Substituted bicyclic compounds

Abstract

The present invention relates to bicyclic compounds. These bicyclic compounds are useful as TEAD binders and / or inhibitors of YAP-TEAD and TAZ-TEAD protein-protein interaction or binding and for the prevention and / or treatment of cancer and other severe disorders and diseases.

Description

[0001] Substituted bicyclic compounds

[0002] Field of the invention

[0003] The present invention relates to bicyclic compounds. These bicyclic compounds are useful as TEAD binders and / or inhibitors of YAP-TEAD and TAZ-TEAD protein-protein interaction or binding and for the prevention and / or treatment of cancer and other severe disorders and diseases.

[0004] Background of the invention

[0005] In recent years the Hippo pathway has become a target of interest for the treatment of hyperproliferative disorders and diseases, in particular cancer (S. A. Smith et al., J. Med. Chem. 2019, 62, 1291 -1305; K. C. Lin et al., Annu. Rev. Cancer Biol. 2018, 2: 59-79; C.-L. Kim et al., Cells (2019), 8, 468; K. F. Harvey et al., Nature Reviews Cancer, Vol. 13, 246-257 (2013)). The Hippo pathway regulates cell growth, proliferation, and migration. It is assumed that in mammals the Hippo pathway acts as a tumor suppressor, and dysfunction of Hippo signaling is frequently observed in human cancers.

[0006] Furthermore, as the Hippo pathway plays a role in several biological processes - like in self-renewal and differentiation of stem cells and progenitor cells, wound healing and tissue regeneration, interaction with other signaling pathways such as Wnt - its dysfunction may also play a role in human diseases other than cancer (C.-L. Kim et al., Cells (2019), 8, 468; Y. Xiao et al., Genes & Development (2019) 33: 1491 -1505; K. F. Harvey et al., Nature Reviews Cancer, Vol. 13, 246-257 (2013)).

[0007] While several aspects of the pathway activity and regulation are still subject to further research, it is already established that in its “switched-on”-state the Hippo pathway involves a cascade of kinases (including Mst 1 / 2 and Lats 1 / 2) in the cytoplasm which results in the phosphorylation of two transcriptional coactivators, YAP (Yes-associated protein) and TAZ (Transcription co-activator with PDZ binding motif). Phosphorylation of YAP / TAZ leads to their sequestration in the cytoplasm and eventually to their degradation. In contrast, when the Hippo pathway is “switched-off” or dysfunctions, the nonphosphorylated, activated YAP / TAZ co-activators are translocated into the cell nucleus. Their major target transcription factors are the four proteins of the Transcriptional enhanced associate domain (TEAD) transcription factor family (TEAD1 -4). Binding of YAP or TAZ to and activation of TEAD (or other transcription factors) have shown to induce the expression of several genes many of which mediate cell survival and proliferation. Thus, activated, nonphosphorylated YAP and TAZ may act as oncogenes, while the activated, switched-on Hippo pathway may act as a tumor suppressor by deactivating, i.e. phosphorylating YAP and TAZ.

[0008] Furthermore, the Hippo pathway may also play a role in resistance mechanisms of cancer cells to oncology and immune-oncology therapy (R. Reggiani et al. , BBA - Reviews on Cancer 1873 (2020) 188341 , 1 -11 ).

[0009] Recently, small molecule inhibtors have been described as pan-TEAD inhibitors, i.e., as compounds which bind not only to one of the TEAD family members but to more than one and in particular to all four human TEAD paralogs and thereby block YAP / TAZ binding (T.J. Hagenbeek, et al., Nature Cancer, 4, 812-828 (2023); WO 2021 / 108483 A1 ).

[0010] Consequently, the dysfunction or aberrant regulation of the Hippo pathway as a tumor suppressor is believed to be an important event in the development of a wide variety of cancer types and diseases.

[0011] Therefore, inhibition of YAP, TAZ, TEAD, and YAP-TEAD or TAZ-TEAD protein-protein interaction by pharmacological intervention appears to be a reasonable and valuable strategy to prevent and / or treat cancer and other hyperproliferative disorders and diseases associated with the dysfunction of the Hippo pathway. It may further be useful to inhibit the binding not only to one family member of TEAD, but even to two, three and / or all four TEAD paralogs. Description of the invention

[0012] The present invention provides compounds that may be useful in the prevention and / or treatment of medical conditions, disorders and / or diseases, in particular of hyperproliferative disorders or diseases, which compounds are TEAD binders and / or inhibitors of YAP-TEAD or TAZ-TEAD protein-protein interaction. Some of the compounds of the present invention may be useful for making other compounds of the present invention.

[0013] The present invention refers in one embodiment to a heteroaromatic compound of formula I wherein

[0014] D-1 D-2

[0015] Ring D together with R2denotes or ;

[0016] X1denotes CRX1or N;

[0017] RX1denotes H, halogen, straight-chain or branched Ci-4-alkyl which is unsubstituted or substituted with independently from each other 1 , 2, or 3 halogen, and / or OH;

[0018] R1denotes straight-chain or branched Ci-6-alkyl, which is unsubstituted or substituted with independently from each other 1 , 2, or 3 halogen, and in which Ci-6-alkyl 1 , 2, 3, 4, 5, 6, or 7 H-atoms may be replaced by deuterium (D-atoms); or C3-7-cycloalkyl, which is unsubstituted or substituted with independently from each other 1 , 2, or 3 halogen, and in which C3-7-cycloalkyl 1 , 2, 3, 4, 5, 6, or 7 H-atoms may be replaced by deuterium (D-atoms), in particular unsubstituted Cs-s-cycloalkyl, specifically cyclopropyl;

[0019] R2denotes H, Aik2, Ar2, Hetar2, Cyc2, Hetcyc2, -L2-Ar2a;

[0020] R3denotes H, halogen, or Ci-6-alkyl, C2-6-alkenyl or C2-e-alkinyl, each of which may be unsubstituted or substituted independently from each other -OH or 1 , 2, or 3 halogen (in particular Ci-4-alkyl, C2-4-alkenyl or C2-4- alkinyl, each of which may be unsubstituted or mono-substituted with - OH);

[0021] A denotes 1 ,3-phenylen or a monocyclic divalent heteroaryl with 5 or 6 rings atoms, wherein 1 , 2, or 3 of said ring atoms are heteroatoms(s) selected from N, 0 and / or S and the remaining are carbon atoms, wherein that 1 ,3-phenylen or monocyclic heteroaryl bears the bicyclic ring system of the compound of formula I in 1 - positon and that L1-B radical of the compound of formula I in 3-position relative to that bicyclic ring system, wherein each of that 1 ,3-phenylen or monocyclic hetereoaryl may further be unsubstituted or mono- or disubstituted with independently from each other halogen, straight-chain or branched C1-4- alkyl, which is unsubstituted or substituted with 1 , 2, or 3 halogen, or C3- 5-cycloalkyl,and in which Ci-4-alkyl or Cs-s-cycloalkyl 1 , 2, 3, 4, 5, 6, or 7 H-atoms may be replaced by deuterium (D-atoms);

[0022] B denotes Ar1, Hetar1, Cyc1, Hetcyc1;

[0023] L1denotes -O-, -N(R4)-, -O-CH2-, -O-CH(R5)-, -O-SO2-, -NH-CH2-, -N(R6)- CH2-, -NH-C(=O)-, -N(R6)-C(=O)-, -CH2-, -CH(R7)-, -CH2CH2-, -CH2-O-;

[0024] R4denotes H, straight-chain or branched Ci-6-alkyl; R5, R6, R7denote independently from each other straight-chain or branched Ci-e-alkyl;

[0025] L2denotes a divalent -S(=O)2- group;

[0026] Aik2denotes straight-chain or branched Ci-6-alkyl, C2-6-alkenyl or C2-e-alkinyl, each of which may be unsubstituted or substituted with independently from each other R2a1, R2a2and / or R2a3;

[0027] Ar1denotes a mono- or bicyclic aryl with 5, 6, 7, 8, 9, 10 ring carbon atoms, wherein that aryl is unsubstituted or substituted with independently from each other RC1, RC2, and / or RC3;

[0028] Ar®, Ar2, Ar2adenote independently from each other a mono- or bicyclic aryl with 5, 6, 7, 8, 9, 10 ring carbon atoms, wherein that aryl may be unsubstituted or substituted with independently from each other RB1, RB2, RB3, RB4, and / or RB5;

[0029] Hetar1denotes a mono- or bicyclic heteroaryl with 5, 6, 7, 8, 9, 10, 11 , 12 ring atoms wherein 1 , 2, 3, 4, 5 of said ring atoms is / are a hetero atom(s) selected from N, 0 and / or S and the remaining are carbon atoms, wherein that heteroaryl is unsubstituted or substituted with independently from each other RC1, RC2, and / or RC3;

[0030] Hetara, Hetar2, Hetar2adenote independently from each other a mono- or bicyclic heteroaryl with 5, 6, 7, 8, 9, 10, 11 , 12 ring atoms wherein 1 , 2, 3, 4, 5 of said ring atoms is / are a hetero atom(s) selected from N, O and / or S and the remaining are carbon atoms, wherein that heteroaryl is unsubstituted or substituted with independently from each other RB1, RB2, RB3, RB4, and / or RB5;

[0031] Cyc1denotes a saturated or partially unsaturated, mono-, bi- or tricyclic carbocycle with 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15 ring carbon atoms, wherein said carbocycle may be unsubstituted or substituted with independently from each other RC6, RC7, RC8, RC9, RC1°, and / or RC11;

[0032] Cyc2, Cyc2adenote independently from each other a saturated or partially unsaturated, mono-, bi- or tricyclic carbocycle with 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15 ring carbon atoms, wherein said carbocycle is unsubstituted or substituted with independently from each other RB6, RB7, RB8, RB9, RB1°, and / or RB11;

[0033] Hetcyc1denotes a saturated or partially unsaturated, mono- or bicylic heterocycle with 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12 ring atoms wherein 1 , 2, 3, 4, 5 of said ring atoms is / are a hetero atom(s) selected from N, 0 and / or S and the remaining are carbon atoms, wherein said heterocycle is unsubstituted or substituted with independently from each other RC6, RC7, RC8, RC9, RC1°, and / or RC11;

[0034] Hetcyca, Hetcyc2, Hetcyc2adenote independently from each other a saturated or partially unsaturated, mono- or bicylic heterocycle with 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12 ring atoms wherein 1 , 2, 3, 4, 5 of said ring atoms is / are a hetero atom(s) selected from N, 0 and / or S and the remaining are carbon atoms, wherein said heterocycle is unsubstituted or substituted with independently from each other RB6, RB7, RB8, RB9, RB1°, and / or RB11;

[0035] R2a1, R2a2 R2a3 denote independently from each other halogen, -CN, -NH2, -NHRa, -NRaRb, -OH, -ORC, -P(=O)RdRe, -SH, -SRf, -S(=O)Rf, -S(=O)2Rf, -S(=O)(=NRg)Rf, -N=S(=O)RfRh, -C(=O)NH2, -C(=O)NHRa, C(=O)NRaRb, -C(=O)OH, -C(=O)ORC, -NH-C(=O)-Ri, Cyc2a, Hetar2a, Hetcyc2a;

[0036] Ra, Rbdenote independently from each other straight-chain or branched Ci-6-alkyl, Ara, Hetara, Hetcyca; or

[0037] Raand Rbform together with the nitrogen atom to which they are attached to a saturated, partially unsaturated or aromatic heterocycle with 3, 4, 5, 6, 7 ring atoms wherein 1 of said ring atoms is said nitrogen atom and no or one further ring atom is a hetero atom selected from N, 0 or S and the remaining are carbon atoms, wherein said heterocycle is unsubstituted or substituted with independently from each other RB6, RB7, RB8, RB9, RB1°, and / or RB11;

[0038] Rcdenotes straight-chain or branched Ci-4-alkyl, C2-4-alkenyl or C2-4-alkinyl, each of which may be unsubstituted or substituted with -OH; C3-7- cycloalkyl which may be unsubstituted or substituted with -OH and / or halogen; Rd, Redenote independently from each other straight-chain or branched C1-6-alkyl; Rf, Rhdenote independently from each other straight-chain or branched C1-6-alkyl; Rgdenotes H, straight-chain or branched C1-6-alkyl; Ridenotes H, straight-chain or branched C1-6-alkyl; RB1, RB2, RB3, RB4, RB5denote independently from each other halogen; -OH; -OC1-4-alkyl; C1-4-alkyl, which may be unsubstituted or substituted with 1, 2, or 3 halogen; RB6, RB7, RB8, RB9, RB10, RB11denote independently from each other halogen; OH; -OC1-4-alkyl; C1-4-alkyl, which is unsubstituted or substituted with 1 or 2 OH and / or 1, 2, or 3 halogen; and / or two of RB6, RB7, RB8, RB9, RB10, RB11which are attached to the same carbon atom of said carbocycle or said heterocycle form a divalent oxo (=O) group; and / or two of RB6, RB7, RB8, RB9, RB10, RB11which are attached to the same sulfur (S) atom of said heterocycle form a divalent oxo (=O) group while at the same time two further of RB6, RB7, RB8, RB9, RB10, RB11which are attached to the same sulfur atom form either a divalent oxo group or a divalent =N-H or =N-C1-4-alkyl group, thereby forming an -S(=O)2, - S(=O)(=NH), or -S(=O)(=N-C1-4-alkyl) moiety; RC1, RC2, RC3denote independently from each other halogen; C1-4-alkyl or -OC1-4-alkyl, each of which may be unsubstituted or substituted with 1, 2, or 3 halogen; RC6, RC7, RC8, RC9, RC10, and / or RC11denote independently from each other halogen; C1-4-alkyl, which is unsubstituted or substituted with 1, 2, or 3 substituents independently from each other selected from halogen; -OC1- 4-alkyl, which is unsubstituted or substituted with 1, 2, or 3 halogen; halogen denotes F, Cl, Br, or I; or any N-oxide, solvate, tautomer or stereoisomer thereof and / or any pharmaceutically acceptable salt of each of the foregoing, including mixtures thereof in all ratios. In another embodiment the present invention refers to a heteroaromatic compound of formula I I wherein Ring D together with R2denotes or ; X1denotes CRX1or N; RX1denotes H, halogen, straight-chain or branched C1-4-alkyl which is unsubstituted or substituted with independently from each other 1, 2, or 3 halogen, and / or OH; R1denotes straight-chain or branched C1-6-alkyl, which is unsubstituted or substituted with independently from each other 1, 2, or 3 halogen; R2denotes H, Alk2, Ar2, Hetar2, Cyc2, Hetcyc2, -L2-Ar2a; R3denotes H or halogen; A denotes 1,3-phenylen or a monocyclic divalent heteroaryl with 5 or 6 rings atoms, wherein 1, 2, or 3 of said ring atoms are heteroatoms(s) selected from N, O and / or S and the remaining are carbon atoms, wherein that 1,3-phenylen or monocyclic heteroaryl bears the bicyclic ring system of the compound of formula I in 1- positon and that L1-B radical of the compound of formula I in 3-position relative to that bicyclic ring system, wherein each of that 1,3-phenylen or monocyclic hetereoaryl may further be unsubstituted or mono- or disubstituted with independently from each other halogen, straight-chain or branched C1-4- alkyl, which is unsubstituted or substituted with 1, 2, or 3 halogen; B denotes Ar1, Hetar1, Cyc1, Hetcyc1; L1denotes -O-, -N(R4)-, -O-CH2-, -O-CH(R5)-, -O-SO2-, -N(R6)-CH2-, -N(R6)- C(=O)-, -CH2-, -CH(R7)-, -CH2CH2-, -CH2-O-; R4denotes H, straight-chain or branched C1-6-alkyl; R5, R6, R7denote independently from each other straight-chain or branched C1-6-alkyl; L2denotes a divalent -S(=O)2- group; Alk2denotes straight-chain or branched C1-6-alkyl, C2-6-alkenyl or C2-6-alkinyl, each of which may be unsubstituted or substituted with independently from each other R2a1, R2a2and / or R2a3; Ar1denotes a mono- or bicyclic aryl with 5, 6, 7, 8, 9, 10 ring carbon atoms, wherein that aryl is unsubstituted or substituted with independently from each other RC1, RC2, and / or RC3; Ara, Ar2, Ar2adenote independently from each other a mono- or bicyclic aryl with 5, 6, 7, 8, 9, 10 ring carbon atoms, wherein that aryl may be unsubstituted or substituted with independently from each other RB1, RB2, RB3, RB4, and / or RB5; Hetar1denotes a mono- or bicyclic heteroaryl with 5, 6, 7, 8, 9, 10, 11, 12 ring atoms wherein 1, 2, 3, 4, 5 of said ring atoms is / are a hetero atom(s) selected from N, O and / or S and the remaining are carbon atoms, wherein that heteroaryl is unsubstituted or substituted with independently from each other RC1, RC2, and / or RC3; Hetara, Hetar2, Hetar2adenote independently from each other a mono- or bicyclic heteroaryl with 5, 6, 7, 8, 9, 10, 11, 12 ring atoms wherein 1, 2, 3, 4, 5 of said ring atoms is / are a hetero atom(s) selected from N, O and / or S and the remaining are carbon atoms, wherein that heteroaryl is unsubstituted or substituted with independently from each other RB1, RB2, RB3, RB4, and / or RB5; Cyc1denotes a saturated or partially unsaturated, mono-, bi- or tricyclic carbocycle with 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 ring carbon atoms, wherein said carbocycle may be unsubstituted or substituted with independently from each other RC6, RC7, RC8, RC9, RC10, and / or RC11; Cyc2denotes a saturated or partially unsaturated, mono-, bi- or tricyclic carbocycle with 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 ring carbon atoms, wherein said carbocycle is unsubstituted or substituted with independently from each other RB6, RB7, RB8, RB9, RB10, and / or RB11; Hetcyc1denotes a saturated or partially unsaturated, mono- or bicylic heterocycle with 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 ring atoms wherein 1, 2, 3, 4, 5 of said ring atoms is / are a hetero atom(s) selected from N, O and / or S and the remaining are carbon atoms, wherein said heterocycle is unsubstituted or substituted with independently from each other RC6, RC7, RC8, RC9, RC10, and / or RC11; Hetcyca, Hetcyc2, Hetcyc2adenote independently from each other a saturated or partially unsaturated, mono- or bicylic heterocycle with 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 ring atoms wherein 1, 2, 3, 4, 5 of said ring atoms is / are a hetero atom(s) selected from N, O and / or S and the remaining are carbon atoms, wherein said heterocycle is unsubstituted or substituted with independently from each other RB6, RB7, RB8, RB9, RB10, and / or RB11; R2a1, R2a2, R2a3denote independently from each other halogen, -CN, -NH2, -NHRa, -NRaRb, -OH, -ORc, -P(=O)RdRe, -SH, -SRf, -S(=O)Rf, -S(=O)2Rf, -S(=O)(=NRg)Rf, -N=S(=O)RfRh, -C(=O)NH2, -C(=O)NHRa, - C(=O)NRaRb, -C(=O)OH, -C(=O)ORc, -NH-C(=O)-Ri, Hetar2a, Hetcyc2a; Ra, Rbdenote independently from each other straight-chain or branched C1-6-alkyl, Ara, Hetara, Hetcyca; or Raand Rbform together with the nitrogen atom to which they are attached to a saturated, partially unsaturated or aromatic heterocycle with 3, 4, 5, 6, 7 ring atoms wherein 1 of said ring atoms is said nitrogen atom and no or one further ring atom is a hetero atom selected from N, O or S and the remaining are carbon atoms, wherein said heterocycle is unsubstituted or substituted with independently from each other RB6, RB7, RB8, RB9, RB10, and / or RB11; Rcdenotes straight-chain or branched C1-4-alkyl, C2-4-alkenyl or C2-4-alkinyl, each of which may be unsubstituted or substituted with -OH; C3-7- cycloalkyl which may be unsubstituted or substituted with -OH and / or halogen; Rd, Redenote independently from each other straight-chain or branched C1-6-alkyl; Rf, Rhdenote independently from each other straight-chain or branched C1-6-alkyl; Rgdenotes H, straight-chain or branched C1-6-alkyl; Ridenotes H, straight-chain or branched C1-6-alkyl; RB1, RB2, RB3, RB4, RB5denote independently from each other halogen; -OH; -OC1-4-alkyl; C1-4-alkyl, which may be unsubstituted or substituted with 1, 2, or 3 halogen; RB6, RB7, RB8, RB9, RB10, RB11denote independently from each other halogen; OH; -OC1-4-alkyl; C1-4-alkyl, which is unsubstituted or substituted with 1 or 2 OH and / or 1, 2, or 3 halogen; and / or two of RB6, RB7, RB8, RB9, RB10, RB11which are attached to the same carbon atom of said carbocycle or said heterocycle form a divalent oxo (=O) group; and / or two of RB6, RB7, RB8, RB9, RB10, RB11which are attached to the same sulfur (S) atom of said heterocycle form a divalent oxo (=O) group while at the same time two further of RB6, RB7, RB8, RB9, RB10, RB11which are attached to the same sulfur atom form either a divalent oxo group or a divalent =N-H or =N-C1-4-alkyl group, thereby forming an -S(=O)2, - S(=O)(=NH), or -S(=O)(=N-C1-4-alkyl) moiety; RC1, RC2, RC3denote independently from each other halogen; C1-4-alkyl or -OC1-4-alkyl, each of which may be unsubstituted or substituted with 1, 2, or 3 halogen; RC6, RC7, RC8, RC9, RC10, and / or RC11denote independently from each other halogen; C1-4-alkyl, which is unsubstituted or substituted with 1, 2, or 3 substituents independently from each other selected from halogen; -OC1- 4-alkyl, which is unsubstituted or substituted with 1, 2, or 3 halogen; halogen denotes F, Cl, Br, or I; or any N-oxide, solvate, tautomer or stereoisomer thereof and / or any pharmaceutically acceptable salt of each of the foregoing, including mixtures thereof in all ratios. In general, all residues, radicals, substituents, groups, moieties, etc. which occur more than once may be identical or different, i.e. are independent of one another. Above and below, the residues and parameters have the meanings indicated for formula I, unless expressly indicated otherwise. Accordingly, the invention relates, in particular, to the compounds of formula I in which at least one of the said residues, radicals, substituents has one of the preferred meanings indicated below. Any of those particular or even preferred embodiments of the present invention as specified below and in the claims do not only refer to the specified compounds of formula I but to N-oxides, solvates, tautomers or stereoisomers thereof as well as the pharmaceutically acceptable salts of each of the foregoing, including mixtures thereof in all ratios, too, unless indicated otherwise. In a particular embodiment, PE1, the compound of the present invention is a bicyclic compound of formula I, wherein Ring D together with R2denotes ; X1denotes CRX1or N; RX1denotes H; and and the remaining radicals and residues are as defined for formula I above or for any of the further particular embodiments described herein above or below. In other words, compounds of PE1 are compounds of formula I-A or I-B: In another particular embodiment, PE1a, of PE1, the compound of the present invention is a bicyclic compound of formula I, wherein X1denotes CH; and the and the remaining radicals and residues are as defined for formula I above or for any of the further particular embodiments described herein above or below. PE1a may also be described as a compound of formula I-A (see above). In still another particular embodiment, PE1b, of PE1, the compound of the present invention is a bicyclic compound of formula I, wherein X1denotes N; and the remaining radicals and residues are as defined for formula I above or for any of the further particular embodiments described herein above or below. PE1b may also be described as a compound of formula I-B (see above). In a further particular embodiment of the present invention, PE2, the compound of the present invention is a bicyclic compound of formula I, wherein Ring D together with R2denotes ; and and the remaining radicals and residues are as defined for formula I above or for any of the further particular embodiments described herein above or below. In other words, compounds of PE2 are compounds of formula I-C: In a further particular embodiment of the present invention, PE3, the compound of the present invention is a bicyclic compound of formula I, wherein R3denotes halogen; and the remaining radicals and residues are as defined for formula I above or for any of the further particular embodiments described herein above or below. It is a further particular embodiment, PE3a, of PE3 in which in formula I R3denotes I; and the remaining radicals and residues are as defined for formula I above or for any of the further particular embodiments described herein above or below. It is another particular embodiment, PE3b, of PE3 in which in formula I R3denotes F; and the remaining radicals and residues are as defined for formula I above or for any of the further particular embodiments described herein above or below. Compounds of PE3 and PE3a may in particular be useful as starting material for preparing modified compounds of formula I, in which R3is replaced by a different functional group, substituent or structural moiety wherein this replacement may be effected by C-C- of C-N- coupling reactions known in the art. In a further particular embodiment of the present invention, PE4, the compound of the present invention is a bicyclic compound of formula I, wherein R3denotes H; and the remaining radicals and residues are as defined for formula I above or for any of the further particular embodiments described herein above or below. In still another particular embodiment of the present invention, PE5, the compound of the present invention is a bicyclic compound of formula I, wherein R1denotes unsubstituted straight-chain or branched C1-6-alkyl, in which C1- 6-alkyl 1, 2, 3, 4, 5, 6, or 7 H-atoms may be replaced by deuterium (D-atoms); and the remaining radicals and residues are as defined for formula I above or for any of the further particular embodiments described herein above or below. It is a further particular embodiment, PE5a, of PE5 in which in formula I R1denotes CH3 or C2H5; and the remaining radicals and residues are as defined for formula I above or for any of the further particular embodiments described herein above or below. It is still a further particular embodiment, PE5aa, of PE5 or PE5a, in which R1denotes CH3; and the remaining radicals and residues are as defined for formula I above or for any of the further particular embodiments described herein above or below. It is a further particular embodiment, PE5b, of PE5 in which in formula I R1denotes CD3 or C2D5, in particular (PE5ba) C2D5; and the remaining radicals and residues are as defined for formula I above or for any of the further particular embodiments described herein above or below. In a further particular embodiment of the present invention, PE6, the compound of the present invention is a bicyclic compound of formula I wherein R2denotes H, Alk2, Hetar2, Hetcyc2, -L2-Ar2a; and the remaining radicals and residues are as defined for formula I above or for any of the further particular embodiments described herein above or below. It is a further particular embodiment, PE6a, of PE6 in which in formula I R2denotes H, Alk2, Hetar2, Hetcyc2, -L2-Ar2a; Alk2denotes denotes straight-chain or branched C1-6-alkyl or C2-6-alkinyl, each of which may be unsubstituted or substituted with independently from each other R2a1, R2a2and / or R2a3; L2denotes a divalent -S(=O)2- group; Ara, Ar2adenote independently from each other phenyl which may be unsubstituted or substituted with independently from each other RB1and / or RB2; Hetara, Hetar2, Hetar2adenote independently from each other a monocyclic heteroaryl with 5 or 6 ring atoms wherein 1, 2, or 3 of said ring atoms is / are a hetero atom(s) selected from N, O and / or S and the remaining are carbon atoms, wherein that heteroaryl is unsubstituted or substituted with independently from each other RB1and / or RB2; Cyc2adenotes a saturated monocyclic carbocycle with 3, 4, 5, 6, or 7 ring carbon atoms, wherein said carbocycle is unsubstituted or substituted with independently from each other RB6and / or RB7; Hetcyca, Hetcyc2, Hetcyc2adenote independently from each other a saturated or partially unsaturated monocylic heterocycle with 3, 4, 5, or 6 ring atoms wherein 1 or 2 of said ring atoms is / are a hetero atom(s) selected from N, O and / or S and the remaining are carbon atoms, wherein said heterocycle is unsubstituted or substituted with independently from each other RB6and / or RB7and / or RB8and RB9together; R2a1, R2a2, R2a3denote independently from each other halogen, -CN, -NH2, -NHRa, -NRaRb, -OH, -ORc, -P(=O)RdRe, -SRf, -S(=O)(=NRg)Rf, - N=S(=O)RfRh, -C(=O)NH2, -C(=O)NHRa, -C(=O)NRaRb, -C(=O)OH, - C(=O)ORc, -NH-C(=O)-Ri, , Cyc2a, Hetar2a, Hetcyc2a; Ra, Rbdenote independently from each other straight-chain or branched C1-6-alkyl, Ara, Hetara, Hetcyca; or Raand Rbform together with the nitrogen atom to which they are attached to a saturated or partially unsaturated heterocycle with 3, 4, 5, 6, 7 ring atoms wherein 1 of said ring atoms is said nitrogen atom and no or one further ring atom is a hetero atom selected from N, O or S and the remaining are carbon atoms, wherein said heterocycle is unsubstituted or substituted with independently from each other RB6and / or RB7and / or RB8and RB9together; Rcdenotes straight-chain or branched C1-4-alkyl which is unsubstituted or substituted with -OH; straight-chain and unsubstituted C2-4-alkinyl; C3-5- cycloalkyl; Rd, Redenote independently from each other straight-chain or branched C1-6-alkyl; Rf, Rhdenote independently from each other straight-chain or branched C1-6-alkyl; Rgdenotes H, straight-chain or branched C1-6-alkyl; Ridenotes H, straight-chain or branched C1-6-alkyl; RB1, RB2denote independently from each other halogen; C1-4-alkyl, which may be unsubstituted or substituted with 1, 2, or 3 halogen; OH; RB6, RB7denote independently from each other halogen; OH; -OC1-4-alkyl; C1-4-alkyl, which is unsubstituted or substituted with 1 OH or 1, 2, or 3 halogen; RB8and RB9which are attached to the same carbon atom of said heterocycle form a divalent oxo (=O) group; and / or two of RB6, RB7, RB8, RB9which are attached to the same sulfur (S) atom of said heterocycle form a divalent oxo (=O) group while at the same time two further of RB6, RB7, RB8, RB9which are attached to the same sulfur atom form either a divalent oxo group or a divalent =N-H or =N-C1- 4-alkyl group, thereby forming an -S(=O)2, -S(=O)(=NH), or -S(=O)(=N- C1-4-alkyl) moiety; and the remaining radicals and residues are as defined for formula I above or for any of the further particular embodiments described herein above or below. In still a further particular embodiment, PE6aa, of PE6 and PE6a, the compound of the present invention is a bicyclic compound of formula I, wherein R2denotes H, Alk2, Hetar2, Hetcyc2; Alk2denotes straight-chain or branched C1-4-alkyl which may be unsubstituted or substituted with independently from each other R2a1and / or R2a2; Hetar2, Hetar2adenote independently from each other a monocyclic heteroaryl with 5 or 6 ring atoms wherein 1, 2, or 3 of said ring atoms is / are a hetero atom(s) selected from N, O and / or S and the remaining are carbon atoms, wherein that heteroaryl is unsubstituted or mono- substituted with C1-4-alkyl which may be unsubstituted or substituted with 1, 2, or 3 halogen; Cyc2adenotes a saturated monocyclic carbocycle with 4 ring carbon atoms, wherein said carbocycle is unsubstituted or mono-substituted with -OH; Hetcyc2denotes a saturated monocylic heterocycle with 5 ring atoms wherein 1 of said ring atoms is a hetero atom selected from O or S the remaining are carbon atoms, wherein said heterocycle is unsubstituted or mono-substituted with OH; Hetcyc2adenotes a saturated monocylic heterocycle with 4, 5 or 6 ring atoms wherein 1 of said ring atoms is a hetero atom(s) selected from N or O and the remaining are carbon atoms, wherein said heterocycle is unsubstituted or mono-substituted with OH, -O-C1-4-alkyl or C1-4-alkyl, wherein said C1-4-alkyl may be unsubstituted or mono-substituted with - OH or -OC1-4-alkyl; R2a1, R2a2denote independently from each other F, -CN, -NH2, -NHRa, - NRaRb, -OH, -ORc, -P(=O)RdRe, -SRf, -S(=O)(=NRg)Rf, -C(=O)NH2, - C(=O)NHRa, C(=O)ORc, -NH-C(=O)-Ri, Cyc2a, Hetar2a, Hetcyc2a; Ra, Rbdenote independently from each other straight-chain or branched C1-6-alkyl; or Raand Rbform together with the nitrogen atom to which they are attached to a saturated or partially unsaturated heterocycle with 4, 5, 6, 7 ring atoms wherein 1 of said ring atoms is said nitrogen atom and no or one further ring atom is a hetero atom selected from N, O or S and the remaining are carbon atoms, wherein said heterocycle is unsubstituted or substituted with independently from each other RB6and / or RB7and / or RB8and RB9together; Rcdenotes straight-chain or branched C1-4-alkyl; Rd, Redenote independently from each other straight-chain or branched C1-6-alkyl; Rfdenotes straight-chain or branched C1-6-alkyl; Rgdenotes H, straight-chain or branched C1-6-alkyl; Ridenotes H, straight-chain or branched C1-6-alkyl; RB6, RB7denote independently from each other OH; RB8and RB9which are attached to the same carbon atom of said heterocycle form a divalent oxo (=O) group; It is another particular embodiment of the present invention, PE6aaa, which also be a particular embodiment of any one of the particular embodiments PE6, PE6a or PE6aa, in which the compound of the present invention is a bicyclic compound of formula I, wherein R2denotes H; -CH3, -CH2-CN, -(CH2)2-CN, -(CH2)2-OH, -(CH2)3-OH, CH2- CH(CH3)-CH2-OH, -CH2-CHF-CH2-OH, -CH2-CH(OH)-CH2-OH, - CH(CH2OH)2, -CH2-CH(OH)-CH2-OCH3, -(CH2)3-S-CH3, -(CH2)2- S(=O)(=NH)CH3, -CH2-P(=O)(CH3)2, -CH2-C(=O)-NH2, -CH2-C(=O)- NHCH3, -(CH2)2-C(=O)-NH2, -(CH2)2-C(=O)-NHCH3, -(CH2)2-NH-C(=O)- H, -(CH2)2-NH-C(=O)-CH3, 2-(3-hydroxypyrrolidin-1-yl)ethyl, 2-(2-oxo- pyrrolidin-1-yl)-ethyl], (2-morpholin-4-yl-ethyl); 1-methyl-1H-imidazol-4- yl, 1-methyl-1H-imidazol-5-yl, 1,2-thiazol-2-yl, 1,3-thiazol-2-yl, 1,3- thiazol-4-yl, pyrazin-2-yl; (1H‐imidazol‐4‐yl)methyl, (1-methyl-1H- imidazol‐4‐yl)methyl, (1-methyl-1H-imidazol‐5‐yl)methyl, (4-methyl-1H- imidazol-2‐yl)methyl, 2-(1H‐imidazol‐4‐yl)-ethyl, (1H‐pyrazol‐4‐yl)methyl, (1‐methyl‐1H‐pyrazol‐3‐yl)methyl, (1‐methyl‐1H‐pyrazol‐4‐yl)methyl, 2- (1‐methyl‐1H‐pyrazol‐4‐yl)-ethyl, 1-oxazol-2-ylmethyl, 1,3-thiazol-5- ylmethyl, 2-methyl-1,3-thiazol-4-ylmethyl, 2-methyl-1,3-thiazol-5- ylmethyl, 1H-1,2,3-triazol-4ylmethyl, 1H-1,2,4-triazol-3ylmethyl, pyrazin- 2-ylmethyl, 3-methylpyrazin-2-ylmethyl, pyridazin-3-ylmethyl, pyrimidin- 2-ylmethyl, pyrimidin-4-ylmethyl, 2-hydroxy-1-(pyrazin-2-yl)ethyl; 1- hydroxycyclobutylmethyl , , ; [3-(hydroxymethyl)oxetan-3-yl]methyl ( ), (3-hydroxyoxolan-3-yl)methyl ( ), (4- hydroxyoxan-4-yl)methyl ( );and the remaining radicals and residues are as defined for formula I above or for any of the further particular embodiments described herein above or below. It is another particular embodiment of the present invention, PE6aaaa, which also be a particular embodiment of any one of the particular embodiments PE6, PE6a, PE6aa or PE6aaa, in which the compound of the present invention is a bicyclic compound of formula I, wherein R2denotes H; -CH3, -CH2-CN, -(CH2)2-CN, -(CH2)2-OH, -(CH2)3-OH, - CH(CH2OH)2, -(CH2)2-S(=O)(=NH)CH3, -CH2-P(=O)(CH3)2, -CH2-C(=O)- NH2, -CH2-C(=O)-NHCH3, -(CH2)2-C(=O)-NH2, -(CH2)2-C(=O)-NHCH3, - (CH2)2-NH-C(=O)-H, -(CH2)2-NH-C(=O)-CH3, (1H‐imidazol‐4‐yl)methyl, (1-methyl-1H-imidazol‐4‐yl)methyl, (1-methyl-1H-imidazol‐5‐yl)methyl, (1‐methyl‐1H‐pyrazol‐4‐yl)methyl, 1,3-thiazol-5-ylmethyl, 2-methyl-1,3- thiazol-5-ylmethyl, pyrazin-2-ylmethyl, 3-methylpyrazin-2-ylmethyl, pyrimidin-4-ylmethyl, 2-hydroxy-1-(pyrazin-2-yl)ethyl; -CH-(pyrazin-2-yl)- C(=O)OCH3; , , ; and the remaining radicals and residues are as defined for formula I above or for any of the further particular embodiments described herein above or below. In a further particular embodiment of the present invention, PE7, the compound of the present invention is a bicyclic compound of formula I, wherein , , , , , , , , wherein denotes the point of attachment of the ring A to the bicyclic ring system of the compound of formula I , and denotes the point of attachment to the L1-B radical of the compound of formula I; and the remaining radicals and residues are as defined for formula I above or for any of the further particular embodiments described herein above or below. In another particular embodiment, P7a, of PE7 the compound of the present invention is a bicyclic compound of formula I, wherein , , , wherein denotes the point of attachment of the ring A to the bicyclic ring system of the compound of formula I , and denotes the point of attachment to the L1-B radical of the compound of formula I; and the remaining radicals and residues are as defined for formula I above or for any of the further particular embodiments described herein above or below. In still another particular embodiment, PE7aa, of PE7 or PE7a the compound of the present invention is a bicyclic compound of formula I, wherein , , wherein denotes the point of attachment of the ring A to the bicyclic ring system of the compound of formula I , and denotes the point of attachment to the L1-B radical of the compound of formula I; and the remaining radicals and residues are as defined for formula I above or for any of the further particular embodiments described herein above or below. In a further particular embodiment of the present invention, PE8, the compound of the present invention is a bicyclic compound of formula I, wherein B denotes Ar1, Hetar1, Cyc1; L1denotes -O-, -N(R4)-, -O-CH2-, -O-SO2-; R4denotes H or CH3; Ar1denotes phenyl, wherein that phenyl is mono-substituted with RC1; Hetar1denotes a mono-cyclic heteroaryl with 5 or 6 ring atoms wherein 1 or 2 of said ring atoms is / are a hetero atom(s) selected from N, O and / or S and the remaining are carbon atoms, wherein that heteroaryl is monosubstituted with RC1or di-substituted with RC1and RC2; Cyc1denotes a saturated, mono- or bi-cyclic carbocycle with 4, 5, 6, or 7 ring carbon atoms, wherein said carbocycle is mono-substituted with RC6or di-substituted with RC6and RC7; RC1denotes F, Cl, CH3, CHF2, or CF3; optionally CF3; RC2denotes CH3 or C2H5; RC6denotes F, Cl; CH3, CHF2, CF3, -OCH3, -OCHF2, -OCF3; optionally CF3; RC7denotes F; and the remaining radicals and residues are as defined for formula I above or for any of the further particular embodiments described herein above or below. In still another particular embodiment of the present invention, PE9, the compound of the present invention is a bicyclic compound of formula I, wherein L1denotes -O-, -NH- or -O-CH2-; and the remaining radicals and residues are as defined for formula I above or for any of the further particular embodiments described herein above or below. In even a further particular embodiment of the present invention, PE10, the compound of the present invention is a bicyclic compound of formula I, wherein , , , , , , ; , ; , , , , , , or ; and the remaining radicals and residues are as defined for formula I above or for any of the further particular embodiments described herein above or below. It is a further particular embodiment, PE10a, of PE10 in which in formula I , , ; , and the remaining radicals and residues are as defined for formula I above or for any of the further particular embodiments described herein above or below. In a further particular embodiment of the present invention, PE11, the compound of the present invention is a bicyclic compound of formula I wherein L1denotes -O-; , ; , ; and the remaining radicals and residues are as defined for formula I above or for any of the further particular embodiments described herein above or below. It is a further particular embodiment, PE11a, of PE11 in which in formula I L1denotes -O-; ; , and the remaining radicals and residues are as defined for formula I above or for any of the further particular embodiments described herein above or below. It is a further particular embodiment, PE11aa, of PE11 or PE11a in which in formula I , , ; , and the remaining radicals and residues are as defined for formula I above or for any of the further particular embodiments described herein above or below. It is still another particular embodiment, PE11aaa, of PE11, PE11a or PE11aa in which , , ; , and the remaining radicals and residues are as defined for formula I above or for any of the further particular embodiments described herein above or below. In a further particular embodiment of the present invention, PE12, the compound of the present invention is a bicyclic compound of formula I wherein A denotes ; L1denotes -NH-; B denotes ; and the remaining radicals and residues are as defined for formula I above or for any of the further particular embodiments described herein above or below. In a further particular embodiment of the present invention, PE13, the compound of the present invention is a bicyclic compound of formula I wherein L1denotes -O-CH2-; , ; ; and the remaining radicals and residues are as defined for formula I above or for any of the further particular embodiments described herein above or below. It is a further particular embodiment, PE13a, of PE13 in which in formula I , , , , ; ; and the remaining radicals and residues are as defined for formula I above or for any of the further particular embodiments described herein above or below. It is still another particular embodiment, PE13aa, of PE13 or PE13a in which in formula I , , ; ; and the remaining radicals and residues are as defined for formula I above or for any of the further particular embodiments described herein above or below. In another particular embodiment of the present invention, PE14, the compound of the present invention is a bicyclic compound of formula I wherein,, , , ,

