TEAD INHIBITORS The present invention covers heterocyclic compounds of general formula (I) selected from the group consisting of pyridine-3-carboxamide compounds of general formula (1), pyridine-2-carboxamide compounds of general formula (2), pyrazine-carboxamide compounds of general formula (3), and pyrimidine-carboxamide compounds of general formula (4), as described and defined herein, methods of preparing said compounds, intermediate compounds useful for preparing said compounds, pharmaceutical compositions and combinations comprising said compounds, and the use of said compounds for manufacturing pharmaceutical compositions for the treatment or prophylaxis of diseases, in particular of cancer, as a sole agent or in combination with other active ingredients. BACKGROUND The present invention covers heterocyclic compounds of general formula (I) selected from the group consisting of pyridine-3-carboxamide compounds of general formula (1), pyridine-2-carboxamide compounds of general formula (2), pyrazine-carboxamide compounds of general formula (3), and pyrimidine-carboxamide compounds of general formula (4), which inhibit the activity of transcription enhancer associate domain (TEAD) (TEA/ATTS domain family) transcription factors, the downstream effectors of the Hippo pathway, leading to inhibition of YES-associated protein (YAP1) and /or its paralog transcriptional coactivator with PDZ-binding motif (TAZ) – TEAD mediated target gene transcription and blockade of cancer cell proliferation.The present invention covers pyridine-3-carboxamide compounds of general formula (I) which inhibit YES-associated protein (YAP1). The Hippo pathway regulates cell proliferation and differentiation as well as organ size during embryonic development and has key roles in tissue regeneration, wound healing and immune modulation (Dey A. et al., Nat. Rev. Drug Disc.2020). It was first discovered in Drosophila, in which tumor-suppressive roles for the pathway were identified (Justice R. W., 1995; Tapon N. et al., Cell 2002; Jia J. et al., Genes Dev. 2003) and is well conserved in mammals where its dysregulation plays a role in various human cancers and other diseases. The Hippo pathway integrates a network of signals that converge to a core kinase cascade to regulate the activity of the paralogous transcription regulators YAP1 and TAZ. Upstream signals regulating the Hippo pathway include cell polarity and adhesion regulators through KIBRA/NF2, mechanical cues acting through Rho GTPase and actin dynamics, hormones and growth factors for GPCRs, and cellular stress signals (Ma et al., Annu. Rev. Biochem.2019). When the Hippo pathway is activated, sterile 20-like kinase 1/2 (MST1/2) along with adaptor protein Salvador homolog 1 (SAV1) phosphorylate and activate the key serine/threonine kinases large tumor suppressor 1/2 (LATS1/2). Besides MST1/2, MAP4K and TAOK families of kinases are also able to phosphorylate and activate LATS1/2. Consequently, LATS1/2 together with adaptor protein Mps one binder kinase activator 1A/B (MOB1A/B) phosphorylate YAP/TAZ which then associate with 14-3-3 proteins and are thus retained in the cytoplasm and directed to proteasomal degradation, preventing nuclear localisation and reducing target gene expression. Deactivation of the Hippo pathway leads to hypo-phosphorylated YAP/TAZ being able to translocate into the nucleus and promoting transcription of downstream genes by forming complexes with various transcription factors, most notably TEAD family members. Besides recruiting transcriptional coactivators YAP/TAZ, TEADs can also bind to corepressors VGLL1-4 (Deng X. & Fang L., Am J Cancer Res 2018) and other signaling transduction pathway transcription factors (Huh H.D., et al., Cells 2019). Therefore, TEADs are crucial in regulating the transcriptional output of the Hippo pathway and seem to be key mediators of the growth and tumorigenic potential of hyperactivated YAP/TAZ by inducing target genes such as canonical CTGF, Cyr61, ANKRD1, IGFBP3, FGF1 but also genes involved in DNA synthesis and repair or in mitosis. (Zhao ef al., Genes Dev 2008, 22, 1962-1971; Wang L et al., Tumour Biol 2014, 14, 463-468; Stein C. et al., PLOS Genet. 2015; Zanconato F. et al. Nat. Cell Biol. 2015). Increased YAP/TAZ-TEAD activity due to deregulation of the Hippo pathway is found in many tumors such as sarcoma, brain, lung, skin, ovarian, cervical, colorectal, prostate, pancreas, thyroid, esophagus, head and neck, gastric, genitourinary, liver and breast cancer and often correlate with poor prognosis and increased therapeutic resistance (Dey A. et al., Nat. Rev. Drug Disc.2020; Zanconato F. et al., Cancer Cell 2016; Harvey et al., Nat Rev Cancer 2013,13, 246-257; Steinhardt et al., Hum Pathol 2008, 39, 1582-1589; Garcia-Rendueles M.E.R. et al., Cancer Discov.2015, 5, 1178-1193; Wang et al., Cancer Sci.2010, 101, 1279-85). Disruption of upstream YAP/TAZ regulators like NF2 (encoding merlin) can lead to YAP nuclear activation and has been observed in tumors arising from the nervous system, such as schwannomas, meningiomas and ependymomas (Zanconato F. et al., Cancer Cell 2016). NF2-deficiency in papillary renal cell carcinoma cells causes YAP1 nuclear localisation and activation leading to expression of targets genes like BIRC5 (surviving), CTGF or CCDN1 driving cell growth (Sourbier et al. Oncotarget 2018). Furthermore, loss of SAV1 expression results in nuclear sequestration of YAP in patients with clear cell renal cell carcinoma (ccRCC) and YAP down-regulation impaired proliferation and migration of ccRCC cell lines as well as tumor growth in a ccRCC xenograft model (Schütte et al. Translational Oncology 2014). Mutations in NF2 and LATS2 as well as YAP amplification have also been observed in malignant mesothelioma leading to YAP activation in more than 70% of malignant mesothelioma cases. About 80% of mesothelioma cases are linked to asbestos particle exposure; the remainder may be related to genetic predisposition, spontaneous occurrence or prior chest radiation. Malignant pleural mesothelioma is a highly lethal cancer with a high unmet medical need. Treatment options include surgery, chemo- or radiotherapy or a combination of the two or three options with median overall survival time of about 13 months, so new treatments are urgently needed (Bianchi et al. Natl Acad. Sci. USA, 1995, 92, 10854-10858; Bueno R. et al. Nature Genetics 2016; Cantini et al., Front. Oncol.2020). Targeting TEAD function, especially its ability to activate gene transcription through its interaction with YAP/TAZ may therefore be a promising approach for diseases, in particularly cancer, with deregulated Hippo pathway and hyperactivated YAP/TAZ. TEAD proteins interact with co-transcription factors like YAP/TAZ and DNA through various interfaces that constitute potential target sites to interrupt their function (Pobbati A.V. & Rubin B.P. Molecules 2020; Holden J.K. & Cunningham C.N. Cancers 2018). In addition, TEAD´s YAP/TAZ binding domain contains a hydrophobic central pocket with a conserved cysteine that is modified by post-translational palmitoylation. This lipid modification has been shown to be required for TEAD stability and function and to be targetable by small-molecule inhibitors (Noland C.L. et al. Structure 2016; Pobbati A.V. et al. Structure 2015; Kaneda A. et al. Am J Cancer Res 2020; Karatas H. et al. J. Med. Chem.2020; Tang et al. Mol Cancer Ther 2021). However, the state of the art does not describe the heterocyclic compounds of general formula (I) selected from the group consisting of pyridine-3-carboxamide compounds of general formula (1), pyridine-2-carboxamide compounds of general formula (2), pyrazine- carboxamide compounds of general formula (3), and pyrimidine-carboxamide compounds of general formula (4), of the present invention as described and defined herein. It has now been found, and this constitutes the basis of the present invention, that the compounds of the present invention have surprising and advantageous properties. In particular, the compounds of the present invention have surprisingly been found to effectively inhibit YES-associated protein (YAP1) for which data are given in biological experimental section and may therefore be used for the treatment or prophylaxis of cancer. DESCRIPTION of the INVENTION In accordance with a first aspect, the present invention covers compounds of general formula (1): wherein R ¹ represents C ₃ -C ₆ -cycloalkyl, 4- to 6-membered heterocycloalkyl, heterospirocycloalkyl, phenyl, or heteroaryl, wherein said groups are optionally substituted, one or more times, independently of each other, with R ⁵ , or R ⁸ R ⁹ N-; R ² represents phenyl, or pyridyl, which is optionally substituted, one or more times, independently of each other, with R ⁶ ; R ³ represents hydrogen or C ₁ -C ₄ -alkyl; R ⁴ represents C ₁ -C ₆ -alkyl, C ₂ -C ₆ -hydroxyalkyl, C ₁ -C ₄ -haloalkyl, hydroxy-C ₂ -C ₆ - haloalkyl, R ⁸ R ⁹ N-(C ₂ -C ₄ -alkyl)-, (C ₁ -C ₄ -alkyl)-CO-NR ⁹ -(C ₂ -C ₄ -alkyl)-, (C ₂ -C ₄ - alkyl)-O-CO-NR ⁹ -(C ₂ -C ₄ -alkyl)-, R ¹⁰ O-CO-(C ₁ -C ₄ -alkyl)-, R ⁸ R ⁹ N-CO-(C ₁ -C ₄ - alkyl)-, R ⁸ R ⁹ N-CO-(C ₂ -C ₄ -hydroxyalkyl)-, (C ₁ -C ₄ -alkoxy)-(C ₂ -C ₄ -alkyl)-, C ₃ -C ₆ - cycloalkyl, 5- to 6-membered heterocycloalkyl, heterospirocycloalkyl, bridged heterocycloalkyl, adamantyl, phenyl, heteroaryl, C ₃ -C ₆ -cycloalkyl-(C ₁ -C ₃ -alkyl)-, C ₃ -C ₆ -hydroxycycloalkyl-(C ₁ -C ₃ -alkyl)-, C ₃ -C ₆ -cycloalkyl-(C ₂ -C ₆ -hydroxyalkyl)-, C ₃ -C ₆ -cycloalkyl-(C ₁ -C ₄ -haloalkyl)-, 5- to 6-membered heterocycloalkyl-(C ₁ -C ₃ - alkyl)-, heterospirocycloalkyl-(C ₁ -C ₃ -alkyl)-, bridged heterocycloalkyl-(C ₁ -C ₃ - alkyl)-, adamantyl-(C ₁ -C ₃ -alkyl)-, phenyl-(C ₁ -C ₃ -alkyl)-, or heteroaryl-(C ₁ -C ₃ - alkyl)-, wherein said C ₃ -C ₆ -cycloalkyl, 5- to 6-membered heterocycloalkyl, heterospirocycloalkyl, phenyl, or heteroaryl groups are optionally substituted, one or more times, independently of each other, with R ⁷ ; R ⁵ represents halogen, cyano, hydroxy, R ⁸ R ⁹ N-(CO)-CH ₂ -, C ₁ -C ₄ -alkyl, C ₁ -C ₄ - haloalkyl, C ₁ -C ₄ -hydroxyalkyl, C ₁ -C ₃ -alkoxy, or C ₁ -C ₃ -haloalkoxy; R ⁶ represents C ₁ -C ₄ -alkyl, C ₁ -C ₄ -haloalkyl, C ₁ -C ₄ -alkoxy, C ₁ -C ₄ -haloalkoxy, C ₁ -C ₄ - alkylthio, C ₁ -C ₄ -haloalkylthio, C ₃ -C ₆ -cycloalkyl, halogen, or −SF ₅ ; R ⁷ represents hydroxy, halogen, cyano, C ₁ -C ₄ -alkyl, C ₁ -C ₄ -hydroxyalkyl, C ₁ -C ₄ - haloalkyl, C ₁ -C ₃ -alkoxy, C ₁ -C ₃ -haloalkoxy, or oxo; R ⁸ represents hydrogen, C ₁ -C ₄ -alkyl, C ₁ -C ₄ -haloalkyl, or C ₃ -C ₆ -cycloalkyl; R ⁹ represents hydrogen or C ₁ -C ₄ -alkyl; R ¹⁰ represents hydrogen or C ₁ -C ₄ -alkyl; and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same. In accordance with a second aspect, the present invention covers compounds of general formula (2): wherein R ¹ represents C ₃ -C ₆ -cycloalkyl, 4- to 6-membered heterocycloalkyl, heterospirocycloalkyl, phenyl, or heteroaryl, wherein said groups are optionally substituted, one or more times, independently of each other, with R ⁵ , or R ⁸ R ⁹ N-; R ² represents phenyl, which is optionally substituted, one or more times, independently of each other, with R ⁶ ; R ³ represents hydrogen or C ₁ -C ₄ -alkyl; R ⁴ represents C ₁ -C ₆ -alkyl, C ₂ -C ₆ -hydroxyalkyl, C ₁ -C ₄ -haloalkyl, hydroxy-C ₂ -C ₆ - haloalkyl, R ⁸ R ⁹ N-(C ₂ -C ₄ -alkyl)-, (C ₂ -C ₄ -alkyl)-O-CO-NH-(C ₂ -C ₄ -alkyl)-, H ₂ N-CO- (C ₁ -C ₄ -alkyl)-, H ₂ N-CO-(C ₂ -C ₄ -hydroxyalkyl)-, (C ₁ -C ₄ -alkoxy)-(C ₂ -C ₄ -alkyl)-, C ₃ - C ₆ -cycloalkyl, 5- to 6-membered heterocycloalkyl, heterospirocycloalkyl, phenyl, heteroaryl, C ₃ -C ₆ -cycloalkyl-(C ₁ -C ₃ -alkyl)-, C ₃ -C ₆ -cycloalkyl-(C ₂ -C ₆ -hydroxyalkyl)- , C ₃ -C ₆ -cycloalkyl-(C ₁ -C ₄ -haloalkyl)-, 5- to 6-membered heterocycloalkyl-(C ₁ -C ₃ - alkyl)-, heterospirocycloalkyl-(C ₁ -C ₃ -alkyl)-, phenyl-(C ₁ -C ₃ -alkyl)-, or heteroaryl- (C ₁ -C ₃ -alkyl)-, wherein said C ₃ -C ₆ -cycloalkyl, 5- to 6-membered heterocycloalkyl, heterospirocycloalkyl, phenyl, or heteroaryl groups are optionally substituted, one or more times, independently of each other, with R ⁷ ; R ⁵ represents halogen, cyano, C ₁ -C ₄ -alkyl, C ₁ -C ₄ -haloalkyl, C ₁ -C ₄ -hydroxyalkyl, C ₁ -C ₃ -alkoxy, or C ₁ -C ₃ -haloalkoxy; R ⁶ represents C ₁ -C ₄ -alkyl, C ₁ -C ₄ -haloalkyl, C ₁ -C ₄ -alkoxy, C ₁ -C ₄ -haloalkoxy, C ₁ -C ₄ - alkylthio, C ₁ -C ₄ -haloalkylthio, C ₃ -C ₆ -cycloalkyl, or −SF ₅ ; R ⁷ represents hydroxy, halogen, cyano, C ₁ -C ₄ -alkyl, C ₁ -C ₄ -hydroxyalkyl, C ₁ -C ₄ - haloalkyl, C ₁ -C ₃ -alkoxy, C ₁ -C ₃ -haloalkoxy, or oxo; R ⁸ represents hydrogen, C ₁ -C ₄ -alkyl, or C ₃ -C ₆ -cycloalkyl; R ⁹ represents hydrogen or C ₁ -C ₄ -alkyl; and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same. In accordance with a third aspect, the present invention covers compounds of general formula (3): wherein R ¹ represents C ₃ -C ₆ -cycloalkyl, 4- to 6-membered heterocycloalkyl, heterospirocycloalkyl, phenyl, or heteroaryl, wherein said groups are optionally substituted, one or more times, independently of each other, with R ⁵ , or R ⁸ R ⁹ N-; R ² represents phenyl, which is optionally substituted, one or more times, independently of each other, with R ⁶ ; R ³ represents hydrogen or C ₁ -C ₄ -alkyl; R ⁴ represents C ₁ -C ₆ -alkyl, C ₂ -C ₆ -hydroxyalkyl, C ₁ -C ₄ -haloalkyl, hydroxy-C ₂ -C ₆ - haloalkyl, R ⁸ R ⁹ N-(C ₂ -C ₄ -alkyl)-, (C ₂ -C ₄ -alkyl)-O-CO-NH-(C ₂ -C ₄ -alkyl)-, H ₂ N-CO- (C ₁ -C ₄ -alkyl)-, H ₂ N-CO-(C ₂ -C ₄ -hydroxyalkyl)-, (C ₁ -C ₄ -alkoxy)-(C ₂ -C ₄ -alkyl)-, C ₃ - C ₆ -cycloalkyl, 5- to 6-membered heterocycloalkyl, heterospirocycloalkyl, phenyl, heteroaryl, C ₃ -C ₆ -cycloalkyl-(C ₁ -C ₃ -alkyl)-, C ₃ -C ₆ -cycloalkyl-(C ₂ -C ₆ -hydroxyalkyl)- , C ₃ -C ₆ -cycloalkyl-(C ₁ -C ₄ -haloalkyl)-, 5- to 6-membered heterocycloalkyl-(C ₁ -C ₃ - alkyl)-, heterospirocycloalkyl-(C ₁ -C ₃ -alkyl)-, phenyl-(C ₁ -C ₃ -alkyl)-, or heteroaryl- (C ₁ -C ₃ -alkyl)-, wherein said C ₃ -C ₆ -cycloalkyl, 5- to 6-membered heterocycloalkyl, heterospirocycloalkyl, phenyl, or heteroaryl groups are optionally substituted, one or more times, independently of each other, with R ⁷ ; R ⁵ represents halogen, cyano, C ₁ -C ₄ -alkyl, C ₁ -C ₄ -haloalkyl, C ₁ -C ₄ -hydroxyalkyl, C ₁ -C ₃ -alkoxy, or C ₁ -C ₃ -haloalkoxy; R ⁶ represents C ₁ -C ₄ -alkyl, C ₁ -C ₄ -haloalkyl, C ₁ -C ₄ -alkoxy, C ₁ -C ₄ -haloalkoxy, C ₁ -C ₄ - alkylthio, C ₁ -C ₄ -haloalkylthio, C ₃ -C ₆ -cycloalkyl, or −SF ₅ ; R ⁷ represents hydroxy, halogen, cyano, C ₁ -C ₄ -alkyl, C ₁ -C ₄ -hydroxyalkyl, C ₁ -C ₄ - haloalkyl, C ₁ -C ₃ -alkoxy, C ₁ -C ₃ -haloalkoxy, or oxo; R ⁸ represents hydrogen, C ₁ -C ₄ -alkyl, or C ₃ -C ₆ -cycloalkyl; R ⁹ represents hydrogen or C ₁ -C ₄ -alkyl; and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same. In accordance with a fourth aspect, the present invention covers compounds of general formula (4): wherein R ¹ represents C ₃ -C ₆ -cycloalkyl, 4- to 6-membered heterocycloalkyl, heterospirocycloalkyl, phenyl, or heteroaryl, wherein said groups are optionally substituted, one or more times, independently of each other, with R ⁵ , or R ⁸ R ⁹ N-; R ² represents phenyl, which is optionally substituted, one or more times, independently of each other, with R ⁶ ; R ³ represents hydrogen or C ₁ -C ₄ -alkyl; R ⁴ represents C ₁ -C ₆ -alkyl, C ₂ -C ₆ -hydroxyalkyl, C ₁ -C ₄ -haloalkyl, hydroxy-C ₂ -C ₆ - haloalkyl, R ⁸ R ⁹ N-(C ₂ -C ₄ -alkyl)-, (C ₂ -C ₄ -alkyl)-O-CO-NH-(C ₂ -C ₄ -alkyl)-, H ₂ N-CO- (C ₁ -C ₄ -alkyl)-, H ₂ N-CO-(C ₂ -C ₄ -hydroxyalkyl)-, (C ₁ -C ₄ -alkoxy)-(C ₂ -C ₄ -alkyl)-, C ₃ - C ₆ -cycloalkyl, 5- to 6-membered heterocycloalkyl, heterospirocycloalkyl, phenyl, heteroaryl, C ₃ -C ₆ -cycloalkyl-(C ₁ -C ₃ -alkyl)-, C ₃ -C ₆ -cycloalkyl-(C ₂ -C ₆ -hydroxyalkyl)- , C ₃ -C ₆ -cycloalkyl-(C ₁ -C ₄ -haloalkyl)-, 5- to 6-membered heterocycloalkyl-(C ₁ -C ₃ - alkyl)-, heterospirocycloalkyl-(C ₁ -C ₃ -alkyl)-, phenyl-(C ₁ -C ₃ -alkyl)-, or heteroaryl- (C ₁ -C ₃ -alkyl)-, wherein said C ₃ -C ₆ -cycloalkyl, 5- to 6-membered heterocycloalkyl, heterospirocycloalkyl, phenyl, or heteroaryl groups are optionally substituted, one or more times, independently of each other, with R ⁷ ; R ⁵ represents halogen, cyano, C ₁ -C ₄ -alkyl, C ₁ -C ₄ -haloalkyl, C ₁ -C ₄ -hydroxyalkyl, C ₁ -C ₃ -alkoxy, or C ₁ -C ₃ -haloalkoxy; R ⁶ represents C ₁ -C ₄ -alkyl, C ₁ -C ₄ -haloalkyl, C ₁ -C ₄ -alkoxy, C ₁ -C ₄ -haloalkoxy, C ₁ -C ₄ - alkylthio, C ₁ -C ₄ -haloalkylthio, C ₃ -C ₆ -cycloalkyl, or −SF ₅ ; R ⁷ represents hydroxy, halogen, cyano, C ₁ -C ₄ -alkyl, C ₁ -C ₄ -hydroxyalkyl, C ₁ -C ₄ - haloalkyl, C ₁ -C ₃ -alkoxy, C ₁ -C ₃ -haloalkoxy, or oxo; R ⁸ represents hydrogen, C ₁ -C ₄ -alkyl, or C ₃ -C ₆ -cycloalkyl; R ⁹ represents hydrogen or C ₁ -C ₄ -alkyl; and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same. In an embodiment of the first aspect, the invention relates to compounds of formula (1) as described supra, wherein: R ¹ represents cyclopropyl, 4- to 5-membered heterocycloalkyl, phenyl, or 5- or 6- membered heteroaryl, wherein said groups are optionally substituted, one or two times, with R ⁵ ; R ² represents phenyl, or pyridyl, which is optionally substituted, one time with R ⁶ ; R ³ represents hydrogen or methyl; R ⁴ represents C ₁ -C ₃ -alkyl, C ₂ -C ₆ -hydroxyalkyl, hydroxy-C ₂ -C ₄ -haloalkyl, R ⁸ R ⁹ N-(C ₂ - C ₃ -alkyl)-, tert.-butyl-O-CO-NR ⁹ -(C ₂ -C ₄ -alkyl)-, R ⁸ R ⁹ N-CO-(C ₁ -C ₃ -alkyl)-, R ⁸ R ⁹ N-CO-(C ₂ -C ₃ -hydroxyalkyl)-, (C ₁ -C ₃ -alkoxy)-(C ₂ -C ₃ -alkyl)-, C ₃ -C ₅ -cycloalkyl, 5-membered heterocycloalkyl, adamantyl, phenyl, 5- or 6-membered heteroaryl, cyclopropyl-(C ₁ -C ₃ -alkyl)-, cyclopropyl-(C ₁ -C ₃ -haloalkyl)-, cyclopropyl-(C ₂ -C ₃ - hydroxyalkyl)-, 5-membered heterocycloalkyl-methyl-, adamantyl-(C ₁ -C ₂ -alkyl)-, or 5- or 6-membered heteroaryl-methyl-, wherein said cyclopropyl or C ₃ -C ₅ -cycloalkyl, 5-membered heterocycloalkyl, phenyl, or 5- or 6-membered heteroaryl groups are optionally substituted, one or two times, independently of each other, with R ⁷ ; R ⁵ represents halogen, hydroxy, R ⁸ R ⁹ N-(CO)-CH ₂ -, C ₁ -C ₄ -alkyl, C ₁ -C ₄ -haloalkyl, C ₁ - C ₄ -hydroxyalkyl, or C ₁ -C ₃ -alkoxy; R ⁶ represents halogen, C ₁ -C ₄ -alkyl, C ₁ -C ₂ -haloalkyl, C ₁ -C ₂ -haloalkoxy, cyclopropyl, or −SF ₅ ; R ⁷ represents hydroxy, halogen, C ₁ -C ₃ -alkyl, hydroxymethyl, or oxo; R ⁸ represents hydrogen, methyl, or C ₁ -C ₂ -haloalkyl; R ⁹ represents hydrogen or methyl; and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same. In another embodiment of the first aspect, the invention relates to compounds of formula (1) as described supra, wherein: R ¹ represents cyclopropyl, azetidin-1-yl, pyrrolidin-1-yl, 1H-pyrazol-3-yl, phenyl, 3,3- dimethylazetidin-1-yl, 2-methylpyrrolidin-1-yl, 1-methyl-1H-pyrazol-4-yl, 1-methyl- 1H-pyrazol-3-yl, 1-methyl-1H-1,2,4-triazol-3-yl, 5-methyl-1,3-oxazol-2-yl, 3- fluoropyrrolidin-1-yl, 3,3-difluoroazetidin-1-yl, 5-methyl-1,3-thiazol-2-yl, 4-methyl- 1,3-thiazol-2-yl, 3-methylphenyl, 6-methylpyridin-2-yl, 4-methylpyridin-2-yl, 1,5- dimethyl-1H-pyrazol-3-yl, 2-hydroxyphenyl, 2-fluorophenyl, 3-fluorophenyl, 5- fluoropyridin-3-yl, 3-chlorophenyl, 2-(hydroxymethyl)phenyl, 4-fluoro-2- methoxyphenyl, 2-(difluoromethyl)phenyl, 2-(carbamoylmethyl)phenyl, ; R ² represents 4-methylphenyl, 3-fluorophenyl, 4-chlorophenyl, 3-chlorophenyl, 4- ethylphenyl, 4-(propan-2-yl)phenyl, 3-(propan-2-yl)phenyl, 4-cyclopropylphenyl, 3-tert-butylphenyl, 4-tert-butylphenyl, 4-(trifluoromethyl)phenyl, 3- (trifluoromethyl)phenyl, 3-(trifluoromethoxy)phenyl, 4-(trifluoromethoxy)phenyl, r R ³ represents hydrogen or methyl; R ⁴ represents methyl, cyclopropyl, 2-aminoethyl, 2-hydroxyethyl, cyclopropylmethyl, 3-aminopropyl, 1-aminopropan-2-yl, 2-(methylamino)ethyl, 2-hydroxypropyl, 2- hydroxypropyl, 3-hydroxypropyl, 1-hydroxypropan-2-yl, 1-hydroxypropan-2-yl, 2- methoxyethyl, carbamoylmethyl, carboxymethyl, 1-cyclopropylethyl, 1- cyclopropylethyl, 2-(dimethylamino)ethyl, 3-hydroxybutan-2-yl, 3-hydroxybutan-2- yl, 3-hydroxybutan-2-yl, 3-hydroxybutan-2-yl, 1-hydroxy-2-methylpropan-2-yl, 3- hydroxybutyl, 3-hydroxybutyl, 2-hydroxy-2-methylpropyl, 1-hydroxybutan-2-yl, 1- hydroxybutan-2-yl, 1-hydroxybutan-2-yl, 4-hydroxybutan-2-yl, 4-hydroxybutan-2- yl, 3-hydroxy-2-methylpropyl, (1-hydroxycyclopropyl)methyl, oxolan-3-yl, 1- (hydroxymethyl)cyclopropyl, 1H-pyrazol-4-yl, (methylcarbamoyl)methyl, 1- carbamoylethyl, 1,3-dihydroxypropan-2-yl, 4-hydroxy-2-methylbutan-2-yl, 1- hydroxy-3-methylbutan-2-yl, 1-hydroxypentan-3-yl, 1-cyclopropyl-2-hydroxyethyl, (1H-imidazol-2-yl)methyl, 1-methyl-1H-pyrazol-4-yl, 1-carbamoylpropyl, 2- acetamidoethyl, (dimethylcarbamoyl)methyl, 2-oxopyrrolidin-3-yl, 5-oxopyrrolidin- 3-yl, 1,3-dihydroxybutan-2-yl, 1,3-dihydroxybutan-2-yl, 4-hydroxyoxolan-3-yl, 4- hydroxyoxolan-3-yl, 1-carbamoyl-2-hydroxyethyl, (1,3-thiazol-2-yl)methyl, (pyridin-2-yl)methyl, (pyridin-3-yl)methyl, 1-hydroxy-4-methylpentan-2-yl, 1- (hydroxymethyl)cyclopentyl, 2-cyclopropyl-3-hydroxypropyl, 1-cyclopropyl-3- hydroxypropyl, 3,5-dimethyl-1H-pyrazol-4-yl, (5-oxopyrrolidin-3-yl)methyl, (5- oxopyrrolidin-2-yl)methyl, −CH ₂ CHOHCF ₃ , 2-chlorophenyl, adamantan-1-yl, (adamantan-1-yl)methyl, 2-(adamantan-1-yl)ethyl, and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same. In another embodiment of the first aspect, the invention relates to compounds of formula (1) as described supra, wherein: R ¹ represents 1-methyl-1H-pyrazol-3-yl; R ² represents phenyl, which is substituted one time with R ⁶ ; R ³ represents hydrogen; R ⁴ represents −CHCH ₃ CH ₂ OH; R ⁶ represents trifluoromethyl; and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same. DEFINITIONS The term “substituted” means that one or more hydrogen atoms on the designated atom or group are replaced with a selection from the indicated group, provided that the designated atom's normal valency under the existing circumstances is not exceeded. Combinations of substituents and/or variables are permissible. The term “optionally substituted” means that the number of substituents can be equal to or different from zero. Unless otherwise indicated, it is possible that optionally substituted groups are substituted with as many optional substituents as can be accommodated by replacing a hydrogen atom with a non-hydrogen substituent on any available carbon or nitrogen atom. Commonly, it is possible for the number of optional substituents, when present, to be 1, 2, 3, 4 or 5, in particular 1, 2 or 3. As used herein, the term “one or more”, e.g. in the definition of the substituents of the compounds of general formula (I) of the present invention, means “1, 2, 3, 4 or 5, particularly 1, 2, 3 or 4, more particularly 1, 2 or 3, even more particularly 1 or 2”. As used herein, an oxo substituent represents an oxygen atom, which is bound to a carbon atom or to a sulfur atom via a double bond. The term “comprising” when used in the specification includes “consisting of”. If within the present text any item is referred to as “as mentioned herein”, it means that it may be mentioned anywhere in the present text. The terms as mentioned in the present text have the following meanings: The term “halogen atom” means a fluorine, chlorine, bromine or iodine atom, particularly a fluorine, chlorine or bromine atom. The term “C ₁ -C ₆ -alkyl” means a linear or branched, saturated, monovalent hydrocarbon group having 1, 2, 3, 4, 5 or 6 carbon atoms, e.g. a methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, isobutyl, tert-butyl, pentyl, isopentyl, 2-methylbutyl, 1-methylbutyl, 1-ethylpropyl, 1,2-dimethylpropyl, neo-pentyl, 1,1-dimethylpropyl, hexyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1-ethylbutyl, 2-ethylbutyl, 1,1-dimethylbutyl, 2,2-dimethylbutyl, 3,3-dimethylbutyl, 2,3-dimethylbutyl, 1,2-dimethylbutyl or 1,3-dimethylbutyl group, or an isomer thereof. Particularly, said group has 1, 2, 3 or 4 carbon atoms (“C ₁ -C ₄ -alkyl”), e.g. a methyl, ethyl, propyl, isopropyl, butyl, sec-butyl isobutyl, or tert-butyl group, more particularly 1, 2 or 3 carbon atoms (“C ₁ -C ₃ -alkyl”), e.g. a methyl, ethyl, n-propyl or isopropyl group. The term “C ₁ -C ₆ -hydroxyalkyl” means a linear or branched, saturated, monovalent hydrocarbon group in which the term “C ₁ -C ₆ -alkyl” is defined supra, and in which 1, 2 or 3 hydrogen atoms are replaced with a hydroxy group, e.g. a hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, 1,2-dihydroxyethyl, 3-hydroxypropyl, 2-hydroxypropyl, 1-hydroxypropyl, 1-hydroxypropan-2-yl, 2-hydroxypropan-2-yl, 2,3-dihydroxypropyl, 1,3-dihydroxypropan-2-yl, 3-hydroxy-2-methyl-propyl, 2-hydroxy-2-methyl-propyl, 1-hydroxy-2-methyl-propyl, 3-hydroxybutyl, 1-hydroxybutan-2-yl, 4-hydroxybutan-2-yl, 1,3-dihydroxybutan-2-yl, 4-hydroxy-2-methylbutan-2-yl, 1-hydroxy-3-methylbutan-2-yl, 1- hydroxypentan-3-yl, 1-hydroxy-4-methylpentan-2-yl, 1-hydroxy-3,3-dimethylbutan-2-yl group. The term “C ₁ -C ₆ -haloalkyl” means a linear or branched, saturated, monovalent hydrocarbon group in which the term “C ₁ -C ₆ -alkyl” is as defined supra, and in which one or more of the hydrogen atoms are replaced, identically or differently, with a halogen atom. Particularly, said halogen atom is a fluorine atom. Said C ₁ -C ₆ -haloalkyl group is, for example, fluoromethyl, difluoromethyl, trifluoromethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, pentafluoroethyl, 3,3,3-trifluoropropyl or 1,3-difluoropropan-2-yl. The term “hydroxy-C ₁ -C ₆ -haloalkyl” means a linear or branched, saturated, monovalent hydrocarbon group in which the term “C ₁ -C ₆ -alkyl” is as defined supra, and in which one or more of the hydrogen atoms are replaced, identically or differently, with a halogen atom and additionally one further hydrogen atom is replaced with a hydroxy group, e.g. a 1,1,1- trifluoro-3-hydroxypropan-2-yl, 3,3,3-trifluoro-2-hydroxypropyl, 4,4,4-trifluoro-3- hydroxybutan-2-yl group. The term “C ₁ -C ₆ -alkoxy” means a linear or branched, saturated, monovalent group of formula (C ₁ -C ₆ -alkyl)-O-, in which the term “C ₁ -C ₆ -alkyl” is as defined supra, e.g. a methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, sec-butoxy, isobutoxy, tert-butoxy, pentyloxy, isopentyloxy or n-hexyloxy group, or an isomer thereof. The term “C ₁ -C ₆ -haloalkoxy” means a linear or branched, saturated, monovalent C ₁ -C ₆ -alkoxy group, as defined supra, in which one or more of the hydrogen atoms is replaced, identically or differently, with a halogen atom. Particularly, said halogen atom is a fluorine atom. Said C ₁ -C ₆ -haloalkoxy group is, for example, fluoromethoxy, difluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy or pentafluoroethoxy. The term “C ₃ -C ₆ -cycloalkyl” means a saturated, monovalent, monocyclic hydrocarbon ring which contains 3, 4, 5, or 6 carbon atoms (“C ₃ -C ₆ -cycloalkyl”). Said C ₃ -C ₆ -cycloalkyl group is for example, a cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl group. The term "spirocycloalkyl" means a saturated, monovalent bicyclic hydrocarbon group in which the two rings share one common ring carbon atom, and wherein said bicyclic hydrocarbon group contains 5, 6, 7, 8, 9, 10 or 11 carbon atoms, it being possible for said spirocycloalkyl group to be attached to the rest of the molecule via any one of the carbon atoms except the spiro carbon atom. Said spirocycloalkyl group is, for example, spiro[2.2]pentyl, spiro[2.3]hexyl, spiro[2.4]heptyl, spiro[2.5]octyl, spiro[2.6]nonyl, spiro[3.3]heptyl, spiro[3.4]octyl, spiro[3.5]nonyl, spiro[3.6]decyl, spiro[4.4]nonyl, spiro[4.5]decyl, spiro[4.6]undecyl or spiro[5.5]undecyl. The term “bridged heterocycloalkyl” means a bicyclic, saturated heterocycle with 7, 8, 9 or 10 ring atoms in total, in which the two rings share two common ring atoms which are not adjacent, which “bridged heterocycloalkyl” contains one or two identical or different ring heteroatoms from the series: N, O, S; it being possible for said bridged heterocycloalkyl group to be attached to the rest of the molecule via any one of the carbon atoms or, if present, a nitrogen atom. Said bridged heterocycloalkyl group is, for example, azabicyclo[2.2.1]heptyl, oxazabicyclo[2.2.1]heptyl, thiazabicyclo[2.2.1]heptyl, diazabicyclo[2.2.1]heptyl, azabicyclo-[2.2.2]octyl, diazabicyclo[2.2.2]octyl, oxazabicyclo[2.2.2]octyl, thiazabicyclo[2.2.2]octyl, azabi-cyclo[3.2.1]octyl, diazabicyclo[3.2.1]octyl, oxazabicyclo[3.2.1]octyl, thiazabicyclo[3.2.1]octyl, azabicyclo[3.3.1]nonyl, diazabicyclo[3.3.1]nonyl, oxazabicyclo[3.3.1]nonyl, thiazabicyclo[3.3.1]-nonyl, azabicyclo[4.2.1]nonyl, diazabicyclo[4.2.1]nonyl, oxazabicyclo[4.2.1]nonyl, thiaza- bicyclo[4.2.1]nonyl, azabicyclo[3.3.2]decyl, diazabicyclo[3.3.2]decyl, oxazabicyclo[3.3.2]decyl, thiazabicyclo[3.3.2]decyl or azabicyclo[4.2.2]decyl. The terms “4- to 7-membered heterocycloalkyl” and “4- to 6-membered heterocycloalkyl” mean a monocyclic, saturated heterocycle with 4, 5, 6 or 7 or, respectively, 4, 5 or 6 ring atoms in total, which contains one or two identical or different ring heteroatoms from the series N, O and S, it being possible for said heterocycloalkyl group to be attached to the rest of the molecule via any one of the carbon atoms or, if present, a nitrogen atom. Said heterocycloalkyl group, without being limited thereto, can be a 4-membered ring, such as azetidinyl, oxetanyl or thietanyl, for example; or a 5-membered ring, such as tetrahydrofuranyl, 1,3-dioxolanyl, thiolanyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, 1,1-dioxidothiolanyl, 1,2-oxazolidinyl, 1,3-oxazolidinyl or 1,3-thiazolidinyl, for example; or a 6-membered ring, such as tetrahydropyranyl, tetrahydrothiopyranyl, piperidinyl, morpholinyl, dithianyl, thiomorpholinyl, piperazinyl, 1,3-dioxanyl, 1,4-dioxanyl or 1,2-oxazinanyl, for example, or a 7-membered ring, such as azepanyl, 1,4-diazepanyl or 1,4-oxazepanyl, for example. Particularly, “4- to 6-membered heterocycloalkyl” means a 4- to 6-membered heterocycloalkyl as defined supra containing one ring nitrogen atom and optionally one further ring heteroatom from the series: N, O, S. More particularly, “5- or 6-membered heterocycloalkyl” means a monocyclic, saturated heterocycle with 5 or 6 ring atoms in total, containing one ring nitrogen atom and optionally one further ring heteroatom from the series: N, O. The term “heterospirocycloalkyl” means a bicyclic, saturated heterocycle with 6, 7, 8, 9, 10 or 11 ring atoms in total, in which the two rings share one common ring carbon atom, which “heterospirocycloalkyl” contains one or two identical or different ring heteroatoms from the series: N, O, S; it being possible for said heterospirocycloalkyl group to be attached to the rest of the molecule via any one of the carbon atoms, except the spiro carbon atom, or, if present, a nitrogen atom. Said heterospirocycloalkyl group is, for example, azaspiro[2.3]hexyl, azaspiro[3.3]heptyl, oxaazaspiro[3.3]heptyl, thiaazaspiro[3.3]heptyl, oxaspiro[3.3]heptyl, oxazaspiro[5.3]nonyl, oxazaspiro[4.3]octyl, azaspiro[4,5]decyl, oxazaspiro [5.5]undecyl, diazaspiro[3.3]heptyl, thiazaspiro[3.3]heptyl, thiazaspiro[4.3]octyl, azaspiro[5.5]undecyl, or one of the further homologous scaffolds such as spiro[3.4]-, spiro[4.4]-, spiro[2.4]-, spiro[2.5]-, spiro[2.6]-, spiro[3.5]-, spiro[3.6]-, spiro[4.5]- and spiro[4.6]-. The term “heteroaryl” means a monovalent, monocyclic, bicyclic or tricyclic aromatic ring having 5, 6, 8, 9, 10, 11, 12, 13 or 14 ring atoms (a “5- to 14-membered heteroaryl” group), particularly 5, 6, 9 or 10 ring atoms, which contains at least one ring heteroatom and optionally one, two or three further ring heteroatoms from the series: N, O and/or S, and which is bound via a ring carbon atom or optionally via a ring nitrogen atom (if allowed by valency). Said heteroaryl group can be a 5-membered heteroaryl group, such as, for example, thienyl, furanyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl, thiadiazolyl or tetrazolyl; or a 6-membered heteroaryl group, such as, for example, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl or triazinyl; or a tricyclic heteroaryl group, such as, for example, carbazolyl, acridinyl or phenazinyl; or a 9- membered heteroaryl group, such as, for example, benzofuranyl, benzothienyl, benzoxazolyl, benzisoxazolyl, benzimidazolyl, benzothiazolyl, benzotriazolyl, indazolyl, indolyl, isoindolyl, indolizinyl or purinyl; or a 10-membered heteroaryl group, such as, for example, quinolinyl, quinazolinyl, isoquinolinyl, cinnolinyl, phthalazinyl, quinoxalinyl or pteridinyl. In general, and unless otherwise mentioned, the heteroaryl groups include all possible isomeric forms thereof, e.g.: tautomers and positional isomers with respect to the point of linkage to the rest of the molecule. Thus, for some illustrative non-restricting examples, the term pyridinyl includes pyridin-2-yl, pyridin-3-yl and pyridin-4-yl; or the term thienyl includes thien-2-yl and thien-3-yl. Particularly, the heteroaryl group is a pyrazolyl group. The term “C ₁ -C ₆ ”, as used in the present text, e.g. in the context of the definition of “C ₁ -C ₆ -alkyl”, “C ₁ -C ₆ -haloalkyl”, “C ₁ -C ₆ -hydroxyalkyl”, “C ₁ -C ₆ -alkoxy” or “C ₁ -C ₆ -haloalkoxy” means an alkyl group having a finite number of carbon atoms of 1 to 6, i.e.1, 2, 3, 4, 5 or 6 carbon atoms. Further, as used herein, the term “C ₃ -C ₈ ”, as used in the present text, e.g. in the context of the definition of “C ₃ -C ₈ -cycloalkyl”, means a cycloalkyl group having a finite number of carbon atoms of 3 to 8, i.e.3, 4, 5, 6, 7 or 8 carbon atoms. When a range of values is given, said range encompasses each value and sub-range within said range. For example: "C ₁ -C ₆ " encompasses C ₁ , C ₂ , C ₃ , C ₄ , C ₅ , C ₆ , C ₁ -C ₆ , C ₁ -C ₅ , C ₁ -C ₄ , C ₁ -C ₃ , C ₁ -C ₂ , C ₂ -C ₆ , C ₂ - C ₅ , C ₂ -C ₄ , C ₂ -C ₃ , C ₃ -C ₆ , C ₃ -C ₅ , C ₃ -C ₄ , C ₄ -C ₆ , C ₄ -C ₅ , and C ₅ -C ₆ ; "C ₂ -C ₆ " encompasses C ₂ , C ₃ , C ₄ , C ₅ , C ₆ , C ₂ -C ₆ , C ₂ -C ₅ , C ₂ -C ₄ , C ₂ -C ₃ , C ₃ -C ₆ , C ₃ -C ₅ , C ₃ -C ₄ , C ₄ -C ₆ , C ₄ -C ₅ , and C ₅ -C ₆ ; "C ₃ -C ₁₀ " encompasses C ₃ , C ₄ , C ₅ , C ₆ , C ₇ , C ₈ , C ₉ , C ₁₀ , C ₃ -C ₁₀ , C ₃ -C ₉ , C ₃ -C ₈ , C ₃ -C ₇ , C ₃ -C ₆ , C ₃ -C ₅ , C ₃ -C ₄ , C ₄ -C ₁₀ , C ₄ -C ₉ , C ₄ -C ₈ , C ₄ -C ₇ , C ₄ -C ₆ , C ₄ -C ₅ , C ₅ -C ₁₀ , C ₅ -C ₉ , C ₅ -C ₈ , C ₅ -C ₇ , C ₅ -C ₆ , C ₆ -C ₁₀ , C ₆ -C ₉ , C ₆ -C ₈ , C ₆ -C ₇ , C ₇ -C ₁₀ , C ₇ -C ₉ , C ₇ -C ₈ , C ₈ -C ₁₀ , C ₈ -C ₉ and C ₉ -C ₁₀ ; "C ₃ -C ₈ " encompasses C ₃ , C ₄ , C ₅ , C ₆ , C ₇ , C ₈ , C ₃ -C ₈ , C ₃ -C ₇ , C ₃ -C ₆ , C ₃ -C ₅ , C ₃ -C ₄ , C ₄ -C ₈ , C ₄ - C ₇ , C ₄ -C ₆ , C ₄ -C ₅ , C ₅ -C ₈ , C ₅ -C ₇ , C ₅ -C ₆ , C ₆ -C ₈ , C ₆ -C ₇ and C ₇ -C ₈ ; "C ₃ -C ₆ " encompasses C ₃ , C ₄ , C ₅ , C ₆ , C ₃ -C ₆ , C ₃ -C ₅ , C ₃ -C ₄ , C ₄ -C ₆ , C ₄ -C ₅ , and C ₅ -C ₆ ; "C ₄ -C ₈ " encompasses C ₄ , C ₅ , C ₆ , C ₇ , C ₈ , C ₄ -C ₈ , C ₄ -C ₇ , C ₄ -C ₆ , C ₄ -C ₅ , C ₅ -C ₈ , C ₅ -C ₇ , C ₅ -C ₆ , C ₆ -C ₈ , C ₆ -C ₇ and C ₇ -C ₈ ; "C ₄ -C ₇ " encompasses C ₄ , C ₅ , C ₆ , C ₇ , C ₄ -C ₇ , C ₄ -C ₆ , C ₄ -C ₅ , C ₅ -C ₇ , C ₅ -C ₆ and C ₆ -C ₇ ; "C ₄ -C ₆ " encompasses C ₄ , C ₅ , C ₆ , C ₄ -C ₆ , C ₄ -C ₅ and C ₅ -C ₆ ; "C ₅ -C ₁₀ " encompasses C ₅ , C ₆ , C ₇ , C ₈ , C ₉ , C ₁₀ , C ₅ -C ₁₀ , C ₅ -C ₉ , C ₅ -C ₈ , C ₅ -C ₇ , C ₅ -C ₆ , C ₆ -C ₁₀ , C ₆ -C ₉ , C ₆ -C ₈ , C ₆ -C ₇ , C ₇ -C ₁₀ , C ₇ -C ₉ , C ₇ -C ₈ , C ₈ -C ₁₀ , C ₈ -C ₉ and C ₉ -C ₁₀ ; "C ₆ -C ₁₀ " encompasses C ₆ , C ₇ , C ₈ , C ₉ , C ₁₀ , C ₆ -C ₁₀ , C ₆ -C ₉ , C ₆ -C ₈ , C ₆ -C ₇ , C ₇ -C ₁₀ , C ₇ -C ₉ , C ₇ - C ₈ , C ₈ -C ₁₀ , C ₈ -C ₉ and C ₉ -C ₁₀ . Where the plural form of the word compounds, salts, polymorphs, hydrates, solvates and the like, is used herein, this is taken to mean also a single compound, salt, polymorph, isomer, hydrate, solvate or the like. By "stable compound' or "stable structure" is meant a compound that is sufficiently robust to survive isolation to a useful degree of purity from a reaction mixture, and formulation into an efficacious therapeutic agent. The compounds of the present invention optionally contain one or more asymmetric centres, depending upon the location and nature of the various substituents desired. It is possible that one or more asymmetric carbon atoms are present in the (R) or (S) configuration, which can result in racemic mixtures in the case of a single asymmetric centre, and in diastereomeric mixtures in the case of multiple asymmetric centres. In certain instances, it is possible that asymmetry also be present due to restricted rotation about a given bond, for example, the central bond adjoining two substituted aromatic rings of the specified compounds. Preferred compounds are those which produce the more desirable biological activity. Separated, pure or partially purified isomers and stereoisomers or racemic or diastereomeric mixtures of the compounds of the present invention are also included within the scope of the present invention. The purification and the separation of such materials can be accomplished by standard techniques known in the art. The optical isomers can be obtained by resolution of the racemic mixtures according to conventional processes, for example, by the formation of diastereoisomeric salts using an optically active acid or base or formation of covalent diastereomers. Examples of appropriate acids are tartaric, diacetyltartaric, ditoluoyltartaric and camphorsulfonic acid. Mixtures of diastereoisomers can be separated into their individual diastereomers on the basis of their physical and/or chemical differences by methods known in the art, for example, by chromatography or fractional crystallisation. The optically active bases or acids are then liberated from the separated diastereomeric salts. A different process for separation of optical isomers involves the use of chiral chromatography (e.g., HPLC columns using a chiral phase), with or without conventional derivatisation, optimally chosen to maximise the separation of the enantiomers. Suitable HPLC columns using a chiral phase are commercially available, such as those manufactured by Daicel, e.g., Chiracel OD and Chiracel OJ, for example, among many others, which are all routinely selectable. Enzymatic separations, with or without derivatisation, are also useful. The optically active compounds of the present invention can likewise be obtained by chiral syntheses utilizing optically active starting materials. In order to distinguish different types of isomers from each other reference is made to IUPAC Rules Section E (Pure Appl Chem 45, 11-30, 1976). The present invention includes all possible stereoisomers of the compounds of the present invention as single stereoisomers, or as any mixture of said stereoisomers, e.g. (R)- or (S)- isomers, in any ratio. Isolation of a single stereoisomer, e.g. a single enantiomer or a single diastereomer, of a compound of the present invention is achieved by any suitable state of the art method, such as chromatography, especially chiral chromatography, for example. Further, it is possible for the compounds of the present invention to exist as tautomers. For example, any compound of the present invention which contains an imidazopyridine moiety as a heteroaryl group for example can exist as a 1H tautomer, or a 3H tautomer, or even a mixture in any amount of the two tautomers, namely: The present invention includes all possible tautomers of the compounds of the present invention as single tautomers, or as any mixture of said tautomers, in any ratio. Further, the compounds of the present invention can exist as N-oxides, which are defined in that at least one nitrogen of the compounds of the present invention is oxidised. The present invention includes all such possible N-oxides. The present invention also covers useful forms of the compounds of the present invention, such as metabolites, hydrates, solvates, prodrugs, salts, in particular pharmaceutically acceptable salts, and/or co-precipitates. The compounds of the present invention can exist as a hydrate, or as a solvate, wherein the compounds of the present invention contain polar solvents, in particular water, methanol or ethanol for example, as structural element of the crystal lattice of the compounds. It is possible for the amount of polar solvents, in particular water, to exist in a stoichiometric or non-stoichiometric ratio. In the case of stoichiometric solvates, e.g. a hydrate, hemi-, (semi-), mono-, sesqui-, di-, tri-, tetra-, penta- etc. solvates or hydrates, respectively, are possible. The present invention includes all such hydrates or solvates. Further, it is possible for the compounds of the present invention to exist in free form, e.g. as a free base, or as a free acid, or as a zwitterion, or to exist in the form of a salt. Said salt may be any salt, either an organic or inorganic addition salt, particularly any pharmaceutically acceptable organic or inorganic addition salt, which is customarily used in pharmacy, or which is used, for example, for isolating or purifying the compounds of the present invention. The term “pharmaceutically acceptable salt" refers to an inorganic or organic acid addition salt of a compound of the present invention. For example, see S. M. Berge, et al. “Pharmaceutical Salts,” J. Pharm. Sci.1977, 66, 1-19. A suitable pharmaceutically acceptable salt of the compounds of the present invention may be, for example, an acid-addition salt of a compound of the present invention bearing a nitrogen atom, in a chain or in a ring, for example, which is sufficiently basic, such as an acid-addition salt with an inorganic acid, or “mineral acid”, such as hydrochloric, hydrobromic, hydroiodic, sulfuric, sulfamic, bisulfuric, phosphoric, or nitric acid, for example, or with an organic acid, such as formic, acetic, acetoacetic, pyruvic, trifluoroacetic, propionic, butyric, hexanoic, heptanoic, undecanoic, lauric, benzoic, salicylic, 2-(4-hydroxybenzoyl)-benzoic, camphoric, cinnamic, cyclopentanepropionic, digluconic, 3-hydroxy-2-naphthoic, nicotinic, pamoic, pectinic, 3-phenylpropionic, pivalic, 2-hydroxyethanesulfonic, itaconic, trifluoromethanesulfonic, dodecylsulfuric, ethanesulfonic, benzenesulfonic, para-toluenesulfonic, methanesulfonic, 2-naphthalenesulfonic, naphthalinedisulfonic, camphorsulfonic acid, citric, tartaric, stearic, lactic, oxalic, malonic, succinic, malic, adipic, alginic, maleic, fumaric, D-gluconic, mandelic, ascorbic, glucoheptanoic, glycerophosphoric, aspartic, sulfosalicylic, or thiocyanic acid, for example. Further, another suitably pharmaceutically acceptable salt of a compound of the present invention which is sufficiently acidic, is an alkali metal salt, for example a sodium or potassium salt, an alkaline earth metal salt, for example a calcium, magnesium or strontium salt, or an aluminium or a zinc salt, or an ammonium salt derived from ammonia or from an organic primary, secondary or tertiary amine having 1 to 20 carbon atoms, such as ethylamine, diethylamine, triethylamine, ethyldiisopropylamine, monoethanolamine, diethanolamine, triethanolamine, dicyclohexylamine, dimethylaminoethanol, diethylaminoethanol, tris(hydroxymethyl)aminomethane, procaine, dibenzylamine, N-methylmorpholine, arginine, lysine, 1,2-ethylenediamine, N- methylpiperidine, N-methyl-glucamine, N,N-dimethyl-glucamine, N-ethyl-glucamine, 1,6- hexanediamine, glucosamine, sarcosine, serinol, 2-amino-1,3-propanediol, 3-amino-1,2- propanediol, 4-amino-1,2,3-butanetriol, or a salt with a quarternary ammonium ion having 1 to 20 carbon atoms, such as tetramethylammonium, tetraethylammonium, tetra(n- propyl)ammonium, tetra(n-butyl)ammonium, N-benzyl-N,N,N-trimethylammonium, choline or benzalkonium. Those skilled in the art will further recognise that it is possible for acid addition salts of the claimed compounds to be prepared by reaction of the compounds with the appropriate inorganic or organic acid via any of a number of known methods. Alternatively, alkali and alkaline earth metal salts of acidic compounds of the present invention are prepared by reacting the compounds of the present invention with the appropriate base via a variety of known methods. The present invention includes all possible salts of the compounds of the present invention as single salts, or as any mixture of said salts, in any ratio. In the present text, in particular in the Experimental Section, for the synthesis of intermediates and of examples of the present invention, when a compound is mentioned as a salt form with the corresponding base or acid, the exact stoichiometric composition of said salt form, as obtained by the respective preparation and/or purification process, is, in most cases, unknown. Unless specified otherwise, suffixes to chemical names or structural formulae relating to salts, such as "hydrochloride", "trifluoroacetate", "sodium salt", or "x HCl", "x CF ₃ COOH", "x Na ⁺ ", for example, mean a salt form, the stoichiometry of which salt form not being specified. This applies analogously to cases in which synthesis intermediates or example compounds or salts thereof have been obtained, by the preparation and/or purification processes described, as solvates, such as hydrates, with (if defined) unknown stoichiometric composition. Furthermore, the present invention includes all possible crystalline forms, or polymorphs, of the compounds of the present invention, either as single polymorph, or as a mixture of more than one polymorph, in any ratio. Moreover, the present invention also includes prodrugs of the compounds according to the invention. The term “prodrugs” here designates compounds which themselves can be biologically active or inactive, but are converted (for example metabolically or hydrolytically) into compounds according to the invention during their residence time in the body. In accordance with a further embodiment of the first aspect, the present invention covers compounds of general formula (1), supra, in which: R ¹ represents C ₃ -C ₆ -cycloalkyl, 4- to 6-membered heterocycloalkyl, heterospirocycloalkyl, phenyl, or heteroaryl, wherein said groups are optionally substituted, one or more times, independently of each other, with R ⁵ , or R ⁸ R ⁹ N-; R ² represents phenyl, which is optionally substituted, one or more times, independently of each other, with R ⁶ ; R ³ represents hydrogen or C ₁ -C ₄ -alkyl; R ⁴ represents C ₁ -C ₆ -alkyl, C ₂ -C ₆ -hydroxyalkyl, C ₁ -C ₄ -haloalkyl, hydroxy-C ₂ -C ₆ - haloalkyl, R ⁸ R ⁹ N-(C ₂ -C ₄ -alkyl)-, (C ₂ -C ₄ -alkyl)-O-CO-NH-(C ₂ -C ₄ -alkyl)-, H ₂ N-CO- (C ₁ -C ₄ -alkyl)-, H ₂ N-CO-(C ₂ -C ₄ -hydroxyalkyl)-, (C ₁ -C ₄ -alkoxy)-(C ₂ -C ₄ -alkyl)-, C ₃ - C ₆ -cycloalkyl, 5- to 6-membered heterocycloalkyl, heterospirocycloalkyl, phenyl, heteroaryl, C ₃ -C ₆ -cycloalkyl-(C ₁ -C ₃ -alkyl)-, C ₃ -C ₆ -cycloalkyl-(C ₂ -C ₆ -hydroxyalkyl)- , C ₃ -C ₆ -cycloalkyl-(C ₁ -C ₄ -haloalkyl)-, 5- to 6-membered heterocycloalkyl-(C ₁ -C ₃ - alkyl)-, heterospirocycloalkyl-(C ₁ -C ₃ -alkyl)-, phenyl-(C ₁ -C ₃ -alkyl)-, or heteroaryl- (C ₁ -C ₃ -alkyl)-, wherein said C ₃ -C ₆ -cycloalkyl, 5- to 6-membered heterocycloalkyl, heterospirocycloalkyl, phenyl, or heteroaryl groups are optionally substituted, one or more times, independently of each other, with R ⁷ ; R ⁵ represents halogen, cyano, C ₁ -C ₄ -alkyl, C ₁ -C ₄ -haloalkyl, C ₁ -C ₄ -hydroxyalkyl, C ₁ -C ₃ -alkoxy, or C ₁ -C ₃ -haloalkoxy; R ⁶ represents C ₁ -C ₄ -alkyl, C ₁ -C ₄ -haloalkyl, C ₁ -C ₄ -alkoxy, C ₁ -C ₄ -haloalkoxy, C ₁ -C ₄ - alkylthio, C ₁ -C ₄ -haloalkylthio, C ₃ -C ₆ -cycloalkyl, or −SF ₅ ; R ⁷ represents hydroxy, halogen, cyano, C ₁ -C ₄ -alkyl, C ₁ -C ₄ -hydroxyalkyl, C ₁ -C ₄ - haloalkyl, C ₁ -C ₃ -alkoxy, C ₁ -C ₃ -haloalkoxy, or oxo; R ⁸ represents hydrogen, C ₁ -C ₄ -alkyl, or C ₃ -C ₆ -cycloalkyl; R ⁹ represents hydrogen or C ₁ -C ₄ -alkyl; and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same. In accordance with a further embodiment of the first aspect, the present invention covers compounds of general formula (1), supra, in which: R ¹ represents cyclopropyl, 4- to 5-membered heterocycloalkyl, or 5-membered heteroaryl, wherein said groups are optionally substituted, one or two times, with R ⁵ ; R ² represents phenyl, which is optionally substituted, one time with R ⁶ ; R ³ represents hydrogen or methyl; R ⁴ represents C ₁ -C ₃ -alkyl, C ₂ -C ₆ -hydroxyalkyl, hydroxy-C ₂ -C ₄ -haloalkyl, H ₂ N-(C ₂ -C ₃ - alkyl)-, tert.