(Aza)indole-, benzothiophene-, and benzofuran-3-sulfonamides

Abstract

The present invention discloses sulfonamide compounds with GPR17 modulating properties, which can be used to treat or prevent various CNS and other diseases, in particular for preventing and treating myelinating diseases or disorders.

Description

[0001] This application is a divisional application of the Chinese patent application with application number 201780081379.5, application date December 27, 2017, and invention name “(Aza)indole-, benzothiophene- and benzofuran-3-sulfonamides”. background

[0002] G-protein-coupled receptors (GPCRs) constitute the largest family of membrane receptors in cells. They transduce extracellular signals to intracellular effector systems and are involved in a variety of physiological phenomena, thus representing the most common target for pharmaceutical drugs, although current therapies target only a small subset of GPCRs.

[0003] GPCRs respond to a variety of ligands. Due to advances in human genome sequencing, for approximately 25% of the more than 400 GPCRs that have been identified (excluding olfactory GPCRs), there is still a lack of a defined physiologically relevant ligand. These receptors are referred to as "orphan GPCRs." It is expected that "deorphanization" and identification of their in vivo effects will elucidate new regulatory mechanisms and therefore disclose new drug targets. Whether GPR17 is such an orphan receptor remains a matter of debate. Phylogenetically, GPR17 is closely related to the nucleotide P2Y receptor and the cysteinyl leukotriene (CysLT1, CysLT2) receptor, with amino acid sequence identities of approximately 30% to approximately 35%, respectively.

[0004] Western blot and RT-PCR analysis of multiple tissues indicate that GPR17 is expressed predominantly in the central nervous system (CNS) (Ciana et al., 2006, EMBO J 25(19):4615; Blasius et al., 1998, J Neurochem 70(4):1357) and additionally in the heart and kidney, organs that commonly undergo ischemic injury. Two human GPR17 isoforms have been identified that differ in the length of their N-termini. The short GPR17 isoform encodes a 339 amino acid-residue protein with a typical rhodopsin type 7 transmembrane motif. The long isoform encodes a receptor with a 28 amino acid-long N-terminus (Blasius et al., 1998). GPR17 is highly conserved across vertebrate species (approximately 90% identity to the amino acid sequence of the mouse and rat orthologs), which may constitute an advantageous feature for the development of small molecule ligands and animal models in the context of drug discovery.

[0005] In the initial de novo report, GPR17 was identified as a dual receptor for uracil nucleotides and cysteinyl leukotrienes (cysLTs) LTC4 and LTD4, respectively, based on 35SGTPγS binding and cAMP inhibition assays as well as single-cell calcium imaging (Ciana et al., 2006, supra). Evidence for GPR17 function was provided in different cell backgrounds, such as 1321N1, COS7, CHO and HEK293 cells (Ciana et al., 2006, supra). Subsequently, an independent study confirmed that GPR17 is activated by uracil nucleotides but failed to recapitulate activation by CysLT (Benned-Jensen and Rosenkilde, 2010, Br J Pharmacol, 159(5):1092). However, recent independent reports (Maekawa et al., 2009, PNAS 106(28), 11685; Qi et al., 2013, J Pharmacol Ther 347, 1, 38; Hennen et al., 2013, Sci Signal 6, 298) suggest a lack of GPR17 responsiveness to uracil nucleotides and CysLTs in different cell backgrounds stably expressing GPR17 (1321N1, CHO, HEK293 cells). A novel regulatory role for GPR17 has also been proposed: GPR17—when co-expressed with the CysLT1 receptor—renders the CysLT1 receptor unresponsive to its endogenous lipid mediators, LTC4 and LTD4. Clearly, additional in vitro studies are needed to more deeply probe the pharmacology and function of GPR17.

[0006] Drugs that modulate GPR17 activity may have neuroprotective, anti-inflammatory, and anti-ischemic effects and may therefore be useful in treating cerebral, cardiac, and renal ischemia and stroke (WO2006 / 045476), and / or in improving recovery from these events (Bonfanti et al., Cell Death and Disease, 2017, 8, e2871).

[0007] GPR17 modulators are also thought to be involved in food intake, insulin and leptin responses and therefore have been claimed to have a role in the treatment of obesity (WO 2011 / 113032).

[0008] In addition, there is strong evidence that GPR17 is involved in the myelination process, and negative GPR17 modulators (antagonists or inverse agonists) may be valuable drugs for treating or alleviating myelination disorders such as multiple sclerosis or spinal cord injury (Chen et al., Nature neuroscience 2009, 12(11): 1398-406; Ceruti et al., Brain: ajournal of neurology 2009 132(Pt 8): 2206-18; Hennen et al., Sci Signal, 6, 2013, 298; Simon et al. J Biol Chem 291, 2016, 705; Fumagalli et al., Neuropharmacology 104, 2016, 82). Activation of GPR17 has been shown to inhibit the maturation of oligodendrocyte precursor cells (OPCs), thereby preventing effective myelination (Simon et al., supra). Therefore, the identification of potent and selective GPR17 antagonists or inverse agonists will be of great significance in the treatment of myelinating disorders.

[0009] Several serious myelinating diseases are known to be caused by disturbances in myelination, either due to a loss of myelin (commonly referred to as demyelination) and / or due to the body's inability to form myelin normally (sometimes referred to as dysmyelination). Myelinating diseases may be idiopathic or secondary to certain triggering events, such as traumatic brain injury or viral infection. Myelinating diseases may primarily affect the central nervous system (CNS), but may also be associated with the peripheral nervous system. Myelinating diseases include, in particular, multiple sclerosis, neuromyelitis optica (also known as Devic's disease), leukoencephalopathy, Guillain-Barré syndrome and many other diseases, as described in further detail below (see also, for example, Love, J Clin Pathol, 59, 2006, 1151, Fumagalli et al., supra). Neurodegenerative diseases such as Alzheimer's disease, Huntington's disease, Parkinson's disease, amyotrophic lateral sclerosis (ALS) and multiple system atrophy (MSA) have also recently been closely associated with reduced myelination (see, e.g., Ettle et al., Mol Neurobiol 53, 2016, 3046; Jellinger and Welling, Movement Disorders, 31, 2016; 1767; Kang et al., Nature Neurosci 6, 2013, 571; Bartzokis, Neurochem Res (2007) 32: 1655).

[0010] Multiple sclerosis (MS) is a chronic, progressive disease. It is an inflammatory autoimmune disease that causes oligodendrocyte damage, demyelination, and eventual axonal loss, leading to a wide spectrum of signs and symptoms of severe neurological disease, such as fatigue, dizziness, problems moving and walking, difficulty speaking and swallowing, pain, and others. MS has several forms, with new symptoms occurring in isolated attacks (relapsing forms) or gradually developing over time (progressive forms). While some symptoms may disappear completely between isolated attacks, serious neurological problems often remain, especially as the disease progresses to a more progressive form. According to the Multiple Sclerosis Society, approximately 400,000 people in the United States and as many as 2.5 million people worldwide have been diagnosed with MS, with an estimated 10,000 new cases diagnosed in the United States each year. Multiple sclerosis is two to three times more common in women than in men.

[0011] There is no known causal treatment or cure for multiple sclerosis or many other myelinating disorders. Treatment is typically symptomatic and attempts to improve function after an episode and prevent new episodes by addressing the inflammatory component of the disease. These immunomodulatory drugs are often only modestly effective, particularly if the disease progresses, but can have side effects and be poorly tolerated. Furthermore, most available drugs, such as beta-interferon, glatiramer acetate, or therapeutic antibodies, are only available in injectable form and / or address only the inflammatory component of the disease rather than directly addressing demyelination. Other drugs, such as corticosteroids, exhibit relatively modest anti-inflammatory and immunosuppressive effects and may therefore lead to chronic side effects, such as those manifesting as Cushing's syndrome.

[0012] Therefore, there is a strong need for a safe and effective drug for treating myelinating diseases such as MS, preferably a drug suitable for oral administration. Ideally, such a drug would reverse the demyelinating process by reducing demyelination and / or by promoting remyelination of affected neurons. Compounds that effectively reduce the activity of the GPR17 receptor could meet these requirements.

[0013] However, only a few compounds are known to effectively modulate GPR17 activity.

[0014] WO2005 / 103291 proposes the endogenous molecules 5-aminolevulinic acid (5-ALA) and porphobilinogen (PBG) as activating ligands for GPR17, discloses the analgesic effects of GPR17 agonists, and proposes the use of GPR17 agonists for the treatment of neuropathic pain and as tools for GPR17 screening assays. However, the reported affinities of 5-ALA and PBG are very low, and the amounts required in the assays are significant, i.e., in the triple-digit micromolar range for 5-ALA or even in the millimolar range for PBG, making both compounds unsuitable for routine screening assays or even for therapeutic use. Furthermore, PBG is a chemically unstable active compound that rapidly decomposes upon exposure to air and light, making conventional handling impractical. Therefore, these compounds do not provide a promising starting point for the development of therapeutically effective negative GPR17 modulators.

[0015] Montelukast and pranlukast were originally developed as leukotriene receptor antagonists, and recently it was found that they also act on GPR17 receptors (Ciana et al., EMBO J.2006, 25, 4615-4627). However, subsequent functional assay results were contradictory for Montelukast (Hennen et al., 2013, supra), while pharmacological inhibition of GPR17 with pranlukast promoted the differentiation of oligodendrocytes in primary mice (Hennen et al., 2013, supra) and rats (Ou et al., J. Neurosci.36, 2016, 10560-10573). Pranlukast can even show the effect of GPR17 inhibition in the lysolecithin model of focal demyelination, because wild-type mice treated with GPR17 knockout and pranlukast showed earlier myelin regeneration (Ou, supra). These results strongly support the hypothesis that GPR17 inhibitors offer potential for treating human demyelinating diseases.

[0016] However, the affinities of montelukast and pranlukast for GPR17 are only in the high micromolar range ( et al., ACS Med. Chem. Lett. 2014, 5, 326-330). Given the high protein binding of both compounds and their poor brain penetration, it is unlikely that they would reach sufficiently high free concentrations to bind to the GPR17 receptor in amounts suitable for human therapy. Furthermore, due to their high affinity for the CYSLT1 receptor, it is difficult to interpret the results obtained with these compounds in vivo.

[0017] US8,623,593 discloses certain indole-2-carboxylic acids as GPR17 agonists and their use in screening assays. However, these derivatives are all potent agonists and are not suitable for downregulating GPR17 activity required for the treatment of myelin formation disorders such as MS. In addition, such GPR17 activators cannot adequately cross the blood-brain barrier due to their easily ionized carboxyl groups, so there is no suitable lead compound to generate negative GPR17 modulators. See also Baqi et al., Med. Chem. Commun., 2014, 5, 86 and et al., 2014, supra.

[0018] WO2013 / 167177 proposes certain phenyltriazoles and benzodiazepines (benzodiazepine) compounds as GPR17 antagonists. However, the disclosed compounds were selected based solely on computer screening results, and no biological data were provided. The inventors of the present application have been unable to confirm the GPR17 antagonist modulating activity of any of the so-called ligands proposed by the authors of this prior patent application to date.

[0019] Therefore, there is a need to identify effective modulators of GPR17, preferably negative modulators, that are capable of effectively reducing GPR17 activity, preferably by oral administration.

[0020] Mehra et al. (Eur J Med Chem, 92, 2015, 78-90) disclosed a variety of compounds with Escherichia coli acetyltransferase inhibitory activity, including four phenyl-substituted pyrrolo[2,3-b]pyridine-3-sulfonamides (compound 20 [N-(3,4-difluorophenyl 1H-pyrrolo[2,3-b]pyridine-3-sulfonamide], 32 [N-(3,5-dimethoxyphenyl 1H-pyrrolo[2,3-b]pyridine-3-sulfonamide], compound 37 [N-(2,5-difluorophenyl 1H-pyrrolo[2,3 [-b]pyridine-3-sulfonamide] and compound 43 [N-(3,5-difluorophenyl 1H-pyrrolo[2,3-b]pyridine-3-sulfonamide]]. These four azaindole compounds differ structurally from the compounds disclosed herein in that the azaindole core in Mehra et al. is not further substituted. Furthermore, Mehra et al. do not suggest GPR17 inhibitory properties for any of these compounds and / or any use of their compounds for treating myelin formation disorders. Instead, Mehra et al. disclose the compounds as potential antibiotics.

[0021] Attached photos:

[0022] Figure 1The expression of myelin basic protein (MBP), a marker of oligodendrocyte maturation, is shown in a Western blot assay. Following administration to oligodendrocyte progenitor cells (OPCs), compounds of the invention, particularly compounds 1-112, 1-185, 1-108, and 1-116, stimulated MBP expression compared to vehicle alone.

[0023] Figure 2 The effect of the compound of the present invention (I-116) on the length of myelin sheaths expressed by OPCs is shown. After administration to OPCs, compound I-116 induced the formation of longer myelin sheaths compared to OPCs after addition of vehicle alone.

[0024] Figure 3 Shown are the plasma and brain exposures of Compound 1-1 of the invention following intraperitoneal administration in mice.

[0025] Figure 4 Shown are two relevant areas of the mouse brain, area 1 ( Figure 4 .1) and area 2( Figure 4 .2) in the distribution of PLP (myelin marker). This setup was used to measure the effects of the compounds of the invention in the cuprizone model (results are shown in Figure 5 middle).

[0026] Figure 5 The effect of a compound of the invention (I-228) on PLP expression in mice during recovery from cuprizone treatment, as measured by immunohistochemical staining, is shown. Following oral administration of 6 mg / kg and 20 mg / kg I-228 to mice, the myelin-associated protein PLP reappeared significantly faster in certain mouse brain regions than after vehicle administration alone.

[0027] Description of the Invention

[0028] The present invention relates to a class of chemical compounds that are negative GPR17 modulators.

[0029] These compounds have the general structure of Formula I:

[0030]

[0031] in

[0032] X1 is N or C (R7),

[0033] X2 is NH, S or O,

[0034] X3 is N or C (R12),

[0035] R4 is selected from hydrogen, methoxy and halogen, including fluorine, and is preferably hydrogen,

[0036] R5 is selected from hydrogen, halogen, cyano, C 1-6 Alkyl, C 2-3 Alkenyl, C 2-3 Alkynyl, C 1-6 Alkoxy, C 1-3 Alkylcarbonyl, C 1-3 Alkoxycarbonyl, C 1-3 Alkylsulfinyl and C 1-3 Alkylsulfonyl, wherein each alkyl or alkoxy group may be optionally substituted one or more times with a substituent selected from halogen, C 1-3 Alkoxy, cyano, azido, hydroxyl, C 1-3 Alkylamino and di(C 1-3 alkyl)amino and C 1-3 Alkylaminocarbonyl (wherein preferred optional substituents of said alkyl and alkoxy groups are halogen and C 1-6 alkoxy), or R5 and R6 together form a ring as described herein,

[0037] R6 is selected from hydrogen, hydroxy, halogen, cyano, azido, nitro, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Alkoxy, C 3-7 Cycloalkyl, C 3-6 Cycloalkenyl, C 3-7 Heterocycloalkyl, C 3-7 Heterocycloalkenyl, phenyl, C 5-10 Heteroaryl, C 8-10 heterocyclyl, -ORx, -SRx, -SORx, SO2Rx, -pentafluorosulfanyl, NRyRzz, -NRyCORx, -NRyCO2Rx, -NRxCONRyRz, -NRySORx, -NRySO2Rx, -CORx, -CO2Rx, -CONRyRz, wherein each alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, heterocycloalkyl, cycloalkenyl, phenyl, heteroaryl or heterocyclyl group in R6 may be unsubstituted or substituted by one or more residues preferably selected from halogen, hydroxy, oxo, cyano, azido, nitro, C 1-6 Alkyl, halo (C 1-6 ) alkyl, C 1-6 Alkoxy (C 1-3 ) alkyl, C 3-7 Cycloalkyl, C 3-7 Heterocycloalkyl, phenyl, C 5-10 (Preferred C 5-6)heteroaryl, ORx, -SRx, -SORx, SO2Rx, -pentafluorosulfanyl, NRyRz, -NRyCORx, -NRyCO2Rx, -CORx, -CO2Rx, -CONRyRz,

[0038] wherein Rx, Ry, Rz and Rzz are independently selected from hydrogen, C 1-6 Alkyl, C 3-7 Cycloalkyl, C 3-6 Cycloalkenyl, C 3-7 Cycloalkyl (C 1-6 ) alkyl, phenyl, phenyl (C 1-6 ) alkyl, C 3-7 Heterocycloalkyl, C 3-7 Heterocycloalkyl (C 1-6 ) alkyl, C 5-6 Heteroaryl or heteroaryl (C 1-6 )alkyl, any one of which may be unsubstituted or substituted by one or more substituents selected from those described above, and wherein Rzz is preferably different from hydrogen,

[0039] Alternatively, Ry and Rz or Ry and Rzz together with the amino atoms to which they are both attached may form an aromatic or non-aromatic, unsubstituted or substituted C 5-6 heterocyclic ring, wherein any substituent is selected from the substituents described above,

[0040] or R6 and R5 or R7 together with the carbon atoms to which they are attached form a 5- or 6-membered aromatic or non-aromatic ring, which may optionally contain one or more heteroatoms selected from S, O and N, and wherein the ring may be unsubstituted or substituted by one or more substituents,

[0041] wherein preferably (i) R6 and R7 together with the carbon atom to which R6 and R7 are attached form an unsubstituted or substituted phenyl group, an unsubstituted or substituted pyridyl group, an unsubstituted or substituted cyclopentyl group or an unsubstituted or substituted cyclohexyl group,

[0042] wherein each substituent of the ring formed by R6 and R7, if present, is preferably selected from halogen, hydroxy, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-7 Cycloalkyl, C 3-7 Cycloalkyl (C 1-3 ) alkyl, C 3-7 Heterocycloalkyl (C 1-3 ) alkyl and C 1-6 Alkoxy, wherein each alkyl or alkoxy group may be unsubstituted or substituted with one or more substituents selected from halogen, hydroxy, and unsubstituted or fluorinated C1-3 Alkoxy, C 3-7 Cycloalkyl and C 3-7 heterocycloalkyl, wherein any substituents of phenyl, pyridyl, cyclopentyl and cyclohexyl are preferably selected from fluorine, chlorine, cyano, hydroxy, methyl, fluoromethyl, methoxy and fluoromethoxy,

[0043] or (ii) R6 and R5 together with the carbon atom to which R6 and R5 are attached form a 1,3-dioxolane ring which may be unsubstituted or substituted with one or two substituents selected from fluorine and methyl, or

[0044] R7, if present, is selected from hydrogen, halogen, cyano, azido, nitro, amino, C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkynyl, C 2-6 Alkenyl, C 1-6 Alkylcarbonyl, C 1-6 Alkoxycarbonyl, C 1-6 Alkylsulfonyl, C 1-6 Alkylsulfinyl, C 1-6 Alkylthio, C 1-3 Alkylcarbonylamino, C 1-6 Alkylaminocarbonyl, di(C 1-3 )alkylaminocarbonyl, C 3-7 Cycloalkyl, C 3-7 Cycloalkoxy, C 3-7 Heterocycloalkyl, C 3-6 Heterocycloalkoxy, phenyl, phenyloxy, phenyl (C 1-2 ) alkyl, phenyl (C 1-2 ) alkoxy, phenylsulfonyl, phenylsulfinyl, C 5-6 Heteroaryl, C 5-6 Heteroaryloxy, C 5-6 Heteroaryl (C 1-3 ) alkyl, C 5-6 Heteroaryl (C 1-3 ) alkoxy, C 3-6 Cycloalkyl (C 1-2 ) alkyl, C 3-6 Cycloalkyl (C 1-3 ) alkoxy, C 3-6 Heterocycloalkyl (C 1-2 ) alkyl, C 3-6 Heterocycloalkyl (C 1-2 ) alkoxy, and wherein each group in R7, in particular each alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, heterocycloalkyl, phenyl or heteroaryl group, may be unsubstituted or substituted by one or more substituents selected from halogen, hydroxy, cyano, unsubstituted or halogenated C 1-6Alkyl and unsubstituted or halogenated C 1-6 Alkoxy,

[0045] R8 is selected from hydrogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Alkoxy, C 1-3 Alkylsulfinyl, C 1-3 Alkylsulfonyl, C 1-3 Alkylthio, cyano and halogen, wherein each alkyl or alkoxy group may be unsubstituted or substituted with one or more substituents selected from halogen and unsubstituted or fluorinated C 1-3 alkoxy, or together with R9, to form a ring system as described herein,

[0046] R9 is selected from hydrogen, halogen, cyano, azido, C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl and halogen, wherein each alkyl or alkoxy group may be unsubstituted or substituted with one or more substituents selected from halogen and unsubstituted or fluorinated C 1-3 Alkoxy,

[0047] or R9 and R8 or R10 together with the C atom to which they are attached form a 5- or 6-membered ring, which may optionally be further substituted and which may contain one or more ring-forming heteroatoms selected from N, S, O and Se;

[0048] wherein the ring formed by R9 and R8 or R10 forms a bicyclic ring system with the ring to which they are attached, said bicyclic ring system being preferably selected from (a) 2,1,3-benzothiadiazole, (b) 2,1,3-benzoselenadiazole, (c) 2,1,3-benzoxadiazole, (d) 1,3-benzothiazole, (e) 1,3-benzoxazole, which may be unsubstituted or may be partially hydrogenated and unsubstituted or substituted by oxo, (f) 1,3-benzodioxole, which may be unsubstituted or substituted by one or two substituents selected from fluoro and methyl, (g) benzothiophene, which may be unsubstituted or may be partially hydrogenated and unsubstituted or substituted by one or two substituents selected from oxo, methyl or fluoro, wherein benzothiophene is preferably partially hydrogenated to 1,3-dioxole. (h) benzofuran, which may be unsubstituted or may be partially hydrogenated and unsubstituted or substituted by one or two groups selected from oxo, fluoro and methyl, preferably by one oxo group, wherein benzofuran is preferably partially hydrogenated to 1,3-dihydro-2-benzofuran, which is preferably substituted by oxo to form 3-oxo-1,3-dihydrobenzofuran, which may optionally be further substituted, for example, by methyl, and (i) 2,3-dihydro-1H-isoindole, which is preferably substituted by oxo to give 3-oxo-2,3-dihydro-1H-isoindole, which may optionally be further substituted.

[0049] R10 is selected from hydrogen, halogen, C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, cyano, cyano (C 1-6 )alkyl, cyano (C 1-6 ) alkyloxy, C 1-6 Alkylcarbonyl, C 1-6 Alkoxycarbonyl, C 1-6 Alkylsulfonyl, C 1-6 Alkylsulfinyl, C 1-6 Alkylthio, C 3-6 Cycloalkyl, C 3-6 Cycloalkyloxy, C 3-6 Heterocycloalkyl, C 3-6 Heterocycloalkyloxy, amino, azido, pentafluorosulfanyl, nitro, C 1-5 Alkylcarbonylamino, C 1-5 Alkylaminocarbonyl, di(C 1-3 )alkylaminocarbonyl, C 1-3 Alkylsulfinyl and C 1-3Alkylsulfonyl, wherein each alkyl, alkenyl, alkynyl or alkoxy group may be unsubstituted or substituted with one or more substituents selected from halogen, C 1-6 Alkoxy, halo (C 1-6 ) alkoxy hydroxy (C 1-6 ) alkoxy, optionally halogenated C 1-6 Alkylthio, optionally halogenated C 1-3 Alkylcarbonyl, optionally halogenated C 1-3 Alkyloxycarbonyl, optionally halogenated C 1-3 Alkylsulfonyl, optionally halogenated C 1-3 Alkylsulfinyl, C 1-3 Alkylcarbonylamino, C 1-3 Alkylaminocarbonyl, di(C 1-3 )alkylaminocarbonyl, hydroxy, cyano, nitro, oxo, C 3-6 Cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Heterocycloalkyl, C 3-6 Heterocycloalkoxy, phenyl, phenyloxy and C 5-6 Heteroaryl, wherein any C 3-6 Cycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Heterocycloalkyl, C 3-6 Heterocycloalkoxy, phenyl and heteroaryl may be unsubstituted or substituted with one or more residues selected from halogen, hydroxy, hydroxymethyl, oxo, cyano, nitro, amino, optionally halogenated or hydroxylated C 1-3 Alkyl, optionally hydroxylated or halogenated C 1-3 Alkoxy, optionally halogenated C 1-3 Alkylcarbonyl and optionally halogenated C 1-3 Alkoxycarbonyl, wherein the amino group may be substituted by one or two groups selected from C 1-3 Alkyl, C 1-3 Alkylsulfonyl, C 1-3 Alkylcarbonyl and C 1-3 alkoxycarbonyl, or as described herein R10 and R9 together form a ring system,

[0050] R11 is selected from hydrogen, halogen, cyano, azido, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylcarbonyl, C 1-6 Alkoxycarbonyl, C 1-6 Alkylsulfonyl, and C 1-6 Alkylsulfinyl, C 2-6 Alkenyl and C 2-6Alkynyl, wherein each alkyl or alkoxy group may be unsubstituted or substituted by one or more substituents selected from halogen and halogenated, preferably fluorinated, or unsubstituted C 1-3 Alkoxy,

[0051] R12, if present, is selected from hydrogen, C 1-6 Alkyl, C 1-6 Alkoxy and halogen, wherein each alkyl or alkoxy group may be unsubstituted or substituted by one or more substituents selected from halogen and halogenated, preferably fluorinated or unsubstituted C 1-3 Alkoxy,

[0052] and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof.

[0053] In one embodiment, in the compound of formula I,

[0054] X1 is N or C (R7),

[0055] X2 is NH or O,

[0056] X3 is N or C (R12),

[0057] R4 is selected from hydrogen and fluorine, and is preferably hydrogen,

[0058] R5 is selected from hydrogen, halogen, cyano, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-3 Alkylcarbonyl, C 1-3 Alkoxycarbonyl, C 1-3 Alkylsulfinyl and C 1-3 Alkylsulfonyl, wherein each alkyl or alkoxy group may be optionally substituted one or more times with a substituent selected from halogen, C 1-3 Alkoxy, C 2-3 Alkynyl, C 2-3 alkenyl, cyano, azido, hydroxyl and optionally C 1-3 Alkylated amino (wherein the preferred optional substituents of the alkyl and alkoxy groups are halogen and C 1-6 alkoxy), or R5 and R6 together form a ring as described herein,

[0059] R6 is selected from hydrogen, hydroxy, halogen, cyano, azido, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Alkoxy, C 3-7 Cycloalkyl, C 3-6 Cycloalkenyl, C 3-7 Heterocycloalkyl, C 3-7 Heterocycloalkenyl, phenyl, C 5-10Heteroaryl, C 8-10 heterocyclyl, -ORx, -SRx, -SORx, SO2Rx, -pentafluorosulfanyl, NRyRzz, -NRyCORx, -NRyCO2Rx, -NRxCONRyRz, -CORx, -CO2Rx, -CONRyRz, wherein each alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, heterocycloalkyl, cycloalkenyl, phenyl, heteroaryl or heterocyclyl group in R6 may be unsubstituted or substituted by one or more substituents, preferably selected from halogen, hydroxy, oxo, cyano, azido, nitro, C 1-6 Alkyl, C 1-6 Alkoxy (C 1-3 ) alkyl, C 3-7 Cycloalkyl, C 3-7 Heterocycloalkyl, phenyl, C 5-10 (Preferred C 5-6 )heteroaryl, ORx, -SRx, -SORx, SO2Rx, -pentafluorosulfanyl, NRyRz, -NRyCORx, -NRyCO2Rx, -CORx, -CO2Rx, -CONRyRz,

[0060] wherein Rx, Ry, Rz and Rzz are independently selected from hydrogen, C 1-6 Alkyl, C 3-7 Cycloalkyl, C 3-6 Cycloalkenyl, C 3-7 Cycloalkyl (C 1-6 ) alkyl, phenyl, phenyl (C 1-6 ) alkyl, C 3-7 Heterocycloalkyl, C 3-7 Heterocycloalkyl (C 1-6 ) alkyl, C 5-6 Heteroaryl or heteroaryl (C 1-6 ) alkyl, any one of which may be unsubstituted or substituted by one or more substituents, or Ry and Rz or Ry and Rzz together with the amino atom to which they are both attached may form an aromatic or non-aromatic, unsubstituted or substituted C 5-6 heterocyclic ring, wherein Rzz is preferably different from hydrogen,

[0061] or R6 and R5 or R7 together with the carbon atoms to which they are attached form a 5- or 6-membered aromatic or non-aromatic ring, which may optionally contain one or more heteroatoms selected from S, O and N, and wherein the ring may be unsubstituted or substituted by one or more substituents,

[0062] wherein preferably (i) R6 and R7 together with the carbon atom to which R6 and R7 are attached form unsubstituted or substituted phenyl, unsubstituted or substituted pyridyl, unsubstituted or substituted cyclopentyl or unsubstituted or substituted cyclohexyl, wherein each substituent, if present, is selected from halogen, C 1-3 Alkyl, C 3-7 Cycloalkyl, C 3-7 Cycloalkyl (C 1-3 ) alkyl, C 3-7 Heterocycloalkyl (C 1-3 ) alkyl, C 1-3 Alkoxy and C 1-3 Alkoxy (C 1-3 ) alkyl, wherein each alkyl or alkoxy group may be unsubstituted or substituted by one or more radicals selected from halogen and C 1-3 or (ii) R6 and R5 together with the carbon atom to which R6 and R5 are attached form a 1,3-dioxolane ring which may be unsubstituted or substituted with one or two substituents selected from fluoro and methyl, or

[0063] R7 is selected from H, halogen, cyano, C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkynyl, C 2-6 Alkenyl, C 1-6 Alkylcarbonyl, C 1-6 Alkoxycarbonyl, C 1-6 Alkylsulfonyl, C 1-6 Alkylsulfinyl, C 3-7 Cycloalkyl, C 3-7 Heterocycloalkyl, phenyl, C 5-6 Heteroaryl, wherein each alkyl, alkenyl, alkynyl or alkoxy group may be unsubstituted or substituted by one or more alkyl radicals selected from halogen and C 1-6 Alkoxy substituents are substituted,

[0064] R8 is selected from hydrogen, C 1-6 Alkyl, C 1-6 Alkoxy and halogen, wherein each alkyl or alkoxy group may be unsubstituted or substituted by one or more groups selected from halogen and C 1-3 The substituents of the alkoxy group are substituted, or together with R9, form a ring system as described herein,

[0065] R9 is selected from hydrogen, halogen, cyano, azido, C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl and halogen, wherein each alkyl or alkoxy group may be unsubstituted or substituted by one or more radicals selected from halogen and C 1-3 Alkoxy substituents are substituted,

[0066] or R9 and R8 or R10 together with the C atom to which they are attached form a 5- or 6-membered ring, which may optionally be further substituted and which may contain one or more ring-forming heteroatoms selected from N, S, O and Se;

[0067] wherein the ring formed by R9 and R8 or R10 and the ring to which they are attached is preferably selected from a bicyclic ring system selected from (a) 2,1,3-benzothiadiazole, (b) 2,1,3-benzoselenadiazole, (c) 2,1,3-benzoxadiazole, (d) 1,3-benzothiazole, (e) 1,3-benzoxazole, which may be unsubstituted or may be partially hydrogenated and unsubstituted or substituted by oxo, (f) 1,3-benzodioxole, which may be unsubstituted or substituted by one or two substituents selected from fluoro and methyl, (g) benzothiophene, which may be unsubstituted or may be partially hydrogenated and unsubstituted or substituted by one or two substituents selected from oxo, methyl or fluoro, or (h) benzofuran, which may be unsubstituted or may be partially hydrogenated and unsubstituted or substituted by one or two groups selected from oxo, fluoro and methyl, preferably substituted by one oxo group,

[0068] R10 is selected from hydrogen, halogen, C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, cyano, cyano (C 1-6 ) alkyl, C 1-6 Alkylcarbonyl, C 1-6 Alkoxycarbonyl, C 1-6 Alkylsulfonyl, C 1-6 Alkylsulfinyl, azido, pentafluorosulfanyl and nitro, wherein each alkyl, alkenyl, alkynyl or alkoxy group may be unsubstituted or substituted by one or more radicals selected from halogen and C 1-6 or R10 and R9 taken together to form a ring system as described herein,

[0069] R11 is selected from hydrogen, halogen, cyano, azido, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylcarbonyl, C 1-6 Alkoxycarbonyl, C 1-6 Alkylsulfonyl, and C 1-6 Alkylsulfinyl, C 2-6 Alkenyl and C 2-6 Alkynyl, wherein each alkyl or alkoxy group may be unsubstituted or substituted by one or more radicals selected from halogen and C 1-3 Alkoxy substituents are substituted,

[0070] R12 is selected from hydrogen, C1-6 Alkyl, C 1-6 Alkoxy and halogen, wherein each alkyl or alkoxy group may be unsubstituted or substituted by one or more groups selected from halogen and C 1-3 Alkoxy substituents are substituted,

[0071] and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof.

[0072] Typically, in the compounds of the present invention, when R8 and R9 or R9 and R10 together form a bicyclic ring system such as 2,1,3-benzothiadiazole, 2,1,3-benzoselenadiazole, 2,1,3-benzoxadiazole, dihydro(1,3)-benzoxazole, 1,3-benzothiazole, dihydrobenzothiophene, dihydrobenzofuran, dihydroisoindole or 1,3-benzodioxole, as described herein, all phenyl portions of these bicyclic groups may generally be substituted or unsubstituted as determined by the respective definitions of the substituents R8, R10, R11 and R12 herein, and the cyclic portion of the dihydrobenzothiophene, dihydrobenzofuran, dihydrobenzoxazole or benzodioxole formed by R8 and R9, or R9 and R10, respectively, may be optionally substituted as specifically defined herein. As a non-limiting example, when the 1,3-dihydro-2-benzofuran formed by R8 and R9 or R9 and R10 and the ring to which they are attached is said to be optionally substituted with one or two groups selected from oxo, fluoro and methyl, this particular oxo, fluoro or methyl substitution is a substitution of the ring formed by R8 and R9 or R9 and R10, as the case may be, and the phenyl ring to which R8 and R9 or R9 and R10 are attached may independently be further substituted as defined herein for the residues R8, R10, R11 and R12. Similarly, for example, if a benzodioxole group is defined as unsubstituted, this would mean that the ring formed by R8 and R9 or R9 and R10, and the phenyl ring to which they are attached may be substituted according to the definitions of R8, R10, R11 and R12 herein.

[0073] In a preferred embodiment, in the compounds of formula I, if R6 is hydrogen and X1 is N, then R5 is different from hydrogen; in a preferred embodiment, R5 is iodine.

[0074] In one embodiment, R5, R6 and R7, if present, are not all hydrogen at the same time.

[0075] In one embodiment, R4, R5, R6 and R7, if present, are not all hydrogen at the same time.

[0076] In one embodiment, R5, R6, R7 (if R7 is present), R8, R9, R10 and R11 are not all hydrogen at the same time.

[0077] In a preferred embodiment of the present invention, in the compound of formula I, or

[0078] (a) X1 is CR7 and X2 is NH, S or O, or

[0079] (b) X1 is N and X2 is NH.

[0080] In one embodiment of the present invention, in the compound of formula I, X2 is NH or O. In this embodiment, X1 is preferably CR7. In one embodiment of the present invention, in the compound of formula I, X2 is S. In this embodiment, X1 is preferably CR7.

[0081] In one embodiment of the invention, in the compounds of formula I, X2 is NH.

[0082] In one embodiment of the invention, in the compounds of formula I, X2 is O. In this embodiment, X1 is preferably CR7.

[0083] In a preferred embodiment of the invention, in the compounds of formula I, if X1 is N, then X2 is also N. In this embodiment, preferably at least one of R4, R5 and R6 is different from hydrogen.

[0084] In a preferred embodiment, in the compounds of the present invention, at least one of R8, R9, R10 and R11 is different from hydrogen. In another preferred embodiment, at least one of R8, R9, R10 and R11 is different from hydrogen and unsubstituted alkyl.

[0085] In one aspect, the subject matter of the present invention does not include the compounds N-(3,4-difluorophenyl 1H-pyrrolo[2,3-b]pyridine-3-sulfonamide, N-(3,5-dimethoxyphenyl 1H-pyrrolo[2,3-b]pyridine-3-sulfonamide, N-(2,5-difluorophenyl 1H-pyrrolo[2,3-b]pyridine-3-sulfonamide, and N-(3,5-difluorophenyl 1H-pyrrolo[2,3-b]pyridine-3-sulfonamide per se, typically for use as a medicament or as an active ingredient in a pharmaceutical composition. In one aspect, the present invention includes these compounds for use in the prevention and / or treatment of myelinating disorders as further defined herein, in particular for use in a method of preventing and / or treating multiple sclerosis and / or treating or preventing GPR17-related disorders, in particular myelinating disorders, such as multiple sclerosis.

[0086] In a specific aspect, the compounds of the present invention do not include [N-(4-methylphenyl)-1H-pyrrolo[2,3-b]pyridine-3-sulfonamide], [N-[4-methoxy-3-(2-methoxyethoxy)phenyl]-1H-pyrrolo[2,3-b]pyridine-3-sulfonamide], [N-(4-methoxyphenyl)-1H-pyrrolo[2,3-b]pyridine-3-sulfonamide], N-(4-fluoro-2-methylphenyl)-1H-pyrrolo[2,3-b]pyridine-3-sulfonamide], [N-(2-chloro-4-fluorophenyl)-1H-pyrrolo[2,3-b]pyridine-3-sulfonamide], [N-(6-bromo-2-pyridyl)-1H-pyrrolo[2,3-b ]pyridine-3-sulfonamide], [N-(5-chloro-2-pyridinyl)1H-pyrrolo[2,3-b]pyridine-3-sulfonamide], [N-(2,4-dichlorophenyl)-1H-pyrrolo[2,3-b]pyridine-3-sulfonamide], [N-(3-ethylphenyl)-1H-pyrrolo[2,3-b]pyridine-3-sulfonamide], N-(2,5-dimethylphenyl)-1H-pyrrolo[2,3-b]pyridine-3-sulfonamide], [N-[4-(ethylsulfonyl)phenyl]-1H-pyrrolo[2,3-b]pyridine-3-sulfonamide], [N-(4-fluorophenyl)-1H-pyrrolo[2,3-b]pyridine-3-sulfonamide], 1[N-(3- [(6-amino-4-methoxyphenyl)-1H-pyrrolo[2,3-b]pyridine-3-sulfonamide], [N-(2-ethyl-6-methylphenyl)-1H-pyrrolo[2,3-b]pyridine-3-sulfonamide], [N-(2,4-difluorophenyl)-1H-pyrrolo[2,3-b]pyridine-3-sulfonamide], [N-[2-(trifluoromethoxy)phenyl]-1H-pyrrolo[2,3-b]pyridine-3-sulfonamide], [6-amino-N-(3-bromophenyl)-1H-indole-3-sulfonamide], [6-amino-N-(2-fluorophenyl)-1H-indole-3-sulfonamide], [6-amino-N-(3-bromo-2-pyridyl)-1H-indole-3-sulfonamide] amine], [N-(4-chloro-2-methylphenyl)-1H-pyrrolo[2,3-b]pyridine-3-sulfonamide] and [N-(4-propylphenyl)-1H-pyrrolo[2,3-b]pyridine-3-sulfonamide themselves. On the other hand, the present invention includes these specific compounds for use in (a) treatment and / or diagnosis, (b) treatment or prevention of dysmyelination and / or any other disease or condition associated with GPR17, such as GPR17 dysfunction, (c) as an active ingredient in a pharmaceutical composition together with an optional pharmaceutical carrier, and / or (d) a method of treating or preventing disorders associated with GPR17, such as GPR17 dysfunction, in particular dysmyelination, such as multiple sclerosis.

[0087] In a further embodiment, in the compound of formula I,

[0088] R6 is selected from hydrogen, fluorine, chlorine, bromine, iodine, cyano, azido, nitro, unsubstituted or substituted C 1-3 Alkyl, preferably methyl, ethyl, isopropyl, mono-, di- or trifluoromethyl, unsubstituted or substituted C 2-3 Alkenyl, unsubstituted or substituted C 2-3 Alkynyl, unsubstituted or substituted C 1-3 Alkylcarbonyl, unsubstituted or substituted C 1-3 Alkoxycarbonyl, unsubstituted or substituted C 1-3 Alkylsulfinyl, preferably methylsulfinyl, which may be further substituted with one to three fluorines, unsubstituted or substituted C 1-3 Alkylsulfonyl, preferably methylsulfonyl, which may be further substituted with one to three fluorines, unsubstituted or substituted benzylsulfonyl, unsubstituted or substituted benzylsulfinyl, unsubstituted or substituted C 3-7 Cycloalkyl, preferably cyclopropyl, unsubstituted or substituted C 3-7 Cycloalkyl (C 1-3 ) alkyl, preferably cyclopropylmethyl, unsubstituted or substituted C 3-7 Cycloalkyl (C 1-3 ) alkyloxy, preferably cyclopropylmethoxy, unsubstituted or substituted C 3-7 Heterocycloalkyl, preferably tetrahydrofuranyl, unsubstituted or substituted C 3-7 Heterocycloalkyl (C 1-3 ) alkyl, unsubstituted or substituted C 3-7 Heterocycloalkyl (C 1-3 ) alkyloxy, preferably tetrahydrofuranylmethoxy, unsubstituted or substituted C 1-3 Alkoxy, preferably methoxy or ethoxy, each of which may be optionally substituted by one or more halogen, preferably fluorine, unsubstituted or substituted C 3-6 Cycloalkoxy, unsubstituted or substituted C 3-6 Heterocycloalkoxy, unsubstituted or substituted C 1-3 Alkoxy (C 1-3 ) alkoxy, preferably methoxyethoxy, unsubstituted or substituted C 1-3 Alkoxy (C 1-3 )alkyl, unsubstituted or substituted (C 3-6 )cycloalkyl(C 1-3 ) alkoxy, preferably cyclopropylmethoxy, unsubstituted or substituted (C 3-6 )heterocycloalkyl(C 1-3)alkoxy, preferably tetrahydrofuranylmethoxy, unsubstituted or substituted phenyl, unsubstituted or substituted phenyloxy, unsubstituted or substituted thienyl, unsubstituted or substituted pyridyl, preferably unsubstituted pyridyl, unsubstituted or substituted oxazolyl, unsubstituted or substituted thiazolyl, unsubstituted or substituted isoxazolyl, unsubstituted or substituted phenyl (C 1-3 ) alkoxy, preferably benzyloxy, wherein each optional substituent in R6 is preferably selected from fluorine, chlorine, bromine, unsubstituted or fluorinated methyl, unsubstituted or fluorinated methoxy, hydroxy and cyano,

[0089] or

[0090] (i) R6 and R7 together with the carbon atom to which R6 and R7 are attached form an unsubstituted or substituted phenyl group, an unsubstituted or substituted pyridyl group, an unsubstituted or substituted cyclopentyl group or an unsubstituted or substituted cyclohexyl group,

[0091] wherein each substituent, if present, is selected from halogen, hydroxy, C 1-3 Alkyl, C 3-7 Cycloalkyl, C 3-7 Cycloalkyl (C 1-3 ) alkyl, C 3-7 Heterocycloalkyl (C 1-3 ) alkyl, C 1-3 Alkoxy and C 1-3 Alkoxy (C 1-3 ) alkyl, wherein each alkyl or alkoxy group may be unsubstituted or substituted by one or more radicals selected from halogen and C 1-3 Alkoxy substituents are substituted,

[0092] or

[0093] (ii) R6 and R5 together with the carbon atom to which R6 and R5 are attached form a 1,3-dioxolane ring which may be unsubstituted or substituted with one or two substituents selected from fluorine and methyl,

[0094] Among them, preferably, if R6 is hydrogen and X1 is N, then R5 is preferably different from hydrogen and more preferably is iodine.

