Bicyclic (hetero)arylene WRN inhibitory compounds

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 WRN inhibitors, and can be used in a method of treatment of cancer, in particular, the cancer is treatable by inhibition of WRN, and / or the cancer characterized by MSI-H and / or dMMR

Description

[0001] New PCT Patent Application based on US 63 / 614,186 and US 63 / 574,703 FoRx Therapeutics AG Vossius Ref.: AG4386 PCT BS WRN inhibitory compounds 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 WRN inhibitors, and can be used in a method of treatment of cancer, in particular, the cancer is treatable by inhibition of WRN, and / or the cancer characterized by MSI-H and / or dMMR. Background of the invention Cancer is a leading cause of death worldwide. A limitation of prevailing therapeutic approaches, e.g. chemotherapy is that their cytotoxic effects are not restricted to cancer cells and adverse side effects can occur within normal tissues. Consequently, novel strategies are needed to better target cancer cells. Synthetic lethality (SL) arises when a combination of genetic deficiencies (e.g. gene mutations, silencing or global genomic lesions) and / or molecular perturbations (e.g. gene expression knockout / knockdown, pharmacological inhibition / activation) corresponding to two or more genes impaired cell wellbeing, whereas presence of single deficiency / perturbation does not (Dobzhansky, T., Genetics 1946; 31, 269-290, Huang et al., Nature Reviews Drug Discovery 2020; volume 19, pages 23-38). Microsatellite instability is a genomic lesion caused by defects in mismatch repair machinery (dMMR). MSI status is present in colorectal cancer, endometrial cancer, gastric cancer and other cancer types. Mutation or silencing of MMR genes, including MLH1, MSH2, MSH6 and PMS2, abrogates cell’s ability to repair DNA mismatch mutations (Baudrin et al., Front. Oncol.2018). As a consequence, tumor with MSI-H status carries higher mutation burden, disrupted microsatellite repeat sequences and extended TA dinucleotide repeat sequences across the genome (van Wietmarschen N. et al., Nature 2020; 586, pages 292-298). MSI status can be assessed by molecular testing of certain microsatellites, next-generation sequencing of patient genome or by immunohistochemical evaluation of expression of certain MMR proteins. Tumors can be categorized into MSI high (MSI-H), MSI low (MSI-L) and MSS depending on the number of tested microsatellite showing instability. Based on a consensus NCI- Reference Panel (Bethesda, 1998), MSI can be assessed by molecular testing of five microsatellites - including two mononucleotides (BAT25 and BAT26) and three dinucleotides (D2S123, D5S346, D17S250). Tumors are denoted as MSI-high (MSI-H) if two or more of the microsatellite markers show instability, MSI-low (MSI-L) if only one microsatellite marker shows instability, and MS-stable (MSS) if none of the five microsatellite markers show instability. In some instances, for example where molecular testing or immunohistochemical evaluation is not able to distinguish between MSI-L and general chromosomal instability, tumors can be classified as a MSS neoplasms. WRN (WRN RecQ helicase) has been identified as a synthetic lethality vulnerability to cancer cells with high microsatellite instability status (MSI-H). WRN contains an exonuclease domain and an ATP - dependent helicase domain. It is localized to the nucleus and unwinds double strand DNA, particularly secondary structures (fork DNA, holliday junction, G4-quadruaplex, DNA hairpin and cruciform etc.) during DNA replication, damage and repair processes. Its helicase activity has been shown to be indispensable to the survival of MSI cell lines as helicase-deficient WRN mutant is insufficient to rescue impaired cell viability from WRN knockout or knockdown. The absence of either the WRN protein or inhibition of its helicase activity prevents normal DNA damage and repair processes, leading to increased DNA double- strand breaks (DSB) and subsequent growth arrest and cell death. Covalent inhibitors represent a class of small molecules which form covalent bonds with their biological targets to inhibit activities of these targets in physiological or pathological conditions. In general, covalent inhibitors engage with nucleophilic residues (e.g. Cysteine, Serine, Threonine, Histidine, Arginine, Tyrosine) lining specific binding pockets on target proteins, in a nucleophilic addition or substitution reaction, with their reactive electrophilic warhead. To date, a variety of reactive warheads have been identified, including epoxide, aziridine, ester, ketone, a, -unsaturated carbonyl, nitrile, etc. Covalent inhibitors have been discovered as medicines for more than a century, starting with Aspirin being manufactured and marketed as painkillers and anti-inflammatory drug, although its mechanism of action was not revealed until 1970s to be an irreversible inhibitor of cyclooxygenase- 1 (COX- 1). Other notable covalent inhibitors used as medicine include antibiotics Penicillin, proton pump inhibitor Omeprazole and Lansoprazole, anticoagulant Clopidogrel. Document WO 2023 / 062575 discloses certain cyclic vinyl sulfone compounds as WRN inhibitors. Documents WO 2024 / 010782 and WO 2024 / 010784 disclose certain covalent WRN inhibitors. Further covalent inhibitors of WRN are disclosed in document WO 2024 / 028169. Document WO 2022 / 249060 discloses certain compounds as WRN reversible inhibitors. Summary of the invention It was an objective technical problem of the present invention to provide compounds that are cell- permeable inhibitors of WRN. The technical problem of the present invention is solved by the embodiments described herein and as characterized by the claims. In a first embodiment, the present invention relates to a compound of formula (I) or a pharmaceutically acceptable salt thereof. In a second embodiment, the present invention relates to a pharmaceutical composition comprising a compound of formula (I). In a third embodiment, the present invention relates to a compound of formula (I) for use as a medicament. In a fourth embodiment, the present invention relates to a compound of formula (I) for use in the treatment of cancer. It is preferred that the cancer is characterized by high microsatellite instability (MSI) and / or by defective DNA mismatch repair system (dMMR) in a patient. In a fifth embodiment, the present invention relates to use of a compound of formula (I) in a manufacture of a medicament. In a sixth embodiment, the present invention relates to use of a compound of formula (I) in a manufacture of a medicament for the treatment of cancer. It is preferred that the cancer is characterized by high microsatellite instability (MSI) and / or by defective DNA mismatch repair system (dMMR) in a patient In a seventh embodiment, the present invention relates to a method of treatment of cancer in a subject in need thereof, the method comprising the step of administering the compound of formula (I) to said subject. Typically, a therapeutically effective amount of the compound of formula (I) is administered. It is preferred that the cancer is characterized by high microsatellite instability (MSI) and / or by defective DNA mismatch repair system (dMMR) in a patient. 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 C2-4 alkynyl. 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 “C0-3alkylene” 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 “C2-5alkenylene” 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 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 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 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 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 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” (or Hal) refers to fluoro (-F), chloro (-Cl), bromo (-Br), or iodo (-I). Preferred halogen is fluoro. 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). 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), A is selected from aryl, heteroaryl, heterocycloalkyl, heterocycloalkenyl, cycloalkyl, cycloalkenyl, -N(C1-5 alkyl)(C1-5 alkyl), C2-haloalkyl (such as -CF2CH3) and –(C1-2 haloalkylene)-cycloalkyl (such as -CF2-cyclopropyl),and C2 alkynyl, wherein said aryl, said heteroaryl, said heterocycloalkyl, said heterocycloalkenyl, said cycloalkyl and said cycloalkenyl are each optionally substituted with one or more R1, and wherein said C2alkynyl is optionally substituted with C1-6alkyl or C1-6haloalkyl, preferably C1-6 alkyl. Preferably, A is selected from aryl, heteroaryl, heterocycloalkyl, heterocycloalkenyl, cycloalkyl, cycloalkenyl, C2-haloalkyl (such as -CF2CH3) and –(C1-2 haloalkylene)-cycloalkyl (such as -CF2- cyclopropyl), and C2 alkynyl, wherein said aryl, said heteroaryl, said heterocycloalkyl, said heterocycloalkenyl, said cycloalkyl and said cycloalkenyl are each optionally substituted with one or more R1, and wherein said C2 alkynyl is optionally substituted with C1-6 alkyl or C1-6 haloalkyl, preferably C1-6 alkyl. More preferably, A is selected from aryl, heteroaryl, heterocycloalkyl, heterocycloalkenyl, cycloalkyl, cycloalkenyl and C2 alkynyl, wherein said aryl, said heteroaryl, said heterocycloalkyl, said heterocycloalkenyl, said cycloalkyl and said cycloalkenyl are each optionally substituted with one or more R1, and wherein said C2 alkynyl is optionally substituted with C1-6 alkyl or C1-6 haloalkyl, preferably C1-6 alkyl. It is to be understood that said cyclopropyl in -CF2-cyclopropyl is not substituted. Particularly suitable aryl, heteroaryl, heterocycloalkyl, heterocycloalkenyl, cycloalkyl and cycloalkenyl in A are each a single-ring system. Thus, preferably, A is selected from a single ring aryl, a single ring heteroaryl, a single ring heterocycloalkyl, a single ring heterocycloalkenyl, a single ring cycloalkyl, a single ring cycloalkenyl and C2 alkynyl, wherein said aryl, said heteroaryl, said heterocycloalkyl, said heterocycloalkenyl, said cycloalkyl and said cycloalkenyl are each optionally substituted with one or more R1, and wherein said C2 alkynyl is optionally substituted with C1-6 alkyl or C1- 6 haloalkyl. If A is aryl, heteroaryl, heterocycloalkyl, heterocycloalkenyl, cycloalkyl or cycloalkenyl that is optionally substituted with one or more R1, then said aryl, said heteroaryl, said heterocycloalkyl, said heterocycloalkenyl, said cycloalkyl or said cycloalkenyl may preferably be substituted with 0, 1, 2, 3 or 4 groups R1. Preferably, said aryl, said heteroaryl, said heterocycloalkyl, said heterocycloalkenyl, said cycloalkyl or said cycloalkenyl is substituted with 0, 1 or 2 groups R1. Preferably, A is selected from aryl, heteroaryl and cycloalkyl, wherein said aryl, said heteroaryl and said cycloalkyl are each optionally substituted with one or more R1. More preferably, A is aryl or heteroaryl wherein said aryl, and said heteroaryl are each optionally substituted with one or more R1. Still more preferably, A is aryl, optionally substituted with one or more R1. However, A may also be C2-haloalkyl. An exemplary suitable C2-haloalkyl as A is -CF2CH3. In one embodiment, A is -CF2-cyclopropyl. In one embodiment, A is -N(C1-5alkyl)(C1-5alkyl), such as -N(CH3)(CH(CH3)2). In formula (I), each R1is independently selected from C1-5 alkyl, C2-5 alkenyl, C2-5 alkynyl, -(C0-3 alkylene)-OH, -(C0-3 alkylene)-O(C1-5 alkyl), -(C0-3 alkylene)-O(C1-5 alkylene)-OH, -(C0-3 alkylene)-O(C1-5 alkylene)-O(C1-5 alkyl), -(C0-3 alkylene)-SH, -(C0-3 alkylene)-S(C1-5 alkyl), -(C0-3 alkylene)-S(C1-5 