[0039] , , ; ; ; ; ; ; and the remaining radicals and residues are as defined for formula I above or for any of the further particular embodiments described herein above or below. It is a further particular embodiment, PE14a, of PE14 in which in formula I , , , , , , , , ; , , , , ; and the remaining radicals and residues are as defined for formula I above or for any of the further particular embodiments described herein above or below. It is still a further particular embodiment, PE14aa, of PE14 in which in formula I , , , ; and the remaining radicals and residues are as defined for formula I above or for any of the further particular embodiments described herein above or below. In a particular embodiment of the present invention, PE15, the compound of the present invention is a bicyclic compound of formula I wherein Ring D together wit R2denotes ; X1denotes CH or N; R1denotes CH3; R2denotes H; -CH3, -CH2-CN, -(CH2)2-CN, -(CH2)2-OH, -(CH2)3-OH, - CH(CH2OH)2, -(CH2)2-S(=O)(=NH)CH3, -CH2-P(=O)(CH3)2, -CH2-C(=O)- NH2, -CH2-C(=O)-NHCH3, -(CH2)2-C(=O)-NH2, -(CH2)2-C(=O)-NHCH3, - (CH2)2-NH-C(=O)-H, -(CH2)2-NH-C(=O)-CH3, (1H‐imidazol‐4‐yl)methyl, (1-methyl-1H-imidazol‐4‐yl)methyl, (1-methyl-1H-imidazol‐5‐yl)methyl, (1‐methyl‐1H‐pyrazol‐4‐yl)methyl, 1,3-thiazol-5-ylmethyl, 2-methyl-1,3- thiazol-5-ylmethyl, pyrazin-2-ylmethyl, 2-methylpyrazin-3-ylmethyl, pyrimidin-4-ylmethyl, 2-hydroxy-1-(pyrazin-2-yl)ethyl; -CH-(pyrazin-2-yl)- , , , , , , , , , , , , ; or any N-oxide, solvate, tautomer or stereoisomer thereof and / or any pharmaceutically acceptable salt of each of the foregoing, including mixtures thereof in all ratios. It is a further particular embodiment, PE15a, of PE15 in which in formula I