-butyl-O-CO-NH-(C ₂ -C ₄ -alkyl)-, H ₂ N-CO-(C ₁ -C ₃ -alkyl)-, H ₂ N-CO-(C ₂ - C ₃ -hydroxyalkyl)-, (C ₁ -C ₃ -alkoxy)-(C ₂ -C ₃ -alkyl)-, C ₃ -C ₅ -cycloalkyl, 5-membered heterocycloalkyl, phenyl, 5-membered heteroaryl, cyclopropyl-(C ₁ -C ₃ -alkyl)-, cyclopropyl-(C ₁ -C ₃ -haloalkyl)-, cyclopropyl-(C ₂ -C ₃ -hydroxyalkyl)-, 5-membered heterocycloalkyl-methyl-, or 5-membered heteroaryl-methyl-, wherein said C ₃ -C ₅ -cycloalkyl, 5-membered heterocycloalkyl, phenyl, or 5- membered heteroaryl groups are optionally substituted, one or two times, independently of each other, with R ⁷ ; R ⁵ represents halogen, C ₁ -C ₄ -alkyl, or C ₁ -C ₄ -haloalkyl; R ⁶ represents C ₁ -C ₄ -alkyl, C ₁ -C ₂ -haloalkyl, C ₁ -C ₂ -haloalkoxy, cyclopropyl, or −SF ₅ ; R ⁷ represents hydroxy, halogen, C ₁ -C ₃ -alkyl, C ₁ -C ₃ -hydroxyalkyl, or oxo; and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same. In accordance with a further embodiment of the first aspect, the present invention covers compounds of general formula (1), supra, in which: R ¹ represents cyclopropyl, azetidin-1-yl, pyrrolidin-1-yl, 1H-pyrazol-3-yl, 3,3- dimethylazetidin-1-yl, 2-methylpyrrolidin-1-yl, 1-methyl-1H-pyrazol-4-yl, 1- methyl-1H-pyrazol-3-yl, 1-methyl-1H-1,2,4-triazol-3-yl, 5-methyl-1,3-oxazol-2-yl, 3-fluoropyrrolidin-1-yl, 3,3-difluoroazetidin-1-yl, 5-methyl-1,3-thiazol-2-yl, 4- methyl-1,3-thiazol-2-yl, 1,5-dimethyl-1H-pyrazol-3-yl, 2-methyltetrazol-5-yl, or 1-(difluoromethyl)pyrazol-3-yl; R ² represents phenyl, which is optionally substituted, one time with R ⁶ ; R ³ represents hydrogen or methyl; R ⁴ represents methyl, −CH ₂ CH ₂ NH ₂ , −CH ₂ CH ₂ OH, cyclopropylmethyl, −CHCH ₃ CH ₂ NH ₂ , −CH ₂ CH ₂ CH ₂ NH ₂ , −CH ₂ CH ₂ OCH ₃ , −CH ₂ CHCH ₃ OH, −CHCH ₃ CH ₂ OH, −CH ₂ CH ₂ CH ₂ OH, 1-cyclopropylethyl, 1-cyclopropylethyl, −CHCH ₃ CH ₂ CH ₂ OH, −CH ₂ CHCH ₃ CH ₂ OH, 1-hydroxybutan-2-yl, −CH ₂ CH ₂ CHCH ₃ OH, −CH ₂ CH ₂ CHCH ₃ OH, (1-hydroxycyclopropyl)methyl, 1- (hydroxymethyl)cyclopropyl, 1H-pyrazol-4-yl, −CHCH ₃ CNH ₂ O, 1,3- dihydroxypropan-2-yl, 1-hydroxypentan-3-yl, 1-hydroxy-3-methylbutan-2-yl, −C(CH ₃ ) ₂ CH ₂ CH ₂ OH, 1-cyclopropyl-2-hydroxyethyl, 1-methyl-1H-pyrazol-4-yl, (1H-imidazol-2-yl)methyl, 1-carbamoylpropyl, 5-oxopyrrolidin-3-yl, 2- oxopyrrolidin-3-yl, 1,3-dihydroxybutan-2-yl, 1-carbamoyl-2-hydroxyethyl, 1- hydroxy-4-methylpentan-2-yl, 2-cyclopropyl-3-hydroxypropyl, 1-cyclopropyl-3- hydroxypropyl, 1-(hydroxymethyl)cyclopentyl, 3,5-dimethyl-1H-pyrazol-4-yl, (5- oxopyrrolidin-2-yl)methyl, (5-oxopyrrolidin-3-yl)methyl, −CH ₂ CHOHCF ₃ , 2- chlorophenyl, R ⁶ represents hydrogen, methyl, ethyl, −CH(CH ₃ ) ₂ , cyclopropyl, −C(CH ₃ ) ₃ , trifluoromethyl, −OCF ₃ , or −SF ₅ ; and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same. In accordance with an embodiment of the second aspect, the present invention covers compounds of general formula (2), supra, in which: R ¹ represents 4- to 6-membered heterocycloalkyl, heterospirocycloalkyl, phenyl, or heteroaryl, wherein said groups are optionally substituted, one time, with R ⁵ , or R ⁸ R ⁹ N-; R ² represents phenyl, which is optionally substituted, one time, with R ⁶ ; R ³ represents hydrogen; R ⁴ represents C ₁ -C ₂ -alkyl, C ₃ -C ₆ -hydroxyalkyl, H ₂ N-CO-(C ₃ -alkyl)-, methoxy-ethyl-, cyclopropyl, cyclopropyl-(C ₁ -C ₂ -alkyl)-, or 3,5-dimethyl-1H-pyrazol-4-yl; R ⁵ represents fluoro, methyl, or hydroxymethyl; R ⁶ represents trifluoromethyl; R ⁸ represents cyclopropyl; R ⁹ represents methyl; and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same. In accordance with another embodiment of the second aspect, the present invention covers compounds of general formula (2), supra, in which: R ¹ represents cyclopropyl(methyl)amino, 1-methyl-1H-pyrazol-3-yl, 3-fluorophenyl, azetidin-1-yl, pyrrolidin-1-yl, 1-piperidyl, 4-morpholino, or wherein said azetidin-1-yl and pyrrolidin-1-yl groups are optionally substituted, one time, with R ⁵ ; R ² represents 4-(trifluoromethyl)phenyl; R ³ represents hydrogen; R ⁴ represents ethyl, cyclopropyl, −CH(R ¹⁰ )CH ₂ CH ₂ R ¹¹ , −CH(R ¹² )CH(R ¹⁴ )OR ¹³ , 3,5-dimethyl-1H-pyrazol-4-yl, R ⁵ represents methyl or hydroxymethyl; R ¹⁰ represents hydrogen, methyl, or −C(O)NH ₂ ; R ¹¹ represents hydrogen or hydroxy; R ¹² represents hydrogen, methyl, or −CH ₂ CH(CH ₃ ) ₂ ; R ¹³ represents hydrogen or methyl; R ¹⁴ represents hydrogen or methyl; and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same. In accordance with an embodiment of the third aspect, the present invention covers compounds of general formula (3), supra, in which: R ¹ represents phenyl or 1H-pyrazol-3-yl, wherein said groups are optionally substituted, one time, with R ⁵ ; R ² represents phenyl, which is optionally substituted, one time, with R ⁶ ; R ³ represents hydrogen; R ⁴ represents C ₂ -C ₃ -hydroxyalkyl; R ⁵ represents fluoro or methyl; R ⁶ represents C ₁ -haloalkyl; and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same. In accordance with another embodiment of the third aspect, the present invention covers compounds of general formula (I), supra, in which: R ¹ represents 1-methyl-1H-pyrazol-3-yl or 3-fluorophenyl; R ² represents 4-(trifluoromethyl)phenyl; R ³ represents hydrogen; R ⁴ represents −CHCH ₃ CH ₂ OH; and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same. In accordance with an embodiment of the fourth aspect, the present invention covers compounds of general formula (I), supra, in which: R ¹ 5-membered heteroaryl, which is optionally substituted, one time, with R ⁵ ; R ² represents phenyl, which is optionally substituted, one time, with R ⁶ ; R ³ represents hydrogen; R ⁴ represents C ₂ -C ₄ -hydroxyalkyl, cyclopropyl-(C ₂ -C ₃ -hydroxyalkyl)-, or 5- membered heteroaryl, which is optionally substituted, one or two times, with R ⁷ ; R ⁵ represents methyl; R ⁶ represents trifluoromethyl; R ⁷ represents methyl; and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same. In accordance with another embodiment of the fourth aspect, the present invention covers compounds of general formula (I), supra, in which: R ¹ represents 1-methyl-1H-pyrazol-3-yl; R ² represents 4-(trifluoromethyl)phenyl; R ³ represents hydrogen; R ⁴ represents −CHCH ₃ CH ₂ OH, 1-hydroxybutan-2-yl, 1-cyclopropyl-2-hydroxyethyl, or 3,5-dimethyl-1H-pyrazol-4-yl; and stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, and mixtures of same. The present invention covers any sub-combination within any embodiment or aspect of the present invention of compounds of general formula (I), supra. The present invention covers the compounds of general formula (I) which are disclosed in the Example Section of this text, infra. The present invention covers methods of preparing compounds of the present invention of general formula (I), said methods comprising the steps as described in the Experimental Section herein. The compounds of general formula (I) of the present invention can be converted to any salt, preferably pharmaceutically acceptable salts, as described herein, by any method which is known to the person skilled in the art. Similarly, any salt of a compound of general formula (I) of the present invention can be converted into the free compound, by any method which is known to the person skilled in the art. Compounds of the present invention can be utilized to inhibit, block, reduce, decrease, etc., cell proliferation and/or cell division, and/or produce apoptosis. This method comprises administering to a mammal in need thereof, including a human, an amount of a compound of general formula (I) of the present invention, or a pharmaceutically acceptable salt, isomer, polymorph, metabolite, hydrate, solvate or ester thereof, which is effective to treat the disorder. Hyperproliferative disorders include, but are not limited to, for example : psoriasis, keloids, and other hyperplasias affecting the skin, benign prostate hyperplasia (BPH), solid tumours, such as cancers of the breast, respiratory tract, brain, reproductive organs, digestive tract, urinary tract, eye, liver, skin, head and neck, thyroid, parathyroid and their distant metastases. Those disorders also include lymphomas, sarcomas, and leukaemias. Examples of breast cancers include, but are not limited to, invasive ductal carcinoma, invasive lobular carcinoma, ductal carcinoma in situ, and lobular carcinoma in situ. Examples of cancers of the respiratory tract include, but are not limited to, small-cell and non-small-cell lung carcinoma, as well as bronchial adenoma and pleuropulmonary blastoma. Examples of brain cancers include, but are not limited to, brain stem and hypophtalmic glioma, cerebellar and cerebral astrocytoma, medulloblastoma, ependymoma, as well as neuroectodermal and pineal tumour. Tumours of the male reproductive organs include, but are not limited to, prostate and testicular cancer. Tumours of the female reproductive organs include, but are not limited to, endometrial, cervical, ovarian, vaginal, and vulvar cancer, as well as sarcoma of the uterus. Tumours of the digestive tract include, but are not limited to, anal, colon, colorectal, oesophageal, gallbladder, gastric, pancreatic, rectal, small-intestine, and salivary gland cancers. Tumours of the urinary tract include, but are not limited to, bladder, penile, kidney, renal pelvis, ureter, urethral and human papillary renal cancers. Eye cancers include, but are not limited to, intraocular melanoma and retinoblastoma. Examples of liver cancers include, but are not limited to, hepatocellular carcinoma (liver cell carcinomas with or without fibrolamellar variant), cholangiocarcinoma (intrahepatic bile duct carcinoma), and mixed hepatocellular cholangiocarcinoma. Skin cancers include, but are not limited to, squamous cell carcinoma, Kaposi’s sarcoma, malignant melanoma, Merkel cell skin cancer, and non-melanoma skin cancer. Head-and-neck cancers include, but are not limited to, laryngeal, hypopharyngeal, nasopharyngeal, oropharyngeal cancer, lip and oral cavity cancer and squamous cell. Lymphomas include, but are not limited to, AIDS-related lymphoma, non-Hodgkin’s lymphoma, cutaneous T-cell lymphoma, Burkitt lymphoma, Hodgkin’s disease, and lymphoma of the central nervous system. Sarcomas include, but are not limited to, sarcoma of the soft tissue, osteosarcoma, malignant fibrous histiocytoma, lymphosarcoma, and rhabdomyosarcoma. Leukemias include, but are not limited to, acute myeloid leukemia, acute lymphoblastic leukemia, chronic lymphocytic leukemia, chronic myelogenous leukemia, and hairy cell leukemia. The term “treating” or “treatment” as stated throughout this document is used conventionally, for example the management or care of a subject for the purpose of combating, alleviating, reducing, relieving, improving the condition of a disease or disorder, such as a carcinoma. The compounds of the present invention can be used in particular in therapy and prevention, i.e. prophylaxis, of tumour growth and metastases, especially in solid tumours of all indications and stages with or without pre-treatment of the tumour growth. Generally, the use of chemotherapeutic agents and/or anti-cancer agents in combination with a compound or pharmaceutical composition of the present invention will serve to: 1. yield better efficacy in reducing the growth of a tumour or even eliminate the tumour as compared to administration of either agent alone, 2. provide for the administration of lesser amounts of the administered chemo- therapeutic agents, 3. provide for a chemotherapeutic treatment that is well tolerated in the patient with fewer deleterious pharmacological complications than observed with single agent chemotherapies and certain other combined therapies, 4. provide for treating a broader spectrum of different cancer types in mammals, especially humans, 5. provide for a higher response rate among treated patients, 6. provide for a longer survival time among treated patients compared to standard chemotherapy treatments, 7. provide a longer time for tumour progression, and/or 8. yield efficacy and tolerability results at least as good as those of the agents used alone, compared to known instances where other cancer agent combinations produce antagonistic effects. In addition, the compounds of general formula (I) of the present invention can also be used in combination with radiotherapy and/or surgical intervention. In a further embodiment of the present invention, the compounds of general formula (I) of the present invention may be used to sensitize a cell to radiation, i.e. treatment of a cell with a compound of the present invention prior to radiation treatment of the cell renders the cell more susceptible to DNA damage and cell death than the cell would be in the absence of any treatment with a compound of the present invention. In one aspect, the cell is treated with at least one compound of general formula (I) of the present invention. Thus, the present invention also provides a method of killing a cell, wherein a cell is administered one or more compounds of the present invention in combination with conventional radiation therapy. The present invention also provides a method of rendering a cell more susceptible to cell death, wherein the cell is treated with one or more compounds of general formula (I) of the present invention prior to the treatment of the cell to cause or induce cell death. In one aspect, after the cell is treated with one or more compounds of general formula (I) of the present invention, the cell is treated with at least one compound, or at least one method, or a combination thereof, in order to cause DNA damage for the purpose of inhibiting the function of the normal cell or killing the cell. In other embodiments of the present invention, a cell is killed by treating the cell with at least one DNA damaging agent, i.e. after treating a cell with one or more compounds of general formula (I) of the present invention to sensitize the cell to cell death, the cell is treated with at least one DNA damaging agent to kill the cell. DNA damaging agents useful in the present invention include, but are not limited to, chemotherapeutic agents (e.g. cis platin), ionizing radiation (X-rays, ultraviolet radiation), carcinogenic agents, and mutagenic agents. In other embodiments, a cell is killed by treating the cell with at least one method to cause or induce DNA damage. Such methods include, but are not limited to, activation of a cell signalling pathway that results in DNA damage when the pathway is activated, inhibiting of a cell signalling pathway that results in DNA damage when the pathway is inhibited, and inducing a biochemical change in a cell, wherein the change results in DNA damage. By way of a non-limiting example, a DNA repair pathway in a cell can be inhibited, thereby preventing the repair of DNA damage and resulting in an abnormal accumulation of DNA damage in a cell. In one aspect of the invention, a compound of general formula (I) of the present invention is administered to a cell prior to the radiation or other induction of DNA damage in the cell. In another aspect of the invention, a compound of general formula (I) of the present invention is administered to a cell concomitantly with the radiation or other induction of DNA damage in the cell. In yet another aspect of the invention, a compound of general formula (I) of the present invention is administered to a cell immediately after radiation or other induction of DNA damage in the cell has begun. In another aspect, the cell is in vitro. In another embodiment, the cell is in vivo. In accordance with a further aspect, the present invention covers compounds of general formula (I), as described supra, or stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, particularly pharmaceutically acceptable salts thereof, or mixtures of same, for use in the treatment or prophylaxis of diseases, in particular cancer. In accordance with a further aspect, the present invention covers use of a compound of general formula (I), as described supra, or stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, particularly pharmaceutically acceptable salts thereof, or mixtures of same, for the preparation of a pharmaceutical composition, preferably a medicament, for the prophylaxis or treatment of diseases, in particular cancer. In accordance with a further aspect, the present invention covers a method of treatment or prophylaxis of diseases, in particular cancer, using an effective amount of a compound of general formula (I), as described supra, or stereoisomers, tautomers, N-oxides, hydrates, solvates, and salts thereof, particularly pharmaceutically acceptable salts thereof, or mixtures of same. In accordance with a further aspect, the present invention covers pharmaceutical compositions, in particular a medicament, comprising a compound of general formula (I), as described supra, or a stereoisomer, a tautomer, an N-oxide, a hydrate, a solvate, a salt thereof, particularly a pharmaceutically acceptable salt, or a mixture of same, and one or more excipients), in particular one or more pharmaceutically acceptable excipient(s). Conventional procedures for preparing such pharmaceutical compositions in appropriate dosage forms can be utilized. The present invention furthermore covers pharmaceutical compositions, in particular medicaments, which comprise at least one compound according to the invention, conventionally together with one or more pharmaceutically suitable excipients, and to their use for the above mentioned purposes. It is possible for the compounds according to the invention to have systemic and/or local activity. For this purpose, they can be administered in a suitable manner, such as, for example, via the oral, parenteral, pulmonary, nasal, sublingual, lingual, buccal, rectal, vaginal, dermal, transdermal, conjunctival, otic route or as an implant or stent. For these administration routes, it is possible for the compounds according to the invention to be administered in suitable administration forms. For oral administration, it is possible to formulate the compounds according to the invention to dosage forms known in the art that deliver the compounds of the invention ·apidly and/or in a modified manner, such as, for example, tablets (uncoated or coated tablets, for example with enteric or controlled release coatings that dissolve with a delay or are insoluble), orally-disintegrating tablets, films/wafers, films/lyophylisates, capsules (for example hard or soft gelatine capsules), sugar-coated tablets, granules, pellets, powders, emulsions, suspensions, aerosols or solutions. It is possible to incorporate the compounds according to the invention in crystalline and/or amorphised and/or dissolved form into said dosage forms. Parenteral administration can be effected with avoidance of an absorption step (for example intravenous, intraarterial, intracardial, intraspinal or intralumbal) or with inclusion of absorption (for example intramuscular, subcutaneous, intracutaneous, percutaneous or intraperitoneal). Administration forms which are suitable for parenteral administration are, inter alia, preparations for injection and infusion in the form of solutions, suspensions, emulsions, lyophylisates or sterile powders. Examples which are suitable for other administration routes are pharmaceutical forms for inhalation [inter alia powder inhalers, nebulizers], nasal drops, nasal solutions, nasal sprays; tablets/films/wafers/capsules for lingual, sublingual or buccal administration; suppositories; eye drops, eye ointments, eye baths, ocular inserts, ear drops, ear sprays, ear powders, ear-rinses, ear tampons; vaginal capsules, aqueous suspensions (lotions, mixturae agitandae), lipophilic suspensions, emulsions, ointments, creams, transdermal therapeutic systems (such as, for example, patches), milk, pastes, foams, dusting powders, implants or stents. The compounds according to the invention can be incorporated into the stated administration forms. This can be effected in a manner known per se by mixing with pharmaceutically suitable excipients. Pharmaceutically suitable excipients include, inter alia, • fillers and carriers (for example cellulose, microcrystalline cellulose (such as, for example, Avicel ^® ), lactose, mannitol, starch, calcium phosphate (such as, for example, Di-Cafos ^® )), • ointment bases (for example petroleum jelly, paraffins, triglycerides, waxes, wool wax, wool wax alcohols, lanolin, hydrophilic ointment, polyethylene glycols), • bases for suppositories (for example polyethylene glycols, cacao butter, hard fat), • solvents (for example water, ethanol, isopropanol, glycerol, propylene glycol, medium chain-length triglycerides fatty oils, liquid polyethylene glycols, paraffins), • surfactants, emulsifiers, dispersants or wetters (for example sodium dodecyl sulfate), lecithin, phospholipids, fatty alcohols (such as, for example, Lanette ^® ), sorbitan fatty acid esters (such as, for example, Span ^® ), polyoxyethylene sorbitan fatty acid esters (such as, for example, Tween ^® ), polyoxyethylene fatty acid glycerides (such as, for example, Cremophor ^® ), polyoxethylene fatty acid esters, polyoxyethylene fatty alcohol ethers, glycerol fatty acid esters, poloxamers (such as, for example, Pluronic ^® ), • buffers, acids and bases (for example phosphates, carbonates, citric acid, acetic acid, hydrochloric acid, sodium hydroxide solution, ammonium carbonate, trometamol, triethanolamine), • isotonicity agents (for example glucose, sodium chloride), • adsorbents (for example highly-disperse silicas), • viscosity-increasing agents, gel formers, thickeners and/or binders (for example polyvinylpyrrolidone, methylcellulose, hydroxypropylmethylcellulose, hydroxypropylcellulose, carboxymethylcellulose-sodium, starch, carbomers, polyacrylic acids (such as, for example, Carbopol ^® ); alginates, gelatine), • disintegrants (for example modified starch, carboxymethylcellulose-sodium, sodium starch glycolate (such as, for example, Explotab ^® ), cross- linked polyvinylpyrrolidone, croscarmellose-sodium (such as, for example, AcDiSol ^® )), • flow regulators, lubricants, glidants and mould release agents (for example magnesium stearate, stearic acid, talc, highly-disperse silicas (such as, for example, Aerosil ^® )), • coating materials (for example sugar, shellac) and film formers for films or diffusion membranes which dissolve rapidly or in a modified manner (for example polyvinylpyrrolidones (such as, for example, Kollidon ^® ), polyvinyl alcohol, hydroxypropylmethylcellulose, hydroxypropylcellulose, ethylcellulose, hydroxypropylmethylcellulose phthalate, cellulose acetate, cellulose acetate phthalate, polyacrylates, polymethacrylates such as, for example, Eudragit ^® )), • capsule materials (for example gelatine, hydroxypropylmethylcellulose), • synthetic polymers (for example polylactides, polyglycolides, polyacrylates, polymethacrylates (such as, for example, Eudragit ^® ), polyvinylpyrrolidones (such as, for example, Kollidon ^® ), polyvinyl alcohols, polyvinyl acetates, polyethylene oxides, polyethylene glycols and their copolymers and blockcopolymers), • plasticizers (for example polyethylene glycols, propylene glycol, glycerol, triacetine, triacetyl citrate, dibutyl phthalate), • penetration enhancers, • stabilisers (for example antioxidants such as, for example, ascorbic acid, ascorbyl palmitate, sodium ascorbate, butylhydroxyanisole, butylhydroxytoluene, propyl gallate), • preservatives (for example parabens, sorbic acid, thiomersal, benzalkonium chloride, chlorhexidine acetate, sodium benzoate), • colourants (for example inorganic pigments such as, for example, iron oxides, titanium dioxide), • flavourings, sweeteners, flavour- and/or odour-masking agents. The present invention furthermore relates to a pharmaceutical composition which comprise at least one compound according to the invention, conventionally together with one or more pharmaceutically suitable excipient(s), and to their use according to the present invention. In accordance with another aspect, the present invention covers pharmaceutical combinations, in particular medicaments, comprising at least one compound of general formula (I) of the present invention and at least one or more further active ingredients, in particular for the treatment and/or prophylaxis of cancer. Particularly, the present invention covers a pharmaceutical combination, which comprises: • one or more first active ingredients, in particular compounds of general formula (I) as defined supra, and • one or more further active ingredients, in particular “(chemotherapeutic) anti- cancer agents”. The term “combination” in the present invention is used as known to persons skilled in the art, it being possible for said combination to be a fixed combination, a non-fixed combination or a kit-of-parts. A “fixed combination” in the present invention is used as known to persons skilled in the art and is defined as a combination wherein, for example, a first active ingredient, such as one or more compounds of general formula (I) of the present invention, and a further active ingredient are present together in one unit dosage or in one single entity. One example of a “fixed combination” is a pharmaceutical composition wherein a first active ingredient and a further active ingredient are present in admixture for simultaneous administration, such as in a formulation. Another example of a “fixed combination” is a pharmaceutical combination wherein a first active ingredient and a further active ingredient are present in one unit without being in admixture. A non-fixed combination or “kit-of-parts” in the present invention is used as known to persons skilled in the art and is defined as a combination wherein a first active ingredient and a further active ingredient are present in more than one unit. One example of a non- fixed combination or kit-of-parts is a combination wherein the first active ingredient and the further active ingredient are present separately. It is possible for the components of the non-fixed combination or kit-of-parts to be administered separately, sequentially, simultaneously, concurrently or chronologically staggered. The compounds of the present invention can be administered as the sole pharmaceutical agent or in combination with one or more other pharmaceutically active ingredients where the combination causes no unacceptable adverse effects. The present invention also covers such pharmaceutical combinations. For example, the compounds of the present invention can be combined with known “(chemotherapeutic) anti-cancer agents”. The term “(chemotherapeutic) anti-cancer agents” relates to any agent that reduces the survival or proliferation of a cancer cell, and includes but is not limited to 131I-chTNT, abarelix, abemaciclib, abiraterone, acalabrutinib, aclarubicin, adalimumab, ado-trastuzumab emtansine, afatinib, aflibercept, aldesleukin, alectinib, alemtuzumab, alendronic acid, alitretinoin, alpharadin, altretamine, amifostine, aminoglutethimide, hexyl aminolevulinate, amrubicin, amsacrine, anastrozole, ancestim, anethole dithiolethione, anetumab ravtansine, angiotensin II, antithrombin III, apalutamide, aprepitant, arcitumomab, arglabin, arsenic trioxide, asparaginase, atezolizumab, avelumab, axicabtagene ciloleucel, axitinib, azacitidine, basiliximab, belotecan, bendamustine, besilesomab, belinostat, bevacizumab, bexarotene, bicalutamide, bisantrene, bleomycin, blinatumomab, bortezomib, bosutinib, buserelin, brentuximab vedotin, brigatinib, busulfan, cabazitaxel, cabozantinib, calcitonine, calcium folinate, calcium levofolinate, capecitabine, capromab, carbamazepine carboplatin, carboquone, carfilzomib, carmofur, carmustine, catumaxomab, celecoxib, celmoleukin, cemiplimab, ceritinib, cetuximab, chlorambucil, chlormadinone, chlormethine, cidofovir, cinacalcet, cisplatin, cladribine, clodronic acid, clofarabine, cobimetinib, copanlisib, crisantaspase, crizotinib, cyclophosphamide, cyproterone, cytarabine, dacarbazine, dactinomycin, daratumumab, darbepoetin alfa, dabrafenib, dasatinib, daunorubicin, decitabine, degarelix, denileukin diftitox, denosumab, depreotide, deslorelin, dianhydrogalactitol, dexrazoxane, dibrospidium chloride, dianhydrogalactitol, diclofenac, dinutuximab, docetaxel, dolasetron, doxifluridine, doxorubicin, doxorubicin + estrone, dronabinol, durvalumab, eculizumab, edrecolomab, elliptinium acetate, elotuzumab, eltrombopag, enasidenib, endostatin, enocitabine, enzalutamide, epirubicin, epitiostanol, epoetin alfa, epoetin beta, epoetin zeta, eptaplatin, eribulin, erlotinib, esomeprazole, estradiol, estramustine, ethinylestradiol, etoposide, everolimus, exemestane, fadrozole, fentanyl, filgrastim, fluoxymesterone, floxuridine, fludarabine, fluorouracil, flutamide, folinic acid, formestane, fosaprepitant, fotemustine, fulvestrant, gadobutrol, gadoteridol, gadoteric acid meglumine, gadoversetamide, gadoxetic acid, gallium nitrate, ganirelix, gefitinib, gemcitabine, gemtuzumab, Glucarpidase, glutoxim, GM-CSF, goserelin, granisetron, granulocyte colony stimulating factor, histamine dihydrochloride, histrelin, hydroxycarbamide, I-125 seeds, lansoprazole, ibandronic acid, ibritumomab tiuxetan, ibrutinib, idarubicin, ifosfamide, imatinib, imiquimod, improsulfan, indisetron, incadronic acid, ingenol mebutate, inotuzumab ozogamicin, interferon alfa, interferon beta, interferon gamma, iobitridol, iobenguane (123I), iomeprol, ipilimumab, irinotecan, Itraconazole, ixabepilone, ixazomib, lanreotide, lansoprazole, lapatinib, Iasocholine, lenalidomide, lenvatinib, lenograstim, lentinan, letrozole, leuprorelin, levamisole, levonorgestrel, levothyroxine sodium, lisuride, lobaplatin, lomustine, lonidamine, lutetium Lu 177 dotatate, masoprocol, medroxyprogesterone, megestrol, melarsoprol, melphalan, mepitiostane, mercaptopurine, mesna, methadone, methotrexate, methoxsalen, methylaminolevulinate, methylprednisolone, methyltestosterone, metirosine, midostaurin, mifamurtide, miltefosine, miriplatin, mitobronitol, mitoguazone, mitolactol, mitomycin, mitotane, mitoxantrone, mogamulizumab, molgramostim, mopidamol, morphine hydrochloride, morphine sulfate, mvasi, nabilone, nabiximols, nafarelin, naloxone + pentazocine, naltrexone, nartograstim, necitumumab, nedaplatin, nelarabine, neratinib, neridronic acid, netupitant/palonosetron, nivolumab, pentetreotide, nilotinib, nilutamide, nimorazole, nimotuzumab, nimustine, nintedanib, niraparib, nitracrine, nivolumab, obinutuzumab, octreotide, ofatumumab, olaparib, olaratumab, omacetaxine mepesuccinate, omeprazole, ondansetron, oprelvekin, orgotein, orilotimod, osimertinib, oxaliplatin, oxycodone, oxymetholone, ozogamicine, p53 gene therapy, paclitaxel, palbociclib, palifermin, palladium-103 seed, palonosetron, pamidronic acid, panitumumab, panobinostat, pantoprazole, pazopanib, pegaspargase, PEG-epoetin beta (methoxy PEG-epoetin beta), pembrolizumab, pegfilgrastim, peginterferon alfa-2b, pembrolizumab, pemetrexed, pentazocine, pentostatin, peplomycin, Perflubutane, perfosfamide, Pertuzumab, picibanil, pilocarpine, pirarubicin, pixantrone, plerixafor, plicamycin, poliglusam, polyestradiol phosphate, polyvinylpyrrolidone + sodium hyaluronate, polysaccharide-K, pomalidomide, ponatinib, porfimer sodium, pralatrexate, prednimustine, prednisone, procarbazine, procodazole, propranolol, quinagolide, rabeprazole, racotumomab, radium-223 chloride, radotinib, raloxifene, raltitrexed, ramosetron, ramucirumab, ranimustine, rasburicase, razoxane, refametinib, regorafenib, ribociclib, risedronic acid, rhenium-186 etidronate, rituximab, rolapitant, romidepsin, romiplostim, romurtide, rucaparib, samarium (153Sm) lexidronam, sargramostim, sarilumab, satumomab, secretin, siltuximab, sipuleucel-T, sizofiran, sobuzoxane, sodium glycididazole, sonidegib, sorafenib, stanozolol, streptozocin, sunitinib, talaporfin, talimogene laherparepvec, tamibarotene, tamoxifen, tapentadol, tasonermin, teceleukin, technetium (99mTc) nofetumomab merpentan, 99mTc-HYNIC-[Tyr3]-octreotide, tegafur, tegafur + gimeracil + oteracil, temoporfin, temozolomide, temsirolimus, teniposide, testosterone, tetrofosmin, thalidomide, thiotepa, thymalfasin, thyrotropin alfa, tioguanine, tisagenlecleucel, tislelizumab, tocilizumab, topotecan, toremifene, tositumomab, trabectedin, trametinib, tramadol, trastuzumab, trastuzumab emtansine, treosulfan, tretinoin, trifluridine + tipiracil, trilostane, triptorelin, trametinib, trofosfamide, thrombopoietin, tryptophan, ubenimex, valatinib, valrubicin, vandetanib, vapreotide, vemurafenib, vinblastine, vincristine, vindesine, vinflunine, vinorelbine, vismodegib, vorinostat, vorozole, yttrium-90 glass microspheres, zinostatin, zinostatin stimalamer, zoledronic acid, and zorubicin. EXPERIMENTAL SECTION NMR peak forms are stated as they appear in the spectra, possible higher order effects have not been considered. The ¹ H-NMR data of selected compounds are listed in the form of ¹ H-NMR peaklists. Therein, for each signal peak the δ value in ppm is given, followed by the signal intensity, reported in round brackets. The δ value-signal intensity pairs from different peaks are separated by commas. Therefore, a peaklist is described by the general form: δ ₁ (intensity ₁ ), δ ₂ (intensity ₂ ), ... , δ _i (intensity _i ), ... , δ _n (intensity _n ). The intensity of a sharp signal correlates with the height (in cm) of the signal in a printed NMR spectrum. When compared with other signals, this data can be correlated to the real ratios of the signal intensities. In the case of broad signals, more than one peak, or the center of the signal along with their relative intensity, compared to the most intense signal displayed in the spectrum, are shown. A ¹ H-NMR peaklist is similar to a classical ¹ H-NMR readout, and thus usually contains all the peaks listed in a classical NMR interpretation. Moreover, similar to classical ¹ H-NMR printouts, peaklists can show solvent signals, signals derived from stereoisomers of the particular target compound, peaks of impurities, ¹³ C satellite peaks, and/or spinning sidebands. The peaks of stereoisomers, and/or peaks of impurities are typically displayed with a lower intensity compared to the peaks of the target compound (e.g., with a purity of >90%). Such stereoisomers and/or impurities may be typical for the particular manufacturing process, and therefore their peaks may help to identify a reproduction of the manufacturing process on the basis of "by-product fingerprints". An expert who calculates the peaks of the target compound by known methods (MestReC, ACD simulation, or by use of empirically evaluated expectation values), can isolate the peaks of the target compound as required, optionally using additional intensity filters. Such an operation would be similar to peak-picking in classical ¹ H-NMR interpretation. A detailed description of the reporting of NMR data in the form of peaklists can be found in the publication "Citation of NMR Peaklist Data within Patent Applications" (cf. http://www.researchdisclosure.com/searching-disclosures, Research Disclosure Database Number 605005, 2014, 01 Aug 2014). In the peak picking routine, as described in the Research Disclosure Database Number 605005, the parameter "MinimumHeight" can be adjusted between 1% and 4%. However, depending on the chemical structure and/or depending on the concentration of the measured compound it may be reasonable to set the parameter "MinimumHeight" <1%. Chemical names were generated using the ACD/Name software from ACD/Labs. In some cases generally accepted names of commercially available reagents were used in place of ACD/Name generated names. The following table 1 lists the abbreviations used in this paragraph and in the Examples section as far as they are not explained within the text body. Other abbreviations have their meanings customary per se to the skilled person. Table 1: Abbreviations The following table lists the abbreviations used herein. Aq. Aqueous Dba Dibenzylideneacetone DCM Dichloromethane DIPEA N,N-Diisopropylethylamine DMF N,N-Dimethylformamide DMSO Dimethylsulfoxide Eq Equivalent HATU (1-[Bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyr idinium-3- oxide hexafluorophosphate HCl Hydrochloric acid HPLC High Performance Liquid Chromatography KOAc Potassium acetate LC Liquid chromatography LiOH Lithium hydroxide M Molar MeOH Methanol MS Mass spectrometry N Normal NaHCO ₃ Sodium bicarbonate NaOH Sodium hydroxide Na ₂ SO ₄ Sodium sulfate NMP N-Methylpyrrolidone NMR Nuclear magnetic resonance Sat. saturated TEA Triethylamine TFA Trifluoroacetic acid THF Tetrahydrofuran UPLC Ultra Performance Liquid Chromatography The various aspects of the invention described in this application are illustrated by the following examples which are not meant to limit the invention in any way. The example testing experiments described herein serve to illustrate the present invention and the invention is not limited to the examples given. EXPERIMENTAL SECTION - GENERAL PART All reagents, for which the synthesis is not described in the experimental part, are either commercially available, or are known compounds or may be formed from known compounds by known methods by a person skilled in the art. The compounds and intermediates produced according to the methods of the invention may require purification. Purification of organic compounds is well known to the person skilled in the art and there may be several ways of purifying the same compound. In some cases, no purification may be necessary. In some cases, the compounds may be purified by crystallization. In some cases, impurities may be stirred out using a suitable solvent. In some cases, the compounds may be purified by chromatography, particularly flash column chromatography, using for example prepacked silica gel cartridges, e.g. Biotage SNAP cartidges KP-Sil ^® or KP-NH ^® in combination with a Biotage autopurifier system (SP4 ^® or Isolera Four ^® ) and eluents such as gradients of hexane/ethyl acetate or DCM/methanol. In some cases, the compounds may be purified by preparative HPLC using for example a Waters autopurifier equipped with a diode array detector and/or on- line electrospray ionization mass spectrometer in combination with a suitable prepacked reverse phase column and eluents such as gradients of water and acetonitrile which may contain additives such as trifluoroacetic acid, formic acid or aqueous ammonia. In some cases, purification methods as described above can provide those compounds of the present invention which possess a sufficiently basic or acidic functionality in the form of a salt, such as, in the case of a compound of the present invention which is sufficiently basic, a trifluoroacetate or formate salt for example, or, in the case of a compound of the present invention which is sufficiently acidic, an ammonium salt for example. A salt of this type can either be transformed into its free base or free acid form, respectively, by various methods known to the person skilled in the art, or be used as salts in subsequent biological assays. It is to be understood that the specific form (e.g. salt, free base etc.) of a compound of the present invention as isolated and as described herein is not necessarily the only form in which said compound can be applied to a biological assay in order to quantify the specific biological activity. Preparative HPLC Method 1: Instrument: Waters Autopurificationsystem; Column: Waters XBrigde C185µ 100x30mm; Eluent A: water + 0.1 Vol-% formic acid (99%), Eluent B: acetonitrile, DAD scan: 210-400 nm Method 2: Instrument: Waters Autopurificationsystem; column: Waters XBrigde C185µ 100x30mm; Eluent A: water + 0.2 Vol-% aqueous ammonia (32%), Eluent B: acetonitrile, DAD scan: 210-400 nm Method 3: Instrument: pump: Labomatic HD-5000 or HD-3000, head HDK 280, lowpressure gradient module ND-B1000; manual injection valve: Rheodyne 3725i038; detector: Knauer Azura UVD 2.15; collector: Labomatic Labocol Vario-4000; column: Chromatorex RP C-1810 µm, 125x30mm; eluent acidic/basic; gradient A-F; UV-detection: 210-254 nm. Eluent acidic: solvent A: water + 0.1 vol-% formic acid, solvent B: acetonitrile Eluent basic: solvent A: water + 0.2 vol-% ammonia (32%), solvent B: acetonitrile Gradient A: 0.00-2.50 min 30% B (150 ml/min), 2.50–8.00 min 30-70% B (150 ml/min), 8.00-8.10 min 70-100% B (150 ml/min), 8.10-10.00 min 100% B (150 ml/min) Gradient B: 0.00-0.50 min 40% B (150 ml/min), 0.50–6.00 min 40-70% B (150 ml/min), 6.00-6.05 min 70-100% B (150 ml/min), 6.05-8.00 min 100% B (150 ml/min) Gradient C: 0.00-5.00 min 15% B (60 ml/min), 5.00–17.00 min 15-55% B (60 ml/min), 17.00-17.10 min 55-100% B (60 ml/min), 17.10-20.00 min 100% B (60 ml/min) Gradient D: 0.00-5.00 min 30% B (60 ml/min), 5.00–17.00 min 30-70% B (60 ml/min), 17.00-17.10 min 70-100% B (60 ml/min), 17.10-20.00 min 100% B (60 ml/min) Analytical LCMS Method 1: Instrument: Waters Acquity UPLCMS SingleQuad; Column: Acquity UPLC BEH C181.7 µm, 50x2.1mm; eluent A: water + 0.1 vol % formic acid (99%), eluent B: acetonitrile; gradient: 0-1.6 min 1-99% B, 1.6-2.0 min 99% B; flow 0.8 ml/min; temperature: 60 °C; DAD scan: 210-400 nm. Method 2: Instrument: Waters Acquity UPLCMS SingleQuad; Column: Acquity UPLC BEH C181.7 µm, 50x2.1mm; eluent A: water + 0.2 vol % aqueous ammonia (32%), eluent B: acetonitrile; gradient: 0-1.6 min 1-99% B, 1.6-2.0 min 99% B; flow 0.8 ml/min; temperature: 60 °C; DAD scan: 210-400 nm. Method 3: Instrument: Waters Acquity UPLCMS SingleQuad; Column: Acquity UPLC BEH C181.7 50x2.1mm; eluent A: water + 0.1 vol % formic acid (99%), eluent B: acetonitrile; gradient: 0-1.6 min 1-99% B, 1.6-2.0 min 99% B; flow 0.8 ml/min; temperature: 60 °C; DAD scan: 210-400 nm Method 4: Instrument: Waters Acquity UPLCMS SingleQuad; Colum: Acquity UPLC BEH C181.7 50x2.1mm; eluent A: water + 0.2 vol % aqueous ammonia (32%), eluent B: acetonitrile; gradient: 0-1.6 min 1-99% B, 1.6-2.0 min 99% B; flow 0.8 ml/min; temperature: 60 °C; DAD scan: 210-400 nm Method 5: Instrument: Agilent 1290 UPLCMS 6230 TOF; column: BEH C 181.7 µm, 50x2.1mm; Eluent A: water + 0.05 % formic acid (99%); Eluent B: acetonitrile + 0.05 % formic acid (99%); gradient: 0-1.72-90% B, 1.7-2.090% B; flow 1.2 ml/min; temperature: 60°C; DAD scan: 190-400 nm. EXPERIMENTAL SECTION - INTERMEDIATES 1. Intermediates for compounds of general formula (1): Intermediate 1.1a: Methyl 5-bromo-6-[4-(trifluoromethyl)phenoxy]pyridine-3- carboxylate 4-(Trifluoromethyl)phenol (707 mg, 4.36 mmol), methyl 5-bromo-6-chloro-pyridine-3- carboxylate (1040 mg, 4.15 mmol), potassium carbonate (2.87 g, 20.76 mmol) in acetonitrile (10 ml) were heated at 80°C for 17 hours. The solid material was filtered of and the filtrate concentrated in vacuo. The crude product was purified by column chromatography (silica gel, ethyl acetate/ n-hexane gradient) to give 800 mg (49 % yield) of the target compound. 1H NMR (DMSO-d ₆ ) δ: 8.63 (d, J=2.0 Hz, 1H), 8.58 (d, J=2.0 Hz, 1H), 7.85 (d, J=8.4 Hz, 2H), 7.48 (d, J=8.4 Hz, 2H), 3.87 (s, 3H). LC-MS (method 5): Rt = 1.45 min. MS (ESI+): m/z = 376.1 [M+H] ⁺ . Intermediates 1.1b and 1.1c were prepared in analogy to intermediate 1.1a. Intermediate 1.2: 5-Bromo-6-[4-(trifluoromethyl)phenoxy]pyridine-3-carboxylic acid A mixture of Intermediate 1a (21 g, 55.83 mmol), lithium hydroxide (83.75 mmol, 84 ml, 1M in water) in methanol (290 ml) was stirred at room temperature overnight. Methanol was removed under reduced pressure, the pH-value adjusted to pH: 5 by addition of 2N HCl solution and 300 ml water added. A white solid formed which was removed by filtration and dried under vacuum to give 18.0 g (89 % yield) of the target compound which was used without further purification. ¹ H NMR (DMSO-d ₆ ) δ: 13.19-13.92 (m, 1H), 8.60 (d, J=2.0 Hz, 1H), 8.54 (d, J=2.0 Hz, 1H), 7.84 (d, J=8.6 Hz, 2H), 7.47 (d, J=8.4 Hz, 2H). Intermediate 1.3a: 5-Bromo-N-[(1R)-2-hydroxy-1-methyl-ethyl]-6-[4- (trifluoromethyl)phenoxy]pyridine-3-carboxamide A mixture of Intermediate 1.2 (4.62 g, 12.76 mmol), (2R)-2-aminopropan-1-ol (1.01g, 13.4 mmol), HATU (5.09 g, 13.39 mmol), DIPEA (3.30, 25.52 mmol) in DMF (40 ml) was stirred at room temperature overnight. 200 ml Water were added. A white solid formed which was removed by filtration, washed with water (10 ml, 3x) and dried under vacuum to give 4.5 g (80 % yield) of the target compound which was used without further purification. ¹ H NMR (DMSO-d ₆ ) δ: 8.65 (d, J=2.0 Hz, 1H), 8.54 (d, J=2.3 Hz, 1H), 8.32 (d, J=7.9 Hz, 1H), 7.83 (d, J=8.6 Hz, 2H), 7.43 (d, J=8.4 Hz, 2H), 4.75 (t, J=5.8 Hz, 1H), 3.94-4.06 (m, 1H), 3.40-3.48 (m, 1H), 3.30-3.38 (m, 1H, under H2O peak), 1.12 (d, J=6.6 Hz, 3H). LC-MS (method 5): R _t = 1.15 min. MS (ESI+): m/z = 419.1 [M+H] ⁺ . Intermediate 1.4: (5-{[(2R)-1-Hydroxypropan-2-yl]carbamoyl}-2-[4-(trifluoromet hyl) phenoxy]pyridin-3-yl)boronic acid A mixture of Intermediate 1.3a (1.91 g, 4.56 mmol), bis(pinacolato)diboron (2.31g, 9.11 mmol), potassium acetate (1.56 g, 15.95 mmol), [1,1´-Bis(diphenylphosphino)ferrocene] dichloropalladium(II) (333 mg, 456 µmol; CAS-RN:[72287-26-4]) in dioxane (60 ml) was stirred at 80°C for 2 hours. Dichloromethane and water were added, and the phases separated. The aqueous phase was extracted with water (3x) and the combined organic phases were concentrated under reduced pressure. The crude material was purified by column chromatography (silica gel, ethyl acetate/ n-hexane gradient) to give 1.3 g (74 % yield) of the title compound. LC-MS (method 1): R _t = 0,92 min. MS (ESI+): m/z = 385.1 [M+H] ⁺ . Intermediate 1.5: [5-Methoxycarbonyl-2-[4-(trifluoromethyl)phenoxy]-3- pyridyl]boronic acid A mixture of Intermediate 1.1a (1.97 g, 5.24 mmol), bis(pinacolato)diboron (2.66g, 10.47 mmol), potassium acetate (1.8 g, 18.33 mmol), [1,1´- Bis(diphenylphosphino)ferrocene]dichloropalladium(II) (383 mg, 0.52 mmol; CAS- RN:[72287-26-4]) in dioxane (69 ml) was stirred at 70°C for 18 hours. Dichloromethane and water were added, and the phases separated. The aqueous phase was extracted with water (3x) and the combined organic phases were concentrated under reduced pressure. The crude material was purified by column chromatography (silica gel, ethyl acetate/ n-hexane gradient) to give 2.8 g (78 % yield) of the title compound. LC-MS (method 1): R _t = 1,16 min. MS (ESI+): m/z = 342.0 [M+H] ⁺ . Intermediate 1.6a: Methyl 5-(1-methylpyrazol-3-yl)-6-[4-(trifluoromethyl)phenoxy] pyridine-3-carboxylate Route 1: Intermediate 1.1a (1.54 g, 4.094 mmol), 1-methyl-3-(4,4,5,5-tetramethyl-1,3,2- dioxaborolan-2-yl)-1H-pyrazole (894 mg, 4.299 mmol; CAS-RN: 1020174-04-2), potassium carbonate (4.09 ml, 2M in water), were suspended in THF (30.8 ml), [1,1´- Bis(diphenylphosphino)ferrocene]dichloropalladium(II) (149.8 mg, 204.7 µmol; CAS-RN: 72287-26-4) was added and the mixture was heated at 60°C overnight. Water and dichloromethane were added, and the phases separated. The aqueous phase was extracted three more times with dichloromethane. The organic phases were then combined and concentrated in vacuo. The crude product was purified by column chromatography silica gel, ethyl acetate/ n-hexane gradient) to give 1.2 g (78 % yield) of the title compound. LC-MS (method 2): R _t = 1.37 min. MS (ESI+): m/z = 378.6 [M+H] ⁺ . Route 2: Intermediate 1.5 (4.95 g, 14.513 mmol), 3-bromo-1-methyl-1H-pyrazole (2.57 g, 15.965 mmol), potassium carbonate (43.5 ml, 1M in water), were suspended in THF (100 ml), [1,1´-Bis(diphenylphosphino)ferrocene]dichloropalladium(II) (1.593 g, 2.177 mmol; CAS-RN: 72287-26-4) was added and the mixture was heated at 70°C for 21 hours. Water and ethyl acetate were added, and the phases separated. The aqueous phase was extracted two more times with ethyl acetate. The organic phases were then combined dried over water-repellent filter, filtrated and the filtrate concentrated in vacuo. The crude product was purified by column chromatography (silica gel, ethyl acetate/ n-hexane gradient) to give 2.3 g (42 % yield) of the title compound. LC-MS (method 2): R _t = 1.37 min. MS (ESI+): m/z = 378.7 [M+H] ⁺ . Intermediates 1.6b and 1.6c were prepared in analogy to intermediate 1.6a.

