Novel bicyclo heteroaryl PARG inhibitors

Abstract

The present invention relates to a compound of formula (I) or a pharmaceutically acceptable salt thereof. The present invention further relates to the compound of formula (I) of the present invention for use in therapy. Instant compounds are particularly useful as PARG inhibitors, and can be used in a method of treatment of a proliferative disorder, preferably of cancer.

Description

[0001] New PCT-Patent Application based on US 63 / 614,140 FoRx Therapeutics AG Vossius Ref.: AG4297 PCT BS Novel PARG inhibitors Field of the invention The present invention relates to a compound of formula (I) or a pharmaceutically acceptable salt thereof. The present invention further relates to the compound of formula (I) of the present invention for use in therapy. Instant compounds are particularly useful as PARG inhibitors, and can be used in a method of treatment of a proliferative disorder, preferably of cancer. Background of the invention Cancer is a leading cause of death worldwide. Although progression-free survival and overall survival of cancer patients has improved over the past two decades, millions of cancer patients still have few therapeutic options and poor survival outcomes (Jemal et al., J. Natl. Cancer Inst.2017, 109, 1975). DNA replication stress (DRS) is a hallmark of cancer cells and a major source of genomic instability (a) Halazonetis et al., Science 2008, 319, 1352; b) Negrini et al., Nat. Rev. Mol. Cell Biol.2010, 11, 220). In broad terms, DRS refers to the deregulation of DNA replication and cell cycle progression. DRS can be induced from endogenous or exogenous causes such as oncogene activation and chemotherapeutics, respectively (Zeman and Cimprich, Nat. Cell Biol.2013, 16, 2). At the level of the replication fork, DRS leads to replication fork stalling, disengagement of the replisome and eventually collapse. Several DNA repair proteins are involved in replication fork stability, protection, and restart under DRS conditions (a) Costantino et al., Science 2014, 343, 88; b) Scully et al., Curr. Opin. Genet. Dev.202171, 154). Poly(ADP)ribosylation (PARylation) is a transient and reversible post-translational modification that occurs at DNA damaged sites and is catalyzed by the poly (ADP-ribose) polymerase (PARP) family of proteins (Cohen and Chang, Nat. Chem. Biol.2018, 14, 236). PARylation of various DNA repair proteins leads to their activation. Degradation of the poly(ADP) ribose chains is mediated primarily by the poly(ADP-ribose) glycohydrolase (PARG) protein. DNA damage dependent PARylation / dePARylation is a rapid and dynamic process which needs to be well regulated since imbalances between the two processes can lead to DNA damage. Human PARG encodes a 111 kDa protein of 976 amino acids. It contains a N-terminal regulatory domain, a catalytic domain and an ADP-ribose binding macrodomain. Five human PARG transcripts have been identified. Full length PARG is mostly nuclear; the smaller isoforms localize primarily to the cytoplasm. PARG functions primarily as an exo-hydrolase and it releases mainly mono(ADP-ribose) byhydrolyzing the -O-glycosidic ribose-ribose bond in PAR. PARG can also act as an endo-hydrolase. PARG preferentially degrades long and linear PAR chains whereas its activity with small and branched PAR chains is significantly reduced (O’Sullivan et al., Nat. Commun.2019, 10, 1182). Although PARG is the dominant cellular PAR degrading enzyme, it cannot act on the terminal protein–ribose bond. Additional hydrolases such as terminal ADP-ribose protein glycohydrolase (TARG1) and ADP-ribosylhydrolase 3 (ARH3) are also known to catalyze PAR-degradation. TARG1 and ARH3 complete the reversal of PARylation by removing protein-bound mono(ADP-ribose) moieties (a) Fontana et al., Elife 2017, doi: 10.7554 / eLife.28533; b) Rack et al., Genes Dev.2020, 34, 263). TARG1 is located in the nucleus and cytoplasm. ARH3 is found primarily in the cytoplasm but it can also be found in the mitochondria and in the nucleus (Rack et al., Genes Dev.2020, 34, 263). Genomic aberrations targeting tumor suppressor genes or oncogenes, often make cancer cells dependent on specific DNA repair pathways. For instance, it is well known that PARP inhibitors are particularly effective against tumors carrying mutations in the BRCA1 and BRCA2 genes (a) Bryant et al., Nature 2005, 434, 913; b) Farmer et al., Nature 2005, 434, 917). Targeting synthetic lethal interactions like the one between PARP and BRCA is an attractive novel therapeutic approach for cancer treatment. PARG participates in DNA replication and in various DNA repair mechanisms including single- strand break (SSB) repair and replication fork restart. PARG inhibitors have shown synthetic lethal phenotype in cells with high levels of DRS caused by low expression of genes involved in DNA replication and / or replication fork stability (Pillay et al., Cancer Cell.2019, 35, 519). Moreover, PARG inactivation, depletion or inhibition sensitizes cells to irradiation and to DNA damaging agents such as alkylating agents (e.g. temozolomide and methyl methanesulfonate) (a) Fujihara et al., Curr. Cancer Drug Targets 2009, 9, 953; b) Gogola et al., Cancer Cell 2018, 33, 1078; c) Houl et al., Nat Commun.2019, 10, 5654). Given the therapeutic potential of PARG inhibitors in cancer treatment, there is an increased need for the development of highly potent and selective PARG inhibitors beyond the ones that have already been described (a) James et al., ACS Chem. Biol.2016, 11, 3179; b) Waszkowycz et al., J. Med. Chem. 2018, 61, 10767). Certain compounds that are useful as PARG inhibitors are further disclosed in documents WO 2016 / 092326, WO 2016 / 097749 and WO 2021 / 055744. Document WO 2023 / 154913 further discloses certain sulfonamides and related compounds which are inhibitors of PARG and are useful in the treatment of cancer. Summary of the invention It was an objective technical problem of the present invention to provide compounds that are cell- permeable inhibitors of PARG. The technical problem of the present invention is solved by the embodiments described herein and as characterized by the claims. The compound of the invention are potent and cell-permeable inhibitors of PARG, which makes them suitable for therapeutic applications against cancer. The inhibitors of PARG of the present invention show advantageous properties, including good hERG inhibition profile, good metabolic stability and good solubility, which further supports their therapeutic use in human subjects. Accordingly, the present invention is based, at least in part, on the surprising discovery of the present inventors that introduction of a particular substituted cycloalkyl or heterocycloalkyl moiety, in particular of a specifically substituted cyclopropyl moiety in the compounds of formula (I) comprising imidazo[1,5-a]pyridine core (or a similar ring system with a bridging nitrogen atom) leads to a beneficial reduction of hERG inhibition properties, at the same time improving cellular potency and selectivity of the compounds, as well as their metabolic stability. In a first embodiment, the present invention relates to a compound of formula (I): or a pharmaceutically acceptable salt thereof. A further embodiment of the present invention relates to a pharmaceutical composition comprising the compound of formula (I) or a pharmaceutically acceptable salt, hydrate or solvate thereof, and a pharmaceutically acceptable carrier. In a further embodiment, the present invention relates to the compound of formula (I) of the present invention or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of the present invention, for use in therapy. The compounds of formula (I) are useful for treating a disease or disorder in which PARG activity is implicated. The compounds of formula (I) are useful for a method of treating a proliferative disorder. In a preferred embodiment of the present invention, the proliferative disorder is cancer, preferably a human cancer. Definitions The following definitions apply throughout the present specification and the claims, unless specifically indicated otherwise. The term “hydrogen” is herein used to refer to protium, deuterium and / or tritium, preferably to protium. Accordingly, the term “non-hydrogen atom” refers to any atoms that is not hydrogen, i.e. that is not protium, deuterium or tritium. The term “hydrocarbon group” refers to a group consisting of carbon atoms and hydrogen atoms. The term “alicyclic” is used in connection with cyclic groups and denotes that the corresponding cyclic group is non-aromatic. As used herein, the term “alkyl” refers to a monovalent saturated acyclic (i.e., non-cyclic) hydrocarbon group which may be linear or branched. Accordingly, an “alkyl” group does not comprise any carbon-to-carbon double bond or any carbon-to-carbon triple bond. A “C1-5 alkyl” denotes an alkyl group having 1 to 5 carbon atoms. Preferred exemplary alkyl groups are methyl, ethyl, propyl (e.g., n-propyl or isopropyl), or butyl (e.g., n-butyl, isobutyl, sec-butyl, or tert-butyl). Unless defined otherwise, the term “alkyl” preferably refers to C1-4 alkyl, more preferably to methyl or ethyl, and even more preferably to methyl. As used herein, the term “alkenyl” refers to a monovalent unsaturated acyclic hydrocarbon group which may be linear or branched and comprises one or more (e.g., one or two) carbon-to-carbon double bonds while it does not comprise any carbon-to-carbon triple bond. The term “C2-5 alkenyl” denotes an alkenyl group having 2 to 5 carbon atoms. Preferred exemplary alkenyl groups are ethenyl, propenyl (e.g., prop-1-en-1-yl, prop-1-en-2-yl, or prop-2-en-1-yl), butenyl, butadienyl (e.g., buta-1,3-dien-1-yl or buta-1,3- dien-2-yl), pentenyl, or pentadienyl (e.g., isoprenyl). Unless defined otherwise, the term “alkenyl” preferably refers to C2-4 alkenyl. As used herein, the term “alkynyl” refers to a monovalent unsaturated acyclic hydrocarbon group which may be linear or branched and comprises one or more (e.g., one or two) carbon-to-carbon triple bonds and optionally one or more (e.g., one or two) carbon-to-carbon double bonds. The term “C2-5 alkynyl” denotes an alkynyl group having 2 to 5 carbon atoms. Preferred exemplary alkynyl groups are ethynyl, propynyl (e.g., propargyl), or butynyl. Unless defined otherwise, the term “alkynyl” preferably refers to C2-4alkynyl. As used herein, the term “alkylene” refers to an alkanediyl group, i.e. a divalent saturated acyclic hydrocarbon group which may be linear or branched. A “C1-5 alkylene” denotes an alkylene group having 1 to 5 carbon atoms, and the term “C0-3 alkylene” indicates that a covalent bond (corresponding to the option “C0 alkylene”) or a C1-3 alkylene is present. Preferred exemplary alkylene groups are methylene (- CH2-), ethylene (e.g., -CH2-CH2- or -CH(-CH3)-), propylene (e.g., -CH2-CH2-CH2-, -CH(-CH2-CH3)-, -CH2- CH(-CH3)-, or -CH(-CH3)-CH2-), or butylene (e.g., -CH2-CH2-CH2-CH2-). Unless defined otherwise, the term “alkylene” preferably refers to C1-4 alkylene (including, in particular, linear C1-4 alkylene), more preferably to methylene or ethylene, and even more preferably to methylene. As used herein, the term “alkenylene” refers to an alkenediyl group, i.e. a divalent unsaturated acyclic hydrocarbon group which may be linear or branched and comprises one or more (e.g., one or two) carbon-to-carbon double bonds while it does not comprise any carbon-to-carbon triple bond. A “C2- 5 alkenylene” denotes an alkenylene group having 2 to 5 carbon atoms. Unless defined otherwise, the term “alkenylene” preferably refers to C2-4 alkenylene (including, in particular, linear C2-4 alkenylene). As used herein, the term “alkynylene” refers to an alkynediyl group, i.e. a divalent unsaturated acyclic hydrocarbon group which may be linear or branched and comprises one or more (e.g., one or two) carbon-to-carbon triple bonds and optionally one or more (e.g., one or two) carbon-to-carbon double bonds. A “C2-5 alkynylene” denotes an alkynylene group having 2 to 5 carbon atoms. Unless defined otherwise, the term “alkynylene” preferably refers to C2-4 alkynylene (including, in particular, linear C2-4 alkynylene). As used herein, the term “carbocyclyl” refers to a hydrocarbon ring group, including monocyclic rings as well as bridged ring, spiro ring and / or fused ring systems (which may be composed, e.g., of two or three rings), wherein said ring group may be saturated, partially unsaturated (i.e., unsaturated but not aromatic) or aromatic. Unless defined otherwise, “carbocyclyl” preferably refers to aryl, cycloalkyl or cycloalkenyl. As used herein, the term “heterocyclyl” refers to a ring group, including monocyclic rings as well as bridged ring, spiro ring and / or fused ring systems (which may be composed, e.g., of two or three rings), wherein said ring group comprises one or more (such as, e.g., one, two, three, or four) ring heteroatoms independently selected from O, S, N, P and Si, and the remaining ring atoms are carbon atoms, wherein one or more S ring atoms (if present) and / or one or more N ring atoms (if present) and / or one or more P ring atoms (if present) may optionally be oxidized, wherein one or more carbon ring atoms may optionally be oxidized (i.e., to form an oxo group), and further wherein said ring group may be saturated, partially unsaturated (i.e., unsaturated but not aromatic) or aromatic. For example, each heteroatom-containing ring comprised in said ring group may contain one or two O atoms and / or one or two S atoms (which may optionally be oxidized) and / or one, two, three or four N atoms (which may optionally be oxidized), provided that the total number of heteroatoms in the corresponding heteroatom-containing ring is 1 to 4 and that there is at least one carbon ring atom (which may optionally be oxidized) in the corresponding heteroatom- containing ring. Unless defined otherwise, “heterocyclyl” preferably refers to heteroaryl, heterocycloalkyl or heterocycloalkenyl. Preferably, the term “heterocyclyl” refers to a ring group, including monocyclic rings as well as bridged ring, spiro ring and / or fused ring systems (which may be composed, e.g., of two or three rings), wherein said ring group comprises one or more (such as, e.g., one, two, three, or four) ring heteroatoms independently selected from O, S and N, and the remaining ring atoms are carbon atoms, wherein one or more S ring atoms (if present) and / or one or more N ring atoms (if present) may optionally be oxidized, wherein one or more carbon ring atoms may optionally be oxidized (i.e., to form an oxo group), and further wherein said ring group may be saturated, partially unsaturated (i.e., unsaturated but not aromatic) or aromatic. For example, each heteroatom-containing ring comprised in said ring group may contain one or two O atoms and / or one or two S atoms (which may optionally be oxidized) and / or one, two, three or four N atoms (which may optionally be oxidized), provided that the total number of heteroatoms in the corresponding heteroatom-containing ring is 1 to 4 and that there is at least one carbon ring atom (which may optionally be oxidized) in the corresponding heteroatom-containing ring. Unless defined otherwise, “heterocyclyl” preferably refers to heteroaryl, heterocycloalkyl or heterocycloalkenyl. As used herein, the term “aryl” refers to an aromatic hydrocarbon ring group, including monocyclicaromatic rings as well as bridged ring and / or fused ring systems containing at least one aromatic ring (e.g., ring systems composed of two or three fused rings, wherein at least one of these fused rings is aromatic; or bridged ring systems composed of two or three rings, wherein at least one of these bridged rings is aromatic). “Aryl” may, e.g., refer to phenyl, naphthyl, dialinyl (i.e., 1,2-dihydronaphthyl), tetralinyl (i.e., 1,2,3,4-tetrahydronaphthyl), indanyl, indenyl (e.g., 1H-indenyl), anthracenyl, phenanthrenyl, 9H- fluorenyl, or azulenyl. Unless defined otherwise, an “aryl” preferably has 6 to 14 ring atoms, more preferably 6 to 10 ring atoms, even more preferably refers to phenyl or naphthyl, and most preferably refers to phenyl. As used herein, the term “arylene” refers to an aryl group, as defined herein above, but having twopoints of attachment, i.e. a divalent aromatic hydrocarbon ring group, including monocyclic aromatic rings as well as bridged ring and / or fused ring systems containing at least one aromatic ring (e.g., ring systems composed of two or three fused rings, wherein at least one of these fused rings is aromatic; or bridged ring systems composed of two or three rings, wherein at least one of these bridged rings is aromatic). “Arylene” may, e.g., refer to phenylene (e.g., phen-1,2-diyl, phen-1,3-diyl, or phen-1,4-diyl), naphthylene (e.g., naphthalen-1,2-diyl, naphthalen-1,3-diyl, naphthalen-1,4-diyl, naphthalen-1,5-diyl, naphthalen-1,6- diyl, naphthalen-1,7-diyl, naphthalen-2,3-diyl, naphthalen-2,5-diyl, naphthalen-2,6-diyl, naphthalen-2,7- diyl, or naphthalen-2,8-diyl), 1,2-dihydronaphthylene, 1,2,3,4-tetrahydronaphthylene, indanylene, indenylene, anthracenylene, phenanthrenylene, 9H-fluorenylene, or azulenylene. Unless defined otherwise, an “arylene” preferably has 6 to 14 ring atoms, more preferably 6 to 10 ring atoms, even more preferably refers to phenylene or naphthylene, and most preferably refers to phenylene (particularly phen- 1,4-diyl). As used herein, the term “heteroaryl” refers to an aromatic ring group, including monocyclic aromatic rings as well as bridged ring and / or fused ring systems containing at least one aromatic ring (e.g., ring systems composed of two or three fused rings, wherein at least one of these fused rings is aromatic; or bridged ring systems composed of two or three rings, wherein at least one of these bridged rings is aromatic), wherein said aromatic ring group comprises one or more (such as, e.g., one, two, three, or four) ring heteroatoms independently selected from O, S and N, and the remaining ring atoms are carbon atoms, wherein one or more S ring atoms (if present) and / or one or more N ring atoms (if present) may optionally be oxidized, and further wherein one or more carbon ring atoms may optionally be oxidized (i.e., to form an oxo group). For example, each heteroatom-containing ring comprised in said aromatic ring group may contain one or two O atoms and / or one or two S atoms (which may optionally be oxidized) and / or one, two, three or four N atoms (which may optionally be oxidized), provided that the total number of heteroatoms in the corresponding heteroatom-containing ring is 1 to 4 and that there is at least one carbon ring atom (which may optionally be oxidized) in the corresponding heteroatom-containing ring. “Heteroaryl” may, e.g., refer to thienyl (i.e., thiophenyl), benzo[b]thienyl, naphtho[2,3-b]thienyl, thianthrenyl, furyl (i.e., furanyl), benzofuranyl, isobenzofuranyl, chromanyl, chromenyl (e.g., 2H-1- benzopyranyl or 4H-1-benzopyranyl), isochromenyl (e.g., 1H-2-benzopyranyl), chromonyl, xanthenyl, phenoxathiinyl, pyrrolyl (e.g., 1H-pyrrolyl), imidazolyl, pyrazolyl, pyridyl (i.e., pyridinyl; e.g., 2-pyridyl, 3- pyridyl, or 4-pyridyl), pyrazinyl, pyrimidinyl, pyridazinyl, indolyl (e.g., 3H-indolyl), isoindolyl, indazolyl, indolizinyl, purinyl, quinolyl, isoquinolyl, phthalazinyl, naphthyridinyl, quinoxalinyl, cinnolinyl, pteridinyl,carbazolyl, -carbolinyl, phenanthridinyl, acridinyl, perimidinyl, phenanthrolinyl (e.g.,[1,10]phenanthrolinyl, [1,7]phenanthrolinyl, or [4,7]phenanthrolinyl), phenazinyl, thiazolyl, isothiazolyl, phenothiazinyl, oxazolyl, isoxazolyl, oxadiazolyl (e.g., 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl (i.e., furazanyl), or 1,3,4-oxadiazolyl), thiadiazolyl (e.g., 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl, or 1,3,4-thiadiazolyl), phenoxazinyl, pyrazolo[1,5-a]pyrimidinyl (e.g., pyrazolo[1,5-a]pyrimidin-3-yl), 1,2-benzoisoxazol-3-yl, benzothiazolyl, benzothiadiazolyl, benzoxazolyl, benzisoxazolyl, benzimidazolyl, benzo[b]thiophenyl (i.e., benzothienyl), triazolyl (e.g., 1H-1,2,3-triazolyl, 2H-1,2,3-triazolyl, 1H-1,2,4-triazolyl, or 4H-1,2,4-triazolyl), benzotriazolyl, 1H-tetrazolyl, 2H-tetrazolyl, triazinyl (e.g., 1,2,3-triazinyl, 1,2,4-triazinyl, or 1,3,5-triazinyl), furo[2,3-c]pyridinyl, dihydrofuropyridinyl (e.g., 2,3-dihydrofuro[2,3-c]pyridinyl or 1,3-dihydrofuro[3,4- c]pyridinyl), imidazopyridinyl (e.g., imidazo[1,2-a]pyridinyl or imidazo[3,2-a]pyridinyl), quinazolinyl, thienopyridinyl, tetrahydrothienopyridinyl (e.g., 4,5,6,7-tetrahydrothieno[3,2-c]pyridinyl), dibenzofuranyl, 1,3-benzodioxolyl, benzodioxanyl (e.g., 1,3-benzodioxanyl or 1,4-benzodioxanyl), or coumarinyl. Unless defined otherwise, the term “heteroaryl” preferably refers to a 5 to 14 membered (more preferably 5 to 10 membered) monocyclic ring or fused ring system comprising one or more (e.g., one, two, three or four) ring heteroatoms independently selected from O, S and N, wherein one or more S ring atoms (if present) and / or one or more N ring atoms (if present) are optionally oxidized, and wherein one or more carbon ring atoms are optionally oxidized; even more preferably, a “heteroaryl” refers to a 5 or 6 membered monocyclic ring comprising one or more (e.g., one, two or three) ring heteroatoms independently selected from O, S and N, wherein one or more S ring atoms (if present) and / or one or more N ring atoms (if present) are optionally oxidized, and wherein one or more carbon ring atoms are optionally oxidized. As used herein, the term “heteroarylene” refers to a heteroaryl group, as defined herein above, but having two points of attachment, i.e. a divalent aromatic ring group, including monocyclic aromatic rings as well as bridged ring and / or fused ring systems containing at least one aromatic ring (e.g., ring systems composed of two or three fused rings, wherein at least one of these fused rings is aromatic; or bridged ring systems composed of two or three rings, wherein at least one of these bridged rings is aromatic), wherein said aromatic ring group comprises one or more (such as, e.g., one, two, three, or four) ring heteroatoms independently selected from O, S and N, and the remaining ring atoms are carbon atoms, wherein one or more S ring atoms (if present) and / or one or more N ring atoms (if present) may optionally be oxidized, and further wherein one or more carbon ring atoms may optionally be oxidized (i.e., to form an oxo group). For example, each heteroatom-containing ring comprised in said aromatic ring group may contain one or two O atoms and / or one or two S atoms (which may optionally be oxidized) and / or one, two, three, or four N atoms (which may optionally be oxidized), provided that the total number of heteroatoms in the corresponding heteroatom-containing ring is 1 to 4 and that there is at least one carbon ring atom (which may optionally be oxidized) in the corresponding heteroatom-containing ring. “Heteroarylene” may, e.g., refer to thienylene (i.e., thiophenylene; e.g., thien-2,3-diyl, thien-2,4-diyl, or thien-2,5-diyl), benzo[b]thienylene, naphtho[2,3-b]thienylene, thianthrenylene, furylene (i.e., furanylene; e.g., furan-2,3-diyl, furan-2,4-diyl, or furan-2,5-diyl), benzofuranylene, isobenzofuranylene, chromanylene, chromenylene, isochromenylene, chromonylene, xanthenylene, phenoxathiinylene, pyrrolylene, imidazolylene, pyrazolylene, pyridylene (i.e., pyridinylene), pyrazinylene, pyrimidinylene, pyridazinylene, indolylene, isoindolylene, indazolylene, indolizinylene, purinylene, quinolylene, isoquinolylene, phthalazinylene, naphthyridinylene, quinoxalinylene, cinnolinylene, pteridinylene, carbazolylene, -carbolinylene, phenanthridinylene, acridinylene, perimidinylene, phenanthrolinylene, phenazinylene, thiazolylene (e.g., thiazol-2,4-diyl, thiazol-2,5-diyl, or thiazol-4,5-diyl), isothiazolylene (e.g., isothiazol-3,4- diyl, isothiazol-3,5-diyl, or isothiazol-4,5-diyl), phenothiazinylene, oxazolylene (e.g., oxazol-2,4-diyl, oxazol-2,5-diyl, or oxazol-4,5-diyl), isoxazolylene (e.g., isoxazol-3,4-diyl, isoxazol-3,5-diyl, or isoxazol-4,5- diyl), oxadiazolylene (e.g., 1,2,4-oxadiazol-3,5-diyl, 1,2,5-oxadiazol-3,4-diyl, or 1,3,4-oxadiazol-2,5-diyl), thiadiazolylene (e.g., 1,2,4-thiadiazol-3,5-diyl, 1,2,5-thiadiazol-3,4-diyl, or 1,3,4-thiadiazol-2,5-diyl), phenoxazinylene, pyrazolo[1,5-a]pyrimidinylene, 1,2-benzoisoxazolylene, benzothiazolylene, benzothiadiazolylene, benzoxazolylene, benzisoxazolylene, benzimidazolylene, benzo[b]thiophenylene (i.e., benzothienylene), triazolylene (e.g., 1H-1,2,3-triazolylene, 2H-1,2,3-triazolylene, 1H-1,2,4- triazolylene, or 4H-1,2,4-triazolylene), benzotriazolylene, 1H-tetrazolylene, 2H-tetrazolylene, triazinylene (e.g., 1,2,3-triazinylene, 1,2,4-triazinylene, or 1,3,5-triazinylene), furo[2,3-c]pyridinylene, dihydrofuropyridinylene (e.g., 2,3-dihydrofuro[2,3-c]pyridinylene or 1,3-dihydrofuro[3,4-c]pyridinylene), imidazopyridinylene (e.g., imidazo[1,2-a]pyridinylene or imidazo[3,2-a]pyridinylene), quinazolinylene, thienopyridinylene, tetrahydrothienopyridinylene (e.g., 4,5,6,7-tetrahydrothieno[3,2-c]pyridinylene), dibenzofuranylene, 1,3-benzodioxolylene, benzodioxanylene (e.g., 1,3-benzodioxanylene or 1,4-benzodioxanylene), or coumarinylene. Unless defined otherwise, the term “heteroarylene” preferably refers to a divalent 5 to 14 membered (more preferably 5 to 10 membered) monocyclic ring or fused ring system comprising one or more (e.g., one, two, three or four) ring heteroatoms independently selected from O, S and N, wherein one or more S ring atoms (if present) and / or one or more N ring atoms (if present) are optionally oxidized, and wherein one or more carbon ring atoms are optionally oxidized; even more preferably, a “heteroarylene” refers to a divalent 5 or 6 membered monocyclic ring comprising one or more (e.g., one, two or three) ring heteroatoms independently selected from O, S, and N, wherein one or more S ring atoms (if present) and / or one or more N ring atoms (if present) are optionally oxidized, and wherein one or more carbon ring atoms are optionally oxidized. A “heteroarylene”, including any of the specific heteroarylene groups described herein, may be attached through two carbon ring atoms, particularly through those two carbon ring atoms that have the greatest distance from one another (in terms of the number of ring atoms separating them by the shortest possible connection) within one single ring or within the entire ring system of the corresponding heteroarylene. As used herein, the term “cycloalkyl” refers to a saturated hydrocarbon ring group, including monocyclic rings as well as bridged ring, spiro ring and / or fused ring systems (which may be composed, e.g., of two or three rings; such as, e.g., a fused ring system composed of two or three fused rings). “Cycloalkyl” may, e.g., refer to cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, decalinyl (i.e., decahydronaphthyl), or adamantyl. Unless defined otherwise, “cycloalkyl” preferably refers to a C3-11 cycloalkyl, and more preferably refers to a C3-7 cycloalkyl. A particularly preferred “cycloalkyl” is a monocyclic saturated hydrocarbon ring having 3 to 7 ring members (e.g., cyclopropyl or cyclohexyl). As used herein, the term “cycloalkylene” refers to a cycloalkyl group, as defined herein above, buthaving two points of attachment, i.e. a divalent saturated hydrocarbon ring group, including monocyclic rings as well as bridged ring, spiro ring and / or fused ring systems (which may be composed, e.g., of two or three rings; such as, e.g., a fused ring system composed of two or three fused rings). “Cycloalkylene” may, e.g., refer to cyclopropylene (e.g., cyclopropan-1,1-diyl or cyclopropan-1,2-diyl), cyclobutylene (e.g., cyclobutan-1,1-diyl, cyclobutan-1,2-diyl, or cyclobutan-1,3-diyl), cyclopentylene (e.g., cyclopentan-1,1-diyl, cyclopentan-1,2-diyl, or cyclopentan-1,3-diyl), cyclohexylene (e.g., cyclohexan-1,1-diyl, cyclohexan-1,2-diyl, cyclohexan-1,3-diyl, or cyclohexan-1,4-diyl), cycloheptylene, decalinylene (i.e., decahydronaphthylene), or adamantylene. Unless defined otherwise, “cycloalkylene” preferably refers to a C3-11 cycloalkylene, and more preferably refers to a C3-7 cycloalkylene. A particularly preferred “cycloalkylene” is a divalent monocyclic saturated hydrocarbon ring having 3 to 7 ring members (e.g., cyclopropylene or cyclohexylene). As used herein, the term “heterocycloalkyl” refers to a saturated ring group, including monocyclic rings as well as bridged ring, spiro ring and / or fused ring systems (which may be composed, e.g., of two or three rings; such as, e.g., a fused ring system composed of two or three fused rings), wherein said ring group contains one or more (such as, e.g., one, two, three, or four) ring heteroatoms independently selected from O, S, N, P and Si, and the remaining ring atoms are carbon atoms, wherein one or more S ring atoms (if present) and / or one or more N ring atoms (if present) and / or one or more P ring atoms (if present) may optionally be oxidized, further wherein one or more S ring atoms (if present) may be modified with =NH or =N(C1-3 alkyl) and further wherein one or more carbon ring atoms may optionally be oxidized (i.e., to form an oxo group). For example, each heteroatom-containing ring comprised in said saturated ring group may contain one or two O atoms and / or one or two S atoms (which may optionally be oxidized) and / or one, two, three or four N atoms (which may optionally be oxidized), provided that the total number of heteroatoms in the corresponding heteroatom-containing ring is 1 to 4 and that there is at least one carbon ring atom (which may optionally be oxidized) in the corresponding heteroatom-containing ring. “Heterocycloalkyl” may, e.g., refer to aziridinyl, azetidinyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, piperidinyl, piperazinyl, azepanyl, diazepanyl (e.g., 1,4-diazepanyl), oxazolidinyl, isoxazolidinyl, thiazolidinyl, isothiazolidinyl, morpholinyl (e.g., morpholin-4-yl), thiomorpholinyl (e.g., thiomorpholin-4-yl), oxazepanyl, oxiranyl, oxetanyl, tetrahydrofuranyl, 1,3-dioxolanyl, tetrahydropyranyl, 1,4-dioxanyl, oxepanyl, thiiranyl, thietanyl, tetrahydrothiophenyl (i.e., thiolanyl), 1,3-dithiolanyl, thianyl, 1,1-dioxothianyl, thiepanyl, decahydroquinolinyl, decahydroisoquinolinyl, or 2-oxa-5-aza-bicyclo[2.2.1]hept-5-yl. Unless defined otherwise, “heterocycloalkyl” preferably refers to a 3 to 11 membered saturated ring group, which is a monocyclic ring or a fused ring system (e.g., a fused ring system composed of two fused rings), wherein said ring group contains one or more (e.g., one, two, three, or four) ring heteroatoms independently selected from O, S and N, wherein one or more S ring atoms (if present) and / or one or more N ring atoms (if present) are optionally oxidized, and wherein one or more carbon ring atoms are optionally oxidized; more preferably, “heterocycloalkyl” refers to a 5 to 7 membered saturated monocyclic ring group containing one or more (e.g., one, two, or three) ring heteroatoms independently selected from O, S and N, wherein one or more S ring atoms (if present) and / or one or more N ring atoms (if present) are optionally oxidized, and wherein one or more carbon ring atoms are optionally oxidized. Preferably, the term “heterocycloalkyl” refers to a saturated ring group, including monocyclic rings as well as bridged ring, spiro ring and / or fused ring systems (which may be composed, e.g., of two or three rings; such as, e.g., a fused ring system composed of two or three fused rings), wherein said ring group contains one or more (such as, e.g., one, two, three, or four) ring heteroatoms independently selected from O, S and N, and the remaining ring atoms are carbon atoms, wherein one or more S ring atoms (if present) and / or one or more N ring atoms (if present) may optionally be oxidized, and further wherein one or more carbon ring atoms may optionally be oxidized (i.e., to form an oxo group). For example, each heteroatom-containing ring comprised in said saturated ring group may contain one or two O atoms and / or one or two S atoms (which may optionally be oxidized) and / or one, two, three or four N atoms (which may optionally be oxidized), provided that the total number of heteroatoms in the corresponding heteroatom-containing ring is 1 to 4 and that there is at least one carbon ring atom (which may optionally be oxidized) in the corresponding heteroatom-containing ring. “Heterocycloalkyl” may, e.g., refer to aziridinyl, azetidinyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, piperidinyl, piperazinyl, azepanyl, diazepanyl (e.g., 1,4-diazepanyl), oxazolidinyl, isoxazolidinyl, thiazolidinyl, isothiazolidinyl, morpholinyl (e.g., morpholin-4-yl), thiomorpholinyl (e.g., thiomorpholin-4-yl), oxazepanyl, oxiranyl, oxetanyl, tetrahydrofuranyl, 1,3-dioxolanyl, tetrahydropyranyl, 1,4-dioxanyl, oxepanyl, thiiranyl, thietanyl, tetrahydrothiophenyl (i.e., thiolanyl), 1,3-dithiolanyl, thianyl, 1,1-dioxothianyl, thiepanyl, decahydroquinolinyl, decahydroisoquinolinyl, or 2-oxa-5-aza-bicyclo[2.2.1]hept-5-yl. Unless defined otherwise, “heterocycloalkyl” preferably refers to a 3 to 11 membered saturated ring group, which is a monocyclic ring or a fused ring system (e.g., a fused ring system composed of two fused rings), wherein said ring group contains one or more (e.g., one, two, three, or four) ring heteroatoms independently selected from O, S and N, wherein one or more S ring atoms (if present) and / or one or more N ring atoms (if present) are optionally oxidized, and wherein one or more carbon ring atoms are optionally oxidized; more preferably, “heterocycloalkyl” refers to a 5 to 7 membered saturated monocyclic ring group containing one or more (e.g., one, two, or three) ring heteroatoms independently selected from O, S and N, wherein one or more S ring atoms (if present) and / or one or more N ring atoms (if present) are optionally oxidized, and wherein one or more carbon ring atoms are optionally oxidized. As used herein, the term “heterocycloalkylene” refers to a heterocycloalkyl group, as defined hereinabove, but having two points of attachment, i.e. a divalent saturated ring group, including monocyclic rings as well as bridged ring, spiro ring and / or fused ring systems (which may be composed, e.g., of two or three rings; such as, e.g., a fused ring system composed of two or three fused rings), wherein said ring group contains one or more (such as, e.g., one, two, three, or four) ring heteroatoms independently selected from O, S, N, P and Si, and the remaining ring atoms are carbon atoms, wherein one or more S ring atoms (if present) and / or one or more N ring atoms (if present) and / or one or more P ring atoms (if present) may optionally be oxidized, further wherein one or more S ring atoms (if present) may be modified with =NH or =N(C1-3 alkyl) and further wherein one or more carbon ring atoms may optionally be oxidized (i.e., to form an oxo group). For example, each heteroatom-containing ring comprised in said saturated ring group may contain one or two O atoms and / or one or two S atoms (which may optionally be oxidized) and / or one, two, three or four N atoms (which may optionally be oxidized), provided that the total number of heteroatoms in the corresponding heteroatom-containing ring is 1 to 4 and that there is at least one carbon ring atom (which may optionally be oxidized) in the corresponding heteroatom-containing ring. “Heterocycloalkylene” may, e.g., refer to aziridinylene, azetidinylene, pyrrolidinylene, imidazolidinylene, pyrazolidinylene, piperidinylene, piperazinylene, azepanylene, diazepanylene (e.g., 1,4-diazepanylene), oxazolidinylene, isoxazolidinylene, thiazolidinylene, isothiazolidinylene, morpholinylene, thiomorpholinylene, oxazepanylene, oxiranylene, oxetanylene, tetrahydrofuranylene, 1,3-dioxolanylene, tetrahydropyranylene, 1,4-dioxanylene, oxepanylene, thiiranylene, thietanylene, tetrahydrothiophenylene (i.e., thiolanylene), 1,3-dithiolanylene, thianylene, 1,1-dioxothianylene, thiepanylene, decahydroquinolinylene, decahydroisoquinolinylene, or 2-oxa-5-aza-bicyclo[2.2.1]hept-5-ylene. Unless defined otherwise, “heterocycloalkylene” preferably refers to a divalent 3 to 11 membered saturated ring group, which is a monocyclic ring or a fused ring system (e.g., a fused ring system composed of two fused rings), wherein said ring group contains one or more (e.g., one, two, three, or four) ring heteroatoms independently selected from O, S and N, wherein one or more S ring atoms (if present) and / or one or more N ring atoms (if present) are optionally oxidized, and wherein one or more carbon ring atoms are optionally oxidized; more preferably, “heterocycloalkylene” refers to a divalent 5 to 7 membered saturated monocyclic ring group containing one or more (e.g., one, two, or three) ring heteroatoms independently selected from O, S and N, wherein one or more S ring atoms (if present) and / or one or more N ring atoms (if present) are optionally oxidized, and wherein one or more carbon ring atoms are optionally oxidized. Preferably, the term “heterocycloalkylene” refers to a heterocycloalkyl group, as defined hereinabove, but having two points of attachment, i.e. a divalent saturated ring group, including monocyclic rings as well as bridged ring, spiro ring and / or fused ring systems (which may be composed, e.g., of two or three rings; such as, e.g., a fused ring system composed of two or three fused rings), wherein said ring group contains one or more (such as, e.g., one, two, three, or four) ring heteroatoms independently selected from O, S and N, and the remaining ring atoms are carbon atoms, wherein one or more S ring atoms (if present) and / or one or more N ring atoms (if present) may optionally be oxidized, and further wherein one or more carbon ring atoms may optionally be oxidized (i.e., to form an oxo group). For example, each heteroatom-containing ring comprised in said saturated ring group may contain one or two O atoms and / or one or two S atoms (which may optionally be oxidized) and / or one, two, three or four N atoms (which may optionally be oxidized), provided that the total number of heteroatoms in the corresponding heteroatom-containing ring is 1 to 4 and that there is at least one carbon ring atom (which may optionally be oxidized) in the corresponding heteroatom-containing ring. “Heterocycloalkylene” may, e.g., refer to aziridinylene, azetidinylene, pyrrolidinylene, imidazolidinylene, pyrazolidinylene, piperidinylene, piperazinylene, azepanylene, diazepanylene (e.g., 1,4-diazepanylene), oxazolidinylene, isoxazolidinylene, thiazolidinylene, isothiazolidinylene, morpholinylene, thiomorpholinylene, oxazepanylene, oxiranylene, oxetanylene, tetrahydrofuranylene, 1,3-dioxolanylene, tetrahydropyranylene, 1,4-dioxanylene, oxepanylene, thiiranylene, thietanylene, tetrahydrothiophenylene (i.e., thiolanylene), 1,3-dithiolanylene, thianylene, 1,1-dioxothianylene, thiepanylene, decahydroquinolinylene, decahydroisoquinolinylene, or 2-oxa-5-aza-bicyclo[2.2.1]hept-5-ylene. Unless defined otherwise, “heterocycloalkylene” preferably refers to a divalent 3 to 11 membered saturated ring group, which is a monocyclic ring or a fused ring system (e.g., a fused ring system composed of two fused rings), wherein said ring group contains one or more (e.g., one, two, three, or four) ring heteroatoms independently selected from O, S and N, wherein one or more S ring atoms (if present) and / or one or more N ring atoms (if present) are optionally oxidized, and wherein one or more carbon ring atoms are optionally oxidized; more preferably, “heterocycloalkylene” refers to a divalent 5 to 7 membered saturated monocyclic ring group containing one or more (e.g., one, two, or three) ring heteroatoms independently selected from O, S and N, wherein one or more S ring atoms (if present) and / or one or more N ring atoms (if present) are optionally oxidized, and wherein one or more carbon ring atoms are optionally oxidized. As used herein, the term “N-heterocycloalkyl” refers to the heterocycloalkyl groups as defined hereinabove wherein said heterocycloalkyl includes at least one nitrogen atom which serves as an attachment point of said heterocycloalkyl. As used herein, the term “cycloalkenyl” refers to an unsaturated alicyclic (non-aromatic) hydrocarbon ring group, including monocyclic rings as well as bridged ring, spiro ring and / or fused ring systems (which may be composed, e.g., of two or three rings; such as, e.g., a fused ring system composed of two or three fused rings), wherein said hydrocarbon ring group comprises one or more (e.g., one or two) carbon-to-carbon double bonds and does not comprise any carbon-to-carbon triple bond. “Cycloalkenyl” may, e.g., refer to cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, cyclohexadienyl, cycloheptenyl, or cycloheptadienyl. Unless defined otherwise, “cycloalkenyl” preferably refers to a C3-11 cycloalkenyl, and more preferably refers to a C3-7 cycloalkenyl. A particularly preferred “cycloalkenyl” is a monocyclic unsaturated alicyclic hydrocarbon ring having 3 to 7 ring members and containing one or more (e.g., one or two; preferably one) carbon-to-carbon double bonds. As used herein, the term “cycloalkenylene” refers to a cycloalkenyl group, as defined hereinabove, but having two points of attachment, i.e. a divalent unsaturated alicyclic (non-aromatic) hydrocarbon ring group, including monocyclic rings as well as bridged ring, spiro ring and / or fused ring systems (which may be composed, e.g., of two or three rings; such as, e.g., a fused ring system composed of two or three fused rings), wherein said hydrocarbon ring group comprises one or more (e.g., one or two) carbon-to- carbon double bonds and does not comprise any carbon-to-carbon triple bond. As used herein, the term “heterocycloalkenyl” refers to an unsaturated alicyclic (non-aromatic) ring group, including monocyclic rings as well as bridged ring, spiro ring and / or fused ring systems (which may be composed, e.g., of two or three rings; such as, e.g., a fused ring system composed of two or three fused rings), wherein said ring group contains one or more (such as, e.g., one, two, three, or four) ring heteroatoms independently selected from O, S, N, P and Si, and the remaining ring atoms are carbon atoms, wherein one or more S ring atoms (if present) and / or one or more N ring atoms (if present) and / or one or more P ring atoms (if present) may optionally be oxidized, wherein one or more S ring atoms (if present) may be modified with =NH or =N(C1-3 alkyl), wherein one or more carbon ring atoms may optionally be oxidized (i.e., to form an oxo group), and further wherein said ring group comprises at least one double bond between adjacent ring atoms and does not comprise any triple bond between adjacent ring atoms. For example, each heteroatom-containing ring comprised in said unsaturated alicyclic ring group may contain one or two O atoms and / or one or two S atoms (which may optionally be oxidized) and / or one, two, three or four N atoms (which may optionally be oxidized), provided that the total number of heteroatoms in the corresponding heteroatom-containing ring is 1 to 4 and that there is at least one carbon ring atom (which may optionally be oxidized) in the corresponding heteroatom-containing ring. “Heterocycloalkenyl” may, e.g., refer to imidazolinyl (e.g., 2-imidazolinyl (i.e., 4,5-dihydro-1H-imidazolyl), 3-imidazolinyl, or 4-imidazolinyl), tetrahydropyridinyl (e.g., 1,2,3,6-tetrahydropyridinyl), dihydropyridinyl (e.g., 1,2-dihydropyridinyl or 2,3-dihydropyridinyl), pyranyl (e.g., 2H-pyranyl or 4H-pyranyl), thiopyranyl (e.g., 2H-thiopyranyl or 4H-thiopyranyl), dihydropyranyl, dihydrofuranyl, dihydropyrazolyl, dihydropyrazinyl, dihydroisoindolyl, octahydroquinolinyl (e.g., 1,2,3,4,4a,5,6,7-octahydroquinolinyl), or octahydroisoquinolinyl (e.g., 1,2,3,4,5,6,7,8-octahydroisoquinolinyl). Unless defined otherwise, “heterocycloalkenyl” preferably refers to a 3 to 11 membered unsaturated alicyclic ring group, which is a monocyclic ring or a fused ring system (e.g., a fused ring system composed of two fused rings), wherein said ring group contains one or more (e.g., one, two, three, or four) ring heteroatoms independently selected from O, S and N, wherein one or more S ring atoms (if present) and / or one or more N ring atoms (if present) are optionally oxidized, wherein one or more carbon ring atoms are optionally oxidized, and wherein said ring group comprises at least one double bond between adjacent ring atoms and does not comprise any triple bond between adjacent ring atoms; more preferably, “heterocycloalkenyl” refers to a 5 to 7 membered monocyclic unsaturated non-aromatic ring group containing one or more (e.g., one, two, or three) ring heteroatoms independently selected from O, S and N, wherein one or more S ring atoms (if present) and / or one or more N ring atoms (if present) are optionally oxidized, wherein one or more carbon ring atoms are optionally oxidized, and wherein said ring group comprises at least one double bond between adjacent ring atoms and does not comprise any triple bond between adjacent ring atoms. Preferably, the term “heterocycloalkenyl” refers to an unsaturated alicyclic (non-aromatic) ring group, including monocyclic rings as well as bridged ring, spiro ring and / or fused ring systems (which may be composed, e.g., of two or three rings; such as, e.g., a fused ring system composed of two or three fused rings), wherein said ring group contains one or more (such as, e.g., one, two, three, or four) ring heteroatoms independently selected from O, S and N, and the remaining ring atoms are carbon atoms, wherein one or more S ring atoms (if present) and / or one or more N ring atoms (if present) may optionally be oxidized, wherein one or more carbon ring atoms may optionally be oxidized (i.e., to form an oxo group), and further wherein said ring group comprises at least one double bond between adjacent ring atoms and does not comprise any triple bond between adjacent ring atoms. For example, each heteroatom-containing ring comprised in said unsaturated alicyclic ring group may contain one or two O atoms and / or one or two S atoms (which may optionally be oxidized) and / or one, two, three or four N atoms (which may optionally be oxidized), provided that the total number of heteroatoms in the corresponding heteroatom-containing ring is 1 to 4 and that there is at least one carbon ring atom (which may optionally be oxidized) in the corresponding heteroatom-containing ring. “Heterocycloalkenyl” may, e.g., refer to imidazolinyl (e.g., 2-imidazolinyl (i.e., 4,5-dihydro-1H-imidazolyl), 3-imidazolinyl, or 4-imidazolinyl), tetrahydropyridinyl (e.g., 1,2,3,6-tetrahydropyridinyl), dihydropyridinyl (e.g., 1,2- dihydropyridinyl or 2,3-dihydropyridinyl), pyranyl (e.g., 2H-pyranyl or 4H-pyranyl), thiopyranyl (e.g., 2H-thiopyranyl or 4H-thiopyranyl), dihydropyranyl, dihydrofuranyl, dihydropyrazolyl, dihydropyrazinyl, dihydroisoindolyl, octahydroquinolinyl (e.g., 1,2,3,4,4a,5,6,7-octahydroquinolinyl), or octahydroisoquinolinyl (e.g., 1,2,3,4,5,6,7,8-octahydroisoquinolinyl). Unless defined otherwise, “heterocycloalkenyl” preferably refers to a 3 to 11 membered unsaturated alicyclic ring group, which is a monocyclic ring or a fused ring system (e.g., a fused ring system composed of two fused rings), wherein said ring group contains one or more (e.g., one, two, three, or four) ring heteroatoms independently selected from O, S and N, wherein one or more S ring atoms (if present) and / or one or more N ring atoms (if present) are optionally oxidized, wherein one or more carbon ring atoms are optionally oxidized, and wherein said ring group comprises at least one double bond between adjacent ring atoms and does not comprise any triple bond between adjacent ring atoms; more preferably, “heterocycloalkenyl” refers to a 5 to 7 membered monocyclic unsaturated non-aromatic ring group containing one or more (e.g., one, two, or three) ring heteroatoms independently selected from O, S and N, wherein one or more S ring atoms (if present) and / or one or more N ring atoms (if present) are optionally oxidized, wherein one or more carbon ring atoms are optionally oxidized, and wherein said ring group comprises at least one double bond between adjacent ring atoms and does not comprise any triple bond between adjacent ring atoms. As used herein, the term “heterocycloalkenylene” refers to a heterocycloalkenyl group, as defined hereinabove, as defined hereinabove, but having two points of attachment, i.e. a divalent unsaturated alicyclic (non-aromatic) ring group, including monocyclic rings as well as bridged ring, spiro ring and / or fused ring systems (which may be composed, e.g., of two or three rings; such as, e.g., a fused ring system composed of two or three fused rings), wherein said ring group contains one or more (such as, e.g., one, two, three, or four) ring heteroatoms independently selected from O, S, N, P and Si and the remaining ring atoms are carbon atoms, wherein one or more S ring atoms (if present) and / or one or more N ring atoms (if present) and / or one or more P ring atoms (if present) may optionally be oxidized, wherein one or more S ring atoms (if present) may be modified with =NH or =N(C1-3 alkyl), wherein one or more carbon ring atoms may optionally be oxidized (i.e., to form an oxo group), and further wherein said ring group comprises at least one double bond between adjacent ring atoms and does not comprise any triple bond between adjacent ring atoms. For example, each heteroatom-containing ring comprised in said unsaturated alicyclic ring group may contain one or two O atoms and / or one or two S atoms (which may optionally be oxidized) and / or one, two, three or four N atoms (which may optionally be oxidized), provided that the total number of heteroatoms in the corresponding heteroatom-containing ring is 1 to 4 and that there is at least one carbon ring atom (which may optionally be oxidized) in the corresponding heteroatom- containing ring. Preferably, the term “heterocycloalkenylene” refers to a heterocycloalkenyl group, as defined hereinabove, as defined hereinabove, but having two points of attachment, i.e. a divalent unsaturated alicyclic (non-aromatic) ring group, including monocyclic rings as well as bridged ring, spiro ring and / or fused ring systems (which may be composed, e.g., of two or three rings; such as, e.g., a fused ring system composed of two or three fused rings), wherein said ring group contains one or more (such as, e.g., one, two, three, or four) ring heteroatoms independently selected from O, S and N, and the remaining ring atoms are carbon atoms, wherein one or more S ring atoms (if present) and / or one or more N ring atoms (if present) may optionally be oxidized, wherein one or more carbon ring atoms may optionally be oxidized (i.e., to form an oxo group), and further wherein said ring group comprises at least one double bond between adjacent ring atoms and does not comprise any triple bond between adjacent ring atoms. For example, each heteroatom-containing ring comprised in said unsaturated alicyclic ring group may contain one or two O atoms and / or one or two S atoms (which may optionally be oxidized) and / or one, two, three or four N atoms (which may optionally be oxidized), provided that the total number of heteroatoms in the corresponding heteroatom-containing ring is 1 to 4 and that there is at least one carbon ring atom (which may optionally be oxidized) in the corresponding heteroatom-containing ring. As used herein, the term “halogen” refers to fluoro (-F), chloro (-Cl), bromo (-Br), or iodo (-I). As it is to be understood for the skilled person, the terms “halogen” and “halo” may be used interchangeably. As used herein, the term “haloalkyl” refers to an alkyl group substituted with one or more (preferably 1 to 6, more preferably 1 to 3) halogen atoms which are selected independently from fluoro, chloro, bromo and iodo, and are preferably all fluoro atoms. It will be understood that the maximum number of halogen atoms is limited by the number of available attachment sites and, thus, depends on the number of carbon atoms comprised in the alkyl moiety of the haloalkyl group. “Haloalkyl” may, e.g., refer to -CF3, -CHF2, -CH2F, -CF2-CH3, -CH2-CF3, -CH2-CHF2, -CH2-CF2-CH3, -CH2-CF2-CF3, or -CH(CF3)2. A particularly preferred “haloalkyl” group is -CF3. The terms “bond” and “covalent bond” are used herein synonymously, unless explicitly indicated otherwise or contradicted by context. As used herein, the terms “optional”, “optionally” and “may” denote that the indicated feature may be present but can also be absent. Whenever the term “optional”, “optionally” or “may” is used, the present invention specifically relates to both possibilities, i.e., that the corresponding feature is present or, alternatively, that the corresponding feature is absent. For example, the expression “X is optionally substituted with Y” (or “X may be substituted with Y”) means that X is either substituted with Y or is unsubstituted. Likewise, if a component of a composition is indicated to be “optional”, the invention specifically relates to both possibilities, i.e., that the corresponding component is present (contained in the composition) or that the corresponding component is absent from the composition. Various groups are referred to as being “optionally substituted” in this specification. Generally, these groups may carry one or more substituents, such as, e.g., one, two, three or four substituents. It will be understood that the maximum number of substituents is limited by the number of attachment sites available on the substituted moiety. Unless defined otherwise, the “optionally substituted” groups referred to in this specification carry preferably not more than two substituents and may, in particular, carry only one substituent. Moreover, unless defined otherwise, it is preferred that the optional substituents are absent, i.e. that the corresponding groups are unsubstituted. A skilled person will appreciate that the substituent groups comprised in the compounds of the present invention may be attached to the remainder of the respective compound via a number of different positions of the corresponding specific substituent group. Unless defined otherwise, the preferred attachment positions for the various specific substituent groups are as illustrated in the examples. As used herein, unless explicitly indicated otherwise or contradicted by context, the terms “a”, “an” and “the” are used interchangeably with “one or more” and “at least one”. Thus, for example, a composition comprising “a” compound of formula (I) can be interpreted as referring to a composition comprising “one or more” compounds of formula (I). It is to be understood that wherever numerical ranges are provided / disclosed herein, all values and subranges encompassed by the respective numerical range are meant to be encompassed within the scope of the invention. Accordingly, the present invention specifically and individually relates to each value that falls within a numerical range disclosed herein, as well as each subrange encompassed by a numerical range disclosed herein. As used herein, the term “about” preferably refers to ±10% of the indicated numerical value, more preferably to ±5% of the indicated numerical value, and in particular to the exact numerical value indicated. If the term “about” is used in connection with the endpoints of a range, it preferably refers to the range from the lower endpoint -10% of its indicated numerical value to the upper endpoint +10% of its indicated numerical value, more preferably to the range from of the lower endpoint -5% to the upper endpoint +5%, and even more preferably to the range defined by the exact numerical values of the lower endpoint and the upper endpoint. As used herein, the term “comprising” (or “comprise”, “comprises”, “contain”, “contains”, or “containing”), unless explicitly indicated otherwise or contradicted by context, has the meaning of “containing, inter alia”, i.e., “containing, among further optional elements, …”. In addition thereto, this term also includes the narrower meanings of “consisting essentially of” and “consisting of”. For example, the term “A comprising B and C” has the meaning of “A containing, inter alia, B and C”, wherein A may contain further optional elements (e.g., “A containing B, C and D” would also be encompassed), but this term also includes the meaning of “A consisting essentially of B and C” and the meaning of “A consisting of B and C” (i.e., no other components than B and C are comprised in A). As understood herein, two bolded (i.e., drawn with thick lines) bonds from a ring atom to a substituent, or two dashed / dotted bonds from a ring atom to a substituent, without any indication of being directed “above” or “below” the ring, are assumed to be directed to substituents on the same side of the ring. As further understood herein, two such configurations are possible, either with two bonds “above” the ring or with two bonds “below” the ring. Such configuration is referred to as cis configuration, and implies the presence of at least two compounds (e.g. of two enantiomers or, if further chiral center(s) are present, of diastereoisomers). Similarly, one bolded bond and one dashed bond from the ring to a substituent, without any indication of being directed “above” or “below” the ring, are assumed to be directed to substituents on the opposite sides of the ring. Brief description of figures The invention is further illustrated using the following figures, which serve merely illustrative purpose and do not limit the scope of protection in any way. Fig.1 presents crystal structure (ORTEP view) of intermediate 1.10a, based on which absolute stereoconfiguration of diastereoisomer 1 of example 1 (also referred to as compound 1a)has been determined. Detailed description of the invention The invention is described in detail in the following. It is to be understood that the present invention specifically relates to each and every combination of features and embodiments described herein, including any combination of general and / or preferred features / embodiments. In a first embodiment, the present invention relates to a compound of formula (I): or a pharmaceutically acceptable salt thereof. In formula (I), Z is selected from: More preferably, Z is selected from: Even more preferably, Z is selected from: . Again more preferably, Z is selected from: Alternatively, if Z moiety may have the following configuration: Alternatively, if Z moiety . R1, R2 and R3 in Z are as defined in the following. In formula (I), R1 is -H, -CN, C1-2 alkyl, C2 alkenyl, C2 alkynyl, C1-2 haloalkyl, -(C1-2 alkylene)-OH or -(C1-2 alkylene)-O-(C1-2 alkyl). R1 is preferably -CN, methyl, fluoromethyl, difluoromethyl or trifluoromethyl, more preferably R1 is methyl or fluoromethyl, even more preferably R1 is methyl. In an embodiment, wherein R1 is methyl, particularly preferred R1 is CD3. In an alternative embodiment, R1 is fluoromethyl. In again an alternative embodiment, R1 is -CN. R2 is -H, C1-2 alkyl (such as methyl) or -F. Preferably, R2 is -H or F. More preferably, R2 is -H. R3 is selected from -H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, and -CN, wherein said alkyl, said alkenyl, and said alkynyl are each optionally substituted with one or more groups independently selected from RS1. Preferably, R3 is selected from -H, C1-2 alkyl, C2 alkenyl, C2 alkynyl, C1-2 haloalkyl, and -CN, wherein said alkyl, said alkenyl, and said alkynyl are each optionally substituted with one or more groups independently selected from RS1. More preferably, R3 is selected from -H, C1-2 alkyl, and C1-2 haloalkyl wherein said alkyl is optionally substituted with one or more groups independently selected from RS1. Even more preferably, R3 is selected from -H, and C1-2 alkyl, wherein said alkyl is optionally substituted with one or more groups independently selected from RS1. Particularly suitable C1-2 alkyl is methyl. However, C1-2 alkyl may also be