[0040] Ring D together wit R2denotes ; X1denotes CH or N; R1denotes CH3; R2denotes -(CH2)2-OH, 1H-imidazol-4-ylmethyl, 1-methyl-1H-pyrazol-4- ylmethyl; R3denotes H; , , , ; or any N-oxide, solvate, tautomer or stereoisomer thereof and / or any pharmaceutically acceptable salt of each of the foregoing, including mixtures thereof in all ratios. In still another particular embodiment, PE16, the compound of the present invention is a bicyclic compound selected from the compounds shown in Table 1 and Table 1a below, or any N-oxide, solvate, tautomer or stereoisomer thereof and / or any pharmaceutically acceptable salt of each of the foregoing, including mixtures thereof in all ratios. In yet another particular embodiment, PE16a, of PE16, the compound is selected from Table 1 and Table 1a and is a compound of formula I as described hereinabove and in the claims. It is understood that each single compound depicted in Table 1 and Table 1a as well as any N-oxide, solvate, tautomer or stereoisomer thereof and / or any pharmaceutically acceptable salt of such compound represents a particular embodiment of the present invention. In yet a further particular embodiment, PE16aa, of PE16 or PE16a, the compound is selected from Table 1 and Table 1a, is a compound of formula I as described hereinabove and in the claims, and is within Group A in the SK-HEP-1 reporter assay and / or within Group A in the H226 viability assay and / or within Group A in the H292 viability assay as provided in Table 2 below. As used herein, the following definitions shall apply unless otherwise indicated or defined specifically elsewhere in the description and / or the claims for specific substituents, radicals, residues, groups or moieties. The term “aliphatic” or “aliphatic group”, as used herein, means a straight- chain (i.e., unbranched) or branched, substituted or unsubstituted hydrocarbon chain (also referred to as “acyclic”) that is completely saturated or that contains one or more units of unsaturation; or a monocyclic hydrocarbon or bicyclic hydrocarbon or tricyclic hydrocarbon that is completely saturated or that contains one or more units of unsaturation, such as one or more C=C double bond(s) and / or C≡C triple bond(s), but which is not aromatic (also referred to herein as “carbocycle”, “cycloaliphatic” or “cycloalkyl”), that has – in general and if not defined otherwise in this specification or the accompanied claims – a single point of attachment to the rest of the molecule. Unless otherwise specified, aliphatic groups contain 1 to 10 (i.e., 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10) 1 to 8 (i.e., 1, 2, 3, 4, 5, 6, 7, or 8) or 1 to 6 (i.e., 1, 2, 3, 4, 5, or 6) aliphatic carbon atoms (“C1-10-aliphatic”, “C1-8-aliphatic” and “C1-6-aliphatic”, respectively). In some embodiments, aliphatic groups contain 1-5 (i.e., 1, 2, 3, 4, or 5) aliphatic carbon atoms (“C1-5-aliphatic”). In other embodiments, aliphatic groups contain 1-4 (i.e., 1, 2, 3, or 4) aliphatic carbon atoms (“C1-4-aliphatic”). In still other embodiments, aliphatic groups contain 1-3 (i.e., 1, 2, or 3) aliphatic carbon atoms (“C1-3-aliphatic”), and in yet other embodiments, aliphatic groups contain 1-2 aliphatic carbon atoms (“C1-2-aliphatic”). In some embodiments, “cycloaliphatic” (“cycloalkyl”) refers to a monocyclic C3- C7 hydrocarbon (i.e., a monocyclic hydrocarbon with 3, 4, 5, 6, or 7 ring carbon atoms) or to a bicyclic C5-8 hydrocarbon (i.e. a bicyclic hydrocarbon with 5, 6, 7, or 8 ring carbon atoms) that is completely saturated or that contains one or more units of unsaturation, but which is not aromatic, that has a single point of attachment to the rest of the molecule. In another embodiment the term “cycloaliphatic” or “carbocycle” refers to a monocyclic or bicyclic cycloaliphatic ring system which is fused to an aromatic, heteroaromatic or heterocyclic ring or ring system via 2 adjacent ring atoms of that aromatic, heteroaromatic or heterocyclic ring or ring system; in other words, such carbocycle shares two ring atoms with the ring or ring system to which it is fused thereby having two points of attachment to the rest of the molecule. In another embodiment the term “carbocycle” refers to bicyclic spiro-cycles in which two monocyclic carbocycles are fused to each other via the same single carbon atom. In general, the term “aliphatic” encompasses, to the extent chemically possible, straight-chain, i.e. unbranched, as well as branched hydrocarbon chains, if not defined differently in a particular instance. Also, in general this term encompasses, to the extent chemically possible, unsubstituted and substituted hydrocarbon moieties, if not defined differently in a particular instance. Typical substituents of an aliphatic group include, but are not limited to halogen, in particular F, cyano, hydroxy, alkoxy, unsubstituted or mono- or di-substituted amino, aryl, in particular unsubstituted or substituted phenyl, heteroaryl, in particular unsubstituted or substituted pyridyl or pyrimidinyl, heterocyclyl, in particular unsubstituted or substituted pyrrolidinyl, piperidinyl, piperazinyl or morpholinyl. Suitable aliphatic groups include, but are not limited to, linear or branched, substituted or unsubstituted alkyl, alkenyl, alkynyl (alkinyl), cycloalkyl, cycloalkenyl groups and hybrids thereof as (cycloalkyl)alkyl, (cycloalkenyl)alkyl or (cycloalkyl)alkenyl. The term "alkyl" usually refers to a saturated aliphatic and acyclic moiety, while the term “alkenyl” usually refers to an unsaturated aliphatic and acyclic moiety with one or more C=C double bonds and the term “alkynyl” (or “alkinyl”) usually refers to an aliphatic and acyclic moiety with one or more C≡C triple bonds. It is understood that the term “alkenyl” comprises all forms of isomers, i.e. E- isomers, Z-isomers as well as mixtures thereof (E / Z-isomers). Exemplary aliphatic groups are linear or branched, substituted or unsubstituted C1-10-alkyl, C1-8-alkyl, C1-6-alkyl, C1-4-alkyl, C1-3-alkyl, C1-2-alkyl, C2-8-alkenyl, C2-6-alkenyl, C2-4-alkenyl, C2-8-alkynyl (C2-8-alkinyl), C2-6-alkynyl (C2-6-alkinyl), C2-4-alkynyl (C2-4-alkinyl) groups and hybrids thereof such as (cycloalkyl)alkyl, (cycloalkenyl)alkyl or (cycloalkyl)alkenyl. In particular, the term “C1-3-alkyl” refers to alkyl groups, i.e. saturated acyclic aliphatic groups, having 1, 2 or 3 carbon atoms. Exemplary C1-3-alkyl groups are methyl, ethyl, propyl and isopropyl. The term “C1-4-alkyl” refers to alkyl groups having 1, 2, 3 or 4 carbon atoms. Exemplary C1-4-alkyl groups are methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and tert-butyl. The term “C1-6- alkyl” refers to alkyl groups having 1, 2, 3, 4, 5 or 6 carbon atoms. Exemplary C1-6-alkyl groups are methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, n-pentyl, 2-pentyl, n-hexyl, and 2-hexyl. The term “C1-8-alkyl” refers to alkyl groups having 1, 2, 3, 4, 5, 6, 7, or 8 carbon atoms. Exemplary C1-8-alkyl groups are methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, n-pentyl, 2-pentyl, n-hexyl, 2-hexyl n-heptyl, 2-heptyl, n-octyl, 2-octyl, and 2,2,4- trimethylpentyl. The term “C1-10-alkyl” refers to alkyl groups having 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 carbon atoms. Exemplary C1-10-alkyl groups are methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, n-pentyl, 2-pentyl, n-hexyl, 2- hexyl n-heptyl, 2-heptyl, n-octyl, 2-octyl, 2,2,4-trimethylpentyl, and n-decyl. Each of these alkyl groups may be straight-chain or – except for C1-alkyl and C2-alkyl – branched and may be unsubstituted or substituted with 1, 2 or 3 substituents that may be the same or different and may be, if not specified differently elsewhere in this specification and / or the accompanying claims, selected from the group comprising halogen, in particular F, cyano, hydroxy, alkoxy, thiol, thioalkoxy, dialkylphosphoryl, in particular, -P(=O)(CH3)2, unsubstituted or mono- or di-substituted amino, sulfoxide, sulfone, iminoalkylsulfone, in particular -S(=O)(=NH)CH3, iminodialkylsulfone, in particular -N=S(=O)(CH3)2, carboxylic acid, carboxylic acid ester, carboxylic acid amide (primary, secondary, tertiary), carbamate, aryl, in particular unsubstituted or substituted phenyl, heteroaryl, in particular unsubstituted or substituted pyridyl or pyrimidinyl, saturated or partially unsaturated heterocyclyl, in particular unsubstituted or substituted pyrrolidinyl, piperidinyl, piperazinyl or morpholinyl. Exemplary substituted alkyl groups are difluoromethyl, trifluoromethyl, 2,2,2-trifluoroethyl, hydroxymethyl, 2- hydroxyethyl, difluoromethoxy, trifluoromethoxy. In some instances the C1-3-alkyl, C1-4-alkyl, C1-6-alkyl, C1-8-alkyl, C1-10-alkyl groups – both unbranched and branched – may also comprise those residues in which 1 or 2 of non-terminal and non-adjacent –CH2- (methylene) groups are replaced by –O-, -S- and / or 1 or 2 non-terminal and non-adjacent –CH2- or –CH- groups are replaced by –NH- or –N-. These replacements yield, for instance, (modified) alkyl groups like –CH2-CH2-O-CH3, –CH2-CH2-CH2-S- CH3, CH2-CH2-NH-CH2-CH3, CH2-CH2-O-CH2-CH2-O-CH3, CH2-CH2-O-CH2- CH2-O-CH2-CH3, CH2-CH2-N(CH3)-CH2-CH3, and the like. Further and / or different replacements of –CH– and –CH2– groups may be defined for specific alkyl substituents or radicals elsewhere in the description and / or the claims. As described for “unmodified” alkyl groups hereinabove these “modified” alkyl groups may optionally be substituted with 1, 2 or 3 substituents that may be the same or different and may be, if not specified differently elsewhere in this specification and / or the accompanying claims, selected from the group comprising halogen, in particular F, hydroxy, alkoxy, unsubstituted or mono- or di-substituted amino, aryl, in particular unsubstituted or substituted phenyl, heteroaryl, in particular unsubstituted or substituted pyridyl or pyrimidinyl, heterocyclyl, in particular unsubstituted or substituted pyrrolidinyl, piperidinyl, piperazinyl or morpholinyl. Examplary modified alkyl groups are CH2-CH2-O- CH2-CH2-O-CH2-CH2-NH2, CH2-CH2-O-CH2-CH2-O-CH2-CH2-NH-C(=O)-CH3, CH2-CH2-O-CH2-CH2-O-CH2-CH2-NH-C(=O)-OC(CH3)3 CH2-CH2-CH2-CH2- CH2-O-CH2-CH2-NH2, CH2-CH2-CH2-CH2-CH2-O-CH2-CH2-NH-C(=O)-CH3, CH2-CH(OH)-CH2-CH2-O-CH2-CH2-O-CH2-CH2-NH2, CHR-CH(OH)-CH2-CH2- O-CH2-CH2-O-CH2-CH2-NH2 wherein “R” denotes another substituent. The term “carbocycle” refers in general, if not defined differently elsewhere, to a saturated or partially unsaturated but not aromatic ring system with 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 ring carbon atoms and non ring hetero atoms; that carbocycle may be monocyclic (C3-15) or bicyclic (C5-15) or tricyclic (C8-15). It will be understood that a bicyclic carbocycle may be (a) a carbocycle in which the two carbocyclic moieties are attached to each other via two different ring carbon atoms, like in bicyclo[1.1.1]pentanyl or bicyclo[3.1.0]hexanyl; or (b) a carbocycle in which the two carbocyclic moieties are attached to each other via the same ring carbon atom, thereby forming a sprio ring, like in spiro[3.3]heptanyl. The same applies, mutatis mutandis, to tricyclic carbocycles. Carbocycles may be unsubstituted or substituted. The term “cycloalkyl” refers to a cycloaliphatic hydrocarbon, or carbocycle, as defined above. The term “C3-7-cycloalkyl” refers to a cycloaliphatic hydrocarbon, or carbocycle, as defined above, with 3, 4, 5, 6 or 7 ring carbon atoms. Likewise, the term “C3-6-cycloalkyl” refers to a cycloaliphatic hydrocarbon, or carbocycle, with 3, 4, 5, or 6 ring carbon atoms. The terms “cycloalkyl”, “C3-7-cycloalkyl” and “C3-6-cycloalkyl” as used herein comprise cyclic hydrocarbons, or carbocycles, which are saturated or contain one or more units of unsaturation, such as a C=C double bond; such cyclic hydrocarbons having at least one unit of unsaturation may also referred to as “cycloalkenyl” group. C3-7-cycloalkyl groups may be unsubstituted or substituted with – unless specified differently elsewhere in this specification – 1, 2 or 3 substituents that may be the same of different and are – unless specified differently elsewhere in this specification – selected from the group comprising C1-6-alkyl, O-C1-6-alkyl (alkoxy), halogen, hydroxy, unsubstituted or mono- or di-substituted amino, aryl, in particular unsubstituted or substituted phenyl. If substituted, C3-7-cycloalkyl comprises all possible stereoisomers. Exemplary C3-7-cycloalkyl groups are cyclopropyl, 2-methyl-cyclopropyl, cyclopropenyl, cyclobutyl, cyclobutenyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cycloheptenyl. The term “bicyclic C5-8- cycloalkyl” refers to a bicyclic cycloaliphatic hydrocarbon, as defined above, with 5, 6, 7, or 8 ring carbon atoms; it includes spirocyclic ring systems, i.e. ring systems in which the two carbocycles of the bicyclic C5-8-cycloalkyl are attached to each other via the same carbon atom. Bicylic C5-8-cycloalkyl groups may be unsubstituted or substituted with – unless specified differently elsewhere in this specification – 1, 2 or 3 substituents that may be the same of different and are – unless specified differently elsewhere in this specification – selected from the group comprising C1-6-alkyl, which may be substituted with 1, 2, or 3 halogen, O-C1-6-alkyl (alkoxy), , which may be substituted with 1, 2, or 3 halogen, hydroxy, halogen, unsubstituted or mono- or di-substituted amino. If substituted, bicyclic C5-8-cycloalkyl comprises all possible stereoisomers. Exemplary bicyclic C5-8-cycloalkyls are spiro[3.3]heptanyl, bicyclo[1.1.1]pentanyl, bicyclo[3.1.0]hexanyl, bicyclo[2.2.1]heptan‐2‐yl, bicyclo[2.2.2]octan‐2‐yl, bicyclo[2.2.1]hept‐5‐en‐2‐ylmethyl, bi- cyclo[3.1.1]hept‐2‐en‐2‐yl. The term “aliphatoxy” refers to saturated or unsaturated aliphatic groups or substituents as defined above that are connected to another structural moiety via an oxygen atom (-O-). The term “C1-6-aliphatoxy” refers to an aliphatoxy radical with 1, 2, 3, 4, 5, or 6 carbon atoms within the aliphatic group. The term “alkoxy” refers to a particular subgroup of saturated aliphatoxy, i.e. to alkyl substituents and residues that are connected to another structural moiety via an oxygen atom (-O-). Sometimes, it is also referred to as “O-alkyl” and more specifically as “O-C1-2-alkyl”, “O-C1-3-alkyl”, “O-C1-4-alkyl”, “O-C1-6-alkyl”, “O-C1- 8-alkyl”. Like the similar alkyl groups, it may be straight-chain or – except for – O-C1-alkyl and –O-C2-alkyl – branched and may be unsubstituted or substituted with 1, 2 or 3 substituents that may be the same or different and are, if not specified differently elsewhere in this specification, selected from the group comprising halogen, unsubstituted or mono- or di-substituted amino. Exemplary alkoxy groups are methoxy, fluoromethoxy, difluoromethoxy, trifluoromethoxy, ethoxy, 2,2,2-trifluoroethoxy, n-propoxy, iso-propoxy, n- butoxy, sec-butoxy, tert-butoxy, n-pentoxy. The term “alkylene” refers to a divalent aliphatic group and in particular a divalent alkyl group. An “alkylene chain” is a polymethylene group, i.e., – (CH2)j–, wherein j is a positive integer, preferably 1, 2, 3, 4, 5 or 6. In the context of the present invention“"C1-3-alkylene”" refers to an alkylene moiety with 1, 2 and 3, respectively, -CH2- groups; the term“"alkylene”", however, not only comprises linear alkylene groups, i.e.“"alkylene chains", but branched alkylene groups as well. The term "C1-6-alkylene" refers to an alkylene moiety that is either linear, i.e. an alkylene chain, or branched and has 1, 2, 3, 4, 5 or 6 carbon atoms. The term "C2-6-alkylene" refers to an alkylene moiety with 2, 3, 4, 5, or 6 carbon atoms, while a "C3-4-alkylene" refers to an alkylene moiety with 3 or 4 carbon atoms and"C2-3-alkylene" refers to an alkylene moiety with 2 or 3 carbon atoms. A substituted alkylene is a group in which one or more methylene hydrogen atoms are replaced by (or with) a substituent. Suitable substituents include those described herein for a substituted alkyl group. In some instances 1 or 2 methylene groups of the alkylene chain may be replaced by, for instance, O, S and / or NH or N-C1-4-alkyl. Exemplary alkylene groups are –CH2-, –CH2–CH2-, –CH2–CH2–CH2–CH2-, –O–CH2–CH2-, –O–CH2–CH2– CH2-, –CH2–O–CH2–CH2-, -O–CH2-O-, -O–CH2–CH2-O-, -O–CH2–CH2–CH2- O-, –CH2-NH–CH2–CH2-, –CH2-N(CH3)–CH2–CH2-. The term “alkenylene” refers to a divalent alkenyl group. A substituted alkenylene chain is a polymethylene group containing at least one double bond in which one or more hydrogen atoms are replaced with a substituent. Suitable substituents include those described herein for a substituted aliphatic group. The term “alkenylene” not only refers to straight-chain divalent alkenylene radicals, i.e. an alkenylene chain, but to branched alkenylene groups as well. The term “C2-6-alkenylene” refers to an alkenylene radical having 2, 3, 4, 5, or 6 carbon atoms. The term “halogen” means F, Cl, Br, or I. In particular, “halogen” refers to F. The term “heteroatom” means one or more of oxygen (O), sulfur (S), or nitrogen (N), including any oxidized form of nitrogen or sulfur, e.g. N-oxides, sulfoxides and sulfones; the quaternized form of any basic nitrogen or a substitutable nitrogen of a heterocyclic or heteroaromatic ring, for example N (as in 3,4-dihydro-2H-pyrrolyl), NH (as in pyrrolidinyl) or N-SUB with SUB being a suitable substituent (as in N-substituted pyrrolidinyl). The term “aryl” used alone or as part of a larger moiety as in “aralkyl”, “aralkoxy”, or “aryloxyalkyl”, refers to monocyclic, bicyclic and tricyclic ring systems having a total of five to fourteen ring members, that ring members being carbon atoms, wherein at least one ring in the system is aromatic, i.e., it has (4n+2) π (pi) electrons (with n being an integer selected from 0, 1, 2, 3, 4, 5), which electrons are delocalized over the system, and wherein each ring in the system contains three to seven ring members. Preferably, all rings in the aryl system or the entire ring system are aromatic. The term “aryl” is used interchangeably with the term “aryl ring”. In certain embodiments of the present invention, “aryl” refers to an “aromatic ring system”. More specifically, those aromatic ring systems may be mono-, bi- or tricyclic with 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 ring carbon atoms. Even more specifically, those aromatic ring systems may be mono- or bicyclic with 6, 7, 8, 9, 10 ring carbon atoms. Exemplary aryl groups are phenyl, biphenyl, naphthyl, anthracyl and the like, which may be unsubstituted or substituted with one or more identical or different substituents. Also included within the scope of the terms “aryl” or “aromatic ring system”, as they are used herein, is a group in which an aromatic ring is fused to one or more non–aromatic rings, such as indanyl, phthalimidyl, naphthimidyl, phenanthridinyl, or tetrahydronaphthyl, and the like. In the latter case the "aryl" group or substituent is attached to its pendant group via the aromatic part of the ring system. The term “benzo” refers to a six-membered aromatic ring (with carbon ring atoms) that is fused via two adjacent carbon atoms to another ring, being it a cycloaliphatic, aromatic, heteroaromatic or heterocyclic (heteroaliphatic) ring; as a result a ring system with at least two rings is formed in which the benzo ring shares two common carbon atoms with the other ring to which it is fused. For example, if a benzo ring is fused to a phenyl ring, a napthaline ring system is formed, while fusing a benzo ring to a pyridine provides for either a quinoline or an isoquinoline; fusing a benzo ring to a cyclopentene ring provides an indene ring. The terms “heteroaryl” and “heteroar–”, used alone or as part of a larger moiety, e.g., “heteroaralkyl”, or “heteroaralkoxy”, refer to groups having 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 ring atoms (which atoms are carbon and hetero atoms), preferably 5, 6, 9 or 10 ring atoms; having 6, 10, or 14 π (pi) electrons shared in a cyclic array; and having, in addition to carbon atoms, 1, 2, 3, 4 or 5 heteroatoms. The term “heteroatom” refers to nitrogen, oxygen, or sulfur, and includes any oxidized form of nitrogen or sulfur, and any quaternized form of a basic nitrogen. In other words, a “heteroaryl” ring or ring system (or a heteroaromatic ring or ring system) may also be described as an aromatic heterocycle. Heteroaryl groups include, without limitation, thienyl, furanyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, isothiazolyl, thiadiazolyl, furazanyl, pyridyl (pyridinyl), pyridazinyl, pyrimidinyl, pyrazinyl, indolizinyl, purinyl, naphthyridinyl, pteridinyl, and pyrrolopyridinyl, in particular pyrrolo[2,3-b]pyridinyl. The terms “heteroaryl” and “heteroar–”, as used herein, also include groups in which a heteroaromatic ring is fused to one or more aryl, cycloaliphatic, or heterocyclyl rings, where the radical or point of attachment is preferably on the heteroaromatic or, if present, the aryl ring. Nonlimiting examples include indolyl, isoindolyl, benzothienyl (benzothiophenyl), benzofuranyl, dibenzofuranyl, indazolyl, benzimidazolyl, benzothiazolyl, quinolyl, isoquinolyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, 4H–quinolizinyl, carbazolyl, acridinyl, phenazinyl, phenothiazinyl, phenoxazinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, 9H-carbazolyl, dibenzofuranyl and pyrido[2,3–b]–1,4–oxazin–3(4H)–one. For example, an indolyl ring may be attached via one of the ring atoms of the six- membered aryl ring or via one of the ring atoms of the five-membered heteroaryl ring. A heteroaryl group is optionally mono-, bi- or tricyclic. The term “heteroaryl” is used interchangeably with the terms “heteroaryl ring”, “heteroaryl group”, or “heteroaromatic”, any of which terms include rings that are unsubstituted or substituted with one or more identical or different substituents. The term “heteroaralkyl” refers to an alkyl group substituted by a heteroaryl, wherein the alkyl and heteroaryl portions independently are optionally substituted. A heteroaryl ring can be attached to its pendant group at any of its hetero or carbon ring atoms which attachment results in a stable structure or molecule: any of the ring atoms may be unsubstituted or substituted. As used herein, the terms “heterocycle”, “heterocyclyl”, “heterocyclic radical”, and “heterocyclic ring” are used interchangeably and refer to a stable mono- bi- or tricyclic heterocyclic moiety with 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 ring atoms wherein 1, 2, 3, 4, 5 of said ring atoms are hetero atoms and wherein that heterocyclic moiety is either saturated or partially unsaturated; heterocyclic moieties that are aromatic rings or ring systems are usually referred to as “heteroaryl” moieties as described hereinabove. Preferably, the heterocycle is a stable saturated or partially unsaturated 3-, 4-, 5-, 6-, or 7-membered monocyclic or 6-, 7-, 8-, 9-, 10-, or 11-membered bicyclic or 11-, 12-, 13-, or 14-membered tricyclic heterocyclic moiety. When used in reference to a ring atom of a heterocycle, the term “nitrogen” includes a substituted nitrogen. As an example, in a saturated or partially unsaturated ring having 1–3 heteroatoms selected from oxygen, sulfur or nitrogen, the nitrogen is N (as in 3,4–dihydro–2H–pyrrolyl), NH (as in pyrrolidinyl), or N-SUB with SUB being a suitable substituent (as in N– substituted pyrrolidinyl). In the context of the term "heterocycle" the term "saturated" refers to a completely saturated heterocyclic system, like pyrrolidinyl, piperidinyl, morpholinyl, piperidinonyl, tetrahydrofuranyl, thianyl, and dioxothianyl. With regard to the term "heterocycle" the term "partially unsaturated" refers to heterocyclic systems (i) that contain one or more units of unsaturation, e.g. a C=C or a C=Heteroatom bond, but that are not aromatic, for instance, tetrahydropyridinyl; or (ii) in which a (saturated or unsaturated but non- aromatic) heterocyclic ring is fused with an aromatic or heteroaromatic ring system, wherein, however, the "partially unsaturated heterocycle" is attached to the rest of the molecule (its pendant group) via one of the ring atoms of the "heterocyclic" part of the system and not via the aromatic or heteroaromatic part. This first class (i) of "partially unsaturated" heterocycles may also be referred to as "non-aromatic partially unsaturated" heterocycles. This second class (ii) of "partially unsaturated" heterocycles may also be referred to as (bicyclic or tricyclic) "partially aromatic" heterocycles indicating that at least one of the rings of that heterocycle is a saturated or unsaturated but non- aromatic heterocycle that is fused with at least one aromatic or heteroaromatic ring system. Typical examples of these "partially aromatic" heterocycles are 1,2,3,4-tetrahydroquinolinyl and 1,2,3,4-tetrahydroisoquinolinyl. A heterocyclic ring can be attached to its pendant group at any heteroatom or carbon atom that results in a stable structure and any of the ring atoms may be unsubstituted or substituted. Examples of such saturated or partially unsaturated heterocyclic radicals include, without limitation, tetrahydrofuranyl, tetrahydropyranyl, thianyl, dioxothianyl, tetrahydrothiophenyl, pyrrolidinyl, piperidinyl, pyrrolinyl, morpholinyl, tetrahydroquinolinyl, tetrahydro- isoquinolinyl, decahydroquinolinyl, oxazolidinyl, piperazinyl, dioxanyl, dioxolanyl, diazepinyl, oxazepinyl, thiazepinyl, morpholinyl, and quinuclidinyl. The terms “heterocycle”, “heterocyclyl”, “heterocyclyl ring”, “heterocyclic group”, “heterocyclic moiety”, and “heterocyclic radical”, are used interchangeably herein, and also include groups in which a heterocyclyl ring is fused to one or more aryl, heteroaryl, or cycloaliphatic rings, such as indolinyl, 3H–indolyl, chromanyl, phenanthridinyl, or tetrahydroquinolinyl, where the radical or point of attachment is on the heterocyclyl ring. A heterocyclyl group is optionally mono–, bi- or tricyclic. The term “heterocyclylalkyl” refers to an alkyl group substituted by a heterocyclyl, wherein the alkyl and heterocyclyl portions independently are unsubstituted or substituted. The term “unsaturated”, as used herein, means that a moiety or group or substituent has one or more units of unsaturation. As used herein with reference to any rings, ring systems, ring moieties, and the like, the term “partially unsaturated” refers to a ring moiety that includes at least one double or triple bond. The term “partially unsaturated” is intended to encompass rings having multiple sites of unsaturation. In particular, it encompasses (i) non-saturated (mono-, bi- or tricyclic) ring systems without any aromatic or heteroaromatic moiety or part; and (ii) bi- or tricyclic ring systems in which one of the rings of that system is an aromatic or heteroaromatic ring which is fused with another ring that is neither an aromatic nor a heteroaromatic ring, e.g. tetrahydronaphthyl or tetrahydroquinolinyl. The first class (i) of "partially unsaturated" rings, ring systems, ring moieties may also be referred to as "non-aromatic partially unsaturated" rings, ring systems, ring moieties, while the second class (ii) may be referred to as "partially aromatic" rings, ring systems, ring moieties. As used herein, the term “bicyclic”, “bicyclic ring” or “bicyclic ring system” refers to any bicyclic ring system, i.e. carbocyclic or heterocyclic, saturated or having one or more units of unsaturation, i.e. being partially unsaturated or aromatic, having one or more atoms in common between the two rings of the ring system. Thus, the term includes any permissible ring fusion, such as ortho- fused or spirocyclic. As used herein, the term “heterobicyclic” is a subset of “bicyclic” that requires that one or more heteroatoms are present in one or both rings of the bicycle. Such heteroatoms may be present at ring junctions and are optionally substituted, and may be selected from nitrogen (including N- oxides), oxygen, sulfur (including oxidized forms such as sulfones and sulfonates), phosphorus (including oxidized forms such as phosphates), boron, etc. In some embodiments, a bicyclic group has 7-12 ring members and 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. Likewise, the term “tricyclic”, “tricyclic ring” or “tricyclic ring system” refers to any tricyclic ring system, i.e. carbocyclic or heterocyclic, saturated or having one or more units of unsaturation, i.e. being partially unsaturated or aromatic, in which a bicyclic ring system (as defined above) is fused with another, third ring. Thus, the term includes any permissible ring fusion. As used herein, the term “heterotricyclic” is a subset of “tricyclic” that requires that one or more heteroatoms are present in one or both rings of the tricycle. Such heteroatoms may be present at ring junctions and are optionally substituted, and may be selected from nitrogen (including N-oxides), oxygen, sulfur (including oxidized forms such as sulfones and sulfonates), phosphorus (including oxidized forms such as phosphates), boron, etc. In some embodiments, a tricyclic group has 10-14 ring members and 0-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur. As described herein, certain compounds of the invention contain “substituted” or “optionally substituted” moieties. In general, the term “substituted”, whether preceded by the term “optionally” or not, means that one or more hydrogens of the designated moiety are replaced with a suitable substituent. “Substituted” applies to one or more hydrogens that are either explicit or implicit from the structure. Unless otherwise indicated, a “substituted” or “optionally substituted” group has a suitable substituent at each substitutable position of the group, and when more than one position in any given structure is substituted with more than one substituent selected from a specified group, the substituent is either the same or different at every position. If a certain group, substituent, moiety or radical is "mono-substituted", it bears one (1) substituent. If it is "di- substituted", it bears two (2) substituents, being either the same or different; if it is "tri-substituted", it bears three (3) substituents, wherein all three are the same or two are the same and the third is different or all three are different from each other. Combinations of substituents envisioned by this invention are preferably those that result in the formation of stable or chemically feasible compounds. The term “stable”, as used herein, refers to compounds that are not substantially altered when subjected to conditions to allow for their production, detection, and, in certain embodiments, their recovery, purification, and use for one or more of the purposes disclosed herein. If not specified otherwise elsewhere in the specification or the accompanying claims it is understood that each optional substituent on a substitutable carbon is a monovalent substituent independently selected from halogen; –(CH2)0– 4Ro; –(CH2)0–4ORo; -O(CH2)0-4Ro, –O–(CH2)0–4C(O)OR°; –(CH2)0–4CH(ORo)2; – (CH2)0–4SRo; –(CH2)0–4Ph, which may be substituted with one or more R°; – (CH2)0–4O(CH2)0–1Ph which may be substituted with one or more R°; – CH=CHPh, which may be substituted with one or more R°; –(CH2)0–4O(CH2)0– 1-pyridyl which may be substituted with one or more R°; –NO2; –CN; – N3; -(CH2)0–4N(Ro)2; –(CH2)0–4N(Ro)C(O)Ro; –N(Ro)C(S)Ro; –(CH2)0– 4N(Ro)C(O)NRo2; -N(Ro)C(S)NRo2; –(CH2)0–4N(Ro)C(O)ORo; – N(Ro)N(Ro)C(O)Ro; -N(Ro)N(Ro)C(O)NRo2; -N(Ro)N(Ro)C(O)ORo; –(CH2)0– 4C(O)Ro; –C(S)Ro; –(CH2)0–4C(O)ORo; –(CH2)0–4C(O)SRo; -(CH2)0– 4C(O)OSiRo3; –(CH2)0–4OC(O)Ro; –OC(O)(CH2)0–4SR–, SC(S)SR°; –(CH2)0– 4SC(O)Ro; –(CH2)0–4C(O)NRo2; –C(S)NRo2; –C(S)SR°; –SC(S)SR°, -(CH2)0– 4OC(O)NRo2; -C(O)N(ORo)Ro; –C(O)C(O)Ro; –C(O)CH2C(O)Ro; – C(NORo)Ro; -(CH2)0–4SSRo; –(CH2)0–4S(O)2Ro; –(CH2)0–4S(O)2ORo; –(CH2)0– 4OS(O)2Ro; –S(O)2NRo2; –S(O)(NR°)R°; –S(O)2N=C(NR°2)2; -(CH2)0– 4S(O)Ro; -N(Ro)S(O)2NRo2; –N(Ro)S(O)2Ro; –N(ORo)Ro; –C(NH)NRo2; – P(O)2Ro; -P(O)Ro2; -OP(O)Ro2; –OP(O)(ORo)2; SiRo3; –(C1–4 straight or branched alkylene)O–N(Ro)2; or –(C1–4 straight or branched alkylene)C(O)O– N(Ro)2. It is understood that “Ph” means phenyl; and that “–(CH2)0-4” means that there is either no alkylene group if the subscript is “0” (zero) or an alkylene group with 1, 2, 3 or 4 CH2 units. Each Rois independently hydrogen, halogen, C1–6 aliphatic, –CH2Ph, – O(CH2)0–1Ph, -CH2-(5-6 membered heteroaryl ring), or a 5–6–membered saturated, partially unsaturated, or aryl ring having 0–4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or, notwithstanding the definition above, two independent occurrences of Ro, taken together with their intervening atom(s), form a 3–12–membered saturated, partially unsaturated, or aryl mono– or bicyclic ring having 0–4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, which may be substituted by a divalent substituent on a saturated carbon atom of Roselected from =O and =S; or each Rois optionally substituted with a monovalent substituent independently selected from halogen, –(CH2)0–2R●, –(haloR●), – (CH2)0–2OH, –(CH2)0–2OR●, –(CH2)0–2CH(OR●)2; O(haloR●), –CN, –N3, – (CH2)0–2C(O)R●, –(CH2)0–2C(O)OH, –(CH2)0–2C(O)OR●, –(CH2)0–2SR●, – (CH2)0–2SH, –(CH2)0–2NH2, –(CH2)0–2NHR●, –(CH2)0–2NR●2, –NO2, –SiR●3, – OSiR●3, C(O)SR●, –(C1–4 straight or branched alkylene)C(O)OR●, or –SSR●. It is understood that “Ph” means phenyl; “halo” means halogen; and “–(CH2)0-2” means that there is either no alkylene group if the subscript is “0” (zero) or an alkylene group with 1 or 2 CH2 units. Each R●is independently selected from C1–4 aliphatic, –CH2Ph, –O(CH2)0–1Ph, or a 5–6–membered saturated, partially unsaturated, or aryl ring having 0–4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, and wherein each R●is unsubstituted or where preceded by halo is substituted only with one or more halogens; or wherein an optional substituent on a saturated carbon is a divalent substituent independently selected from =O, =S, =NNR*2, =NNHC(O)R*, =NNHC(O)OR*, =NNHS(O)2R*, =NR*, =NOR*, –O(C(R*2))2–3O– , or –S(C(R*2))2–3S–, or a divalent substituent bound to vicinal substitutable carbons of an “optionally substituted” group is –O(CR*2)2–3O–, wherein each independent occurrence of R*is selected from hydrogen, C1–6 aliphatic or an unsubstituted 5–6–membered saturated, partially unsaturated, or aryl ring having 0–4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. When R*is C1–6 aliphatic, R*is optionally substituted with halogen, –R●, (haloR●), OH, –OR^, –O(haloR●), –CN, –C(O)OH, –C(O)OR●, –NH2, –NHR●, –NR●2, or –NO2, wherein each R●is independently selected from C1– 4 aliphatic, –CH2Ph, –O(CH2)0–1Ph, or a 5–6–membered saturated, partially unsaturated, or aryl ring having 0–4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, and wherein each R●is unsubstituted or where preceded by halo is substituted only with one or more halogens. An optional substituent on a substitutable nitrogen is independently –R†, – NR†2, –C(O)R†, –C(O)OR†, –C(O)C(O)R†, – C(O)CH2C(O)R†, -S(O)2R†, -S(O)2NR†2, –C(S)NR†2, –C(NH)NR†2, or – N(R†)S(O)2R†; wherein each R†is independently hydrogen, C1–6 aliphatic, unsubstituted –OPh, or an unsubstituted 5–6–membered saturated, partially unsaturated, or aryl ring having 0–4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or, two independent occurrences of R†, taken together with their intervening atom(s) form an unsubstituted 3–12–membered saturated, partially unsaturated, or aryl mono– or bicyclic ring having 0–4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; wherein when R†is C1–6 aliphatic, R†is optionally substituted with halogen, – R●, -(haloR●), -OH, –OR●, –O(haloR●), –CN, –C(O)OH, –C(O)OR●, –NH2, – NHR●, –NR●2, or –NO2, wherein each R●is independently selected from C1– 4 aliphatic, –CH2Ph, –O(CH2)0–1Ph, or a 5–6–membered saturated, partially unsaturated, or aryl ring having 0–4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, and wherein each R●is unsubstituted or where preceded by halo is substituted only with one or more halogens. It is understood that “Ph” means phenyl; and “halo” means halogen. The term “solvates” means addition forms of the compounds of the present invention with solvents, preferably pharmaceutically acceptable solvents that contain either stoichiometric or non-stoichiometric amounts of solvent. Some compounds have a tendency to trap a fixed molar ratio of solvent molecules in the crystalline solid state, thus forming a solvate. If the solvent is water the solvate formed is a hydrate, e.g. a hemi-, mono- or dihydrate. If the solvent is alcohol, the solvate formed is an alcoholate, e.g., a methanolate or ethanolate. If the solvent is an ether, the solvate formed is an etherate, e.g., diethyl etherate. The term "N-oxides" means such compounds of the present invention that contain an amine oxide moiety, i.e. the oxide of a tertiary amine group. The compounds of formula I may – also depending on the nature of substituents they may bear – have one or more centers of chirality. They may accordingly occur in various enantiomeric and diastereomeric forms, as the case may be, and be in racemic or optically active form. The invention, therefore, also relates to the optically active forms, enantiomers, racemates, diastereomers, mixtures thereof in all ratios, collectively: “stereoisomers” for the purpose of the present invention, of these compounds. Since the pharmaceutical activity of the racemates or stereoisomers of the compounds according to the invention may differ, it may be desirable to use a specific stereoisomer, e.g. one specific enantiomer or diastereomer. In these cases, a compound according to the present invention obtained as a racemate or even intermediates thereof – may be separated into the stereoisomeric (enantiomeric, diastereoisomeric) compounds by chemical or physical measures known to the person skilled in the art. Another approach that may be applied to obtain one or more specific stereoisomers of a compound of the present invention in an enriched or pure form makes use of stereoselective synthetic procedures, e.g. applying starting material in a stereoisomerically enriched or pure form (for instance using the pure or enriched (R)- or (S)- enantiomer of a particular starting material bearing a chiral center) or utilizing chiral reagents or catalysts, in particular enzymes. In the context of the present invention the term "pure enantiomer" usually refers to a relative purity of one enantiomer over the other (its antipode) of equal to or greater than 95%, preferably ≥ 98 %, more preferably ≥ 98.5%, still more preferably ≥ 99%. Thus, for example, the compounds of the invention which have one or more centers of chirality and which occur as racemates or as mixtures of enantiomers or diastereoisomers can be fractionated or resolved by methods known per se into their optically pure or enriched isomers, i.e. enantiomers or diastereomers. The separation of the compounds of the invention can take place by chromatographic methods, e.g. column separation on chiral or nonchiral phases, or by recrystallization from an optionally optically active solvent or by use of an optically active acid or base or by derivatization with an optically active reagent such as, for example, an optically active alcohol, and subsequent elimination of the radical. In the context of the present invention the term “tautomer” refers to compounds of the present invention that may exist in tautomeric forms and show tautomerism; for instance, carbonyl compounds may be present in their keto and / or their enol form and show keto-enol tautomerism. Those tautomers may occur in their individual forms, e.g., the keto or the enol form, or as mixtures thereof and are claimed separately and together as mixtures in any ratio. The same applies for cis / trans isomers, E / Z isomers, conformers and the like. In one embodiment the compounds of the present invention are in the form of free base or acid – as the case may be -, i.e. in their non-salt (or salt-free) form. In another embodiment the compounds of the present invention are in the form of a pharmaceutically acceptable salt, a pharmaceutically acceptable solvate, or a pharmaceutically acceptable solvate of a pharmaceutically acceptable salt. The term "pharmaceutically acceptable salts" refers to salts prepared from pharmaceutically acceptable bases or acids, including inorganic bases or acids and organic bases or acids. In cases where the compounds of the present invention contain one or more acidic or basic groups, the invention also comprises their corresponding pharmaceutically acceptable salts. Thus, the compounds of the present invention which contain acidic groups, such as carboxyl groups, can be present in salt form, and can be used according to the invention, for example, as alkali metal salts, alkaline earth metal salts, aluminium salts or as ammonium salts. More precise examples of such salts include lithium salts, sodium salts, potassium salts, calcium salts, magnesium salts, barium salts or salts with ammonia or organic amines such as, for example, ethylamine, ethanolamine, diethanolamine, triethanolamine, piperdine, N-methylglutamine or amino acids. These salts are readily available, for instance, by reacting the compound having an acidic group with a suitable base, e.g. lithium hydroxide, sodium hydroxide, sodium propoxide, potassium hydroxide, potassium ethoxide, magnesium hydroxide, calcium hydroxide or barium hydroxide. Other base salts of compounds of the present invention include but are not limited to copper(I), copper(II), iron(II), iron (III), manganese(II) and zinc salts. Compounds of the present invention which contain one or more basic groups, e.g. groups which can be protonated, can be present in salt form, and can be used according to the invention in the form of their addition salts with inorganic or organic acids. Examples of suitable acids include hydrogen chloride, hydrogen bromide, hydrogen iodide, phosphoric acid, sulfuric acid, nitric acid, methanesulfonic acid, p- toluenesulfonic acid, naphthalenedisulfonic acid, sulfoacetic acid, trifluoroacetic acid, oxalic acid, acetic acid, tartaric acid, lactic acid, salicylic acid, benzoic acid, carbonic acid, formic acid, propionic acid, pivalic acid, diethylacetic acid, malonic acid, succinic acid, pimelic acid, fumaric acid, malonic acid, maleic acid, malic acid, embonic acid, mandelic acid, sulfaminic acid, phenylpropionic acid, gluconic acid, ascorbic acid, isonicotinic acid, citric acid, adipic acid, taurocholic acid, glutaric acid, stearic acid, glutamic acid or aspartic acid, and other acids known to the person skilled in the art. The salts which are formed are, inter alia, hydrochlorides, chlorides, hydrobromides, bromides, iodides, sulfates, phosphates, methanesulfonates (mesylates), tosylates, carbonates, bicarbonates, formates, acetates, sulfoacetates, triflates, oxalates, malonates, maleates, succinates, tartrates, malates, embonates, mandelates, fumarates, lactates, citrates, glutarates, stearates, aspartates and glutamates. The stoichiometry of the salts formed from the compounds of the invention may moreover be an integral or non-integral multiple of one. Compounds of the present invention which contain basic nitrogen-containing groups can be quaternized using agents such as (C1-C4)alkyl halides, for example methyl, ethyl, isopropyl and tert-butyl chloride, bromide and iodide; di(C1-C4)alkyl sulfates, for example dimethyl, diethyl and diamyl sulfate; (C10- C18)alkyl halides, for example decyl, dodecyl, lauryl, myristyl and stearyl chloride, bromide and iodide; and aryl(C1-C4)alkyl halides, for example benzyl chloride and phenethyl bromide. Both water- and oil-soluble compounds according to the invention can be prepared using such salts. If the compounds of the present invention simultaneously contain acidic and basic groups in the molecule, the invention also includes, in addition to the salt forms mentioned, inner salts or betaines (zwitterions). The respective salts can be obtained by customary methods which are known to a person skilled in the art, for example by contacting these with an organic or inorganic acid or base in a solvent or dispersant, or by anion exchange or cation exchange with other salts. The present invention also includes all salts of the compounds of the present invention which, owing to low physiological compatibility, are not directly suitable for use in pharmaceuticals but which can be used, for example, as intermediates for chemical reactions or for the preparation of pharmaceutically acceptable salts. Therefore, the following items are also in accordance with the invention: (a) all stereoisomers or tautomers of the compounds, including mixtures thereof in all ratios; (b) pharmaceutically acceptable salts of the compounds and of the items mentioned under (a); (c) pharmaceutically acceptable solvates of the compounds and of the items mentioned under (a) and (b); (d) N-oxides of the compounds and of the items mentioned under (a), (b), and (c). It will be understood that all references to compounds above and below are meant to include these items, in particular pharmaceutically acceptable solvates of the compounds, or pharmaceutically acceptable solvates of their pharmaceutically acceptable salts. There is furthermore intended that a compound of the present invention includes isotope-labelled forms thereof. An isotope-labelled form of a compound of the formula I is identical to this compound apart from the fact that one or more atoms of the compound have been replaced by an atom or atoms having an atomic mass or mass number which differs from the atomic mass or mass number of the atom which usually occurs naturally. Examples of isotopes which are readily commercially available and which can be incorporated into a compound of the present invention by well-known methods include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, sulfur, fluorine and chlorine, for example2H (D),3H,13C,14C,15N,18O,17O,31P,32P,33S,34S,35S,36S,18F and36CI, respectively. A compound of formula I or a pharmaceutically acceptable salt thereof which contains one or more of the above-mentioned isotopes and / or other isotopes of other atoms is intended to be part of the present invention. An isotope-labelled compound of formula I can be used in a number of beneficial ways. For example, an isotope-labelled compound of the present invention into which, for example, a radioisotope, such as3H or14C, has been incorporated is suitable for medicament and / or substrate tissue distribution assays. These radioisotopes, i.e. tritium (3H) and carbon-14 (14C), are particularly preferred owing to simple preparation and excellent detectability. Incorporation of heavier isotopes, for example deuterium (2H), into a compound of formula I has therapeutic advantages owing to the higher metabolic stability of this isotope-labelled compound. Higher metabolic stability translates directly into an increased in vivo half-life or lower dosages, which under most circumstances would represent a preferred embodiment of the present invention. An isotope-labelled compound of formula I can usually be prepared by carrying out the procedures disclosed in the synthesis schemes and the related description, in the example part and in the preparation part in the present text, replacing a non-isotope-labelled reactant by a readily available isotope-labelled reactant. Deuterium (2H; D) can also be incorporated into a compound of formula I for the purpose of manipulating the oxidative metabolism of the compound by way of the primary kinetic isotope effect. The primary kinetic isotope effect is a change of the rate for a chemical reaction that results from exchange of isotopic nuclei, which in turn is caused by the change in ground state energies necessary for covalent bond formation after this isotopic exchange. Exchange of a heavier isotope usually results in a lowering of the ground state energy for a chemical bond and thus cause a reduction in the rate in rate-limiting bond breakage. If the bond breakage occurs in or in the vicinity of a saddle-point region along the coordinate of a multi-product reaction, the product distribution ratios can be altered substantially. For explanation: if deuterium is bonded to a carbon atom at a non-exchangeable position, rate differences of kM / kD = 2-7 are typical. If this rate difference is successfully applied to a compound of the formula I that is susceptible to oxidation, the profile of this compound in vivo can be drastically modified and result in improved pharmacokinetic properties. When discovering and developing therapeutic agents, the person skilled in the art attempts to optimize pharmacokinetic parameters while retaining desirable in vitro properties. It is reasonable to assume that many compounds with poor pharmacokinetic profiles are susceptible to oxidative metabolism. In vitro liver microsomal assays currently available provide valuable information on the course of oxidative metabolism of this type, which in turn permits the rational design of deuterated compounds of the formula I with improved stability through resistance to such oxidative meta-bolism. Significant improvements in the pharmacokinetic profiles of compounds of the formula I are thereby obtained, and can be expressed quantitatively in terms of increases in the in vivo half-life (t1 / 2), concentration at maximum therapeutic effect (Cmax), area under the dose response curve (AUC), and F; and in terms of reduced clearance, dose and materials costs. The following is intended to illustrate the above: a compound of formula I which has multiple potential sites of attack for oxidative metabolism, for example benzylic hydrogen atoms and hydrogen atoms bonded to a nitrogen atom, is prepared as a series of analogues in which various combinations of hydrogen atoms are replaced by deuterium atoms, so that some, most or all of these hydrogen atoms have been replaced by deuterium atoms. Half-life determinations enable favourable and accurate determination of the extent of the extent to which the improvement in resistance to oxidative metabolism has improved. In this way, it is deter-mined that the half-life of the parent compound can be extended by up to 100% as the result of deuterium-hydrogen exchange of this type. Deuterium-hydrogen exchange in a compound of the present invention can also be used to achieve a favourable modification of the metabolite spectrum of the starting compound in order to diminish or eliminate undesired toxic metabolites. For example, if a toxic metabolite arises through oxidative carbon- hydrogen (C-H) bond cleavage, it can reasonably be assumed that the deuterated analogue will greatly diminish or eliminate production of the unwanted metabolite, even if the particular oxidation is not a rate-determining step. Further information on the state of the art with respect to deuterium- hydrogen exchange may be found, for example in Hanzlik et al., J. Org. Chem. 55, 3992-3997, 1990, Reider et al., J. Org. Chem. 52, 3326-3334, 1987, Foster, Adv. Drug Res.14, 1-40, 1985, Gillette et al, Biochemistry 33(10) 2927- 2937, 1994, and Jarman et al. Carcinogenesis 16(4), 683-688, 1995. Furthermore, the present invention relates to pharmaceutical compositions comprising at least one compound of formula I, or its N-oxides, solvates, tautomers or stereoisomers thereof as well as the pharmaceutically acceptable salts of each of the foregoing, including mixtures thereof in all ratios, as active ingredient, together with a pharmaceutically acceptable carrier. For the purpose of the present invention the term “pharmaceutical composition” (or “pharmaceutical formulation”) refers to a composition or product comprising one or more active ingredients, and one or more inert ingredients that make up the carrier, as well as any product which results, directly or indirectly, from combination, complexation or aggregation of any two or more of the ingredients, or from dissociation of one or more of the ingredients, or from other types of reactions or interactions of one or more of the ingredients. Accordingly, the pharmaceutical compositions of the present invention encompass any composition made by admixing at least one compound of the present invention and a pharmaceutically acceptable carrier. It may further comprise physiologically acceptable excipients, auxiliaries, adjuvants, diluents and / or additional pharmaceutically active substance other than the compounds of the invention. The pharmaceutical compositions include compositions and pharmaceutical formulations suitable for oral, rectal, topical, parenteral (including subcutaneous, intramuscular, and intravenous), ocular (ophthalmic), pulmonary (nasal or buccal inhalation), or nasal administration, although the most suitable route in any given case will depend on the nature and severity of the conditions being treated and on the nature of the active ingredient. They may be conveniently presented in unit dosage form and prepared by any of the methods well-known in the art of pharmacy. A pharmaceutical composition of the present invention may additionally comprise one or more other compounds as active ingredients (drugs), such as one or more additional compounds of the present invention. In a particular embodiment the pharmaceutical composition further comprises a second active ingredient or its N-oxides, solvates, tautomers or stereoisomers thereof as well as the pharmaceutically acceptable salts of each of the foregoing, including mixtures thereof in all ratios, wherein that second active ingredient is other than a compound of formula I; preferably, that second active ingredient is a compound that is useful in the treatment, prevention, suppression and / or amelioration of medicinal conditions or pathologies for which the compounds of the present invention are useful as well and which are listed elsewhere hereinbefore or hereinafter. Such combination of two or more active ingredients or drugs may be safer or more effective than either drug or active ingredient alone, or the combination is safer or more effective than it would be expected based on the additive properties of the individual drugs. Such other drug(s) may be administered, by a route and in an amount commonly used contemporaneously or sequentially with a compound of the invention. When a compound of the invention is used contemporaneously with one or more other drugs or active ingredients, a combination product containing such other drug(s) and the compound of the invention – also referred to as “fixed dose combination” – is preferred. However, combination therapy also includes therapies in which the compound of the present invention and one or more other drugs are administered on different overlapping schedules. It is contemplated that when used in combination with other active ingredients, the compound of the present invention or the other active ingredient or both may be used effectively in lower doses than when each is used alone. Accordingly, the pharmaceutical compositions of the present invention include those that contain one or more other active ingredients, in addition to a compound of the invention. The compounds of the present invention – or N-oxides, solvates, tautomers or stereoisomers thereof and / or the pharmaceutically acceptable salts of each of the foregoing, including mixtures thereof in all ratios – can be used as medicaments. They have been found to exhibit pharmacological activity by binding to TEAD and / or disrupting and / or inhibiting YAP-TEAD and / or TAZ- TEAD protein-protein interaction. It is worth mentioning that some of the compounds of the present invention may not only bind to one of the TEAD family members (TEAD 1, 2, 3, or 4) but to more than one TEAD paralog, i.e., to two, three or even all four TEAD paralogs, thereby exhibiting activity as pan- TEAD inhibitors. It is assumed that by this activity the compounds of the present invention may prevent or reverse dysfunction of the Hippo pathway. By preventing its dysfunction, the Hippo pathway may be capable of playing its role as a tumor suppressor. Apart from preventing or reversing dysfunction of the Hippo pathway and independent of upstream Hippo regulation, the pharmacological activity of the compounds of the present invention may also be useful in other pathophysiological scenarios where inhibition or disruption of TEAD binding and / or aberrant YAP-TEAD and / or aberrant TAZ-TEAD signaling would be beneficial. Thus, the compounds of the present invention being TEAD binders and / or inhibitors of YAP-TEAD and / or TAZ-TEAD interaction are useful in particular in the treatment, prevention, suppression and / or amelioration of hyperproliferative disorders and cancer, in particular tumors including solid tumors, of breast cancer, lung cancer, mesothelioma, epithelioid hemangioendothelioma, uveal melanoma, liver cancer, ovarian cancer, squamous cancer, renal cancer, gastric cancer, medulloblastoma, colon cancer, pancreatic cancer, schwannoma, meningioma, glioma, basal cell carcinoma. Without wishing to commit to any specific theory or explanation it may be assumed that the compounds might be able to achieve this by direct effects on the cancer cells and / or indirectly by modulating the response of the immune system against the tumor. Furthermore, the compounds of the present invention may also be useful in the treatment, prevention, suppression and / or amelioration of non-cancerous disorders and diseases, e.g. cardiovascular diseases and fibrosis (like liver fibrosis). In a particular embodiment the compounds of the present invention are for use in the prevention and / or treatment, especially in the treatment of any of the disorders or diseases listed above, preferably of cancer, in particular tumors including solid tumors, of the specific types of cancer disclosed in the previous paragraph; or of any of the non-cancerous disorders or diseases disclosed in the previous paragraph. Another particular embodiment of the present invention is a method for preventing and / or treating, preferably treating a disorder or disease selected from the group consisting of hyperproliferative disorders and cancer, in particular tumors including solid tumors, of the specific types of cancer disclosed in the previous paragraphs; or of any of the non-cancerous disorders or diseases disclosed in the previous paragraphs. Still another particular embodiment of the invention is the use of a compound of the present invention – or N-oxides, prodrugs, solvates, tautomers or stereoisomers thereof and / or the pharmaceutically acceptable salts of each of the foregoing, including mixtures thereof in all ratios – for the manufacturing of a medicament, in particular for preventing and / or treating, preferably treating a disorder or disease selected from the group consisting of hyperproliferative disorders and cancer, in particular tumors including solid tumors, of the specific types of cancer disclosed in the previous paragraphs; or of any of the non- cancerous disorders or diseases disclosed in the previous paragraphs. Preferably, the present invention relates to a compound of the present invention for use in the prevention and / or treatment of a disease – or, alternatively, a method for preventing and / or treating a disease by administering an effective amount of a compound of the present invention ; or, in another alternative, a use of a compound of the present invention for the manufacturing of a medicament for the prevention and / or treatment of a disease – wherein that disease is a cancer, in particular tumors including solid tumors, of the specific types of cancer disclosed in the previous paragraphs; and more preferably, wherein administration of the compound is simultaneous, sequential or in alternation with administration of at least one other active drug agent. The disclosed compounds of the present invention and in particular of formula I can be administered in combination with other known therapeutic agents, including anticancer agents. As used here, the term "anticancer agent" relates to any agent which is administered to a patient with cancer for the purposes of treating the cancer. The anti-cancer treatment defined above may be applied as a monotherapy or may involve, in addition to the herein disclosed compounds of the present invention, conventional surgery or radiotherapy or medicinal therapy. Such medicinal therapy, e.g. a chemotherapy or a targeted therapy, may include one or more, but preferably one, of the following anti- tumor agents: Alkylating agents such as altretamine, bendamustine, busulfan, carmustine, chlorambucil, chlormethine, cyclophosphamide, dacarbazine, ifosfamide, improsulfan, tosilate, lomustine, melphalan, mitobronitol, mitolactol, nimustine, ranimustine, temozolomide, thiotepa, treosulfan, mechloretamine, carboquone; apaziquone, fotemustine, glufosfamide, palifosfamide, pipobroman, trofosfamide, uramustine, evofosfamide, VAL-083(dianhydrogalactitol); Platinum Compounds such as carboplatin, cisplatin, eptaplatin, miriplatine hydrate, oxaliplatin, lobaplatin, nedaplatin, picoplatin, satraplatin; DNA altering agents such as amrubicin, bisantrene, decitabine, mitoxantrone, procarbazine, trabectedin, clofarabine; Topoisomerase Inhibitors such as etoposide, irinotecan, razoxane, sobuzoxane, teniposide, topotecan; amonafide, belotecan, elliptinium acetate, voreloxin; Microtubule modifiers such as cabazitaxel, docetaxel, eribulin, ixabepilone, paclitaxel, vinblastine, vincristine, vinorelbine, vindesine, vinflunine; fosbretabulin, tesetaxel; Antimetabolites such as asparaginase, pegaaspargase, azacitidine, calcium levofolinate, capecitabine, cladribine, cytarabine, enocitabine, floxuridine, fludarabine, fluorouracil, gemcitabine, mercaptopurine, methotrexate, nelarabine, pemetrexed, pralatrexate, azathioprine, thioguanine, carmofur; doxifluridine, elacytarabine, raltitrexed, sapacitabine, tegafur, trimetrexate; Anticancer antibiotics such as bleomycin, dactinomycin, doxorubicin, epirubicin, idarubicin, levamisole, miltefosine, mitomycin C, romidepsin, streptozocin, valrubicin, zinostatin, zorubicin, daunurobicin, plicamycin; aclarubicin, peplomycin, pirarubicin; Hormones / Antagonists such as abarelix, abiraterone, bicalutamide, buserelin, calusterone, chlorotrianisene, degarelix, dexamethasone, estradiol, fluocortolone, fluoxymesterone, flutamide, fulvestrant, goserelin, histrelin, leuprorelin, megestrol, mitotane, nafarelin, nandrolone, nilutamide, octreotide, prednisolone, raloxifene, tamoxifen, thyrotropin alfa, toremifene, trilostane, triptorelin, diethylstilbestrol; acolbifene, danazol, deslorelin, epitiostanol, orteronel, enzalutamide; Aromatase inhibitors such as aminoglutethimide, anastrozole, exemestane, fadrozole, letrozole, testolactone; formestane; Small molecule kinase inhibitors such as crizotinib, dasatinib, erlotinib, imatinib, lapatinib, nilotinib, pazopanib, regorafenib, ruxolitinib, sorafenib, sunitinib, vandetanib, vemurafenib, bosutinib, gefitinib, axitinib; afatinib, alisertib, dabrafenib, dacomitinib, dinaciclib, dovitinib, enzastaurin, nintedanib, lenvatinib, linifanib, linsitinib, masitinib, midostaurin, motesanib, neratinib, orantinib, perifosine, ponatinib, radotinib, rigosertib, tepotinib, tipifarnib, tivantinib, tivozanib, trametinib, pimasertib, brivanib alaninate, cediranib, apatinib (rivoceranib), cabozantinib S-malate, ibrutinib, icotinib, buparlisib, cipatinib, cobimetinib, idelalisib, fedratinib, tesevatinib; Photosensitizers such as methoxsalen; porfimer sodium, talaporfin, temoporfin; Antibodies such as alemtuzumab, besilesomab, brentuximab vedotin, cetuximab, denosumab, ipilimumab, ofatumumab, panitumumab, rituximab, tositumomab, trastuzumab, bevacizumab, pertuzumab; catumaxomab, elotuzumab, epratuzumab, farletuzumab, mogamulizumab, necitumumab, nimotuzumab, obinutuzumab, ocaratuzumab, oregovomab, ramucirumab, rilotumumab, siltuximab, tocilizumab, zalutumumab, zanolimumab, matuzumab, dalotuzumab, onartuzumab, racotumomab, tabalumab, abituzumab, atezolizumab, durvalumab, pembrolizumab, nivolumab; Cytokines such as aldesleukin, interferon alfa2, interferon alfa2a, interferon alfa2b; celmoleukin, tasonermin, teceleukin, oprelvekin, recombinant interferon beta- 1a; Drug Conjugates such as denileukin diftitox, ibritumomab tiuxetan, iobenguane I 123, prednimustine, trastuzumab emtansine, estramustine, gemtuzumab, ozogamicin, aflibercept; cintredekin besudotox, edotreotide, inotuzumab ozogamicin, naptumomab estafenatox, oportuzumab monatox, technetium (99mTc) arcitumomab, vintafolide; PARP inhibitors such as olaparib, veliparib, niraparib, rucaparib, talzaoparib, pamiparib; KRAS inhibitors such as sotorasib, adagrasib; Miscellaneous such as alitretinoin, bexarotene, bortezomib, everolimus, ibandronic acid, imiquimod, lenalidomide, lentinan, metirosine, mifamurtide, pamidronic acid, pegaspargase, pentostatin, sipuleucel, sizofiran, tamibarotene, temsirolimus, thalidomide, tretinoin, vismodegib, zoledronic acid, vorinostat; celecoxib, cilengitide, entinostat, etanidazole, ganetespib, idronoxil, iniparib, ixazomib, lonidamine, nimorazole, panobinostat, peretinoin, plitidepsin, pomalidomide, procodazol, ridaforolimus, tasquinimod, telotristat, thymalfasin, tirapazamine, tosedostat, trabedersen, ubenimex, valspodar, gendicine, picibanil, reolysin, retaspimycin hydrochloride, trebananib, virulizin, carfilzomib, endostatin, immucothel, belinostat; In a particular embodiment of the present invention, the medical therapy includes a combination of a compound of the present invention, which inhibits the activity of TEAD, with a KRAS inhibitor. In another aspect of the invention, a set or kit is provided comprising a therapeutically effective amount of at least one compound of the invention and / or at least one pharmaceutical composition as described herein and a therapeutically effective amount of at least one further pharmacologically active substance other than the compounds of the invention. It is preferred that this set or kit comprises separate packs of a) an effective amount of a compound of formula I, or any of its N-oxides, solvates, tautomers or stereoisomers thereof as well as the pharmaceutically acceptable salts of each of the foregoing, including mixtures thereof in all ratios, and b) an effective amount of a further active ingredient that further active ingredient not being a compound of formula I. A further embodiment of the present invention is a process for the manufacture of the pharmaceutical compositions of the present invention, characterized in that one or more compounds according to the invention and one or more compounds selected from the group consisting of solid, liquid or semiliquid excipients, auxiliaries, adjuvants, diluents, carriers and pharmaceutically active agents other than the compounds according to the invention, are converted in a suitable dosage form. The pharmaceutical compositions (formulations) of the present invention may be administered by any means that achieve their intended purpose. For example, administration may be via oral, parenteral, topical, enteral, intravenous, intramuscular, inhalant, nasal, intraarticular, intraspinal, transtracheal, transocular, subcutaneous, intraperitoneal, transdermal, or buccal routes. Alternatively, or concurrently, administration may be via the oral route. The dosage administered will be dependent upon the age, health, and weight of the recipient, kind of concurrent treatment, if any, frequency of treatment, and the nature of the effect desired. Parenteral administration is preferred. Oral administration is especially preferred. Suitable dosage forms include, but are not limited to capsules, tablets, pellets, dragees, semi-solids, powders, granules, suppositories, ointments, creams, lotions, inhalants, injections, cataplasms, gels, tapes, eye drops, solution, syrups, aerosols, suspension, emulsion, which can be produced according to methods known in the art. In general, non-chemical routes for the production of pharmaceutical compositions and / or pharmaceutical preparations comprise processing steps on suitable mechanical means known in the art that transfer one or more compounds of the invention into a dosage form suitable for administration to a patient in need of such a treatment. Usually, the transfer of one or more compounds of the invention into such a dosage form comprises the addition of one or more compounds, selected from the group consisting of carriers, excipients, auxiliaries, and pharmaceutical active ingredients other than the compounds of the invention. Suitable processing steps include, but are not limited to combining, milling, mixing, granulating, dissolving, dispersing, homogenizing, casting and / or compressing the respective active and nonactive ingredients. Mechanical means for performing said processing steps are known in the art. In this respect, active ingredients are preferably at least one compound of the invention and optionally one or more additional compounds other than the compounds of the invention, which show valuable pharmaceutical properties, preferably those pharmaceutical active agents other than the compounds of the invention, which are disclosed herein. Particularly suitable for oral use are tablets, pills, coated tablets, capsules, powders, granules, syrups, juices or drops, suitable for rectal use are suppositories, suitable for parenteral use are solutions, preferably oil-based or aqueous solutions, furthermore suspensions, emulsions or implants, and suitable for topical use are ointments, creams or powders. The compounds of the invention may also be lyophilized and the resultant lyophilizates used, for example, for the preparation of injection preparations. The preparations indicated may be sterilized and / or comprise assistants, such as lubricants, preservatives, stabilizers and / or wetting agents, emulsifiers, salts for modifying the osmotic pressure, buffer substances, dyes, flavors and / or a plurality of further active ingredients, for example one or more vitamins. Suitable excipients are organic or inorganic substances, which are suitable for enteral (for example oral), parenteral or topical administration and do not react with the compounds of the invention, for example water, vegetable oils, benzyl alcohols, alkylene glycols, polyethylene glycols, glycerol triacetate, gelatin, carbohydrates, such as lactose, sucrose, mannitol, sorbitol or starch (maize starch, wheat starch, rice starch, potato starch), cellulose preparations and / or calcium phosphates, for example tricalcium phosphate or calcium hydrogen phosphate, magnesium stearate, talc, gelatin, tragacanth, methyl cellulose, hydroxypropylmethylcellulose, sodium carboxymethylcellulose, polyvinyl pyrrolidone and / or vaseline. If desired, disintegrating agents may be added such as the above-mentioned starches and also carboxymethyl-starch, cross-linked polyvinyl pyrrolidone, agar, or alginic acid or a salt thereof, such as sodium alginate. Auxiliaries include, without limitation, flow-regulating agents and lubricants, for example, silica, talc, stearic acid or salts thereof, such as magnesium stearate or calcium stearate, and / or polyethylene glycol. Dragee cores are provided with suitable coatings, which, if desired, are resistant to gastric juices. For this purpose, concentrated saccharide solutions may be used, which may optionally contain gum arabic, talc, polyvinyl pyrrolidone, polyethylene glycol and / or titanium dioxide, lacquer solutions and suitable organic solvents or solvent mixtures. In order to produce coatings resistant to gastric juices or to provide a dosage form affording the advantage of prolonged action, the tablet, dragee or pill can comprise an inner dosage and an outer dosage component the latter being in the form of an envelope over the former. The two components can be separated by an enteric layer, which serves to resist disintegration in the stomach and permits the inner component to pass intact into the duodenum or to be delayed in release. A variety of materials can be used for such enteric layers or coatings, such materials including a number of polymeric acids and mixtures of polymeric acids with such materials as shellac, acetyl alcohol, solutions of suitable cellulose preparations such as acetyl-cellulose phthalate, cellulose acetate or hydroxypropylmethyl-cellulose phthalate, are used. Dye stuffs or pigments may be added to the tablets or dragee coatings, for example, for identification or in order to characterize combinations of active compound doses. Suitable carrier substances are organic or inorganic substances which are suitable for enteral (e.g. oral) or parenteral administration or topical application and do not react with the novel compounds, for example water, vegetable oils, benzyl alcohols, polyethylene glycols, gelatin, carbohydrates such as lactose or starch, magnesium stearate, talc and petroleum jelly. In particular, tablets, coated tablets, capsules, syrups, suspensions, drops or suppositories are used for enteral administration, solutions, preferably oily or aqueous solutions, furthermore suspensions, emulsions or implants, are used for parenteral administration, and ointments, creams or powders are used for topical application. The compounds of the invention can also be lyophilized and the lyophilizates obtained can be used, for example, for the production of injection preparations. Other pharmaceutical preparations, which can be used orally include push-fit capsules made of gelatin, as well as soft, sealed capsules made of gelatin and a plasticizer such as glycerol or sorbitol. The push-fit capsules can contain the active compounds in the form of granules, which may be mixed with fillers such as lactose, binders such as starches, and / or lubricants such as talc or magnesium stearate and, optionally, stabilizers. In soft capsules, the active compounds are preferably dissolved or suspended in suitable liquids, such as fatty oils, or liquid paraffin. In addition, stabilizers may be added. The liquid forms in which the novel compositions of the present invention may be incorporated for administration orally include aqueous solutions, suitably flavored syrups, aqueous or oil suspensions, and flavored emulsions with edible oils such as cottonseed oil, sesame oil, coconut oil or peanut oil, as well as elixirs and similar pharmaceutical vehicles. Suitable dispersing or suspending agents for aqueous suspensions include synthetic and natural gums such as tragacanth, acacia, alginate, dextran, sodium carboxymethylcellulose, methylcellulose, polyvinyl-pyrrolidone or gelatin. Suitable formulations for parenteral administration include aqueous solutions of the active compounds in water-soluble form, for example, water-soluble salts and alkaline solutions. In addition, suspensions of the active compounds as appropriate oily injection suspensions may be administered. Suitable lipophilic solvents or vehicles include fatty oils, for example, sesame oil, or synthetic fatty acid esters, for example, ethyl oleate or triglycerides or polyethylene glycol-400 (the compounds are soluble in PEG-400). Aqueous injection suspensions may contain substances, which increase the viscosity of the suspension, including, for example, sodium carboxymethyl cellulose, sorbitol, and / or dextran, optionally, the suspension may also contain stabilizers. Possible pharmaceutical preparations, which can be used rectally include, for example, suppositories, which consist of a combination of one or more of the active compounds with a suppository base. Suitable suppository bases are, for example, natural or synthetic triglycerides, or paraffin hydrocarbons. In addition, it is also possible to use gelatin rectal capsules, which consist of a combination of the active compounds with a base. Possible base materials include, for example, liquid triglycerides, polyethylene glycols, or paraffin hydrocarbons. The pharmaceutical preparations can be employed as medicaments in human and veterinary medicine. As used herein, the term "effective amount" means that amount of a drug or pharmaceutical agent that will elicit the biological or medical response of a tissue, system, animal or human that is being sought, for instance, by a researcher or clinician. Furthermore, the term also includes within its scope a "therapeutically effective amount" which means any amount which, as compared to a corresponding subject who has not received such amount, results in improved treatment, healing, prevention, or amelioration of a disease, disorder, or side effect, or a decrease in the rate of advancement of a disease or disorder, or of symptoms associated with such disease or disorder; it may also refer to preventing or providing prophylaxis for the disease or disorder in a subject having or at risk for developing a disease disclosed herein. The term also includes within its scope amounts effective to enhance normal physiological function. Said therapeutic effective amount of one or more of the compounds of the invention is known to the skilled artisan or can be easily determined by standard methods known in the art. "Treating" or “treatment” as used herein, means an alleviation, in whole or in part, of symptoms associated with a disorder or disease, or slowing, or halting of further progression or worsening of those symptoms, or prevention or prophylaxis of the disease or disorder in a subject at risk for developing the disease or disorder. The compounds of the present invention and the optional additional active substances are generally administered analogously to commercial preparations. Usually, suitable doses that are therapeutically effective lie in the range between 0.0005 mg and 1000 mg, preferably between 0.005 mg and 500 mg and especially between 0.5 mg and 100 mg per dose unit. The daily dose is preferably between about 0.001 mg / kg and 10 mg / kg of body weight. Those of skill will readily appreciate that dose levels can vary as a function of the specific compound, the severity of the symptoms and the susceptibility of the subject to side effects. Some of the specific compounds are more potent than others. Preferred dosages for a given compound are readily determinable by those of skill in the art by a variety of means. A preferred means is to measure the physiological potency of a given compound. The specific dose for the individual patient, in particular for the individual human patient, depends, however, on the multitude of factors, for example on the efficacy of the specific compounds employed, on the age, body weight, general state of health, the sex, the kind of diet, on the time and route of administration, on the excretion rate, the kind of administration and the dosage form to be administered, the pharmaceutical combination and severity of the particular disorder to which the therapy relates. The specific therapeutic effective dose for the individual patient can readily be determined by routine experimentation, for example by the doctor or physician, which advises or attends the therapeutic treatment. The compounds of the present invention can be prepared according to the procedures of the following Schemes and Examples, using appropriate materials, and as further exemplified by the following specific examples. They may also be prepared by methods known per se, as described in the literature, to be precise under reaction conditions which are known and suitable for the said reactions. Use can also be made of variants which are known per se, but are not mentioned here in greater detail. Likewise, the starting materials for the preparation of compounds of the present invention can be prepared by methods as described in the examples or by methods known per se, as described in the literature of synthetic organic chemistry and known to the skilled person, or can be obtained commercially. The starting materials for the processes claimed and / or utilized may, if desired, also be formed in situ by not isolating them from the reaction mixture, but instead immediately converting them further into the compounds of the invention or intermediate compounds. On the other hand, in general it is possible to carry out the reaction stepwise. It will be recognized by those skilled in the art that some of the compounds of formula I may serve as starting material for making other compounds of formula I. For instance, a compound of formula I bearing a carboxylic functional group may readily be converted into a related compound of formula I bearing an amide functional group by utilizing appropriate synthetic methods. Preferably, the reaction of the compounds is carried out in the presence of a suitable solvent, which is preferably inert under the respective reaction conditions. Examples of suitable solvents comprise but are not limited to hydrocarbons, such as hexane, petroleum ether, benzene, toluene or xylene; chlorinated hydrocarbons, such as trichlorethylene, 1,2-dichloroethane, tetrachloromethane, chloroform or dichloromethane; alcohols, such as methanol, ethanol, isopropanol, n-propanol, n-butanol or tert-butanol; ethers, such as diethyl ether, diisopropyl ether, tetrahydrofuran (THF) or dioxane; glycol ethers, such as ethylene glycol monomethyl or monoethyl ether or ethylene glycol dimethyl ether (diglyme); ketones, such as acetone or butanone; amides, such as acetamide, dimethylacetamide, dimethylformamide (DMF) or N-methyl pyrrolidinone (NMP); nitriles, such as acetonitrile; sulfoxides, such as dimethyl sulfoxide (DMSO); nitro compounds, such as nitromethane or nitrobenzene; esters, such as ethyl acetate, or mixtures of the said solvents or mixtures with water. The reaction temperature is between about -100°C and 300°C, depending on the reaction step and the conditions used. Reaction times are generally in the range between a fraction of a minute and several days, depending on the reactivity of the respective compounds and the respective reaction conditions. Suitable reaction times are readily determinable by methods known in the art, for example reaction monitoring. Based on the reaction temperatures given above, suitable reaction times generally lie in the range between 10 minutes and 48 hours. Moreover, by utilizing the procedures described herein, in conjunction with ordinary skills in the art, additional compounds of the present invention claimed herein can be readily prepared. The compounds illustrated in the examples are not, however, to be construed as forming the only genus that is considered as the invention. The examples further illustrate details for the preparation of the compounds of the present invention. Those skilled in the art will readily understand that known variations of the conditions and processes of the following preparative procedures can be used to prepare these compounds. The present invention also refers to a process for manufacturing a compound of formula I in its most general form as well as any of the particular embodiments, PE1, PE1a, PE1b, PE2, PE3, PE3a, PE3b PE4, PE5, PE5a, PE5aa, PE5b, PE5ba, PE6, PE6a, PE6aa, PE6aaa, PE6aaaa, PE7, PE7a, PE7aa, PE8, PE9, PE10, PE10a, PE11, PE11a, PE11aa, PE11aaa, PE12, PE13, PE13a, PE13aa, PE14, PE14a, PE14aa, PE15, PE15a, PE16, PE16a, and PE16aa described herein, or N-oxides, solvates, tautomers or stereoisomers thereof as well as the pharmaceutically acceptable salts of each of the foregoing, the process being characterized in that (A) in a first reaction step a compound of formula II II wherein R1, R3, and X1are defined as for formula I above or in any one of claims 1 to 25; Y1denotes H or a suitable protecting group, PG1; Hal1denotes Cl, Br, or I; is reacted under suitable C-C coupling reaction conditions with a compound of formula III Y2-A-L1-B III wherein A, L1, and B are defined as for formula I above or in any one of claims 1 to 25; Y2denotes a suitable boronate functional group; to provide a compound of formula IV