alkylene)-SH, -(C0-3 alkylene)-S(C1-5 alkylene)-S(C1-5 alkyl), -(C0-3 alkylene)-NH2, -(C0-3 alkylene)-NH(C1-5 alkyl), -(C0-3 alkylene)-N(C1-5 alkyl)(C1-5 alkyl), -(C0-3 alkylene)-NH-OH, -(C0-3 alkylene)-N(C1-5 alkyl)-OH, -(C0-3 alkylene)-NH-O(C1-5 alkyl), -(C0-3 alkylene)-N(C1-5 alkyl)-O(C1-5 alkyl), -(C0-3 alkylene)-halogen, -(C0-3 alkylene)-(C1-5 haloalkyl), -(C0-3 alkylene)-O-(C1-5 haloalkyl), -(C0-3 alkylene)-CN, -(C0-3 alkylene)-NO2, -(C0-3 alkylene)-CHO, -(C0-3 alkylene)-CO-(C1-5 alkyl), -(C0-3 alkylene)-COOH, -(C0-3 alkylene)-CO-O-(C1-5 alkyl), -(C0-3 alkylene)-O-CO-(C1-5 alkyl), -(C0-3 alkylene)-CO-NH2, -(C0-3 alkylene)-CO-NH(C1-5 alkyl), -(C0-3 alkylene)-CO-N(C1-5 alkyl)(C1-5 alkyl), -(C0-3 alkylene)-NH-CO-(C1-5 alkyl), -(C0-3 alkylene)-N(C1-5 alkyl)-CO-(C1-5 alkyl), -(C0-3 alkylene)-NH-CO-O-(C1-5 alkyl), -(C0-3 alkylene)-N(C1-5 alkyl)-CO-O-(C1-5 alkyl), -(C0-3 alkylene)-O-CO-NH-(C1-5 alkyl), -(C0-3 alkylene)-O-CO-N(C1-5 alkyl)-(C1-5 alkyl), -(C0-3 alkylene)-SO2-NH2, -(C0-3 alkylene)-SO2-NH(C1-5 alkyl), -(C0-3 alkylene)-SO2-N(C1-5 alkyl)(C1-5 alkyl), -(C0-3 alkylene)-NH-SO2-(C1-5 alkyl), -(C0-3 alkylene)-N(C1-5 alkyl)-SO2-(C1-5 alkyl), -(C0-3 alkylene)-SO2-(C1-5 alkyl), -(C0-3 alkylene)-SO-(C1-5 alkyl), -(C0-3 alkylene)-Si(C1-5 alkyl)(C1-5 alkyl)(C1-5 alkyl), -(C0-3 alkylene)-SF5, -O-(C0-3 alkylene)-carbocyclyl, -O-(C0-3 alkylene)-heterocyclyl, -(C0-3 alkylene)-carbocyclyl, and -(C0-3 alkylene)-heterocyclyl, wherein the carbocyclyl moiety in said -O-(C0-3 alkylene)-carbocyclyl, the carbocyclyl moiety in said -(C0-3 alkylene)-carbocyclyl, the heterocyclyl moiety in said -O-(C0-3 alkylene)-heterocyclyl and the heterocyclyl moiety in said -(C0-3 alkylene)-heterocyclyl are each optionally substituted with one or more groups independently selected from C1-4 alkyl, halogen, -CN, -NO2, -OH, -O- (C1-4 alkyl), -SH, -S-(C1-4 alkyl), -NH2, -NH(C1-4 alkyl), -N(C1-4 alkyl)(C1-4 alkyl), -COOH, -COO(C1-4 alkyl), -CONH2, -CONH(C1-4 alkyl), -CON(C1-4 alkyl)(C1-4 alkyl), -NHCO(C1-4 alkyl) and -N(C1-4 alkyl)-CO(C1-4 alkyl). Preferably, each R1is independently selected from C1-5alkyl, C2-5alkenyl, C2-5alkynyl, -(C0-3alkylene)-OH, -(C0-3 alkylene)-O(C1-5 alkyl), -(C0-3 alkylene)-O(C1-5 alkylene)-OH, -(C0-3 alkylene)-O(C1-5 alkylene)-O(C1-5 alkyl), -(C0-3 alkylene)-SH, -(C0-3 alkylene)-S(C1-5 alkyl), -(C0-3 alkylene)-S(C1-5 alkylene)-SH, -(C0-3 alkylene)-S(C1-5 alkylene)-S(C1-5 alkyl), -(C0-3 alkylene)-NH2, -(C0-3 alkylene)-NH(C1-5 alkyl), -(C0-3 alkylene)-N(C1-5 alkyl)(C1-5 alkyl), -(C0-3 alkylene)-NH-OH, -(C0-3 alkylene)-N(C1-5 alkyl)-OH, -(C0-3 alkylene)-NH-O(C1-5 alkyl), -(C0-3 alkylene)-N(C1-5 alkyl)-O(C1-5 alkyl), -(C0-3 alkylene)-halogen, -(C0-3 alkylene)-(C1-5 haloalkyl), -(C0-3 alkylene)-O-(C1-5 haloalkyl), -(C0-3 alkylene)-CN, -(C0-3 alkylene)-NO2, -(C0-3 alkylene)-CHO, -(C0-3 alkylene)-CO-(C1-5 alkyl), -(C0-3 alkylene)-COOH, -(C0-3 alkylene)-CO-O-(C1-5 alkyl), -(C0-3 alkylene)-O-CO-(C1-5 alkyl), -(C0-3 alkylene)-CO-NH2, -(C0-3alkylene)-CO-NH(C1-5alkyl), -(C0-3alkylene)-CO-N(C1-5alkyl)(C1-5alkyl), -(C0-3alkylene)-NH-CO-(C1-5 alkyl), -(C0-3 alkylene)-N(C1-5 alkyl)-CO-(C1-5 alkyl), -(C0-3 alkylene)-NH-CO-O-(C1-5 alkyl), -(C0-3 alkylene)-N(C1-5 alkyl)-CO-O-(C1-5 alkyl), -(C0-3 alkylene)-O-CO-NH-(C1-5 alkyl), -(C0-3 alkylene)-O-CO-N(C1-5 alkyl)-(C1-5 alkyl), -(C0-3 alkylene)-SO2-NH2, -(C0-3 alkylene)-SO2-NH(C1-5 alkyl), -(C0-3 alkylene)-SO2-N(C1-5 alkyl)(C1-5 alkyl), -(C0-3 alkylene)-NH-SO2-(C1-5 alkyl), -(C0-3 alkylene)-N(C1-5 alkyl)-SO2-(C1-5 alkyl), -(C0-3 alkylene)-SO2-(C1-5 alkyl), and -(C0-3 alkylene)-SO-(C1-5 alkyl). More preferably, each R1is independently selected from C1-5 alkyl, C2-5 alkenyl, C2-5 alkynyl, -(C0-3 alkylene)-OH, -(C0-3 alkylene)-O(C1-5 alkyl), -(C0-3 alkylene)-SH, -(C0-3 alkylene)-NH2, -(C0-3 alkylene)-NH(C1-5 alkyl), -(C0-3 alkylene)-N(C1-5 alkyl)(C1-5 alkyl), -(C0-3 alkylene)-N(C1-5 alkyl)-OH, -(C0-3 alkylene)-NH-O(C1-5 alkyl), -(C0-3 alkylene)-N(C1-5 alkyl)-O(C1-5 alkyl), -(C0-3 alkylene)-halogen, and -(C0-3 alkylene)-(C1-5 haloalkyl). Even more preferably, each R1is independently selected from C1-5 alkyl, C2-5 alkenyl, C2-5 alkynyl, -OH, -O(C1-5 alkyl), -NH2, -NH(C1-5 alkyl), -N(C1-5 alkyl)(C1-5 alkyl), halogen and -(C1-5 haloalkyl),. Even more preferably, each R1is independently selected from -OH and halogen. Particularly suitable A are selected from: , , In formula (I), B is selected from bicyclic arylene and bicyclic heteroarylene, wherein said arylene and said hereroarylene are each optionally substituted with one or more R2. It is to be understood that any H atom connected directly to the ring system can be subject to optional substitution, as defined herein. Preferably, B is bicyclic heteroarylene, optionally substituted with one or more R2. More preferably, B is according to formula: , even more preferably according to formula: , and is optionally substituted with one or more R2. As it is apparent to the skilled person, B is a bivalent moiety and accordingly, as understood herein, preferably the left side of B (in other words, the left empty valence of B) as shown in the specific structural formulas herein, is connected to A, and the right side of B (i.e., the right empty valence of B) is connected to X. In B, Z1 Z2 is selected from -NH-CO-, -NR-CO-, -CO-NH-, -CO-NR-, -CH=N-, -CR=N-,-CH=NO-, -CR=NO-, -N=N-, -CR=CR-, -CH=CH-, -N=CH-, and -N=CR-, wherein R (or each R independently, as applicable) is selected from -H, C1-5 alkyl, C2-5 alkenyl, C2-5 alkynyl, -O(C1-5 alkyl), - S(C1-5 alkyl), -O-aryl, -S-aryl, -O-heteroaryl, -S-heteroaryl, -OH, -CN, -NH2, -NH(C1-5 alkyl), -N(C1-5 alkyl)(C1-5 alkyl) and Hal, preferably selected from -H, C1-5 alkyl, C2-5 alkenyl, C2-5 alkynyl, -O(C1-5 alkyl), - S(C1-5 alkyl), -CN, -NH2, -NH(C1-5 alkyl), -N(C1-5 alkyl)(C1-5 alkyl) and Hal, more preferably selected from C1-5 alkyl, C2-5 alkenyl, C2-5 alkynyl, -O(C1-5 alkyl), -S(C1-5 alkyl), -CN, -NH2, -NH(C1-5 alkyl) , -N(C1-5 alkyl)(C1-5 alkyl) and Hal, wherein said alkyl, said alkenyl and said alkynyl are each optionally substituted by one or more Hal (such as -F). Particularly preferred R is C1-5alkyl or -O(C1-5alkyl), wherein said C1-5alkyl is preferably methyl or ethyl, more preferably methyl. Preferably, Z1 Z2 is selected from -NH-CO-, -CH=N-, -CR=N-, -CH=NO-, -N=CH-, and -N=CR-, wherein R is selected from C1-5 alkyl, C2-5 alkenyl, C2-5 alkynyl, -O(C1-5 alkyl), -S(C1-5 alkyl), -CN, NH2, -NH(C1-5 alkyl) , -N(C1-5 alkyl)(C1-5 alkyl)and Hal. Particularly preferred R is C1-5 alkyl or -O(C1-5 alkyl), wherein said C1-5 alkyl is preferably methyl or ethyl, more preferably methyl. More preferably, is selected from -NH-CO-, -CH=N-, -CH=NO- (to be understoodas -CH=N+(O-)-), and -N=CH-. Even more preferably, Z1 Z2 is selected from -NH-CO-, and -CH=NO- (to be understoodas -CH=N+(O-)-). Alternatively, Z1 Z2 is selected from -CH=N- and -N=CH-. In one specific embodiment,Z1 Z2 is -CH=N-. In an alternative embodiment, Z1 Z2 is -N=CH-.As it is to be understood herein, the left side of each of the formulae shown as Z1 Z2both corresponds to the left side of said Z1 Z2 , and the right side of each of the formulas shownas Z1 Z2 corresponds to the right side of Z1 Z2 .In B, Z3is selected from -N=CH-, -CH=N-, -SO2-, -SO-, -CR=CR-, -CH=CH-, -N=CR-, -CR=N-, - N+(O-)=CR-, -CR=N+(O-)-, -N=N-, -CO-NH-, -NH-CO-, -CO-NR-, -NR-CO-, -NH-, -N(C1-5 alkyl)- (such as - N(CH3)-), -N+O--, -O- and -S-, preferably Z3is -N=CH-, -CH=N-, -SO2-, -SO-, -CR=CR-, -CH=CH-, -N=CR- , -CR=N-, -N=N-, -CO-NH-, -NH-CO-, -CO-NR-, -NR-CO-, -NH-, -N(C1-5 alkyl)- (such as -N(CH3)-), -O- and -S-,wherein R (or each R independently, as applicable) is selected from -H, C1-5 alkyl, C2-5 alkenyl, C2-5 alkynyl, -O(C1-5 alkyl), -S(C1-5 alkyl), -CN, -NH2, -NH(C1-5 alkyl) and Hal, preferably selected from C1-5 alkyl, C2-5 alkenyl, C2-5 alkynyl, -O(C1-5 alkyl), -S(C1-5 alkyl), -CN, -NH2, -NH(C1-5 alkyl) , -N(C1-5 alkyl)(C1-5 alkyl) and Hal, wherein said alkyl, said alkenyl and said alkynyl are each optionally substituted by one or more Hal (such as -F). Particularly preferred R is C1-5 alkyl or -O(C1-5 alkyl), wherein said C1-5 alkyl is preferably methyl or ethyl, more preferably methyl. Preferably, Z3 is selected from -CH=CH-, -NH-, -N(C1-5 alkyl)- (such as -N(CH3)-), -O- and -S-. More preferably, Z3 is selected from -NH-, -N(C1-5 alkyl)- (such as -N(CH3)-), -O- and -S-. Even more preferably, Z3 is selected from -NH-, and -N(C1-5 alkyl)-. Again more preferably, Z3 is -NH-. Alternatively, Z3 is selected from -O- and -S-. Accordingly, Z3 may be -O-. In one embodiment, however, Z3 may be -S-. In one particularly preferred embodiment, Z3 may be -CH=CH-. In B, Z4 is CR, CH or N. R is selected from C1-5 alkyl, C2-5 alkenyl, C2-5 alkynyl, -OH, -O(C1-5 alkyl), -S(C1-5 alkyl), -CN, -NH2, -NH(C1-5 alkyl), -N(C1-5 alkyl)(C1-5 alkyl) and Hal, wherein said alkyl, said alkenyl and said alkynyl are each optionally substituted by one or more Hal (such as -F). Preferably, R is selected from C1-5 alkyl, C2-5 alkenyl, C2-5 alkynyl, -O(C1-5 alkyl), -S(C1-5 alkyl), -CN, -NH2, -NH(C1-5 alkyl), -N(C1-5 alkyl)(C1-5 alkyl) and Hal, wherein said alkyl, said alkenyl and said alkynyl are each optionally substituted by one or more Hal (such as -F). Particularly preferred R is C1-5 alkyl or -O(C1-5 alkyl), wherein said C1-5 alkyl is preferably methyl or ethyl, more preferably methyl. Preferably, Z4is CH or N. More preferably, Z4is CH. Alternatively, Z4 may be N. In B, Z8 is CR, CH or N. R is selected from C1-5 alkyl, C2-5 alkenyl, C2-5 alkynyl, -OH, -O(C1-5 alkyl), -S(C1-5 alkyl), -CN, -NH2, -NH(C1-5 alkyl), -N(C1-5 alkyl)(C1-5 alkyl) and Hal, wherein said alkyl, said alkenyl and said alkynyl are each optionally substituted by one or more Hal (such as -F). Preferably, R is selected from C1-5 alkyl, C2-5 alkenyl, C2-5 alkynyl, -O(C1-5 alkyl), -S(C1-5 alkyl), -CN, -NH2, -NH(C1-5 alkyl), -N(C1-5 alkyl)(C1-5 alkyl) and Hal, wherein said alkyl, said alkenyl and said alkynyl are each optionally substituted by one or more Hal (such as -F). Particularly preferred R is C1-5 alkyl or -O(C1-5 alkyl), wherein said C1-5 alkyl is preferably methyl or ethyl, more preferably methyl. Preferably, Z8 is CH or N. More preferably, Z8 is CH. However, alternatively, Z8is N. More preferably, B is selected from: 5 , which are each optionally substituted with one or more R2. As it is apparent to the skilled person, B is a bivalent moiety and accordingly, as understood herein, preferably the left empty valence of B as shown in the specific structural formulas herein is connected to A, and the right empty valence of B as shown herein is connected to X. Preferably, B is selected from: optionally substituted with one or more R2. As it is apparent to the skilled person, B is a bivalent moiety and accordingly, as understood herein, preferably the left empty valence of B as shown in the specific structural formulas herein is connected to A, and the right empty valence of B as shown herein is connected to X. More preferably, B is selected from: , which are each optionally substituted with one or more R2. As it is apparent tothe skilled person, B is a bivalent moiety and accordingly, as understood herein, preferably the left empty valence of B as shown in the specific structural formulas herein is connected to A, and the right empty valence of B as shown herein is connected to X. Alternatively, in a particularly preferred embodiment, B is bicyclic heteroarylene comprising two fused six-membered rings, optionally substituted with one or more R2. Thus, in one particularly preferred embodiment, B may which are