ethyl. Accordingly, in one embodiment, R3 is -H. In one embodiment, R3 is methyl. In one embodiment, R3 is hydroxymethyl. It is preferred that in R3 said alkyl, said alkenyl, and said alkynyl are not substituted. Alternatively, R2 and R3 together with the carbon atom to which they are attached form cyclopropyl optionally substituted with one or more groups independently selected from RS2. Preferably, saidcyclopropyl is optionally substituted with one or more -F (fluoro groups).It is however preferred that R2 and R3 do not form, together with the carbon atom to which they are attached, a cyclopropyl ring, and that R2and R3are as defined hereinabove. In a particularly preferred embodiment, R1 is methyl, R2 is H and R3 is methyl. Further a proviso applies that , then at least one of R2 and R3 is not -H. It is particularly preferred that Z is according to formula .In formula (I), X2 is C-YC2-RC2. YC2is selected from a covalent bond, C1-8 alkylene, C2-8 alkenylene, C2-8 alkynylene, cycloalkylene and heterocycloalkylene wherein said alkylene, said alkenylene and said alkynylene are each optionally substituted with one or more groups independently selected from RS1, and further wherein one or more - CH2- units comprised in said alkylene, said alkenylene or said alkynylene are each optionally replaced by a group independently selected from -O-, -NH-, -N(C1-5 alkyl)-, -CO-, -S-, -SO-, and -SO2-, and wherein said cycloalkylene and heterocycloalkylene are each optionally substituted with one or more groups independently selected RS2. RC2 is selected from hydrogen, halogen, -OH, -NH2, -SH, -CN, C1-12 alkyl, C2-12 alkenyl, C2-12 alkynyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, and heteroaryl; wherein said alkyl, alkenyl, and alkynyl in X2 are each optionally substituted with one or more groups independently selected from RS1, and wherein said cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl and heteroaryl in X2 are each optionally substituted with one or more groups independently selected from RS2. Preferably, YC2 is selected from a covalent bond, -(C1-3 alkylene)-, -CO-(C1-3 alkylene)-, (C1-3 alkylene)-CO-, -CONH-(C1-3 alkylene)-, -(C1-3 alkylene)-CONH-, -NHCO-(C1-3 alkylene)-, -(C1-3 alkylene)- NHCO-, -NH-(C1-3 alkylene)-, -(C1-3 alkylene)-NH-, -N(C1-5 alkyl)-, -O-(C1-3 alkylene)-, -(C1-3 alkylene)-O- , -SO2-(C1-3 alkylene)-, -(C1-3 alkylene)-SO2-, -CONH-, -NHCO-, -NH-, -O-, -CO- and -SO2-, wherein said alkylene, said alkenylene and said alkynylene are each optionally substituted with one or more groups independently selected from RS1. C1-3 alkylene is herein preferably a -CH2- group. Preferably, RC2 is selected from hydrogen, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, and heteroaryl wherein said cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl and heteroaryl are each optionally substituted with one or more groups independently selected from RS2. More preferably, RC2 is selected from hydrogen, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl wherein said cycloalkyl, heterocycloalkyl, aryl and heteroaryl are each optionally substituted with one or more groups independently selected from RS2. Even more preferably, RC2is selected from cycloalkyl, heterocycloalkyl, aryl, and heteroaryl, wherein said cycloalkyl, heterocycloalkyl, aryl and heteroaryl in X2 are each optionally substituted with one or more groups independently selected from RS2. Even more preferably, RC2 is selected from heterocycloalkyl, aryl, and heteroaryl, wherein said heterocycloalkyl, aryl and heteroaryl in X2 are each optionally substituted with one or more groups independently selected from RS2. Even more preferably, RC2 is heterocycloalkyl, wherein said heterocycloalkyl, in X2 is optionally substituted with one or more groups independently selected from RS2. Thus preferably, -YC2-RC2 is is selected from -O-C1-12 alkyl, -NH-C1-12 alkyl, -N(C1-5 alkyl)-C1-12 alkyl, -O-C2-12 alkenyl, -NH-C2-12 alkenyl, -N(C1-5 alkyl)-C2-12 alkenyl, -O-C2-12 alkynyl, -NH-C2-12 alkynyl, - N(C1-5alkyl)-C2-12alkynyl, -(C0-3alkylene)-cycloalkyl, -CO-(C0-3alkylene)-cycloalkyl, -(C0-3alkylene)-CO- cycloalkyl, -CONH-(C0-3 alkylene)-cycloalkyl, (C0-3 alkylene)-CONH-cycloalkyl, -NHCO-(C0-3 alkylene)- cycloalkyl, -(C0-3 alkylene)-NHCO-cycloalkyl, -NH-(C0-3 alkylene)-cycloalkyl, -(C0-3 alkylene)-NH- cycloalkyl, -O-(C0-3 alkylene)-cycloalkyl, -(C0-3 alkylene)-O-cycloalkyl, -SO2-(C0-3 alkylene)-cycloalkyl, -(C0- 3 alkylene)-SO2-cycloalkyl, -CONH-cycloalkyl, -NHCO-cycloalkyl, -NH-cycloalkyl, -O-cycloalkyl, -CO- cycloalkyl, -SO2-cycloalkyl, -(C0-3 alkylene)-cycloalkenyl, -CO-(C0-3 alkylene)-cycloalkenyl, -(C0-3 alkylene)-CO-cycloalkenyl, -CONH-(C0-3 alkylene)-cycloalkenyl, (C0-3 alkylene)-CONH-cycloalkenyl, - NHCO-(C0-3 alkylene)-cycloalkenyl, -(C0-3 alkylene)-NHCO-cycloalkenyl, -NH-(C0-3 alkylene)-cycloalkenyl, -(C0-3 alkylene)-NH-cycloalkenyl, -O-(C0-3 alkylene)-cycloalkenyl, -(C0-3 alkylene)-O-cycloalkenyl, -SO2- (C0-3 alkylene)-cycloalkenyl, -(C0-3 alkylene)-SO2-cycloalkenyl, -CONH-cycloalkenyl, -NHCO-cycloalkenyl, -NH-cycloalkenyl, -O-cycloalkenyl, -CO-cycloalkenyl, -SO2-cycloalkenyl, -(C0-3 alkylene)-heterocycloalkyl, -CO-(C0-3 alkylene)-heterocycloalkyl, -(C0-3 alkylene)-CO-heterocycloalkyl, -CONH-(C0-3 alkylene)- heterocycloalkyl, -(C0-3 alkylene)-CONH-heterocycloalkyl, -NHCO-(C0-3 alkylene)-heterocycloalkyl, -(C0-3 alkylene)-NHCO-heterocycloalkyl, -NH-(C0-3 alkylene)-heterocycloalkyl, -(C0-3 alkylene)-NH- heterocycloalkyl, -O-(C0-3 alkylene)-heterocycloalkyl, -(C0-3 alkylene)-O-heterocycloalkyl, -SO2-(C0-3 alkylene)-heterocycloalkyl, -(C0-3 alkylene)-SO2-heterocycloalkyl, -CONH-heterocycloalkyl, -NHCO- heterocycloalkyl, -NH-heterocycloalkyl, -O-heterocycloalkyl, -CO-heterocycloalkyl, -SO2-heterocycloalkyl, -(C0-3 alkylene)-heterocycloalkenyl, -CO-(C0-3 alkylene)-heterocycloalkenyl, -(C0-3 alkylene)-CO- heterocycloalkenyl, -CONH-(C0-3 alkylene)-heterocycloalkenyl, -(C0-3 alkylene)-CONH- heterocycloalkenyl, -NHCO-(C0-3 alkylene)-heterocycloalkenyl, -(C0-3 alkylene)-NHCO- heterocycloalkenyl, -NH-(C0-3 alkylene)-heterocycloalkenyl, -(C0-3 alkylene)-NH-heterocycloalkenyl, -O- (C0-3 alkylene)-heterocycloalkenyl, -(C0-3 alkylene)-O-heterocycloalkyl, -SO2-(C0-3 alkylene)- heterocycloalkyl, -(C0-3 alkylene)-SO2-heterocycloalkyl, -CONH-heterocycloalkyl, -NHCO- heterocycloalkyl, -NH-heterocycloalkyl, -O-heterocycloalkyl, -CO-heterocycloalkyl, -SO2-heterocycloalkyl, -(C0-3 alkylene)-aryl, -CO-(C0-3 alkylene)-aryl, -(C0-3 alkylene)-CO-aryl, -CONH-(C0-3 alkylene)-aryl, -(C0-3 alkylene)-CONH-aryl, -NHCO-(C0-3alkylene)-aryl, -(C0-3alkylene)-NHCO-aryl, -NH-(C0-3alkylene)-aryl, - (C0-3 alkylene)-NH-aryl, -O-(C0-3 alkylene)-aryl, -(C0-3 alkylene)-O-aryl, -SO2-(C0-3 alkylene)-aryl, -(C0-3 alkylene)-SO2-aryl, -CONH-aryl, -NHCO-aryl, -NH-aryl, -O-aryl, -CO-aryl, -SO2-aryl, -(C0-3 alkylene)- heteroaryl, -CO-(C0-3 alkylene)-heteroaryl, -(C0-3 alkylene)-CO-heteroaryl, -CONH-(C0-3 alkylene)- heteroaryl, -(C0-3 alkylene)-CONH-heteroaryl, -NHCO-(C0-3 alkylene)-heteroaryl, -(C0-3 alkylene)-NHCO- heteroaryl, -NH-(C0-3 alkylene)-heteroaryl, -(C0-3 alkylene)-NH-heteroaryl, -O-(C0-3 alkylene)-heteroaryl, - (C0-3 alkylene)-O-heteroaryl, -SO2-(C0-3 alkylene)-heteroaryl, -(C0-3 alkylene)-SO2-heteroaryl, -CONH- heteroaryl, -NHCO-heteroaryl, -NH-heteroaryl, -O-heteroaryl, -CO-heteroaryl and -SO2-heteroaryl, wherein said alkylene is optionally substituted with one or more groups independently selected from RS1, and wherein said cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl and heteroaryl are each optionally substituted with one or more groups independently selected from RS2. More preferably, -YC2-RC2 is selected from -(C0-3 alkylene)-heterocycloalkyl, -CO-(C0-3 alkylene)heterocycloalkyl, -(C0-3 alkylene)-CO-heterocycloalkyl, -CONH-(C0-3 alkylene)heterocycloalkyl, - (C0-3 alkylene)-CONH-heterocycloalkyl, -NHCO-(C0-3 alkylene)heterocycloalkyl, -(C0-3 alkylene)-NHCO- heterocycloalkyl, -NH-(C0-3 alkylene)heterocycloalkyl, -(C0-3 alkylene)-NH-heterocycloalkyl, -O-(C0-3 alkylene) heterocycloalkyl, (C0-3 alkylene)-O-heterocycloalkyl, -SO2-(C0-3 alkylene)heterocycloalkyl, -(C0-3 alkylene)-SO2-heterocycloalkyl, -CONH-heterocycloalkyl, -NHCO-heterocycloalkyl, -NH-heterocycloalkyl, -O-heterocycloalkyl, -CO-heterocycloalkyl, -SO2-heterocycloalkyl, -(C0-3 alkylene)-heterocycloalkenyl, - CO-(C0-3 alkylene)heterocycloalkenyl, -(C0-3 alkylene)-CO-heterocycloalkenyl, -CONH-(C0-3alkylene)heterocycloalkenyl, -(C0-3 alkylene)-CONH-heterocycloalkenyl, -NHCO-(C0-3alkylene)heterocycloalkenyl, -(C0-3 alkylene)-NHCO-heterocycloalkenyl, -NH-(C0-3alkylene)heterocycloalkenyl, -(C0-3 alkylene)-NH-heterocycloalkenyl, -O-(C0-3 alkylene) heterocycloalkenyl, (C0-3 alkylene)-O-heterocycloalkenyl, -SO2-(C0-3 alkylene)heterocycloalkenyl, -(C0-3 alkylene)-SO2-heterocycloalkenyl, -CONH-heterocycloalkenyl, -NHCO-heterocycloalkenyl, -NH- heterocycloalkenyl, -O-heterocycloalkenyl, -CO-heterocycloalkenyl, -SO2-heterocycloalkenyl, -(C0-3 alkylene)aryl, -CO-(C0-3 alkylene)aryl, -(C0-3 alkylene)-CO-aryl, -CONH-(C0-3 alkylene)aryl, -(C0-3 alkylene)-CONH-aryl, -NHCO-(C0-3 alkylene)aryl, -(C0-3 alkylene)-NHCO-aryl, -NH-(C0-3 alkylene)aryl, - (C0-3 alkylene)-NH-aryl, -O-(C0-3 alkylene)aryl, -(C0-3 alkylene)-O-aryl, -SO2-(C0-3 alkylene)aryl, -(C0-3 alkylene)-SO2-aryl, -CONH-aryl, -NHCO-aryl, -NH-aryl, -O-aryl, -CO-aryl, -SO2-aryl, -(C0-3 alkylene)heteroaryl, -CO-(C0-3 alkylene)heteroaryl, -(C0-3 alkylene)-CO-heteroaryl, -CONH-(C0-3 alkylene)heteroaryl, -(C0-3 alkylene)-CONH-heteroaryl, -NHCO-(C0-3 alkylene)heteroaryl, -(C0-3 alkylene)- NHCO-heteroaryl, -NH-(C0-3 alkylene)heteroaryl, -(C0-3 alkylene)-NH-heteroaryl, -O-(C0-3 alkylene)heteroaryl, -(C0-3 alkylene)-O-heteroaryl, -SO2-(C0-3 alkylene)heteroaryl, -(C0-3 alkylene)-SO2- heteroaryl, -CONH-heteroaryl, -NHCO-heteroaryl, -NH-heteroaryl, -O-heteroaryl, -CO-heteroaryl and -SO2-heteroaryl, wherein said alkylene is optionally substituted with one or more groups independently selected from RS1, and wherein said heterocycloalkyl, heterocycloalkenyl, aryl and heteroaryl are each optionally substituted with one or more groups independently selected from RS2. Even more preferably, -YC2-RC2 is selected from -(C0-3 alkylene)-heterocycloalkyl, -CONH- heterocycloalkyl, -NHCO-heterocycloalkyl, -NH-heterocycloalkyl, -O-heterocycloalkyl, -CO- heterocycloalkyl, -SO2-heterocycloalkyl, -(C0-3 alkylene)-heterocycloalkenyl, -CONH-heterocycloalkenyl, -NHCO-heterocycloalkenyl, -NH-heterocycloalkenyl, -O-heterocycloalkenyl, -CO-heterocycloalkenyl, -SO2-heterocycloalkenyl, -(C0-3 alkylene)aryl, -CONH-aryl, -NHCO-aryl, -NH-aryl, -O- aryl, -CO-aryl, -SO2-aryl, -(C0-3 alkylene)heteroaryl, -CONH-heteroaryl, -NHCO-heteroaryl, -NH- heteroaryl, -O-heteroaryl, -CO-heteroaryl and -SO2-heteroaryl, (preferably -(C0-3 alkylene)- heterocycloalkyl, -CONH-heterocycloalkyl, -NHCO-heterocycloalkyl, -NH-heterocycloalkyl, -O- heterocycloalkyl, -CO-heterocycloalkyl, -SO2-heterocycloalkyl, -(C0-3 alkylene)-heterocycloalkenyl, - CONH-heterocycloalkenyl, -NHCO-heterocycloalkenyl, -NH-heterocycloalkenyl, -O-heterocycloalkenyl, - CO-heterocycloalkenyl, and -SO2-heterocycloalkenyl), wherein said alkylene is optionally substituted with one or more groups independently selected from RS1, and wherein said heterocycloalkyl, heterocycloalkenyl, aryl and heteroaryl are each optionally substituted with one or more groups independently selected from RS2. Even more preferably, -YC2-RC2 is selected from -(C0-3 alkylene)heterocycloalkyl, -(C0-3 alkylene)heterocycloalkenyl, -(C0-3 alkylene)aryl, and -(C0-3 alkylene)heteroaryl, wherein said heterocycloalkyl, heterocycloalkenyl, aryl and heteroaryl are each optionally substituted with one or more groups independently selected from RS2.. Even more preferably, -YC2-RC2 is selected from heterocycloalkyl, and heterocycloalkenyl, wherein said heterocycloalkyl, and said heterocycloalkenyl are each optionally substituted with one or more groups independently selected from RS2. In an embodiment of the compound of formula (I) wherein -YC2-RC2 is selected from heterocycloalkyl, and heterocycloalkenyl, wherein said heterocycloalkyl, and said heterocycloalkenyl are each optionally substituted with one or more groups independently selected from RS2, -YC2-RC2 is preferably is selected fromH, andH, more preferably isH.Even more preferably, -YC2-RC2 is heterocycloalkyl wherein said heterocycloalkyl is optionally substituted with one or more groups independently selected from RS2. Particularly preferred heterocycloalkyl moieties are described hereinabove. In formula (I), R4 is YR5-RR5. YR5 is selected from a covalent bond, C1-4 alkylene, C2-4 alkenylene, and C2-4 alkynylene, wherein said alkylene, said alkenylene and said alkynylene are each optionally substituted with one or more groups independently selected from RS1and further wherein one or more -CH2- units comprised in said alkylene, said alkenylene or said alkynylene are each optionally replaced by a group independently selected from - O-, -NH-, -N(C1-5 alkyl)-, -CO-, -COO-, -S-, -SO-, and -SO2-, preferably selected from -O-, -NH-, -N(C1-5 alkyl)-, -CO-, -S-, -SO-, and -SO2-. Preferably, YR5 is selected from a covalent bond, C1-2 alkylene, -CO- (C1-2 alkylene)-, -(C1-2 alkylene)-CO-, -CONH-(C1-2 alkylene)-, -(C1-2 alkylene)-CONH-, -NHCO-(C1-2 alkylene)-, -(C1-2 alkylene)-NHCO-, -NH-(C1-2 alkylene)-, -(C1-2 alkylene)-NH-, -O-(C1-2 alkylene)-, -(C1-2 alkylene)-O-, -SO2-(C1-2 alkylene)-, -(C1-2 alkylene)-SO2-, -CONH-, -CON(C1-5 alkyl)-, -NHCO-, -N(C1-5 alkyl)CO-, -NH-, -O-, -CO-, -COO- and -SO2-. C1-2alkylene is herein preferably a -CH2- group. RR5 is selected from C1-12 alkyl, C2-12 alkenyl, C2-12 alkynyl, cycloalkyl, cycloalkenyl heterocycloalkyl, heterocycloalkenyl, aryl, and heteroaryl. Preferably RR5 is selected from cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, and heteroaryl. More preferably, RR5 is selected from cycloalkyl, heterocycloalkyl, aryl, and heteroaryl. Even more preferably, RR5 is selected from heterocycloalkyl, aryl, and heteroaryl. Even more preferably, RR5 is selected from aryl and heteroaryl. Most preferably, RR5 is heteroaryl. Said alkyl, alkenyl, or alkynyl is optionally substituted with one or more groups independently selected from RS1. Said cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl or heteroaryl is optionally substituted with one or more groups independently selected from RS2. Preferably, YR5is selected from a covalent bond, C1-2alkylene, -CO-(C1-2alkylene)-, -(C1-2alkylene)-CO-, -CONH-(C1-2 alkylene)-, -(C1-2 alkylene)-CONH-, -NHCO-(C1-2 alkylene)-, -(C1-2 alkylene)- NHCO-, -NH-(C1-2 alkylene)-, -(C1-2 alkylene)-NH-, -O-(C1-2 alkylene)-, -(C1-2 alkylene)-O-, -SO2-(C1-2 alkylene), -(C1-2 alkylene)-SO2-, -CONH-, -NHCO-, -NH-, -O-, -CO- and -SO2-, wherein said alkylene is optionally substituted with one or more groups independently selected from RS1. Thus, preferably, R4 is selected from -(C0-2 alkylene)-cycloalkyl, -CO-(C0-2 alkylene)-cycloalkyl, - (C0-2 alkylene)-CO-cycloalkyl, -CONH-(C0-2 alkylene)-cycloalkyl, -(C0-2 alkylene)-CONH-cycloalkyl, - NHCO-(C0-2 alkylene)-cycloalkyl, -(C0-2 alkylene)-NHCO-cycloalkyl, -NH-(C0-2 alkylene)-cycloalkyl, -(C0-2 alkylene)-NH-cycloalkyl, -O-(C0-2 alkylene)-cycloalkyl, -(C0-2 alkylene)-O-cycloalkyl, -SO2-(C0-2 alkylene)- cycloalkyl, -(C0-2 alkylene)-SO2-cycloalkyl, -CONH-cycloalkyl, -NHCO-cycloalkyl, -NH-cycloalkyl, -O- cycloalkyl, -CO-cycloalkyl, -SO2-cycloalkyl, -(C0-2 alkylene)-cycloalkenyl, -CO-(C0-2 alkylene)-cycloalkenyl, -(C0-2 alkylene)-CO-cycloalkenyl, -CONH-(C0-2 alkylene)-cycloalkenyl, -(C0-2 alkylene)-CONH- cycloalkenyl, -NHCO-(C0-2 alkylene)-cycloalkenyl, -(C0-2 alkylene)-NHCO-cycloalkenyl, -NH-(C0-2 alkylene)-cycloalkenyl, -(C0-2 alkylene)-NH-cycloalkenyl, -O-(C0-2 alkylene)-cycloalkenyl, -(C0-2 alkylene)- O-cycloalkenyl, -SO2-(C0-2 alkylene)-cycloalkenyl, -(C0-2 alkylene)-SO2-cycloalkenyl, -CONH-cycloalkenyl, -NHCO-cycloalkenyl, -NH-cycloalkenyl, -O-cycloalkenyl, -CO-cycloalkenyl, -SO2-cycloalkenyl,-(C0-2 alkylene)-heterocycloalkyl, -CO-(C0-2 alkylene)-heterocycloalkyl, -(C0-2 alkylene)-CO-heterocycloalkyl, - CONH-(C0-2 alkylene)-heterocycloalkyl, -(C0-2 alkylene)-CONH-heterocycloalkyl, -NHCO-(C0-2 alkylene)- heterocycloalkyl, -(C0-2 alkylene)-NHCO-heterocycloalkyl, -NH-(C0-2 alkylene)-heterocycloalkyl, -(C0-2 alkylene)-NH-heterocycloalkyl, -O-(C0-2 alkylene)-heterocycloalkyl, -(C0-2 alkylene)-O- heterocycloalkyl, -SO2-(C0-2 alkylene)-heterocycloalkyl, -(C0-2 alkylene)-SO2-heterocycloalkyl, -CONH- heterocycloalkyl, -NHCO-heterocycloalkyl, -NH-heterocycloalkyl, -O-heterocycloalkyl, -CO- heterocycloalkyl, -SO2-heterocycloalkyl,-(C0-2 alkylene)-heterocycloalkenyl, -CO-(C0-2 alkylene)- heterocycloalkenyl, -(C0-2 alkylene)-CO-heterocycloalkenyl, -CONH-(C0-2 alkylene)-heterocycloalkenyl, - (C0-2 alkylene)-CONH-heterocycloalkenyl, -NHCO-(C0-2 alkylene)-heterocycloalkenyl, -(C0-2 alkylene)- NHCO-heterocycloalkenyl, -NH-(C0-2 alkylene)-heterocycloalkenyl, -(C0-2 alkylene)-NH- heterocycloalkenyl, -O-(C0-2 alkylene)-heterocycloalkenyl, -(C0-2 alkylene)-O-heterocycloalkenyl, -SO2- (C0-2 alkylene)-heterocycloalkenyl, -(C0-2 alkylene)-SO2-heterocycloalkenyl, -CONH-heterocycloalkenyl, -NHCO-heterocycloalkenyl, -NH-heterocycloalkenyl, -O-heterocycloalkenyl, -CO-heterocycloalkenyl, -SO2-heterocycloalkenyl, -(C0-2alkylene)-aryl, -CO-(C0-2alkylene)-aryl, -(C0-2alkylene)-CO-aryl, -CONH-(C0-2 alkylene)-aryl, -(C0-2 alkylene)-CONH-aryl, -NHCO-(C0-2 alkylene)-aryl, - (C0-2 alkylene)-NHCO-aryl, -NH-(C0-2 alkylene)-aryl, -(C0-2 alkylene)-NH-aryl, -O-(C0-2 alkylene)-aryl, -(C0- 2 alkylene)-O-aryl, -SO2-(C0-2 alkylene)-aryl, -(C0-2 alkylene)-SO2-aryl, -CONH-aryl, -NHCO-aryl, -NH-aryl, -O-aryl, -CO-aryl, -SO2-aryl, -(C0-2 alkylene)-heteroaryl, -CO-(C0-2 alkylene)-heteroaryl, -(C0-2 alkylene)- CO-heteroaryl, -CONH-(C0-2 alkylene)-heteroaryl, -(C0-2 alkylene)-CONH-heteroaryl, -NHCO-(C0-2 alkylene)-heteroaryl, -(C0-2 alkylene)-NHCO-heteroaryl, -NH-(C0-2 alkylene)-heteroaryl, -(C0-2 alkylene)- NH-heteroaryl, -O-(C0-2 alkylene)-heteroaryl, -(C0-2 alkylene)-O-heteroaryl, -SO2-(C0-2 alkylene)- heteroaryl, -(C0-2 alkylene)-SO2-heteroaryl, -CONH-heteroaryl, -NHCO-heteroaryl, -NH-heteroaryl, -O- heteroaryl, -CO-heteroaryl, and -SO2-heteroaryl. Said alkylene is optionally substituted with one or more groups independently selected from RS1. Said cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl or heteroaryl is optionally substituted with one or more groups independently selected from RS2. More preferably, R4 is selected from -(C0-2 alkylene)-cycloalkyl, -CO-(C0-2 alkylene)-cycloalkyl, - (C0-2 alkylene)-CO-cycloalkyl, -CONH-(C0-2 alkylene)-cycloalkyl, -(C0-2 alkylene)-CONH-cycloalkyl, - NHCO-(C0-2 alkylene)-cycloalkyl, -(C0-2 alkylene)-NHCO-cycloalkyl, -NH-(C0-2 alkylene)-cycloalkyl, -(C0-2 alkylene)-NH-cycloalkyl, -O-(C0-2 alkylene)-cycloalkyl, -(C0-2 alkylene)-O-cycloalkyl, -SO2-(C0-2 alkylene)- cycloalkyl, -(C0-2 alkylene)-SO2-cycloalkyl, -CONH-cycloalkyl, -NHCO-cycloalkyl, -NH-cycloalkyl, -O- cycloalkyl, -CO-cycloalkyl, -SO2-cycloalkyl, -(C0-2 alkylene)-heterocycloalkyl, -CO-(C0-2 alkylene)- heterocycloalkyl, -(C0-2 alkylene)-CO-heterocycloalkyl, -CONH-(C0-2 alkylene)-heterocycloalkyl, -(C0-2 alkylene)-CONH-heterocycloalkyl, -NHCO-(C0-2 alkylene)-heterocycloalkyl, -(C0-2 alkylene)-NHCO- heterocycloalkyl, -NH-(C0-2 alkylene)-heterocycloalkyl, -(C0-2 alkylene)-NH-heterocycloalkyl, -O-(C0-2 alkylene)-heterocycloalkyl, -(C0-2 alkylene)-O-heterocycloalkyl, -SO2-(C0-2 alkylene)-heterocycloalkyl, - (C0-2 alkylene)-SO2-heterocycloalkyl, -CONH-heterocycloalkyl, -NHCO-heterocycloalkyl, -NH- heterocycloalkyl, -O-heterocycloalkyl, -CO-heterocycloalkyl, -SO2-heterocycloalkyl, -(C0-2 alkylene)-aryl, - CO-(C0-2 alkylene)-aryl, -(C0-2 alkylene)-CO-aryl, -CONH-(C0-2 alkylene)-aryl, -(C0-2 alkylene)-CONH-aryl, -NHCO-(C0-2 alkylene)-aryl, -(C0-2 alkylene)-NHCO-aryl, -NH-(C0-2 alkylene)-aryl, -(C0-2 alkylene)-NH-aryl, -O-(C0-2 alkylene)-aryl, -(C0-2 alkylene)-O-aryl, -SO2-(C0-2 alkylene)-aryl, -(C0-2 alkylene)-SO2-aryl, -CONH- aryl, -NHCO-aryl, -NH-aryl, -O-aryl, -CO-aryl, -SO2-aryl, -(C0-2 alkylene)-heteroaryl, -CO-(C0-2 alkylene)- heteroaryl, -(C0-2 alkylene)-CO-heteroaryl, -CONH-(C0-2 alkylene)-heteroaryl, -(C0-2 alkylene)-CONH- heteroaryl, -NHCO-(C0-2 alkylene)-heteroaryl, -(C0-2 alkylene)-NHCO-heteroaryl, -NH-(C0-2 alkylene)- heteroaryl, -(C0-2 alkylene)-NH-heteroaryl, -O-(C0-2 alkylene)-heteroaryl, -(C0-2 alkylene)-O- heteroaryl, -SO2-(C0-2 alkylene)-heteroaryl, -(C0-2 alkylene)-SO2-heteroaryl, -CONH-heteroaryl, -NHCO- heteroaryl, -NH-heteroaryl, -O-heteroaryl, -CO-heteroaryl, and -SO2-heteroaryl. Said alkylene is optionally substituted with one or more groups independently selected from RS1. Said cycloalkyl, heterocycloalkyl, aryl or heteroaryl is optionally substituted with one or more groups independently selected from RS2. Even more preferably, R4 is selected from -(C0-2 alkylene)-aryl, -CO-(C0-2 alkylene)-aryl, -(C0-2 alkylene)-CO-aryl, -CONH-(C0-2 alkylene)-aryl, -(C0-2 alkylene)-CONH-aryl, -NHCO-(C0-2 alkylene)-aryl, - (C0-2 alkylene)-NHCO-aryl, -NH-(C0-2 alkylene)-aryl, -(C0-2 alkylene)-NH-aryl, -O-(C0-2 alkylene)-aryl, -(C0- 2 alkylene)-O-aryl, -SO2-(C0-2 alkylene)-aryl, -(C0-2 alkylene)-SO2-aryl, -CONH-aryl, -NHCO-aryl, -NH-aryl, -O-aryl, -CO-aryl, -SO2-aryl, -(C0-2 alkylene)-heteroaryl, -CO-(C0-2 alkylene)-heteroaryl, -(C0-2 alkylene)- CO-heteroaryl, -CONH-(C0-2 alkylene)-heteroaryl, -(C0-2 alkylene)-CONH-heteroaryl, -NHCO-(C0-2 alkylene)-heteroaryl, -(C0-2 alkylene)-NHCO-heteroaryl, -NH-(C0-2 alkylene)-heteroaryl, -(C0-2 alkylene)- NH-heteroaryl, -O-(C0-2alkylene)-heteroaryl, -(C0-2alkylene)-O-heteroaryl, -SO2-(C0-2alkylene)- heteroaryl, -(C0-2 alkylene)-SO2-heteroaryl, -CONH-heteroaryl, -NHCO-heteroaryl, -NH-heteroaryl, -O- heteroaryl, -CO-heteroaryl, and -SO2-heteroaryl, wherein said alkylene is optionally substituted with one or more groups independently selected from RS1, and wherein said aryl or heteroaryl is optionally substituted with one or more groups independently selected from RS2. More preferably, YR5 is a covalent bond. Thus accordingly, R4 is preferably selected from C1-12 alkyl, C2-12 alkenyl, C2-12 alkynyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, and heteroaryl. More preferably, R4 is preferably selected from cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, and heteroaryl. Even more preferably, R4 is selected from cycloalkyl, heterocycloalkyl, aryl, and heteroaryl. Even more preferably, R4 is selected from aryl, and heteroaryl. Most preferably, R4 is heteroaryl. Said alkyl, alkenyl, or alkynyl is optionally substituted with one or more groups independently selected from RS1. Said cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl or heteroaryl is optionally substituted with one or more groups independently selected from RS2. Preferably, R4 is a five membered heteroaryl, optionally substituted with one or more groups independently selected from RS2. More preferably, R4 is a five membered heteroaryl, optionally substituted with one or more groups independently selected from halogen, -CN, -OH, C1-5 alkyl, C1-5 haloalkyl, -O(C1- 5 alkyl), -O(C1-5 haloalkyl), -SH, -S(C1-5 alkyl), -S(C1-5 haloalkyl), -SO(C1-5 alkyl), -SO(C1-5 haloalkyl), -SO2(C1-5 alkyl), -SO2(C1-5 haloalkyl), -NH2, -NH(C1-5 alkyl), -NH(C1-5 haloalkyl), -N(C1-5 alkyl)(C1-5 alkyl), -N(C1-5 haloalkyl)(C1-5 alkyl), -CONH2, -CONH(C1-5 alkyl), and -CON(C1-5 alkyl)(C1-5 alkyl). The said five membered heteroaryl is preferably selected from imidazolyl, isoxazolyl, pyrazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, thiazolyl, 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,4-thiadiazolyl, or 1,3,4- thiadiazolyl. More preferably, said five membered heteroaryl is 1,3,4-thiadiazolyl, optionally substituted with one or more groups independently selected from halogen, -CN, -OH, C1-5 alkyl, C1-5 haloalkyl, -O(C1- 5 alkyl), -SH, -S(C1-5 alkyl), -NH2, -NH(C1-5 alkyl), -N(C1-5 alkyl)(C1-5 alkyl), -CONH2, -CONH(C1-5 alkyl), and -CON(C1-5alkyl)(C1-5alkyl), preferably optionally substituted with C1-5alkyl, C1-5haloalkyl, -O(C1-5alkyl), -SH, -S(C1-5 alkyl), more preferably optionally substituted with C1-5 alkyl, C1-5 haloalkyl, even more preferably optionally substituted with C1-5 haloalkyl, preferably selected from -CH2F, -CHF2 and CF3, most preferably optionally substituted with -CHF2. In formula (I), X4 is N or C-R5, wherein R5 is selected from -H, C1-2 alkyl, C2 alkenyl, C2 alkynyl, C1-2 haloalkyl, cyclopropyl, cyclobutyl, oxetanyl, and halogen (such as -F or -Cl). Preferably, X4 is C-R5, Preferably R5 is selected from -H, C1-2 alkyl, C2 alkenyl, C2 alkynyl, C1-2 haloalkyl, cyclopropyl and halogen. More preferably, R5 is selected from -H, -CH3, -CF3, cyclopropyl, -F and -Cl. Even more preferably, R5is -H. However, R5may also be -F. In formula (I), X5 is N or C-R6, wherein R6 is selected from -H, halo, C1-6 alkyl, -O(C1-6 alkyl), - S(C1-6 alkyl), -NH(C1-6 alkyl), -N(C1-6 alkyl)C1-6 alkyl and C1-6 haloalkyl. Preferably, X5 is N. However, if X5 is C-R6, then preferably R6 is selected from -H, halo, C1-3 alkyl, -O(C1-3 alkyl), -S(C1-3 alkyl), -NH(C1-3 alkyl), and C1-3 haloalkyl. More preferably, R6 is selected from -H, halo, C1-3 alkyl, and C1-3 haloalkyl. Preferably not more than one of X4 and X5 is N. In certain preferred embodiments, X4 is N and X5 is C-R6, preferably X4 is N and X5 is CH. In certain preferred embodiments, X4 is C-R5 and X5 is N, preferably X4 is CH and X5 is N. In certain preferred embodiments, X4 is C-R5 and X5 is C-R6. In certain preferred embodiments X4 is CH and X5 is CH. In one alternative embodiment, X4 is N and X5 is N. In formula (I), RS1is selected from halogen, -CN, -OH, -O(C1-5 alkyl), -O(C1-5 haloalkyl), C1-5 haloalkyl, -SH, -S(C1-5 alkyl), -SO2(C1-5 alkyl), -S(O)(NH)(C1-5 alkyl), -S(O)(N-C1-3 alkyl)(C1-5 alkyl), -N=S(O)(C1-5 alkyl)(C1-5 alkyl), -S(C1-5 haloalkyl), -P(O)(C1-5 alkyl)(C1-5 alkyl), -P(O)(O-C1-5 alkyl) (O-C1-5 alkyl), -P(O)(O-C1-5 alkyl)(C1-5 alkyl), -NH2, -NH(C1-5 alkyl), -NH(C1-5 haloalkyl), -N(C1-5 alkyl)(C1-5 alkyl), -N(C1-5 haloalkyl)(C1-5 alkyl), -(N-heterocycloalkyl), -CO(C1-5 alkyl), -CONH2, -CONH(C1-5 alkyl), -CON(C1-5 alkyl)(C1-5 alkyl), -CO-(N-heterocycloalkyl), -NHCO-(C1-5 alkyl), -N(C1-5 alkyl)-CO-(C1-5 alkyl), -NHCONH2, -NHCONH-(C1-5 alkyl), -NHCON(C1-5 alkyl)(C1-5 alkyl), -N(C1-5 alkyl)CONH2, -N(C1-5 alkyl)CONH-(C1-5 alkyl), and -N(C1-5 alkyl)CON(C1-5 alkyl)(C1-5 alkyl). Preferably, RS1is selected from halogen, -CN, -OH, -O(C1-5 alkyl), -O(C1-5 haloalkyl), C1-5 haloalkyl, -SH, -S(C1-5 alkyl), -S(C1-5 haloalkyl), -NH2, -NH(C1-5 alkyl), -NH(C1-5 haloalkyl), -N(C1-5 alkyl)(C1- 5 alkyl), -N(C1-5 haloalkyl)(C1-5 alkyl), -(N-heterocycloalkyl), -CO(C1-5 alkyl), -CONH2, -CONH(C1-5 alkyl), -CON(C1-5 alkyl)(C1-5 alkyl), -CO-(N-heterocycloalkyl), -NHCO-(C1-5 alkyl), -N(C1-5 alkyl)-CO-(C1-5 alkyl), -NHCONH2, -NHCONH-(C1-5 alkyl), -NHCON(C1-5 alkyl)(C1-5 alkyl), -N(C1-5 alkyl)CONH2, -N(C1-5 alkyl)CONH-(C1-5 alkyl), and -N(C1-5 alkyl)CON(C1-5 alkyl)(C1-5 alkyl). More preferably, RS1is selected from halogen, -CN, -OH, -O(C1-5 alkyl), -O(C1-5 haloalkyl), C1-5 haloalkyl, -SH, -S(C1-5 alkyl), -S(C1-5 haloalkyl), -NH2, -NH(C1-5 alkyl), -NH(C1-5 haloalkyl), -N(C1-5 alkyl)(C1-5alkyl), -N(C1-5haloalkyl)(C1-5alkyl), -(N-heterocycloalkyl), -CONH2, -CONH(C1-5alkyl), -CON(C1-5alkyl)(C1-5 alkyl), -CO-(N-heterocycloalkyl), -NHCO-(C1-5 alkyl), -N(C1-5 alkyl)-CO-(C1-5 alkyl), -NHCONH2, -NHCONH-(C1-5 alkyl), -NHCON(C1-5 alkyl)(C1-5 alkyl), -N(C1-5 alkyl)CONH2, -N(C1-5 alkyl)CONH-(C1-5 alkyl), and -N(C1-5 alkyl)CON(C1-5 alkyl)(C1-5 alkyl). Even more preferably, RS1is selected from halogen, -CN, -OH, -O(C1-5 alkyl), -O(C1-5 haloalkyl), C1-5 haloalkyl, -SH, -S(C1-5 alkyl), -S(C1-5 haloalkyl), -NH2, -NH(C1-5 alkyl), -NH(C1-5 haloalkyl), -N(C1-5 alkyl)(C1-5 alkyl), -N(C1-5 haloalkyl)(C1-5 alkyl), and -(N-heterocycloalkyl). Even more preferably, RS1is selected from halogen, -CN, -OH, -SH, and -NH2. In formula (I), RS2is selected from halogen, -CN, -OH, C1-5 alkyl, C1-5 haloalkyl, -O(C1-5 alkyl), - O(C1-5haloalkyl), -SH, -S(C1-5alkyl), -S(O)(C1-5alkyl), -SO2(C1-5alkyl), -S(O)(NH)(C1-5alkyl), -S(O)(N-C1-3 alkyl)(C1-5 alkyl), -N=S(O)(C1-5 alkyl)(C1-5 alkyl), -S(C1-5 haloalkyl), -S(O)(C1-5 haloalkyl), -SO2(C1-5 haloalkyl), -P(O)(C1-5 alkyl)(C1-5 alkyl), -P(O)(O-C1-5 alkyl)(O-C1-5 alkyl), -P(O)(O-C1-5 alkyl)(C1-5 alkyl), -NH2, -NH(C1-5 alkyl), -NH(C1-5 haloalkyl), -N(C1-5 alkyl)(C1-5 alkyl), -N(C1-5 haloalkyl)(C1-5 alkyl), - (N-heterocycloalkyl), -CO(C1-5 alkyl), -COOH, -COO(C1-5 alkyl), -CONH2, -CONH(C1-5 alkyl), -CON(C1-5 alkyl)(C1-5 alkyl), -CO-(N-heterocycloalkyl), -NHCO-(C1-5 alkyl), -N(C1-5 alkyl)-CO-(C1-5 alkyl), -NHCONH2, -NHCONH-(C1-5 alkyl), -NHCON(C1-5 alkyl)(C1-5 alkyl), -N(C1-5 alkyl)CONH2, -N(C1-5 alkyl)CONH-(C1-5 alkyl), and -N(C1-5 alkyl)CON(C1-5 alkyl)(C1-5 alkyl), -(C1-5 alkylene)-CN, -(C1-5 alkylene)-OH, -(C1-5 alkylene)-O(C1-5 alkyl), -(C1-5 alkylene)-O(C1-5 haloalkyl), -(C1-5 alkylene)-SH, -(C1-5 alkylene)-S(C1-5 alkyl), -(C1-5 alkylene)-S(O)(C1-5 alkyl), -(C1-5 alkylene)-SO2(C1-5 alkyl), -(C1-5 alkylene)-S(O)(NH)(C1-5 alkyl), -(C1-5 alkylene)-S(O)(N-C1-3 alkyl)(C1-5 alkyl), -(C1-5 alkylene)-N=S(O)(C1-5 alkyl)(C1-5 alkyl), -(C1-5 alkylene)-S(C1-5 haloalkyl), -(C1-5 alkylene)-S(O)(C1-5 haloalkyl), -(C1-5 alkylene)- S(O)2(C1-5 haloalkyl), -(C1-5 alkylene)-P(O)(C1-5 alkyl)(C1-5 alkyl), -(C1-5 alkylene)-P(O)(O-C1-5 alkyl)(O-C1-5 alkyl), -(C1-5 alkylene)-P(O)(O-C1-5 alkyl)(C1-5 alkyl), -(C1-5 alkylene)-NH2, -(C1-5 alkylene)-NH(C1-5 alkyl), - (C1-5 alkylene)-NH(C1-5 haloalkyl), -(C1-5 alkylene)-N(C1-5 alkyl)(C1-5 alkyl), -(C1-5 alkylene)-N(C1-5 alkyl)(C1- 5 haloalkyl), -(C1-5 alkylene)-(N-heterocycloalkyl), -(C1-5 alkylene)-N(C1-5 haloalkyl)(C1-5 alkyl), -COO-(C1-5 alkylene)-NH2, -COO-(C1-5 alkylene)-NH(C1-5 alkyl), -COO-(C1-5 alkylene)-NH(C1-5 haloalkyl), -COO-(C1-5 alkylene)-N(C1-5 alkyl)(C1-5 alkyl), -COO-(C1-5 alkylene)-N(C1-5 alkyl)(C1-5 haloalkyl), -COO-(C1-5 alkylene)-(N-heterocycloalkyl), -COO-(C1-5 alkylene)-N(C1-5 haloalkyl)(C1-5 alkyl), CONH-(C1-5 alkylene)-NH2, -CONH-(C1-5 alkylene)-NH(C1-5 alkyl), -CONH-(C1-5 alkylene)-NH(C1-5 haloalkyl), -CONH- (C1-5 alkylene)-N(C1-5 alkyl)(C1-5 alkyl), -CONH-(C1-5 alkylene)-N(C1-5 alkyl)(C1-5 haloalkyl), -CONH-(C1-5 alkylene)-(N-heterocycloalkyl), -CONH-(C1-5 alkylene)-N(C1-5 haloalkyl)(C1-5 alkyl),CO-N(C1-5 alkyl)-(C1-5 alkylene)-NH2, -CO-N(C1-5 alkyl)-(C1-5 alkylene)-NH(C1-5 alkyl), -CO-N(C1-5 alkyl)-(C1-5 alkylene)-NH(C1-5 haloalkyl), -CO-N(C1-5 alkyl)-(C1-5 alkylene)-N(C1-5 alkyl)(C1-5 alkyl), -CO-N(C1-5 alkyl)-(C1-5 alkylene)-N(C1- 5 alkyl)(C1-5 haloalkyl), -CO-N(C1-5 alkyl)-(C1-5 alkylene)-(N-heterocycloalkyl), -CO-N(C1-5 alkyl)-(C1-5 alkylene)-N(C1-5haloalkyl)(C1-5alkyl), -(C1-5alkylene)-CO(C1-5alkyl), -(C1-5alkylene)-COO(C1-5alkyl), - (C1-5 alkylene)-COOH, -(C1-5 alkylene)-CONH2, -(C1-5 alkylene)-CONH(C1-5 alkyl), -(C1-5 alkylene)-CON(C1-5 alkyl)(C1-5 alkyl), -(C1-5 alkylene)-CO-(N-heterocycloalkyl), -(C1-5 alkylene)-NHCO-(C1- 5 alkyl), -(C1-5 alkylene)-N(C1-5 alkyl)-CO-(C1-5 alkyl), -(C1-5 alkylene)-NHCONH2, -(C1-5 alkylene)-NHCONH-(C1-5 alkyl), -(C1-5 alkylene)-NHCON(C1-5 alkyl)(C1-5 alkyl), -(C1-5 alkylene)-N(C1-5 alkyl)CONH2, -(C1-5 alkylene)-N(C1-5 alkyl)CONH-(C1-5 alkyl), and -(C1-5 alkylene)-N(C1-5 alkyl)CON(C1-5 alkyl)(C1-5 alkyl). Preferably, RS2is selected from halogen, -CN, -OH, C1-5 alkyl, C1-5 haloalkyl, -O(C1-5 alkyl), -O(C1- 5 haloalkyl), -SH, -S(C1-5 alkyl), -S(O)(C1-5 alkyl), -SO2(C1-5 alkyl), -S(O)(NH)(C1-5 alkyl), -S(O)(N-C1-3 alkyl)(C1-5alkyl), -N=S(O)(C1-5alkyl)(C1-5alkyl), -S(C1-5haloalkyl), -S(O)(C1-5haloalkyl), -SO2(C1-5haloalkyl), -P(O)(C1-5 alkyl)(C1-5 alkyl), -P(O)(O-C1-5 alkyl)(O-C1-5 alkyl), -P(O)(O-C1-5 alkyl)(C1-5 alkyl), -NH2, -NH(C1-5 alkyl), -NH(C1-5 haloalkyl), -N(C1-5 alkyl)(C1-5 alkyl), -N(C1-5 haloalkyl)(C1-5 alkyl), - (N-heterocycloalkyl), -CO(C1-5 alkyl), -COOH, -COO(C1-5 alkyl), -CONH2, -CONH(C1-5 alkyl), -CON(C1-5 alkyl)(C1-5 alkyl), -CO-(N-heterocycloalkyl), -NHCO-(C1-5 alkyl), -N(C1-5 alkyl)-CO-(C1-5 alkyl), -NHCONH2, -NHCONH-(C1-5 alkyl), -NHCON(C1-5 alkyl)(C1-5 alkyl), -N(C1-5 alkyl)CONH2, -N(C1-5 alkyl)CONH-(C1-5 alkyl), and -N(C1-5 alkyl)CON(C1-5 alkyl)(C1-5 alkyl), -(C1-5 alkylene)-CN, -(C1-5 alkylene)-OH, -(C1-5 alkylene)-O(C1-5 alkyl), -(C1-5 alkylene)-O(C1-5 haloalkyl), -(C1-5 alkylene)-SH, -(C1-5 alkylene)-S(C1-5 alkyl), -(C1-5 alkylene)-S(O)(C1-5 alkyl), -(C1-5 alkylene)-SO2(C1-5 alkyl), -(C1-5 alkylene)-S(O)(NH)(C1-5 alkyl), -(C1-5 alkylene)-S(O)(N-C1-3 alkyl)(C1-5 alkyl), -(C1-5 alkylene)-N=S(O)(C1-5 alkyl)(C1-5 alkyl), -(C1-5 alkylene)-S(C1-5 haloalkyl), -(C1-5 alkylene)-S(O)(C1-5 haloalkyl), -(C1-5 alkylene)- S(O)2(C1-5 haloalkyl), -(C1-5 alkylene)-P(O)(C1-5 alkyl)(C1-5 alkyl), -(C1-5 alkylene)-P(O)(O-C1-5 alkyl)(O-C1-5 alkyl), -(C1-5 alkylene)-P(O)(O-C1-5 alkyl)(C1-5 alkyl), -(C1-5 alkylene)-NH2, -(C1-5 alkylene)-NH(C1-5 alkyl), - (C1-5 alkylene)-NH(C1-5 haloalkyl), -(C1-5 alkylene)-N(C1-5 alkyl)(C1-5 alkyl), -(C1-5 alkylene)-N(C1-5 alkyl)(C1- 5 haloalkyl), -(C1-5 alkylene)-(N-heterocycloalkyl), -(C1-5 alkylene)-N(C1-5 haloalkyl)(C1-5 alkyl), -COO-(C1-5 alkylene)-NH2, -COO-(C1-5 alkylene)-NH(C1-5 alkyl), -COO-(C1-5 alkylene)-NH(C1-5 haloalkyl), -COO-(C1-5 alkylene)-N(C1-5 alkyl)(C1-5 alkyl), -COO-(C1-5 alkylene)-N(C1-5 alkyl)(C1-5 haloalkyl), -COO-(C1-5 alkylene)-(N-heterocycloalkyl), -COO-(C1-5 alkylene)-N(C1-5 haloalkyl)(C1-5 alkyl), -(C1-5 alkylene)-CO(C1-5 alkyl), -(C1-5 alkylene)-COO(C1-5 alkyl), -(C1-5 alkylene)-COOH, -(C1-5 alkylene)-CONH2, -(C1-5 alkylene)-CONH(C1-5 alkyl), -(C1-5 alkylene)-CON(C1-5 alkyl)(C1-5 alkyl), -(C1-5 alkylene)-CO-(N- heterocycloalkyl), -(C1-5 alkylene)-NHCO-(C1-5 alkyl), -(C1-5 alkylene)-N(C1-5 alkyl)-CO-(C1-5 alkyl), -(C1-5 alkylene)-NHCONH2, -(C1-5 alkylene)-NHCONH-(C1-5 alkyl), -(C1-5 alkylene)-NHCON(C1-5 alkyl)(C1-5 alkyl), -(C1-5 alkylene)-N(C1-5 alkyl)CONH2, -(C1-5 alkylene)-N(C1-5 alkyl)CONH-(C1-5 alkyl), and -(C1-5 alkylene)-N(C1-5 alkyl)CON(C1-5 alkyl)(C1-5 alkyl). More preferably, RS2is selected from halogen, -CN, -OH, C1-5 alkyl, C1-5 haloalkyl, -O(C1-5 alkyl), -O(C1-5haloalkyl), -SH, -S(C1-5alkyl), -S(O)(C1-5alkyl), -SO2(C1-5alkyl), -S(O)(NH)(C1-5alkyl), -S(O)(N-C1-3 alkyl)(C1-5 alkyl), -N=S(O)(C1-5 alkyl)(C1-5 alkyl), -S(C1-5 haloalkyl), -S(O)(C1-5 haloalkyl), -SO2(C1-5 haloalkyl), -P(O)(C1-5 alkyl)(C1-5 alkyl), -P(O)(O-C1-5 alkyl)(O-C1-5 alkyl), -P(O)(O-C1-5 alkyl)(C1-5 alkyl), -NH2, -NH(C1-5 alkyl), -NH(C1-5 haloalkyl), -N(C1-5 alkyl)(C1-5 alkyl), -N(C1-5 haloalkyl)(C1-5 alkyl), - (N-heterocycloalkyl), -CO(C1-5 alkyl), -COOH, -COO(C1-5 alkyl), -CONH2, -CONH(C1-5 alkyl), -CON(C1-5 alkyl)(C1-5 alkyl), -CO-(N-heterocycloalkyl), -NHCO-(C1-5 alkyl), -N(C1-5 alkyl)-CO-(C1-5 alkyl), -NHCONH2, -NHCONH-(C1-5 alkyl), -NHCON(C1-5 alkyl)(C1-5 alkyl), -N(C1-5 alkyl)CONH2, -N(C1-5 alkyl)CONH-(C1-5 alkyl), and -N(C1-5 alkyl)CON(C1-5 alkyl)(C1-5 alkyl), -(C1-5 alkylene)-CN, -(C1-5 alkylene)-OH, -(C1-5 alkylene)-O(C1-5 alkyl), -(C1-5 alkylene)-O(C1-5 haloalkyl), -(C1-5 alkylene)-SH, -(C1-5 alkylene)-S(C1-5alkyl), -(C1-5alkylene)-S(O)(C1-5alkyl), -(C1-5alkylene)-SO2(C1-5alkyl), -(C1-5alkylene)-S(O)(NH)(C1-5 alkyl), -(C1-5 alkylene)-S(O)(N-C1-3 alkyl)(C1-5 alkyl), -(C1-5 alkylene)-N=S(O)(C1-5 alkyl)(C1-5 alkyl), -(C1-5 alkylene)-S(C1-5 haloalkyl), -(C1-5 alkylene)-S(O)(C1-5 haloalkyl), -(C1-5 alkylene)- S(O)2(C1-5 haloalkyl), -(C1-5 alkylene)-P(O)(C1-5 alkyl)(C1-5 alkyl), -(C1-5 alkylene)-P(O)(O-C1-5 alkyl)(O-C1-5 alkyl), -(C1-5 alkylene)-P(O)(O-C1-5 alkyl)(C1-5 alkyl), -(C1-5 alkylene)-NH2, -(C1-5 alkylene)-NH(C1-5 alkyl), - (C1-5 alkylene)-NH(C1-5 haloalkyl), -(C1-5 alkylene)-N(C1-5 alkyl)(C1-5 alkyl), -(C1-5 alkylene)-N(C1-5 alkyl)(C1- 5 haloalkyl), -(C1-5 alkylene)-(N-heterocycloalkyl), -(C1-5 alkylene)-N(C1-5 haloalkyl)(C1-5 alkyl), -(C1-5 alkylene)-CO(C1-5 alkyl), -(C1-5 alkylene)-COO(C1-5 alkyl), -(C1-5 alkylene)-COOH, -(C1-5 alkylene)-CONH2, -(C1-5 alkylene)-CONH(C1-5 alkyl), -(C1-5 alkylene)-CON(C1-5 alkyl)(C1-5 alkyl), -(C1-5 alkylene)-CO-(N- heterocycloalkyl), -(C1-5 alkylene)-NHCO-(C1-5 alkyl), -(C1-5 alkylene)-N(C1-5 alkyl)-CO-(C1-5 alkyl), -(C1-5 alkylene)-NHCONH2, -(C1-5 alkylene)-NHCONH-(C1-5 alkyl), -(C1-5 alkylene)-NHCON(C1-5 alkyl)(C1-5 alkyl), -(C1-5 alkylene)-N(C1-5 alkyl)CONH2, -(C1-5 alkylene)-N(C1-5 alkyl)CONH-(C1-5 alkyl), and -(C1-5 alkylene)-N(C1-5 alkyl)CON(C1-5 alkyl)(C1-5 alkyl). Even more preferably, RS2is selected from halogen, -CN, -OH, C1-5 alkyl, C1-5 haloalkyl, -O(C1-5 alkyl), -O(C1-5 haloalkyl), -SH, -S(C1-5 alkyl), -SO2(C1-5 alkyl), -S(O)(NH)(C1-5 alkyl), -S(O)(N-C1-3 alkyl)(C1-5 alkyl), -N=S(O)(C1-5 alkyl)(C1-5 alkyl), -S(C1-5 haloalkyl), -P(O)(C1-5 alkyl)(C1-5 alkyl), -P(O)(O-C1-5 alkyl)(O- C1-5 alkyl), -P(O)(O-C1-5 alkyl)(C1-5 alkyl), -NH2, -NH(C1-5 alkyl), -NH(C1-5 haloalkyl), -N(C1-5 alkyl)(C1-5 alkyl), -N(C1-5 haloalkyl)(C1-5 alkyl), -(N-heterocycloalkyl), -CO(C1-5 alkyl), -CONH2, -CONH(C1-5 alkyl), -CON(C1-5 alkyl)(C1-5 alkyl), -CO-(N-heterocycloalkyl), -NHCO-(C1-5 alkyl), -N(C1-5 alkyl)-CO-(C1-5 alkyl), -NHCONH2, -NHCONH-(C1-5 alkyl), -NHCON(C1-5 alkyl)(C1-5 alkyl), -N(C1-5 alkyl)CONH2, -N(C1-5 alkyl)CONH-(C1-5 alkyl), and -N(C1-5 alkyl)CON(C1-5 alkyl)(C1-5 alkyl), -(C1-5 alkylene)-CN, -(C1-5 alkylene)-OH, -(C1-5 alkylene)-O(C1-5 alkyl), -(C1-5 alkylene)-O(C1-5 haloalkyl), -(C1-5 alkylene)-SH, -(C1-5 alkylene)-S(C1-5 alkyl), -(C1-5 alkylene)-SO2(C1-5 alkyl), -(C1-5 alkylene)-S(O)(NH)(C1-5 alkyl), -(C1-5 alkylene)-S(O)(N-C1-3 alkyl)(C1-5 alkyl), -(C1-5 alkylene)-N=S(O)(C1-5 alkyl)(C1-5 alkyl), -(C1-5 alkylene)- S(C1-5 haloalkyl), -(C1-5 alkylene)-P(O)(C1-5 alkyl)(C1-5 alkyl), -(C1-5 alkylene)-P(O)(O-C1-5 alkyl)(O-C1-5 alkyl), -(C1-5alkylene)-P(O)(O-C1-5alkyl)(C1-5alkyl), -(C1-5alkylene)-NH2, -(C1-5alkylene)-NH(C1-5alkyl), - (C1-5 alkylene)-NH(C1-5 haloalkyl), -(C1-5 alkylene)-N(C1-5 alkyl)(C1-5 alkyl), -(C1-5 alkylene)-N(C1-5 alkyl)(C1- 5 haloalkyl), -(C1-5 alkylene)-(N-heterocycloalkyl), -(C1-5 alkylene)-N(C1-5 haloalkyl)(C1-5 alkyl), -(C1-5 alkylene)-CO(C1-5 alkyl), -(C1-5 alkylene)-CONH2, -(C1-5 alkylene)-CONH(C1-5 alkyl), -(C1-5 alkylene)-CON(C1-5 alkyl)(C1-5 alkyl), -(C1-5 alkylene)-CO-(N-heterocycloalkyl), -(C1-5 alkylene)-NHCO-(C1- 5 alkyl), -(C1-5 alkylene)-N(C1-5 alkyl)-CO-(C1-5 alkyl), -(C1-5 alkylene)-NHCONH2, -(C1-5 alkylene)-NHCONH-(C1-5 alkyl), -(C1-5 alkylene)-NHCON(C1-5 alkyl)(C1-5 alkyl), -(C1-5 alkylene)-N(C1-5 alkyl)CONH2, -(C1-5 alkylene)-N(C1-5 alkyl)CONH-(C1-5 alkyl), and -(C1-5 alkylene)-N(C1-5 alkyl)CON(C1-5 alkyl)(C1-5 alkyl). Still more preferably, RS2is selected from halogen, -CN, -OH, C1-5alkyl, C1-5haloalkyl, -O(C1-5alkyl), -O(C1-5 haloalkyl), -SH, -S(C1-5 alkyl), -S(C1-5 haloalkyl), -NH2, -NH(C1-5 alkyl), -NH(C1-5 haloalkyl), -N(C1-5 alkyl)(C1-5 alkyl), -N(C1-5 haloalkyl)(C1-5 alkyl), -(N-heterocycloalkyl), -CO(C1-5 alkyl), -CONH2, -CONH(C1-5 alkyl), -CON(C1-5 alkyl)(C1-5 alkyl), -CO-(N-heterocycloalkyl), -NHCO-(C1-5 alkyl), -N(C1-5 alkyl)-CO-(C1-5 alkyl), -NHCONH2, -NHCONH-(C1-5 alkyl), -NHCON(C1-5 alkyl)(C1-5 alkyl), -N(C1-5 alkyl)CONH2, -N(C1-5 alkyl)CONH-(C1-5 alkyl), -N(C1-5 alkyl)CON(C1-5 alkyl)(C1-5 alkyl), -(C1- 5 alkylene)-CN, -(C1-5 alkylene)-OH, -(C1-5 alkylene)-O(C1-5 alkyl), -(C1-5 alkylene)-O(C1-5 haloalkyl), -(C1- 5 alkylene)-SH, -(C1-5 alkylene)-S(C1-5 alkyl), -(C1-5 alkylene)-S(C1-5 haloalkyl), -(C1-5 alkylene)-NH2, -(C1-5 alkylene)-NH(C1-5 alkyl), -(C1-5 alkylene)-NH(C1-5 haloalkyl), -(C1-5 alkylene)-N(C1-5 alkyl)(C1-5 alkyl), -(C1- 5 alkylene)-N(C1-5 alkyl)(C1-5 haloalkyl), -(C1-5 alkylene)-(N-heterocycloalkyl), -(C1-5 alkylene)-N(C1-5 haloalkyl)(C1-5 alkyl), -(C1-5 alkylene)-CO(C1-5 alkyl), -(C1-5 alkylene)-CONH2, -(C1-5 alkylene)-CONH(C1-5 alkyl), -(C1-5 alkylene)-CON(C1-5 alkyl)(C1-5 alkyl), -(C1-5 alkylene)-CO-(N-heterocycloalkyl), -(C1-5 alkylene)-NHCO-(C1-5 alkyl), -(C1-5 alkylene)-N(C1-5 alkyl)-CO-(C1-5 alkyl), -(C1-5 alkylene)-NHCONH2, - (C1-5 alkylene)-NHCONH-(C1-5 alkyl), -(C1-5 alkylene)-NHCON(C1-5 alkyl)(C1-5 alkyl), -(C1-5 alkylene)-N(C1- 5 alkyl)CONH2, -(C1-5 alkylene)-N(C1-5 alkyl)CONH-(C1-5 alkyl), and -(C1-5 alkylene)-N(C1-5 alkyl)CON(C1-5 alkyl)(C1-5 alkyl). Again more preferably, RS2is selected from halogen, -CN, -OH, C1-5 alkyl, C1-5 haloalkyl, -O(C1-5 alkyl), -O(C1-5 haloalkyl), -SH, -S(C1-5 alkyl), -S(C1-5 haloalkyl), -NH2, -NH(C1-5 alkyl), -NH(C1-5haloalkyl), -N(C1-5 alkyl)(C1-5 alkyl), -N(C1-5 haloalkyl)(C1-5 alkyl), -(N-heterocycloalkyl), -CONH2, -CONH(C1-5 alkyl), -CON(C1-5 alkyl)(C1-5 alkyl), -CO-(N- heterocycloalkyl), -NHCO-(C1-5 alkyl), -N(C1-5 alkyl)-CO-(C1-5 alkyl), -NHCONH2, -NHCONH-(C1-5 alkyl), -NHCON(C1-5 alkyl)(C1-5 alkyl), -N(C1-5 alkyl)CONH2, -N(C1-5 alkyl)CONH-(C1-5 alkyl), -N(C1-5 alkyl)CON(C1-5 alkyl)(C1-5 alkyl), -(C1-5 alkylene)-CN, -(C1-5 alkylene)-OH, -(C1-5 alkylene)-O(C1-5 alkyl), - (C1-5 alkylene)-O(C1-5 haloalkyl), -(C1-5 alkylene)-SH, -(C1-5 alkylene)-S(C1-5 alkyl), -(C1-5 alkylene)-S(C1-5 haloalkyl), -(C1-5 alkylene)-NH2, -(C1-5 alkylene)-NH(C1-5 alkyl), -(C1-5 alkylene)-NH(C1-5 haloalkyl), -(C1-5 alkylene)-N(C1-5alkyl)(C1-5alkyl), -(C1-5alkylene)-N(C1-5alkyl)(C1-5haloalkyl), -(C1-5alkylene)-(N- heterocycloalkyl), -(C1-5 alkylene)-N(C1-5 haloalkyl)(C1-5 alkyl), -(C1-5 alkylene)-CONH2, -(C1-5 alkylene)-CONH(C1-5 alkyl), -(C1-5 alkylene)-CON(C1-5 alkyl)(C1-5 alkyl), -(C1-5 alkylene)-CO-(N- heterocycloalkyl), -(C1-5 alkylene)-NHCO-(C1-5 alkyl), -(C1-5 alkylene)-N(C1-5 alkyl)-CO-(C1-5 alkyl), -(C1-5 alkylene)-NHCONH2, -(C1-5 alkylene)-NHCONH-(C1-5 alkyl), -(C1-5 alkylene)-NHCON(C1-5 alkyl)(C1-5 alkyl), -(C1-5 alkylene)-N(C1-5 alkyl)CONH2, -(C1-5 alkylene)-N(C1-5 alkyl)CONH-(C1-5 alkyl), and -(C1-5 alkylene)-N(C1-5 alkyl)CON(C1-5 alkyl)(C1-5 alkyl). Again more preferably, RS2is selected from halogen, -CN, -OH, C1-5 alkyl, C1-5 haloalkyl, -O(C1-5 alkyl), -O(C1-5 haloalkyl), -SH, -S(C1-5 alkyl), -S(C1-5 haloalkyl), -NH2, -NH(C1-5 alkyl), -NH(C1-5 haloalkyl), -N(C1-5alkyl)(C1-5alkyl), -N(C1-5haloalkyl)(C1-5alkyl), -(N-heterocycloalkyl), -(C1-5alkylene)- CN, -(C1-5 alkylene)-OH, -(C1-5 alkylene)-O(C1-5 alkyl), -(C1-5 alkylene)-O(C1-5 haloalkyl), -(C1-5 alkylene)-SH, -(C1-5 alkylene)-S(C1-5 alkyl), -(C1-5 alkylene)-S(C1-5 haloalkyl), -(C1-5 alkylene)-NH2, -(C1-5 alkylene)-NH(C1-5 alkyl), -(C1-5 alkylene)-NH(C1-5 haloalkyl), -(C1-5 alkylene)-N(C1-5 alkyl)(C1-5 alkyl), -(C1- 5 alkylene)-N(C1-5 alkyl)(C1-5 haloalkyl), -(C1-5 alkylene)-(N-heterocycloalkyl), -(C1-5 alkylene)-N(C1-5 haloalkyl)(C1-5 alkyl), -(C1-5 alkylene)-CONH2, -(C1-5 alkylene)-CONH(C1-5 alkyl), -(C1-5 alkylene)-CON(C1- 5 alkyl)(C1-5 alkyl), and -(C1-5 alkylene)-CO-(N-heterocycloalkyl). Again even more preferably, RS2is selected from halogen, -CN, -OH, -SH, -NH2, -(C1-5 alkylene)- CN, -(C1-5 alkylene)-OH, -(C1-5 alkylene)-SH, and -(C1-5 alkylene)-NH2. Most preferably, RS2is selected from halogen, -CN, -OH, -SH, and -NH2. The compounds of the present invention will be described in the following preferred embodiments. It is to be understood that only some of the features Z, R1, R2, R3, R4, R5, and X2 will be recited when defining said particular embodiment. For any feature that is absent in the definition it is to be understood that said feature is as defined for formula (I) or any specific embodiment defined herein. In particular, if only one or more of R1, R2, R3 are recited, the recitation is applicable to any one of possible Z group, including each of them individually, as well as including any specific stereoconfiguration thereof. In a first specific embodiment, of the compound of formula (I), R1 is methyl. One possible methyl group is CD3. However, if not specifically indicated otherwise, R1 in this specific embodiment is methyl. In a second specific embodiment of the compound of formula (I), R1 is -CN. In a third specific embodiment of the compound of formula (I), R2 and R3 are both -H. In a fourth specific embodiment of the compound of formula (I), R2 is H, and R3 is methyl (which may also specifically refer to -CD3). In a fifth specific embodiment of the compound of formula (I), R1 is methyl, R2 is H, and R3 is methyl. In a sixth specific embodiment of the compound of formula In this sixth specific embodiment, R1, R2, and R3 are as defined in formula (I) or in any one of specific embodiments referred to herein. Preferably, in this sixth specific embodiment, R1 is methyl, R2 is H, and R3 is methyl. In this sixth embodiment, further specific combinations of R1, R2, and R3 are considered particularly suitable: R1 R2 R3 -CH3 -H -CH2CN-CH3 -H -CH2CH2OH-CH3 -H -CH2CH3-CN -H -CH=CH2-CN -H -CH2CH3-CN -H -CH2CH2OH-CN -H -CH2CH2OCH3-CN -H -CH2OHAccordingly, the present invention provides, within this specific sixth embodiment, each individual combination of R1, R2, and R3 as provided herein. In this sixth specific embodiment, the Z moiety may have the following configuration: . However, in this sixth specific embodiment, the Z moiety may also have the following configuration: . Alternatively, in this sixth specific embodiment, the Z moiety may have the following configuration: . Further alternatively, the Z moiety may have the following configuration: . Accordingly, the present invention specifically relates to each of the recited individual configurations of the compound of formula (I), according to this sixth embodiment. In a seventh specific embodiment of the compound of formula In this seventh specific embodiment, R1, R2, and R3 are as defined in formula (I) or in any one of specific embodiments referred to herein. Preferably, in this seventh specific embodiment, R1 is methyl, R2 is H, and R3 is methyl. In this seventh specific embodiment, the Z moiety may have the following configuration: . However, in this seventh specific embodiment, the Z moiety may also have the following configuration: . In an eighth specific embodiment of the compound of formula In this eighth specific embodiment, R1, R2, and R3 are as defined in formula (I) or in any one of specific embodiments referred to herein. Preferably, in this eighth specific embodiment, R1 is methyl, R2 is H, and R3 is methyl. In this eighth specific embodiment, the Z moiety may have the following configuration: . However, in this eighth specific embodiment, the Z moiety may also have the following configuration: . In a ninth specific embodiment of the compound of formula In this ninth specific embodiment, R1, R2, and R3 are as defined in formula (I) or in any one of specific embodiments referred to herein. Preferably, in this ninth specific embodiment, R1 is methyl, R2 is H, and R3 is methyl. In this ninth embodiment, further specific combinations of R1, R2, and R3 are considered particularly suitable: R1 R2 R3 -CH3 -H -H-CN -H -H-CHF2 -H -H-CH2F -H -H-CH3 -H -CH3-CN -H -CH3-H -H -CH2OHAccordingly, the present invention provides, within this specific ninth embodiment, each individual combination of R1, R2, and R3 as provided herein. In this ninth specific embodiment, the Z moiety may have the following configuration: . However, in this ninth specific embodiment, the Z moiety may also have the following configuration: . Alternatively, in this ninth specific embodiment, the Z moiety may have the following configuration: . Further alternatively, the Z moiety may have the following configuration: . Accordingly, the present invention specifically relates to each of the recited individual configurations of the compound of formula (I), according to this ninth embodiment. In a tenth specific embodiment of the compound of formula In this tenth specific embodiment, R1, R2, and R3 are as defined in formula (I) or in any one of specific embodiments referred to herein. Preferably, in this tenth specific embodiment, R1 is methyl, R2 is H, and R3 is methyl. In this tenth embodiment, further specific combinations of R1, R2, and R3 are considered particularly suitable: R1 R2 R3 -CH3 -H -H-CN -H -H-CHF2 -H -H-CH2F -H -H-CH3 -H -CH3-CN -H -CH3-H -H -CH2OHAccordingly, the present invention provides, within this specific tenth embodiment, each individual combination of R1, R2, and R3 as provided herein. In this tenth specific embodiment, the Z moiety may have the following configuration: . However, in this tenth specific embodiment, the Z moiety may also have the following configuration: . Alternatively, in this tenth specific embodiment, the Z moiety may have the following configuration: Further alternatively, the Z moiety may have the following configuration: Accordingly, the present invention specifically relates to each of the recited individual configurations of the compound of formula (I), according to this tenth embodiment. In an eleventh specific embodiment of the compound of formula In this eleventh specific embodiment, R1, R2, and R3 are as defined in formula (I) or in any one of specific embodiments referred to herein. Preferably, in this eleventh specific embodiment, R1 is methyl, R2 is H, and R3 is methyl. In this eleventh embodiment, further specific combinations of R1, R2, and R3 are considered particularly suitable: R1 R2 R3 -CH3 -H -H-CN -H -H-CHF2 -H -H-CH2F -H -H-CH3 -H -CH3-CN -H -CH3-H -H -CH2OHAccordingly, the present invention provides, within this specific eleventh embodiment, each individual combination of R1, R2, and R3 as provided herein. In this eleventh specific embodiment, the Z moiety may have the following configuration: . However, in this eleventh specific embodiment, the Z moiety may also have the R3following configuration: . Alternatively, in this eleventh specific embodiment, the Z moietymay have the following configuration: . Further alternatively, the Z moiety may have thefollowing configuration: . Accordingly, the present invention specifically relates to eachof the recited individual configurations of the compound of formula (I), according to this eleventh embodiment. In a twelfth specific embodiment of the compound of formula In this twelfth specific embodiment, R1, R2, and R3 are as defined in formula (I) or in any one of specific embodiments referred to herein. Preferably, in this twelfth specific embodiment, R1 is methyl, R2 is H, and R3 is methyl. In this twelfth specific embodiment, the Z moiety may have the following configuration: . However, in this twelfth specific embodiment, the Z moiety may also have the followingconfiguration:. Alternatively, in this twelfth specific embodiment, the Z moiety may havethe following configuration: . Further alternatively, the Z moiety may have the followingconfiguration: . Accordingly, the present invention specifically relates to each of therecited individual configurations of the compound of formula (I), according to this twelfth embodiment. In a thirteenth specific embodiment of the compound of formula In this thirteenth specific embodiment, R1, R2, and R3 are as defined in formula (I) or in any one of specific embodiments referred to herein. Preferably, in this thirteenth specific embodiment, R1 is methyl, R2 is H, and R3 is methyl. In this thirteenth specific embodiment, the Z moiety may have the following configuration: . However, in this thirteenth specific embodiment, the Z moiety may also have thefollowing configuration: . Alternatively, in this thirteenth specific embodiment, the Zmoiety may have the following configuration: . Further alternatively, the Z moiety mayhave the following configuration: . Accordingly, the present invention specifically relatesto each of the recited individual configurations of the compound of formula (I), according to this thirteenth embodiment. In a fourteenth specific embodiment of the compound of formula (I), Z is .In a fifteenth specific embodiment of the compound of formula (I), -YC2-RC2 is aryl, preferably - YC2-RC2 is phenyl, wherein said aryl (said phenyl) is optionally substituted with one or more groups independently selected from halogen, CN, OH, C1-5 alkyl, C1-5 haloalkyl, O(C1-5 alkyl), -O(C1-5 haloalkyl), SH, S(C15 alkyl), S(C15 haloalkyl), NH2, NH(C1-5 alkyl), NH(C1-5 haloalkyl), N(C1-5 alkyl)(C1-5 alkyl), -N(C1-5 haloalkyl)(C1-5 alkyl), -CO(C1-5 alkyl), CONH2, CONH(C1-5 alkyl), and CON(C1-5 alkyl)(C1-5 alkyl). In a sixteenth specific embodiment of the compound of formula (I), -YC2-RC2 is heteroaryl,preferably selected from imidazolyl, pyridazinyl, thiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, and indazolyl, wherein said heteroaryl is optionally substituted with one or more groups independently selected from halogen, CN, OH, C1-5 alkyl, C1-5 haloalkyl, O(C1-5 alkyl), -O(C1-5 haloalkyl), SH, S(C15 alkyl), S(C15 haloalkyl), NH2, NH(C1-5 alkyl), NH(C1-5 haloalkyl), N(C1-5 alkyl)(C1-5 alkyl), -N(C1-5 haloalkyl)(C1-5 alkyl), - CO(C1-5 alkyl), CONH2, CONH(C1-5 alkyl), and CON(C1-5 alkyl)(C1-5 alkyl). In a seventeenth specific embodiment of the compound of formula (I), -YC2-RC2 is heterocycloalkyl, preferably selected from morpholinyl, 1,1-dioxothiomorpholinyl, azetinyl, pyrrolidinyl, piperidinyl, 6-oxo-1,6- dihydropyridinyl, or piperazinyl, wherein said heterocycloalkyl is optionally substituted with one or more groups independently selected from RS2. More preferably, -YC2-RC2 is piperazinyl, optionally substituted with one or more groups independently selected from halogen, -CN, -OH, C1-5 alkyl, C1-5 haloalkyl, -O(C1-5 alkyl), -O(C1-5 haloalkyl), -SH, -S(C1-5 alkyl), -S(C1-5 haloalkyl), -NH2, -NH(C1-5 alkyl), -NH(C1-5 haloalkyl), -N(C1-5 alkyl)(C1-5 alkyl), -N(C1-5 haloalkyl)(C1-5 alkyl), -CO(C1-5alkyl), -CONH2, -CONH(C1-5alkyl), and -CON(C1-5alkyl)(C1-5alkyl). Even more preferably, -YC2- RC2 is piperazinyl (preferably N-piperazinyl) optionally substituted (preferably N-substituted) with -CO(C1- 5 alkyl), -CONH2, -CONH(C1-5 alkyl), and -CON(C1-5 alkyl)(C1-5 alkyl). Most preferably, -YC2-RC2 is piperazinyl (preferably N-piperazinyl) substituted (preferably N-substituted, preferably at a different N- atom than that attached to the ring system as shown in formula (I)), with -CON(C1-5 alkyl)(C1-5 alkyl), preferably with -CON(CH3)2. In an eighteenth specific embodiment of the compound of formula (I), -YC2-RC2 is heterocycloalkyl, wherein said heterocycle comprises a spiro ring system, optionally selected from 2-oxaspiro[3.5]non-6- en-7-yl, 2-oxaspiro[3.5]non-7-yl, 2-oxa-8-azaspiro[4.5]dec-8-yl, 9-oxa-3-azaspiro[5.5]undec-3-yl, 2-oxa-6- azaspiro[3.4]oct-6-yl, 1-oxa-7-azaspiro[3.5]non-7-yl, 1-oxa-8-azaspiro[4.5]dec-8-yl, 6-oxa-2- azaspiro[3.3]hept-2-yl, 2,8-diazaspiro[4.5]dec-8-yl, 7-oxa-3-azabicyclo[3.3.0]oct-3-yl, 8-oxa-3- azabicyclo[4.3.0]non-3-yl, 2-oxa-6-azaspiro[3.5]non-6-yl, 7-oxo-3,6,8-triazabicyclo[4.3.0]non-3-yl, 3- pyrrolino[3,4-c]pyrazol-2-yl, 3,6- diazabicyclo[3.1.1]hept-3-yl, and 2,7-diazaspiro[3.5]non-7-yl. In a nineteenth specific embodiment of the compound of formula (I), -YC2-RC2 is heterocycloalkenyl, wherein said heterocycloalkenyl is optionally substituted with one or more groups independently selected from RS2. Preferably, in this nineteenth specific embodiment, -YC2-RC2 is oxacyclohexenyl or azacyclohexenyl, optionally substituted with one or more groups independently selected from RS2. More preferably, -YC2-RC2 is azacyclohexenyl substituted (preferably N-substituted) with -CON(C1-5 alkyl)(C1-5 alkyl), preferably with -CON(CH3)2. In a twentieth specific embodiment of the compound of formula (I), -YC2-RC2 is selected from: optionally substituted with a methyl group. In a twenty-first specific embodiment of the compound of formula (I), -YC2-RC2 is selected from: ,, alkyl) alkyl) . In a twenty-second specific embodiment of the compound of formula (I), -YC2-RC2 is .In a twenty-third specific embodiment of the compound of formulapreferably In a in a twenty-fourth specific embodiment of the compound of formula (I), -YC2-RC2 is In a twenty-sixth specific embodiment of the compound of formula (I), -YC2-RC2 is . Accordingly, -YC2-RC2 is selected from In a twenty-seventh specific embodiment of the compound of formula (I), -YC2-RC2 is selected from (preferably selected from In a twenty-eighth specific embodiment of the compound of formula (I), -YC2-RC2 is selected from In a twenty-ninth specific embodiment of the compound of formula (I), R4 is a heteroaryl optionally substituted with one or more RS2. In this thirtieth specific embodiment, preferably R4 is selected from . In a thirtieth specific embodiment of the compound of formula (I), X4 is C-R5 wherein R5 is hydrogen. It is preferred than X5 is N. In a thirty-first specific embodiment of the compound of formula (I), X4 is C-R5 wherein R5 is -F. It is preferred than X5 is N. In a thirty-second specific embodiment of the compound of formula (I), X4 is N and X5 is C-R6. In a thirty-third specific embodiment of the compound of formula (I), X4 is N and X5 is N. In a thirty-fourth specific embodiment, R1 is -CN, R2 is -H and R3 is methyl. In a thirty-fifth specific embodiment, R1 is methyl, R2 is -H and R3 is -F. In a thirty-fifth specific embodiment, R1 is methyl, R2 is -H and R3 is ethyl. It is to be understood that, in each of the specific embodiments of the compound of formula (I) as recited hereinabove, the definitions of any of Z, R1, R2, R3, R4, R5, and X2 which are not explicitly recited in the disclosure of said specific embodiments, are as in formula (I) hereinabove. The compound of formula (I) may be a compound of formula (Ia): or a pharmaceutically acceptable salt thereof. In formula (Ia), R1, R2, R3, R4, R5 and X2 are defined as for formula (I), including any specific embodiment of the compound of formula (I). Preferably, in formula (Ia), R1 is methyl, R2 is -H, and R3 is methyl. Preferably, in formula (Ia), R4 is a heteroaryl optionally substituted with one or more RS2,preferably selected from Most preferably, in the compound of formula Preferably, in formula (Ia), R5is -H or -F. More preferably, R5is -H. However, alternatively, R5can be -F. Preferably, in formula (Ia), -YC2-RC2 is selected from Alternatively, The compound of formula (Ia) may be a compound of formula (Ia-1): (Ia-1) or a pharmaceutically acceptable salt thereof. In formula (Ia-1), R1, R2, R3, R4, R5 and X2 are defined as for formula (I), including any specific embodiment of the compound of formula (I), or as defined for formula (Ia). The compound of formula (Ia) may be a compound of formula (Ia-2): or a pharmaceutically acceptable salt thereof. In formula (Ia-2), R1, R2, R3, R4, R5 and X2 are defined as for formula (I), including any specific embodiment of the compound of formula (I), or as defined for formula (Ia). The compound of formula (Ia) may be a compound of formula (Ia-2): (Ia-3) or a pharmaceutically acceptable salt thereof. In formula (Ia-3), R1, R2, R3, R4, R5 and X2 are defined as for formula (I), including any specific embodiment of the compound of formula (I), or as defined for formula (Ia). The compound of formula (Ia) may be a compound of formula (Ia-4): or a pharmaceutically acceptable salt thereof. In formula (Ia-4), R1, R2, R3, R4, R5 and X2 are defined as for formula (I), including any specific embodiment of the compound of formula (I), or as defined for formula (Ia). Considering the stereoconfiguration of the chiral centers in the substituted cyclopropyl group of the compound of formula (Ia), the present inventors have purified diastereoisomers of an exemplarycompound 1 and have found that particularly advantageous properties are shown by the compound 1a.This diastereoisomer can also be defined as a diastereoisomer characterized by the shortest retention time when purified using SFC according to Method 1 described herein. It is accordingly preferred that the compound of formula (Ia) has the same stereoconfiguration ofthe chiral centers in the substituted cyclopropyl moiety as in the exemplary compound 1a. This applies inparticular if R1, R2, and R3, is as in compound or compound 1a, i.e. R1 is methyl, R2 is H and R3 ismethyl.Particularly preferred compound of formula (I)pharmaceutically acceptable salt. Accordingly, a particularly preferred compound of formula (I) may be its pharmaceutically acceptable salt. Alternatively, a particularly preferred compound of formula (I) may be its pharmaceutically acceptable salt. Alternatively, a particularly preferred compound of formula (I) may be its pharmaceutically acceptable salt. Alternatively, a particularly preferred compound of formula (I) may be its pharmaceutically acceptable salt. In other words, a particularly preferred compound of formula (I) is 1a.As understood herein, the compound 1a is a compound according to formula: . In