N-(4-(Azaindazol-6-yl)-phenyl)-sulfonamides and their use as pharmaceuticals

The present invention relates to N-(4-(azaindazol-6-yl)-phenyl)-sulfonamides of the formula I,

wherein Ar, n, X, Z, R1 , R2 and R3 have the meanings indicated below. The compounds of the formula I are valuable pharmacologically active compounds which modulate protein kinase activity, specifically the activity of serum and glucocorticoid regulated kinase (SGK), in particular of serum and glucocorticoid regulated kinase isoform 1 (SGK-1 , SGK1 ), and are suitable for the treatment of diseases in which SGK activity is inappropriate, for example degenerative joint disorders or

inflammatory processes such as osteoarthritis or rheumatism. The invention furthermore relates to processes for the preparation of the compounds of the formula I, their use as pharmaceuticals, and pharmaceutical compositions comprising them.

Due to their physiologic importance, variety, and ubiquity, protein kinases have become one of the most important and widely-studied family of enzymes in biochemical and medical research. Studies have shown that the currently known about 500 different protein kinases are key regulators of many cell functions, including signal transduction, transcriptional regulation, cell motility, growth, differentiation, division and destruction. They act through reversible phosphorylation of the hydroxyl groups of distinct amino acids in proteins. Several oncogenes have been shown to encode protein kinases, suggesting that kinases play a role also in oncogenesis. These processes are highly regulated, often by complex intermeshed pathways where each kinase itself will be regulated by one or more kinases.

Consequently, aberrant or inappropriate protein kinase activity can contribute to the rise of disease states associated with such aberrant kinase activity.

The protein kinase family is typically classified into two main subfamilies, protein tyrosine kinases, which phosphorylate tyrosine residues, and protein serine/threonine kinases (PSTK) which phosphorylate serine and threonine residues. The PSTK subfamily is usually cytoplasmic or associated with the particulate fractions of cells, possibly by anchoring proteins. Aberrant PSTK activity has been implicated or is suspected in a number of pathologies such as rheumatoid arthritis, psoriasis, septic shock, bone loss, many cancers and other proliferative diseases. Accordingly,

PSTKs and their associated signal transduction pathways are important targets for drug design.

Serum and glucocorticoid regulated kinases, also designated as serum/glucocorticoid regulated kinase, serum and glucocorticoid induced kinase, serum and glucocorticoid inducible kinase or serum and glucocorticoid dependent kinase, form a family of PSTKs. Currently three members are known, designated as SGK-1 , SGK-2 and SGK-3. They are also designated as SGKL (SGK-like) and CISK (cytokine-independent survival kinase). At the protein level the three isoforms show a homology of at least 80% in their catalytic domain. SGK-1 was described in 1993 for the first time as an "immediate early gene" in a rat mammary cancer cell line

(Webster, M.K. et al., Immediate-early Transcriptional Regulation and Rapid mRNA Turnover of a Putative Serine/Threonine Protein Kinase, J. Biol. Chem. 1993, 268, 1 1482-1 1485). SGK-1 mRNA is expressed ubiquitously in almost all adult tissues and in several embryonic tissues. SGK-2 is expressed with greatest abundance in epithelial tissues, such as in the kidney, liver, pancreas, and specific areas of the brain, whereas SGK-3 was detected in all tested tissues, especially in the adult heart and spleen (Kobayashi, T. et al., Characterization of the structure and regulation of two novel isoforms of serum and glucocorticoidinduced protein kinase, Biochem. J. 1999, 344, 189-197).

A distinguishing feature of SGK to many other kinases is based on the stringent stimulus-dependent regulation of transcription, cellular localization and enzymatic activation of the molecule (Firestone, G.L. et al., Stimulus-Dependent Regulation of Serum and Glucocorticoid Inducible Protein Kinase (SGK) Transcription, Subcellular Localization and Enzymatic Activity, Cell. Physiol. Biochem. 2003, 13, 1 -12). A variety of stimuli are known which induce and activate SGK-1 . These include mineralocorticoids, gonadotropins, 1 ,25(OH)2D3, p53, osmotic, hypotonic and cellular volume changes, and cytokines such as GM-CSF, TNF-alpha and TGF-beta (reviewed in Lang, F. et al., (Patho)physiological Significance of the Serum- and Glucocorticoid-Inducible Kinase Isoforms, Physiol. Rev. 2006, 86, 1 151 -1 178). In further growth-dependent signaling pathways SGK is induced by serum, insulin and IGF-1 , FSH, Fibroblast and Platelet-derived growth factor, activators of the Erk signaling cascade and TPA (reviewed in Lang, F. et al., Physiol. Rev. 2006, 86, 1 151 -1 178). SGK-1 is also known to be activated in pathological changes such as ischemic brain injury (Imaizumi, K. et al., Differential expression of sgk mRNA, a member of the Ser/Thr protein kinase gene family, in rat brain after CNS injury, Mol. Brain Res. 1994, 26, 189-196), pulmonary fibrosis (Warntges, S. et al., Excessive Transcription of the Human Serum and Glucocorticoid Dependent Kinase hSGK1 in Lung Fibrosis, Cell. Physiol. Biochem. 2002, 12, 135-142) or cardiac fibrosis (Funder, J., Mineralocorticoids and Cardiac Fibrosis: The Decade in Review, Clin. Exp.

Pharmacol. Physiol. 2001 , 28, 1002-1006).

In order to be converted into its functional form, SGK-1 requires activation by phosphorylation. This is mediated by a signaling cascade involving the

phosphatidylinositol 3 (PI-3) kinase and phosphoinositide 3-dependent kinases PDK1 and PDK2. The activation of SGK-1 through the PI-3 kinase signaling pathway is known to be a response to insulin, IGF and growth factors. For activation the phosphorylation of two amino acid residues is necessary, threonine256 on the T-loop (mediated by PDK1 ) and serine422 at the hydrophobic motif of the protein (catalyzed by a putative PDK2) (reviewed in Lang, F. et al., Physiol. Rev. 2006, 86, 1 151 -1 178).

For the function of SGK, there are a series of studies that show regulatory influence of SGK-1 , SGK-2 and SGK-3 on cell membrane channels. It was shown that the epithelial Na+ channel (ENaC), the main transporter for the mineralocorticoid-regulated Na+ reabsorption in the renal tubule, is a target of SGK-1 , SGK-2 and SGK-3 (Faletti, C.J. et al., sgk: an essential convergence point for peptide and steroid hormone regulation of ENaCmediated Na+ transport, Am. J. Physiol. Cell Physiol. 2002, 282, C494-C500; Friedrich, B. et al., The serine/threonine kinases SGK2 and SGK3 are potent stimulators of the epithelial Na+ Channel alpha, beta, gamma-ENaC, Pflugers Arch. - Eur. J. Physiol. 2003, 445, 693-696). The interaction of ENaC and SGK is not by direct phosphorylation, but due to the inactivation of the ubiquitin ligase Nedd4-2 (Debonneville, C. et al., Phosphorylation of Nedd4-2 by Sgk1 regulates epithelial Na+ channel cell surface expression, EMBO J. 2001 , 20, 7052-7059) as a result of phosphorylation by SGK. As a result, the amount and residence time of ENaC in the cell membrane is increased (Staub, O. et al., Regulation of stability and function of the epithelial Na+ channel (ENaC) by ubiquitination, EMBO J. 1997, 16, 6325-6336). It has also been shown that the renal outer medullary potassium channel (ROMK1 ) and the sodium-hydrogen exchanger 3 (NHE3) are indirectly regulated by SGK, via the Na+/H+ exchange regulating factor 2 (NHERF2) as an intermediary molecule (Yun, C.C. et al., Glucocorticoid Activation of Na+/H+ Exchanger Isoform 3 Revisited. The Roles of SGK1 and NHERF2, J. Biol. Chem. 2002, 277, 7676-7683; Yun, C.C, Concerted Roles of SGK1 and the Na+/H+

Exchanger Regulatory Factor 2 (NHERF2) in Regulation of NHE3, Cell. Physiol, Biochem. 2003, 13, 29-40). In addition it has also been shown that SGK influences the Kv1 .3 channel-dependent K+ current (Gamper, N. et al., IGF-1 up-regulates K+ Channels via PI3-kinase, PDK1 and SGK1 , Pflugers Arch. 2002, 443, 625-634) and regulates the amino acid transporter SN1 and 4F2/LAT (Wagner, C.A. et al., The heterodimeric amino acid transporter 4F2hc/LAT1 is associated in Xenopus oocytes with a non-selective cation channel that is regulated by the serine/threonine kinase sgk-1 , J. Physiol. 2000, 526.1 , 35-46; Boehmer, C. et al., Properties and regulation of glutamine transporter SN1 by protein kinases SGK and PKB, Biochem. Biophys. Res. Commun. 2003, 306, 156-162). SGK-1 has also been shown to play a role in cell proliferation and electrolyte homeostasis (Vallon, V. et al., New insights into the role of serum- and glucocorticoid-inducible kinase SGK1 in the regulation of renal function and blood pressure, Curr. Opin. Nephrol. Hypertens. 2005, 14, 59-66; Lang, F. et al., Regulation of Channels by the Serum and Glucocorticoid-linducible Kinase -Implications for Transport, Excitability and Cell Proliferation, Cell. Physiol. Biochem. 2003, 13, 41 -50). SGK-1 is thought to regulate several cellular mechanisms that contribute to disease states. For example, SGK-1 has been shown to mediate fibronectin formation in diabetic nephropathy (Feng, Y. et al., SGK1 -mediated

Fibronectin Formation in Diabetic Nephropathy, Cell. Physiol. Biochem. 2005, 16, 237-244). SGK1 has also been shown to mediate insulin, IGF-1 , and aldosterone-induced Na+ retention in renal and cardiovascular disease (Vallon, V. et al., Curr. Opin. Nephrol. Hypertens. 2005, 14, 59-66; Lang, F. et al., Cell. Physiol. Biochem. 2003, 13, 41 -50). SGK1 has furthermore been shown to be activated by loss of laforin in Lafora disease, a genetic form of myoclonic epilepsy, SGK1 inhibition resulting in a reduction of abnormal glycogen accumulation and offering a way of treating Lafora disease (Singh, P. K. et al., Activation of serum/glucocorticoid-induced kinase 1 (SGK1 ) underlies increased glycogen levels, mTOR activation, and autophagy defects in Lafora disease, Mol. Biol. Cell 2013, 24, 3776-3786).

Osteoarthritis (OA) is one of the most common degenerative joint diseases and leads in an advanced stage to a loss of joint function. During the chronic course of illness, there is a destruction of the articular cartilage down to the underlying bone tissue, which makes a joint replacement surgery in affected patients necessary. In addition to the destruction of the cartilage, pathological changes in the synovial membrane and the ligaments can also be observed. The disease is temporarily accompanied by inflammatory processes like in rheumatoid arthritis, but differs from it. The exact causes of the disease are still unknown, however, several factors come into question, such as metabolic changes, mechanical stress, genetic disorders or joint injuries. Regardless of the original trigger, the degradation of articular cartilage occurs as a common pathological feature of OA. A key feature of the pathological condition of OA is the proteolytic cleavage of collagens and proteoglycans. Simultaneously a number of other processes occur such as anabolic repair mechanisms, ^differentiation of the cells or cell death. The precise molecular mechanisms underlying these processes are still poorly understood.

The healthy functioning of the adult cartilage is created by its unique biomechanical properties, providing both the resistance against high pressure as well as the necessary elasticity of the tissue. The decisive factor is the special organization of the cartilage tissue. Unlike most other tissues, the cartilage cells are not in direct contact but are embedded separately from each other in an extracellular matrix (ECM). The macromolecules of this ECM guarantee the viability of the articular cartilage and joints. The basic structure of the ECM consists of a network that is formed by fibrils of collagen types II, IX and XI. Proteoglycans, mainly aggrecan, are embedded in the ECM producing an extremely high osmotic water binding capacity. The water pressure generated in connection with the properties of the collagen backbone guarantees the specific properties of the cartilage. A main feature of the pathogenesis of OA is the loss of the ECM of the cartilage and the articular cartilage tissue. The function of the affected joint is restricted by or lost by this mechanism. In addition, various symptomatic parameters such as pain appear during symptomatic progression of the disease. Current treatments for osteoarthritis are limited mostly to the alleviation of symptomatic complaints. A causal therapy based on drugs, which leads to the decrease of cartilage degeneration, is not possible to current knowledge. Therefore, there is a considerable need for novel drugs for the prevention and/or therapy of osteoarthritis.

It has been shown, through comparative gene expression analysis of samples of total-cellular RNA from healthy and degenerated/degenerating cartilage that SGK-1 is expressed in degenerated/degenerating osteoarthritic cartilage, while it is not detectable in healthy articular cartilage (Bartnik, E. et al., Use of a

Serum/Glucocorticoid-regulated Kinase, WO 2006/061 130). Moreover, further experiments gave evidence of the causal implication of SGK in the pathogenesis of degenerative cartilage changes (Bartnik, E. et al., WO 2006/061 130). As a

conclusion of these studies, SGK-1 is specifically involved in pathological conditions of the cartilage, for example in the context of rheumatoid arthritis or osteoarthritis, in particular in the context of osteoarthritis, and thus represents a key molecule inducing cartilage degradative processes. Due to the high homology between the SGK family members, it is assumed that this also applies to the SGK-2 and SGK-3.

The identification of these relationships allows the discovery of drugs for the prevention or therapy of degenerative cartilage changes by determining the effect of potential drugs on the activity of SGK and/or the levels of SGK by known test methods. The causal implication of SGK in the pathogenesis of degenerative joint disease allows a focused search for therapeutic agents that target regulatory mechanisms for the restoration of normal cell physiology of cartilage. In the joints of mouse embryos SGK-1 mRNA was detected specifically in hypertrophic

chondrocytes but not in proliferative cells. The role of SGK-1 in this model of skeletal development and endochondral ossification shows that the natural occurrence of SGK-1 in cartilage is not associated with the synthesis and maintenance of cartilage, but exerts its function in the conversion (hypertrophy) and degradation. The expression of SGK-1 in osteoarthritic cartilage is thus a process that causes or promotes the pathology of OA. Due to its regulatory properties SGK-1 could be a key molecule for the induction of early pathological changes in cartilage as well as for the later degradative activities. Therefore, SGK-1 is a very relevant target for the pharmacological intervention in osteoarthritis.

To specifically study the function of SGK-1 during differentiation of cartilage, human SGK-1 was overexpressed in murine ATDC5 cells. In these experiments, it was clearly demonstrated that overexpression of SGK-1 causes inhibition of cartilage synthesis. Both the amount of Alcian blue stained proteoglycan as well as aggrecan mRNA was significantly reduced. A kinase deficient SGK-1 form, however, had no negative effect on these parameters. Regarding the effect of SGK-1 in OA-diseased articular cartilage, several conclusions can be drawn from these experiments. On the one hand, SGK-1 expressing chondrocytes are no longer able to synthesize sufficient extracellular matrix such as proteoglycans, which are essential for the function of the tissue. On the other hand, the cartilage cells are inhibited to compensate for, or repair, degradation processes by increasing the expression of genes such as

aggrecan. Therefore a function of SGK-1 as a potential cause and central factor of OA pathology is confirmed. SGK-1 thus represents a highly relevant target molecule for the development of novel drugs for the treatment of degenerative cartilage changes, especially osteoarthritis.

In view of the relevance of SGK-1 for various physiological processes outlined above, inhibitors of SGK-1 such as the compounds of the present invention can be used in the treatment, including therapy and prophylaxis, of various disease states in which SGK-1 activity plays a role or which are associated with an inappropriate SGK-1 activity, or in which an inhibition, regulation or modulation of signal transduction by SGK-1 is desired by the physician, for example degenerative joint disorders and degenerative cartilage changes including osteoarthritis, osteoarthrosis, rheumatoid arthritis, spondylosis, chondrolysis following joint trauma and prolonged joint immobilization after meniscus or patella injuries or ligament tears, connective tissue disorders such as collagenoses, periodontal disorders, wound-healing disturbances, diabetes including diabetes mellitus, diabetic nephropathy, diabetic neuropathy, diabetic angiopathy and microangiopathy, obesity, metabolic syndrome

(dyslipidaemia), systemic and pulmonary hypertension, cerebral infarctions, cardiovascular diseases including cardiac fibrosis after myocardial infarction, cardiac hypertrophy and heart failure, arteriosclerosis, renal diseases including

glomerulosclerosis, nephrosclerosis, nephritis, nephropathy and electrolyte excretion disorder, and any type of fibrosis and inflammatory processes including liver cirrhosis, lung fibrosis, fibrosing pancreatitis, rheumatism, arthritis, gout, Crohn's disease, chronic bronchitis, radiation fibrosis, sclerodermatitis, cystic fibrosis, scar formation and Alzheimer's disease. Inhibitors of SGK-1 such as the compounds of the present invention can also be used in the treatment of pain including acute pain like pain following injuries, post-operative pain, pain in association with an acute attack of gout and acute pain following jaw-bone surgery interventions, and chronic pain like pain associated with chronic musculoskeletal diseases, back pain, pain associated with osteoarthritis or rheumatoid arthritis, pain associated with inflammation, amputation pain, pain associated with multiple sclerosis, pain associated with neuritis, pain associated with carcinomas and sarcomas, pain associated with AIDS, pain

associated with chemotherapy, trigeminus neuralgia, headache, migraine, cephalalgia, neuropathic pains and post-herpes zoster neuralgia. Inhibitors of SGK-1 such as the compounds of the present invention can also be used in tumor therapy for inhibiting the growth of tumor cells and tumor metastases, and for the treatment of chronic disorders of the locomotor system such as inflammatory, immunologically or metabolically-related acute and chronic arthritides, arthropathies, myalgias and disturbances of bone metabolism. Further, inhibitors of SGK-1 such as the

compounds of the present invention can be used in the treatment of peptic ulcers, especially in forms that are triggered by stress, in the treatment of tinnitus, in the treatment of bacterial infections and in anti-infective therapy, for increasing the learning ability and attention, for counteracting cellular aging and stress and thus increasing life expectancy and fitness in the elderly, in states of neuronal excitability including epilepsy and progressive myoclonic epilepsy of the Lafora type (Lafora disease), in the treatment of glaucoma or cataracts, and in the treatment of

coagulopathies including dysfibrinogenaemia, hypoproconvertinaennia, haemophilia B, Stuart-Prower defect, prothrombin complex deficiency, consumption coagulopathy, fibrinolysis, immunokoagulopathy or complex coagulopathies. Further details about the physiological role of SGK are found in the literature, for example in the mentioned literature articles and others.

The identification of small compounds that specifically inhibit, regulate or modulate signal transduction by SGK, is therefore desirable and an object of the present invention. But besides being effective SGK inhibitors, it is desirable that such inhibitors also have further advantageous properties, for example high bioavailability, stability in plasma and liver, and selectivity versus other kinases or receptors whose inhibition or activation is not intended. Thus, it is an object of the present invention to provide SGK inhibitors which effectively inhibit an aberrant activity of SGK in a pathological context and which have further advantageous properties, for example high bioavailability, stability in plasma and liver, and selectivity versus other kinases and receptors which are not intended to be influenced in an agonistic or antagonistic manner. This object is achieved by providing the novel compounds of the formula I

which exhibit excellent SGK-1 inhibitory activity and are favorable agents with high bioavailability and stability in plasma and liver.

Thus, a subject of the present invention are the compounds of the formula I, in any of their stereoisomeric forms or a mixture of stereoisomeric forms in any ratio, and the pharmaceutically acceptable salts thereof,

wherein

Ar is selected from the series consisting of phenyl and a 5-membered or 6-membered, monocyclic, aromatic, heterocyclic group which comprises 1 , 2 or 3 identical or different ring heteroatoms selected from the series consisting of nitrogen, oxygen and sulfur, and is bonded via a ring carbon atom, which all are unsubstituted or

substituted by one or more identical or different substituents R5;

n is selected from the series consisting of 0, 1 and 2;

X is selected from the series consisting of N and CH;

Z is selected from the series consisting of a direct bond, O, S and N(R10);

R1 is selected from the series consisting of H, -N(R1 1 )-R12, -N(R13)-C(O)-R14, -N(R13)-S(O)2-R15, -N(R13)-C(O)-NH-R16, (Ci-C4)-alkyl and -(Ci-C4)-alkyl-O-R17;

R2 is selected from the series consisting of halogen, (Ci-C4)-alkyl, -O-(Ci-C4)-alkyl and -CN;

R3 is selected from the series consisting of H, (d-CeJ-alkyl, R30 and -(Ci-C4)-alkyl-R30, wherein (Ci-Cs)-alkyl is unsubstituted or substituted by one or more identical or different substituents R31 ;

R5 is selected from the series consisting of halogen, (Ci-C4)-alkyl, (C3-C7)-cycloalkyl, -(Ci-C4)-alkyl-(C3-C7)-cycloalkyl, -0-(Ci-C4)-alkyl, -O-(C3-C7)-cycloalkyl, -O-(d-C4)-alkyl-(C3-C7)-cycloalkyl, -C(O)-N(R6)-R7 and -CN,

and two groups R5 bonded to adjacent ring carbon atoms in Ar, together with the carbon atoms carrying them, can form a 5-membered to 8-membered, monocyclic, unsaturated ring which comprises 0, 1 or 2 identical or different ring heteroatoms selected from the series consisting of nitrogen, oxygen and sulfur, and which is unsubstituted or substituted by one or more identical or different substituents R8;

R6 and R7 are independently of one another selected from the series consisting of H and (Ci-C4)-alkyl;

R8 is selected from the series consisting of halogen, (Ci-C4)-alkyl, -O-(Ci-C4)-alkyl and -CN;

R10 is selected from the series consisting of H and (Ci-C4)-alkyl;

R1 1 and R12 are independently of one another selected from the series consisting of H, (Ci-C4)-alkyl, (C3-C7)-cycloalkyl, -(Ci-C4)-alkyl-(C3-C7)-cycloalkyl, Het1 , -(d-C4)-alkyl-Hetl and -(Ci-C4)-alkyl-phenyl, wherein phenyl is unsubstituted or substituted by one or more identical or different substituents R50,

or R1 1 and R12, together with the nitrogen atom carrying them, form a 4-membered to 7-membered, monocyclic, saturated, heterocyclic group which, in addition to the nitrogen atom carrying R1 1 and R12, comprises 0 or 1 further ring heteroatom selected from the series consisting of nitrogen, oxygen and sulfur, and which is

unsubstituted or substituted by one or more identical or different substituents selected from the series consisting of fluorine and (Ci-C4)-alkyl;

R13 is selected from the series consisting of H, (Ci-C4)-alkyl and (C3-C7)-cycloalkyl;

R14 and R16 are independently of one another selected from the series consisting of (Ci-C8)-alkyl, (C3-C7)-cycloalkyl, -(Ci-C4)-alkyl-(C3-C7)-cycloalkyl, phenyl, -(d-C4)-alkyl-phenyl, Het2 and -(Ci-C4)-alkyl-Het2, wherein (Ci-C8)-alkyl and (C3-C7)-cycloalkyl all are unsubstituted or substituted by one or more identical or different substituents selected from the series consisting of -OH and -O-(Ci-C4)-alkyl, and wherein phenyl and Het2 all are unsubstituted or substituted by one or more identical or different substituents R50;

R15 is selected from the series consisting of (Ci-CsJ-alkyl, phenyl and Het3, wherein phenyl and Het3 all are unsubstituted or substituted by one or more identical or different substituents R50;

R17 is selected from the series consisting of H and (Ci-C4)-alkyl;

R30 is a 3-membered to 12-membered, monocyclic or bicyclic, saturated, partially unsaturated or aromatic, cyclic group which comprises 0, 1 , 2 or 3 identical or different ring heteroatoms selected from the series consisting of nitrogen, oxygen and sulfur, which is unsubstituted or substituted by one or more identical or different substituents R32;

R31 is selected from the series consisting of halogen, -OH, -O-(Ci-C4)-alkyl, -O-(C3-C7)-cycloalkyl, -O-(Ci-C4)-alkyl-(C3-C7)-cycloalkyl, -N(R33)-R34, -CN and -C(O)-N(R35)-R36;

R32 is selected from the series consisting of halogen, (Ci-C4)-alkyl, (C3-C7)-cycloalkyl, -(Ci-C4)-alkyl-(C3-C7)-cycloalkyl, -(Ci-C4)-alkyl-O-R37, -(d-C4)-alkyl- N(R38)-R39, -(Ci-C4)-alkyl-CN, -C(0)-(Ci-C4)-alkyl, -CN, -OH, =O, -O-(d-C4)-alkyl, -N(R40)-R41 , -C(0)-0-(Ci-C4)-alkyl and -C(O)-N(R42)-R43;

R33, R34, R35, R36, R37, R38, R39, R40, R41 , R42 and R43 are independently of one another selected from the series consisting of H and (Ci-C4)-alkyl;

R50 is selected from the series consisting of halogen, (Ci-C4)-alkyl, -O-(Ci-C4)-alkyl and -CN;

Het1 is a 4-membered to 7-membered, monocyclic, saturated, heterocyclic group which comprises 1 or 2 identical or different ring heteroatoms selected from the series consisting of nitrogen, oxygen and sulfur, and is bonded via a ring carbon atom, and which is unsubstituted or substituted by one or more identical or different substituents selected from the series consisting of fluorine and (Ci-C4)-alkyl;

Het2 is a 4-membered to 7-membered, monocyclic, saturated, partially unsaturated or aromatic, heterocyclic group which comprises 1 or 2 identical or different ring heteroatoms selected from the series consisting of nitrogen, oxygen and sulfur, and is bonded via a ring carbon atom;

Het3 is a 5-membered or 6-membered, monocyclic, aromatic, heterocyclic group which comprises 1 , 2 or 3 identical or different ring heteroatoms selected from the series consisting of nitrogen, oxygen and sulfur, and is bonded via a ring carbon atom;

wherein all cycloalkyi groups, independently of any other substituents which can be present on a cycloalkyi group, can be substituted by one or more identical or different substituents selected from the series consisting of fluorine and (Ci-C4)-alkyl;

wherein all alkyl groups, independently of any other substituents which can be present on an alkyl group, can be substituted by one or more fluorine substituents.