[0095] In a further embodiment, in the compound of formula I,

[0096] R6 is selected from hydrogen, fluorine, chlorine, bromine, iodine, cyano, azido, unsubstituted or substituted C 1-3 Alkyl, preferably methyl, ethyl, isopropyl or trifluoromethyl, unsubstituted or substituted C 2-3 Alkenyl, unsubstituted or substituted C 2-3 Alkynyl, unsubstituted or substituted C 1-3 Alkylcarbonyl, unsubstituted or substituted C 1-3Alkoxycarbonyl, unsubstituted or substituted C 1-3 Alkylsulfinyl, preferably methylsulfinyl, unsubstituted or substituted C 1-3 Alkylsulfonyl, preferably methylsulfonyl, unsubstituted or substituted C 3-7 Cycloalkyl, preferably cyclopropyl, unsubstituted or substituted C 3-7 Cycloalkyl (C 1-3 ) alkyl, preferably cyclopropylmethyl, unsubstituted or substituted C 3-7 Heterocycloalkyl, preferably tetrahydrofuranyl, unsubstituted or substituted C 3-7 Heterocycloalkyl (C 1-3 ) alkyl, unsubstituted or substituted C 1-3 Alkoxy, preferably methoxy, unsubstituted or substituted C 3-6 Cycloalkoxy, unsubstituted or substituted C 3-6 Heterocycloalkoxy, unsubstituted or substituted C 1-3 Alkoxy (C 1-3 ) alkoxy, preferably methoxyethoxy, unsubstituted or substituted (C 3-6 )cycloalkyl(C 1-3 ) alkoxy, preferably cyclopropylmethoxy, unsubstituted or substituted (C 3-6 )heterocycloalkyl(C 1-3 )alkoxy, preferably tetrahydrofuranylmethoxy, unsubstituted or substituted phenyl, unsubstituted or substituted phenyloxy, unsubstituted or substituted thienyl, unsubstituted or substituted pyridyl, preferably unsubstituted pyridyl, unsubstituted or substituted oxazole, unsubstituted or substituted thiazole, unsubstituted or substituted isoxazole, unsubstituted or substituted phenyl (C 1-3 ) alkoxy, preferably benzyloxy, wherein each optional substituent in R6 is preferably selected from fluorine, chlorine, bromine, methyl, methoxy and cyano,

[0097] or

[0098] (iii) R6 and R7 together with the carbon atom to which they are attached form an unsubstituted or substituted phenyl group, an unsubstituted or substituted pyridyl group, an unsubstituted or substituted cyclopentyl group or an unsubstituted or substituted cyclohexyl group,

[0099] wherein each substituent, if present, is selected from halogen, C 1-3 Alkyl, C 3-7 Cycloalkyl, C 3-7 Cycloalkyl (C 1-3 ) alkyl, C 3-7 Heterocycloalkyl (C 1-3 ) alkyl, C 1-3 Alkoxy and C 1-3 Alkoxy (C 1-3) alkyl, wherein each alkyl or alkoxy group may be unsubstituted or substituted by one or more radicals selected from halogen and C 1-3 Alkoxy substituents are substituted,

[0100] or

[0101] (iv) R6 and R5 together with the carbon atom to which R6 and R5 are attached form a 1,3-dioxolane ring which may be unsubstituted or substituted with one or two substituents selected from fluorine and methyl,

[0102] Among them, preferably, if R6 is hydrogen and X1 is N, then R5 is preferably different from hydrogen and more preferably is iodine.

[0103] In each case, where the compounds of the present invention contain R6 and R7 groups, which together with the ring atoms of the bicyclic ring system to which they are attached form another ring selected from phenyl, pyridyl, cyclopentyl and cyclohexyl, the ring together with its cyclized bicyclic moiety forms a tricyclic moiety, preferably selected from 1H-benzo[g]indol-3-yl, 1H-pyrrolo[3,2-h]quinolin-3-yl, 1,6,7,8-tetrahydrocyclopenta[g]indol-3-yl and 6,7,8,9-tetrahydro-1H-benzo[g]indol-3-yl. In one embodiment, any substitution of the 1H-pyrrolo[3,2-h]quinolin-3-yl moiety is preferably at the 8-position, so as to provide, for example, 8-(fluoromethyl)-1H-pyrrolo[3,2-h]quinoline.

[0104] In a preferred embodiment, in the compound of formula I,

[0105] X1 is N or C (R7),

[0106] X2 is NH, S or O, preferably NH,

[0107] X3 is N or C (R12),

[0108] R4 is selected from hydrogen, methoxy and halogen, and is preferably hydrogen or fluorine, most preferably hydrogen,

[0109] R5 is selected from hydrogen, halogen, cyano, C 1-3 Alkyl, C 1-3 Alkoxy, C 1-3 Alkylcarbonyl, C 1-3 Alkoxycarbonyl, C 1-3 Alkylsulfinyl and C 1-3 Alkylsulfonyl, wherein each alkyl and alkoxy group may be optionally substituted one or more times with a substituent selected from halogen, C 1-3 Alkoxy, cyano, azido, C 1-3 Alkylamino and di(C 1-3alkyl)amino, preferably methoxy or halogen, or R5 and R6 together form a ring as described below,

[0110] R6 is selected from hydrogen, fluorine, chlorine, bromine, iodine, cyano, azido, nitro, unsubstituted or substituted C 1-3 Alkyl, preferably methyl, ethyl, isopropyl or mono-, di- or trifluoromethyl, unsubstituted or substituted C 1-3 Alkoxy, preferably methoxy, ethoxy, mono-, di- or trifluoromethoxy and mono-, di- or trifluoroethoxy, unsubstituted or substituted C 2-3 Alkenyl, unsubstituted or substituted C 2-3 Alkynyl, unsubstituted or substituted C 1-3 Alkylcarbonyl, unsubstituted or substituted C 1-3 Alkoxycarbonyl, unsubstituted or substituted C 1-3 Alkylsulfinyl, preferably methylsulfinyl, unsubstituted or substituted C 1-3 Alkylsulfonyl, preferably methylsulfonyl, unsubstituted or substituted benzylsulfonyl, unsubstituted or substituted benzylsulfinyl, unsubstituted or substituted C 3-7 Cycloalkyl, preferably cyclopropyl, unsubstituted or substituted C 3-7 Cycloalkyl (C 1-3 ) alkyl, preferably cyclopropylmethyl, unsubstituted or substituted C 3-7 Heterocycloalkyl, preferably tetrahydrofuranyl and oxetanyl, unsubstituted or substituted C 3-7 Heterocycloalkyl (C 1-3 ) alkyl, unsubstituted or substituted C 3-6 Cycloalkoxy, unsubstituted or substituted C 3-6 Heterocycloalkoxy, unsubstituted or substituted C 1-5 Alkoxy (C 1-5 ) alkyl, unsubstituted or substituted C 1-3 Alkoxy (C 1-3 ) alkoxy, preferably methoxyethoxy, unsubstituted or substituted (C 3-6 )cycloalkyl(C 1-3 ) alkoxy, preferably cyclopropylmethoxy, unsubstituted or substituted (C 3-6 )heterocycloalkyl(C 1-3 )alkoxy, preferably tetrahydrofuranylmethoxy, unsubstituted or substituted phenyl, unsubstituted or substituted phenyloxy, unsubstituted or substituted thienyl, unsubstituted or substituted pyridyl, preferably unsubstituted pyridyl, unsubstituted or substituted oxazole, unsubstituted or substituted thiazole, unsubstituted or substituted isoxazole, unsubstituted or substituted phenyl (C 1-3) alkoxy, preferably benzyloxy, wherein each optional substituent in R6 is preferably selected from one or more of fluorine, chlorine, bromine, unsubstituted or fluorinated methyl, unsubstituted or fluorinated methoxy, hydroxyl and cyano,

[0111] or

[0112] (i) R6 and R7 together with the carbon atom to which R6 and R7 are attached form an unsubstituted or substituted phenyl group, an unsubstituted or substituted pyridyl group, an unsubstituted or substituted cyclopentyl group or an unsubstituted or substituted cyclohexyl group,

[0113] wherein each substituent, if present, is selected from halogen, hydroxy, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-7 Cycloalkyl, C 3-7 Cycloalkyl (C 1-3 ) alkyl, C 3-7 Heterocycloalkyl (C 1-3 ) alkyl, C 1-6 Alkoxy and C 1-6 Alkoxy (C 1-3 ) alkyl, wherein each alkyl or alkoxy group may be unsubstituted or substituted by one or more radicals selected from halogen and C 1-3 Alkoxy substituents are substituted,

[0114] wherein each alkyl or alkoxy group may be unsubstituted or substituted by one or more radicals selected from halogen and C 1-3 Alkoxy substituents are substituted,

[0115] or

[0116] (ii) R6 and R5 together with the carbon atom to which R6 and R5 are attached form a 1,3-dioxolane ring which may be unsubstituted or substituted with one or two substituents selected from fluorine and methyl,

[0117] R7 is selected from H, halogen, cyano, C 1-3 Alkyl, C 1-3 Alkoxy, C 1-3 Alkylcarbonyl, C 1-3 Alkoxycarbonyl, C 1-3 Alkylsulfonyl, C 1-3 Alkylsulfinyl, C 5-6 Heteroaromatic, preferably isoxazole, and C 5-6 Heteroaryl (C 1-3 ) alkoxy, preferably pyridylmethoxy, wherein each alkyl or alkoxy portion may be substituted by one or more substituents, preferably halogen, halo(C 1-6 ) alkoxy or C 1-3substituted by alkoxy, and each heteroaryl group may be substituted by one or more substituents, preferably substituted by halogen, methyl, hydroxy or methoxy, or R7 and R6 together form a ring as described herein,

[0118] R8 is selected from hydrogen, C 1-3 Alkyl, C 1-3 alkoxy, cyano and halogen, wherein each alkyl or alkoxy group may be unsubstituted or substituted with one or more substituents selected from halogen, cyano and methoxy, or R8 and R9 together form a ring system as described herein,

[0119] R9 is selected from hydrogen, C 1-3 Alkyl, C 1-3 alkoxy, fluorine, chlorine, bromine and iodine, wherein each alkyl or alkoxy group may be unsubstituted or substituted with one or more substituents selected from halogen and methoxy,

[0120] or R9 and R8 or R10 together with the ring to which they are attached form a bicyclic ring system selected from 2,1,3-benzothiadiazole, 2,1,3-benzoselenadiazole, 2,1,3-benzoxadiazole, 1,3-benzothiazole, 1,3-benzoxazole, which may be unsubstituted or may be partially hydrogenated and substituted with oxo to form 2-oxo-2,3-dihydro-1,3-benzoxazole, 1,3-benzodioxole, which may be unsubstituted or substituted with one or two substituents selected from fluoro and methyl to preferably form 2,2-difluoro-1,3-benzodioxole, 2,3-dihydrobenzothiazole phene, which may be unsubstituted or substituted by one or two oxo groups to preferably form 1,1-dioxo-2,3-dihydro-1-benzothiophene, 1,3-dihydro-2-benzofuran, which may be unsubstituted or substituted by one or two groups selected from oxo, fluoro and methyl, preferably substituted by at least one oxo group to form 3-oxo-1,3-dihydro-2-benzofuran or 1-methyl-3-oxo-1,3-dihydro-2-benzofuran, and dihydroisoindole, which may be unsubstituted or substituted by one or more substituents selected from oxo, fluoro and methyl and which is preferably 3-oxo-2,3-dihydro-1H-isoindole,

[0121] R10 is selected from hydrogen, fluorine, chlorine, bromine, iodine, C 1-5 Alkyl, preferably C 1-3 Alkyl, C 1-5 Alkoxy, preferably C 1-3 Alkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-4 Cycloalkyl, C 3-4 Heterocycloalkyl, cyano, cyanomethyl, cyanomethoxy, C 1-3 Alkylcarbonyl, C1-3 Alkoxycarbonyl, azido, pentafluorosulfanyl and nitro, wherein each alkyl, alkenyl, alkynyl or alkoxy group may be unsubstituted or substituted with one or more substituents selected from halogen, unsubstituted or fluorinated C 1-3 Alkoxy, unsubstituted or fluorinated C 1-3 Alkoxycarbonyl, unsubstituted or fluorinated C 1-3 alkylcarbonyl, cyano, hydroxy, cyclopropyl and pyridyl, wherein the pyridyl may be optionally substituted by halogen, unsubstituted or fluorinated methyl and / or unsubstituted or fluorinated methoxy, and wherein any cycloalkyl or heterocycloalkyl may be unsubstituted or substituted by a group selected from halogen, cyano, hydroxy (C 1-2 ) alkyl, C 1-2 Alkoxy and C 1-2 alkoxycarbonyl, or as described herein R10 and R8 together form a ring system,

[0122] R11 is selected from hydrogen, C 1-3 Alkyl, C 1-3 Alkoxy, fluorine, chlorine, bromine, iodine, cyano, C 1-3 Alkylcarbonyl, C 1-3 Alkoxycarbonyl, wherein each alkyl and alkoxy group may be unsubstituted or substituted with one or more substituents selected from fluorine, chlorine, bromine, iodine and C 1-3 Alkoxy,

[0123] R12, if present, is selected from hydrogen, C 1-3 Alkyl, C 1-3 Alkoxy, fluorine, chlorine, bromine and iodine, wherein each alkyl and alkoxy group may be unsubstituted or substituted with one or more substituents selected from fluorine, chlorine, bromine, iodine and C 1-3 Alkoxy,

[0124] Wherein in a preferred embodiment, if R6 is hydrogen and X1 is N, R5 is different from hydrogen and is particularly preferably iodine,

[0125] wherein, in a preferred embodiment, at least one of R8, R9, R10 and R11 is different from hydrogen, and more preferably at least one of R8, R9, R10 and R11 is also different from unsubstituted alkyl,

[0126] and wherein in another preferred embodiment at least one of R5, R6 and R7, if present, is different from hydrogen,

[0127] and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof.

[0128] In a preferred embodiment, in the compound of formula I,

[0129] X1 is N or C (R7),

[0130] X2 is NH or O, preferably NH,

[0131] X3 is N or C (R12),

[0132] R4 is hydrogen or fluorine, preferably hydrogen,

[0133] R5 is selected from hydrogen, halogen, cyano, C 1-3 Alkyl, C 1-3 Alkoxy, C 1-3 Alkylcarbonyl, C 1-3 Alkoxycarbonyl, C 1-3 Alkylsulfinyl and C 1-3 Alkylsulfonyl, wherein each alkyl or alkoxy group may be optionally substituted one or more times with a substituent selected from halogen, C 1-3 alkoxy, cyano, azido and optionally alkylated amino groups, preferably methoxy or halogen, or R5 and R6 together form a ring as described below,

[0134] R6 is selected from hydrogen, fluorine, chlorine, bromine, iodine, cyano, azido, unsubstituted or substituted C 1-3 Alkyl, preferably methyl, ethyl, isopropyl or trifluoromethyl, unsubstituted or substituted C 1-3 Alkoxy, preferably methoxy, unsubstituted or substituted C 2-3 Alkenyl, unsubstituted or substituted C 2-3 Alkynyl, unsubstituted or substituted C 1-3 Alkylcarbonyl, unsubstituted or substituted C 1-3 Alkoxycarbonyl, unsubstituted or substituted C 1-3 Alkylsulfinyl, preferably methylsulfinyl, unsubstituted or substituted C 1-3 Alkylsulfonyl, preferably methylsulfonyl, unsubstituted or substituted C 3-7 Cycloalkyl, preferably cyclopropyl, unsubstituted or substituted C 3-7 Cycloalkyl (C 1-3 ) alkyl, preferably cyclopropylmethyl, unsubstituted or substituted C 3-7 Heterocycloalkyl, preferably tetrahydrofuranyl, unsubstituted or substituted C 3-7 Heterocycloalkyl (C 1-3 ) alkyl, unsubstituted or substituted C 3-6 Cycloalkoxy, unsubstituted or substituted C 3-6 Heterocycloalkoxy, unsubstituted or substituted C 1-3 Alkoxy (C 1-3 ) alkoxy, preferably methoxyethoxy, unsubstituted or substituted (C 3-6 )cycloalkyl(C1-3 ) alkoxy, preferably cyclopropylmethoxy, unsubstituted or substituted (C 3-6 )heterocycloalkyl(C 1-3 )alkoxy, preferably tetrahydrofuranylmethoxy, unsubstituted or substituted phenyl, unsubstituted or substituted phenyloxy, unsubstituted or substituted thienyl, unsubstituted or substituted pyridyl, preferably unsubstituted pyridyl, unsubstituted or substituted oxazole, unsubstituted or substituted thiazole, unsubstituted or substituted isoxazole, unsubstituted or substituted phenyl (C 1-3 ) alkoxy, preferably benzyloxy, wherein each optional substituent in R6 is preferably selected from fluorine, chlorine, bromine, methyl, methoxy and cyano,

[0135] or

[0136] (i) R6 and R7 together with the carbon atom to which R6 and R7 are attached form an unsubstituted or substituted phenyl group, an unsubstituted or substituted pyridyl group, an unsubstituted or substituted cyclopentyl group or an unsubstituted or substituted cyclohexyl group,

[0137] wherein each substituent, if present, is selected from halogen, C 1-3 Alkyl, C 3-7 Cycloalkyl, C 3-7 Cycloalkyl (C 1-3 ) alkyl, C 3-7 Heterocycloalkyl (C 1-3 ) alkyl, C 1-3 Alkoxy and C 1-3 Alkoxy (C 1-3 )alkyl,

[0138] wherein each alkyl or alkoxy group may be unsubstituted or substituted by one or more radicals selected from halogen and C 1-3 Alkoxy substituents are substituted,

[0139] or

[0140] (ii) R6 and R5 together with the carbon atom to which R6 and R5 are attached form a 1,3-dioxolane ring which may be unsubstituted or substituted with one or two substituents selected from fluorine and methyl,

[0141] R7 is selected from H, halogen, cyano, C 1-3 Alkyl, C 1-3 Alkoxy, C 1-3 Alkylcarbonyl, C 1-3 Alkoxycarbonyl, C 1-3 Alkylsulfonyl and C 1-3 Alkylsulfinyl, wherein each alkyl or alkoxy moiety may be substituted by one or more substituents, preferably by halogen or C 1-3 Alkoxy substituted, or R7 and R6 together form a ring as described herein,

[0142] R8 is selected from hydrogen, C 1-3 Alkyl, C 1-3 alkoxy and halogen, wherein each alkyl or alkoxy group may be unsubstituted or substituted with one or more substituents selected from halogen, cyano and methoxy, or R8 and R9 together form a ring system as described herein,

[0143] R9 is selected from hydrogen, C 1-3 Alkyl, C 1-3 alkoxy, fluorine, chlorine, bromine and iodine, wherein each alkyl or alkoxy group may be unsubstituted or substituted with one or more substituents selected from halogen and methoxy,

[0144] or R9 and R8 or R10 together with the ring to which they are attached form a bicyclic ring system selected from 2,1,3-benzothiadiazole, 2,1,3-benzoselenadiazole, 2,1,3-benzooxadiazole, 1,3-benzothiazole, 1,3-benzoxazole, which may be unsubstituted or may be partially hydrogenated and substituted by oxo, 1,3-benzodioxole, which may be unsubstituted or substituted by one or two substituents selected from fluoro and methyl, 2,3-dihydrobenzothiophene, which may be unsubstituted or substituted by one or two oxo groups, and 1,3-dihydro-2-benzofuran, which may be unsubstituted or substituted by one or two groups selected from oxo, fluoro and methyl, preferably substituted by one oxo group,

[0145] R10 is selected from hydrogen, fluorine, chlorine, bromine, iodine, C 1-3 Alkyl, C 1-3 Alkoxy, C 2-4 Alkenyl, C 2-4 Alkynyl, cyano, cyanomethyl, C 1-3 Alkylcarbonyl, C 1-3 Alkoxycarbonyl, azido, pentafluorosulfanyl and nitro, wherein each alkyl, alkenyl, alkynyl or alkoxy group may be unsubstituted or substituted by one or more radicals selected from halogen and C 1-3 or R10 and R8 are taken together to form a ring system as described herein,

[0146] R11 is selected from hydrogen, C 1-3 Alkyl, C 1-3 Alkoxy, fluorine, chlorine, bromine, iodine, C 1-3 Alkylcarbonyl, C 1-3 Alkoxycarbonyl, wherein each alkyl and alkoxy group may be unsubstituted or substituted with one or more substituents selected from fluorine, chlorine, bromine, iodine and C 1-3 Alkoxy,

[0147] R12 is selected from hydrogen, C 1-3 Alkyl, C1-3 Alkoxy, fluorine, chlorine, bromine and iodine, wherein each alkyl and alkoxy group may be unsubstituted or substituted with one or more substituents selected from fluorine, chlorine, bromine, iodine and C 1-3 Alkoxy,

[0148] wherein if R6 is hydrogen and X1 is N, R5 is preferably different from hydrogen and is particularly preferably iodine,

[0149] wherein, in a preferred embodiment, at least one of R8, R9, R10 and R11 is different from hydrogen, and more preferably at least one of R8, R9, R10 and R11 is also different from unsubstituted alkyl,

[0150] and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof.

[0151] A further embodiment relates to compounds of formula I,

[0152] in

[0153] X1 is N or C (R7),

[0154] X2 is NH, S or O, preferably NH,

[0155] X3 is N or C (R12),

[0156] R4 is hydrogen or fluorine, preferably hydrogen,

[0157] R5 is selected from hydrogen, fluorine, chlorine, bromine, iodine, unsubstituted or fluorinated C 1-2 Alkyl, preferably methyl or trifluoromethyl, unsubstituted or fluorinated C 1-2 Alkyloxy, unsubstituted or fluorinated C 1-2 Alkylcarbonyl, unsubstituted or fluorinated C 1-2 Alkyloxycarbonyl, C 1-2 Alkylsulfinyl, preferably methylsulfinyl, and C 1-2 Alkylsulfonyl, preferably methylsulfonyl, wherein R5 is preferably selected from hydrogen, methyl, fluorine, chlorine, bromine and iodine, or R5 and R6 together form a ring as described herein,

[0158] R6 is selected from hydrogen, fluorine, chlorine, bromine, iodine, cyano, azido, unsubstituted or substituted C 1-3 Alkyl, preferably methyl, ethyl, isopropyl or trifluoromethyl, unsubstituted or fluorinated C 1-3 Alkylcarbonyl, preferably acetyl, unsubstituted or fluorinated C 1-3 Alkoxycarbonyl, preferably methoxycarbonyl, unsubstituted or fluorinated (C 1-3 )alkylsulfinyl, preferably methylsulfinyl, unsubstituted or fluorinated (C 1-3) alkylsulfonyl, preferably methylsulfonyl, unsubstituted or substituted C 3-6 Cycloalkyl, preferably cyclopropyl, unsubstituted or substituted C 3-6 Cycloalkyl (C 1-3 ) alkyl, preferably cyclopropylmethyl, unsubstituted or substituted C 3-6 Heterocycloalkyl, unsubstituted or substituted C 3-6 Cycloalkoxy, unsubstituted or substituted C 3-6 Heterocycloalkoxy, unsubstituted or substituted C 1-3 Alkoxy, preferably methoxy, ethoxy, fluoromethoxy and fluoroethoxy, unsubstituted or substituted C 1-3 Alkoxy (C 1-3 ) alkoxy, preferably methoxyethoxy, unsubstituted or substituted C 1-3 Alkoxy (C 1-3 ) alkyl, unsubstituted or substituted C 3-6 Cycloalkyl (C 1-3 ) alkoxy, preferably cyclopropylmethoxy, unsubstituted or substituted phenyl, unsubstituted or substituted phenyl (C 1-3 ) alkoxy, preferably benzyloxy, unsubstituted or substituted phenyloxy, unsubstituted or substituted phenyl (C 1-3 ) alkylsulfonyl, preferably benzylsulfonyl, unsubstituted or substituted phenyl (C 1-3 ) alkylsulfinyl, preferably benzylsulfinyl, unsubstituted or substituted thienyl, pyridyl, oxazole, thiazole and isoxazole, and wherein each optional substituent in R6 is preferably selected from fluorine, chlorine, unsubstituted or fluorinated methyl, unsubstituted or fluorinated methoxy, hydroxy and cyano,

[0159] Provided that if R6 is hydrogen and X1 is N, then R5 is preferably different from hydrogen and is preferably iodine,

[0160] or

[0161] (i) R6 and R7 together with the carbon atom to which R6 and R7 are attached form an unsubstituted or substituted phenyl group, an unsubstituted or substituted pyridyl group, an unsubstituted or substituted cyclopentyl group or an unsubstituted or substituted cyclohexyl group,

[0162] wherein each substituent, if present, is selected from halogen, hydroxy, methyl or methoxy, wherein each methyl or methoxy may be unsubstituted or substituted with one or more substituents selected from halogen, preferably fluorine, and methoxy,

[0163] or

[0164] (ii) R6 and R5 together with the carbon atom to which R6 and R5 are attached form a 1,3-dioxolane ring which may be unsubstituted or substituted with one or two substituents selected from fluorine and methyl,

[0165] R7 is selected from hydrogen, fluorine, chlorine, bromine, iodine, cyano, C 1-3 Alkyl, preferably methyl, C 1-3 Alkyloxy, preferably methoxy, fluoro (C 1-3 ) alkyl, preferably mono-, di- or fluoromethyl, fluoro(C 1-3 ) alkoxy, preferably mono-, di- or trifluoromethoxy and mono-, di- and trifluoroethoxy, unsubstituted or fluorinated C 1-3 Alkylcarbonyl, unsubstituted or fluorinated C 1-3 Alkoxycarbonyl, methylsulfinyl, methylsulfonyl, fluorinated methylsulfinyl, fluorinated methylsulfonyl, substituted or unsubstituted C 5-6 Heteroaryl, substituted or unsubstituted C 5-6 Heteroaryloxy and C 5-6 heteroarylmethoxy, wherein the heteroaryl is preferably selected from pyridyl, oxazole and isoxazole, and wherein the heteroaryl may be substituted by one or more substituents selected from halogen, unsubstituted or fluorinated methyl, unsubstituted or fluorinated methoxy, or R7 and R6 together form a ring as described herein,

[0166] R8 is selected from hydrogen, fluorine, chlorine, bromine, iodine, cyano, C 1-3 Alkyloxy, preferably methoxy, fluoro (C 1-3 ) alkoxy, C 1-3 Alkyl, preferably methyl, and fluorine (C 1-3 )alkyl, preferably trifluoromethyl, or R8 and R10 together form a ring system as described herein,

[0167] R9 is selected from hydrogen, fluorine, chlorine, bromine, iodine, C 1-3 Alkyloxy, preferably methoxy, fluoro (C 1-3 ) alkoxy, C 1-3 Alkyl, preferably methyl, cyano, and fluoro (C 1-3 )alkyl, preferably trifluoromethyl, and preferably hydrogen, fluorine, chlorine or bromine,

[0168] or R9 and R8 together with the ring to which they are attached form a bicyclic ring system selected from 2,1,3-benzothiadiazole, 2,1,3-benzoselenadiazole, 2,1,3-benzoxadiazole, 1,3-benzoxazole, which may be unsubstituted or may be partially hydrogenated and substituted with oxo (to give 2-oxo-2,3-dihydro-1,3-benzoxazole), and 1,3-benzodioxole, which is optionally substituted with one or two fluorines,

[0169] or R9 and R10 together with the ring to which they are attached form a bicyclic ring system selected from 2,1,3-benzothiadiazole, 2,1,3-benzoselenadiazole, 2,1,3-benzoxadiazole, 1,3-benzothiazole, 3-oxo-2,3-dihydro-1H-isoindole, 2,3-dihydro-1-benzothiophene substituted with one or two oxo groups (preferably substituted with two oxo groups to give 1,1-dioxo-2,3-dihydro-1-benzothiophene), 3-oxo-1,3-dihydro-2-benzofuran, optionally substituted with methyl to give 1-methyl-3-oxo-1,3-dihydro-2-benzofuran, and 1,3-benzodioxole, optionally substituted with one or two fluorine groups,

[0170] R10 is selected from hydrogen, fluorine, chlorine, bromine, iodine, C 1-3 Alkyl, halo (C 1-3 ) alkyl, preferably fluoro(C 1-3 ) alkyl, especially trifluoromethyl, C 2-3 Alkynyl, C 1-3 Alkyloxy, halo(C 1-3 ) alkyloxy, preferably fluoro(C 1-2 ) alkoxy, cyclopropylcyano, cyanomethyl, cyanoethyl, unsubstituted or fluorinated C 1-3 Alkylcarbonyl, preferably acetyl, unsubstituted or fluorinated C 1-3 Alkoxycarbonyl, preferably methoxycarbonyl, azido, pentafluorosulfanyl and nitro, wherein each alkyl, cyclopropyl, alkoxy, alkenyl or alkynyl in R10, unless otherwise specified, may be optionally further substituted by one or more substituents selected from fluoro, chloro, cyano, hydroxy, C 1-3 Alkoxy, preferably methoxy, halo C 1-3 Alkoxy and unsubstituted or fluorinated C 1-3 alkoxycarbonyl, wherein each alkyl and alkoxy group may also be substituted by cyclopropyl, which may be optionally substituted as defined above, or R10 and R9 together form a ring system as described herein,

[0171] R11 is selected from hydrogen, fluorine, chlorine, bromine, iodine, C 1-3 Alkyl, preferably methyl, fluoro (C 1-3 ) alkyl, preferably fluorinated methyl such as trifluoromethyl, C 1-3 Alkyloxy, preferably methoxy, fluoro (C 1-3 ) alkoxy, preferably fluoro(C 1-2 ) alkoxy, unsubstituted or fluorinated C 1-3 Alkylcarbonyl, preferably acetyl, unsubstituted or fluorinated C 1-3 alkoxycarbonyl, preferably methoxycarbonyl, and cyano, and more preferably hydrogen, fluorine, chlorine or bromine,

[0172] R12, if present, is selected from hydrogen, fluorine, chlorine, bromine, iodine, C 1-3 Alkyl, preferably methyl, fluoro (C 1-3 ) alkyl, preferably trifluoromethyl, C 1-3 Alkyloxy, preferably methoxy, fluoro (C 1-3 ) alkoxy, preferably fluoro(C 1-2 )alkoxy, and cyano, and more preferably hydrogen, fluorine, chlorine or bromine,

[0173] wherein, in a preferred embodiment, at least one of R8, R9, R10 and R11 is different from hydrogen, and more preferably at least one of R8, R9, R10 and R11 is also different from unsubstituted alkyl,

[0174] and wherein in another preferred embodiment, at least one of R5, R6 and R7, if present, is different from hydrogen, and wherein in a preferred embodiment, if X1 is N, then X2 is NH,

[0175] and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof.

[0176] A further embodiment relates to compounds of formula I,

[0177] in

[0178] X1 is N or C (R7),

[0179] X2 is NH or O, preferably NH,

[0180] X3 is N or C (R12),

[0181] R4 is hydrogen,

[0182] R5 is selected from hydrogen, fluorine, chlorine, bromine, iodine, unsubstituted or fluorinated C 1-2 Alkyl, preferably methyl or trifluoromethyl, unsubstituted or fluorinated C 1-2 Alkyloxy, unsubstituted or fluorinated C 1-2 Alkylcarbonyl, unsubstituted or fluorinated C 1-2 Alkyloxycarbonyl, C 1-2 Alkylsulfinyl, preferably methylsulfinyl, and C 1-2 alkylsulfonyl, preferably methylsulfonyl, preferably hydrogen, methyl or iodine, or R5 and R6 together form a ring as described herein,

[0183] R6 is selected from hydrogen, fluorine, chlorine, bromine, iodine, cyano, azido, unsubstituted or substituted C 1-3 Alkyl, preferably methyl, ethyl, isopropyl or trifluoromethyl, unsubstituted or fluorinated C 1-3Alkylcarbonyl, preferably acetyl, unsubstituted or fluorinated C 1-3 Alkoxycarbonyl, preferably methoxycarbonyl, (C 1-3 ) alkylsulfinyl, preferably methylsulfinyl, (C 1-3 ) alkylsulfonyl, preferably methylsulfonyl, C 3-6 Cycloalkyl, preferably cyclopropyl, C 3-6 Cycloalkyl (C 1-3 ) alkyl, preferably cyclopropylmethyl, C 3-6 Heterocycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Heterocycloalkoxy, unsubstituted or substituted C 1-3 Alkoxy, preferably methoxy, unsubstituted or substituted C 1-3 Alkoxy (C 1-3 ) alkoxy, preferably methoxyethoxy, C 3-6 Cycloalkyl (C 1-3 ) alkoxy, preferably cyclopropylmethoxy, unsubstituted or substituted phenyl, unsubstituted or substituted phenyl (C 1-3 )alkoxy, preferably benzyloxy, unsubstituted or substituted phenyloxy, unsubstituted or substituted thienyl, pyridyl, oxazole, thiazole and isoxazole, and wherein each optional substituent in R6 is preferably selected from fluorine, chlorine, methyl, methoxy and cyano,

[0184] Provided that if R6 is hydrogen and X1 is N, then R5 is preferably different from hydrogen and is preferably iodine,

[0185] or

[0186] (i) R6 and R7 together with the carbon atom to which R6 and R7 are attached form an unsubstituted or substituted phenyl group, an unsubstituted or substituted pyridyl group, an unsubstituted or substituted cyclopentyl group or an unsubstituted or substituted cyclohexyl group,

[0187] wherein each substituent, if present, is selected from halogen, methyl or methoxy, wherein each methyl or methoxy may be unsubstituted or substituted with one or more substituents selected from fluoro and methoxy,

[0188] or

[0189] (ii) R6 and R5 together with the carbon atom to which R6 and R5 are attached form a 1,3-dioxolane ring which may be unsubstituted or substituted with one or two substituents selected from fluorine and methyl,

[0190] R7 is selected from hydrogen, fluorine, chlorine, bromine, iodine, cyano, C 1-3 Alkyl, C 1-3 Alkyloxy, fluoro(C 1-3 ) alkyl, preferably trifluoromethyl, fluoro(C 1-3) alkoxy, preferably trifluoromethoxy, unsubstituted or fluorinated C 1-3 Alkylcarbonyl, unsubstituted or fluorinated C 1-3 alkoxycarbonyl, methylsulfinyl and methylsulfonyl, or R7 and R6 together form a ring as described herein,

[0191] R8 is selected from hydrogen, fluorine, chlorine, bromine, iodine, C 1-3 Alkyloxy, preferably methoxy, fluoro (C 1-3 ) alkoxy, C 1-3 Alkyl, preferably methyl, and fluorine (C 1-3 )alkyl, preferably trifluoromethyl, or R8 and R10 together form a ring system as described herein,

[0192] R9 is selected from hydrogen, fluorine, chlorine, bromine, iodine, C 1-3 Alkyloxy, preferably methoxy, fluoro (C 1-3 ) alkoxy, C 1-3 Alkyl, preferably methyl, cyano, and fluoro (C 1-3 )alkyl, preferably trifluoromethyl, and preferably hydrogen, fluorine, chlorine or bromine,

[0193] or R9 and R8 together with the ring to which they are attached form a bicyclic ring system selected from 2,1,3-benzothiadiazole, 2,1,3-benzoselenadiazole, 2,1,3-benzoxadiazole, 1,3-benzoxazole, which may be unsubstituted or may be partially hydrogenated and substituted with oxo (to give 2-oxo-2,3-dihydro-1,3-benzoxazole), and 1,3-benzodioxole, which is optionally substituted with one or two fluorines,

[0194] or R9 and R10 together with the ring to which they are attached form a bicyclic ring system selected from 2,1,3-benzothiadiazole, 2,1,3-benzoselenadiazole, 2,1,3-benzoxadiazole, 1,3-benzothiazole, 2,3-dihydro-1-benzothiophene substituted with one or two oxo groups (preferably substituted with two oxo groups to give 1,1-dioxo-2,3-dihydro-1-benzothiophene), 3-oxo-1,3-dihydro-2-benzofuran, and 1,3-benzodioxole, optionally substituted with one or two fluorine groups,

[0195] R10 is selected from hydrogen, fluorine, chlorine, bromine, iodine, C 1-3 Alkyl, halo (C 1-3 ) alkyl, preferably fluoro(C 1-3 ) alkyl, especially trifluoromethyl, C 2-3 Alkynyl, C 1-3 Alkyloxy, halo(C 1-3 ) alkyloxy, preferably fluoro(C 1-2) alkoxy, cyano, cyanomethyl, unsubstituted or fluorinated C 1-3 Alkylcarbonyl, preferably acetyl, unsubstituted or fluorinated C 1-3 alkoxycarbonyl, preferably methoxycarbonyl, azido, pentafluorosulfanyl and nitro, or R10 and R9 together form a ring system as described herein,

[0196] R11 is selected from hydrogen, fluorine, chlorine, bromine, iodine, C 1-3 Alkyl, preferably methyl, fluoro (C 1-3 ) alkyl, preferably trifluoromethyl, C 1-3 Alkyloxy, preferably methoxy, fluoro (C 1-3 ) alkoxy, preferably fluoro(C 1-2 ) alkoxy, unsubstituted or fluorinated C 1-3 Alkylcarbonyl, preferably acetyl, unsubstituted or fluorinated C 1-3 alkoxycarbonyl, preferably methoxycarbonyl, and cyano, and more preferably hydrogen, fluorine, chlorine or bromine,

[0197] R12 is selected from hydrogen, fluorine, chlorine, bromine, iodine, C 1-3 Alkyl, preferably methyl, fluoro (C 1-3 ) alkyl, preferably trifluoromethyl, C 1-3 Alkyloxy, preferably methoxy, fluoro (C 1-3 ) alkoxy, preferably fluoro(C 1-2 )alkoxy, and cyano, and more preferably hydrogen, fluorine, chlorine or bromine,

[0198] wherein, in a preferred embodiment, at least one of R8, R9, R10 and R11 is different from hydrogen, and more preferably at least one of R8, R9, R10 and R11 is also different from unsubstituted alkyl,

[0199] and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof.

[0200] In a preferred embodiment, in the compounds of formula I as described herein, if X2 is O, then X1 is C(R7).

[0201] A further embodiment relates to compounds of formula I,

[0202] in

[0203] X1 is N or C (R7),

[0204] X2 is NH, S or O, provided that if X1 is N, then X2 is preferably also N,

[0205] X3 is N or C (R12),

[0206] R4 is hydrogen or fluorine, preferably hydrogen,

[0207] R5 is selected from hydrogen, methyl, fluorine, chlorine and bromine,

[0208] or R5 and R6 together form a ring as described herein,

[0209] R6 is selected from hydrogen, halogen, cyano, nitro, azido, C 1-3 Alkyl, C 1-3 Alkylsulfinyl, preferably methylsulfinyl, C 1-3 Alkylsulfonyl, preferably methylsulfonyl, cyclopropyl, cyclopropylmethyl, cyclopropyloxy, C 1-3 Alkoxy, preferably methoxy or ethoxy, phenyl, phenyloxy, benzyl, phenyl (C 1-3 ) alkoxy, preferably benzyloxy, benzylsulfinyl, benzylsulfonyl, tetrahydrofuranyl and 5-6 membered heteroaryl, preferably selected from thienyl, pyridyl, oxazole and isoxazole, and wherein each alkyl, alkoxy, cyclopropyl, tetrahydrofuranyl, phenyl or heteroaryl group may be optionally substituted one or more times by a substituent selected from fluorine, chlorine, hydroxy, unsubstituted or fluorinated C 1-2 Alkyl, unsubstituted or fluorinated C 1-2 Alkoxy and cyano groups,

[0210] or

[0211] (i) R6 and R7 together with the carbon atom to which R6 and R7 are attached form an unsubstituted or substituted phenyl group, an unsubstituted or substituted pyridyl group, an unsubstituted or substituted cyclopentyl group or an unsubstituted or substituted cyclohexyl group,

[0212] wherein each substituent, if present, is selected from halogen, hydroxy, methyl or methoxy, wherein each methyl or methoxy may be unsubstituted or substituted with one or more substituents selected from halogen, preferably fluorine, and methoxy,

[0213] or

[0214] (ii) R6 and R5 together with the carbon atom to which R6 and R5 are attached form a 1,3-dioxolane ring which may be unsubstituted or substituted with one or two substituents selected from fluorine and methyl,

[0215] R7 is selected from hydrogen, halogen, cyano, C 1-3 Alkyl, C 1-3 Alkyloxy, fluoro(C 1-3 ) alkyl, preferably mono-, di- and trifluoromethyl, fluoro(C 1-3 ) alkoxy, preferably mono-, di- and trifluoromethoxy or mono-, di- and trifluoroethoxy, unsubstituted or fluorinated methylsulfinyl, unsubstituted or fluorinated methylsulfonyl, C 5-6 Heteroaryl, C5-6 Heteroaryloxy, C 5-6 Heteroarylmethyl and C 5-6 heteroarylmethoxy, wherein the heteroaryl (in each occurrence of R7) is preferably selected from pyridyl, oxazole and isoxazole, and wherein the heteroaryl is unsubstituted or substituted by one or more substituents selected from halogen, cyano, unsubstituted or fluorinated methyl and unsubstituted or fluorinated methoxy, or R7 and R6 together form a ring as described herein,

[0216] R8 is selected from hydrogen, fluorine, chlorine, bromine, C 1-3 Alkyloxy, preferably methoxy, fluoro (C 1-3 ) alkoxy, preferably fluoromethoxy, and unsubstituted or fluorinated C 1-3 alkyl, preferably fluoromethyl, or R8 and R10 together form a ring system as described herein,

[0217] R9 is selected from hydrogen, fluorine, chlorine, methoxy, fluoromethoxy, methyl and fluoromethyl,

[0218] or R9 and R8 together with the ring to which they are attached form a bicyclic ring system selected from 2,1,3-benzothiadiazole, 2,1,3-benzoselenadiazole, 2,1,3-benzoxadiazole, 1,3-benzoxazole, which may be unsubstituted or may be partially hydrogenated and substituted with oxo (to give 2-oxo-2,3-dihydro-1,3-benzoxazole), and 1,3-benzodioxole, which is optionally substituted with one or two fluorines,

[0219] or R9 and R10 together with the ring to which they are attached form a bicyclic ring system selected from 2,1,3-benzothiadiazole, 2,1,3-benzoselenadiazole, 2,1,3-benzoxadiazole, 1,3-benzothiazole, 3-oxo-2,3-dihydro-1H-isoindole, 2,3-dihydro-1-benzothiophene substituted with one or two oxo groups (preferably substituted with two oxo groups to give 1,1-dioxo-2,3-dihydro-1-benzothiophene), 3-oxo-1,3-dihydro-2-benzofuran, optionally substituted with methyl to give 1-methyl-3-oxo-1,3-dihydro-2-benzofuran, and 1,3-benzodioxole, optionally substituted with one or two fluorine groups,

[0220] R10 is selected from hydrogen, halogen, cyano, azido, pentafluorosulfanyl, nitro, C 1-3 Alkyl, C 2-3 Alkenyl, C 2-3 Alkynyl, C 1-3 Alkyloxy, C 1-3 Alkylcarbonyl, preferably acetyl, C 3-6 Cycloalkyl, preferably cycloalkyl, C 3-6Cycloalkyloxy, preferably cycloalkyloxy, C 3-6 Heterocycloalkyl, C 3-6 Heterocycloalkyloxy, wherein each cycloalkyl is optionally substituted by one or more substituents selected from fluoro, cyano, unsubstituted or fluorinated C 1-2 Alkoxy and unsubstituted or fluorinated C 1-2 Alkoxycarbonyl, and wherein each alkyl, alkoxy, alkenyl or alkynyl in R10 may optionally be further substituted by one or more substituents selected from cyclopropyl, halogen, preferably fluorine, cyano, hydroxyl, C 1-3 Alkoxy, halo (C 1-3 ) alkoxy, preferably fluoro(C 1-3 ) alkoxy, unsubstituted or fluorinated C 1-3 Alkylcarbonyl and unsubstituted or fluorinated C 1-3 alkoxycarbonyl, or as described herein R10 and R9 together form a ring system,

[0221] R11 is selected from hydrogen, fluorine, chlorine, bromine, C 1-3 Alkyl, preferably methyl, fluoro (C 1-3 ) alkyl, preferably fluoromethyl, C 1-3 Alkyloxy, preferably methoxy, fluoro (C 1-3 ) alkoxy, preferably fluoromethoxy, and cyano,

[0222] R12, if present, is selected from hydrogen, fluorine, chlorine, bromine, methyl, fluoromethyl, methoxy and fluoromethoxy, wherein preferably, R12 is hydrogen or fluorine,

[0223] and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof;

[0224] wherein, in a preferred embodiment, at least one, more preferably two, of R8, R10 and R11 are different from hydrogen, and more preferably at least one of R8, R10 and R11 is also different from unsubstituted alkyl,

[0225] And wherein in another preferred embodiment, at least one of R5, R6 and R7, if present, is different from hydrogen.