[0041] or (B) in a first reaction step a compound of formula V V wherein R1, R3, and X1are defined as for formula I above or in any one of claims 1 to 25; Y1denotes H or a suitable protecting group, PG1; Y3denotes a suitable boronate functional group; is reacted under suitable C-C coupling reaction conditions with a compound of formula VI Hal2-A-L1-B VI wherein A, L1, and B are defined as for formula I above or in any one of claims 1 to 25; Hal2denotes Cl, Br, or I; to provide a compound of formula IV; and, optionally, after step (A) or (B) (C) (1) if in formula IV above Y1denotes PG1, in a second reaction step PG1is removed under suitable reaction conditions to provide a compound of formula IV with Y1being H, which can also be described as a compound of formula I with R2being H; and / or (C) (2) if in formula IV above Y1denotes H, in another reaction step that compound of formula IV is reacted under suitable reaction conditions with a compound of formula VII R2-LG1VII wherein R2is defined as above or in any one of claims 1 to 25 with the exception of H; and LG1denotes a suitable leaving group; to provide a compound of formula I above or as defined in any one of claims 1 to 25; or (D) in a first reaction step a compound of formula VIII VIII wherein R1and R3are defined as for formula I above or in any one of claims 1 to 25; Y1denotes H or a suitable protecting group, PG1; Hal1denotes Cl, Br, or I; is reacted under suitable C-C coupling reaction conditions with a compound of formula III Y2-A-L1-B III wherein A, L1, and B are defined as for formula I above or in any one of claims 1 to 25; Y2denotes a suitable boronate functional group; to provide a compound of formula IX or (E) in a first reaction step a compound of formula X X wherein R1and R3are defined as for formula I above or in any one of claims 1 to 25; Y1denotes H or a suitable protecting group, PG1; Y3denotes a suitable boronate functional group; is reacted under suitable C-C coupling reaction conditions with a compound of formula VI Hal2-A-L1-B VI wherein A, L1, and B are defined as for formula I above or in any one of claims 1 to 25; Hal2denotes Cl, Br, or I; to provide a compound of formula IX; and, optionally, after step (D) or (E) (F) (1) if in formula IX above Y1denotes PG1, in a second reaction step PG1is removed under suitable reaction conditions to provide a compound of formula IX with Y1being H, which can also be described as a compound of formula I with R2being H; and / or (F) (2) if in formula IX above Y1denotes H, in another reaction step that compound of formula IX is reactied under suitable reaction conditions with a compound of formula VII R2-LG1VII wherein R2is defined as in any one of claims 1 to 25 with the exception of H; and LG1denotes a suitable leaving group; to provide a compound of formula I as defined above or in any one of claims 1 to 25. As will be understood by the person skilled in the art of organic synthesis compounds of the present invention, in particular compounds of formula I, are readily accessible by various synthetic routes, some of which are exemplified in the accompanying Experimental Part. The skilled artisan will easily recognize which kind of reagents and reactions conditions are to be used and how they are to be applied and adapted in any particular instance – wherever necessary or useful – in order to obtain the compounds of the present invention. Furthermore, some of the compounds of the present invention can readily be synthesized by reacting other compounds of the present invention under suitable conditions, for instance, by converting one particular functional group being present in a compound of the present invention, or a suitable precursor molecule thereof, into another one by applying standard synthetic methods, like reduction, oxidation, addition or substitution reactions; those methods are well known to the skilled person. Likewise, the skilled artisan will apply – whenever necessary or useful – synthetic protecting (or protective) groups; suitable protecting groups as well as methods for introducing and removing them are well-known to the person skilled in the art of chemical synthesis. In the following general synthetic routes that may be utilized to prepare compounds of the present invention are described in more detail in Schemes A to E below (unless indicated otherwise the various radicals and substituents depicted in the following Schemes have the same meaning as throughout the specification and the accompanying claims): The 1H-pyrrolo[3,2-b]pyridine derivative of formula A is in reaction step a treated with a suitable iodination reagent under appropriate reaction conditions (for instance, with NIS (N-iodo succinimide) in DMF at room temperature) to yield the respective iodo-substituted compound of formula B. In reaction b the compound of formula B is then converted into the compound of formula C by introducing a suitable protecting group, Y1, utilizing a suitable reagent bearing Y1under appropriate reaction conditions. For instance, the compound of formula B may be reacted with p-tolyl sulfonyl chloride (TsCl) in the presence of triethylamine and 4-dimethylaminopyrdine (DMAP) to provide the compound of formula C with Y1being p-tolylsulfonyl. Other suitable protecting groups would be, for instance, tert.-butyl carboxylate (-C(=O)-O-tert.-butyl), or triphenylmethyl (trityl). In the next reaction step, step c, the azaindole derivative of formula C is converted into the lactam derivative of formula D utilizing a suitable reagent to cleave the ether moiety in 2-position of the bicyclic ring system, e.g., hydrobromide in acetic acid. This is followed by alkylation of the lactam nitrogen (step d) using both a suitable base to deprotonate the lactam nitrogen and a suitable alkylating agent to yield alkylated bicyclic compound of formula E. A typical procedure would employ a strong lithium organic base like LiHMDS (lithium bis(trimethylsilyl)amide) in DMF and an alkyliodide like methyl iodide or ethyl iodide. The alkylated lactam derivative of formula E may then be converted (step e) into the functionalized bicyclic compound of formula F by replacing the iodine substituent with a suitable boronate, Y3, the introduction of which permits further transformation by C-C or C-N coupling reactions. For instance, to a solution of a compound of formula E in dioxane and triethylamine a suitable boronic acid reagent like 4,4,5,5-tetramethyl-1,3.2-dioxaborolane and a suitable organopalladium catalyst like Pd(PPh3)4 is added introducing the dioxaborolanyl moiety as functional group Y3into the compound of formula F. Both compounds of formula E and F may be utilized as intermediates for the synthesis of compounds of formula I of the present invention (see Schemes D and E below).

[0042] Scheme B Compounds of formula E (as depicted in Scheme A above) may alternatively synthesized according the general reaction Scheme B above: By reacting with p-tosyl chloride in triethylamine in the presence of catalytic amounts of DMAP the 1H-pyrrolo[3,2-b]pyridine derivative of formula A is transformed into the toyslated derivative of formula A-Ts (Ts = p-tolylsulfonyl) (reaction step f) which in turn is converted into the bicyclic compound of formula H utilizing a suitable reagent to cleave the ether moiety in 2-position, e.g., hydrobromide in acetic acid (step g). Subsequent alkylation (step h) utilizing both a suitable base and a suitable alkylating agent yields the alkylated bicyclic compound of formula J. A typical procedure would employ a strong lithium organic base like LiHMDS (lithium bis(trimethylsilyl)amide) in DMF and an alkyliodide like methyl iodide or ethyl iodide. The p-tosyl protecting group may then be removed by means of a suitable base (step j), e.g., by reacting compound J with sodium ethanolate in ethanol, to provide the bicyclic compound of formula K, which in turn may be reacted with an appropriate iodination reagent under suitable reaction conditions (step k), for instance, iodine and potassium hydroxide. Compound E may then be obtained by reacting compound K with a suitable reagent bearing protecting group Y1under appropriate reaction conditions. For instance, the compound of formula K may be reacted with p-tolyl sulfonyl chloride (TsCl) in the presence of triethylamine and DMAP to provide the compound of formula C with Y1being p-tolylsulfonyl. Scheme C Compounds of formulas S and T, which may be useful intermediates for making bicyclic compound of formula I with X1being N, are available via the synthetic route shown in Scheme C above. The chloro-substituted bicyclic compound of formula M is converted to the tosylated compound of formula N under similar reaction conditions described for Schemes A and B above (reaction step m). Replacing the chloro substituent by an hydroxy group is effected, for instance, by reacting the compound of formula N with K3PO4 in the presence of suitable organopalladium catalysts, e.g., Pd2dba3.CHCl3 (tris- (dibenzylideneacetone)dipalladium (0) and tBuBrettPhos (2-di-tert- butylphosphin-3,6-dimethoxy-2’,4’,6’-triisopropyl-1,1’-biphenyl)-2-(2’-amino- 1,1’-biphenyl) (step n), to yield compound P. Alkylation with a suitable alkylhalide in the presence of a strong base, e.g., methyliodine and LiHMDS (lithium bis(trimethylsilyl)amide), provides the lactam derivative of formula Q (step p). Removing the p-tosyl protecting group (step q) to provide compound R and subsequently reacting with an iodination reagent like NIS (step r) provides the bicyclic compound of formula S. The alkylated lactam derivative of formula S may then be converted (step s) into the functionalized bicyclic compound of formula T by introducing a suitable protecting group Y1under conditions similar to those described for reaction step b in Scheme A. Compound T may then be converted into a compound of formula U by replacing the iodine substituent with a suitable boronate, Y3, the introduction of which permits further transformation by C-C or C-N coupling reactions. The reagents and reaction conditions of step t may be similar to those of reaction step e in Scheme A. Scheme D Scheme D depicts a synthetic route for making certain compounds of the present invention of formula I starting from intermediate F (see Scheme A). Compound F bearing a boronate functional group Y3is reacted in reaction step u with a compound of formula W in which A, L1, and B are as defined for formula I and Hal3denotes Br or I, under typical reaction conditions of C-C cross-coupling reactions like the Suzuki coupling, for instance by reacting a compound of formula F with compound of formula W in the presence of sodium carbonate and Pd(dppf)Cl2-CH2Cl2 ([1,1'-Bis(diphenylphosphino)- ferrocene]palladium(II) dichloride). Compounds of formula W are readily available either from commercial sources or by methods well-known in the art. Reaction step u provides the compound of formula Z, the protecting group Y1of which may be cleaved of by standard methods depending on the specific nature of Y1to yield the bicyclic compound of formula AA. If, for instance, Y1is a p-tosyl group, it may be removed by utilizing sodium ethanolate in ethanol. Finally, compound AA is converted in reaction step w to compound CC by reacting it with the compound of formula BB, LG1-R2wherein LG1is a suitable leaving group and R2is as defined for formula I hereinabove. For instance, if LG1is a halogen selected from Cl, Br or I, then reaction step w may be a nucleophilic substitution reaction of the compound of formula AA with LG1-R2. Depending on the specific nature of LG1-R2this reaction step w may be performed by deprotonating the NH group utilizing a suitable base such as sodium hydride or cesium carbonate and subsequent reaction of the intermediate with a suitable compound of formula BB, e.g., an alkyliodide like CH3-I, a brominated compound like Br-CH2CN, or a chlorinated compound like chloromethylimidazole hydrochloride. Substituent R2of the compound of formula CC may further be modified to obtain further compounds of formula CC. It is to be noted that compounds of formulas AA and CC represent certain embodiments of compounds of the present invention of formula I. It should further be noted that compound of formula U may be converted into compounds of formula I with Ring D together with R2being D-1 and X1being N, i.e., compounds of formula I-B ) by utilizing areaction route similar to the one depicted in Scheme D. Alternatively, compounds of formula I may be obtained by first reacting a compound of formula E with a compound of Y3-A-L1-B, wherein A, L1, and B are as defined for formula I and Y3is a suitable boronate moiety, under typical C-C coupling reaction conditions (as described for reaction step u in Scheme D) to provide a compound of formula Z, which is then further converted into a compound of formula AA or CC as depicted in Scheme D above. It is a further alternative to react a compound of formula L (Scheme B) instead of formula E with a compound of formula Y3-A-L1-B under similar reaction conditions which provides a compound of formula AA directly. It will be understood that a similar reaction sequence could be applied to compounds of formula S or T (Scheme C) to eventually obtain compounds of formula I-B. It should further be noted that compounds of formula I with ring D together R2being D-2, i.e., compounds of formula I-C, are accessible from compounds of formula S in Scheme C above by performing reaction step s under suitable conditions so that besides the compound of formula T the respective regio- isomer of formula T-isomer ( ) is obtained andseparated from its isomer of formula T by appropriate means, e.g., column chromatography. That compound T-isomer may then further be converted into the compound of formula U-isomer ( ) under reactionconditions similar to reaction step t in Scheme C above. The compound of formula U-isomer may then be converted into compounds of formula I-C by utilizing a reaction route similar to the one depicted in Scheme D. Scheme E Scheme E depicts a synthetic procedure for making compounds of the present invention in which (in formula I) R3denotes halogen: A compound of formula CC in which R2is a suitable protecting group, e.g., a tosylate, is reacted in reaction step x with an appropriate halogenating agent under suitable reaction conditions to yield the respective halogenated compound of formula DD (with Hal being F, Cl, Br, or I). Such an appropriate halogenation reagent can be, for instance, a fluoronating reagent (Hal = F) like 1-chlormethyl-4-fluor-1,4- diazoniabicyclo[2.2.2]octan-bis(tetrafluorborat) (Selectfluor) in acetonitrile and water; or a iodinating reagent (Hal = Br) like N-iodosuccinimide (NIS) in dimethylformamide in the presence of an organic acid like trifluoroacetic acid. Reactions of compounds of formula CC with similar chlorinating or brominating reagents (like NCS or NBS) provide the respective compounds of formula DD with Hal = Cl and Br, respectively. Halogenated compounds of formula I with ring D being D-1 and X1being N (i.e., compounds of formula I-B) and R3being halogen can be prepared in a similar fashion starting with a compound of formula EE (with R2being a suitable protecting group, e.g., tosylate): . Likewise, compounds of formula I-C with R3being halogen can be prepared in a similar manner starting from a compound of formula FF ( It is to be noted that – except for instances where it is specifically stated or the context provides for a different meaning – in general the number of a term, i.e. its singular and plural form, is used and can be read interchangeably. For example, the term “compound” in its singular form may also comprise or refer to a plurality of compounds, while the term “compounds” in its plural form may also comprise or refer to a singular compound. Examples and Experimental Part The compounds of the present invention can be prepared according to the procedures of the following Schemes and Examples, using appropriate materials and are further exemplified by the following specific examples. The compounds are shown in Table 1 and Table 1a. Analytical data of compounds made according to the following examples are shown in Table 1 and Table 1a, too. The invention will be illustrated, but not limited, by reference to the specific embodiments described in the following examples. Unless otherwise indicated in the schemes, the variables have the same meaning as described above and in the claims. Unless otherwise specified, all starting materials are obtained from commercial suppliers and used without further purifications or are available by synthetic methods similar to those specifically described herein. Unless otherwise specified, all temperatures are expressed in °C and all reactions are conducted at room temperature (RT). Compounds are purified by either silica chromatography or preparative HPLC. Purity of reaction products which were used in subsequent reaction steps (intermediates) were usually confirmed by GC-MS (without further characterizing the intermediates).1H NMR:1H-NMR data is provided in Table 1 and Table 1a below.1H NMR spectra were usually acquired on a 300 MHz, 400 MHz, 500 MHz, or 700 MHz NMR spectrometers such as a Bruker Avance DRX 500, a Bruker Avance 400, a Bruker DPX 300 or a Bruker Avance III 700 MHz NMR spectrometer under standard conditions using TMS (tetramethylsilane) as internal reference and DMSO-d6 as standard solvents, if not reported otherwise. NS (Number of Scans): 32, SF (Spectrometer Frequency) as indicated. TE (Temperature): 297 K. Chemical shifts (δ) are reported in ppm relative to the TMS signal.1H NMR data are reported as follows: chemical shift (multiplicity, coupling constants and number of hydrogens). Multiplicity is abbreviated as follows: s (singlet), d (doublet), t (triplet), q (quartet), m (multiplet), dd (doublet of doublets), tt (triplet of triplets), td (triplet of doublets) br (broad) and coupling constants (J) are reported in Hz. LC-MS: LC-MS data provided in Table 1 and Table 1a are given with mass in m / z. The results can be obtained by one of the methods described below. Syntheses Intermediate 1: 4-methyl-1-(4-methylbenzenesulfonyl)-3-(4,4,5,5-tetramethyl- 1,3,2-dioxaborolan-2-yl)-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one Int 1.1: 3-iodo-5-methoxy-1H-pyrrolo[32-b]pyridine The solution of 5-methoxy-1H-pyrrolo[3,2-b]pyridine (10 g; 64.12 mmol) and NIS (18 g; 76 mmol) in DMF (100 mL) was stirred overnight at RT. After dilution with EtOAc (50 mL) the mixture was washed with brine. The combined organic layers were dried over Na2SO4, filtrated and concentrated under reduced pressure to afford the crude product (12 g; 42 %) as yellow liquid which was used without further purification. Int 1.2: 3-iodo-5-methoxy-1-(4-methylbenzenesulfonyl)-1H-pyrrolo[3,2- b]pyridine To a stirred solution of 3-iodo-5-methoxy-1H-pyrrolo[3,2-b]pyridine (30 g; 102 mmol) in DCM (500 mL) were added Et3N (45 mL) and DMAP (1.40 g; 10.89 mmol) at 0°C. To the resulting mixture was added 3-(3-hydroxypropoxy)- propan-1-ol (29 g; 205 mmol) overnight at RT. The reaction mixture was concentrated under vacuum and the residue was purified by chromatography to provide the product (51 g; 56 %) as brown solid. Int 1.3: 3-iodo-1-(4-methylbenzenesulfonyl)-1H,4H,5H-pyrrolo[3,2-b]pyridin-5- one

[0043] To a stirred solution of 3-iodo-5-methoxy-1-(4-methylbenzenesulfonyl)-1H- pyrrolo[3,2-b]pyridine (26 g; 58.61 mmol) in AcOH (300 mL) was added HBr in H2O (30 mL) at 25°C. The resulting mixture was stirred for 4 h at 80°C. The mixture was neutralized to pH 8 with NaHCO3 (aq). The precipitating solid was collected by filtration and washed with H2O. This resulted in the product (23 g; 87 %) as yellow solid. Int 1.4: 3-iodo-4-methyl-1-(4-methylbenzenesulfonyl)-1H,4H,5H-pyrrolo[3,2- b]pyridin-5-one To a stirred solution of 3-iodo-1-(4-methylbenzenesulfonyl)-1H,4H,5H- pyrrolo[3,2-b]pyridin-5-one (12 g; 26.67 mmol) in DMF (100 mL) was added LiHMDS (29 mL; 29.34 mmol) and CH3I (2.62 mL; 40 mmol) at 0°C. The resulting mixture was stirred for 1 h at 25°C under N2 atmosphere. After aqueous work-up the resulting mixture was extracted with EtOAc. The combined organic layers were washed with brine and dried over MgSO4. After filtration, the filtrate was concentrated under reduced pressure and the residue was purified by chromatography to afford the product (5.90 g; 43 %) as off- white solid. Int 1.5: 4-methyl-1-(4-methylbenzenesulfonyl)-3-(4,4,5,5-tetramethyl-1,3,2- dioxaborolan-2-yl)-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one To a stirred mixture of 3-iodo-4-methyl-1-(4-methylbenzenesulfonyl)- 1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (400 mg; 0.78 mmol) and 4,4,5,5- tetramethyl-1,3,2-dioxaborolane (210 mg; 1.56 mmol) in dioxane (10 mL) and TEA (3 mL) was added Pd(PPh3)4 (94.80 mg; 0.08 mmol) at 25°C. The resulting mixture was stirred for 2 h at 100°C under N2 atmosphere. The reaction mixture was concentrated under vacuum and the residue was purified by chromatography to provide the product (500 mg; 87 %) as brown oil. Intermediate 2: 4-ethyl-1-(4-methylbenzenesulfonyl)-3-(4,4,5,5-tetramethyl- 1,3,2-dioxaborolan-2-yl)-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one Int 2.1: 5-methoxy-1-(4-methylbenzenesulfonyl)-1H-pyrrolo[3,2-b]pyridine To a stirred solution of 5-methoxy-1H-pyrrolo[3,2-b]pyridine (10 g; 64.12 mmol) and TEA (28.14 mL) in DCM (100 mL) was added TsCl (1.5 g; 76.94 mmol) and DMAP (2.5 g; 19.23 mmol) at 25°C for 5 h. After concentration the residue was purified by chromatography to afford the product (18 g; 92 %) as brown semi solid. Int 2.2: 1-(4-methylbenzenesulfonyl)-1H-pyrrolo[3,2-b]pyridin-5-ol To a stirred solution of 5-methoxy-1-(4-methylbenzenesulfonyl)-1H- pyrrolo[3,2-b]pyridine (18 g; 58.95 mmol) in AcOH (100 mL) was added HBr in AcOH (10 mL) at 25°C. The resulting mixture was stirred for 3 h at 80°C and then concentrated under vacuum. The residue was basified to pH 7 with NaHCO3 (aq) and the precipitate was filtered and washed with H2O to give the product (17 g; 98 %) as brown-orange solid. Int 2.3: 4-ethyl-1-(4-methylbenzenesulfonyl)-1H,4H,5H-pyrrolo[3,2-b]pyridin- 5-one To a stirred solution of 1-(4-methylbenzenesulfonyl)-1H-pyrrolo[3,2-b]pyridin- 5-ol (17 g; 57.59 mmol) in DMF (150 mL) was added LiHMDS (53.16 mL; 69.11 mmol) and iodoethane (18.33 g; 115.18 mmol) at 0°C under N2 atmosphere. The resulting mixture was stirred for 2 h at 25°C and after the addition of H2O (100 mL) the resulting mixture was extracted with EtOAc. The combined organic layers were washed with brine and dried over MgSO4. After filtration, the filtrate was concentrated under reduced pressure and the residue was purified by chromatography to afford the product (12.50 g; 68 %) as brown powder. Int 2.4: 4-ethyl-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one

[0044] To a stirred solution of 4-ethyl-1-(4-methylbenzenesulfonyl)-1H,4H,5H- pyrrolo[3,2-b]pyridin-5-one (12.50 g; 39.01 mmol) in EtOH (150 mL) was added EtONa / EtOH (w / w 21%; 25.28 g; 78.01 mmol) at 25°C for 2 h. After the addition of H2O (100 mL) the resulting mixture was extracted with EtOAc. The combined organic layers were washed with brine and dried over anhydrous MgSO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by chromatography to afford the product (6 g; 89 %) as off-white solid. Int 2.5: 4-ethyl-3-iodo-1H4H5H-pyrrolo[32-b]pyridin-5-one To a stirred mixture of 4-ethyl-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (6 g; 34.59 mmol) in DMF (100 mL) was added KOH (8.16 g; 138.34 mmol) and I2 (9.24 g; 34.59 mmol) at 25°C for 1 h. H2O (100 mL) was added and the resulting mixture was extracted with EtOAc. The combined organic layers were washed with brine, dried over MgSO4, and concentrated under reduced pressure after filtration. This resulted in crude product (6.40 g; 63 %) as yellow solid which was used in the next step without further purification. Int 2.6: 4-ethyl-3-iodo-1-(4-methylbenzenesulfonyl)-1H,4H,5H-pyrrolo[3,2- b]pyridin-5-one

[0045] To a stirred mixture of 4-ethyl-3-iodo-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (6.40 g; 21.88 mmol) and TEA (9.60 mL; 65.63 mmol) in DCM (100 mL) was added TsCl (5.27 g; 26.25 mmol) and DMAP (1.41 g; 10.94 mmol) at 25°C for 2 h. The reaction mixture was concentrated under vacuum and the residue was purified by chromatography to afford the product (10.50 g; 97 %) as yellow solid. Int 2.7: 4-ethyl-1-(4-methylbenzenesulfonyl)-3-(4,4,5,5-tetramethyl-1,3,2- dioxaborolan-2-yl)-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one To a stirred mixture of 4-ethyl-3-iodo-1-(4-methylbenzenesulfonyl)-1H,4H,5H- pyrrolo[3,2-b]pyridin-5-one (5 g; 10.12 mmol) and TEA (10 mL) in dioxane (100 mL) was added 4,4,5,5-tetramethyl-1,3,2-dioxaborolane (2.64 g; 20.24 mmol) and Pd(PPh3)4 (1.23 g; 1.01 mmol) at 25°C. The resulting mixture was stirred for 2 h at 100°C under N2 atmosphere. The reaction mixture was concentrated under vacuum and the residue was purified by chromatography to afford the product (3.80 g; 83 %) as brown oil. Intermediate 3: 3-iodo-2,4-dimethyl-1-(4-methylbenzenesulfonyl)-1H,4H,5H- pyrrolo[3,2-b]pyridin-5-one esulfonyl)-1H-pyrrolo[3,2-b]pyridine The solution of 5-methoxy-1H-pyrrolo[3,2-b]pyridine (2 g; 12.82 mmol), TsCl (4 g; 19.93 mmol), TEA (2.50 mL; 17.09 mmol) and DMAP (100 mg; 0.78 mmol) in DCM (50 mL) was stirred overnight at RT. The reaction mixture was diluted with EtOAc and then washed with brine. The organic layer was dried over Na2SO4, filtrated and concentrated under reduced pressure. The residue was purified by chromatography to afford the product (800 mg; 20 %) as white solid. Int 3.2: 5-methoxy-2-methyl-1-(4-methylbenzenesulfonyl)-1H-pyrrolo[3,2- b]pyridine To a solution of 5-methoxy-1-(4-methylbenzenesulfonyl)-1H-pyrrolo[3,2- b]pyridine (150 mg; 0.47 mmol), TMEDA (0.16 mL; 1.05 mmol) in THF (2.50 mL) was added n-BuLi in hexane (0.27 mL; 0.68 mmol) at -78°C for 0.5 h. Then CH3I (0.10 mL; 1.53 mmol) was added dropwise and the mixture was warmed to RT for 2 h. After quenching with NH4Cl (aq.) the mixture was diluted with EtOAc and then washed with brine. The organic layer was dried over Na2SO4, filtrated and concentrated under reduced pressure. The residue was purified by chromatography to afford the product (80 mg; 52 %) as white solid. Int 3.3: 3-iodo-5-methoxy-2-methyl-1-(4-methylbenzenesulfonyl)-1H- The solution of 5-methoxy-2-methyl-1-(4-methylbenzenesulfonyl)-1H- pyrrolo[3,2-b]pyridine (6.50 g; 19.93 mmol) and NIS (9.30 g; 39.27 mmol) in DMF (10 mL) was stirred overnight at 80°C. The reaction was quenched by the addition of H2O at RT. The resulting mixture was extracted with EtOAc, and the combined organic layers were dried over Na2SO4. After filtration, the filtrate was concentrated under reduced pressure and the residue was purified by chromatography to afford the product (6.20 g; 65 %) as yellow brown solid. Int 3.4: 3-iodo-2-methyl-1-(4-methylbenzenesulfonyl)-1H,4H,5H-pyrrolo[3,2- b]pyridin-5-one The solution of 3-iodo-5-methoxy-2-methyl-1-(4-methylbenzenesulfonyl)-1H- pyrrolo[3,2-b]pyridine (2 g; 4.16 mmol) and HBr (1 mL) in AcOH (20 mL) was stirred for 1 h at 100°C under N2 atmosphere. The reaction was quenched by the addition of H2O at RT. The resulting mixture was extracted with EtOAc, and the combined organic layers were dried over Na2SO4. After filtration, the filtrate was concentrated under reduced pressure and the residue was purified by chromatography to afford the product (440 mg; 24 %) as yellow brown solid. Int 3.5: 3-iodo-2,4-dimethyl-1-(4-methylbenzenesulfonyl)-1H,4H,5H- pyrrolo[3,2-b]pyridin-5-one To a stirred mixture of 3-iodo-2-methyl-1-(4-methylbenzenesulfonyl)- 1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (1.05 g; 2.33 mmol) and LiHMDS (1 M in toluene, 3 mL) in DMF (5 mL) was added CH3I (378 µL) at 0°C under N2 atmosphere. The resulting mixture was stirred for 1 h at RT. The reaction was quenched by the addition of H2O at 0°C. The resulting mixture was extracted with EtOAc. The combined organic layers were dried over Na2SO4. After filtration, the filtrate was concentrated under reduced pressure and the residue was purified by chromatography to afford the product (340 mg; 29 %) as brown solid. Intermediate 4: 4-methyl-3-(trimethylstannyl)-1-(triphenylmethyl)-1H,4H,5H- pyrazolo[4,3-b]pyridin-5-one Int 4.1: 5-chloro-1-(4-methylbenzenesulfonyl)-1H-pyrazolo[4,3-b]pyridine To a stirred solution of 5-chloro-1H-pyrazolo[4,3-b]pyridine (10 g; 61.86 mmol) in DCM (200 mL) was added TsCl (14.90 g; 74.23 mmol), TEA (27.15 mL; 185.58 mmol) and DMAP (1.59 g; 12.37 mmol) for 4 h at RT under N2 atmosphere. After evaporation the residue was purified by chromatrography to afford the product (19.30 g; 97 %) as white solid. Int 4.2: 1-(4-methylbenzenesulfonyl)-1H-pyrazolo[4,3-b]pyridin-5-ol To a suspension of 5-chloro-1-(4-methylbenzenesulfonyl)-1H-pyrazolo[4,3- b]pyridine (19 g; 59.21 mmol) and K3PO4 (26 g; 116.37 mmol) in dioxane (400 mL) were added H2O (40 mL), Pd2dba3.CHCl3 (5.60 g; 5.36 mmol) and t- BuBrettPhos (6 g; 11.76 mmol) at RT under N2 atmosphere. Then the resulting mixture was stirred for 4 h at 100°C. After evaporation the residue was purified by chromatography to afford the product (16 g; 90 %) as yellow solid. Int 4.3: 4-methyl-1-(4-methylbenzenesulfonyl)-1H,4H,5H-pyrazolo[4,3- b]pyridin-5-one To a stirred solution of1-(4-methylbenzenesulfonyl)-1H-pyrazolo[4,3-b]pyridin- 5-ol (15.90 g; 52.76 mmol) in DMF (350 mL) was added CH3I (6.84 mL; 104.41 mmol) and LiHMDS (66 mL; 66 mmol) for 2 h at RT. After evaporation the residue was purified by chromatography to afford the product (10.80 g; 67 %) as yellow solid.

[0046] To a stirred solution of 4-methyl-1-(4-methylbenzenesulfonyl)-1H,4H,5H- pyrazolo[4,3-b]pyridin-5-one (4 g; 13.04 mmol) in THF (100 mL) was added TBAF in THF (1M, 16 mL; 16 mmol) at RT. Then the mixture was stirred for 4 h at 50°C. The mixture was concentrated under reduced pressure to afford the crude product (2.20 g; 97 %) as brown oil. Int 4.5: 3-iodo-4-methyl-1H4H5H-pyrazolo[43-b]pyridin-5-one To a stirred solution of 4-methyl-1H,4H,5H-pyrazolo[4,3-b]pyridin-5-one (2.20 g; 12.60 mmol) in DMF (50 mL) was added NIS (3.28 g; 13.85 mmol) at RT for 2 h. After evaporation the residue was purified by chromatography to afford the product (3 g; 74 %) as yellow solid. Int 4.6: 3-iodo-4-methyl-1-(triphenylmethyl)-1H,4H,5H-pyrazolo[4,3-b]pyridin- 5-one To a stirred solution of 3-iodo-4-methyl-1H,4H,5H-pyrazolo[4,3-b]pyridin-5- one (2 g; 6.18 mmol) in DMF (50 mL) was added NaH (370 mg; 9.25 mmol) at 0°C. (Chlorodiphenylmethyl)benzene (2.11 g; 7.42 mmol) was added after 30 min. The resulting mixture was stirred for 2 h at RT. After evaporation the residue was purified by chromatography to afford the product (2.30 g; 67 %) as yellow solid. Int 4.7: 4-methyl-3-(trimethylstannyl)-1-(triphenylmethyl)-1H,4H,5H- pyrazolo[4,3-b]pyridin-5-one To a stirred solution of 3-iodo-4-methyl-1-(triphenylmethyl)-1H,4H,5H- pyrazolo[4,3-b]pyridin-5-one (2.30 g; 4.14 mmol) in dioxane (40 mL) was added hexamethyldistannane (2.06 g; 6.22 mmol) and PdCl2(PPh3)2 (320 mg; 0.41 mmol) for 2 h at 100°C under N2 atmosphere. After evaporation the residue was purified by chromatography to afford the product (1.10 g; 46 %) as yellow solid. Intermediate 5: 4,4,5,5-tetramethyl-2-{3-methyl-5-[4-(trifluoromethyl)- phenoxy]phenyl}-1,3,2-dioxaborolane Int 5.1: 1-bromo-3-methyl-5-[4-(trifluoromethyl)phenoxy]benzene To a stirred mixture of 3-bromo-5-methylphenol (2.40 g; 12.19 mmol) and 1- fluoro-4-(trifluoromethyl)benzene (2.11 g; 12.19 mmol) in DMA (40 mL) was added K2CO3 (5.32 g; 36.57 mmol) at 120°C overnight. The reaction was quenched by the addition of H2O (120 mL) at RT. The resulting mixture was extracted with EtOAc. The combined organic layers were dried over Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by chromatography to provide the product (1.20 g; 30 %) as colorless liquid. Int 5.2: 4,4,5,5-tetramethyl-2-{3-methyl-5-[4-(trifluoromethyl)phenoxy]phenyl}- 1,3,2-dioxaborolane To a solution of 1-bromo-3-methyl-5-[4-(trifluoromethyl)phenoxy]benzene (100 mg; 0.30 mmol) and BPD (161 mg; 0.60 mmol) in dioxane (1 mL) were added AcOK (90 mg; 0.91 mmol) and Pd(dppf)Cl2.CH2Cl2 (26 mg; 0.03 mmol). After stirring for overnight at 100°C under N2 atmosphere, the resulting mixture was concentrated under reduced pressure. The residue was purified by chromatography to provide the product (30 mg; 26 %) as colorless oil. Intermediate 6: 4-chloro-2-methyl-6-[4-(trifluoromethyl)phenoxy]pyrimidine Int 6.1: 4-chloro-2-methyl-6-[4-(trifluoromethyl)phenoxy]pyrimidine To a stirred solution of 4,6-dichloro-2-methylpyrimidine (5 g; 29.75 mmol) and 4-(trifluoromethyl)phenol (4.90 g; 28.72 mmol) in DMSO (150 mL) were added K2CO3 (12.70 g; 87.30 mmol) at RT. Then the resulting mixture was stirred for 2 h at 50°C under N2 atmosphere. The reaction mixture was extracted with EtOAc. The organic layer was washed with brine and dried over Na2SO4. After filtration, the filtrate was concentrated under reduced pressure to afford the crude product (8.30 g; 79 %) as yellow oil which was used without further purification. Intermediate 7: 4,4,5,5-tetramethyl-2-(3-{[4-(trifluoromethyl)phenyl]methoxy}- phenyl)-1,3,2-dioxaborolane Int 7.1: 4,4,5,5-tetramethyl-2-(3-{[4-(trifluoromethyl)phenyl]methoxy}phenyl)- 1,3,2-dioxaborolane To a mixture of 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (2.20 g; 10 mmol,1-(chloromethyl)-4-(trifluoromethyl)benzene (2.93 g; 15.06 mmol) in DMF (50 mL) was added K2CO3 (4.18 g; 30.24 mmol) under N2 atmosphere for 16 h at 80°C under N2. The reaction was washed with H2O (100 mL) and extracted with EtOAc. The organic layer was dried with Na2SO4 and concentrated to give the crude product (3 g; 66 %) as yellow solid. Intermediate 8: 2-methyl-4-[4-(trifluoromethyl)phenoxy]-6-(trimethylstannyl)- pyrimidine Int 8.1: 2-methyl-4-[4-(trifluoromethyl)phenoxy]-6-(trimethylstannyl)pyrimidine To a stirred solution of 4-chloro-2-methyl-6-[4-(trifluoromethyl)- phenoxy]pyrimidine (Intermediate 6) (300 mg; 0.94 mmol) and Pd(PPh3)4 (99 mg; 0.08 mmol) in dioxane (6 mL) was added hexamethyldistannane (0.32 mL; 1.51 mmol) for 1 h at 100°C under N2 atmosphere. The resulting mixture was filtered, the filter cake was washed with EtOAc. The filtrate was concentrated under reduced pressure to afford the product (380 mg; 78 %) as brown dark oil which was used without further purification. Intermediate 9: 4-iodo-2-methyl-6-[4-(trifluoromethyl)phenoxy]pyrimidine Int 9.1: 4-iodo-2-methyl-6-[4-(trifluoromethyl)phenoxy]pyrimidine To a stirred solution of 4-chloro-2-methyl-6-[4-(trifluoromethyl)- phenoxy]pyrimidine (Intermediate 6) (4 g; 11.38 mmol) in HI (57% in H2O, 40 mL) was added NaI (400 mg; 2.54 mmol) for 2 h. The mixture was filtered, the filter cake was washed with DCM and the filtrate was concentrated under reduced pressure. The crude product (3.50 g; 66 %, brown oil) was used without further purification. Intermediate 10: 5-fluoro-4-iodo-2-methyl-6-{[(1r,4r)-4-(trifluoromethyl)cyclo- hexyl]oxy}pyrimidine Int 10.1: 4-chloro-5-fluoro-2-methyl-6-{[(1r,4r)-4-(trifluoromethyl)cyclohexyl]- oxy}pyrimidine To a stirred solution of 4,6-dichloro-5-fluoro-2-methylpyrimidine (1 g; 5.25 mmol) and (1r,4r)-4-(trifluoromethyl)cyclohexan-1-ol (0.90 g; 5.25 mmol) in THF (40 mL) was added KHMDS (6.20 mL; 6.20 mmol) at 0°C under N2 atmosphere. The mixture was stirred for 1 h at RT and then extracted with EtOAc. The combined organic layers were washed with brine and dried over Na2SO4. After filtration, the filtrate was concentrated under reduced pressure and the residue was purified by chromatography to afford the product (750 mg; 34 %) as colorless oil. Int 10.2: 5-fluoro-4-iodo-2-methyl-6-{[(1r,4r)-4-(trifluoromethyl)cyclohexyl]- oxy}pyrimidine To a stirred solution of 4-chloro-5-fluoro-2-methyl-6-{[(1r,4r)-4- (trifluoromethyl)cyclohexyl]oxy}pyrimidine (1.8 g; 5.16 mmol) in HI (57% in H2O, 20 mL) was added NaI (1 g; 6.34 mmol) overnight at RT. The reaction mixture was extracted with EtOAc, and the combined organic layers were washed with brine and dried over Na2SO4. After filtration, the filtrate was concentrated under reduced pressure and the residue was purified by chromatography to afford the product (1 g; 48 %) as brown oil. Intermediate 11: 1-bromo-3-chloro-5-{[(1r,4r)-4-(trifluoromethyl)cyclohexyl]- oxy}benzene Int 11.1: 1-bromo-3-chloro-5-{[(1r,4r)-4-(trifluoromethyl)cyclohexyl]oxy}- benzene To a stirred solution of (1r,4r)-4-(trifluoromethyl)cyclohexan-1-ol (1.61 g; 9.07 mmol) in DMA (40 mL) was added NaH (0.40 g; 9.98 mmol) at 0°C for 20 min under N2 atmosphere. 1-bromo-3-chloro-5-fluorobenzene (2 g; 9.07 mmol) was added and the reaction mixture was stirred for additional 3 h at 60°C. For work up the resulting mixture was extracted with EtOAc, and the organic layer was washed with brine and dried over MgSO4. After filtration, the filtrate was concentrated under reduced pressure and the residue was purified by chromatography to afford the product (2.60 g; 76 %) as clear colorless oil. Intermediate 12: 5-[(2-bromo-6-methylpyridin-4-yl)oxy]-2-(trifluoromethyl)- pyrimidine Int.12.1: 5-[(2,6-dibromopyridin-4-yl)oxy]-2-(trifluoromethyl)pyrimidine To 2-(trifluoromethyl)pyrimidin-5-ol (1 g; 6.09 mmol) in DMF (30 mL) was added NaH (0.49 g; 12.19 mmol) at 0°C for 30 min. Then 2,6-dibromo-4- nitropyridine (3.51 g; 12.19 mmol) in DMF was added dropwise. The mixture was stirred for additional 5 h at RT. The reaction was quenched by the addition of NH4Cl (aq.) at 0°C and the mixture was extracted with EtOAc. The combined organic layers were dried over Na2SO4. After filtration, the filtrate was concentrated under reduced pressure and the residue was purified by chromatography to afford the product (0.99 g; 41 %) as white solid. Int.12.2: 5-[(2-bromo-6-methylpyridin-4-yl)oxy]-2-(trifluoromethyl)pyrimidine To a solution of 5-[(2,6-dibromopyridin-4-yl)oxy]-2-(trifluoromethyl)pyrimidine (Int.12.1) (2.99 mg; 7.46 mmol) and trimethyl-1,3,5,2,4,6-trioxatriborinane (1.98 g; 14.99 mmol) in dioxane (45 mL) and H2O (9 mL) were added K2CO3 (2.72 g; 18.74 mmol) and Pd(PPh3)4 (912 mg; 0.75 mmol) for 16 h at 100°C under a N2 atmosphere. Then the mixture was extracted with EtOAc, and the combined organic layers were dried over Na2SO4. After filtration, the filtrate was concentrated under reduced pressure and the residue was purified by chromatography to afford the product (800 mg; 32 %) as light-yellow solid. Intermediate 13: 3-iodo-4-methyl-1-(4-methylbenzenesulfonyl)-1H,4H,5H- pyrazolo[4,3-b]pyridin-5-one Int.13.1: 3-iodo-4-methyl-1-(4-methylbenzenesulfonyl)-1H,4H,5H- pyrazolo[4,3-b]pyridin-5-one To a stirred solution of 3-iodo-4-methyl-1H,4H,5H-pyrazolo[4,3-b]pyridin-5- one (Int.4.6) (1 g; 3.37 mmol) and TEA (1.48 mL; 10.12 mmol) in DCM (20 mL) was added TsCl (744 mg; 3.71 mmol) and DMAP (44 mg; 0.34 mmol) at 25°C for 1 h under N2 atmosphere. The resulting mixture was concentrated under vacuum and the residue was purified by chromatography to afford the product (1.20 g; 68 %) as yellow solid. Example 1: 4-methyl-3-(3- (trifluoromethyl)phenyl]methoxy}phenyl)- 1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Compound No.2) Ex. 1.1: 4-methyl-3-(3-{[4-(trifluoromethyl)phenyl]methoxy}phenyl)-1H,4H,5H- pyrrolo[3,2-b]pyridin-5-one To a mixture of 4,4,5,5-tetramethyl-2-(3-{[4-(trifluoromethyl)phenyl]methoxy}- phenyl)-1,3,2-dioxaborolane (Intermediate 7) (400 mg; 0.88 mmol), 3-iodo-4- methyl-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (accessible by analogy with the procedures for the synthesis of Intermediate 2, Int.2.5) (200 mg; 0.58 mmol) and K2CO3 (242 mg; 1.75 mmol) in dioxane (16 mL) and H2O (4 mL) was added Pd(Amphos)Cl2 (41 mg; 0.06 mmol) for 4 h at 50°C under N2 atmosphere. H2O was separated and after evaporation the residue was purified by chromatography to give the product (127 mg; 54 %) as colorless solid. Example 2: 4-methyl-3-{3-methyl-5-[4-(trifluoromethyl)phenoxy]phenyl}- 1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Compound No.1) Ex.2.1: 4-methyl-3-{3-methyl-5-[4-(trifluoromethyl)phenoxy]phenyl}- 1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one To a mixture of 3-iodo-4-methyl-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (accessible by analogy with the procedures for the synthesis of Intermediate 2, Int.2.5) (200 mg; 0,58 mmol), 4,4,5,5-tetramethyl-2-{3-methyl-5-[4-(trifluoro- methyl)phenoxy]phenyl}-1,3,2-dioxaborolane (accessible by analogy with the procedures for the synthesis of Intermediate 7) (400 mg; 0.85 mmol) and K2CO3 (242 mg; 1.75 mmol) in dioxane (16 mL) and H2O (4 mL) was added Pd(Amphos)2Cl2 (41.3 mg; 0.06 mmol). The mixture was stirred at 50°C under N2 for 4 h. H2O was separated and after evaporation the residue was purified by chromatography to give the desired product (145 mg; 61 %) as white solid. midin-4- 4-yl}-1- (4-methylbenzenesulfonyl)-1H,4H,5H-p 3,2-b]pyridin-5-one

