedures: The key intermediate benzazepine derived from general formula (XIII) can be prepared according to the following Method A (Figure 3) and Method B (Figure 4): Method A: Figure 3 In step a) of Figure 3, the amino group of the amino acid derivative of general formula (VIII), which is commercially available or can be prepared according to the methods described in the Examples, - where R1 is as defined above for IF-2019-03 566964-APN-ANP#INPI 62 Page 62 of 272 the general formula (I) - is protected by a fer-butoxycarbonyl protecting group, then with the obtained protected amino acid derivative (IX) - where R1 is as defined above for the general formula (I) - The Arndt-Eistert reaction (Arndt, F., Eistert, B. Chem Ber 1935, 68(1):200-208) is carried out in two steps: first, the acid chloride prepared in situ from the compound of general formula (IX) is subjected to reaction with diazomethane (steps b) and c)) to form the diazo compound of general formula (X) - where R1 is as defined above for general formula (I) - where in step d) is converted to the amino acid derivative of general formula (XI) in the presence of a silver salt - where R1 is as defined above for general formula (I). The nitro group of the latter is reduced (step e)) to obtain an amine of general formula (XII) - where R1 is as defined above for the general formula (I) -, which is closed in its ring by means of a reagent capable of forming an amide bond (step f)) to obtain the benzazepine derivative of general formula (XIII) - where R1 is as defined above for general formula (I). Preferred embodiments are, for example, the following: step a) dl-fer-butyl dicarbonate, 1,4-dioxane, aqueous sodium hydroxide solution, room temperature, 4 to 20 hours; step b) isobutyl chloroform, triethylamine, diethyl ether, -30 °C, 15 to 45 minutes; step c) solution in diazomethane ether, -30 °C to 0 °C, 1 to 3 hours; step d) piata benzoate, 1,4-dioxane, water, room temperature, 4 to 20 hours; step e) i) sodium borohydride, methanol, nickel chloride, room temperature, 4 to 20 hours, or i) hydrogenation in the presence of Pt / C catalyst, toluene, room temperature, 4 to 20 hours; stepf) / V,A / -dimethylformamide, A / ,A / -diisopropylethylamine, A / -(3-dimethylaminopropyl)- / Vethylcarbodiimide hydrochloride, 1 -hydroxybenzotriazole hydrate, room temperature, 4 to 20 hours. IF-2019-03 566964-APN-ANP#INPI Page 63 of 272 Method B: In step a) of Figure 4, the phenylacetic acid derivative of general formula (XIV), which is commercially available or can be prepared according to the methods described in the Examples - where R1 is as defined further above for the general formula (I) - is reacted with Meldrum acid to obtain the compound of general formula (XV) - where R1 is as defined above for the general formula (I) which is reacted with a suitable alcohol (step b)) to obtain the keto ester derivative of general formula (XVI) - where R1 is as defined above for the general formula (I) and Alk is Ci-4alkyl group the latter is converted to the compound of general formula (XVII) by adding ammonium acetate (step c)) - where R1 is as defined above for general formula (I) and Alk is Ci4alkyl group that is reduced in step d) and the amino compound resulting from general formula (XVIII) is obtained - where R1 is as defined above for general formula (I) and Alk is Ci-4alkyl group - of which the amino group is protected with tert-butoxycarbonyl group (step e)) to obtain the compound of general formula (XIX) - where R1 is as defined above for general formula (I) and Alk is Ci^alkyl group. The nitro group of the latter is reduced in step f) and the compound thus obtained of general formula (XX) - where R1 is as defined above for the general formula (I) and Alk is C-^alkyl group - is closed in its ring in the presence of a suitable base (step g)) IF-2019-03 566964-APN-ANP#INPI Page 64 of 272 i to obtain the compound of formula (XIII) - where R1 is as defined above for the general formula (I). The compound of formula (XIII) can also be prepared by hydrolyzing the compound of general formula (XIX) - where R1 is as defined above for general formula (I) and Alk is Ci-4alkyl group - in the presence of a base suitable (step h)) and the resulting compound of formula (XI) - where R1 is as defined above for general formula (I) - is converted to the compound of general formula (XIII) through the steps illustrated in Method A (step i) of Method B is identical to step e) of Method A and step j) of Method B is identical to step f) of Method A). Preferred embodiments are, for example, the following: step a) Meldrum acid, acetonitrile, Λ / , / V-diisopropylethylamine, pivaloyl chloride, 4-dimethylaminopyridine, 20 to 50 °C, 4 to 6 hours; step b) methanol, toluene, 110 to 120 °C, 1 to 6 hours; step c) ammonium acetate, methanol, room temperature, 20 to 75 hours or 60 °C for 5 to 20 hours; step d) sodium triacetoxyborohydride, acetic acid, room temperature, 2 to 48 hours; step e) sodium bicarbonate, methanol, di-tert-butyl dicarbonate, 5 to 25 °C; 1 to 20 hours; step f) i) hydrogenation in the presence of Ρΐ / C catalyst, toluene, room temperature, 4 to 20 hours, or ii) hydrogenation in the presence of Pt / C catalyst, methanol, room temperature, 4 to 20 hours; step g) i) methanol, sodium methoxide, room temperature, 2 to 20 hours, or ü) tetrahydrofuran, potassium tert-butoxide, 0 to 25 °C, 2 to 20 hours; step h) lithium hydroxide, methanol, water, tetrahydrofuran, room temperature, 4 to 20 hours. Benzazepine-thione derivatives of general formula (III) and methylsulfanylbenzazepine derivatives of general formula (IV) are prepared (Figure 5) by reacting a compound of general formula (XIII) obtained by Method A or B Figure 5 IF-2019-03 566964-APN-ANP#INPI Page 65 of 272 - where R1 is as defined above for the general formula (I) - where the Lawesson reagent (step a)), then the benzazepine-thione of general formula (lll-a) thus obtained - where R1 is as was defined above for the general formula (I) - it is methylated (step b)) to form the methylsulfanyl-benzazepine derivative of general formula (IV-a) - where R1 is as defined above for the general formula (I ). Preferred embodiments are, for example, the following: step a) i) Lawesson's reagent, pyridine, 90 to 120°C, 4 to 20 hours, or ii) Lawesson's reagent, tetrahydrofuran, room temperature, 4 to 20 hours; step b) iodomethane, potassium carbonate, acetone, room temperature, 4 to 24 hours. Compounds of general formula (l-b) are prepared by reacting a compound of general formula (lll-a) or a compound of general formula (IV-a) with a compound of general formula (II) (Figure 6) Figure 6 - wherein ring B, Y, R1 is as defined above for general formula (I), ring A is a saturated 4- to 7-membered cycloalkyl or heterocycle containing 1 N, wherein ring A is attached through the nitrogen of the ring to Y. Preferred embodiments of step a) of Figure 6 are, for example, the following: i) reaction of (II) and (lll-a) in xylene at 140 °C for 20 to 150 hours, or ii) reaction of (II) and (lll-a) in n-butanol at 110 °C for 20 to 50 hours, or iii) reaction of (II) and (lll-a) in 1,4-dioxane at 110 °C for 4 to 20 hours, or iv) reaction of (II) and (IV-a) in xylene in presence of catalytic hydrogen chloride at 140°C for 4 to 20 hours, or v) reaction of (II) and (IV-a) in 1,4-dioxane in the presence of catalytic hydrogen chloride at 110 °C for 4 to 20 hours. The compounds thus obtained of general formula (l-b) if desired can also be converted into another compound of the general formula (I) through known methods with the introduction of new substituents and / or with the modification, removal of the IF-2019 -03 566964-APN-ANP#INPI 66 Page 66 of 272 existing substituents and / or with salt formation and / or with release of the base from the salts and / or with the preparation of the enantiomers from the racemic mixtures. This is illustrated in detail in Figure 7: Figure 7 The protecting group of the compound of general formula (l-b) can be removed in a suitable acid medium (step a)), the compounds thus obtained of general formula (l-c) wherein the ring B, Y, R1 are as defined above for general formula (I), ring A is a saturated 4- to 7-membered cycloalkyl or heterocycle containing 1 N, where ring A is linked via the ring nitrogen to Y - they can be sulfonated or acylated (step b)) and the compounds of general formula (l-d) - where R is C(O)R7or S(O2)R10as defined in the general formula (I) in the meaning of R4or R5can be optionally alkylated (step c)) In this way, the compounds of general formula (l-e) are obtained. After alkylation (step d)) of the compounds of general formula (l-b) followed by deprotection (step g)) it forms the mono-alkyl derivatives of general formula (l-g) which can be converted with further alkylation (step h) ) in di-alkyl derivatives of general formula (l-h). The two alkyl groups may be different and / or identical. The monoalkyl or Cy1 derivatives of general formula (l-g) can be prepared by reductive amination (step e)) from the amine derivative of general formula (l-c). The dialkyl derivatives of general formula (l-h) can also be prepared from the amine derivatives of general formula (Ιο) by reductive amination (step f)) if the two alkyl groups are identical. Compounds of general formula (l-w) - where R4 and R5 taken together with the N to which they are attached form a heterocycle - can also be obtained from IF-2019-03 566964-APN-ANP#INPI 67 Page 67 of 272 compounds of general formula (l-c) (step k)) using a suitable dihalogen compound in the presence of a base. Pure enantiomers can be obtained by chiral HPLC or resolution of compounds of general formula (l-c) from which acyl and / or alkyl derivatives can also be prepared. When the compound of general formula (l-c) is a pure enantiomer, the chiral compound of general formula (l-b) is prepared to produce other chiral monoalkyl derivatives. In the general formulas (l-e), (l-f), (l-g) and (l-h), the term "alkyl" is optionally substituted Ci-4alkyl as defined in the general formula (I) in the meaning of R4 or R5y in the formula general (l-g) Cy1es as defined for formula (I). Preferred embodiments are, for example, the following: step a) and g) hydrogen chloride in ethyl acetate, room temperature, 1 to 20 hours step b) i) sulfonyl chloride, pyridine, room temperature, 4 to 20 hours, or li) sulfonyl chloride, dlchloromethane, triethylamine or / V, / V-diisopropylethylamine, room temperature, 4 to 20 hours, or iii) acyl chloride, pyridine, at room temperature for 4 to 20 hours, or iv) acyl chloride, dichloromethane, triethylamine or N, / V-diisopropylethylamine , room temperature, 4 to 20 hours, or v) acid anhydride, pyridine, room temperature, 4 to 20 hours, or vi) acid, ^^ / V^ / V-tetramethyl-O^IH-benzotriazol-l-IOuronium hexafluorophosphate, A / , / V-dimethylformamide, W, / \ / -diisopropylethylamine or triethylamine, room temperature, 4 to 20 hours, or vii) acid, A / -(3-dimethylaminopropíl)- / V'-ethylcarbodiimide hydrochloride, N:Ndiisopropylethylamine, N,A / - dimethylformamide, 1-hydroxybenzotrlazole hydrate, room temperature, 4 to 20 hours; step c) d) and h) alkyl halide, sodium hydride, tetrahydrofuran or N,Ndimethylformamide, room temperature, 4 to 20 hours; step e) aldehyde or ketone, 1,2-dichloroethane, acetic acid, sodium triacetoxy borohydride, room temperature, 4 to 20 hours; step f) aldehyde or ketone, methanol, acetic acid, sodium triacetoxy borohydride, room temperature, 4 to 20 hours; step k) dihalogen derivative, Λ / , / V-dimethylformamide, cesium carbonate, 20-60 °C, 10-30 hours. IF-2019-03 566964-APN-ANP#INPI Page 68 of 272 Provided that, in the compound of general formula (I), R2 is hydrogen, R3 is -OSi(CH3)2-fbutyl group, benzazepine-thione derivatives of general formula (III) can be prepared by the procedure of Figure 8. Figure 8 The keto group of the keto ester of general formula (XVI) - where R1 is as defined above for general formula (I) and Alk is Ci-4alkyl group - is reduced (step a)) and then the hydroxy group of the compound of general formula (XXI) - where R1 is as defined above for general formula (I) and Alk is Ci^alkyl group - is protected by a silyl protecting group (step b)) to obtain the compound of general formula (XXII) - where R1 is as defined above for formula (I) and Alk is Ci4alkyl group. The ester group of the latter is hydrolyzed (step c)), then the nitro group of the compound thus obtained of general formula (XXIII) - where R1 is as defined above for the general formula (I) - is reduced (step d )) to form the amine derivative of general formula (XXIV) - where R1 is as defined above for the general formula (I) - which is closed in its ring by means of a reagent capable of forming an amide bond (step e)) to obtain the benzazepine of general formula (XXV) - where R1 is as defined above for the general formula (I) - which is subjected to reaction with Lawesson reagent (step f)) to form the benzazepine derivative -general formula thione (lll-b) - where R1 is as defined above for the general formula (I). Preferred embodiments are, for example, the following: step a) sodium borohydride, methanol, room temperature, 4 to 20 hours; step b) 1H-imidazole, tert-butyl-dimethylchlorosilane, A / , / V-dimethylformamide, room temperature, 4 to 20 hours; IF-2019-03 566964-APN-ANP#INPI Page 69 of 272 step c) lithium hydroxide, methanol, water, tetrahydrofuran, room temperature, 4 to 20 hours; step d) hydrogenation in the presence of a Pt / C catalyst, toluene, room temperature, 4 to 20 hours; step e) / V-(3-dimethylaminopropyl)-A / -ethylcarbodi¡mide hydrochloride, Λ / ,Λ / diisopropylethylamine, Λ / , / V-dimethylformamide, 1-hydroxybenzotriazole hydrate, room temperature, 4 to 20 hours; step f) Lawesson's reagent, pyridine, 120 °C, 4 to 20 hours. Compounds of general formula (l-i) can be prepared by reacting compounds of general formula (IIl-b) and compounds of general formula (II) (Figure 9): Figure 9 - wherein ring B, Y, R1 are as defined above for general formula (I), ring A is a saturated 4- to 7-membered cycloalkyl or heterocycle containing 1 N, wherein ring A is attached through the nitrogen of the ring to Y. A preferred embodiment is, for example, the following: step a) xylene at 140 °C for 20 to 120 hours. The silyl protecting group of the compounds of general formula (l-i) is removed (Figure 10) to obtain the hydroxy derivatives of general formula (l-j), Figure 10 IF-2019-03 566964-APN-ANP#INPI Page 70 of 272 - wherein ring B, Y, R1 are as defined above for general formula (I), ring A is a saturated 4- to 7-membered cycloalkyl or heterocycle containing 1 N, wherein ring A is attached through the nitrogen of the ring to Y. A preferred embodiment is, for example, the following: step a) tetrabutylammonium fluoride, tetrahydrofuran, room temperature, 3 to 10 hours. Provided that, in the compound of formula (I), R2 and R3 together represent O-(CH2)m-O- group and ring A is a cycloalkyl or a 4- to 7-membered saturated heterocycle containing 1 N, wherein ring A is linked via the ring nitrogen to Y, the compounds of general formula (I) of the present invention are prepared by reacting compounds of formula (II) NH—NHZo(II) - wherein ring B and Y are as defined above for general formula (I) and ring A is a saturated 4- to 7-membered cycloalkyl or heterocycle containing 1 N, wherein ring A is bonded by medium of the ring nitrogen to Y - with the compound prepared in situ of general formula (XXVI), - where R1 and m are as defined above for the general formula (I). The procedure is illustrated in detail in Figure 11: NH—NH2ajX A preferred embodiment is, for example, the following: step a) dichloromethane, trifluoroacetic acid, trimethyloxonium tetrafluoroborate, 40 ° C, 20 to 40 hours. IF-2019-03 566964-APN-ANP#INPI Page 71 of 272 The methoxybenzazepine derivative of general formula (XXVI) can be prepared according to the procedure of Figure 12: Figure 12 The keto group of the keto ester of general formula (XVI) is protected by a suitable a:ro-C2-5diol (step a)) followed by the reduction of the nitro group of the compound of general formula (XXVII) - where R1y m are as defined above for the general formula (I) and Alk is Ci-4alkyl group - to form the compound of general formula (XXVIII) (step b)) - where R1 and m are as defined above for the general formula (I) and Alk is Ci-4alkyl group - the latter is closed in its ring in the presence of a suitable base (step c)) to obtain the benzazepine of general formula (XXIX) - where R1y m are as defined above for the general formula (I) and Alk is Ci-4alkyl group - from which the methoxybenzazepine derivative of general formula (XXVI) - where R1y m are as defined above for the general formula (I) and Alk is C < 4alkyl group - is prepared by methylation (step d))t and the latter without isolation is subjected to reaction with an acid hydrazide of general formula (II) (step e)) - where the ring B and Y are as shown defined above for general formula (l), ring A is a saturated 4- to 7-membered cycloalkyl or heterocycle containing 1 N, where ring A is linked via the ring nitrogen to Y - to obtain the compound of general formula (l-k) - wherein ring B, Y, R1 and m are as defined above for general formula (I) and ring A is a cycloalkyl or a 4- to 7-membered saturated heterocycle containing 1 N, where ring A is bonded via the ring nitrogen to Y - after removing the ketal protecting group (step f)) to form the oxo compound of general formula (l-l) - where ring B, Y , R1 and m are as defined above for the general formula (I) and IF-2019-03 566964-APN-ANP#INPI Page 72 of 272 ring A is a saturated 4- to 7-membered cycloalkyl or heterocycle containing 1 N, where ring A is bonded via the ring nitrogen to Y - then the latter is reduced (step g)) to obtain the hydroxy derivative of general formula (l-j) - wherein the ring B, Y, R1 and m are as defined above for the general formula (I) and the ring A is a cycloalkyl or a saturated heterocycle of 4 to 7 members containing 1 N, where ring A is bonded via the ring nitrogen to Y. Preferred embodiments are, for example, the following: step a) trimethyl orthoformate, methanol, ethylene glycol, p-toluenesulfonic acid, 50 °C, 50 to 100 hours; step b) hydrogenation in the presence of a Pt / C catalyst, toluene, room temperature, 4 to 20 hours; step c) tetrahydrofuran, potassium tert-butoxide, room temperature, 2 to 20 hours; step d) dichloromethane, trifluoroacetic acid, trimethyloxonium tetrafluoroborate, room temperature, 20 to 25 hours; step e) hydrazide of acid of formula (II), dichloromethane, 50 ° C, 6 to 20 hours; step f) methanol, cc. hydrochloric acid, 70 °C, 2 to 6 hours; step g) methanol, sodium borohydride, 0 to 25 °C, 2 to 4 hours. The compounds of formula (l-k) if desired can also be converted into another compound of the general formula (I) through known methods with the introduction of new substituents and / or with the modification, removal of existing substituents. The hydroxy derivatives of general formula (l-j) prepared from the compound of general formula (l-i) or the compound of general formula (l-l) if desired can also be converted into another compound of general formula (I) through known methods with the introduction of new substituents and / or with the modification, removal of existing substituents and / or with salt formation and / or with release of the base from the salts and / or with the preparation of the enantiomers from racemic mixtures. This is illustrated in detail in Figure 13. Figure 13 IF-2019-03 566964-APN-ANP#INPI Page 73 of 272 Preferred embodiments of step a) of Figure 13 are, for example, the following: i) alkyl halide, sodium hydride, tetrahydrofuran or Λ / ,Ν-dimethylformamide, room temperature, 4 to 20 hours, or i) acyl chloride, dichloromethane, triethylamine or N, / V-diisopropylethylamine, room temperature, 4 to 20 hours, or ii) acyl chloride, pyridine, room temperature, 4 to 20 hours. Pure enantiomers can be obtained by chiral HPLC from the compounds of