one, particularly preferred embodiment, the compound of formula (I) is a compound of formula (Ib): or its pharmaceutically acceptable salt. In formula (Ib), R4, R5 and X2 are defined as for formula (I), including any specific embodiment of the compound of formula (I), or as defined for formula (Ia). Particularly preferred compound of formula (I) is selected from the following compounds, and their pharmaceutically acceptable salts: 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-1,2-dimethylcyclopropyl)-8-((3S,5S)-3,5-dimethylpiperazin- 1-yl)imidazo[1,5-a]pyridine-6-sulfonamide; 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-8-((3S,5S)-3,5-dimethylpiperazin-1-yl)-N-(2-fluoro-1- methylcyclopropyl)imidazo[1,5-a]pyridine-6-sulfonamide; N-1-cyano-2-methylcyclopropyl)-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-8-(-5-(methoxymethyl)-3,3- dimethylpiperazin-1-yl)imidazo[1,5-a]pyridine-6-sulfonamide; 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-(1,2-dimethylcyclopropyl)-8-((3S,5S)-3,5-dimethylpiperazin- 1-yl)-[1,2,4]triazolo[4,3-a]pyridine-6-sulfonamide; N-( 1-cyano-2-methylcyclopropyl)-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-8-((3S,5S)-3,5- dimethylpiperazin-1-yl)imidazo[1,5-a]pyridine-6-sulfonamide; 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-8-((3S,5S)-3,5-dimethylpiperazin-1-yl)-N-(1,2,2- trimethylcyclopropyl)imidazo[1,5-a]pyridine-6-sulfonamide; 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-(1,2-dimethylcyclopropyl)-8-(5-(hydroxymethyl)-3,3- dimethylpiperazin-1-yl)imidazo[1,5-a]pyridine-6-sulfonamide; 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-(1,2-dimethylcyclopropyl)-8-((3S,5S)-3,5-dimethylpiperazin- 1-yl)-1-fluoroimidazo[1,5-a]pyridine-6-sulfonamide; 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-(1,2-dimethylcyclopropyl)-8-((3S,5S)-3,5-dimethylpiperazin- 1-yl)imidazo[1,2-a]pyridine-6-sulfonamide; 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-(1,2-dimethylcyclopropyl)-8-((3S,5S)-3,5-dimethylpiperazin- 1-yl)indolizine-6-sulfonamide; 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-1,2-dimethylcyclopropyl)-8-(3,3-dimethylpiperazin-1- yl)imidazo[1,5-a]pyridine-6-sulfonamide; 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-1,2-dimethylcyclopropyl)-8-(3-methylpiperazin-1- yl)imidazo[1,5-a]pyridine-6-sulfonamide (preferably 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-1,2- dimethylcyclopropyl)-8-((S)-3-methylpiperazin-1-yl)imidazo[1,5-a]pyridine-6-sulfonamide); 8-chloro-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-(1,2-dimethylcyclopropyl)imidazo[1,2-a]pyridine-6- sulfonamide; 8-chloro-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-(1,2-dimethylcyclopropyl)indolizine-6-sulfonamide; 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-8-((3S,5S)-3,5-dimethylpiperazin-1-yl)-N-(2-ethyl-1- methylcyclopropyl)imidazo[1,5-a]pyridine-6-sulfonamide; 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-8-((3S,5S)-3,5-dimethylpiperazin-1-yl)-N-(1-methyl-2-(methyl- d3)cyclopropyl-2,3,3-d3)imidazo[1,5-a]pyridine-6-sulfonamide; N-(1-cyano-2-methylcyclopropyl)-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-8-(3,3,5-trimethylpiperazin- 1-yl)imidazo[1,5-a]pyridine-6-sulfonamide; 1-cyano-2-methylcyclopropyl)-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-8-(5-(hydroxymethyl)-3,3- dimethylpiperazin-1-yl)imidazo[1,5-a]pyridine-6-sulfonamide; 8-chloro-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-(2-fluoro-1-methylcyclopropyl)imidazo[1,5- a]pyridine-6-sulfonamide;and 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-8-((2S,6S)-2,6-dimethylmorpholino)-N-2-fluoro-1- methylcyclopropyl)imidazo[1,5-a]pyridine-6-sulfonamide. Preferably, the compound of formula (I) is selected from the following compounds, and their pharmaceutically acceptable salts: 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-1,2-dimethylcyclopropyl)-8-((3S,5S)-3,5-dimethylpiperazin- 1-yl)imidazo[1,5-a]pyridine-6-sulfonamide; 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-8-((3S,5S)-3,5-dimethylpiperazin-1-yl)-N-(2-fluoro-1- methylcyclopropyl)imidazo[1,5-a]pyridine-6-sulfonamide; N-1-cyano-2-methylcyclopropyl)-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-8-(-5-(methoxymethyl)-3,3- dimethylpiperazin-1-yl)imidazo[1,5-a]pyridine-6-sulfonamide; 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-(1,2-dimethylcyclopropyl)-8-((3S,5S)-3,5-dimethylpiperazin- 1-yl)-[1,2,4]triazolo[4,3-a]pyridine-6-sulfonamide; N-( 1-cyano-2-methylcyclopropyl)-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-8-((3S,5S)-3,5- dimethylpiperazin-1-yl)imidazo[1,5-a]pyridine-6-sulfonamide; 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-8-((3S,5S)-3,5-dimethylpiperazin-1-yl)-N-(1,2,2- trimethylcyclopropyl)imidazo[1,5-a]pyridine-6-sulfonamide; 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-(1,2-dimethylcyclopropyl)-8-(5-(hydroxymethyl)-3,3- dimethylpiperazin-1-yl)imidazo[1,5-a]pyridine-6-sulfonamide; 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-(1,2-dimethylcyclopropyl)-8-((3S,5S)-3,5-dimethylpiperazin- 1-yl)-1-fluoroimidazo[1,5-a]pyridine-6-sulfonamide; 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-(1,2-dimethylcyclopropyl)-8-((3S,5S)-3,5-dimethylpiperazin- 1-yl)imidazo[1,2-a]pyridine-6-sulfonamide; 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-(1,2-dimethylcyclopropyl)-8-((3S,5S)-3,5-dimethylpiperazin- 1-yl)indolizine-6-sulfonamide; 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-1,2-dimethylcyclopropyl)-8-(3,3-dimethylpiperazin-1- yl)imidazo[1,5-a]pyridine-6-sulfonamide; 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-1,2-dimethylcyclopropyl)-8-(3-methylpiperazin-1- yl)imidazo[1,5-a]pyridine-6-sulfonamide (preferably 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-1,2- dimethylcyclopropyl)-8-((S)-3-methylpiperazin-1-yl)imidazo[1,5-a]pyridine-6-sulfonamide); 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-8-((3S,5S)-3,5-dimethylpiperazin-1-yl)-N-(2-ethyl-1- methylcyclopropyl)imidazo[1,5-a]pyridine-6-sulfonamide; 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-8-((3S,5S)-3,5-dimethylpiperazin-1-yl)-N-(1-methyl-2-(methyl- d3)cyclopropyl-2,3,3-d3)imidazo[1,5-a]pyridine-6-sulfonamide; N-(1-cyano-2-methylcyclopropyl)-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-8-(3,3,5-trimethylpiperazin- 1-yl)imidazo[1,5-a]pyridine-6-sulfonamide; 1-cyano-2-methylcyclopropyl)-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-8-(5-(hydroxymethyl)-3,3- dimethylpiperazin-1-yl)imidazo[1,5-a]pyridine-6-sulfonamide; and 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-8-((2S,6S)-2,6-dimethylmorpholino)-N-2-fluoro-1- methylcyclopropyl)imidazo[1,5-a]pyridine-6-sulfonamide. More preferably, the compound of formula (I) is selected from the following compounds, and their pharmaceutically acceptable salts: 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-1,2-dimethylcyclopropyl)-8-((3S,5S)-3,5-dimethylpiperazin- 1-yl)imidazo[1,5-a]pyridine-6-sulfonamide; 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-(1,2-dimethylcyclopropyl)-8-((3S,5S)-3,5-dimethylpiperazin- 1-yl)-[1,2,4]triazolo[4,3-a]pyridine-6-sulfonamide; 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-(1,2-dimethylcyclopropyl)-8-(5-(hydroxymethyl)-3,3- dimethylpiperazin-1-yl)imidazo[1,5-a]pyridine-6-sulfonamide; 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-(1,2-dimethylcyclopropyl)-8-((3S,5S)-3,5-dimethylpiperazin- 1-yl)-1-fluoroimidazo[1,5-a]pyridine-6-sulfonamide; 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-(1,2-dimethylcyclopropyl)-8-((3S,5S)-3,5-dimethylpiperazin- 1-yl)imidazo[1,2-a]pyridine-6-sulfonamide; 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-(1,2-dimethylcyclopropyl)-8-((3S,5S)-3,5-dimethylpiperazin- 1-yl)indolizine-6-sulfonamide; 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-1,2-dimethylcyclopropyl)-8-(3,3-dimethylpiperazin-1- yl)imidazo[1,5-a]pyridine-6-sulfonamide; and 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-1,2-dimethylcyclopropyl)-8-(3-methylpiperazin-1- yl)imidazo[1,5-a]pyridine-6-sulfonamide (preferably 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-1,2- dimethylcyclopropyl)-8-((S)-3-methylpiperazin-1-yl)imidazo[1,5-a]pyridine-6-sulfonamide). More preferably, the compound of formula (I) is selected from the following compounds, and their pharmaceutically acceptable salts: 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-(1S,2R)-1,2-dimethylcyclopropyl)-8-((3S,5S)-3,5- dimethylpiperazin-1-yl)imidazo[1,5-a]pyridine-6-sulfonamide; 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-(1S,2R)-(1,2-dimethylcyclopropyl)-8-((3S,5S)-3,5- dimethylpiperazin-1-yl)-[1,2,4]triazolo[4,3-a]pyridine-6-sulfonamide; 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-(1S,2R)-(1,2-dimethylcyclopropyl)-8-(5-(hydroxymethyl)- 3,3-dimethylpiperazin-1-yl)imidazo[1,5-a]pyridine-6-sulfonamide; 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-(1S,2R)-(1,2-dimethylcyclopropyl)-8-((3S,5S)-3,5- dimethylpiperazin-1-yl)-1-fluoroimidazo[1,5-a]pyridine-6-sulfonamide; 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-(1S,2R)-(1,2-dimethylcyclopropyl)-8-((3S,5S)-3,5- dimethylpiperazin-1-yl)imidazo[1,2-a]pyridine-6-sulfonamide; 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-(1S,2R)-(1,2-dimethylcyclopropyl)-8-((3S,5S)-3,5- dimethylpiperazin-1-yl)indolizine-6-sulfonamide; 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-(1S,2R)-1,2-dimethylcyclopropyl)-8-(3,3-dimethylpiperazin- 1-yl)imidazo[1,5-a]pyridine-6-sulfonamide; and 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-(1S,2R)-1,2-dimethylcyclopropyl)-8-(3-methylpiperazin-1- yl)imidazo[1,5-a]pyridine-6-sulfonamide (preferably 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N- (1S,2R)-1,2-dimethylcyclopropyl)-8-((S)-3-methylpiperazin-1-yl)imidazo[1,5-a]pyridine-6-sulfonamide). Even more preferably, the compound of formula (I) is 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)- N-(1S,2R)-dimethylcyclopropyl)-8-((3S,5S)-3,5-dimethylpiperazin-1-yl)imidazo[1,5-a]pyridine-6- sulfonamide or its pharmaceutically acceptable salt. Further preferred compound of formula (I) is selected from: Cis-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-8-((3S,5S)-3,5-dimethylpiperazin-1-yl)-N-(2- fluoro-1-methylcyclopropyl)imidazo[1,5-a]pyridine-6-sulfonamide and N-((cis)-1-cyano-2-methylcyclopropyl)-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-8-(5- (methoxymethyl)-3,3-dimethylpiperazin-1-yl)imidazo[1,5-a]pyridine-6-sulfonamide or its pharmaceutically acceptable salt. As understood herein, cis-3-(5-(difluoromethyl)-1,3,4- thiadiazol-2-yl)-8-((3S,5S)-3,5-dimethylpiperazin-1-yl)-N-(2-fluoro-1-methylcyclopropyl)imidazo[1,5-a]pyridine-6-sulfonamide is selected from . As understood herein, N-((cis)-1-cyano-2-methylcyclopropyl)-3-(5- (difluoromethyl)-1,3,4-thiadiazol-2-yl)-8-(5-(methoxymethyl)-3,3-dimethylpiperazin-1-yl)imidazo[1,5- , Each of the compounds recited in the foregoing is further provided in its each possible stereoisomeric form (such as enantiomeric / diastereomeric form). Accordingly, reference to a particular compounds includes individual and specific evidence to each of its stereoisomers. Further particularly preferred is a compound selected from the compounds disclosed in Table 1 or Table 2, or its pharmaceutically acceptable salt (or a salt-free form). As understood herein, 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-8-((3S,5S)-3,5-dimethylpiperazin-1-yl)-N-(2-fluoro-1-methylcyclopropyl)imidazo[1,5-a]pyridine-6-sulfonamide preferably is Cis-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-8-((3S,5S)-3,5-dimethylpiperazin-1-yl)-N-(2-fluoro-1- methylcyclopropyl)imidazo[1,5-a]pyridine-6-sulfonamide. As understood herein, N-(1-cyano-2-methylcyclopropyl)-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2- yl)-8-(-5-(methoxymethyl)-3,3-dimethylpiperazin-1-yl)imidazo[1,5-a]pyridine-6-sulfonamide preferably is N-((cis)-1-cyano-2-methylcyclopropyl)-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-8-(-5-(methoxymethyl)- 3,3-dimethylpiperazin-1-yl)imidazo[1,5-a]pyridine-6-sulfonamide. As understood herein, N-(1-cyano-2-methylcyclopropyl)-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2- yl)-8-((3S,5S)-3,5-dimethylpiperazin-1-yl)imidazo[1,5-a]pyridine-6-sulfonamide is preferably trans-N-( 1- cyano-2-methylcyclopropyl)-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-8-((3S,5S)-3,5-dimethylpiperazin- 1-yl)imidazo[1,5-a]pyridine-6-sulfonamide or cis-N-( 1-cyano-2-methylcyclopropyl)-3-(5-(difluoromethyl)- 1,3,4-thiadiazol-2-yl)-8-((3S,5S)-3,5-dimethylpiperazin-1-yl)imidazo[1,5-a]pyridine-6-sulfonamide. As understood herein, trans-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-8-((3S,5S)-3,5-dimethylpiperazin-1-yl)-N-(2-fluoro-1-methylcyclopropyl)imidazo[1,5-a]pyridine-6-sulfonamide ispreferably trans-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-8-((3S,5S)-3,5-dimethylpiperazin-1-yl)-N-(2- fluoro-1-methylcyclopropyl)imidazo[1,5-a]pyridine-6-sulfonamide. As understood herein, 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-8-((3S,5S)-3,5-dimethylpiperazin-1-yl)-N-(2-ethyl-1-methylcyclopropyl)imidazo[1,5-a]pyridine-6-sulfonamide ispreferably 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-8-((3S,5S)-3,5-dimethylpiperazin-1-yl)-N-((cis)-2- ethyl-1-methylcyclopropyl)imidazo[1,5-a]pyridine-6-sulfonamide. As understood herein, 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-8-((3S,5S)-3,5-dimethylpiperazin-1-yl)-N-2-ethyl-1-methylcyclopropyl)imidazo[1,5-a]pyridine-6-sulfonamide is preferably 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-8-((3S,5S)-3,5-dimethylpiperazin-1-yl)-N-(trans)-2-ethyl-1- methylcyclopropyl)imidazo[1,5-a]pyridine-6-sulfonamide. As understood herein, 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-8-((3S,5S)-3,5-dimethylpiperazin-1-yl)-N-(2-ethyl-1-methylcyclopropyl)imidazo[1,5-a]pyridine-6-sulfonamide ispreferably 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-8-((3S,5S)-3,5-dimethylpiperazin-1-yl)-N-((cis)-2- ethyl-1-methylcyclopropyl)imidazo[1,5-a]pyridine-6-sulfonamide or 3-(5-(difluoromethyl)-1,3,4-thiadiazol- 2-yl)-8-((3S,5S)-3,5-dimethylpiperazin-1-yl)-N-(trans)-2-ethyl-1-methylcyclopropyl)imidazo[1,5- a]pyridine-6-sulfonamide As understood herein, N-(1-cyano-2-methylcyclopropyl)-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2- yl)-8-(3,3,5-trimethylpiperazin-1-yl)imidazo[1,5-a]pyridine-6-sulfonamide is preferably N-((cis)-1-cyano-2- methylcyclopropyl)-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-8-(3,3,5-trimethylpiperazin-1- yl)imidazo[1,5-a]pyridine-6-sulfonamide or N-((trans)-1-cyano-2-methylcyclopropyl)-3-(5-(difluoromethyl)- 1,3,4-thiadiazol-2-yl)-8-(3S,3,5-trimethylpiperazin-1-yl)imidazo[1,5-a]pyridine-6-sulfonamide. As understood herein, N-(1-cyano-2-methylcyclopropyl)-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2- yl)-8-(5-(hydroxymethyl)-3,3-dimethylpiperazin-1-yl)imidazo[1,5-a]pyridine-6-sulfonamide is preferably N- ((cis)-1-cyano-2-methylcyclopropyl)-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-8-(5-(hydroxymethyl)-3,3- dimethylpiperazin-1-yl)imidazo[1,5-a]pyridine-6-sulfonamide. As understood herein, N-(1-cyano-2-methylcyclopropyl)-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2- yl)-8-(5-(hydroxymethyl)-3,3-dimethylpiperazin-1-yl)imidazo[1,5-a]pyridine-6-sulfonamide is preferably N- ((cis)-1-cyano-2-methylcyclopropyl)-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-8-(5-(hydroxymethyl)-3,3- dimethylpiperazin-1-yl)imidazo[1,5-a]pyridine-6-sulfonamide. As understood herein, 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-8-((2S,6S)-2,6-dimethylmorpholino)-N-(2-fluoro-1-methylcyclopropyl)imidazo[1,5-a]pyridine-6-sulfonamide is preferably 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-8-((2S,6S)-2,6-dimethylmorpholino)-N-((cis)-2-fluoro-1- methylcyclopropyl)imidazo[1,5-a]pyridine-6-sulfonamide. It is to be understood that whenever reference is made to formula (I), it includes any preferred definition of the compound of formula (I), as well as any example of the compound of formula (I), as well as examples and definitions of the compounds of formula (Ia). The present invention also relates to each of the intermediates described further below in the examples section of this specification, including any one of these intermediates in non-salt form or in the form of a salt (e.g., a pharmaceutically acceptable salt) of the respective compound. Such intermediates can be used, in particular, in the synthesis of the compounds of formula (I). The scope of the invention embraces all pharmaceutically acceptable salt forms of the compounds of formula (I) which may be formed, e.g., by protonation of an atom carrying an electron lone pair which is susceptible to protonation, such as an amino group, with an inorganic or organic acid, or as a salt of an acid group (such as a carboxylic acid group) with a physiologically acceptable cation. Exemplary base addition salts comprise, for example: alkali metal salts such as sodium or potassium salts; alkaline earth metal salts such as calcium or magnesium salts; zinc salts; ammonium salts; aliphatic amine salts such as trimethylamine, triethylamine, dicyclohexylamine, ethanolamine, diethanolamine, triethanolamine, procaine salts, meglumine salts, ethylenediamine salts, or choline salts; aralkyl amine salts such as N,N- dibenzylethylenediamine salts, benzathine salts, benethamine salts; heterocyclic aromatic amine salts such as pyridine salts, picoline salts, quinoline salts or isoquinoline salts; quaternary ammonium salts such as tetramethylammonium salts, tetraethylammonium salts, benzyltrimethylammonium salts, benzyltriethylammonium salts, benzyltributylammonium salts, methyltrioctylammonium salts or tetrabutylammonium salts; and basic amino acid salts such as arginine salts, lysine salts, or histidine salts. Exemplary acid addition salts comprise, for example: mineral acid salts such as hydrochloride, hydrobromide, hydroiodide, sulfate salts (such as, e.g., sulfate or hydrogensulfate salts), nitrate salts, phosphate salts (such as, e.g., phosphate, hydrogenphosphate, or dihydrogenphosphate salts), carbonate salts, hydrogencarbonate salts, perchlorate salts, borate salts, or thiocyanate salts; organic acid salts such as acetate, propionate, butyrate, pentanoate, hexanoate, heptanoate, octanoate, cyclopentanepropionate, decanoate, undecanoate, oleate, stearate, lactate, maleate, oxalate, fumarate, tartrate, malate, citrate, succinate, adipate, gluconate, glycolate, nicotinate, benzoate, salicylate, ascorbate, pamoate (embonate), camphorate, glucoheptanoate, or pivalate salts; sulfonate salts such as methanesulfonate (mesylate), ethanesulfonate (esylate), 2-hydroxyethanesulfonate (isethionate), benzenesulfonate (besylate), p-toluenesulfonate (tosylate), 2-naphthalenesulfonate (napsylate), 3-phenylsulfonate, or camphorsulfonate salts; glycerophosphate salts; and acidic amino acid salts such as aspartate or glutamate salts. Preferred pharmaceutically acceptable salts of the compounds of formula (I) include a hydrochloride salt, a hydrobromide salt, a mesylate salt, a sulfate salt, a tartrate salt, a fumarate salt, an acetate salt, a citrate salt, and a phosphate salt. A particularly preferred pharmaceutically acceptable salt of the compound of formula (I) is a hydrochloride salt. Accordingly, it is preferred that the compound of formula (I), including any one of the specific compounds of formula (I) described herein, is in the form of a hydrochloride salt, a hydrobromide salt, a mesylate salt, a sulfate salt, a tartrate salt, a fumarate salt, an acetate salt, a citrate salt, or a phosphate salt, and it is particularly preferred that the compound of formula (I) is in the form of a hydrochloride salt. The present invention also specifically relates to the compound of formula (I), including any one of the specific compounds of formula (I) described herein, in non-salt form. Moreover, the scope of the invention embraces the compounds of formula (I) in any solvated form, including, e.g., solvates with water (i.e., as a hydrate) or solvates with organic solvents such as, e.g., methanol, ethanol, isopropanol, acetic acid, ethyl acetate, ethanolamine, DMSO, or acetonitrile. All physical forms, including any amorphous or crystalline forms (i.e., polymorphs), of the compounds of formula (I) are also encompassed within the scope of the invention. It is to be understood that such solvates and physical forms of pharmaceutically acceptable salts of the compounds of the formula (I) are likewise embraced by the invention. Furthermore, the compounds of formula (I) may exist in the form of different isomers, in particular stereoisomers (including, e.g., geometric isomers (or cis / trans isomers), enantiomers and diastereomers) or tautomers (including, in particular, prototropic tautomers, such as keto / enol tautomers or thione / thiol tautomers). All such isomers of the compounds of formula (I) are contemplated as being part of the present invention, either in admixture or in pure or substantially pure form. As for stereoisomers, the invention embraces the isolated optical isomers of the compounds according to the invention as well as any mixtures thereof (including, in particular, racemic mixtures / racemates). The racemates can be resolved by physical methods, such as, e.g., fractional crystallization, separation or crystallization of diastereomeric derivatives, or separation by chiral column chromatography. The individual optical isomers can also be obtained from the racemates via salt formation with an optically active acid followed by crystallization. The present invention further encompasses any tautomers of the compounds of formula (I). It will be understood that some compounds may exhibit tautomerism. In such cases, the formulae provided herein expressly depict only one of the possible tautomeric forms. The formulae and chemical names as provided herein are intended to encompass any tautomeric form of the corresponding compound and not to be limited merely to the specific tautomeric form depicted by the drawing or identified by the name of the compound. The scope of the invention also embraces compounds of formula (I), in which one or more atoms are replaced by a specific isotope of the corresponding atom. For example, the invention encompasses compounds of formula (I), in which one or more hydrogen atoms (or, e.g., all hydrogen atoms) are replacedby deuterium atoms (i.e., 2H; also referred to as “D”). Accordingly, the invention also embraces compoundsof formula (I) which are enriched in deuterium. Naturally occurring hydrogen is an isotopic mixture comprising about 99.98 mol-% hydrogen-1 (1H) and about 0.0156 mol-% deuterium (2H or D). The content of deuterium in one or more hydrogen positions in the compounds of formula (I) can be increased using deuteration techniques known in the art. For example, a compound of formula (I) or a reactant or precursor to be used in the synthesis of the compound of formula (I) can be subjected to an H / D exchange reaction using, e.g., heavy water (D2O). Further suitable deuteration techniques are described in: Atzrodt J et al.,Bioorg Med Chem, 20(18), 5658-5667, 2012; William JS et al., Journal of Labelled Compounds andRadiopharmaceuticals, 53(11-12), 635-644, 2010; Modvig A et al., J Org Chem, 79, 5861-5868, 2014.The content of deuterium can be determined, e.g., using mass spectrometry or NMR spectroscopy. Unless specifically indicated otherwise, it is preferred that the compound of formula (I) is not enriched indeuterium. Accordingly, the presence of naturally occurring hydrogen atoms or 1H hydrogen atoms in thecompounds of formula (I) is preferred. The present invention also embraces compounds of formula (I), in which one or more atoms arereplaced by a positron-emitting isotope of the corresponding atom, such as, e.g., 18F, 11C, 13N, 15O, 76Br,77Br, 120I and / or 124I. Such compounds can be used as tracers, trackers or imaging probes in positronemission tomography (PET). The invention thus includes (i) compounds of formula (I), in which one ormore fluorine atoms (or, e.g., all fluorine atoms) are replaced by 18F atoms, (ii) compounds of formula (I),in which one or more carbon atoms (or, e.g., all carbon atoms) are replaced by 11C atoms, (iii) compoundsof formula (I), in which one or more nitrogen atoms (or, e.g., all nitrogen atoms) are replaced by 13N atoms,(iv) compounds of formula (I), in which one or more oxygen atoms (or, e.g., all oxygen atoms) are replacedby 15O atoms, (v) compounds of formula (I), in which one or more bromine atoms (or, e.g., all bromineatoms) are replaced by 76Br atoms, (vi) compounds of formula (I), in which one or more bromine atoms(or, e.g., all bromine atoms) are replaced by 77Br atoms, (vii) compounds of formula (I), in which one ormore iodine atoms (or, e.g., all iodine atoms) are replaced by 120I atoms, and (viii) compounds of formula(I), in which one or more iodine atoms (or, e.g., all iodine atoms) are replaced by 124I atoms. In general, itis preferred that none of the atoms in the compounds of formula (I) are replaced by specific isotopes. The present invention further embraces the prodrugs of the compounds of formula (I). As preferably understood herein, the term “prodrug” of the compound of formula (I) refers to a derivative of the compounds of formula (I) that upon administration to a subject becomes metabolized to the said compound of formula (I). Said prodrugs of the compound of formula (I) may include modifications of -OH, -NH2, or -COOH group if present in the compound of formula (I), which preferably can be hydrolyzed to - OH, -NH2, or -COOH groups, respectively, e.g. upon administration to the subject. For example, as known to the skilled person, such prodrugs may preferably include for the compounds of formula (I) which comprise -OH moiety derivatives wherein said -OH moiety is turned into an -ORxmoiety, wherein Rxpreferably comprises a moiety selected from -CO-, -CH2-O-CO, -CH2-O-CO-O-, and -CH(CH3)-O-COO-, more preferably wherein Rx is selected from -CO-Ry, -CH2-O-CO-Ry, -CH2-O-CO-O-Ry, and -CH(CH3)-O- COO-Ry, wherein Ry is preferably carbocyclyl, heterocyclyl, C1-5 alkyl, -NH-(C1-5 alkyl) or -S-(C1-5 alkyl), wherein the said alkyl is optionally substituted with a group selected from halogen, -CN, -OH, C1-5 alkyl, C1-5 haloalkyl, -O(C1-5 alkyl), -O(C1-5 haloalkyl), -SH, -S(C1-5 alkyl), -S(C1-5 haloalkyl), -NH2, -NH(C1-5 alkyl), -NH(C1-5 haloalkyl), -N(C1-5 alkyl)(C1-5 alkyl), -N(C1-5 haloalkyl)(C1-5 alkyl), -CONH2, -CONH(C1-5 alkyl), and -CON(C1-5 alkyl)(C1-5 alkyl), and wherein the said carbocyclyl and heterocyclyl are each optionally substituted with a group selected from halogen, -CN, -OH, C1-5 alkyl, C1-5 haloalkyl, -O(C1-5 alkyl), -O(C1-5 haloalkyl), -SH, -S(C1-5 alkyl), -S(C1-5 haloalkyl), -NH2, -NH(C1-5 alkyl), -NH(C1-5 haloalkyl), -N(C1-5 alkyl)(C1-5 alkyl), -N(C1-5 haloalkyl)(C1-5 alkyl), -CONH2, -CONH(C1-5 alkyl), and -CON(C1-5 alkyl)(C1-5 alkyl). Furthermore, for example, as known to the skilled person, such prodrugs may preferably include for the compounds of formula (I) which comprise -NH2 moiety derivatives wherein said -NH2 moiety is turned into -NHCOO-Ry moiety, wherein Ry is as defined hereinabove. Furthermore, for examples, as known to the skilled person, such prodrugs may preferably include for the compounds of formula (I) which comprise -COOH moiety derivatives wherein said -COOH group is turned into -COORy moiety, wherein Ry is as defined hereinabove. Further examples of groups that can be derivatized to yield prodrugs are known to the skilled person. Pharmaceutical compositions The compounds provided herein may be administered as compounds per se or may be formulatedas medicaments. The medicaments / pharmaceutical compositions may optionally comprise one or more pharmaceutically acceptable excipients, such as carriers, diluents, fillers, disintegrants, lubricating agents, binders, colorants, pigments, stabilizers, preservatives, antioxidants, and / or solubility enhancers. The pharmaceutical compositions may comprise one or more solubility enhancers, such as, e.g., poly(ethylene glycol), including poly(ethylene glycol) having a molecular weight in the range of about 200 to about 5,000 Da (e.g., PEG 200, PEG 300, PEG 400, or PEG 600), ethylene glycol, propylene glycol, glycerol, a non-ionic surfactant, tyloxapol, polysorbate 80, macrogol-15-hydroxystearate (e.g., Kolliphor®HS 15, CAS 70142-34-6), a phospholipid, lecithin, dimyristoyl phosphatidylcholine, dipalmitoylphosphatidylcholine, distearoyl phosphatidylcholine, a cyclodextrin, -cyclodextrin, -cyclodextrin, -cyclodextrin, hydroxyethyl- -cyclodextrin, hydroxypropyl- -cyclodextrin, hydroxyethyl- -cyclodextrin,hydroxypropyl- -cyclodextrin, dihydroxypropyl- -cyclodextrin, sulfobutylether- -cyclodextrin,sulfobutylether- -cyclodextrin, glucosyl- -cyclodextrin, glucosyl- -cyclodextrin, diglucosyl- -cyclodextrin,maltosyl- -cyclodextrin, maltosyl- -cyclodextrin, maltosyl- -cyclodextrin, maltotriosyl- -cyclodextrin,maltotriosyl- -cyclodextrin, dimaltosyl- -cyclodextrin, methyl- -cyclodextrin, a carboxyalkyl thioether,hydroxypropyl methylcellulose, hydroxypropylcellulose, polyvinylpyrrolidone, a vinyl acetate copolymer, vinyl pyrrolidone, sodium lauryl sulfate, dioctyl sodium sulfosuccinate, or any combination thereof. The pharmaceutical compositions may also comprise one or more preservatives, particularly one or more antimicrobial preservatives, such as, e.g., benzyl alcohol, chlorobutanol, 2-ethoxyethanol, m-cresol, chlorocresol (e.g., 2-chloro-3-methyl-phenol or 4-chloro-3-methyl-phenol), benzalkonium chloride, benzethonium chloride, benzoic acid (or a pharmaceutically acceptable salt thereof), sorbic acid (or a pharmaceutically acceptable salt thereof), chlorhexidine, thimerosal, or any combination thereof. The pharmaceutical compositions can be formulated by techniques known to the person skilled in the art, such as the techniques published in “Remington: The Science and Practice of Pharmacy”, Pharmaceutical Press, 22ndedition. The pharmaceutical compositions can be formulated as dosage forms for oral, parenteral, such as intramuscular, intravenous, subcutaneous, intradermal, intraarterial, intracardial, rectal, nasal, topical, aerosol or vaginal administration. Dosage forms for oral administration include coated and uncoated tablets, soft gelatin capsules, hard gelatin capsules, lozenges, troches, solutions, emulsions, suspensions, syrups, elixirs, powders and granules for reconstitution, dispersible powders and granules, medicated gums, chewing tablets and effervescent tablets. Dosage forms for parenteral administration include solutions, emulsions, suspensions, dispersions and powders and granules for reconstitution. Emulsions are a preferred dosage form for parenteral administration. Dosage forms for rectal and vaginal administration include suppositories and ovula. Dosage forms for nasal administration can be administered via inhalation and insufflation, for example by a metered inhaler. Dosage forms for topical administration include creams, gels, ointments, salves, patches and transdermal delivery systems. The compounds of formula (I) or the above described pharmaceutical compositions comprising a compound of formula (I) may be administered to a subject by any convenient route of administration, whether systemically / peripherally or at the site of desired action, including but not limited to one or more of: oral (e.g., as a tablet, capsule, or as an ingestible solution), topical (e.g., transdermal, intranasal, ocular, buccal, and sublingual), parenteral (e.g., using injection techniques or infusion techniques, and including, for example, by injection, e.g., subcutaneous, intradermal, intramuscular, intravenous, intraarterial, intracardiac, intrathecal, intraspinal, intracapsular, subcapsular, intraorbital, intraperitoneal, intratracheal, subcuticular, intraarticular, subarachnoid, or intrasternal by, e.g., implant of a depot, for example, subcutaneously or intramuscularly), pulmonary (e.g., by inhalation or insufflation therapy using, e.g., an aerosol, e.g., through mouth or nose), gastrointestinal, intrauterine, intraocular, subcutaneous, ophthalmic (including intravitreal or intracameral), rectal, or vaginal administration. If said compounds or pharmaceutical compositions are administered parenterally, then examples of such administration include one or more of: intravenously, intraarterially, intraperitoneally, intrathecally, intraventricularly, intraurethrally, intrasternally, intracardially, intracranially, intramuscularly or subcutaneously administering the compounds or pharmaceutical compositions, and / or by using infusion techniques. For parenteral administration, the compounds are best used in the form of a sterile aqueous solution which may contain other substances, for example, enough salts or glucose to make the solution isotonic with blood. The aqueous solutions should be suitably buffered (preferably to a pH of from 3 to 9), if necessary. The preparation of suitable parenteral formulations under sterile conditions is readily accomplished by standard pharmaceutical techniques well known to those skilled in the art. Said compounds or pharmaceutical compositions can also be administered orally in the form of tablets, capsules, ovules, elixirs, solutions or suspensions, which may contain flavoring or coloring agents, for immediate-, delayed-, modified-, sustained-, pulsed- or controlled-release applications. The tablets may contain excipients such as microcrystalline cellulose, lactose, sodium citrate, calcium carbonate, dibasic calcium phosphate and glycine, disintegrants such as starch (preferably corn, potato or tapioca starch), sodium starch glycolate, croscarmellose sodium and certain complex silicates, and granulation binders such as polyvinylpyrrolidone, hydroxypropylmethylcellulose (HPMC), hydroxypropylcellulose (HPC), sucrose, gelatin and acacia. Additionally, lubricating agents such as magnesium stearate, stearic acid, glyceryl behenate and talc may be included. Solid compositions of a similar type may also be employed as fillers in gelatin capsules. Preferred excipients in this regard include lactose, starch, a cellulose, or high molecular weight polyethylene glycols. For aqueous suspensions and / or elixirs, the agent may be combined with various sweetening or flavoring agents, coloring matter or dyes, with emulsifying and / or suspending agents and with diluents such as water, ethanol, propylene glycol and glycerin, and combinations thereof. For oral administration, the compounds or pharmaceutical compositions are preferably administered by oral ingestion, particularly by swallowing. The compounds or pharmaceutical compositions can thus be administered to pass through the mouth into the gastrointestinal tract, which can also be referred to as “oral-gastrointestinal” administration. Alternatively, said compounds or pharmaceutical compositions can be administered in the form of a suppository or pessary, or may be applied topically in the form of a gel, hydrogel, lotion, solution, cream, ointment or dusting powder. The compounds of the present invention may also be dermally or transdermally administered, for example, by the use of a skin patch. Said compounds or pharmaceutical compositions may also be administered by sustained release systems. Suitable examples of sustained-release compositions include semi-permeable polymer matrices in the form of shaped articles, e.g., films, or microcapsules. Sustained-release matrices include, e.g., polylactides, copolymers of L-glutamic acid and gamma-ethyl-L-glutamate, poly(2-hydroxyethyl methacrylate), ethylene vinyl acetate, or poly-D-(–)-3-hydroxybutyric acid. Sustained-release pharmaceutical compositions also include liposomally entrapped compounds. The present invention thus also relates to liposomes containing a compound of the invention. Said compounds or pharmaceutical compositions may also be administered by the pulmonary route, rectal routes, or the ocular route. For ophthalmic use, they can be formulated as micronized suspensions in isotonic, pH adjusted, sterile saline, or, preferably, as solutions in isotonic, pH adjusted, sterile saline, optionally in combination with a preservative such as a benzalkonium chloride. Alternatively, they may be formulated in an ointment such as petrolatum. It is also envisaged to prepare dry powder formulations of the compounds of formula (I) for pulmonary administration, particularly inhalation. Such dry powders may be prepared by spray drying under conditions which result in a substantially amorphous glassy or a substantially crystalline bioactive powder. Accordingly, dry powders of the compounds of the present invention can be made according to an emulsification / spray drying process. For topical application to the skin, said compounds or pharmaceutical compositions can be formulated as a suitable ointment containing the active compound suspended or dissolved in, for example, a mixture with one or more of the following: mineral oil, liquid petrolatum, white petrolatum, propylene glycol, emulsifying wax and water. Alternatively, they can be formulated as a suitable lotion or cream, suspended or dissolved in, for example, a mixture of one or more of the following: mineral oil, sorbitan monostearate, a polyethylene glycol, liquid paraffin, polysorbate 60, cetyl esters wax, 2-octyldodecanol, benzyl alcohol and water. The present invention thus relates to the compounds or the pharmaceutical compositions provided herein, wherein the corresponding compound or pharmaceutical composition is to be administered by any one of: an oral route; topical route, including by transdermal, intranasal, ocular, buccal, or sublingual route; parenteral route using injection techniques or infusion techniques, including by subcutaneous, intradermal, intramuscular, intravenous, intraarterial, intracardiac, intrathecal, intraspinal, intracapsular, subcapsular, intraorbital, intraperitoneal, intratracheal, subcuticular, intraarticular, subarachnoid, intrasternal, intraventricular, intraurethral, or intracranial route; pulmonary route, including by inhalation or insufflation therapy; gastrointestinal route; intrauterine route; intraocular route; subcutaneous route; ophthalmic route, including by intravitreal, or intracameral route; rectal route; or vaginal route. Preferred routes of administration are oral administration or parenteral administration. For each of the compounds or pharmaceutical compositions provided herein, it is particularly preferred that the respective compound or pharmaceutical composition is to be administered orally (particularly by oral ingestion). Typically, a physician will determine the actual dosage which will be most suitable for an individual subject. The specific dose level and frequency of dosage for any particular individual subject may be varied and will depend upon a variety of factors including the activity of the specific compound employed, the metabolic stability and length of action of that compound, the age, body weight, general health, sex, diet, mode and time of administration, rate of excretion, drug combination, the severity of the particular condition, and the individual subject undergoing therapy. A proposed, yet non-limiting dose of the compounds according to the invention for oral administration to a human (of approximately 70 kg body weight) may be 0.05 to 2000 mg, preferably 0.1 mg to 1000 mg, of the active ingredient per unit dose. The unit dose may be administered, e.g., 1 to 3 times per day. The unit dose may also be administered 1 to 7 times per week, e.g., with not more than one administration per day. It will be appreciated that it may be necessary to make routine variations to the dosage depending on the age and weight of the patient / subject as well as the severity of the condition to be treated. The precise dose and also the route of administration will ultimately be at the discretion of the attendant physician or veterinarian. Therapeutic use In one embodiment, the present invention relates to the compound of formula (I), or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition as defined herein for use in therapy. The present invention provides compounds that function as inhibitors of PARG. Thus, the present invention provides a method of inhibiting PARG enzyme activity in vitro or in vivo, said method comprising contacting a cell with an effective amount of the compound of formula (I), or a pharmaceutically acceptable salt, hydrate or solvate thereof, as defined herein. The present invention also provides a method of selectively inhibiting PARG enzyme activity over PARP1 or ARH3 enzyme activity in vitro or in vivo. The said method comprises the steps of contacting a cell with an effective amount of a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, as defined herein. In a further embodiment, the present invention relates to the compound of formula (I), as disclosed herein, for use in a method of treating a disease or disorder in which PARG activity is implicated in a subject or patient in need of such treatment. Said method of treatment comprises administering to said subject / patient a therapeutically effective amount of a compound of formula (I), or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition as defined herein. In other words, in one embodiment the present invention relates to the compound of formula (I), as disclosed herein, for use in treating a disease or disorder in which PARG activity is implicated. In a further embodiment, the present invention relates to a method of inhibiting cell proliferation, in vitro or in vivo, said method comprising contacting a cell with an effective amount of the compound of formula (I), or a pharmaceutically acceptable salt, hydrate or solvate thereof, as defined herein. Thus, the present invention relates to the compound of formula (I) or a pharmaceutically acceptable salt thereof for use in of inhibiting cell proliferation, in vitro or in vivo. Thus, in a further embodiment, the present invention relates to a method of treating a proliferative disorder in a subject or patient in need of such treatment. The said method of treating a proliferative disorder in a subject or patient in need thereof comprises administering to said subject / patient a therapeutically effective amount of the compound of formula (I), or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition as defined herein. Preferably as disclosed herein, the proliferative disorder is cancer. Thus, the present invention relates to a method of treating cancer in a subject or patient in need thereof. The said method of treating cancer in a subject or patient in need thereof comprises administering to said subject / patient a therapeutically effective amount of the compound of formula (I), or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition as defined herein. In a particular embodiment, the cancer is human cancer. In one embodiment, the present invention relates to the compound of formula (I) or a pharmaceutically acceptable salt, hydrate or solvate thereof, for use in treating a proliferative disorder. Preferably as disclosed herein, the proliferative disorder is cancer. Therefore, the present invention relates to the compound of formula (I) or a pharmaceutically acceptable salt, hydrate or solvate thereof for use in treating cancer. In a particular embodiment, the cancer is human cancer. In a further embodiment, the present invention relates to the compound of formula (I), or a pharmaceutically acceptable salt, hydrate or solvate thereof, as defined herein, for use in the manufacture of a medicament for the treatment of a proliferative condition. In a preferred embodiment, the proliferative condition is cancer, more preferably a human cancer. Thus, preferably the present invention relates to the compound of formula (I), or a pharmaceutically acceptable salt, hydrate or solvate thereof, as defined herein, for use in the manufacture of a medicament for the treatment of cancer, preferably for the treatment of human cancer. In a further embodiment, the present invention relates to the compound of formula (I), or a pharmaceutically acceptable salt, hydrate or solvate thereof, as defined herein, for use in the manufacture of a medicament for the inhibition of PARG enzyme activity. Preferably, the inhibition of PARG enzyme activity is selective inhibition of PARG enzyme activity over PARP1 or ARH3 enzyme activity. Thus, the present invention relates to the compound of formula (I), or a pharmaceutically acceptable salt, hydrate or solvate thereof, as defined herein, for use in the manufacture of a medicament for the selective inhibition of PARG enzyme activity over PARP1 or ARH3 enzyme activity. The present invention further provides the compound of formula (I), or a pharmaceutically acceptable salt, hydrate or solvate thereof, as defined herein for use in the manufacture of a medicament for the treatment of a disease or disorder in which PARG activity is implicated, as defined herein. As understood herein, the term "proliferative disorder" are used interchangeably herein and pertain to an unwanted or uncontrolled cellular proliferation of excessive or abnormal cells which is undesired, such as, neoplastic or hyperplastic growth, whether in vitro or in vivo. Examples of proliferative conditions include, but are not limited to, pre-malignant and malignant cellular proliferation, including but not limited to, malignant neoplasms and tumours, cancers, leukemias, psoriasis, bone diseases, fibroproliferative disorders (e.g., of connective tissues), and atherosclerosis. Any type of cell may be treated, including but not limited to, lung, colon, breast, ovarian, prostate, liver, pancreas, brain, and skin. Preferably, the proliferative disorder, as referred to herein, is cancer. The cancer to be treated in accordance with the present invention may be a solid cancer or a hematological cancer. Preferably, the cancer is selected from lung cancer (e.g., small cell lung cancer, non-small cell lung cancer, large celllung carcinoma, lung adenocarcinoma, including also lung adenocarcinoma with EGFR mutation E746-A750, or squamous cell carcinoma of the lung), renal cancer (or kidney cancer; e.g., renal carcinoma), gastrointestinal cancer, stomach cancer, colorectal cancer (e.g., colorectal carcinoma), colon cancer, anal cancer, genitourinary cancer, bladder cancer, liver cancer (e.g., hepatocellular carcinoma), pancreatic cancer (e.g., pancreatic adenocarcinoma or pancreatic ductal adenocarcinoma), cervical cancer, endometrial cancer, vaginal cancer, vulvar cancer, ovarian cancer (e.g., ovarian carcinoma), uterine cancer, prostate cancer (e.g., hormone-refractory prostate cancer), testicular cancer, biliary tract cancer, hepatobiliary cancer, neuroblastoma, brain cancer (e.g., glioblastoma), breast cancer (e.g., triple-negative breast cancer, breast cancer having a BRCA1 and / or BRCA2 gene mutation, or breast adenocarcinoma), head and / or neck cancer (e.g., head and neck squamous cell carcinoma), skin cancer, melanoma, Merkel- cell cancer (e.g., Merkel-cell carcinoma), epidermoid cancer, squamous cell cancer (or squamous cell carcinoma; including, e.g., oral squamous cell carcinoma / squamous-cell mouth carcinoma, squamous- cell skin cancer, squamous-cell lung carcinoma, squamous-cell thyroid carcinoma, squamous-cell esophageal carcinoma, or squamous-cell vaginal carcinoma), bone cancer (e.g., osteosarcoma or osteogenic sarcoma), fibrosarcoma, Ewing’s sarcoma, malignant mesothelioma, esophageal cancer, laryngeal cancer, mouth cancer, thymoma, neuroendocrine cancer (e.g., neuroendocrine carcinoma), goblet cell cancer (e.g., goblet cell carcinoid), hematological cancer, leukemia (e.g., acute lymphoblastic leukemia, acute myeloid leukemia, chronic lymphocytic leukemia, or chronic myeloid leukemia), lymphoma (e.g., Hodgkin lymphoma or non-Hodgkin lymphoma, such as, e.g., follicular lymphoma or diffuse large B-cell lymphoma), and multiple myeloma. Moreover, the cancer to be treated (including any one of the aforementioned specific types of cancer) may also be a chemoresistant and / or a metastatic cancer. According to the present invention, the cancer may be characterized by a reduction or absence of BRCA1 and / or BRCA2 gene expression, the absence or mutation of BRCA1 and / or BRCA2 genes, or reduced function of BRCA1 and / or BRCA2 proteins. According to the present invention, the cancer may be selected from breast cancer, ovarian cancer, prostate cancer, pancreatic cancer, colorectal cancer, gastric cancer, skin cancer, endometrial cancer, cervical cancer, brain cancer, liver cancer, bladder cancer, esophageal cancer, kidney cancer, colorectal cancer, stomach cancer, thyroid cancer, lymphoma, leukemia, melanoma, uterine cancer, mantle cell lymphoma, renal cell carcinoma, appendicle cancer, hematologic cancer, MYH-related polyposis, gallbladder cancer, bile duct cancer, testicular cancer, bone cancer, and head and neck cancer. Preferably, the cancer is selected from gastric, lung, colon, breast, ovarian, prostate, liver, pancreas, brain, and skin cancer. More preferably, the cancer is selected from lung, colon, breast, ovarian, prostate, liver, pancreas, brain, and skin cancer. Alternatively, in one embodiment, the cancer is selected from ovarian, gastric, and breast cancer. Accordingly, in one embodiment, the cancer is ovarian cancer. In one embodiment, the cancer is gastric cancer. In one embodiment, the cancer is breast cancer. The anti-proliferative effects of the compound of formula (I) of the present invention have particular application in the treatment of human cancers (by virtue of their inhibition of PARG enzyme activity). The anti-cancer effect may arise through one or more mechanisms, including but not limited to, the regulation of cell proliferation, the inhibition of angiogenesis (the formation of new blood vessels), the inhibition of metastasis (the spread of a tumour from its origin), the inhibition of invasion (the spread of tumour cells into neighbouring normal structures), or the promotion of apoptosis (programmed cell death). The antiproliferative treatment with the compound of formula (I) or a pharmaceutically acceptable salt, hydrate or solvate thereof, as defined hereinbefore, may be applied as a sole therapy or may involve, in addition to the compound of the invention, conventional surgery or radiotherapy or chemotherapy. Such chemotherapy may include one or more of the following categories of anti-tumour agents: (i) other antiproliferative / antineoplastic drugs and combinations thereof, as used in medical oncology, such as alkylating agents (for example cis-platin, oxaliplatin, carboplatin, cyclophosphamide, nitrogen mustard, melphalan, chlorambucil, busulphan, temozolamide and nitrosoureas); antimetabolites (for example gemcitabine and antifolates such as fluoropyrimidines like 5-fluorouracil and tegafur, raltitrexed, methotrexate, cytosine arabinoside, and hydroxyurea); antitumour antibiotics (for example anthracyclines like adriamycin, bleomycin, doxorubicin, daunomycin, epirubicin, idarubicin, mitomycin-C, dactinomycin and mithramycin); antimitotic agents (for example vinca alkaloids like vincristine, vinblastine, vindesine and vinorelbine and taxoids like taxol and taxotere and polokinase inhibitors); and topoisomerase inhibitors (for example epipodophyllotoxins like etoposide and teniposide, amsacrine, topotecan and camptothecin); (ii) cytostatic agents such as antioestrogens (for example tamoxifen, fulvestrant, toremifene, raloxifene, droloxifene and iodoxyfene), antiandrogens (for example bicalutamide, flutamide, nilutamide and cyproterone acetate), LHRH antagonists or LHRH agonists (for example goserelin, leuprorelin and buserelin), progestogens (for example megestrol acetate), aromatase inhibitors (for example as anastrozole, letrozole, vorazole and exemestane) and inhibitors of 5oc-reductase such as finasteride; (iii) anti-invasion agents [for example c-Src kinase family inhibitors like 4-(6-chloro-2,3- methylenedioxyanilino)-7-[2-(4-methylpiperazin-1 -yl)ethoxy]-5-tetrahydropyran-4- yloxyquinazoline (AZD0530; International Patent Application WO 01 / 94341 ), N-(2-chloro-6- methylphenyl)-2-{6-[4-(2- hydroxyethyl)piperazin-1 -yl]-2-methylpyrimidin-4-ylamino}thiazole- 5-carboxamide (dasatinib, BMS- 354825; J. Med. Chem., 2004, 47, 6658-6661 ) and bosutinib (SKI-606), and metalloproteinase inhibitors like marimastat, inhibitors of urokinase plasminogen activator receptor function or antibodies to Heparanase]; (iv) inhibitors of growth factor function: for example such inhibitors include growth factor antibodies and growth factor receptor antibodies (for example the anti-erbB2 antibody trastuzumab [Herceptin™], the anti-EGFR antibody panitumumab, the anti-erbB1 antibody cetuximab [Erbitux, C225] and any growth factor or growth factor receptor antibodies disclosed by Stern et al. (Critical reviews in oncology / haematology, 2005, Vol.54, pp11 -29); such inhibitors also include tyrosine kinase inhibitors, for example inhibitors of the epidermal growth factor family (for example EGFR family tyrosine kinase inhibitors such as N-(3-chloro- 4-fluorophenyl)-7-methoxy-6-(3-morpholinopropoxy)quinazolin-4-amine (gefitinib, ZD1839), N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)quinazolin-4-amine (erlotinib, OSI-774) and 6- acrylamido-N-(3-chloro-4-fluorophenyl)-7-(3-morpholinopropoxy)-quinazolin-4-amine (CI 1033), erbB2 tyrosine kinase inhibitors such as lapatinib); inhibitors of the hepatocyte growth factor family; inhibitors of the insulin growth factor family; inhibitors of the platelet-derived growth factor family such as imatinib and / or nilotinib (AMN107); inhibitors of serine / threonine kinases (for example Ras / Raf signalling inhibitors such as farnesyl transferase inhibitors, for example sorafenib (BAY 43-9006), tipifarnib (R1 15777) and lonafarnib (SCH66336)), inhibitors of cell signalling through MEK and / or AKT kinases, c-kit inhibitors, abl kinase inhibitors, PI3 kinase inhibitors, Plt3 kinase inhibitors, CSF-1 R kinase inhibitors, IGF receptor (insulin-like growth factor) kinase inhibitors; aurora kinase inhibitors (for example AZD1152, PH739358, VX-680, MLN8054, R763, MP235, MP529, VX-528 AND AX39459) and cyclin dependent kinase inhibitors such as CDK2 and / or CDK4 inhibitors; (v) antiangiogenic agents such as those which inhibit the effects of vascular endothelial growth factor, [for example the anti-vascular endothelial cell growth factor antibody bevacizumab (Avastin™) and for example, a VEGF receptor tyrosine kinase inhibitor such as vandetanib (ZD6474), vatalanib (PTK787), sunitinib (SU11248), axitinib (AG-013736), pazopanib (GW 786034) and 4-(4-fluoro-2-methylindol-5- yloxy)-6-methoxy-7-(3-pyrrolidin-1 - ylpropoxy)quinazoline (AZD2171 ; Example 240 within WO 00 / 47212), compounds such as those disclosed in International Patent Applications W097 / 22596, WO 97 / 30035, WO 97 / 32856 and WO 98 / 13354 and compounds that work by other mechanisms (for examplelinomide, inhibitors of integrin 3 function and angiostatin)]; (vi) vascular damaging agents such as Combretastatin A4 and compounds disclosed in International Patent Applications WO 99 / 02166, WO 00 / 40529, WO 00 / 41669, WO 01 / 92224, WO 02 / 04434 and WO 02 / 08213; (vii) an endothelin receptor antagonist, for example zibotentan (ZD4054) or atrasentan; (viii) antisense therapies, for example those which are directed to the targets listed above, such as ISIS 2503, an anti-ras antisense; (ix) gene therapy approaches, including for example approaches to replace aberrant genes such as aberrant p53 or aberrant BRCA1 or BRCA2, GDEPT (gene-directed enzyme pro-drug therapy) approaches such as those using cytosine deaminase, thymidine kinase or a bacterial nitroreductase enzyme and approaches to increase patient tolerance to chemotherapy or radiotherapy such as multi- drug resistance gene therapy; and (x) immunotherapy approaches, including for example ex-vivo and in-vivo approaches to increase the immunogenicity of patient tumour cells, such as transfection with cytokines such as interleukin 2, interleukin 4 or granulocyte-macrophage colony stimulating factor, approaches to decrease T-cell anergy, approaches using transfected immune cells such as cytokine-transfected dendritic cells, approaches using cytokine-transfected tumour cell lines and approaches using anti-idiotypic antibodies. In a particular embodiment, the antiproliferative treatment defined hereinbefore may involve, in addition to the compound of formula (I) of the invention, conventional surgery or radiotherapy or chemotherapy.Such conjoint treatment may be achieved by way of the simultaneous, sequential or separate dosing of the individual components of the treatment. Such combination products employ the compounds of this invention within the dosage range described hereinbefore and the other pharmaceutically-active agent within its approved dosage range. According to this aspect the present invention further relates to the compound of formula (I) or a pharmaceutically acceptable salt, hydrate or solvate thereof, as defined herein, for use in the treatment of a cancer (for example a cancer involving a solid tumour) in combination with another anti-tumour agent. The anti-tumour agent is preferably selected from the anti-tumour agents as listed hereinabove. As understood herein, the term "combination" refers to simultaneous, separate or sequential administration. In one aspect of the invention "combination" refers to simultaneous administration. In another aspect of the invention "combination" refers to separate administration. In a further aspect of the invention "combination" refers to sequential administration. Where the administration is sequential or separate, the delay in administering the second component should not be such as to lose the beneficial effect of the combination. Examples The following examples are merely illustrative of the present invention and should not be construed to limit the scope of the invention which is defined by the appended claims. Synthesis of the compounds of formula (I) The syntheses of preferred embodiments of the compounds of formula (I) according to the present invention are preferably carried out per analogy to the synthesis of Example 1. In addition to said routes described below, also other routes may be used to synthesize the target compounds, in accordance with common general knowledge of a person skilled in the art of organic synthesis. The order of transformations exemplified in the following Examples is therefore not intended to be limiting, and suitable synthesis steps from various schemes can be combined to form additional synthesis sequences. In addition, modification of any of the substituents can be achieved before and / or after the exemplified transformations. These modifications can be such as the introduction of protective groups, cleavage of protective groups, reduction or oxidation of functional groups, halogenation, metallation, metal-catalyzed coupling reactions, substitution or other reactions known to a person skilled in the art. These transformations include those which introduce a functionality allowing for further interconversion of substituents. Appropriate protective groups and their introduction and cleavage are well-known to a person skilled in the art (see for example: Greene's Protective Groups in Organic Synthesis; Editor: P.G.M. Wuts, 5th edition, Wiley 2014). Specific examples are described in the subsequent paragraphs. Further, it is possible that two or more successive steps may be performed without work-up being performed between said steps, e.g. a “one-pot” reaction, as it is well-known to a person skilled in the art. It is further understood to the skilled person that a reaction can lead to side product(s) which, when appropriate, can be used for the preparation of compounds of formula (I) using similar procedures as reported in the general schemes hereinbelow, or reported in the specific examples hereinbelow. Scheme 1

