Modulators of the adenosine a2a and a2b receptor

Abstract

The present invention relates to the compound of formula (I) and salts, stereoisomers, tautomers, isotopologues, or N-oxides thereof. The present invention is further concerned with inter alia the use of such a compound or salt, stereoisomer, tautomer, isotopologues, or N-oxide thereof as medicament and a pharmaceutical composition comprising said compound.

Description

[0001] Ryvu Therapeutics S.A. R10559WO Ryvu Therapeutics S.A. ul. Leona Henryka Sternbacha 2 30-394 Kraków Poland BioNTech SE An der Goldgrube 12 55131 Mainz Germany Modulators of the adenosine A2A and A2B receptor Field of the Invention The present invention relates to substituted imidazo[1,2‐a]pyrazine compounds and salts, stereoisomers, tautomers, isotopologues, or N-oxides thereof. The present invention is inter alia further concerned with the use of substituted imidazo[1,2‐a]pyrazine com- pounds or salts, stereoisomers, tautomers, isotopologues, or N-oxides thereof as medica- ment and a pharmaceutical composition comprising said compounds. Background of the Invention Cancer cells produce large quantities of mutated proteins (called neoantigens), which - when presented to the immune system - might lead to natural eradication of the tumor. However, to counteract this process, cancer cells produce also specific immunosuppressive metabolites that change the microenvironment and impair the function of immune cells. One of the key metabolites, which works this way is adenosine. Its immunosuppressive function is mediated by adenosine receptors, which are members of the G protein-coupled receptor (GPCR) family and possess seven transmembrane alpha helices. There are 4 sub- types of adenosine receptors described so far: A1, A2A, A2B, A3. They can be coupled to adenylate cyclase either positively (A2A, A2B) or negatively (A1, A3). Only forms A1 and A2A are heavily distributed in immune cells and mainly responsible for immunosuppression me- diated by adenosine. Stressed or injured tissues (i.e. tumor tissue) release endogenous ATP, which works as a proinflammatory agent. Hydrolysis of ATP by endonucleases (such as CD39 and CD73) leads to adenosine formation. Its binding to A2A and A2B receptors leads to cAMP elevation in immune cells and results in the activation of the CREB / ATF pathway (cAMP-responsive element (CRE)-binding protein / activating transcription factor), the cell’s main immunosup- pressive mechanism [Grenz et al Antioxid Redox Signal 2011;15:2221-34,23. Fredholm et al Prog Neurobiol 2007;83:263-76.,24.Sitkovsky Trends Immunol 2009;30:102-8]. Its activation has been shown to either induce anergy of CD4+ T cells or their conversion into Tregs. This subpopulation of T cells is further activated by adenosine and produces immunosuppressive cytokines such as TGF-β and IL-10. Another group of immunosuppressing cells which re- Ryvu Therapeutics S.A. and BioNTech SE R10559WO 2 spond to higher concentration of adenosine are MDSC, which undergo differentiation upon activation by this metabolite (Morrello et al Oncoimmunology. 2016 Mar; 5(3): e1108515). On the other hand, stimulation of adenosine might also lead to decreased cytotoxic activity, e.g. CD8+ lymphocytes lower their secretion of IL-2, Th1 cytokines and IFN-γ, while NK cells produce lower levels of GzmB, NKG2d, CD69 andCD27 [Sitkovsky Trends Immunol 2009;30:102-8]. Dendritic cells and macrophages are also affected by increased amounts of adenosine upon which they start to produce immunosuppressing agents such as IL-8, IL10 and TGFb, and stop production of immunostimulatory cytokines such as IL12, TNFa, IFNg. Adenosine also stimulates in macrophages the conversion of M1 to M2. [Allard et al Curr Opin Pharmacol. 2016 Aug;29:7-16; Allard et al. Immunol Cell Biol 2017 Apr; 95(4) :333- 339.] The above clearly shows that antagonizing adenosine receptors and thus reactivating the anti-tumor immune response may be an effective way of fighting all types of cancer. [Allard et al Curr Opin Pharmacol. 2016 Aug;29:7-16]. It was shown in an allograft model that the use of A2A antagonists not only slows down the tumor growth but also blocks metastasis (in this particular case to lungs). Moreover, a strong synergistic correlation with checkpoint inhibitor antibodies has been demonstrated, likely improving the treatment [Iannone Am J Cancer Res.2014 Mar 1;4(2):172-81, Cancer Immunol Res. 2015 May;3(5):506-17; Allard et al. Immunol Cell Biol 2017 Apr; 95(4) :333-339.]. Antagonists of the A2A receptor have already been shown as promising therapeutic for other diseases. The A2A receptor is abundant in the brain, where it plays a crucial role in the regulation of dopamine and glutamate release. Not surprisingly, the A2A receptor antag- onists have been proposed useful in treatment of neurodegenerative disorders such as Parkinson's, Huntington's and Alzheimer's disease causing motor impairment, which can be improved by employment of A2A antagonists [Tuite P, et al., J. Expert Opin. Investig. Drugs. 2003; 12, 1335-52; Popoli P. et al. J Neurosci. 2002; 22, 1967-75; and Dall'lgna, et al., Experi- mental Neurology, 2007, 241-245]. Additionally, A2A antagonists may be used for the treat- ment of psychosis, stroke, extra pyramidal syndrome, e.g., dystonia, akathisia, pseu- doparkinsonism and tardive dyskinesia (see Jenner P. J Neurol. 2000; 247 Suppl2: 1143-50) and attention related disorders such as attention deficit disorder (ADD) and attention deficit hyperactivity disorder (ADHD). Furthermore, A2A antagonists have been shown as useful agents for the treatment of amyotrophic lateral sclerosis (US 2007037033), cirrhosis, fibrosis and fatty liver (WO 01 / 058241) and the mitigation of addictive behavior (WO 06 / 009698). Adenosine A2A antagonists may be useful for the treatment and prevention of dermal fibrosis in diseases such as scleroderma (Chan et al. Arthritis & Rheumatism, 2006, 54(8), 2632-2642). Recently antagonists of A2A receptors were shown to possess the thera- peutic potential as neuroprotectants (Stone TW. et al., Drag. Dev. Res.2001 , 52, 323-330), in the treatment of migraine (Kurokowa et al., 2009. Program No. 714.4 / B101. 2009 Neuro- science Meeting Planner. Chicago, IL: Society for Neuroscience) and a sleep disorder (Dun- widdie TV et al., Ann. Rev. Neurosci. 2001 , 24, 31- 55). WO 2017 / 098421 discloses in- hibitors of CD73, wherein CD73 catalyzes the conversion of AMP to adenosine and is thought to be the major contributor to extracellular adenosine, in particular in the tumor mi- croenvironment. CD73 inhibition results in decreased extracellular adenosine such that the activity of the A2A receptor is decreased, resulting in less (or no) immunosuppression – ex- actly the effect achieved with A2A receptor antagonists. It can thus be assumed that the diseases disclosed in WO 2017 / 098421 may also be treated by A2A antagonists. Ryvu Therapeutics S.A. and BioNTech SE R10559WO 3 There is growing evidence that also the A2B receptor plays an important role in cancer pro- gression, especially in immune suppression in tumor microenvironment, as well as tumor proliferation, angiogenesis, metastasis (Zhan-Guo Gao et al., Int J Mol Sci. 2019; 20(20): 5139). It was shown that A2BR expression is significantly upregulated under many patho- logical conditions such as hypoxia, inflammation, and cancer (Borea PA et al.,Trends Phar- macol Sci. 2016; 37(6):419-434, Borea PA et al., Physiol Rev.2018 ; 98(3):1591-1625, Cekic C and Linden J Nat Rev Immunol. 2016; 16(3):177-92.). Particularly bladder urothelial carci- noma expresses high levels of A2BAR and it is suggested to be associated with a poor pa- tient prognosis (Zhou Y et al.; Oncotarget. 2017; 8(30):48755-48768). Moreover, it was pos- tulated that A2BR controls cellular proliferation via HIF-1α activation, which may indicate that A2BR may be a key regulator of oral squamous cell carcinoma progression (Kasama H et al. BMC Cancer. 2015; 15:563). Additionally, A2BR antagonists have already been sug- gested as promising therapeutic approach for other diseases such as idiopathic pulmonary fibrosis (J. Clin. Invest.116:2173–2182 (2006), Liu et al., Journal of Nanobiotechnology. 2018, 17(45); Karmouty-Quintana et al., FASEB J.29, 50-60 (2015)), systemic sclerosis (H Kar- mouty‐Quintana; Arthritis & Reumatology 2018; Vol. 70, No.10, 1673–1684) and broader - all the fibrotic diseases (Bruce N. Cronstein F1000 Biol Reports 2011, 3:21). Yet another in- dication where A2BR might play significant role is Irritable Bowel Disease (Teita Asano and Mitsuko Takenaga J Clin Med. 20176(11): 104). Moreover, it was shown that analgesic ef- fects might be achieved by antagonization of A2BR (J Pharmacol Exp Ther. 2004; 308(1):358-66.). Finally, there is a link between chronic kidney disease, in particular diabetic nephropathy, and A2B such that the use of A2B-antagonists seems to be promising for the treatment of chronic kidney disease, in particular diabetic nephropathy (Cardenas et al., Lab Invest.2013 Jan; 93(1):135-44). In view of the above, there is the need for further compounds, which antagonize the A2A receptor in order to be capable of treating the afore-mentioned diseases. Furthermore, there is also the need for further compounds, which antagonize the A2B receptor and in particular both, the A2A and the A2B receptors. Objects and Summary of the Invention It is an object of the present invention to provide compounds, which antagonize the adenosine A2A receptor. It is another object of the present invention to provide compounds, which are capable of treating diseases, which are linked to the adenosine A2A receptor. It is another object of the present invention to provide compounds, which antagonize the adenosine A2B receptor. It is another object of the present invention to provide compounds, which are capable of treating diseases, which are linked to the adenosine A2B receptor. It is another object of the present invention to provide compounds, which antagonize the adenosine A2A and A2B receptors. It is another object of the present invention to provide compounds, which are capable of treating diseases, which are linked to the adenosine A2A and A2B receptors. It is another object of the present invention to provide compounds, which antagonize the adenosine A2A receptor at a low agonist, e.g. adenosine, concentration. Ryvu Therapeutics S.A. and BioNTech SE R10559WO 4 It is another object of the present invention to provide compounds, which antagonize the adenosine A2B receptor at a low agonist, e.g. adenosine, concentration. It is another object of the present invention to provide compounds, which antagonize the adenosine A2A and A2B receptors at a low agonist, e.g. adenosine, concentration. It is another object of the present invention to provide compounds, which antagonize the adenosine A2A receptor at a high agonist, e.g. adenosine, concentration. It is another object of the present invention to provide compounds, which antagonize the adenosine A2B receptor at a high agonist, e.g. adenosine, concentration. It is another object of the present invention to provide compounds, which antagonize the adenosine A2A and A2B receptors at a high agonist, e.g. adenosine, concentration. In combination with the afore-mentioned objects, it is another object of the present inven- tion to provide compounds, which in addition exhibit a low CYP-inhibition profile. It is still another object of the present invention to provide compounds, which are suitable for the treatment of a disease selected from the group consisting of cancer, Parkinson's dis- ease, Huntington's disease, Alzheimer's disease, psychosis, stroke, extra pyramidal syn- drome, attention deficit disorder (ADD), attention deficit hyperactivity disorder (ADHD), amyotrophic lateral sclerosis, cirrhosis, fibrosis, fatty liver, addictive behavior, dermal fibro- sis, a sleep disorder, AIDS, autoimmune diseases, infections, atherosclerosis and ischemia- reperfusion injury. In particular, it is an object of the present invention to provide compounds, which are suit- able for the treatment of cancer, wherein this relates to the treatment of the tumor and the block of metastases. The above objects and others can be achieved in particular by the compounds of formula (I) as defined herein in the first aspect, as well as the further aspect disclosed herein. The inventors of the present invention inter alia found that the compounds of formula (I), as defined herein below in the first aspect, antagonize adenosine A2A receptor activity. Fur- thermore, the inventors of the present invention inter alia found that the compounds of for- mula (I), as defined herein below in the first aspect, antagonize adenosine A2B receptor ac- tivity. Furthermore, the inventors of the present invention inter alia found that the com- pounds of formula (I), as defined herein below in the first aspect, antagonize both adeno- sine A2A and A2B receptor activity. Accordingly, the compounds of formula (I) or a pharmaceutical composition comprising a compound of formula (I), as defined herein below in the second aspect can be used for the treatment of diseases linked to the adenosine A2A receptor, in particular the diseases given herein and most preferably cancer. Furthermore, the compounds of formula (I) or a pharma- ceutical composition comprising a compound of formula (I) as defined herein below in the second aspect can be used for the treatment of diseases linked to the adenosine A2B re- ceptor, in particular the diseases given herein and most preferably cancer. Furthermore, the compounds of formula (I) or a pharmaceutical composition comprising a compound of for- mula (I) as defined herein below in the second aspect can be used for the treatment of dis- eases linked to both the adenosine A2A and A2B receptors, in particular the diseases given herein and most preferably cancer. Ryvu Therapeutics S.A. and BioNTech SE R10559WO 5 Therefore, in the first aspect, the present invention relates to a compound of formula (I) or a salt, stereoisomer, tautomer, isotopologue, or N-oxide thereof, wherein G1is phenyl, wherein one or two of the substitutable carbon atoms in the aforementioned phenyl is substituted with same or different substituents selected from the group con- sisting of halogen, CN, NO2, C1-C4-alkyl, C1-C4-haloalkyl, C2-C4-alkenyl, C2-C4- haloalkenyl, C2-C4-alkynyl, C2-C4-haloalkynyl, OH, O(C1-C4-alkyl), NH2, NH(C1-C4- alkyl), an d N(C1-C4-alkyl)(C1-C4-alkyl); G2is selected from the group co nsisting of G3is C(=O)N(R4a)(R4b); R1ais selected from the group consisting of H, halogen, CN, NO2, C1-C4-alkyl, C1-C4- haloalkyl, C2-C4-alkenyl, C2-C4-haloalkenyl, C2-C4-alkynyl, C2-C4-haloalkynyl, OH, O(C1- C4-alkyl), NH2, NH(C1-C4-alkyl), and N(C1-C4-alkyl)(C1-C4-alkyl); R1bis selected from the group consisting of H, halogen, CN, NO2, C1-C4-alkyl, C1-C4- haloalkyl, C2-C4-alkenyl, C2-C4-haloalkenyl, C2-C4-alkynyl, C2-C4-haloalkynyl, OH, O(C1- C4-alkyl), NH2, NH(C1-C4-alkyl), and N(C1-C4-alkyl)(C1-C4-alkyl); R1cis selected from the group consisting of H, halogen, CN, NO2, C1-C4-alkyl, C1-C4- haloalkyl, C2-C4-alkenyl, C2-C4-haloalkenyl, C2-C4-alkynyl, C2-C4-haloalkynyl, OH, O(C1- C4-alkyl), NH2, NH(C1-C4-alkyl), and N(C1-C4-alkyl)(C1-C4-alkyl); R2ais selected from the group consisting of H, halogen, CN, NO2, C1-C4-alkyl, C1-C4- haloalkyl, C2-C4-alkenyl, C2-C4-haloalkenyl, C2-C4-alkynyl, C2-C4-haloalkynyl, OH, O(C1- C4-alkyl), NH2, NH(C1-C4-alkyl), and N(C1-C4-alkyl)(C1-C4-alkyl); R2bis selected from the group consisting of H, halogen, CN, NO2, C1-C4-alkyl, C1-C4- haloalkyl, C2-C4-alkenyl, C2-C4-haloalkenyl, C2-C4-alkynyl, C2-C4-haloalkynyl, OH, O(C1- C4-alkyl), NH2, NH(C1-C4-alkyl), and N(C1-C4-alkyl)(C1-C4-alkyl); R2cis selected from the group consisting of H, halogen, CN, NO2, C1-C4-alkyl, C1-C4- haloalkyl, C2-C4-alkenyl, C2-C4-haloalkenyl, C2-C4-alkynyl, C2-C4-haloalkynyl, OH, O(C1- C4-alkyl), NH2, NH(C1-C4-alkyl), and N(C1-C4-alkyl)(C1-C4-alkyl); R4ais selected from the group consisting of H, C1-C4-alkyl, C1-C4-haloalkyl, C2-C4-alkenyl, C2-C4-haloalkenyl, C2-C4-alkynyl, and C2-C4-haloalkynyl; R4bis a 5-membered saturated, partially unsaturated or fully unsaturated carbobicyclic or heterobicyclic ring, wherein said heterobicyclic ring comprises one or more, same or different heteroatoms selected from O, N or S, wherein said N- and / or S-atoms are in- Ryvu Therapeutics S.A. and BioNTech SE R10559WO 6 dependently oxidized or non-oxidized, and wherein each substitutable carbon or het- ero-atom in the aforementioned moieties is unsubstituted or substituted with one or more, same or different substituents R5; wherein R5(i) is selected from the group consisting of halogen, CN, NO2, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, a 3- to 9-membered saturated, partially unsaturated or fully unsatu- rated carbocyclic or heterocyclic ring, and a 4- to 14-membered saturated, partially unsaturated or fully unsaturated carbobicyclic or heterobicyclic ring, wherein said heterocyclic or heterobicyclic ring comprises one or more, same or different het- eroatoms selected from O, N or S, wherein said N- and / or S-atoms are indepen- dently oxidized or non-oxidized, and wherein each substitutable carbon or hetero- atom in the aforementioned moieties is unsubstituted or substituted with one or more, same or different substituents R6; or (ii) is selected from the group consisting of C(=O)R7, C(=O)OR8, C(=O)N(R8a)(R8b), OR8, N(R8a)(R8b), N(R8)C(=O)R7, N(R8)C(=O)OR8, and N(R8)C(=O)N(R8a)(R8b); or (iii) together with a second R5on one carbon atom forms =O; wherein R6(i) is selected from the group consisting of halogen, CN, NO2, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, a 3- to 9-membered saturated, partially unsaturated or fully unsatu- rated carbocyclic or heterocyclic ring, and a 4- to 14-membered saturated, partially unsaturated or fully unsaturated carbobicyclic or heterobicyclic ring, wherein said heterocyclic or heterobicyclic ring comprises one or more, same or different het- eroatoms selected from O, N or S, wherein said N- and / or S-atoms are indepen- dently oxidized or non-oxidized, and wherein each substitutable carbon or hetero- atom in the aforementioned moieties is unsubstituted or substituted with one or more, same or different substituents R9; or (ii) is selected from the group consisting of C(=O)R10, C(=O)OR11, C(=O)N(R11a)(R11b), OR11, N(R11a)(R11b), N(R11)C(=O)R10, N(R11)C(=O)OR11, and N(R11)C(=O)N(R11a)(R11b); wherein R7, R8, R8a, R8bare independently selected from the group consisting of H, C1-C6- alkyl, C2-C6-alkenyl, C2-C6-alkynyl, a 3- to 9-membered saturated, partially unsatu- rated or fully unsaturated carbocyclic or heterocyclic ring, and a 4- to 14-membered saturated, partially unsaturated or fully unsaturated carbobicyclic or heterobicyclic ring, wherein said heterocyclic or heterobicyclic ring comprises one or more, same or different heteroatoms selected from O, N or S, wherein said N- and / or S-atoms are in- dependently oxidized or non-oxidized, and wherein each substitutable carbon or het- ero-atom in the aforementioned moieties is unsubstituted or substituted with one or more, same or different substituents R12; wherein R9is selected from the group consisting of halogen, CN, NO2, C1-C6-alkyl, C2-C6- alkenyl, C2-C6-alkynyl, a 3- to 9-membered saturated, partially unsaturated or fully un- saturated carbocyclic or heterocyclic ring, and a 4- to 14-membered saturated, par- tially unsaturated or fully unsaturated carbobicyclic or heterobicyclic ring, wherein said heterocyclic or heterobicyclic ring comprises one or more, same or different het- eroatoms selected from O, N or S, wherein said N- and / or S-atoms are independently oxidized or non-oxidized, and wherein each substitutable carbon or hetero-atom in the aforementioned moieties is unsubstituted or substituted with one or more, same or different substituents R13; Ryvu Therapeutics S.A. and BioNTech SE R10559WO 7 wherein R10, R11, R11a, R11bare independently selected from the group consisting of H, C1-C4- alkyl, C1-C4-haloalkyl, C2-C4-alkenyl, C2-C4-haloalkenyl, C2-C4-alkynyl, and C2-C4- haloalkynyl; wherein R12is selected from the group consisting of halogen, CN, NO2, OH, O(C1-C4-alkyl), NH2, NH(C1-C4-alkyl), and N(C1-C4-alkyl)(C1-C4-alkyl), C1-C6-alkyl, C2-C6-alkenyl, C2- C6-alkynyl, a 3- to 9-membered saturated, partially unsaturated or fully unsaturated carbocyclic or heterocyclic ring, and a 4- to 14-membered saturated, partially unsatu- rated or fully unsaturated carbobicyclic or heterobicyclic ring, wherein said hetero- cyclic or heterobicyclic ring comprises one or more, same or different heteroatoms se- lected from O, N or S, wherein said N- and / or S-atoms are independently oxidized or non-oxidized, and wherein each substitutable carbon or hetero-atom in the aforemen- tioned moieties is unsubstituted or substituted with one or more, same or different substituents R14; and wherein R13, R14are independently selected from the group consisting of halogen, CN, NO2, C1-C6-alkyl, C1-C6-haloalkyl, C2-C6-alkenyl, C2-C6-haloalkenyl, C2-C6-alkynyl, C2-C6- haloalkynyl, OH, O(C1-C4-alkyl), NH2, NH(C1-C4-alkyl), and N(C1-C4-alkyl)(C1-C4-alkyl). In an embodiment of the first aspect, G1is phenyl, wherein one or two of the substitutable carbon atoms in the aforementioned phenyl is substituted with same or different sub- stituents selected from the group consisting of CH3, halogen and CN. In a further embodiment of the first aspect, G1is phenyl, wherein one or two of the substi- tutable carbon atoms in the aforementioned phenyl is substituted with same or different substituents selected from the group consisting of CH3, F, and CN. In a further embodiment of the first aspect, G1is phenyl, wherein one or two of the substi- tutable carbon atoms in the aforementioned phenyl is substituted with F. In a preferred embodiment of the first aspect, G1is 4-fluorophenyl. In another embodiment of the first aspect, R1ais selected from the group consisting of H and halogen. It can be preferred in this embodiment that R1ais selected from the group con- sisting of H and Cl. In another embodiment of the first aspect, R1bis selected from the group consisting of H and halogen. It can be preferred in this embodiment that R1bis selected from the group con- sisting of H and Cl. In another embodiment of the first aspect, R1cis selected from the group consisting of H and halogen. It can be preferred in this embodiment that R1cis selected from the group con- sisting of H and Cl. In another embodiment of the first aspect, R2ais C1-C3-alkyl. It can be preferred in this em- bodiment that R2ais CH3. Ryvu Therapeutics S.A. and BioNTech SE R10559WO 8 In another embodiment of the first aspect, R2bis C1-C3-alkyl. It can be preferred in this em- bodiment that R2bis CH3. In another embodiment of the first aspect, R2cis C1-C3-alkyl. It can be preferred in this em- bodiment that R2cis CH3. In yet another embodiment of the first aspect, R4ais H. In a preferred embodiment of the first aspect, G1is phenyl, wherein one or two of the sub- stitutable carbon atoms in the aforementioned phenyl is substituted with same or different substituents selected from the group consisting of CH3, F, and CN; R1ais selected from the group consisting of H and Cl; R1bis selected from the group consisting of H and Cl; R1cis selected from the group consisting of H and Cl; R2ais CH3; R2bis CH3; R2cis CH3; and R4ais H. In another preferred embodiment of the first aspect, G1is phenyl, wherein one or two of the substitutable carbon atoms in the aforementioned phenyl is substituted with same or different substituents selected from the group con- sisting of CH3, F and CN; G2is selected from the group co nsisting of G3is C(=O)N(R4a)(R4b); R1ais selected from the group consisting of H and Cl; R1bis selected from the group consisting of H and Cl; R1cis selected from the group consisting of H and Cl; R2ais CH3; R2bis CH3; R2cis CH3; R4ais H; R4bis a 5-membered saturated, partially unsaturated or fully unsaturated carbobicyclic or heterobicyclic ring, wherein said heterobicyclic ring comprises one or more, same or different heteroatoms selected from O, N or S, wherein said N- and / or S-atoms are in- dependently oxidized or non-oxidized, and wherein each substitutable carbon or het- ero-atom in the aforementioned moieties is unsubstituted or substituted with one or more, same or different substituents R5; wherein R5 Ryvu Therapeutics S.A. and BioNTech SE R10559WO 9 (i) is selected from the group consisting of halogen, CN, NO2, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, a 3- to 9-membered saturated, partially unsaturated or fully unsatu- rated carbocyclic or heterocyclic ring, and a 4- to 14-membered saturated, partially unsaturated or fully unsaturated carbobicyclic or heterobicyclic ring, wherein said heterocyclic or heterobicyclic ring comprises one or more, same or different het- eroatoms selected from O, N or S, wherein said N- and / or S-atoms are indepen- dently oxidized or non-oxidized, and wherein each substitutable carbon or hetero- atom in the aforementioned moieties is unsubstituted or substituted with one or more, same or different substituents R6; or (ii) is selected from the group consisting of C(=O)R7, C(=O)OR8, C(=O)N(R8a)(R8b), OR8, N(R8a)(R8b), N(R8)C(=O)R7, N(R8)C(=O)OR8, and N(R8)C(=O)N(R8a)(R8b); or (iii) together with a second R5on one carbon atom forms =O; wherein R6(i) is selected from the group consisting of halogen, CN, NO2, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, a 3- to 9-membered saturated, partially unsaturated or fully unsatu- rated carbocyclic or heterocyclic ring, and a 4- to 14-membered saturated, partially unsaturated or fully unsaturated carbobicyclic or heterobicyclic ring, wherein said heterocyclic or heterobicyclic ring comprises one or more, same or different het- eroatoms selected from O, N or S, wherein said N- and / or S-atoms are indepen- dently oxidized or non-oxidized, and wherein each substitutable carbon or hetero- atom in the aforementioned moieties is unsubstituted or substituted with one or more, same or different substituents R9; or (ii) is selected from the group consisting of C(=O)R10, C(=O)OR11, C(=O)N(R11a)(R11b), OR11, N(R11a)(R11b), N(R11)C(=O)R10, N(R11)C(=O)OR11, and N(R11)C(=O)N(R11a)(R11b); wherein R7, R8, R8a, R8bare independently selected from the group consisting of H, C1-C6- alkyl, C2-C6-alkenyl, C2-C6-alkynyl, a 3- to 9-membered saturated, partially unsatu- rated or fully unsaturated carbocyclic or heterocyclic ring, and a 4- to 14-membered saturated, partially unsaturated or fully unsaturated carbobicyclic or heterobicyclic ring, wherein said heterocyclic or heterobicyclic ring comprises one or more, same or different heteroatoms selected from O, N or S, wherein said N- and / or S-atoms are in- dependently oxidized or non-oxidized, and wherein each substitutable carbon or het- ero-atom in the aforementioned moieties is unsubstituted or substituted with one or more, same or different substituents R12; wherein R9is selected from the group consisting of halogen, CN, NO2, C1-C6-alkyl, C2-C6- alkenyl, C2-C6-alkynyl, a 3- to 9-membered saturated, partially unsaturated or fully un- saturated carbocyclic or heterocyclic ring, and a 4- to 14-membered saturated, par- tially unsaturated or fully unsaturated carbobicyclic or heterobicyclic ring, wherein said heterocyclic or heterobicyclic ring comprises one or more, same or different het- eroatoms selected from O, N or S, wherein said N- and / or S-atoms are independently oxidized or non-oxidized, and wherein each substitutable carbon or hetero-atom in the aforementioned moieties is unsubstituted or substituted with one or more, same or different substituents R13; wherein R10, R11, R11a, R11bare independently selected from the group consisting of H, C1-C4- alkyl, C1-C4-haloalkyl, C2-C4-alkenyl, C2-C4-haloalkenyl, C2-C4-alkynyl, and C2-C4- haloalkynyl; Ryvu Therapeutics S.A. and BioNTech SE R10559WO 10 wherein R12is selected from the group consisting of halogen, CN, NO2, OH, O(C1-C4-alkyl), NH2, NH(C1-C4-alkyl), and N(C1-C4-alkyl)(C1-C4-alkyl), C1-C6-alkyl, C2-C6-alkenyl, C2- C6-alkynyl, a 3- to 9-membered saturated, partially unsaturated or fully unsaturated carbocyclic or heterocyclic ring, and a 4- to 14-membered saturated, partially unsatu- rated or fully unsaturated carbobicyclic or heterobicyclic ring, wherein said hetero- cyclic or heterobicyclic ring comprises one or more, same or different heteroatoms se- lected from O, N or S, wherein said N- and / or S-atoms are independently oxidized or non-oxidized, and wherein each substitutable carbon or hetero-atom in the aforemen- tioned moieties is unsubstituted or substituted with one or more, same or different substituents R14; and wherein R13, R14are independently selected from the group consisting of halogen, CN, NO2, C1-C6-alkyl, C1-C6-haloalkyl, C2-C6-alkenyl, C2-C6-haloalkenyl, C2-C6-alkynyl, C2-C6- haloalkynyl, OH, O(C1-C4-alkyl), NH2, NH(C1-C4-alkyl), and N(C1-C4-alkyl)(C1-C -alkyl). 