[0226] A further embodiment relates to compounds of formula I,

[0227] in

[0228] X1 is N or C (R7),

[0229] X2 is NH, S or O, preferably NH or O,

[0230] X3 is N or C (R12),

[0231] R4 is hydrogen,

[0232] R5 is selected from hydrogen, fluorine, chlorine and bromine,

[0233] R6 is selected from fluorine, chlorine, bromine, iodine, cyano, azido, amino, nitro, methyl, ethyl, n-propyl, isopropyl, trifluoromethyl, vinyl, ethynyl, propargyl, methylsulfinyl, methylsulfonyl, cyclopropyl, cyclopropyloxy, cyclopropylmethyl, methoxy, ethoxy, propoxy, methoxyethoxy, ethoxymethoxy, cyclopropylmethoxy, oxetanyl, oxetanylmethoxy, tetrahydrofuranyl, tetrahydrofuranylmethoxy, phenyl, benzyloxy, phenyloxy, benzylsulfinyl, thienyl, pyridyl, oxazole, thiazole and isoxazole, wherein each phenyl, thienyl, pyridyl, oxazole, thiazole and isoxazole may be optionally substituted one or more times by substituents preferably selected from halogen, methoxy and methyl, and wherein each alkyl, alkenyl, alkynyl and alkoxy group may be substituted one or more times by halogen, preferably fluorine, methoxy, fluoromethoxy and hydroxy,

[0234] or R6 and R7 together with the carbon atom to which they are attached form a ring selected from phenyl, pyridyl, cyclohexyl and cyclopentyl, each of which may be unsubstituted or further substituted with one or more residues selected from halogen, hydroxy, unsubstituted or fluorinated methyl and unsubstituted or fluorinated methoxy,

[0235] R7 is selected from hydrogen, fluorine, chlorine, bromine, iodine, cyano, methylsulfinyl, methylsulfonyl, methoxy, fluoromethoxy, fluoroethoxy, methyl, fluoromethyl and fluoroethyl, or R7 and R6 together form a ring as described herein,

[0236] R8 is selected from hydrogen, fluorine, chlorine, bromine, iodine, methoxy, fluoromethoxy, cyano, methyl and fluoromethyl, or R8 and R10 together form a ring system as described herein,

[0237] R9 is selected from hydrogen, fluorine and chlorine, and is preferably hydrogen,

[0238] or R9 and R8 or R10 together with the ring to which they are attached form a bicyclic ring system selected from 2,1,3-benzothiadiazole, 2,1,3-benzoxadiazole, 2-oxo-2,3-dihydro-1,3-benzoxazole and 1,3-benzodioxole, which are optionally substituted with two fluorines,

[0239] or R9 and R10 together with the ring to which they are attached form a bicyclic ring system selected from 3-oxo-2,3-dihydro-1H-isoindole, 2,3-dihydro-1-benzothiophene substituted with one or two oxo groups (preferably substituted with two oxo groups to give 1,1-dioxo-2,3-dihydro-1-benzothiophene), and optionally methylated 3-oxo-1,3-dihydro-2-benzofuran,

[0240] R10 is selected from hydrogen, fluorine, chlorine, bromine, iodine, methyl, ethyl, n-propyl, isopropyl, vinyl, n-propenyl, isopropenyl, ethynyl, propargyl, fluorine (C 1-3 ) alkyl, preferably trifluoromethyl, methoxy, ethoxy, propoxy, fluoro(C 1-3 ) alkoxy C 1-3 Alkoxy (C 1-3 ) alkyl, C 1-3 Alkoxy (C 1-3 ) alkoxy, C 1-3 Alkoxy (C 2-3 ) alkenyl, C 1-3 Alkoxy (C 2-3 ) alkynyl, C 1-3 Alkoxycarbonyl (C 1-3 ) alkyl, C 1-3 Alkylcarbonyl (C 1-3 ) alkyl, C 1-3 Alkylcarbonyl (C 1-3 )alkyloxy, cyano, acetyl, azido, nitro, pentafluorosulfanyl, cyclopropyl, cyclopropyloxy, cyclopropylmethoxy, and C 1-3 Alkoxycarbonyl, including methoxycarbonyl, wherein each alkyl, alkenyl, alkynyl and alkoxy group in R10 may be unsubstituted or substituted by one or more residues selected from halogen, preferably fluorine, cyano and / or hydroxy, and wherein the cyclopropyl group is optionally substituted by one or more residues selected from cyano, optionally fluorinated C 1-2 Alkoxy and optionally fluorinated C 1-2 alkoxycarbonyl, or as described herein R10 and R9 together form a ring system,

[0241] R11 is selected from hydrogen, fluorine, chlorine, bromine, cyano, methyl, fluoromethyl, methoxy and fluoromethoxy,

[0242] R12, if present, is selected from hydrogen, fluorine, chlorine and bromine, and is preferably hydrogen or fluorine,

[0243] wherein, in a preferred embodiment, at least one, more preferably at least one or at least two, and most preferably all of R8, R10, and R11 are different from hydrogen, and at least one, preferably at least two, of R8, R10, and R11 are also preferably different from unsubstituted alkyl,

[0244] and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof.

[0245] A further embodiment relates to compounds of formula I,

[0246] in

[0247] X1 is N or C (R7),

[0248] X2 is NH, S or O, preferably NH or O,

[0249] X3 is N or C (R12),

[0250] R4 is hydrogen,

[0251] R5 is selected from hydrogen, fluorine, chlorine and bromine,

[0252] R6 is selected from fluorine, chlorine, bromine, azido, nitro, methyl, ethyl, isopropyl, trifluoromethyl, methylsulfinyl, methylsulfonyl, cyclopropyl, methoxy, phenyl, benzyloxy, phenylsulfinyl, benzylsulfinyl, thien-2-yl and thien-3-yl, wherein each alkyl and alkoxy group in R6 may be substituted one or more times by fluorine, methoxy, cyano and hydroxy,

[0253] or R6 and R7 together with the carbon atom to which R6 and R7 are attached form a ring selected from phenyl, pyridyl, cyclohexyl and cyclopentyl, each of which may be optionally substituted one or more times with a group selected from methyl, fluorinated methyl, methoxy, fluorinated methoxy and fluorine,

[0254] R7 is selected from hydrogen, fluorine, chlorine, bromine, cyano, methyl, ethyl, methylsulfonyl, methylsulfinyl, methoxy, ethoxy, mono-, di- and trifluoromethoxy, mono-, di- and trifluoroethoxy, mono-, di- and trifluoromethyl, mono-, di- and trifluoroethyl, or R7 and R6 together form a ring as described herein,

[0255] R8 is selected from hydrogen, fluorine, chlorine, bromine, methoxy, cyano, and mono-, di- and trifluoromethyl, or R8 and R10 together form a ring system as described herein,

[0256] R9 is hydrogen or fluorine, preferably hydrogen,

[0257] or R9 and R8 or R10 together with the ring to which they are attached form a bicyclic ring system selected from 2,1,3-benzothiadiazole, 2,1,3-benzoxadiazole, 1,3-benzodioxole or 2,2-difluoro-1,3-benzodioxole,

[0258] or R9 and R10 together with the ring to which they are attached form a bicyclic ring system selected from 3-oxo-2,3-dihydro-1H-isoindole, 3-oxo-1,3-dihydro-2-benzofuran and 1-methyl-3-oxo-1,3-dihydro-2-benzofuran,

[0259] R10 is selected from hydrogen, fluorine, chlorine, bromine, iodine, methyl, ethyl, propyl, vinyl, propenyl, ethynyl, propargyl, methoxy, ethoxy, propoxy, cyano, cyanomethyl, cyanoethyl, cyanomethoxy, fluorine (C 1-3 ) alkyl, including trifluoromethyl, fluorinated and / or hydroxylated C 1-3 Alkoxy, preferably fluoro (C 1-2 ) alkoxy, unsubstituted or fluorinated and / or hydroxylated C 1-2 Alkoxy (C 1-3 ) alkyl, preferably methoxypropyl, ethoxyethyl and fluoromethoxymethyl, unsubstituted or fluorinated and / or hydroxylated C 1-2 Alkoxy (C 1-3 ) alkoxy, preferably fluoromethoxyethoxy, unsubstituted or fluorinated and / or hydroxylated C 1-2 Alkoxy (C 2-3 ) alkenyl, preferably methoxypropylene and ethoxyvinyl, C 1-2 Alkoxycyclopropyl, C 1-2 Alkoxycarbonylcyclopropyl, cyclopropyl (C 1-2 ) alkoxy, acetyl, azido and pentafluorosulfanyl, or R10 and R9 together form a ring system as described herein, and wherein in preferred embodiments, R8 and R10 are not both hydrogen,

[0260] R11 is selected from hydrogen, fluorine, fluoromethyl, chlorine, methoxy and fluoromethoxy,

[0261] R12, if present, is selected from hydrogen and fluorine,

[0262] and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof,

[0263] In a preferred embodiment, if R9 does not form a ring with R8, then R10 is different from hydrogen.

[0264] One embodiment relates to compounds of formula I,

[0265] in

[0266] X1 is N or C (R7),

[0267] X2 is NH, S or O, preferably NH or O, preferably NH,

[0268] R4 is hydrogen,

[0269] R5 is selected from hydrogen, fluorine, chlorine and bromine,

[0270] R6 is selected from fluorine, bromine, chlorine, nitro, azido, cyano, methyl, fluoromethyl, ethyl, fluoroethyl, isopropyl, cyclopropyl, cyclopropylmethyl, cyclopropylmethoxy, methoxy, ethoxy, fluoromethoxy, fluoroethoxy, methylsulfinyl, methylsulfonyl, benzyloxy, thienyl, and is preferably chlorine,

[0271] R7 is selected from hydrogen, methoxy, fluorine, chlorine, bromine, cyano, fluoromethoxy, fluoroethoxy, and mono-, di- and trifluoromethyl,

[0272] X3 is N or C (R12),

[0273] R8 is selected from hydrogen, fluorine, chlorine and methoxy,

[0274] R9 is hydrogen or fluorine, preferably hydrogen,

[0275] R10 is selected from fluorine, chlorine, bromine, cyano, cyanomethyl, cyanoethyl, cyanomethoxy, azido, methyl, ethyl, propyl, vinyl, propenyl, ethynyl, propargyl, mono-, di- and trifluoromethyl, cyclopropylmethoxy, cyclopropylethoxy, methoxycyclopropyl, ethoxycyclopropyl, methoxycarbonylcyclopropyl, ethoxycarbonylcyclopropyl, mono-, di- and trifluoromethoxy, mono-, di- and trifluoroethoxy, ethoxymethyl, methoxyethyl, ethoxyethyl, methoxypropyl, fluoroethoxymethyl, fluoromethoxyethyl, fluoroethoxyethyl, fluoromethoxypropyl, ethoxymethoxy, methoxyethoxy, methoxypropoxy, fluoroethoxymethoxy, fluoromethoxyethoxy, fluoromethoxypropoxy, methoxyvinyl, methoxypropenyl, fluoromethoxyvinyl, fluoromethoxyvinyl, ethynyl, propargyl and pentafluorosulfanyl,

[0276] R11 is selected from hydrogen, fluorine, chlorine, fluoromethyl, methoxy and fluoromethoxy,

[0277] R12, if present, is hydrogen or fluorine, preferably hydrogen,

[0278] wherein, in a preferred embodiment, at least one of R8 and R11 is different from hydrogen,

[0279] and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof.

[0280] A preferred embodiment relates to compounds of formula I,

[0281] in

[0282] X1 is N or C (R7),

[0283] X2 is NH, S or O, preferably NH,

[0284] R4 and R5 are both hydrogen,

[0285] R6 is methoxy, chlorine or bromine, preferably chlorine,

[0286] R7 is hydrogen, methoxy, fluorine or trifluoromethyl,

[0287] X3 is N or C (R12),

[0288] R9 and R8 together with the phenyl ring to which R8 and R9 are attached form 2,1,3-benzothiadiazole, 1,3-benzodioxole or 2,2-difluoro-1,3-benzodioxole,

[0289] R10 is hydrogen or fluorine,

[0290] R11 is selected from hydrogen, fluorine, cyano and methoxy, and is preferably hydrogen,

[0291] R12, if present, is hydrogen or fluorine, preferably hydrogen,

[0292] and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof.

[0293] A preferred embodiment relates to compounds of formula I,

[0294] in

[0295] X1 is N or C (R7),

[0296] X2 is NH, S or O,

[0297] R4 and R5 are both hydrogen,

[0298] R6 is selected from fluorine, chlorine, bromine, cyano, azido, methyl, ethyl, isopropyl, fluoromethyl, cyclopropyl, methoxy, fluoromethoxy, methylsulfinyl, methylsulfonyl, thien-2-yl, thien-3-yl and benzyloxy, and is preferably chlorine or bromine,

[0299] R7 is selected from hydrogen, methoxy, fluorine, chlorine, bromine, cyano, mono-, di- and trifluoromethyl, methylsulfinyl, methylsulfonyl and fluorine (C 1-2 ) alkoxy,

[0300] X3 is N or C (R12),

[0301] R8 is selected from fluorine and methoxy,

[0302] R9 is hydrogen,

[0303] R10 is selected from fluorine, chlorine, bromine, azido, cyano, cyanomethyl, cyanoethyl, cyanomethoxy, cyclopropyl (C 1-2 )alkyl, cyclopropyl (C 1-2 ) alkoxy, C 1-2 Alkoxycyclopropyl, C 1-2 Alkoxycarbonylcyclopropyl, unsubstituted or fluorinated C 1-3 Alkyl, preferably methyl, ethyl and fluoromethyl, unsubstituted or fluorinated C 1-3 Alkoxy, preferably methoxy, difluoromethoxy, difluoroethoxy and trifluoroethoxy, unsubstituted or fluorinated C 2-3 Alkenyl, unsubstituted or fluorinated C 2-3 Alkynyl, unsubstituted or fluorinated C 1-3 Alkoxy (C 1-3 ) alkyl, preferably methoxypropyl, ethoxyethyl and fluoromethoxymethyl, unsubstituted or fluorinated C 1-3 Alkoxy (C 1-3 ) alkoxy, preferably methoxyethoxy and fluoromethoxyethoxy, unsubstituted or fluorinated C 1-3 Alkoxy (C 2-3 ) alkenyl, preferably methoxypropenyl, ethoxyvinyl and fluoromethoxypropenyl, and pentafluorosulfanyl,

[0304] R11 is selected from hydrogen, fluorine and methoxy,

[0305] R12, if present, is hydrogen,

[0306] and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof.

[0307] A further embodiment relates to compounds of formula I,

[0308] in

[0309] X1 is N or C (R7),

[0310] X2 is NH or O,

[0311] X3 is N or C (R12),

[0312] R4 and R5 are both hydrogen,

[0313] R6 is selected from the group consisting of fluorine, chlorine, bromine, iodine, cyano, azido, methyl, ethyl, isopropyl, trifluoromethyl, methylsulfinyl, methylsulfonyl, cyclopropyl, cyclopropylmethyl, methoxy, ethoxy, methoxyethoxy, cyclopropylmethoxy, phenyl, benzyloxy, phenyloxy, thienyl, pyridyl, oxazole, thiazole and isoxazole,

[0314] or R6 and R7 together with the carbon atom to which R6 and R7 are attached form a ring selected from phenyl, pyridyl and cyclopentyl,

[0315] R7 is selected from hydrogen, fluorine, chlorine, bromine, iodine, methoxy, difluoromethoxy, trifluoromethoxy, methyl, difluoromethyl and trifluoromethyl, or R7 and R6 together form a ring as described herein,

[0316] R8 is selected from hydrogen, fluorine, chlorine, bromine, iodine, methoxy, methyl and trifluoromethyl, or R8 and R10 together form a ring system as described herein,

[0317] R9 is selected from hydrogen, fluorine and chlorine, and is preferably hydrogen,

[0318] or R9 and R8 or R10 together with the ring to which they are attached form a bicyclic ring system selected from 2,1,3-benzothiadiazole, 2,1,3-benzoxadiazole, 2-oxo-2,3-dihydro-1,3-benzoxazole and 1,3-benzodioxole, which are optionally substituted with two fluorines,

[0319] R10 is selected from hydrogen, fluorine, chlorine, bromine, iodine, methyl, ethynyl, propargyl, fluorine (C 1-2 ) alkyl, preferably trifluoromethyl, methoxy, fluoro(C 1-2 )alkoxy, cyano, cyanomethyl, acetyl, azido, pentafluorosulfanyl and methoxycarbonyl, or R10 and R9 together form a ring system as described herein,

[0320] R11 is selected from hydrogen, fluorine, chlorine, bromine and methoxy,

[0321] R12 is selected from hydrogen, fluorine, chlorine or bromine,

[0322] wherein, in a preferred embodiment, at least one of R8, R9, R10 and R11 is different from hydrogen and unsubstituted alkyl,

[0323] and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof.

[0324] A further embodiment relates to compounds of formula I,

[0325] in

[0326] X1 is N or C (R7),

[0327] X2 is NH or O,

[0328] X3 is N or C (R12),

[0329] R4 and R5 are both hydrogen,

[0330] R6 is selected from fluorine, chlorine, bromine, azido, methyl, isopropyl, trifluoromethyl, methylsulfonyl, cyclopropyl, methoxy, phenyl, benzyloxy, thiophen-2-yl and thiophen-3-yl,

[0331] or R6 and R7 together with the carbon atom to which R6 and R7 are attached form a ring selected from phenyl, pyridyl and cyclopentyl,

[0332] R7 is selected from hydrogen, fluorine, chlorine and methoxy, or R7 and R6 together form a ring as described herein,

[0333] R8 is selected from hydrogen, fluorine, chlorine, bromine, methoxy and trifluoromethyl, or R8 and R10 together form a ring system as described herein,

[0334] R9 is hydrogen or fluorine, preferably hydrogen,

[0335] or R9 and R8 or R10 together with the ring to which they are attached form a bicyclic ring system selected from 2,1,3-benzothiadiazole, 2,1,3-benzoxadiazole, 1,3-benzodioxole or 2,2-difluoro-1,3-benzodioxole,

[0336] R10 is selected from hydrogen, fluorine, chlorine, bromine, iodine, ethynyl, propargyl, methoxy, cyano, cyanomethyl, trifluoromethyl, fluorine (C 1-2 ) alkoxy, acetyl, azido and pentafluorosulfanyl, or R10 and R9 together form a ring system as described herein, and wherein, in preferred embodiments, R8 and R10 are not both hydrogen,

[0337] R11 is selected from hydrogen, fluorine, chlorine and methoxy,

[0338] R12 is selected from hydrogen and fluorine,

[0339] and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof.

[0340] One embodiment relates to compounds of formula I,

[0341] in

[0342] X1 is N or C (R7),

[0343] X2 is NH or O, preferably NH,

[0344] R4 and R5 are both hydrogen,

[0345] R6 is bromine or chlorine, preferably chlorine,

[0346] R7 is hydrogen, methoxy, fluorine or trifluoromethyl,

[0347] X3 is N or C (R12),

[0348] R8 is selected from hydrogen, fluorine, chlorine and methoxy,

[0349] R9 is hydrogen or fluorine, preferably hydrogen,

[0350] R10 is selected from fluorine, chlorine, bromine, cyano, cyanomethyl, trifluoromethyl, difluoroethoxy, trifluoroethoxy and pentafluorosulfanyl,

[0351] R11 is selected from hydrogen, fluorine, chlorine and methoxy,

[0352] R12 is hydrogen or fluorine, preferably hydrogen,

[0353] wherein, in a preferred embodiment, at least one of R8, R9, R10 and R11 is different from hydrogen,

[0354] and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof.

[0355] A preferred embodiment relates to compounds of formula I,

[0356] in

[0357] X1 is N or C (R7),

[0358] X2 is NH or O, preferably NH,

[0359] R4 and R5 are both hydrogen,

[0360] R6 is chlorine or bromine, preferably chlorine,

[0361] R7 is hydrogen, methoxy, fluorine or trifluoromethyl,

[0362] X3 is N or C (R12),

[0363] R9 and R8 together with the phenyl ring to which R8 and R9 are attached form 2,1,3-benzothiadiazole or 2,2-difluoro-1,3-benzodioxole,

[0364] R10 is hydrogen or fluorine,

[0365] R11 is selected from hydrogen, fluorine and methoxy,

[0366] R12 is hydrogen or fluorine, preferably hydrogen,

[0367] and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof.

[0368] A preferred embodiment relates to compounds of formula I,

[0369] in

[0370] X1 is N or C (R7),

[0371] X2 is NH,

[0372] R4 and R5 are both hydrogen,

[0373] R6 is chlorine or bromine, preferably chlorine,

[0374] R7 is hydrogen, methoxy, fluorine or trifluoromethyl,

[0375] X3 is N or C (R12),

[0376] R8 is selected from fluorine and methoxy,

[0377] R9 is hydrogen,

[0378] R10 is selected from fluorine, chlorine, bromine, cyano, cyanomethyl, trifluoromethyl, difluoroethoxy, trifluoroethoxy and pentafluorosulfanyl,

[0379] R11 is selected from hydrogen, fluorine and methoxy,

[0380] R12 is hydrogen,

[0381] and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof.

[0382] One embodiment of the present invention relates to compounds of formula I-2,

[0383]

[0384] in

[0385] R2 is selected from hydrogen, fluorine, chlorine, bromine, iodine and methoxy, preferably selected from hydrogen and fluorine, and wherein R4, R5, R6, R7, if present, R8, R9, R10, R11, X1, X2 and X3 are as described herein for the compounds of formula I.

[0386] One embodiment relates to compounds of formula I-2,

[0387] in

[0388] X1 is N or C (R7),

[0389] X2 is NH, S or O, preferably NH or O, more preferably NH,

[0390] R2 is hydrogen or fluorine,

[0391] R4 is hydrogen or fluorine,

[0392] R5 is selected from hydrogen and halogen,

[0393] R6 is selected from hydrogen, fluorine, chlorine, bromine, iodine, cyano, azido, nitro, unsubstituted or fluorinated C 1-3 Alkyl, unsubstituted or fluorinated C 1-3alkoxy, methylsulfinyl, methylsulfonyl, cyclopropyl, cyclopropylmethyl, cyclopropylmethoxy, benzyloxy, benzylsulfinyl, thienyl and pyridyl, and preferably chlorine or bromine,

[0394] R7 is selected from hydrogen, fluorine, chlorine, bromine, cyano, methyl, methoxy, fluoromethyl, fluoromethoxy, methylsulfinyl and methylsulfonyl,

[0395] X3 is N or C (R12),

[0396] R8 is selected from hydrogen, fluorine, chlorine, cyano, methoxy and fluoromethoxy,

[0397] R9 is hydrogen or fluorine, preferably hydrogen,

[0398] R10 is selected from fluorine, chlorine, bromine, iodine, azido, cyano, oxetanyl, cyano (C 1-2 )alkyl, cyano (C 1-2 ) alkoxy, cyclopropyl (C 1-2 )alkyl, cyclobutyl (C 1-2 )alkyl, cyclopropyl (C 1-2 ) alkoxy, optionally fluorinated C 1-2 Alkoxycyclopropyl, optionally fluorinated C 1-2 Alkoxycarbonylcyclopropyl, unsubstituted or fluorinated C 1-3 Alkyl, preferably methyl, ethyl and fluoromethyl, unsubstituted or fluorinated C 1-3 Alkoxy, preferably methoxy, difluoromethoxy, difluoroethoxy and trifluoroethoxy, unsubstituted or fluorinated C 2-3 Alkenyl, unsubstituted or fluorinated C 2-3 Alkynyl, unsubstituted or fluorinated C 1-3 Alkoxy (C 1-3 ) alkyl, preferably methoxypropyl, ethoxyethyl and fluoromethoxymethyl, unsubstituted or fluorinated C 1-3 Alkoxy (C 1-3 ) alkoxy, preferably methoxyethoxy and fluoromethoxyethoxy, unsubstituted or fluorinated C 1-3 Alkoxy (C 2-3 ) alkenyl, preferably methoxypropenyl, ethoxyvinyl and fluoromethoxypropenyl, and pentafluorosulfanyl,

[0399] R11 is selected from hydrogen, fluorine, chlorine, methoxy, fluoromethoxy and fluoromethyl,

[0400] R12, if present, is hydrogen or fluorine, preferably hydrogen,

[0401] wherein, in a preferred embodiment, at least one of R8 and R11 is different from hydrogen,

[0402] Wherein, in another preferred embodiment, R6 is not hydrogen,

[0403] and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof.

[0404] A preferred embodiment relates to compounds of formula I-2,

[0405] in

[0406] X1 is N or C (R7),

[0407] X2 is NH, S or O, preferably NH,

[0408] R2 is hydrogen,

[0409] R4 is selected from hydrogen and fluorine,

[0410] R5 is selected from hydrogen, fluorine, chlorine and bromine,

[0411] R6 is selected from halogen, azido, cyano, benzyloxy, thienyl, preferably thien-2-yl, unsubstituted or fluorinated C 1-3 Alkyl, preferably isopropyl and fluoromethyl, cyclopropyl, cyclopropylmethyl, cyclopropylmethoxy, unsubstituted or fluorinated C 1-3 Alkoxy, preferably methoxy, fluoromethoxy and fluoroethoxy, methylsulfinyl and methylsulfonyl, wherein R6 is preferably chlorine or bromine,

[0412] R7 is selected from hydrogen, fluorine, bromine, chlorine, cyano, methyl, fluoromethyl, methoxy, fluoromethoxy, fluoroethoxy, methylsulfinyl and methylsulfonyl,

[0413] X3 is N or C (R12),

[0414] R8 is selected from hydrogen, fluorine, methoxy and fluoromethoxy, and is preferably fluorine or methoxy,

[0415] R9 is selected from hydrogen, fluorine and methoxy, and is preferably hydrogen,

[0416] R10 is selected from fluorine, chlorine, bromine, iodine, cyano, azido, nitro, pentafluorosulfanyl, C 1-3 Alkyl, C 1-3 Alkoxy, C 2-3 Alkenyl, C 2-3 Alkynyl, cyclopropyl, cyclopropylmethoxy and cyclopropylethoxy, wherein each alkyl, alkenyl and alkoxy group in R10 may be substituted by one or more residues selected from fluorine, chlorine, cyano, C 1-3 Alkyloxy and fluorine (C 1-3 )alkyloxy, and wherein each cycloalkyl group may be unsubstituted or substituted with a residue selected from fluoro, methyl, C 1-2 Alkoxy, C1-2 Alkoxycarbonyl and cyano,

[0417] R11 is selected from hydrogen, fluorine, methyl, fluoromethyl, methoxy and fluoromethoxy,

[0418] R12, if present, is hydrogen or fluorine, preferably hydrogen,

[0419] and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof,

[0420] Wherein in a preferred embodiment, if X1 is N, then X2 is also N, and

[0421] In another preferred embodiment, at least one of R8 and R11 is different from hydrogen.

[0422] A preferred embodiment relates to compounds of formula I-2,

[0423] in

[0424] X1 is N or C (R7),

[0425] X2 is NH,

[0426] R2, R4 and R5 are all hydrogen,

[0427] R6 is selected from fluorine, chlorine, bromine, azido, isopropyl, cyclopropyl, methoxy, fluoromethyl, fluoromethoxy, methylsulfonyl, methylsulfinyl and benzyloxy, and is preferably chlorine or bromine,

[0428] R7 is selected from hydrogen, fluorine, chlorine, bromine, cyano, methyl, ethyl, fluoromethyl, fluoroethyl, methoxy, fluoromethoxy, fluoroethoxy, methylsulfinyl and methylsulfonyl,

[0429] X3 is N or C (R12),

[0430] R8 is selected from fluorine and methoxy,

[0431] R9 is hydrogen,

[0432] R10 is selected from the group consisting of fluorine, chlorine, bromine, iodine, cyano, azido, cyanomethyl, cyanoethyl, cyanomethoxy, cyanoethoxy, methyl, ethyl, propyl, cyclopropyl, cyclopropylmethyl, cyclopropylethyl, methoxymethyl, methoxyethyl, methoxypropyl, ethoxymethyl, ethoxyethyl, methoxy, ethoxy, propoxy, cyclopropylmethoxy, cyclopropylethoxy, methoxymethoxy, methoxyethoxy, methoxypropoxy, ethoxymethoxy, ethoxyethoxy, propoxymethoxy, vinyl, propenyl, methoxyvinyl, methoxypropenyl, ethynyl, propynyl, methoxycarbonylethyl, ethoxycarbonylethyl, methoxycarbonylvinyl, ethoxycarbonylvinyl and pentafluorosulfanyl, wherein each alkyl or alkoxy group in R10 may be fluorinated and / or hydroxylated, preferably fluorinated one or more times, and wherein each cyclopropyl group may be substituted by a substituent selected from the group consisting of fluorine, C 1-2 Alkoxy and C 1-2 Alkoxycarbonyl,

[0433] R11 is selected from hydrogen, fluorine, chlorine, fluoromethyl, methoxy and fluoromethoxy,

[0434] R12, if present, is hydrogen or fluorine,

[0435] and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof.

[0436] One embodiment relates to compounds of formula I or I-2, wherein

[0437] X1 is N or C (R7),

[0438] X2 is NH, S or O, and is preferably NH,

[0439] X3 is N or CR12,

[0440] R2, if present, R4, R5 and R9 are all hydrogen,

[0441] R6 is selected from halogen, cyano, C 1-3 Alkoxy, C 1-3 Alkyl, C 3-6 Cycloalkyl, preferably C 3-4 Cycloalkyl, C 3-6 Cycloalkyloxy, preferably C 3-4 Cycloalkyloxy, C 3-6 Heterocycloalkyl, preferably C 3-4 Heterocycloalkyl, and C 3-6 Heterocycloalkyloxy, preferably C 3-4 Heterocycloalkyloxy, each of which may be optionally substituted by a residue selected from fluorine and unsubstituted or fluorinated C 1-3 Alkoxy,

[0442] R7 is selected from hydrogen, halogen, cyano, C 1-3 Alkoxy, C 1-3 Alkyl, C 3-6 Cycloalkyl, preferably C 3-4 Cycloalkyl, C 3-6 Cycloalkyloxy, preferably C 3-4 Cycloalkyloxy, C 3-6 Heterocycloalkyl, preferably C 3-4 Heterocycloalkyl, and C 3-6 Heterocycloalkyloxy, preferably C 3-4 Heterocycloalkyloxy, each of which may be optionally substituted by a residue selected from fluorine and unsubstituted or fluorinated C 1-3 Alkoxy,

[0443] R8 is selected from fluorine, methoxy and fluoromethoxy, preferably selected from fluorine and methoxy,

[0444] R10 is selected from halogen, C 1-4 Alkoxy, C 1-4 Alkyl, C 2-3 Alkenyl, C 2-3 Alkynyl, C 3-6 Cycloalkyl, preferably C 3-4 Cycloalkyl, C 3-6 Cycloalkyloxy, preferably C 3-4 Cycloalkyloxy, C 3-6 Heterocycloalkyl, preferably C 3-4 Heterocycloalkyl, and C 3-6 Heterocycloalkyloxy, preferably C 3-4 Heterocycloalkyloxy, each of which may be optionally substituted by a residue selected from fluorine, cyano and unsubstituted or fluorinated C 1-3 Alkoxy,

[0445] R11 is selected from hydrogen, fluorine, methoxy and fluoromethoxy, preferably selected from fluorine and methoxy,

[0446] and R12, if present, is selected from hydrogen, fluoro, fluoromethyl, methoxy and fluoromethoxy.

[0447] One embodiment of the present invention relates to compounds of formula I, wherein X1 is CR7 and X2 is NH, thus having the structure of formula II

[0448]

[0449] wherein R4, R5, R6, R7, R8, R9, R10, R11, R12, if present, and X3 are as described herein for Formula I, and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof.

[0450] Another embodiment relates to compounds of formula I, wherein X1 is N and X2 is NH, thus having the structure of formula III

[0451]

[0452] wherein R4, R5, R6, R8, R9, R10, R11, R12, if present, and X3 are as described herein for Formula I, and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof.

[0453] Another embodiment relates to compounds of formula I, wherein X2 is O and X1 is C(R7), thus having the structure of formula IV

[0454]

[0455] wherein R4, R5, R6, R7, R8, R9, R10, R11, R12, if present, and X3 are as described herein for Formula I, and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof.

[0456] Another embodiment relates to compounds of formula I wherein X2 is S and X1 is C(R7), thus having the structure of formula V

[0457]

[0458] wherein R4, R5, R6, R7, R8, R9, R10, R11, R12, if present, and X3 are as described herein for Formula I, and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof.

[0459] It is to be understood that, subsequently in any definition of substituents for compounds of Formulae II, III, IV and V, potential reference to R7 applies only to compounds of Formulae II, IV and V, while other substitutions also apply to compounds of Formula III.

[0460] In one embodiment of the compounds of Formula I, II, III, IV and V, X3 is C(R12).

[0461] In one embodiment of the compounds of Formula I, II, III, IV and V, X3 is N.

[0462] In one embodiment, in the compound of formula III, at least one of R4, R5 and R6 is different from hydrogen, in particular at least one of R5 and R6 is different from hydrogen.

[0463] In one embodiment, in the compound of formula III, if R6 is hydrogen, then R5 is halogen; in a specific embodiment, R5 is iodine.

[0464] In one embodiment, in the compounds of Formula I, II, IV and / or V, at least one of R5, R6 and R7 is different from hydrogen.

[0465] In one embodiment, in the compounds of formula I, II, III, IV and / or V, if R6 is hydrogen, R7 is different from hydrogen and is preferably selected from fluorine, chlorine, bromine, cyano, methoxy, unsubstituted or fluorinated C 1-2 Alkyl, unsubstituted or fluorinated C 1-2 Alkoxy, unsubstituted or fluorinated methylsulfonyl and unsubstituted or fluorinated methylsulfinyl, and is preferably selected from fluorine, chlorine, bromine, methyl, methoxy, fluoromethyl, fluoromethoxy, fluoroethoxy, methylsulfonyl and methylsulfinyl.

[0466] In a preferred embodiment, in the compounds of formula I, II, III, IV and V, if R10 is hydrogen, both R8 and R11 are different from hydrogen.

[0467] Further embodiments relate to compounds of formula II, III, IV or V,

[0468] in

[0469] X3 is N or C (R12),

[0470] R4 is hydrogen,

[0471] R5 is selected from hydrogen, fluorine, chlorine and bromine,

[0472] R6 is selected from fluorine, chlorine, bromine, iodine, cyano, azido, nitro, methyl, ethyl, n-propyl, isopropyl, trifluoromethyl, methylsulfinyl, methylsulfonyl, cyclopropyl, cyclopropylmethyl, methoxy, ethoxy, methoxymethoxy, methoxyethoxy, ethoxymethoxy, cyclopropylmethoxy, phenyl, benzyloxy, phenyloxy, benzylsulfinyl, benzylsulfonyl, thienyl, pyridyl, oxazole, thiazole and isoxazole, wherein each alkyl and alkoxy group in R6 may be substituted by one or more residues selected from fluorine, cyano and hydroxy, and wherein each Phenyl, thienyl, pyridyl, oxazole, thiazole and isoxazole may optionally be substituted one or more times, preferably with substituents selected from halogen, methoxy, fluoromethoxy, methyl and fluoromethyl, or in the compounds of formula II, IV or V, in particular in the compounds of formula II, R6 and R7 together with the carbon atom to which R6 and R7 are attached may form a ring selected from phenyl, pyridyl, cyclohexyl and cyclopentyl, each of which may be unsubstituted or substituted one or more times with groups selected from methyl, fluorinated methyl, methoxy, fluorinated methoxy, hydroxy, chlorine and fluorine,

[0473] R7 is selected from hydrogen, fluorine, chlorine, bromine, iodine, cyano, methoxy, ethoxy, methylsulfinyl, methylsulfonyl, methyl, ethyl, fluoromethyl, fluoroethyl and fluorine (C 1-2 ) alkoxy, or R7 and R6 together form a ring as described herein,

[0474] R8 is selected from hydrogen, fluorine, chlorine, bromine, iodine, methoxy, fluoromethyl and fluoromethoxy, or R8 and R10 together form a ring system as described herein,

[0475] R9 is selected from hydrogen, methyl, methoxy, fluorine and chlorine, and is preferably hydrogen,

[0476] or R9 and R8 or R10 together with the ring to which they are attached form a bicyclic ring system selected from 2,1,3-benzothiadiazole, 2,1,3-benzoxadiazole, 2-oxo-2,3-dihydro-1,3-benzoxazole and 1,3-benzodioxole, which are optionally substituted with two fluorines,

[0477] or R9 and R10 together with the ring to which they are attached form a bicyclic ring system selected from 3-oxo-2,3-dihydro-1H-isoindole, 1,1-dioxo-2,3-dihydro-1-benzothiophene, 3-oxo-1,3-dihydro-2-benzofuran, which may be optionally methylated at 1 position,

[0478] R10 is selected from hydrogen, fluorine, chlorine, bromine, iodine, unsubstituted or fluorinated C 1-3 Alkenyl, including vinyl and propenyl, unsubstituted or fluorinated C 1-3 Alkynyl, including ethynyl and propargyl, unsubstituted or fluorinated and / or hydroxylated C 1-3 Alkyl, including methyl, ethyl, isopropyl and trifluoromethyl, unsubstituted or fluorinated and / or hydroxylated C 1-3 Alkoxy, including methoxy and fluoro (C 1-2 ) alkoxy, cyano, cyanomethyl, cyanomethoxy, cyclopropyl, cyclopropylmethoxy, cyclopropylethoxy, acetyl, azido, nitro, pentafluorosulfanyl, unsubstituted or fluorinated and / or hydroxylated C 1-3 Alkoxy (C 1-3 ) alkyl, preferably methoxypropyl and ethoxyethyl, unsubstituted or fluorinated and / or hydroxylated C 1-3 Alkoxy (C 1-3 ) alkoxy, preferably methoxyethoxy and fluoromethoxyethoxy, unsubstituted or fluorinated and / or hydroxylated C 1-3 Alkoxy (C 2-3 ) alkenyl, preferably methoxypropylene and ethoxyvinyl, unsubstituted or fluorinated and / or hydroxylated C 1-3 Alkoxy (C 2-3) alkynyl, unsubstituted or fluorinated and / or hydroxylated C 1-3 Alkoxycarbonyl (C 1-3 ) alkyl, preferably ethoxycarbonylethyl, and unsubstituted or fluorinated and / or hydroxylated C 1-3 Alkoxycarbonyl (C 1-3 ) alkenyl, preferably ethoxycarbonylvinyl, wherein each cyclopropyl group in R10 may be unsubstituted or further substituted by one or more substituents selected from fluorine, chlorine, cyano, optionally fluorinated C 1-2 Alkoxy and optionally fluorinated C 1-2 alkoxycarbonyl, or as described herein R10 and R9 together form a ring system,

[0479] R11 is selected from hydrogen, fluorine, chlorine, bromine, unsubstituted or fluorinated methyl and unsubstituted or fluorinated methoxy,

[0480] R12, if present, is selected from hydrogen, fluorine, chlorine or bromine, and is preferably hydrogen or fluorine;

[0481] wherein, in a preferred embodiment, at least one, preferably two, of R8, R10 and R11 are different from hydrogen and unsubstituted alkyl,

[0482] and wherein in one embodiment the residue in R10 is preferably unsubstituted or fluorinated,

[0483] and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof.

[0484] One embodiment relates to compounds of formula II, III, IV and V, wherein

[0485] X3 is N or C (R12),

[0486] R4 is hydrogen,

[0487] R5 is selected from hydrogen, fluorine, chlorine and bromine,

[0488] R6 is selected from fluorine, chlorine, bromine, azido, cyano, methyl, ethyl, n-propyl, isopropyl, trifluoromethyl, methylsulfinyl, methylsulfonyl, cyclopropyl, methoxy, phenyl, benzyloxy, thien-2-yl and thien-3-yl, wherein each alkyl and alkoxy group in R6 may be unsubstituted or substituted by one or more residues selected from fluorine, cyclopropyl and methoxy, preferably fluorine,

[0489] R7 is selected from hydrogen, fluorine, chlorine, bromine, cyano, methyl, ethyl, methylsulfinyl, methylsulfonyl, fluoromethyl, fluoroethyl, methoxy, fluoromethoxy, fluoroethoxy and fluoropropoxy,

[0490] R8 is selected from hydrogen, fluorine, chlorine, bromine, methoxy, fluoromethyl and fluoromethoxy, or R8 and R10 together form a ring system as described herein,

[0491] R9 is hydrogen or fluorine, preferably hydrogen,

[0492] or R9 and R8 or R10 together with the ring to which they are attached form a bicyclic ring system selected from 2,1,3-benzothiadiazole, 2,1,3-benzoxadiazole, 2-oxo-2,3-dihydro-1,3-benzoxazole, 1,3-benzodioxole or 2,2-difluoro-1,3-benzodioxole,

[0493] or R9 and R10 together with the ring to which they are attached form a bicyclic ring system selected from 3-oxo-2,3-dihydro-1H-isoindole, 1,1-dioxo-2,3-dihydro-1-benzothiophene, 3-oxo-1,3-dihydro-2-benzofuran and 1-methyl-3-oxo-1,3-dihydro-2-benzofuran,

[0494] R10 is selected from hydrogen, fluorine, chlorine, bromine, iodine, methyl, ethyl, propyl, vinyl, propenyl, ethynyl, propargyl, fluorine (C 1-3 ) alkyl, preferably trifluoromethyl, methoxy, ethoxy, fluoro(C 1-3 ) alkoxy, cyano, cyanomethyl, cyanoethyl, cyanomethoxy, acetyl, azido, unsubstituted or fluorinated C 1-3 Alkoxy (C 1-3 ) alkyl, unsubstituted or fluorinated C 1-3 Alkoxy (C 1-3 ) alkoxy, unsubstituted or fluorinated C 1-3 Alkoxy (C 2-3 )alkenyl, unsubstituted or fluorinated C 1-3 Alkoxy (C 2-3 ) alkynyl, unsubstituted or fluorinated C 1-3 Alkoxycyclopropyl, unsubstituted or fluorinated C 1-3 alkoxycarbonylcyclopropyl and pentafluorosulfanyl, or R10 and R9 together form a ring system as described herein, and wherein, in preferred embodiments, R8 and R10 are not both hydrogen,

[0495] R11 is selected from hydrogen, fluorine, chlorine, fluorinated methyl and unsubstituted or fluorinated methoxy,

[0496] R12, if present, is selected from hydrogen and fluorine,

[0497] and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof.