Intermediate 1.7a: 5-(1-Methylpyrazol-3-yl)-6-[4-(trifluoromethyl)phenoxy]pyrid ine- 3-carboxylic acid A mixture of Intermediate 1.6a (2.297 g, 6.087 mmol), lithium hydroxide (12.174 mmol, 12.17 ml, 1M in water) in methanol (32.8 ml) was stirred at room temperature until complete conversion. Methanol was removed under reduced pressure, 2N aqueous HCl solution added and the resulting suspension filtrated to give 1.96 g (89 % yield) of the title compound which was used without further purification in the next step. 1H NMR (DMSO-d ₆ ) δ: 13.35 (br s, 1H), 8.85 (d, J=2.3 Hz, 1H), 8.58 (d, J=2.3 Hz, 1H), 7.79-7.86 (m, 3H), 7.46 (d, J=8.4 Hz, 2H), 6.84 (d, J=2.3 Hz, 1H), 3.95 (s, 3H). LC-MS (method 5): R _t = 1.14 min. MS (ESI+): m/z = 364.2 [M+H] ⁺ . Intermediates 1.7b and 1.7c were prepared in analogy to intermediate 1.7a.

Intermediate 1.8: Methyl 6-hydroxy-5-(1-methyl-1H-pyrazol-3-yl)pyridine-3- carboxylate To a suspension of 1000 mg (4.31 mmol) methyl 5-bromo-6-hydroxypyridine-3- carboxylate, 897 mg (4.31 mmol) 1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2- yl)-1H-pyrazole, 4.31 ml potassium carbonate (8.62 mmol, 2M in water) in THF, 315 mg Bis(diphenylphosphino)ferrocene]dichloropalladium (431 µmol) was added and the mixture was heated under argon at 60°C for 3 hours. Subsequently, another 200 mg 1- methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-py razole, 4.31 ml potassium carbonate (2M in water) and 315 mg Bis(diphenylphosphino)ferrocene]dichloropalladium were added and the mixture stirred overnight. The reaction mixture was treated with water, ethyl acetate was added, the phases were separated, and the aqueous layer was extracted 2 more times with ethyl acetate. The organic phases were combined and evaporated to dryness under vacuo. The crude product was purified by column chromatography (silica gel, ethyl acetate/ n-hexane gradient) to give 472 mg of the title compound which still contains unreacted 5-bromo-6-hydroxypyridine-3-carboxylate. This material was used in the next step. Intermediate 1.9: Methyl 6-chloro-5-(1-methyl-1H-pyrazol-3-yl)pyridine-3- carboxylate A mixture of 840 mg intermediate 8 (containing 5-bromo-6-hydroxypyridine-3-carboxylate as impurity) and 10 ml phosphorus oxychloride was stirred at 115°C for 3 hours. The reaction mixture was slowly added to ice water and extracted three times with DCM. The combined organic layers were evaporated to dryness to give 657 mg of the title compound which also contains methyl 5-bromo-6-chloro-pyridine-3-carboxylate as impurity. This material was used without further purification in the next step. Intermediate 1.10: 6-Chloro-5-(1-methyl-1H-pyrazol-3-yl)pyridine-3-carboxylic acid A mixture of 657 mg intermediate 1.9 (containing methyl 5-bromo-6-chloro-pyridine-3- carboxylate as impurity), 3.92 ml aqueous LiOH-solution (1N) in 14 ml MeOH was stirred at room temperature for 3 hours. The solvent was removed under reduced pressure. Aqueous HCl-solution (2N) was added to adjust the pH to pH: 5.10 ml water were added, the white solid removed by filtration and dried under vacuo to give 500 mg of the title compound which also contains 5-bromo-6-chloro-pyridine-3-carboxylic acid as impurity. This material was used without further purification in the next step. Intermediate 1.11: 6-Chloro-N-[(2R)-1-hydroxypropan-2-yl]-5-(1-methyl-1H-pyrazo l- 3-yl)pyridine-3-carboxamide