If structural elements such as groups, substituents or numbers, for example, can occur several times in the compounds of the formula I, they are all independent of each other and can in each case have any of the indicated meanings, and they can in each case be identical to or different from any other such element. In a

dialkylamino group, for example, the alkyl groups can be identical or different.

Alkyl groups, i.e. saturated hydrocarbon residues, can be linear (straight-chain) or branched. This also applies if these groups are substituted or are part of another group, for example an -O-alkyl group (alkyloxy group, alkoxy group) or an HO-substituted alkyl group (-alkyl-OH, hydroxyalkyl group). Depending on the respective definition, the number of carbon atoms in an alkyl group can be 1 , 2, 3, 4, 5, 6, 7 or 8, or 1 , 2, 3, 4, 5 or 6, or 1 , 2, 3 or 4, or 1 , 2 or 3, or 1 or 2, or 1 . Examples of alkyl are methyl, ethyl, propyl including n-propyl and isopropyl, butyl including n-butyl, sec-butyl, isobutyl and tert-butyl, pentyl including n-pentyl, 1 -methylbutyl, isopentyl, neopentyl and tert-pentyl, hexyl including n-hexyl, 2,2-dimethylbutyl, 3,3-dimethylbutyl, 2-methylpentyl, 3-methylpentyl and isohexyl, heptyl including n-heptyl, and octyl including n-octyl and 2,2-dimethylhexyl. Examples of -O-alkyl groups are methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, tert-butoxy, n-pentoxy.

A substituted alkyl group can be substituted in any positions, provided that the respective compound is sufficiently stable and is suitable as a pharmaceutical active compound. The prerequisite that a specific group and a compound of the formula I are sufficiently stable and suitable as a pharmaceutical active compound, applies in general with respect to the definitions of all groups in the compounds of the formula I. Independently of any other substituents which can be present on an alkyl group, and unless specified otherwise, alkyl groups can be substituted by one or more fluorine substituents, for example by 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10 or 1 1 fluorine substituents, or by 1 , 2, 3, 4 or 5 fluorine substituents, or by 1 , 2 or 3 fluorine substituents, which can be located in any positions. I.e., independently of any other substituents which can be present on an alkyl group, an alkyl group can be unsubstituted by fluorine substituents, i.e. not carry fluorine substituents, or substituted by fluorine substituents, wherein all alkyl groups in the compounds of the formula I are independent of one

another with regard to the optional substitution by fluorine substituents. For example, in a fluoro-substituted alkyl group one or more methyl groups can carry three fluorine substituents each and be present as trifluoromethyl groups, and/or one or more methylene groups (CH2) can carry two fluorine substituents each and be present as difluoromethylene groups. The explanations with respect to the substitution of a group by fluorine also apply if the group additionally carries other substituents and/or is part of another group, for example of an -O-alkyl group. Examples of fluoro-substituted alkyl groups are -CF3 (trifluoromethyl), -CHF2, -CH2F, -CHF-CF3, -CHF-CHF2, -CHF-CH2F, -CH2-CF3, -CH2-CHF2, -CH2-CH2F, -CF2-CF3, -CF2-CHF2, -CF2-CH2F, -CH2-CHF-CF3, -CH2-CHF-CHF2, -CH2-CHF-CH2F, -CH2-CH2-CF3, -CH2-CH2-CHF2, -CH2-CH2-CH2F, -CH2-CF2-CF3, -CH2-CF2-CHF2, -CH2-CF2-CH2F, -CHF-CHF-CF3, -CHF-CHF-CHF2, -CHF-CHF-CH2F, -CHF-CH2-CF3, -CHF-CH2-CHF2, -CHF-CH2-CH2F, -CHF-CF2-CF3, -CHF-CF2-CHF2, -CHF-CF2-CH2F, -CF2-CHF-CF3, -CF2-CHF-CHF2, -CF2-CHF-CH2F, -CF2-CH2-CF3, -CF2-CH2-CHF2, -CF2-CH2-CH2F, -CF2-CF2-CF3, -CF2-CF2-CHF2, or -CF2-CF2-CH2F. Examples of fluoro-substituted -O-alkyl groups are trifluoromethoxy (-O-CF3), 2,2,2-trifluoroethoxy, pentafluoroethoxy and 3,3,3-trifluoropropoxy. With respect to all groups or substituents in the compounds of the formula I which can be an alkyl group which can generally contain one or more fluorine substituents, as an example of groups or substituents containing fluorine-substituted alkyl, which may be included in the definition of the group or substituent, the group CF3 (trifluoromethyl), or a respective group such as -O-CF3, may be mentioned.

The above explanations with respect to alkyl groups apply correspondingly to alkyl groups which in the definition of a group in the compounds of the formula I are bonded to two adjacent groups, or linked to two groups, and may be regarded as divalent alkyl groups (alkanediyl groups), like in the case of the alkyl part of a substituted alkyl group. Thus, such groups can also be linear or branched, the bonds to the adjacent groups can be located in any positions and can start from the same carbon atom or from different carbon atoms, and they can be unsubstituted or substituted by fluorine substituents independently of any other substituents.

Examples of such divalent alkyl groups are -CH2-, -CH2-CH2-, -CH2-CH2-CH2-,

-CH2-CH2-CH2-CH2-, -CH2-CH2-CH2-CH2-CH2-, -CH2-CH2-CH2-CH2-CH2-CH2-, -CH(CH3)-, -C(CH3)2-, -CH(CH3)-CH2-, -CH2-CH(CH3)-, -C(CH3)2-CH2-,

-CH2-C(CH3)2-. Examples of fluoro-substituted alkanediyl groups, which can contain 1 , 2, 3, 4, 5 or 6 fluorine substituents, or 1 , 2, 3 or 4 fluorine substituents, or 1 or 2 fluorine substituents, for example, are -CF2-, -CHF-, -CHF-CHF2-, -CHF-CHF-, -CH2-CF2-, -CH2-CHF-, -CF2-CF2-, -CF2-CHF-, -CH2-CHF-CF2-, -CH2-CHF-CHF-, -CH2-CH2-CF2-, -CH2-CH2-CHF, -CH2-CF2-CF2-, -CH2-CF2-CHF-, -CHF-CHF-CF2-, -CHF-CHF-CHF-, -CHF-CH2-CF2-, -CHF-CH2-CHF-, -CHF-CF2-CF2-, -CHF-CF2-CHF-, -CF2-CHF-CF2-, -CF2-CHF-CHF-, -CF2-CH2-CF2-, -CF2-CH2-CHF-, -CF2-CF2-CF2-, or -CF2-CF2-CHF-.

The number of ring carbon atoms in a (C3-C7)-cycloalkyl group can be 3, 4, 5, 6 or 7. Examples of cycloalkyi are cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl. Independently of any other substituents which can be present on a cycloalkyi group, and unless specified otherwise, cycloalkyi groups can be

substituted by one or more (Ci-C4)-alkyl substituents, for example by 1 , 2, 3 or 4 identical or different (Ci-C4)-alkyl substituents, for example by methyl groups, which can be located in any positions. I.e., independently of any other substituents which can be present on a cycloalkyi group, a cycloalkyi group can be unsubstituted by (Ci-C4)-alkyl substituents, i.e. not carry (Ci-C4)-alkyl substituents, or substituted by (Ci-C4)-alkyl substituents, wherein all cycloalkyi groups in the compounds of the formula I are independent of one another with regard to the optional substitution by (Ci-C4)-alkyl substituents. Examples of such alkyl-substituted cycloalkyi groups are 1 -methylcyclopropyl, 2,2-dimethylcyclopropyl, 1 -methylcyclopentyl, 2,3-dimethylcyclopentyl, 1 -methylcyclohexyl, 4-methylcyclohexyl, 4-isopropylcyclohexyl, 4-tert-butylcyclohexyl, 3,3,5,5-tetramethylcyclohexyl. Independently of any other substituents including (Ci-C4)-alkyl substituents which can be present on a cycloalkyi group, and unless specified otherwise, cycloalkyi groups can further be substituted by one or more fluorine substituents, for example by 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10 or 1 1 fluorine substituents, or by 1 , 2, 3, 4 or 5 fluorine substituents, or by 1 , 2 or 3 fluorine substituents, which can be located in any positions and can also be present in a (Ci-C4)-alkyl substituent. I.e., independently of any other substituents which can be

present on a cycloalkyl group, a cycloalkyl group can be unsubstituted by fluorine substituents, i.e. not carry fluorine substituents, or substituted by fluorine substituents, wherein all cycloalkyl groups in the compounds of the formula I are independent of one another with regard to the optional substitution by fluorine substituents.

Examples of fluoro-substituted cycloalkyl groups are 1 -fluorocyclopropyl, 2,2-difluorocyclopropyl, 3,3-difluorocyclobutyl, 1 -fluorocyclohexyl, 4,4-difluorocyclohexyl, 3,3,4,4,5,5-hexafluorocyclohexyl. Cycloalkyl groups can also be substituted

simultaneously by fluorine and alkyl. Examples of the group -(Ci-C4)-alkyl-(C3-C7)-cycloalkyl are cyclopropylmethyl-, cyclobutylmethyl-, cyclopentylmethyl-,

cyclohexylmethyl-, cycloheptylmethyl-, 1 -cyclopropylethyl-, 2-cyclopropylethyl-, 1 -cyclobutylethyl-, 2-cyclobutylethyl-, 1 -cyclopentylethyl-, 2-cyclopentylethyl-, 1 -cyclohexylethyl-, 2-cyclohexylethyl-, 1 -cycloheptylethyl-, 2-cycloheptylethyl-. In one embodiment of the invention, a -(Ci-C4)-alkyl-(C3-C7)-cycloalkyl group in any one or more occurrences of such a group, independently of any other occurrences, is a -(Ci-C2)-alkyl-(C3-C7)-cycloalkyl group, in another embodiment a -CH2-(C3-C7)-cycloalkyl group. In the group -(Ci-C4)-alkyl-(C3-C7)-cycloalkyl, and likewise in all other groups, the terminal hyphen denotes the free bond via which the group is bonded, and thus indicates via which subgroup a group composed of subgroups is bonded.

In substituted phenyl groups, including phenyl groups representing Ar, for example, the substituents can be located in any positions. In monosubstituted phenyl groups, the substituent can be located in position 2, in position 3 or in position 4. In

disubstituted phenyl groups, the substituents can be located in positions 2 and 3, in positions 2 and 4, in positions 2 and 5, in positions 2 and 6, in positions 3 and 4, or in positions 3 and 5. In trisubstituted phenyl groups, the substituents can be located in positions 2, 3 and 4, in positions 2, 3 and 5, in positions 2, 3 and 6, in positions 2, 4 and 5, in positions 2, 4 and 6, or in positions 3, 4 and 5. If a phenyl group carries four substituents, some of which can be fluorine atoms, for example, the substituents can be located in positions 2, 3, 4 and 5, in positions 2, 3, 4 and 6, or in positions 2, 3, 5 and 6. If a polysubstituted phenyl group or any other polysubstituted group carries different substituents, each substituent can be located in any suitable position, and the present invention comprises all positional isomers. The number of substituents in

a substituted phenyl group can be 1 , 2, 3, 4 or 5. In one embodiment of the invention, the number of substituents in a substituted phenyl group, is 1 , 2, 3 or 4, in another embodiment 1 , 2 or 3, in another embodiment 1 or 2, in another embodiment 1 , wherein the number of substituents in any occurrence of such a substituted group is independent of the number of substituents in other occurrences.

In heterocyclic groups, including the groups Het1 , Het2, Het3, heterocyclic groups representing Ar, heterocyclic groups R30 and other heterocyclic rings which can be present in the compounds of the formula I, such as rings formed by two group together with the atom or atoms carrying them, the hetero ring members can be present in any combination and located in any suitable ring positions, provided that the resulting group and the compound of the formula I are suitable and sufficiently stable as a pharmaceutical active compound. In one embodiment of the invention, two oxygen atoms in any heterocyclic ring in the compounds of the formula I cannot be present in adjacent ring positions. In another embodiment of the invention, two hetero ring members selected from the series consisting of oxygen atoms and sulfur atoms cannot be present in adjacent ring positions in any heterocyclic ring in the compounds of the formula I. In another embodiment of the invention, two hetero ring members selected from the series consisting of nitrogen atoms carrying an exocyclic group like a hydrogen atom or a substituent, sulfur atoms and oxygen atoms cannot be present in adjacent ring positions in any heterocyclic ring in the compounds of the formula I. The choice of hetero ring members in an aromatic heterocyclic ring is limited by the prerequisite that the ring is aromatic, i.e. it comprises a cyclic system of six delocalized pi electrons in case of a monocycle or 10 delocalized pi electrons in case of a bicycle. Monocyclic aromatic heterocycles are 5-membered or 6-membered rings and, in the case of a 5-membered ring, comprise one ring heteroatom selected from the series consisting of oxygen, sulfur and nitrogen, wherein this ring nitrogen carries an exocyclic group like a hydrogen atom or a substituent, and optionally one or more further ring nitrogen atoms, and, in the case of a 6-membered ring, comprise one or more nitrogen atoms as ring heteroatoms, but no oxygen atoms and sulfur atoms as ring heteroatoms. Heterocyclic groups in the compounds of the formula I can be bonded via a ring carbon atom or a ring nitrogen atom, unless specified

otherwise in the definition of the respective group, wherein a heterocyclic group can be bonded via any suitable carbon atom or nitrogen atom, respectively, in the ring. In substituted heterocyclic groups, the substituents can be located in any positions.

The number of ring heteroatoms which can be present in a heterocyclic group in the compounds of the formula I, the number of ring members which can be present, and the degree of saturation, or hydrogenation, i.e. whether the heterocyclic group is saturated and does not contain a double bond within the ring, or whether it is partially unsaturated and contains one or more, for example one or two, double bonds within the ring but is not aromatic, or whether it is aromatic and thus contains two double bonds within the ring in the case of a 5-membered monocyclic aromatic heterocycle and three double bonds within the ring in the case of a 6-membered monocyclic aromatic heterocycle, for example, is specified in the definitions of the individual groups in the compounds of the formula I. Examples of heterocyclic ring systems, from which heterocyclic groups in the compounds of the formula I including, for example, Het1 , Het2, Het3, heterocyclic groups representing Ar, heterocyclic groups R30 and rings formed by two groups together with the atom or atoms carrying them, can be derived, and from any one or more of which any of the heterocyclic groups in the compounds of the formula I is selected in one embodiment of the invention, provided that the ring system is comprised by the definition of the group, are oxetane, thietane, azetidine, furan, tetrahydrofuran, thiophene, tetrahydrothiophene, pyrrole, pyrroline, pyrrolidine, [1 ,3]dioxole, [1 ,3]dioxolane, isoxazole ([1 ,2]oxazole),

isoxazoline, isoxazolidine, oxazole ([1 ,3]oxazole), oxazoline, oxazolidine, isothiazole ([1 ,2]thiazole), isothiazoline, isothiazolidine, thiazole ([1 ,3]thiazole), thiazoline, thiazolidine, pyrazole, pyrazoline, pyrazolidine, imidazole, imidazoline, imidazolidine, [1 ,2,3]triazole, [1 ,2,4]triazole, [1 ,2,4]oxadiazole, [1 ,3,4]oxadiazole, [1 ,2,5]oxadiazole, [1 ,2,4]thiadiazole, pyran, tetrahydropyran, thiopyran, tetrahydrothiopyran, 2,3-dihydro[1 ,4]dioxine, 1 ,4-dioxane, pyridine, 1 ,2,5,6-tetrahydropyridine, piperidine, morpholine, thiomorpholine, piperazine, pyridazine, pyrimidine, pyrazine,

[1 ,2,4]triazine, oxepane, thiepane, azepane, [1 ,3]diazepane, [1 ,4]diazepane,

[1 ,4]oxazepane, [1 ,4]thiazepane, benzofuran, isobenzofuran, benzothiophene

(benzo[b]thiophene), 1 H-indole, 2,3-dihydro-1 H-indole, 2H-isoindole, 2-aza-

spiro[4.4]nonane, 2-aza-spiro[4.5]decane, 2-aza-spiro[4.6]undecane, 2-aza-spiro[5.5]undecane, 3-aza-spiro[5.5]undecane, 6-aza-spiro[2.5]octane, 7-aza-spiro[3.5]nonane, 8-aza-spiro[4.5]decane, benzo[1 ,3]dioxole, benzoxazole,

benzthiazole, 1 H-benzimidazole, chroman, isochroman, thiochroman,

benzo[1 ,4]dioxane, 3,4-dihydro-2H-benzo[b][1 ,4]dioxepine (3,4-dihydro-2H-1 ,5-benzodioxepine), 3,4-dihydro-2H-benzo[1 ,4]oxazine, 1 -oxa-8-aza-spiro[4.5]decane, 2-oxa-6-aza-spiro[3,3]heptane, 2-oxa-6-aza-spiro[3.4]octane, 2-oxa-6-aza-spiro[3.5]nonane, 2-oxa-7-aza-spiro[3,5]nonane, 8-oxa-2-aza-spiro[4.5]decane, 3,4-dihydro-2H-benzo[1 ,4]thiazine, quinoline, 5,6,7,8-tetrahydroquinoline, isoquinoline, 5,6,7,8-tetrahydroisoquinoline, cinnoline, quinazoline, quinoxaline, phthalazine and [1 ,8]naphthyhdine, which can all be unsubstituted or substituted in any suitable positions as specified in the definition of the respective group in the compounds of the formula I, wherein the given degree of unsaturation is by way of example only, and in the individual groups also ring systems with a higher or lower degree of saturation or unsaturation can be present as specified in the definition of the group. Ring sulfur atoms, in particular in saturated and partially unsaturated heterocycles, can generally carry one or two oxo groups, i.e. doubly bonded oxygen atoms (=O), and in such heterocycles, besides a ring sulfur atom, also an S(O) group (S(=O)) and an S(O)2 group (S(=O)2) can be present as hetero ring member.

As mentioned, unless specified otherwise in the definition of the respective group in the compounds of the formula I, heterocyclic groups can be bonded via any suitable ring carbon atom and ring nitrogen atom, for example in the case of heterocyclic groups representing R30. Thus, for example, among others can an oxetane and a thietane ring be bonded via positions 2 and 3, an azetidine ring via positions 1 , 2 and 3, a furan ring, a tetrahydrofuran ring, a thiophene ring and a tetrahydrothiophene ring via positions 2 and 3, a pyrrole ring and a pyrrolidine ring via positions 1 , 2 and 3, an isoxazole ring and an isothiazole ring via positions 3, 4 and 5, a pyrazole ring via positions 1 , 3, 4 and 5, an oxazole ring and a thiazole ring via positions 2, 4 and 5, an imidazole ring and an imidazolidine ring via positions 1 , 2, 4 and 5, a tetrahydropyran ring and a tetrahydrothiopyran ring via positions 2, 3 and 4, a 1 ,4-dioxane ring via position 2, a pyridine ring via positions 2, 3 and 4, a piperidine ring via positions 1 , 2, 3 and 4, a morpholine ring and a thiomorpholine ring via positions 2, 3 and 4, a piperazine ring via positions 1 and 2, a pyrimidine ring via positions 2, 4 and 5, a pyrazine ring via position 2, an azepane ring via positions 1 , 2, 3 and 4, a benzofuran ring and a benzothiophene ring via positions 2, 3, 4, 5, 6 and 7, a 1 H-indole ring and a 2,3-dihydro-1 H-indole ring via positions 1 , 2, 3, 4, 5, 6 and 7, a benzo[1 ,3]dioxole ring via positions 4, 5, 6 and 7, a benzoxazole ring and a benzthiazole ring via positions 2, 4, 5, 6 and 7, a 1 H-benzimidazole ring via positions 1 , 2, 4, 5, 6 and 7, a benzo[1 ,4]dioxane ring via positions 5, 6, 7 and 8, a quinoline ring via positions 2, 3, 4, 5, 6, 7 and 8, a 5,6,7,8-tetrahydroquinoline ring via positions 2, 3 and 4, an isoquinoline ring via positions 1 , 3, 4, 5, 6, 7 and 8, a 5,6,7,8-tetrahydroisoquinoline ring via positions 1 , 3 and 4, wherein the resulting residues of the heterocyclic groups can all be unsubstituted or substituted in any suitable positions as specified in the definition of the respective group in the compounds of the formula I.

Halogen is fluorine, chlorine, bromine or iodine. In one embodiment of the invention, halogen is in any of its occurrences fluorine, chlorine or bromine, in another embodiment fluorine or chlorine, in another embodiment fluorine, in another embodiment chlorine, wherein all occurrences of halogen are independent of each other.