general formula (l-j) from which acyl and / or alkyl derivatives can be prepared. Provided that, in the compound of general formula (l), R2 is hydrogen, R3 is NHBoc or R2 and R3 together represent group -O-(CH2)m-O- and ring A is a saturated 4 to 7 membered heterocycle containing 1 or 2 N , wherein the A ring is linked via a ring nitrogen to the triazole ring of the 5,6-dihydro-4H[1,2,4]triazolo[4,3-a][1]benzazepine nucleus, the Compounds of general formula (I) of the present invention are prepared by reacting compounds of general formula (XXX) (XXX) - wherein ring B and Y are as defined above for general formula (I) and ring A is a saturated 4 to 7-membered heterocycle containing 1 or 2 N - and compounds of general formula (XXXI) ( XXXI) - where R1 is as defined above for the general formula (I), R2 is hydrogen, R3 is -NHBoc or R2 and R3 together represent group -O-(CH2)m-O- and m is as defined above for the general formula (I) . The procedure is illustrated in detail in Figure 14: IF-2019-03 566964-APN-ANP#INPI Page 74 of 272 Figure 14 The preferred embodiment of step a) of Figure 14 is, for example, the following: i) fusion (without solvent) at 120-150 °C for 3 to 72 hours. Amine derivatives of general formula (XXX) are commercially available or can be prepared according to the methods described in the Examples. As long as R2 is hydrogen, R3 is -NHBoc, triazolo-benzazepine derivatives of general formula (XXXI) can be prepared according to the procedure of Error! The source of the reference cannot be found: Compounds of general formula (IV-a) are subjected to reaction with formyl hydrazine (step a)) and the resulting compound of general formula (XXXII) - where R1 is as defined for general formula (I) - is brominated ( step b)), the bromine derivative of general formula (XXXI-a) is therefore obtained - where R1 is as defined above for the general formula (I). Preferred embodiments are, for example, the following: step a) formyl hydrazine, 1,4-dloxane, 90 °C, 3 to 10 hours; step b) N-bromosuccinimide, tetrahydrofuran, 70 °C, 10 to 60 minutes. As illustrated in Figure 16, the compounds of general formula (XXXI-a) are subjected to reaction with the compound of general formula (XXX) (step a)) - where ring B and Y are as defined further above for general formula (I) and ring A is a 4- to 7-membered saturated heterocycle containing 1 or 2 N, where ring A is linked via a ring nitrogen to the triazole ring of the core of 5 ,6-dihydro-4H[1,2,4]triazolo[4,3-a][1]benzazepine -, the protecting group is removed from the compound IF-2019-03 566964-APN-ANP#INPI 75 Page 75 of 272 resulting from general formula (l-o) (step b)), then the amine derivatives obtained in this way from general formula (l-p) - where the ring B, Y and R1 are as defined above for the formula general (I) and ring A is a 4- to 7-membered saturated heterocycle containing 1 or 2 N, wherein ring A is linked via a ring nitrogen to the triazole ring of the 5,6-dihydro core -4H-[1,2,4]triazolo[4,3a][1]benzazepine - can be sulfonated, acylated or alkylated (step c)) to obtain the compounds of general formula (l-q) - where the ring B, Y and R1 are as defined above for general formula (I) and ring A is a 4- to 7-membered saturated heterocycle containing 1 or 2 N, where ring A is linked via a ring nitrogen to triazole ring of the 5,6-dihydro-4H-[1,2,4]triazolo[4,3a][1]benzazepine nucleus and R' is optionally substituted Ci_4alkyl, C(O)R7or S(O2)R10as shown defined under the meaning of R4 or R5 in the general formula (I). Preferred embodiments are, for example, the following: step a) melting (without solvent), 120-150 °C, 3 to 72 hours; step b) hydrogen chloride in ethyl acetate, room temperature, 4 to 20 hours; step c) i) sulfonyl chloride, pyridine, room temperature, 4 to 20 hours, or i) sulfonyl chloride, dichloromethane, trilethylamine or / V,A / -diisopropylethylamine, room temperature, 4 to 20 hours, or iii) chloride acyl, pyridine, room temperature, 4 to 20 hours, or iv) acyl chloride, dichloromethane, triethylamine or / V, / V-diisopropylethylamine, room temperature, 4 to 20 hours, or v) acid anhydride, pyridine, room temperature, 4 to 20 hours, or IF-2019-03 566964-APN-ANP#INPI Page 76 of 272 vi) acid, / V, / V,A / ;A / '-tetramethyl-O-(1 / - / -benzotriazol-1-yl)uronium hexafluorophosphate, / V, / V-dimethylformamide, A / ,A / -diisopropylethylamine, room temperature, 4 to 20 hours, or vii) acid, A / -(3-dimethylaminopropyl)“ / \ / -ethylcarbodiimide hydrochloride, Λ / ,Λ / diisopropylethylamine, Λ / , / V- dimethylformamide, 1-hydroxybenzotriazole hydrate, room temperature, 4 to 20 hours, or viii) alkyl halide, sodium hydride, tetrahydrofuran or A / ,A / -dimethylformamide, room temperature, 4 to 20 hours, or ix) aldehyde or ketone, 1,2-dichloroethane, acetic acid, sodium triacetoxy borohydride, room temperature, 4 to 20 hours. When R2 and R3 together represent -O-(CH2)m-O- group, the triazolo-benzazepine derivatives of general formula (XXXI) can be prepared according to the procedure of Figure 17: (XXIX) (XXVI) (XXXIII) (XXXI-b) Figure 17 The methoxybenzazepine derivative of general formula (XXVI) obtained in situ from the compound of general formula (XXIX) is subjected to reaction with formyl hydrazine (steps a) and b)) and the resulting compounds of general formula (XXXIII) - where R1y m are as defined above for the general formula (I) - they are brominated (step c)), so bromine compounds of general formula (XXXI-b) are obtained - where R1y m are as defined further above for the general formula (I). Preferred embodiments are, for example, the following: step a) dichloromethane, trifluoroacetic acid, trimethyloxonium tetrafluoroborate, room temperature, 20 to 25 hours; step b) formyl hydrazine, dichloromethane, 40 °C, optional solvent change to dioxane, 90 °C, 15 to 40 hours; step c) A / -bromosuccinimide, tetrahydrofuran, 70 °C, 10 to 60 minutes. According to Figure 18, the compounds of general formula (XXXI-b) are reacted with the compounds of general formula (XXX) (step a)) - where the ring B and Y are as defined above for the general formula (I) and ring A is a 4- to 7-membered saturated heterocycle containing 1 or 2 N -, the protecting group of IF-2019-03 566964-APN-ANP#INPI 77 Page 77 of 272 the resulting compounds of general formula (l-r) are removed (step b)), and the resulting keto derivatives of general formula (l-s) are reduced (step c)) - where the ring B, Y, m and R1 are as defined above for general formula (I) and ring A is a 4- to 7-membered saturated heterocycle containing 1 or 2 N, where ring A is linked via a ring nitrogen to the ring triazole of the nucleus of 5,6-dihydro-4H[1,2,4]triazolo[4,3-a][1]benzazepine - to obtain the hydroxy derivatives of general formula (l-t) that can be added or alkylated ( step d)), whereby the compounds of general formula (l-u) are obtained - where the ring B, Y, R1 and R are as defined above for the general formula (I) and the ring A is a saturated heterocycle of 4 to 7 members containing 1 or 2 N, wherein ring A is linked via a ring nitrogen to the triazole ring of the 5;6-dihydro-4H-[1,2,4]triazolo[4] core ,3a][1]benzazepine. Figure 18 Preferred embodiments are, for example, the following: step a) melting (without solvent), 130 to 140 °C, 3 to 72 hours; step b) methanol, cc. hydrochloric acid, 70 °C, 2 to 6 hours; step c) methanol, sodium borohydride, 0 to 25 °C, 2 to 4 hours; step d) i) acyl chloride, pyridine, room temperature, 4 to 20 hours, or i) acyl chloride, dichloromethane, triethylamine or / V,A / -diisopropylethylamine, room temperature, 4 to 20 hours, or iii) alkyl halide, sodium hydride, tetrahydrofuran or / V,A / -d Iformam ida, room temperature, 4 to 20 hours. IF-2019-03 566964-APN-ANP#INPI Page 78 of 272 Hydroxy derivatives of general formula (l-t) if desired can also be converted to another compound of general formula (I) through known methods with the introduction of new substituents and / or with the modification, removal of existing substituents and / or or with salt formation and / or with release of the base from the salts and / or with the preparation of the enantiomers from the racemic mixtures. Provided that, in the compound of general formula (I), R2 is hydrogen, R3 is NR4R5 and R4 and R5 taken together with the N to which they are attached form a heterocycle, the compounds of general formula (I) of the present invention are prepared according to the procedure of Figure 19 such that: Figure 19 the compounds of the general formulas (l-j) or (l-t) are sulfonylated (step a)) and the resulting compounds of general formula (l-v) are subjected to reaction - where ring B, Y, ring A and R1 are as defined above for the general formula (I) and R" is methyl, trifluoromethyl or 4-methylphenyl group - with an amine of formula NHR4R5 (step b)) where R4 and R5 taken together with the N to which they are attached form a heterocycle - to obtain compounds of general formula (l-w). Amines of the formula NHR4R5 are commercially available or can be synthesized through known methods. Preferred embodiments are, for example, the following: step a) i) sulfonyl chloride, pyridine, room temperature, 4 to 20 hours, or ii) sulfonyl chloride, dichloromethane, triethylamine or N, / V-diisopropylethylamine, temperature environment, 4 to 8 p.m.; step b) NHR4R5, / V,A / -dimethylformamide, 60 to 120 °C, 4 to 24 hours. Provided that, in the compounds of general formula (I), R2 is Ci-4alkyl, R3 is OR6 group, the compounds of general formula (I) of the present invention are prepared according to Figures 20 and 21 such that: IF-2019-03 566964-APN-ANP#INPI Page 79 of 272 Figure 20 Compounds of general formula (XXXIV) are protected (step a)) to obtain compounds of general formula (XXXIV) - where R1 and m are as defined above for general formula (I) and PG1 is a protecting group (Peter G. M. Wuts: Greene's Protective Groups in Organic Synthesis: Fifth Edition, Chapter 7. Protection for the Amino Group, pages 895-1193), preferably 4-methoxybenzyl protecting group - and then the ketal is removed with a suitable acid (step b)), and the obtained oxo derivative of general formula (XXXV) which is subjected to reaction with a suitable alkyl lithium or Grignard reagent (step c)) to obtain the compound of general formula (XXXVI) - where R1 is as defined above for the general formula (I) and PG1 is a protecting group, preferably 4-methoxybenzyl protecting group and R2 is CMalkyl group. By protecting the hydroxy group of compounds of general formula (XXXVI) (step d)), protected hydroxy derivatives of general formula (XXXVII) - where R1 is as defined above for general formula (I), PG1 is a protecting group, preferably 4-methoxybenzyl protecting group, R2 is an alkyl group and PG2 is a protecting group (Peter G. M. Wuts: Greene's Protective Groups in Organic Synthesis: Fifth Edition, Chapter 2 Protection for the Hydroxyl Group, Including 1,2- and 1,3-Diols, pages 17471), preferably silyl protecting group - are obtained. After deprotection (step e)) of the compounds of general formula (XXXVII), then of the thus obtained compounds of general formula (XXXVIII) the benzazepinationa derivatives of general formula (XXXIX) are prepared with Lawesson's reagent (step f )), followed by methylation (step g)) to obtain the compounds of general formula (XL). Preferred embodiments are, for example, the following: step a) 4-methoxybenzylchloride, sodium hydride, Λ / W-dimethylformamide, 0 to 25 °C, 3 to 6 hours; step b) acetic acid, reflux, 6 to 20 hours; IF-2019-03 566964-APN-ANP#INPI Page 80 of 272 -I .1 step c) i) alkyl lithium, tetrahydrofuran, (-78) °C, 1 to 4 hours, or ii) R2MgClxLICI, tetrahydrofuran, (-20 °C) to (-15 °C), 1 at 6 hours, or iii) R2MgCI, tetrahydrofuran, CeCI3, (-78) at 0 °C, 12 to 70 hours; step d) 1 / 7-imidazole, silyl chloride, Λ / , / V-dimethylformamide, room temperature, 4 to 20 hours; step e) i) cerium ammonium nitrate, water, acetonitrile, 0 to 25 °C, 6 to 18 hours, or ii) trifluoroacetic acid, dichloromethane, room temperature, 12 to 24 hours, or iii) trifluoromethanesulfonic acid, dichloromethane, room temperature, 2 to 12 hours; step f) Lawesson's reagent, pyridine, reflux, 4 to 5 hours; step g) iodomethane, potassium carbonate, acetone, room temperature, 4 to 24 hours. The compounds of the general formulas (XXXIX) or (XL) are subjected to reaction with the compounds of general formula (II) (step a) of Figure 21), to form the compounds of general formula (l-x) - where the ring B, Y, ring A and R1 are as defined above for general formula (I), PG2 is a protective group (Peter G. M. Wuts: Greene's Protective Groups in Organic Synthesis: Fifth Edition, Chapter 2 Protection for the Hydroxyl Group, Including 1,2- and 1,3-Diols, pages 17-471), preferably silyl protecting group, and R2 is Ci^alkyl group. The protecting group is removed (step b)) from the resulting compounds of general formula (l-x) to obtain the compounds of general formula (l-y). Figure 21 Hydroxy derivatives of general formula (l-y) if desired can also be converted into another compound of general formula (I) through methods known with IF-2019-03 566964-APN-ANP#INPI 81 Page 81 of 272 introduction of new substituents and / or with the modification, removal of existing substituents and / or with salt formation and / or with liberation of the base from the salts and / or with the preparation of the enantiomers to from the racemic mixtures, for example using the methods described in step c). Preferred embodiments are, for example, the following: step a) i) reaction of (II) and (XXXIX) in xylene at 140 °C for 20 to 150 hours, or ii) reaction of (II) and (XXXIX) in n-butanol at 110 °C for 20 to 50 hours, or iii) reaction of (II) and (XXXIX) in 1,4-dioxane at 110 °C for 4 to 20 hours, or iv) reaction of (II) and (XL) in xylene in the presence of hydrogen chloride catalytic at 140°C for 4 to 20 hours, or v) reaction of (II) and (XL) in 1,4-dioxane in the presence of catalytic hydrogen chloride at 110 °C for 4 to 20 hours; step b) tetrabutylammonium fluoride, no tetrahyd cleavage, room temperature, 3 to 10 hours; step c) i) alkyl halide, sodium hydride, tetrahydrofuran or Λ / , / V-dimethylformamide, room temperature, 4 to 20 hours, or ii) acyl chloride, dichloromethane, triethylamine or Λ / , / V-diisopropylethylamine, temperature room, 4 to 20 hours, or iii) acyl chloride, pyridine, room temperature, 4 to 20 hours. Provided that, in the compound of general formula (I), R2 is hydrogen, R3 is -OCH3 group, benzazepine-thione derivatives of general formula (III) can be prepared by the procedure of Figure 22: IF-2019-03 566964-APN-ANP#INPI Figure 22 Page 82 of 272 The hydroxy group of the compound of general formula (XXI) - where R1 is as defined above for general formula (I) and Alk is Ci-4alkyl group - is methylated (step a)) to obtain the compound of general formula ( XLI) - where R1 is as defined above for general formula (I) and Alk is Ci-4alkyl group. The ester group of the latter is hydrolyzed (step b)), then the nitro group of the compound thus obtained of general formula (XLI I) - where R1 is as defined above for the general formula (I) - is reduced (step c)) to form the amine derivative of general formula (XLIII) - where R1 is as defined above for the general formula (I) - which is closed in its ring by means of a reagent capable of forming an amide bond ( step d)) to obtain the benzazepine of general formula (XLIV) - where R1 is as defined above for the general formula (I) - which is subjected to reaction with Lawesson's reagent (step e)) to obtain the derivative of benzazepine-thione of general formula (I ll-c) - where R1 is as defined above for the general formula (I). Preferred embodiments are, for example, the following: step a) dichloromethane, 1,8-bis(dimethylamino)naphthalene, trimethyloxonium tetrafluoroborate, room temperature, 20 to 25 hours; step b) sodium hydroxide, methanol, water, room temperature, 4 to 20 hours; step c) hydrogenation in the presence of a Pt / C catalyst, toluene, room temperature, 4 to 20 hours; step d) A / -(3-dimethylaminopropyl)-A / '-ethylcarbodiimide hydrochloride, Λ / ,ΛΛdiisopropylethylamine, Ν, / V-dimethylformamide, 1-hydroxybenzotriazole hydrate, room temperature, 4 to 20 hours; step e) Lawesson's reagent, tetrahydrofuran, room temperature, 2 to 20 hours; Compounds of general formula (l-aa) can be prepared by reacting compounds of general formula (Ill-c) and compounds of general formula (II) (Figure 23) IF-2019-03 566964-APN-ANP#INPI Figure 23 Page 83 of 272 - wherein ring B, Y, R1 are as defined above for general formula (I), ring A is a saturated 4- to 7-membered cycloalkyl or heterocycle containing 1 N, wherein ring A is attached through the nitrogen of the ring to Y. A preferred embodiment is, for example, the following: step a) butanol at 140 °C for 20 to 120 hours. The compound of general formula (l-aa) can also be synthesized from the compound of general formula (XLIV) according to the method illustrated in Figure 24. (XLIV) (XLV) (l-aa) Figure 24 The compound of general formula (XLIV) is methylated with trimethyloxonium tetrafluoroborate (step a)) and the compound of general formula (XLV) obtained in this way is subjected to reaction in situ with the compound of general formula (II) - where ring B, Y, R1 are as defined above for general formula (I), ring A is a saturated 4- to 7-membered cycloalkyl or heterocycle containing 1 N, where ring A is linked via the ring nitrogen to Y - (step b)) to obtain compounds of general formula (l-aa). A preferred embodiment is, for example, the following: step a) dichloromethane, trifluoroacetic acid, trimethyloxonium tetrafluoroborate, room temperature, 20 to 40 hours; step b) i) compound of formula (II), dichloromethane, 40 °C, 2 to 20 hours ¡i) compound of formula (II), acetonitrile, reflux temperature, 1 to 10 hours. The reagent capable of forming an amide bond used for the preparation of the compounds of the general formulas (XIII), (XXV) and (XLIV) may be, for example, hydroxybenzotriazole (HOBt) and N-(3-dimethylaminopropyl)- / V-ethylcarbodiimide hydrochloride (EDC) or 0-(benzotriazoL1-yl)-A / .A / ,A / 'Λ / '-tetramethyluronium hexafluorophosphate (HBTU). The reaction is preferably carried out in the presence of a base - such as triethylamine or N,Ndiisopropylethylamine (DIPEA) - in a suitable solvent - such as Λ / , / V-dimethylformamide, acetonitrol, hydrocarbons or chlorinated hydrocarbons, or mixtures thereof. themselves - to one IF-2019-03 566964-APN-ANP#INPI Page 84 of 272 temperature between room temperature and O °C. The reaction is followed by thin layer chromatography. The reaction time required is 4 to 20 hours. The detailed reagents and process steps required for the above reactions are set out in the Examples. One aspect of the present invention is based on the novel intermediates represented by the general formulas (lll-a), (lll-b), (lll-c), (IV-a), (XIII), (XXV), ( XXIX) and (XLIV) synthesized in the process to prepare the compound of general formula (I) wherein R1 is as defined above for general formula (I), especially fer-butyl (7-chloro-2-oxo-2 ,3,4,5-tetrahydro-1H-1-benzazepin-4-yl)carbamate (Intermediate 3), tert-butyl (7-chloro-2-thioxo-2,3,4,5-tetrahydro-1 H- 1-benzazepin-4-yl)carbamate (Intermediate 4), tert-butyl [7-chloro-2-(methylsulfanyl)-4,5-dihydro-3H-1-benzazepin-4-yl]carbamate (Intermediate 5), ter- butyl-(7-bromo-2-oxo-2;3,4,5-tetrahydro-1 H-1-benzazepin-4-II)carbamate (Intermediate 32), fer-butyl-(7-bromo-2-thioxo -2,3,4,5-tetrahydro-1H-1-benzazepin-4-¡l)carbamate (Intermediate 33), 7-bromo-1,5-dihydrospiro[1-benzazepine-4,2'-[1, 3]dioxolane]-2(3H)-one (Intermediate 36), 7-chloro-1,5-dihydrospiro[1-benzazepine-4,2>¿1[3]dioxolane]-2(3H)-one (Intermediate 53), 4-{[tert-butyl(dimethyl)silyl]oxy}-7-chloro-1,3,4,5-tetrahydro-2H-1-benzazepin2-one (Intermediate 62), 4-{[ tert-butyl(dimethyl)silyl]oxy}-7-chloro-1,3,4,5-tetrahydro-2H-1 benzazepin-2-thione (Intermediate 63), 7-chloro-4-methoxy-1,3, 4,5-tetrahydro-2H-1benzazepin-2-one (step d) of Intermediate 103) or 7-chloro-4-methoxy-1,3,4,5“tetrahydro-2H 1-benzazepine-2-thione ( Intermediary 103). The activity data of each of the compounds of general formula (I) of the present invention are determined in vitro and in vivo by means of the methods described below. Vasopressin V1a receptor binding assay in humans Cells and radioligand The immortalized 1321N1 cell line (Perkin Elmer, ES-361-M400-UA) that constitutively and stably expresses the human vasopressin receptor V1a and the compound vasopressin (8-L-Arginine), labeled with [Phenylalanyl-3, 4,5-3H(N)] (Perkin Elmer Ufe and Analytical Sciences) as radioligand were used to determine the affinity of the prepared compounds. Method IF-2019-03 566964-APN-ANP#INPI 85 Page 85 of 272 Membrane preparation: Membrane preparation of immortalized 1321N1 cells expressing the propagated human vasopressin V1a receptor was performed according to the Jarvis method (Jarvis et al., J Pharmacol Exp Ther 2004, 310: 40716). Cells were suspended in preparative buffer (50 mM Tris, 1 mM EDTA, 0.1 mM PMSF) and homogenized with a glass homogenizer vessel. To separate the raw membrane fraction, two consecutive centrifugation procedures were performed (40,000 g for 20 minutes at 4 °C), then the membrane was introduced into the preparatory buffer during a final washing step, divided into aliquots that were stored. at -80°C until measurement. The protein content of the prepared membrane was determined according to the Lowry method using a standard dilution line of bovine serum albumin (BSA) (Lowry et al., J Biol Chem 1951, 193: 265- 75). Receptor binding assay: In the receptor binding assay, substances with unknown affinity were used at a minimum of 8 different concentrations, with 3 parallels at each concentration. To determine the final affinity value, the results of at least two independent experiments were taken into account. The assay mixture included incubation buffer (50 mM Tris-HCl, pH 7.4 + 3% BSA), membrane preparation of 1321N1 cells expressing human vasopressin V1a receptor (167 pg / ml), and Vasopressin (8-L-arginine), [Phenylalanyl-3,4,5-3H(N)] as radioligand (1 nM). Non-specific binding values ​​were determined in the presence of unlabeled 1.2x10sM (Arg8)-vasopressin. Samples were incubated in a total volume of 0.33 ml for 60 minutes at 27°C. Free and membrane-bound ligands were separated by filtration through UniFilter® GF / B™ impregnated with 0.5% polyethyleneimine. After drying the filter plates, 40 μl of Microscint-20 scintillation cocktail (Packard) was added to the samples. Finally, radioactivity was measured using MicroBeta2Microplate Counter (Perkin Elmer). The IC50 data (i.e., the concentration of the unknown substance that displaces 50% of the specific bound radioligand) are calculated from the concentration-displacement curve using the mathematical sigmoidal fitting method y = (A1-A2) / ( 1 + (x / x0)p)+A2 with Origin 7.5 software. (OriginLab Corporation, Northampton, USA). During fitting, the asymptotes are not fixed. K¡ (inhibition constant) values ​​are given with the Cheng-Prusoff equation K¡ = ICso / [1 +(L / Kd)J where [L] is the concentration of radioligand used in the experiment and [KD] is the affinity of the ligand IF-2019-03 566964-APN-ANP#INPI Page 86 of 272 radioactively marked for the given receiver. The Kd value is determined in advance using the Scatchard curve. Functional assay to evaluate compounds on the cell line that expresses the human vasopressin receptor V1a Cells The immortalized 1321N1 cell line (Perkin Elmer, ES-361-M400-UA) that constitutively and stably expresses the human vasopressin V1a receptor was used to measure the prepared compounds. The common secondary messenger pathway of the measured GPCR receptor was used: the Gqendogen-associated system. Method Using 30,000 cells / plate, compounds were measured in 96-well plates. The composition of the measurement buffer was as follows (expressed in mM): 140 NaCl, 5 KCI, 2 CaCl2, 2 MgCl2, 10 glucose, 10 HEPES (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid), 2 probenecid , pH = 7.4. The FLIPR Calcium 5 kit (Molecular Devices) was used as the fluorescent dye, the medium was not removed before filling with the dye, and the cells were not washed before or after. Incubation was carried out at room temperature, the final concentration of DMSO was 1%. The materials to be measured were administered in a 15 to 20 minute pretreatment, and at least two parallels of each compound were measured at each concentration. The fluorescence signal was used to determine the intracellular Ca2+ level, the reader was FlexStation II96. Cytoplasmic Ca2+ concentrations were measured fluorometrically using the FlexStation II96 plate reader (excitation: 485 nm, emission: 525 nm). The fluorescence signal was recorded every 1.4 seconds for 1 minute. The reference compounds used were the following: (Arg8)-vasopressin as agonist at the EC80 concentration, determined for each plate, and relcovaptan as antagonist at 1 μΜ. The % inhibition at each concentration and the IC50 value of the compounds were determined, where a concentration line was also measured. The total AVP concentration-response curve was recorded on each plate. The effect of the measured compounds was expressed by the percentage of relative inhibition compared to the control response. For the graphical representation of the data, alignments of four non-linear parameters were applied using the SoftMaxPro software according to the following formula: y = A-D / 1+(x / C)AB)+D, where: A = 0 and IF-2019-03 566964-APN-ANP#INPI 87 Page 87 of 272 D = 100 - fixed lower / upper asymptotes, y = percentage of inhibition, x - logarithm of concentrations of the tested compound, B = slope of the curve and C - IC50 (concentration belongs to 50% inhibition of the control response) . Average IC50 values ​​were calculated from at least three independent measurements in all cases. Table 1: The effectiveness of the compounds of the present invention measured in the human vasopressin V1a receptor binding assay and functional assay. Example No. K¡ (nWI) in hV1a cell line ICso(nM) in hV1a cell line Example No. K¡(nlW) in hV1a cell line ICso(nM) in hV1a cell line 1 6 95 21 0.7 4 2 7 170 22 0.5 2.8 3 2.1 16 23 1 6.4 4 70 825 24 1 7 5 3.8 17 25 2.3 23 6 2 9 26 0.7 4.5 7 2.1 20 27 1.1 7 8 1.3 6.8 28 0.7 5.4 9 0.8 3 29 0.6 5.4 10 1.8 12 30 1.4 15 11 32 480 31 17 260 12 0.8 9 32 6 85 13 5 45 33 111 480 14 1.1 10 34 52 700 15 0.4 3.7 35 9.7 160 16 3 10 36 36 610 17 2.1 35 37 7 100 18 0.5 1, 6 38 2 30 19 0.4 1.8 39 1.4 8.3 20 0.7 1 40 0.9 8.4 Example K¡ (nM) IC5o(nM) Example Ki(nM) ICsofnM) No. in line in line No. in line in line IF-2019-03 566964-APN-ANP#INPI Page 88 of 272 hV1a cell hV1a cell hV1a cell hV1a cell hV1a cell 41 600 N,D, 71 14 22 42 42% at 1 μΜ N,D, 72 7.5 21 43 88 210 73 1.6 3.3 44 26 480 74 4 2.6 45 38 870 75 3.7 10.4 46 23 410 76 1.1 2.2 47 0.8 2.3 77 1.9 18 48 18 340 78 1.7 12 49 7.5 140 79 71 1855 50 2 .7 20 80 58 520 51 7.6 55 81 0.2 1.4 52 11 60 82 29 445 53 0.3 0.9 83 4 4 44 54 0.6 1.2 84 11.4 72 55 0. 3 1.1 85 0.4 1.8 56 0.3 1.2 86 2.2 12 57 0.3 1.8 87 2.5 57 58 0.3 1.4 88 0.3 0.9 59 0.8 2.5 89 0.4 1.9 60 2.0 45 90 10.2 152 61 0.4 2.5 91 9.1 45 62 0.2 1.1 92 1.9 16 63 0. 3 1.4 93 3.2 16 64 0.5 1.1 94 2.0 23 65 0.5 1.0 95 547 22% at 1 μΜ 66 0.8 2.2 96 0.2 0.8 67 0.6 2.3 97 122 34% at 1 μΜ 68 9.4 33 98 2.1 39 69 10 139 99 0.3 2.5 70 0.4 1.2 100 0.2 1.5 Example K¡ (nM) IC50(nM) Example Ki(nlW) IC50(nM) IF-2019-03 566964-APN-ANP#INPI Page 89 of 272 No. in hV1a cell line in hV1a cell line No. in hV1a cell line in hV1a cell line 101 0.2 1.3 131 0.3 0.7 102 5.9 23 132 0.3 2.5 103 0.2 0.7 133 0.4 6.5 104 0.2 0.6 134 0.2 1.5 105 0.3 1.4 135 2.9 54 106 0.1 1.8 136 0.2 1.6 107 1.0 12 137 0.7 9.2 108 0.2 4.9 138 0.2 5 109 0.4 2.7 139 9.3 130 110 2.1 8.3 140 2.4 57 111 0 .3 2.4 141 0.7 8.9 112 45.4 213 142 14.3 225 113 21 305 143 5.0 156 114 26.5 205 144 34 168 115 0.5 0.8 145 12.7 47 116 0.7 2.1 146 3.2 78 117 0.9 4.3 147 1.0 9.4 118 66 251 148 1.2 26 119 27 111 149 0.8 15 120 52 465 150 5.6 94 121 79 442 151 30 209 122 3 14 152 67 737 123 2.1 6.3 153 20.5 307 124 1.7 5.1 154 0.8 21 125 0.8 2.3 155 0.04 0.7 126 0.6 1.8 156 0.5 9.5 127 2.8 17 157 0.1 0.5 128 2 14 158 62 1510 129 0.5 20 159 8 216 130 2.4 6.1 160 0. 4 4.9 IF-2019-03 566964-APN-ANP#INPI Page 90 of 272 Example No. Ki(nM) in hV1a cell line iC50(nWI) in hV1a cell line Example No. Ki(nM) in hV1a cell line ICso(nM) in hV1a cell line 161 1.8 34 191 0.3 2.9 162 0.5 2.9 192 0.8 6.3 163 1.0 6.2 193 0.1 0.9 164 0.3 0.9 194 1.1 22 165 1.5 21 195 0.3 1 .6 166 6.2 169 196 0.5 2.7 167 0.4 2.6 197 0.3 4.1 168 0.4 0.8 198 0.2 0.9 169 0.9 2.3 199 2.2 23 170 15.3 38 200 114 1187 171 0.6 1.2 201 3.9 19 172 0.7 5.6 202 0.4 1.0 173 1.6 11 203 10.1 210 174 0 .7 3 204 0.2 2.7 175 50.5 323 205 0.2 2.7 176 0.4 1.1 206 0.2 0.9 yy 0.3 0.9 207 0.3 4.2 178 3.9 19 208 0.1 2.2 179 0.2 1.4 209 0.2 1.6 180 1.1 4.1 210 56 292 181 0.5 1.8 211 0.7 1.3 182 19 416 212 2.8 34 183 102 2120 213 0.6 5.5 184 0.6 25 214 66 672 185 4.1 19 215 0.2 3.7 186 0.4 1.2 216 0.7 1 .5 187 86 4750 217 0.3 1.4 188 0.5 5.3 218 97 1253 189 10 229 219 0.2 22 190 5.3 105 220 0.4 2.6 IF-2019-03 566964-APN-ANP#INPI Page 91 of 272 Example No. K¡ (nM) in hV1a cell line ECso(nM) in hV1a cell line Example No. Ki(nM) in hV1a cell line IC5o(nM) in hV1a cell line 221 0.9 9.8 238 0.7 8.2 222 5.8 40 239 1.2 5.6 223 1.6 8.1 240 0.5 3.1 224 0.7 3.6 241 0.4 2.6 225 48 854 242 0.5 1.8 226 0.5 4.2 243 0.4 2.8 227 1.0 51 244 25 263 228 0.8 6.1 245 130 229 0.4 2.1 246 0.5 3.4 230 0 .7 12 247 5 30 231 1.1 5.9 248 2.3 22 232 1.3 9.2 249 0.8 7 233 6.9 53 250 2.9 27 234 3.8 57 251 18.5 152 235 0.3 22 252 0.7 8.2 236 0.9 4.2 253 5 66 237 0.2 1.5 Vasopressin V1a receptor binding assay in mice Cells and radioligand The immortalized 1321N1 cell line (clone B9 / 1321N1) that constitutively and stably expresses the mouse vasopressin receptor V1a, compound vasopressin (8-L-Arginine), labeled with [Phenylalanyl-3,4,5-3H( N)] (Perkin Elmer Life and Analytical Sciences) as radioligand were used to determine the affinity of the prepared compounds. Method Membrane preparation: Membrane preparation of immortalized 1321N1 cells expressing the propagated mouse vasopressin V1a receptor was performed according to the method of Jarvis (Jarvis et al., J Pharmacol Exp Ther 2004, 310: IF-2019-03 566964-APN-ANP#INPI 92 Page 92 of 272 407-16). Cells were suspended in preparative buffer (50 mM Tris, 1 mM EDTA, 0.1 mM PMSF) and homogenized with a glass homogenizer vessel. To separate the raw membrane fraction, two consecutive centrifugation procedures were performed (40,000 g for 25 minutes at 40C), then the membrane was introduced into the preparatory buffer during a final washing step, divided into aliquots that were stored at - 800C until the time of measurement. The protein content of the prepared membrane was determined according to the Lowry method using a standard dilution line of bovine serum albumin (BSA) (Lowry et al., J Biol Chem 1951, 193: 265- 75). Receptor binding assay: In the receptor binding assay, substances with unknown affinity were used at a minimum of 8 different concentrations, with 3 parallels at each concentration. To determine the final affinity value, the results of at least two independent experiments were taken into account. The assay mixture included incubation buffer (50 mM Tris-HCl, pH 7.4 + 3% BSA), membrane preparation of 1321N1 cells expressing the mouse vasopressin V1a receptor (152 pg / ml). and Vasopressin (8-L-arginine), [Phenilalanyl-3,4,5-3H(N)J as radioligand (~ 35-50% KD concentration). Non-specific binding values ​​were determined in the presence of unlabeled 1.2x106M(Arg8)-vasopressin. Samples were incubated in a total volume of 0.33 ml for 60 minutes at 27°C. Free and membrane-bound ligands were separated by filtration through UniFilter® GF / B™ impregnated with 0.5% polyethyleneimine. After drying the filter plates, 40 μΙ of Microscint20 scintillation cocktail (Packard) was added to the samples. Finally, radioactivity was measured using MicroBeta2Microplate Counter (Perkin Elmer). The radioligand binding capacity of a substance is determined in at least two independent experiments. Specific binding of radioligands can be defined as the difference between total and non-specific binding in the presence of a saturating amount of the unlabeled ligand or different concentrations of the substance to be evaluated. The results are provided as a percentage of the specific binding inhibition achieved in the presence of the substance to be evaluated. The IC50 data (i.e., the concentration of the unknown substance that displaces 50% of the specific bound radioligand) are calculated from the concentration-displacement curve using the mathematical sigmoidal fitting method y = (A1-A2) / ( 1 + (x / x0)p)+A2 with Origin 7.5 software. (OriginLab Corporation, Northampton, USA. IF-2019-03 566964-APN-ANPAINPI Page 93 of 272 USA). During fitting, the asymptotes are not fixed. K¡ (inhibition constant) values ​​are given with the Cheng-Prusoff equation K = ICso / [1 +(L / Kd)] where [L] is the concentration of radioligand used in the experiment and [Kd] is the affinity of the radioactively labeled ligand for the given receptor. The Kd value is determined in advance using the Scatchard curve, Table 2: The binding affinity of certain compounds of the present invention measured in the mouse vasopressin V1α receptor binding assay Example No. K¡ (nM) in cell line mV1a 8 161 9 31 24 25 25 353 26 15 53 1.1 54 43 55 21 57 12 62 0.6 63 13 Vasopressin V2 receptor binding assay in humans Cells and radioligand The immortalized 1321N1 cell line (Perkin Elmer, ES-363-M400UA) (Lot No: 1765208) that stably and constitutively expresses the V2 receptor, human vasopressin receptor V2 that expresses the cell membrane CHO-K1 (Perkin Elmer , 6110541400UA), and the compound vasopressin (8-L-Arginine), labeled with [Phenylalanyl3,4,5-3H(N)] (Perkin Elmer Ufe and Analytical Sciences) as radioligand were used to determine the affinity of the prepared compounds . Method Receptor binding assay: In the receptor binding assay, substances with unknown affinity were used at a minimum of 8 different concentrations, with 3 IF-2019-03 566964-APN-ANP#INPI 94 Page 94 of 272 parallels in each concentration. To determine the final affinity value, the results of at least two independent experiments were taken into account. The assay mixture included incubation buffer (50 mM Tris-HCI, pH 7.4 + 3% BSA), membrane preparation of 1321N1 cells expressing human vasopressin V2 receptor (1.82 pg / ml ) and Vasopressin (8-L-arginine), [Phenylalanyl-3,4,5-3H(N)J as radioligand (-Kd concentration). Non-specific binding values ​​were determined in the presence of unlabeled 1.2x10'6M (Arg8)-vasopressin. Samples were incubated in a total volume of 0.55 ml for 90 minutes at 27°C. Free and membrane-bound ligands were separated by filtration through UniFilter® GF / B™ impregnated with 0.5% polyethyleneimine. After drying the filter plates, 40 μΙ of Microscint20 scintillation cocktail (Packard) was added to the samples. Finally, radioactivity was measured using MicroBeta2Microplate Counter (Perkin Elmer). The radioligand displacement capacity of a substance is determined in at least two independent experiments. Specific binding of radioligands can be defined as the difference between total and non-specific binding in the presence of a saturating amount of the unlabeled ligand or different concentrations of the substance to be evaluated. The results are provided as a percentage of the specific binding inhibition achieved in the presence of the substance to be evaluated. The IC50 data (i.e., the concentration of the unknown substance that displaces 50% of the specific bound radioligand) are calculated from the concentration-displacement curve using the mathematical sigmoidal fitting method y = (A1 -A2) / ( 1 + (x / x0)p)+A2 with Origin 7.5 software. (OriginLab Corporation, Northampton, USA). During fitting, the asymptotes are not fixed. K¡ (inhibition constant) values ​​are given with the Cheng-Prusoff equation K¡ = ICso / [1 +(L / Kd)] where [L] is the concentration of radioligand used in the experiment and [Kd] is the affinity of the radioactively labeled ligand for the given receptor. The Kd value is determined in advance using the Scatchard curve. Table 3: The binding affinity of certain compounds of the present invention measured in the human vasopressin V2 receptor binding assay on the 1321N1 cell line Example No. K¡o % inhibition at 1μΜ In cell line hV2 1321N1 1 4% IF-2019-03 566964-APN-ANP#INPI Page 95 of 272 6 3% 8 3050 nM 9 1190nM 18 255 nM 19 610 nM 20 365 nM 21 35% 24 2190 nM 25 6% 26 36% 47 366 nM 53 40 nM 54 662 nM 55 469 n M 57 446 nM 62 53 nM 63 575 nM Method Receptor binding assays were performed at at least 8 concentrations, with two or rather three parallel samples at each concentration, in at least two independent experiments using an incubation buffer (50 mM Tris-HCl, 5 mM MgCh, pH 7 ,4 + 0.1% BSA), membrane preparation of CHO-K1 cells (Perkin Elmer, 6110541400UA) expressing the human vasopressin V2 receptor (7 pg / μΙ) and Vasopressin (8-L-Arginine), [Phenylalan¡l-3,4,5'3H(N)J as radioligand (~ Kd concentration). Non-specific binding values ​​can be determined in the presence of unlabeled 1.2x10'6M (Arg8)-vasopressin. Samples were incubated in a total volume of 0.55 mL for 90 minutes at 27 °C. Free and membrane-bound ligands were separated by filtration through UniFilter® GF / BTM impregnated with polyethylenimine. The filter plates were washed three times with 0.5 mL of ice-cold wash buffer (50 mM Tris-HCl, pH 7.4). After drying the filter plates, 40 μl of Microscint-20 scintillation cocktail (Packard) was added to each well. Finally, the IF-2019-03 566964-APN-ANP#INPI Page 96 of 272 radioactivity was measured using the Tri-Carb 2900TR liquid scintillation analyzer (Perkin Elmer). The radioligand displacement capacity of a substance is determined in at least two independent experiments. Specific binding of radioligands can be defined as the difference between total and non-specific binding in the presence of a saturating amount of the unlabeled ligand or different concentrations of the substance to be evaluated. The results are provided as a percentage of the specific binding inhibition achieved in the presence of the substance to be evaluated. IC50 data (i.e., the concentration of the unknown substance that displaces 50% of the specific bound radioligand) are calculated from the concentration-displacement curve using the mathematical sigmoidal fit method y = (A1-A2) / ( 1 + (x / x0)p)+A2 with Origin 7.5 software. (OriginLab Corporation, Northampton, USA). During fitting, the asymptotes are not fixed. K¡ (inhibition constant) values ​​are given with the Cheng-Prusoff equation K¡ = ICso / [1 +(L / Kd)J where [L] is the concentration of radioligand used in the experiment and [KD] is the affinity of the radioactively labeled ligand for the given receptor. The Kd value is determined in advance using the Scatchard curve. The affinity data (K¡) measured in the 1321N1 cell line that expresses the human vasopressin V2 receptor are in a very close correlation with the K¡ results generated with the CHO-K1 cell line that expresses the V2 receptor of the human vasopressin. In vivo assay of functional V1a Animals Male mice (NMRI, ToxiCoop) weighing 18-40 g were used. The animals were kept for at least 5 days after birth; During housing and measurements, they were fed and watered ad libitum. The experiments were permitted by the Local Animal Protection Committee, and were carried out in accordance with the European Animal Protection Directives (EU Directive 2010 / 63 / EU). Method Animal behavior was measured through an automated behavior analysis system (LABORAS™). Sensors located under the platforms detect the mechanical vibration generated by the movement of the animal and IF-2019-03 566964-APN-ANP#INPI 97 Page 97 of 272 transformed into an electrical signal (Quinn et al., J Neurosci Methods 2003, 130: 83-92). After analyzing the signals, the system analyzes the elapsed time with the following behavioral parameters: locomotion, immobility, climbing, grooming. The grooming algorithm by definition is capable of measuring the scratching behavioral response. During the experiment, the mice were pretreated with the vehicle or the test substance, and after the pretreatment period, the scratching-inducing compound (s.c. 0.3 mg / kg oxytocin) was administered, and then the animals were placed individually in measuring cages. Their behavior was observed for 1 hour. To reduce exploratory activity, animals were measured after a 1-h habituation to the cage. Behavioral parameters were compared with parallel measured parameters of control animals. The behavioral inhibitory effect of the substances was calculated with average values ​​of the vehicle-treated groups measured in parallel and presented as the percentage of inhibition: 0% was expressed as the average value of the scratching behavior of the pre-treated animals with vehicle (and s.c. saline with vehicle pretreatment), while 100% was expressed as the average scratch value of vehicle-pretreated animals that received oxytocin subcutaneously. One-way analysis of variance (ANOVA) with Tukey's post hoc test was used for statistical analysis. Surprisingly, it has been found that certain compounds of the present invention produced a significant effect on the in vivo functional assay of the mouse V1a receptor. Table 4: The efficacy of certain compounds of the present invention in the in vivo mouse V1a functional assay: inhibition of oxytocin-induced scratching behavioral response after pretreatment with 10 mg / kg p.o. in mice. Example No. inhibition (%) Example No. inhibition (%) 8. 