The present invention relates to 8-aryl-substituted and 8-heteroaryl-substituted 9H-pyrido[3,4-b]indoles of the formula I,
in which A, E, G, R1 to R6 and R10 are as defined below, which stimulate
chondrogenesis and cartilage matrix synthesis and can be used in the treatment of cartilage disorders and conditions in which a regeneration of damaged cartilage is desired, for example joint diseases such as osteoarthritis. The invention furthermore relates to processes for the synthesis of the compounds of the formula I, their use as pharmaceuticals, and pharmaceutical compositions comprising them.
Osteoarthritis, which in the following is also abbreviated as "OA" and sometimes is also referred to as osteoarthrosis, is the most common degenerative disease which primarily involves cartilage damage in joints. With increasing age, up to 80% of the population is affected. Although clinical signs of the disease are rather
heterogeneous, patients suffering from OA generally demonstrate a common pathological phenotype. At early disease stages, which are characterized by moderate degradation of the cartilage lining of the joints, pain is the most prominent symptom. With progressing degradation of the cartilage and cartilage loss, an increase in pain results that is commonly accompanied by an increasing deficit in mobility of the affected joints and ultimately total immobility and loss of function. As a result of degradation of cartilage and cartilage loss, also subchondral structures start to change their morphology, leading to remodeling processes of the bone, such as a compaction of bone matter, and to the formation of cysts. In part patients also show signs of inflammation that additionally affects the synovial lining of the joint. At late stages of the disease, a total destruction of the joint is observed.
There is still an incomplete understanding of the pathophysiology of cartilage disorders such as OA, and until today no structure-modifying, or disease-modifying, therapies are available (cf. K. Wang et al., Expert Opin. Investig. Drugs, 2015, 24, 1539-1556; T. Aigner et al., Adv. Drug Deliv. Rev. 2006, 58, 128-149). Currently OA is generally treated with drugs which target pain and inflammation systemically or locally. Different non-steroidal anti-inflammatory drugs (NSAIDs) are used, as well as glucocorticoids which are administered locally by intra-articular injection. Both therapeutic strategies result in pain relief, but do not halt or reverse the progression of cartilage destruction. On top of such drug interventions, physical therapy and/or local intra-articular injections of hyaluronic acid are applied. Ultimately, a partial or total replacement of an affected joint, such as a knee or hip joint, is the only remaining choice for relieving patients from severe joint pain and restoring joint mobility and function.
Recently evidence has been generated that in particular in early stages of OA cartilage has still some potential for regeneration and self-healing, and it has been proposed to induce chondrogenesis, i.e. the process by which cartilage is generated, or stimulate cartilage growth, in order to reverse, or compensate for, cartilage destruction in OA. This concept was confirmed by recent data from clinical trials with recombinant human FGF18 (fibroblast growth factor 18, Sprifermin, AS902330), which showed cartilage protective effects in knee OA in humans (L. S. Lohmander et al., Arthritis Rheumatol. 2014, 66, 1820-1831 ; S. Onuora, Nature Rev. Rheumatol. 2014, 10, 322; WO 2008/023063). FGF18 is assumed to stimulate osteoblasts and, via the activation of chondrocytes, the formation of cartilage, and thus support healing, and not merely alleviate symptoms.
Articular cartilage functions as a low-friction, wear-resistant surface that covers the ends of bones and supports load transfer and motion of diarthrodial joints. These properties and functions of cartilage are owed to the composition of articular cartilage. Cartilage tissue, which is a kind of connective tissue and besides in joints is also present in intervertebral disks, for example, is built up by and contains a specialized cell type, the chondrocytes, that produce and maintain an extensive extracellular matrix composed mainly of collagen, mostly collagen type II and minor amounts of other types of collagen, of proteoglycans, mostly aggrecan, and of hyaluronic acid. The fibrillar collagen network and the highly negatively charged aggrecan confer tensile strength and compressive stiffness to the tissue (D.
Heinegard et al., Nature Rev. Rheumatol. 201 1 , 7, 50-56). Chondrocytes, which may account to only 2% of the volume of the tissue in normal articular cartilage, maintain homeostasis of the tissue by regulation of extracellular matrix anabolism and catabolism. This continuous rebuilding of cartilage in an equilibrium of formation and degradation of the matrix, which is present under normal conditions, is disturbed in disease states such as OA, in which catabolic processes predominate.
Besides biomechanically induced modulation of the chondrocyte biosynthetic activity, several soluble factors, such as growth/differentiation factors and cytokines, have been identified to modulate anabolic and catabolic activity of chondrocytes. Anabolic cytokines that are considered to participate in cartilage repair processes, are IGF-1 (insulin-like growth factor 1 ), members of the TGF-β (transforming growth factor β) superfamily (for example TGF-βΙ , GDF5 (growth/differentiation factor 5), BMP2 (bone morphogenetic protein 2), BMP4, BMP7) and FGFs (fibroblast growth factors). bFGF (basic fibroblast growth factor) is the most potent chondrocyte mitogen, and other FGF family members, for example FGF18, may interact with IGF-1 and TGF-β to promote and maintain specific chondrocyte activities depending on the stage of the chondrocyte cell or differentiation status (M. B. Goldring, Arthritis Rheum. 2000, 43, 1916-1926). In addition to an anabolic, or synthesis promoting function, growth factors and cytokines can exert an anti-catabolic function. BMP7, which is also known as OP-1 (osteogenic protein 1 ), for example, has been shown to counteract low doses of IL-1 β (interleukin 1 β) by inhibition of the expression of
metal loproteinases MMP3 (matrix metalloproteinase 3; also known as stromelysin 1 ) and MMP13 (also known as collagenase 3).
Among the catabolic cytokines, proinflammatory IL-1 a and IL-1 β as well as TNF-a (tumor necrosis factor a) are considered key factors which lead to extracellular matrix degradation by induction of the expression of proteinases, such as MMP3, MMP13, ADAMTS-4 ("A Disintegrin And Metalloproteinase with Thrombospondin Motifs"-4) and ADAMTS-5, which function as aggrecanase cleaving aggrecan, and by repression of the synthesis of the extracellular matrix synthesis components collagen II and aggrecan. Other catabolic cytokines known are IL-18, LIF (leukemia inhibitory factor) and OSM (Oncostatin M). In early osteoarthritis, chondrocytes attempt to repair a disturbed equilibrium of formation and degradation of the matrix by an endogenous repair process, but during progression of OA chondrocytes fail to maintain tissue homoeostasis, and the balance between anabolic and catabolic activity is lost and catabolic activity prevails (X. Houard et al., Curr. Rheumatol. Rep. 2013, 15, Article 375). Influencing anabolic and/or catabolic activities in favor of an increase in cartilage formation by means of appropriate active agents, similarly as observed with FGF18 in the study referred to above, offers an opportunity for treating OA.

Furthermore, recent evidence suggests the existence of progenitor cells within cartilage which might contribute to a repair response (S. Koelling et al., Cell Stem Cell 2009, 4, 324-335). Therefore, enhancement of chondrogenesis by influencing chondrocyte progenitor cells or mesenchymal stem cells arises as another therapeutic concept for treating osteoarthritis. In addition, chondrogenesis in the context of cell therapy is of relevance for cartilage repair. In particular in such approaches processes of cell differentiation and gene expression and influencing them by appropriate agents play a role. The SOX (SRY (sex determining region Y) box, or SRY-related HMG (high mobility group) box) family of transcription factors are the main inducers of chondrogenic differentiation, in particular SOX-9 which induces mesenchymal condensation and differentiation of cartilage precursor cells, followed by SOX-5 and SOX-6, which regulate the synthesis of cartilage matrix genes (B. de
Crombrugghe et al., Curr. Opin. Cell Biol. 2001 , 13, 721 -727). However, as indicated above, until today no structure-modifying therapies for the treatment of disease states like OA have become available, and there continues to be need for concepts or active agents, which can stimulate chondrogenesis and lead to cartilage
regeneration.
In WO 2010/038153 it has been described that a number of compounds of varying structures, mainly natural products such as flavonoid derivatives, are SOX

transcription factor activators and stimulate chondrogenesis. In E. S. Hara et al., Biochimie 2013, 95, 374-381 , and in JP 2012-171947 it has recently been described that the naturally occurring 7-alkoxy-substituted-pyrido[3,4-b]indole harmine (1 -methyl-7-methoxy-9H-pyrido[3,4-b]indole or 1 -methyl-7-methoxy-9H- -carboline) has a chondrogenic effect. But as the authors point out, in view of its property profile harmine itself does not seem to be a suitable drug substance for the treatment of degenerative joint diseases, and some structurally related compounds did not exhibit an analogous activity.

Surprisingly it has been found that the 8-aryl-substituted and 8-heteroaryl-substituted 9H-pyrido[3,4-b]indoles of the formula I are potent stimulators of chondrogenesis and of cartilage formation, and exhibit other suitable properties and can be designed to exhibit a property profile suitable for the intended use, for example with regard to their solubility, which can be desired to be either high or low, in the latter case allowing for a long residence time in a joint after intra-articular administration. The compounds of the formula I induce the synthesis of major articular cartilage matrix components such as collagen type II and aggrecan in chondrocytes. Furthermore, they lead to strong induction of SOX-5, SOX-6 and SOX-9. The compounds of the formula I thus are useful as active agents for regenerating cartilage and treating joint diseases such as OA, for example.

Various other 9H-pyrido[3,4-b]indoles, which are also designated as 9H- -carbolines, 9H-beta-carbolines or 9H-betacarbolines, have been described. For example, in US 4631 149 certain 9H-pyrido[3,4-b]indoles are disclosed which have antiviral,

antibacterial and antitumor activity. In US 5604236 9H-pyrido[3,4-b]indoles are disclosed which contain an acidic group and inhibit thromboxane synthetase, and are useful for the treatment of thromboembolic diseases. In WO 01/68648 and WO 03/039545 9H-pyrido[3,4-b]indoles are disclosed which inhibit the activity of ΙκΒ kinase and are useful for the treatment of cancer and other diseases. In WO

2008/132454 9H-pyrido[3,4-b]indoles are disclosed which are ligands for the GABAA receptor and are radiolabeled, and are useful as diagnostics in CNS disorders. In C. Domonkos et al., RSC Advances 2015, 5, 53809-53818, certain 9H-pyrido[3,4-b]indoles carrying an alkoxy substituent or substituted alkoxy substituent in position 7 of the ring system are disclosed which have anticancer activity. In WO 2015/083750 certain benzothiazole derivatives and certain 9H-pyrido[3,4-b]indole derivatives carrying an alkoxy-substituent or another substituent linked via an oxygen atom in position 7 of the ring system are disclosed which activate neuropoiesis via inhibition of dual-specificity tyrosine phosphorylation-regulated kinases (DYRK). 9H-pyrido[3,4-b]indoles which carry in the 8-position of the ring system a directly bonded

carbocyclic or heterocyclic aromatic group attached via a ring carbon atom, and which do not carry a directly bonded aromatic group in another position of the ring system and do not carry an alkoxy substituent or another substituent linked via an oxygen atom in position 7 of the ring system, have not yet been described, except for the compound 8-phenyl-9H-pyrido[3,4-b]indole, which has been prepared in studies about transition metal-catalyzed C-H bond functionalizations and is disclosed in N. Wu et al., Chem. Eur. J. 2014, 20, 3408-3418.

Thus, a subject of the present invention are compounds of the formula I and the pharmaceutically acceptable salts thereof,

wherein

A is selected from the series consisting of phenyl and a monocyclic or bicyclic, 5-membered to 10-membered, aromatic heterocyclic group, which comprises 1 or 2 identical or different hetero ring members selected from the series consisting of N, N(R20), O and S and is bonded via a ring carbon atom, wherein phenyl and the heterocyclic group are unsubstituted or substituted on ring carbon atoms by one or more identical of different substituents R21;

E is a direct bond or a chain consisting of 1 to 5 chain members of which 0, 1 or 2 chain members are identical or different hetero chain members selected from the series consisting of N(R25), O and S(O)m, and the other chain members are identical or different groups C(R26)(R27);

G is selected from the series consisting of hydrogen, halogen, (C1-C4)-alkyl, cyano and R30;

R1, R3, R4 and R6 are independently of each other selected from the series consisting of hydrogen, halogen and (C1-C4)-alkyl;

R2 is selected from the series consisting of hydrogen, halogen, (C1-C4)-alkyl and (C1-C4)-alkyl-O-C(O)-;

R5 is selected from the series consisting of hydrogen, halogen, (C1-C4)-alkyl, (C1-C4)-alkyl-O-, cyano, R7-O-C(O)- and R8-N(R9)-C(O)-;

R7, R8, R9, R20, R22, R25, R31, R33, R34 and R40 are independently of each other selected from the series consisting of hydrogen and (C1-C4)-alkyl;

R10 is selected from the series consisting of hydrogen, (C1-C6)-alkyl, (C2-C6)-alkenyl, (C2-C6)-alkynyl and (C3-C7)-cycloalkyl, wherein alkyl is unsubstituted or substituted by 1 or 2 identical or different substituents selected from the series consisting of (C3-C7)- cycloalkyl, Het, cyano and (C1-C4)-alkyl-O-, wherein all cycloalkyl groups are unsubstituted or substituted by one or more identical or different substituents selected from the series consisting of fluorine and (C1-C4)-alkyl;

R21 is selected from the series consisting of halogen, (CrC4)-alkyl, (C1-C4)-alkyl-O-and cyano, and two groups R21 bonded to adjacent ring carbon atoms in the group A, together with the carbon atoms carrying them, can form a 5-membered to 7-membered mono-unsaturated ring, which comprises 0, 1 or 2 identical or different hetero ring members selected from the series consisting of N(R22), O and S(O)m and which is unsubstituted or substituted on ring carbon atoms by one or more identical or different substituents selected from the series consisting of fluorine and (C1-C4)-alkyl;

R26 and R27 are independently of each other selected from the series consisting of hydrogen, fluorine, (C1-C4)-alkyl and hydroxy, and in one or two groups C(R26)(R27) the groups R26 and R27 bonded to the same carbon atom together can be oxo;

R30 is a monocyclic or bicyclic, 3-membered to 10-membered ring, which is saturated or unsaturated and comprises 0, 1 , 2 or 3 identical or different hetero ring members selected from the series consisting of N, N(R31), O and S(O)m, and which is unsubstituted or substituted on ring carbon atoms by one or more identical or different substituents R32;

R32 is selected from the series consisting of halogen, (C1-C4)-alkyl, hydroxy, oxo, (C1-C4)-alkyl-O-, cyano, R33-N(R34)- and Het;

Het is a monocyclic, 4-membered to 7-membered, saturated heterocyclic group, which comprises 1 or 2 identical or different hetero ring members selected from the series consisting of N, N(R40), O and S(O)m, and which is unsubstituted or substituted on ring carbon atoms by one or more identical or different substituents selected from the series consisting of fluorine and (C1-C4)-alkyl;

m is selected from the series consisting of 0, 1 and 2, wherein all numbers m are independent of each other and can be identical or different;

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

provided that the compound of the formula I is not 8-phenyl-9H-pyrido[3,4-b]indole.

If structural elements such as groups, substituents or numbers, like alkyi groups, substituents R21 or the numbers m, 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 alkyi groups can be identical or different.