4 In yet another em bodiment of the first aspect, G2is selected from the group consisting of In another preferred embodiment of the first aspect, G2is In another em ent of the fi rst asp ect, G2is selected from the gr oup consisting of wherein R1ais H; R1bis H; R1cis H; R2ais CH3; R2bis CH3; and R2cis CH3. In another embodim ent of the first a spect, G2is se lected from the group consisting of Ryvu Therapeutics S.A. and BioNTech SE R10559WO 11 wherein R1bis H; R1cis H; R2bis CH3; and R2cis CH3. In a preferred embo diment of the first aspect, G2is wherein R1bis H; and R2bis CH3. In a further embodiment of the first aspect, G3is C(=O)N(R4a)(R4b), wherein R4ais H; and R4bis bicyclo[1.1.1]pentan-1-yl, wherein each substitutable carbon-atom in the aforementioned bicyclo[1.1.1]pentan-1-yl is unsubstituted or substituted with one or more, same or different substituents R5; wherein R5(i) is selected from the group consisting of halogen, CN, NO2, C1-C6-alkyl, C2-C6- alkenyl, C2-C6-alkynyl, a 3- to 9-membered saturated, partially unsaturated or fully unsaturated carbocyclic or heterocyclic ring, and a 4- to 14-membered saturated, partially unsaturated or fully unsaturated carbobicyclic or heterobicyclic ring, wherein said heterocyclic or heterobicyclic ring comprises one or more, same or dif- ferent heteroatoms selected from O, N or S, wherein said N- and / or S-atoms are independently oxidized or non-oxidized, and wherein each substitutable carbon or hetero-atom in the aforementioned moieties is unsubstituted or substituted with one or more, same or different substituents R6; or (ii) is selected from the group consisting of C(=O)R7, C(=O)OR8, C(=O)N(R8a)(R8b), OR8, N(R8a)(R8b), N(R8)C(=O)R7, N(R8)C(=O)OR8, and N(R8)C(=O)N(R8a)(R8b); or (iii) together with a second R5on one carbon atom forms =O; wherein R6(i) is selected from the group consisting of halogen, CN, NO2, C1-C6-alkyl, C2-C6- alkenyl, C2-C6-alkynyl, a 3- to 9-membered saturated, partially unsaturated or fully unsaturated carbocyclic or heterocyclic ring, and a 4- to 14-membered saturated, partially unsaturated or fully unsaturated carbobicyclic or heterobicyclic ring, wherein said heterocyclic or heterobicyclic ring comprises one or more, same or dif- ferent heteroatoms selected from O, N or S, wherein said N- and / or S-atoms are independently oxidized or non-oxidized, and wherein each substitutable carbon or hetero-atom in the aforementioned moieties is unsubstituted or substituted with one or more, same or different substituents R9; or (ii) is selected from the group consisting of C(=O)R10, C(=O)OR11, C(=O)N(R11a)(R11b), OR11, N(R11a)(R11b), N(R11)C(=O)R10, N(R11)C(=O)OR11, and N(R11)C(=O)N(R11a)(R11b); Ryvu Therapeutics S.A. and BioNTech SE R10559WO 12 wherein R7, R8, R8a, R8bare independently selected from the group consisting of H, C1-C6- alkyl, C2-C6-alkenyl, C2-C6-alkynyl, a 3- to 9-membered saturated, partially unsatu- rated or fully unsaturated carbocyclic or heterocyclic ring, and a 4- to 14-membered saturated, partially unsaturated or fully unsaturated carbobicyclic or heterobicyclic ring, wherein said heterocyclic or heterobicyclic ring comprises one or more, same or different heteroatoms selected from O, N or S, wherein said N- and / or S-atoms are in- dependently oxidized or non-oxidized, and wherein each substitutable carbon or het- ero-atom in the aforementioned moieties is unsubstituted or substituted with one or more, same or different substituents R12; wherein R9is selected from the group consisting of halogen, CN, NO2, C1-C6-alkyl, C2-C6- alkenyl, C2-C6-alkynyl, a 3- to 9-membered saturated, partially unsaturated or fully un- saturated carbocyclic or heterocyclic ring, and a 4- to 14-membered saturated, par- tially unsaturated or fully unsaturated carbobicyclic or heterobicyclic ring, wherein said heterocyclic or heterobicyclic ring comprises one or more, same or different het- eroatoms selected from O, N or S, wherein said N- and / or S-atoms are independently oxidized or non-oxidized, and wherein each substitutable carbon or hetero-atom in the aforementioned moieties is unsubstituted or substituted with one or more, same or different substituents R13; wherein R10, R11, R11a, R11bare independently selected from the group consisting of H, C1-C4- alkyl, C1-C4-haloalkyl, C2-C4-alkenyl, C2-C4-haloalkenyl, C2-C4-alkynyl, and C2-C4- haloalkynyl; wherein R12is selected from the group consisting of halogen, CN, NO2, OH, O(C1-C4-alkyl), NH2, NH(C1-C4-alkyl), and N(C1-C4-alkyl)(C1-C4-alkyl), C1-C6-alkyl, C2-C6-alkenyl, C2- C6-alkynyl, a 3- to 9-membered saturated, partially unsaturated or fully unsaturated carbocyclic or heterocyclic ring, and a 4- to 14-membered saturated, partially unsatu- rated or fully unsaturated carbobicyclic or heterobicyclic ring, wherein said hetero- cyclic or heterobicyclic ring comprises one or more, same or different heteroatoms se- lected from O, N or S, wherein said N- and / or S-atoms are independently oxidized or non-oxidized, and wherein each substitutable carbon or hetero-atom in the aforemen- tioned moieties is unsubstituted or substituted with one or more, same or different substituents R14; and wherein R13, R14are independently selected from the group consisting of halogen, CN, NO2, C1-C6-alkyl, C1-C6-haloalkyl, C2-C6-alkenyl, C2-C6-haloalkenyl, C2-C6-alkynyl, C2-C6- haloalkynyl, OH, O(C1-C4-alkyl), NH2, NH(C1-C4-alkyl), and N(C1-C4-alkyl)(C1-C4-alkyl). In another embodiment of the first aspect, G3is C(=O)N(R4a)(R4b), wherein R4ais H; and R4bis bicyclo[1.1.1]pentan-1-yl, wherein each substitutable carbon-atom in the aforementioned bicyclo[1.1.1]pentan-1-yl is unsubstituted or substituted with one or more, same or different substituents R5; wherein R5is selected from the group consisting of halogen, C1-C4-alkyl, a 3- to 9-mem- bered saturated, partially unsaturated or fully unsaturated carbocyclic or heterocyclic ring and a 4- to 14-membered saturated, partially unsaturated or fully unsaturated carbobicyclic or heterobicyclic ring, wherein said heterocyclic or heterobicyclic ring comprises one or more, same or different heteroatoms selected from O, N or S, wherein said N- and / or S-atoms are independently oxidized or non-oxidized, and Ryvu Therapeutics S.A. and BioNTech SE R10559WO 13 wherein each substitutable carbon or hetero-atom in the aforementioned moieties is unsubstituted or substituted with one or more, same or different substituents R6; wherein R6(i) is selected from the group consisting of halogen, C1-C4-alkyl, a 3- to 9-membered sat- urated, partially unsaturated or fully unsaturated carbocyclic or heterocyclic ring, and a 4- to 14-membered saturated, partially unsaturated or fully unsaturated carbobi- cyclic or heterobicyclic ring, wherein said heterocyclic or heterobicyclic ring comprises one or more, same or different heteroatoms selected from O, N or S, wherein said N- and / or S-atoms are independently oxidized or non-oxidized, and wherein each substi- tutable carbon or hetero-atom in the aforementioned moieties is unsubstituted or sub- stituted with one or more, same or different substituents R9; or (ii) is selected from the group consisting of C(=O)R10, C(=O)OR11, C(=O)N(R11a)(R11b), OR11, N(R11a)(R11b), N(R11)C(=O)R10, N(R11)C(=O)OR11, and N(R11)C(=O)N(R11a)(R11b); wherein R9is selected from the group consisting of halogen and C1-C4-alkyl, wherein each substitutable carbon in the aforementioned C1-C4-alkyl is unsubstituted or substituted with one or more, same or different substituents R13; wherein R10, R11, R11a, R11bare independently selected from the group consisting of H, C1-C4- alkyl, and C1-C4-haloalkyl; and wherein R13is selected from the group consisting of halogen, C1-C4-alkyl, and C1-C4- haloalkyl. In another preferred embodiment of the first aspect, G3is C(=O)N(R4a)(R4b), wherein R4ais H; R4bis unsubstituted bicyclo[1.1.1]pentan-1-yl. In yet another embodiment of the first aspect, said compound is selected from the group consisting of 8-amino-N-{3-[(dimethylamino)methyl]bicyclo[1.1.1]pentan-1-yl}-6-(4- fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide; 8-amino-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}-N-{3-[(morpholin-4- yl)methyl]bicyclo[1.1.1]pentan-1-yl}imidazo[1,2-a]pyrazine-2-carboxamide; 8-amino-6-(4- fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}-N-{3-[(4-methylpiperazin-1- yl)methyl]bicyclo[1.1.1]pentan-1-yl}imidazo[1,2-a]pyrazine-2-carboxamide; 8-amino-6-(4- fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}-N-[3-({2-oxa-6-azaspiro[3.3]heptan- 6-yl}methyl)bicyclo[1.1.1]pentan-1-yl]imidazo[1,2-a]pyrazine-2-carboxamide; 8-amino-N- (3-{[(2,2-difluoroethyl)amino]methyl}bicyclo[1.1.1]pentan-1-yl)-6-(4-fluorophenyl)-5-{3- methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide; 8-amino-N-(3- {[(2,2-difluoroethyl)(methyl)amino]methyl}bicyclo[1.1.1]pentan-1-yl)-6-(4-fluorophenyl)-5- {3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide; 8-amino-N-{3- [(4,4-difluoropiperidin-1-yl)methyl]bicyclo[1.1.1]pentan-1-yl}-6-(4-fluorophenyl)-5-{3- methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide; 8-amino-N-(3- {[(2-fluoroethyl)amino]methyl}bicyclo[1.1.1]pentan-1-yl)-6-(4-fluorophenyl)-5-{3-methylim- idazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide; 8-amino-N-{3-[(3,3-di- fluoropyrrolidin-1-yl)methyl]bicyclo[1.1.1]pentan-1-yl}-6-(4-fluorophenyl)-5-{3-methylim- idazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide; 8-amino-6-(4- fluorophenyl)-N-(3-{[methyl(2,2,2-trifluoroethyl)amino]methyl}bicyclo[1.1.1]pentan-1-yl)-5- {3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide; 8-amino-6-(4- fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}-N-(3-{[(2,2,2-trifluoro- Ryvu Therapeutics S.A. and BioNTech SE R10559WO 14 ethyl)amino]methyl}bicyclo[1.1.1]pentan-1-yl)imidazo[1,2-a]pyrazine-2-carboxamide; 8- amino-N-{3-[(3,3-difluoroazetidin-1-yl)methyl]bicyclo[1.1.1]pentan-1-yl}-6-(4- fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide; 8-amino-N-{3-[(3-fluoroazetidin-1-yl)methyl]bicyclo[1.1.1]pentan-1-yl}-6-(4-fluorophenyl)- 5-{3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide; 8-amino-N- (3-{[(1,3-difluoropropan-2-yl)amino]methyl}bicyclo[1.1.1]pentan-1-yl)-6-(4-fluorophenyl)- 5-{3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide; 8-amino-6- (4-fluorophenyl)-N-{3-[(N-methylacetamido)methyl]bicyclo[1.1.1]pentan-1-yl}-5-{3-methyl- imidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide; 8-amino-N-{3-fluorobi- cyclo[1.1.1]pentan-1-yl}-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}im- idazo[1,2-a]pyrazine-2-carboxamide; 8-amino-6-(4-fluorophenyl)-N-[3-(1-hydroxyethyl)bi- cyclo[1.1.1]pentan-1-yl]-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2- carboxamide; 8-amino-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}-N-[3- (pyrrolidin-1-yl)bicyclo[1.1.1]pentan-1-yl]imidazo[1,2-a]pyrazine-2-carboxamide; 8-amino- 6-(4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}-N-[3-(piperidin-1-yl)bi- cyclo[1.1.1]pentan-1-yl]imidazo[1,2-a]pyrazine-2-carboxamide; 8-amino-6-(4- fluorophenyl)-N-[3-(2-hydroxypropan-2-yl)bicyclo[1.1.1]pentan-1-yl]-5-{3-methylim- idazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide; 8-amino-6-(4- fluorophenyl)-N-[3-(hydroxymethyl)bicyclo[1.1.1]pentan-1-yl]-5-{3-methylimidazo[1,2- a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide; 8-amino-6-(4-fluorophenyl)-N-[3- (methoxymethyl)bicyclo[1.1.1]pentan-1-yl]-5-{3-methylimidazo[1,2-a]pyridin-6-yl}im- idazo[1,2-a]pyrazine-2-carboxamide; 8-amino-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2- a]pyridin-6-yl}-N-{3-[(piperazin-1-yl)methyl]bicyclo[1.1.1]pentan-1-yl}imidazo[1,2- a]pyrazine-2-carboxamide; 8-amino-6-(4-fluorophenyl)-N-{3-[(methylamino)methyl]bi- cyclo[1.1.1]pentan-1-yl}-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2- carboxamide; 8-amino-N-[3-(aminomethyl)bicyclo[1.1.1]pentan-1-yl]-6-(4-fluorophenyl)-5- {3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide; 8-amino-N-[3- (acetamidomethyl)bicyclo[1.1.1]pentan-1-yl]-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2- a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide; 8-amino-6-(4-fluorophenyl)-N-[3-(2- hydroxy-2-methylpropyl)bicyclo[1.1.1]pentan-1-yl]-5-{3-methylimidazo[1,2-a]pyridin-6- yl}imidazo[1,2-a]pyrazine-2-carboxamide; 8-amino-6-(4-fluorophenyl)-N-[3-(2-hy- droxyethyl)bicyclo[1.1.1]pentan-1-yl]-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2- a]pyrazine-2-carboxamide; Propan-2-yl N-({3-[8-amino-6-(4-fluorophenyl)-5-{3-methylim- idazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-amido]bicyclo[1.1.1]pentan-1- yl}methyl)carbamate; 8-amino-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}- N-[3-(piperazin-1-yl)bicyclo[1.1.1]pentan-1-yl]imidazo[1,2-a]pyrazine-2-carboxamide; 8- amino-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}-N-[3-(morpholin-4-yl)bi- cyclo[1.1.1]pentan-1-yl]imidazo[1,2-a]pyrazine-2-carboxamide; 8-amino-N-{bi- cyclo[1.1.1]pentan-1-yl}-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}im- idazo[1,2-a]pyrazine-2-carboxamide; and 8-amino-N-{bicyclo[1.1.1]pentan-1-yl}-6-(4- fluorophenyl)-5-(1-methyl-1H-1,3-benzodiazol-6-yl)imidazo[1,2-a]pyrazine-2-carboxamide. In yet another embodiment of the first aspect, said compound is selected from the group consisting of 8-amino-N-{3-[(dimethylamino)methyl]bicyclo[1.1.1]pentan-1-yl}-6-(4- fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide; 8-amino-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}-N-{3-[(morpholin-4- Ryvu Therapeutics S.A. and BioNTech SE R10559WO 15 yl)methyl]bicyclo[1.1.1]pentan-1-yl}imidazo[1,2-a]pyrazine-2-carboxamide; 8-amino-6-(4- fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}-N-{3-[(4-methylpiperazin-1- yl)methyl]bicyclo[1.1.1]pentan-1-yl}imidazo[1,2-a]pyrazine-2-carboxamide; 8-amino-6-(4- fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}-N-[3-({2-oxa-6-azaspiro[3.3]heptan- 6-yl}methyl)bicyclo[1.1.1]pentan-1-yl]imidazo[1,2-a]pyrazine-2-carboxamide; 8-amino-N- (3-{[(2,2-difluoroethyl)amino]methyl}bicyclo[1.1.1]pentan-1-yl)-6-(4-fluorophenyl)-5-{3- methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide; 8-amino-N-(3- {[(2,2-difluoroethyl)(methyl)amino]methyl}bicyclo[1.1.1]pentan-1-yl)-6-(4-fluorophenyl)-5- {3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide; 8-amino-N-{3- [(4,4-difluoropiperidin-1-yl)methyl]bicyclo[1.1.1]pentan-1-yl}-6-(4-fluorophenyl)-5-{3- methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide; 8-amino-N-(3- {[(2-fluoroethyl)amino]methyl}bicyclo[1.1.1]pentan-1-yl)-6-(4-fluorophenyl)-5-{3-methylim- idazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide; 8-amino-N-{3-[(3,3-di- fluoropyrrolidin-1-yl)methyl]bicyclo[1.1.1]pentan-1-yl}-6-(4-fluorophenyl)-5-{3-methylim- idazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide; 8-amino-6-(4- fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}-N-(3-{[(2,2,2-trifluoro- ethyl)amino]methyl}bicyclo[1.1.1]pentan-1-yl)imidazo[1,2-a]pyrazine-2-carboxamide; 8- amino-N-{3-[(3,3-difluoroazetidin-1-yl)methyl]bicyclo[1.1.1]pentan-1-yl}-6-(4- fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide; 8-amino-N-{3-[(3-fluoroazetidin-1-yl)methyl]bicyclo[1.1.1]pentan-1-yl}-6-(4-fluorophenyl)- 5-{3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide; 8-amino-N- (3-{[(1,3-difluoropropan-2-yl)amino]methyl}bicyclo[1.1.1]pentan-1-yl)-6-(4-fluorophenyl)- 5-{3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide; 8-amino-6- (4-fluorophenyl)-N-{3-[(N-methylacetamido)methyl]bicyclo[1.1.1]pentan-1-yl}-5-{3-methyl- imidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide; 8-amino-N-{3-fluorobi- cyclo[1.1.1]pentan-1-yl}-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}im- idazo[1,2-a]pyrazine-2-carboxamide; 8-amino-6-(4-fluorophenyl)-N-[3-(1-hydroxyethyl)bi- cyclo[1.1.1]pentan-1-yl]-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2- carboxamide; 8-amino-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}-N-[3- (pyrrolidin-1-yl)bicyclo[1.1.1]pentan-1-yl]imidazo[1,2-a]pyrazine-2-carboxamide; 8-amino- 6-(4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}-N-[3-(piperidin-1-yl)bi- cyclo[1.1.1]pentan-1-yl]imidazo[1,2-a]pyrazine-2-carboxamide; 8-amino-6-(4- fluorophenyl)-N-[3-(2-hydroxypropan-2-yl)bicyclo[1.1.1]pentan-1-yl]-5-{3-methylim- idazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide; 8-amino-6-(4- fluorophenyl)-N-[3-(hydroxymethyl)bicyclo[1.1.1]pentan-1-yl]-5-{3-methylimidazo[1,2- a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide; 8-amino-6-(4-fluorophenyl)-N-[3- (methoxymethyl)bicyclo[1.1.1]pentan-1-yl]-5-{3-methylimidazo[1,2-a]pyridin-6-yl}im- idazo[1,2-a]pyrazine-2-carboxamide; 8-amino-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2- a]pyridin-6-yl}-N-{3-[(piperazin-1-yl)methyl]bicyclo[1.1.1]pentan-1-yl}imidazo[1,2- a]pyrazine-2-carboxamide; 8-amino-6-(4-fluorophenyl)-N-{3-[(methylamino)methyl]bi- cyclo[1.1.1]pentan-1-yl}-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2- carboxamide; 8-amino-N-[3-(aminomethyl)bicyclo[1.1.1]pentan-1-yl]-6-(4-fluorophenyl)-5- {3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide; 8-amino-N-[3- (acetamidomethyl)bicyclo[1.1.1]pentan-1-yl]-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2- a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide; 8-amino-6-(4-fluorophenyl)-N-[3-(2- hydroxy-2-methylpropyl)bicyclo[1.1.1]pentan-1-yl]-5-{3-methylimidazo[1,2-a]pyridin-6- Ryvu Therapeutics S.A. and BioNTech SE R10559WO 16 yl}imidazo[1,2-a]pyrazine-2-carboxamide; 8-amino-6-(4-fluorophenyl)-N-[3-(2-hy- droxyethyl)bicyclo[1.1.1]pentan-1-yl]-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2- a]pyrazine-2-carboxamide; Propan-2-yl N-({3-[8-amino-6-(4-fluorophenyl)-5-{3-methylim- idazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-amido]bicyclo[1.1.1]pentan-1- yl}methyl)carbamate; 8-amino-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}- N-[3-(piperazin-1-yl)bicyclo[1.1.1]pentan-1-yl]imidazo[1,2-a]pyrazine-2-carboxamide; 8- amino-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}-N-[3-(morpholin-4-yl)bi- cyclo[1.1.1]pentan-1-yl]imidazo[1,2-a]pyrazine-2-carboxamide; 8-amino-N-{bi- cyclo[1.1.1]pentan-1-yl}-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}im- idazo[1,2-a]pyrazine-2-carboxamide; and 8-amino-N-{bicyclo[1.1.1]pentan-1-yl}-6-(4- fluorophenyl)-5-(1-methyl-1H-1,3-benzodiazol-6-yl)imidazo[1,2-a]pyrazine-2-carboxamide. In an embodiment of the first aspect, said compound is selected from the group consisting of 8-amino-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}-N-[3-({2-oxa-6-aza- spiro[3.3]heptan-6-yl}methyl)bicyclo[1.1.1]pentan-1-yl]imidazo[1,2-a]pyrazine-2-carboxam- ide; 8-amino-N-(3-{[(2,2-difluoroethyl)amino]methyl}bicyclo[1.1.1]pentan-1-yl)-6-(4-fluo- rophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide; 8- amino-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}-N-(3-{[(2,2,2-trifluo- roethyl)amino]methyl}bicyclo[1.1.1]pentan-1-yl)imidazo[1,2-a]pyrazine-2-carboxamide; 8- amino-N-(3-{[(1,3-difluoropropan-2-yl)amino]methyl}bicyclo[1.1.1]pentan-1-yl)-6-(4-fluo- rophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide; 8- amino-N-{3-fluorobicyclo[1.1.1]pentan-1-yl}-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2- a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide; 8-amino-6-(4-fluorophenyl)-N-[3-(1- hydroxyethyl)bicyclo[1.1.1]pentan-1-yl]-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2- a]pyrazine-2-carboxamide; 8-amino-6-(4-fluorophenyl)-N-[3-(hydroxymethyl)bicy- clo[1.1.1]pentan-1-yl]-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-car- boxamide; 8-amino-6-(4-fluorophenyl)-N-[3-(methoxymethyl)bicyclo[1.1.1]pentan-1-yl]-5- {3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide; 8-amino-N-[3- (aminomethyl)bicyclo[1.1.1]pentan-1-yl]-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2- a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide; 8-amino-N-[3-(acetamidomethyl)bi- cyclo[1.1.1]pentan-1-yl]-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imi- dazo[1,2-a]pyrazine-2-carboxamide; 8-amino-6-(4-fluorophenyl)-N-[3-(2-hydroxy-2- methylpropyl)bicyclo[1.1.1]pentan-1-yl]-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2- a]pyrazine-2-carboxamide; 8-amino-6-(4-fluorophenyl)-N-[3-(2-hydroxyethyl)bicy- clo[1.1.1]pentan-1-yl]-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-car- boxamide; Propan-2-yl N-({3-[8-amino-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2- a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-amido]bicyclo[1.1.1]pentan-1-yl}methyl)carbamate; 8-amino-N-{bicyclo[1.1.1]pentan-1-yl}-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2- a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide; and 8-amino-N-{bicyclo[1.1.1]pen- tan-1-yl}-6-(4-fluorophenyl)-5-(1-methyl-1H-1,3-benzodiazol-6-yl)imidazo[1,2-a]pyrazine- 2-carboxamide. In another embodiment of the first aspect, said compound is selected from the group con- sisting of 8-amino-N-{3-[(dimethylamino)methyl]bicyclo[1.1.1]pentan-1-yl}-6-(4-fluo- rophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide; 8- amino-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}-N-{3-[(4-methylpiperazin- Ryvu Therapeutics S.A. and BioNTech SE R10559WO 17 1-yl)methyl]bicyclo[1.1.1]pentan-1-yl}imidazo[1,2-a]pyrazine-2-carboxamide; 8-amino-6- (4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}-N-[3-({2-oxa-6-azaspiro[3.3]hep- tan-6-yl}methyl)bicyclo[1.1.1]pentan-1-yl]imidazo[1,2-a]pyrazine-2-carboxamide; 8-amino- N-(3-{[(2,2-difluoroethyl)amino]methyl}bicyclo[1.1.1]pentan-1-yl)-6-(4-fluorophenyl)-5-{3- methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide; 8-amino-N-{3- [(3,3-difluoropyrrolidin-1-yl)methyl]bicyclo[1.1.1]pentan-1-yl}-6-(4-fluorophenyl)-5-{3- methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide; 8-amino-6-(4-flu- orophenyl)-N-[3-(1-hydroxyethyl)bicyclo[1.1.1]pentan-1-yl]-5-{3-methylimidazo[1,2- a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide; 8-amino-6-(4-fluorophenyl)-5-{3- methylimidazo[1,2-a]pyridin-6-yl}-N-[3-(pyrrolidin-1-yl)bicyclo[1.1.1]pentan-1-yl]imi- dazo[1,2-a]pyrazine-2-carboxamide; 8-amino-6-(4-fluorophenyl)-N-[3-(2-hydroxypropan-2- yl)bicyclo[1.1.1]pentan-1-yl]-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine- 2-carboxamide; 8-amino-6-(4-fluorophenyl)-N-[3-(hydroxymethyl)bicyclo[1.1.1]pentan-1- yl]-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide; 8-amino- 6-(4-fluorophenyl)-N-{3-[(methylamino)methyl]bicyclo[1.1.1]pentan-1-yl}-5-{3-methylimi- dazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide; 8-amino-N-[3- (aminomethyl)bicyclo[1.1.1]pentan-1-yl]-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2- a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide; 8-amino-N-[3-(acetamidomethyl)bi- cyclo[1.1.1]pentan-1-yl]-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imi- dazo[1,2-a]pyrazine-2-carboxamide; 8-amino-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2- a]pyridin-6-yl}-N-[3-(piperazin-1-yl)bicyclo[1.1.1]pentan-1-yl]imidazo[1,2-a]pyrazine-2- carboxamide; 8-amino-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}-N-[3- (morpholin-4-yl)bicyclo[1.1.1]pentan-1-yl]imidazo[1,2-a]pyrazine-2-carboxamide; and 8- amino-N-{bicyclo[1.1.1]pentan-1-yl}-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin- 6-yl}imidazo[1,2-a]pyrazine-2-carboxamide. In yet another embodiment of the first aspect, said compound is selected from the group consisting of 8-amino-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}-N-[3-({2- oxa-6-azaspiro[3.3]heptan-6-yl}methyl)bicyclo[1.1.1]pentan-1-yl]imidazo[1,2-a]pyrazine-2- carboxamide; 8-amino-N-(3-{[(2,2-difluoroethyl)amino]methyl}bicyclo[1.1.1]pentan-1-yl)-6- (4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carbox- amide; 8-amino-6-(4-fluorophenyl)-N-[3-(1-hydroxyethyl)bicyclo[1.1.1]pentan-1-yl]-5-{3- methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide; 8-amino-6-(4-flu- orophenyl)-N-[3-(hydroxymethyl)bicyclo[1.1.1]pentan-1-yl]-5-{3-methylimidazo[1,2- a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide; 8-amino-N-[3-(aminomethyl)bicy- clo[1.1.1]pentan-1-yl]-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imi- dazo[1,2-a]pyrazine-2-carboxamide; 8-amino-N-[3-(acetamidomethyl)bicyclo[1.1.1]pentan- 1-yl]-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2- carboxamide; and 8-amino-N-{bicyclo[1.1.1]pentan-1-yl}-6-(4-fluorophenyl)-5-{3- methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide. In a preferred embodiment of the first aspect, said compound is 8-amino-6-(4-fluo- rophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}-N-[3-({2-oxa-6-azaspiro[3.3]heptan-6- yl}methyl)bicyclo[1.1.1]pentan-1-yl]imidazo[1,2-a]pyrazine-2-carboxamide. Ryvu Therapeutics S.A. and BioNTech SE R10559WO 18 In another preferred embodiment of the first aspect, said compound is 8-amino-N-(3-{[(2,2- difluoroethyl)amino]methyl}bicyclo[1.1.1]pentan-1-yl)-6-(4-fluorophenyl)-5-{3-methylimi- dazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide. In another preferred embodiment of the first aspect, said compound is 8-amino-6-(4-fluo- rophenyl)-N-[3-(1-hydroxyethyl)bicyclo[1.1.1]pentan-1-yl]-5-{3-methylimidazo[1,2- a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide. In another preferred embodiment of the first aspect, said compound is 8-amino-6-(4-fluo- rophenyl)-N-[3-(hydroxymethyl)bicyclo[1.1.1]pentan-1-yl]-5-{3-methylimidazo[1,2- a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide. In another preferred embodiment of the first aspect, said compound is 8-amino-N-[3- (aminomethyl)bicyclo[1.1.1]pentan-1-yl]-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2- a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide. In another preferred embodiment of the first aspect, said compound is 8-amino-N-[3-(ac- etamidomethyl)bicyclo[1.1.1]pentan-1-yl]-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2- a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide. In another preferred embodiment of the first aspect, said compound is 8-amino-N-{bicy- clo[1.1.1]pentan-1-yl}-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imi- dazo[1,2-a]pyrazine-2-carboxamide. In the second aspect, the present invention relates to a pharmaceutical composition com- prising the compound according to the first aspect and optionally a pharmaceutically ac- ceptable carrier, diluent and / or excipient. In a preferred embodiment of the second aspect, the pharmaceutical composition com- prises the compound according to the first aspect in a pharmaceutically effective amount. All embodiments of the first aspect including of course all preferred embodiments of the first aspect equally apply to the second aspect. Thus, in a preferred embodiment of the second aspect, said pharmaceutical composition comprises 8-amino-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}-N-[3-({2- oxa-6-azaspiro[3.3]heptan-6-yl}methyl)bicyclo[1.1.1]pentan-1-yl]imidazo[1,2-a]pyrazine-2- carboxamide