The present invention comprises all stereoisomeric forms of the compounds of the formula I, for example all enantiomers and diastereomers including cis/trans isomers. The invention likewise comprises mixtures of two or more stereoisomeric forms, for example mixtures of enantiomers and/or diastereomers including cis/trans isomers, in all ratios. Asymmetric centers contained in the compounds of the formula I can all independently of each other have S configuration or R configuration. The invention relates to enantiomers, both the levorotatory and the dextrorotatory antipode, in enantiomerically pure form and essentially enantiomerically pure form, and in the form of their racemate, i.e. a mixture of the two enantiomers in molar ratio of 1 :1 , and in the form of mixtures of the two enantiomers in all ratios. The invention likewise relates to diastereomers in the form of pure and essentially pure diastereomers and in the form of mixtures of two or more diastereomers in all ratios. The invention also comprises all cis/trans isomers of the compounds of the formula I in pure form and essentially pure form, and in the form of mixtures of the cis isomer and the trans isomer in all ratios. Cis/trans isomerism can occur in substituted rings. The preparation of individual stereoisomers, if desired, can be carried out by resolution of a mixture according to customary methods, for example, by chromatography or crystallization, or by use of stereochemically uniform starting compounds in the synthesis, or by stereoselective reactions. Optionally, before a separation of stereoisomers a derivatization can be carried out. The separation of a mixture of stereoisomers can be carried out at the stage of the compound of the formula I or at the stage of an intermediate in the course of the synthesis. For example, in the case of a compound of the formula I containing an asymmetric center the individual enantiomers can be prepared by preparing the racemate of the compound of the formula I and resolving it into the enantiomers by high pressure liquid

chromatography on a chiral phase according to standard procedures, or resolving the racemate of any intermediate in the course of its synthesis by such chromatography or by crystallization of a salt thereof with an optically active amine or acid and converting the enantiomers of the intermediate into the enantiomeric forms of the final compound of the formula I, or by performing an enantioselective reaction in the course of the synthesis. The invention also comprises all tautomeric forms of the compounds of the formula I.

Besides the free compounds of the formula I, i.e. compounds in which acidic and basic groups are not present in the form of a salt, the present invention comprises also salts of the compounds of the formula I, in particular their physiologically acceptable salts, or toxicologically acceptable salts, or pharmaceutically acceptable salts, which can be formed on one or more acidic or basic groups in the compounds of the formula I, for example on basic heterocyclic moieties. The compounds of the formula I may thus be deprotonated on an acidic group by an inorganic or organic base and be used, for example, in the form of the alkali metal salts. Compounds of the formula I comprising at least one basic group may also be prepared and used in the form of their acid addition salts, for example in the form of pharmaceutically acceptable salts with inorganic acids and organic acids, such as salts with

hydrochloric acid and thus be present in the form of the hydrochlorides, for example. Salts can in general be prepared from acidic and basic compounds of the formula I by reaction with an acid or base in a solvent or diluent according to customary procedures. If the compounds of the formula I simultaneously contain an acidic and a basic group in the molecule, the invention also includes internal salts (betaines, zwitterions) in addition to the salt forms mentioned. The present invention also comprises all salts of the compounds of the formula I which, because of low physiological tolerability, are not directly suitable for use as a pharmaceutical, but are suitable as intermediates for chemical reactions or for the preparation of

physiologically acceptable salts, for example by means of anion exchange or cation exchange.

In one embodiment of the invention, an aromatic heterocycle representing the group Ar comprises 1 or 2 identical or different ring heteroatoms, in another embodiment 1 or 2 identical or different ring heteroatoms which are selected from the series consisting of nitrogen and sulfur. In another embodiment, an aromatic heterocycle representing Ar is a 5-membered heterocycle which comprises 1 or 2 identical or different ring heteroatoms which are selected from the series consisting of nitrogen and sulfur, or it is a 6-membered heterocycle which comprises 1 or 2 ring

heteroatoms which are nitrogen atoms, in another embodiment it is a 5-membered heterocycle which comprises 1 or 2 identical or different ring heteroatoms which are selected from the series consisting of nitrogen and sulfur, which heterocycles are all unsubstituted or substituted by one or more substituents identical or different R5. In another embodiment, an aromatic heterocycle representing Ar is selected from the series consisting of thiophene, thiazole, pyrazole, imidazole, pyridine, pyridazine, pyrimidine and pyrazine, in another embodiment from the series consisting of thiophene, thiazole, pyrazole, imidazole and pyridine, in another embodiment from the series consisting of thiophene, thiazole, pyrazole and imidazole, in another embodiment from the series consisting of thiophene and pyrazole, in another embodiment it is thiophene, and in another embodiment it is pyrazole, which heterocycles are all unsubstituted or substituted by one or more identical or different substituents R5. In one embodiment of the invention, Ar is phenyl which is

unsubstituted or substituted by one or more identical or different substituents R5, in another embodiment Ar is phenyl which is substituted by one or more identical or different substituents R5, in another embodiment Ar is a 5-membered or 6-membered aromatic heterocycle which is unsubstituted or substituted by one or more identical or different substituents R5, and in another embodiment Ar is a 5-membered or 6-membered aromatic heterocycle which is substituted by one or more identical or different substituents R5. In one embodiment, Ar is substituted by one or more identical or different substituents R5. In one embodiment of the invention, the number of identical or different substituents R5 which can be present in the group Ar is 1 , 2, 3 or 4, in another embodiment it is 1 , 2 or 3, in another embodiment it is 1 or 2, in another embodiment it is 1 , in another embodiment it is 2, 3 or 4, in another embodiment it is 2 or 3, in another embodiment it is 3, in another embodiment it is 2.

In one embodiment of the invention, the number n is selected from the series consisting of 0 and 1 , in another embodiment from the series consisting of 1 and 2, in another embodiment it is 1 , in another embodiment it is 0.

In one embodiment of the invention, X is N, and the compounds of the formula I thus are N-[4-(1 H-pyrazolo[3,4-d]pyrimidin-6-yl)-phenyl]-sulfonamides. In another embodiment of the invention, X is CH, and the compounds of the formula I thus are N-[4-(1 H-pyrazolo[4,3-c]pyridin-6-yl)-phenyl]-sulfonamides.

In case the divalent group Z is a direct bond, the group R3 is directly bonded via a single bond to the ring carbon in position 4 of the bicyclic ring system depicted in formula I which carries Z, and the compound of the formula I thus is a compound of the formula la, wherein Ar, n, X, R1 , R2 and R3 are defined as in the compounds of the formula I. In one embodiment of the invention, Z is selected from the series

consisting of a direct bond, O and N(R10), in another embodiment from the series consisting of a direct bond and O, in another embodiment from the series consisting of a direct bond and N(R10), in another embodiment from the series consisting of O, S and N(R10), in another embodiment from the series consisting of O and N(R10), in another embodiment Z is a direct bond, in another embodiment Z is O, i.e. an oxygen atom, in another embodiment Z is S, i.e. a sulfur atom, and in another embodiment Z is N(R10), i.e. a nitrogen atom carrying the atom or group R10.

In one embodiment of the invention, R1 is selected from the series consisting of H, -N(R1 1 )-R12, -N(R13)-C(O)-R14, -N(R13)-S(O)2-R15, -N(R13)-C(O)-NH-R16 and (Ci-C4)-alkyl, in another embodiment from the series consisting of H, -N(R1 1 )-R12, -N(R13)-C(O)-R14, -N(R13)-S(O)2-R15 and -N(R13)-C(O)-NH-R16, in another embodiment from the series consisting of -N(R1 1 )-R12, -N(R13)-C(O)-R14, -N(R13)-S(O)2-R15, -N(R13)-C(O)-NH-R16 and (Ci-C4)-alkyl, in another embodiment from the series consisting of -N(R1 1 )-R12, -N(R13)-C(O)-R14, -N(R13)-S(O)2-R15 and -N(R13)-C(O)-NH-R16, in another embodiment from the series consisting of -N(R1 1 )-R12 and N(R13)-C(O)-R14, and in another embodiment R1 is -N(R1 1 )-R12. In another embodiment, R1 is selected from the series consisting of H, -N(R1 1 )-R12, -N(R13)-C(O)-R14 and (Ci-C4)-alkyl, in another embodiment from the series consisting of H, -N(R1 1 )-R12 and (Ci-C4)-alkyl, and in another embodiment from the series consisting of -N(R1 1 )-R12 and (Ci-C4)-alkyl. In another embodiment, R1 is selected from the series consisting of H, (Ci-C4)-alkyl and -(Ci-C4)-alkyl-O-R17, in another embodiment from the series consisting of H and (Ci-C4)-alkyl, in another embodiment R1 is H, in another embodiment R1 is (Ci-C4)-alkyl, and in another embodiment R1 is -(Ci-C4)-alkyl-O-R17. In one embodiment, a (Ci-C4)-alkyl group representing R1 or present in -(Ci-C4)-alkyl-O-R17 is (Ci-C3)-alkyl, in another embodiment it is (Ci-C2)-alkyl, in another embodiment it is methyl. As applies to alkyl groups in general, in all these embodiments an alkyl group representing R1 or present in R1 , for example the group (Ci-C4)-alkyl representing R1 , can be

substituted by one or more fluorine substituents, i.e., independently of any other substituents on the alkyl group it is unsubstituted by fluorine substituents or it is substituted by fluorine substituents. In one embodiment, an alkyl group representing R1 or present in R1 , for example the group (Ci-C4)-alkyl representing R1 ,

independently of any other substituents on the alkyl group, is unsubstituted by fluorine substituents. In another embodiment, an alkyl group representing R1 or present in R1 , for example the group (Ci-C4)-alkyl representing R1 , independently of any other substituents on the alkyl group, is substituted by one or more fluorine substituents, for example by 1 , 2, 3, 4 or 5 fluorine substituents or by 1 , 2 or 3 fluorine substituents.

In one embodiment of the invention, R2 is selected from the series consisting of halogen, (Ci-C4)-alkyl and -O-(Ci-C4)-alkyl, in another embodiment from the series consisting of halogen and (Ci-C4)-alkyl, in another embodiment from the series consisting of halogen and -O-(Ci-C4)-alkyl, in another embodiment from the series consisting of halogen, -O-(Ci-C4)-alkyl and -CN, in another embodiment from the series consisting of halogen and -CN, in another embodiment from the series consisting of halogen, wherein in all these embodiments alkyl can be substituted by one or more, for example by 1 , 2, 3, 4 or 5, or by 1 , 2 or 3, fluorine substituents, as applies to alkyl groups in general. In one embodiment, a (Ci-C4)-alkyl group representing R2 or present in R2 is (Ci-C3)-alkyl, in another embodiment it is (C1-C2)-alkyl, in another embodiment it is methyl. In one embodiment, halogen representing R2 is selected from the series consisting of fluorine and chlorine, in another embodiment it is fluorine. Ring carbon atoms in the divalent phenyl group depicted in formula I which are not bonded to adjacent groups depicted in formula I, and which do not carry a group R2, carry hydrogen atoms. Thus, in case the number n is 0 and hence no group R2 is present, all four carbon atoms in the ring positions of the divalent phenyl group depicted in formula I, which in formula Γ are designated as positions 2', 3', 5' and 6', carry hydrogen atoms. In case the number n is 1 and hence one group R2 is present, one of the four carbon atoms in the ring positions of the divalent phenyl group depicted in formula I, which in formula Γ are designated as 2', 3', 5' and 6', carries the group R2 and the other three said carbon atoms carry hydrogen atoms. In case the number n is 2 and hence two groups R2 are present, two of the four carbon atoms in the ring positions of the divalent phenyl group depicted in formula I, which in formula Γ are designated as positions 2', 3', 5' and 6', carry the groups R2 and the other two said carbon atoms carry hydrogen atoms.

Groups R2 can be present in any positions of the divalent phenyl group depicted in formula I which in formula Γ are designated as 2', 3', 5' and 6'. If one group R2 is present, in one embodiment of the invention the group R2 is present in the position which in formula Γ is designated as position 2', which is equivalent to position 6', and in another embodiment it is present in the position which in formula Γ is designated as position 3', which is equivalent to position 5'. If two groups R2 are present, in one embodiment of the invention the groups R2 are present in the positions which in formula Γ are designated as positions 2' and 3', in another embodiment in the positions which in formula Γ are designated as positions 2' and 5', in another embodiment in the positions which in formula Γ are designated as positions 2' and 6', in another embodiment in the positions which in formula Γ are designated as positions 3' and 5'.

In one embodiment of the invention, R3 is selected from the series consisting of H, (Ci-C8)-alkyl and R30, in another embodiment from the series consisting of H, (Ci-Cs)-alkyl and -(Ci-C4)-alkyl-R30, in another embodiment from the series consisting of H and (Ci-CsJ-alkyl, in another embodiment from the series consisting of H and R30, in another embodiment from the series consisting of (Ci-CsJ-alkyl, R30 and -(Ci-C4)- alkyl-R30, in another embodiment from the series consisting of (Ci-Cs)-alkyl and R30, in another embodiment from the series consisting of R30 and -(CrC4)-alkyl-R30, in another embodiment R3 is H, in another embodiment R3 is (Ci-CsJ-alkyl, in another embodiment R3 is R30, and in another embodiment R3 is -(CrC4)-alkyl-R30, wherein in all these embodiments (Ci-Cs)-alkyl is unsubstituted or substituted by one or more identical or different substituents R31 , and wherein in one embodiment of the invention all these embodiments independently apply to compounds of the formula I in which Z is a direct bond on the one hand, and to compounds of the formula I in which Z is selected from the series consisting of O, S and N(R10) on the other hand, and R3 can thus be defined differently for such compounds. For example, in one embodiment R3 is selected from the series consisting of H, (Ci-Cs)-alkyl and R30 in case Z is a direct bond, and R3 is selected from the series consisting of H, (Ci-Cs)-alkyl, R30 and -(Ci-C4)-alkyl-R30 in case Z is selected from the series consisting of O, S and N(R10), in another embodiment R3 is selected from the series consisting of H, (Ci-Cs)-alkyl and R30 in case Z is a direct bond, and R3 is selected from the series consisting of H, (Ci-Cs)-alkyl and R30 in case Z is selected from the series consisting of O, S and N(R10), in another embodiment R3 is selected from the series consisting of H, (Ci-Cs)-alkyl and R30 in case Z is a direct bond, and R3 is selected from the series consisting of (Ci-CsJ-alkyl, R30 and -(Ci-C4)-alkyl-R30 in case Z is selected from the series consisting of O, S and N(R10), in another embodiment R3 is selected from the series consisting of H, (Ci-Cs)-alkyl and R30 in case Z is a direct bond, and R3 is selected from the series consisting of (Ci-Cs)-alkyl and R30 in case Z is selected from the series consisting of O, S and N(R10), in another embodiment R3 is selected from the series consisting of H and R30 in case Z is a direct bond, and R3 is selected from the series consisting of (Ci-CsJ-alkyl, R30 and -(Ci-C4)-alkyl-R30 in case Z is selected from the series consisting of O, S and N(R10), and in another embodiment R3 is selected from the series consisting of H and R30 in case Z is a direct bond, and R3 is selected from the series consisting of (Ci-Cs)-alkyl and R30 in case Z is selected from the series consisting of O, S and N(R10), wherein in all these embodiments (Ci-Cs)-alkyl is unsubstituted or substituted by one or more identical or different substituents R31 . In one embodiment, the number of substituents R31 which is optionally present in alkyl groups representing R3, is 1 , 2, 3, 4 or 5, in another embodiment it is 1 , 2, 3 or 4, in another embodiment it is 1 , 2 or 3, in another embodiment it is 1 or 2, in another embodiment it is 1 , wherein independently of substituents R31 an alkyl group representing R3 can be substituted by one or more fluorine substituents, as applies to alkyl groups in general. In one embodiment, a (Ci-Cs)-alkyl group representing R3 is (Ci-C6)-alkyl, in another embodiment it is (Ci-C4)-alkyl, in another embodiment it is (Ci-C3)-alkyl, in another embodiment it is (C1-C2)-alkyl, which groups all are unsubstituted or substituted by one or more identical or different substituents R31 and/or fluorine substituents. In one embodiment, the (Ci-C4)-alkyl moiety in the group -(Ci-C4)-alkyl-R30 representing R3 is (Ci-C3)-alkyl, in another embodiment it is (Ci-C2)-alkyl, in another embodiment it is methyl.

If two groups R5 bonded to adjacent ring carbon atoms in Ar together with the ring carbon atoms carrying them form a 5-membered to 8-membered ring, this ring is at least mono-unsaturated, i.e., the resulting ring contains at least one double bond within the ring, which double bond is present between the said two adjacent ring carbon in the aromatic ring Ar which are common to the ring Ar and the ring formed by the two groups R5, and because of the rules of nomenclature for fused rings is regarded as a double bond present in both rings. The ring formed by two groups R5 together with the carbon atoms carrying them can contain 1 , 2 or 3 double bonds within the ring. In one embodiment, the formed ring contains 1 or 2 double bonds, in another embodiment 1 double bond within the ring. In the case of a 6-membered carbocyclic or heterocyclic ring or a 5-membered heterocyclic ring the formed ring can be aromatic and, together with the aromatic ring Ar, form a bicydic aromatic ring system, for example a naphthalene ring system, a quinoline ring system, an isoquinoline ring system or a benzothiophene ring system. In one embodiment of the invention, not more than two substituents R5 on Ar, together with the ring carbon atoms in Ar carrying them, form a ring, i.e., in this embodiment not more than one ring formed by two groups R5 together with the ring carbon atoms in Ar carrying them is fused to Ar. If paired groups R5 forming a ring are present, further individual groups R5 can additionally be present on Ar, for example groups like halogen, (Ci-C4)-alkyl or -0-(Ci-C4)-alkyl.

The case that two groups R5 bonded to adjacent ring carbon atoms in Ar together with the carbon atoms carrying them form a 5-membered to 8-membered unsaturated ring, can in other terms be regarded as two groups R5 together forming a divalent residue comprising a chain of 3 to 6 atoms of which 0, 1 or 2 are identical or different heteroatoms selected from the series consisting of nitrogen, oxygen and sulfur, the terminal atoms of which are bonded to the two adjacent ring carbon atoms in Ar. Examples of such divalent residues, from any one or more of which two groups R5 bonded to adjacent ring carbon atoms in Ar are selected in one embodiment of the invention, are the residues -CH2-CH2-CH2-, -CH2-CH2-CH2-CH2-, -CH2-CH2-CH2-CH2-CH2-, -CH=CH-CH=CH-, -N=CH-CH=CH-, -CH=CH-CH=N-, -CH=N-CH=CH-,

-CH=CH-N=CH-,-O-CH2-CH2-,-CH2-CH2-O-, -O-CH2-O-, -O-CH2-CH2-O-, -O-CH2-CH2-CH2-O-, -O-CH2-CH2-CH2-CH2-O-,-S-CH=CH-, -CH=CH-S-, =CH-S-CH=, -N=CH-S-, -S-CH=N-, -N=CH-O-, -O-CH=N-, -NH-CH2-CH2-O-, -O-CH2-CH2-NH-, -S-CH2-CH2-NH- and -NH-CH2-CH2-S-, which can all be substituted by one or more identical or different substituents R8, and can thus also be present, for example, as the divalent residues -O-CF2-O-, -O-C(CH3)2-O-, -S-C(CI)=CH-, -CH=C(CI)-S-, -N(CH3)-CH2-CH2-O-, -O-CH2-CH2-N(CH3)-, -S-CH2-CH2-N(CH3)- and -N(CH3)-CH2-CH2-S-. In one embodiment of the invention, the ring heteroatoms which are optionally present in a ring formed by two groups R5 bonded to adjacent ring carbon atoms in Ar together with the carbon atoms carrying them, are selected from the series consisting of nitrogen and oxygen, in another embodiment from the series consisting of oxygen and sulfur, and in another embodiment they are oxygen atoms. In one embodiment of the invention, the ring which can be formed by two groups R5 bonded to adjacent ring carbon atoms in Ar together with the ring carbon atoms carrying them, is a 5-membered to 7-membered, in another embodiment a 5-membered to 6-membered, in another embodiment a 6-membered to 7-membered, in another embodiment a 5-membered, in another embodiment a 6-membered ring, in another embodiment a 7-membered ring. In one embodiment of the invention, the ring which can be formed by two groups R5 bonded to adjacent carbon atoms in Ar together with the carbon atoms carrying them, comprises 0 ring heteroatoms, i.e. it is a carbocyclic ring, and in another embodiment it comprises 1 or 2 identical or different ring heteroatoms. In one embodiment of the invention, the number of

substituents R8 which can be present in a ring formed by two groups R5 bonded to adjacent ring carbon atoms in Ar together with the carbon atoms carrying them, is 1 , 2, 3 or 4, in another embodiment 1 , 2 or 3, in another embodiment 1 or 2, in another embodiment 1 , in another embodiment it is 0.

In one embodiment of the invention, R5 is selected from the series consisting of halogen, (Ci-C4)-alkyl, (C3-C7)-cycloalkyl, -O-(Ci-C4)-alkyl, -O-(C3-C7)-cycloalkyl, -C(O)-N(R6)-R7 and -CN, in another embodiment from the series consisting of halogen, (Ci-C4)-alkyl, (C3-C7)-cycloalkyl, -O-(Ci-C4)-alkyl, -C(O)-N(R6)-R7 and -CN, in another embodiment from the series consisting of halogen, (Ci-C4)-alkyl, -O-(Ci-C4)-alkyl, -O-(C3-C7)-cycloalkyl, -C(O)-N(R6)-R7 and -CN, in another embodiment from the series consisting of halogen, (Ci-C4)-alkyl, -O-(Ci-C4)-alkyl, -C(O)-N(R6)-R7 and -CN, in another embodiment from the series consisting of halogen, (Ci-C4)-alkyl, -O-(Ci-C4)-alkyl and -CN, in another embodiment from the series consisting of halogen, -(Ci-C4)-alkyl and -CN, in another embodiment from the series consisting of halogen, -O-(Ci-C4)-alkyl and -CN, in another embodiment from the series consisting of -O-(Ci-C4)-alkyl and -CN, in another embodiment from the series consisting of halogen and -CN, in another embodiment from the series consisting of halogen, and in all these embodiments two groups R5 bonded to adjacent ring carbon atoms in Ar, together with the carbon atoms carrying them, can form a 5-membered to 8-membered unsaturated ring which comprises 0, 1 or 2 identical or different ring heteroatoms selected from the series consisting of nitrogen, oxygen and sulfur, and which is unsubstituted or substituted by one or more identical or different substituents R8.

In one embodiment of the invention, R5 is selected from the series consisting of halogen, (Ci-C4)-alkyl, (C3-C7)-cycloalkyl, -O-(Ci-C4)-alkyl, -O-(C3-C7)-cycloalkyl, -C(O)-N(R6)-R7 and -CN, in another embodiment from the series consisting of halogen, (Ci-C4)-alkyl, (C3-C7)-cycloalkyl, -O-(Ci-C4)-alkyl, -C(O)-N(R6)-R7 and -CN, in another embodiment from the series consisting of halogen, (Ci-C4)-alkyl, -O-(Ci-C4)-alkyl, -O-(C3-C7)-cycloalkyl, -C(O)-N(R6)-R7 and -CN, in another embodiment from the series consisting of halogen, (Ci-C4)-alkyl, -O-(Ci-C4)-alkyl, -C(O)-N(R6)-R7 and -CN, in another embodiment from the series consisting of halogen, (Ci-C4)-alkyl, -O-(Ci-C4)-alkyl and -CN, in another embodiment from the series consisting of halogen, -(Ci-C4)-alkyl and -CN, in another embodiment from the series consisting of halogen, -O-(Ci-C4)-alkyl and -CN, in another embodiment from the series consisting of -O-(Ci-C4)-alkyl and -CN, in another embodiment from the series consisting of halogen and -CN, in another embodiment from the series consisting of halogen.