[0498] A further embodiment relates to compounds of formula II, III or IV,

[0499] in

[0500] X3 is N or C (R12),

[0501] R4 and R5 are both hydrogen,

[0502] R6 is selected from the group consisting of fluorine, chlorine, bromine, iodine, cyano, azido, methyl, ethyl, isopropyl, trifluoromethyl, acetyl, methylsulfinyl, methylsulfonyl, cyclopropyl, cyclopropylmethyl, methoxy, ethoxy, methoxyethoxy, cyclopropylmethoxy, phenyl, benzyloxy, phenyloxy, thienyl, pyridyl, oxazole, thiazole and isoxazole,

[0503] or R6 and R7 together with the carbon atom to which R6 and R7 are attached form a ring selected from phenyl, pyridyl and cyclopentyl,

[0504] R7 is selected from hydrogen, fluorine, chlorine, bromine, iodine, methoxy, ethoxy, methyl, trifluoromethyl and fluorine (C 1-2 ) alkoxy, or R7 and R6 together form a ring as described herein,

[0505] R8 is selected from hydrogen, fluorine, chlorine, bromine, iodine, methoxy, methyl and trifluoromethyl, or R8 and R10 together form a ring system as described herein,

[0506] R9 is selected from hydrogen, fluorine and chlorine, and is preferably hydrogen,

[0507] or R9 and R8 or R10 together with the ring to which they are attached form a bicyclic ring system selected from 2,1,3-benzothiadiazole, 2,1,3-benzoxadiazole, 2-oxo-2,3-dihydro-1,3-benzoxazole and 1,3-benzodioxole, which are optionally substituted with two fluorines,

[0508] R10 is selected from hydrogen, fluorine, chlorine, bromine, iodine, ethynyl, propargyl, trifluoromethyl, methoxy, fluorine (C 1-2 )alkoxy, cyano, cyanomethyl, acetyl, azido, pentafluorosulfanyl and methoxycarbonyl, or R10 and R9 together form a ring system as described herein,

[0509] R11 is selected from hydrogen, fluorine, chlorine, bromine and methoxy,

[0510] R12 is selected from hydrogen, fluorine, chlorine or bromine,

[0511] wherein, in a preferred embodiment, at least one of R8, R9, R10 and R11 is different from hydrogen and unsubstituted alkyl,

[0512] and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof.

[0513] One embodiment relates to compounds of formula II, III and IV, wherein

[0514] X3 is N or C (R12),

[0515] R4 and R5 are both hydrogen,

[0516] R6 is selected from fluorine, chlorine, bromine, azido, methyl, isopropyl, trifluoromethyl, methylsulfonyl, cyclopropyl, methoxy, phenyl, benzyloxy, thiophen-2-yl and thiophen-3-yl,

[0517] R7 is selected from hydrogen, fluorine, chlorine and methoxy,

[0518] R8 is selected from hydrogen, fluorine, chlorine, bromine, methoxy and trifluoromethyl, or R8 and R10 together form a ring system as described herein,

[0519] R9 is hydrogen or fluorine, preferably hydrogen,

[0520] or R9 and R8 or R10 together with the ring to which they are attached form a bicyclic ring system selected from 2,1,3-benzothiadiazole, 2,1,3-benzoxadiazole, 2-oxo-2,3-dihydro-1,3-benzoxazole, 1,3-benzodioxole or 2,2-difluoro-1,3-benzodioxole,

[0521] R10 is selected from hydrogen, fluorine, chlorine, bromine, iodine, methyl, ethynyl, trifluoromethyl, methoxy, fluorine (C 1-2 )alkoxy, cyano, cyanomethyl, acetyl, azido and pentafluorosulfanyl, or R10 and R9 together form a ring system as described herein, and wherein, in preferred embodiments, R8 and R10 are not both hydrogen,

[0522] R11 is selected from hydrogen, fluorine, chlorine and methoxy,

[0523] R12 is selected from hydrogen and fluorine,

[0524] and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof.

[0525] One embodiment relates to compounds of formula II, III, IV or V,

[0526] in

[0527] R4 and R5 are both hydrogen,

[0528] R6 is methoxy, trifluoromethyl, bromine or chlorine, preferably chlorine,

[0529] R7 is hydrogen, fluorine, methoxy or trifluoromethyl,

[0530] X3 is C(R12),

[0531] R9 and R8 or R10 together with the phenyl ring to which R8 and R9 or R9 and R10 are attached form 2,1,3-benzothiadiazole or 2,2-difluoro-1,3-benzodioxole,

[0532] R10 is selected from hydrogen and fluorine,

[0533] R11 is selected from hydrogen, fluorine and methoxy, and is preferably hydrogen, and

[0534] R12, if present, is hydrogen or fluorine,

[0535] and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof.

[0536] One embodiment relates to compounds of formula II, III or IV,

[0537] in

[0538] R4 and R5 are both hydrogen,

[0539] R6 is bromine or chlorine, preferably chlorine,

[0540] R7 is hydrogen, fluorine, methoxy or trifluoromethyl,

[0541] X3 is C(R12),

[0542] R9 and R8 or R10 together with the phenyl ring to which R8 and R9 or R9 and R10 are attached form 2,1,3-benzothiadiazole or 2,2-difluoro-1,3-benzodioxole,

[0543] R10 is selected from hydrogen and fluorine,

[0544] R11 is selected from hydrogen, fluorine and methoxy, and

[0545] R12 is hydrogen,

[0546] and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof.

[0547] A preferred embodiment relates to compounds of formula I,

[0548] in

[0549] R4 and R5 are both hydrogen,

[0550] R6 is chlorine or bromine, preferably chlorine,

[0551] R7 is hydrogen, fluorine, methoxy or trifluoromethyl,

[0552] X3 is N or C (R12),

[0553] R8 is selected from fluorine, chlorine and methoxy,

[0554] R9 is hydrogen,

[0555] R10 is selected from fluorine, chlorine, bromine, cyano, cyanomethyl, trifluoromethyl and pentafluorosulfanyl,

[0556] R11 is selected from hydrogen, fluorine and methoxy,

[0557] R12 is hydrogen,

[0558] and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof.

[0559] A preferred embodiment of the present invention relates to compounds of formula II, III, IV or V, wherein

[0560] X3 is N or C (R12),

[0561] R4 is hydrogen or fluorine, preferably hydrogen,

[0562] R5 is selected from hydrogen, fluorine, chlorine, bromine, iodine, methyl, methoxy, and fluorinated C 1-2 alkyl, including trifluoromethyl, preferably hydrogen, methyl, fluorine, chlorine, bromine or iodine, or R5 and R6 together form a ring as described herein,

[0563] R6 is selected from hydrogen, fluorine, chlorine, bromine, iodine, cyano, azido, unsubstituted or substituted C 1-3 Alkyl, preferably methyl, ethyl, isopropyl, difluoromethyl, difluoroethyl, trifluoroethyl and / or trifluoromethyl, unsubstituted or substituted C 2-3 Alkenyl, unsubstituted or substituted C 2-3 Alkynyl, unsubstituted or unsubstituted or substituted (C 1-3 ) alkylsulfinyl, preferably methylsulfinyl, unsubstituted or unsubstituted or substituted C 1-3 Alkylsulfonyl, preferably methylsulfonyl, unsubstituted or substituted C 3-6 Cycloalkyl, preferably cyclopropyl, unsubstituted or substituted C 3-6 Cycloalkyl (C 1-3 ) alkyl, preferably cyclopropylmethyl, unsubstituted or substituted C 3-6 Cycloalkyl (C 1-3 ) alkyloxy, preferably cyclopropylmethoxy, unsubstituted or substituted C 3-6 Heterocycloalkyl, unsubstituted or substituted C 3-6 Heterocycloalkyl (C 1-3 ) alkyloxy, preferably heterocyclopropylmethoxy, unsubstituted or substituted C 3-6 Cycloalkoxy, unsubstituted or substituted C 3-6Heterocycloalkoxy, unsubstituted or substituted C 1-3 Alkoxy, preferably methoxy, difluoromethoxy, trifluoromethoxy, difluoroethoxy, trifluoroethoxy, unsubstituted or substituted C 1-3 Alkoxy (C 1-3 ) alkoxy, preferably methoxyethoxy, unsubstituted or substituted C 1-3 Alkoxy (C 1-3 ) alkyl, C 3-6 Cycloalkyl (C 1-3 ) alkoxy, preferably cyclopropylmethoxy, unsubstituted or substituted phenyl, unsubstituted or substituted phenyl (C 1-3 ) alkyl, preferably benzyl, unsubstituted or substituted phenyl (C 1-3 ) alkoxy, preferably benzyloxy, unsubstituted or substituted phenyloxy, unsubstituted or substituted phenyl (C 1-3 ) alkylsulfonyl, preferably benzylsulfonyl, unsubstituted or substituted phenyl (C 1-3 )alkylsulfinyl, preferably benzylsulfinyl, unsubstituted or substituted thienyl, unsubstituted or substituted pyridyl, unsubstituted or substituted oxazole, unsubstituted or substituted thiazole and unsubstituted or substituted isoxazole, and wherein each optional substituent in R6 is preferably selected from fluorine, chlorine, unsubstituted or fluorinated methyl, unsubstituted or fluorinated methoxy, hydroxy and cyano,

[0564] Provided that in the compound of formula III, if R6 is hydrogen, at least one of R5 and R7 is different from hydrogen, wherein R5 is preferably iodine,

[0565] or

[0566] (i) R6 and R7 together with the carbon atom to which R6 and R7 are attached form an unsubstituted or substituted phenyl group, an unsubstituted or substituted pyridyl group, an unsubstituted or substituted cyclopentyl group or an unsubstituted or substituted cyclohexyl group,

[0567] wherein each substituent, if present, is selected from halogen, hydroxy, methyl or methoxy, wherein each methyl or methoxy may be unsubstituted or substituted with one or more substituents selected from halogen, preferably fluorine, and methoxy,

[0568] or

[0569] (ii) R6 and R5 together with the carbon atom to which R6 and R5 are attached form a 1,3-dioxolane ring which may be unsubstituted or substituted with one or two substituents selected from fluorine and methyl,

[0570] R7 is selected from hydrogen, fluorine, chlorine, bromine, iodine, cyano, C 1-3 Alkyl, C 1-3 Alkyloxy, preferably methoxy, fluoro (C1-3 ) alkyl, preferably difluoromethyl or trifluoromethyl, fluoro(C 1-3 ) alkoxy, preferably difluoromethoxy, difluoroethoxy, trifluoroethoxy and trifluoromethoxy, methylsulfinyl, methylsulfonyl, fluorinated methylsulfinyl, fluorinated methylsulfonyl, substituted or unsubstituted C 3-6 Cycloalkyl, substituted or unsubstituted C 3-6 Heterocycloalkyl, substituted or unsubstituted C 3-6 Cycloalkyloxy, substituted or unsubstituted C 3-6 Heterocycloalkyloxy, substituted or unsubstituted C 5-6 Heteroaryl, substituted or unsubstituted C 5-6 Heteroaryloxy and C 5-6 heteroarylmethoxy, wherein the heteroaryl is preferably selected from pyridyl, oxazole and isoxazole, and wherein the heteroaryl may be substituted by one or more substituents selected from halogen, unsubstituted or fluorinated methyl, unsubstituted or fluorinated methoxy, or R7 and R6 together form a ring as described herein,

[0571] R8 is selected from hydrogen, fluorine, chlorine, bromine, iodine, cyano, C 1-3 Alkyloxy, preferably methoxy, fluoro (C 1-3 ) alkoxy, C 1-3 Alkyl, preferably methyl, and fluorine (C 1-3 )alkyl, preferably trifluoromethyl,

[0572] R9 is selected from hydrogen, fluorine, chlorine, bromine, iodine, cyano, C 1-3 Alkyloxy, preferably methoxy, fluoro (C 1-3 ) alkoxy, C 1-3 Alkyl, preferably methyl, and fluorine (C 1-3 )alkyl, preferably trifluoromethyl, and preferably hydrogen, methoxy or fluorine,

[0573] R10 is selected from hydrogen, fluorine, chlorine, bromine, iodine, C 1-3 Alkyl, halo (C 1-3 ) alkyl, preferably fluoro(C 1-3 ) alkyl, preferably trifluoromethyl, C 2-3 Alkenyl, C 2-3 Alkynyl, C 1-3 Alkyloxy, halo(C 1-3 ) alkyloxy, preferably fluoro(C 1-3 ) alkoxy, cyano, cyanomethyl, cyanoethyl, unsubstituted or fluorinated C 1-3 Alkylcarbonyl, preferably acetyl, unsubstituted or fluorinated C 1-3Alkoxycarbonyl, preferably methoxycarbonyl, cyclopropyl, cyclopropyloxy, azido, pentafluorosulfanyl and nitro, wherein any cyclopropyl residue is preferably substituted by a group selected from fluoro, cyano, C 1-3 Alkoxy and C 1-3 Alkoxycarbonyl, and wherein each alkyl, alkoxy, alkenyl or alkynyl in R10 may be optionally further substituted by one or more substituents selected from cyclopropyl, fluoro, chloro, bromo, iodo, cyano, hydroxy, halo (C 1-3 ) alkoxy and C 1-3 Alkoxy, preferably fluoro, methoxy, fluoromethoxy or fluoroethoxy,

[0574] R11 is selected from hydrogen, fluorine, chlorine, cyano, C 1-3 Alkyl, preferably methyl, fluoro (C 1-3 ) alkyl, preferably fluoromethyl, C 1-3 Alkyloxy, preferably methoxy, fluoro (C 1-3 ) alkoxy, preferably fluoro(C 1-2 )alkoxy, and more preferably hydrogen, fluorine, chlorine, methoxy, fluoromethoxy or fluoromethyl,

[0575] R12, if present, is selected from hydrogen, fluorine, chlorine, bromine, iodine, C 1-3 Alkyloxy, preferably methoxy, fluoro (C 1-3 ) alkoxy, preferably fluoro(C 1-2 ) alkoxy, C 1-3 Alkyl, preferably methyl, and fluorine (C 1-3 )alkyl, preferably trifluoromethyl, and more preferably hydrogen, fluorine, or fluoromethyl,

[0576] wherein, in a preferred embodiment, at least one of R8, R10 and R11 is different from hydrogen, and more preferably at least one of R8, R10 and R11 is also different from unsubstituted alkyl,

[0577] and wherein, preferably, in the compound of formula II, at least one of R5, R6 and R7, if present, is not hydrogen,

[0578] and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof.

[0579] A preferred embodiment of the present invention relates to compounds of formula II, III or IV, wherein

[0580] X3 is N or C (R12),

[0581] R4 is hydrogen,

[0582] R5 is selected from hydrogen, fluorine, chlorine, bromine, iodine, methyl, methoxy, acetyl, methoxycarbonyl and trifluoromethyl, preferably hydrogen, methyl or iodine, or R5 and R6 together form a ring as described herein,

[0583] R6 is selected from hydrogen, fluorine, chlorine, bromine, iodine, cyano, azido, unsubstituted or substituted C 1-3 Alkyl, preferably methyl, ethyl, isopropyl or trifluoromethyl, unsubstituted or fluorinated C 1-2 Alkylcarbonyl, unsubstituted or fluorinated C 1-2 Alkoxycarbonyl, (C 1-3 ) alkylsulfinyl, preferably methylsulfinyl, C 1-3 Alkylsulfonyl, preferably methylsulfonyl, C 3-6 Cycloalkyl, preferably cyclopropyl, C 3-6 Cycloalkyl (C 1-3 ) alkyl, preferably cyclopropylmethyl, C 3-6 Heterocycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Heterocycloalkoxy, unsubstituted or substituted C 1-3 Alkoxy, preferably methoxy, unsubstituted or substituted C 1-3 Alkoxy (C 1-3 ) alkoxy, preferably methoxyethoxy, C 3-6 Cycloalkyl (C 1-3 ) alkoxy, preferably cyclopropylmethoxy, unsubstituted or substituted phenyl, unsubstituted or substituted phenyl (C 1-3 )alkoxy, preferably benzyloxy, unsubstituted or substituted phenyloxy, thienyl, pyridyl, oxazole, thiazole and isoxazole, and wherein each optional substituent in R6 is preferably selected from fluoro, chloro, methyl, methoxy and cyano,

[0584] Provided that in the compound of formula III, if R6 is hydrogen, then R5 is different from hydrogen and is preferably iodine,

[0585] or

[0586] (i) R6 and R7 together with the carbon atom to which R6 and R7 are attached form an unsubstituted or substituted phenyl group, an unsubstituted or substituted pyridyl group, an unsubstituted or substituted cyclopentyl group or an unsubstituted or substituted cyclohexyl group,

[0587] wherein each substituent, if present, is selected from halogen, methyl or methoxy, wherein each methyl or methoxy may be unsubstituted or substituted with one or more substituents selected from fluoro and methoxy,

[0588] or

[0589] (ii) R6 and R5 together with the carbon atom to which R6 and R5 are attached form a 1,3-dioxolane ring which may be unsubstituted or substituted with one or two substituents selected from fluorine and methyl,

[0590] R7 is selected from hydrogen, fluorine, chlorine, bromine, iodine, cyano, C 1-3 Alkyl, C 1-3 Alkyloxy, fluoro(C 1-3 ) alkyl, preferably trifluoromethyl, fluoro(C 1-3 ) alkoxy, preferably trifluoromethoxy, unsubstituted or fluorinated C 1-2 Alkylcarbonyl, unsubstituted or fluorinated C 1-2 alkoxycarbonyl, methylsulfinyl and methylsulfonyl, or R7 and R6 together form a ring as described herein,

[0591] R8 is selected from hydrogen, fluorine, chlorine, bromine, iodine, C 1-3 Alkyloxy, preferably methoxy, fluoro (C 1-3 ) alkoxy, C 1-3 Alkyl, preferably methyl, and fluorine (C 1-3 )alkyl, preferably trifluoromethyl,

[0592] R9 is selected from hydrogen, fluorine, chlorine, bromine, iodine, cyano, C 1-3 Alkyloxy, preferably methoxy, fluoro (C 1-3 ) alkoxy, C 1-3 Alkyl, preferably methyl, and fluorine (C 1-3 )alkyl, preferably trifluoromethyl, and preferably hydrogen, fluorine, chlorine or bromine,

[0593] R10 is selected from hydrogen, fluorine, chlorine, bromine, iodine, C 1-3 Alkyl, halo (C 1-3 ) alkyl, preferably fluoro(C 1-3 ) alkyl, especially trifluoromethyl, C 2-3 Alkynyl, C 1-3 Alkyloxy, halo(C 1-3 ) alkyloxy, preferably fluoro(C 1-2 ) alkoxy, cyano, cyanomethyl, unsubstituted or fluorinated C 1-3 Alkylcarbonyl, preferably acetyl, unsubstituted or fluorinated C 1-3 alkoxycarbonyl, preferably methoxycarbonyl, azido, pentafluorosulfanyl and nitro,

[0594] R11 is selected from hydrogen, fluorine, chlorine, bromine, iodine, C 1-3 Alkyl, preferably methyl, fluoro (C 1-3 ) alkyl, preferably trifluoromethyl, C 1-3 Alkyloxy, preferably methoxy, fluoro (C 1-3 ) alkoxy, preferably fluoro(C1-2 ) alkoxy, unsubstituted or fluorinated C 1-3 Alkylcarbonyl, preferably acetyl, unsubstituted or fluorinated C 1-3 alkoxycarbonyl, preferably methoxycarbonyl, and cyano, and more preferably hydrogen, fluorine, chlorine or bromine,

[0595] R12 is selected from hydrogen, fluorine, chlorine, bromine, iodine, C 1-3 Alkyloxy, preferably methoxy, fluoro (C 1-3 ) alkoxy, preferably fluoro(C 1-2 ) alkoxy, C 1-3 Alkyl, preferably methyl, and fluorine (C 1-3 )alkyl, preferably trifluoromethyl, and more preferably hydrogen, fluorine, chlorine or bromine,

[0596] wherein, in a preferred embodiment, at least one of R8, R9, R10 and R11 is different from hydrogen, and more preferably at least one of R8, R9, R10 and R11 is also different from unsubstituted alkyl,

[0597] and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof.

[0598] A preferred embodiment of the present invention relates to compounds of formula II, III, IV or V, wherein

[0599] R4 is hydrogen or fluorine, more preferably hydrogen,

[0600] R5 is selected from hydrogen, fluorine, bromine, chlorine, iodine and methyl,

[0601] R6 is selected from hydrogen, fluorine, chlorine, bromine, iodine, methyl, ethyl, propyl, preferably isopropyl, acetyl, cyano, nitro, azido, methylsulfonyl, methylsulfinyl, fluorine (C 1-2 ) alkyl, methoxy, ethoxy, fluoro(C 1-2 ) alkoxy, C 1-2 Alkoxymethoxy, fluorinated (C 1-2 ) alkoxymethoxy, fluorinated (C 1-2 )alkoxymethyl, phenyl, phenyloxy, benzyloxy, benzylsulfinyl, pyridin-3-yl, thien-2-yl, thien-3-yl, cyclopropyl, cyclopropyloxy, cyclopropylmethyl and cyclopropylmethoxy, wherein each phenyl, thienyl, pyridinyl and cyclopropyl may be optionally substituted one or more times by methoxy, fluorine and / or chlorine, and wherein R6 is preferably not hydrogen,

[0602] Alternatively, in the compound of formula II, R6 and R7 together with the carbon atom to which R6 and R7 are attached form a ring selected from unsubstituted or substituted phenyl, unsubstituted or substituted pyridyl, and unsubstituted or substituted cyclohexyl and unsubstituted or substituted cyclopentyl, wherein any substituent of the phenyl, pyridyl and cyclopentyl is selected from fluorine, chlorine, hydroxy, fluorinated or unsubstituted methoxy and fluorinated or unsubstituted methyl, wherein the ring is preferably selected from unsubstituted phenyl, pyridyl or cyclopentyl,

[0603] R7 is selected from hydrogen, fluorine, chlorine, bromine, cyano, methyl, methoxy, methylsulfonyl, methylsulfinyl, fluoromethyl, fluoroethyl, fluoromethoxy, fluoroethoxy, and optionally methylated isoxazole, which is preferably 3,5-dimethyl-1,2-oxazole,

[0604] X3 is N or C(R12), and preferably C(R12),

[0605] R8 is selected from hydrogen, methoxy, fluoromethoxy, cyano, chlorine and fluorine, and is preferably fluorine, methoxy or fluoromethoxy,

[0606] R9 is selected from hydrogen, methoxy and fluorine,

[0607] R10 is selected from hydrogen, vinyl, propenyl, ethynyl, propargyl, cyano, cyanomethyl, acetyl, fluorine, chlorine, bromine, iodine, azido, nitro, unsubstituted or fluorinated C 1-3 Alkyl, preferably methyl and trifluoromethyl, hydroxy (C 1-3 ) alkoxy, preferably hydroxyethoxy, cyano (C 1-3 ) alkoxy, preferably cyanomethoxy, cyclopropyl (C 1-2 )alkyl, cyclopropyl (C 1-3 ) alkoxy, preferably cyclopropylmethoxy, unsubstituted or fluorinated C 1-3 Alkoxy, preferably difluoroethoxy and trifluoroethoxy, unsubstituted or fluorinated C 1-2 Alkoxy (C 1-3 ) alkyl, preferably methoxypropyl and ethoxyethyl, unsubstituted or fluorinated C 1-2 Alkoxy (C 1-3 ) alkoxy, preferably methoxyethoxy and fluoromethoxyethoxy, unsubstituted or fluorinated C 1-2 Alkoxy (C 2-3 ) alkenyl, preferably methoxypropenyl, unsubstituted or fluorinated C 1-2 Alkoxy (C 2-3 ) alkynyl, and pentafluorosulfanyl, C 1-2 Alkoxycyclopropyl and C 1-2 Alkoxycarbonylcyclopropyl,

[0608] R11 is selected from hydrogen, fluorine, chlorine, cyano, fluoromethyl, methoxy and fluoromethoxy,

[0609] R12 is hydrogen or fluorine,

[0610] and wherein at least one, preferably at least two, of R8, R10 and R11 are different from hydrogen,

[0611] and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof.

[0612] A preferred embodiment of the present invention relates to compounds of formula II, III or IV, wherein

[0613] R4 is hydrogen or fluorine, more preferably hydrogen,

[0614] R5 is hydrogen, iodine or methyl,

[0615] R6 is selected from hydrogen, fluorine, chlorine, bromine, iodine, methyl, ethyl, isopropyl, acetyl, trifluoromethyl, methoxy, ethoxy, fluorine (C 1-2 ) alkoxy, (C 1-2 ) alkoxymethoxy, cyanomethylsulfonyl, phenyl, phenyloxy, benzyloxy, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-thienyl, 3-thienyl, cyclopropyl, cyclopropyloxy and cyclopropylmethoxy,

[0616] or R6 and R7 together with the carbon atom to which R6 and R7 are attached form a ring selected from unsubstituted or substituted phenyl, unsubstituted or substituted pyridyl and unsubstituted or substituted cyclopentyl, wherein any substituent is selected from fluorine, methoxy and methyl, wherein the ring is preferably selected from unsubstituted phenyl, pyridyl or cyclopentyl,

[0617] and wherein in formula II, if R6 is hydrogen, then R5 is iodine,

[0618] R7 is selected from hydrogen, methyl, methoxy, trifluoromethyl, fluorine, chlorine and bromine,

[0619] X3 is N or C(R12), and preferably C(R12),

[0620] R8 is selected from hydrogen, methoxy, cyano, chlorine and fluorine,

[0621] R9 is selected from hydrogen and fluorine,

[0622] R10 is selected from hydrogen, ethynyl, cyano, cyanomethyl, acetyl, fluorine, chlorine, bromine, iodine, azido, nitro, trifluoromethyl, difluoroethoxy, trifluoroethoxy and pentafluorosulfanyl,

[0623] R11 is selected from hydrogen, fluorine, chlorine and methoxy,

[0624] R12 is hydrogen or fluorine

[0625] and wherein at least one of R8, R9, R10 and R11 is different from hydrogen,

[0626] and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof.

[0627] A preferred embodiment of the present invention relates to compounds of formula II, III, IV or V, particularly preferably compounds of formula II or III, wherein

[0628] R4 is hydrogen,

[0629] R5 is selected from hydrogen, fluorine, chlorine and bromine, and is preferably hydrogen,

[0630] R6 is selected from fluorine, chlorine, bromine, cyano, methyl, ethyl, propyl, preferably isopropyl, methylsulfinyl, methylsulfonyl, cyclopropyl, cyclopropyloxy, benzyloxy, thiophene, methoxy, ethoxy, fluorine (C 1-3 ) alkoxy and fluorine (C 1-3 )alkyl, preferably trifluoromethyl,

[0631] R7 is selected from hydrogen, methoxy, fluorine, chlorine, bromine, cyano, methylsulfinyl, methylsulfonyl, C 1-3 Alkoxy, fluorine (C 1-3 ) alkoxy, C 1-3 Alkyl and fluorine (C 1-3 )alkyl, preferably trifluoromethyl,

[0632] Alternatively, in the compound of formula II, R6 and R7 together with the ring-forming C atoms to which they are attached may form a ring selected from phenyl, cyclopentyl and pyridyl, each of which may be unsubstituted or substituted by one or more residues selected from fluorine, chlorine, hydroxyl, fluorinated or unsubstituted methoxy and fluorinated or unsubstituted methyl, wherein the phenyl, cyclopentyl and cyclohexyl rings are preferably unsubstituted, and wherein the pyridyl ring is preferably unsubstituted or substituted at the 8-position,

[0633] X3 is -C(R12)- or N,

[0634] R8 is hydrogen, fluorine, methoxy or fluoromethoxy, and is preferably fluorine or methoxy,

[0635] R9 is hydrogen,

[0636] R10 is selected from halogen, azido, nitro, cyano, C 1-3 Alkyl, C 2-3 Alkenyl, C 2-3 Alkynyl, C 1-3 Alkoxy, C 3-5 Cycloalkyl, preferably cyclopropyl, C 3-5Cycloalkyloxy and pentafluorosulfanyl, wherein each alkyl, alkenyl, alkynyl and alkoxy group may be unsubstituted or substituted by one or more residues selected from halogen, preferably fluorine, cyano, cyclopropyl, C 1-3 Alkoxy and fluorine C 1-3 Alkoxy, and wherein any cycloalkyl moiety may be unsubstituted or substituted by one or more residues selected from fluorine, cyano, unsubstituted or fluorinated C 1-3 Alkoxy and unsubstituted or fluorinated C 1-3 Alkoxycarbonyl,

[0637] R11 is selected from hydrogen, fluorine, chlorine, cyano, methoxy, fluoromethoxy and fluoromethyl, and

[0638] R12 is selected from hydrogen and fluorine,

[0639] wherein preferably at least one of R8 and R11 is different from hydrogen, and wherein preferably at least one of R8 and R11 is selected from fluorine, chlorine and methoxy,

[0640] and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof.

[0641] One embodiment relates to compounds of formula II, III, IV and V, preferably formula II and III;

[0642] in

[0643] R4 and R5 are both hydrogen,

[0644] R6 is selected from methyl, ethyl, propyl, methylsulfonyl, methylsulfinyl, methoxy, mono-, di- and trifluoromethyl, mono-, di- and trifluoroethyl, mono-, di- and trifluoromethoxy, mono-, di- and trifluoroethoxy, cyano, azido, fluorine, bromine and chlorine, and is preferably selected from chlorine and bromine,

[0645] R7, if present, is selected from hydrogen, fluorine, chlorine, bromine, cyano, methoxy, fluoromethoxy, fluoroethoxy, methyl, fluoromethyl, methylsulfinyl and methylsulfonyl,

[0646] X3 is C(R12),

[0647] R8 is selected from hydrogen, fluorine, chlorine and methoxy, or forms a ring with R9 as described herein,

[0648] R9 and R8 or R10 together with the phenyl ring to which R8 and R9 or R9 and R10 are attached form 2,1,3-benzothiadiazole or 1,3-benzodioxole, which is optionally substituted with two fluorines,

[0649] R10 is selected from hydrogen and fluorine, or R10 and R9 together form a ring as described above,

[0650] R11 is selected from hydrogen, fluorine and methoxy,

[0651] R12 is hydrogen,

[0652] and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof.

[0653] A preferred embodiment of the present invention relates to compounds of formula II, III, IV or V, particularly preferably compounds of formula II or III, wherein

[0654] R4 and R5 are both hydrogen,

[0655] R6 is selected from fluorine, chlorine, bromine, methoxy, fluoromethoxy and fluoromethyl,

[0656] R7 is selected from hydrogen, methoxy, fluorine, chlorine, bromine, fluoromethyl, preferably trifluoromethyl, fluoromethoxy, fluoroethoxy, methylsulfinyl and methylsulfonyl,

[0657] X3 is N or CR12,

[0658] R8 is fluorine or methoxy,

[0659] R9 is hydrogen,

[0660] R10 is selected from fluorine, chlorine, bromine, cyano, cyanomethyl, cyanoethyl, cyanomethoxy, unsubstituted or fluorinated C 1-3 Alkyl, preferably methyl, ethyl and fluoromethyl, unsubstituted or fluorinated C 1-3 Alkoxy, preferably fluoromethoxy and fluoroethoxy, unsubstituted or fluorinated C 1-2 Alkoxy (C 1-3 ) alkyl, preferably methoxypropyl, fluorinated methoxypropyl, ethoxyethyl and fluorinated methoxymethyl, unsubstituted or fluorinated C 1-2 Alkoxy (C 2-3 ) alkenyl, including methoxypropylene and ethoxyvinyl, unsubstituted or fluorinated C 1-2 Alkoxy (C 1-3 ) alkoxy, preferably methoxyethoxy, pentafluorosulfanyl and cycloalkyl, which is substituted by a substituent selected from C 1-2 Alkoxy, fluorine (C 1-2 ) alkoxy, C 1-2 Alkoxycarbonyl and fluorine (C 1-2 ) alkoxycarbonyl,

[0661] R11 is selected from hydrogen, methoxy, fluoromethoxy, fluoromethyl and fluorine,

[0662] R12, if present, is hydrogen or fluorine,

[0663] and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof.

[0664] A preferred embodiment of the present invention relates to compounds of formula II, III or IV, particularly preferably compounds of formula II or III, wherein

[0665] R4 and R5 are both hydrogen,

[0666] R6 is selected from fluorine, chlorine, bromine, isopropyl, benzyloxy and trifluoromethyl,

[0667] R7 is hydrogen, methoxy, fluorine or bromine, preferably hydrogen,

[0668] or R6 and R7 together with the ring-forming C atoms to which they are attached form a ring selected from phenyl, cyclopentyl and pyridyl,

[0669] X3 is -C(R12)-,

[0670] R8 is fluorine, hydrogen or methoxy,

[0671] R9 is hydrogen,

[0672] R10 is ethynyl, trifluoromethyl, difluoroethoxy, cyano, chlorine, bromine or iodine,

[0673] R11 is selected from hydrogen and fluorine, and

[0674] R12 is selected from hydrogen and fluorine,

[0675] and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof.

[0676] One embodiment relates to compounds of formula II, III and IV, preferably compounds of formula II and III;

[0677] in

[0678] R4 and R5 are both hydrogen,

[0679] R6 is bromine or chlorine, preferably chlorine,

[0680] R7 is hydrogen, methoxy, fluorine or trifluoromethyl,

[0681] X3 is C(R12),

[0682] R8 is selected from hydrogen, fluorine and methoxy, or forms a ring with R9 as described herein,

[0683] R9 and R8 or R10 together with the phenyl ring to which R8 and R9 or R9 and R10 are attached form 2,1,3-benzothiadiazole or 1,3-benzodioxole, which is optionally substituted with two fluorines,

[0684] R10 is selected from hydrogen and fluorine, or R10 and R9 together form a ring as described above,

[0685] R11 is selected from hydrogen, fluorine and methoxy,

[0686] R12 is hydrogen,

[0687] and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof.

[0688] A preferred embodiment of the present invention relates to compounds of formula II, III or IV, particularly preferably compounds of formula II or III, wherein

[0689] R4, R5 are hydrogen,

[0690] R6 is bromine, chlorine or trifluoromethyl,

[0691] R7 is hydrogen, methoxy, fluorine or trifluoromethyl,

[0692] R8 is fluorine or methoxy,

[0693] R9 is hydrogen,

[0694] R10 is selected from fluorine, chlorine, bromine, cyano, cyanomethyl, trifluoromethyl, difluoroethoxy and pentafluorosulfanyl,

[0695] R11 is selected from hydrogen, methoxy and fluorine,

[0696] and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof.

[0697] One embodiment of the present invention relates to compounds of formula II, III, IV or V, preferably compounds of formula II or III, wherein

[0698] X3 is C(R12),

[0699] R4 is hydrogen or fluorine, preferably hydrogen,

[0700] R5 is selected from hydrogen, fluorine, chlorine, bromine, iodine, methyl and trifluoromethyl, preferably hydrogen, or R5 and R6 together form a ring as described herein,

[0701] R6 is selected from hydrogen, fluorine, chlorine, bromine, iodine, cyano, azido, unsubstituted or substituted C 1-3 Alkyl, preferably methyl, ethyl, isopropyl or trifluoromethyl, C 1-2 Alkylcarbonyl, C 1-2 Alkoxycarbonyl, (C 1-3 ) alkylsulfinyl, preferably methylsulfinyl, (C 1-3 ) alkylsulfonyl, preferably methylsulfonyl, unsubstituted or substituted benzylsulfonyl, unsubstituted or substituted benzylsulfinyl, C 3-6Cycloalkyl, preferably cyclopropyl, C 3-6 Cycloalkyl (C 1-3 ) alkyl, preferably cyclopropylmethyl, C 3-6 Heterocycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Heterocycloalkoxy, unsubstituted or substituted C 1-3 Alkoxy, preferably methoxy, mono-, di- and trifluoroethoxy, unsubstituted or substituted C 1-3 Alkoxy (C 1-3 ) alkoxy, preferably methoxyethoxy, unsubstituted or substituted C 1-3 Alkoxy (C 1-3 )alkyl, (C 3-6 )cycloalkyl(C 1-3 ) alkoxy, preferably cyclopropylmethoxy, unsubstituted or substituted phenyl, unsubstituted or substituted phenyl (C 1-3 )alkoxy, preferably benzyloxy, unsubstituted or substituted phenyloxy, thienyl, pyridyl, oxazole, thiazole and isoxazole, and wherein each optional substituent in R6 is preferably selected from fluorine, chlorine, unsubstituted or fluorinated methyl, unsubstituted or fluorinated methoxy, hydroxy and cyano,

[0702] Provided that in the compound of formula III, if R6 is hydrogen, then R5 is preferably iodine,

[0703] or

[0704] (i) R6 and R7 together with the carbon atom to which R6 and R7 are attached form an unsubstituted or substituted phenyl group, an unsubstituted or substituted pyridyl group, an unsubstituted or substituted cyclopentyl group or an unsubstituted or substituted cyclohexyl group,

[0705] wherein each substituent, if present, is selected from halogen, hydroxy, methyl or methoxy, wherein each methyl or methoxy may be unsubstituted or substituted with one or more substituents selected from halogen, preferably fluorine, and methoxy,

[0706] or

[0707] (ii) R6 and R5 together with the carbon atom to which R6 and R5 are attached form a 1,3-dioxolane ring which may be unsubstituted or substituted with one or two substituents selected from fluorine and methyl,

[0708] R7 is selected from hydrogen, fluorine, chlorine, bromine, iodine, cyano, C 1-3 Alkyl, C 1-3 Alkyloxy, fluoro(C 1-3 ) alkyl, preferably trifluoromethyl, fluoro(C 1-3 ) alkoxy, preferably fluoromethoxy or fluoroethoxy, C 1-2 Alkylcarbonyl, C1-2 alkoxycarbonyl, methylsulfinyl and methylsulfonyl, or R7 and R6 together form a ring as described herein,

[0709] R8 is selected from hydrogen, fluorine, chlorine, bromine, iodine, C 1-3 Alkyloxy, preferably methoxy, fluoro (C 1-3 ) alkoxy, C 1-3 Alkyl, preferably methyl, and fluorine (C 1-3 )alkyl, preferably trifluoromethyl,

[0710] R9 and R10 together with the ring to which they are attached form a bicyclic ring system selected from 2,1,3-benzothiadiazole, 2,1,3-benzoselenadiazole, 2,1,3-benzoxadiazole, 2-oxo-2,3-dihydro-1,3-benzoxazole, 1,3-benzothiazole, 2,3-dihydro-1-benzothiophene which is substituted with one or two oxo groups (preferably substituted with two oxo groups to give 1,1-dioxo-2,3-dihydro-1-benzothiophene), 3-oxo-1,3-dihydro-2-benzofuran-5-yl which may be unsubstituted or substituted with one or more two substituted with groups selected from oxo, fluoro and methyl, preferably substituted with at least one oxo group to form 3-oxo-1,3-dihydro-2-benzofuran or 1-methyl-3-oxo-1,3-dihydro-2-benzofuran, and dihydroisoindole, which may be unsubstituted or substituted with one or more substituents selected from oxo, fluoro and methyl, and which is preferably 3-oxo-2,3-dihydro-1H-isoindole, and 1,3-benzodioxole, which is optionally substituted with one or two fluoro to preferably form 2,2-difluoro-1,3-benzodioxole,

[0711] R11 is selected from hydrogen, fluorine, chlorine, bromine, iodine, C 1-3 Alkyl, preferably methyl, fluoro (C 1-3 ) alkyl, preferably trifluoromethyl, C 1-3 Alkyloxy, preferably methoxy, fluoro (C 1-3 ) alkoxy, preferably fluoro(C 1-2 ) alkoxy, cyano, and more preferably hydrogen, fluorine, chlorine or bromine,

[0712] R12 is selected from hydrogen, fluorine, chlorine, bromine, iodine, C 1-3 Alkyloxy, preferably methoxy, fluoro (C 1-3 ) alkoxy, preferably fluoro(C 1-2 ) alkoxy, C 1-3 Alkyl, preferably methyl, and fluorine (C 1-3 )alkyl, preferably trifluoromethyl, and more preferably hydrogen, fluorine, chlorine or bromine,

[0713] and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof.

[0714] One embodiment of the present invention relates to compounds of formula II, III or IV, preferably compounds of formula II or III, wherein

[0715] X3 is C(R12),

[0716] R4 is hydrogen,

[0717] R5 is selected from hydrogen, fluorine, chlorine, bromine, iodine, methyl and trifluoromethyl, preferably hydrogen or iodine, or R5 and R6 together form a ring as described herein,

[0718] R6 is selected from hydrogen, fluorine, chlorine, bromine, iodine, cyano, azido, unsubstituted or substituted C 1-3 Alkyl, preferably methyl, ethyl, isopropyl or trifluoromethyl, C 1-2 Alkylcarbonyl, C 1-2 Alkoxycarbonyl, (C 1-3 ) alkylsulfinyl, preferably methylsulfinyl, (C 1-3 ) alkylsulfonyl, preferably methylsulfonyl, C 3-6 Cycloalkyl, preferably cyclopropyl, C 3-6 Cycloalkyl (C 1-3 ) alkyl, preferably cyclopropylmethyl, C 3-6 Heterocycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Heterocycloalkoxy, unsubstituted or substituted C 1-3 Alkoxy, preferably methoxy, unsubstituted or substituted C 1-3 Alkoxy (C 1-3 ) alkoxy, preferably methoxyethoxy, (C 3-6 )cycloalkyl(C 1-3 ) alkoxy, preferably cyclopropylmethoxy, unsubstituted or substituted phenyl, unsubstituted or substituted phenyl (C 1-3 )alkoxy, preferably benzyloxy, unsubstituted or substituted phenyloxy, thienyl, pyridyl, oxazole, thiazole and isoxazole, and wherein each optional substituent in R6 is preferably selected from fluoro, chloro, methyl, methoxy and cyano,

[0719] Provided that in the compound of formula II, if R6 is hydrogen, then R5 is preferably iodine, or

[0720] (i) R6 and R7 together with the carbon atom to which R6 and R7 are attached form an unsubstituted or substituted phenyl group, an unsubstituted or substituted pyridyl group, an unsubstituted or substituted cyclopentyl group or an unsubstituted or substituted cyclohexyl group,

[0721] wherein each substituent, if present, is selected from halogen, methyl or methoxy, wherein each methyl or methoxy may be unsubstituted or substituted with one or more substituents selected from fluoro and methoxy,

[0722] or

[0723] (ii) R6 and R5 together with the carbon atom to which R6 and R5 are attached form a 1,3-dioxolane ring which may be unsubstituted or substituted with one or two substituents selected from fluorine and methyl,

[0724] R7 is selected from hydrogen, fluorine, chlorine, bromine, iodine, cyano, C 1-3 Alkyl, C 1-3 Alkyloxy, fluoro(C 1-3 ) alkyl, preferably trifluoromethyl, fluoro(C 1-3 ) alkoxy, preferably trifluoromethoxy, C 1-2 Alkylcarbonyl, C 1-2 alkoxycarbonyl, methylsulfinyl and methylsulfonyl, or R7 and R6 together form a ring as described herein,

[0725] R8 is selected from hydrogen, fluorine, chlorine, bromine, iodine, C 1-3 Alkyloxy, preferably methoxy, fluoro (C 1-3 ) alkoxy, C 1-3 Alkyl, preferably methyl, and fluorine (C 1-3 )alkyl, preferably trifluoromethyl,

[0726] or R9 and R10 together with the ring to which they are attached form a bicyclic ring system selected from 2,1,3-benzothiadiazole, 2,1,3-benzoselenadiazole, 2,1,3-benzooxadiazole, 2-oxo-2,3-dihydro-1,3-benzoxazole, 1,3-benzothiazole, 2,3-dihydro-1-benzothiophene substituted with one or two oxo groups (preferably substituted with two oxo groups to give 1,1-dioxo-2,3-dihydro-1-benzothiophene), 3-oxo-1,3-dihydro-2-benzofuran-5-yl, and 1,3-benzodioxole, optionally substituted with one or two fluorine groups,

[0727] R11 is selected from hydrogen, fluorine, chlorine, bromine, iodine, C 1-3 Alkyl, preferably methyl, fluoro (C 1-3 ) alkyl, preferably trifluoromethyl, C 1-3 Alkyloxy, preferably methoxy, fluoro (C 1-3 ) alkoxy, preferably fluoro(C 1-2 ) alkoxy, cyano, and more preferably hydrogen, fluorine, chlorine or bromine,

[0728] R12 is selected from hydrogen, fluorine, chlorine, bromine, iodine, C 1-3Alkyloxy, preferably methoxy, fluoro (C 1-3 ) alkoxy, preferably fluoro(C 1-2 ) alkoxy, C 1-3 Alkyl, preferably methyl, and fluorine (C 1-3 )alkyl, preferably trifluoromethyl, and more preferably hydrogen, fluorine, chlorine or bromine,

[0729] and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof.