each optionally substituted with one or more R2. As it is apparent to the skilled person, B is a bivalent moiety and accordingly, as understood herein, preferably the left empty valence of B as shown in the specific structural formulas herein is connected to A, and the right empty valence of B as shown herein is connected to X. In a further particularly preferred embodiment, B may , which are each optionally substituted with one or more R2. Alternatively, B may be selected from which are each optionally substituted with one or more R2. Preferably, preferably B is As it is apparent to the skilled person, B is a bivalent moiety and accordingly, as understood herein, preferably the left empty valence of B as shown in the specific structural formulas herein is connected to A, and the right empty valence of B as shown herein is connected to X. Alternatively, B may be according to formula: preferably according to formula: , optionally substituted with one or more R2. As it is apparent to the skilled person, B is a bivalent moiety and accordingly, as understood herein, preferably the left side of B (in other words, the left empty valence of B) as shown in the specific structural formulas herein, is connected to A, and the right side of B (i.e., the right empty valence of B) is connected to X. Therein, is as defined herein, including any preferred definitions and any specificembodiments. In B, Z5 is CR, CH or N. R is selected from C1-5 alkyl, C2-5 alkenyl, C2-5 alkynyl, -O(C1-5 alkyl), - S(C1-5 alkyl), -CN, -NH2, -NH(C1-5 alkyl), -NH(C1-5 alkyl)(C1-5 alkyl) and Hal, wherein said alkyl, said alkenyl and said alkynyl are each optionally substituted by one or more Hal (such as -F). Particularly preferred R is C1-5 alkyl or -O(C1-5 alkyl), wherein said C1-5 alkyl is preferably methyl or ethyl, more preferably methyl. Preferably, Z5 is CH or N. More preferably, Z5 is CH. Alternatively, Z5 may be N. In B, Z6 is selected from -NH-, -N(C1-5 alkyl)- (such as -N(CH3)-), -O- and -S-. Preferably, Z6 is selected from -O- and -S-. More preferably, Z6 is -O-. In B, Z8 is CR, CH or N. R is selected from C1-5 alkyl, C2-5 alkenyl, C2-5 alkynyl, -OH, -O(C1-5 alkyl), -S(C1-5 alkyl), -CN, -NH2, -NH(C1-5 alkyl), -N(C1-5 alkyl)(C1-5 alkyl) and Hal, wherein said alkyl, said alkenyl and said alkynyl are each optionally substituted by one or more Hal (such as -F). Preferably, R is selected from C1-5 alkyl, C2-5 alkenyl, C2-5 alkynyl, -O(C1-5 alkyl), -S(C1-5 alkyl), -CN, -NH2, -NH(C1-5 alkyl), -N(C1-5 alkyl)(C1-5 alkyl) and Hal, wherein said alkyl, said alkenyl and said alkynyl are each optionally substituted by one or more Hal (such as -F). Particularly preferred R is C1-5 alkyl or -O(C1-5 alkyl), wherein said C1-5 alkyl is preferably methyl or ethyl, more preferably methyl. Preferably, Z8 is CH or N. More preferably, Z8 is CH. However, alternatively, Z8 is N.One example of B as described herein . Alternatively, B is: optionally substituted with one or more R2.As it is apparent to the skilled person, B is a bivalent moiety and accordingly, as understood herein, preferably the left side of B (in other words, the left empty valence of B) as shown in the specific structural formulas herein, is connected to A, and the right side of B (i.e., the right empty valence of B) is connected to X. In B, each Z5 is independently CR, CH or N. R (or each R independently) is selected from -H, C1-5 alkyl, C2-5alkenyl, C2-5alkynyl, -O(C1-5alkyl), -S(C1-5alkyl), -O-aryl, -S-aryl, -O-heteroaryl, -S-heteroaryl, -CN, -NH2, -NH(C1-5 alkyl), -NH(C1-5 alkyl)(C1-5 alkyl) and Hal, preferably selected from -H, C1-5 alkyl, C2-5 alkenyl, C2-5 alkynyl, -O(C1-5 alkyl), -S(C1-5 alkyl), -CN, -NH2, -NH(C1-5 alkyl), -NH(C1-5 alkyl)(C1-5 alkyl) and Hal, more preferably selected from C1-5 alkyl, C2-5 alkenyl, C2-5 alkynyl, -O(C1-5 alkyl), -S(C1-5 alkyl), -CN, -NH2, -NH(C1-5 alkyl), -NH(C1-5 alkyl)(C1-5 alkyl) and Hal, wherein said alkyl, said alkenyl and said alkynyl are each optionally substituted by one or more Hal (such as -F). Particularly preferred R is C1-5 alkyl or - O(C1-5 alkyl), wherein said C1-5 alkyl is preferably methyl or ethyl, more preferably methyl. Preferably, Z5 is CH or N. More preferably, Z5 is CH. Alternatively, Z5 may be N. It is to be understood that there are two Z5 groups in the formula. Preferably, Z5 closer to the left side of the bivalent formula is N, and Z5 closer to the right side of the bivalent formula shown above is CH. In B, Z6 is selected from -NH-, -N(C1-5 alkyl)- (such as -N(CH3)-), -O- and -S-. Preferably, Z6 is selected from -O- and -S-. More preferably, Z6 is -O-. In B, Z7 is selected from -HC=CH-, -N=CH-, -CH=N-, -SO2-, -SO-, -CR=CR-, -N=CR-, -CR=N-, - CO-NH-, -NH-CO-, -CO-NR- and -NR-CO-, -NH-, -N(C1-5 alkyl)- (such as -N(CH3)-), -O- and -S-. Z7 is preferably selected from -HC=CH-, -NH-, -N(C1-5 alkyl)- (such as -N(CH3)-), -O- and -S-. More preferably, Z7 is selected from -HC=CH-, -O- and -S-. Even more preferably, Z7 is -O-. Exemplary B as described herein are: . Alternatively, B is selected from: which are each optionally substituted with one or more R2,preferably B is optionally substituted with one or more R2. As it is apparent to the skilled person, B is a bivalent moiety and accordingly, as understood herein, preferably the left side of B (in other words, the left empty valence of B) as shown in the specific structural formulas herein, is connected to A, and the right side of B (i.e., the right empty valence of B) is connected to X. In B, Z5 is CR, CH or N. R is selected from C1-5 alkyl, C2-5 alkenyl, C2-5 alkynyl, -O(C1-5 alkyl), - S(C1-5 alkyl), -CN, -NH2, -NH(C1-5 alkyl), -NH(C1-5 alkyl)(C1-5 alkyl) and Hal, wherein said alkyl, said alkenyl and said alkynyl are each optionally substituted by one or more Hal (such as -F). Particularly preferred R is C1-5 alkyl or -O(C1-5 alkyl), wherein said C1-5 alkyl is preferably methyl or ethyl, more preferably methyl. Preferably, Z5 is CH or N. More preferably, Z5 is CH. Alternatively, Z5 is N. In formula (I), each R2is independently selected from C1-5 alkyl, C2-5 alkenyl, C2-5 alkynyl, -(C0-3 alkylene)-OH, -(C0-3 alkylene)-O(C1-5 alkyl), -(C0-3 alkylene)-O(C1-5 alkylene)-OH, -(C0-3 alkylene)-O(C1-5 alkylene)-O(C1-5 alkyl), -(C0-3 alkylene)-SH, -(C0-3 alkylene)-S(C1-5 alkyl), -(C0-3 alkylene)-S(C1-5 alkylene)-SH, -(C0-3 alkylene)-S(C1-5 alkylene)-S(C1-5 alkyl), -(C0-3 alkylene)-NH2, -(C0-3 alkylene)-NH(C1-5 alkyl), -(C0-3 alkylene)-N(C1-5 alkyl)(C1-5 alkyl), -(C0-3 alkylene)-NH-OH, -(C0-3 alkylene)-N(C1-5 alkyl)-OH, -(C0-3 alkylene)-NH-O(C1-5 alkyl), -(C0-3 alkylene)-N(C1-5 alkyl)-O(C1-5 alkyl), -(C0-3 alkylene)-halogen, -(C0-3 alkylene)-(C1-5 haloalkyl), -(C0-3 alkylene)-O-(C1-5 haloalkyl), -(C0-3 alkylene)-CN, -(C0-3 alkylene)-NO2, -(C0-3 alkylene)-CHO, -(C0-3 alkylene)-CO-(C1-5 alkyl), -(C0-3 alkylene)-COOH, -(C0-3 alkylene)-CO-O-(C1-5 alkyl), -(C0-3 alkylene)-O-CO-(C1-5 alkyl), -(C0-3 alkylene)-CO-NH2, -(C0-3 alkylene)-CO-NH(C1-5 alkyl), -(C0-3 alkylene)-CO-N(C1-5 alkyl)(C1-5 alkyl), -(C0-3 alkylene)-NH-CO-(C1-5 alkyl), -(C0-3 alkylene)-N(C1-5 alkyl)-CO-(C1-5 alkyl), -(C0-3 alkylene)-NH-CO-O-(C1-5 alkyl), -(C0-3 alkylene)-N(C1-5 alkyl)-CO-O-(C1-5 alkyl), -(C0-3 alkylene)-O-CO-NH-(C1-5 alkyl), -(C0-3 alkylene)-O-CO-N(C1-5 alkyl)-(C1-5 alkyl), -(C0-3 alkylene)-SO2-NH2, -(C0-3 alkylene)-SO2-NH(C1-5 alkyl), -(C0-3 alkylene)-SO2-N(C1-5 alkyl)(C1-5 alkyl), -(C0-3 alkylene)-NH-SO2-(C1-5 alkyl), -(C0-3 alkylene)-N(C1-5 alkyl)-SO2-(C1-5 alkyl), -(C0-3 alkylene)-SO2-(C1-5 alkyl), -(C0-3 alkylene)-SO-(C1-5 alkyl), -(C0-3 alkylene)-Si(C1-5 alkyl)(C1-5 alkyl)(C1-5 alkyl), -(C0-3 alkylene)-SF5, -O-(C0-3 alkylene)-carbocyclyl, -O-(C0-3 alkylene)-heterocyclyl -(C0-3 alkylene)-carbocyclyl, and -(C0-3 alkylene)-heterocyclyl, wherein the carbocyclyl moiety in said -O-(C0-3 alkylene)-carbocyclyl, the carbocyclyl moiety in said -(C0-3 alkylene)-carbocyclyl, the heterocyclyl moiety in said -O-(C0-3 alkylene)-heterocyclyl and the heterocyclyl moiety in said -(C0-3 alkylene)-heterocyclyl are each optionally substituted with one or more groups independently selected from C1-4 alkyl, halogen, -CN, -NO2, -OH, -O- (C1-4 alkyl), -SH, -S-(C1-4 alkyl), -NH2, -NH(C1-4 alkyl), -N(C1-4 alkyl)(C1-4 alkyl), -COOH, -COO(C1-4 alkyl), -CONH2, -CONH(C1-4alkyl), -CON(C1-4alkyl)(C1-4alkyl), -NHCO(C1-4alkyl) and -N(C1-4alkyl)-CO(C1-4alkyl). Preferably, each R2is independently selected from C1-5 alkyl, C2-5 alkenyl, C2-5 alkynyl, -(C0-3 alkylene)-OH, -(C0-3 alkylene)-O(C1-5 alkyl), -(C0-3 alkylene)-O(C1-5 alkylene)-OH, -(C0-3 alkylene)-O(C1-5 alkylene)-O(C1-5 alkyl), -(C0-3 alkylene)-SH, -(C0-3 alkylene)-S(C1-5 alkyl), -(C0-3 alkylene)-S(C1-5 alkylene)-SH, -(C0-3 alkylene)-S(C1-5 alkylene)-S(C1-5 alkyl), -(C0-3 alkylene)-NH2, -(C0-3 alkylene)-NH(C1-5 alkyl), -(C0-3 alkylene)-N(C1-5 alkyl)(C1-5 alkyl), -(C0-3 alkylene)-NH-OH, -(C0-3 alkylene)-N(C1-5 alkyl)-OH, -(C0-3 alkylene)-NH-O(C1-5 alkyl), -(C0-3 alkylene)-N(C1-5 alkyl)-O(C1-5 alkyl), -(C0-3 alkylene)-halogen, -(C0-3 alkylene)-(C1-5 haloalkyl), -(C0-3 alkylene)-O-(C1-5 haloalkyl), -(C0-3 alkylene)-CN, -(C0-3alkylene)-NO2, -(C0-3alkylene)-CHO, -(C0-3alkylene)-CO-(C1-5alkyl), -(C0-3alkylene)-COOH, -(C0-3 alkylene)-CO-O-(C1-5 alkyl), -(C0-3 alkylene)-O-CO-(C1-5 alkyl), -(C0-3 alkylene)-CO-NH2, -(C0-3 alkylene)-CO-NH(C1-5 alkyl), -(C0-3 alkylene)-CO-N(C1-5 alkyl)(C1-5 alkyl), -(C0-3 alkylene)-NH-CO-(C1-5 alkyl), -(C0-3 alkylene)-N(C1-5 alkyl)-CO-(C1-5 alkyl), -(C0-3 alkylene)-NH-CO-O-(C1-5 alkyl), -(C0-3 alkylene)-N(C1-5 alkyl)-CO-O-(C1-5 alkyl), -(C0-3 alkylene)-O-CO-NH-(C1-5 alkyl), -(C0-3 alkylene)-O-CO-N(C1-5 alkyl)-(C1-5 alkyl), -(C0-3 alkylene)-SO2-NH2, -(C0-3 alkylene)-SO2-NH(C1-5 alkyl), -(C0-3 alkylene)-SO2-N(C1-5 alkyl)(C1-5 alkyl), -(C0-3 alkylene)-NH-SO2-(C1-5 alkyl), -(C0-3 alkylene)-N(C1-5 alkyl)-SO2-(C1-5 alkyl), -(C0-3 alkylene)-SO2-(C1-5 alkyl), and -(C0-3 alkylene)-SO-(C1-5 alkyl). More preferably, each R2is independently selected from C1-5 alkyl, C2-5 alkenyl, C2-5 alkynyl, -(C0-3 alkylene)-OH, -(C0-3 alkylene)-O(C1-5 alkyl), -(C0-3 alkylene)-SH, -(C0-3 alkylene)-NH2, -(C0-3 alkylene)-NH(C1-5 alkyl), -(C0-3 alkylene)-N(C1-5 alkyl)(C1-5 alkyl), -(C0-3 alkylene)-NH-OH, -(C0-3 alkylene)-N(C1-5 alkyl)-OH, -(C0-3 alkylene)-NH-O(C1-5 alkyl), -(C0-3 alkylene)-N(C1-5 alkyl)-O(C1-5 alkyl), and -(C0-3 alkylene)-halogen. Even more preferably, each R2is independently selected from C1-5 alkyl, C2-5 alkenyl, C2-5 alkynyl, -OH, -O(C1-5 alkyl), -SH, -NH2, -NH(C1-5 alkyl), -N(C1-5 alkyl)(C1-5 alkyl), -NH-OH, -N(C1-5 alkyl)-OH, -NH-O(C1-5 alkyl), -N(C1-5 alkyl)-O(C1-5 alkyl), and halogen. In formula (I), X is selected from -NH-, and -NRN-, wherein RNis selected from C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, -(C0-8 alkylene)-(C1-2 haloalkyl), -(C0-8 alkylene)-heteroaryl, -(C0-8 alkylene)-aryl, -(C0- 8 alkylene)-heterocycloalkyl, -(C0-8 alkylene)-heterocycloalkenyl, -(C0-8 alkylene)-cycloalkyl and -(C0-8 alkylene)-cycloalkenyl, wherein said alkyl, said alkenyl, said alkynyl and said alkylene are each optionally substituted with one or more optional substituents selected from -OH, -O(C1-5 alkyl), -SH, -NH2, -NH(C1-5 alkyl), -N(C1-5 alkyl)(C1-5 alkyl) and halogen, preferably selected from -OH, -O(C1-5 alkyl), -SH, -NH2, -NH(C1-5 alkyl), and halogen, and wherein one or two -CH2– groups in said alkyl, said alkenyl, said alkynyl and said alkylene may independently of each other be replaced with a group selected from -O-, -S-, -NH-, -N(C1-5alkyl)-, -CO-, -CO-NH-, -CO-N(C1-5alkyl)-, -NH-CO-, -N(C1-5alkyl)-CO-, C3-6cycloalkylene and 4-6 membered heterocycloalkylene, wherein