Alkyi groups, i.e. saturated hydrocarbon residues, can be linear, i.e. straight-chain, or branched. This also applies if these groups are substituted or are part of another group, for example an alkyl-O- group (alkyloxy group, alkoxy group) or an alkyloxy-substituted alkyi group. Depending on the respective definition, the number of carbon atoms in an alkyi group can be 1 , 2, 3, 4, 5 or 6, or 1 , 2, 3 or 4, or any subgroup of these numbers, such as 2, 3 or 4, or 1 , 2 or 3, or 1 or 2, or 1 . Examples of alkyi are methyl (C1-alkyl), ethyl (C2-alkyl), propyl (C3-alkyl) including n-propyl and isopropyl, butyl (C4-alkyl) including n-butyl, sec-butyl, isobutyl and tert-butyl, pentyl (C4-alkyl) including n-pentyl, 1 -methylbutyl, isopentyl, neopentyl and tert-pentyl, and hexyl (Ce-alkyi) including n-hexyl, 3,3-dimethylbutyl and isohexyl. Examples of alkyl-O- groups are methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, tert-butoxy, n-pentoxy. A substituted alkyi 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 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 alkyi group, and unless specified otherwise, alkyi groups can be substituted by one or more fluorine substituents, for example by 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 1 1 , 12 or 13 fluorine substituents, or by 1 , 2, 3, 4 or 5 fluorine substituents, or by 1 , 2 or 3 fluorine substituents, or by any other number of fluorine substituents, which can be located in any positions of the alkyi group. I.e., independently of any other substituents which can be present on an alkyi group, an alkyi group can be unsubstituted by fluorine substituents, i.e. not carry fluorine substituents, or substituted by fluorine

substituents, wherein all alkyi 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 alkyi 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 alkyl-O- group. Examples of fluoro-substituted alkyi groups are trifluoromethyl (CF3), fluoromethyl, difluoromethyl, 2-fluoroethyl, 1 -fluoroethyl, 1 ,1 -difluoroethyl, 2,2,2-trifluoroethyl, pentafluoroethyl, 3,3,3-trifluoropropyl, 2,2,3,3,3-pentafluoropropyl, 4,4,4-trifluorobutyl and heptafluoroisopropyl. Examples of fluoro-substituted alkyl-O- groups are trifluoromethoxy (CF3-O-), 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 alkyi group that can generally contain one or more fluorine substituents, the group CF3, or a respective group such as CF3-O-, and other specific fluorine-substituted groups, may be included in the definition of the group or substituent as example of groups or substituents containing fluorine-substituted alkyi.

The above explanations with respect to alkyi groups apply correspondingly to alkyi 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 alkyi groups (alkanediyl groups, alkylene groups), like in the case of the alkyi part of a substituted alkyl group or in the case of the chain E, if E does not contain a heteroatom chain member. 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-, -CH(CH3)-, -C(CH3)2-, -CH(CH3)-CH2-, -CH2-CH(CH3)-,

-C(CH3)2-CH2-, -CH2-C(CH3)2-. Examples of fluoro-substituted divalent alkyl groups, which can contain 1 , 2, 3, 4, 5 or 6 fluorine substituents, for example, are -CHF-, -CF2-, -CF2-CH2-, -CH2-CF2-, -CF2-CF2-, -CF(CH3)-, -C(CF3)2-, -C(CH3)2-CF2-, -CF2-C(CH3)2-.

The above explanations with respect to alkyl groups apply correspondingly to unsaturated hydrocarbon residues, i.e. alkenyl groups, which in one embodiment of the invention contain one double bond, and alkynyl groups, which in one embodiment of the invention contain one triple bond. Thus, for example, alkenyl groups and alkynyl groups can likewise be linear or branched. Double bonds and triple bonds can be present in any positions. The number of carbon atoms in an alkenyl group and an alkynyl group can be 2, 3, 4, 5 or 6, or any subgroup of these numbers, such as 2, 3, 4 or 5, or 3, 4 or 5, or 2, 3 or 4, for example. Examples of alkenyl groups are ethenyl (vinyl), prop-1 -enyl, prop-2-enyl (allyl), but-1 -enyl, but-2-enyl, but-3-enyl, 2-methylprop-2-enyl, 3-methylbut-2-enyl, hex-3-enyl, hex-4-enyl, 4-methylpent-3-enyl. Examples of alkynyl groups are ethynyl, prop-1 -ynyl, prop-2-ynyl (propargyl), but-2-ynyl, but-3-ynyl, pent-2-ynyl, 4-methylpent-2-ynyl, hex-2-ynyl, hex-3-ynyl. In one embodiment of the invention, alkenyl groups and alkynyl groups contain at least three carbon atoms and are bonded to the remainder of the molecule via a carbon atom which is not part of a double bond or triple bond.

The number of ring carbon atoms in a (C3-C7)-cycloalkyl group can be 3, 4, 5, 6 or 7, or any subgroup of these numbers, such as 3, 4, 5 or 6, or 5, 6 or 7, or 3, 4 or 5, or 3 or 4, for example. Examples of cycloalkyl are cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl.

CycloalkyI groups can be substituted by one or more (C1-C4)-alkyl substituents, for example by 1 , 2, 3 or 4, or 1 , 3 or 3, or 1 or 2, identical or different (C1-C4)-alkyl substituents, for example by methyl groups, which can be located in any positions. I.e., cycloalkyi groups can be unsubstituted by (C1-C4)-alkyl substituents, i.e. not carry (C1-C4)-alkyl substituents, or substituted by (C1-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 (C1-C4)-alkyl substituents, cycloalkyi groups can be substituted by one or more fluorine substituents, for example by 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 1 1 , 12 or 13 fluorine substituents, or 1 , 2, 3, 4 or 5 fluorine substituents, or 1 , 2 or 3 fluorine substituents, or 1 or 2 fluorine substituents, which can be located in any positions and can also be present in a (C1-C4)-alkyl substituent. I.e., cycloalkyi groups can be unsubstituted by fluorine substituents, i.e. not carry fluorine substituents, or substituted by fluorine substituents. Examples of fluoro-substituted cycloalkyi groups are 1 -fluorocyclopropyl, 2,2-difluorocyclopropyl, 3,3-difluorocyclobutyl, 1 -fluorocyclohexyl, 4,4-difluorocyclohexyl, 3,3,4,4,5,5-hexafluorocyclohexyl. Cycloalkyi groups can also be substituted simultaneously by fluorine and alkyl substituents.

Examples of (C3-C7)-cycloalkyl-substituted alkyl groups, from any one or more of which a (C3-C7)-cycloalkyl-substituted alkyl group representing R10 is selected in one embodiment of the invention, 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-, 3-cyclopropylpropyl-, 3-cyclobutylpropyl-, 3-cyclopentylpropyl-, 3-cyclohexylpropyl-, 3-cycloheptylpropyl-. In one embodiment of the invention, a (C3-C7)-cycloalkyl-substituted (C1-C6)-alkyl group is a (C3-C7)-cycloalkyl-(C1-C4)-alkyl-group, in another embodiment a (C3-C7)-cycloalkyl-(C1-C2)-alkyl- group, in another

embodiment a (C3-C7)-cycloalkyl-CH2- group. In the group cyclopropylmethyl-, and likewise in all other groups containing one or two terminal hyphens like the group alkyl-O-, for example, the terminal hyphens denote the free bonds via which the group is bonded to the adjacent moieties in the molecule, and thus indicates via which atoms or subgroups a group composed of several atoms or subgroups is bonded.

In substituted phenyl groups, which can represent the group A and the group R30, 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, and in general 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, and likewise the number of substituents in any other substituted group which can carry one or more substituents, such as a heterocyclic group representing the group A, the group R30 or the group Het, 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 which can be present in the compounds of the formula I, including the group Het, aromatic heterocyclic groups representing the group A, heterocyclic groups representing the group R30 and heterocyclic rings formed by two

groups R together with the carbon 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 or S(O)m groups 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 oxygen atoms, sulfur atoms or S(O)m groups, and nitrogen atoms carrying an exocyclic group like a hydrogen atom or a substituent such as an alkyl group, 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 an aromatic monocycle or 10 delocalized pi electrons in case of an aromatic 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 like an alkyl group, and optionally one or more further ring nitrogen atoms which do not carry an exocyclic group, 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 any suitable ring carbon atom and ring nitrogen atom, unless specified otherwise. 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 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, three double bonds within the ring in the case of a 6-membered monocyclic aromatic heterocycle, and four or five double bonds for in the case of bicyclic aromatic heterocycle comprising a 6-membered ring and a 5-membered ring or two 6-membered rings, 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, the group Het, aromatic heterocyclic groups representing the group A, heterocyclic groups representing the group R30 and heterocyclic rings formed by two groups R21 together with the carbon 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 respective 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,

benzo[1 ,3]dioxole, benzoxazole, benzthiazole, 1 H-benzimidazole, chromane, isochromane, thiochromane, 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, 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]naphthyridine, 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 in line with 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), =O), and in such heterocycles a group S(O)m be present as hetero ring member, in which the number m can be 0 (zero) and thus a sulfur atom (-S-) be present in the ring, or m can be 1 and thus the group -S(O)- (-S(=O)-) be present in the ring, or m can be 2 and thus the group -S(O)2- (-S(=O)2-) be present in the ring.

As mentioned, unless specified otherwise, 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. In one embodiment of the invention, any of the heterocyclic groups occurring in the compounds of the formula I in any of its occurrences is, independently of its other occurrences and independently of any other heterocyclic group, bonded via a ring carbon atom, and in another embodiment via a ring nitrogen atom, if applicable. 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 [1 ,2,3]triazole ring via positions 1 , 4 and 5, a [1 ,2,4]triazole ring via positions 1 , 3 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, for example, 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, independently of any other occurrence, fluorine, chlorine or bromine, in another embodiment fluorine or chlorine, in another

embodiment fluorine, in another embodiment chlorine or bromine, 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. A subject of the present invention thus is 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. 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 alkenyl groups and 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, as well as all forms containing a specific isotopic pattern, for example deuterated compounds in which one or more hydrogen atoms are present in form of the deuterium isotop.

Besides the free compounds of the formula I, i.e. the compounds of the formula I themselves in which any acidic and basic groups are not present in the form of a salt and which may also be termed "salt-free" compounds, 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 groups, for example on carboxylic acid groups, or basic groups, for example amino group or basic heterocyclic moieties, in the compounds of the formula I. The compounds of the formula I may thus be deprotonated on an acidic group by an

inorganic or organic base and used, for example, in the form of the alkali metal salts. Compounds of the formula I comprising at least one basic group may 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 heterocyclic group representing the divalent group A is a monocyclic 5-membered or 6-membered group or a bicyclic 8-membered to 10-membered group, in another embodiment a monocyclic 5-membered or 6-membered group or a bicyclic 9-membered or 10-membered group. In one embodiment an aromatic heterocyclic group representing the group A is a monocyclic 5-membered or 6-membered group, in another embodiment it is a monocyclic 5-membered group, in another embodiment it is a monocyclic 6-membered group, in another embodiment it is a bicyclic 9-membered or 10-membered group, in another embodiment it is a bicyclic 9-membered group, and in another embodiment it is a bicyclic 10-membered group. In one embodiment the number of hetero ring members in a heterocycle representing A is 1 , in another embodiment it is 2. In one embodiment the hetero ring members in a heterocycle representing A are selected from the series consisting of N, N(R20) and S, in another embodiment from the series consisting of N, N(R20) and O, in another embodiment from the series consisting of N and N(R20), in another embodiment from the series consisting of N and S, in another embodiment from the series consisting of N and O,

in another embodiment they are N, and in another embodiment they are S. In the case of the group A, the hetero ring member N denotes a ring nitrogen atom which is bonded to the adjacent ring atoms in A via a single bond and a double bond and via which the ring A cannot be bonded to an another moiety in the molecule, as well as a ring nitrogen atom which is bonded to the adjacent ring atoms in A via two single bonds and which has a free valence via which the ring A can be bonded to the moiety G-E-. Examples of heterocycles, from which an aromatic heterocyclic group representing A can be derived and from any one or more of which an aromatic heterocyclic group representing A is selected in one embodiment of the invention, are furan, thiophene, pyrrole, isoxazole, oxazole, isothiazole, thiazole, pyrazole, imidazole, pyridine, pyridazine, pyrimidine, pyrazine, benzofuran, benzothiophene, 1 H-indole, benzoxazole, benzthiazole, 1 H-benzimidazole, 1 H-indazole, 1 H-pyrrolo[2,3-b]pyridine, pyrazolo[1 ,5-a]pyridine, quinoline, isoquinoline, cinnoline, quinazoline, quinoxaline, which can all be unsubstituted or substituted on ring carbon atoms by one or more identical or different substituents R21. In another embodiment, an aromatic heterocyclic group representing A is derived from an aromatic

heterocyclic group selected from the series consisting of thiophene, thiazole, pyrazole, imidazole, pyridine and pyrimidine, in another embodiment from the series consisting of thiophene, thiazole, pyrazole and pyridine, in another embodiment from the series consisting of thiophene, thiazole and pyridine, in another embodiment from the series consisting of thiophene, thiazole and pyrazole, in another embodiment from the series consisting of thiophene and pyridine, in another embodiment from the series consisting of thiazole and pyridine, in another embodiment from the series consisting of pyrazole and pyridine, in another from the series consisting of thiazole and pyrazole, in another embodiment an aromatic heterocyclic group representing A is derived from thiophene, in another embodiment from thiazole, in another embodiment from pyrazole, in another embodiment from pyridine, in another embodiment from pyrimidine, which can all be unsubstituted or substituted on ring carbon atoms by one or more identical or different substituents R21. In one

embodiment A is an aromatic heterocyclic group, which is unsubstituted or substituted on ring carbon atoms by one or more identical of different substituents R21, in another embodiment A is phenyl, which is unsubstituted or substituted by one or more identical of different substituents R . Also a group A that is unsubstituted, i.e. that does not carry any substituents R21, of course carries the group G-E-depicted in formula I, in which G and E can have all their meanings. As specified in the general definition of the group A, the divalent group A is bonded to the 9H-pyrido[3,4-b]indole ring depicted in formula I via a ring carbon atom. The group E, and the group G in case the group E is a direct bond, can be bonded to a ring carbon atom in the group A or to a ring nitrogen atom, i.e. to a hetero ring member N, in the group A.

If the divalent group E is a direct bond, the group G is linked to the group A via a single bond. If the group E is a chain, it consists of 1 , 2, 3, 4 or 5 chain members which are defined as specified in the definition of E, to the terminal chain members of which, or to the sole chain member of which in case the chain consists of 1 chain member only, the groups G and A are bonded. In one embodiment of the invention the divalent group E is a direct bond. In another embodiment, the divalent group E is a chain consisting of 1 , 2, 3, 4 or 5 chain members which are defined as specified in the definition of E. In one embodiment, the number of chain members in a chain E is 1 , 2, 3 or 4, in another embodiment 2, 3, 4 or 5, in another embodiment 1 , 2 or 3, in another embodiment 2, 3 or 4, in another embodiment 2 or 3, in another embodiment 1 , in another embodiment 2, in another embodiment 3, in another embodiment 4. In one embodiment, 0 (zero) or 1 chain members in a chain E are identical or different hetero chain members selected from the series consisting of N(R25), O and S(O)m, in another embodiment 1 or 2 chain members are such hetero chain members, in another embodiment 0 chain member is such a hetero chain member, in another embodiment 1 chain member is such a hetero chain member, and in another embodiment 2 chain members are such heterochain members. If 2 hetero chain members are present in a chain E, in one embodiment they are not present in adjacent positions of the chain, i. e., in this embodiment they are separated by at least 1 chain member C(R26)(R27), in another embodiment they are not present in adjacent positions of the chain unless one of them is the group S(O)m in which m is 1 or 2, and in another embodiment they are separated by 2 or 3, in another

embodiment by 2, in another embodiment by 3, chain members C(R26)(R27). In one

embodiment, hetero chain members in a chain E are selected from the series consisting of N(R25) and O, in another embodiment from the series consisting of O and S(O)m, in another embodiment they are identical or different groups N(R25), in another embodiment they are O, i.e. oxygen atoms, and in another embodiment they are identical or different groups S(O)m. In one embodiment the number m in the hetero chain member S(O)m in a chain E is selected from the series consisting of 0 and 1 , in another embodiment from the series consisting of 1 and 2, in another embodiment from the series consisting of 0 and 2, in another embodiment it is 0, in another embodiment it is 1 , and in another embodiment it is 2. If the terminal chain member in a chain E that is bonded to the group A, or the sole chain member in case the chain consists of 1 chain member only, is bonded to a ring nitrogen atom in A, in one embodiment such terminal chain member or sole chain member is not a hetero chain member, and in another embodiment such terminal chain member or sole chain member is not a hetero chain number selected from the series consisting of N(R25), O and S(O)m in which the number m is 0. If the terminal chain member in a chain E that is bonded to the group G, or the sole chain member in case the chain consists of 1 chain member only, is bonded to a ring nitrogen atom in a ring R30 representing G ot to halogen atom or a cyano group representing G, in one embodiment such terminal chain member is not a hetero chain member, and in another embodiment such terminal chain member is not a hetero chain number selected from the series consisting of N(R25), O and S(O)m in which the number m is 0.