64 63 49 9 106* 66 76 12 34 74 30 23 75 88 79 24 94* 89 50 25 42* 96 49 IF-2019-03 566964-APN-ANP#INPI Page 98 of 272 26 71 99 60 29 89 100 96 53 118 101 105 54 70 103 71 55 91 104 67 56 92 126 43 57 84 157 108 58 96 198 41 60 40 204 65 61 41 205 66 62 99 * after i.p. treatment The Prenatal Valproate Model of Autism Spectrum Disorder (ASD) in Rats The prenatal valproate model has excellent construct and aspect validity, making it a widely accepted animal model of ASD (Christensen et al, JAMA 2013, 309: 1696-1703; Roullet et al, Neurotoxicol Teratol. 2013, 36:45-56). In this model, female Wistar rats (Harías, United Kingdom) were treated with a single dose of valproic acid (VPA, i.p. 600 mg / kg) at 12.5 days of pregnancy. After birth and separation, the examined male offspring were maintained under standard laboratory conditions until the completion of the studies. Four animals were kept together in standard cages at an external temperature of 22-24 °C and on a 12-12 hour light-dark cycle (07:30 a.m. - 07:30 p.m.). Food and water were available ad libitum. After treatment once a day with the test substance for 7 days and pretreatment on the day of measurement, the behavior of the rats in the social preference test was evaluated on day 59 or 60 after delivery. The social preference test is a widely accepted testing method for determining autistic behavior in rodents (Nadler et al., Genes Brain Behav 2004, 3:303-314; Bambini-Junior et al., Brain Res 2011, 1408: 8-16). The test consists of two paradigms, the first is the social contact avoidance test. In this paradigm, the social behavior of the examined animals can be determined with a special three-chamber apparatus. In the apparatus, the contact behavior of the conspecific area and the empty separate area surrounded with a perforated wall can be examined and compared. Rats treated with valproate prenatally IF-2019-03 566964-APN-ANP#INPI 99 Page 99 of 272 produce autistic behavior and spend much less time seeking responses from conspecifics than control animals treated with vehicle in utero. One day later, on postnatal day 60, the rats were tested in the social memory and recognition paradigm. In this, contact behavior with a new, previously unknown conspecific can be measured in comparison to a familiar conspecific. In the social contact avoidance paradigm, rats treated with valproate (VPA / VEH) showed a significant decrease in active time spent with social behavior compared to control animals treated with in utero vehicle (VEH / VEH). Certain 5,6-dihydro-4H-[1,2,4]triazolo[4,3a][1]benzazepine compounds of the present invention substituted in the 5-position were unexpectedly effective in this assay and treatment significantly reversed the statistically the value of VPA / VEH to the value of the animals treated with VEH / VEH. Rats treated with SAHA (suberoil anilide or vorinostat) used as a positive control also showed a statistically significant increase in the time spent in the social search response (Foley et al, Eur J Pharmacol 2014, 727: 8086). In the social memory recognition paradigm, valproate-treated rats showed a significant decrease in active time spent searching for novel, unfamiliar animals compared to in utero vehicle-treated control animals. Certain 5,6-dihydro-4H-[1,2,4]triazolo[4,3a][1]benzazepine compounds of the present invention substituted in the 5 position made the behavior of the animals more socialized and were able to significantly increase the active time spent searching for the response of new animals. Unexpectedly, the treatment reverted the VPA / VEH value to the value of the VEH / VEH-treated animals. SAHA-treated rats used as a positive control also showed a statistically significant increase in time spent searching for a response. Therefore, certain compounds of the present invention exhibited significant behavioral benefits in the present animal model involving the clinical symptoms of ASD, thus providing a therapeutic opportunity for the treatment of human ASD symptoms. IF-2019-03 566964-APN-ANP#INPI 100 Page 100 of 272 Table 5: The effects on active contact time in the social contact avoidance and social memory recognition paradigms of certain compounds of the present invention social contact avoidance social memory recognition active contact time [sec] % effect new active contact time [sec] % effect Example 26Error! Ίο is the origin of the reference. VEH / VEH 147.1 ± 13.8 136.6 ±7.6 VPA / VEH 41.1 ±8.2 18.0 ± 6.2 VPA / SAHA 5 mg / kg i,p, 156.0 ±6 .7 115 155.5 ±5.8 137 VPA / Example 26 1.5 mg / kg i,p, 71.2± 15.9 30 83.7 ± 11.8 66 5 mg / kg i,p, 116 .4 ±22.5 75 133.5 ± 10.0 115 15 mg / kg i,p, 148.7 ±8.3 107 141.9 ±9.1 124 Data presented in the table are provided as mean ± standard error of the mean (S.E.M.) and are rounded to decimal form. Percentages were calculated from the raw data and rounded to integer values ​​(where VEH / VEH = 100%, VPA / VEH = 0%). The present invention will be further illustrated through the following embodiments, without limiting the scope of the present invention thereto. Based on part of the above description and examples, the person skilled in the art can determine the essential characteristics of the invention and, without departing from its essence and scope, can make certain changes and modifications to adapt the invention to various applications and conditions. . As a result, the invention is not limited to the following illustrative examples, but rather to the scope determined by the claims that follow. In general, the compounds of general formula (I) can be prepared according to the common general knowledge of the person skilled in the art and / or the methods described for the working examples and / or intermediates. Solvents, temperatures, IF-2019-03 566964-APN-ANP#INPI 101 Page 101 of 272 pressures and other reaction conditions can be easily selected by the person skilled in the art. The starting materials are commercially available and / or can be easily prepared by one skilled in the art. During the preparation of compounds, combinatorial techniques can be used, for example, when the present intermediate groups are suitable for the use of these methods. In describing the syntheses, the following terms and abbreviations have been used: dry = anhydrous Boc = tert-butoxycarbonyl DIPEA = Λ / , / V-diisopropyl-ethylamine DMAP = 4-dimethylamino-pyridine DMF = Λ / , / V-dimethylformamide EDC = / V-(3-dimethylaminopropyl)- / V-ethylcarbodiimide hydrochloride HOBt - 1-hydroxybenzotriazole hydrate HBTU = A / ,A / ; / V; / V-tetramethyl-O-(1H-benzotriazol-1“yl)uronium hexafluorophosphate K2CO3 = Lawesson's reactive potassium carbonate = 2,4-bis(4-methoxyphenyl)-1,3,2,4-dithiadiphosphetane-2,4-disulfide Meldrum acid = 2,2-dimethyl-1,3-dioxane -4,6-dione MgSCU = magnesium sulfate NaBFL = sodium borohydride NaBH(OAc)3 = sodium triacetoxy borohydride NaHCOs = sodium bicarbonate NaCI = sodium chloride NasCOs = sodium carbonate NaOH - sodium hydroxide Na2SÜ4 = sodium sulfate Pd / C = palladium on carbon Phg = phenylglycine IF-2019-03 566964-APN-ANPAINPI 102 Page 102 of 272 Pt / C = platinum on carbon THF = tetrahydrofuran Intermediate 1 3-r(ter“butoxy¡carbonyl)amino1-4-(5Chloro-2-nitrophen¡l)butanoic acid non2γ'” ΌΟΟΗ Cl Method A) a) 2-[(tert-butoxycarbonyl)amino1-3-(5-cioro-2-nitrophenyl)propanoic acid no2 COOH CL To a stirred and cooled mixture of 3.03 g (12.4 mmol) of 2-amino-3-(5chloro-2-nitrophenyl)propanoic acid (N.A. Meanwell et al., J Med Chem 1991, 34:2906-2916 ), 55 mL of 1,4-dioxane, 12 mL of water and 12.4 mL of 10% NaOH solution, 3.35 g of di-tert-butyl dicarbonate (15.4 mmol) was added and the mixture It was stirred at room temperature overnight. Once the reaction was complete, the pH of the mixture was adjusted to 7 with 10% hydrochloric acid solution, and concentrated. Dichloromethane was added to the residue and stirred at room temperature for 1 hour. The precipitated solid was filtered, washed with dichloromethane, the filtrate was concentrated and the residue was purified by column chromatography using dichloromethane:methanol=9:1 as eluent. In this way, 3.83 g (90%) of the title product was obtained. MS (ESI) m / z 367.1 (M+Na)+. b) ter-butii A / -Í1 -(5-chloro-2-nitrophenyl)-4-diazo-3-oxobutan-2-yl1carbamate NOZ ClN-^N A mixture of 2.55 g (7.4 mmol) of 2-[(tert-butoxycarbonyl)amino]-3-(5-chloro2-nitrophenyl)propanoic acid, 40 mL of diethyl ether and 1.25 mL (9, 0 mmol) of triethylamine was cooled to 30 °C and 1.15 mL (8.9 mmol) of isobutyl chloroformate was added dropwise with stirring. The mixture was stirred at −30 °C for 15 min, then a solution of 0.7 M diazomethane in 50 mL of diethyl ether was added dropwise to maintain the temperature between −25 °C and −30 °C. The mixture was allowed to warm to 0 °C and stirred at this temperature for 1 hour, then the excess diazomethane was decomposed with acetic acid. The reaction mixture is IF-2019-03 566964-APN-ANP#INPI 103 Page 103 of 272 diluted with ethyl acetate, the pH was adjusted to 7 with saturated NaHCCh solution, the phases were separated and the organic phase was washed with saturated NaCl solution, dried in the presence of anhydrous Na2SO4, filtered and concentrated. The residue was purified by column chromatography using dichloromethane:methanol=95:5 as eluent. In this way, 1.72 g (63%) of the title product was obtained. MS (ESI) m / z 391.1 (M+Na)+. c) 3-[(tert-butoxy¡carbonyl)amino]-4-(5-chloro-2-nitrophen¡l)butanoic acid CL A mixture of 8.26 g (22.4 mmol) of fer-butyl N-[1-(5-chloro-2-nitrophenyl)-4-diazo-3oxobutan-2-¡l]carbamate, 300 ml_ of 1, 4-dioxane, 60 mL of water and 0.49 g (2.1 mmol) of silver benzoate were stirred at room temperature for 20 hours, then diluted with 300 mL of ethyl acetate, 300 mL of hydrochloric acid was added to the 5% and the phases were separated. The organic phase was washed with saturated NaCl, dried in the presence of anhydrous Na2SO4, filtered and concentrated. The residue was purified by column chromatography using dichloromethane:methanol=9:1 as eluent. In this way, 5.28 g (66%) of the title product was obtained. MS (ESI) m / z 381.1 (M+Na)+. Method B) a) 5-F2-(5-chloro-2-nitrophenyl)-1-hydroxyethylidene1-2,2-dimethyl-1,3-dioxane-4,6-dione 4.925 g (22.84 mmol) of (5-chloro-2-nitrophenyl) acetic acid (Enamine Ltd.) was dissolved in 250 mL of acetonitrile and 8.95 mL (51.4 mmol) of DIPEA, 279 mg were added (2.3 mmol) of DMAP and 3.72 g (25.1 mmol) of Meldrum acid while stirring. After cooling, 3.1 mL (25.1 mmol) of pivaloyl chloride was added slowly dropwise to maintain the temperature below 30 °C. The reaction mixture was stirred for 4 hours at 45 °C, then the solution was cooled to 0 °C and 90 mL of 1Λ / hydrochloric acid and 90 mL of water were added. The precipitated material was filtered, washed with water, and dried. In this way, 6.62 g (85%) of the title product was obtained as a white powder which was used without further purification in the next step. b) methyl 4-(5-chloro-2-nitrophenyl)-3-oxobutanoate IF-2019-03 566964-APN-ANP#INPI 104 Page 104 of 272 NO COOME CL A mixture of 6.62 g (19.4 mmol) of 5-[2-(5-chloro-2-nitrophenyl)-1-hydroxyethylidenej2,2-dimethyl-1,3-dioxane-4,6-dione. 70 mL of methanol and 280 mL of toluene were refluxed for 3 hours. The mixture was cooled to room temperature, 130 mL of saturated NaCl and 100 mL of ethyl acetate were added, the phases were separated, the organic phase was dried in the presence of anhydrous MgSÜ4, filtered and concentrated. In this way, 5.21 g (99%) of the title product was obtained as a cream-colored oil, which crystallized under standing for a few days. MS (ESI) m / z 272.1 (M+H)+. c) methyl 3-aminO4-(5-chloro-2-nitrophenyl)but-2-enoate no. COOME CL A mixture of 5.40 g (20 mmol) of methyl 4-(5-chloro-2-nitrophenyl)-3-oxobutanoate, 60 mL of methanol and 7.8 g (101 mmol) of ammonium acetate was heated to reflux. for 5 hours, then concentrated. Saturated NaHCO3 solution was added to the residue and extracted with dichloromethane. The organic phase was dried in the presence of anhydrous MgSCU, filtered and concentrated. In this way, 4.85 g (90%) of the title product was obtained as a yellow solid. MS (ESI) m / z 271.7 (M+H)+. d) methyl 3-amino-4-(5-chloro-2-nitrophenyl)butanoate NO, COOME CL 11.23 g (41.5 mmol) of methyl 3-amino-4-(5-chloro-2-nitrophenyl)but-2-enoate was dissolved in 120 mL of acetic acid and 6.27 g (29, 6 mmol) of NaBH(OAc)3during cooling and stirring. The mixture was stirred at room temperature for 2 hours and another 6.27 g (29.6 mmol) of NaBH(OAc)3 was added. The reaction mixture was stirred at room temperature for 20 hours and poured into ice water. The pH of the mixture was adjusted to 8 with solid K2CO3 and extracted with ethyl acetate, the organic phase was dried in the presence of anhydrous MgSCU, filtered and concentrated. In this way, 11.32 g (100%) of the title product was obtained as yellow oil. MS (ESI) m / z 273.7 (M+H)+. e) methyl 3[(fer-butoxycarbonyl)amino]-4-(5-chloro-2-nitropheniQbutanoate IF-2019-03 566964-APN-ANP#INPI 105 Page 105 of 272 .NHBoc NO2^COOME CL To a mixture of 11.32 g (41.5 mmol) of methyl 3-amino-4-(5-chloro-2nitrophenyl)butanoate, 330 mL of methanol and 6.82 g (82.4 mmol) of NaHCOs was added 11.32 g (51.9 mmol) of di-tert-butyl dicarbonate during cooling and stirring, and the mixture was stirred at room temperature for 20 hours. The reaction mixture was concentrated, 500 mL of water was added to the residue, the precipitated product was filtered, washed with water, and dried. In this way, 13.83 g (89%) of the title product was obtained as a yellow powder. MS (ESI) m / z 395.0 (M+Na)+. f) 3-Kter-butoxycarbon¡l)amnol-4-(5-chloro-2-nitropheniQbutanoic acid no2 boc ΈΟΟΗ CL To a stirred mixture of 13.83 g (37.1 mmol) of methyl 3-[(fer-butoxycarbonyl)amino]4-(5-chloro-2-nitrophenyl)butanoate, 260 mL of THF, 130 mL of methanol and To 130 mL of water, 8 g (190 mmol) of lithium hydroxide monohydrate was added while stirring. The reaction mixture was stirred at room temperature for 20 hours, and then concentrated. 300 mL of water was added to the residue, the pH of the mixture was adjusted to 5 with 10% hydrochloric acid, and the mixture was stirred at room temperature for 1 hour. The precipitated product was filtered, washed with water, and dried. In this way, 13.2 g (99%) of the title product was obtained. MS (ESI) m / z 381.1 (M+Na)+. Intermediate 2 4-(2-amino-5-chlorophenyl)-3-r(tert-butoxycarbonyl)aminobutanoic acid nh2 Ό00Η CL Method A) To a mixture of 5.28 g (14.7 mmol) of 3-[(tert-butoxycarbonyl)amino]-4-(5chloro-2-nitrophenyl)butanoic acid (Intermediate 1), 140 mL of methanol and 350 mg (1.47 mmol) of nickel chloride hexahydrate, 1.35 g (35.7 mmol) of NaBH4 was added under ice cooling, then the reaction mixture was stirred at room temperature for 20 hours. The pH of the reaction mixture was adjusted to 6 with 10% hydrochloric acid, the mixture was IF-2019-03 566964-APN-ANP#INPI 106 Page 106 of 272 filtered through Celite, the filtrate was concentrated and the residue was purified by column chromatography using dichloromethane:methanol=9:1 as eluent. In this way, 2.11 g (44%) of the title product was obtained. MS (ESI) m / z 351.2 (M+Na)+. Method B) To a mixture of 3.0 g (8.34 mmol) of 3-[(tert-butoxycarbonyl)amino]-4-(5chloro-2-nitrophenyl)butanoic acid (Intermediate 1) and 400 mL of toluene, 300 mg of 5% Pt / C catalyst under argon, then the reaction mixture was stirred at room temperature in a hydrogen atmosphere. Once the reaction was complete, the catalyst was filtered through Celite, washed with methanol, and the filtrate was concentrated. In this way, 2.64 g (96%) of the title product was obtained. Intermediate 3 tert-butyl (7Chloro-2-oxo-2,3,4,5tetrahydro-1 H-1 -benzazepin-4-yl)carbamate A mixture of 5.52 g (16.79 mmol) 4-(2-amino-5-chlorophenyl)-3-[(terbutoxycarbonyl)amino]butanoic acid (Intermediate 2), 60 mL DMF, 3.9 g (20.34 mmol) of EDC, 7 mL (40.2 mmol) of DIPEA and 3.08 g (20.1 mmol) of HOBt were stirred at room temperature for 20 hours, then the reaction mixture was concentrated. 100 mL of saturated NaHCO3 solution was added to the residue, and the mixture was stirred at room temperature for 1 hour. The crystalline product was completely filtered, washed with water, and dried. In this way, 4.71 g (90%) of the title product was obtained. MS (ESI) m / z 333.1 (M+Na)+. Intermediate 4 tert-butyl (7-chloro-2-thioxo-2,3,4,5-tetrahydro-1H-1-benzazepin-4-yl)carbamate A mixture of 2.35 g (7.56 mmol) of tert-butyl (7-chloro-2-oxo-2,3,4,5-tetrahydro-1H1-benzazepin-4-yl)carbamate (Intermediate 3), 65 mL of pyridine and 3.98 g (9.84 mmol) of Lawesson's reagent were stirred at 120 °C for 4 hours, then the reaction mixture was concentrated. 100 mL of saturated NaHCO3 solution was added to the residue and the mixture was stirred at room temperature for 1 hour. The crystalline product was filtered IF-2019-03 566964-APN-ANP#INPI 107 Page 107 of 272 completely, washed with water, and dried. In this way, 2.32 g (94%) of the title product was obtained. MS (ESI) m / z 327.2 (M+H)+. Intermediate 5 tert-butyl [7-chloro-2-(methylsulfanyl)-4,5-dihydro-3H-1-benzazepin-4-yl1carbamate A mixture of 2.32 g (7.1 mmol) of tert-butyl (7-chloro-2-thioxo-2,3,4,54etrahydro-1H1-benzazepin-4-yl)carbamate (Intermediate 4), 140 mL of acetone, 1.96 g (14.2 mmol) of K2CO3, and 1.33 mL (21.4 mmol) of iodomethane were stirred at room temperature for 20 hours. The reaction mixture was concentrated, water was added to the residue and extracted with ethyl acetate, the organic phase was dried in the presence of anhydrous Na2SO4, filtered, and concentrated. In this way, 2.04 g (84%) of the title product was obtained. MS (ESI) m / z 341.2 (M+H)+. Intermediate 6-ethyl (5-methoxy-2-nítroten i Dacetate To a mixture of 10.18 g (90.7 mmol) of potassium tert-butoxide and 90 mL of dry DMF, a mixture of 3.86 mL (36.3 mmol) of ethyl chloroacetate, 5.56 g (36.3 mmol) of 4-nitroanisole (Merck) and 40 mL of drop-dried DMF at 0 °C under nitrogen. The resulting dark purple reaction mixture was stirred at 0 °C for 2.5 hours, then 35 mL of 3Λ / hydrochloric acid was added dropwise and diluted with water. The mixture was extracted twice with ethyl acetate, the combined organic phases were washed with aqueous NaCl, dried in the presence of anhydrous Na2SO4, filtered and concentrated. In this way, 7.33 g (84%) of the title product was obtained as brown oil. MS (ESI) m / z 240.2 (M+H)+. Intermediate 7 acid (5-methoxy-2-nítroten i Dacetic J300H MeO A mixture of 7.33 g (30.6 mmol) ethyl (5-methoxy-2-nitrophenyl)acetate (Intermediate 6), 1.54 g (36.8 mmol) lithium hydroxide monohydrate, 90 mL THF and 45 mL of water was stirred at room temperature for 16 hours. The organic solvent is IF-2019-03 566964-APN-ANP#INPI 108 Page 108 of 272 evaporated and the residue was extracted with ethyl acetate. 