[0002] Scheme 1 illustrates a preferred synthetic approach to compounds of the general formula (A). As it is to be understandable to the skilled person, the scheme can also be extended to the compounds of formula (I) wherein X4 is N and X5 is C-R6, for example upon functionalization of C-H of compound A to C-RC5 through bromination of the C-H position (see for example: Kim et al, KR2012078530) followed by palladium-catalyzed cross-coupling reactions. In the first step, ethyl 2-chloroacetate 1 is reacted with ethyl formate 2 under basic condition to provide potassium (Z)-2-chloro-3-ethoxy-3-oxoprop-1-en-1-olate 3. The reaction is preferably carried out in solvents like tert-butyl methyl ether, di-isopropyl ether, diethyl ether, 1,2-dimethoxyethane, dioxane, DMF, DME, THF, or a mixture of toluene, diethyl ether, and EtOH in the presence of a base like sodium ethoxide, sodium methoxide, potassium tert-butylate or sodium tert-butylate. (see for examples: a) Stephen et al, US2017 / 369489; b) Murar et al, Eu. J. Med. Chem.2017, 126, 754). The reaction is performed at temperatures ranging from -78°C to the room temperature. The reaction is preferably completed after 1-24 hours. In the second step, a compound of formula 4 is reacted with potassium (Z)-2-chloro-3-ethoxy-3- oxoprop-1-en-1-olate 3 to give a compound of formula 5. This cyclization can be carried out under acidic conditions (see for example: Xi et al, WO2019 / 99311). Preferred is the herein described use of sulfuric acid in EtOH. The reactions are preferably run for 5-24 hours at 70-100°C. In the third step, a compound of formula 5 is converted to a compound of formula 6 in which R4 is as defined for the compound of formula (I) in several synthetic steps. If R4 is a 2-(difluoromethyl)-1,3,4- thiadiazole group, a compound of formula 5 is reacted with hydrazine hydrate to produce a hydrazide. This hydrazide formation can be carried out under neutral condition. (see for example: Dong et al, J. Med. Chem.2020, 63, 3028). The hydrazide formation is preferably performed in EtOH and the reactions are preferably run for 1-24 hours at 50-100°C with heating or microwave conditions. The hydrazide is then reacted with ethyl 2,2-difluoroacetate to produce a di-acyl hydrazine. This reaction can be carried out under basic condition, preferred is the herein described use of DBU in EtOH, THF, or DMF. The reactions are preferably run for 0.5-24 hours at room temperature to 100°C in a microwave oven or in an oil bath. Finally, the di-acyl hydrazine is cyclized by treatment with oxygen / sulfur exchange reagents to a compound of formula 6, in which R4 is 2-(difluoromethyl)-1,3,4-thiadiazole group. (see for example: Brunet et al, WO2020 / 127974). Preferred is the herein described use of Lawessons reagent in toluene or THF. The reactions are preferably run for 0.5-24 hours at 50-130°C. In the fourth step, a compound of formula 6 in which R4is as defined for the compound of formula (I) is reacted with benzyl mercaptan to give a compound of formula 7. This coupling reaction can be carried out by a palladium-catalyzed C-S cross-coupling reaction (see for example: Jiang, Buchwald in ‘Metal- Catalyzed Cross-Coupling Reactions’, 2ndedition.: de Meijere, Diederich, Eds.: Wiley-VCH: Weinheim, Germany, 2004). Preferred is the herein described use of tris(dibenzylideneacetone) dipalladium(0), (9,9- dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphane) and N-ethyl-N-isopropylpropan-2-amine in dioxane. The reactions are preferably run under an atmosphere of argon for 1-48 hours at 80-100°C in a microwave oven or in an oil bath. In the fifth step, a compound of formula 7 in which R4 is as defined for the compound of formula (I) is reacted with chlorination reagent to give a sulfonyl chloride of formula 8. This sulfonyl chloride formation can be carried out by treatment with NCS, sulfonyl chloride, DCDMH, Cl2 etc., in MeCN with equivalent acetic acid and water. (see for example: Sutton et al, WO 2021 / 055744). Preferred is the herein described use of DCDMH in MeCN with equivalent acetic acid and water. The reactions are preferably run under an atmosphere of argon for 0.5-5 hours at 0°C to room temperature. In the sixth step, a compound of formula 8 in which R4 is as defined for the compound of formula (I) is reacted with an amine of formula 9 in which Z is as defined for the compound of formula (I) to give a compound of formula 10. This reaction can be carried out under basic conditions (see for example: Sutton et al, WO 2021 / 055744). Preferred is the herein described use of trimethylamine, pyridine etc., in DCM, THF or DMF. The reactions are preferably run under an atmosphere of argon for 0.5-24 hours at 0°C to room temperature. In the final step, a compound of formula 10 in which Z and R4 are as defined for the compound of formula (I) is coupled with various amines to give a compound of formula A, in which X2 is defined as for the compound of formula (I). This coupling reaction can be carried out by a palladium-catalyzed C-N cross- coupling reaction (see for example: a) Jiang, Buchwald in ‘Metal-Catalyzed Cross-Coupling Reactions’, 2ndedition.: de Meijere, Diederich, Eds.: Wiley-VCH: Weinheim, Germany, 2004; b) Sutton, et al, WO 2021 / 055744). Preferred is the herein described use of cesium carbonate and Pd-PEPPSI-IHept Cl in dioxane. The reactions are preferably run under an atmosphere of argon for 1-48 hours at 80-120°C in a microwave oven or in an oil bath. Preferred is also the herein described use of cesium carbonate RuPhos- Pd-G3, Ruphos in dioxane or palladium acetate, Ruphos, tert-butyl alcohol sodium in THF. The reactions are preferably run under an atmosphere of argon for 1-24 hours at 70-130°C in a microwave oven or in an oil bath. Scheme 2 Scheme 2 illustrates a preferred synthetic approach to compounds of the general formula B. As it is to be understandable to the skilled person, the compounds of formula (I) wherein X4 is C-R5 and X5 is N are obtainable through functionalization of the C-I position in compound 21, e.g. via palladium-catalyzed cross-coupling reactions. In the first step, the cyano group of a compound of formula 11 is reduced to give a compound of formula 12. The reaction is preferably carried out in THF in the presence of a reducing agent like BH3.THF, BH3.Me2S, PtO2 / H2, sodium tetrahydroborate etc., (see for example: Long et al, WO2018 / 71535). The reaction is performed at temperatures ranging from 20-40°C. The reaction is preferably completed after 0.5-24 hours. In the second step, a compound of formula 12 is reacted with ethyl 2-chloro-2-oxoacetate 13 under basic condition to give a compound of formula 14. The acylation is preferably carried out in a solvent like DCM, dioxane or THF, in the presence of a base like trimethylamine or N-ethyl-N-isopropylpropan-2- amine (see for example: Blaquiere et al, WO2015 / 25025). The reaction is performed at temperatures ranging from -5°C to room temperature. The reaction is preferably completed after 1-24 hours. In the third step, a compound of formula 14 is converted to a compound of formula 15. The cyclization is preferably carried out in the presence of dehydration reagents like trichlorophosphate, phosphorus pentoxide and trichlorophosphate, pyridine and trifluoroacetic anhydride etc., in 1,2-dichloro-ethane, toluene or neat conditions. The reaction is performed at temperatures ranging from 70-140°C. The reaction is preferably completed after 1-24 hours. In the fourth step, a compound of formula is converted to a compound of formula 16 in which R4 is as defined for the compound of formula (I) by several synthetic steps. If R4 is 2-(difluoromethyl)-1,3,4- thiadiazole, a compound of formula 15 is reacted with hydrazine hydrate to produce a hydrazide. This hydrazide formation can be carried out under neutral conditions (see for example: Dong et al, J. Med. Chem.2020, 63, 3028). The hydrazide formation is preferably performed in EtOH and the reactions are preferably run for 1-24 hours at 50-100°C with heating or microwave conditions. The hydrazide is then reacted with ethyl 2,2-difluoroacetate to produce a di-acyl hydrazine. This reaction can be carried out by basic condition, preferred is the herein described use of DBU in EtOH, THF, or DMF. The reactions are preferably run for 0.5-24 hours at room temperature to 100°C in a microwave oven or in an oil bath. Finally, the di-acyl hydrazine is cyclized by treatment with oxygen / sulfur exchange reagents to a compound of formula 16, in which R4 is 2-(difluoromethyl)-1,3,4-thiadiazole group. (see for example: Brunet et al, WO2020 / 127974). Preferred is the herein described use of Lawessons reagent in toluene or THF. The reactions are preferably run for 0.5-24 hours at 50-130°C. In the fifth step, a compound of formula 16 in which R4 is as defined for the compound of formula (I) is reacted with benzyl mercaptan to give a compound of formula 17. This coupling reaction can be carried out by a palladium-catalyzed C-S cross-coupling reaction (see for example: Jiang, Buchwald in ‘Metal-Catalyzed Cross-Coupling Reactions’, 2ndedition.: de Meijere, Diederich, Eds.: Wiley-VCH: Weinheim, Germany, 2004). Preferred is the herein described use of tris(dibenzylideneacetone) dipalladium(0), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphane) and N-ethyl-N- isopropylpropan-2-amine in dioxane. The reactions are preferably run under an atmosphere of argon for 1-48 hours at 80-100°C in a microwave oven or in an oil bath. In the sixth step, a compound of formula 17 in which R4 is as defined for the compound of formula (I) is reacted with an iodide reagent to give a compound of formula 18. This iodization can be carried out by treatment with NIS, I2 etc., in MeCN, THF, dioxane, DMF etc. (see for example: Bentley et al; WO2011 / 138266). Preferred is the herein described use of NIS in MeCN. The reactions are preferably run under an atmosphere of argon for 0.5-5 hours at 0°C to room temperature. In the seventh step, a compound of formula 18 in which R4 is as defined for the compound of formula (I) is reacted with chlorination reagent to give a sulfonyl chloride of formula 19. This sulfonyl chloride formation can be carried out by treatment with NCS, sulfonyl chloride, DCDMH, Cl2 etc., in MeCN with equivalent acetic acid and water. (see for example: Sutton et al, WO 2021 / 055744). Preferred is the herein described use of DCDMH in MeCN with equivalent acetic acid and water. The reactions are preferably run under an atmosphere of argon for 0.5-5 hours at 0°C to room temperature. In the eighth step, a compound of formula 19 in which R4 is as defined for the compound of formula (I) is reacted with an amine of formula 20 in which Z is as defined for the compound of formula (I) to give a compound of formula 21. This reaction can be carried out under basic conditions (see for example: Sutton et al, WO 2021 / 055744). Preferred is the herein described use of trimethylamine, pyridine etc., in DCM, THF or DMF. The reactions are preferably run under an atmosphere of argon for 0.5-24 hours at 0°C to room temperature. In the ninth step, the iodide of a compound of formula 21 in which Z and R4 are as defined for the compound of formula (I) is removed by hydrogenation to give a compound of formula 22. The reaction is preferably carried out in THF, MeOH, EtOH, dioxane or DMF in the presence of a hydrogenation catalyst like Pd / C, Pd(OH)2, Raney Ni, PtO2 etc. under an atmosphere of hydrogen (see for example: Aissaoui et al, US2011 / 105514). The reaction is performed at temperatures ranging from 20-80°. The reaction is preferably completed after 0.5-24 hours. In the final step, a compound of formula 22 in which Z and R4 are as defined for the compound of formula (I) is coupled with various amines to give a compound of formula B, in which X2 is defined as for the compound of formula (I). This coupling reaction can be carried out by a palladium-catalyzed C-N cross- coupling reaction (see for example: a) Jiang, Buchwald in ‘Metal-Catalyzed Cross-Coupling Reactions’, 2ndedition.: de Meijere, Diederich, Eds.: Wiley-VCH: Weinheim, Germany, 2004; b) Sutton et al, WO 2021 / 055744). Preferred is the herein described use of cesium carbonate and Pd-PEPPSI-IHept Cl in dioxane. The reactions are preferably run under an atmosphere of argon for 1-48 hours at 80-120°C in a microwave oven or in an oil bath. Preferred is also the herein described use of cesium carbonate RuPhos- Pd-G3, Ruphos in dioxane or palladium acetate, Ruphos, tert-butyl alcohol sodium in THF. The reactions are preferably run under an atmosphere of argon for 1-24 hours at 70-130°C in a microwave oven or in an oil bath. Scheme 3 illustrates an alternative synthetic approach to a compound of formula 22 wherein general X4is CH, X5 is N and Z is as defined for the compound of formula (I). In the first step, a compound of formula 17 in which R4 is as defined for the compound of formula (I) is reacted with chlorination reagent to give a sulfonyl chloride of formula 19a. This sulfonyl chloride formation can be carried out by treatment with NCS, sulfonyl chloride, DCDMH, Cl2 etc., in MeCN with equivalent acetic acid and water. (see for example: Sutton et al, WO 2021 / 055744). Preferred is the herein described use of DCDMH in MeCN with equivalent acetic acid and water. The reactions are preferably run under an atmosphere of argon for 0.5-5 hours at 0°C to room temperature. In the second step, a compound of formula 19s in which R4 is as defined for the compound of formula (I) is reacted with an amine of formula 20 in which Z is as defined for the compound of formula (I) to give a compound of formula 22. This reaction can be carried out under basic conditions (see for example: Sutton et al, WO 2021 / 055744). Preferred is the herein described use of trimethylamine, pyridine etc., in DCM, THF or DMF. The reactions are preferably run under an atmosphere of argon for 0.5-24 hours at 0°C to room temperature. Scheme 4 Scheme 3 illustrates a preferred synthetic approach to the compounds of the general formula C. As it is to be understandable to the skilled person, the compounds of formula (I) wherein X4 is C-R5 are obtainable through functionalization of C-I position of compound 33, e.g. via palladium-catalyzed cross- coupling reactions. As it is to be understandable to the skilled person, the compounds of formula (I) wherein X5 is C-R6 are obtainable through functionalization of the X5 is CH position through bromination of the C-H position (see for example: Yao et al, Org. Lett.2020, 22, 4511) followed by palladium-catalyzed cross-coupling reactions. In the first step a compound of formula 23 is reacted with 4,4,5,5-tetramethyl-2-vinyl-1,3,2- dioxaborolane 24 to give a compound of formula 25. The coupling reaction is catalyzed by palladium catalysts, e.g. by Pd(0) catalysts like tetrakis(triphenylphosphine) palladium(0) [Pd(PPh3)4], tris(dibenzylideneacetone) di-palladium(0) [Pd2(dba)3], or by Pd(II) catalysts like dichlorobis(triphenylphosphine)-palladium(II) [Pd(PPh3)2C12], palladium(II) acetate and triphenylphosphine or by [l,l'-bis(diphenylphosphino)ferrocene]palladium dichloride. The reaction is preferably carried out in a solvent like 1,2-dimethoxyethane, dioxane, DMF, DME, THF, or isopropanol with water and in the presence of a base like potassium carbonate, sodium carbonate, sodium bicarbonate or potassium phosphate. (see for example: Hall, Boronic Acids, 2005 Wiley VCH Verlag GmbH & Co. KGaA, Weinheim, ISBN 3-527- 30991-8 and references cited therein). The reaction is performed at temperatures ranging from room temperature to the boiling point of the respective solvent. Further on, the reaction can be performed at temperatures above the boiling point using pressure tubes and a microwave oven. The reaction is preferably completed after 1 to 36 hours. In the second step, a compound of formula 25 is reacted with 3-methoxy-3-oxopropanoic acid 26 to give a compound of formula 27. The cyclization is preferably carried out in a solvent like 1,2- dimethoxyethane, dioxane, DMF, DME, THF, or MeCN in the presence of N-iodo-succinimide and sodium acetate. (see for example: Tang et al, Adv. Synth. Catalysis, 2016, 358, 2878). The reaction is performed at temperatures ranging from 80-100°C in a microwave oven or in an oil bath. The reaction is preferably completed after 1 to 36 hours. In the third step, a compound of formula 27 is converted to a compound of formula 28 in which R4 is as defined for the compound of formula (I) by several synthetic steps. If R4 is 2-(difluoromethyl)-1,3,4- thiadiazole, a compound of formula 27 is reacted with hydrazine hydrate to produce a hydrazide. This hydrazide formation can be carried out under neutral conditions (see for example: Dong et al, J. Med. Chem.2020, 63, 3028). The hydrazide formation is preferably performed in EtOH and the reactions are preferably run for 1-24 hours at 50-100°C with heating or microwave conditions. The hydrazide is then reacted with ethyl 2,2-difluoroacetate to produce a di-acyl hydrazine. This reaction can be carried out under basic conditions, preferred is the herein described use of DBU in EtOH, THF, or DMF. The reactions are preferably run for 0.5-24 hours at room temperature to 100°C in a microwave oven or in an oil bath. Finally, the di-acyl hydrazine is cyclized by treatment with oxygen / sulfur exchange reagents to a compound of formula 28, in which R4 is 2-(difluoromethyl)-1,3,4-thiadiazole group. (see for example: Brunet et al, WO2020 / 127974). Preferred is the herein described use of Lawessons reagent in toluene or THF. The reactions are preferably run for 0.5-24 hours at 50-130°C. In the fourth step, a compound of formula 28 in which R4 is as defined for the compound of formula (I) is reacted with benzyl mercaptan to give a compound of formula 29. This coupling reaction can be carried out by a palladium-catalyzed C-S cross-coupling reaction (see for example: Jiang, Buchwald in ‘Metal-Catalyzed Cross-Coupling Reactions’, 2ndedition.: de Meijere, Diederich, Eds.: Wiley-VCH: Weinheim, Germany, 2004). Preferred is the herein described use of tris(dibenzylideneacetone) dipalladium(0), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphane) and N-ethyl-N- isopropylpropan-2-amine in dioxane. The reactions are preferably run under an atmosphere of argon for 1-48 hours at 80-100°C in a microwave oven or in an oil bath. In the fifth step, a compound of formula 29 in which R4 is as defined for the compound of formula (I) is reacted with an iodide reagent to give a compound of formula 30. This iodization can be carried out by treatment with NIS, I2 etc., in MeCN, THF, dioxane, DMF etc. (see for example: Bentley et al, WO2011 / 138266). Preferred is the herein described use of NIS in MeCN. The reactions are preferably run under an atmosphere of argon for 0.5-5 hours at 0°C to room temperature. In the sixth step, a compound of formula 30 in which R4 is as defined for the compound of formula (I) is reacted with chlorination reagent to give a sulfonyl chloride of formula 31. This sulfonyl chloride formation can be carried out by treatment with NCS, sulfonyl chloride, DCDMH, Cl2 etc., in MeCN with equivalent acetic acid and water. (see for example: Sutton et al, WO 2021 / 055744). Preferred is the herein described use of DCDMH in MeCN with equivalent acetic acid and water. The reactions are preferably run under an atmosphere of argon for 0.5-5 hours at 0°C to room temperature. In the seventh step, a compound of formula 31 in which R4 is as defined for the compound of formula (I) is reacted with an amine of formula 32 in which Z is as defined for the compound of formula (I) to give a compound of formula 33. This reaction can be carried out under basic conditions (see for example: Sutton et al, WO 2021 / 055744). Preferred is the herein described use of trimethylamine, pyridine etc., in DCM, THF or DMF. The reactions are preferably run under an atmosphere of argon for 0.5-24 In the eighth step, the iodide of a compound of formula 33 in which Z and R4 are as defined for the compound of formula (I) is removed by hydrogenation to give a compound of formula 34. The reaction is preferably carried out in THF, MeOH, EtOH, dioxane or DMF in the presence of a hydrogenation catalyst like Pd / C, Pd(OH)2, Raney Ni, PtO2 etc. under an atmosphere of hydrogen, (see for example: Aissaoui et al, US2011 / 105514). The reaction is performed at temperatures ranging from 20-80°. The reaction is preferably completed after 0.5-24 hours. In the final step, a compound of formula 34 in which Z and R4 are as defined for the compound of formula (I) is coupled with various amines to give a compound of formula C, in which X2 is defined as for the compound of formula (I). This coupling reaction can be carried out by a palladium-catalyzed C-N cross- coupling reaction (see for example: a) Jiang, Buchwald in ‘Metal-Catalyzed Cross-Coupling Reactions’, 2ndedition.: de Meijere, Diederich, Eds.: Wiley-VCH: Weinheim, Germany, 2004; b) Sutton et al, WO 2021 / 055744). Preferred is the herein described use of cesium carbonate and Pd-PEPPSI-IHept Cl in dioxane. The reactions are preferably run under an atmosphere of argon for 1-48 hours at 80-120°C in a microwave oven or in an oil bath. Preferred is also the herein described use of cesium carbonate RuPhos- Pd-G3, Ruphos in dioxane or palladium acetate, Ruphos, tert-butyl alcohol sodium in THF. The reactions are preferably run under an atmosphere of argon for 1-24 hours at 70-130°C in a microwave oven or in an oil bath. Preparation of compounds General considerations Abbreviations used in the descriptions that follow are: AcOH (acetic acid); aq. (aqueous); Ar(Argon); Atm (atmosphere); BH3.THF (boran tetrahydrofuran complex); br. (broad, 1H NMR signal); BnOH(benzyl alcohol); Boc2O (di-tert-butyldicarbonate); Cataxium APdG3 (Mesylate[(di(1-adamantyl)-n-butylphosphine)-2-(2 -amino-1,1 -biphenyl)]palladium(II)); CCl4 (carbon tetrachloride); CDCl3 (deuteratedchloroform); cHex (cyclohexane); CMPB ( Cyanomethylene trimethylphosphorane); Cs2CO3 (cesiumcarbonate); CuI (copper iodide); DABCO ((1,4-diazabicyclo[2.2.2]octane)); DAST (diethylaminosulfurtrifluoride);DBU (1,8-Diazabicyclo(5.4.0)undec-7-ene); DCE (dichloroethane); d (doublet, 1H NMR signal);DCM (dichloromethane); DEA (diethylamine); DIBAL-H (diisobutyl aluminium hydride); DIPEA or DIEA (di-iso-propylethylamine); DMAP (4- N-N-dimethylaminopyridine), DME (1,2-dimethoxyethane), DMEDA(dimethylethylenediamine ); DMF (N-N-dimethylformamide); DMSO (dimethyl sulfoxide); DPPA(diphenylphosphoride azide);dtbbpy (Bis(1,1-dimethylethyl)-2,2 -bipyridine); ES (electrospray); EtOAc orEA (ethyl acetate); EtOH (ethanol); h (hour(s)); FA (formic acid); HATU (1-[Bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate); HFIP ( Hexafluoroisopropanol); 1H NMR(proton nuclear magnetic resonance spectroscopy); HPLC (High Performance Liquid Chromatography), iPrOH (iso-propanol); K3PO4 (tripotassium phosphate); Ir[dF(CF3)(dtbbpy)PF6 ((4,4'-Di-t-butyl-2,2'- bipyridine)bis[3,5-difluoro-2-[5-trifluoromethyl-2-pyridinyl-kN)phenyl-kC]iridium(III) hexafluorophosphate);LiOH (lithium hydroxide); m (multiplet, 1H NMR signal); mCPBA (meta-chloroperoxybenzoic acid), MeCN(acetonitrile), MeOH (methanol); min (minute(s)); MnO2 (Manganese (IV) oxide); MS (mass spectrometry);MTBE (methyl tert-butyl ether); NaBH4 (sodium borohydride); NaH (sodium hydroxide); NaHCO3 (sodiumhydrogenocarbonate); NaIO4 (sodium periodate); Na2S2O3 (sodium thiosulfate); NCS (N- chlorosuccinimide); NH3 (ammonia); NH4Cl (ammonium chloride); NiCl2 (nickel dichloride); NIS (N- Iodosuccinimide); NMP (N-methylpyrrolidone); NMR (nuclear magnetic resonance); Pd / C (palladium on charcoal); Pd2dba3 (tris(dibenzylideneacetone)dipalladium ); Pd(dppf)Cl2 (1,1 - Bis(diphenylphosphino)ferrocene dichloropalladium); Pd(PPh3)2Cl2 (Bis(triphenylphosphine)palladium(II) dichloride ); PE (petroleum ether); Pd-PEPPSI-IPentCl o-picoline ([1,3-bis[2,6-bis(1-ethylpropyl)phenyl]- 4,5-dichloro-imidazol-2-ylidene]-dichloro-(2-methylpyridin-1-ium-1-yl)palladium; Pd(OH)2 (palladium hydroxide); Pd(Ph3)4 (Palladium-tetrakis(triphenylphosphine)); PhI(OAc)2 ((Diacetoxyiodo)benzene)); P(tBu)3 (Tri-tert-butylphosphine ); Py (pyridine); q (quartet, 1H NMR signal); quin (quintet, 1H NMR signal);rac (racemic); RT (retention time); RuCl3.H2O (ruthenium(III) chloride); s (singlet, 1H NMR signal); sat.(saturated); t (triplet, 1H NMR signal); TBAF (tetrabutylammonium fluoride); tert-BuBrettPhos-Pd-G3 ([(2-Di-tert-butylphosphino-3,6-dimethoxy-2 ,4 ,6 -triisopropyl-1,1 -biphenyl)-2-(2 -amino-1,1 -biphenyl)]palladium(II) methanesulfonate); tBuXPhos Pd G3 (Methanesulfonato(2-di-t-butylphosphino- 2',4',6'-tri-i-propyl-1,1'-biphenyl)(2'-amino-1,1'-biphenyl-2-yl)palladium(II))TBDMSCl or TBSCl (tert- butyldimethylsilyl chloride); tBuOH (tert-butanol); TEA (triethylamine) ; TFA (trifluoroacetic acid); TFAA (trifluoroacetic anhydride), THF (tetrahydrofuran); TLC (thin layer chromatography); TMSCHN2 (Trimethylsilyldiazomethane); TMSCN (trimethylsilyl cyanide); TMSOTf (Trimethylsilyl trifluoromethanesulfonate ); TTMSS (trimethylsilane); UPLC (Ultra-High Performance Liquid Chromatography), UV (ultraviolet), wt-% (percent by weight); Xantphos (4,5-Bis(diphenylphosphino)-9,9- dimethylxanthene); Xantphos Pd G4 (Methanesulfonato[9,9-dimethyl-4,5- bis(diphenylphosphino)xanthene](2'-methylamino-1,1'-biphenyl-2-yl)palladium(II)); Zn (Zinc). General Procedure: All starting materials and solvents were obtained either from commercialsources or prepared according to literature references. Commercially available reagents and anhydrous solvents were used as supplied, without further purification. Unless otherwise stated all reactions were stirred. Organic solutions were routinely dried over anhydrous sodium sulfate. Column chromatography was performed on pre-packed silica (100-1000 mesh, 40-63 µm) cartridges using the amount indicated. All air- and moisture-sensitive reactions were carried out in oven-dried (at 120 °C) glassware under an inert atmosphere of nitrogen or argon. Compound names were generated using ChemDraw Professional (Perkin Elmer). In some cases generally accepted names of commercially available reagents were used in place of ChemDraw generated names. Analytical Methods Reverse Phase HPLC conditions for the LCMS Analytical Methods (for final compound) Method 1: SHIMADZU LCMS-2020 Kinetex EVO C182.1X30mm, 5µm at 50 ; Mobile Phase: A:0.0375% TFA in water (v / v); B: 0.01875% TFA in MeCN (v / v); flow rate held at 1.5 mL / min; eluted with the mobile phase over 1.55 min employing UV detection at 220 nm and 254 nm. Gradient information: 0-0.80 min, ramped from 95% A-5% B to 5% A-95% B; 0.80-1.20 min, held at 5% A-95% B; 1.20-1.21 min, returned to 95% A-5% B, 1.21-1.55 min, held at 95% A-5% B. Method 2 SHIMADZU LCMS-2020 Kinetex EVO C18 2.1X30mm, 5µm at 40 MobilePhase A: 0.025% NH3·H2O in water (v / v); B: MeCN; flow rate held at 1.5 mL / min; eluted with the mobilephase over 1.55 min employing UV detection at 220 nm and 254 nm. Gradient information: 0-0.80 min, ramped from 95% A-5% B to 5% A-95% B; 0.80-1.20 min, held at 5% A-95% B; 1.20-1.21 min, returned to 95% A-5% B, 1.21-1.55 min, held at 95% A-5% B. Method 3: Agilent 1200\G6110A Kinetex EVO C18 2.1X30mm, 5µm at 50 ; Mobile Phase: A:0.0375% TFA in water (v / v); B: 0.01875% TFA in MeCN (v / v); flow rate held at 1.5.0 mL / min; eluted with the mobile phase over 0.80 min employing UV detection at 220 nm and 254 nm. Gradient information: 0.01-0.80 min, ramped from 95% A-5% B to 5% A-95% B; 0.80-1.20 min, held at 5% A-95% B; 1.20-1.21 min, returned to 95% A-5% B, 1.21-1.50 min, held at 95% A-5% B. Method 4: SHIMADZU LCMS-2020 Kinetex® EVO C182.1X30 mm 5 m at 50 Mobile Phase:A: 0.0375% TFA in water (v / v); B: 0.01875% TFA in MeCN (v / v); flow rate held at 1.5 mL / min; eluted with the mobile phase over 1.00 min employing UV detection at 220 nm and 254 nm. Gradient information: 0.01-0.80 min, ramped from 95% A-5% B to 5% A-95% B; 0.80-0.95 min, held at 5% A-95% B; 0.95-0.96 min, returned to 95% A-5% B, 0.96-1.00 min, held at 95% A-5% B. SFC method conditions: SFC Method 1: Column: Chiralpak AS-350×4.6mm I.D., 3µm; Mobile phase: Phase A forHeptane, and Phase B for IPA (0.05%DEA); Gradient elution:15% IPA (0.05% DEA) in Heptane; Flow rate: 1mL / min; Detector: PDA; Column Temp: 35°C Back Pressure: 100 Bar. SFC Method 2: Column: Chiralpak AD-350*4.6mm I.D., 3µm; Mobile phase: Phase A for CO2, and Phase B for IPA(0.05%DEA); Gradient elution: IPA(0.05%DEA) in CO2from 5% to 40%; Flow rate:3mL / min; Detector: PDA; Column Temp: 35°C; Back Pressure:100 Bar. SFC Method 3: Column: Chiralcel OD-350*4.6mm I.D., 3µm Mobile phase: Phase A for CO2, and Phase B for EtOH(0.05%DEA); Gradient elution: EtOH (0.05%DEA) in CO2 from 5% to 40%, Flow rate:3mL / min; Detector: PDA; Column Temp: 35°C; Back Pressure:100 Bar. SFC Method 4: Column: Chiralcel OD-350*4.6mm I.D., 3µm; Mobile phase: Phase A for CO2, and Phase B for EtOH(0.05%DEA); Gradient elution: EtOH (0.05%DEA) in CO2 from 20% to 60%, Flow rate:3mL / min; Detector: PDA; Column Temp: 35°C; Back Pressure:100 Bar. SFC Method 5: Column: Lux 3µm Cellulose-450*4.6mm I.D., 3µm Mobile phase: Phase A for CO2, and Phase B for IPA+ACN (0.05%DEA); Gradient elution: From 20% to 60% of IPA+ACN(0.05%DEA) in CO2, Flow rate:3mL / min; Detector: PDA; Column Temp:35 °C;Back Pressure:100Bar SFC Method 6: Column: Chiralpak IH-350*4.6mm I.D., 3µm Mobile phase: Phase A for CO2, and Phase B for EtOH (0.05%DEA); Gradient elution: EtOH (0.05%DEA) in CO2 from 5% to 40%, Flow rate:3mL / min; Detector: PDA; Column Temp:35 °C;Back Pressure:100Bar SFC Method 7: Column: Chiralcel OD-350*4.6mm I.D., 3µm Mobile phase: Phase A for CO2,and Phase B for MeOH(0.05%DEA); Gradient elution: MeOH (0.05%DEA) in CO2 from 5% to 40%, Flow rate:3mL / min; Detector: PDA; Column Temp:35 °C;Back Pressure:100Bar" SFC Method 8: Column: Chiralcel OD-350*4.6mm I.D., 3µm Mobile phase: Phase A for CO2,and Phase B for EtOH (0.05%DEA); Gradient elution: EtOH (0.05%DEA) in CO2 from 10% to 60%, Flow rate:3mL / min; Detector: PDA; Column Temp:35 °C;Back Pressure:100Bar" SFC Method 9: Column: Chiralpak AD-350×4.6mm I.D., 3µm Mobile phase: Phase A for CO2,and Phase B for EtOH (0.05%DEA); Gradient elution: EtOH (0.05%DEA) in CO2 from 5% to 40%; Flow rate: 3mL / min; Detector: PDA; Column Temp: 35 °C;Back Pressure: 100Bar SFC Method 10: Column: Lux 3µm Cellulose-450*4.6mm I.D., 3µm Mobile phase: Phase A forCO2, and Phase B for EtOH (0.05%DEA); Gradient elution: EtOH(0.05%DEA) in CO2 from 5% to 40%,Flow rate:3mL / min; Detector: PDA; Column Temp:35 °C;Back Pressure:100Bar SFC Method 11: Column: Lux 3µm Cellulose-450*4.6mm I.D., 3µm Mobile phase: Phase A forCO2, and Phase B for MeOH(0.05%DEA); Gradient elution: 30% to 60% MeOH(0.05%DEA) in CO2, Flow rate:3mL / min; Detector: PDA Column Temp:35 °C;Back Pressure:100Bar" SFC Method 12: Column: Chiralpak AS-350*4.6mm I.D., 3 µm; Mobile phase: Phase A for CO2, Phase B for IPA (0.05% DEA); Gradient elution: IPA (0.05% DEA) in CO2 from 5% to 40%, Flow rate: 3 mL / min; Detector: PDA; Column Temp: 35 °C; Back Pressure: 100 Bar. SFC Method 13: Column: Chiralcel OD-350*4.6 mm I.D., 3 µm; Mobile phase: Phase A for CO2, Phase B for EtOH (0.05% DEA), Gradient elution: 40% B in CO2, Flow rate: 3 mL / min; Detector: PDA; Column Temp: 35 °C; Back Pressure: 100Bar. SFC Method 14: Column: Lux 3µm Cellulose-250*4.6 mm I.D., 3 µm; Mobile phase: Phase A for CO2, Phase B for MeOH (0.05% DEA); Gradient elution: 50% MeOH (0.05% DEA) in CO2, Flow rate: 3mL / min; Detector: PDA; Column Temp: Back Pressure: 100Bar. SFC Method 15: Column: Chiralcel OD-350*4.6mm I.D.,3µm;Mobile phase: Phase A for CO2, and Phase B for IPA(0.05%DEA);Gradient elution: IPA(0.05%DEA) in CO2 from 5% to 40%,Flow rate:3mL / min; Detector: PDA; Column Temp:35 °C;Back Pressure:100Bar. SFC Method 16: Column: Chiralpak AD-350*4.6mm I.D., 3µm; Mobile phase: Phase A for CO2, and Phase B for MeOH (0.05%DEA);Gradient elution: MeOH (0.05%DEA) in CO2 from 10% to 60%;Flow rate:3mL / min; Detector: PDA;Column Temp: 35 °C;Back Pressure:100Bar. SFC Method 17: Column: Chiralcel OX-350*4.6mm I.D., 3µm, Mobile phase: Phase A for CO2, and Phase B for EtOH (0.05%DEA); Gradient elution: EtOH (0.05%DEA) in CO2 from 5% to 40%, Flow rate:3mL / min; Detector: PDA; Column Temp: 35 °C; Back Pressure:100Bar. SFC Method 18: Column: Chiralpak IE-350×4.6mm I.D., 3µm, Mobile phase: Phase A forHeptane, and Phase B for EtOH(0.05%DEA);Gradient elution:25%B in A, Flow rate: 1mL / min; Detector: PDA; Column Temp: 35 °C; Back Pressure:100Bar. 1H NMR Spectroscopy 1H NMR spectra were acquired on a Bruker Avance III spectrometer at 400 MHz using residual undeuterated solvent as reference.1H NMR signals are specified with their multiplicity / combined multiplicities as apparent from the spectrum; possible higher-order effects are not considered. Chemicalshifts of the signals ( ) are specified as ppm (parts per million).Salt stoichiometry: In the present text, in particular in the experimental section, for the synthesis of intermediates and of examples of the present invention, when a compound is mentioned as a salt form with the corresponding base or acid, the exact stoichiometric composition of said salt form, as obtained by the respective preparation and / or purification process, is, in most cases, unknown. Unless specified otherwise, suffixes to chemical names or structural formulae such as "hydrochloride", "trifluoroacetate", "sodium salt", or "x HO", "x CF3COOH", "x Na+", for example, are to be understood as not a stoichiometric specification, but solely as a salt form. This applies analogously to cases in which synthesis intermediates or example compounds or salts thereof have been obtained, by the preparation and / or purification processes described, as solvates, such as hydrates with (if defined) unknown stoichiometric composition Preparation of Intermediate 1.1 1,2-dimethylcyclopropan-1-amine; hydrogen chloride To a solution of titanium (IV) isopropoxide (2.47 g, 8.69 mmol) in MeCN (0.4 mL) and THF (3 mL) was added dropwise a solution of propylmagnesium bromide in THF (7.8 mL, 2 M, 15.6 mmol) at 0 °. The reaction mixture was stirred at 0 °C for 1 h and BF3.Et2O (3.1 mL, 15.6 mmol) was added dropwise at 0°C. The mixture was further stirred at 25 °C for 1 h, then, cooled to 0 °C and NaOH (aq., 10 mL, 2M) was added dropwise. The resulting solution was extracted with EtOAc (50 mL, 2x). The combined organiclayer was washed with HCl aq., 100 mL, 2M) and the combined aqueous layer was lyophilized to givethe product 1,2-dimethylcyclopropan-1-amine hydrogen chloride (400 mg, 3.29 mmol, crude) as a yellow oil which was used directly in the next step. Preparation of Intermediate 1.2 (5-bromo-3-chloropyridin-2-yl)methanamine To a mixture of 5-bromo-3-chloropicolinonitrile (2.0 g, 9.20 mmol) in THF (10 mL) under ice-water cooling was added BH3.THF (1 M, 11.04 mL) over 5 min. The mixture was stirred at 0°C for 30 min before it was warmed to 20°C and stirred for another 30 min at this temperature. The mixture was cooled to 0°C and quenched with dropwise addition of MeOH (10 mL) over 5 min. The mixture was heated to 70°C and stirred for 30 min at this temperature. The reaction was concentrated under vacuum to give the crude product (2.2 g) as a light brown solid. The crude product was dissolved in HCl (aq.2M, 20 mL), washed with DCM (20 mL; 2x) and the aqueous phase was finally concentrated under vacuum to give the product (5-bromo-3-chloropyridin-2-yl)methanamine (1.5 g, 4.07 mmol, 44.26% yield, 70% purity, HCl salt) as a light brown solid. RT 0.18 min (method 2); m / z 222.9 (M+H)+ (ESI+), 1H NMR (400 MHz, DMSO-d6) = 8.78 (d, J =2.0 Hz, 1H), 8.69 (br, 3H), 8.47 (d, J = 2.0 Hz, 1H), 4.24 (d, J = 6.2 Hz, 2H).Preparation of Intermediate 1.3 Ethyl 2-(((5-bromo-3-chloropyridin-2-yl)methyl)amino)-2-oxoacetate To a mixture of (5-bromo-3-chloro-2-pyridyl)methanamine (1.5 g, 5.82 mmol, HCl salt) in DCM (30 mL) under ice-water cooling was added DIPEA (2.25 g, 17.45 mmol). Then, ethyl 2-chloro-2-oxoacetate (952.77 mg, 6.98 mmol) was added over 5 min and the mixture was stirred at 0°C for 30 min. The mixture was warmed to 20°C and stirred for 30 min at this temperature. The mixture was quenched with aqueous NaHCO3 solution (50 mL) and extracted with DCM (50 mL). The organic phase was separated, dried over anhydrous Na2SO4, filtered and concentrated under vacuum. The residue was purified by column chromatography on silica gel (PE: EtOAc=10:1 to 1:1) to give the product ethyl 2-(((5-bromo-3- chloropyridin-2-yl)methyl)amino)-2-oxoacetate (1300 mg, 3.64 mmol, 62.57% yield, 65.6% purity) as a white solid. RT 0.61min (method 1); m / z 322.8 (M+H)+ (ESI+). The product was used without further purificationin the next step. Preparation of Intermediate 1.4 Ethyl 6-bromo-8-chloroimidazo[1,5-a]pyridine-3-carboxylate To a mixture of ethyl 2-(((5-bromo-3-chloropyridin-2-yl)methyl)amino)-2-oxoacetate (1300 mg, 4.04 mmol) in POCl3 (15 mL) under ice water cooling was added phosphorus pentoxide (2.87 g, 20.21 mmol). The mixture was heated to 110°C and stirred for 5 h at this temperature. The mixture was cooled to 25°C and concentrated under vacuum to give a residue. The residue was dissolved in EtOAc (50 mL) and thesolution was washed with water (30 mL) and an aqueous NaHCO3 solution (30 mL). before it was finallyconcentrated under vacuum to give a residue. The residue was purified by column chromatography on silica gel (PE: EtOAc=10:1 to 3:1) to give the product ethyl 6-bromo-8-chloroimidazo[1,5-a]pyridine-3- carboxylate (900 mg, 2.97 mmol, 73.34% yield) as a white solid. RT 0.718 min (method 1), m / z 304.8(M+H)+ (ESI+), 1H NMR (400 MHz, CDCl3) = 9.47 (s, 1H),7.77 (s, 1H), 7.20 (s, 1H), 4.65-4.42 (m, 2H), 1.57-1.42 (m, 3H). Preparation of Intermediate 1.5 6-bromo-8-chloroimidazo[1,5-a]pyridine-3-carbohydrazide To a mixture of ethyl 6-bromo-8-chloroimidazo[1,5-a]pyridine-3-carboxylate (900 mg, 2.97 mmol) in EtOH (20 mL) was added NH2NH2.H2O (1.48 g, 29.65 mmol, 98%). The mixture was heated to 80°C and stirred for 2 h at this temperature. The reaction was cooled to 25°C and the precipitated solid was separated off. The crude product was triturated with EtOH (5 mL) to give 6-bromo-8-chloroimidazo[1,5- a]pyridine-3-carbohydrazide (650 mg, 2.25 mmol, 75.72% yield) as a white solid.RT 0.56 min (method 1); m / z 290.8 (M+H)+ (ESI+); 1H NMR (400 MHz, DMSO-d6) = 10.02 (s, 1H),9.50 (s, 1H), 7.72 (s, 1H), 7.51 (s, 1H), 4.58 (d, J = 4.0 Hz, 2H).Preparation of Intermediate 1.6 6-bromo-8-chloro-N-(2,2-difluoroacetyl)imidazo[1,5-a]pyridine-3-carbohydrazide To a mixture of 6-bromo-8-chloroimidazo[1,5-a]pyridine-3-carbohydrazide (650 mg, 2.25 mmol) in EtOH (20 mL) was added ethyl 2,2-difluoroacetate (3.10 g, 22.45 mmol) and DBU (683.58 mg, 4.49 mmol). The mixture was heated to 100°C stirred for 16 h at this temperature. The mixture was cooled to 25°C and concentrated under vacuum. The residue was dissolved with DCM (50 mL), washed with an aqueous NH4Cl solution (30 mL; 2x) and concentrated under vacuum to give the crude product. The crude product was purified by column chromatography on silica gel (PE / EtOAc=1: 1 to MeOH: EtOAc=1: 10) to give the product 6-bromo-8-chloro-N-(2,2-difluoroacetyl)imidazo[1,5-a]pyridine-3-carbohydrazide (650 mg, 1.56 mmol, 69.32% yield, 88% purity) as a white solid. RT 0.62 min (method 1); m / z 368.8 (M+H)+ (ESI+); 1H NMR (400 MHz, DMSO-d6) = 10.95 (br,2H), 9.44 (s, 1H), 7.81 (s, 1H), 7.59 (s, 1H), 6.38 (t, J = 53.2, 1H).Preparation of Intermediate 1.7 2-(6-bromo-8-chloroimidazo[1,5-a]pyridin-3-yl)-5-(difluoromethyl)-1,3,4-thiadiazole To a mixture of 6-bromo-8-chloro-N'-(2,2-difluoroacetyl)imidazo[1,5-a]pyridine-3-carbohydrazide (550 mg, 1.50 mmol) in toluene (20 mL) was added Lawesson’s reagent (665.80 mg, 1.65 mmol) under a N2 atmosphere. The mixture was heated to 120°C and stirred for 2 h at this temperature. The mixture was cooled to 25°C and concentrated under vacuum. The residue was triturated with MeOH (10 mL) at 70°C for 1h, filtered and the cake was collected, and dried under vacuum to give the product 2-(6-bromo-8- chloroimidazo[1,5-a]pyridin-3-yl)-5-(difluoromethyl)-1,3,4-thiadiazole (530 mg, 1.45 mmol, 96.88% yield) as a light yellow solid.RT 0.806 min (method 1); m / z 366.8 (M+H)+ (ESI+); 1H NMR (400 MHz, DMSO-d6) = 9.62 (s, 1H),8.64 (s, 1H), 8.09 (s, 1H), 7.70 (t, J = 53.2, 1H).Preparation of Intermediate 1.8 2-(6-(benzylthio)-8-chloroimidazo[1,5-a]pyridin-3-yl)-5-(difluoromethyl)-1,3,4-thiadiazole To a mixture of 2-(6-bromo-8-chloroimidazo[1,5-a]pyridin-3-yl)-5-(difluoromethyl)-1,3,4-thiadiazole (450 mg, 1.23 mmol) and phenylmethanethiol (168.17 mg, 1.35 mmol) in dioxane (10 mL) which was degassed with nitrogen for 2 min was added Pd2(dba)3 (112.72 mg, 123.09 µmol), Xantphos (71.22 mg, 123.09 µmol) and DIEA (477.26 mg, 3.69 mmol) under nitrogen. The mixture was heated to 90°C and stirred for 16 h at this temperature. The mixture was filtered and concentrated under vacuum. The residue was purified by column chromatography on silica gel (PE: EtOAc=20:1 to 5:1) to give the product 2-(6- (benzylthio)-8-chloroimidazo[1,5-a]pyridin-3-yl)-5-(difluoromethyl)-1,3,4-thiadiazole (250 mg, 489.15 µmol, 39.74% yield, 80% purity) as a light yellow solid.RT 0.99 min (method 1); m / z 409.0 (M+H)+ (ESI+);1H NMR (400 MHz, DMSO-d6) 9.20 (s, 1 H), 7.89 (s, 1 H), 7.67 (t, J = 52.8 Hz, 1 H), 7.52 (s, 1 H), 7.40-7.36 (m, 2 H), 7.31-7.26 (m, 2 H), 7.23-7.18 (m, 1 H), 4.34 (s, 2 H). Preparation of intermediate 1.9 8-chloro-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)imidazo[1,5-a]pyridine-6-sulfonyl chloride To a mixture of 2-(6-(benzylthio)-8-chloroimidazo[1,5-a]pyridin-3-yl)-5-(difluoromethyl)-1,3,4- thiadiazole (5.00 g, 12.2 mmol) in AcOH (50 mL, 874 mmol) and water (50 mL) was added 1,3-dichloro- 5,5-dimethyl-imidazolidine-2,4-dione (7.23 g, 36.7 mmol) in batches over 10 min at 0°C. The reaction mixture was then stirred at 0 °C for 0.5 h, poured into ice-water (100 mL), filtered and the filter cake was collected. The filter cake was dissolved in DCM (50 mL) and washed with ice water (50 mL, 3x). The organic layer was dried over anhydrous Na2SO4, filtered and concentrated under vacuum to give the product 8-chloro-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)imidazo[1,5-a]pyridine-6-sulfonyl chloride (3.00 g, 7.79 mmol, 63.69% yield) as a light yellow solid. The crude product was used for the next step directly. RT 0.605 min (method 1); m / z 384.9 (M+H)+(ESI+) Preparation of Intermediate 1.10 8-chloro-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-(1,2-dimethylcyclopropyl)imidazo[1,5- a]pyridine-6-sulfonamide At 0°C, to a solution of 1,2-dimethylcyclopropan-1-amine hydrochloride (600 mg, 4.672 mmol, HCl salt) in DCM (6 mL) was added DIEA (0.83 mL, 4.672 mmol) and the mixture was stirred for 10 min. Then, 8-chloro-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)imidazo[1,5-a]pyridine-6-sulfonyl chloride (600 mg, 1.5576 mmol) was added. The resulting mixture was stirred at 0 °C for 0.5 h and then, poured into water (60 mL). The aqueous layer was extracted with EtOAc (30 mL, 3x). The combined organic layer was washed with brine (20 mL, 2x), dried over anhydrous Na2SO4, filtered and concentrated under vacuum. The resulting residue was purified by flash silica gel chromatography (ISCO; 40 g SepaFlash Silica Flash Column, Eluent of 5~30% EtOAc / PE gradient @ 60 mL / min) and concentrated under vacuum to give the product 8-chloro-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-(1,2-dimethylcyclopropyl)imidazo[1,5- a]pyridine-6-sulfonamide (270 mg, 0.6223 mmol, 72.30% yield) as a brown solid. RT 0.579 min (LCMS method 1); m / z 434.1 (M+H)+ (ESI+); 1H NMR (400 MHz, DMSO-d6) 9.85-9.82(m, 1 H), 8.50 (s, 1H), 8.06 (d, J=0.8 Hz, 1 H), 7.70 (t, J = 53.6 Hz, 1H), 7.53-7.49 (m, 1H), 1.13-1.22 (m,1 H), 1.06-1.13 (m, 3 H), 0.95-0.85 (m, 3 H), 0.53-0.68 (m, 2 H) Preparation of Intermediate 1.11 tert-butyl (2S,6S)-4-(3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-6-(N-(1,2- dimethylcyclopropyl)sulfamoyl)imidazo[1,5-a]pyridin-8-yl)-2,6-dimethylpiperazine-1-carboxylate