and optionally a pharmaceutically acceptable carrier, diluent and / or excipient. In another preferred embodiment of the second aspect, said pharmaceutical composition comprises 8-amino-N-(3-{[(2,2-difluoroethyl)amino]methyl}bicyclo[1.1.1]pentan-1-yl)-6-(4- fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide and optionally a pharmaceutically acceptable carrier, diluent and / or excipient. In another preferred embodiment of the second aspect, said pharmaceutical composition comprises 8-amino-6-(4-fluorophenyl)-N-[3-(1-hydroxyethyl)bicyclo[1.1.1]pentan-1-yl]-5- Ryvu Therapeutics S.A. and BioNTech SE R10559WO 19 {3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide and optionally a pharmaceutically acceptable carrier, diluent and / or excipient. In another preferred embodiment of the second aspect, said pharmaceutical composition comprises 8-amino-6-(4-fluorophenyl)-N-[3-(hydroxymethyl)bicyclo[1.1.1]pentan-1-yl]-5- {3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide and optionally a pharmaceutically acceptable carrier, diluent and / or excipient. In another preferred embodiment of the second aspect, said pharmaceutical composition comprises 8-amino-N-[3-(aminomethyl)bicyclo[1.1.1]pentan-1-yl]-6-(4-fluorophenyl)-5-{3- methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide and optionally a pharmaceutically acceptable carrier, diluent and / or excipient. In another preferred embodiment of the second aspect, said pharmaceutical composition comprises 8-amino-N-[3-(acetamidomethyl)bicyclo[1.1.1]pentan-1-yl]-6-(4-fluorophenyl)- 5-{3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide and optionally a pharmaceutically acceptable carrier, diluent and / or excipient. In another preferred embodiment of the second aspect, said pharmaceutical composition comprises 8-amino-N-{bicyclo[1.1.1]pentan-1-yl}-6-(4-fluorophenyl)-5-{3-methylimi- dazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide and optionally a pharmaceu- tically acceptable carrier, diluent and / or excipient. In the third aspect, the present invention relates to the compound according to the first aspect for use in medicine. All embodiments of the first aspect including of course all preferred embodiments of the first aspect equally apply to the third aspect. Thus, in a preferred embodiment of the third aspect, the compound for use in medicine is 8- amino-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}-N-[3-({2-oxa-6-aza- spiro[3.3]heptan-6-yl}methyl)bicyclo[1.1.1]pentan-1-yl]imidazo[1,2-a]pyrazine-2-carboxam- ide. In another preferred embodiment of the third aspect, the compound for use in medicine is 8-amino-N-(3-{[(2,2-difluoroethyl)amino]methyl}bicyclo[1.1.1]pentan-1-yl)-6-(4-fluo- rophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide. In another preferred embodiment of the third aspect, the compound for use in medicine is 8-amino-6-(4-fluorophenyl)-N-[3-(1-hydroxyethyl)bicyclo[1.1.1]pentan-1-yl]-5-{3- methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide. In another preferred embodiment of the third aspect, the compound for use in medicine is 8-amino-6-(4-fluorophenyl)-N-[3-(hydroxymethyl)bicyclo[1.1.1]pentan-1-yl]-5-{3- methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide. Ryvu Therapeutics S.A. and BioNTech SE R10559WO 20 In another preferred embodiment of the third aspect, the compound for use in medicine is 8-amino-N-[3-(aminomethyl)bicyclo[1.1.1]pentan-1-yl]-6-(4-fluorophenyl)-5-{3-methylimi- dazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide. In another preferred embodiment of the third aspect, the compound for use in medicine is 8-amino-N-[3-(acetamidomethyl)bicyclo[1.1.1]pentan-1-yl]-6-(4-fluorophenyl)-5-{3- methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide. In another preferred embodiment of the third aspect, the compound for use in medicine is 8-amino-N-{bicyclo[1.1.1]pentan-1-yl}-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2- a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide. In the fourth aspect, the present invention relates to the compound according to the first aspect for use in the treatment of a disease selected from the group consisting of cancer, Parkinson's disease, Huntington's disease, Alzheimer's disease, psychosis, stroke, extra pyramidal syndrome, attention deficit disorder (ADD), attention deficit hyperactivity disorder (ADHD), amyotrophic lateral sclerosis, cirrhosis, fibrosis, fatty liver, addictive behavior, der- mal fibrosis, a sleep disorder, AIDS, an autoimmune disease, an infection, atherosclerosis, ischemia-reperfusion injury, idiopathic pulmonary fibrosis, systemic sclerosis, irritable bowel disease, chronic kidney disease and pain. In an embodiment of the fourth aspect, the compound according to the first aspect is for use in the treatment of cancer. In another embodiment of the fourth aspect, at least one further anti-neoplastic agent is coadministered with said compound of the first aspect. In yet another embodiment of the fourth aspect, the afore-mentioned anti-neoplastic agent is selected from the group consisting of a chemotherapeutic agent, a topoisomerase II inhibitor, an antimetabolite, a topoisomerase I inhibitor, a hormone, a hormonal analogue, a signal transduction pathway inhibitor, a tyrosine kinase inhibitor, an angiogenesis inhibitor, a proapoptotic agent, a cell cycle signaling inhibitor, a proteasome inhibitor, an inhibitor of cancer metabolism, and an immunotherapeutic agent. The immunotherapeutic agent (and thus the anti-neoplastic agent) may be a checkpoint inhibitor, wherein the checkpoint in- hibitor may be selected from the group consisting of an antibody or an antigen-binding frag- ment thereof, a small molecule inhibitor and an antisense oligonucleotide. All embodiments of the first aspect including of course all preferred embodiments of the first aspect equally apply to the fourth aspect. Thus, in a preferred embodiment of the fourth aspect, 8-amino-6-(4-fluorophenyl)-5-{3- methylimidazo[1,2-a]pyridin-6-yl}-N-[3-({2-oxa-6-azaspiro[3.3]heptan-6-yl}methyl)bicy- clo[1.1.1]pentan-1-yl]imidazo[1,2-a]pyrazine-2-carboxamide is for use in the treatment of a disease selected from the group consisting of cancer, Parkinson's disease, Huntington's disease, Alzheimer's disease, psychosis, stroke, extra pyramidal syndrome, attention deficit disorder (ADD), attention deficit hyperactivity disorder (ADHD), amyotrophic lateral sclero- Ryvu Therapeutics S.A. and BioNTech SE R10559WO 21 sis, cirrhosis, fibrosis, fatty liver, addictive behavior, dermal fibrosis, a sleep disorder, AIDS, an autoimmune disease, an infection, atherosclerosis, ischemia-reperfusion injury, idio- pathic pulmonary fibrosis, systemic sclerosis, irritable bowel disease, chronic kidney dis- ease and pain. In another preferred embodiment of the fourth aspect, 8-amino-N-(3-{[(2,2-difluo- roethyl)amino]methyl}bicyclo[1.1.1]pentan-1-yl)-6-(4-fluorophenyl)-5-{3-methylimi- dazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide is for use in the treatment of a disease selected from the group consisting of cancer, Parkinson's disease, Huntington's disease, Alzheimer's disease, psychosis, stroke, extra pyramidal syndrome, attention deficit disorder (ADD), attention deficit hyperactivity disorder (ADHD), amyotrophic lateral sclero- sis, cirrhosis, fibrosis, fatty liver, addictive behavior, dermal fibrosis, a sleep disorder, AIDS, an autoimmune disease, an infection, atherosclerosis, ischemia-reperfusion injury, idio- pathic pulmonary fibrosis, systemic sclerosis, irritable bowel disease, chronic kidney dis- ease and pain. In another preferred embodiment of the fourth aspect, 8-amino-6-(4-fluorophenyl)-N-[3-(1- hydroxyethyl)bicyclo[1.1.1]pentan-1-yl]-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2- a]pyrazine-2-carboxamide is for use in the treatment of a disease selected from the group consisting of cancer, Parkinson's disease, Huntington's disease, Alzheimer's disease, psy- chosis, stroke, extra pyramidal syndrome, attention deficit disorder (ADD), attention deficit hyperactivity disorder (ADHD), amyotrophic lateral sclerosis, cirrhosis, fibrosis, fatty liver, addictive behavior, dermal fibrosis, a sleep disorder, AIDS, an autoimmune disease, an in- fection, atherosclerosis, ischemia-reperfusion injury, idiopathic pulmonary fibrosis, systemic sclerosis, irritable bowel disease, chronic kidney disease and pain. In another preferred embodiment of the fourth aspect, 8-amino-6-(4-fluorophenyl)-N-[3- (hydroxymethyl)bicyclo[1.1.1]pentan-1-yl]-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imi- dazo[1,2-a]pyrazine-2-carboxamide is for use in the treatment of a disease selected from the group consisting of cancer, Parkinson's disease, Huntington's disease, Alzheimer's dis- ease, psychosis, stroke, extra pyramidal syndrome, attention deficit disorder (ADD), atten- tion deficit hyperactivity disorder (ADHD), amyotrophic lateral sclerosis, cirrhosis, fibrosis, fatty liver, addictive behavior, dermal fibrosis, a sleep disorder, AIDS, an autoimmune dis- ease, an infection, atherosclerosis, ischemia-reperfusion injury, idiopathic pulmonary fibro- sis, systemic sclerosis, irritable bowel disease, chronic kidney disease and pain. In another preferred embodiment of the fourth aspect, 8-amino-N-[3-(aminomethyl)bicy- clo[1.1.1]pentan-1-yl]-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imi- dazo[1,2-a]pyrazine-2-carboxamide is for use in the treatment of a disease selected from the group consisting of cancer, Parkinson's disease, Huntington's disease, Alzheimer's dis- ease, psychosis, stroke, extra pyramidal syndrome, attention deficit disorder (ADD), atten- tion deficit hyperactivity disorder (ADHD), amyotrophic lateral sclerosis, cirrhosis, fibrosis, fatty liver, addictive behavior, dermal fibrosis, a sleep disorder, AIDS, an autoimmune dis- ease, an infection, atherosclerosis, ischemia-reperfusion injury, idiopathic pulmonary fibro- sis, systemic sclerosis, irritable bowel disease, chronic kidney disease and pain. Ryvu Therapeutics S.A. and BioNTech SE R10559WO 22 In another preferred embodiment of the fourth aspect, 8-amino-N-[3-(acetamidomethyl)bi- cyclo[1.1.1]pentan-1-yl]-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imi- dazo[1,2-a]pyrazine-2-carboxamide is for use in the treatment of a disease selected from the group consisting of cancer, Parkinson's disease, Huntington's disease, Alzheimer's dis- ease, psychosis, stroke, extra pyramidal syndrome, attention deficit disorder (ADD), atten- tion deficit hyperactivity disorder (ADHD), amyotrophic lateral sclerosis, cirrhosis, fibrosis, fatty liver, addictive behavior, dermal fibrosis, a sleep disorder, AIDS, an autoimmune dis- ease, an infection, atherosclerosis, ischemia-reperfusion injury, idiopathic pulmonary fibro- sis, systemic sclerosis, irritable bowel disease, chronic kidney disease and pain. In another preferred embodiment of the fourth aspect, 8-amino-N-{bicyclo[1.1.1]pentan-1- yl}-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-car- boxamide is for use in the treatment of a disease selected from the group consisting of can- cer, Parkinson's disease, Huntington's disease, Alzheimer's disease, psychosis, stroke, extra pyramidal syndrome, attention deficit disorder (ADD), attention deficit hyperactivity disorder (ADHD), amyotrophic lateral sclerosis, cirrhosis, fibrosis, fatty liver, addictive behavior, der- mal fibrosis, a sleep disorder, AIDS, an autoimmune disease, an infection, atherosclerosis, ischemia-reperfusion injury, idiopathic pulmonary fibrosis, systemic sclerosis, irritable bowel disease, chronic kidney disease and pain. In a preferred embodiment of the fourth aspect, 8-amino-6-(4-fluorophenyl)-5-{3- methylimidazo[1,2-a]pyridin-6-yl}-N-[3-({2-oxa-6-azaspiro[3.3]heptan-6-yl}methyl)bicy- clo[1.1.1]pentan-1-yl]imidazo[1,2-a]pyrazine-2-carboxamide is for use in the treatment of cancer. In another preferred embodiment of the fourth aspect, 8-amino-N-(3-{[(2,2-difluo- roethyl)amino]methyl}bicyclo[1.1.1]pentan-1-yl)-6-(4-fluorophenyl)-5-{3-methylimi- dazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide is for use in the treatment of cancer. In another preferred embodiment of the fourth aspect, 8-amino-6-(4-fluorophenyl)-N-[3-(1- hydroxyethyl)bicyclo[1.1.1]pentan-1-yl]-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2- a]pyrazine-2-carboxamide is for use in the treatment of cancer. In another preferred embodiment of the fourth aspect, 8-amino-6-(4-fluorophenyl)-N-[3- (hydroxymethyl)bicyclo[1.1.1]pentan-1-yl]-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imi- dazo[1,2-a]pyrazine-2-carboxamide is for use in the treatment of cancer. In another preferred embodiment of the fourth aspect, 8-amino-N-[3-(aminomethyl)bicy- clo[1.1.1]pentan-1-yl]-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imi- dazo[1,2-a]pyrazine-2-carboxamide is for use in the treatment of cancer. In another preferred embodiment of the fourth aspect, 8-amino-N-[3-(acetamidomethyl)bi- cyclo[1.1.1]pentan-1-yl]-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imi- dazo[1,2-a]pyrazine-2-carboxamide is for use in the treatment of cancer. Ryvu Therapeutics S.A. and BioNTech SE R10559WO 23 In another preferred embodiment of the fourth aspect, 8-amino-N-{bicyclo[1.1.1]pentan-1- yl}-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-car- boxamide is for use in the treatment of cancer. In the fifth aspect, the present invention relates to a method for treating a disease in a subject in need thereof, wherein the method comprises administering a therapeutically ef- fective amount of the compound according to the first aspect to the subject, wherein the disease is selected from the group consisting of cancer, Parkinson's disease, Huntington's disease, Alzheimer's disease, psychosis, stroke, extra pyramidal syndrome, attention deficit disorder (ADD), attention deficit hyperactivity disorder (ADHD), amyotrophic lateral sclero- sis, cirrhosis, fibrosis, fatty liver, addictive behavior, dermal fibrosis, a sleep disorder, AIDS, an autoimmune disease, an infection, atherosclerosis, ischemia-reperfusion injury, idio- pathic pulmonary fibrosis, systemic sclerosis, irritable bowel disease, chronic kidney dis- ease and pain. In an embodiment of the fifth aspect, the present invention relates to a method for treating cancer in a subject in need thereof, wherein the method comprises administering a thera- peutically effective amount of the compound according to the first aspect to the subject. In another embodiment of the fifth aspect, the method further comprises co-administering a therapeutically effective amount of at least one further anti-neoplastic agent with said compound. In yet another embodiment of the fifth aspect, the anti-neoplastic agent is selected from the group consisting of a chemotherapeutic agent, a topoisomerase II inhibitor, an anti- metabolite, a topoisomerase I inhibitor, a hormone, a hormonal analogue, a signal transduc- tion pathway inhibitor, a tyrosine kinase inhibitor, an angiogenesis inhibitor, a proapoptotic agent, a cell cycle signaling inhibitor, a proteasome inhibitor, an inhibitor of cancer metabol- ism, and an immunotherapeutic agent. The immunotherapeutic agent (and thus the anti- neoplastic agent) may be a checkpoint inhibitor, wherein the checkpoint inhibitor may be selected from the group consisting of an antibody or an antigen-binding fragment thereof, a small molecule inhibitor and an antisense oligonucleotide. In another embodiment of the fifth aspect, the method further comprises diagnosing the disease in a subject prior to administering the therapeutically effective amount of the com- pound according to the first aspect. All embodiments of the first aspect including of course all preferred embodiments of the first aspect equally apply to the fifth aspect. Thus, in a preferred embodiment of the fifth aspect, the present invention relates to a method for treating a disease in a subject in need thereof, wherein the method comprises administering a therapeutically effective amount of 8-amino-6-(4-fluorophenyl)-5-{3- methylimidazo[1,2-a]pyridin-6-yl}-N-[3-({2-oxa-6-azaspiro[3.3]heptan-6-yl}methyl)bicy- clo[1.1.1]pentan-1-yl]imidazo[1,2-a]pyrazine-2-carboxamide to the subject, wherein the disease is selected from the group consisting of cancer, Parkinson's disease, Huntington's Ryvu Therapeutics S.A. and BioNTech SE R10559WO 24 disease, Alzheimer's disease, psychosis, stroke, extra pyramidal syndrome, attention deficit disorder (ADD), attention deficit hyperactivity disorder (ADHD), amyotrophic lateral sclero- sis, cirrhosis, fibrosis, fatty liver, addictive behavior, dermal fibrosis, a sleep disorder, AIDS, an autoimmune disease, an infection, atherosclerosis, ischemia-reperfusion injury, idio- pathic pulmonary fibrosis, systemic sclerosis, irritable bowel disease, chronic kidney dis- ease and pain. In another preferred embodiment of the fifth aspect, the present invention relates to a method for treating a disease in a subject in need thereof, wherein the method comprises administering a therapeutically effective amount of 8-amino-6-(4-fluorophenyl)-N-[3-(1-hy- droxyethyl)bicyclo[1.1.1]pentan-1-yl]-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2- a]pyrazine-2-carboxamide to the subject, wherein the disease is selected from the group consisting of cancer, Parkinson's disease, Huntington's disease, Alzheimer's disease, psy- chosis, stroke, extra pyramidal syndrome, attention deficit disorder (ADD), attention deficit hyperactivity disorder (ADHD), amyotrophic lateral sclerosis, cirrhosis, fibrosis, fatty liver, addictive behavior, dermal fibrosis, a sleep disorder, AIDS, an autoimmune disease, an in- fection, atherosclerosis, ischemia-reperfusion injury, idiopathic pulmonary fibrosis, systemic sclerosis, irritable bowel disease, chronic kidney disease and pain. In another preferred embodiment of the fifth aspect, the present invention relates to a method for treating a disease in a subject in need thereof, wherein the method comprises administering a therapeutically effective amount of 8-amino-6-(4-fluorophenyl)-N-[3-(hy- droxymethyl)bicyclo[1.1.1]pentan-1-yl]-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2- a]pyrazine-2-carboxamide to the subject, wherein the disease is selected from the group consisting of cancer, Parkinson's disease, Huntington's disease, Alzheimer's disease, psy- chosis, stroke, extra pyramidal syndrome, attention deficit disorder (ADD), attention deficit hyperactivity disorder (ADHD), amyotrophic lateral sclerosis, cirrhosis, fibrosis, fatty liver, addictive behavior, dermal fibrosis, a sleep disorder, AIDS, an autoimmune disease, an in- fection, atherosclerosis, ischemia-reperfusion injury, idiopathic pulmonary fibrosis, systemic sclerosis, irritable bowel disease, chronic kidney disease and pain. In another preferred embodiment of the fifth aspect, the present invention relates to a method for treating a disease in a subject in need thereof, wherein the method comprises administering a therapeutically effective amount of 8-amino-6-(4-fluorophenyl)-N-[3-(hy- droxymethyl)bicyclo[1.1.1]pentan-1-yl]-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2- a]pyrazine-2-carboxamide to the subject, wherein the disease is selected from the group consisting of cancer, Parkinson's disease, Huntington's disease, Alzheimer's disease, psy- chosis, stroke, extra pyramidal syndrome, attention deficit disorder (ADD), attention deficit hyperactivity disorder (ADHD), amyotrophic lateral sclerosis, cirrhosis, fibrosis, fatty liver, addictive behavior, dermal fibrosis, a sleep disorder, AIDS, an autoimmune disease, an in- fection, atherosclerosis, ischemia-reperfusion injury, idiopathic pulmonary fibrosis, systemic sclerosis, irritable bowel disease, chronic kidney disease and pain. In another preferred embodiment of the fifth aspect, the present invention relates to a method for treating a disease in a subject in need thereof, wherein the method comprises administering a therapeutically effective amount of 8-amino-N-[3-(aminomethyl)bicy- Ryvu Therapeutics S.A. and BioNTech SE R10559WO 25 clo[1.1.1]pentan-1-yl]-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imi- dazo[1,2-a]pyrazine-2-carboxamide to the subject, wherein the disease is selected from the group consisting of cancer, Parkinson's disease, Huntington's disease, Alzheimer's disease, psychosis, stroke, extra pyramidal syndrome, attention deficit disorder (ADD), attention deficit hyperactivity disorder (ADHD), amyotrophic lateral sclerosis, cirrhosis, fibrosis, fatty liver, addictive behavior, dermal fibrosis, a sleep disorder, AIDS, an autoimmune disease, an infection, atherosclerosis, ischemia-reperfusion injury, idiopathic pulmonary fibrosis, sys- temic sclerosis, irritable bowel disease, chronic kidney disease and pain. In another preferred embodiment of the fifth aspect, the present invention relates to a method for treating a disease in a subject in need thereof, wherein the method comprises administering a therapeutically effective amount of 8-amino-N-[3-(acetamidomethyl)bicy- clo[1.1.1]pentan-1-yl]-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imi- dazo[1,2-a]pyrazine-2-carboxamide to the subject, wherein the disease is selected from the group consisting of cancer, Parkinson's disease, Huntington's disease, Alzheimer's disease, psychosis, stroke, extra pyramidal syndrome, attention deficit disorder (ADD), attention deficit hyperactivity disorder (ADHD), amyotrophic lateral sclerosis, cirrhosis, fibrosis, fatty liver, addictive behavior, dermal fibrosis, a sleep disorder, AIDS, an autoimmune disease, an infection, atherosclerosis, ischemia-reperfusion injury, idiopathic pulmonary fibrosis, sys- temic sclerosis, irritable bowel disease, chronic kidney disease and pain. In another preferred embodiment of the fifth aspect, the present invention relates to a method for treating a disease in a subject in need thereof, wherein the method comprises administering a therapeutically effective amount of 8-amino-N-{bicyclo[1.1.1]pentan-1-yl}- 6-(4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carbox- amide to the subject, wherein the disease is selected from the group consisting of cancer, Parkinson's disease, Huntington's disease, Alzheimer's disease, psychosis, stroke, extra pyramidal syndrome, attention deficit disorder (ADD), attention deficit hyperactivity disorder (ADHD), amyotrophic lateral sclerosis, cirrhosis, fibrosis, fatty liver, addictive behavior, der- mal fibrosis, a sleep disorder, AIDS, an autoimmune disease, an infection, atherosclerosis, ischemia-reperfusion injury, idiopathic pulmonary fibrosis, systemic sclerosis, irritable bowel disease, chronic kidney disease and pain. In another preferred embodiment of the fifth aspect, the present invention relates to a method for treating cancer in a subject in need thereof, wherein the method comprises ad- ministering a therapeutically effective amount of 8-amino-6-(4-fluorophenyl)-5-{3- methylimidazo[1,2-a]pyridin-6-yl}-N-[3-({2-oxa-6-azaspiro[3.3]heptan-6-yl}methyl)bicy- clo[1.1.1]pentan-1-yl]imidazo[1,2-a]pyrazine-2-carboxamide to the subject. In another preferred embodiment of the fifth aspect, the present invention relates to a method for treating cancer in a subject in need thereof, wherein the method comprises ad- ministering a therapeutically effective amount of 8-amino-6-(4-fluorophenyl)-N-[3-(1-hy- droxyethyl)bicyclo[1.1.1]pentan-1-yl]-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2- a]pyrazine-2-carboxamide to the subject. Ryvu Therapeutics S.A. and BioNTech SE R10559WO 26 In another preferred embodiment of the fifth aspect, the present invention relates to a method for treating cancer in a subject in need thereof, wherein the method comprises ad- ministering a therapeutically effective amount of 8-amino-6-(4-fluorophenyl)-N-[3-(hydrox- ymethyl)bicyclo[1.1.1]pentan-1-yl]-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2- a]pyrazine-2-carboxamide to the subject. In another preferred embodiment of the fifth aspect, the present invention relates to a method for treating cancer in a subject in need thereof, wherein the method comprises ad- ministering a therapeutically effective amount of 8-amino-6-(4-fluorophenyl)-N-[3-(hydrox- ymethyl)bicyclo[1.1.1]pentan-1-yl]-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2- a]pyrazine-2-carboxamide to the subject. In another preferred embodiment of the fifth aspect, the present invention relates to a method for treating cancer in a subject in need thereof, wherein the method comprises ad- ministering a therapeutically effective amount of 8-amino-N-[3-(aminomethyl)bicy- clo[1.1.1]pentan-1-yl]-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imi- dazo[1,2-a]pyrazine-2-carboxamide to the subject. In another preferred embodiment of the fifth aspect, the present invention relates to a method for treating cancer in a subject in need thereof, wherein the method comprises ad- ministering a therapeutically effective amount of 8-amino-N-[3-(acetamidomethyl)bicy- clo[1.1.1]pentan-1-yl]-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imi- dazo[1,2-a]pyrazine-2-carboxamide to the subject. In another preferred embodiment of the fifth aspect, the present invention relates to a method for treating cancer in a subject in need thereof, wherein the method comprises ad- ministering a therapeutically effective amount of 8-amino-N-{bicyclo[1.1.1]pentan-1-yl}-6- (4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carbox- amide to the subject. In the sixth aspect, the present invention relates to the use of the compound according to the first aspect in the manufacture of a medicament for the treatment of a disease selected from the group consisting of cancer, Parkinson's disease, Huntington's disease, Alzheimer's disease, psychosis, stroke, extra pyramidal syndrome, attention deficit disorder (ADD), at- tention deficit hyperactivity disorder (ADHD), amyotrophic lateral sclerosis, cirrhosis, fibro- sis, fatty liver, addictive behavior, dermal fibrosis, a sleep disorder, AIDS, an autoimmune disease, an infection, atherosclerosis, ischemia-reperfusion injury, idiopathic pulmonary fi- brosis, systemic sclerosis, irritable bowel disease, chronic kidney disease and pain. In an embodiment of the sixth aspect, the present invention relates to the use of the com- pound according to the first aspect in the manufacture of a medicament for the treatment of cancer. In another embodiment of the sixth aspect, at least one further anti-neoplastic agent is co-administered in the treatment of cancer. Ryvu Therapeutics S.A. and BioNTech SE R10559WO 27 In an embodiment of the sixth aspect, the anti-neoplastic agent is selected from the group consisting of a chemotherapeutic agent, a topoisomerase II inhibitor, an antimetabolite, a topoisomerase I inhibitor, a hormone, a hormonal analogue, a signal transduction pathway inhibitor, a tyrosine kinase inhibitor, an angiogenesis inhibitor, a proapoptotic agent, a cell cycle signaling inhibitor, a proteasome inhibitor, an inhibitor of cancer metabolism, and an immunotherapeutic agent. The immunotherapeutic agent (and thus the anti-neoplastic agent) may be a checkpoint inhibitor, wherein the checkpoint inhibitor may be selected from the group consisting of an antibody or an antigen-binding fragment thereof, a small mole- cule inhibitor and an antisense oligonucleotide. All embodiments of the first aspect including of course all preferred embodiments of the first aspect equally apply to the sixth aspect. Thus, in a preferred embodiment of the sixth aspect, the present invention relates to the use of 8-amino-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}-N-[3-({2-oxa-6- azaspiro[3.3]heptan-6-yl}methyl)bicyclo[1.1.1]pentan-1-yl]imidazo[1,2-a]pyrazine-2-car- boxamide in the manufacture of a medicament for the treatment of a disease selected from the group consisting of cancer, Parkinson's