In one embodiment, substituents R5 which are bonded to a ring nitrogen atom in Ar, such as in the case of a pyrrole, pyrazole or imidazole ring representing Ar, are selected from the series consisting of (Ci-C4)-alkyl, (C3-C7)-cycloalkyl, -(Ci-C4)-alkyl-(C3-C7)-cycloalkyl and -C(O)-N(R6)-R7, in another embodiment from the series consisting of (Ci-C4)-alkyl, (C3-C7)-cycloalkyl and -(Ci-C4)-alkyl-(C3-C7)-cycloalkyl, in another embodiment from the series consisting of (Ci-C4)-alkyl.

In one embodiment of the invention, a (Ci-C4)-alkyl group which represents R5 or is present in the group -O-(Ci-C4)-alkyl representing R5, is a (Ci-Cs)-alkyl group, in another embodiment a (Ci-C2)-alkyl group, in another embodiment a methyl group, wherein all these alkyl groups can optionally be substituted by fluorine substituents as applies to alkyl groups in general, and also occur as a trifluoromethyl group, for example. In one embodiment, an alkyl group representing R5 or present in a group representing R5 is, independently of any other alkyl group occurring in R5, not substituted by fluorine substituents. In one embodiment, a (C3-C7)-cycloalkyl group representing R5 or present in a group representing R5, is a (C3-C6)-cycloalkyl group, in another embodiment a (C3-C4)-cycloalkyl group, in another embodiment a

cyclopropyl group. In one embodiment, halogen representing R5 is selected from the series consisting of fluorine and chlorine.

Examples of groups Ar, including the optional substituents R5 on Ar, from any one or more of which Ar is selected in one embodiment of the invention, are 2-chloro-phenyl, 2-fluoro-phenyl, 3-fluoro-phenyl, 2,3-dichloro-phenyl, 2,5-dichloro-phenyl, 2,5-difluoro-phenyl, 2-chloro-3-fluoro-phenyl, 2-chloro-4-fluoro-phenyl, 3-chloro-2-fluoro-phenyl, 5-chloro-2-fluoro-phenyl, 2,3,5-trifluoro-phenyl, 2,4,5-trifluoro-phenyl, 2- chloro-3,5-difluoro-phenyl, 2-chloro-4,5-difluoro-phenyl, 3-chloro-2,5-difluoro-phenyl,

3- chloro-2,6-difluoro-phenyl, 5-chloro-2,4-difluoro-phenyl, 2-fluoro-5-methyl-phenyl, 2-fluoro-5-methoxy-phenyl, 2-chloro-5-methoxy-phenyl, 2-bromo-4,5-dinnethoxy-phenyl, 2-fluoro-4,5-dimethoxy-phenyl, 4,5-dimethoxy-2-methyl-phenyl, 2-cyano-phenyl, 3-cyano-phenyl, 2-cyano-3-fluoro-phenyl, 2-cyano-5-fluoro-phenyl, 3-cyano- 4- fluoro-phenyl, 5-cyano-2-fluoro-phenyl, 3-chloro-2-cyano-phenyl, 5-chloro-2-cyano-phenyl, 2-cyano-5-methyl-phenyl, 5-cyano-2-methyl-phenyl, 2-cyano-5-methoxy-phenyl, 2-carbamoyl-phenyl, 4-bromo-thiophen-2-yl, 4-chloro-thiophen-3-yl, 5-bromo-thiophen-2-yl, 5-chloro-thiophen-2-yl, 2,5-dichloro-thiophen-3-yl, 4,5-dichloro-thiophen-2-yl, 5-chloro-1 ,3-dimethyl-pyrazol-4-yl, 7-chloro-2,3-dihydro-benzo[1 ,4]dioxin-6-yl, 8-bromo-3,4-dihydro-2H-benzo[b][1 ,4]dioxepin-7-yl, 8-chloro-3,4-dihydro-2H-benzo[b][1 ,4]dioxepin-7-yl.

In one embodiment of the invention, R6 and R7 are independently of one another selected from the series consisting of hydrogen and (Ci-C3)-alkyl, in another embodiment from the series consisting of hydrogen and (Ci-C2)-alkyl, in another embodiment from the series consisting of hydrogen and methyl, and in another embodiment R6 and R7 are hydrogen.

In one embodiment of the invention, substituents R8 which can be present in a ring formed by two groups R5 bonded to adjacent ring carbon atoms in Ar together with the carbon atoms carrying them, are selected from the series consisting of halogen, (Ci-C4)-alkyl and -CN, in another embodiment from the series consisting of halogen, -O-(Ci-C4)-alkyl and -CN, in another embodiment from the series consisting of halogen and (Ci-C4)-alkyl, in another embodiment from the series consisting of (Ci-C4)-alkyl. In one embodiment, substituents R8 which are bonded to a ring nitrogen atom in a ring from by two groups R5 bonded to adjacent ring carbon atoms in Ar together with the carbon atoms carrying them, are selected from the series consisting of (Ci-C4)-alkyl.

In one embodiment of the invention, R10 is selected from the series consisting of hydrogen and (Ci-C3)-alkyl, in another embodiment from the series consisting of

hydrogen and (CrC2)-alkyl, in another embodiment from the series consisting of hydrogen and methyl, and in another embodiment R10 is hydrogen.

The monocyclic heterocycle which can be formed by the groups R1 1 and R12 together with the nitrogen atom carrying them, which heterocycle is thus bonded via a ring nitrogen atom, can be 4-membered, 5-membered, 6-membered or 7-membered. In one embodiment of the invention, the heterocycle formed by the groups R1 1 and R12 together with the nitrogen atom carrying them, is 4-membered to 6-membered, in another embodiment it is 5-membered or 6-membered, in another embodiment it is 6-membered. In one embodiment, the further ring heteroatom which is optionally present in a heterocycle formed by the groups R1 1 and R12 together with the nitrogen atom carrying them, is selected from the series consisting of nitrogen and oxygen, in another embodiment it is a nitrogen atom, and in another embodiment it is an oxygen atom, and in another embodiment no further ring heteroatom is present. In one embodiment of the invention, the number of

substituents selected from the series consisting of fluorine and (Ci-C4)-alkyl, which can be present in a ring formed by the groups R1 1 and R12 together with the nitrogen atom carrying them, is 1 , 2 or 3, in another embodiment it is 1 or 2, in another embodiment it is 1 . In one embodiment of the invention, substituents which can be present in a ring formed by the groups R1 1 and R12 together with the nitrogen atom carrying them, are fluorine substituents, and in another embodiment they are (Ci-C4)-alkyl substituents, for example methyl substituents. In one

embodiment are substituents in a ring formed by the groups R1 1 and R12 together with the nitrogen atom carrying them, which are bonded to a ring nitrogen atom, selected from the series consisting of (Ci-C4)-alkyl. Examples of heterocyclic groups, from any one or more of which the heterocyclic group formed by the groups R1 1 and R12 together with the nitrogen atom carrying them is selected in one embodiment of the invention, are azetidin-1 -yl, pyrrolidin-1 -yl, piperidin-1 -yl, morpholin-4-yl, thiomorpholin-4-yl, and 4-methylpiperazin-1 -yl.

In one embodiment of the invention, one of the groups R1 1 and R12 is selected from the series consisting of hydrogen and (Ci-C4)-alkyl, and the other of the groups R1 1 and R12 is selected from the series consisting of hydrogen, (Ci-C4)-alkyl, (C3-C7)-cycloalkyl, -(Ci-C4)-alkyl-(C3-C7)-cycloalkyl, Het1 , -(Ci-C4)-alkyl-Het1 and -(d-C4)-alkyl-phenyl, in another embodiment the other of the groups R1 1 and R12 is selected from the series consisting of hydrogen, (Ci-C4)-alkyl, -(Ci-C4)-alkyl-(C3-C7)-cycloalkyl and -(Ci-C4)-alkyl-Het1 , in another embodiment the other of the groups R1 1 and R12 is selected from the series consisting of hydrogen, (Ci-C4)-alkyl and -(Ci-C4)-alkyl-Het1 , in another embodiment the groups R1 1 and R12 are independently of one another selected from the series consisting of hydrogen, (Ci-C4)-alkyl, -(Ci-C4)-alkyl-(C3-C7)-cycloalkyl and -(Ci-C4)-alkyl-Het1 , in another embodiment the groups R1 1 and R12 are independently of one another selected from the series consisting of hydrogen, (Ci-C4)-alkyl and -(Ci-C4)-alkyl-Het1 , in another embodiment the groups R1 1 and R12 are independently of one another selected from the series consisting of hydrogen and (Ci-C4)-alkyl, and in another embodiment the groups R1 1 and R12 are both hydrogen, i.e., in this latter embodiment the group -N(R1 1 )-R12 representing R1 is the group -NH2 (amino), or in all these embodiments R1 1 and R12, together with the nitrogen atom carrying them, form a monocyclic, 4-membered to 7-membered, saturated heterocycle which, in addition to the nitrogen atom carrying R1 1 and R12, comprises 0 or 1 further ring heteroatom selected from the series consisting of nitrogen, oxygen and sulfur, and which is unsubstituted or substituted by one or more identical or different substituents selected from the series consisting of fluorine and (Ci-C4)-alkyl.

In one embodiment of the invention, R1 1 and R12 are independently of one another selected from the series consisting of hydrogen (H), (Ci-C4)-alkyl, (C3-C7)-cycloalkyl, -(Ci-C4)-alkyl-(C3-C7)-cycloalkyl, Het1 , -(Ci-C4)-alkyl-Het1 and -(Ci-C4)-alkyl-phenyl, wherein phenyl is unsubstituted or substituted by one or more identical or different substituents R50. In another embodiment, one of the groups R1 1 and R12 is selected from the series consisting of hydrogen and (Ci-C4)-alkyl, and the other of the groups R1 1 and R12 is selected from the series consisting of hydrogen, (Ci-C4)-alkyl, (C3-C7)-cycloalkyl, -(Ci-C4)-alkyl-(C3-C7)-cycloalkyl, Het1 , -(Ci-C4)-alkyl-Het1 and -(Ci-C4)-alkyl-phenyl, in another embodiment the other of the groups R1 1 and R12 is selected from the series consisting of hydrogen, (Ci-C4)-alkyl, -(Ci-C4)-alkyl- (C3-C7)-cycloalkyl and -(Ci-C4)-alkyl-Het1 , and in another embodiment the other of the groups R1 1 and R12 is selected from the series consisting of hydrogen, (Ci-C4)-alkyl and -(Ci-C4)-alkyl-Het1 . In one embodiment, the groups R1 1 and R12 are independently of one another selected from the series consisting of hydrogen, (Ci-C4)-alkyl, -(Ci-C4)-alkyl-(C3-C7)-cycloalkyl and -(Ci-C4)-alkyl-Het1 , in another embodiment the groups R1 1 and R12 are independently of one another selected from the series consisting of hydrogen, (Ci-C4)-alkyl and -(Ci-C4)-alkyl-Het1 , in another embodiment the groups R1 1 and R12 are independently of one another selected from the series consisting of hydrogen and (Ci-C4)-alkyl, and in another embodiment the groups R1 1 and R12 are both hydrogen, i.e., in this latter

embodiment the group -N(R1 1 )-R12 representing R1 is the group -NH2.

In one embodiment, one of the groups R1 1 and R12 is hydrogen, and the other of the groups R1 1 and R12 is selected from the series consisting of hydrogen, (Ci-C4)-alkyl, (C3-C7)-cycloalkyl, -(Ci-C4)-alkyl-(C3-C7)-cycloalkyl, Het1 , -(Ci-C4)-alkyl-Het1 and -(Ci-C4)-alkyl-phenyl, in another embodiment the other of the groups R1 1 and R12 is selected from the series consisting of hydrogen, (Ci-C4)-alkyl, -(Ci-C4)-alkyl-(C3-C7)-cycloalkyl and -(Ci-C4)-alkyl-Het1 , in another embodiment the other of the groups R1 1 and R12 is selected from the series consisting of hydrogen, (Ci-C4)-alkyl and -(Ci-C4)-alkyl-Het1 , and in another embodiment the other of the groups R1 1 and R12 is selected from the series consisting of hydrogen and (Ci-C4)-alkyl.

In one embodiment of the invention, R13 is selected from the series consisting of hydrogen and (Ci-C4)-alkyl, in another embodiment from the series consisting of hydrogen and (Ci-C3)-alkyl, in another embodiment from the series consisting of hydrogen and (Ci-C2)-alkyl, in another embodiment from the series consisting of hydrogen and methyl, and in another embodiment R13 is hydrogen.

In one embodiment of the invention, R14 is selected from the series consisting of (C3-C7)-cycloalkyl, -(Ci-C4)-alkyl-(C3-C7)-cycloalkyl, phenyl, -(Ci-C4)-alkyl-phenyl, Het2 and -(Ci-C4)-alkyl-Het2, in another embodiment from the series consisting of (C3-C7)-cycloalkyl, -(Ci-C4)-alkyl-(C3-C7)-cycloalkyl, phenyl, -(Ci-C4)-alkyl-phenyl and Het2, in another embodiment from the series consisting of (C3-C7)-cycloalkyl, phenyl, -(Ci-C4)-alkyl-phenyl, Het2 and -(Ci-C4)-alkyl-Het2, in another embodiment from the series consisting of (C3-C7)-cycloalkyl, phenyl, -(Ci-C4)-alkyl-phenyl and Het2, in another embodiment from the series consisting of (C3-C7)-cycloalkyl, phenyl and Het2, in another embodiment from the series consisting of (C3-C7)-cycloalkyl and Het2, in another embodiment R14 is (C3-C7)-cycloalkyl, in another embodiment R14 is Het2, and in another embodiment R14 is phenyl, wherein in all these embodiments (C3-C7)-cycloalkyl groups all are unsubstituted or substituted by one or more identical or different substituents selected from the series consisting of -OH and -O-(Ci-C4)-alkyl and, independently thereof, one or more identical or different substituents selected from the series consisting of fluorine and (Ci-C4)-alkyl as applies to cycloalkyl groups in general, and phenyl and Het2 groups all are unsubstituted or substituted by one or more identical or different substituents R50. In one embodiment, the number of substituents selected from the series consisting of -OH and -O-(Ci-C4)-alkyl, which can be present in a (Ci-Cs)-alkyl group representing R14 or a (C3-C7)-cycloalkyl group occurring in R14, is 1 , 2 or 3, in another embodiment it is 1 or 2, in another embodiment it is 1 . In one embodiment, the number of substituents R50 which can be present in a phenyl group or Het2 group representing R14 or occurring in R14, is 1 , 2 or 3, in another embodiment it is 1 or 2, in another embodiment it is 1 .

In one embodiment of the invention, R15 is selected from the series consisting of phenyl and Het3, in another embodiment from the series consisting of (Ci-Cs)-alkyl and phenyl, and in another embodiment R15 is phenyl, wherein in all these

embodiments phenyl and Het3 all are unsubstituted or substituted by one or more identical or different substituents R50. In one embodiment, the number of

substituents R50 which can be present in a phenyl group or Het3 group representing R15 is 1 , 2, 3 or 4, in another embodiment it is 1 , 2 or 3, in another embodiment it is 1 or 2, in another embodiment it is 1 .

In one embodiment of the invention, R16 is selected from the series consisting of (Ci-C8)-alkyl, (C3-C7)-cycloalkyl, -(Ci-C4)-alkyl-(C3-C7)-cycloalkyl, -(Ci-C4)-alkyl-phenyl, Het2 and -(Ci-C4)-alkyl-Het2, in another embodiment from the series consisting of

(C3-C7)-cycloalkyl, -(Ci-C4)-alkyl-(C3-C7)-cycloalkyl, -(Ci-C4)-alkyl-phenyl, Het2 and -(CrC4)-alkyl-Het2, in another embodiment from the series consisting of -(Ci-C4)-alkyl-phenyl, Het2 and -(CrC4)-alkyl-Het2, in another embodiment from the series consisting of -(Ci-C4)-alkyl-phenyl and -(CrC4)-alkyl-Het2, wherein (Ci-Cs)-alkyl and (C3-C7)-cycloalkyl all are unsubstituted or substituted by one or more identical or different substituents selected from the series consisting of -OH and -O-(Ci-C4)-alkyl and, independently thereof, fluorine substituents and, in case of cycloalkyl groups, (Ci-C4)-alkyl substituents, and wherein phenyl and Het2 all are unsubstituted or substituted by one or more identical or different substituents R50. In one embodiment, the number of substituents selected from the series consisting of -OH and -O-(Ci-C4)-alkyl, which can be present in a (Ci-Cs)-alkyl group representing R16 or a (C3-C7)-cycloalkyl group occurring in R16, is 1 or 2, in another embodiment it is 1 , and in another embodiment it is 0. In one embodiment, the number of substituents R50 which can be present in a phenyl group or Het2 group representing R16 or occurring in R16, is 1 , 2 or 3, in another embodiment it is 1 or 2, in another embodiment it is 1 , and in another embodiment it is 0.

In one embodiment of the invention, R17 is (Ci-C4)-alkyl, in another embodiment R17 is hydrogen. In one embodiment, a (Ci-C4)-alkyl group representing R17 is (C1-C3)-alkyl, in another embodiment it is (Ci-C2)-alkyl, in another embodiment it is methyl.

The cyclic group R30, which can be monocyclic and bicyclic, can contain 3, 4, 5, 6, 7, 8, 9, 10, 1 1 or 12 ring members. In one embodiment of the invention, R30 contains 3, 4, 5, 6, 7, 8, 9, 10 or 1 1 ring members, in another embodiment 3, 4, 5, 6, 7, 8, 9 or 10 ring members, in another embodiment 3, 4, 5, 6, 7, 8 or 9 ring members. In one embodiment, the number of ring members in a monocyclic group R30 is 3, 4, 5, 6 or 7, in another embodiment 3, 4, 5 or 6, in another embodiment 3 or 4, in another embodiment 5, 6 or 7, in another embodiment 5 or 6, in another embodiment 3, in another embodiment 4, in another embodiment 5, in another embodiment 6, and the number of ring members in a bicyclic group R30 is 6, 7, 8, 9, 10, 1 1 or 12, in another embodiment 6, 7, 8, 9, 10 or 1 1 , in another embodiment 6, 7, 8, 9 or 10, in another embodiment 7, 8, 9, 10 or 1 1 , in another embodiment 7, 8, 9 or 10, in another

embodiment 7, 8 or 9, in another embodiment 8, 9 or 10. In one embodiment, the number of ring members of the cyclic group R30 is from 3 to 12 in the case of a carbocyclic ring, and from 4 to 12 in the case of a heterocyclic ring. In one

embodiment, the cyclic group R30 is monocyclic, in another embodiment it is bicyclic. A bicyclic group R30 can be a fused ring system or a bridged ring system or a spirocyclic ring system. In one embodiment, a bicyclic group R30 is a fused or bridged ring system, in another embodiment it is a fused or spirocyclic ring system, in another embodiment it is a bridged or spirocyclic ring system, in another embodiment it is a fused ring system, in another embodiment it is a bridged ring system, and in another embodiment it is a spirocyclic ring system. In one embodiment, the cyclic group R30 is a saturated group, i.e. it does not contain a double bond within the ring, or it is an aromatic group, i.e. it contains two double bonds within the ring in the case of a 5-membered monocyclic aromatic heterocyde which double bonds, together with an electron pair on a ring heteroatom, form a delocalized cyclic system of six pi electrons, and three double bonds within the ring in the case of a phenyl group or a 6-membered monocyclic aromatic heterocyde, or two, three, four or five double bonds within two fused rings in the case of a bicyclic group comprising one or two aromatic rings. In another embodiment, R30 is a partially unsaturated group, i.e. it contains one or more, for example one or two, double bonds within the ring via which it is bonded, but is not aromatic within this ring. In another embodiment, R30 is a saturated group or it is a partially unsaturated group, in another embodiment R30 is an aromatic group or it is a partially unsaturated group, in another embodiment R30 is a saturated group, and in another embodiment R30 is an aromatic group.

The cyclic group R30 can be a carbocyclic group, i.e. comprise 0 (zero) ring heteroatoms, or a heterocyclic group, i.e. comprise 1 , 2 or 3 identical or different ring heteroatoms. In one embodiment, R30 comprises 0, 1 or 2 identical or different ring heteroatoms, in another embodiment 0 or 1 ring heteroatom. In another embodiment, R30 comprises 0 ring heteroatoms, i.e. R30 is a carbocyclic group. In another embodiment R30 is a heterocyclic group which comprises 1 , 2 or 3 identical or different ring heteroatoms, in another embodiment 1 or 2 identical or different ring heteroatoms, in another embodiment 1 ring heteroatom. In one embodiment, the ring

heteroatoms in R30 are selected from the series consisting of nitrogen and oxygen, in another embodiment from the series consisting of oxygen and sulfur, in another embodiment they are nitrogen atoms, and in another embodiment they are oxygen atoms. Heterocyclic groups representing R30 can be bonded to the group Z via a ring carbon atom or a ring nitrogen atom. In one embodiment, a heterocyclic group representing R30 is bonded via a ring carbon atom, in another embodiment it is bonded via a ring nitrogen atom.

Examples of carbocyclic groups, which may represent R30 and any one or more of which may be included in the definition of R30 in one embodiment of the invention, and from any one or more of which R30 is selected in another embodiment, are cycloalkyl groups such as (C3-C7)-cycloalkyl, including cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl, cycloalkenyl groups such as (C5-C7)-cycloalkenyl, including cyclopentenyl, cyclohexenyl and cycloheptenyl, bicycloalkyl groups such as (C6-Ci2)-bicycloalkyl, phenyl groups, indanyl groups, including indan- 1 - yl and indan-2-yl, and naphthyl groups, including naphthalen-1 -yl and naphthalen- 2- yl, for example, which can all be unsubstituted or substituted by one or more identical or different substituents R32. The explanations given above, for example with respect to cycloalkyl groups and phenyl groups, apply also to such groups representing R30.

Examples of heterocyclic groups, which may represent R30 and any one or more of which may be included in the definition of R30 in one embodiment of the invention, and from any one or more of which R30 is selected in another embodiment, are 4-membered to 7-membered, monocyclic, saturated, partially unsaturated or aromatic, heterocyclic groups which comprise 1 , 2 or 3 identical or different ring heteroatoms selected from the series consisting of nitrogen, oxygen and sulfur and are bonded via a nitrogen atom, 6-membered to 12-membered, bicyclic, saturated or partially unsaturated, heterocyclic groups which comprise 1 , 2 or 3 identical or different ring heteroatoms selected from the series consisting of nitrogen, oxygen and sulfur and are bonded via a nitrogen atom, and the groups Het1 , Het2 and Het3, and more specifically oxetanyl including oxetan-2-yl and oxetan-3-yl, tetrahydrofuranyl including tetrahydrofuran-2-yl and tetrahydrofuran-3-yl, tetrahydropyranyl including tetrahydropyran-2-yl, tetrahydropyran-3-yl and tetrahydropyran-4-yl, oxepanyl including oxepan-2-yl, oxepan-3-yl and oxepan-4-yl, azetidinyl including azetidin-1 -yl, azetidin-2-yl and azetidin-3-yl, pyrrolidinyl including pyrrol id in-1 -yl, pyrrol id in-2-yl and pyrrol id in-3-yl, piperidinyl including piperidin-1 -yl, piperidin-2-yl, piperidin-3-yl and piperidin-4-yl, azepanyl including azepan-1 -yl, azepan-2-yl, azepan-3-yl and azepan- 4- yl, morpholinyl including morpholin-2-yl, morpholin-3-yl and morpholin-4-yl, thiomorpholinyl including thiomorpholin-2-yl, thiomorpholin-3-yl and thiomorpholin-4-yl, piperazinyl including piperazin-1 -yl and piperazin-2-yl, furanyl including furan-2-yl and furan-3-yl, thiophenyl (thienyl) including thiophen-2-yl and thiophen-3-yl, pyrrolyl including pyrrol-1 -yl, pyrrol-2-yl and pyrrol-3-yl, isoxazolyl including isoxazol-3-yl, isoxazol-4-yl and isoxazol-5-yl, oxazolyl including oxazol-2-yl, oxazol-4-yl and oxazol- 5- yl, thiazolyl including thiazol-2-yl, thiazol-4-yl and thiazol-5-yl, pyrazolyl including pyrazol-1 -yl, pyrazol-3-yl, pyrazol-4-yl and pyrazol-5-yl, imidazolyl including

imidazolyl-1 -yl, imidazol-2-yl, imidazol-4-yl and imidazol-5-yl, [1 ,2,4]triazolyl including [1 ,2,4]triazol-1 -yl, [1 ,2,4]triazol-3-yl and [1 ,2,4]triazol-5-yl, pyridinyl (pyridyl) including pyridin-2-yl, pyridin-3-yl and pyridin-4-yl, pyrazinyl including pyrazin-2-yl, for example, which can all be unsubstituted or substituted by one or more identical or different substituents R32. The explanations given above and below, for example with respect to heterocyclic groups in general and the groups Het1 , Het2 and Het3, apply also to such groups representing R30.