[0003] To a solution of 8-chloro-3-[5-(difluoromethyl)-1,3,4-thiadiazol-2-yl]-N-(1,2- dimethylcyclopropyl)imidazo[1,5-a]pyridine-6-sulfonamide (130 mg, 0.2996 mmol) in dioxane (2 mL) was added tert-butyl (2S,6S)-2,6-dimethylpiperazine-1-carboxylate (256 mg, 1.198 mmol), Pd-PEPPSI-IPent Cl (25 mg, 0.0300 mmol) and Cs2CO3 (292 mg, 0.8989 mmol). The mixture was degassed with N2 (3x) and stirred at 100 °C for 0.5 h under a nitrogen atmosphere. After cooling, the resulting mixture was poured into water (20 mL). The aqueous layer was extracted with EtOAc (20 mL, 3x). The combined organic layer was washed with brine (20 mL, 2x), dried over anhydrous Na2SO4, filtered and concentrated under vacuum to give the product tert-butyl (2S,6S)-4-(3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-6-(N- (1,2-dimethylcyclopropyl)sulfamoyl)imidazo[1,5-a]pyridin-8-yl)-2,6-dimethylpiperazine-1-carboxylate (180 mg, 0.294 mmol, crude) as a yellow oil. RT 0.629 min (LCMS method 1); m / z 612.2 (M+H)+ (ESI+);Preparation of Example 1 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-(1,2-dimethylcyclopropyl)-8-((3S,5S)-3,5- dimethylpiperazin-1-yl)imidazo[1,5-a]pyridine-6-sulfonamide A solution of tert-butyl (2S,6S)-4-[3-[5-(difluoromethyl)-1,3,4-thiadiazol-2-yl]-6-[(1,2- dimethylcyclopropyl)sulfamoyl]imidazo[1,5-a]pyridin-8-yl]-2,6-dimethyl-piperazine-1-carboxylate (180 mg, 0.2942 mmol) in TFA (2.0 mL) was stirred at 25 °C for 1 h. The resulting mixture was concentrated under vacuum to give a residue, which was purified by preparative HPLC (column: Welch Ultimate C18 150*25mm*5µm; mobile phase: A: 0.1% trifluoroacetic acid in water, B: MeCN; B%: 22%-52%, 10 min) and lyophilized to give the product 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-(1,2- dimethylcyclopropyl)-8-((3S,5S)-3,5-dimethylpiperazin-1-yl)imidazo[1,5-a]pyridine-6-sulfonamide (130 mg, 0.2118 mmol, 71.98% yield) as a brown gum. RT 0.475 min (LCMS method 4); m / z 512.2 (M+H)+ (ESI+).(400 MHz, CDCl3): 9.89 (s, 1H), 7.71 (s,1H), 7.08 (t, J = 53.8 Hz, 1H), 6.65 (s, 1H), 5.16 (s, 1H), 3.54-3.45 (m, 2H), 3.34-3.25 (m, 2H), 3.16-3.07(m, 2H), 1.35 (d, J = 6.4 Hz, 6H), 1.31-1.20 (m, 3H), 1.10-1.12 (m, 3H), 0.80-0.72 (m, 2H), 0.69-0.64 (m,1H) Preparation of Example 1a 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-1,2-dimethylcyclopropyl)-8-((3S,5S)-3,5-dimethylpiperazin-1-yl)imidazo[1,5-a]pyridine-6-sulfonamide diastereomer 1 (single diastereomerwith unknown absolute configuration for chiral centers where it is not specified) and Example 1b 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-1,2-dimethylcyclopropyl)-8-((3S,5S)-3,5-dimethylpiperazin-1-yl)imidazo[1,5-a]pyridine-6-sulfonamide diastereomer 2 (single diastereomerwith unknown absolute configuration for chiral centers where it is not specified) As explained in the following (see also Figure 1), diastereoisomer 1 has been determined to have the following absolute structure (based on the structure of one of its synthesis intermediates): Accordingly, diastereoisomer 1 includes the (1S,2R)-dimethylcyclopropylamino group. The product 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-(1,2-dimethylcyclopropyl)-8-((3S,5S)-3,5- dimethylpiperazin-1-yl)imidazo[1,5-a]pyridine-6-sulfonamide (130 mg, 0.254 mmol) was purified by SFC (Column: DAICEL Chiralpak AS 250*30mm I.D.,10 µm; Mobile phase: Phase A for Hexane and Phase B for IPA(0.1% NH3·H2O); Gradient elution IPA(0.1% NH3·H2O) in Hexane from 5% to 20%, Flow rate: 85 mL / min; Column Temp: 25 °C) to give 3 fractions: -Fraction 1 which was concentrated under vacuum to give the product 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-(1S,2R)-dimethylcyclopropyl)-8-((3S,5S)-3,5-dimethylpiperazin-1-yl)imidazo[1,5- a]pyridine-6-sulfonamide diastereomer 1 (22 mg, 0.0438 mmol, 17.23% yield) as a light yellow solid. RT 0.451 min (LCMS method 4); m / z 512.1 (M+H)+ (ESI+). RT 2.688 min (SFC Method 1).1H NMR(400 MHz, CDCl3): 9.89 (s, 1H), 7.72 (s, 1H), 7.08 (t, J = 53.8 Hz, 1H), 6.65 (s, 1H), 5.03 (s, 1H), 3.54-3.47 (m, 2H), 3.34-3.25 (m, 2H), 3.16-3.07 (m, 2H), 1.35 (d, J = 6.4 Hz, 6H), 1.31 (s, 3H), 1.12 (d, J = 5.8Hz, 3H), 0.80-0.72 (m, 2H), 0.69-0.64 (m, 1H) -Fraction 2 which was concentrated under vacuum to give the product 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N--1,2-dimethylcyclopropyl)-8-((3S,5S)-3,5-dimethylpiperazin-1-yl)imidazo[1,5- a]pyridine-6-sulfonamide diastereomer 2 (more specifically, 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N- (1R,2S)-1,2-dimethylcyclopropyl)-8-((3S,5S)-3,5-dimethylpiperazin-1-yl)imidazo[1,5-a]pyridine-6- sulfonamide) (11 mg, 0.0208 mmol, 8.19% yield) as a light yellow solid. RT 0.463 min (LCMS method 4); m / z 512.2 (M+H)+ (ESI+). RT 3.740 min (SFC Method 1).1H NMR(400 MHz, CDCl3): 9.89 (s, 1H), 7.72 (s, 1H), 7.08 (t, J = 53.8 Hz, 1H), 6.66 (s, 1H), 5.03 (s, 1H), 3.56-3.47 (m, 2H), 3.34-3.27 (m, 2H), 3.16-3.08 (m, 2H), 1.38 (d, J = 6.4 Hz, 6H), 1.31 (s, 3H), 1.11 (d, J = 5.8Hz, 3H), 0.78-0.72 (m, 2H), 0.70-0.65 (m, 1H) -Fraction 3 (SFC method 1 RT 6.036 min) which was concentrated under vacuum to give a mixtureof products 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N--1,2-dimethylcyclopropyl)-8-((3S,5S)-3,5- dimethylpiperazin-1-yl)imidazo[1,5-a]pyridine-6-sulfonamide diastereomer 3 and 3-(5-(difluoromethyl)- 1,3,4-thiadiazol-2-yl)-N--1,2-dimethylcyclopropyl)-8-((3S,5S)-3,5-dimethylpiperazin-1-yl)imidazo[1,5- a]pyridine-6-sulfonamide diastereomer 4 (5.7 mg, 0.011 mmol, 4.38 % yield) (mixture of diastereomer 3 & diastereomer 4) as a light yellow solid. RT 0.467 min (method 4); m / z 512.2 (M+H)+(ESI+).1H NMR (400 MHz, CDCl3): 9.88 (s, 1H), 7.68(s, 1H), 7.09 (t, J = 53.8 Hz, 1H), 6.74 (s, 1H), 5.70 (s, 1H), 3.79-3.73 (m, 2H), 3.51-3.45 (m, 2H), 3.35-3.28 (m, 2H), 1.54 (d, J = 6.4 Hz, 6H), 1.33 (s, 3H), 1.25-1.12 (m, 2H), 1.06-1.00 (m, 4H).Preparation of Intermediate 1.10a 8-chloro-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-1,2-dimethylcyclopropyl)imidazo[1,5- a]pyridine-6-sulfonamide diastereomer 1, Intermediate 1.10b 8-chloro-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-1,2-dimethylcyclopropyl)imidazo[1,5- a]pyridine-6-sulfonamide diastereomer 2 (single diastereomer with unknown absolute configuration for chiral centers where it is not specified) and intermediate 1.10c Mixture of 8-chloro-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-1,2- dimethylcyclopropyl)imidazo[1,5-a]pyridine-6-sulfonamide diastereomer 3 and 8-chloro-3-(5- (difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-1,2-dimethylcyclopropyl)imidazo[1,5-a]pyridine-6- sulfonamide diastereomer 4 Accordingly, diastereoisomer 1 includes the (1S,2R)-dimethylcyclopropylamino group. 8-chloro-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-(1,2-dimethylcyclopropyl)imidazo[1,5- a]pyridine-6-sulfonamide (270 mg, 0.622 mmol) was purified by preparative SFC (Column: DAICEL Chiralpak AS 250*50 mm I.D.,10 µm; Mobile phase: Phase A for CO2 and Phase B for EtOH (0.1% NH3·H2O); Gradient elution: EtOH(0.1% NH3·H2O) in CO2 from 5% to 30%; Flow rate: 200 g / min; Column Temp: 25°C; Back Pressure: 100 Bar CO2 ) and concentrated under vacuum to give 3 fractions: - Fraction 1: 8-chloro-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-(1S,2R)- dimethylcyclopropyl)imidazo[1,5-a]pyridine-6-sulfonamide diastereomer 1 (43 mg, 0.0991 mmol, 15.93% yield) obtained as a white solid; RT 0.616 min (LCMS Method 2); m / z 434.0 (M+H)+ (ESI+). RT 1.206 min (SFC Method 2).- Fraction 2: 8-chloro-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-(1,2- dimethylcyclopropyl)imidazo[1,5-a]pyridine-6-sulfonamide diastereomer 2 (more specifically, 8-chloro-3- (5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-((1R,2S)-1,2-dimethylcyclopropyl)imidazo[1,5-a]pyridine-6- sulfonamide)(48 mg, 0.111 mmol, 17.78% yield) obtained as a white solid; RT 0.565 min (LCMS Method 2); m / z 434.0 (M+H)+ (ESI+). RT 1.302 min (SFC Method 2).- Fraction 3: mixture of 8-chloro-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N--1,2-dimethylcyclopropyl)imidazo[1,5-a]pyridine-6-sulfonamide diastereomer 3 and 8-chloro-3-(5- (difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-1,2-dimethylcyclopropyl)imidazo[1,5-a]pyridine-6-sulfonamide diastereomer 4 (150 mg, 0.346 mmol, 55.56% yield) obtained as a white solid.RT 0.579 min (LCMS method 2); m / z 434.1 (M+H)+ (ESI+). RT 1.433 &1.456 min (SFC Method 2).1H NMR (400 MHz, CDCl3) 10.09 (s, 1H), 7.90 (s, 1H), 7.38 (d, J = 1.2 Hz, 1H), 7.09 (t, J = 53.6 Hz, 1H),5.27 (s, 1H), 1.37 (s, 3H), 1.30-1.09 (m, 2H), 1.06 (d, J = 6.3 Hz, 3H), 1.04-1.00 (m, 1H)Preparation of Intermediate 1.12 Mixture of tert-butyl (2S,6S)-4-(3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-6-(N-1,2- dimethylcyclopropyl)sulfamoyl)imidazo[1,5-a]pyridin-8-yl)-2,6-dimethylpiperazine-1-carboxylate diastereomer 3 and tert-butyl (2S,6S)-4-(3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-6-(N-1,2- dimethylcyclopropyl)sulfamoyl)imidazo[1,5-a]pyridin-8-yl)-2,6-dimethylpiperazine-1-carboxylate diastereomer 4 To a solution of mixture of 8-chloro-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-1,2- dimethylcyclopropyl)imidazo[1,5-a]pyridine-6-sulfonamide diastereomer 3 and 8-chloro-3-(5- (difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-1,2-dimethylcyclopropyl)imidazo[1,5-a]pyridine-6-sulfonamide diastereomer 4 (50 mg, 0.115 mmol) in 1,4-dioxane (2 mL) was added tert-butyl (2S,6S)-2,6- dimethylpiperazine-1-carboxylate (99 mg, 0.461 mmol), Pd-PEPPSI-IPent Cl (9.7 mg, 0.0115 mmol) and Cs2CO3 (113 mg, 0.346 mmol). The mixture was degassed with N2 (3x), stirred at 100 °C for 2 h under a nitrogen atmosphere and then, poured into water (20 mL). The aqueous layer was extracted with EtOAc (20 mL, 3x). The combined organic layer was washed with brine (20 mL, 2x), dried over anhydrous Na2SO4, filtered and the filtrate was concentrated under vacuum. The resulting residue was purified by preparative HPLC (column: Waters xbridge 150*25mm 10µm; mobile phase: A: 0.05% NH3H2O in water, B: MeCN; B%: 48%-78%, 10 min) and lyophilized to give the product mixture of tert-butyl (2S,6S)-4-(3-(5- (difluoromethyl)-1,3,4-thiadiazol-2-yl)-6-(N--1,2-dimethylcyclopropyl)sulfamoyl)imidazo[1,5-a]pyridin-8- yl)-2,6-dimethylpiperazine-1-carboxylate diastereomer 3 and tert-butyl (2S,6S)-4-(3-(5-(difluoromethyl)- 1,3,4-thiadiazol-2-yl)-6-(N-1,2-dimethylcyclopropyl)sulfamoyl)imidazo[1,5-a]pyridin-8-yl)-2,6- dimethylpiperazine-1-carboxylate diastereomer 4 (40 mg,0.0654 mmol, 56.74 % yield) as a yellow solid.RT 0.765 min (LCMS method 3); m / z 612.3 (M+H)+ (ESI+). RT 1.809 & 2.124 min (SFC Method 3).Preparation of Intermediate 1.11c tert-butyl (2S,6S)-4-(3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-6-(N-1,2- dimethylcyclopropyl)sulfamoyl)imidazo[1,5-a]pyridin-8-yl)-2,6-dimethylpiperazine-1-carboxylate diastereomer 3 (single diastereomer with unknown absolute configuration for chiral centers where it is not specified) and intermediate 1.11d tert-butyl (2S,6S)-4-(3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-6-(N-1,2- dimethylcyclopropyl)sulfamoyl)imidazo[1,5-a]pyridin-8-yl)-2,6-dimethylpiperazine-1-carboxylatediastereomer 4 (single diastereomer with unknown absolute configuration for chiral centers where it isnot specified) The mixture of tert-butyl (2S,6S)-4-(3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-6-(N-1,2- dimethylcyclopropyl)sulfamoyl)imidazo[1,5-a]pyridin-8-yl)-2,6-dimethylpiperazine-1-carboxylate diastereomer 3 and tert-butyl (2S,6S)-4-(3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-6-(N-1,2- dimethylcyclopropyl)sulfamoyl)imidazo[1,5-a]pyridin-8-yl)-2,6-dimethylpiperazine-1-carboxylate diastereomer 4 (40 mg, 0.0654 mmol) was purified by preparative SFC (Column: DAICEL Chiralcel OD 250*30 mm I.D.,10 µm Mobile phase: Phase A for CO2 and Phase B for EtOH(0.1% NH3·H2O); Gradient elution: EtOH(0.1% NH3·H2O) in CO2 from 5% to 40%, Flow rate: 150 g / min; Column Temp: 25 °C; Back Pressure:100 Bar CO2 ) to give the product tert-butyl (2S,6S)-4-(3-(5-(difluoromethyl)-1,3,4-thiadiazol-2- yl)-6-(N--1,2-dimethylcyclopropyl)sulfamoyl)imidazo[1,5-a]pyridin-8-yl)-2,6-dimethylpiperazine-1- carboxylate diastereomer 3 (16 mg, 0.0262 mmol, 40.00 % yield) as a yellow solid RT 0.624 min (LCMS method 2); m / z 612.3 (M+H)+ (ESI+). RT 1.809 min (SFC Method 3)and the product tert-butyl (2S,6S)-4-(3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-6-(N-1,2- dimethylcyclopropyl)sulfamoyl)imidazo[1,5-a]pyridin-8-yl)-2,6-dimethylpiperazine-1-carboxylate diastereomer 4 (16 mg, 0.0262 mmol, 40.00 % yield) as a yellow solid.RT 0.635 min (LCMS method 2); m / z 612.3 (M+H)+ (ESI+). RT 2.124 min (SFC Method 3).Preparation of Example 1c 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-1,2-dimethylcyclopropyl)-8-((3S,5S)-3,5-dimethylpiperazin-1-yl)imidazo[1,5-a]pyridine-6-sulfonamide diastereomer 3 (single diastereomerwith unknown absolute configuration for chiral centers where it is not specified) A solution of tert-butyl (2S,6S)-4-(3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-6-(N-1,2- dimethylcyclopropyl)sulfamoyl)imidazo[1,5-a]pyridin-8-yl)-2,6-dimethylpiperazine-1-carboxylate diastereomer 3 (20 mg, 0.0327 mmol) in TFA (0.50 mL) was stirred at 25 °C for 1 h. The resulting mixture was directly concentrated under vacuum to give the residue, which was purified by preparative HPLC (column: Welch Ultimate C18150*25mm*5µm; mobile phase: A: 0.1% trifluoroacetic acid in water, B: MeCN; B%: 18%-48%, 10 min) and lyophilized to give 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-1,2- dimethylcyclopropyl)-8-((3S,5S)-3,5-dimethylpiperazin-1-yl)imidazo[1,5-a]pyridine-6-sulfonamide diastereomer 3, which was further purified by preparative SFC (Column: DAICEL Chiralpak AS 250*30mm I.D.,10 µm; Mobile phase: Phase A for Hexane and Phase B for IPA(0.1% NH3·H2O); Gradient elution IPA(0.1% NH3·H2O) in Hexane from 5% to 20%, Flow rate: 85 mL / min; Column Temp: 25 °C) to give the product 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N--1,2-dimethylcyclopropyl)-8-((3S,5S)-3,5- dimethylpiperazin-1-yl)imidazo[1,5-a]pyridine-6-sulfonamide diastereomer 3 (5.0 mg, 0.00954 mmol, 29.17% yield) as a yellow solid. RT 0.463 min (LCMS method 4); m / z 512.2 (M+H)+ (ESI+). RT 1.217 min (SFC Method 4).1H NMR(400 MHz, CDCl3): 9.84 (s, 1H), 7.72 (s, 1H), 7.09 (t, J = 53.8 Hz, 1H), 6.65 (s, 1H), 5.35-5.12 (m, 1H),3.56-3.48 (m, 2H), 3.32-3.25 (m, 2H), 3.13-3.05 (m, 2H), 1.38 (d, J = 6.5 Hz, 6H), 1.35 (s, 3H), 1.24-1.16(m, 2H), 1.06-1.01 (m, 4H) Preparation of Example 1d 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N--1,2-dimethylcyclopropyl)-8-((3S,5S)-3,5- dimethylpiperazin-1-yl)imidazo[1,5-a]pyridine-6-sulfonamide 2,2,2-trifluoroacetate diastereomer 4 (single diastereomer with unknown absolute configuration for chiral centers where it is not specified) A solution of tert-butyl (2S,6S)-4-(3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-6-(N--1,2- dimethylcyclopropyl)sulfamoyl)imidazo[1,5-a]pyridin-8-yl)-2,6-dimethylpiperazine-1-carboxylate diastereomer 4 (16 mg, 0.0327 mmol) in TFA (0.50 mL) was stirred at 25 °C for 1 h. The resulting mixture was directly concentrated under vacuum to give a residue, which was purified by preparative HPLC (column: Welch Ultimate C18150*25mm*5µm; mobile phase: A: 0.1% trifluoroacetic acid in water, B: MeCN; B%: 18%-48%, 10 min) and lyophilized to give the product 3-(5-(difluoromethyl)-1,3,4-thiadiazol- 2-yl)-N-1,2-dimethylcyclopropyl)-8-((3S,5S)-3,5-dimethylpiperazin-1-yl)imidazo[1,5-a]pyridine-6- sulfonamide 2,2,2-trifluoroacetate diastereomer 4 (7.0 mg, 0.0110 mmol, 33.66% yield, TFA salt) as a yellow gum. RT 0.464 min (LCMS method 4); m / z 512.2 (M+H)+ (ESI+); RT 1.753 min (SFC Method 4).1H NMR(400 MHz, CDCl3): 9.92 (s, 1H), 9.89-9.66 (m, 2H), 7.67 (s, 1H), 7.09 (t, J = 53.8 Hz, 1H), 6.78 (s, 1H),5.65 (s, 1H), 3.90-3.85 (m, 2H), 3.65-3.50 (m, 2H), 3.45-3.35 (m, 2H), 1.64 (d, J = 6.5 Hz, 6H), 1.33 (s,3H), 1.31-1.07 (m, 2H), 1.06-1.01 (m, 4H) Determination of the absolute configuration of example 1a (diatereomer 1) A new batch of Intermediate 1.10a was prepared following the exemplified procedure and was used for X-ray crystallographic analysis. The crystals are colourless needles with the following dimensions: 0.40 × 0.03 × 0.02 mm3. The symmetry of the crystal structure was assigned the trigonal space group P31 with thefollowing parameters: a = 37.9321(10) Å, b = 37.9321(10) Å, c =6.8147(3) Å, = 90°, = 90°, = 120°,V = 8491.6(6) Å3, Z = 18, Dc = 1.527 g / cm3, F(000) = 3996.0, (CuK ) = 4.241 mm-1, and T = 149.99(10) K. The absolute configuration structure is judged by the value of Flack parameter and the structure of the crystal has been determined as follows (see also ORTEP structure) : Absolute configuration of Intermediate 1.10a The present inventors have further shown that intermediate 1.10b is an enantiomer of intermediate 1.10a. Accordingly, the intermediate 1.10b is 8-chloro-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N- ((1R,2S)-1,2-dimethylcyclopropyl)imidazo[1,5-a]pyridine-6-sulfonamide. This new batch of Intermediate 1.10a was pushed forward according the procedure of “Preparation of Intermediate 1.11” and “Preparation of Example 1” to give after comparing the SFC retention time (RT0.451 min (LCMS method 4); m / z 512.2 (M+H)+ (ESI+); RT 2.626 min (SFC Method 1)) a new batch ofExample 1a (diastereomer 1). Therefore, the absolute configuration of Example 1a is as follows: Absolute configuration structure of Example 1a Preparation of Intermediate 5.1 1-(2-bromo-2-fluoro-1-methylcyclopropyl)-4-methoxybenzene To a solution of 1-methoxy-4-(prop-1-en-2-yl)benzene (2.50 g, 16.9 mmol) and N-benzyl-N,N- diethylethanaminium chloride (1.54 g, 6.75 mmol) in DCM (25 mL) was added dibromofluoromethane (9.71 g, 50.6 mmol) and aq. NaOH (5.3 mL, 202 mmol, 50% wt / wt). The reaction mixture was stirred at 20°C for 12 h. Then, additional dibromofluoromethane (6.47 g, 33.7 mmol) was added and the mixture was stirred at 20°C for another 12 h. The resulting mixture was diluted with water (30 mL) and extracted with DCM (30 mL; 2x). The combined organic layer was washed with brine (30 mL; 2x), dried over anhydrous Na2SO4 and concentrated under vacuum. The residue was purified by flash silica gel chromatography (ISCO; 40 g SepaFlash. Silica Flash Column, Eluent of 0~5% Ethyl acetate / Petroleum ether gradient @ 80 mL / min) to give a mixture of cis and trans product 1-(2-bromo-2-fluoro-1- methylcyclopropyl)-4-methoxybenzene (4.30 g,16.6 mmol, 98.38 % yield) as a colorless oil. 1H NMR (CDCl3, 400 MHz): 7.27-7.19 (m, 2H), 6.92-6.86 (m, 2H), 3.83-3.80 (m, 3H), 1.99-1.34 (m, 5H) Preparation of Intermediate 5.2 1-(2-fluoro-1-methylcyclopropyl)-4-methoxybenzene To a solution of 1-(2-bromo-2-fluoro-1-methylcyclopropyl)-4-methoxybenzene (4.30 g, 16.6 mmol) in ethanol (70 mL) was added NH4Cl (1776 mg, 33.2 mmol) and Zn (6.84 g, 116 mmol). The mixture was stirred at 80°C for 12 h, then filtered and was washed with EtOH(100 mL; 2x). The combined filtrate was concentrated under vacuum. The resulting residue was diluted with ethyl acetate (100 mL), washed with brine (100 mL), dried over anhydrous Na2SO4 and concentrated under vacuum. The residue was purified by flash silica gel chromatography (ISCO; 80 g SepaFlash Silica Flash column, Eluent of 0%-5% Ethyl acetate / Petroleum ether; gradient @ 80 mL / min) to give the product 1-(2-fluoro-1-methylcyclopropyl)-4- methoxybenzene (2100 mg, 11.7 mmol, 70.22 % yield) as colorless oil. 1H NMR (CDCl3, 400 MHz): 7.33-7.27 (m, 1H), 7.19-7.12 (m, 1H), 6.96-6.76 (m, 2H), 4.76-4.42 (m, 1H), 3.89-3.74 (m, 3H), 1.52-1.42 (m, 3H), 1.25-0.82 (m, 2H) Preparation of Intermediate 5.3. 2-fluoro-1-methylcyclopropane-1-carboxylic acid To a solution of 1-(2-fluoro-1-methylcyclopropyl)-4-methoxybenzene (1.90 g, 10.5 mmol) in MeCN (10 mL), CCl4 (10 mL) and water (20 mL) was added NaIO4 (40.59 g, 190 mmol) and RuCl3·H2O (119 mg, 0.527 mmol). The resulting mixture was stirred at 20°C for 12 h, then filtered through celite and the cake was washed with EtOAc (100 mL). The filtrate was concentrated under vacuum to give the product 2-fluoro-1-methylcyclopropane-1-carboxylic acid (1 g, 8.47 mmol, 80.31 % yield) as yellow oil which was used in the next step without further purification. 1H NMR (DMSO-d6, 400 MHz): 12.68-12.24 (m, 1H), 5.01-4.80 (m, 1H), 1.37-1.30 (m, 1H), 1.27 (m, 3H), 1.21-1.14 (m, 1H) Preparation of intermediate 5.4-cis & 5.4-trans Cis-benzyl (2-fluoro-1-methylcyclopropyl)carbamate & Trans-benzyl (2-fluoro-1- methylcyclopropyl)carbamate To a solution of 2-fluoro-1-methylcyclopropane-1-carboxylic acid (1 g, 8.47 mmol) and TEA (4.7 mL, 33.9 mmol) in toluene (20 mL) was added DPPA (2.4 mL, 12.7 mmol) and 4Å molecular sieve (7 g) and the reaction mixture was stirred at 60°C for 15 min. Then, BnOH (2.6 mL, 25.4 mmol) was added. The resulting mixture was stirred at 60°C for 12 h, then filtered and concentrated under vacuum. The residue was purified by flash silica gel chromatography (ISCO; 20 g SepaFlash Silica Flash Column, Eluent of 0%-10% Ethyl acetate / Petroleum ether; gradient @ 70 mL / min) to give a mixture of cis and trans products which was further purified by preparative-TLC (SiO2, petroleum ether:EtOAc=3:1) to give the product cis-benzyl (2-fluoro-1-methylcyclopropyl)carbamate (120 mg, 0.538 mmol, 6.35 % yield) as a white solid and trans-benzyl (2-fluoro-1-methylcyclopropyl)carbamate (210 mg,0.941 mmol, 11.11 % yield) as a white solid. Cis- benzyl (2-fluoro-1-methylcyclopropyl)carbamate: 1H NMR (DMSO-d6, 400 MHz): 7.66 (s, 1H),7.40-7.28 (m, 5H), 5.04 (s, 2H), 4.67-4.33 (m, 1H), 1.17 (d, J = 3.2 Hz, 3H), 1.05-0.95 (m, 1H), 0.91-0.82(m, 1H) Trans-benzyl (2-fluoro-1-methylcyclopropyl)carbamate: 1H NMR (DMSO-d6, ,400 MHz): 7.58 (s,1H), 7.41-7.26 (m, 5H), 4.70 (s, 2H), 4.74-4.46 (m, 1H), 1.17 (d, J = 2.8 Hz, 3H), 1.02-0.96 (m, 1H),0.95-0.88 (m, 1H) Preparation of Intermediate 5.5 Cis-2-fluoro-1-methylcyclopropan-1-amine hydrochloride To a solution of cis-benzyl (2-fluoro-1-methylcyclopropyl)carbamate (150 mg, 0.672 mmol) in methanol (2 mL) was added wet Pd / C (150 mg, 6.25 mmol) and HCl in methanol (1.0 mL, 2 N). Then, the mixture was stirred at 25°C for 12 h under H2 (50 psi). The mixture was filtered through a pad of celite and the cake was washed with MeOH (10 mL). The filtrate was concentrated under vacuum to give the product Cis-2-fluoro-1-methylcyclopropan-1-amine hydrochloride (90 mg, crude) as white gum which was used in the next step without further purification. 1H NMR (DMSO-d6, 400 MHz): 8.71 (br s, 3H), 4.85-4.67 (m, 1H), 1.39-1.30 (m, 1H), 1.29 (d, J =2.8 Hz, 3H), 1.14-1.01 (m, 1H) Preparation of Example 24 Cis-8-chloro-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-(2-fluoro-1- methylcyclopropyl)imidazo[1,5-a]pyridine-6-sulfonamide To a solution of cis-2-fluoro-1-methylcyclopropan-1-amine hydrochloride (86 mg, 0.685 mmol) in DCM (2 mL) was added DIEA (0.31 mL, 1.71 mmol) at 0°C, followed by 8-chloro-3-(5-(difluoromethyl)- 1,3,4-thiadiazol-2-yl)imidazo[1,5-a]pyridine-6-sulfonyl chloride (220 mg, 0.571 mmol) in DCM (2 mL) dropwise. Then, the reaction mixture was stirred at 0°C for 1 h, poured into water (10 mL) and extracted with DCM (10 mL; 2x). The combined organic layer was washed with brine (10 mL; 2x), dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by preparation- TLC (SiO2, petroleum ether: EtOAc=2:1) to give the product cis-8-chloro-3-(5-(difluoromethyl)-1,3,4- thiadiazol-2-yl)-N-(2-fluoro-1-methylcyclopropyl)imidazo[1,5-a]pyridine-6-sulfonamide (20 mg, 0.0445 mmol, 7.80 % yield) as a white solid. LCMS: RT 0.562 min (method 7); m / z 438.0 (M+H)+ (ESI+). SFC: RT 1.899, 2.215 min (method9); 1H NMR (CDCl3, 400 MHz): 10.14 (s, 1H), 7.91 (s, 1H), 7.38 (s, 1H), 7.09 (t, J = 52.6 Hz, 1H), 5.24(s, 1H), 4.43-4.25 (m, 1H), 1.40 (d, J = 2.9 Hz, 3H), 1.24-1.14 (m, 1H), 1.04-0.94 (m, 1H)Preparation of of Intermediate 5.6. cis-8-chloro-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-(2-fluoro-1-methylcyclopropyl)-N- To a solution of cis-8-chloro-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-(2-fluoro-1- methylcyclopropyl)imidazo[1,5-a]pyridine-6-sulfonamide (35 mg, 0.0799 mmol) in DCM (0.5 mL) was added DIEA (0.043 mL, 0.240 mmol) and (2-(chloromethoxy)ethyl)trimethylsilane (27 mg, 0.160 mmol). The reaction mixture was stirred at 0°C for 0.5 h and directly purified by preparative-TLC (SiO2, petroleum ether: EtOAc=1:1) to give the product cis-8-chloro-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-(2-fluoro- 1-methylcyclopropyl)-N-((2-(trimethylsilyl)ethoxy)methyl)imidazo[1,5-a]pyridine-6-sulfonamide (40 mg, 0.0704 mmol, 88.08 % yield) as a white solid. LCMS: RT 0.662 min (method 7); m / z 590.0 (M+Na) + (ESI+).1H NMR (CDCl3, 400 MHz): 10.14(s, 1H), 7.88 (s, 1H), 7.50 (s, 1H), 7.08 (t, J = 52.6 Hz, 1H), 5.09 (d, J = 10.3 Hz, 1H), 4.83 (d, J = 10.3Hz, 1H), 4.60-4.32 (m, 1H), 3.67-3.49 (m, 2H), 1.65-1.59 (m, 1H), 1.37 (d, J = 2.9 Hz, 3H), 1.09-1.00 (m,1H), 0.93-0.85 (m, 2H), 0.05 (s, 9H) Preparation of Intermediate 5.7. Cis-tert-butyl (2S,6S)-4-(3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-6-(N-(fluoro-1- methylcyclopropyl)-N-((2-(trimethylsilyl)ethoxy)methyl)sulfamoyl)imidazo[1,5-a]pyridin-8-yl)-2,6- dimethylpiperazine-1-carboxylate To a mixture of cis-8-chloro-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-(2-fluoro-1- methylcyclopropyl)-N-((2-(trimethylsilyl)ethoxy)methyl)imidazo[1,5-a]pyridine-6-sulfonamide (20 mg, 0.0352 mmol) in 1,4-dioxane (0.5 mL) were added tert-butyl (2S,6S)-2,6-dimethylpiperazine-1-carboxylate (30 mg, 0.141 mmol), Pd-PEPPSI-IPent Cl o-picoline (2-methylpyridine) (3.0 mg, 0.00352 mmol) and Cs2CO3 (34 mg, 0.106 mmol). The reaction mixture was degassed with N2 (3x), stirred at 80°C for 2 h, then poured into water (5 mL) and extracted with ethyl acetate (5 mL; 2x). The combined organic layer was washed with brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure to givethe productcis-tert-butyl (2S,6S)-4-(3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-6-(N-(2-fluoro-1-methylcyclopropyl)-N-((2-(trimethylsilyl)ethoxy)methyl)sulfamoyl)imidazo[1,5-a]pyridin-8-yl)-2,6- dimethylpiperazine-1-carboxylate (26 mg, 0.0349 mmol, 99.01 % yield) as yellow oil which was used in the next step without further purification. RT 0.677 min (method 7); m / z 768.2 (M+Na) + (ESI+).Preparation of Example 5 Cis-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-8-((3S,5S)-3,5-dimethylpiperazin-1-yl)-N-(2- fluoro-1-methylcyclopropyl)imidazo[1,5-a]pyridine-6-sulfonamide trifluoroacetate To a solution of cis-tert-butyl (2S,6S)-4-(3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-6-(N-((1S,2R)- 2-fluoro-1-methylcyclopropyl)-N-((2-(trimethylsilyl)ethoxy)methyl)sulfamoyl)imidazo[1,5-a]pyridin-8-yl)- 2,6-dimethylpiperazine-1-carboxylate (26 mg, 0.0349 mmol) in DCM (0.5 mL) was added TFA (0.10 mL, 1.43 mmol) at 0°C. The mixture was stirred at 20°C for 12 h and concentrated under vacuum at room temperature. The residue was purified by preparative HPLC (column: Phenomenex Synergi Polar-RP 100*25 mm*4 µm; mobile phase: A: 0.1% TFA in water, B: MeCN; B%: 8%-38%, 10 min) and lyophilized directly to give the product cis-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-8-((3S,5S)-3,5- dimethylpiperazin-1-yl)-N-(2-fluoro-1-methylcyclopropyl)imidazo[1,5-a]pyridine-6-sulfonamide 2,2,2- trifluoroacetate (6.7 mg, 0.0104 mmol, 29.86 % yield) as a yellow solid.LCMS: RT 0.439 min (method 7); m / z 516.1 (M+H) + (ESI+). SFC: RT 1.646, 2.011 min (Method2); 1H NMR (CD3CN-d6, 400 MHz): 9.76 (s, 1H), 9.17-8.69 (m, 2H), 7.80 (s, 1H), 7.24 (t, J = 52.6 Hz,1H), 6.73 (s, 1H), 6.49 (s, 1H), 4.47-4.21 (m, 1H), 3.96-3.84 (m, 2H), 3.63-3.51 (m, 2H), 3.42-3.31 (m,2H), 1.52 (d, J = 6.8 Hz, 6H), 1.31-1.27 (m, 1H), 1.15-1.13 (m, 3H), 0.94-0.86 (m, 1H)Preparation of Intermediate 21.1 Trans-1-(benzhydrylideneamino)-2-methyl-cyclopropanecarbonitrile & cis-1- (benzhydrylideneamino)-2-methyl-cyclopropanecarbonitrile To a solution of 2-((diphenylmethylene)amino)acetonitrile (5.00 g, 22.7 mmol) in THF (100 mL) was added NaH (2.72 g, 68.1 mmol, 60% purity) at 0 °C under N2. The mixture was stirred at 0 °C for 0.5 h and1,2-dibromopropane (4.58 g, 22.7 mmol) was added. The reaction mixture was stirred at 20 °C for 3 h, then quenched with slow addition of sat. NH4Cl solution (50 mL) while stirring and the aqueous layer was extracted with EtOAc (200 mL; 2x). The combined organic layer was washed with brine (200 mL; 2x), dried over anhydrous Na2SO4, filtered, and concentrated under vacuum. The residue was purified bypreparative HPLC (column: Waters Xbridge 150*25 mm* 5 m; mobile phase: A : 10 mM aqueous solutionof NH4HCO3; B: MeCN; B%: 45%-75%, 20 min) ) and lyophilized directly to give the product trans-1- (benzhydrylideneamino)-2-methyl-cyclopropanecarbonitrile (210 mg, 0.807 mmol, 3.55% yield) as a brown oil: LCMS: RT 0.746 min (method 2); m / z 261.2 (M+H)+ (ESI+); 1H NMR (400 MHz, CDCl3): 7.58 -7.53 (m, 5H), 7.45 - 7.41 (m, 1H), 7.36-7.33 (m, 4H), 1.74-1.73 (m, 2H), 1.31-1.28 (m, 1H), 1.29-1.21 (d, J = 2.0 Hz, 3H). and the product cis-1-(benzhydrylideneamino)-2-methyl-cyclopropanecarbonitrile (500 mg, 1.92 mmol, 8.09 % yield) as a brown oil: LCMS: RT 0.764 min (method 2); m / z 261.1 (M+H)+ (ESI+); 1H NMR (400 MHz, CDCl3): 7.62 (d,J = 7.2 Hz, 2H), 7.56-7.51 (m, 3H), 7.43 (d, J = 7.2 Hz, 1H), 7.38-7.32 (m, 4H), 1.92-1.81 (m, 1H), 1.79-1.77 (m, 1H), 1.42 (d, J = 6.0 Hz, 3H), 1.29-1.21 (m, 1H).Preparation of Intermediate 21.2 cis-1-amino-2-methylcyclopropane-1-carbonitrile hydrochloride To a solution of cis-1-(benzhydrylideneamino)-2-methyl-cyclopropanecarbonitrile (850 mg, 3.27 mmol) in THF (10 mL) was added HCl / H2O (10 mL, 4N). The reaction mixture was stirred at 20 °C for 16 h, then diluted with water (10 mL). The aqueous layer was washed with EtOAc (10 mL; 3×), separated, collected and lyophilized to give the product cis-1-amino-2-methylcyclopropane-1- carbonitrilehydrochloride (400 mg, 2.66 mmol, 81.34 % yield) as a white solid which was directly in the next step without further purification. 1H NMR (400 MHz, DMSO-d6,): 9.37 (s, 3H), 1.85-1.75 (m, 1H), 1.80-1.65 (m, 1H), 1.36-1.32 (m,1H), 1.26 (d, J = 6.4 Hz, 3H).Preparation of Intermediate 21.3 8-chloro-N-((cis)-1-cyano-2-methylcyclopropyl)-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2- yl)imidazo[1,5-a]pyridine-6-sulfonamide To a solution of cis-1-amino-2-methylcyclopropane-1-carbonitrile hydrochloride (241 mg, 1.82 mmol) in pyridine (2.0 mL, 81.8 mmol) was stirred at 5 °C under N2 and 8-chloro-3-(5-(difluoromethyl)- 1,3,4-thiadiazol-2-yl)imidazo[1,5-a]pyridine-6-sulfonyl chloride (350 mg, 0.909 mmol) in DCM (2 mL) was added dropwise into the solution. The reaction mixture was at 5 °C for 1 h under N2, then, diluted with water (10 mL) and extracted with ethyl acetate (10 mL; 3×). The combined organic layer was washed with brine (30 mL), dried over anhydrous Na2SO4, filtered and concentrated. The residue was purified bypreparative HPLC (ISCO; 40 g Flash Column Welch Ultimate XB_C1820-40 m; 120 A; mobile phase:A: 10 mmol / L FA in water, B: MeCN; B%: 45%-55%, 10 min). The purified fraction was concentrated and the pH was adjusted to 8 by sat. aq. NaHCO3. The aqueous layer was extracted with DCM (100 mL; 3×). The combined organic layer was dried over anhydrous Na2SO4, filtered and concentrated to give the product 8-chloro-N-((cis)-1-cyano-2-methylcyclopropyl)-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2- yl)imidazo[1,5-a]pyridine-6-sulfonamide (190 mg, 0.427 mmol, 47.01 % yield) as a brown solid. LCMS: RT 0.531 min (method 7); m / z 444.9 (M+H)+ (ESI+).1H NMR (400 MHz , DMSO-d6): 9.92(s, 1H), 8.10 (s, 1H), 7.70 (t, J = 12.8 Hz, 1H), 7.53 (d, J = 1.2 Hz, 1H), 1.67-1.66 (m, 2H), 1.21-1.17 (m,1H), 1.14-1.13 (m, 3H). Preparation of Example 21 N-((cis)-1-cyano-2-methylcyclopropyl)-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-8-(5- (methoxymethyl)-3,3-dimethylpiperazin-1-yl)imidazo[1,5-a]pyridine-6-sulfonamide formate To a solution of 8-chloro-N-((cis)-1-cyano-2-methylcyclopropyl)-3-(5-(difluoromethyl)-1,3,4- thiadiazol-2-yl)imidazo[1,5-a]pyridine-6-sulfonamide (50 mg, 0.112 mmol) in DMF (0.5 mL) and 1,4- Dioxane (1 mL) were added Cs2CO3 (73 mg, 0.225 mmol), Pd-PEPPSI-IPentCl o-picoline (9.4 mg, 0.0112 mmol) and 6-(methoxymethyl)-2,2-dimethylpiperazine (36 mg, 0.225 mmol). The mixture was degassed with N2 (3x), stirred at 100 °C for 2 h, poured into water (10 mL) and extracted with ethyl acetate (10 mL, 3x). The combined organic layer was washed with brine (10 mL, 2x), dried over anhydrous Na2SO4, filtered and concentrated under vacuum. The residue was purified by Preparative HPLC (column: Phenomenexluna C18250*50 mm*15 m; mobile phase: A: 0.225% formic acid in water, B: MeCN; B%: 25%-35%, 10min) and lyophilized to give the product N-((cis)-1-cyano-2-methylcyclopropyl)-3-(5-(difluoromethyl)-1,3,4- thiadiazol-2-yl)-8-(5-(methoxymethyl)-3,3-dimethylpiperazin-1-yl)imidazo[1,5-a]pyridine-6-sulfonamide formate (40 mg, 0.0653 mmol, 58.09 % yield, mixture of 4 compounds) as a yellow solid. LCMS: RT 0.456 min (method 7); m / z 567.2 (M+H)+ (ESI+); SFC: RT 1.398 min, 1.462 min,1.485 min, 1.566 min (Method 17); 1H NMR (400 MHz, DMSO-d6): 9.65 (s, 1H), 8.15 (s, 1H), 7.89 (s,1H), 7.68 (t, J = 53.2 Hz, 1H), 6.69 (s, 1H), 3.63-3.60 (m, 1H), 3.53-3.50 (m, 1H), 3.44-3.41 (m, 1H),3.38-3.31 (m, 2H), 3.31 (s, 3H), 2.57-2.51 (m, 2H), 1.65-1.63 (m, 2H), 1.35 (s, 3H), 1.20-1.15 (m, 1H), 1.14 (s, 6H) Preparation of Example 21a Cis-N-(-1-cyano-2-methylcyclopropyl)-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-8-(5-(methoxymethyl)-3,3-dimethylpiperazin-1-yl)imidazo[1,5-a]pyridine-6-sulfonamide (cis-diastereomer 1,single diastereomer with unknown absolute configuration for chiral centers where it is not specified, characterized by cis configuration in cyclopropyl ring, i.e., wherein -NH- and -CH3 substituents are on the same side of the ring) The N-((cis)-1-cyano-2-methylcyclopropyl)-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-8-(5-(methoxymethyl)-3,3-dimethylpiperazin-1-yl)imidazo[1,5-a]pyridine-6-sulfonamide formate (40 mg, 0.0653 mmol) was purified by preparative SFC (column: Chiralpak AD (250mm*50mm,10µm); mobilephase: A: CO2, B: i-PrOH (0.1% NH3H2O); Gradient elution:0% to 25% B, 4.3 mins) to give two fractions:- Fraction 1: N-((cis)-1-cyano-2-methylcyclopropyl)-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-8-(-5-(methoxymethyl)-3,3-dimethylpiperazin-1-yl)imidazo[1,5-a]pyridine-6-sulfonamide diastereomer 1 (6.9 mg,0.0121 mmol, 18.60 % yield) as a light yellow solid (single diastereomer with unknown absolute configuration for chiral centers where it is not specified). LCMS: RT 0.459 min (method 7); m / z 567.2 (M+H)+ (ESI+); SFC: RT 3.525 min (Method 18); 1HNMR (400 MHz, DMSO-d6): 9.65 (s, 1H), 8.15 (s, 1H), 7.89 (s, 1H), 7.68 (t, J = 53.2 Hz, 1H), 6.69 (s,1H), 3.63-3.60 (m, 1H), 3.53-3.50 (m, 1H), 3.44-3.41 (m, 1H), 3.38-3.31 (m, 2H), 3.31 (s, 3H), 2.57-2.51 (m, 2H), 1.65-1.63 (m, 2H), 1.35 (s, 3H), 1.20-1.15 (m, 1H), 1.14 (s, 6H) -Fraction 2: 30 mg of a mixture of cis-diastereomer 2, cis-diastereomer 3 and cis-diastereomer 4. Preparation of Example 21d N-((cis)-1-cyano-2-methylcyclopropyl)-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-8-(5-(methoxymethyl)-3,3-dimethylpiperazin-1-yl)imidazo[1,5-a]pyridine-6-sulfonamide diastereomer 4(single diastereomer with unknown absolute configuration for chiral centers where it is not specified, characterized by cis configuration in cyclopropyl ring, i.e., wherein -NH- and -CH3 substituents are on the same side of the ring) The mixture of diastereomer 2, diastereomer 3, diastereomer 4 (30 mg, 0.0528 mmol) was purified by preparative SFC (column: Chiralpak IE (250mm*30mm,10µm); mobile phase: A: CO2, B: Hexane-EtOH (0.1% NH3.H2O); Gradient elution:0% to 35% B, 15 mins) to give two fractions after concentration: Fraction 1: 20 mg of a mixture of cis-diastereomer 2 and cis-diastereomer 3. -Fraction 2 N-((cis)-1-cyano-2-methylcyclopropyl)-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-8-(5-(methoxymethyl)-3,3-dimethylpiperazin-1-yl)imidazo[1,5-a]pyridine-6- sulfonamide diastereomer 4 (5.6 mg, 0.00988 mmol, 18.67 % yield) as a light yellow solid .(single diastereomer with unknown absolute configuration for chiral centers where it is not specified characterized by cis configuration in cyclopropyl ring, i.e., wherein -NH- and -CH3 substituents are on the same side of the ring). LCMS: RT 0.458 min (method 7); m / z 567.2(M+H)+ (ESI+); SFC: RT 6.558 min (Method 18); 1H NMR (400 MHz, CD3CN): 9.78 (s, 1H),7.83 (s, 1H), 7.68 (t, J = 53.2 Hz, 1H), 6.66 (s, 1H), 3.67-3.58 (m, 1H), 3.58-3.55 (m, 1H),3.55-3.53 (m, 1H), 3.40-3.36 (m, 2H), 3.35 (s, 3H), 2.64-2.58 (m, 2H), 1.62-1.60 (m, 2H), 1.42 (s, 3H), 1.31-1.29 (m, 1H), 1.20 (d, J = 5.6 Hz, 3H), 1.17 (s, 3H).Preparation of Example 21b and Example 21c N-((cis)-1-cyano-2-methylcyclopropyl)-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-8-(5- (methoxymethyl)-3,3-dimethylpiperazin-1-yl)imidazo[1,5-a]pyridine-6-sulfonamide diastereomer 2 (single diastereomer with unknown absolute configuration for chiral centers where it is not specified characterized by cis configuration in cyclopropyl ring, i.e., wherein -NH- and -CH3 substituents are on the same side of the ring) and N-((cis)-1-cyano-2-methylcyclopropyl)-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-8-(5- (methoxymethyl)-3,3-dimethylpiperazin-1-yl)imidazo[1,5-a]pyridine-6-sulfonamide diastereomer 3 ( single diastereomer with unknown absolute configuration for chiral centers where it is not specified characterized by cis configuration in cyclopropyl ring, i.e., wherein -NH- and -CH3 substituents are on the same side of the ring)