[0047] To a stirred solution of 4-chloro-2-methyl-6-[4-(trifluoromethyl)- phenoxy]pyrimidine (Intermediate 6) (96 mg; 0.27 mmol) and 4-methyl-1-(4- methylbenzenesulfonyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)- 1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Intermediate 1) (200 mg; 0.27 mmol) in dioxane (8 mL) and H2O (1 mL) were added Pd(PPh3)4 (33 mg; 0.03 mmol) and Na2CO3 (91 mg; 0.82 mmol) at RT. Then the resulting mixture was stirred for 3 h at 60°C under N2 atmosphere. The crude product was purified by chromatography to provide the product (38.30 mg; 25 %) as off-white solid. Ex.3.2: 4-methyl-3-{2-methyl-6-[4-(trifluoromethyl)phenoxy]pyrimidin-4-yl}- 1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Compound No.26) To 4-methyl-3-{2-methyl-6-[4-(trifluoromethyl)phenoxy]pyrimidin-4-yl}-1-(4- methylbenzenesulfonyl)-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Ex.3.1) (100 mg; 0.17 mmol) in EtOH (4 mL) were added EtONa / EtOH (w / w 21%) (114 mg; 0.35 mmol; 2.01 eq.) at RT for 30 min. Then reaction mixture was extracted with DCM and the combined organic layers were washed with brine and dried over Na2SO4. After filtration, the filtrate was concentrated under reduced pressure.The crude product was purified by chromatography to afford the product (21.8 mg, 31 %) as white solid. Example 4: 4-methyl-3-{6-methyl-4-[4-(trifluoromethyl)phenoxy]pyridin-2-yl}- 1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Compound No.28) Ex 4.1: 4-methyl-3-{6-methyl-4-[4-(trifluoromethyl)phenoxy]pyridin-2-yl}- 1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one To a stirred solution of 4-methyl-3-{6-methyl-4-[4-(trifluoromethyl)- phenoxy]pyridin-2-yl}-1-(4-methylbenzenesulfonyl)-1H,4H,5H-pyrrolo[3,2- b]pyridin-5-one (accessible by analogy with the procedures for the synthesis of Example 3) (220 mg; 0.33 mmol) in EtOH (4 mL) was added EtONa / EtOH (w / w 21%) (0.14 mL; 0.65 mmol) dropwise at RT for 1 h at RT. The resulting mixture was diluted with H2O (40 mL). The resulting mixture was extracted with EtOAc, and the combined organic layers were dried over Na2SO4. After filtration, the filtrate was concentrated under reduced pressure and the residue was purified by chromatography to afford the product (46.50 mg; 36 %) as white solid. Example 5: 4-methyl-3-(6-methyl-4-{[2-(trifluoromethyl)pyrimidin-5- yl]oxy}pyridin-2-yl)-1-(4-methylbenzenesulfonyl)-1H,4H,5H-pyrrolo[3,2- b]pyridin-5-one (Compound No.41) Ex.5.1: 4-methyl-3-(6-methyl-4-{[2-(trifluoromethyl)pyrimidin-5-yl]oxy}pyridin-2-yl)-1- (4-methylbenzenesulfonyl)-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one

[0048] To a solution of 4-methyl-1-(4-methylbenzenesulfonyl)-3-(4,4,5,5-tetramethyl- 1,3,2-dioxaborolan-2-yl)-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Example 3) (170 mg; 0.36 mmol) and 5-[(2-bromo-6-methylpyridin-4-yl)oxy]-2- (trifluoromethyl)pyrimidine (Intermediate 12.2) (183 mg; 0.55 mmol) in DME (3 mL) and H2O (0.60 mL) were added Na2CO3 (121.48 mg; 1.09 mmol) and Pd(PPh3)4 (44.15 mg; 0.04 mmol). After stirring for 16 h at 90°C under a N2 atmosphere, the resulting mixture was concentrated under reduced pressure. The residue was taken up in H2O and EtOAc and the aqueous phase was extracted with EtOAc. The combined organic layers were dried over Na2SO4. After filtration, the filtrate was concentrated under reduced pressure and the residue was purified by chromatography to give the product (35.50 mg; 18 %) as off-white solid. Example 6: 4-methyl-3-(6-methyl-4-{[2-(trifluoromethyl)pyrimidin-5- yl]oxy}pyridin-2-yl)-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Compound No.42 Ex.5.1: 4-methyl-3-(6-methyl-4-{[2-(trifluoromethyl)pyrimidin-5-yl]oxy}pyridin- 2-yl)-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one To a stirred solution of 4-methyl-3-(6-methyl-4-{[2-(trifluoromethyl)pyrimidin-5- yl]oxy}pyridin-2-yl)-1-(4-methylbenzenesulfonyl)-1H,4H,5H-pyrrolo[3,2- b]pyridin-5-one (Example 5, Ex.5.1) (136 mg; 0.16 mmol) in EtOH (2 mL) was added EtONa / EtOH (w / w 21%) (0.07 mL; 0.33 mmol) dropwise at RT. The resulting mixture was stirred for 1 h and then diluted with H2O (40 mL). After extraction with EtOAc the combined organic layers were dried over Na2SO4. After filtration, the filtrate was concentrated under reduced pressure and. the residue was purified by chromatography to give the product (33.70 mg; 51 %) as white solid. Example 7: 4-methyl-3-(3-methyl-5-{[2-(trifluoromethyl)pyrimidin-5- yl]oxy}phenyl)-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Compound No.5) Ex 7.1: 4-methyl-3-(3-methyl-5-{[2-(trifluoromethyl)pyrimidin-5-yl]oxy}phenyl)- 1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one To a stirred solution of 4-methyl-3-(3-methyl-5-{[2-(trifluoromethyl)pyrimidin-5- yl]oxy}phenyl)-1-(4-methylbenzenesulfonyl)-1H,4H,5H-pyrrolo[3,2-b]pyridin-5- one (accessible by analogy with the procedures for the synthesis of Example 3, Ex.3.1) (55 mg; 0.10 mmol) in EtOH (6 mL) was added EtONa / EtOH (w / w 21%) (0.04 mL; 0.20 mmol) for 1 h at RT. After removal of all volatilies in vacuum the residue was purified by chromatography to give the product (16.80 mg; 43 %) as off-white solid. Example 8: 4-methyl-3-(3-methyl-5-{[5-(trifluoromethyl)pyrazin-2- yl]oxy}phenyl)-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Compound No.8) Ex.8.1: 4-methyl-3-(3-methyl-5-{[5-(trifluoromethyl)pyrazin-2-yl]oxy}phenyl)- 1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one

[0049] To a stirred solution of 4-methyl-3-(3-methyl-5-{[5-(trifluoromethyl)pyrazin-2- yl]oxy}phenyl)-1-(4-methylbenzenesulfonyl)-1H,4H,5H-pyrrolo[3,2-b]pyridin-5- one (accessible by analogy with the procedures for the synthesis of Example 3, Ex.3.1) (100 mg; 0.16 mmol) in EtOH (10 mL) was added EtONa (43 mg; 0.61 mmol) for 1.5 h at RT. After removal of all volatilies in vacuum the residue was purified by chromatography to give the produce (13.10 mg; 21 %) as white solid. Example 9: 4-methyl-3-(3-methyl-5-{[6-(trifluoromethyl)pyridin-3- yl]oxy}phenyl)-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Compound No.9) Ex.9.1: To a stirred solution of 4-methyl-3-(3-methyl-5-{[6-(trifluoromethyl)pyridin-3- yl]oxy}phenyl)-1-(4-methylbenzenesulfonyl)-1H,4H,5H-pyrrolo[3,2-b]pyridin-5- one (accessible by analogy with the procedures for the synthesis of Example 3, Ex.3.1) (55 mg; 0.10 mmol) in EtOH (6 mL) was added EtONa / EtOH (w / w 21%) (0.04 mL; 0.20 mmol) for 1 h at RT. After removal of all volatilies in vacuum the residue was purified by chromatography to give the product (23.40 mg; 60 %) as light grey solid. zin-2- .31) Ex 10.1: 4-methyl-3-(6-methyl-4-{[5-(t zin-2-yl 2-yl)-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one To a stirred solution of 4-methyl-3-(6-methyl-4-{[5-(trifluoromethyl)pyrazin-2- yl]oxy}pyridin-2-yl)-1-(4-methylbenzenesulfonyl)-1H,4H,5H-pyrrolo[3,2- b]pyridin-5-one (accessible by analogy with the procedures for the synthesis of Example 3, Ex.3.1) (170 mg; 0.22 mmol) in THF (5 mL) and EtOH (2.50 mL) was added Cs2CO3 (75 mg; 0.22 mmol) for 2 h at 25°C under N2 atmosphere. After removal of all volatiles the residue was purified by chromatography to give the product (6.50 mg; 7 %) as off-white solid. Example 11: N-methyl-3-(4-methyl-3-{2-methyl-6-[4-(trifluoromethyl)- phenoxy]pyrimidin-4-yl}-5-oxo-1H,4H,5H-pyrrolo[3,2-b]pyridin-1- yl)propionamide (Compound No.53) Ex.11.1: N-methyl-3-(4-methyl-3-{2-methyl-6-[4-(trifluoromethyl)- phenoxy]pyrimidin-4-yl}-5-oxo-1H,4H,5H-pyrrolo[3,2-b]pyridin-1- yl)propionamide

[0050] stirred solution of 4-methyl-3-{2-methyl-6-[4-(trifluoromethyl)- phenoxy]pyrimidin-4-yl}-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Example 3, Ex.3.2) (80 mg; 0.19 mmol) in dioxane (5 mL) was added N-methylprop-2- enamide (280 mg; 3.224 mmol) and KOH (80 mg; 1.28 mmol) at RT under N2 atmosphere. The resulting mixture was stirred for 2 h and then extracted with EtOAc. The combined organic layers were washed with brine, dried over Na2SO4 and filtered. The filtrate was concentrated under reduced pressure and the crude product was purified by chromatography to provide the product (21.1 mg; 23 %) as white solid. Example 12: 1-[2-(3-hydroxypyrrolidin-1-yl)ethyl]-4-methyl-3-{2-methyl-6-[4- (trifluoromethyl)phenoxy]pyrimidin-4-yl}-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Compound No.55) Ex.12.1: 1-(2-bromoethyl)-4-methyl-3-{2-methyl-6-[4- (trifluoromethyl)phenoxy]pyrimidin-4-yl}-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one To a stirred mixture of 4-methyl-3-{2-methyl-6-[4-(trifluoromethyl)phenoxy]- pyrimidin-4-yl}-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Example 3, Ex.3.2) (200 mg; 0.49 mmol) and 1,2-dibromoethane (194 mg; 0.98 mmol) in DMF (8 mL) was added K2CO3 (143 mg; 0.98 mmol) at 25°C. The resulting mixture was stirred for 2 h at 70°C and then concentrated under vacuum. The residue was purified by chromatography, to provide the product (120 mg; 43 %) as beige solid. Ex 12.2: 1-[2-(3-hydroxypyrrolidin-1-yl)ethyl]-4-methyl-3-{2-methyl-6-[4- (trifluoromethyl)phenoxy]pyrimidin-4-yl}-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one To a stirred mixture of 1-(2-bromoethyl)-4-methyl-3-{2-methyl-6-[4- (trifluoromethyl)phenoxy]pyrimidin-4-yl}-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (100 mg; 0.17 mmol) and pyrrolidin-3-ol (24 mg; 0.26 mmol) in ACN (0.01 mL) were added K2CO3 (51 mg; 0.35 mmol) and NaI (14 mg; 0.09 mmol) at 25°C. The resulting mixture was stirred for 2 h at 70°C. After removal of all volatiles the crude product was purified by chromatography to afford the product (15.5 mg; 17 %) as white solid. Example 13: 1-{2-[imino(methyl)oxo-λ6-sulfanyl]ethyl}-4-methyl-3-{2-methyl-6- [4-(trifluoromethyl)phenoxy]pyrimidin-4-yl}-1H,4H,5H-pyrrolo[3,2-b]pyridin-5- one (Compound No.51) Ex.13.1: 4-methyl-3-{2-methyl-6-[4-(trifluoromethyl)phenoxy]pyrimidin-4-yl}- 1-[2-(methylsulfanyl)ethyl]-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one

[0051] To a stirred solution of 4-methyl-3-{2-methyl-6-[4-(trifluoromethyl)- phenoxy]pyrimidin-4-yl}-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Example 3, Ex.3.2 (150 mg; 0.32 mmol) in DMF (5 mL) was added NaH (33 mg; 0.83 mmol) at 0°C for 30 min under N2 atmosphere. Then NaI (24 mg; 0.15 mmol) and 1-chloro-2-(methylsulfanyl)ethane (260 mg; 2.23 mmol) were added. Stirring was continued for 2 h at RT. After aqueous work-up the mixture was extracted with EtOAc, and the combined organic layers were washed with brine and dried over Na2SO4. After filtration, the filtrate was concentrated under reduced pressure and the residue was purified by chromatography to provide the product (110 mg; 70 %) as purple solid. Ex.13.2: 1-{2-[imino(methyl)oxo-λ6-sulfanyl]ethyl}-4-methyl-3-{2-methyl-6-[4- (trifluoromethyl)phenoxy]pyrimidin-4-yl}-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one To a stirred solution of 4-methyl-3-{2-methyl-6-[4-(trifluoromethyl)phenoxy]- pyrimidin-4-yl}-1-[2-(methylsulfanyl)ethyl]-1H,4H,5H-pyrrolo[3,2-b]pyridin-5- one (90 mg; 0.18 mmol) in MeOH (5 mL) was added iodobenzene diacetate (169 mg; 0.50 mmol) and NH4OAc (25 mg; 0.31 mmol) for 1 h at RT under N2 atmosphere. After removal of all volatiles the crude product was purified by chromatography to afford the product (48 mg; 49 %) as off-white solid. Example 14: 1-(3-hydroxypropyl)-4-methyl-3-{2-methyl-6-[4- (trifluoromethyl)phenoxy]pyrimidin-4-yl}-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Compound No.50) Ex.14.1: 1-(3-hydroxypropyl)-4-methyl-3-{2-methyl-6-[4- (trifluoromethyl)phenoxy]pyrimidin-4-yl}-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one A mixture of 4-methyl-3-{2-methyl-6-[4-(trifluoromethyl)phenoxy]pyrimidin-4- yl}-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Example 3, Ex.3.2) (100 mg; 0.24 mmol) and K2CO3 (110 mg; 0.76 mmol) in DMF (10 mL) was stirred for 2 h at 100°C. Then the mixture was extracted with EtOAc, and the combined organic layers were washed with brine, dried over Na2SO4 and filtered. The filtrate was concentrated under reduced pressure and the residue was purified by chromatography to give the product (31.70 mg; 29 %) as white solid. Example 15: 1-(2-hydroxyethyl)-4-methyl-3-(6-methyl-4-{[2- (trifluoromethyl)pyrimidin-5-yl]oxy}pyridin-2-yl)-1H,4H,5H-pyrrolo[3,2- b]pyridin-5-one (Compound No.49) Ex.15.1: 1-(2-hydroxyethyl)-4-methyl-3-(6-methyl-4-{[2- (trifluoromethyl)pyrimidin-5-yl]oxy}pyridin-2-yl)-1H,4H,5H-pyrrolo[3,2- b]pyridin-5-one

[0052] To a stirred solution of 4-methyl-3-{6-methyl-4-[4-(trifluoromethyl)phenoxy]- pyridin-2-yl}-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Example 6) (90 mg; 0.22 mmol) and DBU (106 mg; 0.66 mmol) in DMF (2 mL) was added 1,3-dioxolan- 2-one (59 mg; 0.66 mmol) for 12 h at 70°C. After removal of all volatiles the crude product was purified by chromatography to give the produce (34.20 mg; 34 %) as white solid. Example 16: 6-iodo-4-methyl-3-{3-methyl-5-[4-(trifluoromethyl)phenoxy]- phenyl}-1-(4-methylbenzenesulfonyl)-1H,4H,5H-pyrrolo[3,2-b]pyridine-5-one (Compound No.35) Ex.16.1: 4-methyl-3-{3-methyl-5-[4-(trifluoromethyl)phenoxy]phenyl}-1-(4- methylbenzenesulfonyl)-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one To a stirred solution of 3-iodo-4-methyl-1-(4-methylbenzenesulfonyl)- 1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Int.1.4) (4.5 g; 10.30 mmol) in dioxane (32 mL) and H2O (8 mL) was added 4,4,5,5-tetramethyl-2-{3-methyl-5-[4- (trifluoromethyl)phenoxy]phenyl}-1,3,2-dioxaborolane (Int.5.2) (7 g; 16.66 mmol), PdAMPHOS (0.5 g; 0.67 mmol) and K2CO3 (4.5 g; 31 mmol) at RT under N2 atmosphere. The mixture was irradiated with microwave radiation for 1 h at 110°C. The resulting mixture was extracted with EtOAc, and the combined organic layers were washed with brine and dried over Na2SO4. After filtration, the filtrate was concentrated under reduced pressure and the residue was purified by chromatography to afford the product (1.3 g; 23 %) as pink solid. Ex.16.2: 6-iodo-4-methyl-3-{3-methyl-5-[4-(trifluoromethyl)phenoxy]phenyl}- 1-(4-methylbenzenesulfonyl)-1H,4H,5H-pyrrolo[3,2-b]pyridine-5-one To a stirred solution of 4-methyl-3-{3-methyl-5-[4-(trifluoromethyl)- phenoxy]phenyl}-1-(4-methylbenzenesulfonyl)-1H,4H,5H-pyrrolo[3,2-b]- pyridin-5-one (Ex.16.1) (100 mg; 0.172 mmol) in DMF (5 mL) was added NIS (80 mg; 0.338 mmol) and TFA (30 mg; 0.250 mmol) at RT under N2 atmosphere for 2 h. After work-up with NaHCO3 solution the resulting mixture was extracted with EtOAc, and the combined organic layers were washed with brine and dried over Na2SO4. After evaporation the residue was purified by chromatography to give the produce (16 mg; 13 %) as pink solid. Example 17: 6-iodo-4-methyl-3-{3-methyl-5-[4-(trifluoromethyl)- phenoxy]phenyl}-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Compound No.48) Ex.17.1: 6-iodo-4-methyl-3-{3-methyl-5-[4-(trifluoromethyl)phenoxy]phenyl}- 1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one

[0053] To a stirred solution of 6-iodo-4-methyl-3-{3-methyl-5-[4-(trifluoromethyl)- phenoxy]phenyl}-1-(4-methylbenzenesulfonyl)-1H,4H,5H-pyrrolo[3,2- b]pyridin-5-one (Example 16) (100 mg; 0.146 mmol) in EtOH (10 mL) was added EtONa / EtOH (w / w 21%) (0.067 mL; 0.309 mmol) at RT under N2 atmosphere for 2 h. After aqueous work-up the resulting mixture was extracted with EtOAc, and the combined organic layers were washed with brine and dried over Na2SO4. After filtration, the filtrate was concentrated under reduced pressure and the crude product was purified by chromatography to give the product (29.6 mg; 39 %) as white solid. Example 18: 3-(4-methyl-3-{2-methyl-6-[4-(trifluoromethyl)phenoxy]pyrimidin- 4-yl}-5-oxo-1H,4H,5H-pyrrolo[3,2-b]pyridin-1-yl)propanenitrile (Compound No.46) Ex.18.1: 3-(4-methyl-3-{2-methyl-6-[4-(trifluoromethyl)phenoxy]pyrimidin-4- yl}-5-oxo-1H4H5H-pyrrolo[32-b]pyridin-1-yl)propanenitrile To a stirred solution of 4-methyl-3-{2-methyl-6-[4-(trifluoromethyl)phenoxy]- pyrimidin-4-yl}-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Example 3, Ex.3.2) (80 mg; 0.19 mmol) in dioxane (8 mL) was added prop-2-enenitrile (0.124 mL; 1.866 mmol) and KOH (30 mg; 0.481 mmol) at 0°C under N2 atmosphere. The resulting mixture was stirred for 2 h at 50°C. After aqueous work-up the resulting mixture was extracted with EtOAc, and the combined organic layers were washed with brine and dried over Na2SO4. After filtration, the filtrate was concentrated under reduced pressure and the crude product was purified by chromatography to give the product (26.4 mg; 31 %) as white solid. Example 19: 2-(4-methyl-3-{2-methyl-6-[4-(trifluoromethyl)phenoxy]pyrimidin- 4- 5-oxo-1H,4H,5H-pyrrolo[3,2-b]pyridin-1-yl)acetonitrile (Compound No.45) Ex.19.1: 2-(4-methyl-3-{2-methyl-6-[4-(trifluoromethyl)phenoxy]pyrimidin-4- yl}-5-oxo-1H,4H,5H-pyrrolo[3,2-b]pyridin-1-yl)acetonitrile To a stirred solution of 4-methyl-3-{2-methyl-6-[4-(trifluoromethyl)- phenoxy]pyrimidin-4-yl}-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Example 3, Ex.3.2) (100 mg; 0.24 mmol) and 2-bromoacetonitrile (152 mg; 1.20 mmol) in DMF (10 mL) was added Cs2CO3 (238 mg; 0.72 mmol) for 4 h at 100°C. The reaction mixture was concentrated under vacuum and the residue was purified by chromatography to give the product (43.40 mg; 40 %) as white solid. Example 20: 4-methyl-3-{2-methyl-6-[4-(trifluoromethyl)phenoxy]pyrimidin-4- yl}-1-[2-(morpholin-4-yl)ethyl]-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Compound No.44) Ex.20.1: 4-methyl-3-{2-methyl-6-[4-(trifluoromethyl)phenoxy]pyrimidin-4-yl}- 1-[2-(morpholin-4-yl)ethyl]-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one

[0054] To a stirred mixture of 4-methyl-3-{2-methyl-6-[4-(trifluoromethyl)- phenoxy]pyrimidin-4-yl}-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Example 3, Ex.3.2 ) (100 mg; 0.24 mmol) and 4-(2-chloroethyl)morpholine hydrochloride (71 mg; 0.36 mmol) in ACN (10 mL) was added K2CO3 (70 mg; 0.48 mmol) at 25°C and the reaction was stirred for 2 h at 85°C. After removal of all volatiles the residue was purified by chromatography to give the product (53.50 mg; 43 %) as white solid. Example 21: 3-(4-methyl-3-{2-methyl-6-[4-(trifluoromethyl)phenoxy]pyrimidin- 4-yl}-5-oxo-1H,4H,5H-pyrrolo[3,2-b]pyridin-1-yl)propenamide (Compound No.43) Ex.21.1: 3-(4-methyl-3-{2-methyl-6-[4-(trifluoromethyl)phenoxy]pyrimidin-4- yl}-5-oxo-1H,4H,5H-pyrrolo[3,2-b]pyridin-1-yl)propenamide To a stirred solution of 4-methyl-3-{2-methyl-6-[4-(trifluoromethyl)- phenoxy]pyrimidin-4-yl}-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Example 3, Ex.3.2) (80 mg; 0.17 mmol) in dioxane (8 mL) was added prop-2-enamide (200 mg; 2.76 mmol) and KOH (30 mg; 0.48 mmol) at 0°C under N2 atmosphere. The resulting mixture was stirred for 2 h at 50°C. After aqueous work up the mixture was extracted with EtOAc. The combined organic layers were washed with brine and dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by chromatography to give the product (26 mg; 32 %) as white solid. Example 22: N-methyl-2-(4-methyl-3-{2-methyl-6-[4-(trifluoromethyl)- phenoxy]pyrimidin-4-yl}-5-oxo-1H,4H,5H-pyrrolo[3,2-b]pyridin-1-yl)acetamide (Compound No.40) Ex.22.1: N-methyl-2-(4-methyl-3-{2-methyl-6-[4-(trifluoromethyl)- phenoxy]pyrimidin-4-yl}-5-oxo-1H,4H,5H-pyrrolo[3,2-b]pyridin-1-yl)acetamide A mixture of 4-methyl-3-{2-methyl-6-[4-(trifluoromethyl)phenoxy]pyrimidin-4- yl}-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Example 3, Ex.3.2) (80 mg; 0.19 mmol) and K2CO3 (88 mg; 0.60 mmol) in DMF (5 mL) was stirred for 2 h at 100°C. After aqueous work-up the resulting mixture was extracted with EtOAc. The combined organic layers were washed with brine and dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by chromatography to afford the product (54.10 mg; 60 %) as white solid. Example 23: 2-(4-methyl-3-{2-methyl-6-[4-(trifluoromethyl)phenoxy]pyrimidin- 4-yl}-5-oxo-1H,4H,5H-pyrrolo[3,2-b]pyridin-1-yl)acetamide (Compound No.39) Ex.23.1: 2-(4-methyl-3-{2-methyl-6-[4-(trifluoromethyl)phenoxy]pyrimidin-4- yl}-5-oxo-1H,4H,5H-pyrrolo[3,2-b]pyridin-1-yl)acetamide

[0055] To a stirred solution of 4-methyl-3-{2-methyl-6-[4-(trifluoromethyl)- phenoxy]pyrimidin-4-yl}-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Example 3, Ex.3.2.) (80 mg; 0.19 mmol) in DMF (8 mL) was added Cs2CO3 (160 mg; 0.47 mmol), NaI (32 mg; 0.20 mmol) and 2-chloroacetamide (90 mg; 0.91 mmol) at RT under N2 atmosphere. The resulting mixture was stirred for 2 h at 100°C. After aqueous work-up the resulting mixture was concentrated under reduced pressure. The combined organic layers were washed with brine and dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by chromatography to give the product (20.9 mg; 25 %) as white solid. Example 24: 1-(2-hydroxyethyl)-4-methyl-3-{2-methyl-6-[4-(trifluoromethyl)- phenoxy]pyrimidin-4-yl}-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Compound No.37) Ex.24.1: 1-(2-hydroxyethyl)-4-methyl-3-{2-methyl-6-[4-(trifluoromethyl)- phenoxy]pyrimidin-4-yl}-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one To a stirred solution of 4-methyl-3-{2-methyl-6-[4-(trifluoromethyl)- phenoxy]pyrimidin-4-yl}-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (100 mg; 0.25 mmol) and 1,3-dioxolan-2-one (110 mg; 1.24 mmol) in DMF (10 mL) was added DBU (118 mg; 0.74 mmol) at RT and the resulting mixture was stirred for 4 h at 90°C. The resulting mixture was concentrated under vacuum. The residue was purified by chromatography to provide the product (20.80 mg; 19 %) as white solid. Example 25: 1-[2-(3-hydroxypyrrolidin-1-yl)ethyl]-4-methyl-3-{3-methyl-5-[4- (trifluoromethyl)phenoxy]phenyl}-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Compound No.33) Ex.25.1: 1-[2-(3-hydroxypyrrolidin-1-yl)ethyl]-4-methyl-3-{3-methyl-5-[4- (trifluoromethyl)phenoxy]phenyl}-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one To a stirred solution of 1-(2-bromoethyl)-4-methyl-3-{3-methyl-5-[4- (trifluoromethyl)phenoxy]phenyl}-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (accessible in analogy to Example 12, Ex.12.1 starting from Example 2, Ex.2.1 and 1,2-dibromoethane) (130 mg; 0.15 mmol) and pyrrolidin-3-ol (1.60 mg; 0.02 mmol) in ACN (5 mL) were added K2CO3 (64 mg; 0.44 mmol) and NaI (5 mg; 0.03 mmol) at RT. Then the resulting mixture was stirred for 2 h at 80°C. After evaporation the residue was purified by chromatography to afford the product (21.20 mg; 28 %) as white solid. Example 26: 1-(2-hydroxyethyl)-4-methyl-3-{6-methyl-4-[4- (trifluoromethyl)phenoxy]pyridin-2-yl}-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Compound No.29) Ex.26.1: 1-(2-hydroxyethyl)-4-methyl-3-{6-methyl-4-[4- (trifluoromethyl)phenoxy]pyridin-2-yl}-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one

[0056] To a stirred solution of 4-methyl-3-{6-methyl-4-[4-(trifluoromethyl)- phenoxy]pyridin-2-yl}-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Example 4, Ex.4.1) (90 mg; 0.22 mmol) and DBU (106 mg; 0.66 mmol) in DMF (2 mL) was added 1,3-dioxolan-2-one (59 mg; 0.66 mmol) for 5 h at 90°C. After evaporation the crude product was purified by chromatography to afford the product (59.60 mg; 61 %) as white solid. Example 27: 4-methyl-3-{2-methyl-6-[4-(trifluoromethyl)phenoxy]pyrimidin-4- yl}-1-(3-methylpyrazin-2-yl)-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Compound No.27) Ex.27.1: 4-methyl-3-{2-methyl-6-[4-(trifluoromethyl)phenoxy]pyrimidin-4-yl}- 1-(3-methylpyrazin-2-yl)-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one To a stirred solution of 4-methyl-3-{2-methyl-6-[4-(trifluoromethyl)phenoxy]- pyrimidin-4-yl}-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Example 3, Ex.3.2) (100 mg; 0.25 mmol) and 2-bromo-3-methylpyrazine (43 mg; 0.24 mmol) in dioxane (10 mL) were added (1R,2R)-cyclohexane-1,2-diamine (6 mg; 0.05 mmol), K3PO4 (158 mg; 0.71 mmol) and CuI (10 mg; 0.05 mmol) at RT for 2 h at 100°C under N2 atmosphere. After evaporation the residue was purified by chromatography to afford the product (27.50 mg; 22 %) as white solid. yl-5-[4- Ex.28.1: 4-methyl-1-[(1-methyl-1H-pyrazol-4-yl)methyl]-3-{3-methyl-5-[4- (trifluoromethyl)phenoxy]phenyl}-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one To a stirred solution of 4-methyl-3-{3-methyl-5-[4-(trifluoromethyl)- phenoxy]phenyl}-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Example 2, Ex.2.1) (60 mg; 0.15 mmol) and 4-(bromomethyl)-1-methyl-1H-pyrazole hydrobromide (76.32 mg; 0.30 mmol) and Cs2CO3 (256 mg; 0.75 mmol) in DMF (5 mL) was added NaI (23.53 mg; 0.15 mmol) for 16 h at 100°C under N2 atmosphere. The resulting mixture was diluted with H2O (20 mL) and extracted with EtOAc. The combined organic layers were washed with brine and dried over anhydrous Na2SO4. After concentration under reduced pressure the residue was purified by chromatography to provide the product (23.20 mg; 30 %) as brown solid. N-methyl-3-(4-methyl-3-{3-methyl-5-[4-(trifluoromethyl)- (Compound No.23) Ex.29.1: N-methyl-3-(4-methyl-3-{3-methyl-5-[4-(trifluoromethyl)- phenoxy]phenyl}-5-oxo-1H,4H,5H-pyrrolo[3,2-b]pyridin-1-yl)propanamide To a stirred solution of 4-methyl-3-{3-methyl-5-[4-(trifluoromethyl)phenoxy]- phenyl}-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Example 2, Ex.2.1) (80 mg; 0.171 mmol) in dioxane (8 mL) was added KOH (24 mg; 0.39 mmol) and N- methylprop-2-enamide (120 mg; 1.38 mmol) at RT under N2 atmosphere. The resulting mixture was stirred for 2 h at 50°C and then concentrated under reduced pressure. The residue was taken up in H2O and EtOAc followed by extraction with EtOAc. The combined organic layers were washed with brine and dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by chromatography to afford the product (21.6 mg; 26 %) as pink solid. Example 30: 1-[2-(4-methyl-3-{3-methyl-5-[4-(trifluoromethyl)phenoxy]- phenyl}-5-oxo-1H,4H,5H-pyrrolo[3,2-b]pyridin-1-yl)ethyl]pyrrolidin-2-one (Compound No.21) Ex.30.1: 1-[2-(4-methyl-3-{3-methyl-5-[4-(trifluoromethyl)phenoxy]phenyl}-5- oxo-1H,4H,5H-pyrrolo[3,2-b]pyridin-1-yl)ethyl]pyrrolidin-2-one A mixture of 4-methyl-3-{3-methyl-5-[4-(trifluoromethyl)phenoxy]phenyl}- 1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Example 2, Ex.2.1) (100 mg; 0.24 mmol), 1-(2-bromoethyl)pyrrolidine-2-one (50 mg; 0.25 mmol), NaH (20 mg; 0.50 mmol) in DMF (2 mL) was stirred for 4 h at 80°C. After aqueous work-up the resulting mixture was extracted with EtOAc. The combined organic layers were washed with brine and dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by chromatography to provide the product (14.50 mg; 11 %) as white semi solid. Example 31: 1-{2-[imino(methyl)oxo-λ6-sulfanyl]ethyl}-4-methyl-3-{3-methyl-5- [4-(trifluoromethyl)phenoxy]phenyl}-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Compound No.20) Ex.31.1: 1-{2-[imino(methyl)oxo- λ6-sulfanyl]ethyl}-4-methyl-3-{3-methyl-5-[4- (trifluoromethyl)phenoxy]phenyl}-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one To a stirred solution of 4-methyl-3-{3-methyl-5-[4-(trifluoromethyl)phenoxy]- phenyl}-1-[2-(methylsulfanyl)ethyl]-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (accessible in analogy to Example 13, Ex¨13.1 starting from Example 2, Ex.2.1 and 1-chloro-2-(methylsulfanyl)ethane) (200 mg; 0.41 mmol) in MeOH (5 mL) was added iodobenzene diacetate (340 mg; 1 mmol) and NH4OAc (49 mg; 0.60 mmol) at RT for 2 h under N2 atmosphere. After evaporation the crude product was purified by chromatography to afford the product (69.40 mg; 34 %) as off-white solid. Example 32: 1-[(3R,4S)-4-hydroxyoxolan-3-yl]-4-methyl-3-{3-methyl-5-[4- (trifluoromethyl)phenoxy]phenyl}-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Compound No.19) and 1-[(3S,4R)-4-hydroxyoxolan-3-yl]-4-methyl-3-{3-methyl-5-[4- (trifluoromethyl)phenoxy]phenyl}-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Compound No.22) Ex.32.1: racemic mixture of trans-isomers of 1-(4-hydroxyoxolan-3-yl)-4- methyl-3-{3-methyl-5-[4-(trifluoromethyl)phenoxy]phenyl}-1H,4H,5H- pyrrolo[3,2-b]pyridin-5-one

[0057] To a stirred mixture of 4-methyl-3-{3-methyl-5-[4-(trifluoromethyl)phenoxy]- phenyl}-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Example 2, Ex.2.1) (150 mg; 0.37 mmol) and K2CO3 (110 mg; 0.76 mmol) in DMF (10 mL) was added 3,6- dioxabicyclo[3.1.0]hexane (170 mg; 1.88 mmol) at 25°C. The resulting mixture was stirred for 6 h at 120°C and then concentrated under vacuum. The residue was purified by chromatography to afford the product (80 mg; 44 %) as white solid. Ex.32.2: 1-[(3R,4S)-4-hydroxyoxolan-3-yl]-4-methyl-3-{3-methyl-5-[4- (trifluoromethyl)phenoxy]phenyl}-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one and 1-[(3S,4R)-4-hydroxyoxolan-3-yl]-4-methyl-3-{3-methyl-5-[4- (trifluoromethyl)phenoxy]phenyl}-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one