In one embodiment of the invention, the number of substituents R32 which can be present in R30, is 1 , 2, 3, 4, 5 or 6, in another embodiment it is 1 , 2, 3, 4 or 5, in another embodiment it is 1 , 2, 3 or 4, in another embodiment it is 1 , 2 or 3, in another embodiment it is 1 or 2, in another embodiment it is 1 . In another embodiment, R30 is unsubstituted.

In one embodiment of the invention, R31 is selected from the series consisting of halogen, -OH, -O-(Ci-C4)-alkyl, -O-(C3-C7)-cycloalkyl, -O-(Ci-C4)-alkyl-(C3-C7)-cycloalkyl, -N(R33)-R34 and -CN, in another embodiment from the series consisting of halogen, -OH, -O-(Ci-C4)-alkyl, -O-(C3-C7)-cycloalkyl, -N(R33)-R34 and -CN, in

another embodiment from the series consisting of halogen, -OH, -O-(Ci-C4)-alkyl, -O-(C3-C7)-cycloalkyl, -N(R33)-R34, -CN and -C(O)-N(R35)-R36, in another embodiment from the series consisting of halogen, -OH, -O-(Ci-C4)-alkyl, -O-(C3-C7)-cycloalkyl, -O-(Ci-C4)-alkyl-(C3-C7)-cycloalkyl and -N(R33)-R34, in another embodiment from the series consisting of halogen, -OH, -O-(Ci-C4)-alkyl, -O-(C3-C7)-cycloalkyl, -O-(Ci-C4)-alkyl-(C3-C7)-cycloalkyl, -N(R33)-R34 and -C(O)-N(R35)-R36, in another embodiment from the series consisting of halogen, -OH, -O-(Ci-C4)-alkyl, -O-(C3-C7)-cycloalkyl and -N(R33)-R34, in another embodiment from the series consisting of halogen, -OH, -O-(Ci-C4)-alkyl, -O-(C3-C7)-cycloalkyl, -N(R33)-R34 and -C(O)-N(R35)-R36, in another embodiment from the series consisting of halogen, -OH, -O-(Ci-C4)-alkyl and -N(R33)-R34, in another embodiment from the series consisting of halogen, -OH, -O-(Ci-C4)-alkyl, -N(R33)-R34 and -C(O)-N(R35)-R36, in another embodiment from the series consisting of halogen, -OH, -O-(Ci-C4)-alkyl, -N(R33)-R34 and -CN, in another embodiment from the series consisting of halogen, -OH, -O-(Ci-C4)-alkyl, -N(R33)-R34, -CN and -C(O)-N(R35)-R36, in another embodiment from the series consisting of halogen, -OH, -O-(Ci-C4)-alkyl, -O-(C3-C7)-cycloalkyl and -O-(Ci-C4)-alkyl-(C3-C7)-cycloalkyl, in another embodiment from the series consisting of halogen, -OH, -O-(Ci-C4)-alkyl and-O-(C3-C7)-cycloalkyl, in another embodiment from the series consisting of halogen, -OH and -O-(Ci-C4)-alkyl, in another embodiment from the series consisting of halogen and -N(R33)-R34, in another embodiment from the series consisting of -OH, -O-(Ci-C4)-alkyl and -N(R33)-R34, in another embodiment from the series consisting of -OH, -O-(Ci-C4)-alkyl, -N(R33)-R34 and -C(O)-N(R35)-R36, in another embodiment from the series consisting of -OH, -O-(Ci-C4)-alkyl, -O-(C3-C7)-cycloalkyl and -O-(Ci-C4)-alkyl-(C3-C7)-cycloalkyl, in another embodiment from the series consisting of -OH, -O-(Ci-C4)-alkyl and-O-(C3-C7)-cycloalkyl. In one embodiment, halogen representing R31 is selected from the series consisting of fluorine and chlorine, in another embodiment halogen representing R31 is fluorine.

In one embodiment of the invention, R32 is selected from the series consisting of halogen, (Ci-C4)-alkyl, (C3-C7)-cycloalkyl, -(Ci-C4)-alkyl-(C3-C7)-cycloalkyl, -(d-C4)-alkyl-O-R37, -(Ci-C4)-alkyl-N(R38)-R39, -C(O)-(Ci-C4)-alkyl, -OH, =O, -O-(d-C4)-alkyl, -N(R40)-R41 , -C(O)-O-(Ci-C4)-alkyl and -C(O)-N(R42)-R43, in another

embodiment from the series consisting of halogen, (Ci-C4)-alkyl, (C3-C7)-cycloalkyl, -(Ci-C4)-alkyl-(C3-C7)-cycloalkyl, -(Ci-C4)-alkyl-O-R37, -(Ci-C4)-alkyl-N(R38)-R39, -OH, =O, -O-(Ci-C4)-alkyl, -N(R40)-R41 , -C(O)-O-(Ci-C4)-alkyl and -C(O)-N(R42)-R43, in another embodiment from the series consisting of halogen, (Ci-C4)-alkyl, (C3-C7)-cycloalkyl, -(Ci-C4)-alkyl-(C3-C7)-cycloalkyl, -(Ci-C4)-alkyl-O-R37, -(d-C4)-alkyl-N(R38)-R39, -OH, =O, -O-(Ci-C4)-alkyl and -N(R40)-R41 , in another embodiment from the series consisting of halogen, (Ci-C4)-alkyl, (C3-C7)-cycloalkyl, -(Ci-C4)-alkyl-O-R37, -(Ci-C4)-alkyl-N(R38)-R39, -OH, =O, -O-(d-C4)-alkyl and -N(R40)-R41 , in another embodiment from the series consisting of halogen, (Ci-C4)-alkyl, (C3-C7)-cycloalkyl, -(Ci-C4)-alkyl-O-R37, -(Ci-C4)-alkyl-N(R38)-R39, -OH, =O and -O-(d-C4)-alkyl, in another embodiment from the series consisting of halogen, (Ci-C4)-alkyl, (C3-C7)-cycloalkyl, -(Ci-C4)-alkyl-O-R37, -OH, =O and -O-(Ci-C4)-alkyl, in another embodiment from the series consisting of halogen, (Ci-C4)-alkyl, (C3-C7)-cycloalkyl, -(Ci-C4)-alkyl-O-R37, -(Ci-C4)-alkyl-N(R38)-R39, -OH and -O-(Ci-C4)-alkyl, in another embodiment from the series consisting of halogen, (Ci-C4)-alkyl, (C3-C7)-cycloalkyl, -(Ci-C4)-alkyl-O-R37, -(Ci-C4)-alkyl-N(R38)-R39, -OH and =O, in another embodiment from the series consisting of halogen, (Ci-C4)-alkyl, (C3-C7)-cycloalkyl, -(Ci-C4)-alkyl-O-R37 and -OH, in another embodiment from the series consisting of halogen, (Ci-C4)-alkyl, (C3-C7)-cycloalkyl and -OH, in another embodiment from the series consisting of halogen, (Ci-C4)-alkyl and (C3-C7)-cycloalkyl, in another embodiment from the series consisting of halogen, -OH and -O-(Ci-C4)-alkyl, in another embodiment from the series consisting of halogen and -OH, in another embodiment from the series consisting of halogen, (Ci-C4)-alkyl, (C3-C7)-cycloalkyl, -(Ci-C4)-alkyl-O-R37, -OH and -O-(Ci-C4)-alkyl, in another embodiment from the series consisting of halogen, (Ci-C4)-alkyl, (C3-C7)-cycloalkyl, -OH and -O-(Ci-C4)-alkyl, in another embodiment from the series consisting of halogen, (Ci-C4)-alkyl, -OH and -O-(Ci-C4)-alkyl, in another embodiment from the series consisting of halogen, -OH and -O-(Ci-C4)-alkyl, in another embodiment from the series consisting of -OH and -O-(Ci-C4)-alkyl, and in another embodiment R32 is -OH. In another embodiment R32 is selected from the series of halogen, (Ci-C4)-alkyl, (C3-C7)-cycloalkyl, -(Ci-C4)-alkyl-(C3-C7)-cycloalkyl, -(Ci-C4)-alkyl-O-R37, -(d-C4)-alkyl-N(R38)-R39, -C(O)-(Ci-C4)-alkyl, -OH, =O, -O-(Ci-C4)-alkyl, -N(R40)-R41 , -C(O)-O-

(Ci-C4)-alkyl and -C(O)-N(R42)-R43, in another embodiment from the series consisting of halogen, (Ci-C4)-alkyl, (C3-C7)-cycloalkyl, -(Ci-C4)-alkyl-(C3-C7)-cycloalkyl, -(Ci-C4)-alkyl-O-R37, -(Ci-C4)-alkyl-N(R38)-R39, -C(O)-(Ci-C4)-alkyl, -OH, =O, -O-(Ci-C4)-alkyl and -N(R40)-R41 , in another embodiment from the series consisting of halogen, (Ci-C4)-alkyl, (C3-C7)-cycloalkyl, -(Ci-C4)-alkyl-O-R37, -(d-C4)-alkyl-N(R38)-R39, -C(O)-(Ci-C4)-alkyl, -OH, =O, -O-(d-C4)-alkyl and -N(R40)-R41 , in another embodiment from the series consisting of halogen, (Ci-C4)-alkyl, (C3-C7)-cycloalkyl, -(Ci-C4)-alkyl-O-R37, -(Ci-C4)-alkyl-N(R38)-R39, -C(O)-(Ci-C4)-alkyl, -OH, =O and -O-(Ci-C4)-alkyl, in another embodiment from the series consisting of halogen, (Ci-C4)-alkyl, (C3-C7)-cycloalkyl, -(Ci-C4)-alkyl-O-R37,-OH, =O and -O-(d-C4)-alkyl, in another embodiment from the series consisting of halogen, (Ci-C4)-alkyl, (C3-C7)-cycloalkyl, -(Ci-C4)-alkyl-O-R37, -(Ci-C4)-alkyl-N(R38)-R39, -C(O)-(Ci-C4)-alkyl, -OH and -O-(Ci-C4)-alkyl, in another embodiment from the series consisting of halogen, (Ci-C4)-alkyl, (C3-C7)-cycloalkyl, -(Ci-C4)-alkyl-O-R37, -(d-C4)-alkyl-N(R38)-R39, -C(O)-(Ci-C4)-alkyl, -OH and =O, in another embodiment from the series consisting of halogen, (Ci-C4)-alkyl, (C3-C7)-cycloalkyl, -(Ci-C4)-alkyl-O-R37, -C(O)-(Ci-C4)-alkyl and -OH, in another embodiment from the series consisting of halogen, (Ci-C4)-alkyl, (C3-C7)-cycloalkyl, -C(O)-(Ci-C4)-alkyl and -OH, in another embodiment from the series consisting of halogen, (Ci-C4)-alkyl and (C3-C7)-cycloalkyi and -C(O)-(Ci-C4)-alkyl, in another embodiment from the series consisting of halogen, (Ci-C4)-alkyl, (C3-d)-cycloalkyl, -(Ci-C4)-alkyl-O-R37, -C(O)-(Ci-C4)-alkyl, -OH and -O-(Ci-C4)-alkyl, and in another embodiment from the series consisting of halogen, (Ci-C4)-alkyl, (C3-C7)-cycloalkyl, -C(O)-(Ci-C4)-alkyl, -OH and -O-(d-C4)-alkyl.

In one embodiment, substituents R32 which are bonded to ring nitrogen atoms in R30, are selected from the series consisting of (Ci-C4)-alkyl, (C3-C7)-cycloalkyl, -(Ci-C4)-alkyl-(C3-C7)-cycloalkyl, -(Ci-C4)-alkyl-O-R37, -(Ci-C4)-alkyl-N(R38)-R39, -(d-C4)-alkyl-CN, -C(O)-(Ci-C4)-alkyl, -C(O)-O-(Ci-C4)-alkyl and -C(O)-N(R42)-R43, in another embodiment from the series consisting of (Ci-C4)-alkyl, (C3-C7)-cycloalkyl, -(Ci-C4)-alkyl-(C3-C7)-cycloalkyl, -(Ci-C4)-alkyl-O-R37, -(Ci-C4)-alkyl-N(R38)-R39 and -(Ci-C4)-alkyl-CN, in another embodiment from the series consisting of (Ci-C4)-alkyl, (C3-C7)-cycloalkyl, -(Ci-C4)-alkyl-(C3-C7)-cycloalkyl and -(Ci-C4)-alkyl-0-R37, in another embodiment from the series consisting of (CrC4)-alkyl, (C3-C7)-cycloalkyl and -(Ci-C4)-alkyl-O-R37. In one embodiment, the number of oxo substituents (=O) occurring in the cyclic group R30 is not greater than two, in another embodiment it is not greater than one. In one embodiment, halogen representing R32 is selected from the series consisting of fluorine and chlorine, in another embodiment halogen representing R32 is fluorine. In another embodiment, substituents R32 which are bonded to ring nitrogen atoms in R30, are selected from the series consisting of (Ci-C4)-alkyl, (C3-C7)-cycloalkyl, -(Ci-C4)-alkyl-(C3-C7)-cycloalkyl, -(Ci-C4)-alkyl-O-R37, -(Ci-C4)-alkyl-N(R38)-R39 and -C(O)-(Ci-C4)-alkyl, in another embodiment from the series consisting of (Ci-C4)-alkyl, (C3-C7)-cycloalkyl, -(Ci-C4)-alkyl-(C3-C7)-cycloalkyl, -(Ci-C4)-alkyl-O-R37 and -C(O)-(Ci-C4)-alkyl, in another embodiment from the series consisting of (Ci-C4)-alkyl, (C3-C7)-cycloalkyl, -(d-C4)-alkyl-O-R37 and -C(O)-(d-C4)-alkyl, in another embodiment from the series consisting of (Ci-C4)-alkyl, (C3-C7)-cycloalkyl and -C(O)-(Ci-C4)-alkyl. In one embodiment, the number of oxo (=O) substituents R32 occurring in the cyclic group R30 is not greater than two, in another embodiment it is not greater than one. In one embodiment, halogen representing R32 is selected from the series consisting of fluorine and chlorine, in another embodiment halogen representing R32 is fluorine.

In one embodiment of the invention, R33, R34, R35, R36, R37, R38, R39, R40, R41 , R42 and R43 are independently of one another selected from the series consisting of hydrogen and (Ci-C3)-alkyl, in another embodiment from the series consisting of hydrogen and (Ci-C2)-alkyl, in another embodiment from the series consisting of hydrogen and methyl. In another embodiment, any of the groups R33, R34, R35, R36, R37, R38, R39, R40, R41 , R42 and R43 is independently of any other group hydrogen, in another embodiment it is (Ci-C4)-alkyl, in another embodiment (C1-C3)-alkyl, in another embodiment (Ci-C2)-alkyl, and in another embodiment methyl.

In one embodiment of the invention, R50 is in any of its occurrences, independently of its other occurrences, selected from the series consisting of halogen, (Ci-C4)-alkyl and -CN; in another embodiment from the series consisting of halogen, (Ci-C4)-alkyl

and -O-(CrC4)-alkyl, in another embodiment from the series consisting of halogen and (CrC4)-alkyl, in another embodiment from the series consisting of halogen and -CN, in another embodiment from the series consisting of halogen. In one embodiment, a group R50 which is bonded to ring nitrogen atom in a group Het2 or Het3, is selected from the series consisting of (Ci-C4)-alkyl. In one embodiment, a (Ci-C4)-alkyl group representing R50 or occurring in R50 is in any occurrence of R50, independently of other occurrences, selected from (Ci-C3)-alkyl, in another

embodiment from (Ci-C2)-alkyl, and in another embodiment it is methyl.

The group Het1 can contain 4, 5, 6 or 7 ring members. In one embodiment of the invention, Het1 is 4-membered to 6-membered, in another embodiment 5-membered or 6-membered, in another embodiment 6-membered. In one embodiment, Het1 comprises 1 ring heteroatom. In one embodiment, the ring heteroatoms in Het1 are selected from the series consisting of nitrogen and oxygen, in another embodiment from the series consisting of oxygen and sulfur, in another embodiment they are nitrogen atoms, and in another embodiment they are oxygen atoms. Examples of heterocydes, from any one or more of which Het1 is chosen in one embodiment, are oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, oxepanyl, tetrahydrothiophenyl, tetrahydrothiopyranyl, azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, morpholinyl, thiomorpholinyl and piperazinyl. In one embodiment, the number of optional substituents in a group Het1 is 1 , 2, 3 or 4, in another embodiment it is 1 , 2 or 3, in another embodiment it is 1 or 2, in another embodiment it is 1 , and in another embodiment Het1 is unsubstituted. In one embodiment, substituents which are bonded to a ring nitrogen atom in Het1 , are selected from the series consisting of (Ci-C4)-alkyl.

The group Het2 can contain 4, 5, 6 or 7 ring members. In one embodiment of the invention, Het2 is 4-membered to 6-membered, in another embodiment 5-membered or 6-membered, in another embodiment 5-membered, in another embodiment 6-membered. In one embodiment, Het2 is a saturated or aromatic group, in another embodiment a saturated group, in another embodiment an aromatic group. In one embodiment, Het2 comprises 1 ring heteroatom. In one embodiment, the ring

heteroatoms in Het2 are selected from the series consisting of nitrogen and oxygen, in another embodiment from the series consisting of nitrogen and sulfur, in another embodiment from the series consisting of oxygen and sulfur, in another embodiment they are nitrogen atoms, in another embodiment they are oxygen atoms, and in another embodiment they are sulfur atoms. Examples of heterocycles, from any one or more of which Het2 is chosen in one embodiment, are oxetanyl, tetrahydrofuranyl, furanyl, tetrahydropyranyl, oxepanyl, tetrahydrothiophenyl, thiophenyl,

tetrahydrothiopyranyl, azetidinyl, pyrrolidinyl, pyrrolyl, piperidinyl, pyridinyl, azepanyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, morpholinyl, thiomorpholinyl and piperazinyl.

In one embodiment of the invention, the group Het3 is 5-membered, in another embodiment it is 6-membered. In one embodiment, Het3 comprises 1 or 2 identical or different ring heteroatoms, in another embodiment 1 ring heteroatom. In one embodiment, the ring heteroatoms in Het3 are selected from the series consisting of nitrogen and oxygen, in another embodiment from the series consisting of nitrogen and sulfur, in another embodiment they are nitrogen atoms, and in another

embodiment they are sulfur atoms. Examples of heterocycles, from any one or more of which Het3 is chosen in one embodiment, are furanyl, thiophenyl, pyrrolyl, pyridinyl, pyrazolyl, imidazolyl, [1 ,2,4]triazolyl, oxazolyl, isoxazolyl and thiazolyl.

A subject of the invention are all compounds of the formula I wherein any one or more structural elements such as groups, residues, substituents and numbers are defined as in any of the specified embodiments or definitions of the elements, or have one or more of the specific meanings which are mentioned herein as examples of elements, wherein all combinations of one or more definitions of compounds or elements and/or specified embodiments and/or specific meanings of elements are a subject of the present invention. Also with respect to all such compounds of the formula I, all their stereoisomeric forms and mixtures of stereoisomeric forms in any ratio, and their pharmaceutically acceptable salts are a subject of the present invention.

As an example of compounds of the invention which with respect to any structural elements are defined as in specified embodiments of the invention or definitions of such elements, compounds of the formula I may be mentioned, in any of their stereoisomeric forms or a mixture of stereoisomeric forms in any ratio, and the pharmaceutically acceptable salts thereof, wherein

Ar is selected from the series consisting of phenyl and a 5-membered or 6-membered, monocyclic, aromatic, heterocyclic group which comprises 1 or 2 identical or different ring heteroatoms selected from the series consisting of nitrogen, oxygen and sulfur, and is bonded via a ring carbon atom, which all are unsubstituted or substituted by one or more identical or different substituents R5;

n is selected from the series consisting of 0, 1 and 2;

X is selected from the series consisting of N and CH;

Z is selected from the series consisting of a direct bond, O, S and N(R10);

R1 is selected from the series consisting of H, -N(R1 1 )-R12, -N(R13)-C(O)-R14, -N(R13)-S(0)2-R15, -N(R13)-C(O)-NH-R16 and (Ci-C4)-alkyl;

R2 is selected from the series consisting of halogen, (Ci-C4)-alkyl, -O-(Ci-C4)-alkyl and -CN;

R3 is selected from the series consisting of H, (d-CeJ-alkyl, R30 and -(Ci-C4)-alkyl-R30, wherein (Ci-Cs)-alkyl is unsubstituted or substituted by one or more identical or different substituents R31 ;

R5 is selected from the series consisting of halogen, (Ci-C4)-alkyl, (C3-C7)-cycloalkyl, -O-(Ci-C4)-alkyl, -O-(C3-C7)-cycloalkyl, -C(O)-N(R6)-R7 and -CN,

and two groups R5 bonded to adjacent ring carbon atoms in Ar, together with the carbon atoms carrying them, can form a 5-membered to 8-membered, monocyclic, unsaturated ring which comprises 0, 1 or 2 identical or different ring heteroatoms selected from the series consisting of nitrogen, oxygen and sulfur, and which is unsubstituted or substituted by one or more identical or different substituents R8;

R6 and R7 are independently of one another selected from the series consisting of H and (Ci-C4)-alkyl;

R8 is selected from the series consisting of halogen and (Ci-C4)-alkyl;

R10 is selected from the series consisting of H and (Ci-C4)-alkyl;

R1 1 and R12 are independently of one another selected from the series consisting of H, (Ci-C4)-alkyl, (C3-C7)-cycloalkyl, -(Ci-C4)-alkyl-(C3-C7)-cycloalkyl, Het1 , -(d-C4)-alkyl-Hetl and -(Ci-C4)-alkyl-phenyl, wherein phenyl is unsubstituted or substituted by one or more identical or different substituents R50;

R13 is selected from the series consisting of H and (Ci-C4)-alkyl;

R14 and R16 are independently of one another selected from the series consisting of (Ci-C8)-alkyl, (C3-C7)-cycloalkyl, -(Ci-C4)-alkyl-(C3-C7)-cycloalkyl, phenyl, -(d-C4)-alkyl-phenyl, Het2 and -(Ci-C4)-alkyl-Het2, wherein (Ci-C8)-alkyl and (C3-C7)-cycloalkyl all are unsubstituted or substituted by one or more identical or different substituents selected from the series consisting of -OH and -O-(Ci-C4)-alkyl, and wherein phenyl and Het2 all are unsubstituted or substituted by one or more identical or different substituents R50;

R15 is selected from the series consisting of phenyl and Het3, wherein phenyl and Het3 all are unsubstituted or substituted by one or more identical or different substituents R50;

R30 is a 3-membered to 12-membered, monocyclic or bicyclic, saturated, partially unsaturated or aromatic, cyclic group which comprises 0, 1 , 2 or 3 identical or different ring heteroatoms selected from the series consisting of nitrogen, oxygen and sulfur, which is unsubstituted or substituted by one or more identical or different substituents R32;

R31 is selected from the series consisting of halogen, -OH, -O-(Ci-C4)-alkyl, -0-(C-3-C7)-cycloalkyl, -O-(Ci-C4)-alkyl-(C3-C7)-cycloalkyl, -N(R33)-R34 and -CN;

R32 is selected from the series consisting of halogen, (Ci-C4)-alkyl, (C3-C7)-cycloalkyl, -(Ci-C4)-alkyl-(C3-C7)-cycloalkyl, -(Ci-C4)-alkyl-O-R37, -(d-C4)-alkyl-N(R38)-R39, -(Ci-C4)-alkyl-CN, -C(O)-(Ci-C4)-alkyl, -CN, -OH, =O, -O-(d-C4)-alkyl, -N(R40)-R41 , -C(O)-O-(Ci-C4)-alkyl and -C(O)-N(R42)-R43;

R33, R34, R37, R38, R39, R40, R41 , R42 and R43 are independently of one another selected from the series consisting of H and (Ci-C4)-alkyl;

R50 is selected from the series consisting of halogen, (Ci-C4)-alkyl, -O-(Ci-C4)-alkyl and -CN;

Het1 is a 4-membered to 7-membered, monocyclic, saturated, heterocyclic group which comprises 1 or 2 identical or different ring heteroatoms selected from the series consisting of nitrogen, oxygen and sulfur, and is bonded via a ring carbon atom, and which is unsubstituted or substituted by one or more identical or different substituents selected from the series consisting of fluorine and (Ci-C4)-alkyl;

Het2 is a 4-membered to 7-membered, monocyclic, saturated, partially unsaturated or aromatic, heterocyclic group which comprises 1 or 2 identical or different ring heteroatoms selected from the series consisting of nitrogen, oxygen and sulfur, and is bonded via a ring carbon atom;

Het3 is a 5-membered or 6-mennbered, monocyclic, aromatic, heterocyclic group which comprises 1 or 2 identical or different ring heteroatoms selected from the series consisting of nitrogen, oxygen and sulfur, and is bonded via a ring carbon atom;

wherein all cycloalkyi groups, independently of any other substituents which can be present on a cycloalkyi group, can be substituted by one or more identical or different substituents selected from the series consisting of fluorine and (Ci-C4)-alkyl;

wherein all alkyl groups, independently of any other substituents which can be present on an alkyl group, can be substituted by one or more fluorine substituents.