said heteroaryl, said aryl, said heterocycloalkyl, said heterocycloalkenyl, said cycloalkyl and said cycloalkenyl are each optionally substituted with one or more groups selected from R3. Suitable cycloalkylene are e.g., 1,2-cyclopropylene or 1,2-cyclobutylene. Exemplary suitable heterocycloalkylene is e.g. 2,3-oxetanylene. It is further preferred that said -(C0-8 alkylene)- optionally substituted with one or more optional substituents selected from -OH, -O(C1-5 alkyl), -SH, -NH2, -NH(C1-5 alkyl), -N(C1-5 alkyl)(C1-5 alkyl), and halogen, wherein one or two -CH2– groups are independently of each other replaced with a group selected from -O-, -S-, -NH- , -N(C1-5 alkyl)-, -CO-, -CO-N(C1-5 alkyl)-, -N(C1-5 alkyl)-CO-, C3-6 cycloalkylene and 4-6 membered heterocycloalkylene, is preferably -(C0-8alkylene)-, more preferably –(C0-4alkylene)-. In -NRN-, preferably RNis selected from C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, -(C0-8 alkylene)-(C1-2 haloalkyl), -(C0-8 alkylene)-heteroaryl, -(C0-8 alkylene)-aryl, and -(C0-8 alkylene)-cycloalkyl, wherein said alkyl, said alkenyl, said alkynyl and said alkylene are each optionally substituted with one or more optional substituents selected from -OH, -O(C1-5 alkyl), -SH, -NH2, -NH(C1-5 alkyl), -N(C1-5 alkyl)(C1-5 alkyl), and halogen, and wherein one or two -CH2– groups in said alkyl, said alkenyl, said alkynyl and said alkylene are independently of each other replaced with a group selected from -O-, -S-, -NH-, -N(C1-5 alkyl)-, -CO-, -CO-NH-, -CO-N(C1-5 alkyl)-, -NH-CO-, -N(C1-5 alkyl)-CO-, C3-6 cycloalkylene and 4-6 membered heterocycloalkylene, wherein said heteroaryl, said aryl and said cycloalkyl are each optionally substituted with one or more groups selected from R3. More preferably, RNis selected from C1-8 alkyl, -(C0-8 alkylene)-(C1-2 haloalkyl), -(C0-8 alkylene)- heteroaryl, -(C0-8 alkylene)-aryl, and -(C0-8 alkylene)-cycloalkyl, wherein said alkyl, and said alkylene are each optionally substituted with one or more optional substituents selected from -OH, -O(C1-5 alkyl), -SH, -NH2, -NH(C1-5 alkyl), -N(C1-5 alkyl)(C1-5 alkyl), and halogen, and wherein one or two -CH2– groups in said alkyl, and said alkylene are independently of each other replaced with a group selected from -O-, -S-, -NH-, -N(C1-5 alkyl)-, -CO-, -CO-N(C1-5 alkyl)-, -CO-NH-, -N(C1-5 alkyl)-CO-, -NH-CO-, C3-6 cycloalkylene and 4-6 membered heterocycloalkylene, wherein said alkylene is optionally substituted with one or more optional substituents selected from -OH, -O(C1-5 alkyl), -SH, -NH2, -NH(C1-5 alkyl), -N(C1-5 alkyl)(C1-5 alkyl), and halogen, and wherein one or two -CH2– groups in said alkylene are independently of each other replaced with a group selected from -O-, -S-, -NH-, -N(C1-5 alkyl)-, -CO-, -CO-NH-, - CO-N(C1-5 alkyl)-, -NH-CO-, -N(C1-5 alkyl)-CO-, C3-6 cycloalkylene and 4-6 membered heterocycloalkylene, wherein said heteroaryl, said aryl and said cycloalkyl are each optionally substituted with one or more groups selected from R3. More preferably, RNis selected from -(C0-8 alkylene)-(C1-2 haloalkyl), -(C0-8 alkylene)-heteroaryl, - (C0-8 alkylene)-aryl, -(C0-8 alkylene)-cycloalkyl, preferably from -(C0-8 alkylene)-heteroaryl, -(C0-8 alkylene)- aryl, -(C0-8alkylene)-cycloalkyl, wherein said alkylene is optionally substituted with one or more optional substituents selected from -OH, -O(C1-5 alkyl), -SH, -NH2, -NH(C1-5 alkyl), -N(C1-5 alkyl)(C1-5 alkyl), and halogen, and wherein one or two -CH2– groups in said alkylene are independently of each other replaced with a group selected from -O-, -S-, -NH-, -N(C1-5 alkyl)-, -CO-, -CO-NH-, -CO-N(C1-5 alkyl)-, -NH-CO-, - N(C1-5 alkyl)-CO-, C3-6 cycloalkylene and 4-6 membered heterocycloalkylene, wherein said heteroaryl, said aryl and said cycloalkyl are each optionally substituted with one or more groups selected from R3. Even more preferably, RNis selected from -(C0-8 alkylene)-(C1-2 haloalkyl), -(C0-8 alkylene)- heteroaryl, and -(C0-8 alkylene)-aryl, wherein said alkylene is optionally substituted with one or more optional substituents selected from -OH, -O(C1-5 alkyl), -SH, -NH2, -NH(C1-5 alkyl), -N(C1-5 alkyl)(C1-5 alkyl), and halogen, and wherein one or two -CH2– groups in said alkylene are independently of each other replaced with a group selected from -O-, -S-, -NH-, -N(C1-5 alkyl)-, -CO-, -CO-NH-, -CO-N(C1-5 alkyl)-, - NH-CO-, -N(C1-5 alkyl)-CO-, C3-6 cycloalkylene and 4-6 membered heterocycloalkylene, wherein said heteroaryl, and said aryl are each optionally substituted with one or more groups selected from R3. Still more preferably, RNis -(C0-8 alkylene)-(C1-2 haloalkyl) or -(C0-4 alkylene)-heteroaryl, wherein said alkylene is optionally substituted with one or more optional substituents selected from -OH, -O(C1-5 alkyl), -SH, -NH2, -NH(C1-5 alkyl), -N(C1-5 alkyl)(C1-5 alkyl), and halogen, and wherein one or two -CH2– groups in said alkylene are independently of each other replaced with a group selected from -O-, -S-, - NH-, -N(C1-5 alkyl)-, -CO-, -CO-NH-, -CO-N(C1-5 alkyl)-, -NH-CO-, -N(C1-5 alkyl)-CO-, C3-6 cycloalkylene and 4-6 membered heterocycloalkylene, wherein said heteroaryl is optionally substituted with one or more groups selected from R3. Particularly suitable -(C0-8 alkylene)- in RNis -(C0-4 alkylene)-, preferably -(C2-3 alkylene)-, in particular selected from -CH2CH2- and -CH2CH2CH2-. Even more preferably, -(C0-4 alkylene)- in RNis -CH2CH2-. In RN, particularly preferred heteroaryl in -(C0-8 alkylene)-heteroaryl, preferably -(C0-4 alkylene)- heteroaryl is pyridyl or pyridone, in particular 2-pyridyl or 3-pyridyl, more preferably 3-pyridyl. Thus, preferably RNis -(C0-4 alkylene)-heteroaryl selected from -(C0-4 alkylene)-pyrid-2-yl (such as -CH2CH2- pyrid-2-yl) and -(C0-4 alkylene)-pyrid-3-yl (such as -CH2CH2-pyrid-3-yl), more preferably -(C0-4 alkylene)- pyrid-3-yl (such as -CH2CH2-pyrid-3-yl), wherein the heteroaryl is optionally substituted with one or more groups selected from R3. In one particularly preferred embodiment, said heteroaryl moiety is not substituted. In -(C0-4 alkylene)-heteroaryl, may also be 4-pyridyl. Preferably, X is -NH-. However, an embodiment wherein X is -NRN-, as defined herein, is also encompassed by the present invention. In formula (I), each R3is independently selected from C1-5 alkyl, C2-5 alkenyl, C2-5 alkynyl, -(C0-3 alkylene)-OH, -(C0-3 alkylene)-O(C1-5 alkyl), -(C0-3 alkylene)-O(C1-5 alkylene)-OH, -(C0-3 alkylene)-O(C1-5 alkylene)-O(C1-5alkyl), -(C0-3alkylene)-SH, -(C0-3alkylene)-S(C1-5alkyl), -(C0-3alkylene)-S(C1-5alkylene)-SH, -(C0-3 alkylene)-S(C1-5 alkylene)-S(C1-5 alkyl), -(C0-3 alkylene)-NH2, -(C0-3 alkylene)-NH(C1-5 alkyl), -(C0-3 alkylene)-N(C1-5 alkyl)(C1-5 alkyl), -(C0-3 alkylene)-NH-OH, -(C0-3 alkylene)-N(C1-5 alkyl)-OH, -(C0-3 alkylene)-NH-O(C1-5 alkyl), -(C0-3 alkylene)-N(C1-5 alkyl)-O(C1-5 alkyl), -(C0-3 alkylene)-halogen, -(C0-3 alkylene)-(C1-5 haloalkyl), -(C0-3 alkylene)-O-(C1-5 haloalkyl), -(C0-3 alkylene)-CN, -(C0-3 alkylene)-NO2, -(C0-3 alkylene)-CHO, -(C0-3 alkylene)-CO-(C1-5 alkyl), -(C0-3 alkylene)-COOH, -(C0-3 alkylene)-CO-O-(C1-5 alkyl), -(C0-3 alkylene)-O-CO-(C1-5 alkyl), -(C0-3 alkylene)-CO-NH2, -(C0-3 alkylene)-CO-NH(C1-5 alkyl), -(C0-3 alkylene)-CO-N(C1-5 alkyl)(C1-5 alkyl), -(C0-3 alkylene)-NH-CO-(C1-5 alkyl), -(C0-3 alkylene)-N(C1-5 alkyl)-CO-(C1-5 alkyl), -(C0-3 alkylene)-NH-CO-O-(C1-5 alkyl), -(C0-3alkylene)-N(C1-5alkyl)-CO-O-(C1-5alkyl), -(C0-3alkylene)-O-CO-NH-(C1-5alkyl), -(C0-3alkylene)-O-CO-N(C1-5 alkyl)-(C1-5 alkyl), -(C0-3 alkylene)-SO2-NH2, -(C0-3 alkylene)-SO2-NH(C1-5 alkyl), -(C0-3 alkylene)-SO2-N(C1-5 alkyl)(C1-5 alkyl), -(C0-3 alkylene)-NH-SO2-(C1-5 alkyl), -(C0-3 alkylene)-N(C1-5 alkyl)-SO2-(C1-5 alkyl), -(C0-3 alkylene)-SO2-(C1-5 alkyl), -(C0-3 alkylene)-SO-(C1-5 alkyl), -(C0-3 alkylene)-Si(C1-5 alkyl)(C1-5 alkyl)(C1-5 alkyl), -(C0-3 alkylene)-SF5, -O-(C0-3 alkylene)-carbocyclyl, -O-(C0-3 alkylene)-heterocyclyl -(C0-3 alkylene)-carbocyclyl, and -(C0-3 alkylene)-heterocyclyl, wherein the carbocyclyl moiety in said -O-(C0-3 alkylene)-carbocyclyl, the carbocyclyl moiety in said -(C0-3 alkylene)-carbocyclyl, the heterocyclyl moiety in said -O-(C0-3 alkylene)-heterocyclyl and the heterocyclyl moiety in said -(C0-3 alkylene)-heterocyclyl are each optionally substituted with one or more groups independently selected from C1-4 alkyl, halogen, -CN, -NO2, -OH, -O- (C1-4 alkyl), -SH, -S-(C1-4 alkyl), -NH2, -NH(C1-4 alkyl), -N(C1-4 alkyl)(C1-4 alkyl), -COOH, -COO(C1-4 alkyl), -CONH2, -CONH(C1-4 alkyl), -CON(C1-4 alkyl)(C1-4 alkyl), -NHCO(C1-4 alkyl) and -N(C1-4 alkyl)-CO(C1-4 alkyl). Preferably, each R3is independently selected from C1-5 alkyl, C2-5 alkenyl, C2-5 alkynyl, -(C0-3 alkylene)-OH, -(C0-3 alkylene)-O(C1-5 alkyl), -(C0-3 alkylene)-O(C1-5 alkylene)-OH, -(C0-3 alkylene)-O(C1-5 alkylene)-O(C1-5 alkyl), -(C0-3 alkylene)-SH, -(C0-3 alkylene)-S(C1-5 alkyl), -(C0-3 alkylene)-S(C1-5 alkylene)-SH, -(C0-3 alkylene)-S(C1-5 alkylene)-S(C1-5 alkyl), -(C0-3 alkylene)-NH2, -(C0-3 alkylene)-NH(C1-5 alkyl), -(C0-3 alkylene)-N(C1-5 alkyl)(C1-5 alkyl), -(C0-3 alkylene)-NH-OH, -(C0-3 alkylene)-N(C1-5 alkyl)-OH, -(C0-3 alkylene)-NH-O(C1-5 alkyl), -(C0-3 alkylene)-N(C1-5 alkyl)-O(C1-5 alkyl), -(C0-3 alkylene)-halogen, -(C0-3 alkylene)-(C1-5 haloalkyl), -(C0-3 alkylene)-O-(C1-5 haloalkyl), -(C0-3 alkylene)-CN, -(C0-3 alkylene)-NO2, -(C0-3 alkylene)-CHO, -(C0-3 alkylene)-CO-(C1-5 alkyl), -(C0-3 alkylene)-COOH, -(C0-3 alkylene)-CO-O-(C1-5 alkyl), -(C0-3 alkylene)-O-CO-(C1-5 alkyl), -(C0-3 alkylene)-CO-NH2, -(C0-3 alkylene)-CO-NH(C1-5 alkyl), -(C0-3 alkylene)-CO-N(C1-5 alkyl)(C1-5 alkyl), -(C0-3 alkylene)-NH-CO-(C1-5 alkyl), -(C0-3 alkylene)-N(C1-5 alkyl)-CO-(C1-5 alkyl), -(C0-3 alkylene)-NH-CO-O-(C1-5 alkyl), -(C0-3 alkylene)-N(C1-5 alkyl)-CO-O-(C1-5 alkyl), -(C0-3 alkylene)-O-CO-NH-(C1-5 alkyl), -(C0-3 alkylene)-O-CO-N(C1-5alkyl)-(C1-5alkyl), -(C0-3alkylene)-SO2-NH2, -(C0-3alkylene)-SO2-NH(C1-5alkyl), -(C0-3 alkylene)-SO2-N(C1-5 alkyl)(C1-5 alkyl), -(C0-3 alkylene)-NH-SO2-(C1-5 alkyl), -(C0-3 alkylene)-N(C1-5 alkyl)-SO2-(C1-5 alkyl), -(C0-3 alkylene)-SO2-(C1-5 alkyl), and -(C0-3 alkylene)-SO-(C1-5 alkyl). More preferably, each R3is independently selected from C1-5 alkyl, C2-5 alkenyl, C2-5 alkynyl, -(C0-3 alkylene)-OH, -(C0-3 alkylene)-O(C1-5 alkyl), -(C0-3 alkylene)-SH, -(C0-3 alkylene)-NH2, -(C0-3 alkylene)-NH(C1-5 alkyl), -(C0-3 alkylene)-N(C1-5 alkyl)(C1-5 alkyl), -(C0-3 alkylene)-NH-OH, -(C0-3 alkylene)-N(C1-5 alkyl)-OH, -(C0-3 alkylene)-NH-O(C1-5 alkyl), -(C0-3 alkylene)-N(C1-5 alkyl)-O(C1-5 alkyl), and -(C0-3 alkylene)-halogen. Even more preferably, each R3is independently selected from C1-5alkyl, C2-5alkenyl, C2-5alkynyl, -OH, -O(C1-5 alkyl), -SH, -NH2, -NH(C1-5 alkyl), -N(C1-5 alkyl)(C1-5 alkyl), -NH-OH, -N(C1-5 alkyl)-OH, -NH-O(C1-5 alkyl), -N(C1-5 alkyl)-O(C1-5 alkyl), and halogen. alkylene)CN, wherein m is 1 or 2, wherein said -CH2- is optionally substituted with C1-4 alkyl, C1-4 haloalkyl, C3-8 cycloalkyl or 5 or 6-membered heterocyclyl, and wherein said alkenyl is optionally substituted with one or more optional substituents selected from C1-4 alkyl, -COOH, -COO(C1-4 alkyl), -CO(C1-4 alkyl), - CONH(C1-4 alkyl), -CON(C1-4 alkyl)(C1-4 alkyl), -SO3H, -SO2(C1-4 alkyl), -SO(=NRNN)-(C1-4 alkyl), -SO2NH2, -SO2NH(C1-4 alkyl), -SO2N(C1-4 alkyl)(C1-4 alkyl), -(C1-4 alkylene)N(C1-4 alkyl)(C1-4 alkyl), -(C1-4 alkylene)(N- heterocycloalkyl), cycloalkyl, -SO2-cycloalkyl, SO(=NRNN)-cycloalkyl, heterocycloalkyl, -SO2- heterocycloalkyl, SO(=NRNN)-heterocycloalkyl, aryl, -SO2-aryl, -SO(=NRNN)-aryl, heteroaryl, -SO2- heteroaryl, -SO(=NRNN)-heteroaryl, -SO(=N-(C1-4 