[0058] The racemic mixture of trans-isomers of 1-(4-hydroxyoxolan-3-yl)-4-methyl-3- {3-methyl-5-[4-(trifluoromethyl)phenoxy]phenyl}-1H,4H,5H-pyrrolo[3,2- b]pyridin-5-one (Ex.32.1) (80 mg; 0.16 mmol) was purified by chromatography: CHIRALPAK IG-3, 4.6*50mm, 3μm; Mobile Phase A: Hex(0.1%DEA): EtOH=75: 25; Flow rate: 1 mL / min; Gradient: 0% B to 0% B; Injection Volume: 5 µL to afford 1-[(3R,4S)-4-hydroxyoxolan-3-yl]-4-methyl-3- {3-methyl-5-[4-(trifluoromethyl)phenoxy]phenyl}-1H,4H,5H-pyrrolo[3,2- b]pyridin-5-one (27.70 mg; 35 %) as white solid and 1-[(3S,4R)-4- hydroxyoxolan-3-yl]-4-methyl-3-{3-methyl-5-[4-(trifluoromethyl)phenoxy]- phenyl}-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (31.50 mg; 40 %) as white solid. The absolute configurations were assigned arbitrarily to the fractions. Example 33: 2-(4-methyl-3-{3-methyl-5-[4-(trifluoromethyl)phenoxy]phenyl}-5- oxo-1H,4H,5H-pyrrolo[3,2-b]pyridin-1-yl)acetonitrile (Compound No.18) Ex.33.1: 2-(4-methyl-3-{3-methyl-5-[4-(trifluoromethyl)phenoxy]phenyl}-5- oxo-1H,4H,5H-pyrrolo[3,2-b]pyridin-1-yl)acetonitrile To a stirred solution of 4-methyl-3-{3-methyl-5-[4-(trifluoromethyl)- phenoxy]phenyl}-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Example 2, Ex.2.1) (120 mg; 0.26 mmol) in DMF (10 mL) was added NaH (40 mg; 1 mmol) at 0°C under N2 atmosphere. After 15 min, 2-chloroacetonitrile (120 mg; 1.6 mmol) was added and the mixture was stirred for 3 h at 100°C. After aqueous work- up the resulting mixture was extracted with EtOAc. The combined organic layers were washed with brine and dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by chromatography to afford the product (68.4 mg; 61 %) as off- white. Example 34: 1-[(1H-imidazol-4-yl)methyl]-4-methyl-3-{3-methyl-5-[4- (trifluoromethyl)phenoxy]phenyl}-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Compound No.17) Ex.34.1: 1-[(1H-imidazol-4-yl)methyl]-4-methyl-3-{3-methyl-5-[4- (trifluoromethyl)phenoxy]phenyl}-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one To a stirred solution of 4-methyl-3-{3-methyl-5-[4-(trifluoromethyl)- phenoxy]phenyl}-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Example 2, Ex.2.1) (100 mg; 0.25 mmol) in DMF (3 mL) was added NaH (30 mg; 0.75 mmol). The resulting mixture was stirred for 10 min at 0°C under N2 atmosphere and then were added 4-(chloromethyl)-1H-imidazole hydrochloride (58 mg; 0.36 mmol) and TBAI (9 mg; 0.02 mmol) in portions. The resulting mixture was stirred overnight at 120°C and then diluted with H2O and extracted with EtOAc. The combined organic layers were washed with brine and dried over anhydrous Na2SO4. After filtration and concentration under reduced pressure, the residue was purified by chromatography to afford the product (13.80 mg; 12 %) as white solid. Example 35: 4-methyl-3-{3-methyl-5-[4-(trifluoromethyl)phenoxy]phenyl}-1-[2- (morpholin-4-yl)ethyl]-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Compound No.16) Ex.35.1: 4-methyl-3-{3-methyl-5-[4-(trifluoromethyl)phenoxy]phenyl}-1-[2- (morpholin-4-yl)ethyl]-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one A mixture of 4-methyl-3-{3-methyl-5-[4-(trifluoromethyl)phenoxy]phenyl}- 1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Example 2, Ex.2.1) (80 mg; 0.19 mmol), NaI (12 mg; 0.08 mmol), 4-(2-chloroethyl)morpholine (40 mg; 0.25 mmol) and K2CO3 (84 mg; 0.58 mmol) in DMF (1 mL) was stirred overnight at 100°C. After aqueous work-up the mixture was extracted with EtOAc. The combined organic layers were washed with brine and dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by chromatography to afford the product (18.30 mg; 19 %) as purple semi solid. Example 36: 1-(2-hydroxyethyl)-4-methyl-3-(3-methyl-5-{[2-(trifluoromethyl)- pyrimidin-5-yl]oxy}phenyl)-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Compound No.15) Ex.36.1: 1-(2-hydroxyethyl)-4-methyl-3-(3-methyl-5- (trifluoromethyl)- pyrimidin-5-yl]oxy}phenyl)-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one To a stirred solution of 4-methyl-3-(3-methyl-5-{[2-(trifluoromethyl)pyrimidin-5- yl]oxy}phenyl)-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Example 6, Ex.6.1) (80 mg; 0.20 mmol) and 1,3-dioxolan-2-one (90 mg; 1.01 mmol) in DMF (10 mL) was added DBU (96 mg; 0.60 mmol) for 3 h at 100°C under N2 atmosphere. After evaporation the residue was purified by chromatography to afford the product (34.40 mg; 39 %) as white solid. Example 37: 4-methyl-3-{3-methyl-5-[4-(trifluoromethyl)phenoxy]phenyl}-1-(3- methylpyrazin-2-yl)-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Compound No.14) Ex.37.1: 4-methyl-3-{3-methyl-5-[4-(trifluoromethyl)phenoxy]phenyl}-1-(3- methylpyrazin-2-yl)-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one To a stirred solution of 4-methyl-3-{3-methyl-5-[4-(trifluoromethyl)phenoxy]- phenyl}-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Example 2, Ex.2.1) (100 mg; 0.25 mmol) and 2-bromo-3-methylpyrazine (45 mg; 0.25 mmol) in dioxane (5 mL) were added K3PO4 (167 mg; 0.75 mmol), CuI (10 mg; 0.05 mmol) and (1R,2R)-cyclohexane-1,2-diamine (6 mg; 0.05 mmol) at RT. Then the resulting mixture was stirred for 1 h at 100°C under N2 atmosphere. After evaporation the residue was purified to afford the product (69.90 mg; 57 %) as white solid. Example 38: 3-(4-methyl-3-{3-methyl-5-[4-(trifluoromethyl)phenoxy]phenyl}-5- oxo-1H,4H,5H-pyrrolo[3,2-b]pyridin-1-yl)propanenitrile (Compound No.13) Ex.38.1: 3-(4-methyl-3-{3-methyl-5-[4-(trifluoromethyl)phenoxy]phenyl}-5- oxo-1H,4H,5H-pyrrolo[3,2-b]pyridin-1-yl)propanenitrile To a stirred solution of 4-methyl-3-{3-methyl-5-[4- (trifluoromethyl)phenoxy]phenyl}-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Example 2, Ex.2.1) (80 mg; 0.19 mmol) in dioxane (8 mL) were added prop- 2-enenitrile (0.12 ml; 1.87 mmol) and NaOH (16 mg; 0.38 mmol) at 0°C under N2 atmosphere. The resulting mixture was stirred for 2 h at RT. After aqueous work-up and extraction with EtOAc the combined organic layers were washed with brine and dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The crude product was purified by chromatography (13.8 mg; 15 %) as white solid. Example 39: 3-(4-methyl-3-{3-methyl-5-[4-(trifluoromethyl)phenoxy]phenyl}-5- oxo-1H,4H,5H-pyrrolo[3,2-b]pyridin-1-yl)propenamide (Compound No.12) Ex.39.1: 3-(4-methyl-3-{3-methyl-5-[4-(trifluoromethyl)phenoxy]phenyl}-5- oxo-1H,4H,5H-pyrrolo[3,2-b]pyridin-1-yl)propanamide To a stirred solution of 4-methyl-3-{3-methyl-5-[4- (trifluoromethyl)phenoxy]phenyl}-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Example 2, Ex.2.1) (100 mg; 0.21 mmol) in dioxane (10 mL) was added prop- 2-enamide (140 mg; 1.93 mmol) and NaOH (20 mg; 0.48 mmol) at 0°C under N2 atmosphere. The reaction mixture was stirred for 2 h at RT. After aqueous work-up the resulting mixture was extracted with EtOAc. The combined organic layers were washed with brine and dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by chromatography to afford the product (26 mg; 26 %) as off- white solid. Example 40: 1-(2-hydroxyethyl)-4-methyl-3-(3-methyl-5-{[6- (trifluoromethyl)pyridin-3-yl]oxy}phenyl)-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Compound No.11) Ex.40.1: 1-(2-hydroxyethyl)-4-methyl-3-(3-methyl-5-{[6- (trifluoromethyl)pyridin-3-yl]oxy}phenyl)-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one To a stirred mixture of 4-methyl-3-(3-methyl-5-{[6-(trifluoromethyl)pyridin-3- yl]oxy}phenyl)-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (accessible by analogy with the procedures for the synthesis of Example 3, Ex.3.2) (70 mg; 0.17 mmol) and 1,3-dioxolan-2-one (75 mg; 0.84 mmol) in DMF (10 mL) was added DBU (80 mg; 0.50 mmol) at RT. The resulting mixture was stirred for 5 h at 100°C. After removal of all volatiles the residue was purified by chromatography to afford the product (33.20 mg; 44.4 %) as white solid. Example 41: 1-(3-hydroxypropyl)-4-methyl-3-{3-methyl-5-[4- (trifluoromethyl)phenoxy]phenyl}-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Compound No.10) Ex.41.1: 1-(3-hydroxypropyl)-4-methyl-3-{3-methyl-5-[4- (trifluoromethyl)phenoxy]phenyl}-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one

[0059] stirred solution of 4-methyl-3-{3-methyl-5-[4-(trifluoromethyl)- phenoxy]phenyl}-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Example 2, Ex.2.1) (100 mg; 0.249 mmol) in DMF (10 mL) was added Cs2CO3 (240 mg; 0.7 mmol), NaI (40 mg; 0.25 mmol) and 3-chloropropan-1-ol (120 mg; 1.24 mmol) at RT under N2 atmosphere. The resulting mixture was stirred overnight at 100°C. After aqueous work-up the resulting mixture was extracted with EtOAc. The combined organic layers were washed with brine and dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by chromatography to provide the product (17.2 mg; 15 %) as purple semi-solid. Example 42: 1-[(dimethylphosphoryl)methyl]-4-methyl-3-{3-methyl-5-[4- (trifluoromethyl)phenoxy]phenyl}-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Compound No.7) Ex.42.1: 1-[(dimethylphosphoryl)methyl]-4-methyl-3-{3-methyl-5-[4- (trifluoromethyl)phenoxy]phenyl}-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one To a stirred solution of 4-methyl-3-{3-methyl-5-[4-(trifluoromethyl)- phenoxy]phenyl}-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Example 2, Ex.2.1) (100 mg; 0.23 mmol) in DMF (10 mL) was added Cs2CO3 (240 mg; 0.7 mmol), NaI (40 mg; 0.25 mmol) and chloro(dimethylphosphoryl)methane (150 mg; 1.13 mmol) at RT under N2 atmosphere. The resulting mixture was stirred for 4 h at 100°C. After aqueous work-up the resulting mixture was extracted with EtOAc. The combined organic layers were washed with brine and dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by chromatography to provide the product (22.6 mg; 20 %) as off-white solid. Example 43: N-methyl-2-(4-methyl-3-{3-methyl-5-[4-(trifluoromethyl)- phenoxy]phenyl}-5-oxo-1H,4H,5H-pyrrolo[3,2-b]pyridin-1-yl)acetamide (Compound No.6) Ex.43.1: N-methyl-2-(4-methyl-3-{3-methyl-5-[4-(trifluoromethyl)- phenoxy]phenyl}-5-oxo-1H,4H,5H-pyrrolo[3,2-b]pyridin-1-yl)acetamide To a stirred solution of 4-methyl-3-{3-methyl-5-[4-(trifluoromethyl)- phenoxy]phenyl}-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Example 2, Ex.2.1) (100 mg; 0.23 mmol) in DMF (10 mL) was added K2CO3 (100 mg; 0.69 mmol), NaI (40 mg; 0.25 mmol) and 2-bromo-N-methylacetamide (200 mg; 1.29 mmol) at RT under N2 atmosphere. The resulting mixture was stirred overnight at 100°C. After removal of all volatiles the resulting mixture was extracted with EtOAc. The combined organic layers were washed with brine and dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by chromatography (35.4 mg; 32 %) as off- white solid. Example 44: 2-(4-methyl-3-{3-methyl-5-[4-(trifluoromethyl)phenoxy]phenyl}-5- oxo-1H,4H,5H-pyrrolo[3,2-b]pyridin-1-yl)acetamide (Compound No.4) Ex.44.1: 2-(4-methyl-3-{3-methyl-5-[4-(trifluoromethyl)phenoxy]phenyl}-5- oxo-1H,4H,5H-pyrrolo[3,2-b]pyridin-1-yl)acetamide

[0060] To a stirred solution of 4-methyl-3-{3-methyl-5-[4-(trifluoromethyl)- phenoxy]phenyl}-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Example 2, Ex.2.1) (100 mg; 0.23 mmol) in DMF (5 mL) was added Cs2CO3 (240 mg; 0.70 mmol), NaI (40 mg; 0.254 mmol) and 2-chloroacetamide (120 mg; 1.22 mmol) at RT under N2 atmosphere. The resulting mixture was stirred for 4 h at 100°C under N2 atmosphere. After aqueous work-up he resulting mixture was extracted with EtOAc. The combined organic layers were washed with brine and dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by chromatography (44.5 mg; 41 %) as white solid. Example 45: 1-(2-hydroxyethyl)-4-methyl-3-{3-methyl-5-[4- (trifluoromethyl)phenoxy]phenyl}-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Compound No.3) Ex.45.1: 1-(2-hydroxyethyl)-4-methyl-3-{3-methyl-5-[4- (trifluoromethyl)phenoxy]phenyl}-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one To 4-methyl-3-{3-methyl-5-[4-(trifluoromethyl)phenoxy]phenyl}-1H,4H,5H- pyrrolo[3,2-b]pyridin-5-one (Example 2, Ex.2.1) (80 mg; 0.2 mmol) in DMF (3 mL) was added 1,3-dioxolan-2-one (15 µL; 0.22 mmol) and NaOH (4.2 mg; 0.1 mmol). The reaction was stirred for 4 h at 130°C. After removal of all volatiles the residue was purified by chromatography to provide the product (56 mg; 82 %) as white solid. Example 46: 4-ethyl-3-(2-methyl-6-{[(1r,4r)-4-(trifluoromethyl)cyclohexyl]oxy}- pyrimidin-4-yl)-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Compound No.213) Ex.46.1: 4-ethyl-3-(2-methyl-6-{[(1r,4r)-4-(trifluoromethyl)cyclohexyl]oxy}- pyrimidin-4-yl)-1-(4-methylbenzenesulfonyl)-1H,4H,5H-pyrrolo[3,2-b]pyridin- 5-one To a stirred solution of 4-ethyl-1-(4-methylbenzenesulfonyl)-3-(4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Intermediate 2, Int.2.7) (2.50 g; 5.50 mmol) and 4-chloro-2-methyl-6-{[(1r,4r)- 4-(trifluoromethyl)cyclohexyl]oxy}pyrimidine (accessible by analogy with the procedures for the synthesis of Intermediate 10, Int.10.1, starting from 4,6- dichloro-2-methylpyrimidine and (1r,4r)-4-(trifluoromethyl)cyclohexan-1) (1.78 g; 6.05 mmol) in dioxane (50 mL) / H2O (5 mL) was added Pd(PPh3)4 (670 mg; 0.55 mmol) and Na2CO3 (1.84 g; 16.50 mmol). The resulting mixture was stirred for 2 h at 60°C under N2 atmosphere. After removal of the solvent the residue was purified by chromatography to afford the product (2.20 g; 54 %) as off-white solid. Ex.46.2: 4-ethyl-3-(2-methyl-6-{[(1r,4r)-4-(trifluoromethyl)-

[0061] To a stirred solution of 4-ethyl-3-(2-methyl-6-{[(1r,4r)-4- (trifluoromethyl)cyclohexyl]oxy}pyrimidin-4-yl)-1-(4-methylbenzenesulfonyl)- 1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (2.04 g; 2.75 mmol) in EtOH (50 mL) was added EtONa / EtOH (w / w 21%; 1.25 mL; 5.50 mmol). The resulting mixture was stirred for 1 h at RT. After removal of the solvent the residue was purified by chromatography to afford the product (1.15 g; 93 %) as gray solid. Example 47: 4-ethyl-1-(2-hydroxyethyl)-3-(2-methyl-6 -4-(trifluoro- methyl)cyclohexyl]oxy}pyrimidin-4-yl)-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Compound No.214) Ex.47.1: 4-ethyl-1-(2-hydroxyethyl)-3-(2-methyl-6-{[(1r,4r)-4-(trifluoro- methyl)cyclohexyl]oxy}pyrimidin-4-yl)-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one To a stirred solution of 4-ethyl-3-(2-methyl-6-{[(1r,4r)-4-(trifluoromethyl)cyclo- hexyl]oxy}pyrimidin-4-yl)-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Example 46, Ex.46.2) (100 mg; 0.22 mmol) in DMF (8 mL) was added 1,3-dioxolan-2-one (160 mg; 1.80 mmol). The resulting mixture was stirred for 2 h at 100°C under N2 atmosphere. After removal of the solvent, the residue was purified by chromatography to afford the product (61.40 mg; 59 %) as white solid. Example 48: 1-(1,3-dihydroxypropan-2-yl)-4-ethyl-3-(2-methyl-6-{[(1r,4r)-4- (trifluoromethyl)cyclohexyl]oxy}pyrimidin-4-yl)-1H,4H,5H-pyrrolo[3,2-b]pyridin- 5-one (Compound No.282) Ex.48.1: 1-(2,2-dimethyl-1,3-dioxan-5-yl)-4-ethyl-3-(2-methyl-6-{[(1r,4r)-4- (trifluoromethyl)cyclohexyl]oxy}pyrimidin-4-yl)-1H,4H,5H-pyrrolo[3,2-b]pyridin- 5-one To a stirred solution of 4-ethyl-3-(2-methyl-6-{[(1r,4r)-4-(trifluoromethyl)- cyclohexyl]oxy}pyrimidin-4-yl)-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Example 46, Ex.46.2) (200 mg; 0.44 mmol) in toluene (10 mL) was added 2,2-dimethyl-1,3-dioxan-5-ol (90 mg; 0.66 mmol) and 2-(tributyl-5- phosphanylidene)acetonitrile (340 mg; 1.34 mmol). The reaction mixture was stirred for 4 h at 110°C under N2 atmosphere. After evaporation the residue was purified by chromatography to afford the product (80 mg; 26 %) as brown oil. Ex.48.2: 1-(1,3-dihydroxypropan-2-yl)-4-ethyl-3-(2-methyl-6-{[(1r,4r)-4- (trifluoromethyl)cyclohexyl]oxy}pyrimidin-4-yl)-1H,4H,5H-pyrrolo[3,2-b]pyridin- 5-one To a stirred solution of 1-(2,2-dimethyl-1,3-dioxan-5-yl)-4-ethyl-3-(2-methyl-6- {[(1r,4r)-4-(trifluoromethyl)cyclohexyl]oxy}pyrimidin-4-yl)-1H,4H,5H- pyrrolo[3,2-b]pyridin-5-one (Ex.48.1) (70 mg; 0.10 mmol) in THF (5 mL) was added aq. HCl (2 mL; 6.00 mmol) for 1 h at RT. After evaporation the residue was purified by chromatography to afford the product (21 mg; 42 %) as white solid. Example 49: 2,4-dimethyl-3-{2-methyl-6-[4-(trifluoromethyl)phenoxy]- pyrimidin-4-yl}-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Compound No.212) Ex.49.1: 2,4-dimethyl-3-{2-methyl-6-[4-(trifluoromethyl)phenoxy]pyrimidin-4- yl}-1-(4-methylbenzenesulfonyl)-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one A solution of 2-methyl-4-[4-(trifluoromethyl)phenoxy]-6-(trimethylstannyl)- pyrimidine (Intermediate 8) (380 mg; 0.73 mmol), Pd-PEPPSI-IPentCl 2- methylpyridine (30 mg; 0.03 mmol), 3-iodo-2,4-dimethyl-1-(4-methylbenzene- sulfonyl)-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Intermediate 3, Int.3.5) (190 mg; 0.39 mmol), LiCl (45 mg; 1.78 mmol) and CuI (15 mg; 0.08 mmol) in dioxane (5 mL) was reacted for 12 h at 100°C under N2 atmosphere. The resulting mixture was diluted with EtOAc and then washed with brine. The organic layer was dried over anhydrous Na2SO4, filtrated and concentrated under reduced pressure. The residue was purified by chromatography to afford the product (150 mg; 25 %) as white solid. Ex.49.2: 2,4-dimethyl-3-{2-methyl-6-[4-(trifluoromethyl)phenoxy]pyrimidin-4- yl}-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one

[0062] 2,4-dimethyl-3-{2-methyl-6-[4-(trifluoromethyl)phenoxy]pyrimidin-4-yl}-1-(4- methylbenzenesulfonyl)-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Ex.49.1) (100 mg; 0.14 mmol) was stirred in EtONa / EtOH (w / w 21%) (0.08 mL; 0.35 mmol) and EtOH (3 mL) for 2 h at RT. After removal of all volatiles the residue was purified by chromatography to afford the product (14.50 mg; 24 %) as white solid. Example 50: 1-(2-hydroxyethyl)-2,4-dimethyl-3-{2-methyl-6-[4- (trifluoromethyl)phenoxy]pyrimidin-4-yl}-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Compound No.233) Ex.50.1: 1-(2-hydroxyethyl)-2,4-dimethyl-3-{2-methyl-6-[4- (trifluoromethyl)phenoxy]pyrimidin-4-yl}-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one The mixture of 2,4-dimethyl-3-{2-methyl-6-[4-(trifluoromethyl)phenoxy]- pyrimidin-4-yl}-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Example 49, Ex.49.2) (100 mg; 0.22 mmol), 1,3-dioxolan-2-one (80 mg; 0.90 mmol) and DBU (80 mg; 0.50 mmol) in DMF (2.50 mL) was stirred for 2 h at 100°C. After concentration in vacuum the residue was purified by chromatography to afford the product (12.30 mg; 12 %) as light yellow solid. 1-(triphenylmethyl)-1H,4H,5H-pyrazolo[4,3-b]pyridin-5-one To a stirred solution of 4-methyl-3-(trimethylstannyl)-1-(triphenylmethyl)- 1H,4H,5H-pyrazolo[4,3-b]pyridin-5-one (Intermediate 4, Int.4.7) (1.30 g; 2.23 mmol) and 4-iodo-2-methyl-6-[4-(trifluoromethyl)phenoxy]pyrimidine (Intermediate 9, Int.9.1) (1.24 g; 2.68 mmol) in DMF (20 mL) was added Pd(PPh3)4 (270 mg; 0.22 mmol) and CuI (450 mg; 2.24 mmol) for 2 h at 100°C under N2 atmosphere. After evaporation the residue was purified by chromatography to afford the product (1.39 g; 94 %) as yellow solid. Ex.51.2: 4-methyl-3-{2-methyl-6-[4-(trifluoromethyl)phenoxy]pyrimidin-4-yl}- 1H,4H,5H-pyrazolo[4,3-b]pyridin-5-one To a stirred solution of 4-methyl-3-{2-methyl-6-[4-(trifluoromethyl)- phenoxy]pyrimidin-4-yl}-1-(triphenylmethyl)-1H,4H,5H-pyrazolo[4,3-b]pyridin- 5-one (Ex.51.1) (120 mg; 0.18 mmol) in DCM (5 mL) was added TFA (0.20 mL; 2.09 mmol) and Et3SiH (0.10 mL) for 2 h at RT. After evaporation the residue was purified by chromatography to afford the product (23.70 mg; 33 %) as white solid. Example 52: 3-(5-fluoro-2-methyl-6-{[(1r,4r)-4-(trifluoromethyl)cyclohexyl]- oxy}pyrimidin-4-yl)-4-methyl-1H,4H,5H-pyrazolo[4,3-b]pyridin-5-one (Compound No.244) Ex.52.1: 3-(5-fluoro-2-methyl-6-{[(1r,4r)-4-(trifluoromethyl)cyclohexyl]- oxy}pyrimidin-4-yl)-4-methyl-1-(triphenylmethyl)-1H,4H,5H-pyrazolo[4,3- b]pyridin-5-one To a stirred solution of 5-fluoro-4-iodo-2-methyl-6-{[(1r,4r)-4-(trifluoromethyl)- cyclohexyl]oxy}pyrimidine (Intermediate 10, Int.10.2) (1 g; 2.36 mmol) and 4- methyl-3-(trimethylstannyl)-1-(triphenylmethyl)-1H,4H,5H-pyrazolo[4,3- b]pyridin-5-one (Intermediate 4, Int.4.7) (1 g; 1.75 mmol) in DMF (20 mL) were added Pd(PPh3)4 (285 mg; 0.23 mmol) and CuI (470 mg; 2.34 mmol) at RT under N2 atmosphere. Then the reaction mixture was stirred for 2 h at 100°C. For work-up the mixture was extracted with EtOAc, and the combined organic layers were washed with brine and dried over Na2SO4. After filtration, the filtrate was concentrated under reduced pressure and the residue was purified by chromatography to afford the product (1.04 g; 64%) as yellow solid. Ex.52.2: 3-(5-fluoro-2-methyl-6-{[(1r,4r)-4-(trifluoromethyl)cyclohexyl]- oxy}pyrimidin-4-yl)-4-methyl-1H,4H,5H-pyrazolo[4,3-b]pyridin-5-one

[0063] To a stirred solution of 3-(5-fluoro-2-methyl-6-{[(1r,4r)-4-(trifluoromethyl)- cyclohexyl]oxy}pyrimidin-4-yl)-4-methyl-1-(triphenylmethyl)-1H,4H,5H- pyrazolo[4,3-b]pyridin-5-one (Ex.52.1) (900 mg; 1.31 mmol) in DCM (20 mL) was added Et3SiH (2 mL) and TFA (5 mL) at RT. Then the resulting mixture was stirred overnight under N2 atmosphere. After removal of all volatiles the crude was purified by chromatorgarphy to afford the product (580 mg; 99%) as white solid. Example 53: 3-(3-chloro-5-{[(1r,4r)-4-(trifluoromethyl)cyclohexyl]oxy}phenyl)- 4-methyl-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Compound No.260) Ex.53.1: 3-(3-chloro-5-{[(1r,4r)-4-(trifluoromethyl)cyclohexyl]oxy}phenyl)-4- methyl-1-(4-methylbenzenesulfonyl)-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one To a stirred mixture of 4-methyl-1-(4-methylbenzenesulfonyl)-3-(4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Intermediate 1, Int 1.5) (350 mg; 0.81 mmol) and 1-bromo-3-chloro-5-{[(1r,4r)- 4-(trifluoromethyl)cyclohexyl]oxy}benzene (Intermediate 11, Int.11.1) (308 mg; 0.81 mmol) in dioxane (10 mL) and H2O (2 mL) was added Pd(PPh3)4 (99 mg; 0.08 mmol) and Na2CO3 (181 mg; 1.62 mmol) at 25°C. The resulting mixture was stirred for 2 h at 60°C under N2 atmosphere. For work up the resulting mixture was concentrated under vacuum and the residue was purified by chromatography to afford the product (260 mg; 54 %) as yellow solid. Ex.53.2: 3-(3-chloro-5-{[(1r,4r)-4-(trifluoromethyl)cyclohexyl]oxy}phenyl)-4- methyl-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one To a stirred solution of 3-(3-chloro-5-{[(1r,4r)-4-(trifluoromethyl)- cyclohexyl]oxy}phenyl)-4-methyl-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Ex.53.1) (100 mg; 0.23 mmol) in DMF (10 mL) was added NaH (138 mg; 1.17 mmol) at 0°C for 30 min under N2 atmosphere. Then 4-(chloromethyl)-1H- imidazole hydrochloride (76 mg; 0.47 mmol) was added and the reaction mixture was stirred for additional 6 h at 25°C. For work up the reaction mixture was extracted with EtOAc, and the organic layer was washed with brine and dried over Na2SO4. After filtration, the filtrate was concentrated under reduced pressure and the crude product was purified by chromatography to afford the product (16.3 mg; 14 %) as white solid. Example 54: 3-(5-fluoro-2-methyl-6-{[(1r,4r)-4-(trifluoromethyl)cyclohexyl]- oxy}pyrimidin-4-yl)-4-methyl-1-[(1-methyl-1H-pyrazol-4-yl)methyl]-1H,4H,5H- pyrazolo[4,3-b]pyridin-5-one (Compound No.250) and 3-(5-fluoro-2-methyl-6-{[(1r,4r)-4-(trifluoromethyl)cyclohexyl]oxy}pyrimidin-4- yl)-4-methyl-2-[(1-methyl-1H-pyrazol-4-yl)methyl]-2H,4H,5H-pyrazolo[4,3- b]pyridin-5-one (Compound No.252) To a stirred solution of 3-(5-fluoro-2-methyl-6-{[(1r,4r)-4-(trifluoromethyl)- cyclohexyl]oxy}pyrimidin-4-yl)-4-methyl-1H,4H,5H-pyrazolo[4,3-b]pyridin-5- one (Example 52, Ex.52.2) (90 mg; 0.20 mmol) in DMF (8 mL) was added NaH (50 mg; 1.25 mmol) at 0°C unter N2 atmosphere. Then the resulting mixture was stirred at RT for 30 min. 4-(bromomethyl)-1-methyl-1H-pyrazole hydrobromide (108 mg; 0.40 mmol) was added for 1 h. After work up with aqueous NH4Cl, extraction with EtOAc, drying over Na2SO4, filtration and evaporation, the crude product was purified by chromatography to afford product 1 (Compound No.250) (24.80 mg; 24 %) and product 2 (Compound No.252) (1.7 mg; 2%) both as white solids. Example 55: 4-methyl-3-{3-methyl-5-[4-(trifluoromethyl)phenoxy]phenyl}- 1H,4H,5H-pyrazolo[4,3-b]pyridin-5-one (Compound No.201) Ex.55.1: 4-methyl-3-{3-methyl-5-[4-(trifluoromethyl)phenoxy]phenyl}-1-(4- methylbenzenesulfonyl)-1H,4H,5H-pyrazolo[4,3-b]pyridin-5-one To a stirred mixture of 3-iodo-4-methyl-1-(4-methylbenzenesulfonyl)- 1H,4H,5H-pyrazolo[4,3-b]pyridin-5-one (Intermediate 13, Int.13.1) (600 mg; 1.15 mmol) and 4,4,5,5‐tetramethyl‐2‐{3‐methyl‐5‐[4‐(trifluoromethyl)- phenoxy]phenyl}‐1,3,2‐dioxaborolane (Intermediate 5, Int.5.2) (255 mg; 1.15 mmol) in dioxane (10 mL) and H2O (2 mL) were added Pd(dppf)Cl2 (88 mg; 0.11 mmol) and K2CO3 (334 mg; 2.30 mmol) at RT under N2 atmosphere. The resulting mixture was stirred for 1 h at 70°C. Then the mixture was concentrated under vacuum and the residue was purified chromatography to afford the product (250 mg; 33 %) as yellow oil. Ex.55.2: 4-methyl-3-{3-methyl-5-[4-(trifluoromethyl)phenoxy]phenyl}- 1H,4H,5H-pyrazolo[4,3-b]pyridin-5-one To a stirred mixture of 4-methyl-3-{3-methyl-5-[4-(trifluoromethyl)- phenoxy]phenyl}-1-(4-methylbenzenesulfonyl)-1H,4H,5H-pyrazolo[4,3- b]pyridin-5-one (Ex.55.1) (400 mg; 0.61 mmol) in EtOH (10 mL) was added EtONa / EtOH (w / w 21%) (0.20 mL; 0.91 mmol) at RT for 1 h. The mixture was extracted with DCM and the combined organic layers were washed with brine and dried over MgSO4. After filtration, the filtrate was concentrated under reduced pressure and the residue was purified by chromatography to afford the product (250 mg; 99%) as yellow oil. Example 56: 1-[(1H-imidazol-4-yl)methyl]-4-methyl-3-{3-methyl-5-[4- (trifluoromethyl)phenoxy]phenyl}-1H,4H,5H-pyrazolo[4,3-b]pyridin-5-one (Compound No.211) and 2-[(1H-imidazol-4-yl)methyl]-4-methyl-3-{3-methyl-5-[4- (trifluoromethyl)phenoxy]phenyl}-2H,4H,5H-pyrazolo[4,3-b]pyridin-5-one (Compound No.210)

[0064] To a stirred solution of 4-methyl-3-{3-methyl-5-[4-(trifluoromethyl)phenoxy]- phenyl}-1H,4H,5H-pyrazolo[4,3-b]pyridin-5-one (Example 55, Ex.55.2) (80 mg; 0.19 mmol) in DMF (1 mL) was added NaH (23 mg; 0.57 mmol) at 0°C under N2 atmosphere. The mixture was stirred at RT for 30 min. TBAI (15 mg; 0.04 mmol) and 4-(chloromethyl)-1H-imidazole hydrochloride (62 mg; 0.38 mmol) were added for 1 h at 80°C. After work-up with aqueous NH4Cl, extraction with EtOAc, drying over Na2SO4, filtration and evaporation the curde was purified by chromatrography to afford product 1 (5.70 mg; 6 %) and product 2 (2 mg; 2 %) both as white solids. Exampe 5 : 6-fluoro-4-methyl-3-{3-methyl-5-[4- (trifluoromethyl)phenoxy]phenyl}-1-(4-methylbenzenesulfonyl)-1H,4H,5H- pyrrolo[3,2-b]pyridin-5-one (Compound No.63) A mixture of 4-methyl-3-{3-methyl-5-[4-(trifluoromethyl)phenoxy]phenyl}-1-(4- methylbenzenesulfonyl)-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Example 16, Ex.16.1) (1 g; 1.72 mmol) and selectfluor (2.50 g; 6.70 mmol) in ACN (20 mL) and H2O (4 mL) was stirred for 1.5 h at RT. Then the mixture was extracted with EtOAc, and the combined organic layers were washed with brine and dried over Na2SO4. After filtration the filtrate was concentrated under reduced pressure and the residue was purified by chromatography to give the product (32.9 mg; 3 %) as purple solid. Example 58: rel-4-ethyl-3-(5-fluoro-2-methyl-6-{[(1r,4r)-4-(trifluoromethyl)- cyclohexyl]oxy}pyrimidin-4-yl)-1-(2-hydroxyethyl)-1H,4H,5H-pyrrolo[3,2- b]pyridin-5-one Ex.58.1: 4-ethyl-3-(5-fluoro-2-methyl-6-{[(1r,4r)-4-(trifluoromethyl)cyclo- hexyl]oxy}pyrimidin-4-yl)-1-(4-methylbenzenesulfonyl)-1H,4H,5H-pyrrolo[3,2- b]pyridin-5-one To a solution of 4-ethyl-1-(4-methylbenzenesulfonyl)-3-(4,4,5,5-tetramethyl- 1,3,2-dioxaborolan-2-yl)-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Int 2.7) (9.50 g; 20.40 mmol) and rel-5-fluoro-4-iodo-2-methyl-6-{[(1r,4r)-4-(trifluoromethyl)- cyclohexyl]oxy}pyrimidine (Int 10.2) (9.50 g; 22.33 mmol) in CPME (cyclopentyl-methylether) (200 mL) / H2O (20 mL) were added SPhos Pd G3 (1.80 g; 2.06 mmol) and K3PO4 (13.70 g; 61.32 mmol) for 2 h at 60 °C under nitrogen atmosphere. Then the reaction mixture was concentrated under reduced pressure and the residue was purified by chromatography to afford the product (6.40 g; 51 %) as light brown solid. Ex.58.2: rel-4-ethyl-3-(5-fluoro-2-methyl-6-{[(1r,4r)-4-(trifluoromethyl)- cyclohexyl]oxy}pyrimidin-4-yl)-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one