In one embodiment of the invention the divalent group E is chosen from a direct bond and from any one or more of the chains which are present in the following examples of groups G-E-, which groups are bonded to the group A depicted in formula I by the free bond represented by the terminal hyphen, and from which groups the divalent chains E themselves are obtained by removing the group G, wherein in these groups the groups R25, R26 and R27 and the number m are defined as specified above or below:

G-C(R26)(R27)-,

G-C(R^b)(R27)-C(R2b)(R27)-,

G-C(R26)(R27)-C(R26)(R27)-C(R26)(R27)-,

G-C(R26)(R27)-C(R26)(R27)-C(R26)(R27)-C(R26)(R27)-, G-0-,

G-C(R26)(R27)-O-,

G-C(R26)(R27)-C(R26)(R27)-O-,

G-C(R26)(R27)-C(R26)(R27)-C(R26)(R27)-O-,

G-0-C(R26)(R27)-,

G-0-C(R26)(R27)-C(R26)(R27)-,

G-0-C(R26)(R27)-C(R26)(R27)-C(R26)(R27)-,

G-C(R26)(R27)-O-C(R26)(R27)-,

G-C(R26)(R27)-O-C(R26)(R27)-C(R26)(R27)-,

G-C(R26)(R27)-0-C(R26)(R27)-,

G-C(R26)(R27)-C(R26)(R27)-O-C(R26)(R27)-,

G-0-C(R26)(R27)-C(R26)(R27)-O-,

G-0-C(R26)(R27)-C(R26)(R27)-C(R26)(R27)-O-,

G-S(O)m-,

G-C(R26)(R27)-S(0)m-,

G-C(R26)(R27)-C(R26)(R27)-S(O)m-,

G-S(O)m-C(R26)(R27)-,

G-S(O)m-C(R26)(R27)-C(R26)(R27)-,

G-N(R25)-,

G-C(R26)(R27)-N(R25)-,

G-C(R26)(R27)-C(R26)(R27)-N(R25)-,

G-N(R25)-C(R26)(R27)-,

G-N(R25)-C(R26)(R27)-C(R26)(R27)-,

G-N(R25)-C(R26)(R27)-C(R26)(R27)-C(R26)(R27)-, G-N(R25)-C(R26)(R27)-N(R25)-,

G-N(R25)-C(R26)(R27)-C(R26)(R27)-N(R25)-,

G-N(R25)-C(R26)(R27)-C(R26)(R27)-N(R25)-C(R26)(R27)-, G-N(R25)-C(R26)(R27)-C(R26)(R27)-O-,

G-N(R25)-C(R26)(R27)-C(R26)(R27)-C(R26)(R27)-O-,

In one embodiment of the invention the group G is selected from the series consisting of hydrogen, halogen, (C1-C4)-alkyl and R30, in another embodiment from the series consisting of hydrogen, (C1-C4)-alkyl and R30, in another embodiment from the series consisting of hydrogen, halogen and R30, in another embodiment from the series consisting of hydrogen and R30, in another embodiment from the series consisting of hydrogen, halogen and (C1-C4)-alkyl, in another embodiment from the series consisting of of hydrogen, halogen, (C1-C4)-alkyl and cyano, in another embodiment G is hydrogen, and in another embodiment G is R30.

In one embodiment of the invention any one or more of the groups R1, R3, R4 and R6 are independently of each other selected from the series consisting of hydrogen, halogen and (C1-C2)-alkyl, in another embodiment from the series consisting of hydrogen, halogen and C1-alkyl, in another embodiment from the series consisting of hydrogen and halogen, in another embodiment from the series consisting of hydrogen and (C1-C4)-alkyl, in another embodiment from the series consisting of hydrogen and (C1-C2)-alkyl, in another embodiment from the series consisting of hydrogen and C1-alkyl, and in another embodiment they are independently of each other hydrogen, in another embodiment halogen, in another embodiment (C1-C4)- alkyl, in another embodiment (C1-C2)-alkyl and in another embodiment C1-alkyl.

In one embodiment of the invention the group R2 is selected from the series consisting of hydrogen, halogen, (C1-C2)-alkyl and (C1-C2)-alkyl-O-C(O)-, in another embodiment from the series consisting of hydrogen, halogen, C1-alkyl and (C1-C2)- alkyl-O-C(O)-, in another embodiment from the series consisting of hydrogen, halogen and (C1-C4)-alkyl, in another embodiment from the series consisting of hydrogen, halogen and (C1-C2)- alkyl, in another embodiment from the series consisting of hydrogen, halogen and C1-alkyl, in another embodiment from the series consisting of hydrogen and halogen, in another embodiment from the series

consisting of hydrogen and (C1-C4)-alkyl, in another embodiment from the series consisting of hydrogen and (C1-C2)-alkyl, in another embodiment from the series consisting of hydrogen and C1-alkyl, and in another embodiment R2 is hydrogen.

In one embodiment of the invention the group R5 is selected from the series consisting of hydrogen, halogen, (C1-C4)-alkyl, (C1-C4)-alkyl-O- and cyano, in another embodiment from the series consisting of hydrogen, halogen, (C1-C4)-alkyl, cyano, R7-O-C(O)- and R8-N(R9)-C(O)-, in another embodiment from the series consisting of hydrogen, halogen, (C1-C4)-alkyl and cyano, in another embodiment from the series consisting of hydrogen, halogen and (C1-C4)-alkyl, in another embodiment from the series consisting hydrogen and halogen, in another embodiment from the series consisting of halogen and (C1-C4)-alkyl, and in another embodiment R5 is halogen. In one embodiment halogen representing R5 is selected from the series consisting of chlorine and bromine, in another embodiment it is chlorine, and in another

embodiment it is bromine. In one embodiment a (C1-C4)-alkyl group representing R5 or present in R5 is independently of any other such alkyl group a (C1-C2)-alkyl group, in another embodiment a C1-alkyl group.

In one embodiment of the invention any one or more of the groups R7, R8, R9, R20, R22, R25, R31 , R33, R34 und R40 are independently of each other selected from the series consisting of hydrogen and (C1-C2)-alkyl, in another embodiment from the series consisting of hydrogen and C1-alkyl, and in another embodiment they are independently of each other hydrogen, in another embodiment (C1-C4)-alkyl, in another embodiment (C1-C2)-alkyl, in another embodiment C1-alkyl.

In one embodiment of the invention R10 is selected from the series consisting of hydrogen, (C1-C6)-alkyl, (C2-C6)-alkenyl and (C2-C6)-alkynyl, in another embodiment from the series consisting of hydrogen, (C1-C6)-alkyl, (C2-C6)-alkynyl and (C3-C7)-cycloalkyl, in another embodiment from the series consisting of hydrogen, (C1-C6)-alkyl and (C2-C6)-alkynyl, in another embodiment from the series consisting of hydrogen, (C1-C6)-alkyl and (C3-C7)-cycloalkyl, in another embodiment from the series consisting of hydrogen and (C1-C6)-alkyl, in another embodiment from the

series consisting of (C1-C6)-alkyl, (C2-C6)-alkenyl, (C2-C6)-alkynyl and (C3-C7)-cycloalkyl, in another embodiment from the series consisting of (CrC6)-alkyl, (C2-C6)-alkenyl and (C2-C6)-alkynyl, in another embodiment from the series consisting of (C1-C6)-alkyl, (C2-C6)-alkynyl and (C3-C7)-cycloalkyl, in another embodiment from the series consisting of (C1-C6)-alkyl and (C2-C6)-alkynyl, in another embodiment from the series consisting of (C1-C6)-alkyl and (C3-C7)-cycloalkyl, in another embodiment R10 is (CrC6)-alkyl, wherein in all these embodiments (C1-C6)-alkyl is unsubstituted or substituted by 1 or 2 identical or different substituents selected from the series consisting of (C3-C7)-cycloalkyl, Het, cyano and (C1-C4)-alkyl-O-. In one embodiment R10 is hydrogen. In one embodiment a (C1-C6)-alkyl group representing R10 is (C1-C4)-alkyl, in another embodiment (CrC3)-alkyl, in another embodiment (CrC2)-alkyl, in another embodiment C1-alkyl. In one embodiment a (C1-C6)-alkyl group

representing R10 is unsubstituted or substituted by 1 substituent selected from the series consisting of (C3-C7)-cycloalkyl, Het, cyano and (C1-C4)-alkyl-O-. In one embodiment the substituents in a substituted alkyl group representing R10 are selected from the series consisting of (C3-C7)-cycloalkyl, Het and cyano, in another embodiment from the series consisting of (C3-C7)-cycloalkyl, Het and (C1-C4)-alkyl-O-, in another embodiment from the series consisting of (C3-C7)-cycloalkyl and Het, and in another embodiment substituents in a substituted alkyl group representing R10 are (C3-C7)-cycloalkyl groups, and in another embodiment substituents in a

substituted alkyl group representing R10 are groups Het. As stated above and applies to alkyl groups in general, besides the substituents specified in the definition of the group R10 the alkyl group representing R10 can also carry one or more fluorine substituents. Cydoalkyi groups representing R10 or present in R10 can be

unsubstituted or substituted by one or more identical or different substituents selected from the series consisting of fluorine and (C1-C4)-alkyl.

If two groups R21 bonded to adjacent ring carbon atoms in the group A together with the ring carbon atoms carrying them form a 5-membered to 7-membered ring, this ring is mono-unsaturated. I.e., the resulting ring contains one double bond within the ring, which double bond is present between the said two adjacent ring carbon in the aromatic ring A that are common to the ring A and the ring formed by the two groups R , and because of the rules of nomenclature for fused rings this double bond is regarded as a double bond present in either of the two fused rings. If two substituents R21 together with the ring carbon atoms in A carrying them form a ring, further substituents R21 selected from the series consisting of halogen, (C1-C4)-alkyl, (C1-C4)-alkyl-O- and cyano can additionally be present in the group A. The case that two groups R21 bonded to adjacent ring carbon atoms in A together with the carbon atoms carrying them form a 5-membered to 7-membered ring, can in other terms be regarded as two groups R21 together forming a divalent residue comprising a chain of 3 to 5 members, of which 0, 1 or 2 are identical or different heteroatom moieties selected from the series consisting of N(R22), O and S(O)m, the terminal atoms of which are bonded to the two adjacent ring carbon atoms in the group A. Examples of such divalent residues, from any one or more of which two groups R21 bonded to adjacent ring carbon atoms in A are selected in one embodiment of the invention, are the residues -CH2-CH2-CH2-, -CH2-CH2-CH2-CH2-, -CH2-CH2-CH2-CH2-CH2-, -O-CH2-CH2-,-CH2-CH2-O-, -O-CH2-CH2-CH2-, -CH2-CH2-CH2-O-, -O-CH2-O-, -O-CH2-CH2-O-, -O-CH2-CH2-CH2-O-, -N(R22)-CH2-CH2-O-, -O-CH2-CH2-N(R22)-, -S(O)m-CH2-CH2-N(R22)- and -N(R22)-CH2-CH2-S(O)m-, which can all be substituted on carbon atoms by one or more identical or different substituents selected from the series consisting of fluorine and (C1-C4)-alkyl, and can thus also be present, for example, as the residues -O-CF2-O-, -O-C(CH3)2-O-, -O-CH(CH3)-CH2-, -CH(CH3)-CH2-O-, -O- C(CH3)2-CH2-, -C(CH3)2-CH2-O-. In one embodiment, the hetero ring members which are optionally present in a ring formed by two groups R21 bonded to adjacent ring carbon atoms in Ar together with the carbon atoms carrying them, are selected from the series consisting of N(R22) and O, in another embodiment from the series consisting of O and S(O)m, and in another embodiment they are O (oxygen atoms). In one embodiment, the ring which can be formed by two groups R21 bonded to adjacent ring carbon atoms in A together with the ring carbon atoms carrying them, is a 5-membered or 6-membered ring, in another embodiment a 5-membered ring, in another embodiment a 6-membered ring. In one embodiment, the ring which can be formed by two groups R21 bonded to adjacent carbon atoms in A 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 hetero ring members. In one embodiment, the number of substituents selected from the series consisting of fluorine and (C1-C4)-alkyl on a ring formed by two groups R21 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 , and in another embodiment it is 0.

In one embodiment of the invention R21 is selected from the series consisting of halogen, (C1-C4)-alkyl and (C1-C4)-alkyl-O-, in another embodiment from the series consisting of halogen, (C1-C4)-alkyl and cyano, in another embodiment from the series consisting of halogen and (C1-C4)-alkyl, and in another embodiment they are halogen, and in all these embodiments two groups R21 bonded to adjacent ring carbon atoms in A, together with the carbon atoms carrying them, can form a 5-membered to 7-membered mono-unsaturated ring, which comprises 0, 1 or 2 identical or different hetero ring members selected from the series consisting of N(R22), O and S(O)m and which is unsubstituted or substituted on ring carbon atoms by one or more identical or different substituents selected from the series consisting of fluorine and (C1-C4)-alkyl.

In one embodiment of the invention R21 is selected from the series consisting of halogen, (C1-C4)-alkyl, (C1-C4)-alkyl-O- and cyano, in another embodiment from the series consisting of halogen, (C1-C4)-alkyl and (C1-C4)-alkyl-O-, in another

embodiment from the series consisting of halogen, (C1-C4)-alkyl and cyano, in another embodiment from the series consisting of halogen and (C1-C4)-alkyl, and in another embodiment they are halogen, and in all these embodiments two groups R21 bonded to adjacent ring carbon atoms in A, together with the carbon atoms carrying them, do not form a 5-membered to 7-membered mono-unsaturated ring.

In one embodiment a (C1-C4)-alkyl group representing R21 or present in a (C1-C4)-alkyl-O- group representing R21 is independently of any other such alkyl group a (C1-C3)-alkyl group, in another embodiment a (C1-C2)-alkyl group, in another embodiment a C1-alkyl group. In one embodiment halogen representing R21 is selected from the series consisting of fluorine, chlorine and bromine, in another embodiment from the series consisting fluorine and chlorine, in another embodiment it is fluorine, and in another embodiment it is chlorine.

If in a group C(R26)(R27) in a chain E the groups R26 and R27 bonded to the same carbon atom together are oxo, i.e. an oxygen atom bonded via a double bond ((O), =O), they together with the carbon atom carrying them form a divalent carbonyl group (-C(O)-, -(C=O)-). If adjacent to such a carbonyl group a hetero chain member such as N(R25) or O, for example, is present in a chain E, or if such a carbonyl group is bonded to a ring nitrogen in the group A or in the group R30 representing the group G, a carboxylic acid amide moiety, a carboxylic acid ester moiety or a carboxylic acid moiety results. In one embodiment of the invention in one group C(R26)(R27) in a chain E the groups R26 and R27 bonded to the same carbon atom together can be oxo, in another embodiment in none group C(R26)(R27) in a chain E the groups R26 and R27 bonded to the same carbon atom together are oxo.

In one embodiment of the invention R26 and R27 are independently of each other selected from the series consisting of hydrogen, fluorine and (C1-C4)-alkyl, in another embodiment from the series consisting of hydrogen, (C1-C4)-alkyl and hydroxy, in another embodiment from the series consisting of hydrogen and (C1-C4)-alkyl, in another embodiment from the series consisting of hydrogen and fluorine, and in another embodiment they are hydrogen, and in all these embodiments in one or two groups C(R26)(R27) in a chain E the groups R26 and R27 bonded to the same carbon atom together can be oxo.

In one embodiment R26 and R27 are independently of each other selected from the series consisting of hydrogen, fluorine, (C1-C4)-alkyl and hydroxy, in another embodiment from the series consisting of hydrogen, fluorine and (C1-C4)-alkyl, in another embodiment from the series consisting of hydrogen, (C1-C4)-alkyl and hydroxy, in another embodiment from the series consisting of hydrogen and (C1-C4)-alkyl, in another embodiment from the series consisting of hydrogen and fluorine, and in another embodiment they are hydrogen, and in all these embodiments in none of

the groups C(R )(R ) in a chain E the groups R and R bonded to the same carbon atom together are oxo.

In one embodiment a (C1-C4)-alkyl group representing R26 or R27 is independently of any other such alkyl group a (C1-C3)-alkyl group, in another embodiment a (C1-C2)-alkyl group, in another embodiment a C1-alkyl group.