disease, Huntington's disease, Alzheimer's dis- ease, psychosis, stroke, extra pyramidal syndrome, attention deficit disorder (ADD), atten- tion deficit hyperactivity disorder (ADHD), amyotrophic lateral sclerosis, cirrhosis, fibrosis, fatty liver, addictive behavior, dermal fibrosis, a sleep disorder, AIDS, an autoimmune dis- ease, an infection, atherosclerosis, ischemia-reperfusion injury, idiopathic pulmonary fibro- sis, systemic sclerosis, irritable bowel disease, chronic kidney disease and pain. In another preferred embodiment of the sixth aspect, the present invention relates to the use of 8-amino-6-(4-fluorophenyl)-N-[3-(1-hydroxyethyl)bicyclo[1.1.1]pentan-1-yl]-5-{3- methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide in the manufacture of a medicament for the treatment of a disease selected from the group consisting of can- cer, Parkinson's disease, Huntington's disease, Alzheimer's disease, psychosis, stroke, extra pyramidal syndrome, attention deficit disorder (ADD), attention deficit hyperactivity disorder (ADHD), amyotrophic lateral sclerosis, cirrhosis, fibrosis, fatty liver, addictive behavior, der- mal fibrosis, a sleep disorder, AIDS, an autoimmune disease, an infection, atherosclerosis, ischemia-reperfusion injury, idiopathic pulmonary fibrosis, systemic sclerosis, irritable bowel disease, chronic kidney disease and pain. In another preferred embodiment of the sixth aspect, the present invention relates to the use of 8-amino-6-(4-fluorophenyl)-N-[3-(hydroxymethyl)bicyclo[1.1.1]pentan-1-yl]-5-{3- methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide in the manufacture of a medicament for the treatment of a disease selected from the group consisting of can- cer, Parkinson's disease, Huntington's disease, Alzheimer's disease, psychosis, stroke, extra pyramidal syndrome, attention deficit disorder (ADD), attention deficit hyperactivity disorder (ADHD), amyotrophic lateral sclerosis, cirrhosis, fibrosis, fatty liver, addictive behavior, der- mal fibrosis, a sleep disorder, AIDS, an autoimmune disease, an infection, atherosclerosis, ischemia-reperfusion injury, idiopathic pulmonary fibrosis, systemic sclerosis, irritable bowel disease, chronic kidney disease and pain. Ryvu Therapeutics S.A. and BioNTech SE R10559WO 28 In another preferred embodiment of the sixth aspect, the present invention relates to the use of 8-amino-6-(4-fluorophenyl)-N-[3-(hydroxymethyl)bicyclo[1.1.1]pentan-1-yl]-5-{3- methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide in the manufacture of a medicament for the treatment of a disease selected from the group consisting of can- cer, Parkinson's disease, Huntington's disease, Alzheimer's disease, psychosis, stroke, extra pyramidal syndrome, attention deficit disorder (ADD), attention deficit hyperactivity disorder (ADHD), amyotrophic lateral sclerosis, cirrhosis, fibrosis, fatty liver, addictive behavior, der- mal fibrosis, a sleep disorder, AIDS, an autoimmune disease, an infection, atherosclerosis, ischemia-reperfusion injury, idiopathic pulmonary fibrosis, systemic sclerosis, irritable bowel disease, chronic kidney disease and pain. In another preferred embodiment of the sixth aspect, the present invention relates to the use of 8-amino-N-[3-(aminomethyl)bicyclo[1.1.1]pentan-1-yl]-6-(4-fluorophenyl)-5-{3- methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide in the manufacture of a medicament for the treatment of a disease selected from the group consisting of can- cer, Parkinson's disease, Huntington's disease, Alzheimer's disease, psychosis, stroke, extra pyramidal syndrome, attention deficit disorder (ADD), attention deficit hyperactivity disorder (ADHD), amyotrophic lateral sclerosis, cirrhosis, fibrosis, fatty liver, addictive behavior, der- mal fibrosis, a sleep disorder, AIDS, an autoimmune disease, an infection, atherosclerosis, ischemia-reperfusion injury, idiopathic pulmonary fibrosis, systemic sclerosis, irritable bowel disease, chronic kidney disease and pain. In another preferred embodiment of the sixth aspect, the present invention relates to the use of 8-amino-N-[3-(acetamidomethyl)bicyclo[1.1.1]pentan-1-yl]-6-(4-fluorophenyl)-5-{3- methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide in the manufacture of a medicament for the treatment of a disease selected from the group consisting of can- cer, Parkinson's disease, Huntington's disease, Alzheimer's disease, psychosis, stroke, extra pyramidal syndrome, attention deficit disorder (ADD), attention deficit hyperactivity disorder (ADHD), amyotrophic lateral sclerosis, cirrhosis, fibrosis, fatty liver, addictive behavior, der- mal fibrosis, a sleep disorder, AIDS, an autoimmune disease, an infection, atherosclerosis, ischemia-reperfusion injury, idiopathic pulmonary fibrosis, systemic sclerosis, irritable bowel disease, chronic kidney disease and pain. In another preferred embodiment of the sixth aspect, the present invention relates to the use of 8-amino-N-{bicyclo[1.1.1]pentan-1-yl}-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2- a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide in the manufacture of a medicament for the treatment of a disease selected from the group consisting of cancer, Parkinson's dis- ease, Huntington's disease, Alzheimer's disease, psychosis, stroke, extra pyramidal syn- drome, attention deficit disorder (ADD), attention deficit hyperactivity disorder (ADHD), amyotrophic lateral sclerosis, cirrhosis, fibrosis, fatty liver, addictive behavior, dermal fibro- sis, a sleep disorder, AIDS, an autoimmune disease, an infection, atherosclerosis, ischemia- reperfusion injury, idiopathic pulmonary fibrosis, systemic sclerosis, irritable bowel disease, chronic kidney disease and pain. In another preferred embodiment of the sixth aspect, the present invention relates to the use of 8-amino-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}-N-[3-({2-oxa-6- Ryvu Therapeutics S.A. and BioNTech SE R10559WO 29 azaspiro[3.3]heptan-6-yl}methyl)bicyclo[1.1.1]pentan-1-yl]imidazo[1,2-a]pyrazine-2-car- boxamide in the manufacture of a medicament for the treatment of cancer. In another preferred embodiment of the sixth aspect, the present invention relates to the use of 8-amino-6-(4-fluorophenyl)-N-[3-(1-hydroxyethyl)bicyclo[1.1.1]pentan-1-yl]-5-{3- methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide in the manufacture of a medicament for the treatment of cancer. In another preferred embodiment of the sixth aspect, the present invention relates to the use of 8-amino-6-(4-fluorophenyl)-N-[3-(hydroxymethyl)bicyclo[1.1.1]pentan-1-yl]-5-{3- methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide in the manufacture of a medicament for the treatment of cancer. In another preferred embodiment of the sixth aspect, the present invention relates to the use of 8-amino-6-(4-fluorophenyl)-N-[3-(hydroxymethyl)bicyclo[1.1.1]pentan-1-yl]-5-{3- methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide in the manufacture of a medicament for the treatment of cancer. In another preferred embodiment of the sixth aspect, the present invention relates to the use of 8-amino-N-[3-(aminomethyl)bicyclo[1.1.1]pentan-1-yl]-6-(4-fluorophenyl)-5-{3- methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide in the manufacture of a medicament for the treatment of cancer. In another preferred embodiment of the sixth aspect, the present invention relates to the use of 8-amino-N-[3-(acetamidomethyl)bicyclo[1.1.1]pentan-1-yl]-6-(4-fluorophenyl)-5-{3- methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide in the manufacture of a medicament for the treatment of cancer. In another preferred embodiment of the sixth aspect, the present invention relates to the use of 8-amino-N-{bicyclo[1.1.1]pentan-1-yl}-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2- a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide in the manufacture of a medicament for the treatment of cancer. In the seventh aspect, the present invention relates to a method for antagonizing the adenosine A2A receptor, wherein said receptor is exposed to the compound according to the first aspect, wherein said method is preferably performed outside the human or animal body and / or wherein said compound preferably exhibits a low CYP inhibition profile. All embodiments of the first aspect including of course all preferred embodiments of the first aspect equally apply to the seventh aspect. Thus, in a preferred embodiment of the seventh aspect, the present invention relates to a method for antagonizing the adenosine A2A receptor, wherein said receptor is exposed to 8- amino-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}-N-[3-({2-oxa-6-aza- spiro[3.3]heptan-6-yl}methyl)bicyclo[1.1.1]pentan-1-yl]imidazo[1,2-a]pyrazine-2-carboxam- ide, wherein said method is preferably performed outside the human or animal body. Ryvu Therapeutics S.A. and BioNTech SE R10559WO 30 In another preferred embodiment of the seventh aspect, the present invention relates to a method for antagonizing the adenosine A2A receptor, wherein said receptor is exposed to 8- amino-6-(4-fluorophenyl)-N-[3-(1-hydroxyethyl)bicyclo[1.1.1]pentan-1-yl]-5-{3-methylimi- dazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide, wherein said method is preferably performed outside the human or animal body. In another preferred embodiment of the seventh aspect, the present invention relates to a method for antagonizing the adenosine A2A receptor, wherein said receptor is exposed to 8- amino-6-(4-fluorophenyl)-N-[3-(hydroxymethyl)bicyclo[1.1.1]pentan-1-yl]-5-{3-methylimi- dazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide, wherein said method is preferably performed outside the human or animal body. In another preferred embodiment of the seventh aspect, the present invention relates to a method for antagonizing the adenosine A2A receptor, wherein said receptor is exposed to 8- amino-6-(4-fluorophenyl)-N-[3-(hydroxymethyl)bicyclo[1.1.1]pentan-1-yl]-5-{3-methylimi- dazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide, wherein said method is preferably performed outside the human or animal body. In another preferred embodiment of the seventh aspect, the present invention relates to a method for antagonizing the adenosine A2A receptor, wherein said receptor is exposed to 8- amino-N-[3-(aminomethyl)bicyclo[1.1.1]pentan-1-yl]-6-(4-fluorophenyl)-5-{3-methylimi- dazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide, wherein said method is preferably performed outside the human or animal body. In another preferred embodiment of the seventh aspect, the present invention relates to a method for antagonizing the adenosine A2A receptor, wherein said receptor is exposed to 8- amino-N-[3-(acetamidomethyl)bicyclo[1.1.1]pentan-1-yl]-6-(4-fluorophenyl)-5-{3- methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide, wherein said method is preferably performed outside the human or animal body. In another preferred embodiment of the seventh aspect, the present invention relates to a method for antagonizing the adenosine A2A receptor, wherein said receptor is exposed to 8- amino-N-{bicyclo[1.1.1]pentan-1-yl}-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin- 6-yl}imidazo[1,2-a]pyrazine-2-carboxamide, wherein said method is preferably performed outside the human or animal body. In the eight aspect, the present invention relates to a method for antagonizing the adeno- sine A2B receptor, wherein said receptor is exposed to the compound according to the first aspect, wherein said method is preferably performed outside the human or animal body and / or wherein said compound preferably exhibits a low CYP inhibition profile. All embodiments of the first aspect including of course all preferred embodiments of the first aspect equally apply to the eight aspect. Ryvu Therapeutics S.A. and BioNTech SE R10559WO 31 Thus, in a preferred embodiment of the eight aspect, the present invention relates to a method for antagonizing the adenosine A2B receptor, wherein said receptor is exposed to 8- amino-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}-N-[3-({2-oxa-6-aza- spiro[3.3]heptan-6-yl}methyl)bicyclo[1.1.1]pentan-1-yl]imidazo[1,2-a]pyrazine-2-carboxam- ide, wherein said method is preferably performed outside the human or animal body. In another preferred embodiment of the eight aspect, the present invention relates to a method for antagonizing the adenosine A2B receptor, wherein said receptor is exposed to 8- amino-6-(4-fluorophenyl)-N-[3-(1-hydroxyethyl)bicyclo[1.1.1]pentan-1-yl]-5-{3-methylimi- dazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide, wherein said method is preferably performed outside the human or animal body. In another preferred embodiment of the eight aspect, the present invention relates to a method for antagonizing the adenosine A2B receptor, wherein said receptor is exposed to 8- amino-6-(4-fluorophenyl)-N-[3-(hydroxymethyl)bicyclo[1.1.1]pentan-1-yl]-5-{3-methylimi- dazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide, wherein said method is preferably performed outside the human or animal body. In another preferred embodiment of the eight aspect, the present invention relates to a method for antagonizing the adenosine A2B receptor, wherein said receptor is exposed to 8- amino-6-(4-fluorophenyl)-N-[3-(hydroxymethyl)bicyclo[1.1.1]pentan-1-yl]-5-{3-methylimi- dazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide, wherein said method is preferably performed outside the human or animal body. In another preferred embodiment of the eight aspect, the present invention relates to a method for antagonizing the adenosine A2B receptor, wherein said receptor is exposed to 8- amino-N-[3-(aminomethyl)bicyclo[1.1.1]pentan-1-yl]-6-(4-fluorophenyl)-5-{3-methylimi- dazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide, wherein said method is preferably performed outside the human or animal body. In another preferred embodiment of the eight aspect, the present invention relates to a method for antagonizing the adenosine A2B receptor, wherein said receptor is exposed to 8- amino-N-[3-(acetamidomethyl)bicyclo[1.1.1]pentan-1-yl]-6-(4-fluorophenyl)-5-{3- methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide, wherein said method is preferably performed outside the human or animal body. In another preferred embodiment of the eight aspect, the present invention relates to a method for antagonizing the adenosine A2B receptor, wherein said receptor is exposed to 8- amino-N-{bicyclo[1.1.1]pentan-1-yl}-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin- 6-yl}imidazo[1,2-a]pyrazine-2-carboxamide, wherein said method is preferably performed outside the human or animal body. In the ninth aspect, the present invention relates to a method for antagonizing the adeno- sine A2A receptor and the adenosine A2B receptor, wherein said receptors are exposed to the compound according to the first aspect, wherein said method is preferably performed Ryvu Therapeutics S.A. and BioNTech SE R10559WO 32 outside the human or animal body and / or wherein said compound preferably exhibits a low CYP inhibition profile. All embodiments of the first aspect including of course all preferred embodiments of the first aspect equally apply to the ninth aspect. Thus, in a preferred embodiment of the ninth aspect, the present invention relates to a method for antagonizing the adenosine A2A receptor and the adenosine A2B receptor, wherein said receptor is exposed to 8-amino-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2- a]pyridin-6-yl}-N-[3-({2-oxa-6-azaspiro[3.3]heptan-6-yl}methyl)bicyclo[1.1.1]pentan-1- yl]imidazo[1,2-a]pyrazine-2-carboxamide, wherein said method is preferably performed out- side the human or animal body. In another preferred embodiment of the ninth aspect, the present invention relates to a method for antagonizing the adenosine A2A receptor and the adenosine A2B receptor, wherein said receptor is exposed to 8-amino-6-(4-fluorophenyl)-N-[3-(1-hydroxyethyl)bicy- clo[1.1.1]pentan-1-yl]-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-car- boxamide, wherein said method is preferably performed outside the human or animal body. In another preferred embodiment of the ninth aspect, the present invention relates to a method for antagonizing the adenosine A2A receptor and the adenosine A2B receptor, wherein said receptor is exposed to 8-amino-6-(4-fluorophenyl)-N-[3-(hydroxymethyl)bicy- clo[1.1.1]pentan-1-yl]-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-car- boxamide, wherein said method is preferably performed outside the human or animal body. In another preferred embodiment of the ninth aspect, the present invention relates to a method for antagonizing the adenosine A2A receptor and the adenosine A2B receptor, wherein said receptor is exposed to 8-amino-6-(4-fluorophenyl)-N-[3-(hydroxymethyl)bicy- clo[1.1.1]pentan-1-yl]-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-car- boxamide, wherein said method is preferably performed outside the human or animal body. In another preferred embodiment of the ninth aspect, the present invention relates to a method for antagonizing the adenosine A2A receptor and the adenosine A2B receptor, wherein said receptor is exposed to 8-amino-N-[3-(aminomethyl)bicyclo[1.1.1]pentan-1- yl]-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-car- boxamide, wherein said method is preferably performed outside the human or animal body. In another preferred embodiment of the ninth aspect, the present invention relates to a method for antagonizing the adenosine A2A receptor and the adenosine A2B receptor, wherein said receptor is exposed to 8-amino-N-[3-(acetamidomethyl)bicyclo[1.1.1]pentan- 1-yl]-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2- carboxamide, wherein said method is preferably performed outside the human or animal body. In another preferred embodiment of the ninth aspect, the present invention relates to a method for antagonizing the adenosine A2A receptor and the adenosine A2B receptor, Ryvu Therapeutics S.A. and BioNTech SE R10559WO 33 wherein said receptor is exposed to 8-amino-N-{bicyclo[1.1.1]pentan-1-yl}-6-(4-fluo- rophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide, wherein said method is preferably performed outside the human or animal body. In the tenth aspect, the present invention relates to the use of the compound according to the first aspect as adenosine A2A receptor antagonist. All embodiments of the first aspect including of course all preferred embodiments of the first aspect equally apply to the tenth aspect. Thus, in a preferred embodiment of the tenth aspect, the present invention relates to the use of 8-amino-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}-N-[3-({2-oxa-6- azaspiro[3.3]heptan-6-yl}methyl)bicyclo[1.1.1]pentan-1-yl]imidazo[1,2-a]pyrazine-2-car- boxamide as adenosine A2A receptor antagonist. In another preferred embodiment of the tenth aspect, the present invention relates to the use of 8-amino-6-(4-fluorophenyl)-N-[3-(1-hydroxyethyl)bicyclo[1.1.1]pentan-1-yl]-5-{3- methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide as adenosine A2A receptor antagonist. In another preferred embodiment of the tenth aspect, the present invention relates to the use of 8-amino-6-(4-fluorophenyl)-N-[3-(hydroxymethyl)bicyclo[1.1.1]pentan-1-yl]-5-{3- methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide as adenosine A2A receptor antagonist. In another preferred embodiment of the tenth aspect, the present invention relates to the use 8-amino-6-(4-fluorophenyl)-N-[3-(hydroxymethyl)bicyclo[1.1.1]pentan-1-yl]-5-{3- methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide of as adenosine A2A receptor antagonist. In another preferred embodiment of the tenth aspect, the present invention relates to the use of 8-amino-N-[3-(aminomethyl)bicyclo[1.1.1]pentan-1-yl]-6-(4-fluorophenyl)-5-{3- methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide as adenosine A2A receptor antagonist. In another preferred embodiment of the tenth aspect, the present invention relates to the use of 8-amino-N-[3-(acetamidomethyl)bicyclo[1.1.1]pentan-1-yl]-6-(4-fluorophenyl)-5-{3- methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide as adenosine A2A receptor antagonist. In another preferred embodiment of the tenth aspect, the present invention relates to the use of 8-amino-N-{bicyclo[1.1.1]pentan-1-yl}-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2- a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide as adenosine A2A receptor antago- nist. Ryvu Therapeutics S.A. and BioNTech SE R10559WO 34 In the eleventh aspect, the present invention relates to the use of the compound accord- ing to the first aspect as adenosine A2B receptor antagonist. All embodiments of the first aspect including of course all preferred embodiments of the first aspect equally apply to the eleventh aspect. Thus, in a preferred embodiment of the eleventh aspect, the present invention relates to the use of 8-amino-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}-N-[3-({2- oxa-6-azaspiro[3.3]heptan-6-yl}methyl)bicyclo[1.1.1]pentan-1-yl]imidazo[1,2-a]pyrazine-2- carboxamide as adenosine A2B receptor antagonist. In another preferred embodiment of the eleventh aspect, the present invention relates to the use of 8-amino-6-(4-fluorophenyl)-N-[3-(1-hydroxyethyl)bicyclo[1.1.1]pentan-1-yl]-5- {3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide as adenosine A2B receptor antagonist. In another preferred embodiment of the eleventh aspect, the present invention relates to the use of 8-amino-6-(4-fluorophenyl)-N-[3-(hydroxymethyl)bicyclo[1.1.1]pentan-1-yl]-5- {3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide as adenosine A2B receptor antagonist. In another preferred embodiment of the eleventh aspect, the present invention relates to the use 8-amino-6-(4-fluorophenyl)-N-[3-(hydroxymethyl)bicyclo[1.1.1]pentan-1-yl]-5-{3- methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide of as adenosine A2B receptor antagonist. In another preferred embodiment of the eleventh aspect, the present invention relates to the use of 8-amino-N-[3-(aminomethyl)bicyclo[1.1.1]pentan-1-yl]-6-(4-fluorophenyl)-5-{3- methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide as adenosine A2B receptor antagonist. In another preferred embodiment of the eleventh aspect, the present invention relates to the use of 8-amino-N-[3-(acetamidomethyl)bicyclo[1.1.1]pentan-1-yl]-6-(4-fluorophenyl)- 5-{3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide as adenosine A2B receptor antagonist. In another preferred embodiment of the eleventh aspect, the present invention relates to the use of 8-amino-N-{bicyclo[1.1.1]pentan-1-yl}-6-(4-fluorophenyl)-5-{3-methylimi- dazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide as adenosine A2B receptor antagonist. In the twelfth aspect, the present invention relates to the use of the compound according to the first aspect as adenosine A2A receptor and adenosine A2B receptor antagonist. All embodiments of the first aspect including of course all preferred embodiments of the first aspect equally apply to the twelfth aspect. Ryvu Therapeutics S.A. and BioNTech SE R10559WO 35 Thus, in a preferred embodiment of the twelfth aspect, the present invention relates to the use of 8-amino-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}-N-[3-({2-oxa-6- azaspiro[3.3]heptan-6-yl}methyl)bicyclo[1.1.1]pentan-1-yl]imidazo[1,2-a]pyrazine-2-car- boxamide as adenosine A2A receptor and adenosine A2B receptor antagonist. In another preferred embodiment of the twelfth aspect, the present invention relates to the use of 8-amino-6-(4-fluorophenyl)-N-[3-(1-hydroxyethyl)bicyclo[1.1.1]pentan-1-yl]-5- {3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide as adenosine A2A receptor and adenosine A2B receptor antagonist. In another preferred embodiment of the twelfth aspect, the present invention relates to the use of 8-amino-6-(4-fluorophenyl)-N-[3-(hydroxymethyl)bicyclo[1.1.1]pentan-1-yl]-5- {3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide as adenosine A2A receptor and adenosine A2B receptor antagonist. In another preferred embodiment of the twelfth aspect, the present invention relates to the use 8-amino-6-(4-fluorophenyl)-N-[3-(hydroxymethyl)bicyclo[1.1.1]pentan-1-yl]-5-{3- methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide of as adenosine A2A receptor and adenosine A2B receptor antagonist. In another preferred embodiment of the twelfth aspect, the present invention relates to the use of 8-amino-N-[3-(aminomethyl)bicyclo[1.1.1]pentan-1-yl]-6-(4-fluorophenyl)-5-{3- methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide as adenosine A2A receptor and adenosine A2B receptor antagonist. In another preferred embodiment of the twelfth aspect, the present invention relates to the use of 8-amino-N-[3-(acetamidomethyl)bicyclo[1.1.1]pentan-1-yl]-6-(4-fluorophenyl)- 5-{3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide as adenosine A2A receptor and adenosine A2B receptor antagonist. In another preferred embodiment of the twelfth aspect, the present invention relates to the use of 8-amino-N-{bicyclo[1.1.1]pentan-1-yl}-6-(4-fluorophenyl)-5-{3-methylimi- dazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide as adenosine A2A receptor and adenosine A2B receptor antagonist. In the thirteenth aspect, the present invention relates to a method of manufacturing a pharmaceutical composition according to the second aspect, comprising the step of con- tacting the compound according to the first aspect with a pharmaceutically acceptable car- rier, diluent and / or excipient. In an embodiment of the thirteenth aspect, the method further comprises the step of blending the compound according to the first aspect and / or blending the pharmaceutically acceptable carrier, diluent and / or excipient, wherein the compound according to the first aspect and the pharmaceutically acceptable carrier, diluent and / or excipient may optionally be blended together. Ryvu Therapeutics S.A. and BioNTech SE R10559WO 36 In another embodiment of the thirteenth aspect, the method further comprises the step of milling the compound according to the first aspect and / or milling the pharmaceutically ac- ceptable carrier, diluent and / or excipient, wherein the compound according to the first as- pect and the pharmaceutically acceptable carrier, diluent and / or excipient may optionally be milled together. In another embodiment of the thirteenth aspect, the method further comprises the step of sieving the compound according to the first aspect and / or sieving the pharmaceutically ac- ceptable carrier, diluent and / or excipient, wherein the compound according to the first as- pect and the pharmaceutically acceptable carrier, diluent and / or excipient may optionally be sieved together. In another embodiment of the thirteenth aspect, the method further comprises the step of granulating the compound according to the first aspect with a pharmaceutically acceptable carrier, diluent and / or excipient. In another embodiment of the thirteenth aspect, the method further comprises the step of compressing the compound according to the first aspect with a pharmaceutically acceptable carrier, diluent and / or excipient. In another embodiment of the thirteenth aspect, the method further comprises the step of compressing a blend of the compound according to the first aspect and a pharmaceutically acceptable carrier, diluent and / or excipient. All embodiments of the first aspect including of course all preferred embodiments of the first aspect equally apply to the thirteenth aspect. In the fourteenth aspect, the present invention relates to a method of manufacturing a compound according to the first aspect, wherein the manufacturing essentially follows the synthesis scheme provided in the example section of the present application. All embodiments of the first aspect including of course all preferred embodiments of the first aspect equally apply to the fourteenth aspect.