[0730] A preferred embodiment of the present invention relates to compounds of formula II, III or IV, particularly preferably compounds of formula II or III, wherein

[0731] X3 is C(R12),

[0732] R4 and R5 are both hydrogen,

[0733] R6 is selected from fluoro, chloro, bromo, methoxy, trifluoromethyl, methylsulfonyl and cyano,

[0734] or R6 and R7 together with the carbon atom to which R6 and R7 are attached form a ring selected from unsubstituted or substituted phenyl, unsubstituted or substituted pyridyl, unsubstituted or substituted cyclohexyl and unsubstituted or substituted cyclopentyl, wherein any substituent is selected from fluorine, methoxy and methyl, and wherein the ring is preferably selected from unsubstituted phenyl, pyridyl, cyclohexyl or cyclopentyl,

[0735] R7 is selected from hydrogen, methyl, fluoromethyl, preferably trifluoromethyl, methoxy, fluorine, chlorine and bromine, preferably hydrogen, fluorine and trifluoromethyl, or R7 and R6 together form a ring as described herein, R8 is hydrogen or fluorine,

[0736] R9 and R10 together with the C atom to which they are attached form a ring selected from 2,1,3-benzothiadiazole, 2,1,3-benzoxadiazole, 3-oxo-2,3-dihydro-1H-isoindole, 3-oxo-1,3-dihydro-2-benzofuran, 1-methyl-3-oxo-1,3-dihydro-2-benzofuran and 2,2-difluoro-substituted 1,3-benzodioxole, preferably 2,1,3-benzothiadiazole,

[0737] R11 is hydrogen or fluorine, preferably hydrogen, and

[0738] R12 is hydrogen or fluorine,

[0739] and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof.

[0740] A preferred embodiment of the present invention relates to compounds of formula II, III or IV, particularly preferably compounds of formula II or III, wherein

[0741] X3 is C(R12),

[0742] R4 and R5 are both hydrogen,

[0743] R6 is fluorine, chlorine, bromine, trifluoromethyl, methylsulfonyl or cyano,

[0744] or R6 and R7 together with the carbon atom to which R6 and R7 are attached form a ring selected from unsubstituted or substituted phenyl, unsubstituted or substituted pyridyl and unsubstituted or substituted cyclopentyl, wherein any substituent is selected from fluorine, methoxy and methyl, and wherein the ring is preferably selected from unsubstituted phenyl, pyridyl or cyclopentyl,

[0745] R7 is selected from hydrogen, methyl, trifluoromethyl, methoxy, fluorine, chlorine and bromine, preferably hydrogen and bromine, or R7 and R6 together form a ring as described herein,

[0746] R8 is hydrogen or fluorine,

[0747] R9 and R10 together with the C atom to which they are attached form a ring selected from 2,1,3-benzothiadiazole, 2,1,3-benzooxadiazole and 2,2-difluoro-substituted 1,3-benzodioxole, preferably 2,1,3-benzothiadiazole,

[0748] R11 is hydrogen or fluorine, and

[0749] R12 is hydrogen or fluorine,

[0750] and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof.

[0751] Further embodiments relate to compounds of formula II, III, IV or V,

[0752] in

[0753] X3 is C(R12),

[0754] R4 is hydrogen or fluorine, preferably hydrogen,

[0755] R5 is selected from hydrogen, fluorine, chlorine, bromine, iodine, methyl and fluoromethyl, preferably hydrogen, or R5 and R6 together form a ring as described herein,

[0756] R6 is selected from hydrogen, fluorine, chlorine, bromine, iodine, cyano, azido, unsubstituted or substituted C 1-3 Alkyl, preferably methyl, ethyl, propyl, mono-, di- and trifluoromethyl, unsubstituted or substituted C 1-2 Alkylcarbonyl, unsubstituted or substituted C 1-2 Alkoxycarbonyl, (C 1-3 ) alkylsulfinyl, preferably methylsulfinyl, (C 1-3) alkylsulfonyl, preferably methylsulfonyl, C 3-6 Cycloalkyl, preferably cyclopropyl, C 3-6 Cycloalkyl (C 1-3 ) alkyl, preferably cyclopropylmethyl, C 3-6 Heterocycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Heterocycloalkoxy, unsubstituted or substituted C 1-3 Alkoxy, preferably methoxy, mono-, di- and trifluoromethoxy, mono-, di- and trifluoroethoxy, unsubstituted or substituted C 1-3 Alkoxy (C 1-3 ) alkoxy, preferably methoxyethoxy, unsubstituted or substituted C 1-3 Alkoxy (C 1-3 )alkyl, (C 3-6 )cycloalkyl(C 1-3 ) alkoxy, preferably cyclopropylmethoxy, unsubstituted or substituted phenyl, unsubstituted or substituted phenyl (C 1-3 )alkoxy, preferably benzyloxy, unsubstituted or substituted phenyloxy, thienyl, pyridyl, oxazole, thiazole and isoxazole, and wherein each optional substituent in R6 is preferably selected from fluorine, chlorine, methyl, methoxy and cyano, with the proviso that in the compound of formula III, if R6 is hydrogen, then R5 is preferably iodine,

[0757] or

[0758] (i) R6 and R7 together with the carbon atom to which R6 and R7 are attached form an unsubstituted or substituted phenyl group, an unsubstituted or substituted pyridyl group, an unsubstituted or substituted cyclopentyl group or an unsubstituted or substituted cyclohexyl group,

[0759] wherein each substituent, if present, is selected from halogen, hydroxy, methyl or methoxy, wherein each methyl or methoxy may be unsubstituted or substituted with one or more substituents selected from fluoro and methoxy,

[0760] or

[0761] (ii) R6 and R5 together with the carbon atom to which R6 and R5 are attached form a 1,3-dioxolane ring which may be unsubstituted or substituted with one or two substituents selected from fluorine and methyl,

[0762] R7, if present, is selected from hydrogen, fluorine, chlorine, bromine, iodine, cyano, C 1-3 Alkyl, C 1-3 Alkyloxy, fluoro(C 1-3 ) alkyl, preferably trifluoromethyl, fluoro(C 1-3 ) alkoxy, preferably fluoromethoxy or fluoroethoxy, unsubstituted or fluorinated C 1-2 Alkylcarbonyl, unsubstituted or fluorinated C1-2 alkoxycarbonyl, methylsulfinyl, pyridylmethoxy, isoxazole and methylsulfonyl, or R7 and R6 together form a ring as described herein,

[0763] R9 and R8 together with the ring to which they are attached form a bicyclic ring system selected from 2,1,3-benzothiadiazole, 2,1,3-benzoselenadiazole, 2,1,3-benzooxadiazole, 2-oxo-2,3-dihydro-1,3-benzoxazole, and 1,3-benzodioxole, which are optionally substituted with one or two fluorines,

[0764] R10 is selected from hydrogen, fluorine, chlorine, bromine, iodine, C 1-3 Alkyl, halo (C 1-3 ) alkyl, preferably fluoro(C 1-2 ) alkyl, halogenated, preferably fluorinated or unsubstituted C 1-3 Alkoxy (C 1-3 ) alkyl, C 2-3 Alkynyl, halogenated, preferably fluorinated or unsubstituted C 1-3 Alkoxy (C 1-3 )alkenyl, methoxy, ethoxy, halo(C 1-3 ) alkyloxy, preferably fluoro(C 1-2 ) alkoxy, halogenated, preferably fluorinated or unsubstituted C 1-3 Alkoxy (C 1-3 ) alkoxy, cyano, cyanomethyl, cyanoethyl, unsubstituted or fluorinated C 1-3 Alkylcarbonyl, preferably acetyl, unsubstituted or fluorinated C 1-3 Alkoxycarbonyl, preferably methoxycarbonyl, cyclopropylmethoxy, (C 1-2 ) alkoxycyclopropyl, (C 1-2 ) alkoxycarbonylcyclopropyl, azido, pentafluorosulfanyl and nitro, and wherein in one embodiment, R10 is hydrogen, methoxy or halogen,

[0765] R11 is selected from hydrogen, fluorine, chlorine, bromine, iodine, C 1-3 Alkyl, preferably methyl, fluoro (C 1-3 ) alkyl, preferably trifluoromethyl, C 1-3 Alkyloxy, preferably methoxy, fluoro (C 1-3 ) alkoxy, preferably fluoro(C 1-2 ) alkoxy, unsubstituted or fluorinated C 1-3 Alkylcarbonyl, preferably acetyl, unsubstituted or fluorinated C 1-3 alkoxycarbonyl, preferably methoxycarbonyl, and cyano, and more preferably hydrogen, fluorine, chlorine or bromine,

[0766] R12 is selected from hydrogen, fluorine, chlorine, bromine, iodine, C 1-3Alkyloxy, preferably methoxy, fluoro (C 1-3 ) alkoxy, preferably fluoro(C 1-2 ) alkoxy, C 1-3 Alkyl, preferably methyl, and fluorine (C 1-3 )alkyl, preferably trifluoromethyl, and more preferably hydrogen, fluorine, chlorine or bromine,

[0767] and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof.

[0768] A further embodiment relates to compounds of formula II, III or IV,

[0769] in

[0770] X3 is C(R12),

[0771] R4 is hydrogen,

[0772] R5 is selected from hydrogen, fluorine, chlorine, bromine, iodine, methyl and trifluoromethyl, preferably hydrogen or iodine, or R5 and R6 together form a ring as described herein,

[0773] R6 is selected from hydrogen, fluorine, chlorine, bromine, iodine, cyano, azido, unsubstituted or substituted C 1-3 Alkyl, preferably methyl, ethyl, isopropyl or trifluoromethyl, unsubstituted or substituted C 1-2 Alkylcarbonyl, unsubstituted or substituted C 1-2 Alkoxycarbonyl, (C 1-3 ) alkylsulfinyl, preferably methylsulfinyl, (C 1-3 ) alkylsulfonyl, preferably methylsulfonyl, C 3-6 Cycloalkyl, preferably cyclopropyl, C 3-6 Cycloalkyl (C 1-3 ) alkyl, preferably cyclopropylmethyl, C 3-6 Heterocycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Heterocycloalkoxy, unsubstituted or substituted C 1-3 Alkoxy, preferably methoxy, unsubstituted or substituted C 1-3 Alkoxy (C 1-3 ) alkoxy, preferably methoxyethoxy, (C 3-6 )cycloalkyl(C 1-3 ) alkoxy, preferably cyclopropylmethoxy, unsubstituted or substituted phenyl, unsubstituted or substituted phenyl (C 1-3 )alkoxy, preferably benzyloxy, unsubstituted or substituted phenyloxy, thienyl, pyridyl, oxazole, thiazole and isoxazole, and wherein each optional substituent in R6 is preferably selected from fluorine, chlorine, methyl, methoxy and cyano, with the proviso that in the compound of formula II, if R6 is hydrogen, then R5 is preferably iodine,

[0774] or

[0775] (i) R6 and R7 together with the carbon atom to which R6 and R7 are attached form an unsubstituted or substituted phenyl group, an unsubstituted or substituted pyridyl group, an unsubstituted or substituted cyclopentyl group or an unsubstituted or substituted cyclohexyl group,

[0776] wherein each substituent, if present, is selected from halogen, methyl or methoxy, wherein each methyl or methoxy may be unsubstituted or substituted with one or more substituents selected from fluoro and methoxy,

[0777] or

[0778] (ii) R6 and R5 together with the carbon atom to which R6 and R5 are attached form a 1,3-dioxolane ring which may be unsubstituted or substituted with one or two substituents selected from fluorine and methyl,

[0779] R7 is selected from hydrogen, fluorine, chlorine, bromine, iodine, cyano, C 1-3 Alkyl, C 1-3 Alkyloxy, fluoro(C 1-3 ) alkyl, preferably trifluoromethyl, fluoro(C 1-3 ) alkoxy, preferably trifluoromethoxy, unsubstituted or fluorinated C 1-2 Alkylcarbonyl, unsubstituted or fluorinated C 1-2 alkoxycarbonyl, methylsulfinyl and methylsulfonyl, or R7 and R6 together form a ring as described herein,

[0780] R9 and R8 together with the ring to which they are attached form a bicyclic ring system selected from 2,1,3-benzothiadiazole, 2,1,3-benzoselenadiazole, 2,1,3-benzooxadiazole, 2-oxo-2,3-dihydro-1,3-benzoxazole, and 1,3-benzodioxole, which are optionally substituted with one or two fluorines,

[0781] R10 is selected from hydrogen, fluorine, chlorine, bromine, iodine, C 1-3 Alkyl, halo (C 1-3 ) alkyl, preferably fluoro(C 1-2 ) alkyl, C 2-3 Alkynyl, methoxy, ethoxy, halo (C 1-3 ) alkyloxy, preferably fluoro(C 1-2 ) alkoxy, cyano, cyanomethyl, unsubstituted or fluorinated C 1-3 Alkylcarbonyl, preferably acetyl, unsubstituted or fluorinated C 1-3 Alkoxycarbonyl, preferably methoxycarbonyl, azido, pentafluorosulfanyl and nitro, and wherein in one embodiment, R10 is hydrogen, methoxy or halogen,

[0782] R11 is selected from hydrogen, fluorine, chlorine, bromine, iodine, C 1-3 Alkyl, preferably methyl, fluoro (C 1-3 ) alkyl, preferably trifluoromethyl, C 1-3 Alkyloxy, preferably methoxy, fluoro (C 1-3 ) alkoxy, preferably fluoro(C 1-2 ) alkoxy, unsubstituted or fluorinated C 1-3 Alkylcarbonyl, preferably acetyl, unsubstituted or fluorinated C 1-3 alkoxycarbonyl, preferably methoxycarbonyl, and cyano, and more preferably hydrogen, fluorine, chlorine or bromine,

[0783] R12 is selected from hydrogen, fluorine, chlorine, bromine, iodine, C 1-3 Alkyloxy, preferably methoxy, fluoro (C 1-3 ) alkoxy, preferably fluoro(C 1-2 ) alkoxy, C 1-3 Alkyl, preferably methyl, and fluorine (C 1-3 )alkyl, preferably trifluoromethyl, and more preferably hydrogen, fluorine, chlorine or bromine,

[0784] and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof.

[0785] Another embodiment relates to compounds of formula II, III, IV or V, particularly preferably compounds of formula II or III, wherein

[0786] X3 is C(R12),

[0787] R4 and R5 are both hydrogen,

[0788] R6 is selected from fluorine, chlorine, bromine, methoxy, fluoromethoxy, methylsulfinyl, methylsulfonyl and fluoromethyl, and is preferably chlorine, bromine or fluoromethyl,

[0789] or R6 and R7 together with the carbon atom to which R6 and R7 are attached form a ring selected from unsubstituted or substituted phenyl, unsubstituted or substituted pyridyl, unsubstituted or substituted cyclohexyl and unsubstituted or substituted cyclopentyl, wherein any substituent is selected from fluorine, fluorinated or unsubstituted methoxy and fluorinated or unsubstituted methyl, and wherein the ring is preferably selected from unsubstituted phenyl, pyridyl, cyclohexyl or cyclopentyl,

[0790] R7 is selected from hydrogen, fluorine, chlorine, bromine, methoxy, methyl, acetyl, cyano, fluoromethyl, fluoromethoxy and fluoroethoxy, preferably hydrogen and trifluoromethyl, or R7 and R6 together form a ring as described herein,

[0791] R8 and R9 together with the C atom to which they are attached form a ring selected from 2,1,3-benzoselenadiazole, 2,1,3-benzothiadiazole, 2,1,3-benzooxadiazole, unsubstituted 1,3-benzodioxole, 2-oxo-2,3-dihydro-1,3-benzoxazole and 2,2-difluoro-1,3-benzodioxole,

[0792] R10 is selected from hydrogen, fluorine, chlorine, bromine and fluoromethyl,

[0793] R11 is selected from hydrogen, cyano, fluorine and chlorine, and is preferably hydrogen, and

[0794] R12 is selected from hydrogen, fluorine, chlorine and fluoromethyl,

[0795] and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof.

[0796] Another embodiment relates to compounds of formula II, III or IV, particularly preferably compounds of formula II or III, wherein

[0797] X3 is C(R12),

[0798] R4 and R5 are both hydrogen,

[0799] R6 is selected from fluorine, chlorine, bromine, and trifluoromethyl,

[0800] or R6 and R7 together with the carbon atom to which R6 and R7 are attached form a ring selected from unsubstituted or substituted phenyl, unsubstituted or substituted pyridyl and unsubstituted or substituted cyclopentyl, wherein any substituent is selected from fluorine, methoxy and methyl, and wherein the ring is preferably selected from unsubstituted phenyl, pyridyl or cyclopentyl,

[0801] R7 is selected from hydrogen, fluorine, chlorine, bromine, methoxy, methyl, acetyl and trifluoromethyl, preferably hydrogen and trifluoromethyl, or R7 and R6 together form a ring as described herein,

[0802] R8 and R9 together with the C atom to which they are attached form a ring selected from 2,1,3-benzothiadiazole, 2,1,3-benzoxadiazole, unsubstituted 1,3-benzodioxole, 2-oxo-2,3-dihydro-1,3-benzoxazole and 2,2-difluoro-1,3-benzodioxole,

[0803] R10 is hydrogen or fluorine,

[0804] R11 is selected from hydrogen, fluorine, chlorine, bromine and cyano, and

[0805] R12 is hydrogen, fluorine, chlorine and trifluoromethyl,

[0806] and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof.

[0807] Another embodiment relates to compounds of formula II, III, IV or V, particularly preferably compounds of formula II or III, wherein

[0808] X3 is C(R12),

[0809] R4 and R5 are both hydrogen,

[0810] R6 is selected from fluorine, chlorine, bromine and fluoromethyl,

[0811] or R6 and R7 together with the carbon atom to which R6 and R7 are attached form a ring selected from phenyl, pyridyl, cyclohexyl and cyclopentyl,

[0812] R7, if present, is selected from hydrogen, fluorine, chlorine, bromine, methoxy, methyl, fluoromethyl, fluoromethoxy and fluoroethoxy, preferably hydrogen, fluorine and trifluoromethyl, or R7 and R6 together form a ring as described herein,

[0813] R8 and R9 together with the C atom to which they are attached form a ring selected from 2,1,3-benzothiadiazole, 2,1,3-benzooxadiazole and 2,2-difluoro-1,3-benzodioxole,

[0814] R10 is hydrogen or fluorine,

[0815] R11 is selected from hydrogen, fluorine and cyano, and

[0816] R12 is selected from hydrogen, fluorine and fluoromethyl,

[0817] and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof.

[0818] One embodiment relates to compounds of formula II, III, IV and V, which are optionally substituted at the 2-position of the upper bicyclic ring, thus having the structures of formula II-2, III-2, IV-2 and V-2, as shown below:

[0819]

[0820] wherein R2 is selected from hydrogen, fluorine, chlorine, bromine, iodine and methoxy, and is preferably hydrogen or fluorine, particularly preferably hydrogen,

[0821] and wherein R4, R5, R6, R7, if present, R8, R9, R10, R11 and X3 are as described herein for the corresponding compounds of Formula II, III, IV and V, respectively.

[0822] In a preferred embodiment of the present invention, in the compounds of formula II, II-2, III, III-2, IV, IV-2, V and V-2,

[0823] X3 is N or CR12,

[0824] R2, if present, R4, R5 and R9 are all hydrogen,

[0825] R6 is selected from halogen, cyano, C 1-3 Alkoxy, C 1-3 Alkyl, C 3-6 Cycloalkyl, preferably C 3-4 Cycloalkyl, C 3-6 Cycloalkyloxy, preferably C 3-4 Cycloalkyloxy, C 3-6 Heterocycloalkyl, preferably C 3-4 Heterocycloalkyl, and C 3-6 Heterocycloalkyloxy, preferably C 3-4 Heterocycloalkyloxy, each of which may be optionally substituted by a residue selected from fluorine and unsubstituted or fluorinated C 1-3 Alkoxy,

[0826] R7 is selected from hydrogen, halogen, cyano, C 1-3 Alkoxy, C 1-3 Alkyl, C 3-6 Cycloalkyl, preferably C 3-4 Cycloalkyl, C 3-6 Cycloalkyloxy, preferably C 3-4 Cycloalkyloxy, C 3-6 Heterocycloalkyl, preferably C 3-4 Heterocycloalkyl, and C 3-6 Heterocycloalkyloxy, preferably C 3-4 Heterocycloalkyloxy, each of which may be optionally substituted by a residue selected from fluorine and unsubstituted or fluorinated C 1-3 Alkoxy,

[0827] R8 is selected from fluorine, methoxy and fluoromethoxy, preferably selected from fluorine and methoxy,

[0828] R10 is selected from halogen, C 1-4 Alkoxy, C 1-4 Alkyl, C 2-3 Alkenyl, C 2-3 Alkynyl, C 3-6 Cycloalkyl, preferably C 3-4 Cycloalkyl, C 3-6 Cycloalkyloxy, preferably C 3-4 Cycloalkyloxy, C 3-6 Heterocycloalkyl, preferably C 3-4 Heterocycloalkyl, and C 3-6 Heterocycloalkyloxy, preferably C 3-4 Heterocycloalkyloxy, each of which may be optionally substituted by a residue selected from fluorine, cyano and unsubstituted or fluorinated C 1-3 alkoxy, and

[0829] R11 is selected from hydrogen, fluorine, methoxy and fluoromethoxy, preferably selected from fluorine and methoxy,

[0830] and R12, if present, is selected from hydrogen, fluoro, fluoromethyl, methoxy and fluoromethoxy.

[0831] In a further embodiment, the compound of the present invention is represented by one of the following Formulae IIa-IIc:

[0832]

[0833] in

[0834] n is any number from 0 to 4,

[0835] m is 0 or 1,

[0836] p is any number from 0 to 3,

[0837] and

[0838] Any Y is an independently selected substituent selected from halogen, hydroxy, cyano, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-7 Cycloalkyl, C 3-7 Cycloalkyl (C 1-3 ) alkyl, C 3-7 Heterocycloalkyl (C 1-3 ) alkyl, C 1-6 Alkoxy and C 1-6 Alkoxy (C 1-3 ) alkyl, wherein each alkyl or alkoxy group may be unsubstituted or substituted by one or more radicals selected from halogen and C 1-3 Alkoxy substituents are substituted,

[0839] R4, R5, X3, R8, R9, R10, R11 and R12 are as described herein for the compounds of Formulas I and II.

[0840] According to one embodiment, in the compounds of formula II(a)-II(c)

[0841] m is 0 or 1, preferably 0,

[0842] n is any number from 0 to 4, preferably from 0 to 2, more preferably 0 or 1,

[0843] p is any number from 0 to 3, preferably from 0 to 2, more preferably 0 or 1,

[0844] Any Y is an independently selected substituent selected from halogen, hydroxy, cyano, C 1-3 Alkyl, C1-3 Alkoxy and C 1-3 Alkoxy (C 1-3 ) alkyl, wherein each alkyl or alkoxy group may be unsubstituted or substituted by one or more radicals selected from halogen and C 1-3 Alkoxy substituents are substituted,

[0845] R4 is hydrogen or fluorine, preferably hydrogen,

[0846] R5 is selected from hydrogen, halogen, C 1-3 Alkyl and C 1-3 alkoxy, wherein each alkyl or alkoxy group may optionally be substituted one or more times, preferably by methoxy or halogen,

[0847] X3 is N or C (R12),

[0848] R8 is selected from hydrogen, C 1-3 Alkyl, C 1-3 alkoxy and halogen, wherein each alkyl or alkoxy group may be unsubstituted or substituted with one or more substituents selected from halogen, cyano and methoxy, or R8 and R9 together form a ring system as described herein,

[0849] R9 is selected from hydrogen, C 1-3 Alkyl, C 1-3 alkoxy, fluorine, chlorine, bromine and iodine, wherein each alkyl or alkoxy group may be unsubstituted or substituted by one or more substituents selected from halogen and methoxy, and wherein R9 is preferably hydrogen,

[0850] or R9 and R8 or R10 together with the ring to which they are attached form a bicyclic ring system selected from 2,1,3-benzothiadiazole, 2,1,3-benzoselenadiazole, 2,1,3-benzooxadiazole, 1,3-benzoxazole, which may be optionally partially hydrogenated and 2-oxo-substituted, 1,3-benzodioxole, which may be unsubstituted or substituted with one or two substituents selected from fluoro and methyl, 1,3-benzothiazole , 2,3-dihydro-1-benzothiophene, which is substituted by one or two oxo groups (preferably substituted by two oxo groups to give 1,1-dioxo-2,3-dihydro-1-benzothiophene), 3-oxo-2,3-dihydro-1H-isoindole, or 1,3-dihydro-2-benzofuran, which may be unsubstituted or substituted by one or two groups selected from oxo, fluoro and methyl groups, preferably substituted by one oxo group, or by one oxo and one methyl group,

[0851] R10 is selected from hydrogen, fluorine, chlorine, bromine, iodine, C 1-3 Alkyl, C 1-3 Alkoxy, C 2-4 Alkenyl, C 2-4Alkynyl, cyano, cyanomethyl, cyanoethyl, cyanomethoxy, C 1-3 Alkylcarbonyl, C 1-3 Alkoxycarbonyl, azido, pentafluorosulfanyl and nitro, wherein each alkyl, alkenyl, alkynyl or alkoxy group may be unsubstituted or substituted with one or more substituents selected from halogen, cyano, hydroxy, fluoro (C 1-3 ) alkoxy and C 1-3 alkoxy, or as described herein R8 and R10 together form a ring system,

[0852] R11 is selected from hydrogen, C 1-3 Alkyl, C 1-3 Alkoxy, C 1-3 Alkylcarbonyl, C 1-3 Alkoxycarbonyl, fluorine, chlorine, bromine and iodine, wherein each alkyl and alkoxy group may be unsubstituted or substituted with one or more substituents selected from fluorine, chlorine, bromine, iodine and C 1-3 Alkoxy,

[0853] R12, if present, is selected from hydrogen, C 1-3 Alkyl, C 1-3 Alkoxy, fluorine, chlorine, bromine and iodine, wherein each alkyl and alkoxy group may be unsubstituted or substituted with one or more substituents selected from fluorine, chlorine, bromine, iodine and C 1-3 Alkoxy,

[0854] wherein, in a preferred embodiment, at least one of R8, R10 and R11 is different from hydrogen, and more preferably at least one of R8, R9, R10 and R11 is also different from unsubstituted alkyl,

[0855] and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof.

[0856] In a preferred embodiment, in compounds having the structures of Formula IIa, IIb, and IIc, Y is selected from hydrogen, halogen, hydroxy, unsubstituted or fluorinated methyl, and unsubstituted or fluorinated methoxy. In one embodiment, Y is fluorine, chlorine, methoxy, or trifluoromethyl. In a preferred embodiment, the values ​​of n and p are independently 0, 1, or 2.

[0857] In another preferred embodiment, in the compound having the structure of Formula IIa, IIb or IIc, the values ​​of m, n and p are all zero.

[0858] In particularly preferred embodiments of the compounds of formula IIa, IIb and IIc,

[0859] m is 0 or 1,

[0860] n and p are independently 0, 1 or 2,

[0861] Y is selected from halogen, hydroxy, fluorinated methyl and unsubstituted or fluorinated methoxy,

[0862] R4 is hydrogen,

[0863] R5 is hydrogen, methyl, methoxy or halogen, preferably hydrogen,

[0864] X3 is N or C (R12),

[0865] R8 is selected from hydrogen, fluorine, chlorine, bromine, methoxy, fluoromethoxy and fluoromethyl, or R8 and R9 together form a ring system as described herein,

[0866] R9 is hydrogen or fluorine, preferably hydrogen,

[0867] or R9 and R8 or R10 together with the ring to which they are attached form a bicyclic ring system selected from 2,1,3-benzothiadiazole, 2,1,3-benzoxadiazole, 1,3-benzodioxole, 2-oxo-2,3-dihydro-1,3-benzoxazole, 2,2-difluoro-1,3-benzodioxole and 4-methyl-2-oxodihydrobenzofuran,

[0868] R10 is selected from hydrogen, fluorine, chlorine, bromine, iodine, methyl, cyano, cyanomethyl, cyanoethyl, cyanomethoxy, vinyl, propenyl, ethynyl, propargyl, pentafluorosulfanyl, unsubstituted, fluorinated or hydroxylated C 1-3 Alkyloxy, including mono-, di- and trifluoromethoxy and mono-, di- and trifluoroethoxy, unsubstituted or fluorinated C 1-3 Alkyloxy (C 1-3 ) alkyl, unsubstituted or fluorinated C 1-3 Alkyloxy (C 1-3 ) alkyloxy, unsubstituted or fluorinated C 1-3 Alkyloxy (C 2-3 )alkenyl, unsubstituted or fluorinated C 1-3 Alkyloxy (C 2-3 ) alkynyl, unsubstituted or fluorinated C 1-3 Alkyl, including trifluoromethyl, and cyclopropyl, substituted with a substituent selected from hydroxy, hydroxymethyl, C 1-2 Alkoxy and C 1-2 Alkoxycarbonyl,

[0869] or R10 and R9 together form a ring system as described herein,

[0870] R11 is selected from hydrogen, fluorine, chlorine and methoxy,

[0871] R12, if present, is selected from hydrogen and fluorine,

[0872] and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof,

[0873] In a preferred embodiment, if R9 does not form a ring with R8 or R10, R10 is not hydrogen, and more preferably, both R8 and R10 are not hydrogen.

[0874] In particularly preferred embodiments of the compounds of formula IIa, IIb and IIc,

[0875] The values ​​of m, n and p are all 0,

[0876] R4 is hydrogen,

[0877] R5 is hydrogen, methyl, methoxy or halogen, preferably hydrogen,

[0878] X3 is N or C (R12),

[0879] R8 is selected from hydrogen, fluorine, chlorine, bromine, methoxy, fluoromethoxy and mono-, di- and trifluoromethyl, and is preferably selected from fluorine and methoxy, or R8 together with R9 form a ring system as described herein,

[0880] R9 is hydrogen or fluorine, preferably hydrogen,

[0881] or R9 and R8 or R10 together with the ring to which they are attached form a bicyclic ring system selected from 2,1,3-benzothiadiazole, 2,1,3-benzoxadiazole, 1,3-benzodioxole, 2-oxo-2,3-dihydro-1,3-benzoxazole or 2,2-difluoro-1,3-benzodioxole,

[0882] R10 is selected from hydrogen, fluorine, chlorine, bromine, iodine, cyano, cyanomethyl, cyanoethyl, cyanomethoxy, pentafluorosulfanyl, fluorine (C 1-2 ) alkoxy, preferably difluoroethoxy or trifluoroethoxy, and fluoro(C 1-2 )alkyl, preferably trifluoromethyl, or R10 and R9 together form a ring system as described herein,

[0883] R11 is selected from hydrogen, fluorine, chlorine, methoxy and fluoromethoxy, preferably fluorine and methoxy,

[0884] R12, if present, is selected from hydrogen, methoxy and fluoro,

[0885] and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof, wherein

[0886] In a preferred embodiment, if R9 does not form a ring with R8, R10 is not hydrogen, and more preferably both R8 and R10 are not hydrogen.

[0887] In particularly preferred embodiments of the compounds of formula IIa, IIb and IIc,

[0888] The values ​​of m, n and p are all 0,

[0889] R4 is hydrogen,

[0890] R5 is hydrogen, methyl, methoxy or halogen, preferably hydrogen,

[0891] R8 is selected from hydrogen, fluorine, chlorine, bromine, methoxy and trifluoromethyl, or R8 and R9 together form a ring system as described herein,

[0892] R9 is hydrogen or fluorine, preferably hydrogen,

[0893] or R9 and R8 or R10 together with the ring to which they are attached form a bicyclic ring system selected from 2,1,3-benzothiadiazole, 2,1,3-benzoxadiazole, 1,3-benzodioxole, 2-oxo-2,3-dihydro-1,3-benzoxazole or 2,2-difluoro-1,3-benzodioxole,

[0894] R10 is selected from hydrogen, fluorine, chlorine, bromine, cyano, cyanomethyl, pentafluorosulfanyl, difluoroethoxy, trifluoroethoxy and trifluoromethyl, or R10 and R9 together form a ring system as described herein, wherein, in preferred embodiments, R8 and R10 are not both hydrogen,

[0895] R11 is selected from hydrogen, fluorine, chlorine and methoxy,

[0896] R12 is selected from hydrogen and fluorine,

[0897] and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof.

[0898] A further embodiment relates to compounds of formula IIa-IIc, wherein

[0899] m is 0 or 1, preferably 0,

[0900] n is any number from 0 to 3, and is preferably 0 or 1,

[0901] p is any number from 0 to 2, and is preferably 0 or 1,

[0902] Any Y is a substituent independently selected from halogen, hydroxy, C 1-3 Alkyl, C 1-3 Alkoxy, wherein each alkyl or alkoxy group may be unsubstituted or substituted by one or more groups selected from halogen and C 1-3 Alkoxy substituents are substituted,

[0903] R4 is hydrogen,

[0904] R5 is selected from hydrogen, fluorine, chlorine, bromine, iodine, methyl, methoxy and trifluoromethyl, and is preferably hydrogen,

[0905] X3 is N or C (R12),

[0906] R8 is selected from hydrogen, fluorine, chlorine, bromine, iodine, C 1-3 Alkyloxy, preferably methoxy, fluoro (C 1-3 ) alkoxy, C 1-3 Alkyl, preferably methyl, and fluorine (C 1-3 )alkyl, preferably trifluoromethyl,

[0907] R9 is selected from hydrogen, fluorine, chlorine or bromine, and is preferably hydrogen,

[0908] R10 is selected from hydrogen, fluorine, chlorine, bromine, iodine, C 1-3 Alkyl, C 2-3 Alkenyl, C 2-3 Alkynyl, C 1-3 Alkyloxy, cyano, unsubstituted or fluorinated C 1-3 Alkylcarbonyl, preferably acetyl, unsubstituted or fluorinated C 1-3 Alkoxycarbonyl, preferably methoxycarbonyl, azido, pentafluorosulfanyl and nitro, wherein each alkyl, alkoxy, alkenyl or alkynyl group may be optionally substituted by one or more substituents selected from halogen, cyano, hydroxy and unsubstituted or fluorinated and / or hydroxylated C 1-3 Alkoxy,

[0909] R11 is selected from hydrogen, fluorine, chlorine, bromine, iodine, C 1-3 Alkyl, preferably methyl, fluoro (C 1-3 ) alkyl, preferably trifluoromethyl, C 1-3 Alkyloxy, preferably methoxy, fluoro (C 1-3 ) alkoxy, preferably fluoro(C 1-2 ) alkoxy, unsubstituted or fluorinated C 1-3 Alkylcarbonyl, preferably acetyl, unsubstituted or fluorinated C 1-3 alkoxycarbonyl, preferably methoxycarbonyl, and cyano, and more preferably hydrogen, fluorine, chlorine or bromine,

[0910] R12, if present, is selected from hydrogen, fluorine, chlorine, bromine, iodine, C 1-3 Alkyloxy, preferably methoxy, fluoro (C 1-3 ) alkoxy, preferably fluoro(C 1-2 ) alkoxy, C 1-3 Alkyl, preferably methyl, and fluorine (C 1-3 )alkyl, preferably trifluoromethyl, and more preferably hydrogen, fluorine, chlorine or bromine,

[0911] wherein, in a preferred embodiment, at least one of R8, R10 and R11 is different from hydrogen, and preferably at least one of R8, R10 and R11 is also different from unsubstituted alkyl,

[0912] wherein, in a preferred embodiment, R10 is different from hydrogen, and in a particularly preferred embodiment, both R10 and R8 are not hydrogen,

[0913] and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof.

[0914] A further embodiment relates to compounds of formula IIa-IIc, wherein

[0915] m is 0 or 1, preferably 0,

[0916] n is any number from 0 to 3, and is preferably 0 or 1,

[0917] p is any number from 0 to 2, and is preferably 0 or 1,

[0918] Any Y is a substituent independently selected from halogen, C 1-3 Alkyl, C 1-3 Alkoxy, wherein each alkyl or alkoxy group may be unsubstituted or substituted by one or more groups selected from halogen and C 1-3 Alkoxy substituents are substituted,

[0919] R4 is hydrogen,

[0920] R5 is selected from hydrogen, fluorine, chlorine, bromine, iodine, methyl, methoxy and trifluoromethyl, preferably hydrogen or iodine, and preferably hydrogen,

[0921] X3 is N or C (R12),

[0922] R8 is selected from hydrogen, fluorine, chlorine, bromine, iodine, C 1-3 Alkyloxy, preferably methoxy, fluoro (C 1-3 ) alkoxy, C 1-3 Alkyl, preferably methyl, and fluorine (C 1-3 )alkyl, preferably trifluoromethyl,

[0923] R9 is selected from hydrogen, fluorine, chlorine, bromine, iodine, C 1-3 Alkyloxy, preferably methoxy, fluoro (C 1-3 ) alkoxy, C 1-3 Alkyl, preferably methyl, cyano, and fluoro (C 1-3 )alkyl, preferably trifluoromethyl, and preferably hydrogen, fluorine, chlorine or bromine,

[0924] R10 is selected from hydrogen, fluorine, chlorine, bromine, iodine, C 1-3 Alkyl, halo (C 1-3 ) alkyl, preferably fluoro(C1-3 ) alkyl, especially trifluoromethyl, C 2-3 Alkynyl, C 1-3 Alkyloxy, halo(C 1-3 ) alkyloxy, preferably fluoro(C 1-2 ) alkoxy, cyano, cyanomethyl, unsubstituted or fluorinated C 1-3 Alkylcarbonyl, preferably acetyl, unsubstituted or fluorinated C 1-3 alkoxycarbonyl, preferably methoxycarbonyl, azido, pentafluorosulfanyl and nitro, or R10 and R9 together form a ring system as described herein,

[0925] R11 is selected from hydrogen, fluorine, chlorine, bromine, iodine, C 1-3 Alkyl, preferably methyl, fluoro (C 1-3 ) alkyl, preferably trifluoromethyl, C 1-3 Alkyloxy, preferably methoxy, fluoro (C 1-3 ) alkoxy, preferably fluoro(C 1-2 ) alkoxy, unsubstituted or fluorinated C 1-3 Alkylcarbonyl, preferably acetyl, unsubstituted or fluorinated C 1-3 alkoxycarbonyl, preferably methoxycarbonyl, and cyano, and more preferably hydrogen, fluorine, chlorine or bromine,

[0926] R12 is selected from hydrogen, fluorine, chlorine, bromine, iodine, C 1-3 Alkyloxy, preferably methoxy, fluoro (C 1-3 ) alkoxy, preferably fluoro(C 1-2 ) alkoxy, C 1-3 Alkyl, preferably methyl, and fluorine (C 1-3 )alkyl, preferably trifluoromethyl, and more preferably hydrogen, fluorine, chlorine or bromine,

[0927] wherein, in a preferred embodiment, at least one of R8, R9, R10 and R11 is different from hydrogen, and more preferably at least one of R8, R9, R10 and R11 is also different from unsubstituted alkyl,

[0928] and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof.

[0929] Another preferred embodiment relates to compounds having the structure of Formula IIa, IIb or IIc, wherein

[0930] m is 0 or 1,

[0931] n is 0, 1 or 2, and preferably 0 or 1,

[0932] p is 0 or 1,

[0933] Any Y is selected from hydrogen, halogen, hydroxy, unsubstituted or fluorinated methyl and unsubstituted or fluorinated methoxy,

[0934] R4 and R5 are both hydrogen,

[0935] R8 is selected from hydrogen, methoxy, fluoromethoxy, fluorine and chlorine, and is preferably fluorine,

[0936] X3 is N or C (R12),

[0937] R9 is selected from hydrogen, methoxy, fluorine and chlorine, and is preferably hydrogen,

[0938] R10 is selected from hydrogen, ethynyl, cyano, cyanomethyl, cyanoethyl, cyanomethoxy, ethynyl, fluorine, chlorine, bromine, iodine, azido, trifluoromethyl, trifluoromethoxy, difluoroethoxy, trifluoroethoxy and pentafluorosulfanyl,

[0939] R11 is selected from hydrogen, fluorine, chlorine and methoxy, and

[0940] R12, if present, is hydrogen or fluorine,

[0941] and wherein at least one of R8, R9, R10 and R11 is different from hydrogen, and wherein, in a preferred embodiment, at least R10 is different from hydrogen, and wherein in a particularly preferred embodiment, both R8 and R10 are different from hydrogen,

[0942] and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof.

[0943] Another preferred embodiment relates to compounds having the structure of Formula IIa, IIb or IIc, wherein

[0944] m is 0 or 1,

[0945] n is 0, 1 or 2, and preferably 0 or 1,

[0946] p is 0, 1 or 2,

[0947] Any Y is selected from hydrogen, halogen, hydroxy, unsubstituted or fluorinated methyl and unsubstituted or fluorinated methoxy,

[0948] R4 and R5 are both hydrogen,

[0949] R8 is fluorine or methoxy,

[0950] X3 is N or C (R12),

[0951] R9 is selected from hydrogen, methoxy, fluorine and chlorine, and is preferably hydrogen,

[0952] R10 is selected from halogen, ethynyl, propynyl, cyano, cyanomethyl, cyanoethyl, cyanomethoxy, unsubstituted or fluorinated (C1-3 )alkyl, unsubstituted or fluorinated (C 2-3 )alkenyl, unsubstituted or fluorinated (C 2-3 ) alkynyl, unsubstituted or fluorinated C 1-3 Alkyloxy, unsubstituted or fluorinated methoxy (C 1-3 ) alkyl, unsubstituted or fluorinated methoxy (C 1-3 ) alkyloxy, unsubstituted or fluorinated methoxy (C 2-3 )alkenyl, unsubstituted or fluorinated methoxy (C 2-3 ) alkynyl and pentafluorosulfanyl,

[0953] R11 is selected from hydrogen, fluorine and methoxy, and

[0954] R12, if present, is hydrogen or fluorine,

[0955] and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof.