The group R30 representing the group G is a residue of a monocyclic and bicyclic ring containing 3, 4, 5, 6, 7, 8, 9 or 10 ring members. In one embodiment of the invention, 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 4, 5 or 6, 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 or 10, in another embodiment 7, 8, 9 or 10, in another embodiment 8, 9 or 10, in another embodiment 9, and in another embodiment 10. In one embodiment, the number of ring members of the cyclic group R30 is from 3 to 10 in the case of a carbocyclic ring, and from 4 to 10 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 ring system.

An unsaturated group representing R30 can be aromatic, i.e. it contains two double bonds within the ring in the case of a 5-membered monocyclic aromatic heterocycle 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 heterocycle, 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, or it can be partially unsaturated, 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 one embodiment of the invention the cyclic group R is a saturated group, in another embodiment it is an unsaturated group including partially unsaturated groups and aromatic groups. In another embodiment R30 is a saturated group or a partially unsaturated group, in another embodiment it is a saturated group or an aromatic group, in another embodiment it is a saturated group, and in another embodiment it is an aromatic group.

The cyclic group R30 can be a carbocyclic group, i.e. comprise 0 (zero) hetero ring members, or a heterocyclic group, i.e. comprise 1 , 2 or 3 identical or different hetero ring members selected from the series consisting of N, N(R31), O and S(O)m. In the case of the group R30, the hetero ring member N denotes a ring nitrogen atom which is bonded to the adjacent ring atoms via two single bonds and which has a free valence via which the ring R30 is bonded to the group E, as occurs in a pyrrole ring, pyrazole ring, piperidine ring or morpholine ring, for example, as well as a ring nitrogen atom which is bonded to the adjacent ring atoms via a single bond and a double bond or via three single bonds and via which the ring R30 cannot be bonded to the group E, unless quaternization is present, as occurs in a pyridine ring, thiazole ring, quinoline ring or 1 -azabicyclo[2.2.2]octane ring, for example. In one

embodiment, R30 comprises 0, 1 or 2 identical or different hetero ring members, in another embodiment 0 or 1 hetero ring member, and in another embodiment R30 comprises 0 hetero ring member and thus is a carbocyclic group. In another embodiment R30 is a heterocyclic group which comprises 1 , 2 or 3 identical or different hetero ring members, in another embodiment 1 or 2 identical or different hetero ring members, in another embodiment 1 hetero ring members. In one embodiment, the hetero ring members in R30 are selected from the series consisting of N, N(R31) and O, in another embodiment from the series consisting of N, N(R31) and S(O)m, in another embodiment from the series consisting of N, O and S(O)m, in another embodiment from the series consisting of N and N(R31), in another embodiment from the series consisting of N and O, in another embodiment from the series consisting of N(R31) and O, in another embodiment they are N, in another embodiment they are N(R31), and in another embodiment they are O. In one embodiment two hetero ring members in a group R30 can only be present in adjacent ring positions if one them is S(O)m in which m is 1 or 2, or if one of them is N which is bonded to the two adjacent ring atoms via a single bond and a double bond and does not have a free valence via which the ring R30 is bonded to the group E. In the latter embodiment, two oxygen atoms, for example, can thus not be present in adjacent ring positions in R30. Heterocyclic groups R30 can be bonded to the group E via a ring nitrogen atom, i.e. a hetero ring member N, or a ring carbon atom. In one

embodiment a heterocyclic group R30 is bonded via a ring carbon atom, in another embodiment it is bonded via a ring nitrogen atom, i.e. a hetero ring member N.

Examples of carbocyclic groups, which can represent R30 and any one or more of which may be included in the definition of R30 in one embodiment, and from any one or more of which R30 is selected in another embodiment, are cycloalkyi 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-C10)-bicycloalkyl, phenyl groups, indanyl groups including indan-1 -yl and indan-2-yl, and naphthalenyl (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 cycloalkyi groups, for example their optional substitution by fluorine substituents and (C1-C4)-alkyl substituents, and with respect to phenyl groups apply accordingly to such groups representing R30.

Examples of heterocyclic groups, which can represent R30 and any one or more of which may be included in the definition of R30 in one embodiment, and from any one or more of which R30 is selected in another embodiment, are 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, tetrahydrothiophene including tetrahydrothiophen-2-yl and tetrahydrothiophen-3-yl, tetrahydrothiopyranyl including tetrahydrothiopyran-2-yl, tetrahydrothiopyran-3-yl and tetrahydrothiopyran-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, 1 ,2-dihydropyridinyl including 1 ,2-dihydropyridin-1 -yl, 1 ,2-dihydropyridin-2-yl, 1 ,2-dihydropyridin-3-yl, 1 ,2-dihydropyridin-4-yl, 1 ,2-dihydropyridin-5-yl and 1 ,2-dihydropyridin-6-yl, 1 ,2,3,6-tetrahydropyridinyl including 1 ,2,3,6-tetrahydropyridin-1 -yl, 1 ,2,3,6-tetrahyd ropyrid in-2-yl , 1 ,2,3,6-tetrahydropyridin-3-yl, 1 ,2,3,6-tetrahydropyridin-4-yl, 1 ,2,3,6-tetrahydropyridin-5-yl and 1 ,2,3,6-tetrahydropyridin-6-yl, azepanyl including azepan-1 -yl, azepan-2-yl, azepan-3-yl and azepan-4-yl, 1 -azabicyclo[2.2.2]octanyl including 1 -azabicyclo[2.2.2]octan-2-yl, 1 -azabicyclo[2.2.2]octan-3-yl and 1 -azabicyclo[2.2.2]octan-4-yl, [1 ,3]dioxolanyl including [1 ,3]dioxolan-2-yl and

[1 ,3]dioxolan-4-yl, [1 ,4]dioxanyl including [1 ,4]dioxan-2-yl, [1 ,3]oxazolidinyl including [1 ,3]oxazolidin-2-yl, [1 ,3]oxazolidin-3-yl, [1 ,3]oxazolidin-4-yl and [1 ,3]oxazolidin-5-yl, [1 ,3]thiazolidinyl including [1 ,3]thiazolidin-2-yl, [1 ,3]thiazolidin-3-yl, [1 ,3]thiazolidin-4-yl and [1 ,3]thiazolidin-5-yl, imidazolidinyl including imidazolidin-1 -yl, imidazolidin-2-yl, imidazolidin-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, pyridazinyl including pyridazin-3-yl and pyridazin-4-yl, pyrimidinyl including pyhmidin-2-yl, pyrimidin-4-yl and pyhmidiny-5-yl, pyrazinyl including pyrazin-2-yl, indolyl including indol-1 -yl, indol-2-yl, indol-3-yl, indol-4-yl, indol-5-yl, indol-6-yl and indol-7-yl, benzimidazolyl including benzimidazol-1 -yl, benzimidazol-2-yl, benzimidazol-4-yl, benzimidazol-5-yl, benzimidazol-6-yl and benzimidazol-7-yl, quinolinyl including quinolin-2-yl, quinolin-3-yl, quinolin-4-yl, quinolin-5-yl, quinolin-6-yl, quinolin-7-yl and quinolin-8-yl, isoquinolinyl including quinolin-1 -yl, quinolin-3-yl, quinolin-4-yl, quinolin- 5-yl, quinolin-6-yl, quinolin-7-yl and quinolin-8-yl, 2,3-dihydrobenzo[1 ,4]dioxinyl including 2,3-dihydrobenzo[1 ,4]dioxin-2-yl, 2,3-dihydrobenzo[1 ,4]dioxin-5-yl and 2,3-dihydrobenzo[1 ,4]dioxin-6-yl, quinazolinyl including quinazolin-2-yl, quinazolin-4-yl, quinazolin-5-yl, quinazolin-6-yl, quinazolin-7-yl and quinazolin-8-yl, which can all be unsubstituted or substituted on ring carbon atoms by one or more identical or different substituents R32 and, if applicable, which can all carry on ring nitrogen atoms capabable of carrying a substituent a (C1-C4)-alkyl substituent corresponding to the denotation (C1-C4)-alkyl of the group R31 occurring in the hetero ring member N(R31) in R30, and can carry on all ring sulfur atoms capable of carrying oxygen atoms one or two oxygen atoms corresponding to the oxygen atoms in the hetero ring member S(O)m in R30.

In one embodiment of the invention, the number of substituents R32 which can be present on carbon atoms 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 one

embodiment, R30 is unsubstituted.

In one embodiment of the invention the group R32 is selected from the series consisting of halogen, (C1-C4)-alkyl, hydroxy, oxo, (C1-C4)-alkyl-O-, R33-N(R34)- and Het, in another embodiment from the series consisting of halogen, (C1-C4)-alkyl, (C1-C4)-alkyl-O-, R33-N(R34)- and Het, in another embodiment from the series consisting of halogen, (C1-C4)-alkyl, hydroxy, oxo, (C1-C4)-alkyl-O- and R33-N(R34)-, in another embodiment from the series consisting of halogen, (C1-C4)-alkyl, hydroxy, oxo and (C1-C4)-alkyl-O-, in another embodiment from the series consisting of halogen, (C1-C4)-alkyl, oxo and (C1-C4)-alkyl-O-, in another embodiment from the series consisting of halogen, (C1-C4)-alkyl and (C1-C4)-alkyl-O-, in another embodiment from the series consisting of halogen and (C1-C4)-alkyl, in another embodiment they are halogen, and in another embodiment they are (C1-C4)-alkyl. In one embodiment a (C1-C4)-alkyl group representing R32 or present in a (C1-C4)-alkyl-O- group representing R32 is independently of any other such alkyl group a (C1-C3)-alkyl group, in another embodiment a (C1-C2)-alkyl group, in another embodiment a C1-alkyl group. In one

embodiment halogen representing R is selected from the series consisting of fluorine, chlorine and bromine, in another embodiment from the series consisting fluorine and chlorine, in another embodiment it is fluorine, in another embodiment it is chlorine, and in another embodiment it is bromine.

The group Het contains 4, 5, 6 or 7 ring members. In one embodiment of the invention, Het is 4-membered to 6-membered, in another embodiment 4-membered or 5-membered, in another embodiment 5-membered or 6-membered, in another embodiment 4-membered, in another embodiment 5-membered, in another embodiment 6-membered. In one embodiment, Het comprises 1 hetero ring member. In one embodiment, the hetero ring members in Het are selected from the series consisting of N, N(R40) and O, in another embodiment from the series consisting of N and N(R40), in another embodiment from the series consisting of O and S(O)m, in another embodiment they are O. In one embodiment two hetero ring members in a group Het can only be present in adjacent ring positions if one them is S(O)m in which m is 1 or 2, in another embodiment two hetero ring members in a group Het are not present in adjacent ring positions. In the latter embodiment two oxygen atoms, for example, can thus not be present in adjacent ring positions. The group Het can be bonded via a ring nitrogen atom, i.e. a hetero ring member N, or a ring carbon atom. In one embodiment Het is bonded via a ring carbon atom, in another embodiment it is bonded via a ring nitrogen atom, i.e. a hetero ring member N. In the case of the group Het the hetero ring member N denotes a ring nitrogen atom which is bonded to the adjacent ring atoms in Het via two single bonds and which has a free valence via which the ring Het is bonded to another moiety in the molecule, as occurs in the case of a pyrrolidine ring, piperidine ring or morpholine ring, for example. Examples of heterocyclic groups, from any one or more of which Het is chosen in one

embodiment, are oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, oxepanyl,

tetrahydrothiophenyl, tetrahydrothiopyranyl, azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, morpholinyl, thiomorpholinyl and piperazinyl, including the more specific groups in which the binding position is specified and which are listed above in the section relating to the group R30. In one embodiment, the number of optional substituents on ring carbon atoms in a group Het 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 Het is unsubstituted. In one embodiment, substituents on ring carbon atoms in Het are (C1-C4)-alkyl group, in another embodiment (C1-C3)-alkyl groups, in another embodiment (C1-C2)-alkyl groups, in another embodiment C1-alkyl groups.

In one embodiment of the invention the number m, which is an integer, is in any of its occurrences, independently of any other occurrence, selected from the numbers 0 and 2, in another embodiment 1 and 2, in another embodiment it is 0, in another embodiment it is 1 and in another embodiment it is 2.

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, wherein

A is phenyl, which is unsubstituted or substituted on ring carbon atoms by one or more identical of different substituents R21;

E is a direct bond;

G is selected from the series consisting of hydrogen, halogen, (C1-C4)-alkyl and cyano;

and all other groups and numbers are defined as in the general definition of the compounds of the formula I or in any specified embodiments of the invention or definitions of structural elements, and the pharmaceutically acceptable salts thereof.

As another such example compounds of the formula I may be mentioned, wherein A is phenyl, which is unsubstituted or substituted on ring carbon atoms by one or more identical of different substituents R21;

E is a direct bond;

G is R30;

and all other groups and numbers are defined as in the general definition of the compounds of the formula I or in any specified embodiments of the invention or definitions of structural elements, and the pharmaceutically acceptable salts thereof.

As another such example compounds of the formula I may be mentioned, wherein A is phenyl, which is unsubstituted or substituted on ring carbon atoms by one or more identical of different substituents R21;

E is a chain consisting of 1 to 5 chain members of which 0, 1 or 2 chain members are identical or different hetero chain members selected from the series consisting of N(R25), O and S(O)m, and the other chain members are identical or different groups C(R26)(R27);

G is selected from the series consisting of hydrogen, halogen, (C1-C4)-alkyl and cyano;

and all other groups and numbers are defined as in the general definition of the compounds of the formula I or in any specified embodiments of the invention or definitions of structural elements, and the pharmaceutically acceptable salts thereof.

As another such example compounds of the formula I may be mentioned, wherein; A is phenyl, which is unsubstituted or substituted on ring carbon atoms by one or more identical of different substituents R21;

E is a chain consisting of 1 to 5 chain members of which 0, 1 or 2 chain members are identical or different hetero chain members selected from the series consisting of N(R ), O and S(O)m, and the other chain members are identical or different groups

C(R26)(R27);

G is R30;

and all other groups and numbers are defined as in the general definition of the compounds of the formula I or in any specified embodiments of the invention or definitions of structural elements, and the pharmaceutically acceptable salts thereof.

As another such example compounds of the formula I may be mentioned, wherein A is a monocyclic or bicyclic, 5-membered to 10-membered, aromatic heterocyclic group, which comprises 1 or 2 identical or different hetero ring members selected from the series consisting of N, N(R20), O and S and is bonded via a ring carbon atom, and which is unsubstituted or substituted on ring carbon atoms by one or more identical of different substituents R21;

E is a direct bond;

G is selected from the series consisting of hydrogen, halogen, (C1-C4)-alkyl and cyano;

and all other groups and numbers are defined as in the general definition of the compounds of the formula I or in any specified embodiments of the invention or definitions of structural elements, and the pharmaceutically acceptable salts thereof.

As another such example compounds of the formula I may be mentioned, wherein A is a monocyclic or bicyclic, 5-membered to 10-membered, aromatic heterocyclic group, which comprises 1 or 2 identical or different hetero ring members selected from the series consisting of N, N(R20), O and S and is bonded via a ring carbon atom, and which is unsubstituted or substituted on ring carbon atoms by one or more identical of different substituents R21;

E is a direct bond;

G is R30;

and all other groups and numbers are defined as in the general definition of the compounds of the formula I or in any specified embodiments of the invention or definitions of structural elements, and the pharmaceutically acceptable salts thereof.

As another such example compounds of the formula I may be mentioned, wherein A is a monocyclic or bicyclic, 5-membered to 10-membered, aromatic heterocyclic group, which comprises 1 or 2 identical or different hetero ring members selected from the series consisting of N, N(R20), O and S and is bonded via a ring carbon atom, and which is unsubstituted or substituted on ring carbon atoms by one or more identical of different substituents R21;

E is a chain consisting of 1 to 5 chain members of which 0, 1 or 2 chain members are identical or different hetero chain members selected from the series consisting of N(R25), O and S(O)m, and the other chain members are identical or different groups C(R26)(R27);

G is selected from the series consisting of hydrogen, halogen, (C1-C4)-alkyl and cyano;

and all other groups and numbers are defined as in the general definition of the compounds of the formula I or in any specified embodiments of the invention or definitions of structural elements, and the pharmaceutically acceptable salts thereof.