[0002] Ryvu Therapeutics S.A. and BioNTech SE R10559WO 37 Detailed description Definitions The term "compound(s) of the present invention" is to be understood as equivalent to the term "compound(s) according to the invention", therefore also comprising a salt, stereoi- somer, tautomer, isotopologue, or N-oxide thereof. The compounds according to the invention may be amorphous or may exist in one or more different crystalline states (polymorphs) which may have different macroscopic properties such as stability or show different biological properties such as activities. The present in- vention relates to amorphous and crystalline compounds of formula (I), mixtures of different crystalline states of the respective compound of the invention, as well as amorphous or crystalline salts thereof. Salts of the compounds according to the invention are preferably pharmaceutically accept- able salts, such as those containing counterions present in drug products listed in the US FDA Orange Book database. They can be formed in a customary manner, e.g., by reacting the compound with an acid of the anion in question if the compounds according to the in- vention have a basic functionality or by reacting acidic compounds according to the inven- tion with a suitable base. Suitable cationic counterions are in particular the ions of the alkali metals, preferably lithium, sodium and potassium, of the alkaline earth metals, preferably calcium, magnesium and barium, and of the transition metals, preferably manganese, copper, silver, zinc and iron, and also ammonium (NH4+) and substituted ammonium in which one to four of the hy- drogen atoms are replaced by C1-C4-alkyl, C1-C4-hydroxyalkyl, C1-C4-alkoxy, C1-C4-alkoxy- C1-C4-alkyl, hydroxy-C1-C4-alkoxy-C1-C4-alkyl, phenyl or benzyl. Examples of substituted ammonium ions comprise methylammonium, isopropylammonium, dimethylammonium, diisopropylammonium, trimethylammonium, tetramethylammonium, tetraethylammonium, tetrabutylammonium, 2-hydroxyethylammonium, 2-(2-hydroxyethoxy)ethyl-ammonium, bis(2-hydroxyethyl)ammonium, benzyltrimethylammonium and benzyltriethylammonium, furthermore the cations of 1,4-piperazine, meglumine, benzathine and lysine. Suitable acidic counterions are in particular chloride, bromide, hydrogensulfate, sulfate, di- hydrogenphosphate, hydrogenphosphate, phosphate, nitrate, bicarbonate, carbonate, hex- afluorosilicate, hexafluorophosphate, benzoate, and the anions of C1-C4-alkanoic acids, preferably formate, acetate, propionate and butyrate, furthermore lactate, gluconate, and poly acids such as succinate, oxalate, maleate, fumarate, malate, tartrate and citrate, fur- thermore sulfonate anions such as besylate (benzenesulfonate), tosylate (p-toluenesul- fonate), napsylate (naphthalene-2-sulfonate), mesylate (methanesulfonate), esylate (ethanesulfonate), and ethanedisulfonate. They can be formed by reacting compounds ac- cording to the invention that have a basic functionality with an acid of the corresponding anion. Depending on the substitution pattern, the compounds according to the invention may have one or more centres of chirality, including axial chirality. The invention provides both pure enantiomers or pure diastereomers of the compounds according to the invention, and their mixtures, including racemic mixtures. Suitable compounds according to the invention also include all possible geometrical stereoisomers (cis / trans isomers or E / Z isomers) and mixtures thereof. Cis / trans isomers may be present with respect to, e.g., an alkene, carbon- Ryvu Therapeutics S.A. and BioNTech SE R10559WO 38 nitrogen double-bond or amide group. Tautomers may be formed, if a substituent is present at the compound of formula (I), which allows for the formation of tautomers such as keto-enol tautomers, imine-enamine tautomers, amide-imidic acid tautomers or the like. An isotopologue is an isotopically enriched compound. The term "isotopically enriched compound" refers to a compound containing at least one atom having an isotopic composi- tion other than the natural isotopic composition of that atom. Preferably, the isotopologue is a deuterium(i.e. D or ²H)-enriched compound. The term "N-oxide" includes any compound of the present invention which has at least one tertiary nitrogen atom that is oxidized to a N-oxide moiety. The term "substituted", as used herein, means that a hydrogen atom bonded to a desig- nated atom is replaced with a specified substituent, provided that the substitution results in a stable or chemically feasible compound. Unless otherwise indicated, a substituted atom may have one or more substituents and each substituent is independently selected. The term "substitutable", when used in reference to a designated atom, means that at- tached to the atom is a hydrogen, which can be replaced with a suitable substituent. When it is referred to certain atoms or moieties being substituted with “one or more” sub- stituents, the term “one or more” is intended to cover at least one substituent, e.g. 1 to 10 substituents, preferably 1, 2, 3, 4, or 5 substituents, more preferably 1, 2, or 3 substituents, most preferably 1, or 2 substituents. When neither the term “unsubstituted” nor “substitu- ted” is explicitly mentioned concerning a moiety, said moiety is to be considered as unsub- stituted. The organic moieties mentioned in the above definitions of the variables are - like the term halogen - collective terms for individual listings of the individual group members. The prefix Cn-Cmindicates in each case the possible number of carbon atoms in the group. The term “halogen” denotes in each case fluorine, bromine, chlorine or iodine, in particular fluorine or chlorine. The term "alkyl" as used herein denotes in each case a straight-chain or branched alkyl group having usually from 1 to 6 carbon atoms, preferably 1 to 5 or 1 to 4 carbon atoms, more preferably 1 to 3 or 1 to 2 or 1 carbon atoms. Examples of an alkyl group are methyl, ethyl, n-propyl, iso-propyl, n-butyl, 2-butyl, iso-butyl, tert-butyl, n-pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, 1-ethylpropyl, n-hexyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1,1- dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, 1- ethyl-1-methylpropyl, and 1-ethyl-2-methylpropyl. The term "haloalkyl" as used herein denotes in each case a straight-chain or branched alkyl group having usually from 1 to 10 carbon atoms, frequently from 1 to 6 carbon atoms, preferably from 1 to 4 carbon atoms, wherein the hydrogen atoms of this group are partially or totally replaced with halogen atoms. Preferred haloalkyl moieties are selected from C1- C4-haloalkyl, more preferably from C1-C3-haloalkyl or C1-C2-haloalkyl, in particular from C1- C2-fluoroalkyl such as fluoromethyl, difluoromethyl, trifluoromethyl, 1-fluoroethyl, 2-fluo- roethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, pentafluoroethyl, and the like. The term "alkenyl" as used herein denotes in each case an unsaturated hydrocarbon group having usually 2 to 6, preferably 2 to 4 carbon atoms comprising at least one carbon-carbon double bond in any position, e.g. vinyl (ethenyl), allyl (2-propen-1-yl), 1-propen-1-yl, Ryvu Therapeutics S.A. and BioNTech SE R10559WO 39 2-propen-2-yl, methallyl (2-methylprop-2-en-1-yl), 2-buten-1-yl, 3-buten-1-yl, 2-penten-1- yl, 3-penten-1-yl, 4-penten-1-yl, 1-methylbut-2-en-1-yl, 2-ethylprop-2-en-1-yl and the like. If geometric isomers are possible with regard to the double bond, the present invention re- lates to both, the E- and Z-isomers. Preferred alkenyl groups according to the invention are terminal alkenyl groups. The bonding of vinyl is exemplified below. The term "haloalkenyl" as used herein refers to an alkenyl group as defined above, wherein the hydrogen atoms are partially or totally replaced with halogen atoms. The term "alkynyl" as used herein denotes in each case an unsaturated hydrocarbon group having usually 2 to 6, preferably 2 to 5 or 2 to 4 carbon atoms, more preferably 2 to 3 carbon atoms, comprising at least one carbon-carbon triple bond in any position, e.g. ethynyl, propargyl (2-propyn-1-yl), 1-propyn-1-yl, 1-methylprop-2-yn-1-yl), 2-butyn-1-yl, 3-butyn-1- yl, 1-pentyn-1-yl, 3-pentyn-1-yl, 4-pentyn-1-yl, 1-methylbut-2-yn-1-yl, 1-ethylprop-2-yn-1- yl and the like. The term "haloalkynyl" as used herein refers to an alkynyl group as defined above, wherein the hydrogen atoms are partially or totally replaced with halogen atoms. The term "alkoxy" as used herein denotes in each case a straight-chain or branched alkyl group which is bonded via an oxygen atom and has usually from 1 to 6 carbon atoms, preferably 1 to 2 carbon atoms, more preferably 1 carbon atom. Examples of an alkoxy group are methoxy, ethoxy, n-propoxy, iso-propoxy, n-butyloxy, 2-butyloxy, iso-butyloxy, tert.-butyloxy, and the like. The term "haloalkoxy" as used herein denotes in each case a straight-chain or branched alkoxy group having from 1 to 6 carbon atoms, preferably 1 to 2 carbon atoms, more prefer- ably 1 carbon atom, wherein the hydrogen atoms of this group are partially or totally re- placed with halogen atoms, in particular fluorine atoms. Preferred haloalkoxy moieties in- clude C1-haloalkoxy, in particular C1-fluoroalkoxy, such as trifluoromethoxy and the like. The term “carbocyclic” includes, unless otherwise indicated, in general a 3- to 9-mem- bered, preferably a 4- to 8-membered or a 5- to 7-membered, more preferably a 5- or 6- membered monocyclic ring comprising 3 to 9, preferably 4 to 8 or 5 to 7, more preferably 5 or 6 carbon atoms. The carbocycle may be saturated, partially unsaturated, or fully unsatu- rated. Preferably, the term “carbocycle” covers cycloalkyl and cycloalkenyl groups as de- fined above, for example cyclopropane, cyclobutane, cyclopentane and cyclohexane rings. When it is referred to “fully unsaturated” carbocycles, this term also includes “aromatic” carbocycles or aryls. In certain preferred embodiments, a fully unsaturated carbocycle is an aromatic carbocycle as defined below, preferably a 6-membered aromatic carbocycle. Phenyl is a preferred fully unsaturated carbocycle. The term "carbobicyclic" includes in general bicyclic 4- to 14-membered, bicyclic rings comprising 4 to 14, carbon atoms. The carbobicycle may be saturated, partially unsaturated, or fully unsaturated. Preferably, the term “carbobicycle” covers bicycloalkyl, bicycloalkenyl and bicyclic aromatic groups, for example bicyclobutane (such as bicyclo[1.1.0]butane), bi- cyclopentane (such as bicyclo[1.1.1]pentane), bicyclohexane, bicycloheptane (such as nor- bornane), bicyclooctane (such as bicyclo[2.2.2]octane, bicyclo[3.2.1]octane or bicy- clo[4.2.0]octane), bicyclononane (such as bicyclo[3.3.1]nonane or bicyclo[4.3.0]nonane ), bicyclodecane (such as bicyclo[4.4.0]decane), bicycloundecane (such as bicyclo[3.3.3]un- decane), norbornene, naphthalene and the like. Ryvu Therapeutics S.A. and BioNTech SE R10559WO 40 The term “heterocyclic” includes, unless otherwise indicated, in general a 3- to 9-mem- bered, preferably a 4- to 8-membered or 5- to 7-membered, more preferably 5- or 6-mem- bered, in particular 6-membered monocyclic ring. The heterocycle may be saturated, par- tially unsaturated, or fully unsaturated. As used in this context, the term “fully unsaturated” also includes “aromatic”. In a preferred embodiment, a fully unsaturated heterocycle is thus an aromatic heterocycle, preferably a 5- or 6-membered aromatic heterocycle comprising one or more, e.g. 1, 2, 3, or 4, preferably 1, 2, or 3 heteroatoms selected from N, O and S as ring members, where S-atoms as ring members may be present as S, SO or SO2. Examples of aromatic heterocycles are provided below in connection with the definition of “hetaryl”. “Hetaryls” or “heteroaryls” are covered by the term “heterocycles”. The saturated or par- tially unsaturated heterocycles usually comprise 1, 2, 3, 4 or 5, preferably 1, 2 or 3 het- eroatoms selected from N, O and S as ring members, where S-atoms as ring members may be present as S, SO or SO2.Preferably, the S atom will not be present in oxidized form in fully unsaturated compounds. In particular, the following scenarios are covered: A skilled person is aware that resonance structures of the oxidized forms may be possible. Saturated heterocycles include, unless otherwise indicated, in general 3- to 9-membered, preferably 4- to 8-membered or 5- to 7-membered, more preferably 5- or 6-membered monocyclic rings comprising 3 to 9, preferably 4 to 8 or 5 to 7, more preferably 5 or 6 atoms comprising at least one heteroatom, such as pyrrolidine, tetrahydrothiophene, tetrahydrofu- ran, piperidine, tetrahydropyran, dioxane, morpholine or piperazine. The term "hetaryl" or “heteroaryl” or “aromatic heterocycle” or “aromatic heterocyclic ring” includes monocyclic 5- or 6-membered aromatic heterocycles comprising as ring members 1, 2, 3 or 4 heteroatoms selected from N, O and S, where S-atoms as ring members may be present as S, SO or SO2Preferably, the S atom will not be present in oxidized form in fully unsaturated compounds. In particular, the following scenarios are covered: A skilled person is aware that resonance structures of the oxidized forms may be possible. Examples of 5- or 6-membered aromatic heterocycles include pyridyl, i.e. 2-, 3-, or 4-pyridyl, pyrimidinyl, i.e. 2-, 4- or 5-pyrimidinyl, pyrazinyl, pyridazinyl, i.e. 3- or 4-pyridazinyl, thienyl, i.e. 2- or 3-thienyl, furyl, i.e. 2-or 3-furyl, pyrrolyl, i.e. 2- or 3-pyrrolyl, oxazolyl, i.e.2-, 3- or 5- oxazolyl, isoxazolyl, i.e. 3-, 4- or 5-isoxazolyl, thiazolyl, i.e. 2-, 3- or 5-thiazolyl, isothiazolyl, i.e. 3-, 4- or 5-isothiazolyl, pyrazolyl, i.e.1-, 3-, 4- or 5-pyrazolyl, i.e. 1-, 2-, 4- or 5-imida- zolyl, oxadiazolyl, e.g. 2- or 5-[1,3,4]oxadiazolyl, 4- or 5-(1,2,3-oxadiazol)yl, 3- or 5-(1,2,4- oxadiazol)yl, 2- or 5-(1,3,4-thiadiazol)yl, thiadiazolyl, e.g. 2- or 5-(1,3,4-thiadiazol)yl, 4- or 5-(1,2,3-thiadiazol)yl, 3- or 5-(1,2,4-thiadiazol)yl, triazolyl, e.g. 1H-, 2H- or 3H-1,2,3-triazol- 4-yl, 2H-triazol-3-yl, 1H-, 2H-, or 4H-1,2,4-triazolyl and tetrazolyl, i.e.1H- or 2H-tetrazolyl. The term "heterobicyclic" includes in general bicyclic 4- to 14-membered bicyclic rings comprising as ring members 1, 2, 3 or 4 heteroatoms selected from N, O and S, where S- atoms as ring members may be present as S, SO or SO2. The heterobicycle may be satu- rated, partially unsaturated, or fully unsaturated. Examples of heterobicycles include benzo- furanyl, benzothienyl, indolyl, indazolyl, benzimidazolyl, benzoxathiazolyl, benzoxadiazolyl, benzothiadiazolyl, benzoxazinyl, quinolinyl, isoquinolinyl, purinyl, 1,8-naphthyridyl, pteridyl, pyrido[3,2-d]pyrimidyl, pyridoimidazolyl, triethylenediamine or quinuclidine and the like. Ryvu Therapeutics S.A. and BioNTech SE R10559WO 41 As used in the specification and the claims, the singular forms of “a” and “an” also include the corresponding plurals unless the context clearly dictates otherwise. The same applies for plural forms used herein, which also include the singular forms unless the context clearly dictates otherwise. The terms “about” and “approximately” in the context of the present invention denotes an interval of accuracy that a person skilled in the art will understand to still ensure the techni- cal effect of the feature in question. The term typically indicates a deviation from the indi- cated numerical value of ±10% and preferably ±5%. It needs to be understood that the term “comprising” is not limiting. For the purposes of the present invention, the term “consisting of” is considered to be a preferred embodiment of the term “comprising of”. If hereinafter a group is defined to comprise at least a certain number of embodiments, this is also meant to encompass a group which preferably consists of these embodiments only. The term “pharmaceutically acceptable excipient” as used herein refers to an excipient commonly comprised in pharmaceutical compositions, which is known to the skilled person. Examples of a suitable excipient are exemplary listed below. Typically, a pharmaceutically acceptable excipient can be defined as being pharmaceutically inactive. The term “treatment” is to be understood as also including the option of “prophylaxis”. Thus, whenever reference is made herein to a “treatment” or “treating”, this is to be under- stood as “treatment and / or prophylaxis” or “treating and / or preventing”. The term “exhibits a low CYP-inhibition profile” as used herein means a that compound does substantially not inhibit the various members of the Cytochromes P450 (or CYPs), which are enzymes catalyzing the degradation of various (toxic) compounds. This can e.g. indicate a lower risk of drug-drug interactions in case of combination therapies comprising the afore-mentioned compound or co-administration of the afore-mentioned compound with other drugs. Description of pharmaceutical compositions according to the present invention A pharmaceutical composition according to the present invention may be formulated for oral, buccal, nasal, rectal, topical, transdermal or parenteral application. Oral application may be preferred. Parenteral application can also be preferred and includes intravenous, in- traarterial, intratumoral, intrathecal, intravesical, intramuscular or subcutaneous administra- tion. The compound according to formula (I) should be applied in a pharmaceutically effec- tive amount, for example in the amount as set out herein below. A pharmaceutical composition of the present invention may also be designated as formu- lation or dosage form. A compound of formula (I) may also be designated in the following as (pharmaceutically) active agent or active compound. A pharmaceutical composition may be a solid or a liquid dosage form or may have an inter- mediate, e.g. gel-like character depending inter alia on the route of administration. In general, the dosage form can comprise at least one pharmaceutically acceptable excipi- ent, which will be selected depending on which functionality is to be achieved for the dosage form. A “pharmaceutically acceptable excipient” in the meaning of the present in- vention can be any substance used for the preparation of a pharmaceutical dosage form, in- cluding a coating material, a film-forming material, a filler, a disintegrating agent, a release- modifying material, a carrier material, a diluent, a binding agent and any other adjuvant. A Ryvu Therapeutics S.A. and BioNTech SE R10559WO 42 typical pharmaceutically acceptable excipient includes a substance like sucrose, mannitol, sorbitol, starch and starch derivatives, lactose, and a lubricating agent such as magnesium stearate, a disintegrant and a buffering agent. The term “carrier” denotes a pharmaceutically acceptable organic or inorganic carrier sub- stance with which the active ingredient is combined to facilitate the application. A suitable pharmaceutically acceptable carrier includes, for instance, water, an aqueous salt solution, an alcohol, oil, preferably vegetable oil, propylene glycol, polyoxyethelene sorbitan, a poly- ethylene-polypropylene block co-polymer such as poloxamer 188 or poloxamer 407, a poly- ethylene glycol such as polyethylene glycol 200, 300, 400, 600, etc., gelatin, lactose, amy- lose, magnesium stearate, a surfactant, perfume oil, a fatty acid monoglyceride, a diglyc- eride and a triglycerides, a polyoxyethylated medium or a long chain fatty acid such as rici- noleic acid, and a polyoxyethylated fatty acid mono-, di, and triglyceride such as capric or caprilic acid, petroethral fatty acid ester, hydroxymethyl cellulose such as hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxypropyl acetate succinate, polyvinylpyrrolidone, crosspovidone and the like. The pharmaceutical composition can be sterile and, if desired, mixed with an auxiliary agent, like a lubricant, a preservative, a stabilizer, a wetting agent , an emulsifier, a salt for influencing osmotic pressure, a buffer, a coloring, a flavoring and / or aromatic substance and the like which does not deleteriously react with the active com- pound. If a liquid dosage form is considered for the present invention, this can include a pharma- ceutically acceptable emulsion, a solutions, a suspension and a syrups containing an inert diluent commonly used in the art such as water. Such a dosage form may contain e.g. mi- crocrystalline cellulose for imparting bulk, alginic acid or sodium alginate as a suspending agent, methylcellulose as a viscosity enhancer and a sweetener / flavouring agent. For parenteral application, a particularly suitable vehicle consists of a solution, preferably an oily or aqueous solution, as well as a suspension, an emulsions, or an implant. A phar- maceutical formulation for parenteral administration is particularly preferred and includes an aqueous solution of the compounds of formula (I) in water-soluble form. Additionally, a suspension of the compounds of formula (I) may be prepared as an appropriate oily injec- tion suspension. A suitable lipophilic solvent or vehicle includes a fatty oil such as sesame oil, soybean oil, or a tocopherol, or a synthetic fatty acid ester, such as ethyl oleate or triglyceride, or a liposome. An aqueous injection suspension may contain a substance which increases the viscosity of the suspension, such as sodium carboxymethyl cellulose, sorbitol, or dextran. A particularly preferred dosage form is an injectable preparation of a compound of formula (I). Thus, a sterile injectable aqueous or oleaginous suspension can for example be formu- lated according to the known art using a suitable dispersing agent, a wetting agent and / or a suspending agent. A sterile injectable preparation can also be a sterile injectable solution or suspension or an emulsion in a non-toxic parenterally acceptable diluant or solvent. Among the acceptable vehicles and solvents that can be used are water and isotonic sodium chlo- ride solution. A sterile oil is also conventionally used as solvent or suspending medium. A suppository for rectal administration of a compound of formula (I) can be prepared by e.g. mixing the compound of formula (I) with a suitable non-irritating excipient such as co- coa butter, a synthetic triglyceride and a polyethylene glycol which is solid at room tempera- ture but liquid at rectal temperature such that it will melt in the rectum and release the compound according to formula (I) from said suppository. Ryvu Therapeutics S.A. and BioNTech SE R10559WO 43 For administration by inhalation, the compound of formula (I) may be conveniently deliv- ered in the form of an aerosol spray from a pressurized pack or a nebulizer, with the use of a suitable propellant, e.g., dichlorodifluoromethane, trichlorofluoromethane, dichlorote- trafluoroethane, carbon dioxide or other suitable gas. In the case of a pressurized aerosol the dosage unit may be determined by providing a valve to deliver a metered amount. A cap- sule and cartridge of e.g. gelatin for use in an inhaler or insufflator may be formulated con- taining a powder mix of the compound and a suitable powder base such as lactose or starch. An oral dosage form may be liquid or solid and include e.g. a tablet, a troche, a pill, a cap- sule, a powder, an effervescent formulation, a dragee and a granule. A pharmaceutical preparation for oral use can be obtained as solid excipient, optionally grinding a resulting mixture, and processing the mixture of granules, after adding a suitable auxiliary agent, if desired, to obtain a tablet or a dragee core. A suitable excipient is, in particular, a filler such as a sugar, including lactose, sucrose, mannitol, or sorbitol; a cellulose preparation such as, for example, maize starch, wheat starch, rice starch, potato starch, gelatin, gum tragacanth, methyl cellulose, hydroxypropylmethyl cellulose, sodium carboxymethylcellulose, and / or polyvinylpyrrolidone (PVP). If desired, a disintegrating agent may be added, such as the cross-linked polyvinyl pyrrolidone (crosspovidone), agar, or alginic acid or a salt thereof such as sodium alginate. The oral dosage form may be formulated to ensure an immediate release of the compound of formula (I) or a sustained release of the compound of formula (I). A solid dosage form may comprise a film coating. For example, the dosage form may be in the form of a so-called film tablet. A capsule may be a two-piece hard gelatin capsule, a two-piece hydroxypropylmethylcellulose capsule, a two-piece capsule made of vegetable or plant-based cellulose or a two-piece capsule made of polysaccharide. The dosage form comprising the compound of formula (I) may be formulated for topical application. A suitable pharmaceutical application form for such an application may be a topical nasal spray, a sublingual administration form and a controlled and / or sustained re- lease skin patch. For buccal administration, the composition may take the form of a tablet or lozenge formulated in conventional manner. The composition may conveniently be presented in a unit dosage form and may be pre- pared by any of the methods well known in the art of pharmacy. The method can include the step of bringing the compounds into association with a carrier which constitutes one or more accessory ingredient(s). In general, the composition is prepared by uniformly and inti- mately bringing the compound of formula (I) into association with a liquid carrier, a finely di- vided solid carrier, or both, and then, if necessary, shaping the product. A liquid dose unit is a vial or an ampoule. A solid dose unit is a tablet, a capsule and a suppository. As regards human patients, the compound of formula (I) may be administered to a patient in an amount of about 0.001 mg to about 5000 mg per day, preferably of about 0.01 mg to about 1000 mg per day, which is the effective amount. The phrase “effective amount” means an amount of the compound of formula (I) that, when administered to a mammal in need of such treatment, is sufficient to treat or prevent a particular disease or condition. Furthermore, the pharmaceutical composition may also contain the compound of formula (I) as a prodrug such as an ester or amide thereof. A prodrug is any compound which is con- verted under physiological conditions or by solvolysis to any of the compounds of formula Ryvu Therapeutics S.A. and BioNTech SE R10559WO 44 (I). A prodrug may be inactive prior to administration but may be converted to an active compound of the invention in vivo. Indications, for which the compounds of the present invention may be used The compounds according to the present invention are preferably used for the treatment of a disease selected from the group consisting of cancer, Parkinson's disease, Huntington's disease, Alzheimer's disease, psychosis, stroke, extra pyramidal syndrome (in particular dystonia, akathisia, pseudoparkinsonism and tardive dyskinesia), attention deficit disorder (ADD), attention deficit hyperactivity disorder (ADHD), amyotrophic lateral sclerosis, cirrho- sis, fibrosis, fatty liver, addictive behavior, dermal fibrosis (in particular dermal fibrosis in scleroderma), a sleep disorder, AIDS, an autoimmune disease, an infection, atherosclerosis and ischemia-reperfusion injury. Furthermore, the compounds according to the present in- vention are used for idiopathic pulmonary fibrosis, systemic sclerosis, irritable bowel dis- ease, chronic kidney disease (in particular diabetic nephropathy) and as analgesic. The use for the treatment of cancer is particularly preferred. More generally, the compounds according to the present invention can be used for the treatment of a disease selected from the group consisting of a neurodegenerative disease, a proliferative disease, an inflammatory disease, an infectious disease, sickle cell disease, di- abetic nephropathy, a cognition disease and a CNS disease. The proliferative diseases in- clude cancer. A pharmaceutical composition may comprise the compound of formula (I) as the only pharmaceutically active agent. It is to be understood that in connection with the medical uses of the invention, it can be preferred that the compound of formula (I) according to the present invention is administered in combination with an antibody, radiotherapy, surgical therapy, immunotherapy, chemotherapy, toxin therapy, gene therapy, or any other therapy known to those of ordinary skill in the art for treatment of a particular disease. This is par- ticularly relevant in connection with the treatment of cancer. Preferably, the compounds of the present invention may be coadministered with an anti- neoplastic agent and / or an anti-neoplastic agent may be comprised in the pharmaceutical composition according to the present invention. An anti-neoplastic agent has activity versus a tumor and examples can be found in Cancer Principles and Practice of Oncology by V.T. Devita and S. Hellman (editors), 6th edition (February 15, 2001), Lippincott Williams & Wilkins Publishers. Typical anti-neoplastic agents useful in the present invention include a chemotherapeutic agent, a topoisomerase II inhibitor, an antimetabolite, a topoisomerase I inhibitor, a hor- mone and a hormonal analogue, a signal transduction pathway inhibitor, a tyrosine kinase inhibitor, an angiogenesis inhibitor, a proapoptotic agent, a cell cycle signaling inhibitor, a proteasome inhibitor, an inhibitor of cancer metabolism, and an immunotherapeutic agent. It is widely known today that tumors can evade the immune system by suppressing the im- mune response. A strategy against this suppression resides e.g. in the blockade of recep- tors, which act (co-)inhibitory on the immune system (a negative “immune checkpoint” or “checkpoint”). Agents blocking or inhibiting these receptors (thus resulting in a block of the immunosuppressive signals of the tumor) are commonly referred to as “checkpoint in- hibitors” and this reference is also used herein. Such a