A mixture of 500 mg intermediate 1.10 (containing 5-bromo-6-chloro-pyridine-3- carboxylic acid as impurity), 237 mg (2R)-2-aminopropan-1-ol, 880 mg HATU and 0.73 ml DIPEA in 2 ml DMSO was stirred at room temperature overnight. The mixture was treated with water and ethyl acetate and extracted three times with ethyl acetate. The combined organics layers were evaporated to dryness under vacuo and purified by column chromatography (silica gel, ethyl acetate/ n-hexane gradient) to give 577 mg of the title compound which also contains 5-bromo-6-chloro-N-[(2R)-1-hydroxypropan-2-yl]- pyridine-3-carboxamide as impurity. This material was used in the following nucleophilic aromatic substitution step. Intermediate 1.12: 5-Bromo-6-chloro-N-[(2R)-1-hydroxypropan-2-yl]pyridine-3- carboxamide A mixture of 1.51 g 5-bromo-6-chloropyridine-3-carboxylic acid (6.39 mmol), 0.75 ml (2R)-2-aminopropan-1-ol (9.6 mmol), 2.67 g HATU (7.02 mmol), 2.2 ml DIPEA (13 mmol) in 2 ml DMSO was stirred at room temperature overnight. The reaction mixture was treated with water and extracted 3 times with DCM. The organic layers were combined, dried over a water repellent filter and evaporated under vacuo. The crude material was purified by column chromatography (silica gel, ethyl acetate/ n-hexane gradient) to give 1.475 g of the title compound. LC-MS (method 2):R _t = 0.78 min. MS (ESI+): m/z = 295.6 [M+H] ⁺ . Intermediate 1.3b: 5-Bromo-6-(4-cyclopropylphenoxy)-N-[(2R)-1-hydroxypropan-2- yl]pyridine-3-carboxamide A mixture of 145 mg intermediate 12 (494 µmol), 86 mg 4-cyclopropylphenol (642 µmol), 137 mg potassium carbonate (988 µmol) in 3 ml acetonitrile was stirred at 85°C overnight. Another 0.5 eq. of 4-cyclopropylphenol was added and the mixture stirred overnight at 85°C again. The reaction mixture was treated with water and extracted three times with DCM. The organic phases were combined, dried over a water repelent filter and evaporated to dryness. The crude product was purified by preparative HPLC (method 3, basic gradient A) to give 86 mg (45% yield) of the title compound. LC-MS (method 2): R _t = 1.20 min. MS (ESI+): m/z = 393.2 [M+H] ⁺ . Intermediates 1.3c-1.3g were prepared in analogy to intermediate 1.3b. Intermediate 1.13a: Methyl 5-bromo-6-[4-(trifluoromethyl)phenoxy]pyridine-3-carboxylate 4-(Trifluoromethyl)phenol (707 mg, 4.36 mmol), methyl 5-bromo-6-chloro-pyridine-3- carboxylate (1040 mg, 4.15 mmol), potassium carbonate (2.87 g, 20.76 mmol) in acetonitrile (10 ml) were heated at 80°C for 17 hours. The solid material was filtered of and the filtrate concentrated in vacuo. The crude product was purified by column chromatography (silica gel, ethyl acetate/ n-hexane gradient) to give 800 mg (49 % yield) of the target compound. 1H NMR (DMSO-d ₆ ) δ: 8.63 (d, J=2.0 Hz, 1H), 8.58 (d, J=2.0 Hz, 1H), 7.85 (d, J=8.4 Hz, 2H), 7.48 (d, J=8.4 Hz, 2H), 3.87 (s, 3H). LC-MS (Method 1): Rt = 1.45 min. MS (ESI+): m/z = 376.1 [M+H] ⁺ , 100%. The following intermediate was prepared in analogy to Intermediate 1.13a. Intermediate 1.14a:ethyl 5-(3-fluorophenyl)-6-[4-(trifluoromethyl)phenoxy]pyridine-3- carboxylate A mixture of Intermediate 1.13a (4.80g, 12.8 mmol), (3-fluorophenyl)boronic acid (3.57 g, 25.5 mmol; CAS-RN:[768-35-4]), [1,1'-Bis(diphenylphosphino)ferrocene]palladium(II) dichloride (2.08 g, 2.55 mmol), aq. K ₂ CO ₃ - solution (2M, 32 ml) in 40 ml THF was stirred under reflux until complete conversion. The solvent was removed under reduced pressure and the remaining crude product purified by column chromatography (silica gel, ethyl acetate/ n-hexane gradient) to give 3.05 g (61 % yield) of the title compound. 1H NMR (400 MHz, DMSO-d ₆ ) δ ppm 3.88 (s, 3 H) 7.26 - 7.34 (m, 1 H) 7.49 (d, J=8.36 Hz, 2 H) 7.54 - 7.68 (m, 3 H) 7.78 - 7.86 (m, 2 H) 8.35 - 8.38 (m, 1 H) 8.64 - 8.74 (m, 1 H). LC-MS (Method 1): Rt = 1.48 min. MS (ESI+): m/z = 391.9 [M+H] ⁺ , 100%. The following intermediate was prepared in analogy to Intermediate 1.14a. Intermediate 1.15a:5-(3-Fluorophenyl)-6-[4-(trifluoromethyl)phenoxy]pyrid ine-3- carboxylic acid Intermediate 1.14a (3.05 g, 7.79 mmol) was dissolved in 46 ml acetonitrile and 3 eq. aq. LiOH-solution (1M, 23 ml) were added and the reaction mixture stirred at r.t. until complete conversion. The pH-value was adjusted with 1M aq. HCl-solution to pH: 3, the mixture extracted with ethyl acetate, the combined organic layers dried over Na ₂ SO ₄ and evaporated under reduced pressure to give 2.64 g (90% yield) of the title compound. ¹ H NMR (400 MHz, DMSO-d ₆ ) δ ppm 7.26 - 7.33 (m, 1 H) 7.48 (d, J=8.36 Hz, 2 H) 7.52 - 7.66 (m, 3 H) 7.82 (d, J=8.36 Hz, 2 H) 8.33 (d, J=2.28 Hz, 1 H) 8.66 (d, J=2.28 Hz, 1 H) 13.00 - 13.71 (m, 1 H). LC-MS (Method 1): Rt = 1.32 min. MS (ESI+): m/z = 378.1 [M+H] ⁺ , 100%. Intermediate 1.15b:5-(3-Fluorophenyl)-6-[3-(trifluoromethyl)phenoxy]pyrid ine-3- carboxylic acid Intermediate 1.14b (1.90 g, 4.86 mmol) was dissolved in 10 ml ethanol, 3 eq. aq. NaOH- solution (2M, 7.3 ml) were added, and the reaction mixture stirred at r.t. until complete conversion. The pH-value was adjusted with 1M aq. HCl-solution to pH: 5 and the precipitating solid filtered off to give 1.76 g (96% yield) of the title compound. 1H NMR (DMSO-d6) δ: 13.37 (br s, 1H), 8.64 (d, J=2.3 Hz, 1H), 8.31 (d, J=2.3 Hz, 1H), 7.49-7.80 (m, 7H), 7.22-7.36 (m, 1H). LC-MS (Method 1): Rt = 1.36 min. MS (ESI+): m/z = 378.1 [M+H] ⁺ , 100%. Intermediate 1.15c:5-Bromo-6-[4-(trifluoromethyl)phenoxy]pyridine-3-carbo xylic acid Intermediate 1.13a (21.0 g, 55.8 mmol) was dissolved in 290 ml methanol, 1.5 eq. aq. LiOH-solution (1M, 84 ml) were added, and the reaction mixture stirred at r.t. until complete conversion. The pH-value was adjusted with 2N aq. HCl-solution to pH: 5. To this, 300 ml water were added, and the precipitating white solid filtered off to give 18.0 g (89% yield) of the title compound which was used without further purification in the next step. ¹ H NMR (400 MHz, DMSO-d ₆ ) δ ppm 7.47 (d, J=8.36 Hz, 2 H) 7.84 (d, J=8.62 Hz, 2 H) 8.54 (d, J=2.03 Hz, 1 H) 8.60 (d, J=2.03 Hz, 1 H) 13.38 - 13.73 (br s, 1 H). LC-MS (Method 3): Rt = 0.70 min. MS (ESI+): m/z = 364.0 [M+H] ⁺ , 84%. Intermediate 1.16: 5-Bromo-N-[(2R)-1-hydroxypropan-2-yl]-6-[4- (trifluoromethyl)phenoxy] pyridine-3-carboxamide H A mixture of Intermediate 1.15c (4.62 g, 12.8 mmol), (2R)-2-aminopropan-1-ol (1.0 ml, 13 mmol; CAS-RN:[35320-23-1]), DIPEA (4.4 ml, 26 mmol; CAS-RN:[7087-68-5]), HATU (5.09 g, 13.4 mmol; CAS-RN:[148893-10-1]) in 40 ml DMF was stirred at r.t. until complete conversion. To this, 200 ml water were added, and the white precipitate filtered off. The white solid was washed 3-times with 10 ml water and dried in vacuo give 4.50 g (80% yield) of the title compound. ¹ H NMR (DMSO-d ₆ ) δ: 8.65 (d, J=2.0 Hz, 1H), 8.54 (d, J=2.3 Hz, 1H), 8.32 (d, J=7.9 Hz, 1H), 7.83 (d, J=8.6 Hz, 2H), 7.43 (d, J=8.4 Hz, 2H), 4.75 (t, J=5.8 Hz, 1H), 3.94-4.06 (m, 1H), 3.40-3.48 (m, 1H), 3.30-3.38 (m, 1H, under H2O peak), 1.12 (d, J=6.6 Hz, 3H). LC-MS (Method 1): Rt = 1.15 min. MS (ESI+): m/z = 419.1 [M+H] ⁺ , 100%. Intermediate 1.17: Methyl 6-chloro-5-(3-fluorophenyl)pyridine-3-carboxylate A mixture of methyl 5-bromo-6-chloropyridine-3-carboxylate (2.47 g, 9.86 mmol; CAS- RN:[78686-77-8]), 3-fluorophenyl)boronic acid (1.38 g, 9.86 mmol; CAS-RN:[768-35-4]), 0.1 eq. [1,1'-Bis(diphenylphosphino)ferrocene] palladium(II) dichloride (805 mg, 986 µmol; CAS-RN:[72287-26-4]), 2.0 eq. aq. K ₂ CO ₃ - solution (2M, 9.9 ml) in 31 ml THF was stirred at 60°C overnight. Water was added and the reaction mixture extracted with ethyl acetate. The phases were separated and the aqueous extracted two more times with ethyl acetate. The combined organic phases were dried with Na ₂ SO ₄ , filtrated and the filtrate concentrated in vacuo. The crude product was purified by column chromatograph over silica gel (n-hexane/ ethyl acetate gradient) to give 1.5 g (57 % yield) of the title compound. LC-MS (Method 2): Rt = 1.27 min. MS (ESI+): m/z = 266.1 [M+H] ⁺ , 88%. Intermediate 1.18: 6-Chloro-5-(3-fluorophenyl)pyridine-3-carboxylic acid A mixture of methyl 6-chloro-5-(3-fluorophenyl)pyridine-3-carboxylate (1.50 g, 5.65 mmol), 2.0 eq. aq. LiOH-solution (1M, 11.3 ml) in 29 ml acetonitrile was stirred at r.t. overnight.10 ml aq. HCl- solution (2 N) were added. A white solid precipitated which was filtered off and dried to give 1.30 g (94 % yield) of the title compound which was used in the next step without further purification. LC-MS (Method 2): Rt = 1.06 min. MS (ESI+): m/z = 252.1 [M+H] ⁺ , 74%. Intermediate 1.19: 6-Chloro-5-(3-fluorophenyl)-N-[(2R)-1-hydroxypropan-2-yl]pyr idine-3- carboxamide H A mixture of 6-chloro-5-(3-fluorophenyl)pyridine-3-carboxylic acid (690 mg, 2.74 mmol), 1.2 eq. (2R)-2-aminopropan-1-ol (260 µl, 3.3 mmol; CAS-RN:[35320-23-1]), 1.2 eq. HATU (1.25 g, 3.29 mmol; CAS-RN:[148893-10-1]), 2.0 eq. DIPEA (960 µl, 5.5 mmol; CAS-RN:[7087-68-5]) in 5.9 ml DMSO was stirred at rt until complete conversion. Water was added and a white solid precipitated. The solid was separated and dried to give 680 mg (80 % yield) of the title compound which was used in the next step without further purification. LC-MS (Method 2): Rt = 0.98 min. MS (ESI+): m/z = 309.2 [M+H] ⁺ , 83%. Intermediate 1.20: {5-(Methoxycarbonyl)-2-[4-(trifluoromethyl)phenoxy]pyridin-3 - yl}boronic acid A mixture of Intermediate 1.13a (5.45 g, 14.5 mmol), 2.0 eq.4,4,4',4',5,5,5',5'-octamethyl- 2,2'-bi-1,3,2-dioxaborolane (7.36 g, 29.0 mmol), 0.1 eq. 1,1'-Bis(diphenylphosphino) ferrocenpalladium(II)chlorid (1.06 g, 1.45 mmol; CAS-RN: [72287-26-4]), 3.5 eq. KOAc (4.98 g, 50.8 mmol) in 55 ml dioxane was stirred for 18 h at 70 °C. DCM and H ₂ O were added, and the phases separated. The aqueous layer was extracted with DCM (3x) and the combined organic phases evaporated to dryness. The remaining crude material was purified by column chromatography (silica gel, n-hexane/ ethyl acetate gradient) to give 6.13 g (124% yield) of the title compound. LC-MS (Method 3): Rt = 0.66 min. MS (ESI+): m/z = 342.1 [M+H] ⁺ , 73%. Intermediate 1.21a: ethyl 4-methyl-2'-[4-(trifluoromethyl)phenoxy][2,3'-bipyridine]-5' - carboxylate A mixture of Intermediate 1.20 (235 mg, 50 % purity, 345 µmol), 1.1 eq. 2-chloro-4- methylpyridine (48.3 mg, 379 µmol), 0.05 eq. [1,1'- Bis(diphenylphosphino)ferrocene]dichloropalladium(II) (12.6 mg, 17.2 µmol; CAS-RN [72287-26-4]), 2 eq. aq. K ₂ CO ₃ -solution (95.2 mg, 689 µmol) in 6.2 ml THF was stirred at 60 °C until complete conversion. Ethyl acetate and H2O were added, and the phases separated. The aqueous layer was extracted with ethyl acetate (3x). The combined organic phases were evaporated to dryness. The remaining crude material was purified by column chromatography (silica gel, n-hexane/ ethyl acetate gradient) to give 60 mg (45% yield) of the title compound. LC-MS (Method 2): Rt = 1.43 min. MS (ESI+): m/z = 389.8 [M+H] ⁺ , 90%. Intermediate 1.21b was prepared in analogy to Intermediate 1.21a. Intermediate 1.22a: 4-Methyl-2'-[4-(trifluoromethyl)phenoxy][2,3'-bipyridine]-5' -carboxylic acid A solution of Intermediate 1.21a (60.0 mg, 155 µmol), 5 eq. aq.2 N NaOH-solution (30.9 mg, 773 µmol) in MeOH was stirred at r.t. over night. The solvent was removed under reduced pressure ant the remaining material portioned between aq. HCl-solution and DCM. The phases were separated, and the aqueous phase was extracted with DCM (3x). The combined organic phases were evaporated to dryness to give 45 mg (78 % yield) of the title compound which was used in the next step without further purification. LC-MS (Method 2): Rt = 1.21 min. MS (ESI+): m/z = 375.5 [M+H] ⁺ , 85%. Intermediate 1.22b was prepared in analogy to Intermediate 1.22a. 2. Intermediates for compounds of general formula (2) Intermediate 2.1: Methyl 6-bromo-5-[4-(trifluoromethyl)phenoxy]pyridine-2- carboxylate A mixture of 8.3 g methyl 6-bromo-5-fluoropyridine-2-carboxylate (35.5 mmol), 6.04g 4- (trifluoromethyl)phenol (37.2 mmol), 7.35 g potassium carbonate (53.2 mmol) and 60 ml acetonitrile was stirred under argon atmosphere over 3 days at 80 °C. Water and DCM were added and the aqueous layer extracted with DCM (3-times). The combined organic layers were evaporated to dryness.150 ml water were added to the remaining crude material, the solid material filtered of and dried under vacuo to give 6.0 g of the title compound which was used without further purification in the next step. 1H NMR (DMSO-d ₆ ) δ: 8.07-8.11 (m, 1H), 7.81-7.86 (m, 2H), 7.66-7.75 (m, 1H), 7.33- 7.40 (m, 2H), 3.90 (s, 3H). LC-MS (method 2): Rt = 1.35 min. MS (ESI+): m/z = 378.4 [M+H] ⁺ . Intermediate 2.2: Methyl 6-(3-fluorophenyl)-5-[4- (trifluoromethyl)phenoxy]pyridine-2-carboxylate To a mixture of 409 mg (3-fluorophenyl)boronic acid (2.92 mmol), 1.1 g intermediate 2.1 (2.92 mmol), 2.9 ml 2M aqueous potassium carbonate solution and 11 ml THF, 0.1 eq. Bis(diphenylphosphino)ferrocene]dichloropalladium (292 µmol) was added and the mixture was heated under argon atmosphere at 60°C overnight. The reaction mixture was treated with water and extracted with ethyl acetate. The organic phase was separated, and the aqueous phase extracted two times with ethyl acetate. The combined organic phases were dried over a water-repellent filter, filtrated and the filtrate concentrated in vacuo to give 1.1 g of the title compound which was used without further purification in the next step. LC-MS (method 2): Rt = 1.47 min. MS (ESI+): m/z = 392.6 [M+H] ⁺ . Intermediate 2.3: 6-(3-Fluorophenyl)-5-[4-(trifluoromethyl)phenoxy]pyridine-2- carboxylic acid H A mixture of 1.1 g intermediate 2.2 (2.81 mmol), 2.8 ml 2M aqueous NaOH-solution and 22 ml MeOH was stirred at room temperature for 3 days. Methanol was removed under vacuo and the remaining material treated with 2M aqueous HCl-solution to adjust the pH- value to pH: 5. The solid was removed by filtration and dried under vacuo to give 810 mg of the title compound which was used without further purification in the next step. LC-MS (method 2): Rt = 0.81 min. MS (ESI+): m/z = 378.3 [M+H] ⁺ . Intermediate 2.4: Methyl 6-(1-methyl-1H-pyrazol-3-yl)-5-[4- (trifluoromethyl)phenoxy] pyridine-2-carboxylate To a mixture of 852 mg 1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H- pyrazole (4.09 mmol), 1.4 g intermediate 2.1 (3.72 mmol), 3.72 ml 2M aqueous potassium carbonate solution and 15 ml THF, 1.36 g Bis(diphenylphosphino)ferrocene]dichloropalladium (1.86 mmol) was added and the mixture was heated under argon atmosphere at 80°C for 2 hours. The reaction mixture was treated with water and extracted with ethyl acetate. The organic phase was separated, and the aqueous phase extracted two times with ethyl acetate. The combined organic phases were dried over a water-repellent filter, filtrated and the filtrate concentrated in vacuo to give 2.0 g of a crude mixture of intermediates 2.4 and 2.5 (approximately 2.1 :1) which was used without further purification in the next step. LC-MS (method 2): Rt = 0.73 min. MS (ESI+): m/z = 364.4 [M+H] ⁺ & Rt = 1.22 min. MS (ESI+): m/z = 378.6 [M+H] ⁺ . Intermediate 2.5: 6-(1-Methyl-1H-pyrazol-3-yl)-5-[4- (trifluoromethyl)phenoxy]pyridine-2-carboxylic acid A mixture of intermediates 2.4 & 2.5 (2.0 g, 2.1:1), 5.3 ml 2M aqueous NaOH-solution and 10 ml MeOH was stirred at room temperature for 2 hours. Methanol was removed under vacuo and the remaining material treated with 2M aqueous HCl-solution to adjust the pH-value to pH: 5. DCM was added and the aqueous layer extracted with DCM 3- times. The combined organic layers were evaporated to dryness to give 1.5 g of the title compound which was used without further purification in the next step. LC-MS (method 2): Rt = 0.72 min. MS (ESI+): m/z = 364.6 [M+H] ⁺ . Intermediate 2.6: 6-Bromo-5-[4-(trifluoromethyl)phenoxy]pyridine-2-carboxylic acid A mixture of 514 mg intermediate 2.1 (1.37 mmol), 2.73 ml 1 M aqueous LiOH-solution and 6.1 ml MeOH was stirred at room temperature for 2 hours. An aqueous 2M HCl- solution was added to adjust the pH-value to pH: 5. DCM was added, and the aqueous phase was extracted 2-times with DCM. The combined organic phases were concentrated under reduced pressure to give 490 mg of the title compound which was used without further purification in the next step. ¹ H NMR (DMSO-d ₆ ) δ: 13.16-13.96 (m, 1H), 8.05-8.11 (m, 1H), 7.80-7.85 (m, 2H), 7.64- 7.75 (m, 1H), 7.30-7.37 (m, 2H). LC-MS (method 1): Rt = 1.13 min. MS (ESI+): m/z = 362.1 [M+H] ⁺ . Intermediate 2.7: 6-Bromo-N-[(2R)-1-hydroxypropan-2-yl]-5-[4- (trifluoromethyl)phenoxy] pyridine-2-carboxamide A mixture of 3.4 g intermediate 2.6 (9.39 mmol), 1.06 g (2R)-2-aminopropan-1-ol (14.08 mmol), 3.75 g HATU (9.86 mmol), 1.82 g DIPEA (14.08 mmol) and 15 ml DMSO was stirred at room temperature overnight. The reaction mixture was treated with water and extracted with ethyl acetate. The organic phase was isolated, and the aqueous phase extracted two more times with ethyl acetate. The combined organic phases were dried over a water-repellent filter and the filtrate concentrated in vacuo to give 3.5 g of the title compound which was used without further purification in the next step. 1H NMR (DMSO-d ₆ ) δ: 8.20-8.29 (m, 1H), 8.04-8.09 (m, 1H), 7.75-7.85 (m, 3H), 7.26- 7.33 (m, 2H), 4.77-4.95 (m, 1H), 3.95-4.12 (m, 1H), 3.38-3.57 (m, 2H), 1.15-1.18 (m, 3H) LC-MS (method 1): Rt = 1.17 min. MS (ESI+): m/z = 419.0 [M+H] ⁺ . The following intermediates were prepared in analogy to intermediate 2.7. Intermediates 2.9 & 2.10 have been purified by column chromatography (silica gel, n-hexane/ ethyl acetate gradient).