As another such example compounds of the formula I may be mentioned, wherein; A is a monocyclic or bicyclic, 5-membered to 10-membered, aromatic heterocyclic group, which comprises 1 or 2 identical or different hetero ring members selected from the series consisting of N, N(R20), O and S and is bonded via a ring carbon atom, and which is unsubstituted or substituted on ring carbon atoms by one or more identical of different substituents R21;

E is a chain consisting of 1 to 5 chain members of which 0, 1 or 2 chain members are identical or different hetero chain members selected from the series consisting of N(R25), O and S(O)m, and the other chain members are identical or different groups C(R26)(R27);

G is R30;

and all other groups and numbers are defined as in the general definition of the compounds of the formula I or in any specified embodiments of the invention or definitions of structural elements, and the pharmaceutically acceptable salts thereof.

As another such example, compounds of the formula I may be mentioned, wherein

A is selected from the series consisting of phenyl and a monocyclic, 5-membered or 6-membered, aromatic heterocyclic group, which comprises 1 or 2 identical or different hetero ring members selected from the series consisting of N, N(R20), O and S and is bonded via a ring carbon atom, wherein phenyl and the heterocyclic group are unsubstituted or substituted on ring carbon atoms by one or more identical of different substituents R21;

E is a direct bond or a chain consisting of 1 to 4 chain members of which 0, 1 or 2 chain members are identical or different hetero chain members selected from the series consisting of N(R25), O and S(O)m, and the other chain members are identical or different groups C(R26)(R27);

G is selected from the series consisting of hydrogen, halogen, (C1-C4)-alkyl and R30;

R1, R3, R4 and R6 are independently of each other selected from the series consisting of hydrogen, halogen and (C1-C3)-alkyl;

R2 is selected from the series consisting of hydrogen, halogen and (C1-C3)-alkyl;

R5 is selected from the series consisting of hydrogen, halogen, (C1-C4)-alkyl, (C1-C4)-alkyl-O- and cyano;

R10 is selected from the series consisting of hydrogen, (C1-C6)-alkyl and (C3-C7)-cycloalkyi, wherein alkyl is unsubstituted or substituted by 1 substituent selected from the series consisting of (C3-C7)-cycloalkyl, Het, cyano and (C1-C4)-alkyl-O-, and wherein all cycloalkyi groups are unsubstituted or substituted by one or more identical or different substituents selected from the series consisting of fluorine and (C1-C4)-alkyl;

R20, R22, R25, R31 and R40 are independently of each other selected from the series consisting of hydrogen and (C1-C4)-alkyl;

R is selected from the series consisting of halogen, (C1-C4)-alkyl, (C1-C4)-alkyl-O-and cyano, and two groups R21 bonded to adjacent ring carbon atoms in the group A, together with the carbon atoms carrying them, can form a 5-membered or 6-membered mono-unsaturated ring, which comprises 0, 1 or 2 identical or different hetero ring members selected from the series consisting of N(R22), O and S(O)m and which is unsubstituted or substituted on ring carbon atoms by one or more identical or different substituents selected from the series consisting of fluorine and (C1-C4)-alkyl;

R26 and R27 are independently of each other selected from the series consisting of hydrogen, fluorine, (C1-C3)-alkyl and hydroxy, and in one group C(R26)(R27) the groups R26 and R27 bonded to the same carbon atom together can be oxo;

R30 is a monocyclic or bicyclic, 3-membered to 10-membered ring, which is saturated or unsaturated and comprises 0, 1 , 2 or 3 identical or different hetero ring members selected from the series consisting of N, N(R31), O and S(O)m, and which is unsubstituted or substituted on ring carbon atoms by one or more identical or different substituents R32;

R32 is selected from the series consisting of halogen, (C1-C4)-alkyl, hydroxy, oxo, (C1-C4)-alkyl-O- and cyano;

Het is a monocyclic, 4-membered to 6-membered, saturated heterocyclic group, which comprises 1 or 2 identical or different hetero ring members selected from the series consisting of N, N(R40) and O, and which is unsubstituted or substituted on ring carbon atoms by one or more identical or different substituents selected from the series consisting of fluorine and (C1-C4)-alkyl;

m is selected from the series consisting of 0, 1 and 2, wherein all numbers m are independent of each other and can be identical or different;

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;

and the pharmaceutically acceptable salts thereof.

As another such example, compounds of the formula I may be mentioned, wherein

A is selected from the series consisting of phenyl and a monocyclic, 5-membered or 6-membered, aromatic heterocyclic group, which comprises 1 or 2 identical or different hetero ring members selected from the series consisting of N, N(R20), O and S and is bonded via a ring carbon atom, wherein phenyl and the heterocyclic group are unsubstituted or substituted on ring carbon atoms by one or more identical of different substituents R21;

E is a direct bond or a chain consisting of 1 to 4 chain members of which 0, 1 or 2 chain members are identical or different hetero chain members selected from the series consisting of N(R25) and O, and the other chain members are identical or different groups C(R26)(R27);

G is selected from the series consisting of hydrogen, (C1-C4)-alkyl and R30;

R1 and R4 are independently of each other selected from the series consisting of hydrogen, halogen and (C1-C3)-alkyl;

R2 is selected from the series consisting of hydrogen, halogen and (C1-C3)-alkyl;

R3 and R6 are independently of each other selected from the series consisting of hydrogen, halogen and C1-alkyl;

R5 is selected from the series consisting of hydrogen, halogen, (C1-C4)-alkyl and cyano;

R10 is selected from the series consisting of hydrogen, (C1-C6)-alkyl and (C3-C7)-cycloalkyl, wherein alkyl is unsubstituted or substituted by 1 substituent selected from the series consisting of (C3-C7)-cycloalkyl, Het, cyano and (C1-C4)-alkyl-O-, and wherein all cycloalkyi groups are unsubstituted or substituted by one or more identical or different substituents selected from the series consisting of fluorine and (C1-C4)-alkyl;

R20, R22, R25, R31 and R40 are independently of each other selected from the series consisting of hydrogen and (C1-C4)-alkyl;

R21 is selected from the series consisting of halogen, (C1-C4)-alkyl, (C1-C4)-alkyl-O-and cyano, and two groups R21 bonded to adjacent ring carbon atoms in the group A, together with the carbon atoms carrying them, can form a 5-membered or 6-membered mono-unsaturated ring, which comprises 0, 1 or 2 identical or different hetero ring members selected from the series consisting of N(R22) and O, and which is unsubstituted or substituted on ring carbon atoms by one or more identical or different substituents selected from the series consisting of fluorine and C1-alkyl;

R26 and R27 are independently of each other selected from the series consisting of hydrogen, fluorine, (C1-C3)-alkyl and hydroxy, and in one group C(R26)(R27) the groups R26 and R27 bonded to the same carbon atom together can be oxo;

R30 is a monocyclic or bicyclic, 3-membered to 10-membered ring, which is saturated or aromatic and comprises 0, 1 or 2 identical or different hetero ring members selected from the series consisting of N, N(R31), O and S(O)m, and which is unsubstituted or substituted on ring carbon atoms by one or more identical or different substituents R32;

R32 is selected from the series consisting of halogen, (C1-C4)-alkyl, hydroxy, oxo and (C1-C4)-alkyl-O-;

Het is a monocyclic, 4-membered to 6-membered, saturated heterocyclic group, which comprises 1 hetero ring member selected from the series consisting of N(R40) and O, and which is unsubstituted or substituted on ring carbon atoms by one or more identical or different substituents selected from the series consisting of fluorine and (C1-C3)-alkyl;

m is selected from the series consisting of 0, 1 and 2, wherein all numbers m are independent of each other and can be identical or different;

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;

and the pharmaceutically acceptable salts thereof.

As another such example, compounds of the formula I may be mentioned, wherein

A is selected from the series consisting of phenyl and a monocyclic, 5-membered or 6-membered, aromatic heterocyclic group, which comprises 1 or 2 identical or different hetero ring members selected from the series consisting of N, N(R20) and S and is bonded via a ring carbon atom, wherein phenyl and the heterocyclic group are unsubstituted or substituted on ring carbon atoms by one or more identical of different substituents R21;

E is a direct bond or a chain consisting of 1 to 4 chain members of which 0 or 1 chain members are identical or different hetero chain members selected from the series consisting of N(R25) and O, and the other chain members are identical or different groups C(R26)(R27);

G is selected from the series consisting of hydrogen and R30;

R1 and R4 are independently of each other selected from the series consisting of hydrogen, halogen and (C1-C2)-alkyl;

R2 is selected from the series consisting of hydrogen, halogen and (C1-C2)-alkyl;

R3 and R6 are independently of each other selected from the series consisting of hydrogen, halogen and C1-alkyl;

R5 is selected from the series consisting of hydrogen, halogen and (C1-C2)-alkyl;

R10 is selected from the series consisting of hydrogen, (C1-C4)-alkyl and (C3-C5)-cycloalkyi, wherein alkyl is unsubstituted or substituted by 1 substituent selected from the series consisting of (C3-C5)-cycloalkyl and Het, and wherein all cycloalkyi groups are unsubstituted or substituted by one or more identical or different substituents (C1-C2)-alkyl;

R20, R25 and R31 are independently of each other selected from the series consisting of hydrogen and (C1-C3)-alkyl;

R21 is selected from the series consisting of halogen, (C1-C4)-alkyl, (C1-C4)-alkyl-O-and cyano;

R26 and R27 are independently of each other selected from the series consisting of hydrogen, fluorine, C1-alkyl and hydroxy, and in one group C(R26)(R27) the groups R26 and R27 bonded to the same carbon atom together can be oxo;

R30 is a monocyclic 3-membered to 6-membered or bicyclic 9-membered to 10-membered ring, which is saturated or aromatic and comprises 0, 1 or 2 identical or different hetero ring members selected from the series consisting of N, N(R31) and O, and which is unsubstituted or substituted on ring carbon atoms by one or more identical or different substituents R32;

R32 is selected from the series consisting of halogen, (C1-C3)-alkyl, hydroxy and oxo;

Het is a monocyclic, 4-membered or 5-membered, saturated heterocyclic group, which comprises 1 hetero ring member which is O, and which is unsubstituted or substituted on ring carbon atoms by one or more identical or different substituents (C1-C3)-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;

and the pharmaceutically acceptable salts thereof.

As another such example, compounds of the formula I may be mentioned, wherein

A is selected from the series consisting of phenyl and the aromatic heterocyclic groups pyrazolyl and pyridinyl, wherein phenyl and the heterocyclic groups are unsubstituted or substituted on ring carbon atoms by one or more identical of different substituents R21;

E is a direct bond or a chain consisting of 1 to 3 chain members of which 0 or 1 chain member is a hetero chain member which is O, and the other chain members are identical or different groups C(R26)(R27);

G is selected from the series consisting of hydrogen and R30;

R1 and R4 are independently of each other selected from the series consisting of hydrogen, halogen and C1-alkyl;

R2 is selected from the series consisting of hydrogen, halogen and C1-alkyl;

R3 and R6 are hydrogen;

R5 is selected from the series consisting of halogen and (C1-C2)-alkyl;

R10 is selected from the series consisting of hydrogen, (C1-C4)-alkyl and (C3-C5)-cycloalkyl, wherein alkyl is unsubstituted or substituted by 1 substituent selected from the series consisting of (C3-C5)-cycloalkyl and Het;

R21 is selected from the series consisting of halogen, (C1-C4)-alkyl, (C1-C4)-alkyl-O-and cyano;

R26 and R27 are independently of each other selected from the series consisting of hydrogen, fluorine and C1-alkyl;

R30 is a monocyclic, 3-membered to 6-membered ring, which is saturated or aromatic and comprises 0, 1 or 2 identical or different hetero ring members selected from the series consisting of N, N(R31) and O, and which is unsubstituted or substituted on ring carbon atoms by one or more identical or different substituents R32;

R31 is selected from the series consisting of hydrogen and (C1-C3)-alkyl;

R32 is selected from the series consisting of halogen and (C1-C3)-alkyl;

Het is a monocyclic, 4-membered or 5-membered, saturated heterocyclic group, which comprises 1 hetero ring member which is O, and which is unsubstituted or substituted on ring carbon atoms by one or more identical or different substituents (C1-C3)-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;

and the pharmaceutically acceptable salts thereof.

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:

6-Bromo-9-ethyl-1 -methyl-8-(1 -pyridin-3-ylmethyl-1 H-pyrazol-4-yl)-9H-pyrido[3,4-bjindole,

6-Chloro-1 ,5-dimethyl-8-[4-(3-methyl-oxetan-3-ylmethoxy)-phenyl]-9H-pyrido[3,4-bjindole,

2-(4-[6-Chloro-9-(2,2,2-trifluoroethyl)-9H-pyrido[3,4-b]indol-8-yl]pyrazol-1 -yl)ethanol, 6-Chloro-1 -methyl-8-[4-(2-pyrazol-1 -ylethoxy)-phenyl]-9H-pyrido[3,4-b]indole, 6-Bromo-9-ethyl-1 ,3-dimethyl-8-(1 -methyl-1 H-pyrazol-4-yl)-9H-pyrido[3,4-b]indole, 6-Chloro-8-(4-methoxy-phenyl)-1 ,9-dimethyl-9H-pyrido[3,4-b]indole,

6-Chloro-8-(4-methoxy-phenyl)-1 ,5-dimethyl-9H-pyrido[3,4-b]indole,

8-(4-Methoxy-phenyl)-1 -methyl-9H-pyrido[3,4-b]indole-6-carbonitrile,

6-Chloro-1 -methyl-8-[4-(1 -methyl-1 H-imidazol-2-ylmethoxy)-phenyl]-9H-pyrido[3,4-bjindole,

6-Chloro-1 ,5-dimethyl-8-[4-(2-pyrazol-1 -yl-ethoxy)-phenyl]-9H-pyrido[3,4-b]pyridine, 6-Chloro-9-cyclopropylmethyl-8-(2,6-dichloro-pyridin-3-yl)-9H-pyrido[3,4-b]indole, 6-Chloro-8-(2,6-dichloro-pyridin-3-yl)-9-ethyl-9H-pyrido[3,4-b]indole,

8-(2,6-Dichloro-pyridin-3-yl)-1 ,6-dimethyl-9H-pyrido[3,4-b]indole,

6-Chloro-9-ethyl-1 -methyl-8-(1 -pyridin-3-ylmethyl-1 H-pyrazol-4-yl)-9H-pyrido[3,4-bjindole,

6-Chloro-8-(4-chloro-phenyl)-9-ethyl-1 -methyl-9H-pyrido[3,4-b]indole,

6-Chloro-8-(4-methoxy-phenyl)-1 -methyl-9H-pyrido[3,4-b]indole,

6-Chloro-8-chroman-6-yl-1 -methyl-9H-pyrido[3,4-b]indole,

6-Chloro-8-[4-(2-imidazol-1 -yl-ethoxy)-phenyl]-1 -methyl-9H-pyrido[3,4-b]indole, 6-Bromo-9-ethyl-1 -methyl-8-(1 -methyl-1 H-pyrazol-4-yl)-9H-pyrido[3,4-b]indole, 4-(6-Chloro-1 -methyl-9H-pyrido[3,4-b]indol-8-yl)-pyridin-2-ylamine,

6-Chloro-1 -methyl-8-[4-(1 -methyl-pyrrolidin-3-ylmethoxy)-phenyl]-9H-pyrido[3,4-bjindole,

6-Chloro-9-ethyl-1 -methyl-8-[4-(3-methyl-oxetan-3-ylmethoxy)-phenyl]-9H-pyrido[3,4-b]indole,

6-Bromo-9-ethyl-1 -methyl-8-[4-(3-methyl-oxetan-3-ylmethoxy)-phenyl]-9H-pyrido[3,4-b]indole, and

6-Chloro-9-cyclopropylmethyl-8-(1 -pyridin-3-ylmethyl-1 H-pyrazol-4-yl)-9H-pyrido[3,4-b]indole,

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 occurring in the course of their synthesis, and salts thereof, are obtainable. The compounds of the formula I can in general be prepared by using procedures and techniques which per se are known to a person skilled in the art. In one of the processes a compound of the formula I is prepared, for example, by cross-coupling of a compound of the formula II with an organoboron compound of the formula III under the conditions of the well-known Suzuki reaction, also known as Suzuki-Miyaura cross-coupling reaction, or another Suzuki-type reaction or modifications thereof, in the presence of a transition metal catalyst. The reaction is reviewed in F. Alonso et al., Tetrahedron 2008, 64, 3047-3101 , for example.