As another such example, compounds of the formula I may be mentioned, in any of their stereoisomeric forms or a mixture of stereoisomeric forms in any ratio, and the pharmaceutically acceptable salts thereof, wherein

Ar is selected from the series consisting of phenyl and a 5-membered monocyclic, aromatic, heterocyclic group which comprises 1 or 2 identical or different ring heteroatoms selected from the series consisting of nitrogen and sulfur, and is bonded via a ring carbon atom, which all are unsubstituted or substituted by one or more identical or different substituents R5;

n is selected from the series consisting of 0, 1 and 2;

X is selected from the series consisting of N and CH;

Z is selected from the series consisting of a direct bond, O, S and N(R10);

R1 is selected from the series consisting of H, -N(R1 1 )-R12, -N(R13)-C(O)-R14, -N(R13)-S(0)2-R15, -N(R13)-C(O)-NH-R16 and (Ci-C4)-alkyl;

R2 is selected from the series consisting of halogen, (Ci-C4)-alkyl and -O-(Ci-C4)-alkyl;

R3 is selected from the series consisting of H, (d-CsJ-alkyl, R30 and -(Ci-C4)-alkyl-R30, wherein (Ci-Cs)-alkyl is unsubstituted or substituted by one or more identical or different substituents R31 ;

R5 is selected from the series consisting of halogen, (Ci-C4)-alkyl, (C3-C7)-cycloalkyl, -O-(Ci-C4)-alkyl, -O-(C3-C7)-cycloalkyl and -CN,

and two groups R5 bonded to adjacent ring carbon atoms in Ar, together with the carbon atoms carrying them, can form a 5-membered to 7-membered, monocyclic, unsaturated ring which comprises 0, 1 or 2 oxygen atoms as ring heteroatoms, and which is unsubstituted or substituted by one or more identical or different substituents R8;

R8 is selected from the series consisting of halogen and (Ci-C4)-alkyl;

R10 is selected from the series consisting of H and (Ci-C4)-alkyl;

one of the groups R1 1 and R12 is selected from the series consisting of hydrogen and (Ci-C4)-alkyl, and the other of the groups R1 1 and R12 is selected from the series consisting of hydrogen, (Ci-C4)-alkyl, (C3-C7)-cycloalkyl, -(Ci-C4)-alkyl-(C3-C7)-cycloalkyl, Het1 , -(Ci-C4)-alkyl-Het1 and -(Ci-C4)-alkyl-phenyl;

R13 is selected from the series consisting of H and (Ci-C4)-alkyl;

R14 and R16 are independently of one another selected from the series consisting of (Ci-C8)-alkyl, (C3-C7)-cycloalkyl, -(Ci-C4)-alkyl-(C3-C7)-cycloalkyl, phenyl, -(d-C4)-alkyl-phenyl, Het2 and -(Ci-C4)-alkyl-Het2, wherein (Ci-C8)-alkyl and (C3-C7)-cycloalkyl all are unsubstituted or substituted by one or more identical or different substituents selected from the series consisting of -OH and -O-(Ci-C4)-alkyl, and

wherein phenyl and Het2 all are unsubstituted or substituted by one or more identical or different substituents R50;

R15 is phenyl which is unsubstituted or substituted by one or more identical or different substituents R50;

R30 is a 3-membered to 12-membered, monocyclic or bicyclic, saturated, partially unsaturated or aromatic, cyclic group which comprises 0, 1 , 2 or 3 identical or different ring heteroatoms selected from the series consisting of nitrogen and oxygen, which is unsubstituted or substituted by one or more identical or different substituents R32;

R31 is selected from the series consisting of halogen, -OH, -O-(Ci-C4)-alkyl, -0-(C-3-C7)-cycloalkyl, -0-(Ci-C4)-alkyl-(C3-C7)-cycloalkyl and -N(R33)-R34;

R32 is selected from the series consisting of halogen, (Ci-C4)-alkyl, (C3-C7)-cycloalkyl, -(Ci-C4)-alkyl-(C3-C7)-cycloalkyl, -(Ci-C4)-alkyl-O-R37, -(d-C4)-alkyl-N(R38)-R39, -OH, =O, -O-(d-C4)-alkyl and -N(R40)-R41 ;

R33, R34, R37, R38, R39, R40 and R41 are independently of one another selected from the series consisting of H and (Ci-C4)-alkyl;

R50 is selected from the series consisting of halogen, (Ci-C4)-alkyl, -O-(Ci-C4)-alkyl and -CN;

Het1 is a 4-membered to 7-membered, monocyclic, saturated, heterocyclic group which comprises 1 or 2 identical or different ring heteroatoms selected from the series consisting of nitrogen and oxygen, and is bonded via a ring carbon atom, and which is unsubstituted or substituted by one or more identical or different substituents selected from the series consisting of fluorine and (Ci-C4)-alkyl;

Het2 is a 4-membered to 7-membered, monocyclic, saturated, partially unsaturated or aromatic, heterocyclic group which comprises 1 or 2 identical or different ring heteroatoms selected from the series consisting of nitrogen, oxygen and sulfur, and is bonded via a ring carbon atom;

wherein all cycloalkyi groups, independently of any other substituents which can be present on a cycloalkyi group, can be substituted by one or more identical or different substituents selected from the series consisting of fluorine and (Ci-C4)-alkyl;

wherein all alkyl groups, independently of any other substituents which can be present on an alkyl group, can be substituted by one or more fluorine substituents.

As another such example, compounds of the formula I may be mentioned, in any of their stereoisomeric forms or a mixture of stereoisomeric forms in any ratio, and the pharmaceutically acceptable salts thereof, wherein

Ar is phenyl, which is unsubstituted or substituted by one or more identical or different substituents R5;

n is selected from the series consisting of 0 and 1 ;

X is selected from the series consisting of N and CH;

Z is selected from the series consisting of a direct bond, O and N(R10);

R1 is selected from the series consisting of H, -N(R1 1 )-R12, -N(R13)-C(O)-R14 and (Ci-C4)-alkyl;

R2 is selected from the series consisting of halogen and -O-(Ci-C4)-alkyl;

R3 is selected from the series consisting of H, (d-CeJ-alkyl, R30 and -(Ci-C4)-alkyl-R30, wherein (Ci-Cs)-alkyl is unsubstituted or substituted by one or more identical or different substituents R31 ;

R5 is selected from the series consisting of halogen, (CrC4)-alkyl, -O-(Ci-C4)-alkyl and -CN,

and two groups R5 bonded to adjacent ring carbon atoms in Ar, together with the carbon atoms carrying them, can form a 5-membered to 7-membered, monocyclic, unsaturated ring which comprises 0, 1 or 2 oxygen atoms as ring heteroatoms, and which is unsubstituted or substituted by one or more identical or different substituents R8;

R8 is selected from the series consisting of halogen and (Ci-C4)-alkyl;

R10 is selected from the series consisting of H and (Ci-C4)-alkyl;

one of the groups R1 1 and R12 is selected from the series consisting of hydrogen and (Ci-C4)-alkyl, and the other of the groups R1 1 and R12 is selected from the series consisting of hydrogen, (Ci-C4)-alkyl, -(Ci-C4)-alkyl-(C3-C7)-cycloalkyl and -(Ci-C4)-alkyl-Het1 ;

R13 is selected from the series consisting of H and (Ci-C4)-alkyl;

R14 is selected from the series consisting of (C3-C7)-cycloalkyl, phenyl and Het2, wherein (C3-C7)-cycloalkyl is unsubstituted or substituted by one or more identical or different substituents selected from the series consisting of -OH and -O-(Ci-C4)-alkyl, and wherein phenyl and Het2 all are unsubstituted or substituted by one or more identical or different substituents R50;

R30 is a 3-membered to 10-membered, monocyclic or bicyclic, saturated, partially unsaturated or aromatic, cyclic group which comprises 0, 1 , 2 or 3 identical or

different ring heteroatoms selected from the series consisting of nitrogen and oxygen, which is unsubstituted or substituted by one or more identical or different substituents R32;

R31 is selected from the series consisting of halogen, -OH, -O-(Ci-C4)-alkyl, -0-(C-3-C7)-cycloalkyl and -N(R33)-R34;

R32 is selected from the series consisting of halogen, (Ci-C4)-alkyl, (C3-C7)-cycloalkyl, -(Ci-C4)-alkyl-O-R37, -(Ci-C4)-alkyl-N(R38)-R39, -OH, =O, -O-(d-C4)-alkyl and -N(R40)-R41 ;

R33, R34, R37, R38, R39, R40 and R41 are independently of one another selected from the series consisting of H and (Ci-C4)-alkyl;

R50 is selected from the series consisting of halogen, (Ci-C4)-alkyl, -O-(Ci-C4)-alkyl and -CN;

Het1 is a 4-membered to 7-membered, monocyclic, saturated, heterocyclic group which comprises 1 or 2 identical or different ring heteroatoms selected from the series consisting of nitrogen and oxygen, and is bonded via a ring carbon atom, and which is unsubstituted or substituted by one or more identical or different substituents selected from the series consisting of fluorine and (Ci-C4)-alkyl;

Het2 is a 4-membered to 7-membered, monocyclic, saturated or aromatic,

heterocyclic group which comprises 1 or 2 identical or different ring heteroatoms selected from the series consisting of nitrogen, oxygen and sulfur, and is bonded via a ring carbon atom;

wherein all cycloalkyl groups, independently of any other substituents which can be present on a cycloalkyl group, can be substituted by one or more identical or different substituents selected from the series consisting of fluorine and (Ci-C4)-alkyl;

wherein all alkyl groups, independently of any other substituents which can be present on an alkyl group, can be substituted by one or more fluorine substituents.

As another such example, compounds of the formula I may be mentioned, in any of their stereoisomeric forms or a mixture of stereoisomeric forms in any ratio, and the pharmaceutically acceptable salts thereof, wherein

Ar is phenyl, which is unsubstituted or substituted by one or more identical or different substituents R5;

n is selected from the series consisting of 0 and 1 ;

X is selected from the series consisting of N and CH;

Z is selected from the series consisting of a direct bond and O;

R1 is selected from the series consisting of H, -N(R1 1 )-R12 and (Ci-C4)-alkyl;

R2 is selected from the series consisting of halogen;

R3 is selected from the series consisting of H, R30 and -(Ci-C4)-alkyl-R30;

R5 is selected from the series consisting of halogen, (Ci-C4)-alkyl, -O-(Ci-C4)-alkyl and -CN;

R1 1 and R12 are independently of one another selected from the series consisting of hydrogen and (Ci-C4)-alkyl;

R30 is a 3-membered to 7-membered, monocyclic saturated or aromatic, cyclic group which comprises 0, 1 or 2 identical or different ring heteroatoms selected from the series consisting of nitrogen and oxygen, which is unsubstituted or substituted by one or more identical or different substituents R32;

R32 is selected from the series consisting of halogen, (Ci-C4)-alkyl, (C3-C7)-cycloalkyl, -(Ci-C4)-alkyl-O-R37, -(Ci-C4)-alkyl-N(R38)-R39, -OH and =0;

R37, R38 and R39 are independently of one another selected from the series consisting of H and (Ci-C4)-alkyl;

wherein all cycloalkyi groups can be substituted by one or more identical or different substituents selected from the series consisting of fluorine and (Ci-C4)-alkyl;

wherein all alkyl groups, independently of any other substituents which can be present on an alkyl group, can be substituted by one or more fluorine substituents.

A subject of the invention also is a compound of the formula I which is selected from any of the specific compounds of the formula I which are disclosed herein, or is any one of the specific compounds of the formula I which are disclosed herein, irrespective thereof whether they are disclosed as a free compound and/or as a specific salt, or a pharmaceutically acceptable salt thereof, wherein the compound of the formula I is a subject of the invention in any of its stereoisomeric forms or a mixture of stereoisomeric forms in any ratio, if applicable. For example, a subject of the invention is a compound of the formula I which is selected from the series consisting of:

N-[4-(3-Amino-4-cyclopropyl-1 H-pyrazolo[3,4-d]pyrimidin-6-yl)-phenyl]-2-cyano-5-methoxy-benzenesulfonamide,

N-[4-(3-Amino-1 H-pyrazolo[3,4-d]pyrimidin-6-yl)-phenyl]-2,5-difluoro-benzenesulfonamide,

N-[4-(3-Amino-1 H-pyrazolo[3,4-d]pyrimidin-6-yl)-phenyl]-5-chloro-2-cyano-benzenesulfonamide,

2-Chloro-N-{4-[4-(1 -ethyl-piperidin-3-yloxy)-3-methyl-1 H-pyrazolo[3,4-d]pyrimidin-6-yl]-phenyl}-5-methoxy-benzenesulfonamide,

5-Chloro-N-{4-[4-(1 -ethyl-piperidin-3-yloxy)-3-methyl-1 H-pyrazolo[3,4-d]pyrimidin-6-yl]-phenyl}-2-fluoro-benzenesulfonamide,

4- {6-[4-(2,5-Difluoro-benzenesulfonylamino)-phenyl]-3-nnethyl-1 H-pyrazolo[3,4-d]pynnnidin-4-yloxy}-pipendine-1 -carboxylic acid ethyl ester,

N-[4-(3-Amino-4-propoxy-1 H-pyrazolo[3,4-d]pyrinnidin-6-yl)-phenyl]-2,5-difluoro-benzenesulfonamide,

N-[4-(3-Amino-4-ethoxy-1 H-pyrazolo[3,4-d]pyrimidin-6-yl)-phenyl]-5-chloro-2-fluoro-benzenesulfonamide,

N-[4-(3-Amino-4-propoxy-1 H-pyrazolo[3,4-d]pyrinnidin-6-yl)-phenyl]-5-chloro-2-fluoro-benzenesulfonamide,

N-[4-(3-Amino-4-ethoxy-1 H-pyrazolo[3,4-d]pyrimidin-6-yl)-phenyl]-2,5-difluoro-benzenesulfonamide,

2-Fluoro-N-(4-{4-[1 -(2-methoxy-ethyl)-piperidin-4-yloxy]-3-methyl-1 H-pyrazolo[3,4-d]pyrimidin-6-yl}-phenyl)-5-methyl-benzenesulfonamide,

2,5-Difluoro-N-(4-{4-[1 -(2-methoxy-ethyl)-piperidin-4-yloxy]-3-methyl-1 H-pyrazolo[3,4-d]pyrinnidin-6-yl}-phenyl)-benzenesulfonannide,

5-Chloro-2-fluoro-N-(4-{4-[1 -(2-methoxy-ethyl)-piperidin-4-yloxy]-3-nnethyl-1 H-pyrazolo[3,4-d]pyrinnidin-6-yl}-phenyl)-benzenesulfonannide,

N-{4-[4-(1 -Ethyl-piperidin-4-yloxy)-3-methyl-1 H-pyrazolo[3,4-d]pyrimidin-6-yl^^

2-fluoro-5-methoxy-benzenesulfonannide,

2,5-Dichloro-N-{4-[4-(1 -ethyl-piperidin-4-yloxy)-3-nnethyl-1 H-pyrazolo[3,4-d]pyrimidin-6-yl]-phenyl}-benzenesulfonamide,

N-{4-[4-(1 -Ethyl-pipendin-4-yloxy)-3-m

2-fluoro-5-methyl-benzenesulfonannide,

N-{4-[4-(1 -Ethyl-piperidin-4-yloxy)-3-methyl-1 H-pyrazolo[3,4-d]pyrimidin-6-yl^^

2-fluoro-benzenesulfonamide,

5-Chloro-N-{4-[4-(1 -ethyl-piperidin-4-yloxy)-3-methyl-1 H-pyrazolo[3,4-d]pyrimidin-6-yl]-phenyl}-2-fluoro-benzenesulfonamide,

N-{4-[4-(1 -Cyclobutyl-piperidin-4-yloxy)-3-methyl-1 H-pyrazolo[3,4-d]pyrimidin-6-yl^^ phenyl}-2,5-difluoro-benzenesulfonannide,

2,5-Difluoro-N-(4-{4-[1 -(3-methoxy-propyl)-piperidin-4-yloxy]-3-nnethyl-1 H-pyrazolo[3,4-d]pyrinnidin-6-yl}-phenyl)-benzenesulfonannide,

5- Chloro-2-fluoro-N-{4-[4-(3-hydroxy-propoxy)-3-methyl-1 H-pyrazolo[3,4-d]pyrimidin- 6- yl]-phenyl}-benzenesulfonamide,

2,5-Difluoro-N-{4-[4-(1 -isopropyl-piperidin-4-yloxy)-3-nnethyl-1 H-pyrazolo[3,4-d]pyrinnidin-6-yl]-phenyl}-benzenesulfonannide,

2-Fluoro-N-(4-{4-[1 -(2-fluoro-ethyl)-piperidin-4-yloxy]-3-methyl-1 H-pyrazolo[3,4-d]pyrinnidin-6-yl}-phenyl)-benzenesulfonannide,

5-Chloro-2-fluoro-N-{4-[4-(1 -isopropyl-piperidin-4-yloxy)-3-methyl-1 H-pyrazolo[3,4-d]pyrinnidin-6-yl]-phenyl}-benzenesulfonannide,

2,5-Difluoro-N-(4-{4-[1 -(2-fluoro-ethyl)-piperidin-4-yloxy]-3-nnethyl-1 H-pyrazolo[3,4-d]pyrinnidin-6-yl}-phenyl)-benzenesulfonannide,

N-[4-(3-Amino-4-isopropoxy-1 H-pyrazolo[3,4-d]pyrinnidin-6-yl)-phenyl]-2,5-dichloro-benzenesulfonamide,

N-[4-(3-Amino-4-isobutoxy-1 H-pyrazolo[3,4-d]pyrinnidin-6-yl)-phenyl]-2,5-difluoro-benzenesulfonamide,

N-[4-(3-Amino-4-isobutoxy-1 H-pyrazolo[3,4-d]pyrinnidin-6-yl)-phenyl]-2-fluoro-5-methoxy-benzenesulfonamide,

2,5-Dichloro-N-{4-[3-methyl-4-(pipendin-3-yloxy)-1 H-pyrazolo[3,4-d]pyrimidin-6-yl]-phenylj-benzenesulfonamide,

2,5-Difluoro-N-{4-[3-methyl-4-(piperidin-3-yloxy)-1 H-pyrazolo[3,4-d]pynmidin-6-yl]-phenylj-benzenesulfonamide,

2-Fluoro-5-methyl-N-{4-[3-methyl-4-(nnorpholin-2-ylnnethoxy)-1 H-pyrazolo[3,4-d]pyrinnidin-6-yl]-phenyl}-benzenesulfonannide,

N-{4-[4-(3-Aminonnethyl-oxetan-3-ylnnethoxy)-1 H-pyrazolo[3,4-d]pyrinnidin-6-yl]-phenyl}-5-chloro-2-fluoro-benzenesulfonamide,

N-[4-(3-Amino-4-ethoxymethyl-1 H-pyrazolo[3,4-d]pyrinnidin-6-yl)-phenyl]-2-fluoro-5-methyl-benzenesulfonannide,

N-[4-(3-Amino-4-trifluoromethyl-1 H-pyrazolo[3,4-d]pyrimidin-6-yl)-phenyl]-2,5-difluoro-benzenesulfonamide,

2-Fluoro-N-{4-[4-(piperidin-4-yloxy)-1 H-pyrazolo[3,4-d]pyrinnidin-6-yl]-phenyl}-benzenesulfonamide,

N-[4-(3-Amino-1 H-pyrazolo[3,4-d]pyrinnidin-6-yl)-phenyl]-2-fluoro-5-nnethoxy-benzenesulfonamide,

N-[4-(3-Amino-4-nnethoxynnethyl-1 H-pyrazolo[3,4-d]pyhnnidin-6-yl)-phenyl]-5-chloro-2-fluoro-benzenesulfonamide,

N-{4-[4-(3-Amino-propoxy)-3-methyl-1 H-pyrazolo[3,4-d]pyrimidin-6-yl]-phenyl}-5-chloro-2-fluoro-benzenesulfonannide,

N-[4-(3-Amino-1 H-pyrazolo[3,4-d]pyrimidin-6-yl)-phenyl]-2,5-difluoro-benzenesulfonamide,

N-[4-(3-Amino-1 H-pyrazolo[3,4-d]pyrimidin-6-yl)-phenyl]-2,4,5-tnfluoro-benzenesulfonamide,

N-[4-(3-Amino-1 H-pyrazolo[3,4-d]pyrinnidin-6-yl)-phenyl]-2-chloro-4,5-difluoro-benzenesulfonamide,

N-{4-[3-Amino-4-(2,2,2-trifluoro-ethoxy)-1 H-pyrazolo[3,4-d]pynmidin-6-yl]-phenyl^ cyano-5-methyl-benzenesulfonannide,