40 mL of 1Λ / hydrochloric acid was added to the aqueous phase, extracted twice with ethyl acetate, the combined organic phases were dried in the presence of anhydrous Na2SO4, filtered and concentrated. In this way, 2.27 g (35%) of the title product was obtained. MS (ESI) m / z 229.1 (M+NH4)+. Intermediate 8 5[1-hydroxy-2-(5methoxy-2-nitrophenyl)ethylidene1-2,2-dimethyl-1,3-dioxane-4,6-dione no2 OH O OMe To a mixture of 2.27 g (10.7 mmol) of (5-methoxy-2-nitrophenyl)acetic acid (Intermediate 7), 40 mL of dry acetonitrile, 1.70 g (11.8 mmol) of acid Meldrum, 131 mg (1.07 mmol) of DMAP and 4.21 mL (24.2 mmol) of DIPEA, 1.46 mL (11.8 mmol) of trimethylacetyl chloride was added dropwise and the reaction mixture was stirred at 40 °C for 4 hours. The mixture was cooled to 0 °C, 26 mL of 1 / V hydrochloric acid was added dropwise and diluted with 60 mL of water. The precipitated product was completely filtered, washed with water and dried in the presence of phosphorus pentoxide in a vacuum desiccator. In this way, 2.45 g (68%) of the title product was obtained, which was used without further purification. Intermediate 9-methyl 4-(5-methoxy-2-nitrophenyl)-3-oxobutanoate no2 COOME OMe A mixture of 2.45 g (7.26 mmol) of 5-[1-hydroxy-2-(5-methoxy-2-nitrophenyl)ethylidene]2,2-dimethyl-1,3-dioxane-4,6- dione (Intermediate 8), 10 mL of methanol, and 30 mL of toluene were stirred at 115 °C for 1.5 hours. The mixture was cooled to room temperature, ethyl acetate and aqueous NaCl were added. The phases were separated, the organic phase was dried in the presence of anhydrous Na2SO4, filtered and concentrated. Cyclohexane was added to the residue, stirred for 1 hour and the product was filtered completely. In this way, 1.85 g (95%) of the title product was obtained. MS (ESI) m / z 268.2 (M+H)+. Intermediate 10 methyl 3-amino-4-(5-methoxy-2nitrophenyl)but-2-enoate IF-2019-03 566964-APN-ANP#INPI 109 Page 109 of 272 COOME OMe A mixture of 1.07 g (4 mmol) of methyl-4-(5-methoxy-2-nitrophenyl)-3-oxobutanoate (Intermediate 9), 20 mL of methanol and 6.17 g (80 mmol) of acetate ammonium was stirred at room temperature for 16 hours. The mixture was diluted with water, stirred for 1 hour, and the product was filtered completely. In this way, 0.92 g (86%) of the title product was obtained, which was used without further purification. Intermediate 11 methyl 3-anryno-4-(5-methoxy-2-nitrophenyl)butaryate To 9 mL of acetic acid, 0.67 g (17.8 mmol) of NaBhL was added in 45 min while maintaining the temperature at around 10 °C. 0.79 g (3 mmol) of methyl-3-amino-4-(5-methoxy-2-nitrophenyl)but-2-enoate (Intermediate 10) was added to the resulting mixture and stirred at room temperature for 1. 5 hours. The mixture was diluted with water during cooling, then basified with solid K2CO3 and extracted twice with ethyl acetate. The combined organic phases were washed with aqueous K2CO3 solution and then with aqueous NaCl solution, dried in the presence of anhydrous Na2SO4, filtered and concentrated. In this way, 0.69 g (87%) of the title product was obtained. MS (ESI) m / z 269.2 (M+H)+. Intermediate 12 methyl 3-r(tert-butoxycarbonyl)amino1-4-(5-methoxy-2-nitrophenyl)butanoate OMe To a mixture of 0.69 g (2.6 mmol) of methyl 3-amino-4-(5-methoxy-2nitrophenyl)butanoate (Intermediate 11), 20 mL of methanol and 0.7 g (3.22 mmol) di-yer-butyldicarbonate, 0.43 g (5.14 mmol) of NaHCO3 was added at 10°C. The reaction mixture was stirred at room temperature for 1.5 hours, diluted with water, and the precipitated product was filtered. In this way, 0.72 g (76%) of the title product was obtained. MS (ESI) m / z 391.1 (M+Na)+. IF-2019-03 566964-APN-ANP#INPI 110 Page 110 of 272 Intermediate 13 methyl 4-(2-am i no-5-methoxyphenyl )-34( tert-butoxy carbon i Daminolbutanoate .NHBoc COOME 0.72 g (2 mmol) of methyl 3-[(tert-butoxycarbonyl)amino]-4-(5-methoxy-2nitrophenyl)butanoate (Intermediate 12) in 50 mL of methane! was hydrogenated in the presence of 80 mg of 10% Pd / C at room temperature under atmospheric pressure. After filtration of the catalyst, the filtrate was concentrated to form 0.62 g (94%) of the title product. MS (ESI) m / z 339.3 (M+H)+. Intermediate 14 tert-butyl (7-methoxy-2-oxo-2,3A5-tetrahydro-1H-1-benzazepin-4-yl)carbamate H,N· 0.56 g (1.7 mmol) of methyl 4-(2-amino-5-methoxypheniI)-3-[(tert-butoxycarbonyl)amino]butanoate (Intermediate 13) was dissolved in 12 mL of methanol and 0 .26 mL of 30% methanolic sodium methoxide solution, and the mixture was stirred at room temperature for 20 hours. 1.7 mL of 1 / V hydrochloric acid was added to the mixture during cooling, diluted with water, and the resulting precipitate was filtered, washed with water, and dried in the presence of phosphorus pentoxide in a vacuum desiccator. In this way, 0.4 g (80%) of the title product was obtained. MS (ESI) m / z 329.2 (M+Na)*. Intermediate 15 tert-butyl (7-methoxy-2-thioxo-2,3A5-tetrahydro-1H-1-benzazepin-4-yl)carbamate HZS A mixture of 0.44 g (1.4 mmol) of tert-butyl (7-methoxy-2-oxo-2,3,4,5-tetrahydro-1H1-benzazepin-4-yl)carbamate (Intermediate 14), 20 mL of pyridine and 1.34 g (3.3 mmol) of Lawesson's reagent were stirred at 120 °C for 4.5 hours. The reaction mixture was cooled to room temperature, diluted with ethyl acetate, and washed twice with 5% NaHCOs solution. The organic phase was dried in the presence of anhydrous NaaSCU, filtered and concentrated. Diethyl ether was added to the residue and the precipitated solid was filtered completely. IF-2019-03 566964-APN-ANP#INPI 111 Page 111 of 272 after 1 hour of stirring. The crude product was recrystallized from 7 mL of ethanol to form 0.15 g (32%) of the title product. MS (ESI) m / z 345.2 (M+Na)+. Intermediary 16 5-F1 -hydroxy-2-(5-methyl-2-nitrophenyl)ethylidene]-2,2-dimethyl-1,3-dioxane-4,6dione The title product was prepared from 2-(5-methyl-2-nitrophenyl)acetic acid (Astatech Inc.) according to the method described for Intermediate 8, and was used without further purification. Intermediate 17 methyl 4-(5-methyl-2nitrophenyl)-3-oxobutanoate The title product was prepared from 5-[1-hydroxy-2-(5-methyl-2nitrophenyl)ethylidene]-2,2-dimethyl-1,3-dioxane-4,6-dione (Intermediate 16 ) according to the method described for Intermediate 9, and was used without further purification. Intermediate 18 methyl 3-amino-4-(5-methyl-2-nitrophenyl)but-2-enoate The title product was prepared from methyl-4-(5-methyl-2-nitrophenyl)-3oxobutanoate (Intermediate 17) according to the method described for Intermediate 10, and used without further purification. Intermediate 19 methyl 3-amino-4-(5-methyl-2-nitrophenyl)butanoate no2 L ¡1 NH2 IF-2019-03 566964-APN-ANP#INPI 112 Page 112 of 272 The title product was prepared from methyl-3-amino-4-(5-methyl-2-nitrophenyl)but2-enoate (Intermediate 18) according to the method described for Intermediate 11, and used without further purification . Intermediate 20 methyl 3[(tert-butoxycarbonyl)aminof-4-(5methyl-2-nitrophenyl)butanoate no2 H Boc f ¥ ¥ VOOMe The title product was prepared from methyl-3-amino-4-(5“methyl-2nitrophenyl)butanoate (Intermediate 19) according to the method described for Intermediate 12, and used without further purification. Intermediate 21 methyl 4-(2-amino-5-methyl-phenyl)-3-phyter-butoxycarbonyl)amino1butanoate nh2xX / -yNHBoc TOOME The title product was prepared from methyl-3-[(tert-butoxycarbonyl)amino]-4-(5methyl-2-nitrophenyl)butanoate (Intermediate 20) according to the method described for Intermediate 13, and used without additional purification. Intermediate 22 tert-butyl (7-methyl-2-oxo-2,3,4,5-tetrahydro-1 H-1 -benzazepin-4-iDcarbamate NHBoc The title product was prepared from methyl 4-(2-amino-5-methyl-phenyl)-3-[(tert-butoxycarbonyl)amino]butanoate (Intermediate 21) according to the method described for Intermediate 14. MS ( ESI) m / z 313.1 (M+Na)+. Intermediate 23 tert-butyl (7-methyl-2-thioxo-2,3,4,5-tetrahydro-1H-1-benzazepin-4-yl)carbamate NHBoc IF-2019-03 566964-APN-ANP#INPI 113 Page 113 of 272 A mixture of 0.71 g (2.4 mmol) of fer-butyl (7-methyl-2-oxo-2,3,4,5-tetrahydro-1H-1benzazepin-4-yl)carbamate (Intermediate 22), 25 mL of dry THF and 0.59 g (1.47 mmol) of Lawesson's reagent were stirred at room temperature for 16 hours. The solvent was evaporated and the residue was purified by column chromatography using cyclohexane:ethyl acetate=80:20 as eluent to form 0.42 g (56%) of the title product. MS (ESI) m / z 307 (M+H)+. Intermediate 24 ethyl (5-bromo-2-nitrophenioacetate no2 COOEt Br The title product was prepared from 4-nitro-bromobenzene (Combi-Blocks Inc.) according to the method described for Intermediate 6. MS (ESI) m / z 305.1 (M+NH4)Á Intermediate 25 (5-bromo-2-nitrophenyl) acetic acid NO 2 COOH Br The title product was prepared from ethyl-(5-bromo-2-nitrophenyl)acetate (Intermediate 24) according to the method described for Intermediate 7, and was used without further purification. Intermediary 26 5-ri-hydroxy2(5-bromo-2-nitropheniDetylidene1-2,2dimethyl-1,3-dioxane-4,6-dione Br The title product was prepared from (5-bromo-2-nitrophenyl)acetic acid (Intermediate 25) according to the method described for Intermediate 8, and was used without further purification. Intermediate 27 methyl 4-(5-bromo-2-nitrophenyl)-3-oxobutanoate IF-2019-03 566964-APN-ANP#INPI 114 Page 114 of 272 'COOMe The title product was prepared from 5-[1-hydroxy-2-(5-bromo-2nitrophenyl)ethylidene]-2,2-dimethyl-1,3-dioxane-4,6-dione (Intermediate 26) according to the method described for Intermediate 9. MS (ESI) m / z 335.0 (M+NhU)*. Intermediate 28 methyl 3-amino-4-(5bromo-2-nitrophenyl)but-2-enoate 'COOMe The title product was prepared from methyl-4-(5-bromo-2-nitrophenyl)-3oxobutanoate (Intermediate 27) according to the method described for Intermediate 10, and was used without further purification. Intermediate 29 methyl 3amino-4-(5-bromO2nitrophenyl)butanoate COOME The title product was prepared from methyl-3-amino-4-(5-bromo-2nitrophenyl)but-2-enoate (Intermediate 28) according to the method described for Intermediate 11. MS (ESI) m / z 319.0 (M+H)+. Intermediate 30 methyl 3-r(tert-butoxycarbon¡l)aminol-4-(5-bromo-2nitrophenyl)butanoate The title product was prepared from methyl-3-amino-4-(5-bromo-2nitrophenyl)butanoate (Intermediate 29) according to the method described for Intermediate 12, MS (ESI) m / z 439.1 (M+Na)+. Intermediary 31 IF-2019-03 566964-APN-ANP#INPI 115 Page 115 of 272 methyl 4-(2-amino-5-bromo-phenyl)-3-[(ter“butoxycarbonyl)aminobutanoate nh2NHBoc Y' ^COoMe Br 2.45 g (5.87 mmol) of methyl 3-[(tert-butoxycarbonyl)amino]-4-(5-bromo-2nitrophenyl)butanoate (Intermediate 30) in 200 mL of toluene was hydrogenated at room temperature under atmospheric pressure in the presence of 0.25 g of 5% Pt / C catalyst. After filtration of the catalyst, the filtrate was concentrated to form 2.15 g (94%) of the title product. MS (ESI) m / z 409.1 (M+Na)+. Intermediate 32 tert-butyl (7-bromo-2-oxo-2,3,4,5-tetrahydro-1 H-1-benzazepin-4-yl)carbamate h NHBoc To a mixture of 2.15 g (5.55 mmol) of methyl 4-(2-amino-5-bromo-phenyl)-3-[(tert-butoxycarbonyl)amino]butanoate (Intermediate 31) and 60 mL of dry THF, 0.69 g (6.11 mmol) of potassium tert-butoxide was added under nitrogen at 0 °C in 30 minutes and the reaction mixture was stirred at room temperature for 3 hours. Dry ice was then added, and the mixture was then diluted with ethyl acetate and water. The phases were separated, the aqueous phase was extracted with ethyl acetate, the combined organic phases were washed with aqueous NaCl solution, dried in the presence of anhydrous NaaSO4, filtered and concentrated. Diethyl ether was added to the crude product, stirred for 1 hour at room temperature, filtered and washed with diethyl ether. In this way, 0.83 g (42%) of the title product was obtained. MS (ESI) m / z 409.1 (M+Na)+. intermediate 33 tert-butyl í7-bromo-2-thioxo-2,3A5-tetrahydro-1H-1-benzazepin-4-yl)carbamate A mixture of 0.83 g (2.3 mmol) of tert-butyl (7-bromo-2-oxo-2,3:4,5-tetrahydro-1H1-benzazepin-4-yl)carbamate (Intermediate 32), 28 mL of dry THF and 0.57 g (1.4 mmol) of Lawesson's reagent were stirred at room temperature for 16 hours. The solvent was evaporated, diethyl ether was added to the residue and the precipitated solid was completely filtered. IF-2019-03 566964-APN-ANP#INPI 116 Page 116 of 272 after 1 hour of stirring. In this way, 0.79 g (91%) of the title product was obtained. MS (ESI) m / z 371 (M+H)+. Intermediate 34 methyl r2-(5-bromO“2-nitrobenzyl)-1,3“dioxolan-2-yl1acetate COOME A mixture of 3.28 g (10.4 mmol) methyl 4-(5-bromo-2-nitrophenyl)-3-oxobutanoate (Intermediate 27), 1.7 mL methanol, 118 mg (0.6 mmol) of p-toluene-sulfonic acid monohydrate, 5.68 mL (52 mmol) of trimethyl orthoformate and 11.6 mL (207 mmol) of ethylene glycol was stirred at 50 °C for 96 hours. Aqueous K2CO3 solution was added to the reaction mixture, then extracted twice with ethyl acetate. The organic phases were dried in the presence of anhydrous Na2SO4, filtered and concentrated. The residue was purified by column chromatography using cyclohexane:ethyl acetate=80:20 as eluent. In this way, 2.29 g (61%) of the title product was obtained. MS (ESI) m / z 379.1 (M+NH4)+. Intermediate 35 methyl r2-(2-amino-5-bromobenzyl)-1,3-dioxolan-2-¡nacetate ^ / NH2 COOME 2.29 g (6.4 mmol) of methyl-[2-(5-bromo-2-nitrobenzyl)-1,3-dioxolan-2-yl]acetate (Intermediate 34) in 200 mL of toluene was hydrogenated at temperature ambient under atmospheric pressure in the presence of 0.56 g 5% Pt / C catalyst. After filtration of the catalyst, the filtrate was concentrated to form 2.1 g (100%) of the title product. MS (ESI) m / z 330.0 (M+H)+. Intermediary 36 7-bromo-l,5-dihydrospirori-benzazepine-4,2'-M,31dioxolane]-2(3H)-one IF-2019-03 566964-APN-ANPAINPI 117 Page 117 of 272 The title product was prepared from methyl [2-(2-amino-5-bromobenzyl)-1,3dioxolan-2-yl]acetate (Intermediate 35) according to the method described for Intermediate 32. MS (ESI ) m / z 300.0 (M+H)+. Intermediate 37 ethyl [2-nitro-5-(trifluoromethyl)phenyl1acetate 7.45 g (66.55 mmol) of potassium tert-butoxide was added to 75 mL of DMF under stirring and argon. The mixture was cooled to 0 °C and a solution of 5.00 g (26.16 mmol) of 1nitro-4-(trifluoromethyl)benzene (Apollo Scientific Ltd.) and 2.98 mL (28.00 mmol) was added. of ethyl ester of chloroacetic acid in 25 mL of DMF dropwise. A dark purple reaction mixture was obtained and stirred at 0 °C for 1.5 hours. Under cooling with ice water, 5% hydrochloric acid was added to the reaction mixture until the pH of the solution was approximately 3. As a result of acidification, the color of the solution turned yellow. The reaction mixture was extracted with 3x50 mL of ethyl acetate and the combined organic phases were washed with saturated NaHCOs solution and saturated NaCl solution. The solution was dried in the presence of MgSCU, filtered and concentrated. In this way, 6.86 g (95%) of the title product was obtained as orange oil. MS (ESI) m / z 278.2 (M+H)+. Intermediate 38 r2-nitro-5-(trifluorometite)phenyl acetic acid 6.85 g (24.71 mmol) of ethyl [2-nitro-5-(trifluoromethyl)phenyl]acetate (Intermediate 37) was dissolved in the mixture of 100 mL of THF, 50 mL of methanol and 50 mL of water. 5.18 g (123.45 mmol) of lithium hydroxide monohydrate was added to the orange solution, and the reaction mixture was stirred at room temperature for 12 hours. The reaction mixture was concentrated and after dilution with water, the pH was adjusted to approximately 4-5 with 1 A / hydrochloric acid. An orange precipitate appeared and was completely filtered (the starting material from the previous step, 1 -nitro-4(trifluoromethyl)benzene). Additional acidification (pH = 2) generated greater precipitation (expected product), so the suspension was cooled in an ice water bath, the yellow crystalline material was completely filtered and washed with a little water. IF-2019-03 566964-APN-ANP#INPI 118 Page 118 of 272 The acidic aqueous phase was extracted twice with 30 mL of ethyl acetate, the combined organic phases were washed with saturated NaCl solution, dried in the presence of MgSCU, filtered and concentrated. The yellow product was dried in a drying oven. In this way, 4.88 g (79%) of the title product was obtained as a yellow powder. MS (ESI) m / z does not ionize. Intermediate 39 5“{1-hydroxy-2-I2-nitro-5-(trifluoromethyl)phenylethylidene}2,2-dimethyl-1,3-dioxane-4,6dione F 4.79 g (19.23 mmol) of [2-nitro-5-(trifluoromethyl)phenyl]acetic acid (Intermediate 38) was dissolved in 250 mL of acetonitrile. 7.54 mL (43.30 mmol) of DIPEA, 3.05 g (21.20 mmol) of Meldrum acid and 0.24 g (1.92 mmol) of DMAP were added to the solution. With moderate stirring, and measuring the temperature of the solution, 2.61 mL (21.20 mmol) of trimethylacetyl chloride was added dropwise so that the temperature of the mixture did not exceed 30 °C. The reaction mixture was then stirred at 40 °C for 4 hours. The solution was cooled in an ice water bath and the pH was adjusted to acidic pH by adding 90 mL of 1Λ / hydrochloric acid. After the addition of another 90 mL of water, a large precipitation occurred, which was completely filtered, washed with the mother liquor and then with water. The product was dried in vacuo using phosphorus pentoxide at room temperature. In this way, 6.02 g (83%) of the title product was obtained as a white powder. MS (ESI) m / z decomposes. Intermediate 40 methyl 4-r2-nitro-5-(trifluorornetiDphenyl1-3-oxobutanoate 5.11 g (13.60 mmol) of 5-{1-hydroxy¡-2-[2-nitro-5-(trifluoromethyl)phenyl]ethylidene}-2,2dimethyl-1,3-dioxane-4, 6-Dione (Intermediate 39) was dissolved in a mixture of 68 mL of methanol and 264 mL of toluene, and the reaction mixture was stirred at 110 °C for 3 h. IF-2019-03 566964-APN-ANP#INPI 119 Page 119 of 272 After cooling to room temperature, 130 mL of saturated NaCl solution and 100 mL of ethyl acetate were poured into the solution. The phases were separated and the organic phase was dried in the presence of MgSO4, filtered and concentrated. In this way, 4.09 g (98%) of the title product was obtained as a yellow waxy material. MS (ESI) m / z 306.1 (M+H)+; 323.1 (M+NH4)+. Intermediate 41 methyl{2-r2-nitro-5-(trifluoromethyl)benzen-1,3-dioxolan-2-yl}acetate To a mixture of 4.87 g (15.95 mmol) of methyl 4-[2-nitro-5-(trifluoromethyl)phenyl]-3oxobutanoate (Intermediate 40), 2.46 mL (60.80 mmol) of methanol, To 15.00 mL (268.00 mmol) of ethylene glycol, and 7.49 mL (68.50 mmol) of trimethyl orthoformate, 0.18 g (0.94 mmol) of p-toluenesulfonic acid monohydrate was added. The reaction mixture was stirred at 50 °C for 72 hours, then cooled, and 70 mL of saturated Na2CO3 solution and 70 mL of water were added, resulting in a highly precipitated mixture. The mixture was extracted twice with 100 mL of ethyl acetate and the combined organic phases were washed with saturated NaCl solution. After drying in the presence of MgSO4, it was filtered and concentrated. The residue was purified by column chromatography using cyclohexane:ethyl acetate=4:1 as eluent. In this way, 2.75 g (49%) of the title product was obtained as light yellow oil. MS (ESI) m / z 316.1 (M+H)+; 367.1 (M+NH4)+. Intermediate 42 methyl{242-amino-5-(trifluoromethyl)benzyri-1,3-dioxolan-2-yl}acetate 2.19 g (6.27 mmol) of methyl{2-[2-nitro-5-(trifluoromethyl)benzyl]-1,3-dioxolan-2yl}acetate (Intermediate 41) in 50 mL of toluene was hydrogenated at temperature ambient under atmospheric pressure in the presence of 0.219 g of 5% Pt / C catalyst. After filtration of the catalyst, the filtrate was concentrated to form 2.00 g (100%) of the title product as a light orange oil. MS (ESI) m / z 320.2 (M+H)*. Intermediary 43 IF-2019-03 566964-APN-ANP#INPI 120 Page 120 of 272 y-ftrifluorometiD-lS-dihydrospiroM-benzazepine-^Z’-phtaidioxolanol^OI-D-one 2.00 g (6.3 mmol) of methyl{2-[2-amino-5-(trifluoromethyl)benzyl]-1,3-dioxolan-2yljacetate (Intermediate 42) was dissolved in 70 mL of dry THF, then the solution was cooled under argon to 0 °C and 0.78 g (6.91 mmol) of potassium tert-butoxide was added. The dark-colored solution was stirred at room temperature for 4 hours, then dry ice was added to the reaction mixture. The solution was concentrated and the residue was purified by column chromatography using dichloromethane:methanol=95:5 as eluent. In this way, 1.05 g (58%) of the title product was obtained as a white powder. MS (ESI) m / z 288.1 (M+H)+. Intermediate 44 methyl 3-amino-4-f2-nitro-5-(trifluoromethyl)phenyl]butanoate hydrochloride a) methyl 3-amino-4-[2-nitro-5-(tnfluoromethyl)phenylbut-2-enoate 1.00 g (3.3 mmol) of methyl 4-[2-nitro-5-(trifluoromethyl)phenyl]-3oxobutanoate (Intermediate 40) was dissolved in 30 mL of methanol and 2.78 g (36.0 mmol) ammonium-acetate. The reaction mixture was stirred at room temperature for 72 hours. 