[0956] In a preferred embodiment of the compound of formula IIc, p is 1 and Y is attached at the 8-position of the tricyclic ring system to obtain a compound of formula II-c1, wherein Y is preferably selected from halogen, methyl, fluoromethyl, methoxy, fluoromethoxy and hydroxy, and wherein X3, R4, R5, R8, R9, R10 and R11 are as described herein for the compound of formula II-c.

[0957]

[0958] Another preferred embodiment relates to compounds having the structure of Formula IIa, IIb or IIc, wherein

[0959] m is 0 or 1,

[0960] n is 0, 1 or 2, and preferably 0 or 1,

[0961] p is 0, 1, or 2,

[0962] Any Y is selected from hydrogen, halogen, hydroxy, unsubstituted or fluorinated methyl and unsubstituted or fluorinated methoxy,

[0963] R4 and R5 are both selected from hydrogen and fluorine,

[0964] R8 is fluorine or methoxy,

[0965] X3 is N,

[0966] R9 is selected from hydrogen, methoxy, fluorine and chlorine, and is preferably hydrogen,

[0967] R10 is selected from fluorine, chlorine, bromine, ethynyl, propynyl, cyano, cyanomethyl, cyanoethyl, cyanomethoxy, unsubstituted or fluorinated (C1-3 )alkyl, unsubstituted or fluorinated (C 2-3 ) alkenyl, C 2-3 Alkynyl, unsubstituted or fluorinated C 1-3 Alkyloxy, unsubstituted or fluorinated C 1-2 Alkoxy (C 1-3 ) alkyl, unsubstituted or fluorinated C 1-2 Alkoxy (C 1-3 ) alkyloxy, unsubstituted or fluorinated C 1-2 Alkoxy (C 2-3 )alkenyl and pentafluorosulfanyl,

[0968] R11 is selected from hydrogen, fluorine, chlorine, methoxy, fluoromethoxy and fluoromethyl,

[0969] and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof,

[0970] In a preferred embodiment, R10 is selected from chloro, bromo, cyanomethyl, cyanoethyl, cyanomethoxy, unsubstituted or fluorinated (C 1-3 ) alkyl, unsubstituted or fluorinated C 1-3 Alkyloxy, unsubstituted or fluorinated C 1-2 Alkoxy (C 1-2 ) alkyloxy and unsubstituted or fluorinated methoxy (C 1-3 )alkyl, and in another preferred embodiment is chloro.

[0971] Another preferred embodiment relates to compounds having the structure of Formula IIa, IIb or IIc, wherein R10 is selected from halogen, cyano, cyanomethyl and cyanoethyl.

[0972] Another preferred embodiment relates to compounds having the structure of Formula IIa, IIb or IIc, wherein

[0973] m is 0 or 1,

[0974] n is any number from 0 to 3, and is preferably 0 or 1,

[0975] p is any number from 0 to 2, and is preferably 0 or 1,

[0976] Any Y is a substituent independently selected from halogen, hydroxy, cyano, C 1-3 Alkyl, C 1-3 Alkoxy, wherein each alkyl or alkoxy group may be unsubstituted or substituted with one or more substituents selected from halogen, hydroxy and C 1-3 Alkoxy,

[0977] X3 is C(R12),

[0978] R4 is hydrogen,

[0979] R5 is selected from hydrogen, fluorine, chlorine, bromine, iodine, methyl, methoxy and trifluoromethyl, preferably hydrogen or iodine,

[0980] R8 is selected from hydrogen, fluorine, chlorine, bromine, iodine, C 1-3 Alkyl, preferably methyl, and C 1-3 Alkoxy, wherein R8 is preferably selected from fluorine and methoxy,

[0981] or R9 and R10 together with the ring to which they are attached form a bicyclic ring system selected from 2,1,3-benzothiadiazole, 2,1,3-benzoselenadiazole, 2,1,3-benzoxadiazole, 1,3-benzothiazole, 2,3-dihydro-1-benzothiophene substituted with one or two oxo groups (preferably substituted with two oxo groups to give 1,1-dioxo-2,3-dihydro-1-benzothiophene), optionally methylated 3-oxo-1,3-dihydro-2-benzofuran-5-yl, and 1,3-benzodioxole, optionally substituted with one or two fluorine groups,

[0982] R11 is selected from hydrogen, fluorine, chlorine, bromine, iodine and methoxy, and

[0983] R12 is selected from the group consisting of hydrogen, fluorine, chlorine, bromine, methoxy, fluoromethoxy, methyl and fluoromethyl.

[0984] Another preferred embodiment relates to compounds having the structure of Formula IIa, IIb or IIc, wherein

[0985] m is 0 or 1,

[0986] n is 0, 1 or 2, and preferably 0,

[0987] p is 0 or 1, preferably 0,

[0988] Any Y is selected from hydrogen, halogen, unsubstituted or fluorinated methyl and unsubstituted or fluorinated methoxy,

[0989] R4 and R5 are both hydrogen,

[0990] X3 is C(R12),

[0991] R8 is hydrogen, methoxy or fluorine, and is preferably hydrogen,

[0992] R9 and R10 together with the C atom to which they are attached form a ring selected from 2,1,3-benzothiadiazole, 2,1,3-benzooxadiazole, and 2,2-difluoro-1,3-benzodioxole, preferably 2,1,3-benzothiadiazole,

[0993] R11 is hydrogen or fluorine, and

[0994] R12 is hydrogen or fluorine,

[0995] and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof.

[0996] Another preferred embodiment relates to compounds having the structure of Formula IIa, IIb or IIc, wherein

[0997] m is 0 or 1,

[0998] n is any number from 0 to 3, and is preferably 0 or 1,

[0999] p is any number from 0 to 2, and is preferably 0 or 1,

[1000] Any Y is a substituent independently selected from halogen, hydroxyl, C 1-3 Alkyl, C 1-3 Alkoxy, wherein each alkyl or alkoxy group may be unsubstituted or substituted by one or more groups selected from halogen and C 1-3 Alkoxy substituents are substituted,

[1001] X3 is C(R12),

[1002] R4 is hydrogen,

[1003] R5 is selected from hydrogen, fluorine, chlorine, bromine, iodine, methyl, methoxy and trifluoromethyl, preferably hydrogen or iodine,

[1004] R9 and R8 together with the ring to which they are attached form a bicyclic ring system selected from 2,1,3-benzothiadiazole, 2,1,3-benzoselenadiazole, 2,1,3-benzooxadiazole, 2-oxo-2,3-dihydro-1,3-benzoxazole, and 1,3-benzodioxole, which are optionally substituted with one or two fluorines,

[1005] R10 is selected from hydrogen, fluorine, chlorine, bromine, iodine, C 1-3 Alkyl, halo (C 1-3 ) alkyl, preferably fluoro(C 1-3 ) alkyl, especially trifluoromethyl, C 2-3 Alkynyl, C 1-3 Alkyloxy, halo(C 1-3 ) alkyloxy, preferably fluoro(C 1-2 ) alkoxy, cyano, cyanomethyl, cyanoethyl, cyanomethoxy, unsubstituted or fluorinated C 1-3 Alkylcarbonyl, preferably acetyl, unsubstituted or fluorinated C 1-3 Alkoxycarbonyl, preferably methoxycarbonyl, azido, pentafluorosulfanyl and nitro, wherein R10 is preferably hydrogen, fluorine, chlorine or bromine,

[1006] R11 is selected from hydrogen, fluorine, chlorine, bromine, iodine, C 1-3 Alkyl, preferably methyl, fluoro (C 1-3 ) alkyl, preferably trifluoromethyl, C 1-3 Alkyloxy, preferably methoxy, fluoro (C 1-3 ) alkoxy, preferably fluoro(C 1-2 ) alkoxy, unsubstituted or fluorinated C 1-3 Alkylcarbonyl, preferably acetyl, unsubstituted or fluorinated C 1-3 alkoxycarbonyl, preferably methoxycarbonyl, and cyano, and more preferably hydrogen, fluorine, chlorine or bromine,

[1007] R12 is selected from hydrogen, fluorine, chlorine, bromine, iodine, C 1-3 Alkyloxy, preferably methoxy, fluoro (C 1-3 ) alkoxy, preferably fluoro(C 1-2 ) alkoxy, C 1-3 Alkyl, preferably methyl, and fluorine (C 1-3 )alkyl, preferably trifluoromethyl, and more preferably hydrogen, fluorine, chlorine or bromine,

[1008] and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof.

[1009] Another preferred embodiment relates to compounds having the structure of Formula IIa, IIb or IIc, wherein

[1010] m is 0 or 1,

[1011] n is 0, 1 or 2, and preferably 0,

[1012] p is 0 or 1, and preferably 0,

[1013] Any Y is selected from hydrogen, halogen, unsubstituted or fluorinated methyl and unsubstituted or fluorinated methoxy,

[1014] X3 is C(R12),

[1015] R4 and R5 are both hydrogen,

[1016] R8 and R9 together with the ring to which they are attached form a bicyclic ring system selected from 2,1,3-benzothiadiazole, 2,1,3-benzoxadiazole, 2,1,3-benzoselenadiazole, 2-oxo-2,3-dihydro-1,3-benzoxazole, unsubstituted 1,3-benzodioxole and 2,2-difluoro-1,3-benzodioxole,

[1017] R10 is selected from hydrogen, fluorine, chlorine, bromine, trifluoromethyl, trifluoromethoxy, difluoroethoxy, trifluoroethoxy and cyano, and is preferably hydrogen or fluorine,

[1018] R11 is selected from hydrogen, methoxy, fluorine, chlorine, bromine and cyano, and is preferably hydrogen or fluorine,

[1019] R12 is hydrogen, fluorine, chlorine and trifluoromethyl,

[1020] and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof.

[1021] Another preferred embodiment relates to compounds having the structure of formula II,

[1022]

[1023] in

[1024] R4 and R5 are both hydrogen or fluorine;

[1025] R6 is selected from fluorine, chlorine, bromine, amino, nitro, cyano, azido, unsubstituted or fluorinated C 1-3 Alkyl, preferably selected from methyl, ethyl, propyl, preferably isopropyl, fluoromethyl, preferably trifluoromethyl, unsubstituted or fluorinated methylsulfonyl, unsubstituted or fluorinated methylsulfinyl, unsubstituted or fluorinated C 1-3 Alkyloxy, preferably selected from methoxy, fluoromethoxy and fluoroethoxy, unsubstituted or fluorinated C 1-2 Alkyloxy (C 1-2 )alkyloxy, including methoxyethoxy, cyclopropyl, cyclopropylmethoxy, phenyl, phenyloxy, benzyloxy, benzylsulfinyl, 2-thienyl, 3-thienyl, 3-pyridyl, 4-pyridyl, tetrahydrofuranyl, tetrahydrofuranylmethoxy and dimethyloxazole, wherein each phenyl, phenyloxy, benzyloxy, 2-thienyl, 3-thienyl, 3-pyridyl, 4-pyridyl residue may be optionally substituted with one or more fluoro, chloro, unsubstituted or fluorinated methyl or unsubstituted or fluorinated methoxy,

[1026] X3 is C(R12) or N,

[1027] R7 is selected from hydrogen, methyl, fluoro (C 1-2 ) alkyl, preferably mono-, di- or trifluoromethyl, methylsulfonyl, methylsulfinyl, methoxy, fluoro(C 1-2 ) alkoxy, cyano, pyridyl, pyridylmethoxy, phenoxy, oxazole, isoxazole, cyano, fluorine, chlorine or bromine, and preferably hydrogen, methoxy, fluorine or bromine, wherein each pyridyl, isoxazole and phenyl residue may be optionally substituted by one or more fluorine, chlorine, unsubstituted or fluorinated methyl or unsubstituted or fluorinated methoxy;

[1028] R8 and R11 are independently selected from hydrogen, fluorine, chlorine and unsubstituted or fluorinated methoxy;

[1029] R9 is hydrogen,

[1030] R10 is selected from fluorine, chlorine, bromine, iodine, acetyl, azido, nitro, cyano, cyanomethyl, cyanoethyl, cyanomethoxy, unsubstituted or fluorinated C 1-2 Alkoxycyclopropyl, unsubstituted or fluorinated C 1-2 Alkoxycarbonylcyclopropyl, cyclopropylmethoxy, cyclopropylmethyl, unsubstituted or fluorinated C 1-3 Alkyl, preferably selected from methyl and trifluoromethyl, unsubstituted or fluorinated and / or hydroxylated C 1-3 Alkoxy, preferably selected from methoxy, difluoromethoxy, trifluoromethoxy, difluoroethoxy and trifluoroethoxy, unsubstituted or fluorinated C 1-2 Alkoxy (C 1-3 ) alkyl, preferably unsubstituted or fluorinated methoxypropyl, unsubstituted or fluorinated C 1-2 Alkoxy (C 1-3 ) alkoxy, including fluoromethoxyethoxy, unsubstituted or fluorinated C 2-3 Alkenyl, unsubstituted or fluorinated C 2-3 Alkynyl, preferably ethynyl, unsubstituted or fluorinated C 1-2 Alkoxy (C 2-3 ) alkenyl, preferably methoxypropenyl, unsubstituted or fluorinated C 1-2 Alkoxy (C 2-3 ) alkynyl and pentafluorosulfanyl;

[1031] R12, if present, is hydrogen or fluorine,

[1032] and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof.

[1033] Another preferred embodiment relates to compounds having the structure of Formula II, wherein R4 and R5 are both hydrogen; R6 is selected from fluoro, chloro, bromo, methyl, ethyl, isopropyl, trifluoromethyl, methylsulfonyl, methoxy, cyclopropyl, cyclopropylmethoxy, phenyl, phenyloxy, benzyloxy, 2-thienyl, 3-thienyl, 3-pyridyl, 4-pyridyl, tetrahydrofuranyl and dimethyloxazole, X3 is C(R12), R9 is hydrogen; R7 is selected from hydrogen, methyl, trifluoromethyl, methoxy, fluoro, chloro or bromo, and is preferably hydrogen, methoxy or bromo; R8 and R11 are independently selected from hydrogen, fluoro, chloro and methoxy; R10 is fluoro, chloro, bromo, iodo, acetyl, azido, ethynyl, cyano, cyanomethyl, trifluoromethyl, difluoroethoxy, trifluoroethoxy or pentafluorosulfanyl; R12 is hydrogen or fluoro, and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof.

[1034] Another embodiment relates to compounds of formula II, wherein

[1035] R4 is hydrogen or fluorine, preferably hydrogen;

[1036] R5 is selected from hydrogen, fluorine, chlorine, bromine, methoxy and fluoromethoxy,

[1037] R6 is selected from halogen, cyano, amino, nitro, unsubstituted or fluorinated methylsulfonyl, unsubstituted or fluorinated methylsulfinyl, C 1-3 Alkyl, C 1-3 Alkyloxy, C 2-3 alkenyl, cyclopropyl, phenyl, phenyloxy, benzyloxy, benzylsulfinyl, 2-thienyl, 3-thienyl, 3-pyridyl and 4-pyridyl, wherein each phenyl, phenyloxy, benzyloxy, 2-thienyl, 3-thienyl, 3-pyridyl, 4-pyridyl may be optionally substituted with one or more fluorine, chlorine, unsubstituted or fluorinated methyl or unsubstituted or fluorinated methoxy, and wherein each alkyl, alkenyl and alkoxy may be unsubstituted or substituted with one or more groups selected from halogen, methoxy, fluoromethoxy, cyano, cyclopropyl and halogen,

[1038] X3 is C(R12) or N,

[1039] R7 is selected from hydrogen, cyano, fluorine, chlorine, bromine, unsubstituted or fluorinated C 1-3 Alkyl, preferably selected from methyl, fluoromethyl and fluoroethyl, and unsubstituted or fluorinated C 1-3 Alkyloxy, preferably selected from methoxy, fluoromethoxy and fluoroethoxy,

[1040] R8 and R11 are independently selected from hydrogen, fluorine, chlorine, cyano, methyl, fluoromethyl, methoxy and fluoromethoxy;

[1041] R9 is hydrogen or fluorine, preferably hydrogen,

[1042] R10 is selected from halogen, azido, cyano, cyclopropyl, nitro, C 1-3 Alkyl, C 1-3 Alkoxy, C 2-3 Alkenyl, C 2-3 Alkynyl, C 1-3 Alkylcarbonyl (C 1-3 ) alkyl, C 1-3 Alkoxycarbonyl (C 1-3 ) alkyl and pentafluorosulfanyl, wherein each alkyl, alkenyl, alkynyl and alkoxy group may be unsubstituted or substituted by one or more residues selected from fluorine, chlorine, cyano, cyclopropyl and unsubstituted or fluorinated and / or hydroxylated C 1-3 Alkoxy, and wherein each cyclopropyl group may be substituted by one or more residues selected from halogen, hydroxy, hydroxymethyl, C 1-3 Alkoxy, C 1-3 Alkoxycarbonyl and cyano,

[1043] R12, if present, is hydrogen or fluorine,

[1044] and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof.

[1045] Another embodiment relates to compounds of formula II, wherein

[1046] R4 is hydrogen,

[1047] R5 is selected from hydrogen, fluorine, chlorine and bromine,

[1048] R6 is selected from fluorine, chlorine, bromine, iodine, cyano, nitro, methyl, ethyl, isopropyl, fluoromethyl, preferably trifluoromethyl, fluoroethyl, methoxy, fluoromethoxy, fluoroethoxy, cyano, methylsulfinyl, methylsulfonyl, cyclopropyl, phenyl, benzyloxy, 2-thienyl and 3-thienyl,

[1049] R7 is selected from hydrogen, fluorine, chlorine, bromine, cyano, fluorine (C 1-2 )alkyl, preferably trifluoromethyl, and fluoro(C 1-2 )alkoxy, and is preferably selected from hydrogen, fluorine, methoxy, fluoromethoxy and fluoroethoxy,

[1050] X3 is C(R12),

[1051] R8 and R11 are independently selected from hydrogen, fluorine, chlorine, cyano, fluoromethyl, methoxy and fluoromethoxy,

[1052] R9 is hydrogen,

[1053] R10 is selected from fluorine, chlorine, bromine, iodine, azido, unsubstituted or fluorinated C 1-3 Alkyl, preferably trifluoromethyl, unsubstituted or fluorinated C 1-3 Alkyloxy, preferably selected from difluoroethoxy, trifluoromethoxy and trifluoroethoxy, unsubstituted or fluorinated C 1-3 Alkoxy (C 1-3 ) alkyl, unsubstituted or fluorinated C 1-3 Alkoxy (C 1-3 ) alkoxy, unsubstituted or fluorinated C 1-3 Alkoxy (C 2-3 )alkenyl, pentafluorosulfanyl, ethynyl, propynyl, cyano, cyanomethoxy and cyanomethyl, and

[1054] R12 is hydrogen and fluorine,

[1055] Among them, it is preferred that at least one of R8 and R11 is fluorine or chlorine, preferably fluorine.

[1056] Another embodiment relates to compounds of formula II, wherein R4 and R5 are both hydrogen, R6 is selected from fluorine, chlorine, bromine, iodine, methyl, isopropyl, trifluoromethyl, methylsulfonyl, cyclopropyl, phenyl, benzyloxy, 2-thienyl and 3-thienyl, X3 is C(R12), R7 is selected from hydrogen, methyl, methoxy, fluorine, chlorine, bromine and trifluoromethyl, preferably hydrogen, fluorine and bromine, R8 and R11 are independently selected from hydrogen, fluorine, chlorine and methoxy, R9 is hydrogen, R10 is selected from hydrogen, fluorine, chlorine, bromine, iodine, azido, trifluoromethyl, difluoroethoxy, trifluoromethoxy, trifluoroethoxy, pentafluorosulfanyl, ethynyl, cyano and cyanomethyl, R12 is hydrogen and fluorine, wherein preferably at least one of R8 and R11 is fluorine or chlorine, preferably fluorine.

[1057] Another embodiment relates to compounds of formula II, wherein R4 and R5 are both hydrogen, R6 is selected from fluoro, chloro, bromo, isopropyl, trifluoromethyl, cyclopropyl, methoxy, fluoromethoxy, fluoroethoxy, methylsulfinyl and benzyloxy, R7 is hydrogen, methyl, methoxy, fluoromethoxy, fluoroethoxy, fluoromethyl, cyano, bromo or fluoro, X3 is C(R12), R9 is hydrogen, R10 is selected from fluoro, bromo, chloro, iodo, methyl, fluoromethyl, preferably trifluoromethyl, fluoro(C 1-2 )alkoxy, preferably difluoroethoxy and trifluoromethoxy, pentafluorosulfanyl, cyano, cyanomethoxy, cyanomethyl and cyanoethyl, R12 is hydrogen or fluorine, and R8 and R11 are independently selected from hydrogen, fluorine, chlorine, methoxy and fluoromethoxy, and in a preferred embodiment, are different from hydrogen.

[1058] Another embodiment relates to compounds of formula II, wherein R4 and R5 are both hydrogen, R6 is selected from fluorine, chlorine, bromine, isopropyl, trifluoromethyl, cyclopropyl and benzyloxy, R7 is hydrogen, methoxy or fluorine, X3 is C(R12), R9 is hydrogen, R10 is selected from fluorine, bromine, chlorine, iodine, trifluoromethyl, difluoroethoxy, trifluoromethoxy, pentafluorosulfanyl, cyano and cyanomethyl, R12 is hydrogen or fluorine, and R8 and R11 are both different from hydrogen and are preferably fluorine, chlorine, methoxy or cyano, more preferably fluorine.

[1059] Another preferred embodiment relates to compounds of formula II, wherein R4 and R5 are both hydrogen, R6 is selected from fluorine, chlorine, bromine, isopropyl, fluoromethyl, methoxy, fluoromethoxy and phenoxy, R7 is hydrogen, methoxy, fluoromethoxy, fluoroethoxy, cyano, fluorine or chlorine, X3 is C(R12), R9 is hydrogen or fluorine, R10 is hydrogen, R12 is hydrogen or fluorine, and R8 and R11 are both independently selected from fluorine, chlorine and methoxy.

[1060] Another preferred embodiment relates to compounds of formula II, wherein R4 and R5 are both hydrogen, R6 is selected from fluorine, chlorine, bromine, isopropyl, trifluoromethyl and phenoxy, R7 is hydrogen, methoxy or fluorine, X3 is C(R12), R9 is hydrogen or fluorine, R10 is hydrogen, R12 is hydrogen or fluorine, and R8 and R11 are both independently selected from fluorine, chlorine and cyano.

[1061] Another preferred embodiment relates to compounds of formula II, wherein R4 and R5 are both hydrogen, R6 is selected from fluorine, chlorine, bromine, iodine, methyl, ethyl, isopropyl, fluoromethyl, preferably trifluoromethyl, methoxy, methylsulfinyl, methylsulfonyl, cyclopropyl, phenyl, benzyloxy, 2-thienyl and 3-thienyl, and is preferably selected from fluorine, chlorine, bromine and trifluoromethyl, R7 is hydrogen, methoxy or fluorine, preferably hydrogen, X3 is C(R12), R8 is hydrogen, R9 and R10 together with the C atom to which they are attached form 2,1,3-benzothiadiazole, 3-oxo-1,3-dihydro-2-benzofuran or 1-methyl-3-oxo-1,3-dihydro-2-benzofuran, and R11 and R12 are independently selected from hydrogen and fluorine.

[1062] Another embodiment relates to compounds of formula II, wherein R4 and R5 are both hydrogen, R6 is selected from fluorine, chlorine, bromine and methylsulfonyl, R7 is selected from hydrogen, fluorine, bromine, chlorine, methoxy and trifluoromethyl, X3 is C(R12), R8 and R9 together with the ring to which they are attached form 2,1,3-benzothiadiazole, 2,1,3-benzoselenadiazole, 2,1,3-benzoxadiazole or optionally 2,2-fluoro-substituted 1,3-benzodioxole, R10 is hydrogen, fluorine or bromine, R11 is selected from hydrogen, fluorine and cyano, and R12 is hydrogen, fluorine or trifluoromethyl.

[1063] Another embodiment relates to compounds of formula II, wherein R4 is hydrogen, R5 is selected from hydrogen and fluorine, R6 is selected from fluorine, chlorine, bromine, methoxy and trifluoromethyl, R7 is selected from hydrogen, halogen, methylsulfonyl, methoxy, fluoromethoxy, fluoroethoxy and fluoromethyl, preferably trifluoromethyl, X3 is N, R8 is fluorine, chlorine or methoxy, R9 is selected from hydrogen, fluorine, chlorine, methyl and methoxy and is preferably hydrogen, R10 is selected from fluorine, chlorine, bromine, cyano, cyanomethyl, cyanoethyl, pentafluorosulfanyl, mono-, di- and trifluoromethyl, mono-, di- and trifluoromethoxy, mono-, di- and trifluoroethoxy, unsubstituted or fluorinated C 1-2 Alkoxy (C 1-3 ) alkyl, unsubstituted or fluorinated C 1-2 Alkoxy (C 1-2 )alkoxy, ethynyl and cyanomethyl, and R11 is selected from hydrogen, fluorine, chlorine, fluoromethyl, methoxy and fluoromethoxy.

[1064] Another embodiment relates to compounds of formula II, wherein R4, R5 are both hydrogen, R6 is selected from fluorine, chlorine, bromine and methoxy, R7 is selected from hydrogen, fluorine, chlorine, bromine, fluoromethyl, methoxy and fluoromethoxy, X3 is N, R8 is fluorine or methoxy, R9 is hydrogen, R10 is selected from fluorine, chlorine, bromine, cyano, cyanomethyl, acetyl, methyl, ethyl, ethoxyethyl, methoxypropyl, fluorinated methoxypropyl, fluoromethyl, fluoromethoxymethyl, methoxycarbonylcyclopropyl, ethoxycarbonylcyclopropyl, vinyl, ethoxyvinyl, methoxy, fluoromethoxy, fluoroethoxy, fluoropropoxy, methoxyethoxy, fluorinated methoxyethoxy, ethoxyethoxy, fluorinated ethoxyethoxy, methoxypropoxy, fluorinated methoxypropoxy, methoxypropenyl and fluoromethoxypropenyl, and R11 is hydrogen, methoxy, fluorine or chlorine.

[1065] Another embodiment relates to compounds of formula II, wherein R4 and R5 are both hydrogen, R6 is chlorine or bromine, R7 is selected from hydrogen, fluorine, chlorine, bromine and methoxy, and X3 is C(R12) or N, R8 is fluorine, chlorine or methoxy, R9 is hydrogen or fluorine, preferably hydrogen, R10 is selected from fluorine, chlorine, bromine, cyano, C 1-3 Alkyl, C 2-3 Alkenyl and C 1-3 Alkoxy, wherein each alkyl, alkenyl and alkoxy group may be unsubstituted or substituted by one or more substituents selected from halogen, preferably fluorine, cyano, C 1-2 Alkoxy and fluorine (C 1-2 )alkoxy, and R11 is hydrogen, fluorine or methoxy.

[1066] Another embodiment relates to compounds having the formula II(d), II(e), II(f) and II(g),

[1067]

[1068] wherein R4, R5, R6, R7, R8, R10, R11 and R12 are as described herein for Formulas I and II,

[1069] wherein in formula II(d), Q1 is S or O, and

[1070] wherein in formula II(e), R13 and R14 are selected from hydrogen, methyl and fluorine and are preferably both hydrogen or both fluorine,

[1071] Wherein in formula II(f), Q2 is S or O, preferably S,

[1072] and wherein in formula II(g), R16 is selected from hydrogen, fluorine, hydroxy, methyl, fluoromethyl, methoxy and fluoromethoxy, and is preferably selected from hydrogen and methyl,

[1073] and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof.

[1074] One embodiment relates to compounds of formula II(d), II(e), II(f) and II(g),

[1075] in

[1076] wherein in formula II(d), Q1 is S or O, and

[1077] wherein in formula II(e), R13 and R14 are both selected from hydrogen and fluorine,

[1078] Wherein in formula II(f), Q2 is S or O, preferably S,

[1079] Wherein in formula II(g), R16 is selected from hydrogen and methyl,

[1080] R4 is hydrogen,

[1081] R5 is selected from hydrogen, fluorine, chlorine and bromine, and is preferably hydrogen,

[1082] R6 is selected from fluorine, chlorine, bromine, methyl, methoxy, methylsulfonyl, methylsulfinyl, fluoromethyl, fluoromethoxy, cyano and benzyloxy, preferably selected from fluorine, chlorine, bromine and fluoromethyl,

[1083] R7 is selected from hydrogen, fluorine, chlorine, bromine, methoxy, cyano, methyl and fluoromethyl, preferably selected from hydrogen and mono-, di- and trifluoromethyl,

[1084] R8, if present, is selected from hydrogen and halogen, preferably selected from hydrogen and fluorine, and more preferably is hydrogen,

[1085] R10, if present, is selected from hydrogen, fluorine, chlorine, bromine and cyano, preferably hydrogen or fluorine,

[1086] R11 is selected from hydrogen, halogen, methoxy, fluoromethoxy, fluoromethyl and cyano, and is preferably hydrogen or fluorine,

[1087] R12 is selected from hydrogen, halogen, methoxy, fluoromethyl, preferably selected from hydrogen, fluorine and fluoromethyl,

[1088] and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof.

[1089] In a preferred embodiment of the compounds of formula IId and IIe,

[1090] R4 and R5 are both hydrogen,

[1091] R6 is selected from fluorine, chlorine, bromine, trifluoromethyl and phenyl,

[1092] R7 is hydrogen, fluorine, bromine, methoxy or trifluoromethyl, preferably hydrogen or trifluoromethyl,

[1093] R10 is selected from hydrogen and halogen, preferably selected from hydrogen, fluorine and chlorine,

[1094] R11 is selected from hydrogen, halogen, trifluoromethyl and cyano, preferably selected from fluorine and hydrogen,

[1095] R12 is selected from hydrogen, halogen and trifluoromethyl, preferably selected from fluorine and hydrogen,

[1096] R13 and R14, in formula IIe, are both selected from hydrogen and fluorine,

[1097] and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof.

[1098] In a preferred embodiment of the compound of formula II(f),

[1099] R4 and R5 are both hydrogen,

[1100] R6 is selected from fluorine, chlorine, bromine, trifluoromethyl and phenyl,

[1101] R7 is selected from hydrogen, methoxy, fluorine and trifluoromethyl,

[1102] R8 is selected from hydrogen and halogen, preferably selected from hydrogen and fluorine,

[1103] R11 is selected from hydrogen, halogen, trifluoromethyl and cyano, and is preferably hydrogen,

[1104] R12 is selected from hydrogen, halogen and trifluoromethyl, preferably selected from fluorine and hydrogen,

[1105] and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof.

[1106] One embodiment relates to compounds of formula IIa, IIb, IIc, IId, IIe, IIf and IIg, which are further substituted with a group R2, as shown in the general formula II-2 above, thereby obtaining the corresponding compounds of formula II-2a, II-2b, II-2c, II-2d, II-2e, II-2f and II-2g, wherein R2 is selected from hydrogen, fluorine, chlorine, bromine, iodine and methoxy, and wherein R2 is preferably hydrogen or fluorine, and particularly preferably hydrogen, and wherein the other residues are as defined in formula II-2a, II-2b, II-2c, II-2d, II-2e, II-2f and II-2g herein. As non-limiting examples, formula II-2d and II-2f are described below:

[1107]

[1108] Another preferred embodiment relates to compounds having the structure of formula III,

[1109]

[1110] wherein R4 and R5 are both hydrogen,

[1111] R6 is selected from hydrogen, fluorine, chlorine, bromine, fluoromethyl, methoxy, fluoromethoxy and cyclopropyl,

[1112] X3 is C(R12) or N,

[1113] R8 is selected from hydrogen, methoxy and halogen, particularly preferably selected from fluorine, chlorine, methoxy and hydrogen,

[1114] R9 is hydrogen,

[1115] R10 is selected from fluorine, bromine, chlorine, iodine, methyl, fluorine (C 1-3 ) alkyl, preferably trifluoromethyl, unsubstituted or fluorinated methoxy (C 1-3 ) alkyl, unsubstituted or fluorinated C 1-3 Alkyloxy, preferably mono-, di- and trifluoromethoxy and mono-, di- and trifluoroethoxy, unsubstituted or fluorinated methoxy (C 1-3 ) alkyloxy, unsubstituted or fluorinated C 2-3 Alkenyl, unsubstituted or fluorinated methoxy (C 2-3 )alkenyl, ethynyl, propargyl, unsubstituted or fluorinated methoxy (C 2-3 ) alkynyl, azido, pentafluorosulfanyl, cyanomethyl, cyanoethyl and cyano,

[1116] R11 is hydrogen, fluorine, chlorine or methoxy, particularly preferably hydrogen or fluorine,

[1117] R12, if present, is hydrogen or fluorine,

[1118] and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof.

[1119] Another embodiment relates to compounds of formula III, wherein R4 and R5 are both hydrogen, R6 is chlorine or bromine, X3 is C(R12), R12 is hydrogen or fluorine, R8 is selected from hydrogen, methoxy and halogen, particularly preferably selected from fluorine and hydrogen, R9 is hydrogen, R10 is selected from fluorine, bromine, chlorine, iodine, trifluoromethyl, difluoroethoxy, trifluoromethoxy, trifluoroethoxy, ethynyl, azido, acetyl, pentafluorosulfanyl, cyanomethyl and cyano, R11 is hydrogen, fluorine, chlorine or methoxy, particularly preferably hydrogen or fluorine, and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof.

[1120] Another particularly preferred embodiment relates to compounds of formula III, wherein R4 and R5 are both hydrogen, R6 is selected from methyl, fluoromethyl, methoxy, fluoromethoxy, chlorine or bromine, X3 is C(R12), R8 is hydrogen, methoxy or fluorine and preferably fluorine, R9 is hydrogen, R10 is selected from fluorine, bromine, chlorine, iodine, mono-, di- and trifluoromethyl, mono-, di- and trifluoromethoxy, mono-, di- and trifluoroethoxy, pentafluorosulfanyl, ethynyl and cyano, and R11 and R12 are independently selected from hydrogen and fluorine.

[1121] Another preferred embodiment relates to compounds of formula III, wherein R4 and R6 are hydrogen, R5 is iodine, X3 is C(R12) or N, R8 and R11 are each independently selected from hydrogen or fluorine, R10 is selected from fluorine, bromine, chlorine, iodine, mono-, di- and trifluoromethyl, mono-, di- and trifluoromethoxy, mono-, di- and trifluoroethoxy, pentafluorosulfanyl and cyano, R9 is hydrogen, and R12, if present, is hydrogen or fluorine.

[1122] Another preferred embodiment relates to compounds of formula III, wherein R4 and R5 are both hydrogen, R6 is chlorine or bromine, X3 is C(R12), R8 is hydrogen, R9 and R10 together with the phenyl ring to which they are attached form a 2,1,3-benzothiadiazole ring system, R11 is hydrogen and R12 is fluorine or hydrogen.

[1123] Another preferred embodiment relates to compounds of formula III, wherein R4 and R5 are both hydrogen, R6 is chlorine or bromine, X3 is C(R12), R8 and R9 together with the phenyl ring to which they are attached form a 2,1,3-benzothiadiazole, 2,1,3-benzoxadiazole, unsubstituted 1,3-benzoxolane, or 2,3-difluoro-1,3-benzodioxolane group, R10 and R11 are independently selected from hydrogen, methoxy, cyano and halogen, preferably selected from hydrogen and fluorine, and R12 is fluorine, trifluoromethyl or hydrogen.

[1124] Another embodiment relates to compounds of formula III, wherein R4 and R5 are both hydrogen, R6 is selected from fluorine, chlorine, bromine and mono-, di- and trifluoromethyl, X3 is N, R8 is fluorine, chlorine or methoxy, R9 is selected from hydrogen, fluorine, chlorine and methoxy, and is preferably hydrogen, R10 is selected from fluorine, chlorine, bromine, iodine, cyano, mono-, di- and trifluoromethyl, mono-, di- and trifluoromethoxy, mono-, di- and trifluoroethoxy, ethynyl and cyanomethyl, and R11 is hydrogen, fluorine or chlorine.

[1125] Another embodiment relates to compounds of formula III, wherein R4 and R5 are both hydrogen, R6 is selected from chloro, bromo, methoxy, mono-, di- and trifluoromethyl, X3 is C(R12) or N, R8 is selected from hydrogen, fluorine, chlorine, methoxy and fluoromethoxy, R9 is hydrogen, R10 is selected from fluorine, chlorine, bromo, cyano, cyanomethyl, cyanoethyl, cyanomethoxy, mono-, di- and trifluoromethyl, mono-, di- and trifluoromethoxy, mono-, di- and trifluoroethoxy, unsubstituted or fluorinated C 1-2 Alkoxy (C 1-3 ) alkoxy, unsubstituted or fluorinated C 1-2 Alkoxy (C 1-3 ) alkyl, unsubstituted or fluorinated C 2-3 Alkenyl, unsubstituted or fluorinated C 1-2 Alkoxy (C 2-3 ) alkenyl and C 2-3 Alkynyl, R11 is hydrogen, methoxy, fluorine or chlorine, and R12, if present, is hydrogen or fluorine.

[1126] In one embodiment, the compound has a structure selected from Formula III(a)-III(c)

[1127]

[1128] wherein R4, R5, R6, R8, R10, R11 and R12 are as described herein for Formulas I and III,

[1129] wherein in formula III(a), Q1 is S or O, and

[1130] wherein in formula III(b), R13 and R14 are selected from hydrogen, methyl and fluorine, and are preferably both hydrogen or both fluorine, and

[1131] Wherein in formula III (c), Q2 is S or O, preferably S,

[1132] and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof.

[1133] In a preferred embodiment of the compounds of formula III(a)-III(c),

[1134] R4 and R5 are both hydrogen,

[1135] R6 is selected from fluorine, chlorine, bromine, mono-, di- and trifluoromethyl, methoxy and fluoromethoxy,

[1136] R8, if present, is hydrogen or fluorine, preferably hydrogen,

[1137] R10, if present, is selected from hydrogen and halogen, preferably selected from hydrogen, fluorine and chlorine,

[1138] R11 is selected from hydrogen, halogen, trifluoromethyl and cyano, preferably selected from fluorine and hydrogen,

[1139] R12 is selected from hydrogen, halogen and trifluoromethyl, preferably selected from hydrogen and fluorine.

[1140] One embodiment relates to compounds of formula IId, IIe, IIIa and IIIb,

[1141] wherein R4 and R5 are both hydrogen,

[1142] R6 is selected from fluoro, chloro, bromo, mono-, di- and trifluoromethyl, and methoxy,

[1143] R10 is selected from hydrogen and halogen, preferably selected from hydrogen, fluorine and chlorine,

[1144] R11 is selected from hydrogen, halogen, trifluoromethyl and cyano, preferably selected from fluorine and hydrogen,

[1145] R12 is selected from hydrogen, halogen and trifluoromethyl,

[1146] wherein in the compounds of formula II(d) and III(a), Q1 is S or O, and

[1147] Wherein in formula II(e) and III(b), R13 and R14 are selected from hydrogen and fluorine, and are preferably both hydrogen or both hydrogen.

[1148] One embodiment relates to compounds of formula IIf and IIIc,

[1149] wherein R4 and R5 are both hydrogen,

[1150] R6 is selected from fluorine, chlorine, bromine, methylsulfonyl, mono-, di- and trifluoromethyl and phenyl,

[1151] R7, if present, is selected from hydrogen, methoxy, fluoro and trifluoromethyl,

[1152] R8 is selected from hydrogen and halogen, preferably selected from hydrogen and fluorine,

[1153] R11 is selected from hydrogen, halogen, trifluoromethyl and cyano, and is preferably hydrogen,

[1154] R12 is selected from hydrogen, halogen and trifluoromethyl, preferably selected from fluorine and hydrogen,

[1155] Q2 is O or S, and preferably S.

[1156] One embodiment relates to compounds of the sub-formulae IIIa, IIIb and IIIc, which are additionally substituted with a radical R2, as shown in the above-mentioned general formula III-2, thereby obtaining the respective corresponding compounds having the sub-formulae III-2a, III-2b and III-2c, wherein R2 is selected from hydrogen, fluorine, chlorine, bromine, iodine and methoxy, and wherein R2 is preferably hydrogen or fluorine, and particularly preferably hydrogen, and wherein the other residues are as defined in the present formulae IIIa, IIIb and IIIc.

[1157] For example, if the compound of formula III-c also carries an R2 group, the resulting compound of formula III-2c is as follows:

[1158]

[1159] Another aspect of the present invention relates to compounds having the general formula VI, and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof,

[1160]

[1161] wherein X1, X2, R2, R4, R5, R6, R8, R9, R10 and R11 have the meanings as described above for the compounds of formula I-2, II-2, III-2, IV-2 or V-2, and wherein R2 is selected from hydrogen, fluorine, chlorine, bromine, iodine and methoxy, preferably selected from hydrogen and fluorine; more preferably R2 is hydrogen.