3. Intermediates for compounds of general formula (3) Intermediate 3.1: Methyl 6-chloro-5-[4-(trifluoromethyl)phenoxy]pyrazine-2- carboxylate A mixture of 891 mg 4-(trifluoromethyl)phenol (5.50 mmol), 1.10 g methyl 6-chloro-5- fluoropyrazine-2-carboxylate (5.77 mmol), 3.04 g potassium carbonate (22.0 mmol) in 52 ml acetonitrile was stirred at 80°C for 2 hours. The mixture was filtrated, and the filtrate evaporated to dryness. Purification of the remaining material by column chromatography (silica gel, n-hexane/ ethyl acetate gradient) followed by preparative HPLC (method 1) gave 1.10 g of the title compound. ¹ H NMR (DMSO-d6) δ: 8.74 (s, 1H), 7.89 (d, J=8.4 Hz, 2H), 7.57 (d, J=8.4 Hz, 2H), 3.90 (s, 3H). LC-MS (method 1): Rt = 1.29 min. MS (ESI+): m/z = 333.1 [M+H] ⁺ . Intermediate 3.2: Methyl 6-(1-methyl-1H-pyrazol-3-yl)-5-[4-(trifluoromethyl) phenoxy]pyrazine-2-carboxylate A mixture of 500 mg intermediate 3.1 (1.50 mmol), 246 mg (1-methyl-1H-pyrazol-3- yl)boronic acid (1.95 mmol), 1.5 ml 2M aqueous potassium carbonate solution, 55 mg [1,1'-Bis(diphenylphosphino)ferrocene]dichloropalladium(II) (75.1 µmol) in 1.25 ml THF was stirred for 1 h at 60 °C. Ethyl acetate and water was added and the aqueous layer extracted with ethyl actetate (3-times). The combined organic phases were evaporated to dryness under vacuo and the remaining material purified by column chromatography (silica gel, n-hexane/ ethyl acetate gradient) to give 360 mg of the title compound. LC-MS (method 2): Rt = 1.28 min. MS (ESI+): m/z = 379.5 [M+H] ⁺ . Intermediate 3.3: Methyl 6-(3-fluorophenyl)-5-[4- (trifluoromethyl)phenoxy]pyrazine-2-carboxylate In analogy to the synthesis of intermediate 3.2, reaction of 560 mg crude intermediate 3.1 (containing methyl 5,6-bis[4-(trifluoromethyl)phenoxy]pyrazine-2-carboxylate as impurity) with 471 mg (3-fluorophenyl)boronic acid (3.37 mmol) gave 620 mg of the title compound which after column chromatography (silica gel, n-hexane/ ethyl acetate gradient) contains approximately 40% methyl 5,6-bis[4-(trifluoromethyl)phenoxy]pyrazine-2-carboxylate as impurity. LC-MS (method 2): Rt = 1.50 min. MS (ESI+): m/z = 393.4 [M+H] ⁺ & Rt = 1.56 min. MS (ESI+): m/z = 459.3 [M+H] ⁺ . Intermediate 3.4: 6-(1-Methyl-1H-pyrazol-3-yl)-5-[4- (trifluoromethyl)phenoxy]pyrazine-2-carboxylic acid A mixture of 360 mg intermediate 3.2 (952 µmol), 2.4 ml 2M aqueous NaOH-solution and 15 ml MeOH was stirred at room temperature for 2 hours. Aqueous HCl-solution was added, and the pH-value adjusted to pH 7. DCM and water were added and the resulting suspension fltrated to give 120 mg of the title compound which was used without further purification in the next step. LC-MS (method 2): Rt = 1.19 min. MS (ESI+): m/z = 365.3 [M+H] ⁺ . Intermediate 3.5: 6-(3-Fluorophenyl)-5-[4-(trifluoromethyl)phenoxy]pyrazine-2- carboxylic acid In analogy to the synthesis of intermediate 3.4, reaction of 620 mg crude intermediate 3.3 (containing approximately 40% methyl 5,6-bis[4-(trifluoromethyl)phenoxy]pyrazine-2- carboxylate as impurity) with 4.0 ml 2M aqueous NaOH-solution gave 500 mg of the title compound containing approximately 50% additional impurities. This crude material was used without further purification in the following step. LC-MS (method 2): Rt = 1.37 min. MS (ESI+): m/z = 379.2 [M+H] ⁺ & Rt = 1.07 min. MS (ESI+): m/z = 249.2 [M+H] ⁺ & Rt = 1.17 min. MS (ESI+): m/z = 315.2 [M+H] ⁺ . 4. Intermediates for compounds of general formula (4) Intermediate 4.1: 2-Chloro-5-fluoro-4-(1-methyl-1H-pyrazol-3-yl)pyrimidine To a mixture of 100 mg 2,4-dichloro-5-fluoropyrimidine (0.599 mmol), 125 mg 1-methyl- 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.599 mmol) and 0.6 ml potassium carbonate (2M in water) in 2 ml THF were added 43.8 mg [1,1'- bis(diphenylphosphino)ferrocene]dichloropalladium(II) (59.9 µmol) and the mixture stirred under argon atmosphere at 60°C for 2h. The mixture was treated with 10 ml water and 10 ml DCM. The aqueous layer was extracted three times with DCM and the combined organic phases were evaporated to dryness. The remaining crude material was purified by column chromatography (silica gel, n-hexane/ ethyl acetate gradient) to give 104 mg of the title compound. ¹ H NMR (DMSO-d ₆ ) δ: 8.90 (d, J=3.0 Hz, 1H), 7.94 (d, J=2.3 Hz, 1H), 6.93-7.00 (m, 1H), 3.99 (s, 3H). LC-MS (method 2): R _t = 0.82 min. MS (ESI+): m/z = 213.1 [M+H] ⁺ . Intermediate 4.2: Methyl 5-fluoro-4-(1-methyl-1H-pyrazol-3-yl)pyrimidine-2- carboxylate A mixture of 1 g intermediate 4.1 (4.703 mmol), 384 mg [1,1'- bis(diphenylphosphino)ferrocene]dichloropalladium(II)-DCM-co mplex 0.47 mmol), 1.97 ml TEA (14.11 mmol) and 33 ml methanol/ THF (10:1) in an autoclave was flushed two times with carbon monoxide and stirred under a carbon monoxide atmosphere of 11.5 bar at room temperature for 15 minutes. After releasing the pressure, the reaction mixture was stirred under a carbon monoxide atmosphere of 16.5 bar again for 25 hours at 105 °C. The mixture was cooled to room temperature and the pressure released. The reaction mixture was evaporated to dryness under vacuo and the remaining material purified by column chromatography (silica gel, n-hexane/ ethyl acetate gradient) to give 460 mg of the title compound. LC-MS (method 3): R _t = 0.70 min. MS (ESI+): m/z = 237.4 [M+H] ⁺ . Intermediate 4.3: Methyl 4-(1-methyl-1H-pyrazol-3-yl)-5-[4- (trifluoromethyl)phenoxy] pyrimidine-2-carboxylate A mixture of 460 mg intermediate 4.2 (1.95 mmol), 331 mg 4-(trifluoromethyl)phenol (2.04 mmol), 538 mg potassium carbonate in 160 ml acetonitrile was stirred at 80 °C for 17 h. The mixture was evaporated to dryness under vacuo to give 1000 mg crude intermediate 4.3 which was used in the next step without any further purification. Intermediate 4.4: 4-(1-Methyl-1H-pyrazol-3-yl)-5-[4- (trifluoromethyl)phenoxy]pyrimidine-2-carboxylic acid A mixture of 1000 mg crude intermediate 4.3, 6.6 ml aqueous 2M NaOH-solution in 15 ml methanol was stirred overnight at room temperature. The reaction mixture was evaporated to dryness and purified by column chromatography (silica gel, n-hexane/ ethyl acetate/ methanol gradient) followed by preparative HPLC (method 1) to give 264 mg (35% yield over 2 steps) of the title compound. ¹ H NMR (CHLOROFORM-d) δ: 8.60 (s, 1H), 7.68 (d, J=8.6 Hz, 2H), 7.48 (d, J=2.3 Hz, 1H), 7.15 (d, J=8.4 Hz, 2H), 7.09 (d, J=2.3 Hz, 1H), 4.04 (s, 3H). LC-MS (method 1): Rt = 0.96 min. MS (ESI+): m/z = 369.2 [M+H] ⁺ .

EXPERIMENTAL SECTION – EXAMPLES of compounds of general formula (1) Example 1.1 N-[(2R)-1-hydroxypropan-2-yl]-5-(1-methyl-1H-pyrazol-3-yl)-6 -[4- (trifluoromethyl)phenoxy]pyridine-3-carboxamide Intermediate 1.3a (90.0 mg, 215 µmol), (1-methyl-1H-pyrazol-3-yl)boronic acid (40.6 mg, 322 µmol; CAS-RN:[869973-96-6]), potassium carbonate (210 µl, 2M in water), were suspended in THF (1.1 ml), [1,1´-Bis(diphenylphosphino)ferrocene]dichloropalladium(II) (7.85 mg, 10.7 µmol; CAS-RN:[72287-26-4]) was added and the mixture was heated at 60°C overnight. The reaction mixture was quenched with water and extracted with ethyl acetate. The organic phase was separated and the aqueous extracted two more times with ethyl acetate. The organic phases were then combined, dried over water-repellent filter, filtrated and the filtrate concentrated in vacuo. The crude product was dissolved in DMSO and purified by preparative HPLC (method 2) to give 29.0 mg (32 % yield) of the target compound. 1H NMR (DMSO-d6) δ: 8.78-8.84 (m, 1H), 8.48-8.58 (m, 1H), 8.29-8.44 (m, 1H), 7.76- 7.86 (m, 3H), 7.36-7.45 (m, 2H), 6.77-6.85 (m, 1H), 4.70-4.81 (m, 1H), 3.99-4.11 (m, 1H), 3.92-3.99 (m, 3H), 3.43-3.53 (m, 1H), 3.34-3.41 (m, 1H), 1.11-1.17 (m, 3H). LC-MS (method 1): R _t = 1.07 min; MS (ESI+): m/z = 421.3 [M+H] ⁺ . The following examples were prepared in analogy to example 1.1.