150 mL of water was added to the light brown solution and extracted twice with 70 mL of ethyl acetate. The combined organic phases were washed with saturated NaCl solution, dried in the presence of MgSO4, filtered and concentrated, then dried in the presence of phosphorus pentoxide in the desiccator. In this way, 0.96 g (96%) of the title product was obtained. b) methyl 3-amino-4-[2-nitro-5-(trifluoromethyl)phenyl1butanoate hydrochloride 2.00 g (9.4 mmol) of NaBH(OAc)3 was added to 15 mL of glacial acetic acid at 10 °C under aqueous cooling. A mixture of 0.96 g (3.2 mmol) of methyl 3-amino-4¿2-nitro5“(trifluoromethyl)phenyl]but-2-enoate in 5 mL of glacial acetic acid was added dropwise to the solution above. obtained, and the reaction mixture was stirred at room temperature IF-2019-03 566964-APN-ANP#INPI 121 Page 121 of 272 for 2 hours. Then, under cooling with ice water, 50 mL of water and 50 mL of 30% NaOH solution were added to the reaction mixture. The pH was adjusted to approximately 8 with saturated NaHCO3 solution and extracted twice with 70 mL of ethyl acetate. The combined organic phases were washed with saturated NaCl solution, dried in the presence of MgSCU and filtered. The calculated amount of 2.5M hydrogen chloride solution in ethyl acetate solution was added to the filtered ethyl acetate solution, and the mixture was concentrated. The residue was crystallized by trituration with diisopropyl ether. In this way, 0.78 g (72%) of the title product was obtained as a white powder. MS (ESI) m / z 307.1 (M+H)+. Intermediate 45 methyl 3-[(tert-butoxycarbonyl)amino1-4-[2-nitro-5-(trifluoromethyl)phenyl1butanoate 0.78 g (2.3 mmol) of methyl 3-amino-4-[2-nitro-5-(trifluoromethyl)phenyl]butanoate hydrochloride (Intermediate 44) was dissolved in 20 mL of methanol. 0.77 g (9.10 mmol) of NaHCOs was added to the solution thus obtained and 0.62 g (2.85 mmol) of di-yer-butyl dicarbonate was added to the suspension under cooling with ice and stirring, then The reaction mixture was allowed to warm to room temperature and stirred for 16 hours. During shaping, 100 mL of water was poured into the mixture, then the precipitated material was filtered, washed with water, and dried. In this way, 0.88 g (72%) of the title product was obtained as a white powder. MS (ESI) m / z 429.2 (M+Na)+. Intermediate 46 3[(tert-butoxycarbonyl)amino1-4-[2-nitrO“5-(trifluoromethyl)phenyl1butano¡co acid The title product was prepared from methyl 3-[(tert-butoxycarbonyl)amino]-4-[2nitro“5-(trifluoromethyl)phenyl]butanoate (Intermediate 45) according to the method described in step f) of Method B) of Intermediate 1. MS (ESI) m / z 415.1 (M+Na)+. Intermediate 47 4-[2-amino-5-(trifluoromethyl)phenyl-3-[(tert-butoxycarbonyl)amino1butanoic acid IF-2019-03 566964-APN-ANP#INPI 122 Page 122 of 272 NHZ.A. MH B oc L J T 'γ''' xxjoh F™--F F The title product was prepared from 3-[(tert-butoxycarbonyl)amino]-4-[2nitro-5-(trifluoromethyl)phenyl]butanoic acid (Intermediate 46) according to the method described for Intermediate 42. MS (ESI) m / z 385.2 (M+Na)+. Intermediate 48 tert-butyl [2-oxo-7-(trifluoromethyl)-2,3,4,5-tetrahydro-1H-1-benzazepine-4-yl1carbamate A mixture of 0.60 g (1.7 mmol) 4-[2-amino-5“(trifluoromethyl)phenyl]-3-[(tert-butoxycarbonyl)amino]butanoic acid (Intermediate 47), 20 mL DMF, 0 0.60 mL (3.39 mmol) DIPEA, 0.30 g (1.99 mmol) HOBt, and 0.38 g (1.99 mmol) EDC were stirred at room temperature for 16 hours and then concentrated. 30 mL of saturated NaHCO3 solution was poured into the residue and after a brief stirring period the precipitated material was filtered, washed with water, and dried. In this way, 0.49 g (87%) of the title product was obtained as a brown powder. MS (ESI) m / z 367.1 (M+H)*. Intermediate 49 tert-butyl r2-thioxo-7-(trifluoromethyl)-2,3,4t5tetrahydro-1 H-1 -benzazepin-4-illcarbamate A mixture of 0.46 g (1.3 mmol) of tert-butyl [2-oxo-7-(trifluoromethyl)-2,3,4,5tetrahydro-1H-1-benzazepin-4-¡l]carbamate (Intermediate 48), 10 mL of pyridine and 0.70 g (1.7 mmol) of Lawesson's reagent were stirred at 120 °C for 3 hours. The reaction mixture was concentrated and stirred at room temperature for 12 hours after the addition of 10 mL of water and 20 mL of saturated NaHCOs solution. The precipitated material was filtered, washed with water, and dried. In this way, 0.44 g (92%) of the title product was obtained as a brown powder, which was used without further purification. Intermediate 50 tert-butyl r2-(methylsulfanyl)-7-(trifluoromethyl)-4,5-dihydro-3H-1-benzazepin-4ylcarbamate IF-2019-03 566964-APN-ANP#INPI 123 Page 123 of 272 SMe 0.44 g (1.2 mmol) tert-butyl [2-thioxo-7-(trifluoromethyl)-2,3,4,5-tetrahydro-1 H-1 benzazepin-4-yl]carbamate (Intermediate 49) It was dissolved in 30 mL of acetone, and 0.34 g (2.44 mmol) of K2CO3 was added. 0.23 mL (3.7 mmol) of iodomethane was added dropwise to the reaction mixture and stirred at room temperature for 24 hours. 20 mL of ethyl acetate was poured into the reaction mixture and the organic phase was washed first with water, then with saturated NaCl solution, dried in the presence of MgSO4, filtered and concentrated. In this way, 0.46 g (100%) of the title product was obtained as an orange powder. MS (ESI) m / z 375.1 (M+H)+. Intermediate 51 methyl [2-(5-chloro-2-nitrobenzyl)-1,3-dioxolan-2-yl1acetate COOME The title product was prepared from methyl 4-(5-chloro-2-nitrophenyl)-3oxobutanoate (step b) of Method B) of Intermediate 1) according to the method described for Intermediate 41. MS ( ESI) m / z 316.1 (M+H)+; 333.1 (M+NH4)+. Intermediate 52 methyl i2-(2-amino-5-chlorobenzyl)-1,3-dioxolan-2-yllacetate COO Me The title product was prepared from methyl [2-(5-chloro-2-nitrobenzyl)-1,3dioxolan-2-yl]acetate (Intermediate 51) according to the method described for Intermediate 42. MS (ESI ) m / z 286.1 (M+H)+. Intermediary 53 7-chloro-1,5-dihydrospiron -benzazepine-4,2'-ri,31dioxolane1-2(3H)-one IF-2019-03 566964-APN-ANP#INPI 124 Page 124 of 272 The title product was prepared from methyl [2-(2-amino-5-chlorobenzyl)-1,3dioxolan-2-yl]acetate (Intermediate 52) according to the method described for Intermediate 43. MS (ESI ) m / z 254.1 (M+H)+. Intermediate 54 tert-butyl 2-{rtrans-4-(trifluoromethyl)cyclohex¡l1carbonyl}hydrazine carboxylate F, v NH—NHBoc F—.....( p 1—-J o 2.13 g (10.9 mmol) of trans-4-(trifluoromethyl)cyclohexanecarboxylic acid (Manchester Organics Ltd.) was dissolved in 50 mL of DMF. 1.44 g (10.9 mmol) of tert-butylhydrazine carboxylate, 4.75 mL (27.3 mmol) of DIPEA, 2.00 g (13.10 mmol) of HOBt and 2.51 g (13) were added. .1 mmol) of EDC to the solution. The reaction mixture was stirred at room temperature for 36 hours, then concentrated. 40 mL of saturated NaHCOs solution was added to the residue and after a brief stirring period the precipitate was filtered, washed with water and dried in a vacuum oven in the presence of phosphorus pentoxide. In this way, 3.35 g (99%) of the title product was obtained as a white powder. GC-MS (El) m / z 310.1. Trans-4-(trifluoromethyl)cyclohexanecarboxylic acid intermediate 55 hydrazide F / ---v NH-NH, fU...... 3.35 g (10.8 mmol) of tert-butyl 2-{[trans-4-(trifluoromethyl)cyclohexylcarbonyl}hydrazine carboxylate (Intermediate 54) was dissolved in a mixture of 50 mL of ethyl acetate and 20 mL of ethanol, then 30 mL of 2.5 M hydrogen chloride solution in ethyl acetate was added. The reaction mixture was stirred at room temperature for 16 hours, then 150 mL of diethyl ether was added and cooled in an ice-water bath. The precipitated product was filtered and washed with diethyl ether. The filtrate was stirred with 100 mL of saturated NaHCO3 solution (pH ~ 8), filtered, washed with water, and dried in a vacuum oven in the presence of phosphorus pentoxide. In this way, 1.77 g (78%) of the title product was obtained as a white powder. GC-MS (El) m / z 210.1 Intermediate 56 tert-butyl 2-[(3,3-difluorocyclobutyl)carbonyl1hydrazine carboxylate IF-2019-03 566964-APN-ANP#INPI 125 Page 125 of 272 The title product was prepared from carboxylic acid 3,3-difluoro-cyclobutane (Combi-Blocks Inc.) according to the method described for Intermediate 54. GCMS (El) m / z 250.1. Intermediary 57 3,3-difluorocyclobutane carboxylic acid hydrazide F EITHER The title product was prepared from tert-butyl 2-[(3,3difluorocyclobutyl)carbonyl]hydrazine carboxylate (Intermediate 56) according to the method described for Intermediate 55. GC-MS (El) m / z 150, 1. Intermediate 58 methyl 4-(5-chloro-2-nitrophenyl)-3-hydroxybutanoate CL 3.13 g (11.5 mmol) of methyl 4-(5-chloro-2-nitrophenyl)-3-oxobutanoate (step b) of Method B) of Intermediate 1) was dissolved in 100 mL of methanol, the solution was cooled to 0°C, and 0.48 g (12.6 mmol) of NaBH4 was added to the reaction mixture. The resulting mixture was stirred at room temperature for 16 hours. The reaction mixture was concentrated and 100 mL of water was added to the residue, the pH of the solution was adjusted to approximately 7 with 5% hydrochloric acid. The aqueous phase was extracted with diethyl ether, the organic phase was dried in the presence of MgSCU, filtered and concentrated. In this way, 2.85 g (90%) of the title product was obtained, which was used without further purification in the next step. Intermediate 59 methyl 3-{rter-butyl(dimethiDsilyl1oxy}-4-(5-chloro-2-nitrophenyl)butanoate CL 1.36 g (5.0 mmol) of methyl 4-(5-chloro-2-nitrophenyl)-3-hydroxybutanoate (Intermediate 58) was dissolved in 15 mL of DMF, then 0.85 g (12.4 mmol) of 1H-imidazole and 0.90 g (6.0 mmol) of tert-butyl dimethylchlorosilane. The solution was stirred at room temperature for 24 hours. The reaction mixture was poured into water and the product was IF-2019-03 566964-APN-ANP#INPI 126 Page 126 of 272 extracted twice with 50 mL of ethyl acetate. The combined organic phases were washed with saturated NaCl solution, dried in the presence of MgSO4, filtered and concentrated. The residue was purified by column chromatography using n-hexane:ethyl acetate=4:1 as eluent. Fractions containing the expected product were concentrated to form 1.70 g (88%) of the title product. MS (ESI) m / z 388.2 (M+H)+. Intermediate 60 3-{[tert-but¡l(dimethyl)silyl1oxy}-4-(5-chloro-2-nitrophenyl)butanoic acid The title product was prepared from methyl 3-{[tert-butyl(dimethyl)silyl]oxy}-4-(5chloro-2-nitrophenyl)butanoate (intermediate 59) according to the method described for Intermediate 38. MS (ESI) m / z 374.2 (M+H)+. Intermediate 61 4-(2-amino-5-chlorophenyl)3-{rter-butyl(dimethyl)siHlloxy}butanoic acid The title product was prepared from 3-{[ / er-butyl(dimethyl)silyl]oxy}-4-(5chloro-2-nitrophenyl)butanoic acid (Intermediate 60) according to the method described for Intermediate 42 .MS (ESI) m / z 344.2 (M+H)+. Intermediate 62 4-{rter-butylidimethyl)silinoxy}-7Chloro-1,3,4,5-tetrahydro-2H1benzazepine-2-one h ,9 b— The title product was prepared from 4-(2-amino-5-chlorophenyl)-3-{[yerbutyl(dimethyl)silyl]oxy}butanoic acid (Intermediate 61) according to the method described for the Intermediary 48. MS (ESI) m / z 326.2 (M+H)+. Intermediate 63 4-{her-but¡l(dimethiDsilinoxy}-7-chloro-1,3l4l5-tetrahydro-2H-1-benzazepine-2-thione IF-2019-03 566964-APN-ANP#INPI 127 Page 127 of 272 The title product was prepared from 4-{[yerbutyl(dimethyl)silyl]oxy}-7-chloro~ 1,3,4,5-tetrahydro-2H-1-benzazepine-2-one (Intermediate 62) according to the method described for Intermediate 49. MS (ESI) m / z 342.1 (M+H)+. Intermediate 64 methyl trans-4-(piperidin1ylmethyl)cyclohexane carboxylate or \---N y----< {—'COOMe 0.30 g (1.8 mmol) of methyl frans-4-formylcyclohexane carboxylate (Synthonix) was dissolved in 10 mL of 1,2-dichloroethane, and 0.52 mL (5.3 mmol) piperidine and 0. 19 mL (3.4 mmol) of acetic acid to the solution. The resulting mixture was cooled to 0 °C and 1.16 g (5.5 mmol) of NaBH(OAc)3 was added, and the mixture was stirred at room temperature for 16 hours. Next, 30 mL of water was added to the reaction mixture and the pH of the mixture was adjusted to approximately 9 with Na2CO3 solution. The mixture was extracted twice with 20 mL of dichloromethane, the combined organic phases were dried in the presence of anhydrous MgSCu, filtered and concentrated. In this way, 0.40 g (95%) of the title product was obtained, which was used without further purification. Intermediate 65 hydrazide of tranS4-(piperidin-1-ylmethyl)cyclohexane carboxylic acid CZ / * .—. nh-nh2\' or 0.40 g (1.7 mmol) of methyl frans-4-(peridin-1-ylmethyl)cyclohexane carboxylate (Intermediate 64) was dissolved in 5 mL of methanol, and the solution was poured into a resistant glass reactor. to the pressure. 5 mL (100 mmol) of hydrazine hydrate was added and the reaction mixture was stirred at 75 °C for 16 hours. The reaction mixture was concentrated and cyclohexane and anhydrous toluene were completely evaporated from the residue. In this way, 0.39 g (97%) of the title product was obtained as a white powder. GC-MS (El) m / z 239.2. Intermediate 66 tert-butyl 2-1(4,4-difluorocyclohexyl)carbonylhydrazine carboxylate IF-2019-03 566964-APN-ANP#INPI 128 Page 128 of 272 I---1 NH-NHBocf>VvA The title product was prepared from 4,4-difluorocyclohexane carboxylic acid (Combi-Blocks Inc.) according to the method described for Intermediate 54. MS (ESI) m / z 301.2 (M+Na)+ . 4,4-Difluorocyclohexane Carboxylic Acid Intermediate 67 Hydrazide 3.39 g (12.2 mmol) of tert-butyl 2-[(4,4-difluorocyclohexyl)carbonyl]hydrazine carboxylate (Intermediate 66) was dissolved in 50 mL of ethyl acetate, then 50 mL of chloride solution was added. of 2.5 M hydrogen in ethyl acetate to the solution. The reaction mixture was stirred at room temperature for 16 hours and then concentrated. 15 mL of dichloromethane and 15 mL of distilled water were added to the residue, and the pH of the aqueous phase was gasified with saturated NaHCOs solution, then the mixture was concentrated. The residue obtained was suspended in ethyl acetate, the insoluble solid was completely filtered, the filtrate was dried in the presence of MgSO4, filtered and concentrated. In this way, 2.08 g (93%) of the title product was obtained as a white powder. MS (ESI) m / z 179.2 (M+H)+. Intermediate 68 ethyl f2-(2nitrobenzyl)-1,3-dioxoian-2-yl]acetate 2.00 g (8.0 mmol) of ethyl 4-(2-nitrophenyl)-3-oxobutanoate (D. Royer et al., Tetrahedron 2008, 64:9607-9618) was dissolved in 25 mL of toluene, then Added 4.45 mL (79.6 mmol) of ethylene glycol and 0.23 g (1.19 mmol) of p-toluenesulfonic acid monohydrate to the resulting solution. Dean-Stark head was applied to the flask and the reaction mixture was boiled for 6 hours and then stirred at 50 °C for 48 hours. The resulting mixture was concentrated, the residue was mixed with water and extracted with diethyl ether. The organic phase was dried in the presence of MgSO4, filtered and concentrated. The resulting crude product was purified by column chromatography using cyclohexane:ethyl acetate=4:1 as eluent. In this way, 0.68 g (29%) of the title product was obtained as pale yellow oil. MS (ESI) m / z 296.2 (M+H)+. Intermediary 69 IF-2019-03 566964-APN-ANP#INPI 129 Page 129 of 272 ethyl [2-f2-aminobenzyl)-1,3-dioxolan-2-riacetate The title product was prepared from ethyl [2-(2-nitrobenzyl)-1,3-dioxolan-2yl]acetate (Intermediate 68) according to the method described for Intermediate 42. MS (ESI) m / z 266.2 (M+H)+. Intermediary 70 1,5-dihydrospiro[1 -benzazepine-4,2,-H ,31dioxolane1-2(3H)-one The title product was prepared from ethyl [2-(2-aminobenzyl)-1,3-dioxolan-2¡IJacetate (Intermediate 69) according to the method described for Intermediate 43. MS (ESI) m / z 220.2 (M+H)+. Intermediate 71 ethyl 3-amino-4-(2-nitrophenyl)but-2-enoate The title product was prepared from ethyl 4-(2-nitrophenyl)-3-oxobutanoate (D. Royer et al., Tetrahedron 2008, 64:9607-9618) according to the method described in step c) of Method B) of Intermediary 1. MS (ESI) m / z 252.1 (M+H)+. Intermediate 72 ethyl 3-amino-4-(2-nitrophen¡Qbutanoate 1.29 g (6.1 mmol) of NaBH(OAc)3 was dissolved in 10 mL of acetic acid and a solution of 0.51 g (2.03 mmol) of ethyl 3-amino-4“(2-nitrophenyl) but-2-enoate (Intermediate 71) in 5 mL of acetic acid was slowly added dropwise to the above solution. The resulting mixture was stirred at room temperature for 48 hours. Then, the pH was adjusted to 8 with saturated NaHCO3 solution and extracted with dichloromethane, and then the organic phase was dried in the presence of anhydrous MgSO4, filtered and concentrated. This IF-2019-03 566964-APN-ANP#INPI 130 Page 130 272 way, 0.19 g (37%) of the title product was obtained as yellow oil. MS (ESI) m / z 253.2 (M+H)+. intermediate 73 ethyl 3-rter-butoxycarbonyl)amino1-4-(2-nitrophenyl)butanoate no2 NHBoc The title product was prepared from ethyl 3-amino-4-(2-nitrophenyl)butanoate (Intermediate 72) according to the method described in step e) of Method B) of Intermediate 1. MS (ESI) m / z 375.1 (M+Na)+. Intermediate 74 3-iter-butoxycarbonyl)amino1-4-(2“nitrophenyl)butanoic acid NO 2 LL NHBoc The title product was prepared from ethyl 3-[fer-butoxycarbonyl)amino]-4-(2nitrophenyl)butanoate (Intermediate 73) according to the method described in step f) of Method B) of Intermediate 1. MS (ESI) m / z 347.1 (M+Na)+. Intermediate 75 4-(2aminophenyl)-3-nter-butoxycarbonyl)amino]butanoic acid nh2 NHBoc The title product was prepared from 3-[yer-butoxycarbonyl)amino]-4-(2nitrophenyl)butanoic acid (Intermediate 74) according to the method described in Method B) of Intermediate 2. MS (ESI) m / z 295.1 (M+H)+. Intermediate 76 tert-butyl (2-oxO2,3,4,5-tetrahydrO1 H-1 -benzazepin-4-yl)carbamate HO NHBoc The title product was prepared from 4-(2-aminophenyl)-3-[(ferbutoxycarbonyl)amino]butanoic acid (Intermediate 75) according to the method described for Intermediate 3. MS (ESI) m / z 299 .0 (M+Na)+. Intermediate 77 tert-butyl (2thioxo-2,3,4,5-tetrahydro-1 H-1 -benzazepin-4-yl)carbamate IF-2019-03 566964-APN-ANP#INPI 131 Page 131 of 272 Η ,Ν· NHBoc The title product was prepared from tert-butyl (2-oxo-2,3,4,5-tetrahydro-1H-1benzazepin-4-yl)carbamate (Intermediate 76) according to the method described for Intermediate 4 , which was used without additional purification. Intermediate 78 hydrazide of frans-4-(pyrrolidin-1-ílcarbonyl)cyclohexane carboxylic acid a) methyl frans-4-(pyrrolidine-1-ylcarbonyl)cyclohexane carboxyate 'COOME A mixture of 186 mg (1 mmol) frans-4-(methoxylcarbonyl)cyclohexane carboxylic acid (Combi-Blocks Inc.), 83.5 μΙ_ (1 mmol) pyrrolidine, 5 mL dry DMF, 348 pL (2 mmol ) of DIPEA, 230 mg (1.2 mmol) of EDC, and 162 mg (1.2 mmol) of HOBt was stirred at room