The groups R1 to R6 and R10 in the compound of the formula II and the groups A, E and G in the compound of the formula III are defined as in the compound of the formula I, and in addition functional groups can be present in protected form or in the form of a precursor group, which is subsequently converted into the final group. The group X in the compound of the formula II is suitable leaving group, such as halogen selected from the series consisting of chlorine, bromine and iodine, in one

embodiment of the invention from the series consisting of bromine and iodine, or a sulfonyloxy group like trifluoromethanesulfonyloxy (CF3-SO2-O-), for example.

The groups Y in the compound of the formula III are hydrogen, and in this case the compound of the formula III thus is a boronic acid, or (C1-C4)-alkyl, in one

embodiment of the invention (C1-C3)-alkyl like methyl, ethyl or isopropyl, and in this case the compound of the formula III is a boronic acid alkyl ester, or the two groups Y, together with the -O-B-O- moiety to which they are bonded, form a saturated 5-membered or 6-membered ring, which comprises 2 or 3 carbon atoms as ring atoms in addition to the -O-B-O- moiety and is unsubstituted or substituted by one or more (C1-C4)-alkyl substituents, for example methyl substituents, and in this case the compound of the formula III is a cyclic boronic acid alkyl ester. In the latter case the ring formed by the two groups Y, together with the -O-B-O- moiety to which they are bonded, is a 1 ,3,2-dioxaborolane ring or 1 ,3,2-dioxaborinane ring, which are unsubstituted or substituted by one or more (C1-C4)-alkyl substituents, for example a 4,4, 5, 5-tetramethyl-1 ,3,2-dioxaborolane ring as present in the pinacol ester (2,3-dimethyl-2,3-butanediol ester) of the respective boronic acid, or a 5,5-dimethyl-1 ,3,2-dioxaborinane ring as present in the neopentyl glycol ester (2,2-dimethyl-1 ,3-propanediol ester) of the respective boronic acid. In one embodiment of the invention the compound of the formula III is a boronic acid or a cyclic boronic acid alkyl ester as specified afore. In another embodiment the compound of the formula III is a boronic acid or a boronic acid pinacol ester, i.e., the groups Y are hydrogen or, together with the -O-B-O- moiety to which they are bonded, form a 4,4,5,5-tetramethyl-1 ,3,2-dioxaborolane ring. Alternatively, instead of with a compound of the formula III, a compound of the formula II can be reacted with an organotrifluoroborate salt, such as a potassium organotrifluoroborate, i.e. a compound of the formula G-E-A-BF3- K+ in which the groups A, E and G are defined as in the compound of the formula I and in addition functional groups can be present in protected form or in the form of a precursor group, which salts can be obtained from boronic acids and

fluorides such as potassium hydrogen difluoride and are reviewed in S. Darses et al., Chem. Rev. 2008, 108, 288-325, for example.

The reaction of the compounds of the formula II with the compounds of the formula III is generally performed in an inert solvent, such as a hydrocarbon like benzene or toluene, an ether like 1 ,2-dimethoxyethane (DME), tetrahydrofuran (THF) or dioxane, an amide like dimethylformamide (DMF), an alcohol like ethanol or isobutanol, a nitrile like acetonitrile, or water, or a mixture of such solvents, for example in toluene or in a mixture of 1 ,2-dimethoxyethane and water in a ratio of from about 5:1 to about 2:1 by volume, for example in a ratio of about 3:1 by volume. The reaction is generally performed at elevated temperatures, such as at temperatures from about 50 °C to about 150 °C, for example at temperatures from about 90 °C to about 130 °C, in a heated flask or vessel or in a microwave vessel heated in a microwave irradiation device (cf. V. P. Metha et al., Chem. Soc. Rev. 201 1 , 40, 4925-4936). The reaction time generally is from about 5 minutes to about 24 hours, for example from about 10 minutes to about 10 hours, depending on the particulars of the specific case such as the reactivity of the reactants and the chosen temperature.

As transition metal catalyst in Suzuki reactions and similar cross-coupling reactions commonly palladium compounds are employed, but other metal catalysts such as nickel catalysts can also be used (cf. F.-S. Han, Chem. Soc. Rev. 2013, 42, 5270-5298, for example). Examples of palladium compounds which can be employed as catalysts in the reaction of the compounds of the formula II with the compounds of the formula III, are palladium(ll) salts like palladium(ll) diacetate or palladium(ll) dichloride, which can also be employed in the presence of a phosphine such as 1 ,1 '-bis(diphenylphosphino)ferrocene, tricyclohexylphosphine or triphenylphosphine, and palladium complexes like tetrakis(triphenylphosphine)palladium(0), bis(tri-tert-butylphosphine)palladium(O), bis(triphenylphosphine)palladium(ll) dichloride, bis(tri-tert-butylphosphine)palladium(ll) dichloride, 1 ,1 '-bis(diphenylphosphino)ferrocene-palladium(ll) dichloride which is abbreviated herein as "BDFP" and which is commonly employed in the form of a complex with dichloromethane, or

bis(dibenzylideneacetone)palladium(0) in the presence of tri-tert-butylphosphine.

Palladium catalysts on solid supports like iron oxide, magnesium oxide, magnesium lanthanum oxide, apatite or anionic clay materials as well as polymer-supported palladium catalysts can also be used. The amount of the catalyst is generally from about 0.001 mol to about 0.02 mol, for example from about 0.001 to about 0.01 mol, catalyst per mol of compound of the formula II, depending on the reactivity of the compounds to be reacted, the catalyst and the reaction conditions chosen. In one embodiment of the invention tetrakis(triphenylphosphine)palladium(0) or BDFP are employed as catalysts in the reaction of the compounds of the formula II with the compounds of the formula III.

Suzuki reactions and similar cross-coupling reactions are generally performed in the presence of a base. Examples of bases which can be employed in the reaction of the compounds of the formula II with the compounds of the formula III, are alkali metal carbonates like sodium carbonate, potassium carbonate or cesium carbonate, alkali metal phosphates like tripotassium phosphate, alkali metal hydroxides like sodium hydroxide or potassium hydroxide, alkali metal fluorides like potassium fluoride or cesium fluoride, and suitable amines like triethylamine, diisopropylethylamine or 1 ,8-diazabicyclo[5.4.0]undec-7-ene (DBU). In one embodiment of the invention an alkali metal carbonate, for example sodium carbonate, is employed as base in the reaction of the compounds of the formula II with the compounds of the formula III.

Boronic acids and boronic acid esters of the formula III can be obtained via various procedures for the synthesis of such compounds described in the literature, for example from organometallic compounds, such as organolithium compounds or Grignard compounds which can in turn be obtained from the respective halides, i.e. compounds of the formula G-E-A-halogen in which the groups A, E and G are defined as in the compound of the formula I and in addition functional groups can be present in protected form or in the form of a precursor group, such as the respective bromides and iodides, by reaction with borate esters, such as trimethyl borate or triisopropyl borate (cf. A. E. Smith et al., Eur. J. Org. Chem. 2008, 1458-1463; W. Li et al., Org. Synth. 2009, 81 , 89-97; for example), or from the respective halides and diboronic acid (tetrahydroxydiboron) or diboronic acid esters such as the pinacol ester (bis(pinacolato)diboron, 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi-1 ,3,2- dioxaborolane) in the presence of a palladium catalyst (cf. T. Ishiyama et al., Tetrahedron 2001 , 57, 9813-9816; G. A. Molander et al., J. Am. Chem. Soc. 2010, 132, 17701 -17703, for example). In view of the wide synthetic utility of boronic acids and boronic acid esters, a large number of compounds of the formula III and related boronic acids and boronic acid esters, which can be used to prepare the compounds of the formula I according to the present invention, are commercially available.

Compounds of the formula II in which the group X is chlorine, bromine or iodine, can be obtained according to standard procedures for aromatic chlorination, bromination and iodination, for example by means of N-chlorosuccinimide (NCS), N- bromosuccinimide (NBS) and N-iodosuccinimide (NIS) (cf. S. M. Maddox et al., Org. Lett. 2015, 17, 1042-1045; R. H. Mitchell et al., J. Org. Chem. 1979, 44, 4733-4735; K. Rajesh et al., J. Org. Chem. 2007, 72, 5867-5869; G. K. S. Prakash et al., J. Am. Chem. Soc. 2004, 126, 15770-15776, for example). These agents can also be used for the introduction of halogen substituents in other positions of the pyrido[3,4- b]indole ring system, such as in position 6, depending on the substitution pattern in the respective starting compound and the reaction conditions. For example, suitably substituted compounds of the formula IV can be converted into compounds of the formula Ila in which the group Xa is chlorine, bromine or iodine, by treatment with NCS, NBS or NIS, which together are abbreviated herein as NXaS, for example in a solvent such as water in the presence of an acid such as hydrochloric acid, sulfuric acid or phosphoric acid at temperatures from about 20 °C to about 100 °C.

Similarly can compounds of the formula IVa, in which the group R is chlorine, bromine or iodine, be obtained by treatment of suitably substituted compounds of the formula V with NXaS, for example compounds of the formula IVa in which R5a is chlorine by treatment with NCS in water and hydrochloric acid.

In IVa

The groups R1 to R6 and R10 in the compound of the formula lla, IV, IVa and V are defined as in the compound of the formula I, and in addition can functional groups be present in protected form or in the form of a precursor group. Compounds of the formula IVa in which R5a is chlorine can then be converted, for example by treatment with NBS or NIS, into compounds of the formula lla in which R5 is chlorine and Xa is bromine or iodine, which can then be reacted with compounds of the formula III to give compounds of the formula I in which R5 is chlorine, for example.

Compounds of the formula II and related compounds useful for the preparation of compounds of the formula II such as compounds of the formula IV and V can be prepared according to various processes described in the literature, or analogously to processes described in the literature, and many of them are commercially available, such as the compounds harmane (1 -methyl-9H-pyrido[3,4-b]indole), norharmane (9H-pyrido[3,4-b]indole), 6-chloro-9H-pyrido[3,4-b]indole, 6-bromo-9H-pyrido[3,4-b]indole, 6-chloro-1 -methyl-9H-pyrido[3,4-b]indole or 6-bromo-1 -methyl-9H-pyrido[3,4-b]indole, for example. Examples of well-known processes of which use can be made in the preparation of compounds of the formula II and related

compounds, which start from indole precursors which in turn are available via various processes described in literature, are processes involving Bischler-Napieralski type cyclizations or Pictet-Spengler type cyclizations and the cyclization of indole derivatives comprising two oxo-substituted groups in positions 2 and 3 of the indole ring system.

From suitably substituted indole derivatives of the formula VI carrying an optionally substituted 2-acylamino-ethyl moiety in position 3 of the indole ring system, compounds of the formula VII can be obtained in a Bischler-Napieralski type cyclization by treatment with phosphorus oxychloride (phosphoryl trichloride) or a mixture of phosphorus oxychloride and phosphorus pentoxide at elevated

temperatures, such as at temperatures from about 60 °C to about 120 °C, for example at about 80 °C, in an inert solvent such as a hydrocarbon like benzene or a nitrile like acetonitrile or without a solvent. The compounds of the formula VII are then oxidized, or dehydrogenated, to compounds of the formula VIII, for example by treatment with nitrobenzene at elevated temperatures, such as at about reflux temperature, or by treatment with potassium dichromate in a solvent such as water and acetic acid at elevated temperatures, such as at about reflux temperature of the solvent.

From suitably substituted indole derivatives of the formula IX carrying an optionally substituted 2-amino-ethyl moiety in position 3 of the indole ring system, and aldehydes of the formula X compounds of the formula XI can be obtained in a Pictet-Spengler type cydization, for example under acidic conditions such as in water in the presence of sulfuric acid at elevated temperatures, such as at about 65 °C, or in an alcohol such as ethanol in the presence of hydrochloric acid at elevated

temperatures, such as at about reflux temperature of the solvent (cf. E. D. Cox et al., Chem. Rev. 1995, 95, 1797-1842, for example). The compounds of the formula XI are then oxidized, or dehydrogenated, to compounds of the formula VIII, for example by treatment with potassium dichromate in a solvent such as water and acetic acid at elevated temperatures, such as at about reflux temperature of the solvent, or by

treatment with palladium in a solvent such as xylene at elevated temperatures, such as at about reflux temperature of the solvent.

In another synthetic approach to compounds of the formula II and related compounds suitably substituted indole derivatives of the formula XII, which can be obtained by acylating indole derivatives carrying an optionally substituted 2-oxo-ethyl group in position 3 of the indole ring system with an acylating agent in the presence of a catalyst such as zinc chloride, are cyclized to compounds of the formula VIII by treatment with a source of ammonia, such as an ammonium salt like ammonium acetate, in a solvent such as acetic acid at elevated temperatures, such as at about 60 °C.

Rocca et al, Tetrahedron 1993, 49, 49-64.; P. Rocca et al., Tetrahedron 1993, 49, 3325-3342).

The groups R3 to R6 and R10 in the compounds of the formulae VI, VII, VIII, IX, XI, XII and XIII are defined as in the compounds of the formula I, and in addition can functional groups be present in protected form or in the form of a precursor group. The group R1a in the compounds of the formulae VI, VII, VIII, X, XI, XII and XIII is selected from the series consisting of hydrogen and (C1-C4)-alkyl, in one embodiment from the series consisting of hydrogen and (C1-C2)-alkyl, in another embodiment from the series consisting of hydrogen and C1-alkyl, and in another embodiment is hydrogen and in another embodiment is (C1-C4)-alkyl, for example C1-alkyl. The group R2a in the compounds of the formulae VI, VII, VIII, IX, XI, XII and XIII is selected from the series consisting of hydrogen, (C1-C4)-alkyl and (C1-C4)-alkyl-O-C(O)-, in one embodiment from the series consisting of hydrogen and (C1-C4)-alkyl, in another embodiment from the series consisting of hydrogen and (C1-C2)-alkyl, in another embodiment from the series consisting of hydrogen and C1-alkyl, and in another embodiment is hydrogen and in another embodiment is (C1-C4)-alkyl, for example C1-alkyl. The group Z in the compounds of the formulae VI, VII, VIII, IX, XI, XII and XIII is selected from the series consisting of hydrogen, chlorine, bromine, iodine, hydroxy and (C1-C4)-alkyl-O-, in one embodiment from the series consisting of hydrogen, chlorine, bromine and iodine, in another embodiment from the series consisting of hydrogen, bromine and iodine, in another embodiment from the series consisting of chlorine, bromine and iodine, in another embodiment from the series consisting of bromine and iodine, in another embodiment from the series consisting of hydroxy and (C1-C4)-alkyl-O-, in another embodiment it is hydrogen, and in another embodiment it is bromine. Compounds of the formula VIII in which Z is chlorine, bromine or iodine, are compounds of the formulae II and lla which can be used in the reaction with compounds of the formula III to give compounds of the formula I.

Compounds of the formula VIII in which Z is hydrogen, can be converted into compounds of the formulae II and lla, which can be used in the reaction with compounds of the formula III to give compounds of the formula I, by halogenation as outlined above. Compounds of the formula VIII in which Z is (C1-C4)-alkyl-O-, can be converted into compounds of the formula VIII in which Z is hydroxy under standard condition for the cleavage of alkyl ethers, for example by treatment with boron tribromide. Compounds of the formula VIII in which Z is hydroxy can be converted under standard conditions into compounds of the formula II in which the group X is a sulfonyloxy group, for example a trifluoromethanesulfonyloxy group which can be introduced by treatment of the compound of the formula VIII with

trifluoromethanesulfonic acid anhydride, and the obtained compound of the formula II be used in the reaction with compounds of the formula III to give compounds of the formula I.