checkpoint inhibitor may be selected Ryvu Therapeutics S.A. and BioNTech SE R10559WO 45 from the group consisting of an antibody or an antigen-binding fragment thereof, a small molecule inhibitor and an antisense oligonucleotide. Combination therapy may be achieved by use of a single pharmaceutical composition that includes both agents, or by administering two distinct compositions, preferably at the same time, wherein one composition includes a compound of the present invention, and the other includes the second agent(s). The two therapies may be given in either order and may precede or follow the other treat- ment by intervals ranging from minutes to weeks. In embodiments where the other agents are applied separately, one would generally ensure that a significant period of time did not expire between the time of each delivery, such that the agents would still be able to exert an advantageously combined effect on the patient. In such instances, it is contemplated that one may administer both modalities within about 12-24 h of each other and, more preferably, within about 6-12 h of each other. In some situations, it may be desirable to ex- tend the time period for treatment significantly, however, where several days (2, 3, 4, 5, 6 or 7) to several weeks (1, 2, 3, 4, 5, 6, 7 or 8) lapse between the respective administrations. In some embodiments, the compound of the present invention is administered prior to admin- istration of the distinct cancer treatment. In other embodiments, the distinct cancer treat- ment is administered prior to administration of the compound of the present invention. The present invention is further illustrated by the following examples. Examples Part 1: Synthesis General Abbreviations Some abbreviations that may appear in this application are defined hereinafter: Ryvu Therapeutics S.A. and BioNTech SE R10559WO 46 Ryvu Therapeutics S.A. and BioNTech SE R10559WO 47 Ryvu Therapeutics S.A. and BioNTech SE R10559WO 48 All anhydrous solvents were provided by commercial suppliers, e.g., Sigma- Aldrich®, in appropriate containers, e.g., Sure / Seal™ bottles, and used without further purification. Unless otherwise specified, all starting materials were obtained from commercial suppliers and used without further purification. Unless otherwise specified, all temperatures are ex- pressed in °C and all reactions were conducted at RT. Unless otherwise specified, com- pounds were purified by either flash column chromatography (FCC), preparative HPLC or preparative chiral HPLC. Unless otherwise specified, silica (50 mm average particle size) is the stationary phase used for flash column chromatography purification. NMR: 1H NMR was recorded on a Bruker Ascend 400 MHz spectrometer. Chemical shifts (δ) are reported in ppm relative to the residual solvent signal (δ = 2.50 ppm for1H NMR in DMSO- d6, δ = 3.31 ppm for1H NMR in CD3OD, δ = 7.26 ppm for1H NMR in CDCl3).1H NMR data are reported as follows: chemical shift (multiplicity, coupling constants and number of hy- drogens). Multiplicity is abbreviated as follows: s (singlet), d (doublet), t (triplet), q (quar- tet), m (multiplet), dd (doublet of doublets), tt (triplet of triplets), td (triplet of doublets), dt (doublet of triplets), br (broad). NMR data were analyzed using MestReNova v10.0.2 and ul- terior (Mestrelab Research S.L., Santiago de Compostela, Spain, www.mestrelab.com). Analytical methods: UPLC long elution: Four types of eluent systems were used: Ryvu Therapeutics S.A. and BioNTech SE R10559WO 49 Column: ACQUITY UPLC® BEH C181.7 mm, 2.1 x 100 mm Detection: DAD (Diode Array Detector), CAD (Charged Aerosol Detector) Equipment: H Class Waters UPLC-MS Methods: 3 default methods were available for every buffer type (FA, TFA, NH3and neutral), flow rate 0.5 mL / min: Mid-polar long method: Non polar long method: UPLC Eluent composition: Column: ACQUITY UPLC® BEH C181.7um, 2.1 x 100mm Column. Detection: DAD, MS single quadrupole with positive and negative ionization, ESCI or ESI ion sources Methods: 3 default methods were available for UPLC, flow rate 0.5 mL / min: Polar: Ryvu Therapeutics S.A. and BioNTech SE R10559WO 50 Non polar long method: Equipment: • I Class Waters UPLC-MS with SQD2 and ESCI ion source. • I Class Waters UPLC-MS with SQD2 and ESI ion source. Preparative HPLC purification The following equipment was used for Preparative HPLC purification: Waters Autopurifica- tion system (Waters 2767 – Sample Manager, Waters 2545 – Binary Gradient Module, Wa- ters SFO – System Fluidics Organizer, Waters Prep Degasser, Waters 515 – HPLC Pump, Waters UV Fraction Manager) with DAD (Waters 2998 – Photodiode Array Detector) and QDa (Waters Acquity QDa) detection using a Gemini®5µm NX-C18110 Å (00G-4454-P0-AX LC Column 250 x 21.2 mm, AX). Three types of eluent systems were used: General gradient: flow rate 20 mL / min. Ryvu Therapeutics S.A. and BioNTech SE R10559WO 51 Chiral HPLC purifications The following equipment was used for Chiral HPLC purifications: HPLC Shimadzu hard- ware: 2x LC 20AP pumps, SPD M20A DAD detector, CBM -20A, autosampler SIL 10AP, FRC-10A fraction collector. The chiral columns were of 2 types: • CHIRALPAK® AY-H column (amylose tris(5-chloro-2-methylphenylcarbamate) coated on 5 mm silica-gel, 250 mm x 20 mm) • CHIRALPAK® AD-H column (amylose tris-(3,5-dimethylphenylcarbamate) coated on 5 mm silica-gel, 250 mm x 20 mm) Synthesis of common intermediates lithium(1+) 8-amino-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imi- dazo[1,2-a]pyrazine-2-carboxylate, Int-A-06 Step 1: 6-chl 5-(4-fluorophenyl)pyrazin-2-amine, Int-A-01 In a pressure tube were mixed 2-amino-5-bromo-6-chloropyrazine (20 g, 96.0 mmol), 4- fluorophenylboronic acid (14.8 g, 105.5 mmol), sodium carbonate (20.3 g, 191.9 mmol) in a 4:1 mixture of 1,4-dioxane : water (250 mL). The reaction mixture was sparged with argon and Pd(PPh3)4(2.2 g, 2.0 mmol) was then added. The mixture was sparged with argon shortly and the vessel was sealed. The reaction mixture was heated at 100 °C for 20 h. Af- ter that time, the reaction mixture was cooled down to RT, filtered through Celite® pad, ex- Ryvu Therapeutics S.A. and BioNTech SE R10559WO 52 tracted with EtOAc / NaHCO3solution, organic layer was washed with brine and dried over Na2SO4. Then the mixture was concentrated in vacuo to dryness. The crude material was purified by FCC (0 to 50% EtOAc gradient in hexane) to afford the title product as a light- yellow solid (18.2 g, 85%). m / z (ESI): 224.00 [M+H]+. Step 2: 3-bromo-6-chloro-5-(4-fluorophenyl)pyrazin-2-amine, Int-A-02 Into a pressure tube N-bromosuccinimide (12.6 g, 70.6 mmol) was added in 3 portions to a solution of 6-chloro-5-(4-fluorophenyl)pyrazin-2-amine (15 g, 64.2 mmol) in CH3CN (100 mL) at 0°C. The reaction mixture was allowed to warm to RT and then was heated at 70 °C for 1 h. After cooling down the resulting precipitate was filtered off to afford the title product as a light yellow solid (12.6 g, 65%). m / z (ESI): 303.70 [M+H]+. Step 3: ethyl 8-bromo-5-chloro-6-(4-fluorophenyl)imidazo[1,2-a]pyrazine-2-carboxylate, Int-A-03 To 3-bromo-6-chloro-5-(4-fluorophenyl)pyrazin-2-amine (10 g; 33.06 mmol), dissolved in 130 mL of DME, 3-bromopyruvic acid ethyl ester (19.3 g; 99.17 mmol) was added. The reac- tion was stirred for 1 h at room temperature (appearance of a yellow solid was observed) and then heated to 85 °C for 16 h, under an argon atmosphere. After that time extraction was performed (DCM / NaHCO3aq). Combined organic extracts were dried over MgSO4. The crude material was purified by FCC (0 to 5% EtOH gradient in DCM) to afford the title prod- uct as a white solid (4.5 g, 31%). m / z (ESI): 400.05 [M+H]+. Step 4: ethyl 8-amino-5-chloro-6-(4-fluorophenyl)imidazo[1,2-a]pyrazine-2-carboxylate, Int-A-04 To ethyl 8‐bromo‐5‐chloro‐6‐(4‐fluorophenyl)imidazo[1,2‐a]pyrazine‐2‐car- boxylate (11 g; 31.06 mmol) 0.5M ammonia in dioxane (140 mL) was added, the reaction mixture was heated at 110 °C for 20 h. The RM was evaporated to dryness, the crude ma- terial was purified by FCC (0 to 5% EtOH gradient in DCM) to afford the title product as a white solid (10.5 g, 31.06 mmol, quant).1H NMR (400 MHz, DMSO-d6) δ 8.48 (s, 1H), 7.77 – 7.70 (m, 2H), 7.60 (s, 2H), 7.35 – 7.28 (m, 2H), 4.36 (q, J = 7.1 Hz, 2H), 1.34 (t, J = 7.1 Hz, 3H). m / z (ESI): 335.15 [M+H]+. Step 5: ethyl 8-amino-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imi- dazo[1,2-a]pyrazine-2-carboxylate, Int-A-05 A two-neck round bottom flask with FindenserTMwas charged with 3-methyl-6-(4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)imidazo[1,2-a]pyridine (6.82 g, 25.892 mmol, 2.002 eq.), potassium hydrogen carbonate (2.59 g, 25.871 mmol, 2.0 eq.), NMP (21.0 mL, 1.62 mL / mmol) and water (7.3 mL, 0.56 mL / mmol). The mixture was degassed and flushed with N2. Then, Pd(PPh3)4(0.748 g, 0.647 mmol, 0.05 eq.) was added and degassing / flushing op- eration was repeated. The resulting mixture was stirred at 120 °C under nitrogen atmos- phere. In parallel to this, the microwave reaction vial was charged with ethyl 8-amino-5- chloro-6-(4-fluorophenyl)imidazo[1,2-a]pyrazine-2-carboxylate (5.39 g, 12.935 mmol, 1.0 eq.) and NMP (24.0 mL, 1.86 mL / mmol), degassed, flushed with N2and heated to 120 °C. Next, the solution from the microwave reaction vial was immediately transferred to the mix- ture in the 2-neck flask using a glass syringe. RM was stirred at 120 °C for 2.5 h. The RM was cooled to RT and diluted with water. The iInsoluble solid was filtered off, washed with Ryvu Therapeutics S.A. and BioNTech SE R10559WO 53 water and heptane and dried under reduced pressure. Then, the solid was suspended in EtOH and refluxed for 7 min. The hot mixture was filtered off and the resulting grey solid was washed with a fresh portion of EtOH. This procedure (reflux in EtOH) was repeated three times. The insoluble solid was dried under reduced pressure to give ethyl 8-amino-6- (4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxy- late (3.13 g, 6.835 mmol, 53%, grey solid, UPLC purity: 94%). m / z (ESI): 431.1 [M+H]+. Step 6: lithium(1+) 8-amino-6-(4- yl}imidazo[1,2-a]pyrazine-2- To a suspension of ethyl 8-amino-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6- yl}imidazo[1,2-a]pyrazine-2-carboxylate (8.88 g, 18.773 mmol, 1.0 eq.) in ethanol (70 mL) a solution of lithium(1+) hydrate hydroxide (1.19 g, 28.36 mmol, 1.511 eq.) in water (25 mL) was added. The reaction mixture was heated at 90°C for 2 h. The hot reaction mixture was filtered through a pad of Celite® and washed with hot ethanol. Filtrate was concentrated and used without further purification, lithium(1+) 8-amino-6-(4-fluorophenyl)-5-{3- methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxylate (7.8 g, 17.192 mmol, 92%). 1H NMR (400 MHz, DMSO-d6) δ 8.37 (s, 1H), 7.66 – 7.61 (m, 1H), 7.48 – 7.39 (m, 4H), 7.23 (dd, J = 9.3, 1.5 Hz, 1H), 7.10 – 7.01 (m, 2H), 2.35 (s, 3H). A 5 L reactor was prepared by charging with i-PrOAc . Nitrogen gas was purged into the reactor for 60 minutes. Then, 30 mL of solvent was collected using a syringe. Stir- ring was initiated at 200 RPM, and the flask was charged with the following reagents: 6- bromo-3-methylimidazo[1,2-a]pyridine (185.0 g, 832.7 mmol, 1.0 eq.), potassium acetate (196.13 g, 1998.5 mmol, 2.4 eq.), palladium (II) acetate (5.6 g, 24.95 mmol, 0.03 eq.), and cataCXium A (17.92 g, 49.962 mmol, 0.06 eq.). After 5 minutes of stirring, bis(pinacolato)di- boron (296.04 g, 1165.8 mmol, 1.4 eq.) was added, and the addition funnel was rinsed with degassed solvent (30 mL). The reaction mixture was heated to reflux with an internal tem- perature of 100°C and stirred for 4 hours. Analysis using UPLC indicated a small amount of remaining substrate. After an additional 40 minutes, the reaction reached complete conver- sion. The reaction mixture was cooled to 50°C and quenched with a 2 M sodium hydroxide aqueous solution (555 mL). It was then diluted with water (370 mL) to achieve a pH of 8.5. The heating bath was removed, and the mixture was stirred for 30 minutes, resulting in a precipitation of the product. Heptane (2400 mL) was added to the RM. The reaction mixture was further cooled to 10-15°C using an ice bath. The solids were filtered off, washed with water (930 mL) and heptane (1850 mL), and air-dried for 2-3 hours. The crude material was suspended in ethyl acetate (3500 mL), heated to reflux, and stirred for 30 minutes. Acti- vated carbon (30% weight with respect to the product, 65 g) was added in portions. After 1 hour, the hot mixture was filtered through a thin pad of Celite® and a depth filter, and washed with hot ethyl acetate (6200 mL). Solvent exchange to heptane resulted in the for- mation of 3-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)imidazo[1,2-a]pyridine Ryvu Therapeutics S.A. and BioNTech SE R10559WO 54 as a beige solid (156 g, 574.6 mmol, 69%).1H NMR (400 MHz, CDCl3) δ 8.32 (s, 1H), 7.71 (d, J = 9.0 Hz, 1H), 7.56 (d, J = 9.0 Hz, 1H), 7.43 (s, 1H), 2.53 (s, 3H), 1.36 (s, 12H).1H NMR (400 MHz, CDCl3) δ 8.32 (s, 1H), 7.71 (d, J = 9.0 Hz, 1H), 7.56 (d, J = 9.0 Hz, 1H), 7.43 (s, 1H), 2.53 (s, 3H), 1.36 (s , 1 2 H). benzyl N-{3-for mylbicyclo[1.1.1 ]penta n -1-yl}carbamate , Int-C-03 Step 1: methyl 3-{[(benzyloxy)carbonyl]amino}bicyclo[1.1.1]pentane-1-carboxylate, Int-C- 01 А solution of 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (5.3 g, 31.146 mmol, 1.0 eq.) in anhydrous toluene (200 mL) was prepared. Triethylamine (10.0 mL, 71.744 mmol, 2.303 eq.) was added to the solution. The mixture was stirred at room temperature while DPPA (10.0 g, 36.337 mmol, 1.167 eq.) was slowly added dropwise over a period of 15 minutes. The temperature was gradually increased in steps of 10°C every 15 minutes until reaching 95°C. The RM was maintained at 95°C for 3 hours. Subsequently, the reaction mixture was cooled to 50°C and a solution of benzyl alcohol (7.0 mL, 67.32 mmol, 1.922 eq.) in toluene (10 mL) was added dropwise. The resulting mixture was heated to 95°C and kept at that temperature for 9 hours, followed by cooling to room temperature. To themixture at RT aq. sat. Na2CO3was slowly added, and the biphasic solution was stirred for 30minutes. The entire mixture was then concentrated under reduced pressure, resulting in a total volume of approximately 100 mL consisting of toluene and water. The residue was di- luted with water and extracted three times with ethyl acetate. The combined organic ex- tracts were sequentially washed with aq. sat. NaHCO3solution, water, and brine. Afterward, the organic layer was dried over Na2SO4, filtered, and concentrated. The crude material was purified by FCC (0 to 30% EtOAc gradient in hexane) to yield methyl 3-{[(benzyloxy)car- bonyl]amino}bicyclo[1.1.1]pentane-1-carboxylate (7.0 g, 24.918 mmol, 80%, white solid).1H NMR (400 MHz, DMSO) δ 8.10 (s, 1H), 7.42 – 7.32 (m, 5H), 4.99 (s, 2H), 3.60 (s, 3H), 2.17 (s, 6H). Step 2: benzyl N-[3-(hydroxymethyl)bicyclo[1.1.1]pentan-1-yl]carbamate, Int-C-02. A solution of methyl 3-{[(benzyloxy)carbonyl]amino}bicyclo[1.1.1]pentane-1-carboxylate (5.07 g, 17.495 mmol, 1.0 eq.) in anhydrous tetrahydrofuran was prepared and cooled to 0°C. To this solution, lithium borohydride (1.3 g, 59.688 mmol, 3.412 eq.) was added por- tionwise. After the completion of the addition, the RM was allowed to warm to RT and stirred overnight. Subsequently, the RM was cooled in an ice bath and quenched with aq. sat. NH4Cl. The resulting mixture was partitioned between aq. sat. NaHCO3, water and EtOAc. The aqueous phase was extracted with EtOAc, and the combined organic phases were washed with aq. sat. NaHCO3, brine, dried over Na2SO4, filtered, and concentrated. The crude material was purified by FCC (0 to 100% EtOAc gradient in hexane) to yield ben- zyl N-[3-(hydroxymethyl)bicyclo[1.1.1]pentan-1-yl]carbamate (3.44 g, 13.632 mmol, 78%, Ryvu Therapeutics S.A. and BioNTech SE R10559WO 55 colorless oil).1H NMR (400 MHz, DMSO) δ 7.89 (s, 1H), 7.45 – 7.21 (m, 5H), 4.98 (s, 2H), 4.49 (t, J = 5.5 Hz, 1H), 3.44 (d, J = 5.5 Hz, 2H), 1.77 (s, 6H). Step 3: benzyl N-{3-formylbicyclo[1.1.1]pentan-1-yl}carbamate, Int-C-03 Benzyl N-[3-(hydroxymethyl)bicyclo[1.1.1]pentan-1-yl]carbamate (11.38 g, 45.098 mmol, 1.0 eq.) was dissolved in anhydrous DCM and cooled in an ice bath. Dess-Martin periodi- nane (25.0 g, 58.942 mmol, 1.307 eq.) was added portionwise to the RM to maintain temper- ature below 5°C. After the addition was complete, the reaction mixture was kept at 0°C for 1.5 hours. Afterward, a 10% aqueous Na2S2O3was added to the heterogeneous reaction mixture, followed by aq. sat. NaHCO3solution, and the mixture was stirred for 1 h. Then, DCM was added and phases were separated. The organic phase was concentrated. The crude material was purified by FCC (0 to 50% EtOAc gradient in hexane) to yield benzyl N- {3-formylbicyclo[1.1.1]pentan-1-yl}carbamate (6.0 g, 23.973 mmol, 53%, white solid).1H NMR (400 MHz, DMSO) δ 9.59 (s, 1H), 8.11 (s, 1H), 7.34 (m, 5H), 5.00 (s, 2H), 2.16 (s, 6H). Synthesis of examples 8-amino-N- {3-[(d i methylam ino)me t h yl]bicyclo[1.1 .1]pentan-1-yl}-6-(4-fluorophenyl)-5-{3- meth o -a]pyridin-6-yl}im zo[ a]pyraz 2-carboxamide, Ex-001 Step 1: benzyl N-{3-[(dimethylamin [1 pentan-1-yl}carbamate, Int- GP1-01, General Procedure 01 A mixture of dimethylamine (1M in THF, 1.36 mL, 2.711 mmol, 2.0 eq.) and benzyl N-{3- formylbicyclo[1.1.1]pentan-1-yl}carbamate (0.35 g, 1.356 mmol, 1.0 eq.) in DCE (anh.) (10.0 mL, 7.38 mL / mmol) was treated with NaBH(OAc)3(0.40 g, 1.9 mmol, 1.4 eq.) and the RM was stirred under Ar overnight. The RM was then diluted with DCM and the solution was washed with aq. 1 N NaOH and brine. The organic phase was dried over anhydrous Na2SO4, filtered, and evaporated under reduced pressure. The residue was purified by FCC (NH2silica, 0 to 10% MeOH gradient in DCM) to give benzyl N-{3-[(dimethylamino)methyl]bicyclo[1.1.1]pen- tan-1-yl}carbamate (0.29 g, 0.951 mmol, 70%).1H NMR (400 MHz, DMSO-d6) δ 7.90 (s, 1H), 7.35 (tdd, J = 8.3, 4.2, 2.8 Hz, 5H), 4.98 (s, 2H), 2.35 (s, 2H), 2.12 (s, 6H), 1.84 (s, 6H). m / z (ESI): 275.5 [M+H]+. Ryvu Therapeutics S.A. and BioNTech SE R10559WO 56 Intermediates prepared similarly to the protocol described in General Procedure 01 are listed in Table 1 below. Table 1 Ryvu Therapeutics S.A. and BioNTech SE R10559WO 57 Ryvu Therapeutics S.A. and BioNTech SE R10559WO 58 Ryvu Therapeutics S.A. and BioNTech SE R10559WO 59 Step 2: 3-[(dimethylamino)methyl]bicyclo[1.1.1]pentan-1-amine, Int-GP2-01, General Procedure 02. A mixture of 10% Pd / C (29 mg, 10%w.) and benzyl N-{3-[(dimethylamino)methyl]bicy- clo[1.1.1]pentan-1-yl}carbamate (0.29 g, 0.951 mmol, 1.0 eq.) in a mixture of EtOAc and MeOH 1:1 (10.0 mL) was hydrogenated under balloon with hydrogen (1 bar) for 6 h at RT. The RM was filtered through a pad of Celite® and the filter cake was washed with methanol. The filtrate was concentrated under reduced pressure to yield 3-[(dimethylamino)methyl]bi- cyclo[1.1.1]pentan-1-amine (0.136 g, 0.921 mmol, 97%). The crude material was used in the next step without further purification.1H NMR (400 MHz, DMSO-d6) δ 2.30 (s, 2H), 2.11 (s, 8H), 1.59 (s, 6H). Intermediates prepared similarly to the protocol described in General Procedure 02 are listed in Table 2 below. Table 2 Ryvu Therapeutics S.A. and BioNTech SE R10559WO 60 Ryvu Therapeutics S.A. and BioNTech SE R10559WO 61 *- crude compound was used in the next step without characterization, the completion of reaction was controlled by TLC, the yield was calculated as theoretical. Step 3: 8-amino-N-{3-[(dimethylamino)methyl]bicyclo[1.1.1]pentan-1-yl}-6-(4-fluo- rophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide, Ex-001, General Procedure 03. 3-[(dimethylamino)methyl]bicyclo[1.1.1]pentan-1-amine (0.09 g, 0.61 mmol, 1.0 eq.), lithium(1+) 8-amino-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2- a]pyrazine-2-carboxylate (0.25 g, 0.576 mmol, 0.943 eq.) and HATU (0.33 g, 0.864 mmol, 1.4 eq.) were dissolved in anhydrous NMP (5.0 mL) and the RM was stirred for 3h at 50 °C and then overnight at RT. The RM was then diluted with DCM and the solution was washed with aq. 1 N NaOH and brine. The organic phase was dried over anhydrous Na2SO4, filtered, and evaporated under reduced pressure. The crude material was purified by FCC (0 to 10% MeOH gradient in DCM). Then, the residue was treated with CH3CN, filtered, washed with Et2O, dried, to give 8-amino-N-{3-[(dimethylamino)methyl]bicyclo[1.1.1]pentan-1-yl}-6-(4- fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide (Ex-001, 0.12 g, 0.229 mmol, 38%, white solid, UPLC long elution purity: 99.09%) 1H NMR (400 MHz, DMSO-d6) δ 8.48 (s, 1H), 8.43 (s, 1H), 7.90 (s, 1H), 7.62 (d, J = 9.2 Hz, 1H), 7.42 (q, J = 5.0 Hz, 3H), 7.32 (s, 2H), 7.19 (d, J = 9.3 Hz, 1H), 7.07 (t, J = 8.7 Hz, 2H), Ryvu Therapeutics S.A. and BioNTech SE R10559WO 62 2.39 (s, 2H), 2.36 (s, 3H), 2.15 (s, 6H), 2.00 (s, 6H).19F NMR (376 MHz, DMSO-d6) δ - 114.53 (dq, J = 9.6, 6.1, 4.8 Hz). m / z (ESI): 525.4 [M+H]+. Examples prepared similarly to the protocol described in General Procedure 03 are listed in Table 3 below. Table 3 Ryvu Therapeutics S.A. and BioNTech SE R10559WO 63 Ryvu Therapeutics S.A. and BioNTech SE R10559WO 64 Ryvu Therapeutics S.A. and BioNTech SE R10559WO 65 Ryvu Therapeutics S.A. and BioNTech SE R10559WO 66 Ryvu Therapeutics S.A. and BioNTech SE R10559WO 67 Ryvu Therapeutics S.A. and BioNTech SE R10559WO 68 Ryvu Therapeutics S.A. and BioNTech SE R10559WO 69 Ryvu Therapeutics S.A. and BioNTech SE R10559WO 70 Ryvu Therapeutics S.A. and BioNTech SE R10559WO 71 Ryvu Therapeutics S.A. and BioNTech SE R10559WO 72 Ryvu Therapeutics S.A. and BioNTech SE R105 59WO 73 In mediates I - P1-15, Int-GP2- , Int-GP3-01 w syn according t th General Procedures 1, 2 and 3 (description is in the tables) Step 4: 8-amino-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}-N-{3-[(piper- azin-1-yl)methyl]bicyclo[1.1.1]pentan-1-yl}imidazo[1,2-a]pyrazine-2-carboxamide, Ex-023, General procedure 04: Tert-butyl 4-({3-[8-amino-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imi- dazo[1,2-a]pyrazine-2-amido]bicyclo[1.1.1]pentan-1-yl}methyl)piperazine-1-carboxylate (0.2 g, 0.27 mmol, 1.0 eq.) was dissolved in DCM (5.0 mL, 18.5 mL / mmol) and TFA (0.62 mL, 8.11 mmol, 30.0 eq.) was added at RT. The RM was stirred at RT overnight and the volatiles were evaporated under reduced pressure. The residue was partitioned between sat. aq. Na2CO3and DCM. The aqueous phase was extracted with DCM, and the combined organic extracts were dried over anh. Na2SO4, filtered, and concentrated under reduced pressure. The crude material was purified by FCC (PF-NH2, 0 to 10% MeOH gradient in DCM) to afford 8-amino-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}-N-{3- [(piperazin-1-yl)methyl]bicyclo[1.1.1]pentan-1-yl}imidazo[1,2-a]pyrazine-2-carboxamide (Ex-023, 0.103 g, 0.182 mmol, 67%, white powder, UPLC long elution purity: 100%).1H NMR (400 MHz, DMSO-d6) δ 8.49 (s, 1H), 8.43 (t, J = 1.3 Hz, 1H), 7.90 (s, 1H), 7.62 (d, J = 9.2 Hz, 1H), 7.42 (td, J = 5.5, 3.0 Hz, 3H), 7.33 (s, 2H), 7.18 (dd, J = 9.3, 1.7 Hz, 1H), 7.13 – 7.00 (m, 2H), 2.67 (t, J = 4.8 Hz, 4H), 2.41 (s, 2H), 2.36 (s, 3H), 2.31 (d, J = 5.6 Hz, 4H), 1.99 (s, 6H),19F NMR (376 MHz, DMSO-d6) δ -114.51 (ddd, J = 14.8, 9.2, 5.4 Hz). m / z (ESI): 564.1 [M-H]+. 8-amino-6-(4-fluorophenyl)-N-{3-[(N-methylacetamido)methyl]bicyclo[1.1.1]pentan-1-yl}- 5-{3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide, Ex-015 Ryvu Therapeutics S.A. and BioNTech SE R10559WO 74 Step 1: benzyl N-{3-[(N-methylacetamido)methyl]bicyclo[1.1.1]pentan-1-yl}carbamate, Int-D-01. A mixture of methylamine (2M in THF; 6.8 mL, 13.56 mmol, 10.0 eq.) and benzyl N-{3- formylbicyclo[1.1.1]pentan-1-yl}carbamate (0.35 g, 1.356 mmol, 1.0 eq.) in anh. DCE (8.0 mL, 5.11 mL / mmol) was treated with NaBH(OAc)3(0.4 g, 1.9 mmol, 1.4 eq.) and the RM was stirred overnight. The RM was quenched with aq. sat. NaHCO3,extracted with DCM. Com- bined organic extracts were dried over anh. Na2SO4, solids were filtered off. To the resulting solution acetyl chloride (0.145 mL, 2.033 mmol, 1.5 eq.) and NEt3(0.283 mL, 2.033 mmol, 1.5 eq.) were added, RM was stirred overnight. Then the RM was washed with aq. 5% KHSO4and brine. The organic phase was dried over anhydrous Na2SO4, filtered, and evaporated under reduced pressure. The crude material was purified by FCC (0 to 10% MeOH gradient in DCM) to yield benzyl N-{3-[(N-methylacetamido)methyl]bicyclo[1.1.1]pentan-1-yl}carba- mate (0.305 g, 0.958 mmol, 71%).1H NMR (400 MHz, DMSO-d6) δ 7.97 (d, 1H), 7.46 – 7.26 (m, 5H), 4.99 (s, 2H), 3.44 (d, J = 15.1 Hz, 2H), 2.86 (d, J = 64.7 Hz, 3H), 1.95 (d, J = 16.5 Hz, 3H), 1.84 (d, J = 26.9 Hz, 6H). m / z (ESI): 301.0 [M-H]+. Int-GP2-16 was synthesized according to the General procedure 02 (description is in the Table 2); Ex-015 was synthesized according to the General Procedure 03 (description is in the Table 3). 8-amino-6-(4-fluorophenyl)-N-{3-[(methylamino)methyl]bicyclo[1.1.1]pentan-1-yl}-5-{3- methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide, Ex-024 Step 1: benzyl N-[3-({[(tert-butox carbonyl](methyl)amino}methyl)bicyclo[1.1.1]pentan- 1-yl]carbamate, Int-D-02 Ryvu Therapeutics S.A. and BioNTech SE R10559WO 75 A mixture of methylamine (2M in THF; 3.38 mL, 6.77802 mmol, 5.0 eq.) and benzyl N-{3- formylbicyclo[1.1.1]pentan-1-yl}carbamate (0.35 g, 1.356 mmol, 1.0 eq.) in DCE (anh.) (8.0 mL, 5.11 mL / mmol) was treated with NaBH(OAc)3(0.40 g, 1.9 mmol, 1.4 eq.) and RM was stirred overnight. The RM was quenched with aq. sat. NaHCO3, extracted with DCM. Com- bined organic extracts were dried over anhydrous Na2SO4, solids were filtered off. To the re- sulting solution di-tert-butyl dicarbonate (0.44 g, 2.0 mmol, 1.5 eq.) and NEt3(0.283 mL, 2.0 mmol, 1.5 eq.) were added, and RM was stirred overnight. The RM was washed with aq. 5% KHSO4and brine. The organic phase was dried over anhydrous Na2SO4, filtered, and evapo- rated under reduced pressure. The crude material was purified by FCC (0 to 10% MeOH gradient in DCM) to yield benzyl N-[3-({[(tert-butoxy)carbonyl](methyl)amino}methyl)bicy- clo[1.1.1]pentan-1-yl]carbamate (0.11 g, 0.275 mmol, 20%).1H NMR (400 MHz, DMSO-d6) δ 7.92 (s, 1H), 7.42 – 7.24 (m, 5H), 4.98 (s, 2H), 3.29 (s, 2H), 2.77 (d, J = 6.8 Hz, 3H), 1.82 (s, 6H), 1.38 (s, 9H). m / z (ESI): 490.7 [M+H]+. Step 2 was performed according to General Procedure 02. The crude tert-butyl N-({3- aminobicyclo[1.1.1]pentan-1-yl}methyl)-N-methylcarbamate (Int-GP2-17, 0.048 g, 0.201 mmol, 73%) was used in the next step without further purification.1H NMR (400 MHz, DMSO-d6) δ 3.24 (s, 2H), 2.76 (d, J = 5.5 Hz, 3H), 1.57 (s, 6H), 1.38 (s, 9H). Step 3 was performed according to General Procedure 03, using lithium(1+) 8-amino-6- (4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxy- late (0.09 g, 0.201 mmol, 1.0 eq.), HATU (0.12 g, 0.302 mmol, 1.5 eq.), tert-butyl N-({3- aminobicyclo[1.1.1]pentan-1-yl}methyl)-N-methylcarbamate (0.048 g, 0.201 mmol, 1.0 eq.) in NMP. The crude material was purified by FCC (0 to 10% MeOH gradient in DCM) to yield tert-butyl N-({3-[8-amino-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imi- dazo[1,2-a]pyrazine-2-amido]bicyclo[1.1.1]pentan-1-yl}methyl)-N-methylcarbamate (Int- GP3-02, 0.08 g, 0.128 mmol, 64%).1H NMR (400 MHz, DMSO-d6) δ 8.53 (s, 1H), 8.43 (t, J = 1.4 Hz, 1H), 7.90 (s, 1H), 7.62 (dd, J = 9.3, 1.0 Hz, 1H), 7.50 – 7.37 (m, 3H), 7.31 (s, 2H), 7.19 (dd, J = 9.3, 1.7 Hz, 1H), 7.12 – 7.00 (m, 2H), 2.79 (s, 3H), 2.36 (d, J = 1.0 Hz, 3H), 1.97 (s, 6H), 1.39 (s, 9H).19F NMR (376 MHz, DMSO-d6) δ -112.81 – -116.43 (m). m / z (ESI): 611.7 [M+H]+.Step 4 was performed according to General procedure 04, using tert-butyl N-({3-[8- amino-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2- amido]bicyclo[1.1.1]pentan-1-yl}methyl)-N-methylcarbamate (0.08 g, 0.128 mmol, 1.0 eq.), and TFA (0.295 mL, 3.851 mmol, 30.0 eq.) in DCM. The crude material was purified by FCC (25g PF-NH2, 0 to 10% MeOH gradient in DCM) to afford 8-amino-6-(4-fluorophenyl)-N-{3- [(methylamino)methyl]bicyclo[1.1.1]pentan-1-yl}-5-{3-methylimidazo[1,2-a]pyridin-6-yl}im- idazo[1,2-a]pyrazine-2-carboxamide (Ex-024, 0.062 g, 0.115 mmol, 90%, white powder, long elution UPLC purity: 99.63%).1H NMR (400 MHz, DMSO-d6) δ 8.47 (s, 1H), 8.43 (t, J = 1.4 Hz, 1H), 7.90 (s, 1H), 7.62 (dd, J = 9.3, 1.0 Hz, 1H), 7.42 (td, J = 5.5, 3.1 Hz, 3H), 7.33 (s, 2H), 7.19 (dd, J = 9.3, 1.7 Hz, 1H), 7.07 (t, J = 8.9 Hz, 2H), 2.59 (s, 2H), 2.36 (d, J = 1.0 Hz, 3H), 2.28 (s, 3H), 1.95 (s, 6H).19F NMR (376 MHz, DMSO-d6) δ -114.53 (td, J = 10.3, 9.6, 4.7 Hz). m / z (ESI): 511.2 [M+H]+. Ryvu Therapeutics S.A. and BioNTech SE R10559WO 76 5-{3- T a solution of 8-amino-N-[3-(aminomethyl)bi [1.1. 1-yl]-6-(4-fluo- rophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide (0.052 g, 0.101 mmol, 1.0 eq.), and NEt3(0.042 mL, 0.301 2.981 eq.) in DCM acetic acid anhydride (0.012 mL, 0.127 mmol, 1.258 eq.) was added as a solution in DCM. The re- action mixture was stirred at RT overnight. The RM was partitioned between water and DCM and the aqueous layer was extracted with DCM. The organic layer was washed with brine, dried over anhydrous MgSO4, filtered and evaporated under reduced pressure. The crude material was purified by FCC (0 to 10% MeOH gradient in DCM) to yield 8-amino-N- [3-(acetamidomethyl)bicyclo[1.1.1]pentan-1-yl]-6-(4-fluorophenyl)-5-{3-methylimi- dazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide (Ex-026, 0.018 g, 0.033 mmol, 33%, white solid, long elution UPLC purity: 98.95%).1H NMR (400 MHz, DMSO-d6) δ 8.50 (s, 1H), 8.44 – 8.42 (m, 1H), 7.89 (s, 1H), 7.79 (t, J = 5.6 Hz, 1H), 7.64 – 7.60 (m, 1H), 7.45 – 7.38 (m, 3H), 7.31 (s, 2H), 7.18 (dd, J = 9.3, 1.6 Hz, 1H), 7.10 – 7.03 (m, 2H), 3.21 (d, J = 5.7 Hz, 2H), 2.35 (s, 3H), 1.93 (s, 6H), 1.81 (s, 3H).19F NMR (376 MHz, DMSO-d6) δ - 114.47 – -114.57 (m). m / z (ESI): 539.2 [M+H]+.