[0004] The mixture of diastereomer 2 and diastereomer 3 (20 mg, 0.0352mmol) was purified by preparative SFC (column: Chiralpak IE (250mm*30mm,10µm); mobile phase: A: CO2, B: Hexane- EtOH (0.05% DEA); Gradient elution: 0% to 25% B, 10 mins) to give two fractions: -Fraction 1: N-((cis)-1-cyano-2-methylcyclopropyl)-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-8-(5-(methoxymethyl)-3,3-dimethylpiperazin-1-yl)imidazo[1,5-a]pyridine-6-sulfonamide diastereomer 2 (4.43 mg, 0.0076 mmol, 21.58 % yield) as a light yellow solid (singlediastereomer with unknown absolute configuration for chiral centers where it is not specified characterized by cis configuration in cyclopropyl ring, i.e., wherein -NH- and -CH3 substituents are on the same side of the ring). LCMS: RT 0.458 min (method 7); m / z 567.2 (M+H)+ (ESI+); SFC: RT 3.882 min (Method 18); 1HNMR (400 MHz, CD3CN): 9.78 (s, 1H), 7.83 (s, 1H), 7.68 (t, J = 53.2 Hz, 1H), 6.66 (s, 1H), 3.67-3.58 (m,1H), 3.58-3.55 (m, 1H), 3.55-3.53 (m, 1H), 3.40-3.36 (m, 2H), 3.35 (s, 3H), 2.64-2.58 (m, 2H), 1.62-1.60(m, 2H), 1.42 (s, 3H), 1.31-1.29 (m, 1H), 1.20 (d, J = 5.6 Hz, 3H), 1.17 (s, 3H)- Fraction 2: N-((cis)-1-cyano-2-methylcyclopropyl)-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-8-(5-(methoxymethyl)-3,3-dimethylpiperazin-1-yl)imidazo[1,5-a]pyridine-6-sulfonamide diastereomer 3 (4.2 mg, 0.0073 mmol, 20.67 % yield) as a light yellow solid (singlediastereomer with unknown absolute configuration for chiral centers where it is not specified characterized by cis configuration in cyclopropyl ring, i.e., wherein -NH- and -CH3 substituents are on the same side of the ring). LCMS: RT 0.458 min (method 7); m / z 567.2 (M+H)+ (ESI+); SFC: RT 4.238 min (Method 18); 1HNMR (400 MHz, CD3CN): 9.78 (s, 1H), 7.83 (s, 1H), 7.68 (t, J = 53.2 Hz, 1H), 6.66 (s, 1H), 3.67-3.58 (m,1H), 3.58-3.55 (m, 1H), 3.55-3.53 (m, 1H), 3.40-3.36 (m, 2H), 3.35 (s, 3H), 2.64-2.58 (m, 2H), 1.62-1.60(m, 2H), 1.42 (s, 3H), 1.31-1.29 (m, 1H), 1.20 (d, J = 5.6 Hz, 3H), 1.17 (s, 3H) The following Table 1 provides an overview on the compounds described in the Example section. Table 1. Summary of the structures of the prepared compounds. Example Structure Name of compoundNo. 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2- yl)-N-(1S,2R)- Namedimethylcyclopropyl)-8-((3S,5S)- 1a 3,5-dimethylpiperazin-1-yl)imidazo[1,5- a]pyridine-6-sulfonamide (diastereoisomer 1) Diastereomer 1 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2- yl)-N-(1S,2R)-1,2-dimethylcyclopropyl)- 1b 8-((3S,5S)-3,5-dimethylpiperazin-1- yl)imidazo[1,5-a]pyridine-6-sulfonamide diastereomer 2 Diastereomer 2 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2- yl)-N--1,2-dimethylcyclopropyl)-8- 1c ((3S,5S)-3,5-dimethylpiperazin-1- yl)imidazo[1,5-a]pyridine-6-sulfonamide diastereomer 3 Diastereomer 3 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2- 1d yl)-N-1,2-dimethylcyclopropyl)-8- ((3S,5S)-3,5-dimethylpiperazin-1- yl)imidazo[1,5-a]pyridine-6-sulfonamide 2,2,2-trifluoroacetate diastereomer 4 Diastereomer 4 Cis-3-(5-(difluoromethyl)-1,3,4- thiadiazol-2-yl)-8-((3S,5S)-3,5- dimethylpiperazin-1-yl)-N-(2-fluoro-1- methylcyclopropyl)imidazo[1,5- a]pyridine-6-sulfonamide 2,2,2- trifluoroacetate 2 compounds N-((cis)-1-cyano-2-methylcyclopropyl)- 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2- yl)-8-(-5-(methoxymethyl)-3,3-a dimethylpiperazin-1-yl)imidazo[1,5- a]pyridine-6-sulfonamide diastereomer 1