Example 1.3 N-[(2R)-1-hydroxypropan-2-yl]-5-(1-methyl-1H-1,2,4-triazol-3 -yl)-6-[4- (trifluoromethyl)phenoxy]pyridine-3-carboxamide A mixture of Intermediate 1.4 (102 mg, 266 µmol), 3-bromo-1-methyl-1H-1,2,4-triazole (47.3 mg, 292 µmol), [1,1´-Bis(diphenylphosphino)ferrocene]dichloropalladium(II) (9.71 mg, 13.3 µmol; CAS-RN: [72287-26-4]), potassium carbonate (270 µl, 2.0 M) in THF (1.4 ml) was stirred at 80 °C for 1 h. Ethyl acetate and water were added and the phases separated. The aqueous layer was extracted with ethyl acetate (3 x). The combined organic layers were evaporated to dryness and the crude material purified by column chromatography (silica gel, ethyl acetate/ n-hexane gradient) and preparative HPLC (method 2) to give 20.0 mg (18 % yield) of the target compound. 1H NMR (DMSO-d6) δ: 8.85 (d, J=2.5 Hz, 1H), 8.62-8.65 (m, 2H), 8.42 (d, J=7.9 Hz, 1H), 7.79 (d, J=8.6 Hz, 2H), 7.35 (d, J=8.4 Hz, 2H), 4.76 (t, J=5.8 Hz, 1H), 3.99-4.09 (m, 1H), 3.95 (s, 3H), 3.42-3.51 (m, 1H), 3.34-3.39 (m, 1H), 1.14 (d, J=6.8 Hz, 3H). LC-MS (method 5): Rt = 0.88 min. MS (ESI+): m/z = 422.3 [M+H] ⁺ . The following examples were prepared in analogy to example 1.3. Example 1.9 N-[(2R)-1-hydroxypropan-2-yl]-5-(2-methyl-2H-tetrazol-5-yl)- 6-[4- (trifluoromethyl)phenoxy]pyridine-3-carboxamide Step 1: Methyl 5-(2-methyltetrazol-5-yl)-6-[4-(trifluoromethyl)phenoxy]pyri dine-3- carboxylate A mixture of Intermediate 1.5 (280 mg, 50% purity, 410 µmol), 5-bromo-2-methyl-2H- tetrazole (73.6 mg, 452 µmol), [1,1´- Bis(diphenylphosphino)ferrocene]dichloropalladium(II) (15.0 mg, 20.5 µmol; CAS-RN: [72287-26-4]), aqueous potassium carbonate solution (0.82 mmol) in THF (7.4 ml) was stirred at 60 °C for 3 days. Ethyl acetate and water were added, and the phases separated. The aqueous layer was extracted with ethyl acetate (3 x). The combined organic layers were evaporated to dryness and the crude material purified by column chromatography (silica gel, ethyl acetate/ n-hexane gradient) to give 120.0 mg (77 % yield) of the target compound. LC-MS (method 1): R _t = 1,31 min. MS (ESI+): m/z = 380.4 [M+H] ⁺ . Step 2: 5-(2-Methyl-2H-tetrazol-5-yl)-6-[4-(trifluoromethyl)phenoxy] pyridine-3-carboxylic acid A mixture of methyl 5-(2-methyltetrazol-5-yl)-6-[4-(trifluoromethyl)phenoxy]pyri dine-3- carboxylate (120 mg, 0.316 mmol), sodium hydroxide (1.582 mmol, 0.79 ml, 2M in water) in methanol was stirred at room temperature for 3 hours. Methanol was removed under reduced pressure. 2N HCl solution and dichloromethane were added and the phases separated. The aqueous phase was extracted with dichloromethane (3x) and the combined organic phases evaporated to dryness to give the target compound which was used without further purification in the next step. LC-MS (method 1): R _t = 1,14 min. MS (ESI+): m/z = 366.3 [M+H] ⁺ . Step 3: N-[(2R)-1-hydroxypropan-2-yl]-5-(2-methyl-2H-tetrazol-5-yl)- 6-[4- (trifluoromethyl)phenoxy]pyridine-3-carboxamide A mixture of 5-(2-methyl-2H-tetrazol-5-yl)-6-[4-(trifluoromethyl)phenoxy] pyridine-3- carboxylic acid (97.0 mg, 266 µmol), (2R)-2-aminopropan-1-ol (23.9 mg, 319 µmol), HATU (151 mg, 398 µmol; CAS-RN:[148893-10-1]) and DIPEA (140 µl, 800 µmol; CAS- RN:[7087-68-5]) in DMF (5 ml) was stirred at rt for 16 h. Dichloromethane and water were added and the phases separated. The aqueous layer was extracted with dichloromethane (3 x) and the combined organic phases evaporated to dryness. The crude material was purified by preparative HPLC (method 1) to give 55 mg (49 % yield) of the title compound. ¹ H NMR (DMSO-d ₆ ) δ: 8.95 (d, J=2.5 Hz, 1H), 8.73 (d, J=2.5 Hz, 1H), 8.49 (d, J=8.1 Hz, 1H), 7.82 (d, J=8.6 Hz, 2H), 7.42 (d, J=8.4 Hz, 2H), 4.77 (t, J=5.8 Hz, 1H), 4.48 (s, 3H), 3.98-4.11 (m, 1H), 3.43-3.52 (m, 1H), 3.34-3.41 (m, 1H), 1.14 (d, J=6.6 Hz, 3H). LC-MS (method 5): Rt = 0,99 min. MS (ESI+): m/z = 423.2 [M+H]+. The following examples were prepared in analogy to example 1.9 in 3 steps starting from Intermediate 1.5. Example 1.125-(Azetidin-1-yl)-N-[(2R)-1-hydroxypropan-2-yl]-6-[4- (trifluoromethyl)phenoxy]pyridine-3-carboxamide A mixture of intermediate 1.3a (180 mg, 429 µmol), azetidine (140 µl, 2.1 mmol), (9,9- Dimethyl-9H-xanthen-4,5-diyl)bis(diphenylphosphin): (24.8 mg, 42.9 µmol; CAS- RN: 161265-03-8), Pd2(dba)3: (39.3 mg, 42.9 µmol), caesium carbonate (280 mg, 859 µmol; CAS-RN: 534-17-8) in 1,4-dioxane (4.5 ml) was stirred at 80 °C under argon atmosphere until complete conversion. Dichloromethane and water were added, and the phases separated. The aqueous layer was extracted with ethyl acetate (3 x). The combined organic layers were evaporated to dryness and the crude material purified by preparative HPLC (method 3, basic gradient B) to give 56 mg (33 % yield) of the title compound. 1H NMR (DMSO-d6) δ: 8.15 (d, J=8.1 Hz, 1H), 7.98 (d, J=2.0 Hz, 1H), 7.76 (d, J=8.6 Hz, 2H), 7.24-7.31 (m, 3H), 4.74 (t, J=5.8 Hz, 1H), 3.93-4.07 (m, 5H), 3.41-3.49 (m, 1H), 3.29-3.37 (m, 1H, below H2O peak), 2.21-2.32 (m, 2H), 1.12 (d, J=6.6 Hz, 3H) LC-MS (method 5): Rt = 1.13 min. MS (ESI+): m/z = 396.2 [M+H]+ Stereochemistry: Purification, Crystallization and Crystal Structure Determination of TEAD2 in complex with Example 1.12 A construct of TEAD2 (UNIPROT accession code Q15562) comprising residues 217-447 with an additional N-terminal Met residue [all amino acid residue names in three-letter- code] and with a C-terminal hexa-His affinity tag for affinity purification (Leu-Glu-His-His- His-His-His-His) was expressed in E.coli, purified via Ni affinity chromatography and size exclusion chromatography, shock-frozen in liquid nitrogen and stored at -80°C. Frozen aliquots of TEAD2 (concentrated to 5.5 mg/mL) were thawed and crystallized using the hanging drop method. Drops made from 1 μL of protein solution were mixed with 1 μL of reservoir buffer (100 mM HEPES pH 7.2, 1.86-2.00 M sodium formate) and stored at 20 °C. Plate-shaped and rod-shaped crystals grew within 2 to 13 days. Crystals were soaked for 3 days with 3 mM Example 12 (from a 100 mM Stock solution in DMSO), briefly immersed in reservoir buffer supplemented with 25% glycerol and 5 mM inhibitor, and cryo-cooled in liquid nitrogen. A diffraction data sets was collected from one crystal at 100 K at beamline P11 at PETRA III at the Deutsches Elektronen-Synchrotron in Hamburg, Germany. Data were processed using the programs XDS ¹ and XDSAPP ² . The structure was solved using molecular replacement (program PHASER ³ from the CCP4 program suite ⁴ ) with PDB entry 5DQE as search model, refined using REFMAC5 ⁵ and rebuilt using COOT ⁶ . Inhibitor parameter files were generated using CORINA ⁷ . The final data collection and refinement statistics are summarized in the following table (Values in Brackets Refer to the Highest Resolution Shell): 1 Kabsch, W. Integration, scaling, space-group assignment and post-refinement. Acta Crystallographica Section D 2010, 66, 133-144. 2 Sparta, K. M.; Krug, M.; Heinemann, U.; Mueller, U.; Weiss, M. S. XDSAPP2.0. Journal of Applied Crystallography 2016, 49, 1085-1092. 3 McCoy, A. J.; Grosse-Kunstleve, R. W.; Adams, P. D.; Winn, M. D.; Storoni, L. C.; Read, R. J. Phaser crystallographic software. Journal of Applied Crystallography 2007, 40, 658-674. 4 Winn, M. D.; Ballard, C. C.; Cowtan, K. D.; Dodson, E. J.; Emsley, P.; Evans, P. R.; Keegan, R. M.; Krissinel, E. B.; Leslie, A. G.; McCoy, A.; McNicholas, S. J.; Murshudov, G. N.; Pannu, N. S.; Potterton, E. A.; Powell, H. R.; Read, R. J.; Vagin, A.; Wilson, K. S. Overview of the CCP4 suite and current developments. Acta Crystallogr D Biol Crystallogr 2011, 67, 235-242. 5 Murshudov, G. N.; Skubak, P.; Lebedev, A. A.; Pannu, N. S.; Steiner, R. A.; Nicholls, R. A.; Winn, M. D.; Long, F.; Vagin, A. A. REFMAC5 for the refinement of macromolecular crystal structures. Acta Crystallographica Section D 2011, 67, 355- 367. 6 Emsley, P.; Lohkamp, B.; Scott, W. G.; Cowtan, K. Features and development of Coot. Acta Crystallogr D Biol Crystallogr 2010, 66, 486-501. 7 Schwab, C.H. Conformations and 3D pharmacophore searching. Drug Discovery Today: Technologies, Volume 7, Issue 4, Winter 2010, e245-e253 (DOI: 10.1016/j.ddtec.2010.10.003) The resulting crystal structure of Example 1.12 shows the stereochemistry at carbon atom C10: see FIGURE 1/1. The following examples were prepared in analogy to example 1.12. Example 1.18 N-[3-Hydroxy-2-methylpropyl]-5-(1-methyl-1H-pyrazol-3-yl)-6- [4- (trifluoromethyl)phenoxy]pyridine-3-carboxamide, racemate A mixture of Intermediate 1.7a (84 mg, 231 µmol), 3-amino-2-methylpropan-1-ol (30.9 mg, 347 µmol), HATU (96.7 mg, 254 µmol), DIPEA (81 µl, 460 µmol) in DMSO (2.1 ml) was stirred at room temperature for overnight. Water was added, the resulting mixture extracted with ethyl acetate and the phases separated. The aqueous phase was extracted two more times with ethyl acetate. The organic phases were then combined, dried over water-repellent filter, filtrated and the filtrate concentrated in vacuo. The remaining crude material was purified by preparative HPLC (method 2) to give 21 mg (95% purity, 20% yield) of the title compound. ¹ H NMR (DMSO-d6) δ: 8.80 (d, J=2.3 Hz, 1H), 8.67 (t, J=5.7 Hz, 1H), 8.52 (d, J=2.3 Hz, 1H), 7.77-7.84 (m, 3H), 7.41 (d, J=8.4 Hz, 2H), 6.81 (d, J=2.3 Hz, 1H), 4.52 (t, J=5.4 Hz, 1H), 3.95 (s, 3H), 3.23-3.40 (m, 3H, under H2O peak), 3.09-3.20 (m, 1H), 1.76-1.92 (m, 1H), 0.87 (d, J=6.8 Hz, 3H). LC-MS (method 5): Rt = 1.09 min. MS (ESI+): m/z = 435.2 [M+H]+. The following examples were prepared in analogy to example 1.18. Example 1.30 N-[(2R)-1-Hydroxybutan-2-yl]-5-(1-methyl-1H-pyrazol-3-yl)-6- [4- (trifluoromethyl)phenoxy]pyridine-3-carboxamide A mixture of Intermediate 1.7a (100 mg, 275 µmol), (2R)-2-aminobutan-1-ol (27.0 mg, 303 µmol), HATU (110 mg, 289 µmol), DIPEA (240 µl, 1.4 mmol) in DMF (0.86 ml) was stirred at room temperature for 17 hours. The mixture was added to water (10 ml) and the resulting suspension filtrated. The remaining crude material was purified by preparative HPLC (method 3, acidic gradient A) to give 80 mg (67% yield) of the title compound. 1H NMR (DMSO-d ₆ ) δ: 8.81 (d, J=2.5 Hz, 1H), 8.54 (d, J=2.3 Hz, 1H), 8.30 (d, J=8.4 Hz, 1H), 7.76-7.86 (m, 3H), 7.41 (d, J=8.4 Hz, 2H), 6.81 (d, J=2.3 Hz, 1H), 4.71 (t, J=5.8 Hz, 1H), 3.95 (s, 3H), 3.83-3.92 (m, 1H), 3.36-3.52 (m, 2H), 1.57-1.75 (m, 1H), 1.36- 1.54 (m, 1H), 0.88 (t, J=7.4 Hz, 3H) LC-MS (method 5): Rt = 1.11 min. MS (ESI+): m/z = 435.2 [M+H]+. The following examples were prepared in analogy to example 1.30. Example 1.71 N-(2-Aminoethyl)-5-(1-methyl-1H-pyrazol-3-yl)-6-[4-(trifluor omethyl) phenoxy]pyridine-3-carboxamide Step1: tert-Butyl [2-({5-(1-methyl-1H-pyrazol-3-yl)-6-[4-(trifluoromethyl)phen oxy] pyridine-3-carbonyl}amino)ethyl]carbamate A mixture of 100 mg (275 µmol) intermediate 1.7a , 1.5 eq. (65 µl, 410 µmol) tert-butyl (2-aminoethyl)carbamate, 1.1 eq. (115 mg, 303 µmol) HATU, 2.0 eq. (96 µl, 550 µmol) DIPEA in 2 ml DMSO was stirred at room temperature overnight. Another equivalent of tert-butyl (2-aminoethyl)carbamate and HATU was added and the mixture stirred for another 4 hours. The reaction mixture was treated with water and extracted with ethyl acetate. The organic phase was separated and the aqueous extracted two more times with ethyl acetate. The organic phases were then combined, dried over water-repellent filter, and the filtrate concentrated in vacuo. The crude material was purified by preparative HPLC (method 2) to give 73 mg (52% yield) of the title compound. Step 2: N-(2-Aminoethyl)-5-(1-methyl-1H-pyrazol-3-yl)-6-[4-(trifluor omethyl) phenoxy]pyridine-3-carboxamide A solution of 73 mg (144 µmol) tert-butyl [2-({5-(1-methyl-1H-pyrazol-3-yl)-6-[4- (trifluoromethyl)phenoxy] pyridine-3-carbonyl}amino)ethyl]carbamate, 5 eq. (56 µl, 720 µmol) TFA in DCM was stirred for overnight at room temperature. Another 5 eq. of TFA were added and the mixture stirred for 4 hours. The reaction mixture was evaporated in vacuo.5 ml of saturated aqueous sodium bicarbonate solution was added, the mixture was extracted 3 times with ethyl acetate and the combined organic phases evaporated to dryness in vacuo to give 28 mg (44% yield, 93% purity) of the title compound. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 2.17 (s, 1 H) 2.60 - 2.63 (m, 3 H) 2.99 - 3.10 (m, 2 H) 3.05 (s, 1 H) 3.49 - 3.64 (m, 2 H) 3.90 - 3.99 (m, 3 H) 6.81 - 6.86 (m, 1 H) 6.83 (s, 1 H) 7.21 - 7.24 (m, 1 H) 7.31 - 7.47 (m, 2 H) 7.60 - 7.72 (m, 2 H) 8.50 - 8.58 (m, 1 H) 8.68 - 8.73 (m, 1 H) 8.71 (s, 1 H). LC-MS (method 5): Rt = 0.78 min, MS (ESI+): m/z = 406.1 [M+H]+. Example 1.72 N-(3-Aminopropyl)-5-(1-methyl-1H-pyrazol-3-yl)-6-[4- (trifluoromethyl) phenoxy]pyridine-3-carboxamide Step 1: tert-Butyl [3-({5-(1-methyl-1H-pyrazol-3-yl)-6-[4- (trifluoromethyl)phenoxy]pyridine-3-carbonyl}amino)propyl]ca rbamate, example 1.91 A mixture of 104 mg (286 µmol) intermediate 1.7a, 74.8 mg (429 µmol) tert-butyl (3- aminopropyl)carbamate, 120 mg (315 µmol) HATU and 100 µl (570 µmol) DIPEA in 2.0 ml DMSO was stirred at room temperature until complete conversion. The reaction mixture was treated with water and extracted with ethyl acetate. The organic phase was isolated and the aqueous extracted two more times with ethyl acetate. The organic phases were combined, dried over water-repellent filter and the filtrate concentrated in vacuo. The crude material was purified by preparative HPLC (method 3, basic gradient A) to give 52.0 mg (35% yield) of the title compound. 1H NMR (DMSO-d6) δ: 8.76-8.86 (m, 1H), 8.61-8.74 (m, 1H), 8.45-8.56 (m, 1H), 7.75- 7.86 (m, 3H), 7.31-7.47 (m, 2H), 6.73-6.89 (m, 2H), 3.82-4.01 (m, 3H), 3.27 (q, J=6.6 Hz, 2H), 2.86-3.05 (m, 2H), 1.56-1.74 (m, 2H), 1.29-1.42 (m, 9H). LC-MS (method 5): Rt = 1.29 min, MS (ESI+): m/z = 420.2 [(M-Boc)+2H] ⁺ . Step 2: N-(3-Aminopropyl)-5-(1-methyl-1H-pyrazol-3-yl)-6-[4-(trifluo romethyl) phenoxy]pyridine-3-carboxamide To a mixture of 35.0 mg (67.4 µmol) tert-butyl [3-({5-(1-methyl-1H-pyrazol-3-yl)-6-[4- (trifluoromethyl)phenoxy]pyridine-3-carbonyl}amino)propyl]ca rbamate in 0.5 ml dioxane was added 0.084 ml 4M HCl solution in dioxane (337 µmol) and the mixture stirred at room temperature until complete conversion. The reaction mixture was concentrated in vacuo and the remaining material purified by preparative HPLC (method 2) to give 9.0 mg (31% yield) of the title compound. 1H NMR (DMSO-d6) δ: 8.67-8.86 (m, 2H), 8.46-8.54 (m, 1H), 7.73-7.86 (m, 3H), 7.41 (d, J=8.4 Hz, 2H), 6.76-6.89 (m, 1H), 3.88-4.00 (m, 3H), 2.59-2.72 (m, 2H), 1.43-1.72 (m, 2H). LC-MS (method 5): R _t = 0.79 min; MS (ESI+): m/z = 420.1 [M+H] ⁺ . Example 1.73 N-[(2R) or (2S)-1-Aminopropan-2-yl]-5-(1-methyl-1H-pyrazol-3-yl)-6- [4-(trifluoromethyl)phenoxy]pyridine-3-carboxamide, isomer A Step 1: tert-Butyl [(2RS)-2-({5-(1-methyl-1H-pyrazol-3-yl)-6-[4-(trifluoromethy l)phenoxy] pyridine-3-carbonyl}amino)propyl]carbamate, racemate A mixture of 150 mg (413 µmol) intermediate 1.7a, 108 mg (619 µmol) tert-butyl [(2RS)- 2-aminopropyl]carbamate, 173 mg (454 µmol) HATU and 140 µl (830 µmol) DIPEA in 2.0 ml DMSO was stirred at room temperature overnight. Another 0.5 eq. tert-butyl [(2RS)-2-aminopropyl]carbamate and HATU were added and the stirring continued for 3.5 hours. The reaction mixture was treated with water and extracted with ethyl acetate. The organic phase was separated and the aqueous extracted two more times with ethyl acetate. The combined organic phases were dried over water-repellent filter, and the filtrate concentrated in vacuo. The resulting crude material was purified via preparative HPLC (method 1) to give 132 mg of the title compound.The resulting crude racemate was separated into its two enantiomers via preparative chiral HPLC. Step 2: tert-Butyl [(2R) or (2S)-2-({5-(1-methyl-1H-pyrazol-3-yl)-6-[4-(trifluoromethyl) phenoxy]pyridine-3-carbonyl}amino)propyl]carbamate, isomer A Separation of enantiomers via preparative chiral HPLC (instrument: PrepCon Labomatic HPLC-3; column: YMC Amylose SA 5µ, 250x30; eluent A: methyl tert-butyl ether + 0.1 vol % diethylamine; eluent B: methanol; gradient: 0-15 min 0-5% B; flow: 50 ml/min; temperature: 25°C; UV: 280 nm) yields 52 mg of the title compound (isomer A, retention time: 4.5-6.3 min) alongside 62 mg of the isomer B (retention time: 6.6-9.1 min). Analytical chiral HPLC (instrument: Thermo Fisher UltiMate 3000; column: YMC Amylose SA 3µ, 100x4.6; eluent A: methyl tert-butyl ether + 0.1 vol % diethylamine; eluent B: methanol; isocratic: 95%A+5%B; flow: 1.4 ml/min; temperature: 25°C; UV: 280 nm): retention time 2.10 min (ee: 100%). Step 3: N-[(2R) or (2S)-1-Aminopropan-2-yl]-5-(1-methyl-1H-pyrazol-3-yl)-6-[4- (trifluoromethyl)phenoxy]pyridine-3-carboxamide, isomer A A mixture of 52 mg ( 100 µmol) tert-butyl [(2R) or (2S)-2-({5-(1-methyl-1H-pyrazol-3-yl)- 6-[4-(trifluoromethyl) phenoxy]pyridine-3-carbonyl}amino)propyl]carbamate (isomer A) and 77 µl (1.0 mmol) TFA in 3.0 ml DCM was stirred at room temperature for 2h. The reaction mixture was evaporated to dryness in vacuo. The resulting crude material was again treated with 77 µl TFA in 3.0 ml DCM, stirred for another 4 hours at ambient temperature and evaporated to dryness in vacuo.5ml of saturated aqueous sodium bicarbonate solution was added, and the mixture was extracted 3 times with ethyl acetate. The combined organic layers were evaporated dryness and the obtained material purified by preparative HPLC (method 3, acidic gradient C) to give 17 mg of the title compound. 1H NMR (DMSO-d6) δ: 8.82 (d, J=2.5 Hz, 1H), 8.63 (br d, J=7.9 Hz, 1H), 8.55 (d, J=2.3 Hz, 1H), 8.34 (br s, 1H), 7.77-7.85 (m, 3H), 7.40 (d, J=8.4 Hz, 2H), 6.81 (d, J=2.3 Hz, 1H), 4.09-4.25 (m, 1H), 3.95 (s, 3H), 2.76-2.93 (m, 2H), 1.18 (d, J=6.6 Hz, 3H). LC-MS (method 5): R _t = 0.81 min; MS (ESI+): m/z = 420.2 [M+H] ⁺ . Example 1.74 N-[(2R) or (2S)-1-Aminopropan-2-yl]-5-(1-methyl-1H-pyrazol-3-yl)-6- [4-(trifluoromethyl)phenoxy]pyridine-3-carboxamide, isomer B Step 1: tert-Butyl [(2R) or (2S)-2-({5-(1-methyl-1H-pyrazol-3-yl)-6-[4-(trifluoromethyl) phenoxy]pyridine-3-carbonyl}amino)propyl]carbamate, isomer B As described for example 1.73 (step 2), separation of enantiomers via preparative chiral HPLC yields 62 mg of the title compound (isomer B, retention time: 6.6-9.1 min) alongside 52 mg of isomer A (retention time: 4.5-6.3 min). Analytical chiral HPLC (instrument: Thermo Fisher UltiMate 3000; column: YMC Amylose SA 3µ, 100x4.6; eluent A: methyl tert-butyl ether + 0.1 vol % diethyl amine; eluent B: methanol; isocratic: 95%A+5%B; flow: 1.4 ml/min; temperature: 25°C; UV: 280 nm): retention time 3.27 min (ee: 94.7%). Step 2: N-[(2R) or (2S)-1-Aminopropan-2-yl]-5-(1-methyl-1H-pyrazol-3-yl)-6-[4- (trifluoromethyl)phenoxy]pyridine-3-carboxamide, isomer B A mixture of 62 mg (119 µmol) tert-butyl [(2R) or (2S)-2-({5-(1-methyl-1H-pyrazol-3-yl)- 6-[4-(trifluoromethyl) phenoxy]pyridine-3-carbonyl}amino)propyl]carbamate (isomer B) and 92 µl (1.2 mmol) TFA in 2.0 ml DCM was stirred at room temperature overnight. The reaction mixture was evaporated to dryness in vacuo.5ml of saturated aqueous sodium bicarbonate solution was added, and the mixture was extracted 3 times with ethyl acetate. The combined organic layers were evaporated dryness and the obtained material purified by preparative HPLC (method 1) to give 22 mg of the title compound. 1H NMR (DMSO-d6) δ: 8.83 (d, J=2.3 Hz, 1H), 8.71 (br d, J=7.9 Hz, 1H), 8.56 (d, J=2.5 Hz, 1H), 8.29 (s, 2H), 7.78-7.85 (m, 3H), 7.40 (d, J=8.4 Hz, 2H), 6.82 (d, J=2.3 Hz, 1H), 4.16-4.31 (m, 1H), 3.95 (s, 3H), 2.90 (br d, J=6.8 Hz, 2H), 1.19 (d, J=6.8 Hz, 3H). LC-MS (method 5): R _t = 0.80 min; MS (ESI+): m/z = 420.2 [M+H] ⁺ . Example 1.75 N-[(3R) or (3S)-3-Hydroxybutyl]-5-(1-methyl-1H-pyrazol-3-yl)-6-[4- (trifluoromethyl)phenoxy]pyridine-3-carboxamide, isomer A Separation of enantiomers starting from 55 mg racemic N-[(3RS)-3-hydroxybutyl]-5-(1- methyl-1H-pyrazol-3-yl)-6-[4-(trifluoromethyl)phenoxy]pyridi ne-3-carboxamide via preparative chiral HPLC (instrument: PrepCon Labomatic HPLC-3; column: Chiralpak IF 5µ, 250x30; eluent A: Water + 0.1 vol % formic acid; eluent B: acetonitrile; isocratic: 50%A+45%B; flow: 40 ml/min; temperature: 25°C; UV: 280 nm) yields 22 mg of the title compound (isomer A, retention time: 15.7-18.9 min) alongside 19 mg of the isomer B (retention time: 19.9-24.3 min). Analytical chiral HPLC (instrument: Waters Alliance 2695; Column: Chiralpak IF 3µ, 100x4.6; eluent A: water + 0.1 vol % formic acid; eluent B: acetonitrile; isocratic: 55%A+45%B; flow: 1.4 ml/min; temperature: 25°C; UV: 280 nm): retention time 3.42 min (ee: 100%). ¹ H NMR (DMSO-d ₆ ) δ: 8.79 (d, J=2.3 Hz, 1H), 8.66 (t, J=5.6 Hz, 1H), 8.51 (d, J=2.3 Hz, 1H), 7.76-7.86 (m, 3H), 7.41 (d, J=8.4 Hz, 2H), 6.81 (d, J=2.3 Hz, 1H), 4.51 (d, J=4.8 Hz, 1H), 3.95 (s, 3H), 3.62-3.74 (m, 1H), 1.51-1.66 (m, 2H), 1.09 (d, J=6.1 Hz, 3H). LC-MS (method 5): R _t = 1.08 min; MS (ESI+): m/z = 435.2 [M+H] ⁺ . Example 1.76 N-[(3R) or (3S)-3-hydroxybutyl]-5-(1-methyl-1H-pyrazol-3-yl)-6-[4- (trifluoromethyl)phenoxy]pyridine-3-carboxamide, isomer B Separation of enantiomers as described in example 1.75 via preparative chiral HPLC yields 19 mg of the title compound (isomer B, retention time: 19.9-24.3 min) alongside 22 mg of the isomer A (retention time: 15.7-18.9 min). Analytical chiral HPLC (instrument: Waters Alliance 2695; Column: Chiralpak IF 3µ, 100x4.6; eluent A: water + 0.1 vol % formic acid; eluent B: acetonitrile; isocratic: 55%A+45%B; flow: 1.4 ml/min; temperature: 25°C; UV: 280 nm): retention time 4.26 min (ee: 95.6%). ¹ H NMR (DMSO-d ₆ ) δ: 8.79 (d, J=2.3 Hz, 1H), 8.66 (br t, J=5.6 Hz, 1H), 8.51 (d, J=2.3 Hz, 1H), 7.74-7.87 (m, 3H), 7.41 (d, J=8.4 Hz, 2H), 6.81 (d, J=2.3 Hz, 1H), 4.51 (d, J=4.6 Hz, 1H), 3.95 (s, 3H), 3.61-3.74 (m, 1H), 1.50-1.67 (m, 2H), 1.09 (d, J=6.1 Hz, 3H). LC-MS (method 5): R _t = 1.08 min; MS (ESI+): m/z = 435.2 [M+H] ⁺ . Example 1.77 N-[(1R) or (1S)-1-Cyclopropylethyl]-5-(1-methyl-1H-pyrazol-3-yl)-6- [4-(trifluoromethyl)phenoxy]pyridine-3-carboxamide, isomer A Separation of enantiomers starting from 40 mg racemic N-[(1RS)-1-cyclopropylethyl]-5- (1-methyl-1H-pyrazol-3-yl)-6-[4-(trifluoromethyl)phenoxy]pyr idine-3-carboxamide via preparative chiral HPLC (instrument: PrepCon Labomatic HPLC-2; column: YMC Amylose SA 5µ, 250x30; eluent A: methyl tert-butyl ether + 0.1 vol % diethylamine; eluent B: ethanol + 0.1 vol % diethylamine; isocratic: 95%A+5%B; flow: 50 ml/min; temperature: 25°C; UV: 280 nm) yields 13 mg of the title compound (isomer A, retention time: 7.0-9.6 min) alongside 15 mg of isomer B (retention time: 10.8-14.2 min). Analytical chiral HPLC (instrument: Thermo Fisher UltiMate 3000; column: YMC Amylose SA 3µ, 100x4.6; eluent A: methyl tert-butyl ether + 0.1 vol % diethylamine; eluent B: ethanol; isocratic: 95%A+5%B; flow: 1.4 ml/min; temperature: 25°C; UV: 280 nm): retention time 3.07 min (ee: 100%). ¹ H NMR (DMSO-d ₆ ) δ: 8.80 (d, J=2.5 Hz, 1H), 8.61 (d, J=8.4 Hz, 1H), 8.53 (d, J=2.5 Hz, 1H), 7.76-7.85 (m, 3H), 7.41 (d, J=8.4 Hz, 2H), 6.81 (d, J=2.3 Hz, 1H), 3.96 (s, 3H), 3.41-3.56 (m, 1H), 1.23 (d, J=6.6 Hz, 3H), 0.95-1.06 (m, 1H), 0.34-0.52 (m, 2H), 0.26- 0.34 (m, 1H), 0.15-0.26 (m, 1H). Example 1.78 N-[(1R) or (1S)-1-cyclopropylethyl]-5-(1-methyl-1H-pyrazol-3-yl)-6-[4- (trifluoromethyl)phenoxy]pyridine-3-carboxamide, isomer B