[0003] Ryvu Therapeutics S.A. and BioNTech SE R10559WO 77 1-yl]-5- Step 1 benzyl N-[3-(2,2,2-trichloro-1-hydroxyethyl)bicyclo[1.1.1]pentan-1-yl]carbamate, Int-E-01 To a solution of trichloroacetic acid (0.57 g, 3.49 mmol, 1.5 eq.) and sodium trichloroac- etate (0.65 g, 3.51 mmol, 1.5 eq.) in DMF was added benzyl N-{3-formylbicyclo[1.1.1]pen- tan-1-yl}carbamate (0.6 g, 2.324 mmol, 1.0 eq.) in DMF at 0 °C under Ar. After 15 min, the mixture was allowed to warm to RT over 30 min. After stirring at RT for 18 h, the RM was di- luted with EtOAc and quenched with sat. aq. NaHCO3. The layers were separated and aque- ous layer was extracted with EtOAc. The combined organic extracts were washed with brine, dried over Na2SO4, filtered and evaporated. The residue was purified by FCC (0 to 33% EtOAc gradient in hexane) to yield benzyl N-[3-(2,2,2-trichloro-1-hydroxyethyl)bicy- clo[1.1.1]pentan-1-yl]carbamate (0.84 g, 2.188 mmol, 94%, colorless oil).1H NMR (400 MHz, DMSO-d6) δ 7.95 (s, 1H), 7.40 – 7.29 (m, 5H), 6.57 (d, J = 7.3 Hz, 1H), 4.98 (s, 2H), 4.14 (d, J = 7.3 Hz, 1H), 2.04 (s, 6H). Step 22-(3-{[(benzyloxy)carbonyl]amino}bicyclo[1.1.1]pentan-1-yl)acetic acid, Int-E-02. To a solution of benzyl N-[3-(2,2,2-trichloro-1-hydroxyethyl)bicyclo[1.1.1]pentan-1-yl]car- bamate (0.838 g, 2.183 mmol, 1.0 eq.) in t-BuOH was added freshly powdered NaOH (0.262 g, 6.55 mmol, 3.0 eq.) at 30 °C. The mixture was stirred for 10 min, then NaBH4(0.124 g, 3.278 mmol, 1.501 eq.) was added. The heterogeneous mixture was stirred at 55 °C overnight. The RM was evaporated and the residue was suspended in water, acidified to pH 4 by addition of 1M HCl then the resulting mixture was extracted with AcOEt, then with CHCl3 / iPrOH 3:1. The combined organic extracts were washed with brine, dried over Na2SO4, filtrated and evaporated. The crude product was purified by FCC (0 to 10% MeOH gradient in DCM) to give 2-(3-{[(benzyloxy)carbonyl]amino}bicyclo[1.1.1]pentan-1-yl)acetic Ryvu Therapeutics S.A. and BioNTech SE R10559WO 78 acid (0.468 g, 1.275 mmol, 58%).1H NMR (400 MHz, DMSO-d6) δ 12.07 (s, 1H), 7.90 (s, 1H), 7.40 – 7.28 (m, 5H), 4.97 (s, 2H), 2.45 (s, 2H), 1.86 (s, 6H). m / z (ESI): 275.8 [M+H]+.Step 3. Methyl 2-(3-{[(benzyloxy)carbonyl]amino}bicyclo[1.1.1]pentan-1-yl)acetate, Int-E- 03 Thionyl chloride (0.215 mL, 2.964 mmol, 2.997 eq.) was added dropwise to a solution of 2- (3-{[(benzyloxy)carbonyl]amino}bicyclo[1.1.1]pentan-1-yl)acetic acid (0.363 g, 0.99 mmol, 1.0 eq.) in methanol at 0 °C. The mixture was allowed to warm to RT over 30 min. After stirring at RT for 2.5 h, the RM was evaporated. Water was added to the residue. Then, the resulting solution was extracted with DCM. The organic layer was washed with brine, dried over Na2SO4, filtrated and evaporated to give methyl 2-(3-{[(benzyloxy)carbonyl]amino}bicy- clo[1.1.1]pentan-1-yl)acetate (0.353 g, 0.878 mmol, 89%). The crude product was used in the next step without further purification.1H NMR (400 MHz, DMSO-d6) δ 7.92 (s, 1H), 7.39 – 7.28 (m, 5H), 4.97 (s, 2H), 3.57 (s, 3H), 2.56 (s, 2H), 1.86 (s, 6H). m / z (ESI): 290.1 [M+H]+. Step 4. benzyl N-[3-(2-hydroxy-2-methylpropyl)bicyclo[1.1.1]pentan-1-yl]carbamate, Int- E-04 A solution of methyl 2-(3-{[(benzyloxy)carbonyl]amino}bicyclo[1.1.1]pentan-1-yl)acetate (0.35 g, 0.871 mmol, 1.0 eq.) in Et2O was added dropwise to a solution of methyl magnesium bromide (3.0 M in Et2O, 0.96 mL, 2.88 mmol, 3.307 eq.) in Et2O at 0 °C. Then, the mixture was allowed to warm to RT over 30 min. After stirring at RT for 3 h, the RM was quenched with aq. sat. solution of NH4Cl and ex- tracted with EtOAc. Organic layer was washed with brine, dried over Na2SO4, filtrated and evaporated. The crude product was purified by FCC (0 to 10% EtOAc gradient in hexane) to give benzyl N-[3-(2-hydroxy-2-methylpropyl)bicyclo[1.1.1]pentan-1-yl]carbamate (0.202 g, 0.684 mmol, 79%).1H NMR (400 MHz, DMSO-d6) δ 7.83 (s, 1H), 7.39 – 7.28 (m, 5H), 4.97 (s, 2H), 4.08 (s, 1H), 1.85 (s, 6H), 1.62 (s, 2H), 1.07 (s, 6H). Step 5 was performed according to General Procedure 02. The crude 1-{3-aminobicy- clo[1.1.1]pentan-1-yl}-2-methylpropan-2-ol (Int-GP2-18, 0.113 g, 0.692 mmol, 100%) was used in the next step without further purification.1H NMR (400 MHz, DMSO-d6) δ 4.03 (s, 1H), 1.60 (s, 6H), 1.59 (s, 2H), 1.06 (s, 6H). Step 6 was performed according to General Procedure 03, using lithium(1+) 8-amino-6- (4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxy- late (0.28 g, 0.645 mmol, 1.0 eq), HATU (0.27 g, 0.71 mmol, 1.1 eq.), 1-{3-aminobicy- clo[1.1.1]pentan-1-yl}-2-methylpropan-2-ol (0.111 g, 0.679 mmol, 1.054 eq.) in NMP. The crude material was purified by FCC (0 to 10% MeOH gradient in DCM) to yield 8-amino-6- (4-fluorophenyl)-N-[3-(2-hydroxy-2-methylpropyl)bicyclo[1.1.1]pentan-1-yl]-5-{3- methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide (Ex-027, 0.11 g, 0.202 mmol, 31%, white solid, UPLC long elution purity: 98.91%).1H NMR (400 MHz, DMSO- d6) δ 8.44 – 8.42 (m, 1H), 8.41 (s, 1H), 7.88 (s, 1H), 7.63 – 7.59 (m, 1H), 7.44 – 7.39 (m, 3H), 7.32 (s, 2H), 7.18 (dd, J = 9.3, 1.6 Hz, 1H), 7.09 – 7.03 (m, 2H), 4.11 (s, 1H), 2.35 (s, 3H), 2.00 (s, 6H), 1.66 (s, 2H), 1.10 (s, 6H).19F NMR (376 MHz, DMSO-d6) δ -114.48 – -114.57 (m). m / z (ESI): 540.1 [M+H]+. Ryvu Therapeutics S.A. and BioNTech SE R10559WO 79 8-amino-6-(4-fluorophenyl)-N-[3-(2-hydroxyethyl)bicyclo[1.1.1]pentan-1-yl]-5-{3- methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide, Ex-028 Step 1: benzyl N-[3-( hydroxyethyl)bicyclo[1.1.1]pentan-1-yl]carbamate, Int-E-05. Benzyl N-[3-(2,2,2-trichloro-1-hydroxyethyl)bicyclo[1.1.1]pentan-1-yl]carbamate (0.335 g, 0.891 mmol, 1.0 eq.) was dissolved in anhydrous propan-2-ol under Ar atmosphere. Then, lithium borohydride (0.078 g, 3.581 mmol, 4.019 eq.) and freshly powdered NaOH (0.107 g, 2.675 mmol, 3.0 eq.) were added. The RM was stirred at 40°C overnight. After completion of the reaction as indicated by TLC, the reaction mixture was cooled to RT, quenched with sat. aq. NH4Cl and brine. The resulting solution was extracted with EtOAc. The organic phase was dried over Na2SO4, filtered and evaporated. The crude product was purified by FCC (0 to 50% EtOAc gradient in hexane) to yield benzyl N-[3-(2-hydroxyethyl)bicy- clo[1.1.1]pentan-1-yl]carbamate (0.151 g, 0.566 mmol, 64%).1H NMR (400 MHz, DMSO-d6) δ 7.85 (s, 1H), 7.39 – 7.28 (m, 5H), 4.97 (s, 2H), 4.34 (t, J = 5.1 Hz, 1H), 3.37 (q, J = 6.9 Hz, 2H), 1.78 (s, 6H), 1.62 (t, J = 7.0 Hz, 2H). Step 2 was performed according to General Procedure 02. The crude 2-{3-aminobicy- clo[1.1.1]pentan-1-yl}ethan-1-ol (Int-GP2-19, 0.072 g, 0.538 mmol, 96%) was used in the next step without further purification.1H NMR (400 MHz, DMSO-d6) δ 3.35 (t, J = 7.2 Hz, 2H), 1.58 (t, J = 7.1 Hz, 2H), 1.53 (s, 6H). Step 3 was performed according to General Procedure 03 using lithium(1+) 8-amino-6- (4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxy- late (0.21 g, 0.483 mmol, 1.0 eq.), HATU (0.193 g, 0.508 mmol, 1.05 eq.), 2-{3-aminobicy- clo[1.1.1]pentan-1-yl}ethan-1-ol (0.07 g, 0.523 mmol, 1.08 eq.) in NMP. The crude material was purified by two consecutive FCC (first: 0 to 10% MeOH gradient in DCM, second: 0 to 10% MeOH gradient in EtOAc) to yield 8-amino-6-(4-fluorophenyl)-N-[3-(2-hydroxyethyl)bi- cyclo[1.1.1]pentan-1-yl]-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2- carboxamide (Ex-028, 0.05 g, 0.097 mmol, 20%, white solid, long elution UPLC purity: 99.07%).1H NMR (400 MHz, DMSO-d6) δ 8.44 – 8.41 (m, 2H), 7.88 (s, 1H), 7.63 – 7.59 (m, 1H), 7.45 – 7.39 (m, 3H), 7.32 (s, 2H), 7.18 (dd, J = 9.3, 1.6 Hz, 1H), 7.09 – 7.03 (m, 2H), 4.36 (t, J = 5.1 Hz, 1H), 3.44 – 3.38 (m, 2H), 2.35 (s, 3H), 1.93 (s, 6H), 1.66 (t, J = 7.0 Hz, 2H).19F NMR (376 MHz, DMSO-d6) δ -114.48 – -114.58 (m). m / z (ESI): 512.1 [M+H]+. Propan-2-yl N-({3-[8-amino-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}im- idazo[1,2-a]pyrazine-2-amido]bicyclo[1.1.1]pentan-1-yl}methyl)carbamate, Ex-029 Ryvu Therapeutics S.A. and BioNTech SE R10559WO 80 yl]carbamate, Int-I-01. Propan-2-yl carbonochloridate (0.121 g, 0.987 mmol, 1.048 eq.) was added to a solution of tert-butyl N-[3-(aminomethyl)bicyclo[1.1.1]pentan-1-yl]carbamate (0.2 g, 0.942 mmol, 1.0 eq.) and ethylbis(propan-2-yl)amine (0.33 mL, 1.895 mmol, 2.011 eq.) in anhydrous DCM at 0°C. The RM was stirred for overnight, being allowed to slowly come back to RT. The reac- tion was quenched by addition of aq. sat. NaHCO3and the RM was stirred for further 15 min. The phases were separated and the aqueous phase was extracted with DCM. The combined organic extracts were washed with brine, dried over anhydrous Na2SO4, filtered and evaporated under reduced pressure. The crude material was purified by FCC (0 to 50% EtOAc gradient in hexane) to afford tert-butyl N-[3-({[(propan-2-yloxy)car- bonyl]amino}methyl)bicyclo[1.1.1]pentan-1-yl]carbamate (0.232 g, 0.762 mmol, 81%).1H NMR (400 MHz, DMSO-d6) δ 7.40 (s, 1H), 7.00 (t, J = 5.5 Hz, 1H), 4.73 (hept, J = 6.0 Hz, 1H), 3.09 (d, J = 5.8 Hz, 2H), 1.73 (s, 6H), 1.37 (s, 9H), 1.16 (d, J = 6.2 Hz, 6H). Step 2 was performed according to General procedure 04, using tert-butyl N-[3- ({[(propan-2-yloxy)carbonyl]amino}methyl)bicyclo[1.1.1]pentan-1-yl]carbamate (0.13 g, 0.427 mmol, 1.0 eq.) and HCl (4M in dioxane, 2.14 mL, 8.56 mmol, 20.0 eq.) in DCM. The RM was evaporated to dryness to afford propan-2-yl N-({3-aminobicyclo[1.1.1]pentan-1- yl}methyl)carbamate hydrochloride (Int-GP4-01, 0.116 g, 0.428 mmol, 100%). The crude ma- terial was used in the next step without further purification.1H NMR (400 MHz, DMSO-d6) δ 8.75 (s, 3H), 7.11 (t, J = 5.6 Hz, 1H), 4.73 (hept, J = 6.3, 5.9 Hz, 1H), 3.14 (d, J = 5.8 Hz, 2H), 1.83 (s, 6H), 1.15 (d, J = 6.2 Hz, 6H). Step 3 was performed according to General Procedure 03, using lithium(1+) 8-amino-6- (4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxy- late (0.18 g, 0.414 mmol, 1.0 eq.), HATU (0.17 g, 0.447 mmol, 1.079 eq.), propan-2-yl N-({3- aminobicyclo[1.1.1]pentan-1-yl}methyl)carbamate hydrochloride (0.116 g, 0.428 mmol, 1.032 eq.) in NMP. The crude material was purified by FCC (0 to 10% MeOH gradient in DCM) to yield propan-2-yl N-({3-[8-amino-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2- a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-amido]bicyclo[1.1.1]pentan-1-yl}methyl)carbamate (Ex-029, 0.096 g, 0.164 mmol, 40%, white solid, long elution UPLC purity: 99.34%).1H NMR (400 MHz, DMSO-d6) δ 8.47 (s, 1H), 8.44 – 8.41 (m, 1H), 7.89 (s, 1H), 7.61 (d, J = 9.2 Hz, 1H), 7.45 – 7.39 (m, 3H), 7.30 (s, 2H), 7.18 (dd, J = 9.3, 1.5 Hz, 1H), 7.10 – 7.01 (m, 3H), 4.73 Ryvu Therapeutics S.A. and BioNTech SE R10559WO 81 (p, J = 6.3 Hz, 1H), 3.14 (d, J = 5.8 Hz, 2H), 2.35 (s, 3H), 1.91 (s, 6H), 1.15 (d, J = 6.2 Hz, 6H).19F NMR (376 MHz, DMSO-d6) δ -114.46 – -114.59 (m). m / z ( ESI): 583.3 [M+H]+. 1- Step 1 was performed according to General Procedure 03, using lithium(1+) 8-amino-6- (4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxy- late (0.2 g, 0.46 mmol, 1.0 eq.), HATU (0.175 g, 0.46 mmol, 1.0 eq.), tert-butyl 4-{3-aminobi- cyclo[1.1.1]pentan-1-yl}piperazine-1-carboxylate (0.13 g, 0.462 mmol, 1.003 eq.) in NMP. The crude material was purified by FCC (0 to 20% MeOH gradient in DCM) to yield tert- butyl 4-{3-[8-amino-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2- a]pyrazine-2-amido]bicyclo[1.1.1]pentan-1-yl}piperazine-1-carboxylate (Int-GP3-03, 0.209 g, 0.317 mmol, 69%).1H NMR (400 MHz, DMSO-d6) δ 8.57 (s, 1H), 8.48 (s, 1H), 7.92 (s, 1H), 7.64 (d, J = 9.3 Hz, 1H), 7.47 (s, 1H), 7.44 – 7.39 (m, 2H), 7.33 (s, 2H), 7.25 – 7.20 (m, 1H), 7.10 – 7.03 (m, 2H), 2.92 (s, 2H), 2.37 (s, 3H), 2.35 – 2.27 (m, 6H), 2.01 (s, 6H), 1.39 (s, 9H). m / z (ESI): 652.2 [M+H]+. Step 2 was performed according to General procedure 04, using tert-butyl 4-{3-[8-amino- 6-(4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2- amido]bicyclo[1.1.1]pentan-1-yl}piperazine-1-carboxylate (0.205 g, 0.311 mmol, 1.0 eq.) and TFA (0.48 mL, 6.268 mmol, 20.0 eq.) in DCM. The crude material was purified by FCC (NH2 silica, 0 to 10% MeOH gradient in DCM) to afford 8-amino-6-(4-fluorophenyl)-5-{3- methylimidazo[1,2-a]pyridin-6-yl}-N-[3-(piperazin-1-yl)bicyclo[1.1.1]pentan-1-yl]imi- dazo[1,2-a]pyrazine-2-carboxamide (Ex-030, 0.105 g, 0.186 mmol, 60%, white solid, long elution UPLC purity: 97.51%).1H NMR (400 MHz, DMSO-d6) δ 8.54 (s, 1H), 8.44 – 8.42 (m, 1H), 7.90 (s, 1H), 7.61 (dd, J = 9.3, 0.8 Hz, 1H), 7.44 – 7.39 (m, 3H), 7.32 (s, 2H), 7.18 (dd, J = 9.3, 1.6 Hz, 1H), 7.10 – 7.03 (m, 2H), 2.72 – 2.66 (m, 4H), 2.36 (s, 3H), 2.33 – 2.26 (m, 4H),1.99 (s, 6H).19F NMR (376 MHz, DMSO-d6) δ -114.47 – -114.56 (m). m / z (ESI): 552.2 [M+H]+. 8-amino-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}-N-[3-(morpholin-4- yl)bicyclo[1.1.1]pentan-1-yl]imidazo[1,2-a]pyrazine-2-carboxamide, Ex-031 pe u Ryvu Thera t ic s S. A. a nd BioNTech SE R10559WO 82 Int-F-01 A mixture of tert-butyl N-{3-aminobicyclo[1.1.1]pentan-1-yl}carbamate (0.5 g, 2.522 mmol, 1.0 eq.), ethylbis(propan-2-yl)amine (1.1 mL, 6.315 mmol, 2.504 eq.) and 1-bromo-2-(2-bro- moethoxy)ethane (0.644 g, 2.777 mmol, 1.101 eq.) in anhydrous acetonitrile was heated at 85 °C overnight. After cooling to RT, the RM was evaporated to dryness. The residue was partitioned between water and EtOAc and the organic phase was separated. The aqueous phase was extracted with EtOAc, and the combined organic extracts were dried over anhy- drous Na2SO4, filtered and concentrated under reduced pressure. The crude material was purified by FCC (0 to 20% MeOH gradient in DCM) to afford tert-butyl N-[3-(morpholin-4- yl)bicyclo[1.1.1]pentan-1-yl]carbamate (0.455 g, 1.662 mmol, 66%).1H NMR (400 MHz, DMSO-d6) δ 7.49 (s, 1H), 3.60 – 3.53 (m, 4H), 2.34 – 2.27 (m, 4H), 1.82 (s, 6H), 1.37 (s, 9H). Step 2 was performed according to General procedure 04, using tert-butyl N-[3-(mor- pholin-4-yl)bicyclo[1.1.1]pentan-1-yl]carbamate (0.25 g, 0.913 mmol, 1.0 eq.) and HCl (4M in dioxane, 4.6 mL, 18.4 mmol, 20.1 eq.) in DCM. The reaction mixture was evaporated to dryness to afford 3-(morpholin-4-yl)bicyclo[1.1.1]pentan-1-amine dihydrochloride (Int-GP4- 02, 0.22 g, 0.912 mmol, 100%). The crude material was used in the next step without further purification1H NMR (400 MHz, DMSO-d6) δ 9.14 (s, 3H), 3.88 – 3.77 (m, 4H), 3.10 – 2.86 (m, 4H), 2.23 (s, 6H). Step 3 was performed according to General Procedure 03, using lithium(1+) 8-amino-6- (4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxy- late (0.33 g, 0.727 mmol, 1.0 eq.), HATU (0.304 g, 0.8 mmol, 1.1 eq.), 3-(morpholin-4-yl)bicy- clo[1.1.1]pentan-1-amine dihydrochloride (0.211 g, 0.875 mmol, 1.203 eq.) in NMP. The crude material was purified by FCC (0 to 10% MeOH gradient in DCM) to yield 8-amino-6- (4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}-N-[3-(morpholin-4-yl)bicy- clo[1.1.1]pentan-1-yl]imidazo[1,2-a]pyrazine-2-carboxamide (Ex-031, 0.119 g, 0.211 mmol,29%, white solid, long elution UPLC purity: 98.09%).1H NMR (400 MHz, DMSO-d6) δ 8.57 (s, 1H), 8.45 – 8.41 (m, 1H), 7.90 (s, 1H), 7.61 (d, J = 9.2 Hz, 1H), 7.45 – 7.38 (m, 3H), 7.31 (s, Ryvu Therapeutics S.A. and BioNTech SE R10559WO 83 2H), 7.18 (dd, J = 9.3, 1.4 Hz, 1H), 7.10 – 7.02 (m, 2H), 3.62 – 3.54 (m, 4H), 2.39 – 2.31 (m, 7H), 2.01 (s, 6H).19F NMR (376 MHz, DMSO-d6) δ -114.46 – -114.56 (m). m / z (ESI): 553.3 [M+H]+. 8-amino-N-[3-(aminomethyl)bicyclo[1.1.1]pentan-1-yl]-6-(4-fluorophenyl)-5-{3-methylim- idazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide, Ex-025 Step 1 was performed according to General Procedure 03, using lithium(1+) 8-amino-6- (4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxy- late (0.25 g, 0.494 mmol, 1.0 eq.), HATU (0.280 g, 0.74 mmol, 1.5 eq.), tert-butyl ((3-amino- bicyclo[1.1.1]pentan-1-yl)methyl)carbamate (0.158 g, 0.74 mmol, 1.5 eq.) in NMP. The crude material was purified by FCC (0 to 5% MeOH gradient in DCM) to yield tert-butyl N- ({3-[8-amino-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2- a]pyrazine-2-amido]bicyclo[1.1.1]pentan-1-yl}methyl)carbamate (Int-GP3-04, 0.269 g, 0.45 mmol, 91%).1H NMR (400 MHz, DMSO) δ 8.48 (s, 1H), 8.45 – 8.40 (m, 1H), 7.89 (s, 1H), 7.61 (dd, J = 9.3, 0.9 Hz, 1H), 7.46 – 7.36 (m, 3H), 7.30 (s, 2H), 7.18 (dd, J = 9.3, 1.7 Hz, 1H), 7.11 – 7.01 (m, 2H), 6.84 (t, J = 5.9 Hz, 1H), 3.08 (d, J = 5.9 Hz, 2H), 2.35 (d, J = 0.8 Hz, 3H),1.91 (s, 6H), 1.37 (s, 9H).19F NMR (376 MHz, DMSO) δ -114.52 (tt, J = 9.0, 5.7 Hz). m / z (ESI): 597.4 [M+H]+. Step 2 was performed according to General procedure 04, using tert-butyl N-({3-[8- amino-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2- amido]bicyclo[1.1.1]pentan-1-yl}methyl)carbamate (0.265 g, 0.444 mmol, 1.0 eq.) and HCl (3M in MeOH, 2.0 mL, 6.0 mmol, 13.5 eq.) in EtOH. The RM was evaporated to dryness, the residue was partitioned between EtOAc and a solution of aq. sat. Na2CO3. The organic layer was separated and washed with brine, dried over anhydrous Na2SO4, filtered and evapo- rated under reduced pressure. The crude was recrystallized from acetonitrile to afford 8- amino-N-[3-(aminomethyl)bicyclo[1.1.1]pentan-1-yl]-6-(4-fluorophenyl)-5-{3-methylimi- dazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide (Ex-025, 0.105 g, 0.211 mmol, 46%, beige solid, long elution UPLC purity: 97.16%).1H NMR (400 MHz, DMSO) δ 8.48 (s, 1H), 8.42 (d, J = 1.4 Hz, 1H), 7.89 (s, 1H), 7.61 (dd, J = 9.3, 0.9 Hz, 1H), 7.46 – 7.37 (m, 3H), 7.32 (s, 2H), 7.18 (dd, J = 9.3, 1.7 Hz, 1H), 7.11 – 7.01 (m, 2H), 2.65 (s, 2H), 2.35 (d, J = 0.9 Hz, 3H), 1.90 (s, 6H).19F NMR (376 MHz, DMSO) δ -114.51 (tt, J = 9.0, 5.7 Hz). m / z (ESI): 497.3 [M+H]+. Ryvu Therapeutics S.A. and BioNTech SE R10559WO 84 1,3-benzodia- Step 1: ethyl 8-amino-6-(4-fluorophenyl)-5-(1-methyl-1H-1,3-benzodiazol-6-yl)imi- dazo[1,2-a]pyrazine-2-carboxylate, Int-A-07 A mixture of Cs2CO3(6.42 g, 19.72 mmol, 3.0 eq.), (1-methyl-1H-1,3-benzodiazol-6- yl)boronic acid (3.05 g, 11.83 mmol, 1.8 eq.), ethyl 8-amino-5-chloro-6-(4-fluorophenyl)imi- dazo[1,2-a]pyrazine-2-carboxylate (Int-A-04, 2.2 g, 6.57 mmol, 1.0 eq.) in dioxane (54.0 mL) and water (9.0 mL) in a ACE Pressure Tube vial was sparged with Ar for 10 minutes. Then, Pd(PPh3)4(0.38 g, 0.33 mmol, 0.05 eq.) was added, the vial was sealed, and the RM was stirred in a preheated heating block at 100 °C for overnight. After coming back to room temperature, the RM was filtered through a pad of Celite®. The filter cake was washed with methanol followed by DCM and the filtrate was concentrated under reduced pressure. The crude material was purified by FCC (0 to 5 % MeOH gradient in DCM) to yield ethyl 8- amino-6-(4-fluorophenyl)-5-(1-methyl-1H-1,3-benzodiazol-6-yl)imidazo[1,2-a]pyrazine-2- carboxylate (Int-A-07, 2.4 g, 5.65 mmol, 86%).1H NMR (400 MHz, DMSO) δ 8.28 (s, 1H), 7.75 – 7.70 (m, 2H), 7.64 (s, 1H), 7.42 (s, 2H), 7.37 – 7.32 (m, 2H), 7.19 (dd, J = 8.2, 1.7 Hz, 1H), 7.03 – 6.96 (m, 2H), 4.26 (q, J = 7.1 Hz, 2H), 3.79 (s, 3H), 1.24 (t, J = 7.1 Hz, 3H).19F NMR (376 MHz, DMSO) δ -114.81 (ddd, J = 14.9, 8.9, 5.6 Hz). m / z (ESI): 431.4 [M+H]+.Step 2: dazo To a suspension of ethyl 8-amino-6-(4-fluorophenyl)-5-(1-methyl-1H-1,3-benzodiazol-6- yl)imidazo[1,2-a]pyrazine-2-carboxylate (3.5 g, 8.13 mmol, 1.0 eq.) in ethanol (80 mL) a so- lution of LiOH*H2O (1.02 g, 24.39 mmol, 3.0 eq.) in water (50 mL) was added. Reaction mix- ture was heated at 70°C for 2 h. Hot reaction mixture was filtered through a pad of Celite®, washed with hot ethanol. Filtrate was concentrated and used without further purification, lithio 8-amino-6-(4-fluorophenyl)-5-(1-methyl-1H-1,3-benzodiazol-6-yl)imidazo[1,2- a]pyrazine-2-carboxylate (3.28 g, 8.13 mmol, 100%).1H NMR (400 MHz, DMSO) δ 8.27 (s, Ryvu Therapeutics S.A. and BioNTech SE R10559WO 85 1H), 7.71 (d, J = 5.6 Hz, 2H), 7.36 (dd, J = 8.1, 5.5 Hz, 2H), 7.26 (d, J = 9.0 Hz, 1H), 7.15 (d, J = 8.3 Hz, 1H), 6.98 (t, J = 8.8 Hz, 2H), 3.81 (s, 3H). m / z (ESI): 403.01 [M+H]+Step 3 was performed according to General Procedure 03, using lithio 8-amino-6-(4-fluo- rophenyl)-5-(1-methyl-1H-1,3-benzodiazol-6-yl)imidazo[1,2-a]pyrazine-2-carboxylate (0.12 g, 0.3 mmol, 1.0 eq.), HATU (0.136 g, 0.36 mmol, 1.2 eq.), bicyclo[1.1.1]pentan-1-amine hy- drochloride (0.043 g, 0.36 mmol, 1.2 eq.) in DMF. The crude material was converted to hy- drochloride salt, then was purified by FCC (C18 functionalized silica, 0 to 100% MeCN gradi- ent in water) to yield 8-amino-N-{bicyclo[1.1.1]pentan-1-yl}-6-(4-fluorophenyl)-5-(1- methyl-1H-1,3-benzodiazol-6-yl)imidazo[1,2-a]pyrazine-2-carboxamide as its hydrochloride salt (Ex-033, 0.03 g, 0.065 mmol, 22%, white solid, long elution UPLC purity: 100%).1H NMR (400 MHz, DMSO-d6) δ 9.43 (s, 1H), 8.65 (s, 1H), 8.15 (s, 1H), 7.90 (d, J = 8.4 Hz, 1H), 7.83 (s, 1H), 7.45 (dd, J = 8.5, 1.5 Hz, 1H), 7.41 – 7.36 (m, 2H), 7.13 – 7.06 (m, 2H), 4.02 (s, 3H), 2.46 (s, 1H), 2.07 (s, 6H). m / z (ESI): 468.30 [M+H]+.Part 2: Activity A2A activity at low agonist concentrations Examples (see synthesis part above for the structures and names of these compounds) were tested for their antagonistic activity at the rat A2A receptor (endogenously expressed in PC12 cells, which were used in the assay). The antagonistic activity was determined by measuring the effect of each compound on agonist-induced cAMP production using the as- say based on time-resolved fluorescence resonance energy transfer (TR-FRET). General reference as regards the cells and background can be made to Gao et al., “Novel short-acting A2A adenosine receptor agonists for coronary vasodilation: inverse relationship between affinity and duration of action of A2A agonists”, J. Pharmacol. Exp. Ther., 298, 209. More specifically, the assay to test the Examples was performed as follows: The cells were suspended in HBSS buffer (Invitrogen) complemented with 5 mM HEPES (pH 7.4), with 0.1% BSA and 100 µM Rolipram (a phosphodiesterase-4 inhibitor to block the degradation of cAMP), then distributed in microplates at a density of 2.103cells / well (in a 384 well plate) in the presence of either (i) HBSS (basal control) with 0.2% DMSO, (ii) the test com- pound, i.e. each of the Examples or (iii) the reference antagonist ZM 241385. Thereafter, the reference adenosine receptor agonist NECA (e.g. CAS 35920-39-9, Cal- biochem) was added at a final concentration of 43 nM (concentration corresponding to EC80). For basal control measurements, separate assay wells did not contain NECA. Following 30 min incubation at room temperature, the cells were lysed and the detection mix was added (standard reagents used according to a standard protocol; LANCE™ cAMP 384 Kit, PerkinElmer). After 60 min at room temperature, the fluorescence transfer was measured at λex=340 nm and λem= 665 nm using a microplate reader according to a standard protocol (Tecan Spark 20 M). For test compounds % of normalized vehicle control was calculated for each data point and plotted against test compound concentration: ^^ = 100 ― 100 Ryvu Therapeutics S.A. and BioNTech SE R10559WO 86 Sample – mean fluorescence intensity of tested compound Low control – mean fluorescence intensity of NECA 0.043 µM Vehicle control – mean fluorescence intensity of DMSO 0.2% EC50, Hill slope and efficacy parameters were determined by fitting a variable-slope sig- moidal function. The standard reference antagonist used was ZM 241385, which was tested in each experi- ment at several concentrations to generate a concentration-response curve from which its EC50 value was calculated A2A activity at high agonist concentrations Examples (see synthesis part above for the structures and names of these compounds) were tested for their antagonistic activity at the rat A2A receptor (endogenously expressed in PC12 cells, which were used in the assay) at high concentrations of agonist. The antago- nistic activity was determined by measuring the effect of each compound on agonist-in- duced cAMP production using the assay based on time-resolved fluorescence resonance energy transfer (TR-FRET). General reference as regards the cells and background can be made to Gao et al., “Novel short-acting A2A adenosine receptor agonists for coronary vasodilation: inverse relationship between affinity and duration of action of A2A agonists”, J. Pharmacol. Exp. Ther., 298, 209. More specifically, the assay to test the Examples was performed as follows: The cells were suspended in HBSS buffer (Invitrogen) complemented with 5 mM HEPES (pH 7.4), with 0.1% BSA , 100 µM Rolipram (a phosphodiesterase-4 inhibitor to block the degradation of cAMP) and 10 µM EHNA - adenosine deaminase inhibitor, then distributed in microplates at a density of 2.0x103cells / well (in a 384 well plate) in the presence of either (i) HBSS (basal control) with 0.2% DMSO, (ii) the test compound, i.e. each of the Examples, or (iii) the refer- ence antagonist ZM 241385. After 2h incubation at room temperature, the nonselective adenosine receptor agonist – adenosine (e.g. CAS 58-61-7, Tocris) was added at a final concentration of 100 µM (corre- sponding to high adenosine concentration in tumor). For basal control measurements, sepa- rate assay wells did not contain adenosine. Following 30 min incubation at room temperature, the cells were lysed and the detection mix was added (standard reagents used according to a standard protocol; LANCE™ cAMP 384 Kit, PerkinElmer). After 60 min at room temperature, the fluorescence transfer was measured at λex=340 nm and λem= 665 nm using a microplate reader according to a standard protocol (Tecan 20M Spark). For test compounds % of normalized vehicle control was calculated for each data point and plotted against test compound concentration: ^^ = 100 ― 100 Sample – mean fluorescence intensity of tested compound Low control – mean fluorescence intensity of adenosine 100 µM Vehicle control – mean fluorescence intensity of DMSO 0.2% Ryvu Therapeutics S.A. and BioNTech SE R10559WO 87 EC50, Hill slope and efficacy parameters were determined by fitting a variable-slope sig- moidal function. The standard reference antagonist used was ZM 241385, which was tested in each experi- ment at several concentrations to generate a concentration-response curve from which its EC50 value was calculated A2B activity at low agonist concentrations Examples (see synthesis part above for the structures and names of these compounds) were tested for their antagonistic activity at the human A2B receptor (overexpressed in cAMPZen-A2BR-HEK293 cells, which were used in the assay). The antagonistic activity was determined by measuring the effect of each compound on agonist-induced cAMP produc- tion using the assay based on time-resolved fluorescence resonance energy transfer (TR- FRET). General reference as regards the cells and background can be made to Cooper et al., “An endogenous A2B adenosine receptor coupled to cyclic AMP generation in human embryonic kidney (HEK-293) cells”, Brit. J. Pharmacol., 122: 546. More specifically, the assay to test the Examples was performed as follows: The cells were suspended in HBSS buffer (Invitrogen) complemented with 5 mM HEPES (pH 7.4), with 0.1% BSA and adenosine deaminase [0.02 U / ml], then distributed in microplates at a den- sity of 2.5x103cells / well (in a 384 well plate) in the presence of either (i) HBSS (basal con- trol) with 0.2% DMSO, (ii) the test compound, i.e. each of Examples, or (iii) the reference antagonist XAC. Thereafter, the reference adenosine receptor agonist NECA (e.g. CAS 35920-39-9, Cal- biochem) was added at a final concentration of 100 nM (concentration corresponding to EC80). For basal control measurements, separate assay wells did not contain NECA. Following 30 min incubation at room temperature, the cells were lysed and the detection mix was added (standard reagents used according to a standard protocol; LANCE™ cAMP 384 Kit, PerkinElmer). After 60 min at room temperature, the fluorescence transfer was measured at λex=340 nm and λem= 665 nm using a microplate reader according to a standard protocol (Tecan Spark 20 M). For test compounds % of normalized vehicle control was calculated for each data point and plotted against test compound concentration: ^^ = 100 ― 100 Sample – mean fluorescence intensity of tested compound Low control – mean fluorescence intensity of NECA 0.1 µM Vehicle control – mean fluorescence intensity of DMSO 0.2% EC50, Hill slope and efficacy parameters were determined by fitting a variable-slope sig- moidal function. The standard reference antagonist used was XAC, which was tested in each experiment at several concentrations to generate a concentration-response curve from which its EC50 value was calculated. Ryvu Therapeutics S.A. and BioNTech SE R10559WO 88 A2B activity at high agonist concentrations Examples (see synthesis part above for the structures and names of these compounds) were tested for their antagonistic activity at the human A2B receptor (overexpressed in cAMPZen-A2BR-HEK293 cells, which were used in the assay) at high concentrations of ag- onist. The antagonistic activity was determined by measuring the effect of each compound on agonist-induced cAMP production using the assay based on time-resolved fluorescence resonance energy transfer (TR-FRET). General reference as regards the cells and background can be made to Cooper et al., “An endogenous A2B adenosine receptor coupled to cyclic AMP generation in human embryonic kidney (HEK-293) cells”, Brit. J. Pharmacol., 122: 546. More specifically, the assay to test the Examples was performed as follows: The cells were suspended in HBSS buffer (Invitrogen) complemented with 5 mM HEPES (pH 7.4), with 0.1% BSA and EHNA - adenosine deaminase inhibitor [10 µM], then distributed in mi- croplates at a density of 2.5x103cells / well (in a 384 well plate) in the presence of either (i) HBSS (basal control) with 0.2% DMSO, (ii) the test compound, i.e. each of the examples, or (iii) the reference antagonist XAC. After 2h incubation at room temperature, the nonselective adenosine receptor agonist – adenosine (e.g. CAS 58-61-7, Tocris) was added at a final concentration of 100 µM (corre- sponding to high adenosine concentration in tumor). For basal control measurements, sepa- rate assay wells did not contain adenosine. Following 30 min incubation at room temperature, the cells were lysed and the detection mix was added (standard reagents used according to a standard protocol; LANCE™ cAMP 384 Kit, PerkinElmer). After 60 min at room temperature, the fluorescence transfer was measured at λex=340 nm and λem= 665 nm using a microplate reader according to a standard protocol (Tecan Spark 20M). For test compounds % of normalized vehicle control was calculated for each data point and plotted against test compound concentration: ^^ = 100 ― 100 Sample – mean fluorescence intensity of tested compound Low control – mean fluorescence intensity of adenosine 100 µM Vehicle control – mean fluorescence intensity of DMSO 0.2% EC50, Hill slope and efficacy parameters were determined by fitting a variable-slope sig- moidal function. The standard reference antagonist used was XAC, which was tested in each experiment at several concentrations to generate a concentration-response curve from which its EC50 value was calculated. Compounds of the present disclosure, as exemplified in the Examples, showed EC50 val- ues in the following range: +++ = EC50 ≤ 0.1µM; ++ = EC50 > 0.1µM and ≤ 0.3µM; + = EC50 > 0.3µM and ≤ 0.6µM according to Table 4. Ryvu Therapeutics S.A. and BioNTech SE R10559WO 89 Table 4 As can be derived from Table 4, the compounds of the present invention have very low EC50-values when it comes to A2A- and A2B-binding, respectively. Cytokine secretion induction in human moDCs at high concentrations of agonist Examples Ex-032, Ex-030, and Ex-023 (see synthesis part above for the structures and IUPAC-names of the compounds) were tested for their antagonistic activity on cytokine pro- Ryvu Therapeutics S.A. and BioNTech SE R10559WO 90 duction by human moDCs (monocyte derived dendritic cells) at high concentrations of ago- nist. The antagonistic activity was determined by measuring the effect of compound on ago- nist-suppressed TNFα secretion using homogenous AlphaLISA detection method. More specifically, the assay to test the compounds of the present invention was performed as follows: Human monocyte derived dendritic cells (moDCs) were differentiated in culture with 50 ng / ml GM-CSF (Peprotech) and 100 ng / ml IL-4 (Peprotech) for 6 days. Then cells were seeded in 96 well plates (U-bottom) at density 1.8 mln / ml in culture medium supple- mented with differentiation cytokines and pretreated with i) culture medium with 0.1% DMSO, ii) Ex-032, Ex-030, and Ex-023 at concentrations 10 μM – 1 nM. After 1h incubation NECA was added at final concentration of 10 μM. Next, maturation of moDCs was induced by addition of 100 ng / ml LPS (Sigma Aldrich). After 48h cell culture supernatants were collected. The measured effect was TNFα production detected by AlphaLISA (PerkinElmer) performed according to manufacturer instructions. Signal was measured at λem=615 nm using mi- croplate reader (Perkin Elmer). Cytokine concentration in tested samples was calculated based on standard curve. Using GraphPad Prism software nonlinear regression analysis of standard samples was performed and 4-parameter logistic equation was further used to calculate the amount of secreted TNFα in each tested sample. In order to determine EC50 values data were normalized as follows: ^^ = 100 ― 100 Sample – mean cytokine concentration in tested sample Low control – mean cytokine concentration in agonist control – NECA 10 µM Vehicle control – mean cytokine concentration in DMSO 0.1% control EC50, Hill slope and efficacy parameters were determined by fitting a variable-slope sig- moidal function. Compounds of the present disclosure, as exemplified in the Examples, induced TNFα in moDCs with EC50 values according to Table 5. The presented data is (i) the geometrical mean of EC50 values from at least 3 independent experiments for Ex-032, and (ii) the re- sults derived from a single experiment for Ex-030 and Ex-023. Table 5 As can be derived from Table 5, the compounds of the present invention are able to re- verse immunosuppression mediated by an adenosine receptor and rescue proinflammatory TNFα-production by human moDCs. Ryvu Therapeutics S.A. and BioNTech SE R10559WO 91 Description of cytochrome P450 inhibition (single point) assay The cytochrome P450 inhibition (single point) assay utilizes human liver microsomes (HLM), a single concentration of test compound, and a single incubation time. The inhibi- tion of CYP1A2, 2B6, 2C8, 2C9, 2D6 and 3A4 is assessed using cocktail containing probe substrates for each CYP (phenacetin for 1A2, bupropion for 2B6, amodiaquine for 2C8, di- clofenac for 2C9, dextromethorphan for 2D6, and testosterone / midazolam for 3A4), while inhibition of CYP2C19 is conducted separately due to requirements of higher protein con- centration and longer incubation time, and the probe substrate is S-mephenytoin. The preincubation plate comprises HLM diluted with phosphate buffer (100 mM, pH 7.4) and aliquots of test compound stock solution (maximum pre-incubation concentration: 50 µM) or DMSO for the control incubations. Additionally, during each assay run control in- hibitors for each CYP isoform (furafylline for 1A2, ticlopidine for 2B6 and 2C19, gemfibrozil 1-O-β-glucuronide for 2C8, tienilic acid for 2C9, paroxetine for 2D6, and mifepristone for 3A4), and non-selective reversible inhibitor (atipamezole) for all CYP isoforms are tested. The preincubation is initiated by the addition phosphate buffer (100mM, pH 7.4). The prein- cubation plate is then moved into a thermostatic shaker set at 37°C. At the end of the 30 min preincubation, an aliquot of the preincubation mixture is removed and diluted 10-fold with phosphate buffer containing the substrate cocktail or single probe in the case of CYP2C19 along with an additional aliquot of NADPH. The secondary incubation progresses for 10 min or 25 min (CYP2C19) in a thermostatic shaker set at 37°C prior to quenching with ice-cold acetonitrile. The metabolites of the probe CYP substrates are analyzed in the samples using LC / MS-MS technique. Compounds of the present disclosure, as exemplified in the Examples, showed % of inhibi- tion at 5µM in the following range: ++++ = % of inhibition at 5µM ≤ 20%; +++ = % of inhi- bition at 5µM > 20% and ≤ 40%; ++ = % of inhibition at 5µM > 40% and ≤ 70% according to Tables 6 and 7. Table 6 Ryvu Therapeutics S.A. and BioNTech SE R10559WO 92 Table 7 Ryvu Therapeutics S.A. and BioNTech SE R10559WO 93 The above described cytochrome P450 inhibition (single point) assay was also used to test compounds disclosed in WO 2019 / 002606 A1 and WO 2020 / 128036 A1, namely Example 270 of WO 2019 / 002606 A1 (i.e. 8-amino-6-(4-fluorophenyl)-5-(4-methylquinolin-6-yl)imi- dazo[1,2-a]pyrazine-2-carboxamide), Example 272 of WO 2019 / 002606 A1 (i.e. 8-amino-6- (4-fluorophenyl)-N-methyl-5-(4-methylquinolin-6-yl)imidazo[1,2-a]pyrazine-2-carboxam- ide), Example 17 of WO 2020 / 128036 A1 (i.e.8-amino-N-(2,2-difluoroethyl)-6-(4-fluo- rophenyl)-5-(1-methyl-1H-1,3-benzodiazol-6-yl)imidazo[1,2-a]pyrazine-2-carboxamide), and Example 123 of WO 2020 / 128036 A1 (i.e. 8-amino-N-(cyclopropylmethyl)-6-(4-fluo- rophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide). These compounds showed % of inhibition at 5µM in the following range: ++++ = % of in- hibition at 5µM ≤ 20%; +++ = % of inhibition at 5µM > 20% and ≤ 40%; ++ = % of inhibi- tion at 5µM > 40% and ≤ 70%; + = % of inhibition at 5µM > 70% and ≤ 100%; according to Table 8. Table 8 Ryvu Therapeutics S.A. and BioNTech SE R10559WO 94 As can be derived from Tables 6 to 8, the compounds of the present invention generally show a very low inhibitory activity against the different tested CYP-enzymes, whereas the compounds of WO 2019 / 002606 and WO 2020 / 128036 generally display a stronger in- hibitory activity against the different tested CYP-enzymes, in particular when it comes to CYP2C8 and CYP3A4. Accordingly, the compounds of the present invention generally exhibit a lower CYP-inhibition profile compared to the compounds of WO 2019 / 002606 and WO 2020 / 128036. This is particularly positive for in vivo characteristics in mammals because the degradation of (toxic) compounds by the Cytochrome P450-enzymes (or CYPs) is sub- stantially not inhibited and indicates a lower risk of drug-drug interactions in case of combi- nation therapies or co-administration with other drugs.