[0005] N-((cis)-1-cyano-2-methylcyclopropyl)- 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2- yl)-8-(5-(methoxymethyl)-3,3- 21b dimethylpiperazin-1-yl)imidazo[1,5- a]pyridine-6-sulfonamide diastereomer 2 N-((cis)-1-cyano-2-methylcyclopropyl)- 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2- yl)-8-(5-(methoxymethyl)-3,3- 21c dimethylpiperazin-1-yl)imidazo[1,5- a]pyridine-6-sulfonamide diastereomer 3 N-((cis)-1-cyano-2-methylcyclopropyl)- 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2- yl)-8-((methoxymethyl)-3,3- 21d dimethylpiperazin-1-yl)imidazo[1,5- a]pyridine-6-sulfonamide diastereomer 4 8-chloro-3-(5-(difluoromethyl)- 27 1,3,4-thiadiazol-2-yl)-N-(1,2- (see dimethylcyclopropyl)imidazo[1,5- intermediat a]pyridine-6-sulfonamide e 1.10) 4 compounds 8-chloro-3-(5-(difluoromethyl)- 27a 1,3,4-thiadiazol-2-yl)-N-(1S,2R- (see dimethylcyclopropyl)imidazo[1,5- intermediat a]pyridine-6-sulfonamide diastereomer 1 e 1.10a) Diastereomer 1 27b 8-chloro-3-(5-(difluoromethyl)- (see 1,3,4-thiadiazol-2-yl)-N-((1R,2S)-1,2- intermediat dimethylcyclopropyl)imidazo[1,5- e 1.10b) a]pyridine-6-sulfonamide diastereomer 2 Diastereomer 2 Mixture of 8-chloro-3-(5-27c (difluoromethyl)-1,3,4-thiadiazol-2-yl)-N- (see (1,2-dimethylcyclopropyl)imidazo[1,5- intermediat a]pyridine-6-sulfonamide diastereomer 3 e 1.10c and and 8-chloro-3-(5-(difluoromethyl)-1,3,4- 1.10d) thiadiazol-2-yl)-N-(1,2- Mixture of diastereomer 3 and diastereomer 4 dimethylcyclopropyl)imidazo[1,5- a]pyridine-6-sulfonamide diastereomer 4 Trans mixture (methyl groups on the same face of the cyclopropyl ring)

[0006] tert-butyl (2S,6S)-4-(3-(5- 28 (difluoromethyl)-1,3,4-thiadiazol-2-yl)-6- (see (N-(1,2- intermediat dimethylcyclopropyl)sulfamoyl)imidazo[ e 1.11) 1,5-a]pyridin-8-yl)-2,6- dimethylpiperazine-1-carboxylate 4 compounds tert-butyl (2S,6S)-4-(3-(5- (difluoromethyl)-1,3,4-thiadiazol-2-yl)-6- 28c (N-(1,2- (see dimethylcyclopropyl)sulfamoyl)imidazo[ intermediat 1,5-a]pyridin-8-yl)-2,6- e 1.11c) dimethylpiperazine-1-carboxylate diastereoisomer 3 Diastereoisomer 3 tert-butyl (2S,6S)-4-(3-(5- (difluoromethyl)-1,3,4-thiadiazol-2-yl)-6- 28d (N-(1,2- (see dimethylcyclopropyl)sulfamoyl)imidazo[ intermediat 1,5-a]pyridin-8-yl)-2,6- e 1.11d) dimethylpiperazine-1-carboxylate diastereoisomer 4