[1162] One embodiment relates to compounds of formula VI, wherein

[1163] X1 is C-R7 or N,

[1164] X2 is NH, S or O, wherein if X1 is N, then X2 is preferably NH,

[1165] R2 is hydrogen or fluorine, preferably hydrogen,

[1166] R4 is hydrogen or fluorine,

[1167] R5 is selected from hydrogen, halogen, cyano, unsubstituted or fluorinated C 1-3 Alkyl, unsubstituted or fluorinated C 1-3 Alkoxy, unsubstituted or fluorinated C 1-3 Alkylcarbonyl, unsubstituted or fluorinated C 1-3 Alkylsulfinyl and unsubstituted or fluorinated C 1-3 alkylsulfonyl, wherein R5 is preferably selected from hydrogen, halogen, cyano, methyl, methoxy, fluoromethyl and fluoromethoxy, and more preferably selected from hydrogen, fluorine, chlorine and bromine,

[1168] or R5 and R6 together form a ring as described herein,

[1169] R6 is selected from hydrogen, fluorine, chlorine, bromine, iodine, cyano, azido, nitro, amino, C 1-3 Alkyl, C 2-3 Alkenyl, C 2-3 Alkynyl, C 1-3 Alkoxy, C 3-6 Cycloalkyl, C 3-6 Heterocycloalkyl, phenyl, C 5-6 Heteroaryl, C 3-6 Cycloalkyloxy, C 3-6 Heterocycloalkyloxy, phenyloxy, C 5-6 Heteroaryloxy, C 1-3 Alkylsulfinyl, phenylsulfinyl, C 1-3 Alkylsulfonyl, phenylsulfonyl, benzylsulfonyl, C 1-3 Alkylcarbonyl, C 1-3 Alkoxycarbonyl, C 1-3 Alkylaminocarbonyl, di(C 1-3 )alkylaminocarbonyl, C 3-6 Cycloalkyl (C 1-2 ) alkyl, heterocycloalkyl (C 1-2 ) alkyl, phenyl (C 1-2 ) alkyl, C 5-6 Heteroaryl (C 1-2 ) alkyl, C 3-6 Cycloalkyl (C 1-3 ) alkoxy, C 3-6 Heterocycloalkyl (C 1-2 ) alkyloxy, phenyl (C 1-2 ) alkoxy C 5-6 Heteroaryl (C 1-2 ) alkoxy, phenyl (C 1-2 ) alkylsulfinyl, phenyl (C 1-2 ) alkylsulfonyl,

[1170] and wherein each group in R6 may be unsubstituted or substituted by one or more groups selected from fluorine, chlorine, bromine, fluorinated or unsubstituted C 1-3 Alkyl, fluorinated or unsubstituted C 1-3 Alkyloxy, hydroxy and cyano groups are substituted,

[1171] or

[1172] (i) R6 and R7 together with the carbon atom to which R6 and R7 are attached form an unsubstituted or substituted phenyl group, an unsubstituted or substituted pyridyl group, an unsubstituted or substituted cyclopentyl group or an unsubstituted or substituted cyclohexyl group,

[1173] wherein each substituent, if present, is selected from hydroxy, halogen, methyl or methoxy, wherein each methyl or methoxy may be unsubstituted or substituted with one or more substituents selected from halogen and methoxy,

[1174] or

[1175] (ii) R6 and R5 together with the carbon atom to which R6 and R5 are attached form a 1,3-dioxolane ring which may be unsubstituted or substituted with one or two substituents selected from fluorine and methyl,

[1176] R7, if present, is selected from hydrogen, fluorine, chlorine, bromine, iodine, cyano, C 1-3 Alkyl, C 1-3 Alkoxy, C 2-3 Alkynyl, C 2-3 Alkenyl, C 1-3 Alkylcarbonyl, C 1-3 Alkoxycarbonyl, C 1-3 Alkylsulfinyl, C 1-3 Alkylsulfonyl, C 1-3 Alkylthio, C 3-6 Cycloalkyl, C 3-6 Cycloalkyloxy, C 3-6 Heterocycloalkyl, C 3-6 Heterocycloalkyloxy, phenyl, phenyloxy, phenylsulfonyl, phenylsulfinyl, C 5-6 Heteroaryl, C 5-6 Heteroaryloxy, C 5-6 Heteroaryl (C 1-2 ) alkyl and C 5-6 Heteroaryl (C 1-2 ) alkoxy, C 3-6 Cycloalkyl (C 1-2 ) alkyl, C 3-6 Cycloalkyl (C 1-3 ) alkoxy, C 3-6 Heterocycloalkyloxy, C 3-6 Heterocycloalkyl (C 1-2 ) alkyl, heterocycloalkyl (C 1-2 ) alkyloxy, phenyl (C 1-2 ) alkyl, phenyl (C 1-2 ) alkoxy,

[1177] and wherein each group in R7 may be unsubstituted or substituted by one or more groups selected from fluorine, chlorine, bromine, fluorinated or unsubstituted C 1-3 Alkyl, fluorinated or unsubstituted C 1-3 alkyloxy, hydroxyl and cyano groups, or R7 and R6 together form a ring as described herein,

[1178] R8 is selected from hydrogen, optionally halogenated, preferably fluorinated or unsubstituted C1-3 Alkyl, optionally halogenated, preferably fluorinated or unsubstituted C 1-3 Alkyloxy, cyano and halogen,

[1179] R9 is selected from hydrogen, fluorine, chlorine, bromine, iodine, C 1-3 Alkyl, fluorine (C 1-3 ) alkyl, C 1-3 Alkoxy and fluorine (C 1-3 ) alkoxy, wherein R9 is preferably hydrogen or fluorine,

[1180] R10 is selected from hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy, C 2-3 Alkenyl, C 2-3 Alkynyl, cyano, C 1-3 Alkylcarbonyl, C 1-3 Alkoxycarbonyl, C 1-3 Alkylsulfinyl, C 1-3 Alkylsulfonyl, C 1-3 Alkylthio, C 3-6 Cycloalkyl, C 3-6 Cycloalkyloxy, C 3-6 Heterocycloalkyl, C 3-6 Heterocycloalkyloxy, azido, pentafluorosulfanyl, nitro, C 1-3 Alkylaminocarbonyl and di(C 1-3 ) alkylaminocarbonyl, wherein each alkyl, alkenyl, alkynyl or alkoxy group in R10 may be unsubstituted or substituted with one or more substituents selected from halogen, unsubstituted or halogenated C 1-3 Alkoxy, unsubstituted or halogenated C 1-3 Alkylthio, unsubstituted or halogenated C 1-3 Alkylcarbonyl, unsubstituted or halogenated C 1-3 Alkyloxycarbonyl, unsubstituted or halogenated C 1-3 Alkylaminocarbonyl, unsubstituted or halogenated di(C 1-3 )alkylaminocarbonyl, hydroxyl, cyano, C 3-6 Cycloalkyl, C 3-6 Heterocycloalkyl, phenyl and C 5-6 Heteroaryl, wherein any cycloalkyl, heterocycloalkyl, phenyl and heteroaryl may be unsubstituted or substituted by one or more residues selected from halogen, hydroxy, hydroxymethyl, cyano, nitro, unsubstituted or halogenated C 1-3 Alkyl, unsubstituted or halogenated C 1-3 Alkoxy, unsubstituted or halogenated C 1-3 Alkylcarbonyl and unsubstituted or halogenated C 1-3alkoxycarbonyl, and wherein any halogenated substituent in R10 is preferably fluorinated, and wherein R8 and R10 are preferably not hydrogen,

[1181] R11 is selected from hydrogen, fluorine, chlorine, bromine, iodine, cyano, unsubstituted or fluorinated C 1-3 Alkyl and unsubstituted or fluorinated C 1-3 alkyloxy, and is preferably selected from hydrogen, fluorine, chlorine, methyl, fluoromethyl, methoxy and fluoromethoxy,

[1182] and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof.

[1183] One embodiment relates to compounds of formula VI, wherein

[1184] X1 is C-R7 or N,

[1185] X2 is NH, S or O, wherein X2 is preferably NH,

[1186] R2 and R4 are both hydrogen,

[1187] R5 is selected from hydrogen, fluorine, chlorine and bromine,

[1188] R6 is selected from hydrogen, fluorine, chlorine, bromine, cyano, azido, nitro, C 1-3 Alkyl, C 1-3 alkyloxy, cyclopropyl, cyclopropyloxy, oxetanyl, tetrahydrofuranyl, methylsulfonyl, methylsulfinyl, thienyl, pyridyl and benzyloxy, wherein each alkyl or alkoxy group in R6 may be unsubstituted or substituted with one or more groups selected from fluorine, chlorine, bromine, unsubstituted or fluorinated C 1-2 alkyloxy and cyclopropyl, and wherein each cyclopropyl, thienyl, pyridyl and phenyl in R6 may be substituted by one or more groups selected from halogen, methoxy, fluoromethoxy, methyl, fluoromethyl and cyano,

[1189] or R6 and R7 together with the carbon atom to which R6 and R7 are attached form an unsubstituted or substituted phenyl, an unsubstituted or substituted pyridyl, an unsubstituted or substituted cyclopentyl or an unsubstituted or substituted cyclohexyl, wherein each substituent of the ring formed by R6 and R7 is selected from hydroxy, halogen, cyano, methyl or methoxy, wherein each methyl or methoxy group may be unsubstituted or fluorinated,

[1190] R7, if present, is selected from hydrogen, halogen, cyano, C 1-3 Alkyl, C 1-3 Alkoxy, methylsulfinyl and methylsulfonyl, wherein the alkyl or alkoxy group in R7 may be unsubstituted or substituted by one or more groups selected from fluorine, chlorine, cyano and unsubstituted or fluorinated C 1-2alkyloxy, or as described herein R7 and R6 together form a ring,

[1191] R8 is selected from hydrogen, fluorine, chlorine, unsubstituted or fluorinated methyl and unsubstituted or fluorinated methoxy,

[1192] R9 is selected from hydrogen, fluorine, methyl, fluoromethyl, methoxy and fluoromethoxy, and is preferably hydrogen,

[1193] R10 is selected from hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkyloxy, C 2-3 Alkenyl, C 2-3 Alkynyl, C 1-3 Alkylcarbonyl, C 3-4 Cycloalkyl and cyano, wherein each alkyl, alkenyl, alkynyl or alkoxy group may be unsubstituted or substituted with one or more substituents selected from fluorine, chlorine, bromine, fluorinated or unsubstituted C 1-3 Alkyloxy, fluorinated or unsubstituted C 1-3 Alkylcarbonyl, fluorinated or unsubstituted C 1-3 Alkoxycarbonyl, C 3-5 Cycloalkyl, C 3-5 Cycloalkyloxy, C 3-5 Heterocycloalkyl, C 3-5 heterocycloalkyloxy, hydroxy and cyano, wherein any cycloalkyl, heterocycloalkyl, cycloalkyloxy and heterocycloalkyloxy may be unsubstituted or substituted by one or more residues selected from halogen, hydroxy, hydroxymethyl, cyano, fluorinated or unsubstituted methyl, fluorinated or unsubstituted C 1-3 Alkyloxy, fluorinated or unsubstituted C 1-3 Alkyloxycarbonyl and fluorinated or unsubstituted C 1-3 Alkyloxy (C 1-3 ) alkyloxy,

[1194] R11 is selected from hydrogen, fluorine, chlorine, bromine, unsubstituted or fluorinated C 1-3 Alkyl and unsubstituted or fluorinated C 1-3 Alkyloxy,

[1195] and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof.

[1196] In a preferred embodiment of the compound of formula VI, R6 is not hydrogen; in a more preferred embodiment, at least one, preferably two, of R8, R10 and R11 are also different from hydrogen. In one embodiment, both R6 and R10 are not hydrogen.

[1197] In a preferred embodiment of the present invention, in the compound of formula VI, or

[1198] (a) X1 is CR7 and X2 is NH, S or O, or

[1199] (b) X1 is N and X2 is NH.

[1200] Therefore, preferred substructures of formula VI are the following substructures of formulae VIa, VIb, VIc and VId:

[1201]

[1202] wherein any of R2, R4, R5, R6, R7, if present, R8, R9, R10 and R11 are as described herein for compounds of Formula I-2, II-2, III-2, IV-2, V-2 and VI.

[1203] In a preferred embodiment of the present invention, in the compounds of formula VI and VIa-d,

[1204] R2 is hydrogen or fluorine,

[1205] R4 is selected from hydrogen, methoxy and fluorine, and is preferably hydrogen or fluorine, more preferably hydrogen,

[1206] R5 is selected from hydrogen, halogen, cyano, C 1-3 Alkoxy, C 1-3 Alkylcarbonyl, C 1-3 Alkoxycarbonyl, C 1-3 Alkylsulfinyl and C 1-3 Alkylsulfonyl, wherein each alkyl or alkoxy group may be optionally substituted one or more times with a group selected from halogen, C 1-3 Alkoxy, halo (C 1-3 ) alkoxy, cyano, hydroxy and C 1-3 Alkylamino, the preferred optional substituents of the alkyl and alkoxy groups are halogen and C 1-6 alkoxy, or as described herein R5 and R6 together form a ring,

[1207] R6 is selected from hydrogen, hydroxy, halogen, cyano, azido, nitro, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Alkoxy, C 3-7 Cycloalkyl, C 3-6 Cycloalkenyl, C 3-7 Heterocycloalkyl, C 3-7 Heterocycloalkenyl, phenyl, C 5-10 Heteroaryl, preferably C 5-6 Heteroaryl, C 8-10heterocyclyl, -ORx, -SRx, -SORx, SO2Rx, -pentafluorosulfanyl, NRyRzz, -NRyCORx, -NRyCO2Rx, -NRxCONRyRz, -CORx, -CO2Rx, -CONRyRz, wherein each alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, phenyl, heteroaryl or heterocyclyl group in R6 may be unsubstituted or substituted by one or more substituents preferably selected from halogen, hydroxy, oxo, cyano, azido, nitro, C 1-6 Alkyl, C 1-6 Alkoxy (C 1-3 ) alkyl, C 3-7 Cycloalkyl, C 3-7 Heterocycloalkyl, phenyl, C 5-10 (Preferred C 5-6 )heteroaryl, ORx, -SRx, -SORx, SO2Rx, -pentafluorosulfanyl, NRyRz, -NRyCORx, -NRyCO2Rx, -CORx, -CO2Rx, -CONRyRz,

[1208] wherein Rx, Ry, Rz and Rzz are independently selected from hydrogen, C 1-6 Alkyl, C 3-7 Cycloalkyl, C 3-6 Cycloalkenyl, C 3-7 Cycloalkyl (C 1-6 ) alkyl, phenyl, phenyl (C 1-6 ) alkyl, C 3-7 Heterocycloalkyl, C 3-7 Heterocycloalkyl (C 1-6 ) alkyl, C 5-6 Heteroaryl or heteroaryl (C 1-6 ) alkyl, any one of which may be unsubstituted or substituted by one or more substituents, or Ry and Rz or Ry and Rzz together with the amino atom to which they are attached form an aromatic or non-aromatic, unsubstituted or substituted C 5-6 heterocyclic ring, wherein Rzz is preferably different from hydrogen,

[1209] Alternatively, in compounds of formula VI, VIa, VIb or VIc, R6 may form, together with R5 or R7 and the carbon atoms to which they are attached, a 5- or 6-membered aromatic or non-aromatic ring, which may optionally contain one or more heteroatoms selected from S, O and N, and wherein the ring may be unsubstituted or substituted with one or more substituents,

[1210] wherein preferably R6 and R7 together with the carbon atom to which R6 and R7 are attached form unsubstituted or substituted phenyl, unsubstituted or substituted pyridyl, unsubstituted or substituted cyclopentyl or unsubstituted or substituted cyclohexyl, wherein each substituent, if present, is selected from halogen, hydroxy, cyano, C 1-3 Alkyl, C 3-7 Cycloalkyl, C 3-7 Cycloalkyl (C 1-3 ) alkyl, C 3-7 Heterocycloalkyl (C 1-3 ) alkyl, C 1-3 Alkoxy and C 1-3 Alkoxy (C 1-3 ) alkyl, wherein each alkyl or alkoxy group may be unsubstituted or substituted by one or more radicals selected from halogen and C 1-3 or (ii) R6 and R5 together with the carbon atom to which R6 and R5 are attached form a 1,3-dioxolane ring which may be unsubstituted or substituted with one or two substituents selected from fluoro and methyl, or

[1211] R7, if present, is selected from H, halogen, cyano, C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkynyl, C 2-6 Alkenyl, C 1-6 Alkylcarbonyl, C 1-6 Alkoxycarbonyl, C 1-5 Alkylcarbonylamino, C 1-5 Alkylaminocarbonyl, di(C 1-3 )alkylaminocarbonyl, C 1-6 Alkylsulfonyl, C 1-6 Alkylsulfinyl, C 3-7 Cycloalkyl, C 3-7 Heterocycloalkyl, phenyl, C 5-6 Heteroaryl, C 5-6 Heteroaryl (C 1-3 ) alkyl and C 5-6 Heteroaryl (C 1-3 ) alkoxy, wherein each alkyl, alkenyl, alkynyl or alkoxy group may be unsubstituted or substituted with one or more substituents selected from halogen, halo(C 1-6 ) alkoxy, preferably fluoro(C 1-3 ) alkoxy, and C 1-6 Alkoxy,

[1212] R8 is selected from hydrogen, C 1-6 Alkyl, C 1-6 Alkoxy and halogen, wherein each alkyl or alkoxy group may be unsubstituted or substituted with one or more substituents selected from halogen and optionally fluorinated C1-3 Alkoxy,

[1213] R9 is selected from hydrogen, halogen, cyano, azido, C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl and halogen, wherein each alkyl or alkoxy group may be unsubstituted or substituted by one or more radicals selected from halogen and C 1-3 Alkoxy substituents are substituted,

[1214] R10 is selected from hydrogen, halogen, C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, cyano, C 1-6 Alkylcarbonyl, C 1-6 Alkoxycarbonyl, C 1-6 Alkylsulfonyl, C 1-6 Alkylsulfinyl, C 1-6 Alkylthio, C 1-5 Alkylcarbonylamino, C 1-5 Alkylaminocarbonyl, di(C 1-3 )alkylaminocarbonyl, C 3-6 Cycloalkyl, hetero(C 3-6 ) cycloalkyl, azido, pentafluorosulfanyl and nitro, wherein each alkyl, alkenyl, alkynyl or alkoxy group may be unsubstituted or substituted with one or more substituents selected from halogen, C 1-6 Alkoxy, halo (C 1-6 ) alkoxy, unsubstituted or fluorinated C 1-3 Alkoxycarbonyl, unsubstituted or fluorinated C 1-3 Alkylcarbonyl, C 1-6 Alkylthio, unsubstituted or fluorinated C 1-3 Alkylcarbonylamino, unsubstituted or fluorinated C 1-3 Alkylaminocarbonyl, unsubstituted or fluorinated di(C 1-3 )alkylaminocarbonyl, unsubstituted or fluorinated C 1-3 Alkylsulfonyl, unsubstituted or fluorinated C 1-3 Alkylsulfinyl, hydroxyl, cyano, cyclo(C 3-6 ) alkyl, phenyl and C 5-6 Heteroaryl, wherein any cycloalkyl, heterocycloalkyl, phenyl and heteroaryl may be unsubstituted or substituted by one or more residues selected from halogen, hydroxy, cyano, unsubstituted or fluorinated C 1-3 Alkyl, unsubstituted or fluorinated C 1-3 Alkoxy and unsubstituted or fluorinated C 1-3 Alkoxycarbonyl,

[1215] R11 is selected from hydrogen, halogen, cyano, azido, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylcarbonyl, C 1-6 Alkoxycarbonyl, C 1-6 Alkylsulfonyl, and C 1-6 Alkylsulfinyl, C 2-6 Alkenyl and C 2-6 Alkynyl, wherein each alkyl or alkoxy group may be unsubstituted or substituted by one or more radicals selected from halogen and C 1-3 Alkoxy substituents are substituted,

[1216] and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof.

[1217] In one embodiment, in the compounds of formulae VI and VIa-d, at least one of the groups R5, R6 and R7, if present, and at least one, preferably two, of the groups R8, R10 and R11 are different from hydrogen, wherein more preferably at least one substituent is selected from fluorine, chlorine and bromine.

[1218] In one embodiment, in the compounds of Formula VI and VIa-d,

[1219] X1, if present, is N or CR7,

[1220] X2, if present, is NH, S or O, wherein if X1 is N, then X2 is preferably NH,

[1221] R2 is hydrogen or fluorine, preferably hydrogen,

[1222] R4 is hydrogen or fluorine, preferably hydrogen,

[1223] R5 is selected from hydrogen, halogen, cyano, C 1-2 Alkyl and C 1-2 alkyloxy, wherein R5 is preferably hydrogen, methyl or halogen, or R5 and R6 together form a ring as described herein,

[1224] R6 is selected from hydrogen, halogen, cyano, nitro, amino, azido, C 1-3 Alkyl, C 2-3 Alkenyl, C 2-3 Alkynyl, C 1-3 Alkyloxy, C 1-3 Alkylcarbonyl, C 1-3 Alkoxycarbonyl, C 1-3 Alkylcarbonylamino, C 1-3 Alkylaminocarbonyl, di(C 1-3 )alkylaminocarbonyl, (C 1-3 )alkylsulfinyl, (C1-3 ) alkylsulfonyl, C 3-6 Cycloalkyl, C 3-6 Cycloalkyloxy, C 3-6 Cycloalkyl (C 1-2 ) alkyl, C 3-6 Cycloalkyl (C 1-3 ) alkoxy, C 3-6 Heterocycloalkyl, C 3-6 Heterocycloalkyloxy, C 3-6 Heterocycloalkyl (C 1-2 ) alkyl, heterocycloalkyl (C 1-2 ) alkyloxy, phenyl, phenyloxy, phenyl (C 1-2 ) alkyl, phenyl (C 1-2 ) alkoxy, phenylsulfonyl, phenylsulfinyl, phenyl (C 1-2 ) alkylsulfonyl, phenyl (C 1-2 ) alkylsulfinyl, C 5-6 Heteroaryl, C 5-6 Heteroaryloxy, C 5-6 Heteroaryl (C 1-2 ) alkyl and C 5-6 Heteroaryl (C 1-2 ) alkoxy, and wherein each group in R6 may be unsubstituted or substituted by one or more selected from fluorine, chlorine, bromine, fluorinated or unsubstituted C 1-3 Alkyl, fluorinated or unsubstituted C 1-3 Alkyloxy, hydroxy and cyano groups are substituted,

[1225] or

[1226] (i) wherein in the compound of formula VI, VIa, VIb or VIc, R6 and R7 together with the carbon atom to which R6 and R7 are attached form an unsubstituted or substituted phenyl group, an unsubstituted or substituted pyridyl group, an unsubstituted or substituted cyclopentyl group or an unsubstituted or substituted cyclohexyl group,

[1227] wherein each substituent, if present, is selected from hydroxy, halogen, methyl or methoxy, wherein each methyl or methoxy may be unsubstituted or substituted with one or more substituents selected from halogen, preferably fluorine, and methoxy,

[1228] or

[1229] (ii) R6 and R5 together with the carbon atom to which R6 and R5 are attached form a 1,3-dioxolane ring which may be unsubstituted or substituted with one or two substituents selected from fluorine and methyl,

[1230] R7, if present, is selected from hydrogen, fluorine, chlorine, bromine, iodine, cyano, azido, nitro, amino, C 1-3Alkyl, C 2-3 Alkenyl, C 2-3 Alkynyl, C 1-3 Alkyloxy, C 1-3 Alkylcarbonyl, C 1-3 Alkoxycarbonyl, C 1-3 Alkylcarbonylamino, C 1-3 Alkylaminocarbonyl, di(C 1-3 )alkylaminocarbonyl, C 1-3 Alkylsulfinyl, C 1-3 Alkylsulfonyl, C 1-3 Alkylthio, C 3-6 Cycloalkyl, C 3-6 Cycloalkyloxy, C 3-6 Cycloalkyl (C 1-2 ) alkyl, C 3-6 Cycloalkyl (C 1-3 ) alkoxy, C 3-6 Heterocycloalkyl, C 3-6 Heterocycloalkyloxy, C 3-6 Heterocycloalkyl (C 1-2 ) alkyl, heterocycloalkyl (C 1-2 ) alkyloxy, phenyl, phenyloxy, phenyl (C 1-2 ) alkyl, phenyl (C 1-2 ) alkoxy, phenylsulfonyl, phenylsulfinyl, C 5-6 Heteroaryl, C 5-6 Heteroaryloxy, C 5-6 Heteroaryl (C 1-2 ) alkyl and C 5-6 Heteroaryl (C 1-2 ) alkoxy, and wherein each group in R7 may be unsubstituted or substituted by one or more selected from fluorine, chlorine, bromine, fluorinated or unsubstituted C 1-3 Alkyl, fluorinated or unsubstituted C 1-3 alkyloxy, hydroxyl and cyano groups, or R7 and R6 together form a ring as described herein,

[1231] R8 is selected from hydrogen, halogen, cyano, optionally halogenated C 1-3 Alkyloxy, optionally halogenated C 1-3 Alkyl, optionally halogenated (C 1-3 )alkylsulfinyl, optionally halogenated (C 1-3 )alkylsulfonyl and optionally halogenated (C 1-3 )alkylthio,

[1232] R9 is selected from hydrogen, fluorine, chlorine, bromine, iodine, C 1-3 Alkyloxy, fluoro(C 1-3 ) alkoxy, C 1-3 Alkyl and fluorine (C 1-3)alkyl, and preferably hydrogen,

[1233] R10 is selected from hydrogen, fluorine, chlorine, bromine, iodine, cyano, nitro, amino, azido, pentafluorosulfanyl, C 1-3 Alkyl, C 2-3 Alkenyl, C 2-3 Alkynyl, C 1-3 Alkyloxy, C 1-3 Alkylcarbonyl, C 1-3 Alkoxycarbonyl, C 1-3 Alkylaminocarbonyl, di(C 1-3 )alkylaminocarbonyl, (C 1-3 )alkylsulfinyl, (C 1-3 )alkylsulfonyl, (C 1-3 ) alkylthio, C 3-6 Cycloalkyl, C 3-6 Cycloalkyloxy, C 3-6 Cycloalkyl (C 1-2 ) alkyl, C 3-6 Cycloalkyl (C 1-3 ) alkoxy, C 3-6 Heterocycloalkyl, C 3-6 Heterocycloalkyloxy, C 3-6 Heterocycloalkyl (C 1-2 ) alkyl, C 3-6 Heterocycloalkyl (C 1-2 ) alkyloxy, and wherein each group in R10 may be unsubstituted or substituted by one or more selected from fluorine, chlorine, bromine, fluorinated or unsubstituted C 1-3 Alkyl, fluorinated or unsubstituted C 1-3 Alkyloxy, fluorinated or unsubstituted C 1-3 Alkoxycarbonyl, fluorinated or unsubstituted C 1-3 Alkylcarbonyl, C 1-3 Alkylaminocarbonyl, di(C 1-3 ) alkylaminocarbonyl, hydroxyl and cyano groups,

[1234] R11 is selected from hydrogen, fluorine, chlorine, bromine, iodine, C 1-3 Alkyl, fluorine (C 1-3 ) alkyl, C 1-3 Alkyloxy, fluoro(C 1-3 ) alkoxy, unsubstituted or fluorinated C 1-3 Alkylcarbonyl, unsubstituted or fluorinated C 1-3 Alkoxycarbonyl and cyano,

[1235] and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof.

[1236] In a preferred embodiment, R6 and R10 are both different from hydrogen and are independently selected from groups as further defined herein.

[1237] In one embodiment, in the compounds of Formula VI and VIa-d,

[1238] R2 and R4 are both hydrogen,

[1239] R5 is selected from hydrogen, fluorine, chlorine and bromine,

[1240] R6 is selected from fluorine, chlorine, bromine, azido, cyano, benzyloxy, methylsulfonyl, methylsulfinyl, C 1-3 Alkyl, C 1-3 Alkyloxy, cyclopropyl, cyclopropyloxy and cyclopropylmethoxy, wherein each alkyl, alkoxy and cyclopropyl in R6 may be unsubstituted or substituted with one or more groups selected from fluorine, chlorine, bromine and unsubstituted or fluorinated C 1-2 Alkyloxy, wherein R6 is preferably selected from fluorine, chlorine, bromine, fluorinated methyl and unsubstituted or fluorinated methoxy,

[1241] Alternatively, in compounds of Formula VI, VIa, VIb or VIc, R6 and R7, taken together with the carbon atom to which they are attached, may form unsubstituted or substituted phenyl, unsubstituted or substituted pyridyl, unsubstituted or substituted cyclopentyl or unsubstituted or substituted cyclohexyl, wherein each substituent in R7, if present, is selected from hydroxy, halogen, cyano, methyl or methoxy, wherein each methyl or methoxy group may be unsubstituted or fluorinated and / or hydroxylated,

[1242] R7, if present, is selected from hydrogen, halogen, cyano, C 1-3 Alkyl, C 1-3 Alkyloxy, C 3-6 Cycloalkyl, C 3-6 Cycloalkyloxy, methylsulfinyl and methylsulfonyl, wherein each alkyl, alkoxy or cycloalkyl in R7 may be unsubstituted or substituted with one or more groups selected from fluorine, chlorine, cyano and unsubstituted or fluorinated C 1-2 alkyloxy, or as described herein R7 and R6 together form a ring,

[1243] R8 is selected from hydrogen, fluorine, chlorine, unsubstituted or fluorinated methoxy and unsubstituted or fluorinated methyl,

[1244] R9 is selected from hydrogen, fluorine, methyl and methoxy, and is preferably hydrogen,

[1245] R10 is selected from hydrogen, halogen, cyano, C 1-3 Alkyl, C 2-3 Alkenyl, C 2-3 Alkynyl, C1-3 Alkyloxy, C 3-4 Cycloalkyl, C 3-4 Cycloalkyloxy, C 3-4 Heterocycloalkyl and C 3-4 Heterocycloalkyloxy, wherein each alkyl, alkenyl, alkynyl and alkyloxy in R10 may be unsubstituted or substituted with one or more groups selected from fluorine, chlorine, bromine, fluorinated or unsubstituted C 1-3 Alkyloxy, fluorinated or unsubstituted C 1-3 Alkylcarbonyl, fluorinated or unsubstituted C 1-3 Alkoxycarbonyl, C 3-4 Cycloalkyl, C 3-4 Cycloalkyloxy, C 3-4 Heterocycloalkyl, C 3-4 heterocycloalkyloxy, hydroxy and cyano, and wherein each cycloalkyl and heterocycloalkyl group in R10 may be substituted by a residue selected from fluorine, chlorine, bromine, hydroxy, hydroxymethyl, fluorinated or unsubstituted C 1-3 Alkyl, fluorinated or unsubstituted C 1-3 Alkyloxy, fluorinated or unsubstituted C 1-2 Alkyloxy C 1-2 Alkyloxy and fluorinated or unsubstituted C 1-3 Alkoxycarbonyl,

[1246] R11 is selected from hydrogen, fluorine, chlorine, bromine, unsubstituted or fluorinated C 1-3 Alkyl, preferably fluoromethyl, and unsubstituted or fluorinated C 1-3 Alkyloxy, preferably methoxy and fluoromethoxy, wherein R11 is preferably selected from hydrogen, fluorine, chlorine, methoxy and fluoromethyl,

[1247] and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof.

[1248] In a preferred embodiment of the compound of formula VI, R2 is hydrogen.

[1249] In a preferred embodiment of the compounds of formulae VI and VIa-d, R4 is hydrogen or fluorine, particularly preferably hydrogen.

[1250] In a preferred embodiment of the compounds of formula VI and VIa-d, R5 is selected from hydrogen, fluorine, chlorine, bromine, iodine and unsubstituted or fluorinated methyl. In a particularly preferred embodiment, R5 is selected from hydrogen, fluorine, chlorine, bromine and methyl, and is particularly preferably selected from hydrogen, fluorine, chlorine and bromine. In a preferred embodiment of the compounds of formula VI and VIa-d, if R6 is not hydrogen, then R5 is hydrogen.

[1251] In one embodiment of the compounds of formula VIa-c, in particular in the compounds of formula VIa, R6 and R7 together with the C atom to which R6 and R7 are attached form a ring, wherein the ring is preferably selected from phenyl, pyridyl, cyclopentyl and cyclohexyl, each of which may be unsubstituted or substituted with one or more substituents selected from halogen, hydrogen, oxo, C 1-3 Alkyl, C 1-3 Alkoxy, fluorine C 1-3 Alkoxy, fluorine C 1-3 Alkyl, amino, cyano, di(C 1-3 alkyl)amino, acetyl, C 1-3 Alkylsulfonyl, C 1-3 Alkylsulfanyl, C 1-3 alkylthio, and wherein the substituents are preferably selected from fluorine, chlorine, bromine, cyano, hydroxy, methyl, fluoromethyl, methoxy and fluoromethoxy. In a preferred embodiment, in the compound of formula VIa, R6 and R7 form a ring, which together with the connected bicyclic ring forms a tricyclic moiety selected from 1H-benzo[g]indol-3-yl, 1H-pyrrolo[3,2-h]quinolin-3-yl, 1,6,7,8-tetrahydrocyclopenta[g]indol-3-yl and 6,7,8,9-tetrahydro-1H-benzo[g]indol-3-yl. In one embodiment, if R6 and R7 form a pyridyl ring to give 1H-pyrrolo[3,2-h]quinolin-3-yl, the tricyclic ring may be further substituted by a substituent selected from fluoro, chloro, bromo, hydroxy, methoxy, fluoromethyl and fluoromethoxy, preferably at the 8-position to give, for example, 8-hydroxy-1H-pyrrolo[3,2-h]quinoline, 8-(difluoromethyl)-1H-pyrrolo[3,2-h]quinoline or 8-(trifluoromethoxy)-1H-pyrrolo[3,2-h]quinoline. In one embodiment of the compounds of formula VIa-c, in particular in the compounds of formula VIa, R6 and R7 together with the C atom to which R6 and R7 are attached form a ring, wherein the ring is selected from phenyl, pyridyl, cyclopentyl and cyclohexyl, which is unsubstituted or substituted by one or more substituents selected from fluoro, chloro, fluoromethyl and fluoromethoxy, wherein, in a preferred embodiment, the ring is unsubstituted.

[1252] In a preferred embodiment of the compound of formula VIa-c, if R6 and R7 form an optionally substituted ring selected from phenyl, pyridyl, cyclopentyl and cyclohexyl, then R4 and R5 are preferably both hydrogen, R8 is hydrogen, halogen or unsubstituted or fluorinated methoxy, preferably fluorine or methoxy, R9 is hydrogen or fluorine, preferably hydrogen, and R10 is selected from halogen, cyano, cyanomethyl, cyanoethyl, cyanomethoxy, nitro, azido, pentafluorosulfanyl, unsubstituted or fluorinated and / or hydroxylated, preferably unsubstituted or fluorinated C 1-3Alkyl, unsubstituted or fluorinated and / or hydroxylated, preferably unsubstituted or fluorinated C 1-3 Alkylcarbonyl, unsubstituted or fluorinated and / or hydroxylated, preferably unsubstituted or fluorinated C 1-3 Alkoxy, unsubstituted or fluorinated C 2-3 Alkenyl, C 2-3 Alkynyl, unsubstituted or fluorinated and / or hydroxylated, preferably unsubstituted or fluorinated C 1-2 Alkoxy (C 1-3 ) alkyl, unsubstituted or fluorinated and / or hydroxylated, preferably unsubstituted or fluorinated C 1-2 Alkoxy (C 1-3 )alkoxy, R11 is selected from hydrogen, fluorine, chlorine, bromine, unsubstituted or fluorinated methoxy and unsubstituted or fluorinated methyl.

[1253] In one embodiment, in the compound of formula VIa, R6 and R7 form pyridine and the tricyclic ring system formed is optionally substituted 1H-pyrrolo[3,2-h]quinolin-3-yl, preferably 8-substituted 1H-pyrrolo[3,2-h]quinoline.

[1254] In a preferred embodiment of the compound of formula VIa, R6 and R7 form an optionally substituted ring selected from phenyl, pyridyl (to preferably form optionally 8-substituted 1H-pyrrolo[3,2-h]quinolin-3-yl), cyclopentyl and cyclohexyl, R4 and R5 are both hydrogen, R8 is fluorine or unsubstituted or fluorinated methoxy, R9 is hydrogen or fluorine, preferably hydrogen, R10 is selected from fluorine, chlorine, bromine, iodine, cyano, cyanomethyl, cyanoethyl, cyanomethoxy, unsubstituted or fluorinated C 1-3 Alkyl, unsubstituted or fluorinated C 1-3 Alkoxy, unsubstituted or fluorinated C 2-3 Alkenyl, C 2-3 Alkynyl, unsubstituted or fluorinated C 1-2 Alkoxy (C 1-3 ) alkyl and unsubstituted or fluorinated C 1-2 Alkoxy (C 1-3 )alkoxy, R11 is selected from hydrogen, fluorine, chlorine, bromine, unsubstituted or fluorinated methoxy and unsubstituted or fluorinated methyl.

[1255] In a preferred embodiment of the compounds of formula VI and VIa-d, R6 is selected from fluoro, chloro, bromo, iodo, cyano, azido, amino, nitro, C 1-3 Alkyl, C 2-3 Alkenyl, C 2-3 Alkynyl, C 1-3 Alkyloxy, C 1-3 Alkylcarbonylamino, C 1-3 Alkylaminocarbonyl, di(C1-3 )alkylaminocarbonyl, (C 1-3 )alkylsulfinyl, (C 1-3 ) alkylsulfonyl, C 3-6 Cycloalkyl, C 3-6 Cycloalkyloxy, C 3-6 Cycloalkyl (C 1-2 ) alkyl, C 3-6 Cycloalkyl (C 1-3 ) alkoxy, C 3-6 Heterocycloalkyl, C 3-6 Heterocycloalkyloxy, C 3-6 Heterocycloalkyl (C 1-2 ) alkyl, heterocycloalkyl (C 1-2 ) alkyloxy, phenyl, phenyloxy, phenyl (C 1-2 ) alkyl, phenyl (C 1-2 ) alkoxy, phenylsulfonyl, benzylsulfonyl, phenylsulfinyl, benzylsulfinyl, C 5-6 Heteroaryl, C 5-6 Heteroaryloxy, C 5-6 Heteroaryl (C 1-2 ) alkyl and C 5-6 Heteroaryl (C 1-2 ) alkoxy, and wherein each group in R6 may be unsubstituted or substituted by one or more selected from fluorine, chlorine, bromine, fluorinated or unsubstituted C 1-2 Alkyl, fluorinated or unsubstituted C 1-2 Alkoxy, hydroxy and cyano groups are substituted.

[1256] In a preferred embodiment of the compounds of formula VI and VIa-d, R6 is selected from fluoro, chloro, bromo, cyano, cyanomethyl, cyanomethoxy, nitro, azido, cyclopropyl, cyclopropyloxy, cyclopropylmethoxy, unsubstituted or substituted C 1-3 Alkyl, unsubstituted or substituted C 1-3 alkyloxy, methylsulfinyl, methylsulfonyl, pyridyl, optionally halogenated thienyl, and benzyloxy, wherein each substituent in R is selected from halo, methoxy and fluoromethoxy, and preferably fluorine. In a preferred embodiment, R is selected from chlorine, bromine, azido, cyano, cyclopropyl, methylsulfinyl, methylsulfonyl, mono-, di- and trifluoromethyl, methoxy, mono-, di- and trifluoromethoxy and mono-, di- and trifluoroethoxy. In a particularly preferred embodiment, R is selected from fluorine, chlorine, bromine, methoxy, fluoromethoxy, fluoroethoxy and fluoromethyl, and most preferably selected from fluorine, chlorine, bromine and methoxy.

[1257] In a preferred embodiment of the compounds of formula VIa-c, R7 is selected from hydrogen, fluorine, chlorine, bromine, iodine, cyano, nitro, C 1-3 Alkyl, C1-3 Alkyloxy, C 1-3 Alkylsulfinyl, C 1-3 Alkylsulfonyl, C 1-3 Alkylthio, C 3-6 Cycloalkyl, C 3-6 Cycloalkyloxy, C 3-6 Heterocycloalkyl, C 3-6 Heterocycloalkyloxy, phenyl, phenyloxy, phenyl (C 1-2 ) alkyl, phenyl (C 1-2 ) alkoxy, phenylsulfonyl, phenylsulfinyl, C 5-6 Heteroaryl, C 5-6 Heteroaryloxy, C 5-6 Heteroaryl (C 1-2 ) alkyl and C 5-6 Heteroaryl (C 1-2 ) alkoxy, wherein each of R7 may be unsubstituted or substituted by one or more residues selected from fluorine, chlorine, bromine, fluorinated or unsubstituted methyl, fluorinated or unsubstituted C 1-3 Alkyloxy, hydroxy and cyano, and wherein C 5-6 Heteroaryl is preferably selected from pyridyl, oxazole and isoxazole, and it can be substituted as mentioned above separately.In a preferred embodiment, R is selected from hydrogen, fluorine, chlorine, bromine, methyl, fluoromethyl, methoxyl group, fluoromethoxy, fluoroethoxy, methylsulfinyl, methylsulfonyl and the optional substituted isoxazole.In a preferred embodiment, R is selected from hydrogen, fluorine, chlorine, bromine, methyl, fluoromethyl, methoxyl group, fluoromethoxy and methylsulfonyl.

[1258] In a preferred embodiment, in the compounds of formula VI and VIa-d, R8 is selected from hydrogen, halogen, cyano, unsubstituted or fluorinated C 1-3 Alkyl and unsubstituted or fluorinated C 1-3 Alkyloxy is preferably selected from fluorine, chlorine, bromine, methyl, fluoromethyl, methoxy and fluoromethoxy. In a preferred embodiment, R8 is selected from fluorine, methoxy and fluoromethoxy, and in a particularly preferred embodiment, R8 is fluorine or methoxy.

[1259] In a preferred embodiment, in the compounds of formula VI and VIa-d, R9 is selected from hydrogen, fluorine, chlorine, methyl, fluoromethyl, methoxy and fluoromethoxy. In a preferred embodiment, R9 is selected from hydrogen, fluorine, methoxy and fluoromethoxy, and is more preferably hydrogen or fluorine, and is particularly preferably hydrogen.

[1260] In one embodiment, in the compounds of Formula VI and VIa-d, R10 is selected from hydrogen, fluorine, chlorine, bromine, iodine, cyano, nitro, amino, azido, pentafluorosulfanyl, C 1-3 Alkyl, C2-3 Alkenyl, C 2-3 Alkynyl, C 1-3 Alkyloxy, C 1-3 Alkylcarbonyl, C 1-3 Alkoxycarbonyl, C 1-3 Alkylcarbonylamino, C 1-3 Alkylaminocarbonyl, di(C 1-3 )alkylaminocarbonyl, (C 1-3 )alkylsulfinyl, (C 1-3 )alkylsulfonyl, (C 1-3 ) alkylthio, C 3-4 Cycloalkyl, C 3-4 Cycloalkyloxy, C 3-4 Heterocycloalkyl, C 3-4 Heterocycloalkyloxy, C 3-4 Heterocycloalkyl (C 1-2 ) alkyl, C 3-4 Heterocycloalkyl (C 1-2 ) alkoxy, C 5-6 Heteroaryl (C 1-2 ) alkyl and C 5-6 Heteroaryl (C 1-2 ) alkoxy, and wherein each alkyl, alkenyl, alkynyl and alkoxy in R10 may be unsubstituted or substituted with one or more groups selected from fluorine, chlorine, bromine, fluorinated or unsubstituted C 1-3 Alkyloxy, C 1-3 Alkyloxycarbonyl, phenyl, phenyloxy, C 3-6 Cycloalkyl, C 3-6 Cycloalkyloxy, C 3-6 Heterocycloalkyl, C 3-6 Heterocycloalkyloxy, hydroxy and cyano, and wherein each cyclic group in R10 may be unsubstituted or substituted by one or more residues selected from fluorine, chlorine, bromine, fluorinated or unsubstituted C 1-3 Alkyl, fluorinated or unsubstituted C 1-3 Alkyloxy, fluorinated or unsubstituted C 1-3 alkyloxycarbonyl, hydroxy, hydroxymethyl and cyano.

[1261] In one embodiment, in the compounds of Formula VI and VIa-d, R10 is selected from hydrogen, fluorine, chlorine, bromine, iodine, cyano, nitro, amino, azido, pentafluorosulfanyl, C 1-3 Alkyl, C 2-3 Alkenyl, C 2-3 Alkynyl, C 1-3 Alkyloxy, C 1-3 Alkylcarbonyl, C 1-3 Alkoxycarbonyl, (C 1-3 )alkylsulfinyl, (C1-3 )alkylsulfonyl, (C 1-3 ) alkylthio, C 1-3 Alkyloxycyclopropyl and C 1-3 Alkyloxycarbonylcyclopropyl, wherein each alkyl, alkoxy, alkenyl and alkynyl in R10 may be unsubstituted or substituted with one or more groups selected from fluorine, chlorine, bromine, fluorinated or unsubstituted C 1-3 Alkyl, fluorinated or unsubstituted C 1-3 Alkyloxy, fluorinated or unsubstituted C 1-3 Alkyloxycarbonyl, C 3-6 Cycloalkyl and cyano.

[1262] In a preferred embodiment, R10 is selected from hydrogen, fluorine, chlorine, bromine, iodine, cyano, cyanomethyl, cyanoethyl, cyanomethoxy, cyanoethoxy, nitro, azido, pentafluorosulfanyl, C 1-3 Alkyl, C 2-3 Alkenyl, C 2-3 Alkynyl, C 1-3 Alkyloxy, C 1-2 Alkylcarbonyl and substituted cyclopropyl, wherein each of R10 groups may be unsubstituted or substituted by one or more selected from fluorine, unsubstituted or fluorinated and / or hydroxylated, preferably unsubstituted or fluorinated C 1-2 Alkyloxy, unsubstituted or fluorinated and / or hydroxylated, preferably unsubstituted or fluorinated C 1-2 alkyloxycarbonyl, unsubstituted or substituted cyclopropyl and hydroxy groups, provided that any substituent of the cyclopropyl group is selected from halogen, cyano, hydroxymethyl, optionally fluorinated C 1-2 Alkoxy and optionally fluorinated C 1-2 Alkoxycarbonyl.