alkyl))-heteroaryl, -Hal, -CN and -CF3, wherein RNNis selected from H, C1-4 alkyl, cycloalkyl and aryl (preferably wherein RNNis selected from H and C1-4 alkyl), preferably substituted with one or more optional substituents selected from C1-4 alkyl, -COO(C1-4 alkyl), - CO(C1-4 alkyl), -CONH(C1-4 alkyl), -CON(C1-4 alkyl)(C1-4 alkyl), -SO2(C1-4 alkyl), -SO2NH2, -SO2NH(C1-4 alkyl), -SO2N(C1-4 alkyl)(C1-4 alkyl), -(C1-4 alkylene)N(C1-4 alkyl)(C1-4 alkyl), -(C1-4 alkylene)(N- heterocycloalkyl), cycloalkyl, heterocycloalkyl, aryl, heteroaryl, -Hal, -CN and -CF3, more preferably substituted with one or more optional substituents selected from C1-4 alkyl, -CONH-(C1-4 alkyl), and -SO2- optionally substituted by one or more C1-6 alkyl (such as methyl) or Hal (such as F). Preferably, m is 1. Preferably, Y is selected , , , , -CH2(C2 alkenyl), and -(C1-2 alkylene)CN, wherein m is 1 or 2, wherein said -CH2- is optionally substituted with C1-4 alkyl, C1-4 haloalkyl, C3-8 cycloalkyl or 5 or 6-membered heterocyclyl, and wherein said alkenyl is optionally substituted with one or more optional substituents selected from C1-4 alkyl, -COOH, -COO(C1-4 alkyl), -CO(C1-4 alkyl), - CONH(C1-4 alkyl), -CON(C1-4 alkyl)(C1-4 alkyl), -SO3H, -SO2(C1-4 alkyl), -SO2NH2, -SO2NH(C1-4 alkyl), - SO2N(C1-4 alkyl)(C1-4 alkyl), -(C1-4 alkylene)N(C1-4 alkyl)(C1-4 alkyl), -(C1-4 alkylene)(N-heterocycloalkyl), cycloalkyl, -SO2-cycloalkyl, heterocycloalkyl, -SO2-heterocycloalkyl, aryl, -SO2-aryl, heteroaryl, -SO2- heteroaryl, -Hal, -CN and -CF3, preferably substituted with one or more optional substituents selected from C1-4 alkyl, -COO(C1-4 alkyl), -CO(C1-4 alkyl), -CONH(C1-4 alkyl), -CON(C1-4 alkyl)(C1-4 alkyl), -SO2(C1-4 alkyl), -SO2NH2, -SO2NH(C1-4 alkyl), -SO2N(C1-4 alkyl)(C1-4 alkyl), -(C1-4 alkylene)N(C1-4 alkyl)(C1-4 alkyl), - (C1-4 alkylene)(N-heterocycloalkyl), cycloalkyl, heterocycloalkyl, aryl, heteroaryl, -Hal, -CN and -CF3, more preferably substituted with one or more optional substituents selected from C1-4 alkyl, -CONH-(C1-4 alkyl), and -SO2-(C1-4 alkyl),, and wherein said , said optionally substituted by one or more C1-6 alkyl (such as methyl) or Hal (such as F). Preferably, m is 1. optionally substituted by one or more C1-6 alkyl (such as methyl) or Hal (such as F). Even more preferably, wherein m is 1 or 2. It is particularly preferred that m is 1. Said optionally substituted by one or more C1-6 alkyl (such as methyl) or Hal (such as F). As recognized by the skilled person, Y may include chiral sulfur atom, and accordingly the presented formulae, which are drawn without indication of stereochemistry, may represent any of stereoisomers, in particular diastereoisomers or enantiomers embraced by the formula, including each specific possible stereoisomer or diastereoisomer, as well as it may refer to racemic mixtures or mixtures including an excess of one specific stereoisomer, enantiomer or diastereoisomer over another stereoisomer, enantiomer or diastereoisomer differing from the first one by configuration of at least one chiral center. For example, a formula wherein Q is =NH, =NCN, =N(C1-6 alkyl) or is absent may refer to each single one of the following formulae: , , well as it may refer to racemic mixtures or mixtures including an excess of one specific stereoisomer, enantiomer or diastereoisomer over another stereoisomer, enantiomer or diastereoisomer differing from the first one by configuration of at least one chiral center. Similar reasoning applies to the compounds of the present invention including a chiral phosphorus atom. Alternatively, in one embodiment, Y is preferably selected from: , alkenyl), and -(C1-2 alkylene)CN, wherein m is 1 or 2 and wherein said alkenyl is optionally substitutedwith one or more optional substituents selected from C1-4 alkyl, C1-4 haloalkyl, -COO(C1-4 alkyl), -CO(C1-4 alkyl), -CONH(C1-4 alkyl), -CON(C1-4 alkyl)(C1-4 alkyl), -SO2(C1-4 alkyl), -SO2NH2, -SO2NH(C1-4 alkyl), - SO2N(C1-4 alkyl)(C1-4 alkyl), -(C1-4 alkylene)N(C1-4 alkyl)(C1-4 alkyl), -(C1-4 alkylene)(N-heterocycloalkyl), cycloalkyl, heterocycloalkyl, aryl, heteroaryl, -Hal, -CN and -CF3, preferably substituted with one or more optional substituents selected from C1-4 alkyl, -CONH-(C1-4 alkyl), and -SO2-(C1-4 alkyl), and wherein said more C1-6 alkyl (such as methyl) or Hal (such as F). Preferably, m is 1. The compound of formula (I) can be a compound of formula (Ia): or a pharmaceutically acceptable salt thereof. In formula (Ia), A, X, Y, Z1, Z2, Z3 and Z4 are as defined for formula (I), including any preferred definition of the compound of formula (I) and any specific embodiment of the compound of formula (I). The compound of formula (I) may be a compound according to any one of the following specific embodiments. In the following description of each embodiment, not every variable group of formula (I) is explicitly discussed. It is to be understood that all the remaining variable groups are as in the definition of the compound of formula (I), including any preferred definitions and embodiments. Accordingly, for example, while in a first specific embodiment of the compound of formula (I), as discussed hereinbelow, only A is discussed in detail, it is to be understood that in this first specific embodiment of the compound of formula (I) B, X and Y are as in formula (I), including any of provided preferred definitions as well as any of the specific embodiments of the compound pf formula (I). In a first specific embodiment of the compound of formula (I), A is selected from aryl, heteroaryl, cycloalkyl, and cycloalkenyl wherein said aryl, said heteroaryl, said cycloalkyl and said cycloalkenyl are each optionally substituted with one or more R1. In this first specific embodiment, A is preferably selected from aryl and heteroaryl, wherein said aryl and said heteroaryl are each optionally substituted with one or more R1. More preferably, in this first specific embodiment of the compound of formula (I), A is aryl, optionally substituted with one or more R1. Particularly suitable aryl group is phenyl. Accordingly, even more preferably A is phenyl, optionally substituted with one or more R1(such as C1-6 alkyl and C1-6 haloalkyl). Particularly preferred A in this first specific embodiment of the present invention are selectedfrom In a second specific embodiment of the compound of formula wherein the left empty valence is connected to A, and the right empty valence is connected to X. In a third specific embodiment of the compound of formula wherein the left empty valence is connected to A, and the right empty valence is connected to X. In a fourth specific embodiment of the compound of formula wherein the left empty valence is connected to A, and the right empty valence is connected to X. In a fifth specific embodiment of the compound of formula wherein the left empty valence is connected to A, and the right empty valence is connected to X. In a sixth specific embodiment of the compound of formula wherein the left empty valence is connected to A, and the right empty valence is connected to X.In a seventh specific embodiment of the compound of formulawherein the left empty valence is connected to A, and the right empty valence is connected to X. In an eighth specific embodiment of the compound of formula wherein the left empty valence is connected to A, and the right empty valence is connected to X. In a ninth specific embodiment of the compound of formula wherein the left empty valence is connected to A, and the right empty valence is connected to X. In a tenth specific embodiment of the compound of formula wherein the left empty valence is connected to A, and the right empty valence is connected to X. In an eleventh specific embodiment of the compound of formula , wherein the left empty valence is connected to A, and the right empty valence is connected to X.In a twelfth specific embodiment of the compound of formula (I), B is ,wherein the left empty valence is connected to A, and the right empty valence is connected to X. In a thirteenth specific embodiment of the compound of formula , wherein the left empty valence is connected to A, and the right empty valence is connected to X.In a fourteenth specific embodiment of the compound of formula (I), B is , wherein the left empty valence is connected to A, and the right empty valenceis connected to X. In a fifteenth specific embodiment of the compound of formula (I), B is ,wherein the left empty valence is connected to A, and the right empty valence is connected to X. In a sixteenth specific embodiment of the compound of formula , wherein the left empty valence is connected to A, and the right empty valence is connected to X. In a seventeenth specific embodiment of the compound of formula (I), B is , wherein the left empty valence is connected to A, and the right empty valenceis connected to X. In an eighteenth specific embodiments of the compound of formula (I), B is , wherein the left empty valence is connected to A, and the right empty valenceis connected to X. In a nineteenth specific embodiment of the compound of formula (I), B is , wherein the left empty valence is connected to A, and the right empty valenceis connected to X. In a twentieth embodiment of the compound of formula (I), X is -NH-. In a twenty-first embodiment of the compound of formula (I), X is -N(RN)-, wherein RNis C1-6 alkyl. Particularly suitable C1-6 alkyl is selected from -CH2CH2C(CH3)3 and -CH2CH2CH(CH3)2. However, RNmay be C1-2 alkyl, for example methyl. In a twenty-second embodiment of the compound of formula (I), X is -N(RN)-, wherein RNis -(C0- 4 alkylene)-(C1-2 haloalkyl), preferably selected from -CH2CH2-(C1-2 haloalkyl) and -CH2CH2CH2-(C1-2 haloalkyl), more preferably CH2CH2-(C1-2 haloalkyl). As understood herein, particularly preferred haloalkyl is fluoroalkyl. Furthermore, preferred C1-2 haloalkyl is C1 haloalkyl, which is preferably selected from - CHF2 and CF3. Thus, particularly suitable -(C0-4 alkylene)-(C1-2 haloalkyl) is selected from -CH2CH2CHF2- and -CH2CH2CF3. In a twenty-third embodiment of the compound of formula (I), X is -N(RN)-, wherein RNis -(C0-4 alkylene)-aryl, wherein said aryl is optionally substituted with one or more groups selected from R3, preferably selected from -CH2CH2-aryl and -CH2CH2CH2-aryl. Particularly preferred aryl is phenyl. Thus, RNmay be -CH2CH2-phenyl and -CH2CH2CH2-phenyl. Said phenyl may be optionally substituted with one or more groups selected from R3. In a twenty-fourth embodiment of the compound of formula (I), X is -N(RN)-, wherein RNis -(C0-4 alkylene)-cycloalkyl, preferably cycloalkyl, wherein said cycloalkyl is optionally substituted with one or more groups selected from R3. In this embodiment, preferably RNis selected from 3- trifluoromethylcyclobutyl and 3-trifluoromethylcyclopentyl. In a twenty-fifth embodiment of the compound of formula (I), X is -N(RN)-, wherein RNis -(C0-4 alkylene)-heterocycloalkyl, preferably selected from -CH2CH2-heterocycloalkyl and -CH2CH2CH2- heterocycloalkyl, wherein said heterocycloalkyl is optionally substituted with one or more groups selected from R3. In this embodiment, preferably said heterocycloalkyl in RNis tetrahydropyranyl, preferably tetrahydropyran-4-yl. Thus, preferably, RNin this embodiment is selected from -CH2CH2-tetrahydropyran- 4-yl and -CH2CH2CH2-tetrahydropyran-4-yl. In a twenty-sixth specific embodiment of the compound of formula alkyl) , wherein m is 1 or 2, preferably wherein m is 1. Preferably, in this eleventh specific embodiment, In a twenty-seventh specific embodiment of