temperature for 24 hours. Ethyl acetate and aqueous NaHCOs solution were added to the reaction mixture. The phases were separated and the aqueous phase was extracted once with ethyl acetate. The combined organic phases were washed with 1Λ / hydrochloric acid and water, dried in the presence of anhydrous Na2SO4, filtered and concentrated. In this way, 180 mg (75%) of the title product was obtained. GC-MS (El) m / z 239. b) frans-4-(pyrroiidin-1-ylcarbonyl)cyclohexane carboxylic acid hydrazide 180 mg (0.75 mmol) of methyl iron / is-4-(pyrrolidin-1-ylcarbonyl)cyclohexane carboxyate, 1.1 mL of methanol and 1.1 mL of hydrazine hydrate were stirred in a glass reactor. pressure resistant at 75°C for 24 hours. The reaction mixture was concentrated and cyclohexane was added, then completely evaporated. In this way, 183 mg (76%) of the title product was obtained. GC-MS (El) m / z 239. trans-4-(morpholine-1-ylcarbonyl)cyclohexane carboxylic acid intermediate 79 hydrazide a) methyl frans-4-(morpholín-4-ylcarboniQc¡clohexane carboxyate IF-2019-03 566964-APN-ANPAINPI 132 Page 132 of 272 or The title product was prepared from trans-4(methoxycarbonyl)cyclohexane carboxylic acid (Combi-Blocks Inc.) and morpholine according to the method described in step a) of Intermediate 78, GC-MS (El) m / z 255. b) frans-4-(Morfolin-1-ylcarbonyl)cyclohexanecarboxylic acid hydrazide The title product was prepared from methyl frans-4-(morpholin-4ylcarbonyl)cyclohexane carboxylate according to the method described in step b) of Intermediate 78. GC-MS (El) m / z 255. trans-4-(dimethylamino)cyclohexane carboxylic acid hydrazide intermediate 80 The title product was prepared from methyl frans-4-(dimethylamino)cyclohexane carboxylate (EP 1 582 521 A1 (05.10.2005) TANABE SEIYAKU CO.) according to the method described for Intermediate 65. MS (ESI) m / z 186.3 (M+H)+. Trans-4-(morpholin-4-yl)cyclohexane carboxylic acid intermediate 81 hydrazide The title product was prepared from methyl frans-4-(morpholin-4-yl)cyclohexane carboxylate (EP 1 582 521 A1 ¢05.10.2005) TANABE SEIYAKU CO.) according to the method described for Intermediate 65. GC-MS (El) m / z 227 1-(Prím¡din-2-yl)azetidine-3-carboxylic acid intermediate 82 hydrazide The title product was prepared from methyl 1-(pyrimidin-2-yl)azetidine-3carboxylate (WO 2006 / 124748 A2 (23.11.2006) LEXICON GENETICS INCORP.) according to the method described for Intermediate 65. MS (ESI) m / z 194.2 (M+H)+. IF-2019-03 566964-APN-ANP#INPI 133 Page 133 of 272 1-(Pyridin-2-yl)azetidine-3-carboxylic acid intermediate 83 hydrazide either The title product was prepared from methyl 1-(pyridin-2-yl)azetidine-3carboxylate (WO 2017 / 007756 A1 (12.01.2017) RODIN THERAPEUTICS INC.) according to the method described for Intermediate 65. GC -MS (El) m / z 192 Intermediate 84 ethyl (frans)-3-methyl-2-oxo-1-oxa-3-azaspiror4,5]decane-8-carboxylate or and Intermediate 85 ethyl (c / s)-3-methyl-2-oxo-1-oxa-3-azaspiror4,5]decane-8-carboxylate 1.8 g (45.0 mmol) of 60% sodium hydride dispersion in oil was suspended in 60 mL of dry DMF, cooled to 0-5 °C, then 6.00 g (26.4 mmol) of a ~1:1 mixture of ethyl (c / s)-2-oxo-1-oxa-3-azaspiro[4,5]decane-8-carboxylate and ethyl (írans)-2-oxo-1-oxa- 3azaspiro[4,5]decane-8-carboxylate (WO 2008 / 092887 A1, ¢07.08.2008) GLAXO GRUPO LTD.) dissolved in 60 mL of DMF was added dropwise so that the temperature of the mixture was maintained between 0 and 5 °C. The reaction mixture was stirred for 20 minutes at this temperature, then 2.46 mL (39.5 mmol) of iodomethane was added dropwise over 20 minutes. The mixture was stirred for another hour at 0-5 °C, then It was allowed to cool to room temperature and stirred for 3 hours at this temperature. Then, 1.8 mL (31 mmol) of acetic acid was added dropwise in 10 minutes, after stirring for 15 minutes, the reaction mixture was concentrated and 90 mL of n-heptane was completely evaporated from the residue twice. 180 mL of ethyl acetate, 90 mL of saturated NaHCO3 solution and 90 mL of water were added to the residue, the phases were separated, the organic phase was washed with 90 mL of NaCl, dried in the presence of Na2SO4, filtered and concentrated. . The residue was purified by column chromatography using toluene:isopropanol=93:7 as eluent. The appropriate fractions were concentrated and the IF-2019-03 566964-APN-ANP#INPI 134 Page 134 of 272 residues were crystallized with diisopropyl ether. Thus, 1.38 g (22%) of ethyl (trans)-3methyl-2-oxo-1-oxa-3-azaspiro[4,5]decane-8-carboxylate (Intermediate 84) and 2.45 g (39%) of ethyl (c / s)-3-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decane-8-carboxylate (Intermediate 85) were obtained as white powder. GC-MS (El) m / z 241. (trans)-3-methyl-2-oxo-1-oxa“3-azaspiror4,5]decane-8-carboxylic acid intermediate 86 hydrazide The title product was prepared from ethyl (frans)-3-methyl-2-oxo-1-oxa-3azaspiro[4,5]decane-8-carboxylate (Intermediate 84) according to the method described for Intermediate 65. GC-MS (El) m / z 227. (cis)-3-methyl-2-oxo-1-oxa-3-azaspirof4,51decane-8-carboxylic acid intermediate 87 hydrazide The product of! titer was prepared from ethyl (c / 's)-3-methyl-2-oxo-1-oxa-3azaspiro[4,5]decane-8-carboxylate (Intermediate 85) according to the method described for the Intermediate 65. GC-MS (El) m / z 227. Intermediate 88 5-[2-(5-fluoro-2-nitrophen¡l)-1-hydroxyethylidene1-2,2-dimethyl-1,3-dioxane-4,6-dione °y°¥The title product was prepared from (5-fluoro-2-nitrophenyl)acetic acid (Combi-Blocks Inc.) according to the method described for Intermediate 39. MS (ESI) m / z 348.0 (M+Na)+ . Intermediate 89 methyl 4-(5-fluorO2-nitroohen¡l)-3-oxobutanoate IF-2019-03 566964-APN-ANP#INPI 135 Page 135 of 272 ΜΓΪ F The title product was prepared from 5-[2-(5-fluoro-2-nitrophenyl)-1hydroxyethylidene]-2,2-dimethyl-1,3-dioxane-4,6-dione (Intermediate 88) according to with the method described for Intermediate 40. MS (ESI) m / z 273.1 (M+NH4)+. Intermediate 90 methyl F2-(5-fluoro-2-nitrobenzyl)-1,3-dioxolan-2-yl1acetate F The title product was prepared from methyl 4-(5-fluoro-2-nitrophenyl)-3oxobutanoate (Intermediate 89) according to the method described for Intermediate 41. MS (ESI) m / z 317.2 (M +NH4)+. Intermediate 91 methyl F2-(2-amino-5-fluorobenzyl)-1,3-dioxolan2-yllacetate F The title product was prepared from methyl [2-(5-fluoro-2-nitrobenzyl)-1,3dioxolan-2-yl]acetate (Intermediate 90) according to the method described for Intermediate 42. MS (ESI ) m / z 270.2 (M+H)+. Intermediary 92 7-fluoro-1,5-dihydroes pyroM -benzazepine-4,2'41,31dioxolane1“2(3tf)-one The title product was prepared from methyl [2-(2-amino-5-fluorobenzyl)-1,3dioxolan-2-yl]acetate (Intermediate 91) according to the method described for Intermediate 43. MS (ESI ) m / z 238.2 (M+H)+. Intermediate 93 tert-butyl (8-chloro-5<6-dihydro-4H41,2,41triazoloF4,3-alF11benzazepin-5-yl)carbamate IF-2019-03 566964-APN-ANP#INPI 136 Page 136 of 272 NHBoc 164 mg (0.48 mmol) of tert-butyl [7-chloro-2-(methylsulfanyl)-4,5-dihydro-3 / - / -1benzazepin-4-yl]carbamate (Intermediate 5) was dissolved in 3 mL of 1,4-dioxane and the resulting solution was heated to 90 °C. 145 mg (2.41 mmol) of formyl hydrazide was added over 4 hours under argon. The reaction mixture was then stirred at 90 °C for another 8 h and after cooling to room temperature, the solvent was evaporated in vacuo. The residue was purified by column chromatography using dichloromethane:methanol=95:5 as eluent. In this way, 145 mg (95%) of the title product was obtained as a white solid. MS (ESI) m / z 335.1 (M+H)+. Intermediate 94 tert-butyl (1-bromo-8-chlorO5,6-dihydro-4tf-[1,2,4'ltriazolor4,3al[1'|benzazepin5¡Dcarbamate NHBoc 528 mg (1.58 mmol) tert-butyl (8-chloro-5,6-dihydro-4H-[1,2,4]triazolo[4,3a][1]benzazepin-5-yl)carbamate (Intermediate 93) was dissolved in 35 mL of THF. 622 mg (3.5 mmol) of / V-bromosuccinimide was added and the resulting pale yellow solution was stirred at reflux for 60 minutes with illumination by an RH-500 halogen lamp (Tracon Electric). At this time, the color of the solution initially darkened and then gradually became discolored. After cooling to room temperature, the solvent was evaporated in vacuo. The residue was purified by column chromatography using dichloromethane:methanol=97:3 as eluent. In this way, 592 mg (90%) of the product! title was obtained as a white solid. MS (ESI) m / z 415.1 (M+H)+. Intermediary 95 8,-chloro-4,H,6,H-spirori,3-dioxolane-2,5>-ri,2,41triazolor4,3afrnbenzazepine] IF-2019-03 566964-APN-ANP#INPI 137 Page 137 of 272 356.5 mg (1.405 mmol) of 7-chloro-1,5-dihydrospiro[1-benzazepine-4,2'[1,3]dioxolane]-2(3H)-one (Intermediate 53) was dissolved in 22 mL of dichloromethane and 11 pL (0.144 mmol) of trifluoroacetic acid was added. Under argon, 249.4 mg (1.686 mmol) of trimethyloxonium tetrafluoroborate was added and the reaction mixture was stirred at room temperature for 24 hours. At this time, 422.0 mg (7.027 mmol) of formyl hydrazide was added in 5 portions at reflux temperature in 4 hours, then the reaction mixture was stirred at reflux temperature for 15 hours. The reaction mixture was concentrated and the residue was dissolved in 22 mL of dioxane and the mixture was stirred at 80 °C for 2.5 hours. After cooling to room temperature, the solvent was evaporated in vacuo. The residue was purified by column chromatography using dichloromethane: methanol=95:5 as eluent. In this way, 248 mg (64%) of the title product was obtained. MS (ESI) m / z 335.1 (M+H)+. Intermediate 96 r-bromo-8,-chloro-4,fi,e'H-spirori.S-dioxolane-Z,5'41,2,41triazolo[4,3alfllbenzazepinal The title product was prepared from 8'-chloro-4' / 7,6'H-spiro[1,3-dioxolane2,5'-[1,2,4]triazolo[4,3-a][ 1 jbenzazepine] (Intermediate 95) according to the method described for Intermediate 94. MS (ESI) m / z 358.0 (M+H)+. trans-4-(piperidin-1-ylcarbonyl)cyclohexane carboxylic acid intermediate 97 hydrazide a) methyl / rans-44piperidin-1-ílcarboniDcyclohexane carboxylate ''COOMe The title product was prepared from trans-4(methoxycarbonyl)cyclohexane carboxylic acid (Combi-Blocks Inc.) and piperidine according to the method described in step a) of Intermediate 78. GC-MS (El) m / z 253. IF-2019-03 566964-APN-ANP#INPI 138 Page 138 of 272 b) frans-4-(piperidin-1-ylcarbonyl)cyclohexane carboxylic acid hydrazide The title product was prepared from methyl irans-4-(piperidin-1ylcarbonyl)cyclohexane carboxylate according to the method described in step b) of Intermediate 78. GC-MS (El) m / z 253. Intermediary 98 7-chloro-1,5-dihydrospirori -benzazepine-4,2'-ri ,31dioxane1-2(3tf Pona a) methyl [2-(5-chloro-2-nitrobenzyl)-1,3-dioxan-2-yl]acetate The title product was prepared from methyl 4-(5-chloro-2-nitrophenyl)-3oxobutanoate (step b) of Method B) of intermediate 1) and 1,3-propanediol according to the method described for Intermediate 41. MS (ESI) m / z 330.2 (M+H)*. b) methyl r2-(2-amino-5-chlorobenzyl)-1;3-dioxan-2-11acetate The title product was prepared from methyl [2-(5-chloro-2-nitrobenzyl)-1:3dioxan-2-yl]acetate (step a) from Intermediate 98) according to the method described for Intermediate 42 .MS (ESI) m / z 322.2 (M+Na)+. c) 7-chloro-1,5-dihydrospiroF1-benzazepine-4,2'41l31dioxanol-2(3H)-one The title product was prepared from methyl [2-(2-amino-5-chlorobenzyl)-1,3dioxan-2-yl]acetate (step b) of Intermediate 98) according to the method described for Intermediate 43 .MS (ESI) m / z 268.1 (M+H)+. Intermediate 99 methyl (5s,8s)-1-oxO2(propan-2-yl)-2-azaspiror4l5]decane-8-carboxylate and IF-2019-03 566964-APN-ANP#INPI 139 Page 139 of 272 Intermediate 100 methyl (5r,8r)-1-oxo-2-(propan-2-yl)-2-azaspiror4151decane-8-carboxylate \0 / \ | X COOME A mixture of 0.9 g (4.0 mmol) dimethyl tra / 7S-1-(2-oxoethyl)cyclohexane-1,4dicarboxylate (WO 2011 / 143150 A1, (05.10.2011) SANOFI), 40 mL of 1,2-dichloroethane, 316 pL (3.71 mmol) of isopropylamine and 637 pL (11.1 mmol) of acetic acid was cooled to 5 °C and 2.36 g (11.1 mmol) of sodium triacetoxyborohydride was added to the reaction mixture at a rate such as to maintain the internal temperature below 5 °C. After the addition was complete, the reaction mixture was stirred at room temperature for 2 h, then diluted with water. The pH of the mixture was adjusted to 8 by adding 10% K2CO3 solution, the phases were separated and the aqueous phase was extracted with dichloromethane. The combined organic phases were washed successively with 10% K2CO3 solution, water and brine, dried in the presence of Na2SO4, filtered and concentrated. The residue was dissolved in 40 mL of dry THF and 330 mg (2.94 mmol) of potassium tert-butoxide was added. The reaction mixture was stirred at room temperature for 3 h, then neutralized by addition of solid CO2. After addition of water, the THF was evaporated and the aqueous phase was extracted with ethyl acetate. The organic phase was dried in the presence of Na2SO4, filtered and concentrated. The residue was purified by flash column chromatography using mixture of cyclohexane:ethyl acetate = 45:55 as eluent to form 56 mg (6%) of methyl (5s,8s)-1-oxo-2-(propan-2-yl )-2-azaspiro[4,5]decane-8carboxylate (Intermediate 99) as the first fraction and 172 mg (19%) of methyl (5r,8r)-1oxo-2-(propan-2-yl)-2- azaspiro[4,5]decane-8-carboxylate (Intermediate 100) as the second fraction. GC-MS (El) m / z 253. Intermediate 101 (5s,8s)-1 -oxo-2-(propan-2-iQ-2-azaspiro[4,51decane-8-carbohydrazide \0 L r \ O L- / \ / 'NH—NH2 The title compound was prepared methyl (5s,8s)-1-oxo-2-(propan-2-yl)-2azaspiro[4,5]decane-8-carboxylate (Intermediate 99) according to the method described for the Intermediate 65. GC-MS (El) m / z 253. Intermediate 102 (5r,8r)-1-oxo-2-(propan2yl)2-azaspirof4,5ldecane-8-carbohydrazide IF-2019-03 566964-APN-ANP#INPI 140 Page 140 of 272 or NH—NH2 The title compound was prepared from methyl (5r,8r)-1-oxo-2-(propan-2-i!)-2azaspiro[4,5]decane-8-carboxylate (Intermediate 100) according to method described for Intermediate 65. GC-MS (El) m / z 253. Intermediate 103 7-chloro-4-methoxy-1,3,4,5-tetrahydro-2fi-1 -benzazepine-2-thione EITHER' a) methyl 4-(5-chlorO2-nitrophenyl)-3-methoxybutanoate A mixture of 1.37 g (5 mmol) methyl 4-(5-chloro-2-nitrophenyl)-3-hydroxybutanoate (Intermediate 58), 90 mL dichloromethane, 1.4 g molecular sieves 4A, 3.21 g (15 mmol) of 1,8-bis(dimethylamino)naphthalene and 2.22 g (15 mmol) of trimethyloxonium tetrafluoroborate were stirred at room temperature for 20 h, then filtered and the solid material was washed with dichloromethane. The filtrate was washed with 3M HCl solution and water, dried in the presence of Na2SO4, filtered and concentrated. The residue was purified by flash column chromatography using cyclohexane:ethyl acetate = 65:35 as eluent to form 1.097g (76%) of the title compound. MS (ESI) m / z 310.1 (M+Na)+b) 4-(5-chloro-2-nitrophenyl)-3-methoxybutanoic acid CL A mixture of 0.52 g (1.8 mmol) methyl 4-(5-chloro-2-nitrophenyl)-3-methoxybutanoate (Step a) from Intermediate 103), 5 mL methanol, 0.9 mL 4M NaOH and 1.6 mL of water was stirred at room temperature for 20 h, then the reaction mixture was acidified with 1M HCl solution. The precipitated product was filtered completely, washed with water and dried to form 386 mg (78%) of the title compound. MS (ESI) m / z 296.1 (M+Na)+. c) 4-(2-amino-5-chlorophenyl)-3-methoxy¡butanoic acid IF-2019-03 566964-APN-ANP#INPI 141 Page 141 of 272 CL The title compound was prepared from 4-(5-chloro-2-nitrophenyl)-3methoxybutanoic acid (Step b) of Intermediate 103) according to the method described in Method B of Intermediate 2. MS (ESI) m / z 244.1 (M+H)+. d) 7-chloro-4-methoxy¡-1.3.4,5-tetrahydro-2H-1-benzazepine-2-one h NThe title compound was prepared from 4-(2-amino-5-chlorophenyl)-3methoxybutanoic acid (Step c) of Intermediate 103) according to the method described for Intermediate 3. MS (ESI) m / z 226 .1 (M+H)*. e) 7-cioro-4-methoxy~1,3,4,5-tetrahydro-2 / 7-1 -benzazepine-2-thione The title compound was prepared from 7-chloro-4-methoxy-1,3,4,5-tetrahydro2 / 7-1-benzazepin-2-one (Step d) of Intermediate 103) according to the described method for Intermediate 23. MS (ESI) m / z 242.1 (M*H)+. Intermediary 104 7-chloro-1,5-dihydrospiroM -benzazepine-4,2'-M ,31dioxepan1-2(3H)-one a) methyl F2-(5-chloro-2-nitrobenzyl)-1,3-dioxepan-2-yllacetate COOME The title compound was prepared from meti! 4-(5-chloro-2-nitrophenii)-3oxobutanoate (Step b) of Method B of Intermediate 1) and 1,4-butanediol according to the method described for Intermediate 41. MS (ESI) m / z 366, 1 (M+Na)+. b) methyl [2-(2-amino-5-ciorobenzyl)-1,3-dioxepan-2-inacetate IF-2019-03 566964-APN-ANP#INPI 142 Page 142 of 272 COOME The title compound was prepared from methyl [2-(5-chloro-2-nitrobenzyl)-1,3dioxepan-2-yl]acetate (Step a) from Intermediate 104) according to the method described for the Intermediate 42 and was used without further purification in the next step. c) y-chloro-LS-dihydrospiroyl-benzazepine^^’-fl13]dioxepanl-2(,3 / 7)-one The title compound was prepared from methyl [2-(2-amino-5-chlorobenzyl)-1,3dioxepan-2-yl]acetate (Step b) of Intermediate 104) according to the method described for Intermediate 43 .MS (ESI) m / z 282.1 (M+H)+. Intermediate 105 tert-butyl i2-(methylsulfanyl)-4,5-dihydro-3H-1-benzazepin-4-yl1carbamate NHBoc The title compound was prepared from tert-butyl (2-thioxO“2,3,4,5-tetrahydro-1H1-benzazepin-4-yl)carbamate (Intermediate 77) according to the method described for Intermediate 5 and was used without further purification in the next step. Intermediate 106 tert-butyl [7-fluoro-2-(methylsulfanyl)-4,5-dihydro-3H-1-benzazepin-4-yl1carbamate a) methyl 3-amino-4-(5-fluorO2-nitrophenyl)but“2“enoate 'COOME The title compound was prepared from methyl 4-(5-fluoro-2-nitrophenyl)-3oxobutanoate (Intermediate 89) according to the method described in step c) of Method B of Intermediate 1 and used without further purification in the next step. b) methyl 3-amino-4-(5-fluoro-2-nitrophenyl)butanoate IF-2019-03 566964-APN-ANP#INPI 143 Page 143 of 272 NOT· COOME The title compound was prepared from methyl 3-amino-4-(5-fluoro-2nitrophenyl)but-2-enoate (Step a) of Intermediate 106) according to the method described in step d) of Method B of Intermediate 1 and was used without further purification in the next step. c) methyl 3-K / er-butoxycarbonyl)aminol-4-(5-fluoro-2-nitrophenyl)butanoate COOME The title compound was prepared from methyl 3-amino-4-(5-fluoro-2nitrophenyl)butanoate (Step b) of Intermediate 106) according to the method described in step e) of Method B of Intermediate 1. MS (ESI) m / z 379.1 (M+Na)+. d) methyl 4-(2-amino-5fluorophenyl)-3-Kterbutoxycarbonyl)amino1butanoate The title compound was prepared from methyl 3-[(tert-butoxycarbonyl)amino]-4(5-fluoro-2-nitrophenyl)butanoate (Step c) of Intermediate 106) according to the method described for Intermediate 31 and was used without further purification in the next step. e) fer-butyl (7fluorO2-oxo-2131415-tetrahydro-1H-1-benzazepin-4-yl)carbamate The title compound was prepared from methyl 4-(2-amino-5-fluorophenyl)“3-[(tert-butoxycarbonyl)amino]butanoate (Step d) of Intermediate 106) according to the method described for Intermediate 32. MS (ESI) m / z 317.1 (M+Na)+. f) tert-butyl (7-fluoro-2-thioxo-2.3,4.5-tetrahydro-1 / 7-1-benzazepin-4-yl)carbamate H,N NHBoc The title compound was prepared from tert-butyl (7-fluoro-2-oxo-2,3,4,5tetrahydro-1H-1-benzazepin-4-yl)carbamate (Step e) of Intermediate 106) according to with IF-2019-03 566964-APN-ANP#INPI 144 Page 144 of 272 the method described for Intermediate 33 and was used without further purification in the next step. q) fer-butyl [7-fluoro-2-(methylsulfanyl)-4,5-dihydro-3H-1-benzazepin-4-incarbamate The title compound was prepared from tert-butyl (7-fluoro-2-thioxo-2,3,4,5tetrahydro-1 / - / -1-benzazepin-4-yl)carbamate (Step f) from Intermediate 106 ) according to the method described for Intermediate 5 and was used without further purification in the next step. Intermediate 107 trans-4-r(4-methylpiperazin-1-yl)carbon¡Hc¡clohexanecarbohydrád¡da a) methyl frans-4-í(4-methylpiperazin-1 -¡DcarboniHcicIohexanecarboxylate The title compound was prepared from frans-4-(methoxycarbonyl)cyclohexane carboxylic acid and 1-methylpiperazine according to the method described in step a) of Intermediate 78 and was used without further purification in the next step. b) frans-4-i(4-methylpiperazin-1-yl)carbonincyclohexanecarbohydrazide The title compound was prepared from methyl trans-4-[(4-methylpiperazin-1yl)carbonyl]cyclohexanecarboxylate (Step a) of Intermediate 107) according to the method described in step b) of Intermediate 78 and used without additional purification in the next step. Intermediary 108 1-(tetrahydro-2H-pyran-4-yl)piperidine-4-carbohydrazide The title compound was prepared from ethyl 1-(tetrahydro-2 / 7-pyran-4yl)piperidine-4-carboxylate (WO 2016 / 138532 A1 (01.09.2016) VERSION CORPORATION) according to the method described in step b) of Intermediate 78 and was used without further purification in the next step. Intermediary 109 1-r(3S)-tetrahydrofuran-3-inpiperidine-4-carbohydrazide IF-2019-03 566964-APN-ANP#INPI 145 Page 145 of 272 NH-NH. l H H„ a) ethyl 1-[(3S)-tetrahydrofuran-3-yl]piperidine-4-carboxylate O'-'A / \ l and—N 5—“COOEt A mixture of 1.93 g ¢7.97 mmol) of (3R)-tetrahydrofuran-3-yl 4methylbenzenesulfonate (WO 2016 / 91776 A1 (16.06.2016) EVOTEC AG), 2.46 mL (15.9 mmol) of ethyl piperidine-4-carboxylate, 39 mL of acetonitrile, and 4.4 g (31.9 mmol) of K2CO3 were stirred at 70 °C for 24 h, then cooled to room temperature and diluted with ethyl acetate. The mixture thus obtained was washed with water and this aqueous phase was discarded. The organic layer was washed with 1M HCl solution and this acidic aqueous phase was made basic with 10% K2CO3 solution, extracted with ethyl acetate, the combined organic layers were dried over Na2SO4, filtered and concentrated. The residue was purified by flash column chromatography using dichloromethane: methanol = 91:9 as eluent to form 603 mg (27%) of the title compound. GC-MS (El) m / z 227. b) 14(3S)-tetrahydrofuran-3-npiperidine-4-carbohydrazide The title compound was prepared from ethyl 1-[(3S)-tetrahydrofuran-3yl]piperidine-4-carboxylate (Step a) of Intermediate 109) according to the method described in step b) of Intermediate 78 and used without further purification in the next step. Intermediary 110 1-[(3 / ?)