[1263] In a preferred embodiment, in the compounds of the present invention, including but not limited to compounds of Formulas VI and VIa-d, R10 is selected from hydrogen, fluorine, chlorine, bromine, iodine, cyano, cyanomethyl, cyanoethyl, cyanomethoxy, cyanoethoxy, nitro, azido, pentafluorosulfanyl, methyl, ethyl, propyl, fluoromethyl, fluoroethyl, fluoropropyl, methoxymethyl, fluoromethoxymethyl, methoxyethyl, fluoromethoxyethyl, methoxypropyl, fluoromethoxypropyl, ethoxymethyl, fluoroethoxymethyl, ethoxyethyl, fluoroethoxyethyl, propoxymethyl, fluoropropoxymethyl, methoxy, ethoxy, propoxy, fluoromethoxy, fluoroethoxy, fluoropropoxy, methoxymethyl R10, fluoromethoxymethoxy, methoxyethoxy, fluoromethoxyethoxy, methoxypropoxy, fluoromethoxypropoxy, ethoxymethoxy, fluoroethoxymethoxy, ethoxyethoxy, fluoroethoxyethoxy, propoxymethoxy, fluoropropoxymethoxy, vinyl, propenyl, fluorovinyl, fluoropropenyl, methoxyvinyl, fluoromethoxyvinyl, methoxypropenyl, fluoromethoxypropenyl, ethoxyvinyl, fluoroethoxyvinyl, ethynyl, propynyl, methoxyethynyl, fluoromethoxyethynyl, methoxypropynyl, fluoromethoxypropynyl and cyclopropylmethoxy, wherein in one embodiment each of R10 may be further suitably substituted with hydroxy.

[1264] In a preferred embodiment, R10 is a cyclic group selected from C 3-5 Cycloalkyl, C 3-5 Cycloalkyloxy, C 3-5 Cycloalkyl (C 1-3 ) alkyl, preferably cycloalkylmethyl, C 3-5 Cycloalkyl (C 1-3 ) alkoxy, preferably cycloalkylmethoxy, C 3-5 Heterocycloalkyl, C 3-5 Heterocycloalkyloxy, C 3-5 Heterocycloalkyl (C 1-3 ) alkyl, preferably heterocycloalkylmethyl, and C 3-5 Heterocycloalkyl (C 1-3 ) alkoxy, preferably heterocycloalkylmethoxy, wherein each cyclic group may be unsubstituted or substituted by one or more substituents selected from halogen, preferably fluorine, cyano, hydroxymethyl, optionally fluorinated C 1-3 Alkoxy, optionally fluorinated C 1-2 Alkoxy (C 1-2 )alkyl, optionally fluorinated C 1-2 Alkoxy (C 1-2 ) alkoxy and optionally fluorinated C 1-2 In a preferred embodiment, the substituents are preferably selected from fluorine, cyano and optionally fluorinated C 1-3Alkoxy, wherein the cyclic group is preferably cyclopropyl.

[1265] In a preferred embodiment, in the compounds of the present invention, including but not limited to compounds of Formulas VI and VIa-d, R10 is selected from fluorine, chlorine, bromine, iodine, cyano, cyanomethyl, cyanoethyl, cyanomethoxy, cyanoethoxy, pentafluorosulfanyl, methyl, ethyl, propyl, butyl, fluoromethyl, fluoroethyl, fluoropropyl, methoxymethyl, fluoromethoxymethyl, methoxyethyl, fluoromethoxyethyl, methoxypropyl, fluoromethoxypropyl, ethoxymethyl, fluoroethoxymethyl, ethoxyethyl, fluoroethoxyethyl, methoxy, ethoxy, propoxy , butoxy, fluoromethoxy, fluoroethoxy, fluoropropoxy, methoxymethoxy, fluoromethoxymethoxy, methoxyethoxy, fluoromethoxyethoxy, methoxypropoxy, fluoromethoxypropoxy, ethoxymethoxy, fluoroethoxymethoxy, ethoxyethoxy, fluoroethoxyethoxy, vinyl, propenyl, fluorovinyl, fluoropropenyl, methoxyvinyl, fluoromethoxyvinyl, methoxypropenyl, fluoromethoxypropenyl, ethoxyvinyl, fluoroethoxyvinyl, ethynyl, propynyl, ethoxycyclopropyl, ethoxycarbonylcyclopropyl and cyclopropylmethoxy.

[1266] In the compounds of VI and VIa-d, R10 is selected from fluorine, chlorine, bromine, cyano, cyanomethyl, cyanoethyl, methyl, mono-, di- and trifluoromethyl, ethyl, mono-, di- and trifluoroethyl, propyl, mono-, di- and trifluoropropyl, methoxy, mono-, di- and trifluoromethoxy, ethoxy, mono-, di- and trifluoroethoxy, propoxy, mono-, di- and trifluoropropoxy, methoxymethyl, mono-, di- and trifluoromethoxymethyl, methyl oxyethyl, mono-, di- and trifluoromethoxyethyl, methoxypropyl, mono-, di- and trifluoromethoxypropyl, methoxymethoxy, mono-, di- and trifluoromethoxymethoxy, methoxyethoxy, mono-, di- and trifluoromethoxyethoxy, methoxypropoxy, mono-, di- and trifluoromethoxypropoxy, ethoxymethoxy, mono-, di- and trifluoroethoxymethoxy, methoxypropenyl, and mono-, di- and trifluoromethoxypropenyl.

[1267] In a preferred embodiment, R10 is selected from fluorine, chlorine, bromine, iodine, cyano, cyanomethyl, cyanoethyl, cyanomethoxy, cyanoethoxy, unsubstituted or fluorinated C 1-3 Alkyl, unsubstituted or fluorinated C 1-3 Alkoxy, unsubstituted or fluorinated C 1-2 Alkoxy (C 1-3 ) alkyl, unsubstituted or fluorinated C 1-2 Alkoxy (C 1-3 ) alkoxy and unsubstituted or fluorinated C 1-2 Alkoxy (C 2-3) alkenyl.

[1268] In a preferred embodiment, R10 is selected from halogen, C 1-4 Alkoxy, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, preferably C 3-4 Cycloalkyl, C 3-6 Cycloalkyloxy, preferably C 3-4 Cycloalkyloxy, C 3-6 Heterocycloalkyl, preferably C 3-4 Heterocycloalkyl, and C 3-6 Heterocycloalkyloxy, preferably C 3-4 Heterocycloalkyloxy, each of which may be optionally substituted by a residue selected from cyano, fluorine and unsubstituted or fluorinated C 1-3 Alkoxy.

[1269] In one embodiment, in the compounds of Formula VI and VIa-d, R11 is selected from hydrogen, fluorine, chlorine, bromine, iodine, C 1-3 Alkyl, fluorine (C 1-3 ) alkyl, C 1-3 Alkyloxy, fluoro(C 1-3 ) alkoxy, unsubstituted or fluorinated C 1-3 In a preferred embodiment, R11 is selected from hydrogen, fluorine, chlorine, methyl, fluoromethyl, methoxy, fluoromethoxy and cyano, more preferably selected from hydrogen, fluorine, fluoromethyl, methoxy and fluoromethoxy.

[1270] In a preferred embodiment, in the compounds of formula VI and VIa-d,

[1271] R2, R4, R5 and R9 are all hydrogen,

[1272] R6 is selected from halogen, cyano, C 1-3 Alkoxy, C 1-3 Alkyl, C 3-6 Cycloalkyl, preferably C 3-4 Cycloalkyl, C 3-6 Cycloalkyloxy, preferably C 3-4 Cycloalkyloxy, C 3-6 Heterocycloalkyl, preferably C 3-4 Heterocycloalkyl, and C 3-6 Heterocycloalkyloxy, preferably C 3-4 Heterocycloalkyloxy, each of which may be optionally substituted by a residue selected from fluorine and unsubstituted or fluorinated C 1-3 Alkoxy,

[1273] R7 is selected from hydrogen, halogen, cyano, C 1-3Alkoxy, C 1-3 Alkyl, C 3-6 Cycloalkyl, preferably C 3-4 Cycloalkyl, C 3-6 Cycloalkyloxy, preferably C 3-4 Cycloalkyloxy, C 3-6 Heterocycloalkyl, preferably C 3-4 Heterocycloalkyl, and C 3-6 Heterocycloalkyloxy, preferably C 3-4 Heterocycloalkyloxy, each of which may be optionally substituted by a residue selected from fluorine and unsubstituted or fluorinated C 1-3 Alkoxy,

[1274] R8 is selected from fluorine, methoxy and fluoromethoxy, preferably selected from fluorine and methoxy,

[1275] R10 is selected from halogen, C 1-4 Alkoxy, C 1-4 Alkyl, C 2-3 Alkenyl, C 2-3 Alkynyl, C 3-6 Cycloalkyl, preferably C 3-4 Cycloalkyl, C 3-6 Cycloalkyloxy, preferably C 3-4 Cycloalkyloxy, C 3-6 Heterocycloalkyl, preferably C 3-4 Heterocycloalkyl, and C 3-6 Heterocycloalkyloxy, preferably C 3-4 Heterocycloalkyloxy, each of which may be optionally substituted by a residue selected from fluorine, cyano and unsubstituted or fluorinated C 1-3 alkoxy, and

[1276] R11 is selected from hydrogen, fluorine, methoxy and fluoromethoxy, preferably selected from fluorine and methoxy.

[1277] In a preferred embodiment, in the compounds of Formula VI and VIa-d,

[1278] R2 is hydrogen,

[1279] R4 is hydrogen or fluorine, more preferably hydrogen;

[1280] R5 is selected from hydrogen, fluorine, chlorine and bromine;

[1281] R6 is selected from fluorine, chlorine, bromine, azido, cyclopropyl, cyclopropyloxy, cyclopropylmethoxy, unsubstituted or fluorinated C 1-3 Alkyl, unsubstituted or fluorinated C 1-3 alkyloxy, methylsulfinyl, methylsulfonyl, pyridyl, optionally halogenated thienyl and benzyloxy;

[1282] R7, if present, is selected from hydrogen, fluoro, chloro, bromo, methyl, fluoromethyl, methoxy, fluoromethoxy, fluoroethoxy, methylsulfinyl and methylsulfonyl;

[1283] R8 is selected from hydrogen, fluorine, chlorine, bromine, methyl, fluoromethyl, methoxy and fluoromethoxy;

[1284] R9 is selected from hydrogen, fluorine, chlorine, methyl, fluoromethyl, methoxy and fluoromethoxy, and is preferably hydrogen,

[1285] R10 is selected from hydrogen, fluorine, chlorine, bromine, iodine, cyano, nitro, azido, pentafluorosulfanyl, C 1-3 Alkyl, C 2-3 Alkenyl, C 2-3 Alkynyl, C 1-3 Alkyloxy, C 1-3 Alkylcarbonyl, C 1-3 Alkoxycarbonyl and cyclopropyl, wherein the cyclopropyl is optionally substituted by a residue selected from cyano, C 1-2 Alkoxy, fluorine (C 1-2 ) alkoxy, C 1-2 Alkoxy (C 1-2 ) alkoxy, fluorine (C 1-2 ) alkoxy (C 1-2 ) alkoxy, C 1-2 Alkoxycarbonyl and fluorine (C 1-2 ) alkoxycarbonyl, and wherein each alkyl, alkoxy, alkenyl and alkynyl in R10 may be unsubstituted or substituted with one or more groups selected from halogen, fluorinated or unsubstituted C 1-2 Alkyloxy, cyano, cyclopropyl and hydroxy, wherein the substituents are preferably selected from fluorine, fluorinated or unsubstituted C 1-2 Alkyloxy and cyano groups;

[1286] and R11 is selected from hydrogen, fluorine, chlorine, methyl, fluoromethyl, methoxy, fluoromethoxy and cyano,

[1287] and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof.

[1288] In a preferred embodiment, in the compounds of Formulae VI and VIa-d, R2, if present, is hydrogen, R4 is hydrogen or fluorine, more preferably hydrogen; R5 is selected from the group consisting of hydrogen, fluorine, chlorine and bromine and is preferably hydrogen; R6 is selected from the group consisting of fluorine, chlorine, bromine, azido, methylsulfinyl, methylsulfonyl, methyl, mono-, di- and trifluoromethyl, methoxy, mono-, di- and trifluoromethoxy and mono-, di- and trifluoroethoxy; R7, if present, is selected from the group consisting of hydrogen, fluorine, chlorine, bromine, methyl, fluoromethyl, methoxy, fluoromethoxy, fluoroethoxy, methylsulfinyl and methylsulfonyl, R8 is selected from the group consisting of hydrogen, fluorine, chlorine, bromine, methyl, fluoromethyl, methoxy and fluoromethoxy and is preferably fluorine or methoxy; R9 is selected from the group consisting of hydrogen, fluorine, methoxy and fluoromethoxy and is preferably hydrogen; R10 is selected from the group consisting of hydrogen, fluorine, chlorine, bromine, iodine, cyano, cyanomethyl, cyanoethyl, cyanomethoxy, cyanoethoxy, unsubstituted or fluorinated C 1-3 Alkyl, unsubstituted or fluorinated C 1-3 Alkyloxy, unsubstituted or fluorinated C 1-2 Alkyloxy (C 1-3 ) alkyl, unsubstituted or fluorinated C 1-2 Alkyloxy (C 1-3 ) alkyloxy, unsubstituted or fluorinated C 1-2 Alkyloxy (C 2-3 )alkenyl, cyclopropyl, cyclopropyloxy and cyclopropylmethoxy, wherein any cyclopropyl moiety is optionally substituted by a residue selected from fluoro, cyano, C 1-2 Alkoxy, fluorine (C 1-2 ) alkoxy, C 1-2 Alkoxy (C 1-2 ) alkoxy, fluorine (C 1-2 ) alkoxy (C 1-2 ) alkoxy, C 1-2 Alkoxycarbonyl, fluorine (C 1-2 )alkoxycarbonyl; and R11 is selected from hydrogen, fluorine, chlorine, methyl, fluoromethyl, methoxy and fluoromethoxy, wherein preferably at least one, preferably two and more preferably all substituents of R8, R10 and R11 are different from hydrogen, and wherein in a particularly preferred embodiment, R8 and R11 are independently selected from fluorine and methoxy.

[1289] Another embodiment relates to compounds of formula VI and VIa-d, wherein R2, if present, is hydrogen, R4 and R5 are both hydrogen, R6 is selected from fluoro, chloro, bromo, methylsulfinyl, fluoromethyl, methoxy and fluoromethoxy, and R7 is selected from hydrogen, fluoro, chloro, bromo, unsubstituted or fluorinated C 1-2 Alkyl, unsubstituted or fluorinated C 1-2alkoxy, methylsulfinyl and methylsulfonyl, R8 is selected from hydrogen, fluorine, chloromethoxy and fluoromethoxy, R9 is hydrogen, methoxy or fluorine, preferably hydrogen, R10 is selected from fluorine, chlorine, bromine, iodine, cyano, cyanomethyl, cyanoethyl, unsubstituted or fluorinated and / or hydroxylated C 1-3 Alkyl, unsubstituted or fluorinated and / or hydroxylated C 1-3 Alkoxy, unsubstituted or fluorinated and / or hydroxylated C 1-2 Alkoxy (C 1-3 ) alkyl, unsubstituted or fluorinated and / or hydroxylated C 1-2 Alkoxy (C 1-3 ) alkoxy, unsubstituted or fluorinated and / or hydroxylated C 1-2 Alkoxy (C 2-3 ) alkenyl and unsubstituted or fluorinated C 1-2 Alkoxycarbonylcyclopropyl, and is preferably selected from fluorine, chlorine, bromine, iodine, cyano, cyanomethyl, cyanoethyl, unsubstituted or fluorinated C 1-3 Alkyl, unsubstituted or fluorinated C 1-3 Alkoxy, unsubstituted or fluorinated C 1-2 Alkoxy (C 1-3 ) alkyl, unsubstituted or fluorinated C 1-2 Alkoxy (C 1-3 ) alkoxy, unsubstituted or fluorinated C 1-2 Alkoxy (C 2-3 )alkenyl, unsubstituted or fluorinated C 1-2 Alkoxycarbonylcyclopropyl and unsubstituted or fluorinated C 1-3 Alkoxycyclopropyl, and R11 is selected from hydrogen, fluorine, chlorine, fluoromethyl, methoxy and fluoromethoxy, wherein in a particularly preferred embodiment at least one, more preferably both, of R8 and R11 are different from hydrogen.

[1290] Further embodiments relate to compounds of formula VI and VIa-d,

[1291] in

[1292] R2, R4 and R9 are all hydrogen,

[1293] R5 is hydrogen, fluorine, chlorine or bromine, and is preferably hydrogen,

[1294] R6 is selected from fluorine, chlorine, bromine, methoxy, fluoromethoxy, fluoromethyl and azido,

[1295] Alternatively, in the compound of formula VI, VIa, VIb or VIc, R6 and R7 together with the carbon atom to which R6 and R7 are attached form a ring selected from phenyl, pyridyl, cyclohexyl and cyclopentyl, each of which may be unsubstituted or substituted with one or two substituents selected from fluorine, chlorine, hydroxy, cyano, methoxy, fluoromethoxy and fluoromethyl,

[1296] R7 is selected from hydrogen, fluorine, chlorine, bromine, unsubstituted or fluorinated methyl, unsubstituted or fluorinated methoxy and methylsulfinyl,

[1297] R8 is selected from fluorine, chlorine, methoxy and fluoromethoxy,

[1298] R10 is selected from fluorine, chlorine, bromine, iodine, cyano, cyanomethyl, cyanoethyl, cyanomethoxy, unsubstituted or fluorinated C 1-3 Alkyl, unsubstituted or fluorinated C 1-3 Alkoxy, unsubstituted or fluorinated C 1-2 Alkoxy (C 1-3 ) alkyl, unsubstituted or fluorinated C 1-2 Alkoxy (C 1-3 ) alkoxy and unsubstituted or fluorinated C 1-2 Alkoxy (C 2-3 ) alkenyl, wherein R10 is preferably selected from fluorine, chlorine, bromine, cyanomethyl, cyanoethyl, unsubstituted or fluorinated C 1-3 Alkyl, unsubstituted or fluorinated C 1-3 Alkoxy, unsubstituted or fluorinated C 1-2 Alkoxy (C 1-3 ) alkyl, unsubstituted or fluorinated C 1-2 Alkoxy (C 1-3 ) alkoxy, unsubstituted or fluorinated C 1-2 Alkoxy (C 2-3 )alkenyl, unsubstituted or fluorinated C 1-3 Alkoxycyclopropyl, unsubstituted or fluorinated C 1-3 Alkoxycarbonylcyclopropyl and unsubstituted or fluorinated C 1-2 Alkoxy (C 1-2 ) alkoxycyclopropyl,

[1299] R11 is selected from hydrogen, fluorine, chlorine, methyl, fluoromethyl, fluoromethoxy and methoxy,

[1300] and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof.

[1301] In a preferred embodiment, in the compounds of Formulae VI and VIa-d, R6 and R10 are different from hydrogen and are independently selected from groups as further defined herein.

[1302] In a preferred embodiment, in the compounds of Formulae VI and VIa-d, R6, R8 and R10 are all different from hydrogen and are independently selected from groups as further defined herein.

[1303] In a preferred embodiment, in the compounds of Formulae VI and VIa-d, R6, R8, R10 and R11 are all different from hydrogen and are independently selected from groups as further defined herein.

[1304] In one embodiment, in the compounds of Formula VI and VIa-c, R7 is not hydrogen.

[1305] In a preferred embodiment of the compounds of Formulae VI and VIa-d, R6, R8 and at least one of R10 and R11 are all different from hydrogen and are independently selected from groups as further defined herein.

[1306] In one embodiment, in compounds of Formula VI and VIa, R6 and R7 form a ring selected from phenyl, pyridyl, cyclopentyl and cyclohexyl to provide Formula Vie-VIg:

[1307]

[1308] in

[1309] m is 0 or 1,

[1310] n is any number from 0 to 4, preferably from 0 to 2, more preferably 0 or 1,

[1311] p is any number from 0 to 3, preferably from 0 to 2, more preferably 0 or 1,

[1312] Y is selected from the group consisting of hydrogen, fluorine, chlorine, bromine, iodine, cyano, hydroxy, methyl and methoxy, wherein methoxy and methyl are optionally substituted with one or more substituents selected from the group consisting of fluorine, chlorine, bromine, hydroxy, methoxy and fluoromethoxy,

[1313] R2 and R4 are both hydrogen,

[1314] R5 is selected from hydrogen, fluorine and chlorine, more preferably hydrogen,

[1315] R8 is selected from fluorine, fluoromethyl, methoxy and fluoromethoxy,

[1316] R9 is hydrogen or fluorine,

[1317] R10 is selected from hydrogen, fluorine, chlorine, bromine, iodine, cyano, cyanomethyl, cyanoethyl, cyanopropyl, cyanomethoxy, cyanoethoxy, nitro, azido, pentafluorosulfanyl, C 1-3 Alkyl, C 2-3 Alkenyl, C 2-3 Alkynyl, C 1-3 Alkyloxy, C1-2 Alkylcarbonyl, cyclopropyl, cyclopropylmethyl and cyclopropylmethoxy, wherein each of R10 may be unsubstituted or substituted by one or more selected from fluorine, fluorinated or unsubstituted C 1-2 Alkyloxy, fluorinated or unsubstituted C 1-2 Alkyloxycarbonyl and hydroxyl groups are substituted,

[1318] R11 is selected from hydrogen, fluorine, chlorine, fluoromethyl, methoxy and fluoromethoxy,

[1319] and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof.

[1320] In a preferred embodiment, in the compound of formula VIe,

[1321] m is 0 or 1,

[1322] n is 0 or 1, preferably 0,

[1323] Y is selected from fluoro, chloro, cyano, hydroxy, methyl and methoxy, wherein methoxy and methyl are optionally substituted with one or more substituents selected from fluoro, chloro, bromo, hydroxy, methoxy and fluoromethoxy,

[1324] R2 and R4 are hydrogen,

[1325] R5 is hydrogen, fluorine or chlorine, preferably hydrogen,

[1326] R8 is selected from fluorine, fluoromethyl, methoxy and fluoromethoxy, preferably selected from fluorine and methoxy, R9 is hydrogen or fluorine, preferably hydrogen,

[1327] R10 is selected from hydrogen, fluorine, chlorine, bromine, iodine, cyano, cyanomethyl, cyanoethyl, pentafluorosulfanyl, C 1-3 Alkyl, C 2-3 Alkenyl, C 2-3 Alkynyl, C 1-3 Alkyloxy, C 1-2 Alkylcarbonyl and cyclopropyl, wherein each alkyl, alkenyl, alkynyl, alkyloxy and cyclopropyl in R10 may be unsubstituted or suitably substituted by one or more groups selected from fluorine, fluorinated or unsubstituted C 1-2 Alkyloxy, fluorinated or unsubstituted C 1-2 Alkyloxycarbonyl and hydroxy, wherein the substituent is preferably selected from fluorine and fluorinated or unsubstituted C 1-2 Alkyloxy,

[1328] R11 is selected from hydrogen, fluorine, chlorine, fluoromethyl, methoxy and fluoromethoxy,

[1329] and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof.

[1330] In a preferred embodiment, in the compound of formula VI(f),

[1331] n is 0 or 1, preferably 0,

[1332] Y is selected from fluoro, chloro, cyano, hydroxy, methyl and methoxy, wherein methoxy and methyl are optionally substituted with one or more substituents selected from fluoro, chloro, bromo, hydroxy, methoxy and fluoromethoxy,

[1333] R2 and R4 are both hydrogen,

[1334] R5 is hydrogen, fluorine or chlorine, preferably hydrogen,

[1335] R8 is selected from fluorine, fluoromethyl, methoxy and fluoromethoxy,

[1336] R9 is hydrogen or fluorine, preferably hydrogen,

[1337] R10 is selected from hydrogen, fluorine, chlorine, bromine, iodine, cyano, cyanomethyl, cyanoethyl, pentafluorosulfanyl, C 1-3 Alkyl, C 2-3 Alkenyl, C 2-3 Alkynyl, C 1-3 Alkyloxy, C 1-2 Alkylcarbonyl and cyclopropyl, wherein each alkyl, alkenyl, alkynyl, alkyloxy and cyclopropyl in R10 may be unsubstituted or suitably substituted by one or more groups selected from fluorine, fluorinated or unsubstituted C 1-2 Alkyloxy, fluorinated or unsubstituted C 1-2 Alkyloxycarbonyl and hydroxy, wherein the substituent is preferably selected from fluorine and fluorinated or unsubstituted C 1-2 Alkyloxy,

[1338] R11 is selected from hydrogen, fluorine, chlorine, fluoromethyl, methoxy and fluoromethoxy,

[1339] and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof.

[1340] In a preferred embodiment, in the compound of formula VIg,

[1341] p is 0 or 1,

[1342] Y is selected from fluoro, chloro, cyano, hydroxy, methyl and methoxy, wherein methoxy and methyl are optionally substituted with one or more substituents selected from fluoro, chloro, bromo, hydroxy, methoxy and fluoromethoxy,

[1343] R4 is hydrogen,

[1344] R5 is hydrogen or fluorine, preferably hydrogen,

[1345] R8 is selected from fluorine, fluoromethyl, methoxy and fluoromethoxy,

[1346] R9 is hydrogen or fluorine,

[1347] R10 is selected from hydrogen, fluorine, chlorine, bromine, iodine, cyano, cyanomethyl, cyanoethyl, pentafluorosulfanyl, C 1-3 Alkyl, C 2-3 Alkenyl, C 2-3 Alkynyl, C 1-3 Alkyloxy, C 1-2 Alkylcarbonyl and cyclopropyl, wherein each alkyl, alkenyl, alkynyl, alkyloxy and cyclopropyl in R10 may be unsubstituted or suitably substituted by one or more groups selected from fluorine, fluorinated or unsubstituted C 1-2 Alkyloxy, fluorinated or unsubstituted C 1-2 Alkyloxycarbonyl and hydroxy, wherein the substituent is preferably selected from fluorine and fluorinated or unsubstituted C 1-2 Alkyloxy,

[1348] R11 is selected from hydrogen, fluorine, chlorine, fluoromethyl, methoxy and fluoromethoxy,

[1349] and pharmaceutically acceptable salts, solvates, isotopes and cocrystals thereof.

[1350] In a preferred embodiment of the compound of formula VIe-g, R10 is selected from chloro, cyano, cyanomethyl, cyanoethyl, C 1-3 Alkyl and C 1-3 Alkoxy, wherein each alkyl and alkoxy group may be unsubstituted or substituted with one or more substituents selected from fluoro, methoxy, fluoromethoxy, ethoxy and fluoroethoxy, wherein in one embodiment R10 is selected from chloro, bromo, unsubstituted or fluorinated C 1-3 Alkoxy, cyano, cyanomethyl and cyanoethyl. In a preferred embodiment of the compound of formula VIe-g, R10 is chlorine.

[1351] In a preferred embodiment of the compound of formula VIe-g, Y, if present, is selected from fluoro, chloro, cyano, hydroxy, methyl, fluoromethyl, hydroxymethyl, methoxy and fluoromethoxy. In a preferred embodiment of the compound of formula VIg, Y is selected from fluoro, hydroxy, fluoromethyl, methoxy and fluoromethoxy.

[1352] In a preferred embodiment, in the compounds of formulae VIe to VIg, R10 is selected from fluorine, chlorine, bromine, fluoromethyl, fluoroethyl, fluoromethoxy, fluoroethoxy, cyano and cyanomethyl, and is particularly preferably chlorine.

[1353] Another preferred embodiment relates to compounds of the present invention, including but not limited to those having the following structures: I, I-2, II, II-2, IIa, II-2a, IIb, II-2b, IIc, II-2c, IId, II-2d, IIe, II-2e, IIf, II-2f, IIg, II-2g, III, III-2, IIIa, III-2a, IIIb, III-2b, IIIc, III-2c, IV, IV-2, V, V-2, VI, VIa, VIb, VIc, VId, VIe, VIf or VIg, wherein R4 is hydrogen and the other substituents are as disclosed herein.

[1354] Another embodiment relates to compounds of the present invention, including but not limited to those having the following structures: I, I-2, II, II-2, IIa, II-2a, IIb, II-2b, IIc, II-2c, IId, II-2d, IIe, II-2e, IIf, II-2f, IIg, II-2g, III, III-2, IIIa, III-2a, IIIb, III-2b, IIIc, III-2c, IV, IV-2, V, V-2, VI, VIa, VIb, VIc, VId, VIe, VIf or VIg, wherein R5 is selected from hydrogen, halogen, cyano, azido, unsubstituted or fluorinated C 1-2 Alkyl, preferably methyl or trifluoromethyl, unsubstituted or fluorinated C 1-2 Alkyloxy, unsubstituted or fluorinated C 1-2 Alkylcarbonyl, unsubstituted or fluorinated C 1-2 Alkyloxycarbonyl, C 1-2 Alkylsulfinyl, preferably methylsulfinyl, and C 1-2 Alkylsulfonyl, preferably methylsulfonyl, and other substituents are as disclosed herein.

[1355] Another preferred embodiment relates to compounds of the present invention, including but not limited to those having the following structures: I, I-2, II, II-2, IIa, II-2a, IIb, II-2b, IIc, II-2c, IId, II-2d, IIe, II-2e, IIf, II-2f, IIg, II-2g, III, III-2, IIIa, III-2a, IIIb, III-2b, IIIc, III-2c, IV, IV-2, V, V-2, VI, VIa, VIb, VIc, VId, VIe, VIf or VIg, wherein R5 is selected from hydrogen, fluorine, chlorine, bromine, iodine, methyl, trifluoromethyl, methoxy and trifluoromethoxy, and is particularly preferably selected from hydrogen, fluorine, chlorine and bromine, and the other substituents are as disclosed herein.

[1356] Another preferred embodiment relates to compounds of the present invention, including but not limited to those having the following structures: I, I-2, II, II-2, IIa, II-2a, IIb, II-2b, IIc, II-2c, IId, II-2d, IIe, II-2e, IIf, II-2f, IIg, II-2g, III, III-2, IIIa, III-2a, IIIb, III-2b, IIIc, III-2c, IV, IV-2, V, V-2, VI, VIa, VIb, VIc, VId, VIe, VIf or VIg, wherein R5 is iodine and R6 is hydrogen, and the other substituents are as disclosed herein.

[1357] Another preferred embodiment relates to compounds of the present invention, including but not limited to those having the following structures: I, I-2, II, II-2, IIa, II-2a, IIb, II-2b, IIc, II-2c, IId, II-2d, IIe, II-2e, IIf, II-2f, IIg, II-2g, III, III-2, IIIa, III-2a, IIIb, III-2b, IIIc, III-2c, IV, IV-2, V, V-2, VI, VIa, VIb, VIc, VId, VIe, VIf or VIg, wherein R5 is hydrogen and the other substituents are as disclosed herein.

[1358] Another preferred embodiment relates to compounds of the present invention, including but not limited to those having the following structures: I, I-2, II, II-2, IId, II-2d, IIe, II-2e, IIf, II-2f, IIg, II-2g, IV, IV-2, V, V-2, VI, VIa, VIb or VIc, wherein R7, if present, is hydrogen and the other substituents are as disclosed herein.

[1359] Another preferred embodiment relates to compounds of the present invention, including but not limited to those having the following structures: II, I-2, II, II-2, IId, II-2d, IIe, II-2e, IIf, II-2f, IIg, II-2g, IV, IV-2, V, V-2, VI, VIa, VIb or VIc, wherein R7, if present, is fluoro and the other substituents are as disclosed herein.

[1360] Another preferred embodiment relates to compounds of the present invention, including but not limited to those having the following structures: I, I-2, II, II-2, IId, II-2d, IIe, II-2e, IIf, II-2f, IIg, II-2g, IV, IV-2, V, V-2, VI, VIa, VIb or VIc, wherein R7, if present, is C1-3 Alkoxy or fluorine (C 1-3 )alkoxy, preferably mono-, di- or trifluoromethoxy, and other substituents are as disclosed herein.

[1361] Another preferred embodiment relates to compounds of the present invention, including but not limited to those having the following structures: I, I-2, II, II-2, IId, II-2d, IIe, II-2e, IIf, II-2f, IIg, II-2g, IV, IV-2, V, V-2, VI, VIa, VIb or VIc, wherein R7, if present, is methoxy and the other substituents are as disclosed herein.

[1362] Another preferred embodiment relates to compounds of the present invention, including but not limited to those having the following structures: I, I-2, II, II-2, IId, II-2d, IIe, II-2e, IIf, II-2f, IIg, II-2g, IV, IV-2, V, V-2, VI, VIa, VIb or VIc, wherein R7, if present, is selected from hydrogen, cyano, fluoro, chloro, bromo, methoxy, ethoxy, fluoromethoxy, fluoroethoxy, methyl, ethyl, fluoromethyl, fluoroethyl, methylsulfinyl, fluoromethylsulfinyl, methylsulfonyl and fluoromethylsulfonyl, and the other substituents are as disclosed herein.

[1363] Another preferred embodiment relates to compounds of the present inven...

Claims

1. Use of a compound of formula I or a pharmaceutically acceptable salt thereof in the preparation of a medicament for treating GPR17-related central nervous system demyelinating disorders, Formula I in X1 is selected from CR7 and N and X2 is NH, so that the compound has the structure of Formula II or III Formula II Formula III in X3 is N or C (R12), R4 is hydrogen or fluorine, R5 is selected from hydrogen, fluorine, chlorine, bromine, iodine, methyl, methoxy and fluorinated C 1-2 alkyl, R6 is selected from fluorine, chlorine, bromine, iodine, cyano, azido, unsubstituted or substituted C 1-3 Alkyl, unsubstituted or substituted C 2-3 Alkenyl, unsubstituted or substituted C 2-3 Alkynyl, unsubstituted or substituted (C 1-3 )alkylsulfinyl, unsubstituted or substituted C 1-3 Alkylsulfonyl, unsubstituted or substituted C 3-6 Cycloalkyl, unsubstituted or substituted C 3-6 Cycloalkyl (C 1-3 ) alkyl, unsubstituted or substituted C 3-6 Cycloalkyl (C 1-3 ) alkoxy, unsubstituted or substituted C 3-6 Heterocycloalkyl, unsubstituted or substituted C 3-6 Heterocycloalkyl (C 1-3 ) alkoxy, unsubstituted or substituted C 3-6 Cycloalkoxy, unsubstituted or substituted C 3-6 Heterocycloalkoxy, unsubstituted or substituted C 1-3 Alkoxy, unsubstituted or substituted C 1-3 Alkoxy (C 1-3 ) alkoxy, unsubstituted or substituted C 1-3 Alkoxy (C 1-3 ) alkyl, unsubstituted or substituted C 3-6 Cycloalkyl (C 1-3 ) alkoxy, unsubstituted or substituted phenyl, unsubstituted or substituted phenyl (C 1-3 ) alkyl, unsubstituted or substituted phenyl (C 1-3 ) alkoxy, unsubstituted or substituted phenyloxy, unsubstituted or substituted phenyl (C 1-3 )alkylsulfonyl, unsubstituted or substituted phenyl (C 1-3 )alkylsulfinyl, unsubstituted or substituted thienyl, unsubstituted or substituted pyridinyl, unsubstituted or substituted oxazolyl, unsubstituted or substituted thiazolyl and unsubstituted or substituted isoxazolyl, and wherein each optional substituent in R is selected from fluorine, chlorine, unsubstituted or fluorinated methyl, unsubstituted or fluorinated methoxy, hydroxy and cyano, or (i) R6 and R7, if present, together with the carbon atom to which they are attached, form unsubstituted or substituted phenyl, unsubstituted or substituted pyridyl, unsubstituted or substituted cyclopentyl or unsubstituted or substituted cyclohexyl, wherein each substituent, if present, is selected from halogen, hydroxy, methyl and methoxy, wherein each methyl or methoxy may be unsubstituted or substituted with one or more substituents selected from fluoro and methoxy, or (ii) R6 and R5 together with the carbon atom to which R6 and R5 are attached form a 1,3-dioxolane ring which may be unsubstituted or substituted with one or two substituents selected from fluorine and methyl, R7, if present, is selected from hydrogen, fluorine, chlorine, bromine, iodine, cyano, C 1-3 Alkyl, C 1-3 Alkyloxy, fluoro(C 1-3 )alkyl, fluoro(C 1-3 )alkoxy, methylsulfinyl, methylsulfonyl, fluorinated methylsulfinyl, fluorinated methylsulfonyl, C 3-6 Cycloalkyl, C 3-6 Heterocycloalkyl, C 3-6 Cycloalkoxy, C 3-6 Heterocycloalkoxy, substituted or unsubstituted C 5-6 Heteroaryl, substituted or unsubstituted C 5-6 Heteroaryloxy and C 5-6 heteroarylmethoxy, wherein the heteroaryl group may be substituted by one or more substituents selected from halogen, unsubstituted or fluorinated methyl and unsubstituted or fluorinated methoxy, R8 is selected from hydrogen, fluorine, chlorine, bromine, iodine, cyano, C 1-3 Alkoxy, fluorine (C 1-3 ) alkoxy, C 1-3 Alkyl and fluorine (C 1-3 )alkyl, R9 is selected from hydrogen, fluorine, chlorine, bromine, iodine, cyano, C 1-3 Alkoxy, fluorine (C 1-3 ) alkoxy, C 1-3 Alkyl and fluorine (C 1-3 )alkyl, R10 is selected from hydrogen, fluorine, chlorine, bromine, iodine, C 1-3 Alkyl, halo (C 1-3 ) alkyl, C 2-3 Alkenyl, C 2-3 Alkynyl, C 1-3 Alkyloxy, halo(C 1-3 ) alkyloxy, cyano, cyanomethyl, cyanoethyl, unsubstituted or fluorinated C 1-3 Alkylcarbonyl, unsubstituted or fluorinated C 1-3 Alkoxycarbonyl, cyclopropyl, cyclopropyloxy, azido, pentafluorosulfanyl and nitro, wherein any cyclopropyl residue may be selected from fluoro, cyano, C 1-3 Alkoxy and C 1-3 wherein each alkyl, alkoxy, alkenyl or alkynyl group in R10 may be optionally further substituted with one or more substituents selected from cyclopropyl, fluoro, chloro, bromo, iodo, cyano, hydroxy, haloC 1-3 Alkoxy and C 1-3 Alkoxy, R11 is selected from hydrogen, fluorine, chlorine, cyano, C 1-3 Alkyl, fluorine (C 1-3 ) alkyl, C 1-3 Alkyloxy and fluorine (C 1-3 ) alkoxy, R12, if present, is selected from hydrogen, fluorine, chlorine, bromine, iodine, C 1-3 Alkyloxy, fluoro(C 1-3 ) alkoxy, C 1-3 Alkyl and fluorine (C 1-3 )alkyl, wherein at least one of R8, R10 and R11 is different from hydrogen.

2. The method of claim 1, wherein the GPR17-related central nervous system demyelinating disorder is selected from multiple sclerosis and its subtypes, demyelination in response to hypoxia, stroke or ischemia or other cardiovascular disease, and a neurodegenerative disease selected from amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), multiple system atrophy, Parkinson's disease, spinocerebellar ataxia (SCA) and Huntington's disease.

3. The use according to claim 1, wherein the GPR17-related central nervous system demyelinating disorder is relapsing-remitting multiple sclerosis or primary progressive multiple sclerosis.

4. The use of claim 1, wherein the GPR17-related disorder is secondary progressive multiple sclerosis.

5. The use according to any one of claims 1 to 4, wherein the compound is 6-chloro-N-{3,6-difluoro-5-[(1E)-3-methoxyprop-1-en-1-yl]pyridin-2-yl}-1H-indole-3-sulfonamide or a pharmaceutically acceptable salt thereof.

6. The use according to any one of claims 1 to 4, wherein the compound is 6-chloro-N-[4-(difluoromethoxy)-2,5-difluorophenyl]-1H-pyrrolo[2,3-b]pyridine-3-sulfonamide or a pharmaceutically acceptable salt thereof.

7. The use according to any one of claims 1 to 4, wherein the compound is 6-chloro-N-(4-chloro-2,5-difluorophenyl)-1H-pyrrolo[2,3-b]pyridine-3-sulfonamide or a pharmaceutically acceptable salt thereof.

8. The use according to any one of claims 1 to 4, wherein the compound is N-(4-bromo-2,5-difluorophenyl)-6-chloro-1H-pyrrolo[2,3-b]pyridine-3-sulfonamide or a pharmaceutically acceptable salt thereof.

9. The use according to claim 8, wherein the GPR17-related central nervous system demyelinating disorder is multiple sclerosis.

10. The use according to any one of claims 1 to 4, wherein the compound is 6-chloro-N-[2,5-difluoro-4-(trifluoromethyl)phenyl]-1H-pyrrolo[2,3-b]pyridine-3-sulfonamide or a pharmaceutically acceptable salt thereof.

11. The use according to any one of claims 1 to 4, wherein the compound is 6-bromo-N-(4-chloro-2-fluorophenyl)-1H-pyrrolo[2,3-b]pyridine-3-sulfonamide or a pharmaceutically acceptable salt thereof.

12. The use according to any one of claims 1 to 4, wherein the compound is 6-chloro-N-(2,5-difluoro-4-methylphenyl)-1H-pyrrolo[2,3-b]pyridine-3-sulfonamide or a pharmaceutically acceptable salt thereof.

13. The use according to any one of claims 1 to 4, wherein the compound is N-(4-chloro-2,5-difluorophenyl)-6-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine-3-sulfonamide or a pharmaceutically acceptable salt thereof.

14. The use according to any one of claims 1 to 4, wherein the compound is N-[4-(difluoromethoxy)-2,5-difluorophenyl]-6-(difluoromethyl)-1H-pyrrolo[2,3-b]pyridine-3-sulfonamide or a pharmaceutically acceptable salt thereof.

15. The use according to any one of claims 1 to 4, wherein the compound is 6-chloro-N-(5-chloro-3-fluoro-6-methoxypyridin-2-yl)-1H-indole-3-sulfonamide or a pharmaceutically acceptable salt thereof.

16. The use according to any one of claims 1 to 4, wherein the compound is N-(5-bromo-3,6-difluoropyridin-2-yl)-6-chloro-1H-indole-3-sulfonamide or a pharmaceutically acceptable salt thereof.

17. The use according to any one of claims 1 to 4, wherein the compound is 6-chloro-N-[3,6-difluoro-5-(3-methoxypropyl)pyridin-2-yl]-1H-indole-3-sulfonamide or a pharmaceutically acceptable salt thereof.

18. The use according to any one of claims 1 to 4, wherein the compound is 6-chloro-N-(5-chloro-3,6-difluoropyridin-2-yl)-1H-indole-3-sulfonamide or a pharmaceutically acceptable salt thereof.

19. The use according to any one of claims 1 to 4, wherein the compound is 6-chloro-N-[3,6-difluoro-5-(2-fluoroethoxy)pyridin-2-yl]-1H-indole-3-sulfonamide or a pharmaceutically acceptable salt thereof.

20. The use according to any one of claims 1 to 4, wherein the compound is 6-chloro-N-[5-(cyanomethyl)-3-fluoro-6-methoxypyridin-2-yl]-1H-indole-3-sulfonamide or a pharmaceutically acceptable salt thereof.

21. The use according to any one of claims 1 to 4, wherein the compound is 6-chloro-N-(5-chloro-3-fluoro-6-methoxypyridin-2-yl)-7-fluoro-1H-indole-3-sulfonamide or a pharmaceutically acceptable salt thereof.

22. The use according to claim 1, wherein the treatment is carried out by oral administration of a pharmaceutical composition comprising a compound as defined in any one of claims 1 to 21 and a pharmaceutically acceptable carrier.

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