the compound of formula In a twenty-eighth specific embodiment of the compound of formula wherein m is 1 or 2, preferably wherein m is 1. In a twenty-ninth specific embodiment of the compound of formula wherein m is 1 or 2, preferably wherein m is 1. In a thirtieth specific embodiment of the compound of formula (I), Y is selected from -CH2(C2 alkenyl), and -(C1-2alkylene)CN, wherein said -CH2- is optionally substituted with C1-4alkyl, C1-4haloalkyl, C3-8 cycloalkyl or 5 or 6-membered heterocyclyl, and wherein said alkenyl is optionally substituted with one or more optional substituents selected from C1-4 alkyl, -COOH, -COO(C1-4 alkyl), -CO(C1-4 alkyl), - CONH(C1-4 alkyl), -CON(C1-4 alkyl)(C1-4 alkyl), -SO3H, -SO2(C1-4 alkyl), -SO2NH2, -SO2NH(C1-4 alkyl), - SO2N(C1-4 alkyl)(C1-4 alkyl), -(C1-4 alkylene)N(C1-4 alkyl)(C1-4 alkyl), -(C1-4 alkylene)(N-heterocycloalkyl), cycloalkyl, -SO2-cycloalkyl, heterocycloalkyl, -SO2-heterocycloalkyl, aryl, -SO2-aryl, heteroaryl, -SO2- heteroaryl, -Hal, -CN and -CF3, preferably substituted with one or more optional substituents selected from C1-4 alkyl, -COO(C1-4 alkyl), -CO(C1-4 alkyl), -CONH(C1-4 alkyl), -CON(C1-4 alkyl)(C1-4 alkyl), -SO2(C1-4 alkyl), -SO2NH2, -SO2NH(C1-4 alkyl), -SO2N(C1-4 alkyl)(C1-4 alkyl), -(C1-4 alkylene)N(C1-4 alkyl)(C1-4 alkyl), - (C1-4 alkylene)(N-heterocycloalkyl), cycloalkyl, heterocycloalkyl, aryl, heteroaryl, -Hal, -CN and -CF3, more preferably substituted with one or more optional substituents selected from C1-4 alkyl, -CONH-(C1-4 alkyl), and -SO2-(C1-4 alkyl). In a thirty-first specific embodiment of the compound of formula (I), Y is -CH2(C2 alkenyl), wherein said -CH2- is optionally substituted with C1-4 alkyl, C1-4 haloalkyl, C3-8 cycloalkyl or 5 or 6-memberedheterocyclyl, and wherein said alkenyl is optionally substituted with one or more optional substituentsselected from C1-4 alkyl, -COOH, -COO(C1-4 alkyl), -CO(C1-4 alkyl), -CONH(C1-4 alkyl), -CON(C1-4 alkyl)(C1- 4 alkyl), -SO3H, -SO2(C1-4 alkyl), -SO2NH2, -SO2NH(C1-4 alkyl), -SO2N(C1-4 alkyl)(C1-4 alkyl), -(C1-4 alkylene)N(C1-4 alkyl)(C1-4 alkyl), -(C1-4 alkylene)(N-heterocycloalkyl), cycloalkyl, -SO2-cycloalkyl, heterocycloalkyl, -SO2-heterocycloalkyl, aryl, -SO2-aryl, heteroaryl, -SO2-heteroaryl, -Hal, -CN and -CF3, preferably substituted with one or more optional substituents selected from C1-4 alkyl, -COO(C1-4 alkyl), - CO(C1-4 alkyl), -CONH(C1-4 alkyl), -CON(C1-4 alkyl)(C1-4 alkyl), -SO2(C1-4 alkyl), -SO2NH2, -SO2NH(C1-4 alkyl), -SO2N(C1-4 alkyl)(C1-4 alkyl), -(C1-4 alkylene)N(C1-4 alkyl)(C1-4 alkyl), -(C1-4 alkylene)(N- heterocycloalkyl), cycloalkyl, heterocycloalkyl, aryl, heteroaryl, -Hal, -CN and -CF3, more preferably substituted with one or more optional substituents selected from C1-4 alkyl, -CONH-(C1-4 alkyl), and -SO2- (C1-4 alkyl). Preferably, in this thirty-first specific embodiment, Y is a moiety according to formula: wherein Ry1is selected from H, C1-4alkyl (such as methyl), C1-4haloalkyl (such as trifluoromethyl) C3-8 cycloalkyl (such as cyclopropyl), and 5 or 6-membered heterocyclyl, Ry2is selected from -H, -F and - CN, and Ry3is selected from H, C1-4 alkyl (such as methyl), C3-8 cycloalkyl (such as cyclopropyl), and 5 or6-membered heterocyclyl, and wherein the bonds drawn as indicate that both Z and Econfigurations of the double bond are possible. In this specific embodiment, Y is preferably selected from: In thirty-second specific embodiment of the compound of formula (I), Y is according to formula: or according to formula: wherein Ry1is selected from H, C1-4 alkyl (such as methyl), C3-8 cycloalkyl (such as cyclopropyl), and 5 or 6-membered heterocyclyl, and Ry2is selected from -H, -F and -CN, and wherein the bonds drawnas indicate that both Z and E configurations of the double bond are possible.In a thirty-third embodiment of the present invention, Y is a moiety according to formula: wherein Ry1is selected from H, C1-4 alkyl (such as methyl), C1-4 haloalkyl (such as trifluoromethyl) C3-8 cycloalkyl (such as cyclopropyl), and 5 or 6-membered heterocyclyl, Ry2is selected from -H, -F and - CN, Ry3is selected from H, C1-4 alkyl (such as methyl), C3-8 cycloalkyl (such as cyclopropyl), and 5 or 6- membered heterocyclyl, RNNis selected from C1-4 alkyl (such as methyl), cycloalkyl and phenyl, andwherein the bonds drawn as indicate that both Z and E configurations of the double bond arepossible.In a thirty-fourth specific embodiment, optionally substituted with one or more R2, preferably apparent to the skilled person, B is a bivalent moiety and accordingly, as understood herein, preferably the left empty valence of B as shown in the specific structural formulas herein is connected to A, and the right empty valence of B as shown herein is connected to X. In this thirty-fourth specific embodiment, preferably A is -N(C1-5 alkyl)(C1-5 alkyl), such as -N(CH3)(CH(CH3)2). In a thirty-fifth specific embodiment, B is selected from , . Accordingly, in this thirty-fifth specific Alternatively, B may apparent to the skilled person, B is a bivalent moiety and accordingly, as understood herein, preferably the left empty valence of B as shown in the specific structural formulas herein is connected to A, and the right empty valence of B as shown herein is connected to X. Particularly preferred compounds of formula (I) are selected from the following compounds, or their pharmaceutically acceptable salts: . Particularly preferred compounds of formula (I) are selected from the following compounds, or their pharmaceutically acceptable salts: 5

[0002] acceptable salt. Further preferred compounds of formula (I) are selected from the following compounds or their pharmaceutically suitable salts: 3-((3-(3,4-dimethylphenyl)-1-methoxyisoquinolin-8-yl)amino)-2,3-dihydrothiophene 1,1-dioxide; and 3-(3,4-dimethylphenyl)-8-((1,1-dioxido-2,3-dihydrothiophen-3-yl)amino)isoquinolin-1(2H)-one. Further preferred compounds of formula (I) are selected from the following compounds or their pharmaceutically acceptable salts: 3-((3-(3,4-dimethylphenyl)-1-methoxyisoquinolin-8-yl)amino)-2,3-dihydrothiophene 1,1-dioxide; 3-(3,4-dimethylphenyl)-8-((1,1-dioxido-2,3-dihydrothiophen-3-yl)amino)isoquinolin-1(2H)-one; 6-(3,4-dimethylphenyl)-3-((1,1-dioxido-2,3-dihydrothiophen-3-yl)amino)-1,5-dihydro-4H- pyrazolo[4,3-c]pyridin-4-one trifluoroacetate; (E)-N6-isopropyl-N6-methyl-N3-(4-(methylsulfonyl)but-3-en-2-yl)-4-phenoxy-1H-pyrazolo[3,4- d]pyrimidine-3,6-diamine 2,2,2-trifluoroacetate; 3-((6-(3,4-dimethylphenyl)-1H-pyrrolo[3,2-b]48yridine-3-yl)amino)-2,3-dihydrothiophene 1,1- dioxide; 3-((6-(3,4-dimethylphenyl)-1-methyl-1H-pyrrolo[3,2-b]pyridin-3-yl)amino)-2,3-dihydrothiophene 1,1-dioxide; 3-((3-(3,4-dimethylphenyl)quinolin-8-yl)amino)-2,3-dihydrothiophene 1,1-dioxide; (R)-3-((6-phenyl-1H-pyrazolo[4,3-b]pyridin-3-yl)amino)-2,3-dihydrothiophene 1,1-dioxide 2,2,2- trifluoroacetate; (R)-3-((1,1-dioxido-2,3-dihydrothiophen-3-yl)amino)-6-phenyl-1H-pyrazolo[4,3-b]pyridine 4- oxide; (R)-3-((1-methyl-6-phenyl-1H-pyrazolo[4,3-b]pyridin-3-yl)amino)-2,3-dihydrothiophene 1,1- dioxide; (R)-3-((1,1-dioxido-2,3-dihydrothiophen-3-yl)amino)-1-methyl-6-phenyl-1H-pyrazolo[4,3- b]pyridine 4-oxide; 6-(3,4-dimethylphenyl)-3-((1,1-dioxido-2,3-dihydrothiophen-3-yl)amino)isoxazolo[4,5-c]pyridin- 4(5H)-one; (R)-3-(3,4-dimethylphenyl)-8-((1,1-dioxido-2,3-dihydrothiophen-3-yl)amino)-2,6-naphthyridin- 1(2H)-one; (R)-7-(3,4-dimethylphenyl)-4-((1,1-dioxido-2,3-dihydrothiophen-3-yl)amino)-1,6-naphthyridin- 5(6H)-one; (R)-3-(3,4-dimethylphenyl)-8-((1,1-dioxido-2,3-dihydrothiophen-3-yl)amino)-7-fluoroisoquinolin- 1(2H)-one; (R)-3-(3,4-dimethylphenyl)-8-((1,1-dioxido-2,3-dihydrothiophen-3-yl)amino)-6-fluoroisoquinolin- 1(2H)-one; (R)-3-(3,4-dimethylphenyl)-8-((1,1-dioxido-2,3-dihydrothiophen-3-yl)amino)-5-fluoroisoquinolin- 1(2H)-one; (S,E)-3-(3,4-dimethylphenyl)-8-((4-(methylsulfonyl)but-3-en-2-yl)amino)isoquinolin-1(2H)-one; (R)-3-((7-(3,4-dimethylphenyl)-5-methoxy-1,6-naphthyridin-4-yl)amino)-2,3-dihydrothiophene 1,1-dioxide; (R)-3-((3-(3,4-dimethylphenyl)-7-fluoro-1-methoxyisoquinolin-8-yl)amino)-2,3-dihydrothiophene 1,1-dioxide; (R)-3-((3-(3,4-dimethylphenyl)-6-fluoro-1-methoxyisoquinolin-8-yl)amino)-2,3-dihydrothiophene 1,1-dioxide; (R)-3-((3-(3,4-dimethylphenyl)-5-fluoro-1-methoxyisoquinolin-8-yl)amino)-2,3-dihydrothiophene 1,1-dioxide; 3-((6-(3,4-dimethylphenyl)-4-methoxyisoxazolo[4,5-c]pyridin-3-yl)amino)-2,3-dihydrothiophene 1,1-dioxide; (R)-3-(3,4-dimethylphenyl)-8-((1,1-dioxido-2,3-dihydrothiophen-3-yl)amino)-2-methylisoquinolin- 1(2H)-one; (S,E)-3-(3,4-dimethylphenyl)-1-methoxy-N-(4-(methylsulfonyl)but-3-en-2-yl)isoquinolin-8-amine; (S,E)-N2-isopropyl-N2-methyl-N5-(4-(methylsulfonyl)but-3-en-2-yl)-4-phenoxyquinazoline-2,5- diamine; and 6-(3,4-dimethylphenyl)-3-((1,1-dioxido-2,3-dihydrothiophen-3-yl)amino)-7-hydroxy-1,5-dihydro- 4H-pyrazolo[4,3-c]pyridin-4-one. 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 -ORx moiety, wherein Rx preferably 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(C1-5alkyl)(C1-5alkyl). 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, or a pharmaceutical composition as defined herein for use in therapy. The present invention provides compounds that have activity of inhibitors of Werner syndrome ATP- dependent helicase (WRN). Thus, accordingly, the present invention provides a method of inhibiting WRN enzyme activity in vitro and in vivo, said method comprising contacting a cell with an effective amount of the compound of formula (I), or a pharmaceutically acceptable salt thereof, as defined herein. In one embodiment, the present invention provides a method for decreasing proliferation in a proliferative cell having a microsatellite instability (MSI), comprising decreasing the helicase activity of Werner syndrome ATP-dependent helicase (WRN) in the proliferative cell. In some embodiments, decreasing the helicase activity of Wemer syndrome ATP-dependent helicase (WRN) in the proliferative cell is achieved by administering a compound of Formula of (I) (or any embodiment thereof disclosed herein) or a pharmaceutically acceptable salt thereof. In some embodiments, the proliferative cell is characterized as having MSI low (MSI-L). In some embodiments, the proliferative cell is characterized as having high MSI (MSI-H), used interchangeably with MSI-high. Cells can be characterized as MSI, including MSI-L or MSI- H, or as MSS (MS-stable), according to the method known in the art (see, for example, Dudley, Jonathan C., et al., Clinical Cancer Research, 22(4): 813-820, 2016.). MSI-H is used to classify tumors as having a high frequency of MSI. A tumor can be classified as MSI, including MSI-low or MSI-high, using polymerase chain reaction (PCR) and / or immunohistochemistry (IHC) assays. As stated in Dudley et al., a tumor is classified as MSI-H by PCR if (i) there is a shift (usually downward) in the size of at least two microsatellite loci from a reference panel of five microsatellite loci in tumor relative to normal, where the reference panel can be the “Bethesda Panel,” also referred to herein as the “NCI- Reference Panel (Bethesda, 1998)”, which includes two mononucleotide loci (BAT-25 and BAT-26) and three dinucleotide loci (D2S123, D5S346, and D17S250), or alternatively, the reference panel can be Promega Corporation’s MSI Analysis System, which includes five mononucleotide loci (BAT-25, BAT-26, NR-21, NR-24, and MONO-27); or (ii) there is a shift in the size of 30% or more microsatellite loci from a reference panel of more than five microsatellite loci in tumor relative to normal. The