[0065] To a stirred solution of rel-4-ethyl-3-(5-fluoro-2-methyl-6-{[(1r,4r)-4- (trifluoromethyl)cyclohexyl]oxy}pyrimidin-4-yl)-1-(4-methylbenzenesulfonyl)- 1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Ex.58.1) (500 mg; 0.84 mmol) in EtOH (20 mL) was added EtONa / EtOH (w / w 21%; 5 ml; 23.14 mmol) for 3 h at 25°C. The reaction was quenched with H2O at 0°C. The mixture was diluted with DCM and then washed with brine. The organic layer was dried over anhydrous Na2SO4, filtrated and concentrated under reduced pressure. The residue was purified by chromatography to afford the product (340 mg; 76 %) as white solid. Ex.58.3: rel-4-ethyl-3-(5-fluoro-2-me yl-6-{[(1r,4r)-4- (trifluoromethyl)cyclohexyl]oxy}pyrimidin-4-yl)-1-(2-hydroxyethyl)-1H,4H,5H- pyrrolo[3,2-b]pyridin-5-one To a solution of rel-4-ethyl-3-(5-fluoro-2-methyl-6-{[(1r,4r)-4-(trifluoromethyl)- cyclohexyl]oxy}pyrimidin-4-yl)-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Ex.58.2) (45 mg; 0.1 mmol) and 1,3-dioxolan-2-one (120 mg; 1.35 mmol) in DMF (2 mL) was added DBU (50 mg; 0.31 mmol) for 2 h at 80°C. Then the mixture was concentrated under reduced pressure and the residue was purified by chromatography to afford the product (31 mg; 63 %) as off-white solid. Example 59: rel-4-ethyl-3-(5-fluoro-2-methyl-6-{[(1r,4r)-4-(trifluoromethyl)- cyclohexyl]oxy}pyrimidin-4-yl)-1-methyl-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one To a stirred solution of rel-4-ethyl-3-(5-fluoro-2-methyl-6-{[(1r,4r)-4- (trifluoromethyl)cyclohexyl]oxy}pyrimidin-4-yl)-1H,4H,5H-pyrrolo[3,2-b]pyridin- 5-one (Example 58, Ex.58.2) (40 mg; 0.09 mmol) in THF (2 ml) was added NaH (5 mg; 0.13 mmol) for 10 min at 0°C under N2 atmosphere. Then CH3I (0.01 ml; 0.13 mmol) was added at 0°C and the mixture was stirred for 2 h at RT. After concentration under reduced pressure the residue was purified by chromatography to afford the product (24 mg; 60 %) as off-white solid. Example 60: rel-4-ethyl-3-(6-methyl-4-{[(1r,4r)-4-(trifluoromethyl)- cyclohexyl]oxy}pyridin-2-yl)-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one Ex.60.1: rel-2-bromo-6-methyl-4-{[(1r,4r)-4-(trifluoromethyl)cyclohexyl]oxy}- pyridine To a stirred mixture of rel-(1r,4r)-4-(trifluoromethyl)cyclohexan-1-ol (0.77 g; 4.38 mmol) in DMF (20 mL) was added NaH (193 mg; 4.83 mmol) at 0°C for 20 min under N2 atmosphere. Then 2-bromo-6-methyl-4-nitropyridine (1 g; 4.38 mmol) was added for 2 h at 25°C. For work up the mixture was extracted with EtOAc, the organic layer was washed with brine, dried over anhydrous MgSO4, filtered, concentrated under reduced pressure and purified by chromatography to afford the product (840 mg; 57 %) as pink solid. Ex.60.2: rel-4-ethyl-3-(6-methyl-4-{[(1r,4r)-4-(trifluoromethyl)cyclohexyl]oxy}- pyridin-2-yl)-1-(4-methylbenzenesulfonyl)-1H,4H,5H-pyrrolo[3,2-b]pyridin-5- one To a stirred mixture of rel-2-bromo-6-methyl-4-{[(1r,4r)-4-(trifluoromethyl)- cyclohexyl]oxy}pyridine (Ex.60.1) (450 mg; 1.33 mmol) and 4-ethyl-1-(4- methylbenzenesulfonyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)- 1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Int 2.7) (630 mg; 1.28 mmol) in dioxane (10 mL) and H2O (2 mL) was added Pd(PPh3)4 (161 mg; 0.13 mmol) and Na2CO3 (296 mg; 2.65 mmol) for 2 h at 80°C under nitrogen atmosphere. For work up the mixture was concentrated under vacuum. The residue was purified by chromatography to afford the product (600 mg; 72 %) as yellow solid. Ex.60.3: rel-4-ethyl-3-(6-methyl-4-{[(1r,4r)-4-(trifluoromethyl)cyclohexyl]oxy}- pyridin-2-yl)-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one To a stirred solution of rel-4-ethyl-3-(6-methyl-4-{[(1r,4r)-4-(trifluoromethyl)- cyclohexyl]oxy}pyridin-2-yl)-1-(4-methylbenzenesulfonyl)-1H,4H,5H-pyrrolo- [3,2-b]pyridin-5-one (Ex.60.2) (100 mg; 0.16 mmol) in EtOH (10 mL) was added EtONa / EtOH (w / w 21%; 104 mg; 0.32 mmol) for 2 h at 25°C. For work up the reaction was quenched with H2O at 0°C and diluted with DCM. After washing with brine the organic layer was dried over anhydrous Na2SO4, filtrated and concentrated under reduced pressure. The crude product was purified by chromatography to afford the product (21 mg; 32 %) as white solid. Example 61: rel-4-ethyl-3-(2-methyl-6-{[(1r,4r)-4-(trifluoromethyl)cyclohexyl]- oxy}pyridin-4-yl)-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one Ex.61.1: rel-4-iodo-2-methyl-6-{[(1r,4r)-4-(trifluoromethyl)cyclohexyl]oxy}- pyridine To a stirred solution of rel-(1r,4r)-4-(trifluoromethyl)cyclohexan-1-ol (800 mg; 4.66 mmol) in DMF (20 mL) was added NaH (250 mg; 6.25 mmol) for 20 min at 0°C.2-fluoro-4-iodo-6-methylpyridine (1 g; 4.13 mmol) was added for 2 h at 80°C under N2 atmosphere. The reaction was quenched by the addition of ice water and the resulting mixture was diluted with EtOAc. After washing with brine the organic layer was dried over anhydrous Na2SO4, filtrated and concentrated under reduced pressure. The residue was purified by chromatography to afford the product (1.20 g; 63 %) as colorless oil. Ex.61.2: rel-4-ethyl-3-(2-methyl-6-{[(1r,4r)-4-(trifluoromethyl)cyclohexyl]oxy}- pyridin-4-yl)-1-(4-methylbenzenesulfonyl)-1H,4H,5H-pyrrolo[3,2-b]pyridin-5- To a solution of 4-ethyl-1-(4-methylbenzenesulfonyl)-3-(4,4,5,5-tetramethyl- 1,3,2-dioxaborolan-2-yl)-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Int 2.7) (800 mg; 1.72 mmol) and rel-4-iodo-2-methyl-6-{[(1r,4r)-4-(trifluoromethyl)cyclo- hexyl]oxy}pyridine (900 mg; 1.94 mmol) in CPME (20 mL) and H2O (4 mL) were added SPhos Pd G3 (150 mg; 0.17 mmol) and K3PO4 (1.15 g; 5.15 mmol) for 2 h at 60°C under N2 atmosphere. For work up the mixture was diluted with EtOAc and then washed with brine. The organic layer was dried over anhydrous Na2SO4, filtrated and concentrated under reduced pressure. The residue was purified by chromatography to afford the product (550 mg; 54 %) as white solid. Ex.61.3: rel-4-ethyl-3-(2-methyl-6-{[(1r,4r)-4-(trifluoromethyl)cyclohexyl]oxy}- pyridin-4-yl)-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one To a stirred solution of rel-4-ethyl-3-(2-methyl-6-{[(1r,4r)-4-(trifluoromethyl)- cyclohexyl]oxy}pyridin-4-yl)-1-(4-methylbenzenesulfonyl)-1H,4H,5H- pyrrolo[3,2-b]pyridin-5-one (Ex.61.2) (80 mg; 0.14 mmol) in EtOH (5 mL) was added EtONa / EtOH (w / w 21%; 0.06 mL; 0.28 mmol) for 2 h at 25°C. For work up the mixture was diluted with EtOAc and then washed with brine. The organic layer was dried over anhydrous Na2SO4, filtrated and concentrated under reduced pressure. The residue was purified by chromatography to afford the product (39.90 mg; 70 %) as white solid. Example 62: rel-4-ethyl-3-(3-fluoro-6-methyl-2-{[(1r,4r)-4-(trifluoromethyl)- cyclohexyl]oxy}pyridin-4-yl)-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one Ex.62.1: rel-3-fluoro-6-methyl-2-{[(1r,4r)-4-(trifluoromethyl)cyclohexyl]oxy}- pyridine To a stirred solution of rel-(1r,4r)-4-(trifluoromethyl)cyclohexan-1-ol (7.81 g; 44.15 mmol) in DMF (100 mL) was added NaH (2.21 g; 55.19 mmol) for 20 min at 0°C.2,3-difluoro-6-methylpyridine (5 g; 36.79 mmol) was added for 5 h at 60°C under N2 atmosphere. For work up the reaction was then quenched by the addition of ice water. The mixture was diluted with EtOAc and then washed with brine. The organic layer was dried over anhydrous Na2SO4, filtrated and concentrated under reduced pressure. The residue was purified by chromatography to afford the product (9 g; 84 %) as colorless oil. Ex.62.2: rel-3-fluoro-4-iodo-6-methyl-2-{[(1r,4r)-4-(trifluoromethyl)cyclohexyl]- oxy}pyridine To a stirred solution of rel-3-fluoro-6-methyl-2-{[(1r,4r)-4-(trifluoromethyl)- cyclohexyl]oxy}pyridine (Ex.62.1) (1 g; 3.44 mmol) in THF (20 mL) was added LDA in THF (5.20 mL; 10.40 mmol) dropwise for 30 min at -65°C under N2 atmosphere then I2 (1.84 g; 6.89 mmol) in THF was added for 1 h at that temperature. For work up aq. NH4Cl was added and the mixture was diluted with EtOAc. After washing with brine the organic layer was dried over anhydrous Na2SO4, filtrated and concentrated under reduced pressure. The residue was purified by chromatography to afford the product (1.30 g; 90 %) as colorless oil. Ex.62.3: rel-4-ethyl-3-(3-fluoro-6-methyl-2-{[(1r,4r)-4-(trifluoromethyl)cyclo- hexyl]oxy}pyridin-4-yl)-1-(4-methylbenzenesulfonyl)-1H,4H,5H-pyrrolo[3,2- b]pyridin-5-one To a solution of 4-ethyl-1-(4-methylbenzenesulfonyl)-3-(4,4,5,5-tetramethyl- 1,3,2-dioxaborolan-2-yl)-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Int 2.7) (800 mg; 1.72 mmol) and rel-3-fluoro-4-iodo-6-methyl-2-{[(1r,4r)-4-(trifluoromethyl)- cyclohexyl]oxy}pyridine (Ex.62.2) (900 mg; 2.13 mmol) in CPME (20 mL) and H2O (4 mL) were added SPhos Pd G3 (150 mg; 0.17 mmol) and K3PO4 (1.15 g; 5.15 mmol) for 2 h at 60°C under N2 atmosphere. For work up the mixture was diluted with EtOAc and then washed with brine. The organic layer was dried over anhydrous Na2SO4, filtrated and concentrated under reduced pressure. The residue was purified by chromatography to afford the product (750 mg; 61 %) as off-white solid. Ex.62.4: rel-4-ethyl-3-(3-fluoro-6-methyl-2-{[(1r,4r)-4-(trifluoromethyl)cyclo- hexyl]oxy}pyridin-4-yl)-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one

[0066] To a stirred solution of rel-4-ethyl-3-(3-fluoro-6-methyl-2-{[(1r,4r)-4- (trifluoromethyl)cyclohexyl]oxy}pyridin-4-yl)-1-(4-methylbenzenesulfonyl)- 1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one ((Ex.62.3) 100 mg; 0.14 mmol) in EtOH (5 mL) was added EtONa / EtOH (w / w 21%; 0.06 mL; 0.28 mmol) for 2 h at 25°C. EtOAc was added and the mixture was washed with brine. The organic layer was dried over anhydrous Na2SO4, filtrated and concentrated under reduced pressure. The residue was purified by chromatography to afford the product (37 mg; 60 %) as off-white solid. Example 63: rel-6-fluoro-4-methyl-3-(2-methyl-6-{[(1r,4r)-4-(trifluoromethyl)- cyclohexyl]oxy}pyrimidin-4-yl)-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one Ex.63.1: 6-fluoro-3-iodo-1H-pyrrolo[3,2-b]pyridine 6-fluoro-1H-pyrrolo[3,2-b]pyridine (2 g; 13.96 mmol) and NIS (4 g; 16.89 mmol) were reacted in THF (40 mL) for 2 h at RT. Then H2O was added and the mixture was diluted with EtOAc. After washing with brine the organic layer was dried over anhydrous Na2SO4, filtrated and concentrated under reduced pressure to afford the crude product (3.70 g; 99 %) as yellow oil which was used in the next step without further purification. Ex.63.2: 6-fluoro-3-iodo-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[3,2- b]pyridine

[0067] To 6-fluoro-3-iodo-1H-pyrrolo[3,2-b]pyridine (Ex.63.1) (2 g; 7.47 mmol) in DMF (50 mL) was added NaH (600 mg; 15 mmol) and SEM-Cl (2 g; 11.40 mmol) for 4 h at RT under N2 atmosphere. Then the mixture was diluted with EtOAc and then washed with brine. The organic layer was dried over anhydrous Na2SO4, filtrated and concentrated under reduced pressure. The residue was purified by chromatography to afford the product (2 g; 59 %) as yellow solid. Ex.63.3: 6-fluoro-3-iodo-4-methyl-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H- pyrrolo[3,2-b]pyridin-4-ium iodide To 6-fluoro-3-iodo-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[3,2-b]- pyridine (Ex.63.2) (200 mg; 0.50 mmol) in butan-2-one (3 mL) was added MeI (0.20 ml; 3.05 mmol) for 16 h at 40°C. After filtration and washing with EtOAc the product (175 mg; 65 %) was obtained as yellow solid which was used in the next step without further purification. Ex.63.4: 6-fluoro-3-iodo-4-methyl-1-{[2-(t 1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one

[0068] To a stirred solution of 6-fluoro-3-iodo-4-methyl-1-{[2-(trimethylsilyl)ethoxy]- methyl}-1H-pyrrolo[3,2-b]pyridin-4-ium iodide (Ex.63.3) (150 mg; 0.25 mmol) in H2O (15 mL) was added K3Fe(CN)6 (660 mg; 1.90 mmol) for 10 min at 0°C. Then KOH (235 mg; 3.77 mmol; aq.) was added drop by drop, and toluene (25 mL) was added. The resulting mixture was stirred for 5 h at 55°C. For work up Na2S2O3 (aq.) was added at 0°C. The mixture was extracted with EtOAc and the organic layer was washed with brine and dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure and the residue was purified by chromatography to afford the product (110 mg; 96 %) as bright yellow solid. Ex.63.5: rel-6-fluoro-4-methyl-3-(2-methyl-6-{[(1r,4r)-4-(trifluoromethyl)cyclo- hexyl]oxy}pyrimidin-4-yl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H,4H,5H- pyrrolo[3,2-b]pyridin-5-one To a solution of 6-fluoro-3-iodo-4-methyl-1-{[2-(trimethylsilyl)ethoxy]methyl}- 1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Ex.63.4) (100 mg; 0.17 mmol) and rel- 2-methyl-4-{[(1r,4r)-4-(trifluoromethyl)cyclohexyl]oxy}-6-(trimethylstannyl)- pyrimidine (available by a procedure similar to Ex.64.5) (250 mg; 0.26 mmol) in DMF (10 mL) were added Pd(PPh3)4 (14 mg; 0.01 mmol) and CuI (22 mg; 0.11 mmol) for 2 h at 100°C under N2 atmosphere. For work up H2O was added and the resulting mixture was diluted with DCM. After washing with brine the organic layer was dried over anhydrous Na2SO4, filtrated and concentrated under reduced pressure. The residue was purified by chromatography to afford the product (60 mg; 65 %) as white solid. Ex.63.6: rel-6-fluoro-4-methyl-3-(2-methyl-6-{[(1r,4r)-4-(trifluoromethyl)cyclo- hexyl]oxy}pyrimidin-4-yl)-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one A solution of rel-6-fluoro-4-methyl-3-(2-methyl-6-{[(1r,4r)-4-(trifluoromethyl)- cyclohexyl]oxy}pyrimidin-4-yl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H,4H,5H- pyrrolo[3,2-b]pyridin-5-one (Ex.63.5) (60 mg; 0.09 mmol) and TBAF (1M in THF; 200 µL) in THF (5 mL) was stirred for 12 h at 60°C. Then H2O was added and the resulting mixture was diluted with DCM. After washing with brine, the organic layer was dried over anhydrous Na2SO4, filtrated and concentrated under reduced pressure. The residue was purified by chromatography to afford the product (14 mg; 37 %) as white solid. Example 64: rel-3-(5-fluoro-2-methyl-6-{[(1r,4r)-4-(trifluoromethyl)cyclohexyl]- oxy}pyrimidin-4-yl)-4-(2,2,2-trifluoroethyl)-1H,4H,5H-pyrrolo[3,2-b]pyridin-5- one Ex.64.1: 1-(4-methylbenzenesulfonyl)-4-(2,2,2-trifluoroethyl)-1H,4H,5H- pyrrolo[3,2-b]pyridin-5-one

[0069] To a stirred solution of 1-(4-methylbenzenesulfonyl)-1H-pyrrolo[3,2-b]pyridin- 5-ol (Int.2.2) (2000 mg; 0.66 mmol) and 2,2,2-trifluoroethyl trifluoromethane- sulfonate (0.40 mL; 2.77 mmol) in dioxane (10 mL) was added K2CO3 (300 mg; 2.07 mmol) for 1 h at RT and then for 2 h at 120°C in the microwave. Then the mixture was diluted with EtOAc and washed with brine. The organic layer was dried over anhydrous Na2SO4, filtrated and concentrated under reduced pressure. The residue was purified by chromatography afford the product (160 mg; 65 %) as white solid. Ex.64.2: 4-(2,2,2-trifluoroethyl)-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one To a stirred solution of 1-(4-methylbenzenesulfonyl)-4-(2,2,2-trifluoroethyl)- 1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Ex.64.1) (150 mg; 0.40 mmol) in EtOH (5 mL) was added EtONa (55 mg; 0.78 mmol) for 1 h at RT. The reaction was quenched with aq. NH4Cl, the mixture was diluted with EtOAc and then washed with brine. The organic layer was dried over anhydrous Na2SO4, filtrated and concentrated under reduced pressure. The residue was purified by chromatography to afford the product (80 mg; 89 %) as white solid. Ex.64.3: 3-iodo-4-(2,2,2-trifluoroethyl)-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one To a stirred solution of 4-(2,2,2-trifluoroethyl)-1H,4H,5H-pyrrolo[3,2-b]pyridin- 5-one (Ex.64.2) (70 mg; 0.31 mmol) and I2 (80 mg; 0.30 mmol) in DMF (4 mL) was added KOH (80 mg; 1.28 mmol) at 0°C and then for 1 h at RT. Then EtOAc was added and the mixture was washed with brine. The organic layer was dried over anhydrous Na2SO4, filtrated and concentrated under reduced pressure. The residue was purified by chromatography to afford the product (35 mg; 25 %) as white solid. Ex.64.4: 3-iodo-1-(4-methylbenzenesulfonyl)-4-(2,2,2-trifluoroethyl)- 1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one To a stirred solution of 3-iodo-4-(2,2,2-trifluoroethyl)-1H,4H,5H-pyrrolo[3,2- b]pyridin-5-one (Ex.64.3) (1.20 g; 2.69 mmol) and TsCl (650 mg; 3.24 mmol) in DCM (120 mL) was added Et3N (0.73 mL; 4.99 mmol) and DMAP (86 mg; 0.67 mmol) overnight at RT. Then EtOAc was added and the mixture was washed with brine. The organic layer was dried over anhydrous Na2SO4, filtrated and concentrated under reduced pressure. The residue was purified by chromatography to afford the product (1.20 g; 89 %) as white solid. Ex.64.5: rel-5-fluoro-2-methyl-4-{[(1r,4r)-4-(trifluoromethyl)cyclohexyl]oxy}-6- (trimethylstannyl)pyrimidine To a stirred solution of rel-5-fluoro-4-iodo-2-methyl-6-{[(1r,4r)-4-(trifluoro- methyl)cyclohexyl]oxy}pyrimidine (Int 10.1) (500 mg; 0.98 mmol) in dioxane (10 mL) was added hexamethyldistannane (650 mg; 1.96 mmol) and Pd(PPh3)4 (120 mg; 0.10 mmol) for 2 h at 100°C under N2 atmosphere. The mixture was concentrated under reduced pressure to afford the crude product (700 mg; 54 %) as black oil that was used in the next step without further purification. Ex.64.6: rel-3-(5-fluoro-2-methyl-6-{[(1r,4r)-4-(trifluoromethyl)cyclohexyl]oxy}- pyrimidin-4-yl)-1-(4-methylbenzenesulfonyl)-4-(2,2,2-trifluoroethyl)-1H,4H,5H- pyrrolo[3,2-b]pyridin-5-one To a stirred solution of rel-5-fluoro-2-methyl-4-{[(1r,4r)-4-(trifluoromethyl)- cyclohexyl]oxy}-6-(trimethylstannyl)pyrimidine (Ex.64.5) (300 mg; 0.22 mmol), Pd(PPh3)4 (17.60 mg; 0.01 mmol) and CuI (32 mg; 0.15 mmol) in DMF (8 mL) was added 3-iodo-1-(4-methylbenzenesulfonyl)-4-(2,2,2-trifluoroethyl)- 1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Ex.64.4) (120 mg; 0.22 mmol) for 2 h at 30°C. Then the mixture was diluted with EtOAc and washed with brine. The organic layer was dried over anhydrous Na2SO4, filtrated and concentrated under reduced pressure. The residue was purified by chromatography to afford the product (61 mg; 21 %) as brown orange solid. Ex.64.7: rel-3-(5-fluoro-2-methyl-6-{[(1r,4r)-4-(trifluoromethyl)cyclohexyl]oxy}- pyrimidin-4-yl)-4-(2,2,2-trifluoroethyl)-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one To a solution of EtONa (9 mg; 0.13 mmol) in EtOH (2 mL) was added rel-3-(5- fluoro-2-methyl-6-{[(1r,4r)-4-(trifluoromethyl)cyclohexyl]oxy}pyrimidin-4-yl)-1- (4-methylbenzenesulfonyl)-4-(2,2,2-trifluoroethyl)-1H,4H,5H-pyrrolo[3,2- b]pyridin-5-one (Ex.64.6) (56 mg; 0.05 mmol) at 0°C. The mixture was stirred for 1h at RT, diluted with EtOAc and then washed with brine. The organic layer was dried over anhydrous Na2SO4, filtrated and concentrated under reduced pressure. The residue was purified by chromatography to afford the product (14.10 mg; 55 %) as white solid. Example 65: rel-4-ethyl-3-[2-(2H3)methyl-6-{[(1r,4r)-4-(trifluoromethyl)cyclo- hexyl]oxy}pyrimidin-4-yl]-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one Ex.65.1: rel-4-chloro-2-(2H3)methyl-6-{[(1r,4r)-4-(trifluoromethyl)cyclohexyl]- oxy}pyrimidine To a solution of rel-(1r,4r)-4-(trifluoromethyl)cyclohexan-1-ol (496 mg; 2.86 mmol) in THF (14 mL) was added NaH (60% suspension in paraffin oil; 137 mg; 3.43 mmol) for 30 min at 0°C under argon. Then 4,6-Dichlor-2-(methyl- D3)pyrimidine (475 mg; 2.86 mmol) in THF (3 mL) was added and the mixture was allowed to warm up to RT. The reaction was quenched with sat. aqueous NH4Cl-solution under cooling and extracted with EtOAc. The combined organic layers were washed with brine, dried over Na2SO4 and evaporated to dryness after filtration. The residue was purified by chromatography to afford the product (615 mg; 54 %) as colorless gum. Ex.65.2: rel-4-ethyl-3-[2-(2H3)methyl-6-{[(1r,4r)-4-(trifluoromethyl)cyclo- hexyl]oxy}pyrimidin-4-yl]-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H,4H,5H- pyrrolo[3,2-b]pyridin-5-one To 4-ethyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-{[2-(trimethyl- silyl)ethoxy]methyl}-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (available by a procedure similar to Ex.66.4) (316 mg; 0.71 mmol) in dioxane (3 mL) / H2O (0.15 mL) was added rel-4-chloro-2-(2H3)methyl-6-{[(1r,4r)-4- (trifluoromethyl)cyclohexyl]oxy}pyrimidine (200 mg; 0.50 mmol), Cs2CO3 (197 mg; 0.61 mmol) and Tetrakis(triphenylphosphine)palladium(0) (58 mg; 0.05 mmol) for 12 h at 100°C. After addition of water the mixture was extracted with EtOAc and the organic phase was washed with brine, dried over Na2SO4 and filtered. After evaporation the residue is purified by chromatography to provide the product (276 mg; 24 %) as black oil. Ex.65.2: rel-4-ethyl-3-[2-(2H3)methyl-6-{[(1r,4r)-4-(trifluoromethyl)cyclo- hexyl]oxy}pyrimidin-4-yl]-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one

[0070] To rel-4-ethyl-3-[2-(2H3)methyl-6-{[(1r,4r)-4-(trifluoromethyl)cyclohexyl]oxy}- pyrimidin-4-yl]-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H,4H,5H-pyrrolo[3,2- b]pyridin-5-one (Ex.65.1) (276 mg; 0.12 mmol) in DCM (8 ml) was added TFA (2.2 mL) for 3 h at RT. The reaction was evaporated to dryness, the residue was dissolved in dioxane (5.5 mL) and an aqueous ammonia solution (32%; 5.5 mL) was added for 12 h at RT. After evaporation the residue was purified by chromatography to afford the product (11 mg; 21%) as white solid. Example 66: rel-4-[(1,1,2,2,2-2H5)ethyl]-3-(5-fluoro-2-methyl-6-{[(1r,4r)-4-(tri- fluoromethyl)cyclohexyl]oxy}pyrimidin-4-yl)-1H,4H,5H-pyrrolo[3,2-b]pyridin-5- one Ex.66.1: 4-[(1,1,2,2,2-2H5)ethyl]-1-(4-methylbenzenesulfonyl)-1H,4H,5H- pyrrolo[3,2-b]pyridin-5-one 1-(4-methylbenzenesulfonyl)-1H-pyrrolo[3,2-b]pyridin-5-ol Int 2.2) (5 g; 17 mmol) was dissolved in DMF (50 mL) and Lithium bis(trimethylsilyl)amide (1N in THF; 19 mL; 19 mmol) was slowly added at 0 °C followed by the addition of Iodoethane-D5 (3.1 g; 19 mmol) dissolved in DMF (25 mL). The mixture was stirred at 5 to 10 °C for 30 min and at RT over night. The mixture was diluted with H2O and cooled in an ice bath. A precipitate formed. The suspension was filtered by suction and the filter cake was washed with H2O. The filtrate was re-extracted with DCM, the organic layer was evaporated to dryness and the residue was combined with the filter cake. The crude was purified by chromatography to afford the product (3.3 g; 60%) and 5-[(1,1,2,2,2- 2H5)ethoxy]-1-(4-methylbenzenesulfonyl)-1H-pyrrolo[3,2-b]pyridine (0.9 g; 15 %) both as colorless solid. Ex.66.2: 4-[(1,1,2,2,2-2H5)ethyl]-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one 4-[(1,1,2,2,2-2H5)ethyl]-1-(4-methylbenzenesulfonyl)-1H,4H,5H-pyrrolo[3,2- b]pyridin-5-one (Ex.66.3) (3.3 g; 10 mmol) was suspended in EtOH (57 mL) and NaOEt (20% in ethanol; 7.25 mL; 18.7 mmol) was added dropwise. The resulting mixture was stirred at 20 °C for 2 h. The reaction mixture was poured on ice water and extracted with EtOAc. The combined organic layers were evaporated to dryness and the residue was purified by chromatography to afford the product (1.73 g; 97 %) as yellow solid. Ex.66.3: 4-[(1,1,2,2,2-2H5)ethyl]-3-iodo-1H,4H,5H-pyrrolo[3,2-b]pyridin-5- one 4-[(1,1,2,2,2-2H5)ethyl]-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Ex.66.4) (1.73 g; 10 mmol) was suspended in DMF (26 mL) and KOH (2.26 g; 40 mmol) was added. The mixture was cooled to - 20 °C and then a solution of I2 (2.69 g; 10 mmol) in DMF (9 mL) was slowly added via dropping funnel over a period of 30 min. The temperature during the addition was kept constant between -25 to -20 °C. After complete addition the mixture was stirred at - 20 °C for further 15 min. A light brown solution was formed. The mixture was treated with saturated sodium thiosulfate solution and then allowed to warm up to RT. The mixture was poured into H2O and the precipitate was sucked off. The crude product (2 g; 63%) was obtained as colorless solid and used in the next step without further purification. Ex.66.4: 4-[(1,1,2,2,2-2H5)ethyl]-3-iodo-1-{[2-(trimethylsilyl)ethoxy]methyl}- 1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one 4-[(1,1,2,2,2-2H5)ethyl]-3-iodo-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Ex.66.5) (638 mg; 2.14 mmol) was suspended in DMF (30 mL) and cooled to 0 to 5 °C. NaH (60% suspension in paraffin oil; 332 mg; 8.31 mmol) was added in portions and the mixture was stirred at 0 to 5 °C for 45 min. A cloudy light yellow suspension was formed. Subsequently 2-(Trimethylsilyl)ethoxymethyl chloride (1.70 mL; 9.59 mmol) was added via syringe over a period of 5 min. The resulting mixture (pale brown thin suspension) was stirred at 10 to 15 °C for 15 min. The mixture was poured onto ice-water and extracted with DCM. The combined organic layers were washed with H2O and brine, dried with Na2SO4, filtered and evaporated to dryness. The residue was purified by chromatography to afford the product (2.60 g; 95 %) as pale red oil. Ex.66.5: 4-[(1,1,2,2,2-2H5)ethyl]-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2- H-pyrrolo[3,2-b]pyridin-5-one 4-[(1,1,2,2,2-2H5)ethyl]-3-iodo-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H,4H,5H- pyrrolo[3,2-b]pyridin-5-one (Ex.66.6) (2.60 g; 6.05 mmol) and Tetrakis(triphenylphosphine)palladium(0) (736 mg; 0.61 mmol) were dissolved in dioxane (40 mL). TEA (5 mL; 36 mmol) and 4,4,5,5-Tetramethyl-1,3,2- dioxaborolane (1.8 ml; 12 mmol) were added at 100 °C and for 1 h. The mixture was cooled to room temperature and a precipitate was formed. It was filtered by suction and the filter cake was washed with EtOAc. The filtrate was evaporated to dryness and the residue was suspended in EtOAc and sucked off. The filtrate was purified by chromatography to afford the product (2.51 g; 96 %) as orange oil. Ex.66.6: rel-4-[(1,1,2,2,2-2H5)ethyl]-3-(5-fluoro-2-methyl-6-{[(1r,4r)-4- (trifluoromethyl)cyclohexyl]oxy}pyrimidin-4-yl)-1-{[2- (trimethylsilyl)ethoxy]methyl}-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one To rel-5-fluoro-4-iodo-2-methyl-6-{[(1r,4r)-4-(trifluoromethyl)cyclohexyl]oxy}- pyrimidine (Ex.66.7) (1.17 g; 2.88 mmol) in dioxane (50 mL) / H2O (2.50 mL) was added 4-[(1,1,2,2,2-2H5)ethyl]-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan- 2-yl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (1.25 g; 2.88 mmol), Cs2CO3 (Ex.66.7) (1.88 g; 5.76 mmol) and Tetrakis(triphenylphosphine)palladium(0) (333 mg; 0.29 mmol) at 110 °C over night under argon atmosphere. The reaction mixture was diluted with H2O, extracted with EtOAc, the organic layers were washed with brine, dried with Na2SO4, filtered and evaporated. The residue was purified by chromatography to afford the product (1.31 g; 64 %) as orange oil. Ex.66.7: rel-4-[(1,1,2,2,2-2H5)ethyl]-3-(5-fluoro-2-methyl-6-{[(1r,4r)-4- (trifluoromethyl)cyclohexyl]oxy}pyrimidin-4-yl)-1H,4H,5H-pyrrolo[3,2-b]pyridin- 5-one To rel-4-[(1,1,2,2,2-2H5)ethyl]-3-(5-fluoro-2-methyl-6-{[(1r,4r)-4-(trifluoro- methyl)cyclohexyl]oxy}pyrimidin-4-yl)-1-{[2-(trimethylsilyl)ethoxy]methyl}- 1H,4H,5H-pyrrolo[3,2-b]pyridin-5-one (Ex.66.8) (1.31 g; 1.85 mmol) in DCM (40 mL) was added TFA (10 mL) for 5 h at RT. After evaporation to dryness the residue was dissolved in dioxane (30 mL) and Ammonia solution (32 %; 30 mL) overnight at RT. The reaction mixture was sucked off, the filter cake was washed with water and dried at 50 °C under vacuum overnight to afford the product (731 mg; 88 %) as colorless solid. Table 1 and Table 1a Table 1 and Table 1a below show exemplary compounds of the present invention. They have been synthesized as described in the Examples above or similar thereto. Note: Unless indicated otherwise for a specific compound and its structure (e.g., by assigning “Absolute” to a structure), the absolute configuration as depicted for the structures of the compounds in Table 1 and Table 1a below is assigned arbitrarily. Table 1

[0071]

[0072]

[0073] Table 1a

[0074]

[0075]

[0076] LCMS Methods referred to in Table 1a

[0077] Chiral Separation Methods referred to in Table 1a Biological Data SK-HEP-1 reporter assay (“reporter assay”) To identify inhibitors of YAP-TEAD interaction, 8x TEAD responsive elements driving the NanoLuc® luciferase gene were stably integrated into SK-HEP-1 cells (ECACC #: 91091816). For the assay, cells were treated in duplicates with the test compounds in a 10-point dose, with the top concentration starting at 30µM (final concentration in assay). After a 24 hour incubation at 37°C, 95% rH, and 5% CO2, a luciferase substrate / lysis reagent mix (NanoGlo™, Promega) was added to the cells, allowing the quantification of cellular luciferase activity. Cell Media: The cells were cultured in the following media: MEM, +10% FBS, +1x GlutaMAX, +1mM Sodium-Pyruvate, + 100µM Non-essential amino acids, +0.1mg / ml Hygromycin. The media used for the assay was: MEM (w / o Phenol Red), +10% FBS, +1x GlutaMAX, +1mM Sodium-Pyruvate, + 100µM Non- essential amino acids, +0.5% Pen / Strep Reagents: The reagents used are listed below: Cell culture: The cells were examined using an inverted microscope to check for health and cell density. To dissociate adherent cells, the monolayer of cells was washed once with pre-warmed PBS. After removing the PBS, 3 ml pre- warmed Accutase® was added to a F75 flask, dispersed evenly and the flask was allowed to sit in incubator for ~4-5 minutes. When a single cell suspension was obtained, 7 ml of prewarmed growth media was added and resuspended with the cells. The cell suspension was transferred to a sterile 15 ml conical centrifuge tube, and spun for 5 min at 300xg, RT. The supernatant was discarded and the pellet was resuspended in 10 ml of pre-warmed growth media. The total cell count was determined, and 20 µl of the desired cell number was added to each well of a 384 well plate using a Multidrop Combi. The plates were then incubated for 24 hours at 37°C, 95% rH, and 5% CO2. Compound treatment: 24 hours after seeding, the cells were treated with compounds. A 1:333 dilution of compounds, diluted in DMSO, was made to get a final concentration of 0.3% DMSO per well. To transfer the compounds to the assay plate,120nl was shot from Labcyte low dead volume plates to the cell plates containing 20µl media / well with the ECHO 555 liquid handling system. After treatment, the cells were fed with 20µl fresh pre-warmed assay media using a Multidrop combi. The assay plates were then incubated for another 24h at 37°C, 95% rH, and 5% CO2. Luciferase readout: 24 h after treatment, the plates were taken out of the incubator and were allowed to equilibrate to RT. 30 µl of NanoGlo® reagent was added to the plates in the dark. Plates were shaken for 20 min on a Teleshake (~1500 rpm) in the dark. The luminescence was then measured using an EnVision microplate reader. The IC50 values were generated using Genedata Screener®. Viability assay in H226 (Yap-dependent) and SW620 Yap KO (Yap independent) cells The ability of YAP-TEAD inhibitors to inhibit tumor cell growth was evaluated using two different cell lines: NCI-H226, which is a YAP dependent cell line, and SW620 cells, where YAP and TAZ were knocked out using CRISPR to generate a YAP independent cell line. For the assay, cells were treated in duplicates with the test compounds in a 10-point dose, 1:3 dilution steps, with the top concentration starting at 30µM (final concentration in assay). After a 96 hour incubation at 37°C, 95% rH, and 5% CO2, a cell-permeant DNA-binding dye that stains only healthy cells (CyQUANT®, Promega) was added to the cells, allowing the quantification of cell viability. Cell Media: The NCI-H226 cells were cultured in the following media: RPMI 1640, +10% FBS, +1x GlutaMAX, +10mM HEPES, + 0.5% Pen / Strep. The SW620-KO cells were cultured in the following media: DMEM / F-12, +10% FBS, +1x GlutaMAX, +10mM HEPES, +0.5% Pen / Strep. Reagents: The reagents used are listed below: Cell culture: The cells were examined using an inverted microscope to check for health, cell density, etc. To dissociate adherent cells, the monolayer of cells was washed once with pre-warmed PBS. After removing the PBS, 3ml pre- warmed Accutase was added to a F75 flask, dispersed evenly and the flask was allowed to sit in incubator for ~4-5 minutes. When a single cell suspension was obtained, 7ml of prewarmed growth media was added and resuspended with the cells. The cell suspension was transferred to a sterile 15 ml conical centrifuge tube, and spun for 5min at 300xg, RT. The supernatant was discarded and the pellet was resuspended in 10ml of pre-warmed growth media. The total cell count was determined, and 20µl of the desired cell number was added to each well of a 384 well plate using a Multidrop Combi. The plates were then incubated for 24 hours at 37°C, 95% rH, and 5% CO2. Compound treatment: 24 hours after seeding, the cells were treated with compounds. A 1:333 dilution of compounds, diluted in DMSO, was made to get a final concentration of 0.3% DMSO per well. To transfer the compounds to the assay plate,120nl was shot from Labcyte low dead volume plates to the cell plates containing 20µl media / well with the ECHO 555 liquid handling system. After treatment, the cells were fed with 20µl fresh pre-warmed assay media using a Multidrop combi. The assay plates were then incubated for 96h at 37°C, 95% rH, and 5% CO2. CyQuant® Measurement 96h after treatment 30µl of CyQuant® reagent was added to the assay plates using a Multidrop combi in the dark. The plates were then incubated for 1 hour at 37°C, 95% rH and 5% CO2. Thereafter, the assay plates were removed from the incubator and allowed to equilibrate to RT for 30min in the dark without lid. Finally, they were measured using an EnVision microplate reader with a FITC bottom read program. Viability assay in H292 cells (“H292 viability assay”) This assay is used to identify compounds which inhibit cell growth in YAP dependent cells. For the assay, cells were treated in duplicates with the test compounds in a 10-point dose, with the top concentration starting at 30µM (final concentration in assay). After a 96 hour incubation at 37°C, 95% rH, and 5% CO2, a cell permeant DNA binding dye (CyQUANT®) was added to the cells, allowing the quantification of cellular viability. Cell Media: The cells were cultured in the following media: RPMI 1640, +10% FBS, +1x GlutaMAX, +1mM Sodium-Pyruvate, +10mM HEPES, +1% Pen / Strep. Reagents: The reagents used are listed below: Cell culture: The cells were examined using an inverted microscope to check for health and cell density. To dissociate adherent cells, the monolayer of cells was washed once with pre-warmed PBS. After removing the PBS, 3 ml pre- warmed Accutase® was added to a F75 flask, dispersed evenly and the flask was allowed to sit in incubator for ~4-5 minutes. When a single cell suspension was obtained, 7 ml of prewarmed growth media was added and resuspended with the cells. The cell suspension was transferred to a sterile 15 ml conical centrifuge tube, and spun for 5 min at 300xg, RT. The supernatant was discarded and the pellet was resuspended in 10 ml of pre-warmed growth media. The total cell count was determined, and 20 µl of the desired cell number was added to each well of a 384 well plate using a Multidrop Combi. The plates were then incubated for 24 hours at 37°C, 95% rH, and 5% CO2. Compound treatment: 24 hours after seeding, the cells were treated with compounds. A 1:333 dilution of compounds, diluted in DMSO, was made to get a final concentration of 0.3% DMSO per well. To transfer the compounds to the assay plate,120nl was shot from Labcyte low dead volume plates to the cell plates containing 20µl media / well with the ECHO 555 liquid handling system. After treatment, the cells were fed with 20µl fresh pre-warmed assay media using a Multidrop combi. The assay plates were then incubated for another 24h at 37°C, 95% rH, and 5% CO2. CyQuant® Measurement: 96 h after treatment 30 µl of 2x CyQuant® staining solution, which was prepared in 1:5 ratio of suppressor to stain was added to the plates in the dark. Plates were incubated for 1 h at 37°C, 95% rH, and 5% CO2. Then the assay plate was equilibrated to RT for 30 minutes in the dark. The fluorescence was then measured using an EnVision microplate reader using a FITC filter. The IC50 values were generated using Genedata Screener®. Experimental data in SK-HEP-1 reporter assay of the compounds shown in Table 1 and Table 1a are shown in Table 2 (“Reporter”) below and classified in the following groups: Group A IC50 is in the range of 1 nM to 100 nM Group B IC50 is in the range of >100 nM to 1000 nM Group C IC50 is in the range of >1000 nM to 10000 nM Group D IC50 is in the range >10000 to 30000 nM n.d. Not detectable below threshold given in parantheses Experimental data in the viability assays (H226, H292; SW620 Yap KO) of the compounds shown in Table 1 and Table 1a are shown in Table 2 below and classified in the following groups: Group A IC50 is in the range of 1 nM to 100 nM Group B IC50 is in the range of >100 nM to 1000 nM Group C IC50 is in the range of >1000 nM to 10000 nM Group D IC50 is in the range >10000 to 30000 nM n.d. Not detectable below threshold given in parantheses Table 2

[0078] Thermal shift assay Nano Differential Scanning Fluorimetry. NanoDSF was performed on a Prometheus NT.48 instrument (NanoTemper Technologies GmbH). Protein sample was briefly centrifuged before preparation. The final reaction mixture contained 11.8 μM of hsTEAD1 (209-426), 7.3 µM of hsTEAD2 (217-447)-His, 7.9 µM of hsTEAD3 (216-435) or 11.7 µM of hsTEAD4 (217-434)-Thrb-His diluted in 20 mM Tris pH 8.0, 150 mM NaCl, 0.5mM TCEP (not included for peptide 17) to which 1 μL DMSO 100% (apo) or 100 µM of each compound were added. This incubation was performed at 4°C for 2 h. High sensitivity capillaries (NanoTemper Technologies) were filled with 10 μL of sample and placed on the Prometheus NT.48 sample holder. A temperature gradient of 1°C / min was applied from 25°C to 90°C.The intrinsic protein fluorescence at 330 and 350 nm and light scattering were recorded. Data were analysed with respect to the fluorescence (330 nm) and / or aggregation values. The melting temperatures (Tm) were obtained by calculating the midpoint of each transition, using the PR.ThermControl Software™ version 2.16 and Stability Analysis Software™ version 1.1. The thermal stability and aggregation effect of each compound was calculated by subtracting the Tm values in the presence of each compound to those obtained in the presence of DMSO. A change in the Tm was considered significant when the |ΔTm| ≥ 2 °C. Samples were tested in duplicates or triplicates. Table 3