Separation of enantiomers as described in example 1.77 via preparative chiral HPLC yields 15 mg of the title compound (isomer B, retention time: 10.8-14.2 min) alongside 13 mg of the isomer A (retention time: 7.0-9.6 min). Analytical chiral HPLC (instrument: Thermo Fisher UltiMate 3000; column: YMC Amylose SA 3µ, 100x4.6; eluent A: methyl tert-butyl ether + 0.1 vol % diethylamine; eluent B: ethanol; isocratic: 95%A+5%B; flow: 1.4 ml/min; temperature: 25°C; UV: 280 nm): retention time 4.59 min (ee: 100%). 1H NMR (DMSO-d ₆ ) δ: 8.80 (d, J=2.5 Hz, 1H), 8.61 (d, J=8.1 Hz, 1H), 8.53 (d, J=2.5 Hz, 1H), 7.76-7.87 (m, 3H), 7.41 (d, J=8.4 Hz, 2H), 6.81 (d, J=2.3 Hz, 1H), 3.96 (s, 3H), 3.43-3.55 (m, 1H), 1.23 (d, J=6.8 Hz, 3H), 0.94-1.07 (m, 1H), 0.34-0.52 (m, 2H), 0.25- 0.34 (m, 1H), 0.16-0.25 (m, 1H). The following examples were prepared in analogy to example 1.18 from intermediates 1.7b or 1.7c. Example 1.82 N-[(2R)-1-Hydroxypropan-2-yl]-5-(1-methyl-1H-pyrazol-3-yl)-6 -[4- (propan-2-yl)phenoxy]pyridine-3-carboxamide A mixture of 60 mg intermediate 1.11 (0.21 mmol, containing 5-bromo-6-chloro-N-[(2R)- 1-hydroxypropan-2-yl]-pyridine-3-carboxamide as impurity), 83 mg 4-isopropylphenol (0.61 mmol), 141 mg potassium carbonate (1.02 mmol) in 3.0 ml acetonitrile was stirred at 100°C overnight. The reaction mixture was treated with water and extracted three times with DCM. Combined organic phases were dried over a water-repellent filter and the filtrate concentrated in vacuo. The crude material was purified by preparative HPLC (method 3, basic gradient D) to give 5.3 mg of the title compound. 1H NMR (DMSO-d6) δ: 8.75 (d, J=2.3 Hz, 1H), 8.47 (d, J=2.3 Hz, 1H), 8.32 (d, J=8.1 Hz, 1H), 7.81 (d, J=2.0 Hz, 1H), 7.29 (d, J=8.4 Hz, 2H), 7.08 (d, J=8.6 Hz, 2H), 6.81 (d, J=2.3 Hz, 1H), 4.75 (br t, J=5.6 Hz, 1H), 3.98-4.09 (m, 1H), 3.95 (s, 3H), 3.41-3.52 (m, 1H), 2.85-2.99 (m, 1H), 1.23 (d, J=6.8 Hz, 6H), 1.13 (d, J=6.8 Hz, 3H). LC-MS (method 5): R _t = 1.14 min. MS (ESI+): m/z = 395.2 [M+H] ⁺ . The following examples were prepared in analogy to example 1.82. Example 1.856-(4-Cyclopropylphenoxy)-N-[(2R)-1-hydroxypropan-2-yl]-5 -(1- methyl-1H-pyrazol-3-yl)pyridine-3-carboxamide A mixture of 86 mg intermediate 1.3b (0.22 mmol), 50 mg 1-methyl-3-(4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.242 mmol), 0.22 ml aqueous potassium carbonate solution (2M), 8.04 mg Bis(diphenylphosphino)ferrocene]dichloropalladium (11 µmol) in THF was stirred under argon for 5hours at 80 °C. Another 0.5 eq. of 1-methyl-3-(4,4,5,5-tetramethyl-1,3,2- dioxaborolan-2-yl)-1H-pyrazole was added and the stirring continued overnight at 85°C. The reaction mixture was treated with water and extracted three times with DCM. The combined organic phases were dried over a water-repellent filter and the filtrate concentrated in vacuo. The crude material was purified via preparative HPLC (method 2) to give 53 mg of the title compound. 1H NMR (DMSO-d6) δ: 8.75 (d, J=2.5 Hz, 1H), 8.46 (d, J=2.5 Hz, 1H), 8.31 (d, J=8.1 Hz, 1H), 7.81 (d, J=2.0 Hz, 1H), 7.08-7.16 (m, 2H), 6.99-7.07 (m, 2H), 6.81 (d, J=2.0 Hz, 1H), 4.74 (t, J=5.8 Hz, 1H), 3.98-4.09 (m, 1H), 3.95 (s, 3H), 3.42-3.51 (m, 1H), 3.30- 3.39 (m, 1H, below H2O peak), 1.87-2.01 (m, 1H), 1.13 (d, J=6.6 Hz, 3H), 0.92-0.98 (m, 2H), 0.64-0.70 (m, 2H). LC-MS (method 5): R _t = 1.05 min. MS (ESI+): m/z = 393.3 [M+H] ⁺ . The following examples were prepared in analogy to example 1.85 starting with the corresponding intermediates 1.3c-1.3g, respectively. Example 1.91: 5-(3-Fluorophenyl)-N-[(2R)-1-hydroxypropan-2-yl]-6-[4-(trifl uoromethyl) phenoxy] pyridine-3-carboxamide A mixture of Intermediate 1.15a (100 mg, 265 µmol), (2R)-2-aminopropan-1-ol (41 µl, 530 µmol; CAS-RN:[35320-23-1]), DIPEA (180 µl, 1.1 mmol; CAS-RN:[7087-68-5]), HATU (302 mg, 795 µmol; CAS-RN:[148893-10-1]) in 2.7 ml DMF was stirred at r.t. until complete conversion. The reaction mixture was purified via preparative HPLC (method 2) to give 68.0 mg (59% yield) of the title compound. ¹ H NMR (400 MHz, DMSO-d ₆ ) δ ppm 1.14 (d, J=6.84 Hz, 3 H) 3.32 - 3.40 (m, 1 H, under H2O Peak) 3.42 - 3.50 (m, 1 H) 3.97 - 4.10 (m, 1 H) 4.76 (t, J=5.83 Hz, 1 H) 7.26 - 7.33 (m, 1 H) 7.43 (d, J=8.36 Hz, 2 H) 7.52 - 7.67 (m, 3 H) 7.80 (d, J=8.36 Hz, 2 H) 8.32 (d, J=8.11 Hz, 1 H) 8.42 (d, J=2.28 Hz, 1 H) 8.57 (d, J=2.28 Hz, 1 H). LC-MS (Method 5): Rt = 1.23 min. MS (ESI+): m/z = 435.2 [M+H] ⁺ , 100%. The following examples were prepared in analogy to example 1.91.

Example 1.102: 5-(3-Fluorophenyl)-N-[(2R)-1-hydroxypropan-2-yl]-6-[3- (trifluoromethyl)phenoxy]pyridine-3-carboxamide A mixture of Intermediate 1.15b (92.0 mg, 244 µmol), (2R)-2-aminopropan-1-ol (27.5 mg, 366 µmol; CAS-RN:[35320-23-1]), DIPEA (85 µl, 0.488 mmol; CAS-RN:[7087-68-5]), HATU (139 mg, 366 µmol; CAS-RN:[148893-10-1]) in 2.6 ml DMSO was stirred at r.t. until complete conversion. Water and DCM were added, and the phases separated. The aqueous phase was extracted multiple times with DCM. The combined organic phases were filtered over a Whatman filter and concentrated under reduced pressure. The remaining crude material was purified via preparative HPLC (method 1) to give 52.0 mg (49% yield) of the title compound. 1H NMR (DMSO-d ₆ ) δ: 8.55 (d, J=2.5 Hz, 1H), 8.39 (d, J=2.3 Hz, 1H), 8.30 (d, J=7.9 Hz, 1H), 7.51-7.71 (m, 7H), 7.25-7.33 (m, 1H), 4.76 (t, J=5.8 Hz, 1H), 3.98-4.09 (m, 1H), 3.42- 3.50 (m, 1H), 3.34-3.39 (m, 1H), 1.14 (d, J=6.8 Hz, 3H). LC-MS (Method 5): Rt = 1.27 min. MS (ESI+): m/z = 435.2 [M+H] ⁺ , 100%. The following examples were prepared in analogy to example 1.102.

Example 1.139: 2-({5-(3-Fluorophenyl)-6-[4-(trifluoromethyl)phenoxy]pyridin e-3- carbonyl}amino) -N-methylethan-1-aminium trifluoroacetate To a solution of 80.0 mg example 1.38 (150 µmol) in 2.0 ml DCM was added 4.0 eq. TFA (46 µl, 600 µmol; CAS-RN: [76-05-1]) and the reaction mixture was stirred over night at r.t.. The reaction mixture was evaporated to dryness under reduced pressure to give the title compound (39.0 mg, 45 % yield) as a yellow solid. ¹ H NMR (DMSO-d ₆ ) δ: 8.82-8.89 (m, 1H), 8.59 (d, J=2.5 Hz, 1H), 8.36-8.45 (m, 3H), 7.82 (d, J=8.6 Hz, 2H), 7.54-7.65 (m, 3H), 7.44 (d, J=8.4 Hz, 2H), 7.28-7.37 (m, 1H), 3.57 (q, J=5.9 Hz, 2H), 3.04-3.15 (m, 2H), 2.61 (t, J=5.4 Hz, 3H). LC-MS (Method 5): Rt = 0.94 min. MS (ESI+): m/z = 434.2 [M+H] ⁺ , 100%. Example 1.133: tert-Butyl N-{5-(3-fluorophenyl)-6-[4-(trifluoromethyl)phenoxy]pyridine -3- carbonyl}-D-alaninate A mixture of Intermediate 1.15a (90.6 mg, 240 µmol), 1.1 eq. tert-butyl D-alaninate hydrochloride (1:1) (48.0 mg, 264 µmol), 1.1 eq. HATU (100 mg, 264 µmol; CAS-RN: [148893-10-1]), 4.0 eq. DIPEA (170 µl, 960 µmol; CAS-RN: [7087-68-5]) in 2.0 ml DMSO was stirred at r.t. overnight. One additional equivalent of tert-butyl D-alaninate hydrochloride (1:1) was added and the stirring at r.t. continued overnight. The reaction mixture was quenched with water and extracted with ethyl acetate. The organic phase was separated and the aqueous extracted two more times with ethyl acetate. The organic phases were then combined, dried over a water-repellent filter, filtrated and the filtrate concentrated in vacuo. The crude product was purified by preparative HPLC (method 2) to give 41.0 mg (34 % yield) of the title compound. ¹ H NMR (DMSO-d ₆ ) δ: 8.86 (d, J=7.1 Hz, 1H), 8.59 (d, J=2.3 Hz, 1H), 8.45 (d, J=2.3 Hz, 1H), 7.81 (d, J=8.4 Hz, 2H), 7.52-7.68 (m, 3H), 7.46 (d, J=8.4 Hz, 2H), 7.26-7.35 (m, 1H), 4.30-4.45 (m, 1H), 1.41 (s, 9H), 1.39 (d, J=7.4 Hz, 3H). LC-MS (Method 5): Rt = 1.53 min. MS (ESI+): m/z = 505.2 [M+H] ⁺ , 100%. Example 1.134: N-{5-(3-Fluorophenyl)-6-[4-(trifluoromethyl)phenoxy]pyridine -3- carbonyl}glycine Step 1:Methyl N-{5-(3-fluorophenyl)-6-[4-(trifluoromethyl)phenoxy]pyridine -3- carbonyl}glycinate In analogy to the synthesis of example 1.43, 41.0 mg (25 % yield) of the title compound were obtained from 140 mg Intermediate 15a (371 µmol) and 1.1 eq. methyl glycinate hydrochloride (1:1) (51.2 mg, 408 µmol). ¹ H NMR (400 MHz, DMSO-d ₆ ) δ ppm 3.66 (s, 3 H) 4.07 (d, J=5.83 Hz, 2 H) 7.30 (br d, J=1.27 Hz, 1 H) 7.47 (d, J=8.36 Hz, 2 H) 7.55 - 7.67 (m, 3 H) 7.81 (d, J=8.36 Hz, 2 H) 8.43 (d, J=2.28 Hz, 1 H) 8.60 (d, J=2.28 Hz, 1 H) 9.20 (t, J=5.83 Hz, 1 H). LC-MS (Method 5): Rt = 1.33 min. MS (ESI+): m/z = 449.2 [M+H] ⁺ , 91%. Step 2: N-{5-(3-Fluorophenyl)-6-[4-(trifluoromethyl)phenoxy]pyridine -3-carbonyl}glycine A mixture of 110 mg methyl N-{5-(3-fluorophenyl)-6-[4-(trifluoromethyl)phenoxy]pyridine - 3-carbonyl}glycinate (245 µmol), 1.5 eq. aq. LiOH- solution (1M, 370µl) in 3 ml MeOH was stirred at r.t. until complete conversion. The solvent was removed under reduced pressure. Aq. HCl-solution (2N) was added, and the pH adjusted to pH: 5. The white precipitate was removed by filtration and dried to give 100 mg (89 % yield) of the title compound. ¹ H NMR (DMSO-d ₆ ) δ: 12.31-13.07 (m, 1H), 9.06 (t, J=6.0 Hz, 1H), 8.60 (d, J=2.3 Hz, 1H), 8.43 (d, J=2.3 Hz, 1H), 7.81 (d, J=8.6 Hz, 2H), 7.53-7.67 (m, 3H), 7.46 (d, J=8.4 Hz, 2H), 7.27-7.33 (m, 1H), 3.97 (d, J=5.8 Hz, 2H). LC-MS (Method 5): Rt = 1.23 min. MS (ESI+): m/z = 435.1 [M+H] ⁺ , 100%. The following examples were prepared from example 1.134 in analogy to the procedure described for example 1.133.

Example 1.138 5-(2-Fluorophenyl)-N-[(2R)-1-hydroxypropan-2-yl]-6-[4- (trifluoromethyl)phenoxy] pyridine-3-carboxamide A mixture of Intermediate 1.16 (77.5 mg, 185 µmol), 1.5 eq. (2-fluorophenyl)boronic acid (38.8 mg, 277 µmol; CAS-RN:[1993-03-9]), 0.05 eq. [1,1'- Bis(diphenylphosphino)ferrocene] palladium(II) dichloride (6.76 mg, 9.24 µmol; CAS- RN:[72287-26-4]), 2.0 eq. aq. K ₂ CO ₃ - solution (2M, 180 µl) in 0.97 ml THF was stirred at 60°C overnight. Water was added and the reaction mixture extracted with ethyl acetate. The phases were separated and the aqueous extracted two more times with ethyl acetate. The organic phases were then combined, dried over water-repellent filter, filtrated and the filtrate concentrated in vacuo. The crude product was purified by preparative HPLC (method 1) to give 21 mg (26 % yield) of the title compound. ¹ H NMR (DMSO-d ₆ ) δ: 8.64 (d, J=2.3 Hz, 1H), 8.39 (d, J=2.3 Hz, 1H), 8.30 (d, J=7.9 Hz, 1H), 7.79 (d, J=8.4 Hz, 2H), 7.61-7.68 (m, 1H), 7.48-7.58 (m, 1H), 7.30-7.42 (m, 4H), 4.75 (t, J=5.8 Hz, 1H), 3.96-4.09 (m, 1H), 3.41-3.51 (m, 1H), 3.34-3.40 (m, 1H), 1.13 (d, J=6.6 Hz, 3H). LC-MS (Method 5): Rt = 1.25 min. MS (ESI+): m/z = 435.2 [M+H] ⁺ , 100%. The following examples were prepared from Intermediate 1.16 in analogy to the procedure described for example 1.138.

Example 1.147: 6-(4-Chlorophenoxy)-5-(3-fluorophenyl)-N-[(2R)-1-hydroxyprop an-2- yl]pyridine-3-carboxamide A mixture of Intermediate 1.19 (100 mg, 324 µmol), 4-chlorophenol (41.6 mg, 324 µmol; CAS-RN:[106-48-9]), 2.0 eq. K ₂ CO ₃ (89.5 mg, 648 µmol; CAS-RN:[584-08-7]) in 2.0 ml acetonitrile was stirred at 80 °C overnight. Water and DCM were added, and the phases separated. The aqueous phase was extracted with DCM (3 x) and the combined organic phases were evaporated to dryness. The remaining material was purified by preparative HPLC (method 1) to give 26 mg (20 %) yield of the title compound. ¹ H NMR (DMSO-d ₆ ) δ: 8.54 (d, J=2.3 Hz, 1H), 8.38 (d, J=2.5 Hz, 1H), 8.29 (d, J=7.9 Hz, 1H), 7.52-7.66 (m, 3H), 7.48 (d, J=8.9 Hz, 2H), 7.22-7.32 (m, 3H), 4.71-4.79 (m, 1H), 3.97-4.09 (m, 1H), 3.41-3.51 (m, 1H), 3.34-3.39 (m, 1H), 1.14 (d, J=6.6 Hz, 3H). LC-MS (Method 5): Rt = 1.23 min. MS (ESI+): m/z = 401.2 [M+H] ⁺ , 100%. The following examples were prepared from Intermediate 1.19 in analogy to the procedure described for example 1.147.

Example 1.153: N-[(2R)-1-Hydroxypropan-2-yl]-4-methyl-2'-[4- (trifluoromethyl)phenoxy][2,3'-bipyridine]-5'-carboxamide A mixture of Intermediate 1.22a (45.0 mg, 120 µmol), (2R)-2-aminopropan-1-ol (10.8 mg, 144 µmol; CAS-RN:[35320-23-1]), DIPEA (63 µl, 360 µmol; CAS-RN:[7087-68-5]), HATU (68.6 mg, 180 µmol; CAS-RN:[148893-10-1]) in 5.0 ml DMF was stirred at r.t. until complete conversion. Water and DCM were added, and the phases separated. The aqueous phase was extracted multiple times with DCM. The combined organic phases were concentrated under reduced pressure. The remaining crude material was purified via preparative HPLC (method 1) to give 30.0 mg (58% yield) of the title compound. 1H NMR (400 MHz, DMSO-d ₆ ) δ ppm 1.13 (d, J=6.84 Hz, 3 H) 2.39 (s, 3 H) 3.31 - 3.40 (m, 1 H) 3.41 - 3.51 (m, 1 H) 3.96 - 4.10 (m, 1 H) 4.75 (t, J=5.70 Hz, 1 H) 7.26 - 7.32 (m, 1 H) 7.45 (d, J=8.36 Hz, 2 H) 7.81 (d, J=8.36 Hz, 2 H) 7.88 - 7.93 (m, 1 H) 8.37 (d, J=8.11 Hz, 1 H) 8.59 - 8.65 (m, 2 H) 8.77 (d, J=2.53 Hz, 1 H). LC-MS (Method 5): Rt = 1.06 min. MS (ESI+): m/z = 432.2 [M+H] ⁺ , 100%. Example 1.154 was prepared from Intermediate 1.22b in analogy to the procedure described for example 1.153. EXPERIMENTAL SECTION – EXAMPLES of compounds of general formula (2) Example 2.1: 6-(3-Fluorophenyl)-N-[(2R)-1-hydroxypropan-2-yl]-5-[4- (trifluoromethyl)phenoxy]pyridine-2-carboxamide A mixture of 70 mg intermediate 2.3 (186 µmol), 15.3 mg (2R)-2-aminopropan-1-ol (204 µmol), 106 mg HATU (278 µmol), 97 µl DIPEA (560 µmol) and 2 ml DMSO was stirred at room temperature overnight. The reaction mixture was treated with water and extracted with ethyl acetate three times. The combined organic phases were concentrated in vacuo and the remaining material purified by preparative HPLC (method 2) to give 43 mg of the title compound. 1H NMR (DMSO-d6) δ: 8.36 (d, J=8.6 Hz, 1H), 8.08 (d, J=8.6 Hz, 1H), 7.79-7.84 (m, 2H), 7.72-7.78 (m, 3H), 7.48-7.56 (m, 1H), 7.24-7.33 (m, 3H), 4.89 (t, J=5.6 Hz, 1H), 4.00-4.13 (m, 1H), 3.39-3.57 (m, 2H), 1.19 (d, J=6.8 Hz, 3H). LC-MS (method 5): Rt = 1.32 min. MS (ESI+): m/z = 435.2 [M+H] ⁺ . The following examples were prepared in analogy to example 2.1.

Example 2.7: N-[(2R)-1-hydroxypropan-2-yl]-6-(1-methyl-1H-pyrazol-3-yl)-5 -[4- (trifluoromethyl)phenoxy]pyridine-2-carboxamide A mixture of 70 mg intermediate 2.5 (193 µmol), 15.9 mg (2R)-2-aminopropan-1-ol (212 µmol), 110 mg HATU (289 µmol), 101 µl DIPEA (580 µmol) and 41 µl DMSO was stirred at room temperature overnight. The reaction mixture was treated with water and extracted with ethyl acetate three times. The combined organic phases were concentrated in vacuo and the remaining material purified by preparative HPLC (method 2) to give 57 mg of the title compound. 1H NMR (DMSO-d6) δ: 8.29 (d, J=8.6 Hz, 1H), 8.03 (d, J=8.4 Hz, 1H), 7.77 (d, J=8.6 Hz, 1H), 7.75 (d, J=2.0 Hz, 1H), 7.71 (d, J=8.6 Hz, 2H), 7.13 (d, J=8.4 Hz, 2H), 6.95 (d, J=2.3 Hz, 1H), 4.95 (br s, 1H), 4.00-4.13 (m, 1H), 3.82 (s, 3H), 3.45-3.56 (m, 2H), 1.20 (d, J=6.6 Hz, 3H). LC-MS (method 5): Rt = 1.07 min. MS (ESI+): m/z = 421.2 [M+H] ⁺ . The following examples were prepared in analogy to example 2.7.

Example 2.21: 6-(Azetidin-1-yl)-N-[(2R)-1-hydroxypropan-2-yl]-5-[4- (trifluoromethyl) phenoxy]pyridine-2-carboxamide A mixture of 98 mg intermediate 2.7 (234 µmol), 63 µl azetidine (940 µmol), 152 mg caesium carbonate (468 µmol) and 2 ml NMP was stirred for 3 hours at 70°C. Water and ethyl acetate were added and the aqueous layer extracted with ethyl acetate (3-times). The combined organic phases were evaporated to dryness under vacuo and the remaining material purified by preparative HPLC (method 2) to give 31 mg of the title compound. 1H NMR (DMSO-d6) δ: 8.00-8.10 (m, 1H), 7.66-7.81 (m, 2H), 7.29-7.48 (m, 2H), 6.97- 7.15 (m, 2H), 4.72-4.95 (m, 1H), 3.91-4.09 (m, 5H), 3.39-3.54 (m, 2H), 2.14-2.29 (m, 2H), 1.06-1.20 (m, 3H). LC-MS (method 5): Rt = 1.24 min, MS (ESI+): m/z = 396.1 [M+H] ⁺ . The following examples were prepared in analogy to example 2.21.

The following examples were prepared in analogy to example 2.21 starting from the corresponding intermediate. Examples 2.33-2.37 were heated at 90°C for 12 hours. Examples 2.38-2.39 were heated at 90°C for 3 hours.

EXPERIMENTAL SECTION – EXAMPLES of compounds of general formula (3) Example 3.1: N-[(2S)-1-Hydroxypropan-2-yl]-6-(1-methyl-1H-pyrazol-3-yl)-5 -[4- (trifluoromethyl)phenoxy]pyrazine-2-carboxamide A mixture of 50 mg intermediate 3.4 (137 µmol), 11.3 mg (2S)-2-aminopropan-1-ol (151 µmol), 54.8 mg HATU (144 µmol), 120 µl DIPEA (690 µmol) in 430 µl DMF was stirred at room temperature for 2 hours. The reaction mixture was treated with water and DCM and the aqueous phase was extracted with DCM (3-times). The organic layers were combined and evaporated to dryness under vacuo. The crude material was purified by preparative HPLC to give 15 mg of the title compound. 1H NMR (DMSO-d6) δ: 8.62 (s, 1H), 8.20 (d, J=8.6 Hz, 1H), 7.90 (d, J=2.3 Hz, 1H), 7.84 (d, J=8.6 Hz, 2H), 7.50 (d, J=8.4 Hz, 2H), 7.18 (d, J=2.3 Hz, 1H), 4.92 (t, J=5.4 Hz, 1H), 4.03-4.13 (m, 1H), 3.98 (s, 3H), 3.43-3.57 (m, 2H), 1.19 (d, J=6.6 Hz, 3H). LC-MS (method 1): Rt = 1.06 min. MS (ESI+): m/z = 422.2 [M+H] ⁺ . The following examples were prepared in analogy to example 3.1. EXPERIMENTAL SECTION – EXAMPLES of compounds of general formula (4) Example 4.1: N-[(1R)-1-cyclopropyl-2-hydroxyethyl]-4-(1-methyl-1H-pyrazol -3-yl)- 5-[4-(trifluoromethyl)phenoxy]pyrimidine-2-carboxamide A mixture of 40 mg intermediate 4.4 (110 µmol), 16.7 mg (2R)-2-amino-2- cyclopropylethan-1-ol (165 µmol), 54.3 mg HATU (143 µmol), 38 µl DIPEA (220 µmol) in 1 ml DMSO was stirred at room temperature overnight. The reaction mixture was treated with water and extracted 3 times with DCM. The organic layers were combined, dried over a water repellent filter and evaporated under vacuo. The crude material was purified by preparative HPLC (method 2) to give 17 mg of the title compound. 1H NMR (DMSO-d6) δ: 8.86 (s, 1H), 8.57 (d, J=8.9 Hz, 1H), 7.83 (d, J=2.3 Hz, 1H), 7.71 (d, J=8.6 Hz, 2H), 7.22 (d, J=8.4 Hz, 2H), 7.04 (d, J=2.5 Hz, 1H), 4.86 (t, J=5.6 Hz, 1H), 3.84 (s, 3H), 3.56-3.71 (m, 2H), 3.37-3.48 (m, 1H), 1.06-1.17 (m, 1H), 0.26-0.53 (m, 4H). LC-MS (method5): Rt = 1.02 min. MS (ESI+): m/z = 448.3 [M+H] ⁺ . The following examples were prepared in analogy to example 4.1.