MSI-H phenotype is associated with germline defects in the mismatch repair genes MLH1, MSH2, MSH6, and PMS2, and is the primary phenotype observed in tumors from patients with HNPCC / Lynch syndrome. A tumor is classified as MSI-H in IHC test if it shows a loss of protein expression for at least 1 of the above 4 mismatch repair genes. Cells can be similarly classified as MSI-H using the tests described herein for tumors. In some embodiments, a tumor or cell is classified as MSI-H using PCR to amplify the five microsatellite loci of the “Bethesda Panel” (BAT-25, BAT-26, D2S123, D5S346, and D17S250) from both tumor tissue or cells and normal tissue or cells, wherein the tumor or cell is classified as MSI-H if there is a shift in the size of at least two of the microsatellite loci from the tumor tissue or cells relative to the normal tissue or cells. In some embodiments, the shift in size of the microsatellite loci is a downward shift. In some embodiments, a tumor or cell is classified as MSI-H using PCR to amplify the five microsatellite loci of Promega Corporation’s MSI Analysis System (BAT-25, BAT-26, NR- 21, NR-24, and MONO-27) from both tumor tissue or cells and normal tissue or cells, wherein the tumor or cell is classified as MSI-H if there is a shift in the size of at least two of the microsatellite loci from the tumor tissue or cells relative to the normal tissue or cells. In some embodiments, the shift in size of the microsatellite loci is a downward shift. In some embodiments, a tumor is classified as MSI-H using IHC to determine the expression level of the MMR proteins MLH1, MSH2, MSH6, and / or PMS2 in both tumor tissue and normal tissue, wherein the tumor is classified as MSI-H if there is a loss of protein expression for at least one of the MMR proteins in the tumor tissue relative to the normal tissue. In some embodiments, the loss of protein expression is a decrease of at least 20% (such as a decrease of 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 99%, or more). In contrast, a tumor is classified as MSI-L by PCR if (i) there is a shift in the size of one microsatellite locus from a reference panel of five microsatellite loci in tumor relative to normal, where the reference panel can be the “Bethesda Panel” or Promega Corporation’s MSI Analysis System; or (ii) there is a shift in the size of less than 30% microsatellite loci from a reference panel of more than five microsatellite loci in tumor relative to normal. MSI-L tumors are thought to represent a distinct mutator phenotype with potentially different molecular etiology than MSI-H tumors (Thibodeau, 1998; Wu et al., 1999, Am J Hum Genetics 65: 1291-1298). Cells can be similarly classified as MSI-L using the tests described herein for tumors. Cancers classified as MSI-H include, but not limited to, uterine corpus endometrial carcinoma, colon adenocarcinoma, stomach adenocarcinoma, rectal adenocarcinoma, adenoid cystic carcinoma, uterine carcinosarcoma, cervical squamous cell carcinoma, and endocervical adenocarcinoma. In one embodiment, the present invention relates to a method for treating a cancer treatable by inhibition of WRN in a subject in need thereof, the method comprising the step of administering to the subject the compound of formula (I) or a pharmaceutically acceptable salt thereof. It is to be understood that, typically, a therapeutically effective amount is to be administered. In one embodiment, the present invention relates to a method for treating a cancer characterized by MSI-H and / or dMMR in a subject in need thereof, the method comprising the step of administering to the subject the compound of formula (I) or a pharmaceutically acceptable salt thereof. It is to be understood that, typically, a therapeutically effective amount is to be administered. In one embodiment, the present invention relates to use of a compound of formula (I) or pharmaceutically acceptable salt thereof, in the manufacture of a medicament for treating cancer. Preferably, the cancer is treatable by inhibition of WRN. In one embodiment, the cancer is characterized by MSI-H and / or dMMR. In one embodiment, the present invention relates to the compound of formula (I) or a pharmaceutically acceptable salt thereof, for use in treating cancer. Preferably, the cancer is treatable by inhibition of WRN. In one embodiment, the cancer is characterized by MSI-H and / or dMMR. 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 cell lung carcinoma, lung adenocarcinoma, including also lungadenocarcinoma 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. The antiproliferative treatment (i.e. the treatment of cancer) with the compound of formula (I) or a pharmaceutically acceptable salt 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 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 the compounds of formula (I) according to the present invention are preferably carried out according to the general synthetic sequences as shown in Scheme 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 Schemes 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. Scheme 1 Scheme 1 illustrates a preferred synthetic approach to compounds of the general Formula (I) inwhich W1is defined as, but not limited to, a hydrogen, or a functional group leading to a boronic acid, aboronic ester, an organozinc, an organostannic or an organomagnesium compound of formula 1, W2 isdefined as being triflate, Br or I, W3is defined as being Cl, Br or I and all the other variables are definedaccording to the definition of the compound of Formula (I), as referred to hereinabove.In the first step, compound 3 is prepared via cross-coupling reactions of suitably functionalizedbuilding blocks 1 and 2. Formation of a C-C bond between 1 and 2 can be e.g. achieved by the cross-coupling of an aryl, heteroaryl, alkyl, or vinyl boronic acid, borate ester, or borane 1 with an aryl orheteroaryl halide or triflate 2 using a variety of palladium catalysts (Suzuki reaction; see e.g. B. S. Kadu,Catal. Sci. Technol., 2021,11, 1186-1221). The formation of a carbon–carbon bond between a terminalalkyne 1 and an aryl or heteroaryl halide 2 can be achieved by employing palladium catalysts as well ascopper co-catalysts (Sonogashira coupling, see e.g. I. Kanwal et al, Catalysts 2020, 10(4), 443).Moreover, formation of a C-N bond between 1 and 2 can be achieved via the palladium-catalyzed couplingreactions of amines 1 with aryl and heteroaryl halides 2 (Buchwald–Hartwig coupling, see e.g. R. Dorel etal, Angew. Chem. Int. Ed.2019, 58, 17118). In the second step, the formation of C-N bond leading to compound of formula (I) can be a achievedby cross-coupling of compound 3 and compound 4 via palladium-catalyzed coupling reactions (Buchwald–Hartwig coupling, see e.g. R. Dorel et al, Angew. Chem. Int. Ed.2019, 58, 17118). It is to be understood by someone skilled in the art, that on schemes 1 and 3, additional reactions such as alkylation of X can occur once the compound of formula (I) is obtained. Preparative examples General considerations Preparative examples General considerationsAbbreviations used in the descriptions that follow are: AcOH (acetic acid); aq. (aqueous); Ag2CO3 (silvercarbonate); Ar (Argon); Atm (atmosphere); br. (broad, 1H NMR signal); Boc2O (di-tert-butyldicarbonate);(CDCl3 (deuterated chloroform); cHex (cyclohexane); Cs2CO3 (cesium carbonate); CuI (copper iodide);DCE (dichloroethane); d (doublet, 1H NMR signal); DCM (dichloromethane); DIPEA or DIEA (di-iso-propylethylamine); DMAP (4- N-N-dimethylaminopyridine), DME (1,2-dimethoxyethane), DMF (N-N-dimethylformamide); DMSO (dimethyl sulfoxide); ES (electrospray); EtOAc or EA (ethyl acetate); EtOH(ethanol); h (hour(s)); FA (formic acid); HBr (hydrogen bromide); 1H NMR (proton nuclear magneticresonance spectroscopy); HPLC (High Performance Liquid Chromatography), iPrOH (iso-propanol); K2CO3 (potassium carbonate); K3PO4 (tripotassium phosphate); LDA (lithium diisopropyl amide); LiOH(lithium hydroxide); m (multiplet, 1H NMR signal); MeCN (acetonitrile), MeI (methyl iodide); MeONa(sodium methylate); MeOH (methanol); min (minute(s)); MTBE (Methyl tert-butyl ether); MS (mass spectrometry); NaHCO3 (sodium hydrogenocarbonate); NH3 (ammonia); NH4Cl (ammonium chloride);NMR (nuclear magnetic resonance); Pd / C (palladium on charcoal); Pd(dppf)Cl2 ([1,1 -Bis(diphenylphosphino)ferrocen]dichlorpalladium(II)); 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; Py (pyridine); q (quartet, 1H NMR signal); quin (quintet, 1H NMR signal); rac (racemic); RT(retention time); s (singlet, 1H NMR signal); sat. (saturated); t (triplet, 1H NMR signal); tBuOH (tert- butanol); TEA (triethylamine) ; TFA (trifluoroacetic acid); TFAA (trifluoroacetic anhydride), THF (tetrahydrofuran); TLC (thin layer chromatography); THP (tetrahydropyrane); TsOH (p-toluenesulfonic acid); UPLC (Ultra-High Performance Liquid Chromatography), UV (ultraviolet), wt-% (percent by weight). 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, Version 16.0.1.4 (77)). In some cases generally accepted names of commercially available reagents were used in place of ChemDraw generated names. Reversed Phase HPLC conditions for LCMS Analysis of compounds: Method 1: SHIMADZU LCMS-2020 Kinetex EVO C182.1X30mm, 5 µm 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 C182.1X30 mm,5 um at 40°C Mobile PhaseA: 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: SHIMADZU LCMS-2020 HALO C183.0X30mm,5um at 50 ; Mobile Phase: A: 0.0375% TFA inwater (v / v); B: 0.01875% TFA in Acetonitrile (v / v); flow rate held at 1.5 mL / min; eluted with the mobile phase over 1.05 min employing UV detection at 220 nm and 254 nm. Gradient information: 0-0.50 min, ramped from 95% A- 5% B to 5% A-95% B; 0.50-0.80 min, held at 5% A-95% B; 0.80-0.81 min, returned to 95% A-5% B, 0.81-1.05 min, held at 95% A-5% B. Method 4: SHIMADZU LCMS-2020 HALO C183.0X30mm, 5um at 50 ; Mobile Phase: A: 0.0375% TFA inwater (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: 0-0.50 min, ramped from 95% A-5% B to 5% A-95% B; 0.50-0.80 min, held at 5% A-95% B; 0.80-0.81 min, returned to 95% A-5% B, 0.81-1.00 min, held at 95% A-5% BMethod 5: SHIMADZU LCMS-2020 Kinetex EVO C18 2.1X30mm, 5 m at 40 Mobile Phase A:0.025% NH3·H2O in water (v / v); B: MeCN; flow rate held at 1.5 mL / min; eluted with the mobile phase over 1.50 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, 1.21-1.50 min, held at 95% A-5% B. Methods for SFC analysis of compounds: SFC Method 1: Column: Chiralcel OJ-350*4.6 mm I.D.,3 um; 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: 35C; Back Pressure: 100 Bar SFC Method 2: Column: Chiralcel OD-350*4.6mm I.D., 3 um; 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: 35C; Back Pressure: 100Bar SFC Method 3: Column: Chiralpak IC-350*4.6mm I.D., 3 um; Mobile phase: Phase A for CO2, and Phase B for IPA+ACN (0.05% DEA); Gradient elution: IPA+ACN (0.05% DEA) from 20% to 60% in CO2, Flow rate: 3mL / min; Detector: PDA; Column Temp: 35C; Back Pressure: 100Bar SFC Method 4: Column: Chiralcel OD-350*4.6mm I.D., 3um; 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; Colum Temp: 35C; Back Pressure: 100Bar SFC Method 5: Column: Chiralcel OJ-350*4.6mm I.D., 3um 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; Colum Temp: 35C; Back Pressure: 100Bar SFC Method 6: Column: Chiralpak AD-350*4.6mm I.D., 3um; Mobile phase: Phase A for CO2, and Phase B for IPA+ACN (0.05% DEA); Gradient elution: 20% to 60% IPA+ACN (0.05% DEA) in CO2, Flow rate: 3mL / min; Detector: PDA; Column Temp: 35C; Back Pressure: 100Bar SFC Method 7: Column: Chiralpak AD-350*4.6mm I.D., 3um; Mobile phase: Phase A for CO2, and Phase B for EtOH + ACN (0.05% DEA); Gradient elution: 60% EtOH + ACN (0.05% DEA) in CO2, Flow rate: 3mL / min; Detector: PDA; Column Temp: 35C; Back Pressure: 100Bar SFC Method 8: Column:Chiralcel OJ-350*4.6mm I.D.,3um; Mobile phase:Phase A for CO2,and Phase B for IPA(0.05%DEA); Gradient elution:IPA(0.05%DEA) in CO2 from 20% to 60%, Flow rate:3mL / min;Detector:PDA; Colum Temp:35C;Back Pressure:100Bar" SFC Method 9: Column:Chiralpak IG-350*4.6mm I.D.,3um; Mobile phase:Phase A for CO2,and Phase B for IPA+ACN(0.05%DEA); Gradient elution: IPA+ACN(0.05%DEA)from 20% to 60% in CO2, Flow rate:3mL / min;Detector:PDA; Column Temp:35C;Back Pressure:100Bar1H NMR Spectroscopy: 1H NMR spectra were acquired on a Bruker Avance spectrometer at 400 MHz using residualundeuterated solvent as reference. 