As mentioned above, the group R10 in the compounds of the formulae II, lla, IV, IVa, V, VI, VII, VIII, IX, XI, XII and XIII is defined as in the compounds of the formula I, and in addition can functional groups be present in protected form or in the form of a precursor group, and can thus be hydrogen, or be different from hydrogen and be an optionally substituted (C1-C6)-alkyl group, (C2-C6)-alkenyl group, (C2-C6)-alkynyl group and optionally substituted (C3-C7)-cycloalkyl group. Groups R10 which are different from hydrogen, can be present in the starting compound for the synthesis of a compound of the formula I or introduced at any stage in course of the synthesis, for example in a compound of the formula II, lla, IV, IVa, V or VIII, as well as in a final compound of the formula I according to the invention, by reaction of the respective compound in which R10 is hydrogen with an electrophilic compound of the formula XIV, for example an alkylating agent if an optionally substituted alkyl group

representing R10 is to be introduced, as illustrated by the example of a compound of the formula IIb , which is a compound of the formula lla in which R10 is hydrogen and can be converted by reaction with a compound of the formula XIV into a compound of the formula lie.

IIb lie

The groups R1 to R6 and X in the compounds of the formulae IIb and lie are defined as in the compounds of the formula lla. The group R10a in the compounds of the formulae lie and XIV is selected from the series consisting of (C1-C6)-alkyl, (C2-C6)-alkenyl, (C2-C6)-alkynyl and (C3-C7)-cycloalkyl, wherein alkyl is unsubstituted or substituted by 1 or 2 identical or different substituents selected from the series consisting of (C3-C7)-cycloalkyl, Het, cyano and (C1-C4)-alkyl-O-, wherein all cycloalkyl groups are unsubstituted or substituted by one or more identical or different substituents selected from the series consisting of fluorine and (C1-C4)-alkyl. The group L in the compounds of the formula XIV is a nucleophilically substitutable leaving group, such as halogen selected from the series consisting of chlorine, bromine and iodine, or a sulfonyloxy group like methanesulfonyloxy,

trifluoromethanesulfonyloxy or 4-toluenesulfonyloxy, for example. The reaction of compounds of the formula IIb and compounds of the formulae I, II, IV, IVa, V or VIII in which R10 is hydrogen, with compounds of the formula XIV can be performed under standard conditions for the reaction of electrophilic compounds such as alkylating agents, for example, with nitrogen heterocycles and other nitrogen compounds in which a hydrogen atom on the nitrogen atom can be replaced by a group such as an alkyl group, for example. In a favorable manner such reactions are performed in the presence of a base, such an alkali metal hydride like sodium hydride or an alkali metal alkoxide like sodium ethoxide or sodium tert-butoxide or an alkali metal carbonate like potassium carbonate or cesium carbonate, in an inert solvent, such as an amide like dimethylformamide or N-methyl-2-pyrrolidone or a ketone like acetone or butan-2-one or an ether like tetrahydrofuran or dioxane, at temperatures of from about 20 °C to about 100 °C, for example temperatures of from about 20 °C to about 60 °C. In one embodiment, the reaction of a compound of the formula IIb or a compound of the formulae I, II, IV, IVa, V or VIII in which R10 is hydrogen, with a compound of the formula XIV is performed in the presence of an alkali metal carbonate like potassium carbonate or cesium carbonate in a solvent like

dimethylformamide at temperatures of from about 20 °C to about 30 °C.

In another process a compound of the formula I is prepared by chemical modification, or introduction or transformation of functional groups, of a compound which has been prepared from a compound of the formula II and a compound of the formula III as described above. The compound that is modified chemically can be a compound of the formula I according to the present invention, as well as a compound which is not covered by the definition of the compounds of the formula I according to the present invention. Such chemical modifications can be performed in the moiety G-E-A- or in the groups R1 to R6 and R10, for example. Such chemical modifications can also be performed in another stage of the synthesis of the compounds of the formula I, for example in compounds of the formula II.

For example, a hydroxy group can be reacted with a carboxylic acid in the presence of an activating agent, such as carbodiimide or an Ν,Ν'-carbonyldiazole or another customary coupling reagent, or with a reactive carboxylic acid derivative such as a carboxylic acid chloride to give an acyloxy group, i.e. a carboxylic acid ester group. A hydroxy group can be etherified by alkylation with a halogen compound, for example a bromide or iodide, in the presence of a base such an alkali metal hydride like sodium hydride or an alkali metal carbonate like potassium carbonate or cesium carbonate in an inert solvent such as an amide like dimethylformamide or N-methyl-2-pyrrolidone or a ketone like acetone or butan-2-one at temperatures of from about 20 °C to about 120 °C, or with the respective alcohol under the conditions of the Mitsunobu reaction in the presence of a phosphine like triphenylphosphine or tributylphosphine and an azodicarboxylic acid derivative like diethyl azodicarboxylate or diisopropyl azodicarboxylate in an inert solvent such as an ether like tetrahydrofuran. An ether group initially present can be cleaved, for example by means of boron tribromide or an acid, and the resulting hydroxy group then converted into various other groups. By reaction with an isocyanate, a hydroxy group can be converted into an N-substituted carbamic acid ester. By treatment with a halogenating agent such as thionyl chloride or a phosphorus halide a hydroxy group can be replaced by a halogen atom.

Halogen atoms can also be introduced according to various other procedures described in the literature. Fluorine atoms can be introduced by means of reagents such as diethylaminosulfur trifluoride or N-fluoro-2,4,6-trimethylpyridinium triflate, for example, and similar reagents. A halogen atom, as well as a hydroxy group after activation by conversion into a reactive leaving group such as a methanesulfonyloxy group, trifluoromethanesulfonyloxy group or 4-toluenesulfonyloxy group, can be replaced with a variety of groups, including groups such as cyano, trifluoromethyl, pentafluoroethyl, carboxylic acid, carboxamide, amino, alkyl, aryl or heterocyclic groups, in a substitution reaction, which may also be catalyzed by transition metals such as by a palladium catalyst, a nickel catalyst or a copper catalyst. By

halogen/metal exchange, as well as by hydrogen/metal exchange, for example by treatment withan organolithium compound, and subsequent reaction with a wide range of electrophiles various substituents can be introduced.

A carboxylic acid ester group or a cyano group can be hydrolyzed under acidic or basic conditions to give a carboxylic acid. A cyano group can be hydrolyzed partially to give a primary amide. A carboxylic acid group can be activated or converted into a reactive derivative as indicated above, and reacted with an alcohol or an amine or ammonia to give an ester or amide. A carboxylic acid group, which may have been obtained by saponification of an ester group, can be converted into a hydrogen atom by decarboxylation, for example by heating a metal salt of the carboxylic acid. A primary amide can be dehydrated to give a nitrile. A carboxylic acid group, carboxylic acid ester group, aldehyde group or ketone group can be reduced to an alcohol, for example with a complex hydride such as lithium aluminium hydride, lithium

borohydride or sodium borohydride, or reacted with an organometal compound such as a Grignard compound, for example, to give an alcohol. A hydroxy group can be oxidized to an oxo group, for example by means of pyridinium chlorochromate or the Dess-Martin periodinane reagent.

An amino group and a suitable ring nitrogen atom in a heterocycle can be modified under standard conditions for acylation or sulfonylation, for example by reaction with an activated carboxylic acid or a reactive carboxylic acid derivative like a carboxylic acid chloride or anhydride, or a sulfonyl chloride. An amino group and a suitable ring nitrogen atom in a heterocycle can be alkylated by reaction with optionally substituted alkyl halogenides like chlorides, bromides or iodides or sulfonyloxy compounds like toluenesulfonyloxy, methanesulfonyloxy or trifluoromethanesulfonyloxy compounds, generally in the presence of a base such as potassium carbonate, cesium carbonate, sodium hydride or potassium tert-butoxide, for example, or by reductive amination of carbonyl compounds in the presence of a complex hydride reducing agent. A nitro group can be reduced to an amino group with various reducing agents, such as sulfides, dithionites, iron, complex hydrides or by catalytic hydrogenation. A cyano group and a carboxamide group can be reduced to an amino-substituted methyl group. A sulfur atom in an alkyl-S- group or in a heterocyclic ring can be oxidized with a peroxide like hydrogen peroxide or a peracid to give a sulfoxide moiety (S(O)) or a sulfone moiety (S(O)2).

All such reactions useful for the preparation of compounds of the formula I are known per se and can be carried out in a manner familiar to a person skilled in the art according to, or analogously, to procedures which are described in the standard literature, for example in Houben-Weyl, Methods of Organic Chemistry, Thieme; or Organic Reactions, John Wiley & Sons; or R. C. Larock, Comprehensive Organic Transformations: A Guide to Functional Group Preparations, 2. ed. (1999), John Wiley & Sons, and the references quoted therein. As applies in general and is known to the person skilled in the art, it may in certain cases become necessary to specifically adapt reaction conditions or choose specific reagents from a variety of reagents that can in principle be employed in a reaction, or otherwise take specific measures for achieving a desired conversion, for example to use protection group techniques.

In the course of the preparation of the compounds of the formula I it can generally be advantageous or necessary in order to reduce or prevent undesired reactions or side reactions in a synthesis step, to block functional groups temporarily by protecting groups suited to the specific synthesis problem, or to have them present, or introduce them, in the form of precursor groups, and later convert them into the desired functional groups. This applies to all reactions in the course of the synthesis of the compounds of the formula I including the synthesis of intermediates and the synthesis of starting compounds and building blocks. Such strategies are well known to a person skilled in the art and are described, for example, in P. G. M. Wuts and T. W. Greene, Greene's Protective Groups in Organic Synthesis, 4. ed. (2007), John Wiley & Sons. Examples of precursor groups are cyano groups and nitro groups. As already mentioned, a cyano group can in a later step be transformed by hydrolysis into a carboxylic acid derivative or by reduction into a aminomethyl group, and a nitro group can be transformed by reduction like catalytic hydrogenation into an amino group. Examples of protective groups which may be mentioned, are benzyl protective groups, for example benzyl ethers of hydroxy compounds and benzyl esters of carboxylic acids, from which the benzyl group can be removed by catalytic

hydrogenation in the presence of a palladium catalyst, tert-butyl protective groups, for example tert-butyl esters of carboxylic acids or tert-butyl ethers of hydroxy groups, from which the tert-butyl group can be removed by treatment with trifluoroacetic acid, acyl protective groups, for example ester and amides of hydroxy compounds and amino compounds, which can be cleaved again by acidic or basic hydrolysis, or alkoxycarbonyl protective groups, for example tert-butoxycarbonyl derivatives of amino compounds, which can be cleaved again by treatment with trifluoroacetic acid.

WE Claims

1 . A compound of the formula I or a pharmaceutically acceptable salt thereof,
wherein
A is selected from the series consisting of phenyl and a monocyclic or bicyclic, 5-membered to 10-membered, aromatic heterocyclic group, which comprises 1 or 2 identical or different hetero ring members selected from the series consisting of N, N(R20), O and S and is bonded via a ring carbon atom, wherein phenyl and the heterocyclic group are unsubstituted or substituted on ring carbon atoms by one or more identical of different substituents R21;
E is a direct bond or a chain consisting of 1 to 5 chain members of which 0, 1 or 2 chain members are identical or different hetero chain members selected from the series consisting of N(R25), O and S(O)m, and the other chain members are identical or different groups C(R26)(R27);
G is selected from the series consisting of hydrogen, halogen, (C1-C4)-alkyl, cyano and R30;
R1, R3, R4 and R6 are independently of each other selected from the series consisting of hydrogen, halogen and (C1-C4)-alkyl;
R2 is selected from the series consisting of hydrogen, halogen, (C1-C4)-alkyl and (C1-C4)-alkyl-O-C(O)-;
R5 is selected from the series consisting of hydrogen, halogen, (C1-C4)-alkyl, (C1-C4)-alkyl-O-, cyano, R7-O-C(O)- and R8-N(R9)-C(O)-;
R7, R8, R9, R20, R22, R25, R31, R33, R34 and R40 are independently of each other selected from the series consisting of hydrogen and (C1-C4)-alkyl;
R10 is selected from the series consisting of hydrogen, (C1-C6)-alkyl, (C2-C6)-alkenyl, (C2-C6)-alkynyl and (C3-C7)-cycloalkyl, wherein alkyl is unsubstituted or substituted by 1 or 2 identical or different substituents selected from the series consisting of (C3-C7)-cycloalkyl, Het, cyano and (C1-C4)-alkyl-O-, wherein all cycloalkyl groups are unsubstituted or substituted by one or more identical or different substituents selected from the series consisting of fluorine and (C1-C4)-alkyl;
R21 is selected from the series consisting of halogen, (C1-C4)-alkyl, (C1-C4)-alkyl-O-and cyano, and two groups R21 bonded to adjacent ring carbon atoms in the group A, together with the carbon atoms carrying them, can form a 5-membered to 7-membered mono-unsaturated ring, which comprises 0, 1 or 2 identical or different hetero ring members selected from the series consisting of N(R22), O and S(O)m and which is unsubstituted or substituted on ring carbon atoms by one or more identical or different substituents selected from the series consisting of fluorine and (C1-C4)-alkyl;
R26 and R27 are independently of each other selected from the series consisting of hydrogen, fluorine, (C1-C4)-alkyl and hydroxy, and in one or two groups C(R26)(R27) the groups R26 and R27 bonded to the same carbon atom together can be oxo;
R30 is a monocyclic or bicyclic, 3-membered to 10-membered ring, which is saturated or unsaturated and comprises 0, 1 , 2 or 3 identical or different hetero ring members selected from the series consisting of N, N(R31), O and S(O)m, and which is
unsubstituted or substituted on ring carbon atoms by one or more identical or different substituents R32;
R32 is selected from the series consisting of halogen, (C1-C4)-alkyl, hydroxy, oxo, (C1-C4)-alkyl-O-, cyano, R33-N(R34)- and Het;
Het is a monocyclic, 4-membered to 7-membered, saturated heterocyclic group, which comprises 1 or 2 identical or different hetero ring members selected from the series consisting of N, N(R40), O and S(O)m, and which is unsubstituted or substituted on ring carbon atoms by one or more identical or different substituents selected from the series consisting of fluorine and (C1-C4)-alkyl;
m is selected from the series consisting of 0, 1 and 2, wherein all numbers m are independent of each other and can be identical or different;
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;
provided that the compound of the formula I is not 8-phenyl-9H-pyrido[3,4-b]indole.
2. A compound of the formula I according to claim 1 or a pharmaceutically acceptable salt thereof, wherein
A is selected from the series consisting of phenyl and a monocyclic, 5-membered or 6-membered, aromatic heterocyclic group, which comprises 1 or 2 identical or different hetero ring members selected from the series consisting of N, N(R20), O and S and is bonded via a ring carbon atom, wherein phenyl and the heterocyclic group are unsubstituted or substituted on ring carbon atoms by one or more identical of different substituents R21;
E is a direct bond or a chain consisting of 1 to 4 chain members of which 0, 1 or 2 chain members are identical or different hetero chain members selected from the
series consisting of N(R ), O and S(O)m, and the other chain members are identical or different groups C(R26)(R27);
G is selected from the series consisting of hydrogen, halogen, (C1-C4)-alkyl and R30;
R1, R3, R4 and R6 are independently of each other selected from the series consisting of hydrogen, halogen and (C1-C3)-alkyl;

R2 is selected from the series consisting of hydrogen, halogen and (C1-C3)-alkyl;

R5 is selected from the series consisting of hydrogen, halogen, (C1-C4)-alkyl, (C1-C4)-alkyl-O- and cyano;

R10 is selected from the series consisting of hydrogen, (C1-C6)-alkyl and (C3-C7)-cycloalkyi, wherein alkyl is unsubstituted or substituted by 1 substituent selected from the series consisting of (C3-C7)-cycloalkyl, Het, cyano and (C1-C4)-alkyl-O-, and wherein all cycloalkyi groups are unsubstituted or substituted by one or more identical or different substituents selected from the series consisting of fluorine and (C1-C4)-alkyl;

R20, R22, R25, R31 and R40 are independently of each other selected from the series consisting of hydrogen and (C1-C4)-alkyl;

R21 is selected from the series consisting of halogen, (C1-C4)-alkyl, (C1-C4)-alkyl-O-and cyano, and two groups R21 bonded to adjacent ring carbon atoms in the group A, together with the carbon atoms carrying them, can form a 5-membered or 6-membered mono-unsaturated ring, which comprises 0, 1 or 2 identical or different hetero ring members selected from the series consisting of N(R22), O and S(O)m and which is unsubstituted or substituted on ring carbon atoms by one or more identical or different substituents selected from the series consisting of fluorine and (C1-C4)-alkyl;