EXPERIMENTAL SECTION – BIOLOGICAL ASSAYS Examples were tested in selected biological assays one or more times. When tested more than once, data are reported as either average values or as median values, wherein • the average value, also referred to as the arithmetic mean value, represents the sum of the values obtained divided by the number of times tested, and • the median value represents the middle number of the group of values when ranked in ascending or descending order. If the number of values in the data set is odd, the median is the middle value. If the number of values in the data set is even, the median is the arithmetic mean of the two middle values. Examples were synthesized one or more times. When synthesized more than once, data from biological assays represent average values or median values calculated utilizing data sets obtained from testing of one or more synthetic batch. The in vitro activity of the compounds of the present invention can be demonstrated in the following assays: In vitro assay 1: Assay for the detection of YAP1/TAZ activity in MDA-MB-231-TEAD-Luc reporter cells The YAP/TAZ Dual Reporter Assay quantifies the activity of endogenous YAP1 and/or TAZ in MDA-MB-231 cells. The cells contain a stable Firefly luciferase reporter under control of a TEAD-promoter (base pairs 27-304), as described under SEQ ID No. 1 (Figure 2), as well as a thymidine kinase (TK)-Renilla reporter construct (pGL4.74, Promega) for toxicity control. Signals are detected by measuring the firefly luminescence followed by the renilla luminescence using the DualGlo-luciferase assay system detection kit (Promega, part # E2920, E2940). The cells were kept in routine culture in DMEM low glucose, 10% fetal bovine serum (FBS), 1% Glutamax, 250 μg/ml Hygromycin, 0,5 μg/ml Puromycin, harvested, cryopreserved in 90% culture medium + 10% dimethylsulphoxide (DMSO) and stored as frozen aliquots of typically 10-50 million cells/vial at -150°C or below until further use. For the assay, sufficient cells were rapidly thawed in a 37°C water bath and pipetted into prewarmed assay medium (DMEM/Ham's 12, 5 ml Glutamine, 5 ml Penicillin/Streptomycin, 4% FBS). The cells were centrifuged for 5 min at 44 × g (gravitational force). The supernatant was removed and the cell pellet was resuspended in fresh medium to give a suspension of 2.0E+05 cells/ml. The cell concentration may vary depending on the cryopreserved cell batch used. The inhibitor control solution contained assay medium without cells. The assay was performed in white 384-well or 1536-well microplates (Greiner Bio-One, Frickenhausen, Germany) with a total volume of five microliter (μl) or four μl, respectively. Fifty nl (40 nl in 1536-well microplates) of a 100-fold concentrated solution of the test compound in DMSO were transferred into a 384-well microtiter test plate. For this, either a Hummingbird liquid handler (Digilab, MA, USA) or an Echo acoustic system (Labcyte, CA, USA) was used. Five μl of a freshly prepared cell suspension were added to the wells of a test plate. The inhibitor control cell suspension was added to empty wells at the side of the test plate, followed by incubation at 37°C in a 5% carbon dioxide atmosphere for 20-24 hours. For luminescence detection, one μl of the Dual-Glo-Luciferase detection solution, prepared as recommended by the supplier, were added to all wells. The test plate was centrifuged for two minutes at 1200 rpm in a microplate centrifuge (Eppendorf model 5810), incubated at 20°C for 10 min before measurement of the luminescence in a microplate reader (typically Pherastar by BMG, Germany, or ViewLux by Perkin-Elmer, USA). Then, one μl of the Dual-Glo-Stop&Glo Luciferase detection solution, prepared as recommended by the supplier, were added to all wells. The test plate was centrifuged for two minutes at 1200 rpm, incubated at 20°C for 10 min before measurement of the renilla luminescence in a microplate reader. Data were normalized (control wells containing cell solution without inhibitor = 0% inhibition, assay medium control = 100% inhibition). For dose-response evaluation, compounds were tested in duplicates at up to 11 concentrations (for example 20 μM, 5.7 μM, 1.6 μM, 0.47 μM, 0.13 μM, 38 nM, 11 nM, 3.1 nM, 0.89 nM, 0.25 nM and 0.073 nM). Dilution series were made prior to the assay in a 100-fold concentrated form by serial dilution. IC ₅₀ values were calculated by 4-parameter fitting using a commercial software package (Genedata Screener, Switzerland).

Table 2: YAP1/TAZ activity: IC ₅₀ values of examples in in vitro assay 1

In vitro assay 2: Cancer cell proliferation assays The cancer cell proliferation assay quantifies the effect of test compound addition on viability and proliferation of cancer cells. Cancer cells were seeded at appropriate cell numbers in 30 μl of their appropriate growth medium (1000 cells/well for cell lines NCI- H226, NCI-H2052, NCI-H2452 and NCI-H28 in RPMI 1640 medium (Biochrom FG 1215) with 10% FCS (Sigma F2442)) in 384-well plates and incubated in a humidified 37°C incubator for 24 h. Then, test compounds were added to cells by means of a HP D300 digital dispenser in a 20-step dilution series (e.g.10 µM, 6.2 µM, 3.8 µM, 2.3 µM, 1.4 µM, 0.89 µM, 0.55 µM, 0.34 µM, 0.21 µM, 0.13 µM, 79 nM, 49 nM, 30 nM, 18 nM, 12 nM, 6.9 nM, 3.9 nM, 2.6 nM, 1.3 nM, 0.86 nM). After 72 h incubation in a humidified 37°C incubator, cell viability was assessed by addition of 10 μl/well Cell Titer-Glo Luminescent Cell Viability Assay reagent (Promega, G7573). Luminescence, which corresponds to viable cell number, was determined on an Infinite M1000 Tecan plate reader. The half- maximal growth inhibition (IC ₅₀ ) was calculated as compound concentration, which was required to achieve 50% inhibition of luminescence. IC ₅₀ was determined by means of a 4-parameter fit on measurement data which was normalized to vehicle (DMSO) treated cells (=100%) and measurement readings of control wells taken immediately before compound exposure (=0%). Data analysis was performed using GraphPad Prism version 8.4.0. or higher. In vitro assay 3: Target gene expression Target gene expression assays explore the effect of TEAD inhibitors on expression levels of genes that are dependent on TEAD function for transcription. Cancer cells covering various indications (mesothelioma, lung cancer (SCLC, NSCLC), soft tissue sarcoma, urinary tract, kidney, liver, gastric, breast and pharyngeal cancer) were seeded into 6- well plates at appropriate cell numbers in 2 ml of their respective medium and incubated in a humidified 37°C incubator for 24 h. Then, cells were treated with test compounds at a concentration of 1µM or 10µM or with 0.1% DMSO as control or were left untreated. After 24 hours, cells were lysed in 350µl RLT buffer and subjected to RNA extraction using an RNeasy Plus Mini Kit (Qiagen). RNA samples (0.5-1 µg) were reverse- transcribed to complementary DNA (cDNA) using SuperScript™ III First-Strand Synthesis SuperMix (Invitrogen). After dilution, cDNA levels of respective genes were quantified by real-time PCR using TaqMan Gene Expression Assays (Applied Biosystems) on a 7500 Fast Real-Time or a ViiA 7 Real-Time PCR System (Applied Biosystems). The evaluated genes and TaqMan Gene Expression Assays are listed in Table 3 below. Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) was used as a housekeeping gene. Relative mRNA expression was calculated using the ΔΔCt method and endogenous GAPDH mRNA expression as reference.

In vitro assay 4: Caco-2 Permeability Assay Caco-2 cells [purchased from the German Collection of Microorganisms and Cell Cultures (DSMZ), Braunschweig, Germany] were seeded at a density of 4.5 × 10 ⁴ cells/well on 24- well insert plates, 0.4 μm pore size (Costar) and grown for 13-15 days in DMEM supplemented with 10% FCS, 1% GlutaMAX (100×, Gibco), 100 U/mL penicillin, 100 μg/mL streptomycin (Gibco), and 1% nonessential amino acids (100×, Thermo Fischer Scientific). Cells were maintained at 37 °C in a humidified 5% CO2 atmosphere. Medium was changed every 2−3 days. Before the assay was run, the culture medium was replaced by FCS-free HEPES carbonate transport buffer.For the assessment of monolayer integrity, the transepithelial electrical resistance(TEER) was measured. Test compounds were pre-dissolved in DMSO and added either to the apical or basolateral compartment at a final concentration of 2 μM. The organic solvent in the incubations was limited to ≤1% dimethylsulfoxide (DMSO). Before and after incubation for 2 h at 37 °C, samples were taken from both compartments and analyzed by LC−MS/MS after precipitation with MeOH. The apparent permeability coefficient (P _app ) was calculated both for the apical to basolateral (A → B) and the basolateral to apical (B → A) direction using the following equation: P _app = (V _r /P ₀ )(1/S)(P ₂ /t), where V _r is the volume of medium in the receiver chamber, P ₀ is the measured peak area of the test compound in the donor chamber at t = 0, S is the surface area of the monolayer, P ₂ is the measured peak area of the test compound in the acceptor chamber after incubation for 2 h, and t is the incubation time. The efflux ratio (ER) basolateral (B) to apical (A) was calculated by dividing Papp B−A by Papp A−B. In addition, the compound recovery was calculated. As assay control, reference compounds were analyzed in parallel. In vitro assay 5: Metabolic Stability in Liver Microsomes The in vitro metabolic stability of test compounds was determined by incubating them at 1 μM in a suspension of liver microsomes in 100 mM phosphate buffer, pH 7.4 (NaH ₂ PO ₄ ·H ₂ O + Na ₂ HPO ₄ ·2H ₂ O) and at a protein concentration of 1 mg/mL at 37 °C. The microsomes were activated by adding a cofactor mix containing 8 mM glucose-6- phosphate (G-6-P), 0.5 mM NADP, and 1 IU/mL G-6-P dehydrogenase in phosphate buffer, pH 7.4. The metabolic assay was started shortly afterwards by adding the test compound to the incubation at a final volume of 0.55 mL (or 1.21 mL). The organic solvent in the incubations was limited to ≤1% dimethylsulfoxide (DMSO) and acetonitrile. During incubation, the microsomal suspensions were continuously shaken at 550 rpm (or 375 rpm) and aliquots were taken at 2, 8, 16, 30, 45, and 60 min, to which double volumes of cold acetonitrile were immediately added. The samples were frozen at −20 °C overnight, subsequently centrifuged for 15 min at 3700 rpm, and the supernatant was analyzed by LC-MS/MS. The half-life of a test compound was determined from the concentration−time plot. From the half-life, the intrinsic clearances were calculated. Together with the additional parameters, liver blood flow, specific liver weight, and microsomal protein content, the hepatic in vivo blood clearance (CL) and the maximal oral bioavailability (Fmax) were calculated using the “well stirred” liver model. [1] The following parameter values were used: Liver blood flow 1.32 L/(h ·kg) (human), 4.2 L/(h kg) (rat); specific liver weight 21 g/kg (human), 32 g/kg (rat), and microsomal protein content 40 mg/g. [1] Pang, K. S.; Rowland, M. Hepatic clearance of drugs. I. Theoretical considerations of a “well-stirred” model and a “parallel tube” model. Influence of hepatic blood flow, plasma and blood cell binding, and the hepatocellular enzymatic activity on hepatic drug clearance. J. Pharmacokinet. Biopharm.1977, 5, 625−653. In vitro assay 6: Metabolic Stability in Rat Hepatocytes Hepatocytes from Han/Wistar rats were isolated via a two-step perfusion method. After perfusion, the liver was carefully removed from the rat: The liver capsule was opened and the hepatocytes were gently shaken out into a Petri dish with ice-cold Williams medium E (WME). The resulting cell suspension was filtered through a sterile gauze into 50 mL Falcon tubes and centrifuged at 50 g for 3 min at room temperature. The cell pellet was resuspended in WME (30 mL) and centrifuged twice through a Percoll gradient at 100 g. The hepatocytes were washed again with WME and resuspended in a medium containing 5 % FCS. Cell viability was determined by trypan blue exclusion. For the metabolic stability assay, liver cells were distributed in WME containing 5 % FCS into glass vials at a density of 1.0 × 10 ⁶ vital cells/mL. The test compound was added to a final concentration of 1 μM. During incubation, the hepatocyte suspensions were continuously shaken at 580 rpm and aliquots were taken at 2, 8, 16, 30, 45, and 90 min, to which an equal volume of cold MeOH was immediately added. The samples were frozen at −20°C overnight, subsequently centrifuged for 15 min at 3000 rpm, and the supernatant was analyzed by LC-MS/MS. The half-life of a test compound was determined from the concentration− time plot. From the half-life, the intrinsic clearances were calculated.Together with the additional parameters, liver blood flow, specific liver weight, and the amount of liver cells in vivo and in vitro, the hepatic in vivo blood clearance (CL) and the maximal oral bioavailability (Fmax) were calculated using the “well stirred” liver model. [1] The following parameter values were used: liver blood flow 4.2 L/(h kg); specific liver weight 32 g/kg body weight; liver cells in vivo 1.1 × 10 ⁸ cells/g liver; and liver cells in vitro 1.0 × 10 ⁶ /mL. [1] Pang, K. S.; Rowland, M. Hepatic clearance of drugs. I. Theoretical considerations of a “well-stirred” model and a “parallel tube” model. Influence of hepatic blood flow, plasma and blood cell binding, and the hepatocellular enzymatic activity on hepatic drug clearance. J. Pharmacokinet. Biopharm.1977, 5, 625−653. In vitro assay 7: Detection of YAP1/TAZ activity in NCI-H226-TEAD-Luc reporter cells The YAP/TAZ Reporter Assay quantifies the activity of endogenous YAP1 and/or TAZ in NCI-H226 cells. The cells contain a stable Firefly luciferase reporter under control of a TEAD-promoter (base pairs 27-304), as described under SEQ ID No.1 (Figure 2). Signals are detected by measuring firefly luminescence using the OneGlo-luciferase assay system detection kit (Promega, part # E605A, E606A). The cells were kept in culture in DMEM/Ham´s F12, 10% fetal bovine serum (FBS), 1% Glutamax, 250 μg/ml Hygromycin. The assay was performed in white 384-well microplates (Greiner Bio-One, Frickenhausen, Germany) with a total volume of 20 microliter (μl).2000 cells were seeded per well and incubated overnight at 37°C 5% CO2 in a humidified atmosphere. After 16h, test compounds dissolved in DMSO were added in triplicates at up to 11 concentrations (for example 20 μM, 5.7 μM, 1.6 μM, 0.47 μM, 0.13 μM, 38 nM, 11 nM, 3.1 nM, 0.89 nM, 0.25 nM and 0.073 nM) by Hp Dispenser. The cells were incubated for 24h at 37°C 5% CO2 in a humidified atmosphere. For luminescence detection, ten μl of the One-Glo-Luciferase detection solution, prepared as recommended by the supplier, were added to all wells. The test plate was centrifuged for two minutes at 1200 rpm in a microplate centrifuge (Eppendorf model 5810), incubated at 20°C for 10 min before measurement of the luminescence in a microplate reader (typically Pherastar by BMG, Germany, or ViewLux by Perkin-Elmer, USA). Data were normalized (control wells containing cell solution with DMSO only = 0% inhibition, assay medium control = 100% inhibition). IC ₅₀ values were calculated by 4- parameter fitting using a commercial software package (GraphPad Prism). In vitro assay 8: PXR Nuclear Receptor Activation A HepG2 cell line stably-cotransfected with a vector for human PXR and a Luciferase reporter gene under the control of a human CYP3A4 promotor or commercially available DPX2 cells (hepatoma cell line stably-cotransfected with a vector for human PXR and a Luciferase reporter gene under the control of two human CYP3A4 promotors; Puracyp, Carlsbad, CA) were applied. Cells were seeded in a 384 well plate and cultivated at 37°C/5% CO ₂ in humidified air.24h prior read-out the cells were treated with compound in a ten step serial dilution of 1:3 starting at the highest test concentration of 50 µM and ending at 2 nM. Rifampicin was incubated in the same manner as positive control. In addition, for the normalization of the luminescence signal cells were incubated with Rifampicin at a concentration of 16.7 µM corresponding to 100% activation, as well as DMSO for background luminescence corresponding to 0% activation (n=32 wells each). Cells were lyzed and incubated with the Luciferase substrate ONE-Glo™ Reagent (Promega, Madison WI, USA) according to manufacturer’s instructions and luminescence signal was detected in a plate reader. A concentration-dependent increase of the luciferase activity above 10% of Rifampicin control was classified as PXR transactivation. In vitro assay 9: Automated hERG Voltage clamp To investigate whether the test compound inhibits the human Ether-a-go-go-Related Gene (hERG) potassium channel, in vitro automated voltage clamp recordings were performed on recombinant HEK293 cells stably expressing the hERG alpha subunit (hERG cells). Following harvest, cells were transferred to the cell reservoir of a 384 channel automated patch clamp device and stored there at 20°C until usage. Upon start of the automated voltage clamp procedure, hERG cells were transferred to a 384 well patch clamp chip (pipette resistance of ~2-3 M ^) prefilled with external solution (containing in mM: 143 NaCl, 4 KCl, 2 CaCl ₂ , 1 MgCl ₂ , 5 glucose, 10 HEPES; pH 7.4 (NaOH)). Underpressure was applied underneath the glass bottom of the patch clamp chip to position the hERG cells on the recording sites in the glass bottom of the chip. Following successful cell catch, underpressure was stopped and a seal enhancing solution (containing in mM: 78 NaCl, 60 NMDG, 4 KCl, 10 CaCl ₂ , 1 MgCl ₂ , 5 glucose, 10 HEPES; pH 7.4 (HCl)) was added to the hERG cells to facilitate the formation of stable seals between the membranes of the hERG cells and the glass next to the recording sites. Then, hERG cells were washed several times with wash solution (containing in mM: 87 NaCl, 60 NMDG, 4 KCl, 2 CaCl ₂ , 1 MgCl ₂ , 5 glucose, 10 HEPES; pH 7.4 (HCl)) to remove excess seal enhancing solution. In the meantime, the membrane parts of the hERG cells covering the recording sites were exposed to internal solution (containing in mM: 10 NaCl, 123 KF, 10 EGTA, 10 HEPES; pH 7.2 (KOH)) supplemented with 5-20 µM Escin, and the perforated patch configuration was established. Next, the holding potential was stepwise adjusted to -80 mV, capacitance was compensated, and a series of defined voltage commands was initiated to trigger the hERG current response from the hERG cells (-80 mV for 200 ms, +20 mV for 1000 ms, -40 mV for 500 ms; repeated at a frequency of 0.1 Hz). To determine whether the test item inhibits hERG, different solutions were sequentially applied to the hERG cells: First, a negative control (i.e. wash solution supplemented with 0.3% DMSO and 0.01% HSA) was applied for at least 3 min to investigate the basic electrophysiological properties of the hERG cells as well as define their standard current response. Next, a solution containing the test item at a final concentration of (0.1, 1, or 10) µM was applied for 10 min to measure eventual inhibitory effects of the test item on the hERG current (- the test item solution was produced from a 10 mM DMSO stock by using an automated pipetting device and sequential dilution). Finally, a positive control (i.e. wash solution supplemented with 0.3% DMSO, 0.01% HSA, and 10 µM quinidine) was added to the cells for ~3 min to block the hERG current and, thereby, define the maximum inhibition. For data analysis, experimental results were processed using the automated patch clamp device-specific software as well as a custom-made software, and TIBCO Spotfire. For each successful recording, hERG tail current amplitudes were averaged from three consecutive current responses at the end of the negative control phase, test item phase, and positive control phase, respectively. Resulting mean hERG tail current amplitudes were normalized to the mean hERG tail current amplitude at the end of the negative control phase with nominal 0% inhibition as well as the hERG tail current amplitude at the end of the positive control phase with nominal 100% inhibition. Then, the effect of the test item was calculated as a percentage inhibition value at the test item concentration applied. Finally, percentage inhibition values from all successful recordings at a particular test item concentration were averaged and combined to construct a standard sigmoidal dose response curve, determine the half maximal inhibitory concentration (IC ₅₀ ) of the test item as well as extrapolate its IC ₂₀ . The suitability of the compounds of the present invention can be demonstrated in the following animal models: In vivo assay 1: In vivo pharmacodynamic and efficacy studies All mouse experiments were approved by the relevant regulatory agency (federal state of Berlin, Landesamt für Gesundheit und Soziales Berlin) and were conducted in compliance with the German Animal Welfare Act. Animals were kept in a 12-hour light / dark cycle and maintained under standard conditions at a housing temperature of 23°C. Food and water was available ad libitum. The in vivo efficacy of TEAD inhibitory compound was evaluated at maximal tolerated dose (MTD) or sub-MTD dose in a NCI-H226 mesothelioma tumor xenograft model in NMRI nude mice. NCI-H226 tumor cells were cultivated in RPMI 1640 with GlutaMax (Gibco, Invitrogen GmbH) containing 10% fetal bovine serum (FBS; Sigma) at 37 °C and 5% CO ₂ .5x10 ⁶ tumor cells in 100 µl 100% Matrigel were subcutaneously injected into the right flank of female NMRI nude mice. When tumors were approximately the size of 35- 40 mm², the animals were randomized to treatment and control groups with 12 animals each, and treatment was started the following day. Treatment of each animal was based on individual body weight. Formulation of test compound was in Solutol/Ethanol/water (40/10/50) and applied orally via gavage at different doses and schedules. All application volumes were 10 ml/kg. Tumor diameters were measured using a caliper at least twice a week. Tumor volume (mm ³ ) was calculated using the formula 0.5 a × b ² , where a and b are the long and short diameters of the tumor, respectively. The animal body weight was monitored at least twice a week as a measure for treatment-related toxicity. Control groups were stopped according to animal welfare criteria by decapitation of animals under isofluran anesthesia and tumors, blood and organs (e.g. lung, kidney, liver, spleen, colon, stomach, heart, pancreas, brain) collected for further analysis (necropsy I). Treatment was continued in responding groups until tumor regression flattened out and 3-4 animals per group were subjected to necropsy II. Treatment of the remaining animals was stopped until tumor regrowth was observed and 3-4 animals per group were subjected to necropsy III. Therapy was restarted for the remaining animals and continued until tumor regression leveled again and the last animals were sacrificed and subjected to necropsy IV. For PK analysis, blood samples were collected after decapitation in tubes containing EDTA (Sarstedt) 1, 3, 7 and 24h after the last dose, centrifuged for 5 min at 10000 x g and the plasma supernatant was snap frozen and stored at -20°C. Tumors and selected organs were removed, their weights determined and subsequently divided into two pieces, one of which was snap-frozen and stored at -80°C and one formalin-fixed and paraffin-embedded. For determining the in vivo effects of test compounds on TEAD target gene expression, tumor and organ tissue was lysed in RLT buffer and homogenized using a TissueLyser II (Qiagen). Tissue samples were subjected to RNA extraction using an RNeasy Plus Mini Kit (Qiagen). RNA samples (0.5-1µg) were reverse-transcribed to complementary DNA (cDNA) using SuperScript™ III First-Strand Synthesis SuperMix (Invitrogen). After dilution, cDNA levels of respective genes were quantified by real-time PCR using TaqMan Gene Expression Assays (Applied Biosystems) on a 7500 Fast Real-Time or a ViiA 7 Real-Time PCR System (Applied Biosystems. The evaluated genes and TaqMan Gene Expression Assays are listed in Table 4 below. Relative mRNA expression was calculated using the ΔΔCt method and endogenous GAPDH mRNA expression as reference.

In vivo assay 2: Pharmacokinetics in Rats All animal studies were conducted in accordance with the German Animal Welfare Act and the ethical guidelines of Bayer AG and were approved by the local ethics committee. Female and male Wistar rats were obtained from Charles River (Germany) and had access to food and water ad libitum. All animals were housed according to institutional guidelines under a 12 h/12 h light/dark cycle and maintained under standard conditions (20−22 °C, 50−70% humidity). Rats were housed in Makrolon cages type IV, five animals per cage, fed a pelleted diet (Ssniff, Germany), and used for in vivo studies with a weight of 200−300 g. For in vivo pharmacokinetic experiments, test compounds were administered to female or male Wistar rats intravenously at a dose of 0.3 mg/kg and po at a dose of 0.6 mg/kg formulated as solutions using solubilizers such as PEG400 and EtOH in well-tolerated amounts. Blood samples were collected, for example, at 2 (iv only), 8, 15, 30, and 45 min and 1, 2, 4, 7, and 24 after dosing from the vena jugularis into lithium heparin tubes (Monovette, Sarstedt) and centrifuged for 15 min at 3000 rpm. An aliquot of 100 μL from the supernatant (plasma) was taken and precipitated by the addition of cold acetonitrile (400 μL). Samples were frozen at −20 °C overnight and subsequently thawed and centrifuged at 3000 rpm, 4 °C for 20 min. Aliquots of the supernatant were analyzed with an Agilent HPLC system with LC−MS/MS detection. Pharmacokinetic parameters were calculated by noncompartmental analysis using pharmacokinetics calculation software (e.g., Phoenix WinNonlin, Certara USA, Inc.). The suitability of the compounds can also be demonstrated using the following assays: a) Solubility in DMSO/buffer pH 6.5 Aqueous solubility at pH 6.5 was determined by an orientating high throughput screening method. Lit: Onofrey Th., Kazan, G., Barbagallo, C., Blodgett, J., Weiss, A. Millipore Corporation, Life Sciences Division, Danvers, MA USA 01923: Automated Screening of Aqueous Compound Solubility in Drug Discovery (July 31, 2019) Solubility was determined in PBS buffer pH 6.5 containing 1% DMSO. Test compounds were applied as 1mm DMSO solution. After addition of PBS buffer pH 6.5 solutions were shaken for 24 h at room temperature. Undissolved material was removed by filtration. The compound dissolved in the filtrate was quantified by HPLC-UV. The response was fitted to a one-point standard curve prepared in DMSO. b) Equilibrium Shake Flask Solubility Solubility of solid compound in aqueous buffer was determined by an equilibrium shake flask method. Lit: Kerns, E.H., Di, L. Solubility Methods in: Drug-like Properties: Concepts, Structure Design and Methods, p276-286. Burlington, MA: Academic Press (2008) A saturated solution of drug in solvent (~ 2 mg/ml solvent) was prepared and the solution was mixed for 24 h to ensure that equilibrium has been reached. The solution was centrifuged to remove the insoluble fraction and the concentration of the compound in solution was determined by HPLC-UV using a standard calibration curve. c) Biophysical assay: Thermal Shift Assay cDNA fragments of human TEAD1 (Acc. No P28347; aa 209-426), TEAD2 (Acc. No Q15562; aa 217-447), TEAD3 (Acc. No Q99594; aa 219-435) and TEAD4 (Acc. No Q15561; aa 217-434) were cloned into N-terminal His - tag vector using Gateway technologies. The vector was transfected into E. coli BL21(DE3) using LB 184 medium in the presence of 200 µg/mL Ampicillin. The cells were grown at 37°C until the OD550 reached 1, at which point 0.3 mM IPTG was add and the temperature was lowered to 17°C. The cells were harvested after 24 hours.E. coli cell pellet from 10-liter fermenter was resuspended in 800 mL lysis buffer (25 mM Hepes pH 7.5, 300 mM NaCl, 20 mM Imidazole, 5% Glycerol, Complete-EDTAfree protease inhibitor, 1 mM DTT, 2 µg Benzonase) and lysed by Microfluidics. The soluble protein was separated by centrifugation at 27500 xg for an hour at 4°C. The protein was purified via HisTrap HP affinity chromatography using buffer (25 mM Hepes pH 7.5, 300 mM NaCl, 5% Glycerol, 1 mM DTT) with 40 mM Imidazole for washing and 500 mM Imidazole for elution. The eluted protein was then concentrated and further purified by size exclusion chromatography (Superdex 75 26/60) in 25 mM Hepes pH 7.5, 300 mM NaCl, 5% Glycerol, 1 mM DTT. Pools of Eluate were frozen in nitric oxygen. Experiments were carried out with the ViiA 7TM Real-Time PCR system (Thermo Fisher Scientific) in a 384-well plate format with 5 µl reaction volume. Melting curves were obtained at a protein concentration of 3.4 µM and 8xSYPRO Orange (Invitrogen) using buffer containing 25 mM HEPES pH 7.5; 300 mM NaCl; 1 mM DTT. For binding experiments, Compounds were added from 10 mM stock solution to a final concentration of 100 µM. As control 1% DMSO was used. Scans were measured from 25°C to 95 °C at a scanning rate of 4 °C/min. All TSA data were analyzed using Genedata Assay Analyzer.