N-[4-(3-Amino-4-trifluoronnethyl-1 H-pyrazolo[3,4-d]pyrinnidin-6-yl)-phenyl]-5-chloro-2-fluoro-benzenesulfonamide,

N-{4-[3-Amino-4-(2-methoxy-ethyl)-1 H-pyrazolo[3,4-d]pyrimidin-6-yl]-phenyl}-2-cyano-5-methyl-benzenesulfonannide,

2-Cyano-5-methyl-N-{4-[4-(2,2,2-trifluoro-ethoxy)-1 H-pyrazolo[3,4-d]pyrimidin-6-yl]-phenylj-benzenesulfonamide,

N-[4-(3-Amino-4-cyclopropyl-1 H-pyrazolo[3,4-d]pyrimidin-6-yl)-phenyl]-2,4,5-trifluoro-benzenesulfonamide,

N-[4-(3-Amino-4-cyclopropyl-1 H-pyrazolo[3,4-d]pyrimidin-6-yl)-phenyl]-2-fluoro-benzenesulfonamide,

N-[4-(3-Amino-4-cyclopropyl-1 H-pyrazolo[3,4-d]pyrimidin-6-yl)-phenyl]-2,5-difluoro-benzenesulfonamide,

N-[4-(3-Amino-4-nnethoxy-1 H-pyrazolo[3,4-d]pyrinnidin-6-yl)-phenyl]-5-chloro-2-fluoro-benzenesulfonamide,

N-[4-(3-Amino-4-nnethoxy-1 H-pyrazolo[3,4-d]pyrinnidin-6-yl)-phenyl]-5-chloro-2-cyano-benzenesulfonamide,

N-[4-(3-Amino-4-methyl-1 H-pyrazolo[3,4-d]pyrimidin-6-yl)-phenyl]-2-chloro-3,5-difluoro-benzenesulfonamide,

2-Cyano-N-{4-[4-(4-hydroxy-cyclohexyloxy)-1 H-pyrazolo[3,4-d]pyrinnidin-6-yl]-phenyl}-5-methoxy-benzenesulfonamide,

N-[4-(3-Amino-1 H-pyrazolo[4,3-c]pyridin-6-yl)-phenyl]-5-chloro-2,4-difluoro-benzenesulfonamide, and

5-Chloro-2-cyano-N-{4-[4-(4-hydroxy-cyclohexyloxy)-3-methyl-1 H-pyrazolo[3,4-d]pyrinnidin-6-yl]-phenyl}-benzenesulfonannide, and/or the series consisting of:

N-{4-[4-(1 -Cyclopropyl-piperidin-4-yloxy)-3-methyl-1 H-pyrazolo[3,4-d]pyrimidin-6-yl]-phenyl}-2,5-difluoro-benzenesulfonamide,

5-Chloro-N-{4-[4-(1 -cyclopropyl-piperidin-4-yloxy)-3-methyl-1 H-pyrazolo[3,4-d]pyrimidin-6-yl]-phenyl}-2-fluoro-benzenesulfonannide,

N-{4-[4-(1 -Acetyl-piperidin-4-yloxy)-3-methyl-1 H-pyrazolo[3,4-d]pyrimidin-6-yl]-phenyl}-2-fluoro-5-methoxy-benzenesulfonamide,

N-{4-[4-(1 -Acetyl-piperidin-4-yloxy)-3-methyl-1 H-pyrazolo[3,4-d]pyrimidin-6-yl]-phenyl}-2,5-difluoro-benzenesulfonamide,

N-{4-[4-(1 -Acetyl-piperidin-4-yloxy)-3-methyl-1 H-pyrazolo[3,4-d]pyrimidin-6-yl]-phenyl}-5-chloro-2-fluoro-benzenesulfonamide,

5-Chloro-2-fluoro-N-{4-[4-(6-hydroxy-pyridin-3-yloxy)-3-methyl-1 H-pyrazolo[3,4-d]pyrimidin-6-yl]-phenyl}-benzenesulfonannide, and

2-Fluoro-N-{4-[4-(6-hydroxy-pyridin-3-yloxy)-3-methyl-1 H-pyrazolo[3,4-d]pyhmidin-6-yl]-phenyl}-5-methyl-benzenesulfonannide,

or which is any one of these compounds, and its pharmaceutically acceptable salts.

Another subject of the present invention are processes for the preparation of the compounds of the formula I which are outlined below and by which the compounds of the formula I and intermediates and occurring in the course of their synthesis, and salts thereof, are obtainable. The compounds of the formula I can be prepared by utilizing procedures and techniques which per se are known to a person skilled in the art. In general, pyrazolo[3,4-d]pyrimidine and pyrazolo[4,3-c]pyridine compounds of the formula I can be prepared, for example, in the course of a convergent synthesis, by linking two or more fragments which can be derived retrosynthetically from the formula I. More specifically, suitably substituted starting 1 H-pyrazolo[3,4-d]pyrimidine and 1 H-pyrazolo[4,3-c]pyridine derivatives can be employed as building blocks in the preparation of the compounds of formula I, which can be synthesized from suitable precursor compounds, which allow the introduction of a variety of substituents into the various positions of the 1 H-pyrazolo[3,4-d]pyrimidine or 1 H-pyrazolo[4,3-c]pyridine ring system and which can be chemically modified further in order to finally arrive at the compound of the formula I having the desired substituent pattern. For the synthesis of the 1 H-pyrazolo[3,4-d]pyrimidine and 1 H-pyrazolo[4,3-c]pyridine ring system, use can also be made of procedures and transformations which are described in the literature with respect to indazoles. As reviews in which numerous details and literature references on the chemistry of indazoles and on synthetic procedures for their preparation can be found, J. Eiguero in Comprehensive

Heterocyclic Chemistry II, Eds. A. Katritzky, Ch. Rees, E. Scriven, Elsevier 1996, Vol. 3; W. Stadlbauer in Houben-Weyl, Methoden der Organischen Chemie (Methods of Organic Chemistry), Georg Thieme Verlag, Stuttgart, Germany, 1994, Vol. E8b, Hetarene; W. Stadlbauer in Houben-Weyl, Science of Synthesis, Georg Thieme Verlag, Stuttgart, Germany, 2002, vol. 12.2, 227-324, may be mentioned. The starting materials employed in the synthesis of the compounds of the formula I are commercially available or can be prepared according to procedures, or in analogy to procedures, described in the literature or herein.

In one synthetic approach for the preparation of compounds of the formula I, a compound of the formula II and a compound of the formula III are reacted to give a compound of the formula IV, which can already be the final compound of the formula I or which is then converted into the desired final compound of the formula I.

III

More specifically, in particular in case the group R1 in the compound of the formula I is hydrogen or an optionally substituted alkyl group, according to this approach a compound of the formula II is obtained by reacting a compound of the formula V with a hydrazine of the formula VI, reacting the obtained compound of the formula II with a compound of the formula III to give a compound of the formula IV, which can already be the final compound of the formula I, and optionally converting the compound of the formula IV into a compound of the formula I.

Claims

1 . A compound of the formula I, in any of its stereoisomeric forms or a mixture of stereoisomeric forms in any ratio, or a pharmaceutically acceptable salt thereof,

wherein

Ar is selected from the series consisting of phenyl and a 5-membered or 6-membered, monocyclic, aromatic, heterocyclic group which comprises 1 , 2 or 3 identical or different ring heteroatoms selected from the series consisting of nitrogen, oxygen and sulfur, and is bonded via a ring carbon atom, which all are unsubstituted or

substituted by one or more identical or different substituents R5;

n is selected from the series consisting of 0, 1 and 2;

X is selected from the series consisting of N and CH;

Z is selected from the series consisting of a direct bond, O, S and N(R10);

R1 is selected from the series consisting of H, -N(R1 1 )-R12, -N(R13)-C(O)-R14, -N(R13)-S(O)2-R15, -N(R13)-C(O)-NH-R16, (Ci-C4)-alkyl and -(Ci-C4)-alkyl-0-R17;

R2 is selected from the series consisting of halogen, (Ci-C4)-alkyl, -O-(Ci-C4)-alkyl and -CN;

R3 is selected from the series consisting of H, (d-CeJ-alkyl, R30 and -(Ci-C4)-alkyl-R30, wherein (Ci-Cs)-alkyl is unsubstituted or substituted by one or more identical or different substituents R31 ;

R5 is selected from the series consisting of halogen, (Ci-C4)-alkyl, (C3-C7)-cycloalkyl, -(Ci-C4)-alkyl-(C3-C7)-cycloalkyl, -0-(Ci-C4)-alkyl, -O-(C3-C7)-cycloalkyl, -O-(d-C4)-alkyl-(C3-C7)-cycloalkyl, -C(O)-N(R6)-R7 and -CN,

and two groups R5 bonded to adjacent ring carbon atoms in Ar, together with the carbon atoms carrying them, can form a 5-membered to 8-membered, monocyclic, unsaturated ring which comprises 0, 1 or 2 identical or different ring heteroatoms selected from the series consisting of nitrogen, oxygen and sulfur, and which is unsubstituted or substituted by one or more identical or different substituents R8;

R6 and R7 are independently of one another selected from the series consisting of H and (Ci-C4)-alkyl;

R8 is selected from the series consisting of halogen, (Ci-C4)-alkyl, -O-(Ci-C4)-alkyl and -CN;

R10 is selected from the series consisting of H and (Ci-C4)-alkyl;

R1 1 and R12 are independently of one another selected from the series consisting of H, (Ci-C4)-alkyl, (C3-C7)-cycloalkyl, -(Ci-C4)-alkyl-(C3-C7)-cycloalkyl, Het1 , -(d-C4)-alkyl-Hetl and -(Ci-C4)-alkyl-phenyl, wherein phenyl is unsubstituted or substituted by one or more identical or different substituents R50,

or R1 1 and R12, together with the nitrogen atom carrying them, form a 4-membered to 7-membered, monocyclic, saturated, heterocyclic group which, in addition to the nitrogen atom carrying R1 1 and R12, comprises 0 or 1 further ring heteroatom selected from the series consisting of nitrogen, oxygen and sulfur, and which is

unsubstituted or substituted by one or more identical or different substituents selected from the series consisting of fluorine and (Ci-C4)-alkyl;

R13 is selected from the series consisting of H, (Ci-C4)-alkyl and (C3-C7)-cycloalkyl;

R14 and R16 are independently of one another selected from the series consisting of (Ci-C8)-alkyl, (C3-C7)-cycloalkyl, -(Ci-C4)-alkyl-(C3-C7)-cycloalkyl, phenyl, -(d-C4)-alkyl-phenyl, Het2 and -(Ci-C4)-alkyl-Het2, wherein (Ci-C8)-alkyl and (C3-C7)-cycloalkyl all are unsubstituted or substituted by one or more identical or different substituents selected from the series consisting of -OH and -O-(Ci-C4)-alkyl, and wherein phenyl and Het2 all are unsubstituted or substituted by one or more identical or different substituents R50;

R15 is selected from the series consisting of (Ci-CsJ-alkyl, phenyl and Het3, wherein phenyl and Het3 all are unsubstituted or substituted by one or more identical or different substituents R50;

R17 is selected from the series consisting of H and (Ci-C4)-alkyl;

R30 is a 3-membered to 12-membered, monocyclic or bicyclic, saturated, partially unsaturated or aromatic, cyclic group which comprises 0, 1 , 2 or 3 identical or different ring heteroatoms selected from the series consisting of nitrogen, oxygen and sulfur, which is unsubstituted or substituted by one or more identical or different substituents R32;

R31 is selected from the series consisting of halogen, -OH, -O-(Ci-C4)-alkyl, -O-(C3-C7)-cycloalkyl, -O-(Ci-C4)-alkyl-(C3-C7)-cycloalkyl, -N(R33)-R34, -CN and -C(O)-N(R35)-R36;

R32 is selected from the series consisting of halogen, (Ci-C4)-alkyl, (C3-C7)-cycloalkyl, -(Ci-C4)-alkyl-(C3-C7)-cycloalkyl, -(Ci-C4)-alkyl-O-R37, -(d-C4)-alkyl- N(R38)-R39, -(Ci-C4)-alkyl-CN, -C(0)-(Ci-C4)-alkyl, -CN, -OH, =O, -O-(d-C4)-alkyl, -N(R40)-R41 , -C(0)-0-(Ci-C4)-alkyl and -C(O)-N(R42)-R43;

R33, R34, R35, R36, R37, R38, R39, R40, R41 , R42 and R43 are independently of one another selected from the series consisting of H and (Ci-C4)-alkyl;

R50 is selected from the series consisting of halogen, (Ci-C4)-alkyl, -O-(Ci-C4)-alkyl and -CN;

Het1 is a 4-membered to 7-membered, monocyclic, saturated, heterocyclic group which comprises 1 or 2 identical or different ring heteroatoms selected from the series consisting of nitrogen, oxygen and sulfur, and is bonded via a ring carbon atom, and which is unsubstituted or substituted by one or more identical or different substituents selected from the series consisting of fluorine and (Ci-C4)-alkyl;

Het2 is a 4-membered to 7-membered, monocyclic, saturated, partially unsaturated or aromatic, heterocyclic group which comprises 1 or 2 identical or different ring heteroatoms selected from the series consisting of nitrogen, oxygen and sulfur, and is bonded via a ring carbon atom;

Het3 is a 5-membered or 6-membered, monocyclic, aromatic, heterocyclic group which comprises 1 , 2 or 3 identical or different ring heteroatoms selected from the series consisting of nitrogen, oxygen and sulfur, and is bonded via a ring carbon atom;

wherein all cycloalkyi groups, independently of any other substituents which can be present on a cycloalkyi group, can be substituted by one or more identical or different substituents selected from the series consisting of fluorine and (Ci-C4)-alkyl;

wherein all alkyl groups, independently of any other substituents which can be present on an alkyl group, can be substituted by one or more fluorine substituents.

2. A compound of the formula I, in any of its stereoisomeric forms or a mixture of stereoisomeric forms in any ratio, or a pharmaceutically acceptable salt thereof, according to claim 1 , wherein

Ar is selected from the series consisting of phenyl and a 5-membered or 6-membered, monocyclic, aromatic, heterocyclic group which comprises 1 or 2 identical or different ring heteroatoms selected from the series consisting of nitrogen, oxygen and sulfur, and is bonded via a ring carbon atom, which all are unsubstituted or substituted by one or more identical or different substituents R5;

n is selected from the series consisting of 0, 1 and 2;

X is selected from the series consisting of N and CH;

Z is selected from the series consisting of a direct bond, O, S and N(R10);

R1 is selected from the series consisting of H, -N(R1 1 )-R12, -N(R13)-C(O)-R14, -N(R13)-S(O)2-R15, -N(R13)-C(O)-NH-R16 and (Ci-C4)-alkyl;

R2 is selected from the series consisting of halogen, (Ci-C4)-alkyl, -O-(Ci-C4)-alkyl and -CN;

R3 is selected from the series consisting of H, (d-CsJ-alkyl, R30 and -(Ci-C4)-alkyl-R30, wherein (Ci-Cs)-alkyl is unsubstituted or substituted by one or more identical or different substituents R31 ;

R5 is selected from the series consisting of halogen, (Ci-C4)-alkyl, (C3-C7)-cycloalkyl, -O-(Ci-C4)-alkyl, -O-(C3-C7)-cycloalkyl, -C(O)-N(R6)-R7 and -CN,

and two groups R5 bonded to adjacent ring carbon atoms in Ar, together with the carbon atoms carrying them, can form a 5-membered to 8-membered, monocyclic, unsaturated ring which comprises 0, 1 or 2 identical or different ring heteroatoms

selected from the series consisting of nitrogen, oxygen and sulfur, and which is unsubstituted or substituted by one or more identical or different substituents R8;

R6 and R7 are independently of one another selected from the series consisting of H and (Ci-C4)-alkyl;

R8 is selected from the series consisting of halogen and (Ci-C4)-alkyl;

R10 is selected from the series consisting of H and (Ci-C4)-alkyl;

R1 1 and R12 are independently of one another selected from the series consisting of H, (Ci-C4)-alkyl, (C3-C7)-cycloalkyl, -(Ci-C4)-alkyl-(C3-C7)-cycloalkyl, Het1 , -(d-C4)-alkyl-Hetl and -(Ci-C4)-alkyl-phenyl, wherein phenyl is unsubstituted or substituted by one or more identical or different substituents R50;

R13 is selected from the series consisting of H and (Ci-C4)-alkyl;

R14 and R16 are independently of one another selected from the series consisting of (Ci-C8)-alkyl, (C3-C7)-cycloalkyl, -(Ci-C4)-alkyl-(C3-C7)-cycloalkyl, phenyl, -(d-C4)-alkyl-phenyl, Het2 and -(Ci-C4)-alkyl-Het2, wherein (Ci-C8)-alkyl and (C3-C7)-cycloalkyl all are unsubstituted or substituted by one or more identical or different substituents selected from the series consisting of -OH and -O-(Ci-C4)-alkyl, and wherein phenyl and Het2 all are unsubstituted or substituted by one or more identical or different substituents R50;

R15 is selected from the series consisting of phenyl and Het3, wherein phenyl and Het3 all are unsubstituted or substituted by one or more identical or different substituents R50;

R30 is a 3-membered to 12-membered, monocyclic or bicyclic, saturated, partially unsaturated or aromatic, cyclic group which comprises 0, 1 , 2 or 3 identical or different ring heteroatoms selected from the series consisting of nitrogen, oxygen and sulfur, which is unsubstituted or substituted by one or more identical or different substituents R32;

R31 is selected from the series consisting of halogen, -OH, -O-(Ci-C4)-alkyl, -0-(C-3-C7)-cycloalkyl, -O-(Ci-C4)-alkyl-(C3-C7)-cycloalkyl, -N(R33)-R34 and -CN;

R32 is selected from the series consisting of halogen, (Ci-C4)-alkyl, (C3-C7)-cycloalkyl, -(Ci-C4)-alkyl-(C3-C7)-cycloalkyl, -(Ci-C4)-alkyl-O-R37, -(d-C4)-alkyl-N(R38)-R39, -(Ci-C4)-alkyl-CN, -C(O)-(Ci-C4)-alkyl, -CN, -OH, =O, -O-(d-C4)-alkyl, -N(R40)-R41 , -C(O)-O-(Ci-C4)-alkyl and -C(O)-N(R42)-R43;

R33, R34, R37, R38, R39, R40, R41 , R42 and R43 are independently of one another selected from the series consisting of H and (Ci-C4)-alkyl;

R50 is selected from the series consisting of halogen, (Ci-C4)-alkyl, -O-(Ci-C4)-alkyl and -CN;

Het1 is a 4-membered to 7-membered, monocyclic, saturated, heterocyclic group which comprises 1 or 2 identical or different ring heteroatoms selected from the series consisting of nitrogen, oxygen and sulfur, and is bonded via a ring carbon atom, and which is unsubstituted or substituted by one or more identical or different substituents selected from the series consisting of fluorine and (Ci-C4)-alkyl;

Het2 is a 4-membered to 7-membered, monocyclic, saturated, partially unsaturated or aromatic, heterocyclic group which comprises 1 or 2 identical or different ring heteroatoms selected from the series consisting of nitrogen, oxygen and sulfur, and is bonded via a ring carbon atom;

Het3 is a 5-membered or 6-membered, monocyclic, aromatic, heterocyclic group which comprises 1 or 2 identical or different ring heteroatoms selected from the series consisting of nitrogen, oxygen and sulfur, and is bonded via a ring carbon atom;

wherein all cycloalkyi groups, independently of any other substituents which can be present on a cycloalkyi group, can be substituted by one or more identical or different substituents selected from the series consisting of fluorine and (Ci-C4)-alkyl;

wherein all alkyl groups, independently of any other substituents which can be present on an alkyl group, can be substituted by one or more fluorine substituents.

3. A compound of the formula I, in any of its stereoisomeric forms or a mixture of stereoisomeric forms in any ratio, or a pharmaceutically acceptable salt thereof, according to any of claims 1 and 2, wherein

Ar is selected from the series consisting of phenyl and a 5-membered monocyclic, aromatic, heterocyclic group which comprises 1 or 2 identical or different ring heteroatoms selected from the series consisting of nitrogen and sulfur, and is bonded via a ring carbon atom, which all are unsubstituted or substituted by one or more identical or different substituents R5;

n is selected from the series consisting of 0, 1 and 2;

X is selected from the series consisting of N and CH;

Z is selected from the series consisting of a direct bond, O, S and N(R10);

R1 is selected from the series consisting of H, -N(R1 1 )-R12, -N(R13)-C(O)-R14, -N(R13)-S(O)2-R15, -N(R13)-C(O)-NH-R16 and (Ci-C4)-alkyl;

R2 is selected from the series consisting of halogen, (Ci-C4)-alkyl and -O-(Ci-C4)-alkyl;

R3 is selected from the series consisting of H, (d-CeJ-alkyl, R30 and -(Ci-C4)-alkyl-R30, wherein (Ci-Cs)-alkyl is unsubstituted or substituted by one or more identical or different substituents R31 ;

R5 is selected from the series consisting of halogen, (Ci-C4)-alkyl, (C3-C7)-cycloalkyl, -O-(Ci-C4)-alkyl, -O-(C3-C7)-cycloalkyl and -CN,

and two groups R5 bonded to adjacent ring carbon atoms in Ar, together with the carbon atoms carrying them, can form a 5-membered to 7-membered, monocyclic, unsaturated ring which comprises 0, 1 or 2 oxygen atoms as ring heteroatoms, and which is unsubstituted or substituted by one or more identical or different substituents R8;

R8 is selected from the series consisting of halogen and (Ci-C4)-alkyl;

R10 is selected from the series consisting of H and (Ci-C4)-alkyl;

one of the groups R1 1 and R12 is selected from the series consisting of hydrogen and (Ci-C4)-alkyl, and the other of the groups R1 1 and R12 is selected from the series consisting of hydrogen, (Ci-C4)-alkyl, (C3-C7)-cycloalkyl, -(Ci-C4)-alkyl-(C3-C7)-cycloalkyl, Het1 , -(Ci-C4)-alkyl-Het1 and -(Ci-C4)-alkyl-phenyl;

R13 is selected from the series consisting of H and (Ci-C4)-alkyl;

R14 and R16 are independently of one another selected from the series consisting of (Ci-C8)-alkyl, (C3-C7)-cycloalkyl, -(Ci-C4)-alkyl-(C3-C7)-cycloalkyl, phenyl, -(d-C4)-alkyl-phenyl, Het2 and -(Ci-C4)-alkyl-Het2, wherein (Ci-C8)-alkyl and (C3-C7)-cycloalkyl all are unsubstituted or substituted by one or more identical or different substituents selected from the series consisting of -OH and -O-(Ci-C4)-alkyl, and wherein phenyl and Het2 all are unsubstituted or substituted by one or more identical or different substituents R50;

R15 is phenyl which is unsubstituted or substituted by one or more identical or different substituents R50;

R30 is a 3-membered to 12-membered, monocyclic or bicyclic, saturated, partially unsaturated or aromatic, cyclic group which comprises 0, 1 , 2 or 3 identical or different ring heteroatoms selected from the series consisting of nitrogen and oxygen, which is unsubstituted or substituted by one or more identical or different substituents R32;

R31 is selected from the series consisting of halogen, -OH, -O-(Ci-C4)-alkyl, -0-(C-3-C7)-cycloalkyl, -0-(Ci-C4)-alkyl-(C3-C7)-cycloalkyl and -N(R33)-R34;

R32 is selected from the series consisting of halogen, (Ci-C4)-alkyl, (C3-C7)-cycloalkyl, -(Ci-C4)-alkyl-(C3-C7)-cycloalkyl, -(Ci-C4)-alkyl-O-R37, -(d-C4)-alkyl-N(R38)-R39, -OH, =O, -O-(d-C4)-alkyl and -N(R40)-R41 ;

R33, R34, R37, R38, R39, R40 and R41 are independently of one another selected from the series consisting of H and (Ci-C4)-alkyl;

R50 is selected from the series consisting of halogen, (Ci-C4)-alkyl, -O-(Ci-C4)-alkyl and -CN;

Het1 is a 4-membered to 7-membered, monocyclic, saturated, heterocyclic group which comprises 1 or 2 identical or different ring heteroatoms selected from the series consisting of nitrogen and oxygen, and is bonded via a ring carbon atom, and which is unsubstituted or substituted by one or more identical or different substituents selected from the series consisting of fluorine and (Ci-C4)-alkyl;

Het2 is a 4-membered to 7-membered, monocyclic, saturated, partially unsaturated or aromatic, heterocyclic group which comprises 1 or 2 identical or different ring heteroatoms selected from the series consisting of nitrogen, oxygen and sulfur, and is bonded via a ring carbon atom;

wherein all cycloalkyi groups, independently of any other substituents which can be present on a cycloalkyi group, can be substituted by one or more identical or different substituents selected from the series consisting of fluorine and (Ci-C4)-alkyl;

wherein all alkyl groups, independently of any other substituents which can be present on an alkyl group, can be substituted by one or more fluorine substituents.