Claims

Ryvu Therapeutics S.A. and BioNTech SE R10559WO 95 Claims 1. A compound of formula (I)or a salt, stereoisomer, tautomer, isotopologue, or N-oxide thereof, wherein G1is phenyl, wherein one or two of the substitutable carbon atoms in the afore- mentioned phenyl is substituted with same or different substituents selected from the group consisting of halogen, CN, NO2, C1-C4-alkyl, C1-C4-haloalkyl, C2-C4-alkenyl, C2-C4-haloalkenyl, C2-C4-alkynyl, C2-C4-haloalkynyl, OH, O(C1- C4-alkyl), NH2, NH(C1-C4-alkyl), and N(C1-C4-alkyl)(C1-C4-alkyl); G2is selected from the group consistingofG3is C(=O)N(R4a)(R4b); R1ais selected from the group consisting of H, halogen, CN, NO2, C1-C4-alkyl, C1- C4-haloalkyl, C2-C4-alkenyl, C2-C4-haloalkenyl, C2-C4-alkynyl, C2-C4- haloalkynyl, OH, O(C1-C4-alkyl), NH2, NH(C1-C4-alkyl), and N(C1-C4-alkyl)(C1- C4-alkyl); R1bis selected from the group consisting of H, halogen, CN, NO2, C1-C4-alkyl, C1- C4-haloalkyl, C2-C4-alkenyl, C2-C4-haloalkenyl, C2-C4-alkynyl, C2-C4- haloalkynyl, OH, O(C1-C4-alkyl), NH2, NH(C1-C4-alkyl), and N(C1-C4-alkyl)(C1- C4-alkyl); R1cis selected from the group consisting of H, halogen, CN, NO2, C1-C4-alkyl, C1- C4-haloalkyl, C2-C4-alkenyl, C2-C4-haloalkenyl, C2-C4-alkynyl, C2-C4- haloalkynyl, OH, O(C1-C4-alkyl), NH2, NH(C1-C4-alkyl), and N(C1-C4-alkyl)(C1- C4-alkyl); R2ais selected from the group consisting of H, halogen, CN, NO2, C1-C4-alkyl, C1- C4-haloalkyl, C2-C4-alkenyl, C2-C4-haloalkenyl, C2-C4-alkynyl, C2-C4- haloalkynyl, OH, O(C1-C4-alkyl), NH2, NH(C1-C4-alkyl), and N(C1-C4-alkyl)(C1- C4-alkyl); R2bis selected from the group consisting of H, halogen, CN, NO2, C1-C4-alkyl, C1- C4-haloalkyl, C2-C4-alkenyl, C2-C4-haloalkenyl, C2-C4-alkynyl, C2-C4-Ryvu Therapeutics S.A. and BioNTech SE R10559WO 96 haloalkynyl, OH, O(C1-C4-alkyl), NH2, NH(C1-C4-alkyl), and N(C1-C4-alkyl)(C1- C4-alkyl); R2cis selected from the group consisting of H, halogen, CN, NO2, C1-C4-alkyl, C1- C4-haloalkyl, C2-C4-alkenyl, C2-C4-haloalkenyl, C2-C4-alkynyl, C2-C4- haloalkynyl, OH, O(C1-C4-alkyl), NH2, NH(C1-C4-alkyl), and N(C1-C4-alkyl)(C1- C4-alkyl); R4ais selected from the group consisting of H, C1-C4-alkyl, C1-C4-haloalkyl, C2-C4- alkenyl, C2-C4-haloalkenyl, C2-C4-alkynyl, and C2-C4-haloalkynyl; R4bis a 5-membered saturated, partially unsaturated or fully unsaturated carbobicyclic or heterobicyclic ring, wherein said heterobicyclic ring comprises one or more, same or different heteroatoms selected from O, N or S, wherein said N- and / or S-atoms are in- dependently oxidized or non-oxidized, and wherein each substitutable carbon or het- ero-atom in the aforementioned moieties is unsubstituted or substituted with one or more, same or different substituents R5; wherein R5(i) is selected from the group consisting of halogen, CN, NO2, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, a 3- to 9-membered saturated, partially un- saturated or fully unsaturated carbocyclic or heterocyclic ring, and a 4- to 14-membered saturated, partially unsaturated or fully unsaturated carbo- bicyclic or heterobicyclic ring, wherein said heterocyclic or heterobicyclic ring comprises one or more, same or different heteroatoms selected from O, N or S, wherein said N- and / or S-atoms are independently oxidized or non-oxidized, and wherein each substitutable carbon or hetero-atom in the aforementioned moieties is unsubstituted or substituted with one or more, same or different substituents R6; or (ii) is selected from the group consisting of C(=O)R7, C(=O)OR8, C(=O)N(R8a)(R8b), OR8, N(R8a)(R8b), N(R8)C(=O)R7, N(R8)C(=O)OR8, and N(R8)C(=O)N(R8a)(R8b); or (iii) together with a second R5on one carbon atom forms =O; wherein R6(i) is selected from the group consisting of halogen, CN, NO2, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, a 3- to 9-membered saturated, partially un- saturated or fully unsaturated carbocyclic or heterocyclic ring, and a 4- to 14-membered saturated, partially unsaturated or fully unsaturated carbo- bicyclic or heterobicyclic ring, wherein said heterocyclic or heterobicyclic ring comprises one or more, same or different heteroatoms selected from O, N or S, wherein said N- and / or S-atoms are independently oxidized or non-oxidized, and wherein each substitutable carbon or hetero-atom in the aforementioned moieties is unsubstituted or substituted with one or more, same or different substituents R9; or (ii) is selected from the group consisting of C(=O)R10, C(=O)OR11, C(=O)N(R11a)(R11b), OR11, N(R11a)(R11b), N(R11)C(=O)R10, N(R11)C(=O)OR11, and N(R11)C(=O)N(R11a)(R11b); wherein R7, R8, R8a, R8bare independently selected from the group consisting of H, C1- C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, a 3- to 9-membered saturated, par- tially unsaturated or fully unsaturated carbocyclic or heterocyclic ring, andRyvu Therapeutics S.A. and BioNTech SE R10559WO 97 a 4- to 14-membered saturated, partially unsaturated or fully unsaturated carbobicyclic or heterobicyclic ring, wherein said heterocyclic or heterobi- cyclic ring comprises one or more, same or different heteroatoms selected from O, N or S, wherein said N- and / or S-atoms are independently oxidized or non-oxidized, and wherein each substitutable carbon or hetero-atom in the aforementioned moieties is unsubstituted or substituted with one or more, same or different substituents R12; wherein R9is selected from the group consisting of halogen, CN, NO2, C1-C6-alkyl, C2- C6-alkenyl, C2-C6-alkynyl, a 3- to 9-membered saturated, partially unsatu- rated or fully unsaturated carbocyclic or heterocyclic ring, and a 4- to 14- membered saturated, partially unsaturated or fully unsaturated carbobi- cyclic or heterobicyclic ring, wherein said heterocyclic or heterobicyclic ring comprises one or more, same or different heteroatoms selected from O, N or S, wherein said N- and / or S-atoms are independently oxidized or non- oxidized, and wherein each substitutable carbon or hetero-atom in the aforementioned moieties is unsubstituted or substituted with one or more, same or different substituents R13; wherein R10, R11, R11a, R11bare independently selected from the group consisting of H, C1-C4-alkyl, C1-C4-haloalkyl, C2-C4-alkenyl, C2-C4-haloalkenyl, C2-C4- alkynyl, and C2-C4-haloalkynyl; wherein R12is selected from the group consisting of halogen, CN, NO2, OH, O(C1-C4- alkyl), NH2, NH(C1-C4-alkyl), and N(C1-C4-alkyl)(C1-C4-alkyl), C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, a 3- to 9-membered saturated, partially un- saturated or fully unsaturated carbocyclic or heterocyclic ring, and a 4- to 14-membered saturated, partially unsaturated or fully unsaturated carbobi- cyclic or heterobicyclic ring, wherein said heterocyclic or heterobicyclic ring comprises one or more, same or different heteroatoms selected from O, N or S, wherein said N- and / or S-atoms are independently oxidized or non- oxidized, and wherein each substitutable carbon or hetero-atom in the aforementioned moieties is unsubstituted or substituted with one or more, same or different substituents R14; and wherein R13, R14are independently selected from the group consisting of halogen, CN, NO2, C1-C6-alkyl, C1-C6-haloalkyl, C2-C6-alkenyl, C2-C6-haloalkenyl, C2-C6- alkynyl, C2-C6-haloalkynyl, OH, O(C1-C4-alkyl), NH2, NH(C1-C4-alkyl), and N(C1-C4-alkyl)(C1-C4-alkyl).

2. The compound according to claim 1, wherein G1is phenyl, wherein one or two of the substitutable carbon atoms in the aforementioned phenyl is substituted with same or different substituents selected from the group consisting of CH3, halogen and CN.

3. The compound according to claim 1 or 2, wherein R1ais selected from the group consisting of H and halogen.

4. The compound according to any one of the preceding claims, wherein R1bis se- lected from the group consisting of H and halogen.Ryvu Therapeutics S.A. and BioNTech SE R10559WO 98 5. The compound according to any one of the preceding claims, wherein R1cis se- lected from the group consisting of H and halogen.

6. The compound according to any one of the preceding claims, wherein R2ais C1-C3- alkyl.

7. The compound according to any one of the preceding claims, wherein R2bis C1-C3- alkyl.

8. The compound according to any one of the preceding claims, wherein R2cis C1-C3- alkyl.

9. The compound according to any one of the preceding claims, wherein R4ais H.

10. The compound according to any one of the preceding claims, wherein G1is phenyl, wherein one or two of the substitutable carbon atoms in the afore- mentioned phenyl is substituted with same or different substituents selected from the group consisting of CH3, F, and CN; R1ais selected from the group consisting of H and Cl; R1bis selected from the group consisting of H and Cl; R1cis selected from the group consisting of H and Cl; R2ais CH3; R2bis CH3; R2cis CH3; and R4ais H.

11. The compound according to any one of the preceding claims, wherein G2is se-lected from the group consisting of12. The compoundaccording to an one of preceding claims, wherein G2is13. T e com according to any one of the preceding claims, wherein G3is C(=O)N(R4a)(R4b), wherein R4ais H; and R4bis bicyclo[1.1.1]pentan-1-yl, wherein each substitutable carbon-atom in the aforementioned bicyclo[1.1.1]pentan-1-yl is unsubstituted or substituted with one or more, same or different substituents R5;Ryvu Therapeutics S.A. and BioNTech SE R10559WO 99 wherein R5(i) is selected from the group consisting of halogen, CN, NO2, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, a 3- to 9-membered saturated, partially un- saturated or fully unsaturated carbocyclic or heterocyclic ring, and a 4- to 14-membered saturated, partially unsaturated or fully unsaturated carbo- bicyclic or heterobicyclic ring, wherein said heterocyclic or heterobicyclic ring comprises one or more, same or different heteroatoms selected from O, N or S, wherein said N- and / or S-atoms are independently oxidized or non-oxidized, and wherein each substitutable carbon or hetero-atom in the aforementioned moieties is unsubstituted or substituted with one or more, same or different substituents R6; or (ii) is selected from the group consisting of C(=O)R7, C(=O)OR8, C(=O)N(R8a)(R8b), OR8, N(R8a)(R8b), N(R8)C(=O)R7, N(R8)C(=O)OR8, and N(R8)C(=O)N(R8a)(R8b); or (iii) together with a second R5on one carbon atom forms =O; wherein R6(i) is selected from the group consisting of halogen, CN, NO2, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, a 3- to 9-membered saturated, partially un- saturated or fully unsaturated carbocyclic or heterocyclic ring, and a 4- to 14-membered saturated, partially unsaturated or fully unsaturated carbo- bicyclic or heterobicyclic ring, wherein said heterocyclic or heterobicyclic ring comprises one or more, same or different heteroatoms selected from O, N or S, wherein said N- and / or S-atoms are independently oxidized or non-oxidized, and wherein each substitutable carbon or hetero-atom in the aforementioned moieties is unsubstituted or substituted with one or more, same or different substituents R9; or (ii) is selected from the group consisting of C(=O)R10, C(=O)OR11, C(=O)N(R11a)(R11b), OR11, N(R11a)(R11b), N(R11)C(=O)R10, N(R11)C(=O)OR11, and N(R11)C(=O)N(R11a)(R11b); wherein R7, R8, R8a, R8bare independently selected from the group consisting of H, C1- C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, a 3- to 9-membered saturated, par- tially unsaturated or fully unsaturated carbocyclic or heterocyclic ring, and a 4- to 14-membered saturated, partially unsaturated or fully unsaturated carbobicyclic or heterobicyclic ring, wherein said heterocyclic or heterobi- cyclic ring comprises one or more, same or different heteroatoms selected from O, N or S, wherein said N- and / or S-atoms are independently oxidized or non-oxidized, and wherein each substitutable carbon or hetero-atom in the aforementioned moieties is unsubstituted or substituted with one or more, same or different substituents R12; wherein R9is selected from the group consisting of halogen, CN, NO2, C1-C6-alkyl, C2- C6-alkenyl, C2-C6-alkynyl, a 3- to 9-membered saturated, partially unsatu- rated or fully unsaturated carbocyclic or heterocyclic ring, and a 4- to 14- membered saturated, partially unsaturated or fully unsaturated carbobi- cyclic or heterobicyclic ring, wherein said heterocyclic or heterobicyclic ring comprises one or more, same or different heteroatoms selected from O, N or S, wherein said N- and / or S-atoms are independently oxidized or non-Ryvu Therapeutics S.A. and BioNTech SE R10559WO 100 oxidized, and wherein each substitutable carbon or hetero-atom in the aforementioned moieties is unsubstituted or substituted with one or more, same or different substituents R13; wherein R10, R11, R11a, R11bare independently selected from the group consisting of H, C1-C4-alkyl, C1-C4-haloalkyl, C2-C4-alkenyl, C2-C4-haloalkenyl, C2-C4- alkynyl, and C2-C4-haloalkynyl; wherein R12is selected from the group consisting of halogen, CN, NO2, OH, O(C1-C4- alkyl), NH2, NH(C1-C4-alkyl), and N(C1-C4-alkyl)(C1-C4-alkyl), C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, a 3- to 9-membered saturated, partially un- saturated or fully unsaturated carbocyclic or heterocyclic ring, and a 4- to 14-membered saturated, partially unsaturated or fully unsaturated carbobi- cyclic or heterobicyclic ring, wherein said heterocyclic or heterobicyclic ring comprises one or more, same or different heteroatoms selected from O, N or S, wherein said N- and / or S-atoms are independently oxidized or non- oxidized, and wherein each substitutable carbon or hetero-atom in the aforementioned moieties is unsubstituted or substituted with one or more, same or different substituents R14; and wherein R13, R14are independently selected from the group consisting of halogen, CN, NO2, C1-C6-alkyl, C1-C6-haloalkyl, C2-C6-alkenyl, C2-C6-haloalkenyl, C2-C6- alkynyl, C2-C6-haloalkynyl, OH, O(C1-C4-alkyl), NH2, NH(C1-C4-alkyl), and N(C1-C4-alkyl)(C1-C4-alkyl).

14. The compound according to any one of the preceding claims, wherein G3is C(=O)N(R4a)(R4b), wherein R4ais H; and R4bis bicyclo[1.1.1]pentan-1-yl, wherein each substitutable carbon-atom in the aforementioned bicyclo[1.1.1]pentan-1-yl is unsubstituted or substituted with one or more, same or different substituents R5; wherein R5is selected from the group consisting of halogen, C1-C4-alkyl, a 3- to 9-membered saturated, partially unsaturated or fully unsaturated carbocyclic or heterocyclic ring, and a 4- to 14-mem- bered saturated, partially unsaturated or fully unsaturated carbobicyclic or heterobicyclic ring, wherein said heterocyclic or heterobicyclic ring com- prises one or more, same or different heteroatoms selected from O, N or S, wherein said N- and / or S-atoms are independently oxidized or non-oxi- dized, and wherein each substitutable carbon or hetero-atom in the afore- mentioned moieties is unsubstituted or substituted with one or more, same or different substituents R6; wherein R6(i) Is selected from the group consisting of halogen, C1-C4-alkyl, a 3- to 9- membered saturated, partially unsaturated or fully unsaturated carbo- cyclic or heterocyclic ring, and a 4- to 14-membered saturated, partially unsaturated or fully unsaturated carbobicyclic or heterobicyclic ring, wherein said heterocyclic or heterobicyclic ring comprises one or more, same or different heteroatoms selected from O, N or S, wherein said N- and / or S-atoms are independently oxidized or non-oxidized, and wherein each substitutable carbon or hetero-atom in the aforementioned moietiesRyvu Therapeutics S.A. and BioNTech SE R10559WO 101 is unsubstituted or substituted with one or more, same or different sub- stituents R9; or (ii) is selected from the group consisting of C(=O)R10, C(=O)OR11, C(=O)N(R11a)(R11b), OR11, N(R11a)(R11b), N(R11)C(=O)R10, N(R11)C(=O)OR11, and N(R11)C(=O)N(R11a)(R11b); wherein R9is selected from the group consisting of halogen and C1-C4-alkyl, wherein each substitutable carbon in the aforementioned C1-C4-alkyl is un- substituted or substituted with one or more, same or different substituents R13; wherein R10, R11, R11a, R11bare independently selected from the group consisting of H, C1-C4-alkyl, and C1-C4-haloalkyl; and wherein R13is selected from the group consisting of halogen, C1-C4-alkyl, and C1- C4-haloalkyl.

15. The compound according to any one of the preceding claims, wherein G3is C(=O)N(R4a)(R4b), wherein R4ais H; and R4bis unsubstituted bicyclo[1.1.1]pentan- 1-yl.

16. The compound according to any one of the preceding claims, wherein said com- pound is selected from the group consisting of 8-amino-N-{3-[(dimethyl- amino)methyl]bicyclo[1.1.1]pentan-1-yl}-6-(4-fluorophenyl)-5-{3-methylim- idazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide; 8-amino-6-(4- fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}-N-{3-[(morpholin-4- yl)methyl]bicyclo[1.1.1]pentan-1-yl}imidazo[1,2-a]pyrazine-2-carboxamide; 8- amino-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}-N-{3-[(4- methylpiperazin-1-yl)methyl]bicyclo[1.1.1]pentan-1-yl}imidazo[1,2-a]pyrazine-2- carboxamide; 8-amino-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}- N-[3-({2-oxa-6-azaspiro[3.3]heptan-6-yl}methyl)bicyclo[1.1.1]pentan-1-yl]im- idazo[1,2-a]pyrazine-2-carboxamide; 8-amino-N-(3-{[(2,2-difluoro- ethyl)amino]methyl}bicyclo[1.1.1]pentan-1-yl)-6-(4-fluorophenyl)-5-{3-methylim- idazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide; 8-amino-N-(3- {[(2,2-difluoroethyl)(methyl)amino]methyl}bicyclo[1.1.1]pentan-1-yl)-6-(4- fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-car- boxamide; 8-amino-N-{3-[(4,4-difluoropiperidin-1-yl)methyl]bicyclo[1.1.1]pentan- 1-yl}-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2- a]pyrazine-2-carboxamide; 8-amino-N-(3-{[(2-fluoroethyl)amino]methyl}bi- cyclo[1.1.1]pentan-1-yl)-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6- yl}imidazo[1,2-a]pyrazine-2-carboxamide; 8-amino-N-{3-[(3,3-difluoropyrrolidin-1- yl)methyl]bicyclo[1.1.1]pentan-1-yl}-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2- a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide; 8-amino-6-(4-fluorophenyl)- N-(3-{[methyl(2,2,2-trifluoroethyl)amino]methyl}bicyclo[1.1.1]pentan-1-yl)-5-{3- methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide; 8-amino- 6-(4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}-N-(3-{[(2,2,2-trifluoro- ethyl)amino]methyl}bicyclo[1.1.1]pentan-1-yl)imidazo[1,2-a]pyrazine-2-carboxam- ide; 8-amino-N-{3-[(3,3-difluoroazetidin-1-yl)methyl]bicyclo[1.1.1]pentan-1-yl}-6- (4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-Ryvu Therapeutics S.A. and BioNTech SE R10559WO 102 carboxamide; 8-amino-N-{3-[(3-fluoroazetidin-1-yl)methyl]bicyclo[1.1.1]pentan-1- yl}-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2- a]pyrazine-2-carboxamide; 8-amino-N-(3-{[(1,3-difluoropropan-2- yl)amino]methyl}bicyclo[1.1.1]pentan-1-yl)-6-(4-fluorophenyl)-5-{3-methylim- idazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide; 8-amino-6-(4- fluorophenyl)-N-{3-[(N-methylacetamido)methyl]bicyclo[1.1.1]pentan-1-yl}-5-{3- methylimidazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide; 8-amino- N-{3-fluorobicyclo[1.1.1]pentan-1-yl}-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2- a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide; 8-amino-6-(4-fluorophenyl)- N-[3-(1-hydroxyethyl)bicyclo[1.1.1]pentan-1-yl]-5-{3-methylimidazo[1,2-a]pyridin- 6-yl}imidazo[1,2-a]pyrazine-2-carboxamide; 8-amino-6-(4-fluorophenyl)-5-{3- methylimidazo[1,2-a]pyridin-6-yl}-N-[3-(pyrrolidin-1-yl)bicyclo[1.1.1]pentan-1- yl]imidazo[1,2-a]pyrazine-2-carboxamide; 8-amino-6-(4-fluorophenyl)-5-{3- methylimidazo[1,2-a]pyridin-6-yl}-N-[3-(piperidin-1-yl)bicyclo[1.1.1]pentan-1- yl]imidazo[1,2-a]pyrazine-2-carboxamide; 8-amino-6-(4-fluorophenyl)-N-[3-(2-hy- droxypropan-2-yl)bicyclo[1.1.1]pentan-1-yl]-5-{3-methylimidazo[1,2-a]pyridin-6- yl}imidazo[1,2-a]pyrazine-2-carboxamide; 8-amino-6-(4-fluorophenyl)-N-[3-(hy- droxymethyl)bicyclo[1.1.1]pentan-1-yl]-5-{3-methylimidazo[1,2-a]pyridin-6-yl}im- idazo[1,2-a]pyrazine-2-carboxamide; 8-amino-6-(4-fluorophenyl)-N-[3-(methoxy- methyl)bicyclo[1.1.1]pentan-1-yl]-5-{3-methylimidazo[1,2-a]pyridin-6-yl}im- idazo[1,2-a]pyrazine-2-carboxamide; 8-amino-6-(4-fluorophenyl)-5-{3-methylim- idazo[1,2-a]pyridin-6-yl}-N-{3-[(piperazin-1-yl)methyl]bicyclo[1.1.1]pentan-1- yl}imidazo[1,2-a]pyrazine-2-carboxamide; 8-amino-6-(4-fluorophenyl)-N-{3- [(methylamino)methyl]bicyclo[1.1.1]pentan-1-yl}-5-{3-methylimidazo[1,2- a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide; 8-amino-N-[3-(amino- methyl)bicyclo[1.1.1]pentan-1-yl]-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2- a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide; 8-amino-N-[3-(acetamido- methyl)bicyclo[1.1.1]pentan-1-yl]-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2- a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide; 8-amino-6-(4-fluorophenyl)- N-[3-(2-hydroxy-2-methylpropyl)bicyclo[1.1.1]pentan-1-yl]-5-{3-methylim- idazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide; 8-amino-6-(4- fluorophenyl)-N-[3-(2-hydroxyethyl)bicyclo[1.1.1]pentan-1-yl]-5-{3-methylim- idazo[1,2-a]pyridin-6-yl}imidazo[1,2-a]pyrazine-2-carboxamide; Propan-2-yl N- ({3-[8-amino-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}im- idazo[1,2-a]pyrazine-2-amido]bicyclo[1.1.1]pentan-1-yl}methyl)carbamate; 8- amino-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}-N-[3-(piperazin- 1-yl)bicyclo[1.1.1]pentan-1-yl]imidazo[1,2-a]pyrazine-2-carboxamide; 8-amino-6- (4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6-yl}-N-[3-(morpholin-4-yl)bi- cyclo[1.1.1]pentan-1-yl]imidazo[1,2-a]pyrazine-2-carboxamide; 8-amino-N-{bi- cyclo[1.1.1]pentan-1-yl}-6-(4-fluorophenyl)-5-{3-methylimidazo[1,2-a]pyridin-6- yl}imidazo[1,2-a]pyrazine-2-carboxamide; and 8-amino-N-{bicyclo[1.1.1]pentan-1- yl}-6-(4-fluorophenyl)-5-(1-methyl-1H-1,3-benzodiazol-6-yl)imidazo[1,2- a]pyrazine-2-carboxamide.Ryvu Therapeutics S.A. and BioNTech SE R10559WO 103 17. A pharmaceutical composition comprising the compound according to any one of claims 1 to 16 and optionally a pharmaceutically acceptable carrier, diluent and / or excipient.

18. The compound according to any one of claims 1 to 16 for use in medicine.

19. The compound according to any one of claims 1 to 16 for use in the treatment of a disease selected from the group consisting of cancer, Parkinson's disease, Hunt- ington's disease, Alzheimer's disease, psychosis, stroke, extra pyramidal syndrome, attention deficit disorder (ADD), attention deficit hyperactivity disorder (ADHD), amyotrophic lateral sclerosis, cirrhosis, fibrosis, fatty liver, addictive behavior, der- mal fibrosis, a sleep disorder, AIDS, an autoimmune disease, an infection, athero- sclerosis, ischemia-reperfusion injury, idiopathic pulmonary fibrosis, systemic scle- rosis, irritable bowel disease, chronic kidney disease and pain.

20. The compound according to any one of claims 1 to 16 for use in the treatment of cancer.

21. The compound for use according to claim 20, wherein at least one further anti- neoplastic agent is coadministered with said compound.

22. The compound for use according to claim 21, wherein the anti-neoplastic agent is selected from the group consisting of a chemotherapeutic agent, a topoisomerase II inhibitor, an antimetabolite, a topoisomerase I inhibitor, a hormone, a hormonal analogue, a signal transduction pathway inhibitor, a tyrosine kinase inhibitor, an angiogenesis inhibitor, a proapoptotic agent, a cell cycle signaling inhibitor, a pro- teasome inhibitor, an inhibitor of cancer metabolism, and an immunotherapeutic agent.

23. The compound for use according to claim 22, wherein the immunotherapeutic agent is a checkpoint inhibitor.

24. A method for treating a disease in a subject in need thereof, wherein the method comprises administering a therapeutically effective amount of the compound ac- cording to any one of claims 1 to 16 to the subject, wherein the disease is selected from the group consisting of cancer, Parkinson's disease, Huntington's disease, Alzheimer's disease, psychosis, stroke, extra pyramidal syndrome, attention deficit disorder (ADD), attention deficit hyperactivity disorder (ADHD), amyotrophic lat- eral sclerosis, cirrhosis, fibrosis, fatty liver, addictive behavior, dermal fibrosis, a sleep disorder, AIDS, an autoimmune disease, an infection, atherosclerosis, is- chemia-reperfusion injury, idiopathic pulmonary fibrosis, systemic sclerosis, irrita- ble bowel disease, chronic kidney disease and pain.

25. A method for treating cancer in a subject in need thereof, wherein the method comprises administering a therapeutically effective amount of the compound ac- cording to any one of claims 1 to 16 to the subject.Ryvu Therapeutics S.A. and BioNTech SE R10559WO 104 26. The method according to claim 25, wherein the method further comprises co-ad- ministering a therapeutically effective amount of at least one further anti-neoplas- tic agent with said compound.

27. The method according to claim 26, wherein the anti-neoplastic agent is selected from the group consisting of a chemotherapeutic agent, a topoisomerase II inhib- itor, an antimetabolite, a topoisomerase I inhibitor, a hormone, a hormonal ana- logue, a signal transduction pathway inhibitor, a tyrosine kinase inhibitor, an an- giogenesis inhibitor, a proapoptotic agent, a cell cycle signaling inhibitor, a protea- some inhibitor, an inhibitor of cancer metabolism, and an immunotherapeutic agent.

28. The method according to claim 27, wherein the immunotherapeutic agent is a checkpoint inhibitor.

29. Use of the compound according to any one of claims 1 to 16 in the manufacture of a medicament for the treatment of a disease selected from the group consisting of cancer, Parkinson's disease, Huntington's disease, Alzheimer's disease, psychosis, stroke, extra pyramidal syndrome, attention deficit disorder (ADD), attention deficit hyperactivity disorder (ADHD), amyotrophic lateral sclerosis, cirrhosis, fi- brosis, fatty liver, addictive behavior, dermal fibrosis, a sleep disorder, AIDS, an autoimmune disease, an infection, atherosclerosis, ischemia-reperfusion injury, id- iopathic pulmonary fibrosis, systemic sclerosis, irritable bowel disease, chronic kidney disease and pain.

30. Use of the compound according to any one of claims 1 to 16 in the manufacture of a medicament for the treatment of cancer.

31. The use according to claim 30, wherein at least one further anti-neoplastic agent is co-administered in the treatment.

32. The use according to claim 31, wherein the anti-neoplastic agent is selected from the group consisting of a chemotherapeutic agent, a topoisomerase II inhibitor, an antimetabolite, a topoisomerase I inhibitor, a hormone, a hormonal analogue, a signal transduction pathway inhibitor, a tyrosine kinase inhibitor, an angiogenesis inhibitor, a proapoptotic agent, a cell cycle signaling inhibitor, a proteasome inhib- itor, an inhibitor of cancer metabolism, and an immunotherapeutic agent.

33. The use according to claim 32, wherein the immunotherapeutic agent is a check- point inhibitor.

34. A method for antagonizing the adenosine A2A receptor, wherein said receptor is exposed to the compound according to any one of claims 1 to 16, wherein said method is preferably performed outside the human or animal body.Ryvu Therapeutics S.A. and BioNTech SE R10559WO 105 35. A method for antagonizing the adenosine A2B receptor, wherein said receptor is exposed to the compound according to any one of claims 1 to 16, wherein said method is preferably performed outside the human or animal body.

36. A method for antagonizing the adenosine A2A receptor and the adenosine A2B re- ceptor, wherein said receptors are exposed to the compound according to any one of claims 1 to 16, wherein said method is preferably performed outside the human or animal body.

37. Use of the compound according to any one of claims 1 to 16 as adenosine A2A re- ceptor antagonist.

38. Use of the compound according to any one of claims 1 to 16 as adenosine A2B re- ceptor antagonist.

39. Use of the compound according to any one of claims 1 to 16 as adenosine A2A re- ceptor and adenosine A2B receptor antagonist.

40. A method of manufacturing a pharmaceutical composition according to claim 17, comprising the step of contacting the compound according to any one of claims 1 to 16 with a pharmaceutically acceptable carrier, diluent and / or excipient.

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