[0007] Diatereoisomer 4 The example listed in the table below were produced using similar experimental procedures as reported for examples listed in table 1 and were obtained either by SFC purification or starting from intermediates / examples that were either enantiomerically pure or we present as mixtures of cis or trans isomers, respectively, with respect to the configuration of cyclopropyl ring. ExampleLC / MS & SFC data Name ofStructure No. compound RT 0.464 min (LCMS Method 3-(5-(difluoromethyl)-1,3,4- 7), m / z 513.2 (M+H)+(ESI+); thiadiazol-2-yl)-N-(1,2- RT 1.315 min, 1.565 min, dimethylcyclopropyl)-8- 2 1.717 (SFC Method 5); ((3S,5S)-3,5- dimethylpiperazin-1-yl)- [1,2,4]triazolo[4,3- 4 compounds a]pyridine-6-sulfonamide RT 0.468 min (LCMS Method 3-(5-(difluoromethyl)-1,3,4- 7), m / z 513.2 (M+H)+thiadiazol-2-yl)-N-(1,2- (ESI+)(M+H)+(ESI+); RT dimethylcyclopropyl)-8- 1.332 min, (SFC Method 5); ((3S,5S)-3,5- 2a ee%=99.53% dimethylpiperazin-1-yl)- [1,2,4]triazolo[4,3- a]pyridine-6-sulfonamide Diastereomer 1 diastereomer 1 RT 0.458 min (LCMS Method 3-(5-(difluoromethyl)-1,3,4- 7), m / z 513.2 (M+H)+(ESI+); thiadiazol-2-yl)-N-(1,2- RT 1.422 min, (SFC Method dimethylcyclopropyl)-8- 6); ee%>99.9% ((3S,5S)-3,5-b dimethylpiperazin-1-yl)- [1,2,4]triazolo[4,3- a]pyridine-6-sulfonamide Diastereomer 2 diastereomer 2 RT 0.453 min (LCMS Method 3-(5-(difluoromethyl)-1,3,4- 7), m / z 513.1 (M+H)+(ESI+); thiadiazol-2-yl)-N-(1,2- RT 1.422 min, (SFC Method dimethylcyclopropyl)-8- 7); ee%=91.84% ((3S,5S)-3,5-c dimethylpiperazin-1-yl)- [1,2,4]triazolo[4,3- a]pyridine-6-sulfonamide Diastereomer 3 diastereomer 3 RT 0.451 min (LCMS Method 3-(5-(difluoromethyl)-1,3,4- 7), m / z 513.1 (M+H)+(ESI+); thiadiazol-2-yl)-N-(1,2- RT 1.422 min, (SFC Method dimethylcyclopropyl)-8- 7); ee%=89.31% ((3S,5S)-3,5-d dimethylpiperazin-1-yl)- [1,2,4]triazolo[4,3- Diastereomer 4 a]pyridine-6-sulfonamide diastereomer 4 RT 0.456 min (LCMS Method Trans-N-( 1-cyano-2- 7), m / z 523.2 (M+H)+(ESI+); methylcyclopropyl)-3-(5- RT 1.515 min, 1.730 min (difluoromethyl)-1,3,4- (SFC Method 8); thiadiazol-2-yl)-8-((3S,5S)- 3,5-dimethylpiperazin-1- yl)imidazo[1,5-a]pyridine-6- 2 compounds - trans sulfonamide Trifluoroacetate RT 0.451 min (LCMS Method Cis-N-( 1-cyano-2- 7), m / z 523.2 (M+H)+(ESI+); methylcyclopropyl)-3-(5- RT 1.969 min, 2.170 min (difluoromethyl)-1,3,4- (SFC Method 9); thiadiazol-2-yl)-8-((3S,5S)- 3,5-dimethylpiperazin-1- yl)imidazo[1,5-a]pyridine-6- 2 compounds - cis sulfonamide trifluoroacetate RT 0.447 min (LCMS Method 7), m / z 523.2 (M+H)+(ESI+); N-((cis)-1-cyano-2- RT 1.980 min, (SFC Method methylcyclopropyl)-3-(5- 9); ee%=94.12% (difluoromethyl)-1,3,4-a thiadiazol-2-yl)-8-((3S,5S)- 3,5-dimethylpiperazin-1- yl)imidazo[1,5-a]pyridine-6- sulfonamide diastereomer 1 cis-Diastereomer 1 RT 0.456 min (LCMS Method 7), m / z 523.2 (M+H)+(ESI+); N-((cis)-1-cyano-2- RT 1.980 min, (SFC Method methylcyclopropyl)-3-(5- 9); ee%=95.50% (difluoromethyl)-1,3,4-b thiadiazol-2-yl)-8-((3S,5S)- 3,5-dimethylpiperazin-1- yl)imidazo[1,5-a]pyridine-6- sulfonamide diastereomer 2 cis-Diastereomer 2 RT 0.449 min (LCMS Method Trans-3-(5-(difluoromethyl)- 7), m / z 516.1 (M+H)+(ESI+); 1,3,4-thiadiazol-2-yl)-8- RT 1.056 min, 1.312 min ((3S,5S)-3,5- (SFC Method 2); dimethylpiperazin-1-yl)-N- (2-fluoro-1- methylcyclopropyl)imidazo[1 ,5-a]pyridine-6-sulfonamide 2 compounds - trans trifluoroacetate RT 0.476 min (LCMS Method 3-(5-(difluoromethyl)-1,3,4- 7), m / z 526.1 (M+H)+(ESI+); thiadiazol-2-yl)-8-((3S,5S)- 3,5-dimethylpiperazin-1-yl)- N-(1,2,2- trimethylcyclopropyl)imidazo [1,5-a]pyridine-6- sulfonamide trifluoroacetate RT 0.458 min (LCMS Method 3-(5-(difluoromethyl)-1,3,4- 7), m / z 542.3 (M+H)+(ESI+); thiadiazol-2-yl)-N-(1,2- RT 1.778 min, 1.838 min, dimethylcyclopropyl)-8-(5- 1.889 min, 2.004 min, 2.321 (hydroxymethyl)-3,3- min, 2.419 (SFC Method 3); dimethylpiperazin-1- yl)imidazo[1,5-a]pyridine-6- 8 compounds sulfonamide formate RT 0.462 min (LCMS Method 7), m / z 542.3 (M+H)+(ESI+); 3-(5-(difluoromethyl)-1,3,4- RT 1.843 min, 2.016 min thiadiazol-2-yl)-N-(1S,2R)- (SFC Method 3) dimethylcyclopropyl)-8-(5-a (hydroxymethyl)-3,3- dimethylpiperazin-1- yl)imidazo[1,5-a]pyridine-6- sulfonamide 2 compounds RT 0.459 min (LCMS Method 7), m / z 542.3 (M+H)+(ESI+); 3-(5-(difluoromethyl)-1,3,4- RT 1.974 min, 2.197 min thiadiazol-2-yl)-N-(1R,2S)- (SFC Method 10); racemate 1,2-dimethylcyclopropyl)-8-b (5-(hydroxymethyl)-3,3- dimethylpiperazin-1- yl)imidazo[1,5-a]pyridine-6- sulfonamide formate 2 compounds RT 0.461 min (LCMS Method 7), m / z 542.2 (M+H)+(ESI+); 3-(5-(difluoromethyl)-1,3,4- RT 1.777 min, (SFC Method thiadiazol-2-yl)-N-(1S,2R)- 3); ee%>99.9% 1,2-dimethylcyclopropyl)-8-c 5-(R or S)-(hydroxymethyl)- 3,3-dimethylpiperazin-1- yl)imidazo[1,5-a]pyridine-6- (obtained from 8a by SFC sulfonamide separation) RT 0.612 min (LCMS Method 2), m / z 542.3 (M+H)+(ESI+); 3-(5-(difluoromethyl)-1,3,4- RT 1.976 min, (SFC Method thiadiazol-2-yl)-N-(1S,2R)- 3); ee%>99.9% 1,2-dimethylcyclopropyl)-8-d 5-(S or R)-(hydroxymethyl)- 3,3-dimethylpiperazin-1- yl)imidazo[1,5-a]pyridine-6- (obtained from 8a by SFC sulfonamide separation) RT 0.727 min (LCMS Method m / z 530.3 (M+H)+3-(5-(difluoromethyl)-1,3,4- 2), (ESI+); thiadiazol-2-yl)-N-(1,2- RT 1.414 min, 1.474 min, dimethylcyclopropyl)-8- 1.625 min (SFC Method 6); ((3S,5S)-3,5- dimethylpiperazin-1-yl)-1- fluoroimidazo[1,5-a]pyridine- 6-sulfonamide formate 4 compounds RT 0.486 min (LCMS Method 3-(5-(difluoromethyl)-1,3,4- 7), m / z 530.3 (M+H)+(ESI+); thiadiazol-2-yl)-N-(1,2- RT 1.478 min, (SFC Method dimethylcyclopropyl)-8- 11); ee%=98.37% ((3S,5S)-3,5-a dimethylpiperazin-1-yl)-1- fluoroimidazo[1,5-a]pyridine- 6-sulfonamide diastereomer Diastereomer 1 1 RT 0.483 min (LCMS Method 3-(5-(difluoromethyl)-1,3,4- 7), m / z 530.3 (M+H)+(ESI+); thiadiazol-2-yl)-N-(1,2- RT 1.740 min, (SFC Method dimethylcyclopropyl)-8- 11); ee%=98.38% ((3S,5S)-3,5-b dimethylpiperazin-1-yl)-1- fluoroimidazo[1,5-a]pyridine- 6-sulfonamide diastereomer Diastereomer 2 2 RT 0.482 min (LCMS Method 3-(5-(difluoromethyl)-1,3,4- 7), m / z 530.3 (M+H)+(ESI+); thiadiazol-2-yl)-N-(1,2- RT 1.897 min, (SFC Method dimethylcyclopropyl)-8- 7); ee%=99.45% ((3S,5S)-3,5-c dimethylpiperazin-1-yl)-1- fluoroimidazo[1,5-a]pyridine- 6-sulfonamide diastereomer Diastereomer 3 3 RT 0.485 min (LCMS Method 3-(5-(difluoromethyl)-1,3,4- 7), m / z 530.2 (M+H)+(ESI+); thiadiazol-2-yl)-N-(1,2- RT 2.344 min, (SFC Method dimethylcyclopropyl)-8- 7); ee%=99.71% ((3S,5S)-3,5-d dimethylpiperazin-1-yl)-1- fluoroimidazo[1,5-a]pyridine- 6-sulfonamide disatereomer Diastereomer 4 4 RT 0.461 min (LCMS Method 3-(5-(difluoromethyl)-1,3,4- 7), m / z 512.2 (M+H)+(ESI+); thiadiazol-2-yl)-N-(1,2- dimethylcyclopropyl)-8- ((3S,5S)-3,5- dimethylpiperazin-1- yl)imidazo[1,2-a]pyridine-6- 4 compounds sulfonamide formate RT 0.464 min (LCMS Method 3-(5-(difluoromethyl)-1,3,4- 7), m / z 512.2 (M+H)+(ESI+); thiadiazol-2-yl)-N-(1,2- RT 1.735 min, (SFC Method dimethylcyclopropyl)-8- 7); ee%>99.9% ((3S,5S)-3,5-a dimethylpiperazin-1- yl)imidazo[1,2-a]pyridine-6- sulfonamide formate Diastereomer 1 diastereomer 1 RT 0.470 min (LCMS Method 3-(5-(difluoromethyl)-1,3,4- 7), m / z 512.3 (M+H)+(ESI+); thiadiazol-2-yl)-N-(1,2- RT 1.825 min, (SFC Method dimethylcyclopropyl)-8- 7); ee% 99.9%((3S,5S)-3,5-b dimethylpiperazin-1- yl)imidazo[1,2-a]pyridine-6- sulfonamide formate Diastereomer 2 diastereomer 2 RT 0.469 min (LCMS 3-(5-(difluoromethyl)-1,3,4- Method 7), m / z 512.2 (M+H)+thiadiazol-2-yl)-N-(1,2- (ESI+); RT 1.865 min, , (SFC dimethylcyclopropyl)-8- Method 7); ee: 99.9%((3S,5S)-3,5-c dimethylpiperazin-1- yl)imidazo[1,2-a]pyridine-6- Diastereomer 3 sulfonamide formate diastereomer 3 RT 0.467 min (LCMS Method 3-(5-(difluoromethyl)-1,3,4- 7), m / z 512.2 (M+H)+(ESI+); thiadiazol-2-yl)-N-(1,2- RT 2.168 min, , (SFC Method dimethylcyclopropyl)-8- 7); ee: 99.9%((3S,5S)-3,5-d dimethylpiperazin-1- yl)imidazo[1,2-a]pyridine-6- sulfonamide formate Diastereomer 4 diastereomer 4 RT 0.473 min (LCMS Method 3-(5-(difluoromethyl)-1,3,4- 7), m / z 511.2 (M+H)+(ESI+); thiadiazol-2-yl)-N-(1,2- RT 0.806 min, 1.080 min, dimethylcyclopropyl)-8- 1.729 min, 2.076 min , (SFC ((3S,5S)-3,5- Method 14); dimethylpiperazin-1- yl)indolizine-6-sulfonamide 4 compounds RT 0.482 min (LCMS Method 3-(5-(difluoromethyl)-1,3,4- 7), m / z 511.2 (M+H)+(ESI+); thiadiazol-2-yl)-N-1,2- RT 0.799 min , (SFC Method dimethylcyclopropyl)-8-a 14); ee: 98.79% ((3S,5S)-3,5- dimethylpiperazin-1- yl)indolizine-6-sulfonamide Diastereomer 1 diastereomer 1 RT 0.477 min (LCMS Method 3-(5-(difluoromethyl)-1,3,4- 7), m / z 511.2 (M+H)+(ESI+); thiadiazol-2-yl)-N-1,2- RT 1.065 min , (SFC Method dimethylcyclopropyl)-8-b 14); ee: 98.66% ((3S,5S)-3,5- dimethylpiperazin-1- yl)indolizine-6-sulfonamide Diastereomer 2 diastereomer 2 RT 0.478 min (LCMS Method 3-(5-(difluoromethyl)-1,3,4- 7), m / z 511.2 (M+H)+(ESI+); thiadiazol-2-yl)-N-(1,2- RT 1.693 min , (SFC Method dimethylcyclopropyl)-8-c 14); ee: >99.9% ((3S,5S)-3,5- dimethylpiperazin-1- yl)indolizine-6-sulfonamide Diastereomer 3 diastereomer 3 RT 0.486 min (LCMS Method 3-(5-(difluoromethyl)-1,3,4- 7), m / z 511.3 (M+H)+(ESI+); thiadiazol-2-yl)-N-1,2- RT 2.031 min , (SFC Method dimethylcyclopropyl)-8-d 14); ee: >99.9% ((3S,5S)-3,5- dimethylpiperazin-1- yl)indolizine-6-sulfonamide Diastereomer 4 diastereomer 4 RT 0.469 min (LCMS Method 3-(5-(difluoromethyl)-1,3,4- 7), m / z 512.2 (M+H)+(ESI+); thiadiazol-2-yl)-N-(1S,2R)- RT 1.601 min , (SFC Method dimethylcyclopropyl)-8-(3,3- 11); ee: 95.66% dimethylpiperazin-1- yl)imidazo[1,5-a]pyridine-6- (obtained from sulfonamide 2,2,2- intermediate 1.10a) trifluoroacetate RT 0.461 min (LCMS Method 3-(5-(difluoromethyl)-1,3,4- 7), m / z 498.2 (M+H)+(ESI+); thiadiazol-2-yl)-N-(1S,2R)- RT 1.439 min (SFC Method dimethylcyclopropyl)-8-((S)- 11); ee:93.98% 3-methylpiperazin-1- yl)imidazo[1,5-a]pyridine-6- sulfonamide 2,2,2- (obtained from trifluoroacetate intermediate 1.10a) diastereomer 1 RT 0.521 min (LCMS Method 8-chloro-3-(5- 7), m / z 434.0 (M+H)+(ESI+); (difluoromethyl)-1,3,4- RT 1.255 min, 1.301 min, thiadiazol-2-yl)-N-(1,2- 1.434 min, 1.473 min (SFC dimethylcyclopropyl)imidazo4 compounds Method 36); [1,2-a]pyridine-6-sulfonamide RT 0.591 min (LCMS Method 7), m / z 433.0 (M+H)+(ESI+); 8-chloro-3-(5- RT 1.645 min, 1.768 min, (difluoromethyl)-1,3,4- 1.996 min, 2.089 min (SFC thiadiazol-2-yl)-N-(1,2- Method 12); dimethylcyclopropyl)indolizi ne-6-sulfonamide 4 compounds RT 0.484 min (LCMS Method 3-(5-(difluoromethyl)-1,3,4- 7), m / z 526.3 (M+H)+(ESI+); thiadiazol-2-yl)-8-((3S,5S)- RT 0.487 min, 0.579 min 3,5-dimethylpiperazin-1-yl)- (SFC Method 13); Racemate N-((cis)-2-ethyl-1- methylcyclopropyl)imidazo[1 ,5-a]pyridine-6-sulfonamide compounds-cis formate RT 0.485 min (LCMS Method 7), m / z 526.2 (M+H)+(ESI+); 3-(5-(difluoromethyl)-1,3,4- RT 0.629 min, 1.249 min thiadiazol-2-yl)-8-((3S,5S)- (SFC Method 13); Racemate 3,5-dimethylpiperazin-1-yl)- N-(trans)-2-ethyl-1- methylcyclopropyl)imidazo[1 ,5-a]pyridine-6-sulfonamide compounds-trans RT 0.468 min (LCMS Method 3-(5-(difluoromethyl)-1,3,4- 7), m / z 518.2 (M+H)+(ESI+); thiadiazol-2-yl)-8-((3S,5S)- RT 1.872 min, 1.948 min, 3,5-dimethylpiperazin-1-yl)- 2.272 min (SFC Method 7); N-(1-methyl-2-(methyl- d3)cyclopropyl-2,3,3- d3)imidazo[1,5-a]pyridine-6- 4 compounds sulfonamide formate RT 0.464 min (LCMS Method 3-(5-(difluoromethyl)-1,3,4- 7), m / z 518.1 (M+H)+(ESI+); thiadiazol-2-yl)-8-((3S,5S)- RT 1.475 min (SFC Method 3,5-dimethylpiperazin-1-yl)-a 6); ee:93.07% N-(1-methyl-2-(methyl- d3)cyclopropyl-2,3,3- d3)imidazo[1,5-a]pyridine-6- Diastereomer 1 sulfonamide diastereomer 1 RT 0.468 min (LCMS Method 3-(5-(difluoromethyl)-1,3,4- 7), m / z 518.2 (M+H)+(ESI+); thiadiazol-2-yl)-8-((3S,5S)- RT 1.569 min (SFC Method 3,5-dimethylpiperazin-1-yl)-b 6); ee:94.71% N-(1-methyl-2-(methyl- d3)cyclopropyl-2,3,3- d3)imidazo[1,5-a]pyridine-6- Diastereomer 2 sulfonamide diastereomer 2 RT 0.458 min (LCMS Method 3-(5-(difluoromethyl)-1,3,4- 7), m / z 518.1 (M+H)+(ESI+); thiadiazol-2-yl)-8-((3S,5S)- RT 1.734 min (SFC Method 3,5-dimethylpiperazin-1-yl)-c 6); ee:96.89% N-(1-methyl-2-(methyl- d3)cyclopropyl-2,3,3- d3)imidazo[1,5-a]pyridine-6- Diastereomer 3 sulfonamide diastereomer 3 LCMS: RT 0.456 min 3-(5-(difluoromethyl)-1,3,4- (method 3); m / z 518.1 thiadiazol-2-yl)-8-((3S,5S)- (M+H)+(ESI+). SFC: RT 3,5-dimethylpiperazin-1-yl)-d 2.242 min (Method 7); N-(1-methyl-2-(methyl- ee:>99.9% d3)cyclopropyl-2,3,3- d3)imidazo[1,5-a]pyridine-6- Diastereomer 4 sulfonamide diastereomer 4 LCMS: RT 0.453 min N-((cis)-1-cyano-2- (method 3); m / z 537.3 methylcyclopropyl)-3-(5- (M+H)+(ESI+). SFC: RT (difluoromethyl)-1,3,4- 1.885 min, 1.989 min thiadiazol-2-yl)-8-(3,3,5- (Method 15) trimethylpiperazin-1- yl)imidazo[1,5-a]pyridine-6- 2 compounds-cis sulfonamide formate LCMS: RT 0.446 min N-((cis)-1-cyano-2- (method 3); m / z 537.1 methylcyclopropyl)-3-(5- (M+H)+(ESI+). SFC: RT (difluoromethyl)-1,3,4- 1.869 min (Method 15); a thiadiazol-2-yl)-8-(-3S,3,5- ee:>99.9% trimethylpiperazin-1- yl)imidazo[1,5-a]pyridine-6- sulfonamide diastereomer 1 cis-Diastereomer 1 LCMS: RT 0.446 min N-((cis)-1-cyano-2- (method 3); m / z 537.1 methylcyclopropyl)-3-(5- (M+H)+(ESI+). SFC: RT (difluoromethyl)-1,3,4- 1.974 min (Method 15); ee: thiadiazol-2-yl)-8-(3S,3,5-b 94.46% trimethylpiperazin-1- yl)imidazo[1,5-a]pyridine-6- sulfonamide 2,2,2- cis-Diastereomer 2 trifluoroacetate diastereomer 2 LCMS: RT 0.453 min N-((trans)-1-cyano-2- (method 3); m / z 537.2 methylcyclopropyl)-3-(5- (M+H)+(ESI+). SFC: RT (difluoromethyl)-1,3,4- 2.077 min (Method 15); ee: thiadiazol-2-yl)-8-(3S,3,5-a 81.21% trimethylpiperazin-1- yl)imidazo[1,5-a]pyridine-6- sulfonamide 2,2,2- Trans-Diastereomer 1 trifluoroacetate diastereomer 1 LCMS: RT 0.444 min N-(trans)-1-cyano-2- (method 3); m / z 537.1 methylcyclopropyl)-3-(5- (M+H)+(ESI+). SFC: RT (difluoromethyl)-1,3,4- 2.422 min (Method 15); ee: thiadiazol-2-yl)-8-(3S,3,5-b 82.52% trimethylpiperazin-1- yl)imidazo[1,5-a]pyridine-6- sulfonamide 2,2,2- trifluoroacetate Trans-Diastereomer 2 diastereomer 2 LCMS: RT 0.437 min Mixture of N-((cis)-1-cyano- (method 3); m / z 553.2 2-methylcyclopropyl)-3-(5- (M+H)+(ESI+). SFC: RT (difluoromethyl)-1,3,4- 1.988 min, thiadiazol-2-yl)-8-(5- 2.113 min (Method 15) (hydroxymethyl)-3,3- dimethylpiperazin-1- yl)imidazo[1,5-a]pyridine-6- sulfonamide formate diastereomer 1 and N-((cis)- 1-cyano-2- methylcyclopropyl)-3-(5- Mixture of cis- (difluoromethyl)-1,3,4- Diastereomer 1 and cis- thiadiazol-2-yl)-8-(5- Diastereomer 2 (hydroxymethyl)-3,3- dimethylpiperazin-1- yl)imidazo[1,5-a]pyridine-6- sulfonamide formate diastereomer 2 LCMS: RT 0.436 min Mixture of N-((cis)-1-cyano- (method 3); m / z 553.2 2-methylcyclopropyl)-3-(5- (M+H)+(ESI+). SFC: RT (difluoromethyl)-1,3,4- 1.869 min, thiadiazol-2-yl)-8-(5- 1.949 min (Method 15) (hydroxymethyl)-3,3- dimethylpiperazin-1- yl)imidazo[1,5-a]pyridine-6- Mixture of cis- sulfonamide formate Diastereomer 3 and cis- diastereomer 3 and N-((cis)- Diastereomer 4 1-cyano-2- methylcyclopropyl)-3-(5- (difluoromethyl)-1,3,4- thiadiazol-2-yl)-8-(5- (hydroxymethyl)-3,3- dimethylpiperazin-1- yl)imidazo[1,5-a]pyridine-6- sulfonamide formate diastereomer 4 LCMS: RT 0.562 min 8-chloro-3-(5- (method 3); m / z 438.0 (difluoromethyl)-1,3,4- (M+H)+(ESI+). SFC: RT thiadiazol-2-yl)-N-((cis)-2- 1.899 min, fluoro-1- 2.215 min (Method 9) methylcyclopropyl)imidazo[1 2 compounds-cis ,5-a]pyridine-6-sulfonamide LCMS: RT 0.579 min 8-chloro-3-(5- (method 3); m / z 438.0 (difluoromethyl)-1,3,4- (M+H)+(ESI+). SFC: RT thiadiazol-2-yl)-N-((trans)-2- 0.869 min, fluoro-1- 1.658 min (Method 13) methylcyclopropyl)imidazo[1 2 compounds-trans ,5-a]pyridine-6-sulfonamide LCMS: RT 0.580 min (method 3); m / z 517.0 3-(5-(difluoromethyl)-1,3,4- (M+H)+(ESI+). SFC: RT thiadiazol-2-yl)-8-((2S,6S)- 1.341 min, 2,6-dimethylmorpholino)-N- 1.553 min (Method 16) ((cis)-2-fluoro-1- methylcyclopropyl)imidazo[1 ,5-a]pyridine-6-sulfonamide 2 compounds-cis Biological evaluation of the exemplary compounds The compound of formula (I) was tested in selected biological and / or physicochemical assays one or more times. When tested more than once, data are reported as either average values or as median values, wherein the average value, also referred to as the arithmetic mean value, represents the sum of the values obtained divided by the number of times tested, and the median value represents the middle number of the group of values when ranked in ascending or descending order. If the number of values in the data set is odd, the median value is the middle value. If the number of values in the data set is even, the median is the arithmetic mean of the two middle values. The in vitro pharmacological, pharmacokinetic and physicochemical properties of the compounds can be determined according to the following assays and methods. PARG protein expression and purification A codon optimized gene encoding human PARG (448–976 [H446G, L447S, L473S, N479S, S802A, R811K, M841I, S858P, I916T, T924D, D927K, C963S, A967T]) was synthesized by Genscript, and cloned into pET15b (NcoI / BamHI) with an N-terminal, Thrombin protease cleavable 6His-TwinStrep tag.Expression of the protein in E. coli BL21 (DE3) was induced by addition of 0.2 mM IPTG to a shake flaskculture grown to OD600=0.8 at 37°C. Growth was allowed to continue at 30°C for a further 20 hoursbefore harvesting by centrifugation and storage of the cell pellet at 80°C.Protein was purified by IMAC and SEC: frozen cell pellets (typically 40 g wet weight) were resuspended by homogenization in 5 volumes buffer A (25 mM Tris / HCl pH 8.0, 200 mM NaCl, 2 mM DTT), supplemented with 1 mg of DNase I from bovine pancreas (Sigma-Aldrich) and protease inhibitors (Roche Complete™ EDTA-free protease inhibitor tablet), and lysed by passage through a Constant Systems BasicZ homogenizer. The lysate was clarified by centrifugation for 60 minutes at 25,000 g, 4°C, and the lysate supernatant was loaded onto 5 ml StrepTrap HP (Cytiva) pre-equilibrated with buffer A.The column was washed with buffer A ( 10 CV), then buffer B containing 1M KCl ( 5 CV), and then theprotein was eluted with buffer A containing 2.5 mM d-Desthiobiotin. Pooled fractions containing 6HisTwinStrep-TEV-hPARG were incubated with TEV protease overnight at 4°C. hPARG was separated from uncleaved material and Thrombin protease through gel filtration with Superdex75 sizing column (GE Healthcare) pre-equilibrated with SEC buffer (15 mM Tris / HCl pH 8.5, 100 mM NaCl, 2 mM DTT). Pooled fractions containing pure hPARG were concentrated using a 10 k MWCO spin concentrator (VivaSpin) to 10 mg / mL, and then either used immediately for crystallisation or snap-frozen in liquid nitrogen for storageat 80°C.PARG enzymatic IC50 assay PARG enzyme as incubated with compound or vehicle (DMSO) for 2 hours in a 384 well plate. After adding the PARG substrate ADP-ribose-pNP, the plate was read for absorbance intensity at 405 nm. The vehicle (DMSO) with high absorbance intensity represents no inhibition of enzymatic reaction while the low control (no enzyme) with low absorbance intensity represents full inhibition of enzymatic reaction. Materials: hPARG: Peak Protein, 30 nM Substrate: ADP-pNP, 800 µM, Jena Bioscience catalog # NU-955 Reaction time: 60 minutes Assay buffer: 50 mM Tris-HCl pH 8.0, 100 mM NaCl, 2 mM DTT Temperature: 30 °C Total volume: 30 µL Controls: 0% inhibition control: DMSO 100% inhibition control: No enzyme The protocol that was used for enzyme reaction and detection is as follows: 1. Transfer 100 nL of the final concentration of test compounds or vehicle (DMSO) to the appropriate wells of a microtiter plate. 2. Centrifuge the plate at 1000 rpm for 1 minute. 3. Transfer 14.6 L of 2x final concentration of enzyme in assay buffer or assay buffer aloneto the appropriate wells. 4. Centrifuge the plate at 1000 rpm for 1 minute. 5. Incubate the plate at room temperature for 15 minutes or 2 hours. 6. Transfer 15.4 µL of 2x substrate in assay buffer to all the test wells. 7. Centrifuge the plate at 1000 rpm for 1 minute. 8. Read the plate on a plate reader (e.g., Spark Tecan). The Absorbance IC50 value of compounds of Formula (I) in Example 1 is provided in Table 2 below. Cellular PAR chain assay The ability of compounds to inhibit PARG in response to DNA damage, was assessed with U2OS cells pretreated with the compounds for 1 hour, following a 1-hour treatment with or without the DNA alkylating agent temozolomide (TMZ) (250µM). The cells were harvested and fixed in 70% ethanol, rehydrated with glucose and EDTA in PBS and subsequently blocked for 1 hour with PBS 1% BSA and 0.01% Tween-20 (PBT). The cells were incubated for 2 hours at room temperature with a mouse monoclonal antibody against poly (ADP) ribose (PAR) polymer. The cells were washed and incubated with an anti-mouse Alexa-488 conjugated secondary antibody for 1 hour at room temperature. Propidium iodide staining was used to determine DNA content in the cells (staining at 4°C overnight). The fluorescence intensity of the cells was assessed by flow cytometry (Cytoflex from Beckmann) and the percentage of PAR chain positive cells (gated in relation to TMZ+DMSO treated control) was determined. PAR chain positive cells % were fit against the concentration of the compound using a 4 parameter log- logistic function, generating PAR chain EC50 values: The PAR chain EC50 value for compounds of Formula (I) in Example 1 is provided in Table 2 below. Cellular Viability Assay NCI-H460 and MDA-MB-436 as PARG-inhibition sensitive cell lines, and U2OS as PARG-inhibition insensitive cell line, were plated at 1000 cells / well, 5000 cells / well and 2000 cells / well, respectively, in 96- well white plates with clear flat bottom. After 24 hours, the compounds were added with the Tecan digital dispenser (D300e), in duplicates. The outer wells of the plate were excluded. After 96 hours of incubation, 150 µl of the growth medium were removed and 50 µl of Cell Titer-Glo (Promega) were added per well. Following an incubation of 10 minutes, luminescence was read using a plate reader (Tecan) for NCI-H460 and U2OS cell lines, and a 2104 EnVision plate reader for MDA-MB-436. Averaged values of the samples were normalized to DMSO treated control samples. Curves were fit as % of the control vs. log of the compound concentration using a 4 parameter log-logistic function: The PARGi (NCI-H460, MDA-MB-436 and U2OS) cellular viability EC50 values for compounds of Formula (I) are provided in Table 2 below. hERG assay Compounds were solubilised to 33mM in DMSO before dilution in HBPS to 100mM. 8-Point concentration-response curves were generated using serial dilutions from the top test concentration. Electrophysiological recordings were made from a Chinese Hamster Ovary cell lines stably expressing the full-length hERG ion channel (human Kv11.1). Single cell ionic currents were measured inwhole-cell configuration at room temperature (25 C) using a QPatch II automated electrophysiologyplatform (Sophion Bioscience). The internal solution for hERG contained (mM): 120 KCl, 5.374 CaCl2, 1.75 MgCl2,10EGTA, 10 HEPES and was buffered to pH 7.3 with KOH. The external solution (HEPES- buffered saline, HBPS) contained (mM): 138 NaCl, 4.5 KCl, 1.8 CaCl2, 1.0 MgCl2, 10 HEPES, 10 glucose, buffered to pH7.4 with NaOH. Cells were clamped at a holding potential of -80mV. After a depolarising step to +40mV for 1500ms, cells were repolarised to -40mV for 1500ms. Currents were measured from the second step and referenced to the holding current. Compounds were incubated for 120 seconds. Concentration-response curves were generated by cumulative addition of compound with concentrations low to high. In all cases, steady-state inhibition was achieved before the next concentration of compound was added. Table 2: Inhibition of PARG and cellular activity of compounds according to the present invention.The IC50 (inhibitory concentration at 50% of maximal effect) values are indicated in µM, empty space means that the corresponding compounds have not been tested in the respective assay. Example number IC50 in M determined in PARG enzymatic assay (PARG protein and 2 hours incubation)described under PARG enzymatic IC50 assay EC50 in M determined in cellular assay as described under Cellular PAR chain assay(conditions with treatment of TMZ). EC50 in M determined in cellular assay as described under Cellular PAR chain assay(conditions without treatment of TMZ). .EC50 in M determined in NCIH-460 cells as described under Cellular viability assay.EC50 in M determined in U2OS cells as described under Cellular viability assay.EC50 in M determined in MDA-MB-436 cells as described under Cellular viability assayHuman CLint(liver) [mL / min / kg]hERG IC50 (µM) Table 2. 10.011 <0.025 7.1171a 0.011 0.012 5.331 0.024 4.41b 0.016 0.120 6.371c 0.068 1.747 5.7571d 0.019 0.994 2.8962 0.013 0.099 10.5042a 0.011 0.3 8.1572b 0.021 0.106 >202c 0.1142d 0.06753 0.055 7.687 >200.011 0.16 >17.56a 0.014 0.118 >20b 0.011 0.129 3.3590.011 0.054 8.8230.011 0.225 8.4584.0210.025 0.327 6.024a 0.011 0.064 6.544b 0.017 0.21 6.466c 0.026 0.092 >20d 0.037 1.519 >200.03 0.151 1.710.026 0.14 1.665a 0.016 0.206 1.715b 0.017 0.038 1.531c 0.206d 0.026 1.212 1.60 0.019 0.163 5.9210a 0.011 0.217 7.3970b 0.011 0.032 6.3670c 0.2310d 0.017 2.703 6.3581 0.047 0.963 1.7651a 0.02 0.653 1.7431b 0.019 0.144 2.0811c 0.045 2.127 1.7911d 0.4172 0.011 0.064 3.2273 0.011 0.080 5.3214 0.0525 0.5636 0.0757 0.58758 0.036 0.153 6.41318a 0.014 0.018 5.96318b 0.016 0.184 5.8818c 0.076 2.945 2.31418d 1.57 2.69919 0.184 >14.0219a 0.018 0.127 >2019b 0.011 0.109 6.35820a 0.032 1.169 >2020b 0.13121 0.036 0.103 >2021a 1.044 >2021b 0.029 1.765 >2021c 0.023 0.053 >2021d 0.02 0.055 >2022 0.02 12.646 >2023 0.015 1.9987 >2024 0.029 >20 >2025 0.019 >20 >2026 0.023 0.339 >20Further assays Kinetic solubility assay The Kinetic solubility assay employs the shake flask method followed by HPLC-UV analysis. For exemplary compounds, the kinetic solubility was measured according to the following protocol: 1. Samples were weighed and dissolved in 100% DMSO to make a stock solution of 10 mM. About100 L of stock solution is needed to cover this assay.2. Test compounds and controls (10 mM in DMSO, 10 L / tube) were added into the buffer (490L / well) which were placed in a Mini-UniPrep filter. The buffer was prepared as the customer’s requirement. 3. The kinetic solubility samples were vortexed for 2 minutes. 4. The solubility solutions were shaked in an orbital shaker for 24 hr at room temperature. 5. 200 L of each solubility solution were transferd into a 96-deep well for analysis when thesamples were directly filtered by the syringeless filter device. 6. The test compound concentration of the filtrate were determined using HPLC-UV. 7. Three UV standard solutions were injected into HPLC from low to high concentrations, followed by testing of the K.S. supernatant. Testing samples were injected in duplicate. Bidirectional permeability in Caco2 The bidirectional permeability in Caco-2 cells assay was performed for the exemplary compounds of formula (I) according to the following protocol: 1. Caco-2 cells purchased from ATCC were seeded onto polyethylene membranes (PET) in 96- well BD insert plates at 1 x 105 cells / cm2, and refreshed medium every 4~5 days until to the 21stto 28thday for confluent cell monolayer formation. 2. The integrity of the monolayer was verified by performing Lucifer yellow rejection assay. 3. The quality of the monolayer was verified by measuring the unidirectional (A B) permeabilityof fenoterol / nadolol (low permeability marker), propranolol / metopronolol (high permeability marker) and bi-directional permeability of digoxin (a P-glycoprotein substrate marker) in duplicate wells. 4. Standard assay conditions for test compounds: test concentration: 2 M (DMSO 1%);replicates: n=2; directions: bi-directional transport including A B and B A;incubation time: single time point, 2 hours; transport buffer: HBSS containing 10 mM HEPES, pH7.40 ± 0.05; incubation condition: 37±1°C, 5% CO2, relatively saturated humidity. 5. Dosing solution were spiked and mixed with transport buffer and stop solution (containing an appropriate internal standard (IS)) as T0 sample. 6. At the end of incubation, sample solutions from both donor and receiver wells were mixed with stop solution immediately. 7. All samples including T0 samples, donor samples and receiver samples were analyzed using LC / MS / MS. Concentrations of test compound were expressed as peak area ratio of analytes versus IS without a standard curve. Liver Microsomes Stability Assay 1. Materials1.1 Liver microsomesAnimal or human liver microsomes were purchased from Xenotech or Corning and stored in a freezer (lower than -60°C) before use. 1.2 -nicotinamide adenine dinucleotide phosphate reduced form, tetrasodium salt, Vendor: Chem-Impex International, Cat.No.00616 1.3 Control compounds: Testosterone, diclofenac and propafenone.2. Preparation of Working SolutionStock Solution: 10 mM test compound in DMSO. Working solution: 100 µM test or control compounds in 100% acetonitrile (concentration of organic solvent: 1% (v / v) DMSO and 99% (v / v) acetonitrile) 3. Assay ProcedureA total of two sample plates with 96-well format were prepared for incubation, labelled as 'Incubation' T60 and 'Incubation' NCF60. Empty 'Incubation' T60 and NCF60 plates were pre-warmed for 10 min minutes. Liver microsomes were diluted to 0.56 mg / mL in 100 mM phosphate buffer. Microsome working solutions (0.56 mg / mL) were transferred (445 µL) into pre-warmed 'Incubation' T60 and NCF60 plates, followed by incubation for 10 min at 37°C with constant shaking. Liver microsomes (54 µL) were transferred to a Blank60 plate, followed by the addition of 6 µL NAPDH cofactor and 180 µL stop solution (acetonitrile containing internal standards) into each well. An aliquot (5 µL) of compound working solution (100 µM) was added into the 'incubation' plates (T60 and NCF60) containing microsomes and mixed 3 times thoroughly. For the 'Incubation' NCF60 plate, 50 µL of buffer was added and mixed 3 times thoroughly. The plates were incubated at 37°C for 60 min while shaking. samples were mixed once and 60 µL was transferred from the NCF60 incubation plate to the stop plate containing stop solution after the 60-min incubation. Stop solution (180 µL) and NAPDH cofactor (6 µL) were added to 'Quenching' plate T0. Plates were chilled to prevent evaporation. For the 'Incubation' T60 plate: mixed 3 times thoroughly, and immediately removed 54 µL mixture for the 0-min time point to stop plate ('Quenching' plate T0). NAPDH cofactor (44 µL) was added to the 'Incubation' T60 plate. The plate was incubated at 37°C for 60 min while shaking. At 5, 15, 30, 45, and 60 min, 180 µL stop solution was added to the 'Quenching' plates, samples were mixed once, and 60 µL was serially transferred from 'Incubation' T60 plate per time point. Consequently, for the wells containing the test or control compounds, the final concentration was 1 M for test compounds, testosterone, diclofenac and propafenone, 0.5 mg / mL for animal or human liver microsomes, 0.01% (v / v) for DMSO and 0.99% (v / v) for acetonitrile. All sampling plates were shaken for 10 min, then centrifuged at 3220 ×g for 20 minutes at 4°C. Supernatant (80 µL) was transferred into 240 µL HPLC water, and mixed by plate shaker for 10 min. Each bioanalysis plate was sealed and shaken for 10 minutes prior to LC-MS / MS analysis. 4. Bioanalytical Analysis Concentrations of test conpounds and positive controls, testosterone, diclofenac and propafenone in the samples were determined by using a liquid chromatography-tandem mass spectrometry (LC- MS / MS) method. 5. Data CalculationIn the determination of the in vitro elimination constant, ke, of test compound and control compounds, the peak area ratios (PAR) of analyte / internal standard were used to calculate the percentage of remaining (%Remaining) with the f...

Claims

New PCT-Patent Application based on US 63 / 614,140 FoRx Therapeutics AG Vossius Ref.: AG4297 PCT BS Claims1. A compound of formula (I):or a pharmaceutically acceptable salt thereof, wherein: Z is selected from: ,R1 is -H, -CN, C1-2 alkyl, C2 alkenyl, C2 alkynyl, C1-2 haloalkyl, -(C1-2 alkylene)-OH or -(C1-2 alkylene)-O-(C1-2 alkyl); R2 is -H, C1-2 alkyl or -F, and R3 is selected from -H, halogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, and -CN, wherein said alkyl, said alkenyl, and said alkynyl are each optionally substituted with one or more groups independently selected from RS1, or R2 and R3 together with the carbon atom to which they are attached form cyclopropyl optionally substituted with one or more groups independently selected from RS2; X2 is C-YC2-RC2; YC2 is selected from a covalent bond, C1-8 alkylene, C2-8 alkenylene, C2-8 alkynylene, cycloalkylene and heterocycloalkylene wherein said alkylene, said alkenylene and said alkynylene are eachoptionally substituted with one or more groups independently selected from RS1, and further wherein one or more -CH2- units comprised in said alkylene, said alkenylene or said alkynylene are each optionally replaced by a group independently selected from -O-, -NH-, -N(C1-5 alkyl)- , -CO-, -S-, -SO-, and -SO2-, and wherein said cycloalkylene and heterocycloalkylene are each optionally substituted with one or more groups independently selected RS2; RC2 is selected from hydrogen, halogen, -OH, -NH2, -SH, -CN, C1-12 alkyl, C2-12 alkenyl, C2-12 alkynyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, and heteroaryl; wherein said alkyl, alkenyl, and alkynyl in X2 are each optionally substituted with one or more groups independently selected from RS1, and wherein said cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl and heteroaryl in X2 are each optionally substituted with one or more groups independently selected from RS2; R4 is a five membered heteroaryl, optionally substituted with one or more groups independently selected from RS2; X4 is N or C-R5, wherein R5 is selected from -H, C1-2 alkyl, C2 alkenyl, C2 alkynyl, C1-2 haloalkyl, cyclopropyl, cyclobutyl, oxetanyl, and halogen; X5 is N or C-R6, wherein R6 is selected from -H, halo, C1-6 alkyl, -O(C1-6 alkyl), -S(C1-6 alkyl), - NH(C1-6 alkyl), -N(C1-6 alkyl)C1-6 alkyl and C1-6 haloalkyl; RS1is selected from halogen, -CN, -OH, -O(C1-5 alkyl), -O(C1-5 haloalkyl), C1-5 haloalkyl, -SH, -S(C1-5 alkyl), -SO2(C1-5 alkyl), -S(O)(NH)(C1-5 alkyl), -S(O)(N-C1-3 alkyl)(C1-5 alkyl), -N=S(O)(C1-5 alkyl)(C1-5 alkyl), -S(C1-5 haloalkyl), -P(O)(C1-5 alkyl)(C1-5 alkyl), -P(O)(O-C1- 5 alkyl) (O-C1-5 alkyl), -P(O)(O-C1-5 alkyl)(C1-5 alkyl), -NH2, -NH(C1-5 alkyl), -NH(C1-5 haloalkyl), -N(C1-5alkyl)(C1-5alkyl), -N(C1-5haloalkyl)(C1-5alkyl), -(N-heterocycloalkyl), -CO(C1-5alkyl), -CONH2, -CONH(C1-5 alkyl), -CON(C1-5 alkyl)(C1-5 alkyl), -CO-(N- heterocycloalkyl), -NHCO-(C1-5 alkyl), -N(C1-5 alkyl)-CO-(C1-5 alkyl), -NHCONH2, -NHCONH-(C1-5 alkyl), -NHCON(C1-5 alkyl)(C1-5 alkyl), -N(C1-5 alkyl)CONH2, -N(C1-5 alkyl)CONH-(C1-5 alkyl), and -N(C1-5 alkyl)CON(C1-5 alkyl)(C1-5 alkyl); and RS2is selected from halogen, -CN, -OH, C1-5 alkyl, C1-5 haloalkyl, -O(C1-5 alkyl), -O(C1-5 haloalkyl), -SH, -S(C1-5 alkyl), -S(O)(C1-5 alkyl), -SO2(C1-5 alkyl), -S(O)(NH)(C1-5 alkyl), -S(O)(N- C1-3 alkyl)(C1-5 alkyl), -N=S(O)(C1-5 alkyl)(C1-5 alkyl), -S(C1-5 haloalkyl), -S(O)(C1-5 haloalkyl), -SO2(C1-5 haloalkyl), -P(O)(C1-5 alkyl)(C1-5 alkyl), -P(O)(O-C1-5 alkyl)(O-C1-5 alkyl), - P(O)(O-C1-5alkyl)(C1-5alkyl), -NH2, -NH(C1-5alkyl), -NH(C1-5haloalkyl), -N(C1-5alkyl)(C1-5alkyl), -N(C1-5 haloalkyl)(C1-5 alkyl), -(N-heterocycloalkyl), -CO(C1-5 alkyl), -COOH, -COO(C1-5 alkyl), -CONH2, -CONH(C1-5 alkyl), -CON(C1-5 alkyl)(C1-5 alkyl), -CO-(N- heterocycloalkyl), -NHCO-(C1-5 alkyl), -N(C1-5 alkyl)-CO-(C1-5 alkyl), -NHCONH2, -NHCONH-(C1-5alkyl), -NHCON(C1-5 alkyl)(C1-5 alkyl), -N(C1-5 alkyl)CONH2, -N(C1-5 alkyl)CONH-(C1-5 alkyl), and -N(C1-5 alkyl)CON(C1-5 alkyl)(C1-5 alkyl), -(C1-5 alkylene)-CN, -(C1-5 alkylene)-OH, -(C1-5 alkylene)-O(C1-5 alkyl), -(C1-5 alkylene)-O(C1-5 haloalkyl), -(C1-5 alkylene)-SH, -(C1-5 alkylene)-S(C1-5 alkyl), -(C1-5 alkylene)-S(O)(C1-5 alkyl), -(C1-5 alkylene)-SO2(C1-5 alkyl), -(C1-5 alkylene)-S(O)(NH)(C1-5 alkyl), -(C1-5 alkylene)-S(O)(N-C1-3 alkyl)(C1-5 alkyl), -(C1-5 alkylene)-N=S(O)(C1-5 alkyl)(C1-5 alkyl), -(C1-5 alkylene)-S(C1-5 haloalkyl), -(C1-5 alkylene)- S(O)(C1-5 haloalkyl), -(C1-5 alkylene)-S(O)2(C1-5 haloalkyl), -(C1-5 alkylene)-P(O)(C1-5 alkyl)(C1-5 alkyl), -(C1-5 alkylene)-P(O)(O-C1-5 alkyl)(O-C1-5 alkyl), -(C1-5 alkylene)-P(O)(O-C1-5 alkyl)(C1-5 alkyl), -(C1-5 alkylene)-NH2, -(C1-5 alkylene)-NH(C1-5 alkyl), -(C1-5 alkylene)-NH(C1-5 haloalkyl), - (C1-5 alkylene)-N(C1-5 alkyl)(C1-5 alkyl), -(C1-5 alkylene)-N(C1-5 alkyl)(C1-5 haloalkyl), -(C1-5 alkylene)-(N-heterocycloalkyl), -(C1-5 alkylene)-N(C1-5 haloalkyl)(C1-5 alkyl), -COO-(C1-5 alkylene)-NH2, -COO-(C1-5 alkylene)-NH(C1-5 alkyl), -COO-(C1-5 alkylene)-NH(C1-5 haloalkyl), - COO-(C1-5 alkylene)-N(C1-5 alkyl)(C1-5 alkyl), -COO-(C1-5 alkylene)-N(C1-5 alkyl)(C1-5 haloalkyl), - COO-(C1-5 alkylene)-(N-heterocycloalkyl), -COO-(C1-5 alkylene)-N(C1-5 haloalkyl)(C1-5 alkyl), -(C1- 5 alkylene)-CO(C1-5 alkyl), -(C1-5 alkylene)-COO(C1-5 alkyl), -(C1-5 alkylene)-COOH, -(C1-5 alkylene)-CONH2, -(C1-5 alkylene)-CONH(C1-5 alkyl), -(C1-5 alkylene)-CON(C1-5 alkyl)(C1-5 alkyl), - (C1-5 alkylene)-CO-(N-heterocycloalkyl), -(C1-5 alkylene)-NHCO-(C1-5 alkyl), -(C1-5 alkylene)-N(C1- 5 alkyl)-CO-(C1-5 alkyl), -(C1-5 alkylene)-NHCONH2, -(C1-5 alkylene)-NHCONH-(C1-5 alkyl), -(C1-5 alkylene)-NHCON(C1-5 alkyl)(C1-5 alkyl), -(C1-5 alkylene)-N(C1-5 alkyl)CONH2, -(C1-5 alkylene)-N(C1-5 alkyl)CONH-(C1-5 alkyl), and -(C1-5 alkylene)-N(C1-5 alkyl)CON(C1-5 alkyl)(C1-5 alkyl); with the proviso thatthen at least one of R2 and R3 is not -H.

2. The compound of claim 1, wherein R1 is methyl (such as -CD3) or fluoromethyl.

3. The compound of claim 1, wherein R1 is -CN.

4. The compound of any one of claims 1 to 3, whereinR2 is -H or -F, and R3is selected from -H, halogen, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C1-6haloalkyl, and -CN, wherein said alkyl, said alkenyl, and said alkynyl are each optionally substituted with one or moregroups independently selected from RS1.

5. The compound of claim 4, wherein R2 is -H.

6. The compound of claim 4 or 5, wherein R3 is selected from -H, and C1-2 alkyl.

7. The compound of any one of claims 1, 2, or 4 to 6, wherein R1 is methyl, R2 is -H and R3 is methyl.

8. The compound of any one of claims 1 to 7, wherein -YC2-RC2 is selected from heterocycloalkyl,and heterocycloalkenyl, wherein said heterocycloalkyl, and said heterocycloalkenyl are each optionally substituted with one or more groups independently selected from RS2.

9. The compound of claim 7, whereinclaim 7, wherein -YC2-RC2 is.

11. The compound of any one of claims 1 to 10, wherein12. The compound of any one of claims 1 to 11, X4 is N or C-R5, wherein R5 is -H, and X5 is N.

13. The compound of any one of claims 1 to 11, X4 is N or C-R5, wherein R5 is -F, and X5 is N.

14. The compound of any one of claims 1 to 13, wherein the compound is a compound according to formula (Ia):or a pharmaceutically acceptable salt thereof, wherein R1, R2, R3, R4, R5 and X2 are defined as in any one of claims 1 to 13, preferably wherein the configuration of the chiral centers in the cyclopropyl moiety shown in formula (Ia) is the same as in compound 1a.

15. The compound of claim 14, wherein the compound is a compound according to formula (Ia-1):or a pharmaceutically acceptable salt thereof.

16. The compound of claim 14, wherein the compound is a compound according to formula (Ia-2):or a pharmaceutically acceptable salt thereof.

17. The compound of claim 14, wherein the compound is a compound according to formula (Ia-1):(Ia-3) or a pharmaceutically acceptable salt thereof.

18. The compound of claim 14, wherein the compound is a compound according to formula (Ia-4):(Ia-4) or a pharmaceutically acceptable salt thereof.

19. The compound of claim 14, wherein the compound is a compound of formula (Ib):or its pharmaceutically acceptable salt, wherein R4, R5 and X2 are as defined in claim 14.

20. The compound of claim 1, wherein the compound is a compound of formula:or its pharmaceutically acceptable salt.

21. The compound of claim 20, wherein the compound is compound 1a, which is a singlediastereoisomer of the compound of formula shown in claim 19 which is characterized by the shortest retention time of all the diastereoisomers of said compound, when purified using SFC according to the following method: Column: Chiralpak AS-350×4.6mm I.D., 3µm; Mobile phase: Phase A for Heptane, and Phase B for IPA (0.05%DEA); Gradient elution:15% IPA (0.05% DEA) in Heptane; Flow rate: 1mL / min; Detector: PDA; Column Temp: 35°C Back Pressure: 100 Bar.

22. The compound of claim 1, wherein the compound is according to formula:or its pharmaceutically acceptable salt.

23. The compound of claim 1, wherein the compound is according to formula:or its pharmaceutically acceptable salt.

24. The compound of claim 1, wherein the compound is according to formula:or its pharmaceutically acceptable salt.

25. The compound of claim 1, wherein the compound is according to formula:or its pharmaceutically acceptable salt.

26. The compound of claim 1, wherein the compound is a compound selected from: 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-1,2-dimethylcyclopropyl)-8-((3S,5S)-3,5- dimethylpiperazin-1-yl)imidazo[1,5-a]pyridine-6-sulfonamide; 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-8-((3S,5S)-3,5-dimethylpiperazin-1-yl)-N-(2-fluoro-1- methylcyclopropyl)imidazo[1,5-a]pyridine-6-sulfonamide; N-1-cyano-2-methylcyclopropyl)-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-8-(-5- (methoxymethyl)-3,3-dimethylpiperazin-1-yl)imidazo[1,5-a]pyridine-6-sulfonamide; 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-(1,2-dimethylcyclopropyl)-8-((3S,5S)-3,5- dimethylpiperazin-1-yl)-[1,2,4]triazolo[4,3-a]pyridine-6-sulfonamide; N-( 1-cyano-2-methylcyclopropyl)-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-8-((3S,5S)-3,5- dimethylpiperazin-1-yl)imidazo[1,5-a]pyridine-6-sulfonamide; 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-8-((3S,5S)-3,5-dimethylpiperazin-1-yl)-N-(1,2,2- trimethylcyclopropyl)imidazo[1,5-a]pyridine-6-sulfonamide;3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-(1,2-dimethylcyclopropyl)-8-(5-(hydroxymethyl)- 3,3-dimethylpiperazin-1-yl)imidazo[1,5-a]pyridine-6-sulfonamide; 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-(1,2-dimethylcyclopropyl)-8-((3S,5S)-3,5- dimethylpiperazin-1-yl)-1-fluoroimidazo[1,5-a]pyridine-6-sulfonamide; 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-(1,2-dimethylcyclopropyl)-8-((3S,5S)-3,5- dimethylpiperazin-1-yl)imidazo[1,2-a]pyridine-6-sulfonamide; 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-(1,2-dimethylcyclopropyl)-8-((3S,5S)-3,5- dimethylpiperazin-1-yl)indolizine-6-sulfonamide; 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-1,2-dimethylcyclopropyl)-8-(3,3-dimethylpiperazin- 1-yl)imidazo[1,5-a]pyridine-6-sulfonamide; 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-1,2-dimethylcyclopropyl)-8-(3-methylpiperazin-1- yl)imidazo[1,5-a]pyridine-6-sulfonamide; 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-8-((3S,5S)-3,5-dimethylpiperazin-1-yl)-N-(2-ethyl-1- methylcyclopropyl)imidazo[1,5-a]pyridine-6-sulfonamide; 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-8-((3S,5S)-3,5-dimethylpiperazin-1-yl)-N-(1-methyl-2- (methyl-d3)cyclopropyl-2,3,3-d3)imidazo[1,5-a]pyridine-6-sulfonamide; N-(1-cyano-2-methylcyclopropyl)-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-8-(3,3,5- trimethylpiperazin-1-yl)imidazo[1,5-a]pyridine-6-sulfonamide; 1-cyano-2-methylcyclopropyl)-3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-8-(5-(hydroxymethyl)- 3,3-dimethylpiperazin-1-yl)imidazo[1,5-a]pyridine-6-sulfonamide; and 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-8-((2S,6S)-2,6-dimethylmorpholino)-N-2-fluoro-1- methylcyclopropyl)imidazo[1,5-a]pyridine-6-sulfonamide; or a pharmaceutically acceptable salt thereof.

27. The compound of claim 1, wherein the compound is a compound selected from 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-1,2-dimethylcyclopropyl)-8-((3S,5S)-3,5- dimethylpiperazin-1-yl)imidazo[1,5-a]pyridine-6-sulfonamide; 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-(1,2-dimethylcyclopropyl)-8-((3S,5S)-3,5- dimethylpiperazin-1-yl)-[1,2,4]triazolo[4,3-a]pyridine-6-sulfonamide; 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-(1,2-dimethylcyclopropyl)-8-(5-(hydroxymethyl)-3,3- dimethylpiperazin-1-yl)imidazo[1,5-a]pyridine-6-sulfonamide; 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-(1,2-dimethylcyclopropyl)-8-((3S,5S)-3,5- dimethylpiperazin-1-yl)-1-fluoroimidazo[1,5-a]pyridine-6-sulfonamide; 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-(1,2-dimethylcyclopropyl)-8-((3S,5S)-3,5-dimethylpiperazin-1-yl)imidazo[1,2-a]pyridine-6-sulfonamide; 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-(1,2-dimethylcyclopropyl)-8-((3S,5S)-3,5- dimethylpiperazin-1-yl)indolizine-6-sulfonamide; 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-1,2-dimethylcyclopropyl)-8-(3,3-dimethylpiperazin- 1-yl)imidazo[1,5-a]pyridine-6-sulfonamide; and 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-1,2-dimethylcyclopropyl)-8-(3-methylpiperazin-1- yl)imidazo[1,5-a]pyridine-6-sulfonamide; or a pharmaceutically acceptable salt thereof.

28. The compound of claim 1, wherein the compound is a compound selected from: 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-(1S,2R)-1,2-dimethylcyclopropyl)-8-((3S,5S)-3,5- dimethylpiperazin-1-yl)imidazo[1,5-a]pyridine-6-sulfonamide; 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-(1S,2R)-(1,2-dimethylcyclopropyl)-8-((3S,5S)-3,5- dimethylpiperazin-1-yl)-[1,2,4]triazolo[4,3-a]pyridine-6-sulfonamide; 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-(1S,2R)-(1,2-dimethylcyclopropyl)-8-(5- (hydroxymethyl)-3,3-dimethylpiperazin-1-yl)imidazo[1,5-a]pyridine-6-sulfonamide; 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-(1S,2R)-(1,2-dimethylcyclopropyl)-8-((3S,5S)-3,5- dimethylpiperazin-1-yl)-1-fluoroimidazo[1,5-a]pyridine-6-sulfonamide; 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-(1S,2R)-(1,2-dimethylcyclopropyl)-8-((3S,5S)-3,5- dimethylpiperazin-1-yl)imidazo[1,2-a]pyridine-6-sulfonamide; 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-(1S,2R)-(1,2-dimethylcyclopropyl)-8-((3S,5S)-3,5- dimethylpiperazin-1-yl)indolizine-6-sulfonamide; 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-(1S,2R)-1,2-dimethylcyclopropyl)-8-(3,3- dimethylpiperazin-1-yl)imidazo[1,5-a]pyridine-6-sulfonamide; and 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-N-(1S,2R)-1,2-dimethylcyclopropyl)-8-(3- methylpiperazin-1-yl)imidazo[1,5-a]pyridine-6-sulfonamide; or a pharmaceutically acceptable salt thereof.

29. A pharmaceutical composition comprising the compound of any one of claims 1 to 28 or a pharmaceutically acceptable salt, hydrate or solvate thereof, and a pharmaceutically acceptable carrier.

30. The compound of any one of claims 1 to 28, or the pharmaceutical composition of claim 29, for use in therapy.

31. The compound of any one of claims 1 to 28, or the pharmaceutical composition of claim 29, for treating a disease or disorder in which PARG activity is implicated.

32. The compound for use or the pharmaceutical composition for use of claim 31, for treating a proliferative disorder, preferably wherein the proliferative disorder is cancer, preferably a human cancer.

33. The compound for use or the pharmaceutical composition for use of claim 32, wherein the proliferative disorder is cancer, selected from breast cancer, ovarian cancer, prostate cancer, pancreatic cancer, colorectal cancer, gastric cancer, skin cancer, endometrial cancer, cervical cancer, brain cancer, liver cancer, bladder cancer, esophageal cancer, kidney cancer, colorectal cancer, stomach cancer, thyroid cancer, lymphoma, leukemia, melanoma, uterine cancer, mantle cell lymphoma, renal cell carcinoma, appendicle cancer, hematologic cancer, MYH-related polyposis, gallbladder cancer, bile duct cancer, testicular cancer, bone cancer, and head and neck cancer.

34. The compound for use or the pharmaceutical composition for use of claim 32, wherein the proliferative disorder is cancer, selected from lung, colon, breast, ovarian, prostate, liver, pancreas, brain, and skin cancer.

35. Use of the compound of any one of claims 1 to 28, or a pharmaceutically acceptable salt, hydrate or solvate thereof, in the manufacture of a medicament for the treatment of a proliferative condition.

36. The use of claim 35, wherein the proliferative condition is cancer, preferably a human cancer.

37. The use of claim 36, wherein the proliferative disorder is cancer, selected from breast cancer, ovarian cancer, prostate cancer, pancreatic cancer, colorectal cancer, gastric cancer, skin cancer, endometrial cancer, cervical cancer, brain cancer, liver cancer, bladder cancer, esophageal cancer, kidney cancer, colorectal cancer, stomach cancer, thyroid cancer, lymphoma, leukemia, melanoma, uterine cancer, mantle cell lymphoma, renal cell carcinoma, appendicle cancer, hematologic cancer, MYH-related polyposis, gallbladder cancer, bile duct cancer, testicular cancer, bone cancer, and head and neck cancer.

38. The use of claim 36, wherein the proliferative disorder is cancer, selected from lung, colon, breast, ovarian, prostate, liver, pancreas, brain, and skin cancer.

39. Use of the compound of any one of claims 1 to 28, or a pharmaceutically acceptable salt, hydrate or solvate thereof, in the manufacture of a medicament for the treatment of disease or disorder in which PARG activity is implicated.

40. A method of treating a disease or disorder in which PARG activity is implicated, the method comprising the step of administering a therapeutically effective amount of the compound of claim 1 to a subject in need thereof.

41. A method of treating a proliferative disease, the method comprising the step of administering a therapeutically effective amount of the compound of claim 1 to a subject in need thereof.

42. The method according to claim 41, where the proliferative disorder is cancer, preferably a human cancer.

43. The method according to claim 42, wherein the proliferative disorder is cancer, selected from breast cancer, ovarian cancer, prostate cancer, pancreatic cancer, colorectal cancer, gastric cancer, skin cancer, endometrial cancer, cervical cancer, brain cancer, liver cancer, bladder cancer, esophageal cancer, kidney cancer, colorectal cancer, stomach cancer, thyroid cancer, lymphoma, leukemia, melanoma, uterine cancer, mantle cell lymphoma, renal cell carcinoma, appendicle cancer, hematologic cancer, MYH-related polyposis, gallbladder cancer, bile duct cancer, testicular cancer, bone cancer, and head and neck cancer.

44. The method according to claim 42, wherein the proliferative disorder is cancer, selected from lung, colon, breast, ovarian, prostate, liver, pancreas, brain, and skin cancer.

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