Claims

Claims 1. A Compound of formula (I)I whereinRing D together with R2denotes or ; X1denotes CRX1or N; RX1denotes H, halogen, straight-chain or branched C1-4-alkyl which is unsubstituted or substituted with independently from each other 1, 2, or 3 halogen, and / or OH; R1denotes straight-chain or branched C1-6-alkyl, which is unsubstituted or substituted with independently from each other 1, 2, or 3 halogen; or C3- 7-cycloalkyl, which is unsubstituted or substituted with independently from each other 1, 2, or 3 halogen, and in which C1-6-alkyl or C3-7-cycloalkyl 1, 2, 3, 4, 5, 6, or 7 H-atoms may be replaced by deuterium (D-atoms); R2denotes H, Alk2, Ar2, Hetar2, Cyc2, Hetcyc2, -L2-Ar2a; R3denotes H, halogen, or C1-6-alkyl, C2-6-alkenyl or C2-6-alkinyl, each of which may be unsubstituted or substituted independently from each other -OH or 1, 2, or 3 halogen;A denotes 1,3-phenylen or a monocyclic divalent heteroaryl with 5 or 6 rings atoms, wherein 1, 2, or 3 of said ring atoms are heteroatoms(s) selected from N, O and / or S and the remaining are carbon atoms, wherein that 1,3-phenylen or monocyclic heteroaryl bears the bicyclic ring system ofthe compound of formula I in 1- positon and that L1-B radical of the compound of formula I in 3-position relative to that bicyclic ring system, wherein each of that 1,3-phenylen or monocyclic hetereoaryl may further be unsubstituted or mono- or disubstituted with independently from each other halogen, straight-chain or branched C1-4- alkyl, which is unsubstituted or substituted with 1, 2, or 3 halogen, or C3- 5-cycloalkyl,and in which C1-4-alkyl or C3-5-cycloalkyl 1, 2, 3, 4, 5, 6, or 7 H-atoms may be replaced by deuterium (D-atoms); B denotes Ar1, Hetar1, Cyc1, Hetcyc1; L1denotes -O-, -N(R4)-, -O-CH2-, -O-CH(R5)-, -O-SO2-, -NH-CH2-, -N(R6)- CH2-, -NH-C(=O)-, -N(R6)-C(=O)-, -CH2-, -CH(R7)-, -CH2CH2-, -CH2-O-; R4denotes H, straight-chain or branched C1-6-alkyl; R5, R6, R7denote independently from each other straight-chain or branched C1-6-alkyl; L2denotes a divalent -S(=O)2- group; Alk2denotes straight-chain or branched C1-6-alkyl, C2-6-alkenyl or C2-6-alkinyl, each of which may be unsubstituted or substituted with independently from each other R2a1, R2a2and / or R2a3; Ar1denotes a mono- or bicyclic aryl with 5, 6, 7, 8, 9, 10 ring carbon atoms, wherein that aryl is unsubstituted or substituted with independently from each other RC1, RC2, and / or RC3; Ara, Ar2, Ar2adenote independently from each other a mono- or bicyclic aryl with 5, 6, 7, 8, 9, 10 ring carbon atoms, wherein that aryl maybe unsubstituted or substituted with independently from each other RB1, RB2, RB3, RB4, and / or RB5; Hetar1denotes a mono- or bicyclic heteroaryl with 5, 6, 7, 8, 9, 10, 11, 12 ring atoms wherein 1, 2, 3, 4, 5 of said ring atoms is / are a hetero atom(s) selected from N, O and / or S and the remaining are carbon atoms, wherein that heteroaryl is unsubstituted or substituted with independently from each other RC1, RC2, and / or RC3; Hetara, Hetar2, Hetar2adenote independently from each other a mono- or bicyclic heteroaryl with 5, 6, 7, 8, 9, 10, 11, 12 ring atoms wherein 1, 2, 3, 4, 5 of said ring atoms is / are a hetero atom(s) selected from N, O and / or S and the remaining are carbon atoms, wherein that heteroaryl is unsubstituted or substituted with independently from each other RB1, RB2, RB3, RB4, and / or RB5; Cyc1denotes a saturated or partially unsaturated, mono-, bi- or tricyclic carbocycle with 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 ring carbon atoms, wherein said carbocycle may be unsubstituted or substituted with independently from each other RC6, RC7, RC8, RC9, RC10, and / or RC11; Cyc2, Cyc2adenote independently from each other a saturated or partially unsaturated, mono-, bi- or tricyclic carbocycle with 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 ring carbon atoms, wherein said carbocycle is unsubstituted or substituted with independently from each other RB6, RB7, RB8, RB9, RB10, and / or RB11; Hetcyc1denotes a saturated or partially unsaturated, mono- or bicylic heterocycle with 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 ring atoms wherein 1, 2, 3, 4, 5 of said ring atoms is / are a hetero atom(s) selected from N, O and / or S and the remaining are carbon atoms, wherein said heterocycle is unsubstituted or substituted with independently from each other RC6, RC7, RC8, RC9, RC10, and / or RC11; Hetcyca, Hetcyc2, Hetcyc2adenote independently from each other a saturated or partially unsaturated, mono- or bicylic heterocycle with 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 ring atoms wherein 1, 2, 3, 4, 5 of said ring atoms is / are a hetero atom(s) selected from N, O and / or S and theremaining are carbon atoms, wherein said heterocycle is unsubstituted or substituted with independently from each other RB6, RB7, RB8, RB9, RB10, and / or RB11; R2a1, R2a2, R2a3denote independently from each other halogen, -CN, -NH2, -NHRa, -NRaRb, -OH, -ORc, -P(=O)RdRe, -SH, -SRf, -S(=O)Rf, -S(=O)2Rf, -S(=O)(=NRg)Rf, -N=S(=O)RfRh, -C(=O)NH2, -C(=O)NHRa, - C(=O)NRaRb, -C(=O)OH, -C(=O)ORc, -NH-C(=O)-Ri, Cyc2a, Hetar2a, Hetcyc2a; Ra, Rbdenote independently from each other straight-chain or branched C1-6-alkyl, Ara, Hetara, Hetcyca; or Raand Rbform together with the nitrogen atom to which they are attached to a saturated, partially unsaturated or aromatic heterocycle with 3, 4, 5, 6, 7 ring atoms wherein 1 of said ring atoms is said nitrogen atom and no or one further ring atom is a hetero atom selected from N, O or S and the remaining are carbon atoms, wherein said heterocycle is unsubstituted or substituted with independently from each other RB6, RB7, RB8, RB9, RB10, and / or RB11; Rcdenotes straight-chain or branched C1-4-alkyl, C2-4-alkenyl or C2-4-alkinyl, each of which may be unsubstituted or substituted with -OH; C3-7- cycloalkyl which may be unsubstituted or substituted with -OH and / or halogen; Rd, Redenote independently from each other straight-chain or branched C1-6-alkyl; Rf, Rhdenote independently from each other straight-chain or branched C1-6-alkyl; Rgdenotes H, straight-chain or branched C1-6-alkyl; Ridenotes H, straight-chain or branched C1-6-alkyl; RB1, RB2, RB3, RB4, RB5denote independently from each other halogen; -OH; -OC1-4-alkyl; C1-4-alkyl, which may be unsubstituted or substituted with 1, 2, or 3 halogen;RB6, RB7, RB8, RB9, RB10, RB11denote independently from each other halogen; OH; -OC1-4-alkyl; C1-4-alkyl, which is unsubstituted or substituted with 1 or 2 OH and / or 1, 2, or 3 halogen; and / or two of RB6, RB7, RB8, RB9, RB10, RB11which are attached to the same carbon atom of said carbocycle or said heterocycle form a divalent oxo (=O) group; and / or two of RB6, RB7, RB8, RB9, RB10, RB11which are attached to the same sulfur (S) atom of said heterocycle form a divalent oxo (=O) group while at the same time two further of RB6, RB7, RB8, RB9, RB10, RB11which are attached to the same sulfur atom form either a divalent oxo group or a divalent =N-H or =N-C1-4-alkyl group, thereby forming an -S(=O)2, - S(=O)(=NH), or -S(=O)(=N-C1-4-alkyl) moiety; RC1, RC2, RC3denote independently from each other halogen; C1-4-alkyl or -OC1-4-alkyl, each of which may be unsubstituted or substituted with 1, 2, or 3 halogen; RC6, RC7, RC8, RC9, RC10, and / or RC11denote independently from each other halogen; C1-4-alkyl, which is unsubstituted or substituted with 1, 2, or 3 substituents independently from each other selected from halogen; -OC1- 4-alkyl, which is unsubstituted or substituted with 1, 2, or 3 halogen; halogen denotes F, Cl, Br, or I; or any N-oxide, solvate, tautomer or stereoisomer thereof and / or any pharmaceutically acceptable salt of each of the foregoing, including mixtures thereof in all ratios.

2. A Compound of formula (I)I whereinRing D together with R2denotes or ; X1denotes CRX1or N; RX1denotes H, halogen, straight-chain or branched C1-4-alkyl which is unsubstituted or substituted with independently from each other 1, 2, or 3 halogen, and / or OH; R1denotes straight-chain or branched C1-6-alkyl, which is unsubstituted or substituted with independently from each other 1, 2, or 3 halogen; R2denotes H, Alk2, Ar2, Hetar2, Cyc2, Hetcyc2, -L2-Ar2a; R3denotes H or halogen; A denotes 1,3-phenylen or a monocyclic divalent heteroaryl with 5 or 6 rings atoms, wherein 1, 2, or 3 of said ring atoms are heteroatoms(s) selected from N, O and / or S and the remaining are carbon atoms, wherein that 1,3-phenylen or monocyclic heteroaryl bears the bicyclic ring system ofthe compound of formula I in 1- positon andthat L1-B radical of the compound of formula I in 3-position relative to that bicyclic ring system, wherein each of that 1,3-phenylen or monocyclic hetereoaryl may further be unsubstituted or mono- or disubstituted with independently from each other halogen, straight-chain or branched C1-4- alkyl, which is unsubstituted or substituted with 1, 2, or 3 halogen; B denotes Ar1, Hetar1, Cyc1, Hetcyc1; L1denotes -O-, -N(R4)-, -O-CH2-, -O-CH(R5)-, -O-SO2-, -N(R6)-CH2-, -N(R6)- C(=O)-, -CH2-, -CH(R7)-, -CH2CH2-, -CH2-O-; R4denotes H, straight-chain or branched C1-6-alkyl; R5, R6, R7denote independently from each other straight-chain or branched C1-6-alkyl; L2denotes a divalent -S(=O)2- group; Alk2denotes straight-chain or branched C1-6-alkyl, C2-6-alkenyl or C2-6-alkinyl, each of which may be unsubstituted or substituted with independently from each other R2a1, R2a2and / or R2a3; Ar1denotes a mono- or bicyclic aryl with 5, 6, 7, 8, 9, 10 ring carbon atoms, wherein that aryl is unsubstituted or substituted with independently from each other RC1, RC2, and / or RC3; Ara, Ar2, Ar2adenote independently from each other a mono- or bicyclic aryl with 5, 6, 7, 8, 9, 10 ring carbon atoms, wherein that aryl may be unsubstituted or substituted with independently from each other RB1, RB2, RB3, RB4, and / or RB5; Hetar1denotes a mono- or bicyclic heteroaryl with 5, 6, 7, 8, 9, 10, 11, 12 ring atoms wherein 1, 2, 3, 4, 5 of said ring atoms is / are a hetero atom(s) selected from N, O and / or S and the remaining are carbon atoms, wherein that heteroaryl is unsubstituted or substituted with independently from each other RC1, RC2, and / or RC3; Hetara, Hetar2, Hetar2adenote independently from each other a mono- or bicyclic heteroaryl with 5, 6, 7, 8, 9, 10, 11, 12 ring atoms wherein 1, 2, 3, 4, 5 of said ring atoms is / are a hetero atom(s) selected from N, O and / or S and the remaining are carbon atoms, wherein that heteroaryl isunsubstituted or substituted with independently from each other RB1, RB2, RB3, RB4, and / or RB5; Cyc1denotes a saturated or partially unsaturated, mono-, bi- or tricyclic carbocycle with 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 ring carbon atoms, wherein said carbocycle may be unsubstituted or substituted with independently from each other RC6, RC7, RC8, RC9, RC10, and / or RC11; Cyc2denotes a saturated or partially unsaturated, mono-, bi- or tricyclic carbocycle with 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 ring carbon atoms, wherein said carbocycle is unsubstituted or substituted with independently from each other RB6, RB7, RB8, RB9, RB10, and / or RB11; Hetcyc1denotes a saturated or partially unsaturated, mono- or bicylic heterocycle with 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 ring atoms wherein 1, 2, 3, 4, 5 of said ring atoms is / are a hetero atom(s) selected from N, O and / or S and the remaining are carbon atoms, wherein said heterocycle is unsubstituted or substituted with independently from each other RC6, RC7, RC8, RC9, RC10, and / or RC11; Hetcyca, Hetcyc2, Hetcyc2adenote independently from each other a saturated or partially unsaturated, mono- or bicylic heterocycle with 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 ring atoms wherein 1, 2, 3, 4, 5 of said ring atoms is / are a hetero atom(s) selected from N, O and / or S and the remaining are carbon atoms, wherein said heterocycle is unsubstituted or substituted with independently from each other RB6, RB7, RB8, RB9, RB10, and / or RB11; R2a1, R2a2, R2a3denote independently from each other halogen, -CN, -NH2, -NHRa, -NRaRb, -OH, -ORc, -P(=O)RdRe, -SH, -SRf, -S(=O)Rf, -S(=O)2Rf, -S(=O)(=NRg)Rf, -N=S(=O)RfRh, -C(=O)NH2, -C(=O)NHRa, - C(=O)NRaRb, -C(=O)OH, -C(=O)ORc, -NH-C(=O)-Ri, Hetar2a, Hetcyc2a; Ra, Rbdenote independently from each other straight-chain or branched C1-6-alkyl, Ara, Hetara, Hetcyca; or Raand Rbform together with the nitrogen atom to which they are attached to a saturated, partially unsaturated or aromatic heterocycle with 3, 4, 5, 6,7 ring atoms wherein 1 of said ring atoms is said nitrogen atom and no or one further ring atom is a hetero atom selected from N, O or S and the remaining are carbon atoms, wherein said heterocycle is unsubstituted or substituted with independently from each other RB6, RB7, RB8, RB9, RB10, and / or RB11; Rcdenotes straight-chain or branched C1-4-alkyl, C2-4-alkenyl or C2-4-alkinyl, each of which may be unsubstituted or substituted with -OH; C3-7- cycloalkyl which may be unsubstituted or substituted with -OH and / or halogen; Rd, Redenote independently from each other straight-chain or branched C1-6-alkyl; Rf, Rhdenote independently from each other straight-chain or branched C1-6-alkyl; Rgdenotes H, straight-chain or branched C1-6-alkyl; Ridenotes H, straight-chain or branched C1-6-alkyl; RB1, RB2, RB3, RB4, RB5denote independently from each other halogen; -OH; -OC1-4-alkyl; C1-4-alkyl, which may be unsubstituted or substituted with 1, 2, or 3 halogen; RB6, RB7, RB8, RB9, RB10, RB11denote independently from each other halogen; OH; -OC1-4-alkyl; C1-4-alkyl, which is unsubstituted or substituted with 1 or 2 OH and / or 1, 2, or 3 halogen; and / or two of RB6, RB7, RB8, RB9, RB10, RB11which are attached to the same carbon atom of said carbocycle or said heterocycle form a divalent oxo (=O) group; and / or two of RB6, RB7, RB8, RB9, RB10, RB11which are attached to the same sulfur (S) atom of said heterocycle form a divalent oxo (=O) group while at the same time two further of RB6, RB7, RB8, RB9, RB10, RB11which are attached to the same sulfur atom form either a divalent oxo group or a divalent =N-H or =N-C1-4-alkyl group, thereby forming an -S(=O)2, - S(=O)(=NH), or -S(=O)(=N-C1-4-alkyl) moiety;RC1, RC2, RC3denote independently from each other halogen; C1-4-alkyl or -OC1-4-alkyl, each of which may be unsubstituted or substituted with 1, 2, or 3 halogen; RC6, RC7, RC8, RC9, RC10, and / or RC11denote independently from each other halogen; C1-4-alkyl, which is unsubstituted or substituted with 1, 2, or 3 substituents independently from each other selected from halogen; -OC1- 4-alkyl, which is unsubstituted or substituted with 1, 2, or 3 halogen; halogen denotes F, Cl, Br, or I; or any N-oxide, solvate, tautomer or stereoisomer thereof and / or any pharmaceutically acceptable salt of each of the foregoing, including mixtures thereof in all ratios.

3. Compound according to any one of claim 1 or 2 whereinRing D together with R2denotes ; X1denotes CRX1or N; RX1denotes H; and R2, A, L1, and B are as defined in claim 1; or any N-oxide, solvate, tautomer or stereoisomer thereof and / or any pharmaceutically acceptable salt of each of the foregoing, including mixtures thereof in all ratios.

4. Compound according to any one of the preceding claims wherein X1denotes CH;or any N-oxide, solvate, tautomer or stereoisomer thereof and / or any pharmaceutically acceptable salt of each of the foregoing, including mixtures thereof in all ratios.

5. Compound according to any one of claim 1 or 2 whereinRing D together with R2denotes ; and R2, A, L1, and B are as defined in claim 1; or any N-oxide, solvate, tautomer or stereoisomer thereof and / or any pharmaceutically acceptable salt of each of the foregoing, including mixtures thereof in all ratios.

6. Compound according to any one of the preceding claims wherein R3denotes halogen; optionally F or I; in particular F; or any N-oxide, solvate, tautomer or stereoisomer thereof and / or any pharmaceutically acceptable salt of each of the foregoing, including mixtures thereof in all ratios.

7. Compound according to any one of claims 1 to 5 wherein R3denotes H; or any N-oxide, solvate, tautomer or stereoisomer thereof and / or any pharmaceutically acceptable salt of each of the foregoing, including mixtures thereof in all ratios.

8. Compound according to any one of the preceding claims wherein R1denotes unsubstituted straight-chain or branched C1-6-alkyl, in which C1- 6-alkyl 1, 2, 3, 4, 5, 6, or 7 H-atoms may be replaced by deuterium (D- atoms); optionally -CH3, -CD3, -C2H5, or -C2D5; or any N-oxide, solvate, tautomer or stereoisomer thereof and / or any pharmaceutically acceptable salt of each of the foregoing, including mixtures thereof in all ratios 9. Compound according to any one of the preceding claims wherein R2denotes H, Alk2, Hetar2, Hetcyc2, -L2-Ar2a; or any N-oxide, solvate, tautomer or stereoisomer thereof and / or any pharmaceutically acceptable salt of each of the foregoing, including mixtures thereof in all ratios.

10. Compound according to any one of the preceding claims wherein R2denotes H, Alk2, Hetar2, Hetcyc2, -L2-Ar2a; Alk2denotes denotes straight-chain or branched C1-6-alkyl or C2-6-alkinyl, each of which may be unsubstituted or substituted with independently from each other R2a1, R2a2and / or R2a3; L2denotes a divalent -S(=O)2- group; Ara, Ar2adenote independently from each other phenyl which may be unsubstituted or substituted with independently from each other RB1and / or RB2; Hetara, Hetar2, Hetar2adenote independently from each other a monocyclic heteroaryl with 5 or 6 ring atoms wherein 1, 2, or 3 of said ring atoms is / are a hetero atom(s) selected from N, O and / or S and the remaining are carbon atoms, wherein that heteroaryl is unsubstituted or substituted with independently from each other RB1and / or RB2;Cyc2adenotes a saturated monocyclic carbocycle with 3, 4, 5, 6, or 7 ring carbon atoms, wherein said carbocycle is unsubstituted or substituted with independently from each other RB6and / or RB7; Hetcyca, Hetcyc2, Hetcyc2adenote independently from each other a saturated or partially unsaturated monocylic heterocycle with 3, 4, 5, or 6 ring atoms wherein 1 or 2 of said ring atoms is / are a hetero atom(s) selected from N, O and / or S and the remaining are carbon atoms, wherein said heterocycle is unsubstituted or substituted with independently from each other RB6and / or RB7and / or RB8and RB9together; R2a1, R2a2, R2a3denote independently from each other halogen, -CN, -NH2,Ra, Rbdenote independently from each other straight-chain or branched C1-6-alkyl, Ara, Hetara, Hetcyca; or Raand Rbform together with the nitrogen atom to which they are attached to a saturated or partially unsaturated heterocycle with 3, 4, 5, 6, 7 ring atoms wherein 1 of said ring atoms is said nitrogen atom and no or one further ring atom is a hetero atom selected from N, O or S and the remaining are carbon atoms, wherein said heterocycle is unsubstituted or substituted with independently from each other RB6and / or RB7and / or RB8and RB9together; Rcdenotes straight-chain or branched C1-4-alkyl which is unsubstituted or substituted with -OH; straight-chain and unsubstituted C2-4-alkinyl; C3-5- cycloalkyl; Rd, Redenote independently from each other straight-chain or branched C1-6-alkyl; Rf, Rhdenote independently from each other straight-chain or branched C1-6-alkyl; Rgdenotes H, straight-chain or branched C1-6-alkyl;Ridenotes H, straight-chain or branched C1-6-alkyl; RB1, RB2denote independently from each other halogen; C1-4-alkyl, which may be unsubstituted or substituted with 1, 2, or 3 halogen; OH; RB6, RB7denote independently from each other halogen; OH; -OC1-4-alkyl; C1-4-alkyl, which is unsubstituted or substituted with 1 OH or 1, 2, or 3 halogen; RB8and RB9which are attached to the same carbon atom of said heterocycle form a divalent oxo (=O) group; and / or two of RB6, RB7, RB8, RB9which are attached to the same sulfur (S) atom of said heterocycle form a divalent oxo (=O) group while at the same time two further of RB6, RB7, RB8, RB9which are attached to the same sulfur atom form either a divalent oxo group or a divalent =N-H or =N-C1- 4-alkyl group, thereby forming an -S(=O)2, -S(=O)(=NH), or -S(=O)(=N- C1-4-alkyl) moiety; or any N-oxide, solvate, tautomer or stereoisomer thereof and / or any pharmaceutically acceptable salt of each of the foregoing, including mixtures thereof in all ratios.

11. Compound according to any one of the preceding claims wherein R2denotes H, Alk2, Hetar2, Hetcyc2; Alk2denotes straight-chain or branched C1-4-alkyl which may be unsubstituted or substituted with independently from each other R2a1and / or R2a2; Hetar2, Hetar2adenote independently from each other a monocyclic heteroaryl with 5 or 6 ring atoms wherein 1, 2, or 3 of said ring atoms is / are a hetero atom(s) selected from N, O and / or S and the remaining are carbon atoms, wherein that heteroaryl is unsubstituted or mono- substituted with C1-4-alkyl which may be unsubstituted or substituted with 1, 2, or 3 halogen;Cyc2adenotes a saturated monocyclic carbocycle with 4 ring carbon atoms, wherein said carbocycle is unsubstituted or mono-substituted with -OH; Hetcyc2denotes a saturated monocylic heterocycle with 5 ring atoms wherein 1 of said ring atoms is a hetero atom selected from O or S the remaining are carbon atoms, wherein said heterocycle is unsubstituted or mono-substituted with OH; Hetcyc2adenotes a saturated monocylic heterocycle with 4, 5 or 6 ring atoms wherein 1 of said ring atoms is a hetero atom(s) selected from N or O and the remaining are carbon atoms, wherein said heterocycle is unsubstituted or mono-substituted with OH, -O-C1-4-alkyl or C1-4-alkyl, wherein said C1-4-alkyl may be unsubstituted or mono-substituted with - OH or -OC1-4-alkyl; R2a1, R2a2denote independently from each other F, -CN, -NH2, -NHRa, - NRaRb, -OH, -ORc, -P(=O)RdRe, -SRf, -S(=O)(=NRg)Rf, -C(=O)NH2, - C(=O)NHRa, C(=O)ORc, -NH-C(=O)-Ri, Cyc2a, Hetar2a, Hetcyc2a; Ra, Rbdenote independently from each other straight-chain or branched C1-6-alkyl; or Raand Rbform together with the nitrogen atom to which they are attached to a saturated or partially unsaturated heterocycle with 4, 5, 6, 7 ring atoms wherein 1 of said ring atoms is said nitrogen atom and no or one further ring atom is a hetero atom selected from N, O or S and the remaining are carbon atoms, wherein said heterocycle is unsubstituted or substituted with independently from each other RB6and / or RB7and / or RB8and RB9together; Rcdenotes straight-chain or branched C1-4-alkyl; Rd, Redenote independently from each other straight-chain or branched C1-6-alkyl; Rfdenotes straight-chain or branched C1-6-alkyl; Rgdenotes H, straight-chain or branched C1-6-alkyl; Ridenotes H, straight-chain or branched C1-6-alkyl;RB6, RB7denote independently from each other OH; RB8and RB9which are attached to the same carbon atom of said heterocycle form a divalent oxo (=O) group; or any N-oxide, solvate, tautomer or stereoisomer thereof and / or any pharmaceutically acceptable salt of each of the foregoing, including mixtures thereof in all ratios 12. Compound according to any one of the preceding claims wherein R2denotes H; -CH3, -CH2-CN, -(CH2)2-CN, -(CH2)2-OH, -(CH2)3-OH, CH2- CH(CH3)-CH2-OH, -CH2-CHF-CH2-OH, -CH2-CH(OH)-CH2-OH, - CH(CH2OH)2, -CH2-CH(OH)-CH2-OCH3, -(CH2)3-S-CH3, -(CH2)2- S(=O)(=NH)CH3, -CH2-P(=O)(CH3)2, -CH2-C(=O)-NH2, -CH2-C(=O)- NHCH3, -(CH2)2-C(=O)-NH2, -(CH2)2-C(=O)-NHCH3, -(CH2)2-NH-C(=O)- H, -(CH2)2-NH-C(=O)-CH3, 2-(3-hydroxypyrrolidin-1-yl)ethyl, 2-(2-oxo- pyrrolidin-1-yl)-ethyl], (2-morpholin-4-yl-ethyl); 1-methyl-1H-imidazol-4- yl, 1-methyl-1H-imidazol-5-yl, 1,2-thiazol-2-yl, 1,3-thiazol-2-yl, 1,3- thiazol-4-yl, pyrazin-2-yl; (1H‐imidazol‐4‐yl)methyl, (1-methyl-1H- imidazol‐4‐yl)methyl, (1-methyl-1H-imidazol‐5‐yl)methyl, (4-methyl-1H- imidazol-2‐yl)methyl, 2-(1H‐imidazol‐4‐yl)-ethyl, (1H‐pyrazol‐4‐yl)methyl, (1‐methyl‐1H‐pyrazol‐3‐yl)methyl, (1‐methyl‐1H‐pyrazol‐4‐yl)methyl, 2- (1‐methyl‐1H‐pyrazol‐4‐yl)-ethyl, 1-oxazol-2-ylmethyl, 1,3-thiazol-5- ylmethyl, 2-methyl-1,3-thiazol-4-ylmethyl, 2-methyl-1,3-thiazol-5- ylmethyl, 1H-1,2,3-triazol-4ylmethyl, 1H-1,2,4-triazol-3ylmethyl, pyrazin- 2-ylmethyl, 3-methylpyrazin-2-ylmethyl, pyridazin-3-ylmethyl, pyrimidin- 2-ylmethyl, pyrimidin-4-ylmethyl, 2-hydroxy-1-(pyrazin-2-yl)ethyl; 1-hydroxycyclobutylmethyl ( ), , ,hydroxyoxan-4-yl)methyl (or any N-oxide, solvate, tautomer or stereoisomer thereof and / or anypharmaceutically acceptable salt of each of the foregoing, including mixtures thereof in all ratios 13. Compound according to any one of the preceding claims wherein R2denotes H; -CH3, -CH2-CN, -(CH2)2-CN, -(CH2)2-OH, -(CH2)3-OH, - CH(CH2OH)2, -(CH2)2-S(=O)(=NH)CH3, -CH2-P(=O)(CH3)2, -CH2-C(=O)- NH2, -CH2-C(=O)-NHCH3, -(CH2)2-C(=O)-NH2, -(CH2)2-C(=O)-NHCH3, - (CH2)2-NH-C(=O)-H, -(CH2)2-NH-C(=O)-CH3, (1H‐imidazol‐4‐yl)methyl, (1-methyl-1H-imidazol‐4‐yl)methyl, (1-methyl-1H-imidazol‐5‐yl)methyl, (1‐methyl‐1H‐pyrazol‐4‐yl)methyl, 1,3-thiazol-5-ylmethyl, 2-methyl-1,3- thiazol-5-ylmethyl, pyrazin-2-ylmethyl, 3-methylpyrazin-2-ylmethyl, pyrimidin-4-ylmethyl, 2-hydroxy-1-(pyrazin-2-yl)ethyl; -CH-(pyrazin-2-yl)-C(=O)OCH3; , , ; or any N-oxide, solvate, tautomer or stereoisomer thereof and / or anypharmaceutically acceptable salt of each of the foregoing, including mixtures thereof in all ratios14. Compound according to any one of the preceding claims wherein , , , ,,, , ,wherein denotes the point of attachment of the ring A to the bicyclic ringsystem of the compound of formula I , anddenotes the point of attachment to the L1-B radical of the compound of formula I; or any N-oxide, solvate, tautomer or stereoisomer thereof and / or any pharmaceutically acceptable salt of each of the foregoing, including mixtures thereof in all ratios 15. Compound according to any one of the preceding claims wherein, , ,, ; or any N-oxide, solvate, tautomer or stereoisomer thereof and / or any pharmaceutically acceptable salt of each of the foregoing, including mixtures thereof in all ratios 16. Compound according to any one of the preceding claims wherein, ,, , ; or any N-oxide, solvate, tautomer or stereoisomer thereof and / or any pharmaceutically acceptable salt of each of the foregoing, including mixtures thereof in all ratios 17. Compound according to any one of the preceding claims wherein B denotes Ar1, Hetar1, Cyc1; L1denotes -O-, -N(R4)-, -O-CH2-, -O-SO2-; R4denotes H or CH3; Ar1denotes phenyl, wherein that phenyl is mono-substituted with RC1; Hetar1denotes a mono-cyclic heteroaryl with 5 or 6 ring atoms wherein 1 or 2 of said ring atoms is / are a hetero atom(s) selected from N, O and / or S and the remaining are carbon atoms, wherein that heteroaryl is monosubstituted with RC1or di-substituted with RC1and RC2; Cyc1denotes a saturated, mono- or bi-cyclic carbocycle with 4, 5, 6, or 7 ring carbon atoms, wherein said carbocycle is mono-substituted with RC6or di-substituted with RC6and RC7; RC1denotes F, Cl, CH3, CHF2, or CF3; RC2denotes CH3 or C2H5; RC6denotes F, Cl; CH3, CHF2, CF3, -OCH3, -OCHF2, -OCF3;RC7denotes F; or any N-oxide, solvate, tautomer or stereoisomer thereof and / or any pharmaceutically acceptable salt of each of the foregoing, including mixtures thereof in all ratios 18. Compound according to any one of the preceding claims wherein L1denotes -O-, -NH- or -O-CH2-; or any N-oxide, solvate, tautomer or stereoisomer thereof and / or any pharmaceutically acceptable salt of each of the foregoing, including mixtures thereof in all ratios.

19. Compound according to any one of the preceding claims wherein , , , , ,,;, ; , , ,, , , or ; or any N-oxide, solvate, tautomer or stereoisomer thereof and / or any pharmaceutically acceptable salt of each of the foregoing, including mixtures thereof in all ratios.

20. Compound according to any one of the preceding claims wherein, , ; ,or any N-oxide, solvate, tautomer or stereoisomer thereof and / or any pharmaceutically acceptable salt of each of the foregoing, including mixtures thereof in all ratios.

21. Compound according to any one of the preceding claims wherein L1denotes -O-; ,;,; or any N-oxide, solvate, tautomer or stereoisomer thereof and / or any pharmaceutically acceptable salt of each of the foregoing, including mixtures thereof in all ratios.

22. Compound according to any one of the preceding claims wherein L1denotes -O-; ; ,or any N-oxide, solvate, tautomer or stereoisomer thereof and / or any pharmaceutically acceptable salt of each of the foregoing, including mixtures thereof in all ratios 23. Compound according to any one of claims 1 to 20 wherein L1denotes -O-CH2-;, ;; or any N-oxide, solvate, tautomer or stereoisomer thereof and / or any pharmaceutically acceptable salt of each of the foregoing, including mixtures thereof in all ratios.

24. Compound according to any one of the preceding claims wherein , ,,, , ; ,; , , N N O N N F F F , FFF N O N F F F , , ,, ;; ; ; , ,,, , ;; or any N-oxide, solvate, tautomer or stereoisomer thereof and / or any pharmaceutically acceptable salt of each of the foregoing, including mixtures thereof in all ratios.

25. Compound according to any one of the preceding claims whereinRing D together wit R2denotes ;X1denotes CH or N; R1denotes CH3; R2denotes H; -CH3, -CH2-CN, -(CH2)2-CN, -(CH2)2-OH, -(CH2)3-OH, - CH(CH2OH)2, -(CH2)2-S(=O)(=NH)CH3, -CH2-P(=O)(CH3)2, -CH2-C(=O)- NH2, -CH2-C(=O)-NHCH3, -(CH2)2-C(=O)-NH2, -(CH2)2-C(=O)-NHCH3, - (CH2)2-NH-C(=O)-H, -(CH2)2-NH-C(=O)-CH3, (1H‐imidazol‐4‐yl)methyl, (1-methyl-1H-imidazol‐4‐yl)methyl, (1-methyl-1H-imidazol‐5‐yl)methyl, (1‐methyl‐1H‐pyrazol‐4‐yl)methyl, 1,3-thiazol-5-ylmethyl, 2-methyl-1,3- thiazol-5-ylmethyl, pyrazin-2-ylmethyl, 2-methylpyrazin-3-ylmethyl, pyrimidin-4-ylmethyl, 2-hydroxy-1-(pyrazin-2-yl)ethyl; -CH-(pyrazin-2-yl)- , ,, , , , ,,;, , ,, ; or any N-oxide, solvate, tautomer or stereoisomer thereof and / or any pharmaceutically acceptable salt of each of the foregoing, including mixtures thereof in all ratios.

26. Compound according to any one of claim 1 or 2, or any N-oxide, solvate, tautomer or stereoisomer thereof and / or any pharmaceutically acceptable saltof each of the foregoing, including mixtures thereof in all ratios, wherein the compound is selected from the compounds depicted in Table 1 and Table 1a.

27. Compound according to any of the preceeding claims, or any N-oxide, solvate, tautomer or stereoisomer thereof and / or the pharmaceutically acceptable salts of each of the foregoing, including mixtures thereof in all ratios, for use as a medicament.

28. Compound according to any of claims 1 to 26, or any N-oxide, solvate, tautomer or stereoisomer thereof and / or the pharmaceutically acceptable salts of each of the foregoing, including mixtures thereof in all ratios, for use in the prevention and / or treatment of a medical condition or disease that is affected by inhibiting YAP-TEAD and / or TAZ-TEAD interaction.

29. Compound according to any of claims 1 to 26, or any N-oxide, solvate, tautomer or stereoisomer thereof and / or the pharmaceutically acceptable salts of each of the foregoing, including mixtures thereof in all ratios, for use in the prevention and / or treatment of a medical condition or disease selected from the group consisting of: cancer, in particular tumors including solid tumors, of breast cancer, lung cancer, liver cancer, ovarian cancer, squamous cancer, renal cancer, gastric cancer, medulloblastoma, colon cancer, pancreatic cancer; cardiovascular diseases and fibrosis, in particular, liver fibrosis.

30. A pharmaceutical composition comprising at least one compound according to any one of claims 1 to 26, or any N-oxide, solvate, tautomer or stereoisomer thereof and / or the pharmaceutically acceptable salts of each of the foregoing, including mixtures thereof in all ratios, as active ingredient, together with a pharmaceutically acceptable carrier.

31. A pharmaceutical composition comprising (a) as a first active ingredient a compound according to any one of claims 1 to 26, or any N-oxide, solvate, tautomer or stereoisomer thereof and / or the pharmaceutically acceptable saltsof each of the foregoing, including mixtures thereof in all ratios; and (b) a second active ingredient, wherein that second active ingredient is other than a compound of formula I as defined in any one of claims 1 to 26.

32. Process for manufacturing a compound according to any one of claims 1 to 26, or any N-oxide, solvate, tautomer or stereoisomer thereof and / or the pharmaceutically acceptable salts of each of the foregoing, including mixtures thereof in all ratios, the process being characterized in that either (A) in a first reaction step a compound of formula IIII wherein R1, R3, and X1are defined as for formula I in any one of claims 1 to 26; Y1denotes H or a suitable protecting group, PG1; Hal1denotes Cl, Br, or I; is reacted under suitable C-C coupling reaction conditions with a compound of formula III Y2-A-L1-B III wherein A, L1, and B are defined as for formula I in any one of claims 1 to 26; Y2denotes a suitable boronate functional group; to provide a compound of formula IVor (B) in a first reaction step a compound of formula VV wherein R1, R3, and X1are defined as for formula I in any one of claims 1 to 26; Y1denotes H or a suitable protecting group, PG1; Y3denotes a suitable boronate functional group; is reacted under suitable C-C coupling reaction conditions with a compound of formula VI Hal2-A-L1-B VI wherein A, L1, and B are defined as for formula I in any one of claims 1 to 26; Hal2denotes Cl, Br, or I; to provide a compound of formula IV; and, optionally, after step (A) or (B) (C) (1) if in formula IV above Y1denotes PG1, in a second reaction step PG1is removed under suitable reaction conditions to provide a compound of formula IV with Y1being H, which can also be described as a compound of formula I with R2being H; and / or(C) (2) if in formula IV above Y1denotes H, in another reaction step that compound of formula IV is reactied under suitable reaction conditions with a compound of formula VII R2-LG1VII wherein R2is defined as in any one of claims 1 to 26 with the exception of H; and LG1denotes a suitable leaving group; to provide a compound of formula I as defined in any one of claims 1 to 26; or (D) in a first reaction step a compound of formula VIIIVIII wherein R1and R3are defined as for formula I in any one of claims 1 to 26; Y1denotes H or a suitable protecting group, PG1; Hal1denotes Cl, Br, or I; is reacted under suitable C-C coupling reaction conditions with a compound of formula III Y2-A-L1-B III wherein A, L1, and B are defined as for formula I in any one of claims 1 to 26; Y2denotes a suitable boronate functional group; to provide a compound of formula IXor (E) in a first reaction step a compound of formula XX wherein R1and R3are defined as for formula I in any one of claims 1 to 26; Y1denotes H or a suitable protecting group, PG1; Y3denotes a suitable boronate functional group; is reacted under suitable C-C coupling reaction conditions with a compound of formula VI Hal2-A-L1-B VI wherein A, L1, and B are defined as for formula I in any one of claims 1 to 26; Hal2denotes Cl, Br, or I; to provide a compound of formula IX; and, optionally, after step (D) or (E) (F) (1) if in formula IX above Y1denotes PG1, in a second reaction step PG1is removed under suitable reaction conditions to provide a compound of formula IX with Y1being H, which can also be described as a compound of formula I with R2being H; and / or(F) (2) if in formula IX above Y1denotes H, in another reaction step that compound of formula IX is reactied under suitable reaction conditions with a compound of formula VII R2-LG1VII wherein R2is defined as in any one of claims 1 to 26 with the exception of H; and LG1denotes a suitable leaving group; to provide a compound of formula I as defined in any one of claims 1 to 26.

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