R and R are independently of each other selected from the series consisting of hydrogen, fluorine, (C1-C3)-alkyl and hydroxy, and in one group C(R26)(R27) the groups R26 and R27 bonded to the same carbon atom together can be oxo;

R30 is a monocyclic or bicyclic, 3-membered to 10-membered ring, which is saturated or unsaturated and comprises 0, 1 , 2 or 3 identical or different hetero ring members selected from the series consisting of N, N(R31), O and S(O)m, and which is unsubstituted or substituted on ring carbon atoms by one or more identical or different substituents R32;

R32 is selected from the series consisting of halogen, (C1-C4)-alkyl, hydroxy, oxo, (C1-C4)-alkyl-O- and cyano;

Het is a monocyclic, 4-membered to 6-membered, saturated heterocyclic group, which comprises 1 or 2 identical or different hetero ring members selected from the series consisting of N, N(R40) and O, and which is unsubstituted or substituted on ring carbon atoms by one or more identical or different substituents selected from the series consisting of fluorine and (C1-C4)-alkyl;

m is selected from the series consisting of 0, 1 and 2, wherein all numbers m are independent of each other and can be identical or different;

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 according to any of claims 1 and 2 or a

pharmaceutically acceptable salt thereof, wherein

A is selected from the series consisting of phenyl and a monocyclic, 5-membered or 6-membered, aromatic heterocyclic group, which comprises 1 or 2 identical or different hetero ring members selected from the series consisting of N, N(R20), O and S and is bonded via a ring carbon atom, wherein phenyl and the heterocyclic group are unsubstituted or substituted on ring carbon atoms by one or more identical of different substituents R21 ;

E is a direct bond or a chain consisting of 1 to 4 chain members of which 0, 1 or 2 chain members are identical or different hetero chain members selected from the series consisting of N(R25) and O, and the other chain members are identical or different groups C(R26)(R27);

G is selected from the series consisting of hydrogen, (C1-C4)-alkyl and R30;

R1 and R4 are independently of each other selected from the series consisting of hydrogen, halogen and (C1-C3)-alkyl;

R2 is selected from the series consisting of hydrogen, halogen and (C1-C3)-alkyl;

R3 and R6 are independently of each other selected from the series consisting of hydrogen, halogen and C1-alkyl;

R5 is selected from the series consisting of hydrogen, halogen, (C1-C4)-alkyl and cyano;

R10 is selected from the series consisting of hydrogen, (C1-C6)-alkyl and (C3-C7)-cycloalkyl, wherein alkyl is unsubstituted or substituted by 1 substituent selected from the series consisting of (C3-C7)-cycloalkyl, Het, cyano and (C1-C4)-alkyl-O-, and wherein all cycloalkyi groups are unsubstituted or substituted by one or more identical or different substituents selected from the series consisting of fluorine and (C1-C4)-alkyl;

R20, R22, R25, R31 and R40 are independently of each other selected from the series consisting of hydrogen and (C1-C4)-alkyl;

R is selected from the series consisting of halogen, (C1-C4)-alkyl, (C1-C4)-alkyl-O-and cyano, and two groups R21 bonded to adjacent ring carbon atoms in the group A, together with the carbon atoms carrying them, can form a 5-membered or 6-membered mono-unsaturated ring, which comprises 0, 1 or 2 identical or different hetero ring members selected from the series consisting of N(R22) and O, and which is unsubstituted or substituted on ring carbon atoms by one or more identical or different substituents selected from the series consisting of fluorine and C1-alkyl;

R26 and R27 are independently of each other selected from the series consisting of hydrogen, fluorine, (C1-C3)-alkyl and hydroxy, and in one group C(R26)(R27) the groups R26 and R27 bonded to the same carbon atom together can be oxo;

R30 is a monocyclic or bicyclic, 3-membered to 10-membered ring, which is saturated or aromatic and comprises 0, 1 or 2 identical or different hetero ring members selected from the series consisting of N, N(R31), O and S(O)m, and which is unsubstituted or substituted on ring carbon atoms by one or more identical or different substituents R32;

R32 is selected from the series consisting of halogen, (C1-C4)-alkyl, hydroxy, oxo and (C1-C4)-alkyl-O-;

Het is a monocyclic, 4-membered to 6-membered, saturated heterocyclic group, which comprises 1 hetero ring member selected from the series consisting of N(R40) and O, and which is unsubstituted or substituted on ring carbon atoms by one or more identical or different substituents selected from the series consisting of fluorine and (C1-C3)-alkyl;

m is selected from the series consisting of 0, 1 and 2, wherein all numbers m are independent of each other and can be identical or different;

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 according to any of claims 1 and 3 or a pharmaceutically acceptable salt thereof, wherein

A is selected from the series consisting of phenyl and a monocyclic, 5-membered or 6-membered, aromatic heterocyclic group, which comprises 1 or 2 identical or different hetero ring members selected from the series consisting of N, N(R20) and S and is bonded via a ring carbon atom, wherein phenyl and the heterocyclic group are unsubstituted or substituted on ring carbon atoms by one or more identical of different substituents R21;

E is a direct bond or a chain consisting of 1 to 4 chain members of which 0 or 1 chain members are identical or different hetero chain members selected from the series consisting of N(R25) and O, and the other chain members are identical or different groups C(R26)(R27);

G is selected from the series consisting of hydrogen and R30;

R1 and R4 are independently of each other selected from the series consisting of hydrogen, halogen and (C1-C2)-alkyl;

R2 is selected from the series consisting of hydrogen, halogen and (C1-C2)-alkyl;

R3 and R6 are independently of each other selected from the series consisting of hydrogen, halogen and C1-alkyl;

R5 is selected from the series consisting of hydrogen, halogen and (C1-C2)-alkyl;

R10 is selected from the series consisting of hydrogen, (C1-C4)-alkyl and (C3-C5)-cycloalkyi, wherein alkyl is unsubstituted or substituted by 1 substituent selected from the series consisting of (C3-C5)-cycloalkyl and Het, and wherein all cycloalkyi groups are unsubstituted or substituted by one or more identical or different substituents (C1-C2)-alkyl;

R20, R25 and R31 are independently of each other selected from the series consisting of hydrogen and (C1-C3)-alkyl;

R21 is selected from the series consisting of halogen, (C1-C4)-alkyl, (C1-C4)-alkyl-O-and cyano;

R26 and R27 are independently of each other selected from the series consisting of hydrogen, fluorine, C1-alkyl and hydroxy, and in one group C(R26)(R27) the groups R26 and R27 bonded to the same carbon atom together can be oxo;

R30 is a monocyclic 3-membered to 6-membered or bicyclic 9-membered to 10-membered ring, which is saturated or aromatic and comprises 0, 1 or 2 identical or different hetero ring members selected from the series consisting of N, N(R31) and O, and which is unsubstituted or substituted on ring carbon atoms by one or more identical or different substituents R32;

R32 is selected from the series consisting of halogen, (C1-C3)-alkyl, hydroxy and oxo;

Het is a monocyclic, 4-membered or 5-membered, saturated heterocyclic group, which comprises 1 hetero ring member which is O, and which is unsubstituted or substituted on ring carbon atoms by one or more identical or different substituents (C1-C3)-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 according to any of claims 1 and 4 or a

pharmaceutically acceptable salt thereof, wherein

A is selected from the series consisting of phenyl and the aromatic heterocyclic groups pyrazolyl and pyridinyl, wherein phenyl and the heterocyclic groups are unsubstituted or substituted on ring carbon atoms by one or more identical of different substituents R21;

E is a direct bond or a chain consisting of 1 to 3 chain members of which 0 or 1 chain member is a hetero chain member which is O, and the other chain members are identical or different groups C(R26)(R27);

G is selected from the series consisting of hydrogen and R30;

R1 and R4 are independently of each other selected from the series consisting of hydrogen, halogen and C1-alkyl;
R2 is selected from the series consisting of hydrogen, halogen and C1-alkyl;
R3 and R6 are hydrogen;
R5 is selected from the series consisting of halogen and (C1-C2)-alkyl;
R10 is selected from the series consisting of hydrogen, (C1-C4)-alkyl and (C3-C5)-cycloalkyl, wherein alkyl is unsubstituted or substituted by 1 substituent selected from the series consisting of (C3-C5)-cycloalkyl and Het;
R21 is selected from the series consisting of halogen, (C1-C4)-alkyl, (C1-C4)-alkyl-O-and cyano;
R26 and R27 are independently of each other selected from the series consisting of hydrogen, fluorine and C1-alkyl;
R30 is a monocyclic, 3-membered to 6-membered ring, which is saturated or aromatic and comprises 0, 1 or 2 identical or different hetero ring members selected from the series consisting of N, N(R ) and O, and which is unsubstituted or substituted on ring carbon atoms by one or more identical or different substituents R32;
R31 is selected from the series consisting of hydrogen and (C1-C3)-alkyl;
R32 is selected from the series consisting of halogen and (C1-C3)-alkyl;
Het is a monocyclic, 4-membered or 5-membered, saturated heterocyclic group, which comprises 1 hetero ring member which is O, and which is unsubstituted or substituted on ring carbon atoms by one or more identical or different substituents (C1-C3)-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 according to claim 1 or a pharmaceutically acceptable salt thereof, wherein
A is phenyl, which is unsubstituted or substituted on ring carbon atoms by one or more identical of different substituents R21;
E is a direct bond;
G is selected from the series consisting of hydrogen, halogen, (C1-C4)-alkyl and cyano.
7. A compound of the formula I according to claim 1 or a pharmaceutically acceptable salt thereof, wherein
A is phenyl, which is unsubstituted or substituted on ring carbon atoms by one or more identical of different substituents R21;
E is a chain consisting of 1 to 5 chain members of which 0, 1 or 2 chain members are identical or different hetero chain members selected from the series consisting of N(R25), O and S(O)m, and the other chain members are identical or different groups C(R26)(R27);
8. A compound of the formula I according to claim 1 or a pharmaceutically acceptable salt thereof, wherein
A is a monocyclic or bicyclic, 5-membered to 10-membered, aromatic heterocyclic group, which comprises 1 or 2 identical or different hetero ring members selected from the series consisting of N, N(R20), O and S and is bonded via a ring carbon atom, and which is unsubstituted or substituted on ring carbon atoms by one or more identical of different substituents R21 ;
E is a direct bond;
G is selected from the series consisting of hydrogen, halogen, (C1-C4)-alkyl and cyano.
9. A compound of the formula I according to claim 1 or a pharmaceutically acceptable salt thereof, wherein
A is a monocyclic or bicyclic, 5-membered to 10-membered, aromatic heterocyclic group, which comprises 1 or 2 identical or different hetero ring members selected from the series consisting of N, N(R20), O and S and is bonded via a ring carbon atom, and which is unsubstituted or substituted on ring carbon atoms by one or more identical of different substituents R21 ;
E is a chain consisting of 1 to 5 chain members of which 0, 1 or 2 chain members are identical or different hetero chain members selected from the series consisting of N(R25), O and S(O)m, and the other chain members are identical or different groups C(R26)(R27);
G is R30.
10. A compound of the formula I according to any of claims 1 to 3, which is selected from the series consisting of:
6-Bromo-9-ethyl-1 -methyl-8-(1 -pyridin-3-ylmethyl-1 H-pyrazol-4-yl)-9H-pyrido[3,4-b]indole,
6-Chloro-1 ,5-dimethyl-8-[4-(3-methyl-oxetan-3-ylmethoxy)-phenyl]-9H-pyrido[3,4-b]indole,
2-(4-[6-Chloro-9-(2,2,2-trifluoroethyl)-9H-pyrido[3,4-b]indol-8-yl]pyrazol-1 -yl)ethanol, 6-Chloro-1 -methyl-8-[4-(2-pyrazol-1 -ylethoxy)-phenyl]-9H-pyrido[3,4-b]indole, 6-Bromo-9-ethyl-1 ,3-dimethyl-8-(1 -methyl-1 H-pyrazol-4-yl)-9H-pyrido[3,4-b]indole, 6-Chloro-8-(4-methoxy-phenyl)-1 ,9-dimethyl-9H-pyrido[3,4-b]indole,
6-Chloro-8-(4-methoxy-phenyl)-1 ,5-dimethyl-9H-pyrido[3,4-b]indole,
8-(4-Methoxy-phenyl)-1 -methyl-9H-pyrido[3,4-b]indole-6-carbonitrile,
6-Chloro-1 -methyl-8-[4-(1 -methyl-1 H-imidazol-2-ylmethoxy)-phenyl]-9H-pyrido[3,4-b]indole,
6-Chloro-1 ,5-dimethyl-8-[4-(2-pyrazol-1 -yl-ethoxy)-phenyl]-9H-pyrido[3,4-b]pyndine, 6-Chloro-9-cyclopropylmethyl-8-(2,6-dichloro-pyridin-3-yl)-9H-pyndo[3,4-b]indole, 6-Chloro-8-(2,6-dichloro-pyridin-3-yl)-9-ethyl-9H-pyndo[3,4-b]indole,
8-(2,6-Dichloro-pyridin-3-yl)-1 ,6-dimethyl-9H-pyndo[3,4-b]indole,
6-Chloro-9-ethyl-1 -methyl-8-(1 -pyridin-3-ylmethyl-1 H-pyrazol-4-yl)-9H-pyrido[3,4-b]indole,
6-Chloro-8-(4-chloro-phenyl)-9-ethyl-1 -methyl-9H-pyrido[3,4-b]indole,
6-Chloro-8-(4-methoxy-phenyl)-1 -methyl-9H-pyrido[3,4-b]indole,
6-Chloro-8-chroman-6-yl-1 -methyl-9H-pyrido[3,4-b]indole,
6-Chloro-8-[4-(2-imidazol-1 -yl-ethoxy)-phenyl]-1 -methyl-9H-pyrido[3,4-b]indole, 6-Bromo-9-ethyl-1 -methyl-8-(1 -methyl-1 H-pyrazol-4-yl)-9H-pyrido[3,4-b]indole, 4-(6-Chloro-1 -methyl-9H-pyrido[3,4-b]indol-8-yl)-pyridin-2-ylamine,
6-Chloro-1 -methyl-8-[4-(1 -methyl-pyrrolidin-3-ylmethoxy)-phenyl]-9H-pyrido[3,4-b]indole,
6-Chloro-9-ethyl-1 -methyl-8-[4-(3-methyl-oxetan-3-ylmethoxy)-phenyl]-9H-pyrido[3,4-b]indole,
6-Bromo-9-ethyl-1 -methyl-8-[4-(3-methyl-oxetan-3-ylmethoxy)-phenyl]-9H-pyrido[3,4-b]indole, and
6-Chloro-9-cyclopropylmethyl-8-(1 -pyridin-3-ylmethyl-1 H-pyrazol-4-yl)-9H-pyrido[3,4-b]indole,
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,
which comprises reacting a compound of the formula II with a compound of the formula III, wherein the groups A, E, G, R1 to R6 and R10 in the compounds of the formulae II and III 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 X in the compound of the formula II is leaving group, and the groups Y in the compounds of the formula III are hydrogen or (C1-C4)-alkyl or the two groups Y, together with the -O-B-O- moiety to which they are bonded, form a saturated 5-membered or 6-membered ring, which comprises 2 or 3 carbon atoms as ring atoms in addition to the -O-B-O- moiety and is unsubstituted or substituted by one or more (C1-C4)-alkyl substituents.
12. A pharmaceutical composition, comprising a compound of the formula I or a pharmaceutically acceptable salt thereof according to any of claims 1 to 10 and a pharmaceutically acceptable carrier.
13. A compound of the formula I or a pharmaceutically acceptable salt thereof according to any of claims 1 to 10, for use as a pharmaceutical.
14. A compound of the formula I or a pharmaceutically acceptable salt thereof, according to any of claims 1 to 10, for use as a stimulator of chondrogenesis or cartilage formation or as an inducer of SOX transcription factors or for the treatment of degenerative joint disorders, degenerative cartilage changes, fibrosis,
inflammatory processes or pain.
15. Use of a compound of the formula I or a pharmaceutically acceptable salt thereof according to any of claims 1 to 10, for the manufacture of a medicament for stimulating chondrogenesis or cartilage formation or inducing SOX transcription factors or for the treatment of degenerative joint disorders, degenerative cartilage changes, fibrosis, inflammatory processes or pain.