4. A compound of the formula I, in any of its stereoisomeric forms or a mixture of stereoisomeric forms in any ratio, or a pharmaceutically acceptable salt thereof, according to any of claims 1 to 3, wherein

Ar is phenyl, which is unsubstituted or substituted by one or more identical or different substituents R5;

n is selected from the series consisting of 0 and 1 ;

X is selected from the series consisting of N and CH;

Z is selected from the series consisting of a direct bond, O and N(R10);

R1 is selected from the series consisting of H, -N(R1 1 )-R12, -N(R13)-C(O)-R14 and (Ci-C4)-alkyl;

R2 is selected from the series consisting of halogen and -O-(Ci-C4)-alkyl;

R3 is selected from the series consisting of H, (d-CsJ-alkyl, R30 and -(Ci-C4)-alkyl-R30, wherein (Ci-Cs)-alkyl is unsubstituted or substituted by one or more identical or different substituents R31 ;

R5 is selected from the series consisting of halogen, (Ci-C4)-alkyl, -O-(Ci-C4)-alkyl and -CN,

and two groups R5 bonded to adjacent ring carbon atoms in Ar, together with the carbon atoms carrying them, can form a 5-membered to 7-membered, monocyclic, unsaturated ring which comprises 0, 1 or 2 oxygen atoms as ring heteroatoms, and which is unsubstituted or substituted by one or more identical or different substituents R8;

R8 is selected from the series consisting of halogen and (Ci-C4)-alkyl;

R10 is selected from the series consisting of H and (Ci-C4)-alkyl;

one of the groups R1 1 and R12 is selected from the series consisting of hydrogen and (Ci-C4)-alkyl, and the other of the groups R1 1 and R12 is selected from the series consisting of hydrogen, (Ci-C4)-alkyl, -(Ci-C4)-alkyl-(C3-C7)-cycloalkyl and

-(Ci-C4)-alkyl-Het1 ;

R13 is selected from the series consisting of H and (Ci-C4)-alkyl;

R14 is selected from the series consisting of (C3-C7)-cycloalkyl, phenyl and Het2, wherein (C3-C7)-cycloalkyl is unsubstituted or substituted by one or more identical or different substituents selected from the series consisting of -OH and -O-(Ci-C4)-alkyl, and wherein phenyl and Het2 all are unsubstituted or substituted by one or more identical or different substituents R50;

R30 is a 3-membered to 10-membered, monocyclic or bicyclic, saturated, partially unsaturated or aromatic, cyclic group which comprises 0, 1 , 2 or 3 identical or different ring heteroatoms selected from the series consisting of nitrogen and oxygen, which is unsubstituted or substituted by one or more identical or different substituents R32;

R31 is selected from the series consisting of halogen, -OH, -O-(Ci-C4)-alkyl, -0-(C-3-C7)-cycloalkyl and -N(R33)-R34;

R32 is selected from the series consisting of halogen, (Ci-C4)-alkyl, (C3-C7)-cycloalkyl, -(Ci-C4)-alkyl-O-R37, -(Ci-C4)-alkyl-N(R38)-R39, -OH, =O, -O-(d-C4)-alkyl and -N(R40)-R41 ;

R33, R34, R37, R38, R39, R40 and R41 are independently of one another selected from the series consisting of H and (Ci-C4)-alkyl;

R50 is selected from the series consisting of halogen, (Ci-C4)-alkyl, -O-(Ci-C4)-alkyl and -CN;

Het1 is a 4-membered to 7-membered, monocyclic, saturated, heterocyclic group which comprises 1 or 2 identical or different ring heteroatoms selected from the series consisting of nitrogen and oxygen, and is bonded via a ring carbon atom, and which is unsubstituted or substituted by one or more identical or different substituents selected from the series consisting of fluorine and (Ci-C4)-alkyl;

Het2 is a 4-membered to 7-membered, monocyclic, saturated or aromatic,

heterocyclic group which comprises 1 or 2 identical or different ring heteroatoms selected from the series consisting of nitrogen, oxygen and sulfur, and is bonded via a ring carbon atom;

wherein all cycloalkyi groups, independently of any other substituents which can be present on a cycloalkyi group, can be substituted by one or more identical or different substituents selected from the series consisting of fluorine and (Ci-C4)-alkyl;

wherein all alkyl groups, independently of any other substituents which can be present on an alkyl group, can be substituted by one or more fluorine substituents.

5. A compound of the formula I, in any of its stereoisomeric forms or a mixture of stereoisomeric forms in any ratio, or a pharmaceutically acceptable salt thereof, according to any of claims 1 to 4, wherein

Ar is phenyl, which is unsubstituted or substituted by one or more identical or different substituents R5;

n is selected from the series consisting of 0 and 1 ;

X is selected from the series consisting of N and CH;

Z is selected from the series consisting of a direct bond and O;

R1 is selected from the series consisting of H, -N(R1 1 )-R12 and (Ci-C4)-alkyl;

R2 is selected from the series consisting of halogen;

R3 is selected from the series consisting of H, R30 and -(Ci-C4)-alkyl-R30;

R5 is selected from the series consisting of halogen, (Ci-C4)-alkyl, -O-(Ci-C4)-alkyl and -CN;

R1 1 and R12 are independently of one another selected from the series consisting of hydrogen and (Ci-C4)-alkyl;

R30 is a 3-membered to 7-membered, monocyclic, saturated or aromatic, cyclic group which comprises 0, 1 or 2 identical or different ring heteroatoms selected from the series consisting of nitrogen and oxygen, which is unsubstituted or substituted by one or more identical or different substituents R32;

R32 is selected from the series consisting of halogen, (Ci-C4)-alkyl, (C3-C7)-cycloalkyl, -(Ci-C4)-alkyl-O-R37, -(Ci-C4)-alkyl-N(R38)-R39, -OH and =0;

R37, R38 and R39 are independently of one another selected from the series consisting of H and (Ci-C4)-alkyl;

wherein all cycloalkyi groups can be substituted by one or more identical or different substituents selected from the series consisting of fluorine and (Ci-C4)-alkyl;

wherein all alkyl groups, independently of any other substituents which can be present on an alkyl group, can be substituted by one or more fluorine substituents.

6. A compound of the formula I, in any of its stereoisomeric forms or a mixture of stereoisomeric forms in any ratio, or a pharmaceutically acceptable salt thereof, according to any of claims 1 to 5, wherein Z is a direct bond.

7. A compound of the formula I, in any of its stereoisomeric forms or a mixture of stereoisomeric forms in any ratio, or a pharmaceutically acceptable salt thereof, according to any of claims 1 to 5, wherein Z is O.

8. A compound of the formula I, in any of its stereoisomeric forms or a mixture of stereoisomeric forms in any ratio, or a pharmaceutically acceptable salt thereof, according to any of claims 1 to 7, wherein X is N.

9. A compound of the formula I, in any of its stereoisomeric forms or a mixture of stereoisomeric forms in any ratio, or a pharmaceutically acceptable salt thereof, according to any of claims 1 to 7, wherein X is CH.

10. A compound of the formula I according to any of claims 1 to 9, which is selected from the series consisting of:

N-[4-(3-Amino-4-cyclopropyl-1 H-pyrazolo[3,4-d]pyrimidin-6-yl)-phenyl]-2-cyano-5-methoxy-benzenesulfonamide,

N-[4-(3-Amino-1 H-pyrazolo[3,4-d]pyrimidin-6-yl)-phenyl]-2,5-difluoro-benzenesulfonamide,

N-[4-(3-Amino-1 H-pyrazolo[3,4-d]pyrimidin-6-yl)-phenyl]-5-chloro-2-cyano-benzenesulfonamide,

2-Chloro-N-{4-[4-(1 -ethyl-piperidin-3-yloxy)-3-methyl-1 H-pyrazolo[3,4-d]pyrimidi yl]-phenyl}-5-methoxy-benzenesulfonannide,

5-Chloro-N-{4-[4-(1 -ethyl-piperidin-3^^

yl]-phenyl}-2-fluoro-benzenesulfonamide,

4-{6-[4-(2,5-Difluoro-benzenesulfonylamino)-phenyl]-3-nnethyl-1 H-pyrazolo[3,4-d]pyrinnidin-4-yloxy}-pipendine-1 -carboxylic acid ethyl ester,

N-[4-(3-Amino-4-propoxy-1 H-pyrazolo[3,4-d]pyrinnidin-6-yl)-phenyl]-2,5-difluoro-benzenesulfonamide,

N-[4-(3-Amino-4-ethoxy-1 H-pyrazolo[3,4-d]pyrimidin-6-yl)-phenyl]-5-chloro-2-fluoro-benzenesulfonamide,

N-[4-(3-Amino-4-propoxy-1 H-pyrazolo[3,4-d]pyrinnidin-6-yl)-phenyl]-5-chloro-2-fluoro-benzenesulfonamide,

N-[4-(3-Amino-4-ethoxy-1 H-pyrazolo[3,4-d]pyrimidin-6-yl)-phenyl]-2,5-difluoro-benzenesulfonamide,

2-Fluoro-N-(4-{4-[1 -(2-methoxy-ethyl)-piperidin-4-yloxy]-3-nnethyl-1 H-pyrazolo[3,4-d]pyrimidin-6-yl}-phenyl)-5-methyl-benzenesulfonamide,

2,5-Difluoro-N-(4-{4-[1 -(2-methoxy-ethyl)-piperidin-4-yloxy]-3-methyl-1 H-pyrazolo[3,4-d]pyrinnidin-6-yl}-phenyl)-benzenesulfonannide,

5- Chloro-2-fluoro-N-(4-{4-[1 -(2-methoxy-ethyl)-piperidin-4-yloxy]-3-methyl-1 H-pyrazolo[3,4-d]pyrinnidin-6-yl}-phenyl)-benzenesulfonannide,

N-{4-[4-(1 -Ethyl-piperidin-4-yloxy)-3-methyl-1 H-pyrazolo[3,4-d]pyrimidin-6-yl^^

2-fluoro-5-methoxy-benzenesulfonannide,

2,5-Dichloro-N-{4-[4-(1 -ethyl-piperidin-4-yloxy)-3-nnethyl-1 H-pyrazolo[3,4-d]pyrimidin- 6- yl]-phenyl}-benzenesulfonamide,

N-{4-[4-(1 -Ethyl-piperidin-4-yloxy)-3-methyl-1 H-pyrazolo[3,4-d]pyrimidin-6-yl]-phenyl}-2-fluoro-5-methyl-benzenesulfonannide,

N-{4-[4-(1 -Ethyl-piperidin-4-yloxy)-3-methyl-1 H-pyrazolo[3,4-d]pyrimidin-6-yl^^

2-fluoro-benzenesulfonamide,

5-Chloro-N-{4-[4-(1 -ethyl-piperidin-4-yloxy)-3-methyl-1 H-pyrazolo[3,4-d]pyrimi^ yl]-phenyl}-2-fluoro-benzenesulfonamide,

N-{4-[4-(1 -Cyclobutyl-piperidin-4-yloxy)-3-methyl-1 H-pyrazolo[3,4-d]pyrimidin-6-yl^^ phenyl}-2,5-difluoro-benzenesulfonannide,

2,5-Difluoro-N-(4-{4-[1 -(3-nnethoxy-propyl)-piperidin-4-yloxy]-3-nnethyl-1 H-pyrazolo[3,4-d]pyrinnidin-6-yl}-phenyl)-benzenesulfonannide,

5- Chloro-2-fluoro-N-{4-[4-(3-hydroxy-propoxy)-3-methyl-1 H-pyrazolo[3,4-d]pyrimidin- 6- yl]-phenyl}-benzenesulfonamide,

2,5-Difluoro-N-{4-[4-(1 -isopropyl-piperidin-4-yloxy)-3-methyl-1 H-pyrazolo[3,4-d]pyrinnidin-6-yl]-phenyl}-benzenesulfonannide,

2-Fluoro-N-(4-{4-[1 -(2-fluoro-ethyl)-piperidin-4-yloxy]-3-methyl-1 H-pyrazolo[3,4-d]pyrinnidin-6-yl}-phenyl)-benzenesulfonannide,

5-Chloro-2-fluoro-N-{4-[4-(1 -isopropyl-piperidin-4-yloxy)-3-methyl-1 H-pyrazolo[3,4-d]pyrinnidin-6-yl]-phenyl}-benzenesulfonannide,

2,5-Difluoro-N-(4-{4-[1 -(2-fluoro-ethyl)-piperidin-4-yloxy]-3-nnethyl-1 H-pyrazolo[3,4-d]pyrinnidin-6-yl}-phenyl)-benzenesulfonannide,

N-[4-(3-Amino-4-isopropoxy-1 H-pyrazolo[3,4-d]pyrinnidin-6-yl)-phenyl]-2,5-dichloro-benzenesulfonamide,

N-[4-(3-Amino-4-isobutoxy-1 H-pyrazolo[3,4-d]pyrinnidin-6-yl)-phenyl]-2,5-difluoro-benzenesulfonamide,

N-[4-(3-Amino-4-isobutoxy-1 H-pyrazolo[3,4-d]pyrimidin-6-yl)-phenyl]-2-fluoro-5-methoxy-benzenesulfonannide,

2,5-Dichloro-N-{4-[3-methyl-4-(pipendin-3-yloxy)-1 H-pyrazolo[3,4-d]pyrinnidin-6-yl]-phenylj-benzenesulfonamide,

2,5-Difluoro-N-{4-[3-methyl-4-(piperidin-3-yloxy)-1 H-pyrazolo[3,4-d]pynmidin-6-yl]-phenylj-benzenesulfonamide,

2-Fluoro-5-methyl-N-{4-[3-methyl-4-(nnorpholin-2-ylnnethoxy)-1 H-pyrazolo[3,4-d]pyrinnidin-6-yl]-phenyl}-benzenesulfonannide,

N-{4-[4-(3-Aminonnethyl-oxetan-3-ylnnethoxy)-1 H-pyrazolo[3,4-d]pyrinnidin-6-yl]-phenyl}-5-chloro-2-fluoro-benzenesulfonamide,

N-[4-(3-Amino-4-ethoxynnethyl-1 H-pyrazolo[3,4-d]pyrinnidin-6-yl)-phenyl]-2-fluoro-5-methyl-benzenesulfonannide,

N-[4-(3-Amino-4-trifluoromethyl-1 H-pyrazolo[3,4-d]pyrimidin-6-yl)-phenyl]-2,5-difluoro-benzenesulfonamide,

2-Fluoro-N-{4-[4-(piperidin-4-yloxy)-1 H-pyrazolo[3,4-d]pyrinnidin-6-yl]-phenyl}-benzenesulfonamide,

N-[4-(3-Amino-1 H-pyrazolo[3,4-d]pynnnidin-6-yl)-phenyl]-2-fluoro-5-nnethoxy-benzenesulfonamide,

N-[4-(3-Amino-4-methoxynnethyl-1 H-pyrazolo[3,4-d]pyrinnidin-6-yl)-phenyl]-5-chloro-2-fluoro-benzenesulfonamide,

N-{4-[4-(3-Amino-propoxy)-3-methyl-1 H-pyrazolo[3,4-d]pyrimidin-6-yl]-phenyl}-5-chloro-2-fluoro-benzenesulfonamide,

N-[4-(3-Amino-1 H-pyrazolo[3,4-d]pyrimidin-6-yl)-phenyl]-2,5-difluoro-benzenesulfonamide,

N-[4-(3-Amino-1 H-pyrazolo[3,4-d]pyrimidin-6-yl)-phenyl]-2,4,5-tnfluoro-benzenesulfonamide,

N-[4-(3-Amino-1 H-pyrazolo[3,4-d]pyrinnidin-6-yl)-phenyl]-2-chloro-4,5-difluoro-benzenesulfonamide,

N-{4-[3-Amino-4-(2,2,2-trifluoro-ethoxy)-1 H-pyrazolo[3,4-d]pynmidin-6-yl]-phenyl^ cyano-5-methyl-benzenesulfonannide,

N-[4-(3-Amino-4-trifluoromethyl-1 H-pyrazolo[3,4-d]pyrinnidin-6-yl)-phenyl]-5-chloro-2-fluoro-benzenesulfonamide,

N-{4-[3-Amino-4-(2-methoxy-ethyl)-1 H-pyrazolo[3,4-d]pyrimidin-6-yl]-phenyl}-2-cyano-5-methyl-benzenesulfonamide,

2-Cyano-5-methyl-N-{4-[4-(2,2,2-trifluoro-ethoxy)-1 H-pyrazolo[3,4-d]pynmidin-6-yl]-phenylj-benzenesulfonamide,

N-[4-(3-Amino-4-cyclopropyl-1 H-pyrazolo[3,4-d]pyrimidin-6-yl)-phenyl]-2,4,5-trifluoro-benzenesulfonamide,

N-[4-(3-Amino-4-cyclopropyl-1 H-pyrazolo[3,4-d]pyrimidin-6-yl)-phenyl]-2-fluoro-benzenesulfonamide,

N-[4-(3-Amino-4-cyclopropyl-1 H-pyrazolo[3,4-d]pyrimidin-6-yl)-phenyl]-2,5-difluoro-benzenesulfonamide,

N-[4-(3-Amino-4-nnethoxy-1 H-pyrazolo[3,4-d]pyrinnidin-6-yl)-phenyl]-5-chloro-2-fluoro-benzenesulfonamide,

N-[4-(3-Amino-4-nnethoxy-1 H-pyrazolo[3,4-d]pyrinnidin-6-yl)-phenyl]-5-chloro-2-cyano-benzenesulfonamide,

N-[4-(3-Amino-4-methyl-1 H-pyrazolo[3,4-d]pyrimidin-6-yl)-phenyl]-2-chloro-3,5-difluoro-benzenesulfonamide,

2-Cyano-N-{4-[4-(4-hydroxy-cyclohexyloxy)-1 H-pyrazolo[3,4-d]pyrimidin-6-yl]-phenyl}-5-methoxy-benzenesulfonannide,

N-[4-(3-Amino-1 H-pyrazolo[4,3-c]pyridin-6-yl)-phenyl]-5-chloro-2,4-difluoro-benzenesulfonamide,

5-Chloro-2-cyano-N-{4-[4-(4-hydroxy-cyclohexyloxy)-3-methyl-1 H-pyrazolo[3,4-d]pyrinnidin-6-yl]-phenyl}-benzenesulfonannide,

N-{4-[4-(1 -Cyclopropyl-piperidin-4-yloxy)-3-meth^^

phenyl}-2,5-difluoro-benzenesulfonannide,

5-Chloro-N-{4-[4-(1 -cyclopropyl-piperidin-4-yloxy)-3-methyl-1 H-pyrazolo[3,4-d]pyrinnidin-6-yl]-phenyl}-2-fluoro-benzenesulfonannide,

N-{4-[4-(1 -Acetyl-piperidin-4-yloxy)-3-methyM ^

phenyl}-2-fluoro-5-methoxy-benzenesulfonannide,

N-{4-[4-(1 -Acetyl-piperidin-4-yloxy)-3-phenyl}-2,5-difluoro-benzenesulfonannide,

N-{4-[4-(1 -Acetyl-piperidin-4-yloxy)-3-methyl-1 H-pyrazolo[3,4-d]pyrimidin-6-yl]-phenyl}-5-chloro-2-fluoro-benzenesulfonamide,

5-Chloro-2-fluoro-N-{4-[4-(6-hydroxy-pyridin-3-yloxy)-3-methyl-1 H-pyrazolo[3,4-d]pyrinnidin-6-yl]-phenyl}-benzenesulfonannide, and

2-Fluoro-N-{4-[4-(6-hydroxy-pyridin-3-yloxy)-3-methyl-1 H-pyrazolo[3,4-d]pyrinnidin-6-yl]-phenyl}-5-methyl-benzenesulfonannide,

or a pharmaceutically acceptable salt thereof.

1 1 . A process for the preparation of a compound of the formula I according to any of claims 1 to 10,

III

which comprises reacting a compound of the formula II and a compound of the formula III to give a compound of the formula IV, and optionally converting the compound of the formula IV into a compound of the formula I, wherein X, Z, R1 to R3 and n in the compounds of the formulae II, III and IV are defined as in the compound of the formula I or functional groups are present in protected form or in the form of a precursor group, the group G1 in the compound of the formula II is halogen or a sulfonyloxy group, the group G3 in the compounds of formulae II and IV is hydrogen or a protecting group, the group G4 in the compounds of formulae III and IV is the group of the formula Ar-S(O)2-NH- in which Ar is defined as in the compound of the formula I or functional groups are present in protected form or in the form of a precursor group, or G4 is an amino group, a protected amino group or a precursor group of an amino group, and the group G5 in the compound of formula III is a trialkylstannyl group or a boronic acid group, a boronic acid ester group or cyclic boronic acid ester group.

12. A compound of the formula I, in any of its stereoisomeric forms or a mixture of stereoisomeric forms in any ratio, or a pharmaceutically acceptable salt thereof, according to any of claims 1 to 10, for use as a pharmaceutical.

13. A pharmaceutical composition, comprising a compound of the formula I, in any of its stereoisomeric forms or a mixture of stereoisomeric forms in any ratio, or a pharmaceutically acceptable salt thereof, according to any of claims 1 to 10, and a pharmaceutically acceptable carrier.

14. A compound of the formula I, in any of its stereoisomeric forms or a mixture of stereoisomeric forms in any ratio, or a pharmaceutically acceptable salt thereof, according to any of claims 1 to 10, for use as an inhibitor of serum and glucocorticoid regulated kinase (SGK) or in the treatment of degenerative joint disorders, degenerative cartilage changes, diabetes, cardiovascular diseases, fibrosis, inflammatory processes, epilepsy, pain, tumors or cerebral infarctions.

15. Use of a compound of the formula I, in any of its stereoisomeric forms or a mixture of stereoisomeric forms in any ratio, or a pharmaceutically acceptable salt thereof, according to any of claims 1 to 10, for the manufacture of a medicament for inhibition of serum and glucocorticoid regulated kinase (SGK) or for the treatment of degenerative joint disorders, degenerative cartilage changes, diabetes,

cardiovascular diseases, fibrosis, inflammatory processes, epilepsy, pain, tumors or cerebral infarctions.