-tetrahydrofuran-3-yl]piperidine-4-carbohydrazide a) ethyl 1-[(3REtetrahydrofuran-3-iHpiperidine-4-carboxylate The title compound was prepared from (3S)-tetrahydrofuran-3-yl 4methylbenzenesulfonate (WO 2016 / 91776 A1 (16.06.2016) EVOTEC AG) according to the method described in step a) of Intermediate 109. GC- MS (El) m / z 227. b) 14(3fi)tetrahydrofuran-3-yl1piper¡dina-4-carbohydrazide The title compound was prepared from ethyl 1¿(3R)-tetrahydrofuran-3yl]piperidine-4-carboxylate (Step a) of Intermediate 110) according to the method described in step b) of Intermediate 78 and used without additional purification in the next step. Intermediary 111 IF-2019-03 566964-APN-ANP#INPI 146 Page 146 of 272 ethyl cis-4-(4-methylpiperazin-1-ipcyclohexanecarboxylate and Intermediate 112 ethyl frans-4-(4-methylpiperazin-1-ipcyclohexanecarboxylate A mixture of 1.27 mL (8 mmol) of ethyl 4-oxocyclohexanecarboxylate, 887 pL (8 mmol) of 1-methylpiperazine, 4 mL of methanol and 20 mL of dichloromethane was cooled to 5°C and 3.39 g (16 mmol) of sodium triacetoxyborohydride was added to the reaction mixture at a rate such as to maintain the internal temperature below 5 °C. After the addition was complete, the reaction mixture was stirred at room temperature for 24 h, then concentrated. The residue was dissolved in 1M HCl solution and extracted with dichloromethane. The acidic aqueous phase was made basic with 10% K2CO3 solution, extracted with ethyl acetate, the combined organic layers were dried in the presence of Na2SC>4, filtered and concentrated to form 640 mg (30%) of the compounds of the titles as a mix. GC-MS (El) m / z 254. Intermediate 113 c7s-4-(4-methylpiperazin-1 -¡Pcyclohexanecarbohydrazide and Intermediate 114 frans-4-(4-methylpiperazin-1-¡Dcyclohexanecarbohydrazide The title compounds were prepared from a mixture of ethyl c / s-4-(4methylpiperazin-1-yl)cyclohexanecarboxylate (Intermediate 111) and ethyl trans-4-(4methylpiperazin-1-yl)cyclohexanecarboxylate (Intermediate 112). according to the method described in step b) of Intermediate 78. GC-MS (El) m / z 240. Intermediary 115 1-(pyridin3ylmethyl)pyrrolidine-3-carbohydrazide IF-2019-03 566964-APN-ANP#INPI 147 Page 147 of 272 a) methyl 1-(pyridin-3-ylmethyl)pyrrolidine-3-carboxylate COQMe The title compound was prepared from metí! pyrrolidine-3-carboxylate and pyridine-3-carbaldehyde according to the method described for Intermediate 111 and 112 and used without further purification in the next step. b) 1 -(pyridin-3-ylmethyl)pyrrolidine-3-carbohydrazide The title compound was prepared from methyl 1-(pyridin-3-ylmethyl)pyrrolidine-3carboxylate (Step a) of Intermediate 115) according to the method described in step b) of Intermediate 78, GC-MS (El ) m / z 220. Intermediary 116 1-(pyridin-2ylmethyl)pyrrolidine-3-carbohydrazide a) methyl 1-(pyridin-2-ylmethyl)pyrrolidine-3Carboxylate COOME The title compound was prepared from methyl pyrrolidine-3-carboxylate and pyridine-2-carbaldehyde according to the method described for Intermediate 111 and 112. MS (ESI) m / z 221.2 (M+H)+ . b) 1 -(pyridin-2-ylmethyl)pyrrolidine-3-carbohydrazide The title compound was prepared from methyl 1-(pyridin-2-ylmethyl)pyrrolidine-3carboxylate (Step a) of Intermediate 116) according to the method described in step b) of Intermediate 78 and used without purification additional in the next step. Intermediary 117 1-(pyridin-3-ylcarbonyl)pyrrolidine-3-carbohydrazide or a) methyl 1-(pyridin-3-ylcartjonyl)pyrrolidine-3-carboxylate IF-2019-03 566964-APN-ANP#INPI 148 Page 148 of 272 or COOME The title compound was prepared from pyridine-3-carboxylic acid and methyl pyrrolidine-3-carboxylate according to the method described in step a) of Intermediate 78. MS (ESI) m / z 235.1 (M+ H)+. b) 1 -(pyridin-3-ylcarbonyl)pyrrolidine-3-carbohydrazide The title compound was prepared from methyl 1-(pyridin-3-ylcarbonyl)pyrrolidine3-carboxylate (Step a) of Intermediate 117) according to the method described in step b) of Intermediate 78. GC-MS (The ) m / z 234. Intermediary 118 1(pyridin-2-ylcarbonihpyrrolidine-3-carbohydrazide NH\ NH2 a) methyl 1-(pyridin-2-ylcarbon¡l)pyrroídina-3-carboxylate COOME The title compound was prepared from pyridine-2-carboxylic acid and methyl pyrrolidine-3-carboxylate according to the method described in step a) of Intermediate 78. MS (ESI) m / z 235.2 (M+ H)+. b) 1-(pyridin-2ylcarbonyl)pyrrolidine-3-carboxylic acid COOH The title compound was prepared from methyl 1-(pyridin-2-ylcarbonyl)pyrrolidine3-carboxylate (Step a) from Intermediate 118) according to the method described for Intermediate 7. MS (ESI) m / z 221 ,1 (M+H)+. c) fer-butyl 2-{[1-(pyr¡din-2-ílcarbonií)pyrrolídin-3-íncarboníl}hydrazínecarboxylate or NH\NHBoc IF-2019-03 566964-APN-ANP#INPI 149 Page 149 of 272 The title compound was prepared from 1-(pyridin-2-ylcarbonyl)pyrrolidine3-carboxylic acid (Step b) of Intermediate 118) according to the method described for Intermediate 54. MS (ESI) m / z 335, 2 (M+H)+. d) 1-(pyridin-2-ylcarbonyl)pyrrolidine-3-carbohydrazide The title compound was prepared from er-butyl 2-{[1-(pyridin-2ylcarbonyl)pyrrolidin-3-yl]carbonyl}hydrazinecarboxylate (Step c) of Intermediate 118) according to the method described for Intermediate 55 and was used without further purification in the next step. Intermediary 119 4-methoxy-4methylcyclohexanecarbohydrazide a) ethyl 4-hydroxy-4-methylcyclohexanecarboxylate H.O. COOEt Under argon, to a stirred solution of 100 mL (220 mmol) of 2M trimethylaluminum in toluene a solution of 8.7 mL (55 mmol) of ethyl 4-oxocyclohexanecarboxylate in 50 mL of toluene was added over 2.5 h at -60° c. Once the addition was complete, the mixture was stirred at −60 °C for 0.5 h, then allowed to warm to −20 °C over 2 h. The reaction mixture was transferred in 25-30 min through a cannula to an ice-cold mixture of 180 mL ethyl acetate, 425 mL water, 75 mL concentrated hydrochloric acid, and 100 g crushed ice while maintaining the internal temperature below 10 °C. The phases were separated, the organic phase was washed successively with 400 mL of water and 400 mL of brine, dried in the presence of Na2SO4, filtered and concentrated to form 5.44 g (53%) of the title compound. According to 1H NMR spectroscopy, it was a 28:72 mixture of c / 's- and frans-isomers. This mixture was used in the next step without further purification. b) ethyl 4-methoxy-4-methylcyclohexanecarboxylate COOEt Under argon, to a stirred mixture of 2.16 g (54 mmol) of 60% sodium hydride in mineral oil, 34 mL of dry THF, 200 mg (0.54 mmol) of tetrabutylammonium iodide, 49 mg (0 .72 mmol) of imidazole and 3.36 mL (54 mmol) of iodomethane, a IF-2019-03 566964-APN-ANP#INPI 150 Page 150 of 272 solution of 3.36 g (18 mmol) of ethyl 4-hydroxy-4-methylcyclohexanecarboxylate (Step a) of Intermediate 119) in 21 mL of dry THF in 30-40 min at 20-25 °C. The reaction mixture was stirred at room temperature for 3 h, then cooled to 0–5 °C and 2.28 mL (40 mmol) of acetic acid was added in 10 min. The mixture was stirred for 15 min, then poured into a mixture of 280 mL of diethyl ether and 120 mL of saturated NaHCOs solution. The phases were separated, the organic phase was washed with brine, dried in the presence of Na2SC>4, filtered and concentrated. The residue was purified by column chromatography using n-hexane:ethyl acetate=85:15 as eluent to form 2.3 g (64%) of the title compound. According to 1H NMR spectroscopy, it was a 21:79 mixture of c / s- and trans-isomers. c) 4-methoxy-4-methylcyclohexanecarbohydrazide The title compound was prepared from ethyl 4-methoxy-4methylcyclohexanecarboxylate (Step b) of Intermediate 119) according to the method described for Intermediate 65. According to 1H NMR spectroscopy, it was a 21:79 mixture of c / s- and trans-isomers. Intermediary 120 4-(2-oxopyrrolidin-1 -Dcyclohexanecarbohydrazide The title compound was prepared from ethyl 4-(2-oxopyrrolidin-1-yl)cyclohexanecarboxylate (WO2010 / 108052 A2 (20.03.2009) H. LUNDBECK A / S) according to the method described for Intermediate 65 and used without further purification in the next step. Intermediate 121 methyl trans-4-methoxy-4-(trifluoromethyl)cyclohexanecarboxylate COOMe and Intermediate 122 methyl c / s-4-methoxy¡-4-(trifluoromethyl)cyclohexanecarboxylate \'COOMe 0^ V— / IF-2019-03 566964-APN-ANPAINPI 151 Page 151 of 272 Under argon, to a stirred mixture of 573 mg (2.7 mmol) of 4-hydroxy-4(trifluoromethyl)cyclohexanecarboxylic acid, 5 mL of dry DMF and 5 mL of dry THF, 324 mg (8.1 mmol) were added. of 60% sodium hydride in mineral oil at 0°C. The reaction mixture was stirred at this temperature for 0.5 h, then 1.18 mL (18.9 mmol) of iodomethane was added and the reaction mixture was allowed to warm to room temperature. After 3 h of stirring at room temperature, 0.59 mL (9.45 mmol) of iodomethane was added and stirring continued for 5 h. The reaction was stopped by adding 9 mL of 1M hydrochloric acid solution, then diluted with dichloromethane and the phases separated. The organic phase was washed with saturated NaHCO3 solution, dried in the presence of NazSCU, filtered and concentrated. The residue was purified by column chromatography using cyclohexane:dichloromethane=1:1 as eluent to form 242 mg (37%) of methyl frans-4-methoxy-4-(trifluoromethyl)cyclohexane-carboxylate (Intermediate 121) as the first fraction and 277 mg (43%) of methyl c / s-4-methoxy-4(trifluoromethyl)cyclohexanecarboxylate (Intermediate 122) as the second fraction. Intermediate 123 c / s-4-methoxy-4-(trifluoromethyl|cyclohexanecarbohydrazide NH—-NH2 The title compound was prepared from methyl c / 's-4-methoxy-4(trifluoromethyl)cyclohexanecarboxylate (Intermediate 122) according to the method described for Intermediate 65. GC-MS (El) m / z 240. Intermediate 124 tra / 7s-4-methoxy-4-(trifluoromethyl)cyclohexanecarbohydrazide O \-- / NH—NH2 The title compound was prepared from methyl frans-4-methoxy-4(trifluoromethyl)cyclohexanecarboxylate (Intermediate 121) according to the method described for Intermediate 65. GC-MS (El) m / z 240. Intermediate 125 trans-4-r(4-methoxybenzyl)aminocycloliexanecarbohydrazide IF-2019-03 566964-APN-ANP#INPI 152 Page 152 of 272 a) methyl frans-4-[(4-methoxybenzyl)amino1cytiumhexanecarboxylate A mixture of 2.0 g (10.3 mmol) methyl ira / 7s-4-aminocyclohexanecarboxylate hydrochloride (Combi-Blocks), 20 mL 1,2-dichloroethane, 1.38 mL (11.4 mmol) 4-methoxybenzaldehyde and 1.12 mL (19.6 mmol) of acetic acid was cooled to 5 °C and 6.78 g (32.0 mmol) of sodium triacetoxyborohydride was added to the reaction mixture at a rate such as to maintain the temperature internal below 5 °C. After the addition was complete, the reaction mixture was stirred at room temperature for 20 h, then diluted with water. The pH of the mixture was adjusted to 8 by adding 10% Na2CO3 solution, the phases were separated and the aqueous phase was extracted with dichloromethane. The combined organic phases were dried in the presence of MgSCU, filtered and concentrated to form 1.48 g (52%) of the title compound. MS (ESI) m / z 278.2 (M+H)+. b) frans-4-í(4-methoxybenzyl)amino1cyclohexanecarbohydrate The title compound was prepared from methyl frans-4-[(4methoxybenzyl)amino]cyclohexanecarboxylate (Step a) of Intermediate 125) according to the method described for Intermediate 65 and used without further purification in the next step. Intermediate 126 tra / ?s-4-ethoxy-4-ethylcyclohexane-carbohydrazide a) ethyl 4-ethyl-4“hydroxycyclohexanecarboxylate H.O. The title compound was prepared from ethyl 4-oxocyclohexanecarboxylate and 25% triethylaluminum solution in toluene according to the method described in step a) of Intermediate 119. According to 1H NMR spectroscopy, it was a 27:73 mixture of c / s- and frans-isomers. This mixture was used in the next step without further purification. IF-2019-03 566964-APN-ANP#INPI 153 Page 153 of 272 b) ethyl frans-4-ethoxy-4-ethylcyclohexanecarboxylate Under argon, to a stirred mixture of 1.32 g (33 mmol) of 60% sodium hydride in mineral oil, 22 mL of dry toluene, 406 mg (1.1 mmol) of tetrabutylammonium iodide and 2.85 mL (22 mmol) of ethyl trifluoromethanesulfonate, a solution of 2.2 g (11 mmol) of ethyl 4-ethyl-4-hydroxycyclohexanecarboxylate (Step a) of Intermediate 126) in 11 mL of dry toluene was added in 30-40 min to 20-25°C. The reaction mixture was stirred at room temperature for 20 h, then cooled to 0-5 °C and poured into an ice-cold mixture of 220 mL ethyl acetate, 110 mL saturated NaHCOa solution, and 30 mL water. . The mixture was stirred at 5 °C for 0.5 h, then at room temperature for 20 h. The phases were separated, the organic phase was washed with brine, dried in the presence of Na2SO4, filtered and concentrated. The residue was purified by column chromatography using n-hexane:ethyl acetate=94:6 as eluent to form 1.77 g (71%) of the title compound. According to 1H NMR spectroscopy, it was a 3:97 mixture of c / s- and frans-isomers. c) frans-4-ethoxy¡-4-ethylcytiumhexane-carbohydrate¡draz¡da The title compound was prepared from ethyl 4-ethoxy-4ethylcyclohexanecarboxylate (Step b) of Intermediate 126) according to the method described for Intermediate 65. According to 1H NMR spectroscopy, it was a 3:97 mixture of c / s - and frans-isomers. This mixture was used in the next step without further purification. Intermediate 127 4-ethyl-4-methoxycyclohexane-carbohydrazide. nh~nh2( 1 / o a) ethyl 4-methoxy-4-ethylcyclohexanecarboxylate fy \ JX >--COOEt The title compound was prepared from ethyl 4-ethyl-4-hydroxycyclohexanecarboxylate (Step a) of Intermediate 126) and methyl trifluoromethanesulfonate according to the method described in step b) of Intermediate 126. According to 1H NMR spectroscopy, it was a 19:81 mixture of cis- and frans-isomers. b) 4-ethyl-4-methoxycyclohexane-carbohydrazide IF-2019-03 566964-APN-ANP#INPI 154 Page 154 of 272 The compound of! titer was prepared from ethyl 4-methoxy-4-ethylcyclohexanecarboxylate (Step a) of Intermediate 127) according to the method described for Intermediate 65. According to 1H NMR spectroscopy, it was a 20:80 mixture of c / s- and frans-isomers. This mixture was used in the next step without further purification. Intermediate 128 trans-4-ethoxy4-methylcyclohexanecarbohydrazide / ---x nh-nh2'—> or a) ethyl theans-4-ethoxy-4-methylcyclohexanecarboxylate / \y-ncooEt The title compound was prepared from ethyl 4-hydroxy-4methylcyclohexanecarboxylate (Step a) of Intermediate 119) and ethyl trifluoromethanesulfonate according to the method described in step b) o...

Claims

1. A compound, characterized in that it has general formula (I) (FORMULA) wherein ring A is a saturated 4- to 6-membered carbocyclic group, or a saturated 4- to 7-membered heterocycle containing 1 or 2 N linked by a nitrogen ring to Y or to the triazole ring of the 5,6-dihydro-4H-[1,2,4]triazolo[4,3-a][1]benzazepine core; in BY, Y is -O-, -C(O)-, -CH2-, -NH-, -CH2-N(R 18 )- or bond and ring B is a 6-membered mono-heteroaryl group, a 6-membered mono-heteroaryl group substituted with one or more C1-4 alkyl, C1-4 alkoxy, oxo groups or halogens, a 5- to 6-membered saturated monocyclic heterocycle containing 1 or 2 heteroatoms selected from O, S or N, or a 5- to 6-membered saturated monocyclic heterocycle containing 1 or 2 heteroatoms selected from O, S or N substituted with one or more C1-4 alkyl, C1-4 alkoxy, oxo groups or halogens;or BY collectively represents -N(CH3)2, C(O)OC1-4 alkyl, C1-3 alkyl, trifluoromethyl, C1-2 alkoxy group or fluorine; or BYA- collectively represents a 3H-spiro[2-benzofuran-1,4'-piperidin-1'-yl] group; or group (FORMULA); or group (FORMULA); or group (FORMULA); R1 is hydrogen, fluorine, chlorine, bromine, methyl, methoxy, CF3 or CN; R2 is hydrogen; R3 is NR4R5, OR6 group or fluorine; or R2 and R3 collectively represent -O-(CH2)mO-, oxo or =N-OH group; R4 and R5 are independently hydrogen; C1-4 alkyl, C2 alkyl substituted with OH, fluorine, cyclopropyl, fluorine-substituted phenyl or NR8R9 group; Cy1; C(O)R7; -S(O2)R10 or C2-4 alkynyl group; or R4 and R5 taken together with the N to which they are attached form a saturated heterocyclyl group of 4 to 6 members containing 1 O and 1 N, or 1 N; R6 is a hydrogen; C1-4 alkyl, C1-2 alkyl substituted with an OH group, Cy2, C1-2 alkoxy, -S(O)2-C1-2 alkyl or NR11R12; C(O)R13; Si(CH3)2-t-butyl group or C2-4 alkynyl group;R 7 is a C1-4 alkyl, C1-3 alkyl substituted with OH, C1 alkyl substituted with CN, trifluoromethyl, benzyl, C1 alkyl substituted with group NR 11 R 12; tert-butoxy group, C2 alkenyl, Cy 3 or N(CH3)2; R 8 and R 9 are independently a hydrogen, methyl group, or C(O)OR 21; R 10 is a methyl group, or NR 14 R 15; R 11 and R 12 are independently a hydrogen or methyl group; R 13 is a methyl, C1 alkyl substituted with group CN or NR 19 R 20, or Cy 3; R 14 and R 15 are independently a hydrogen or methyl group; R16 and R17 are independently a hydrogen, C1-4 alkyl, aryl or aryl substituted with one or more C1-4 alkyl, C1-4 alkoxy, oxo or halogen groups; R18 is a hydrogen or methyl group; R21 is a tert-butyl group; R19 and R20 are a methyl group; Cy1 is a saturated 4- to 6-membered carbocyclic group;a saturated 4- to 6-membered carbocyclic group substituted with fluorine, a saturated 4- to 7-membered heterocyclyl group containing 1 O, or a 6-membered monoheteroaryl group containing 1 or 2 N; Cy2 is a cyclopropyl group; Cy3 is a phenyl, a fluorophenyl, a saturated 3- to 6-membered carbocyclic group, a saturated 3- to 6-membered carbocyclic group substituted with fluorine, or a saturated 4- to 6-membered heterocyclyl group containing 1 O or 1 N; X is an isopropyl; Z is a methyl group; m is 2, 3, or 4, and salts thereof. 6 Claims follow;