1H NMR signals are specified with their multiplicity / combinedmultiplicities as apparent from the spectrµm; 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 8-bromo-3-(3,4-dimethylphenyl)isoquinolin-1-ol To a mixture of methyl 2-bromo-6-methylbenzoate (5.00 g, 21.8 mmol) and 3,4-dimethylbenzonitrile ( 3.15 g, 24.0 mmol) in THF (20 mL) was added LDA in THF ( 14 mL, 2 M, 28.0 mmol) over 30 min at -78 °C under N2. The mixture was stirred at -78 °C for 3 h, then quenched with NH4Cl (aq., sat., 20 mL) and extracted with EtOAc (60 mL; 2x). The combined organic layer was washed with brine (30 mL; 2x), separated, a dried over anhydrous Na2SO4 filtered and concentrated under reduce pressure. The crude product was triturated with EtOAc (10 mL) at room temperature for 30 min, then filtered and the filtrate cake was dried under vacuum to give the product 8-bromo-3-(3,4-dimethylphenyl)isoquinolin-1-ol (1.38 g,4.20 mmol, 19.26 % yield) as a white solid. LCMS RT 0.579 min (Method 1); m / z 328 (M+H)+ (ESI+), 330 (M+2+H)+ (ESI+); 1 HNMR (DMSO-d6, 400 MHz): 11.38 (s, 1 H), 7.72-7.64 (m, 2 H), 7.60 (d, J = 1.2 Hz, 1 H), 7.55-7.47 (m, 2 H), 7.25 (d, J= 8.0 Hz, 1 H), 6.89 (s, 1 H), 2.29 (s, 3 H), 2.27 (s, 3 H) Preparation of Intermediate 2 8-bromo-3-(3,4-dimethylphenyl)-1-methoxyisoquinoline To a mixture of 8-bromo-3-(3,4-dimethylphenyl)isoquinolin-1-ol (1.10 g, 3.35 mmol) and Ag2CO3 (1.11 g, 4.02 mmol) in THF (10 mL) was added MeI (0.63 mL, 10.1 mmol). The mixture was stirred at 60 °C for 16 h, then, filtered and the filtrate was concentrated under reduced pressure. The residue was purified by flash silica gel chromatography (ISCO; 20 g SepaFlash Silica Flash Column, Eluent of 0%-3% Ethyl acetate / Petroleum ether; gradient @ 80 mL / min) and concentrated under vacuum to give the product 8- bromo-3-(3,4-dimethylphenyl)-1-methoxyisoquinoline (730 mg, 2.13 mmol, 63.64 % yield) as a white solid. LCMS RT 0.747 min (Method 1); m / z 342.0 (M+H)+ (ESI+); 1 HNMR (CDCl3, 400 MHz): 7.93 (s,1H), 7.90 (d, J = 7.6 Hz, 1H), 7.78 (dd, J = 0.8, 7.6 Hz, 1H), 7.71 (d, J = 7.6 Hz, 1H), 7.64 (s, 1H), 7.37 (t,J = 7.6 Hz, 1H), 7.29-7.26 (m, 1H), 4.23 (s, 3H), 2.39 (s, 3H), 2.34 (s, 3H) Preparation of Example 1 3-((3-(3,4-dimethylphenyl)-1-methoxyisoquinolin-8-yl)amino)-2,3-dihydrothiophene 1,1- dioxide To a solution of 3-amino-2,3-dihydrothiophene 1,1-dioxide hydrobromide (75 mg, 0.351 mmol) in 1,4- dioxane (2 mL) and DMF (1 mL) was added Cs2CO3 (121 mg, 0.877 mmol).The mixture was stirred at 25 °C for 5 min. Then, 8-bromo-3-(3,4-dimethylphenyl)-1-methoxyisoquinoline (100 mg, 0.292 mmol) and Pd-PEPPSI-IPent Cl o-picoline (2-methylpyridine) (25 mg, 0.0292 mmol) were added t.The mixture was stirred at 100 °C under N2 for 12 h, then diluted with H2O (15 mL) and extracted with EtOAc (15 mL, 2x). The combined organic layer was washed with brine (15 mL, 2x), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by preparative TLC (petroleum ether: ethyl acetate= 1:1) to give the product 3-((3-(3, 4-dimethylphenyl)-1-methoxyisoquinolin-8-yl)amino)-2,3- dihydrothiophene 1,1-dioxide (25 mg, 0.0634 mmol, 21.69 % yield) as a yellow solid. LCMS RT 0.625 min (Method 1); m / z 395.2 (M+H)+ (ESI+). 1 HNMR (CDCl3, 400 MHz): 7.93 (s,1H), 7.90 (d, J = 7.6 Hz, 1H), 7.58 (s, 1H), 7.45 (t, J = 7.6 Hz, 1H), 7.24 (d, J = 7.6 Hz, 1H), 7.15 (d, J =7.6 Hz, 1H), 6.92 (dd, J = 2.8, 7.6 Hz, 1H), 6.88 (d, J = 7.6 Hz, 1H), 6.50 (d, J = 7.6 Hz, 1H), 5.09 (br, 1H), 3.83 (dd, J = 7.6, 13.6 Hz, 1H), 3.26 (dd, J = 4.0, 13.6 Hz, 1H), 2.37 (s, 3H), 2.34 (s, 3H) Preparation of Example 2 3-(3,4-dimethylphenyl)-8-((1,1-dioxido-2,3-dihydrothiophen-3-yl)amino)isoquinolin-1(2H)- one To a solution of 3-((3-(3,4-dimethylphenyl)-1-methoxyisoquinolin-8-yl)amino)-2,3-dihydrothiophene 1,1- dioxide (25 mg, 0.0634 mmol) in DMF (1 mL) was added TsOH (55 mg, 0.317 mmol) and LiCl (13 mg, 0.317 mmol). The mixture was stirred at 100 °C for 2 h, then; diluted with H2O (5 mL) and extracted with EtOAc (5 mL, 2x). The combined organic layer was washed with brine (5 mL, 2x), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by preparative HPLC (column: YMC-Actus Triart C18150*30 mm*7 µm; mobile phase: A: 0.225% formic acid in water, B: MeCN; B%: 35%-65%, 10 min) and lyophilized directly to give the product 3-(3,4-dimethylphenyl)-8-((1,1- dioxido-2,3-dihydrothiophen-3-yl)amino)isoquinolin-1(2H)-one (2.4 mg, 0.00618 mmol, 9.75 % yield) as an off-white solid. LCMS: RT 0.567 min (LCMS Method 1); m / z 381.3 (M+H)+ (ESI+); 1 HNMR (CDCl3, 400 MHz):9.64 (br, 1H), 8.65 (br, 1H), 7.47 (t, J = 8.0 Hz, 1H), 7.39 (s, 1H), 7.37-7.33 (d, J = 8.0 Hz, 1H), 7.27-7.24(m, 1H), 6.91-6.80 (m, 3H), 6.65 (s, 1H), 6.48 (d, J = 8.0 Hz, 1H), 5.06 (br, 1H), 3.83 (dd, J = 7.6, 13.4 Hz,1H), 3.23 (dd, J = 5.2, 13.4 Hz, 1H), 2.36 (s, 3H), 2.34 (s, 3H)Preparation of Examples 2a & 2b (R or S)-3-(3,4-dimethylphenyl)-8-((1,1-dioxido-2,3-dihydrothiophen-3-yl)amino)isoquinolin- 1(2H)-one & (S or R)-3-(3,4-dimethylphenyl)-8-((1,1-dioxido-2,3-dihydrothiophen-3- yl)amino)isoquinolin-1(2H)-one 3-(3,4-dimethylphenyl)-8-((1,1-dioxido-2,3-dihydrothiophen-3-yl)amino)isoquinolin-1(2H)-one (65 mg, 0.171 mmol) was purified by preparative SFC (Column: DAICEL CHIRALPAK OJ (250 mm*30 mm,10 µm), Mobile Phase: 45% EtOH (0.1% NH3.H2O additive) in Supercritical CO2. Flow Rate: 150 g / min, Cycle Time: 5.76 min. Back Pressure: 80 bar to keep the CO2 in Supercritical flow) to give a solution of peak 1 and a solution of peak 2. The solution of peak 1 was concentrated under reduced pressure, lyophilized to give the product (R or S)-3-(3,4-dimethylphenyl)-8-((1,1-dioxido-2,3-dihydrothiophen-3- yl)amino)isoquinolin-1(2H)-one (19 mg, 0.0495 mmol, 29.00 % yield) as an off-white solid. LCMS: RT 0.555 min, (LCMS Method 2); m / z 381.1 (M+H)+ (ESI+); SFC: RT 2.336 min, ee 99.9%(SFC Method 1); 1 HNMR (DMSO-d6, 400 MHz): 11.20 (br s, 1H), 9.57 (d, J = 8.0 Hz, 1H), 7.57 (s, 1H),7.49 (br d, J = 8.0 Hz, 1H), 7.44 (t, J = 8.0 Hz, 1H), 7.35 (dd, J = 1.6, 6.4 Hz, 1H), 7.24 (d, J = 8.0 Hz, 1H),7.10 (dd, J = 3.2, 6.4 Hz, 1H), 6.86 (d, J = 8.0 Hz, 1H), 6.76 (s, 1H), 6.65 (d, J = 8.0 Hz, 1H), 5.19 - 5.10(m, 1H), 3.91 (dd, J = 7.6, 14.0 Hz, 1H), 3.08 (dd, J = 3.2, 14.0 Hz, 1H), 2.29 (s, 3H), 2.27 (s, 3H)The solution of peak 2 was concentrated under reduced pressure and lyophilized to give the product (S or R)-3-(3,4-dimethylphenyl)-8-((1,1-dioxido-2,3-dihydrothiophen-3-yl)amino)isoquinolin-1(2H)-one (21 mg, 0.0544 mmol, 31.85 % yield) as an off-white solid. LCMS: RT 0.559 min (LCMS Method 2); m / z 381.1 (M+H)+ (ESI+); SFC: RT 2.722 min, ee 99.6%;(SFC Method 1); 1 HNMR (DMSO-d6, 400 MHz): 11.20 (br s, 1H), 9.57 (d, J = 8.0 Hz, 1H), 7.57 (s, 1H),7.49 (br d, J = 8.0 Hz, 1H), 7.44 (t, J = 8.0 Hz, 1H), 7.35 (d, J = 6.4 Hz, 1H), 7.24 (d, J = 8.0 Hz, 1H), 7.10(dd, J = 3.2, 6.4 Hz, 1H), 6.86 (d, J = 8.0 Hz, 1H), 6.76 (s, 1H), 6.65 (d, J = 8.0 Hz, 1H), 5.15 (br s, 1H),3.91 (dd, J = 7.6, 14.0 Hz, 1H), 3.08 (dd, J = 3.2, 14.0 Hz, 1H), 2.29 (s, 3H), 2.27 (s, 3H)Examples 2a and 2b are enantiomers, but exact configurations of their chiral centers has not been unambiguously assigned. Thus, the reference to (R or S) and (S or R) configuration is made, as if 2a has an R configuration, then 2b must have an S configuration, and vice versa. Preparation of Intermediate 3.1 4,6-dichloro-2-(tetrahydro-2H-pyran-2-yl)-2H-pyrazolo[4,3-c]pyridine To a mixture of 4,6-dichloro-1H-pyrazolo[4,3-c]pyridine (2.50 g, 13.3 mmol) in THF (20 mL) were added 4-methylbenzenesulfonic acid (0.33 g, 1.33 mmol) and 3,4-dihydro-2H-pyran (6.1 mL, 66.5 mmol) at 0 °C under N2 atmosphere. The reaction mixture was stirred at 60 °C for 2 h, then poured into water (30 mL) and extracted with EtOAc (30 mL, 3x). The combined organic layers was washed with brine (10 mL, 2x), dried over anhydrous Na2SO4, filtered and concentrated under vacuum. The residue was purified by flash silica gel chromatography (ISCO; 120 g SepaFlash Silica Flash Column, Eluent of 0~30% Ethyl acetate / Petroleum ether gradient @ 100 mL / min) and concentrated under vacuum to give the product 4,6- dichloro-2-(tetrahydro-2H-pyran-2-yl)-2H-pyrazolo[4,3-c]pyridine (2.3 g, 8.45 mmol, 63.56% yield) as a white solid. RT 0.536 min (method 3); m / z 272.0. (M+H)+ (ESI+).1H NMR (DMSO-d6, ,400 MHz): 9.06 (s, 1H),7.86 (s, 1H), 5.85-5.81 (m, 1H), 4.10-4.01 (m, 1H), 3.81-3.75 (m, 1H), 2.26-2.18 (m, 1H), 2.17-2.10 (m, 1H), 2.05-1.94 (m, 1H), 1.83-1.71 (m, 1H), 1.69-1.60 (m, 2H). Preparation of Intermediate 3.2 6-chloro-4-methoxy-2-(tetrahydro-2H-pyran-2-yl)-2H-pyrazolo[4,3-c]pyridine A solution of 4,6-dichloro-2-(tetrahydro-2H-pyran-2-yl)-2H-pyrazolo[4,3-c]pyridine (2.3 g, 8.45 mmol) in MeONa / MeOH ( 20 mL, 108 mmol, 5.4 mol / L) was stirred at 60 °C for 2 h. The mixture was poured into water (100 mL) and extracted with EtOAc (80 mL, 3x).The combined organic layer was washed with brine (30 mL, 2x), dried over anhydrous Na2SO4, filtered and concentrated under vacuum. The residue, which was purified by column chromatography (SiO2, Petroleum ether / Ethyl acetate=10 / 1 to 3 / 1) to give the product 6-chloro-4-methoxy-2-(tetrahydro-2H-pyran-2-yl)-2H-pyrazolo[4,3-c]pyridine (2 g, 7.47 mmol, 88.39% yield) as colorless oil. LCMS RT 0.542 min (method 3); m / z 268.0. (M+H) + (ESI+).1H NMR (DMSO-d6, ,400 MHz): 8.74(s, 1H), 7.24 (s, 1H), 5.73-5.69 (m, 1H), 4.00 (s, 3H), 3.98-3.90(m, 1H), 3.75-3.65 (m, 1H), 2.24-2.10 (m, 1H), 2.05-1.97 (m, 1H), 1.96-1.89 (m, 1H), 1.77-1.64 (m, 1H), 1.60-1.51 (m, 2H) Preparation of Intermediate 3.3 6-(3,4-dimethylphenyl)-4-methoxy-2-(tetrahydro-2H-pyran-2-yl)-2H-pyrazolo[4,3-c]pyridine To a solution of 6-chloro-4-methoxy-2-(tetrahydro-2H-pyran-2-yl)-2H-pyrazolo[4,3-c]pyridine (2 g, 7.47 mmol), in 1,4-Dioxane (20 mL) and water (4 mL) were added (3,4-dimethylphenyl)boronic acid (2.24 g, 14.9 mmol), Pd(dppf)Cl2 (0.82 g, 1.12 mmol) and K2CO3 (3.10 g, 22.4 mmol). The mixture was degassed with N2 (3x), stirred at 90 °C for 16 h, then, cooled to 20 °C and filtered. The filtrate was diluted with water (100 mL) and extracted with EtOAc (80 mL, 3x). The combined organic layer was washed with brine (50 mL) and dried over anhydrous Na2SO4, filtered and concentrated. The residue was purified by flash silica gel chromatography (ISCO; 120 g SepaFlash, Silica Flash Column, Eluent of 0~30% Ethyl acetate / Petroleum etherg radient @ 100 mL / min) and concentrated under vacuum to give the product 6- (3,4-dimethylphenyl)-4-methoxy-2-(tetrahydro-2H-pyran-2-yl)-2H-pyrazolo[4,3-c]pyridine (2 g, 5.93 mmol, 79.34% yield) as a yellow solid. LCMS RT 0.639 min (method 3); m / z 338.1 (M +H) + (ESI+).1H NMR (DMSO-d6, ,400 MHz): 8.66(s, 1H), 7.92 (s, 1H), 7.86 (d, J = 8.0 Hz, 1H), 7.64 (s, 1H), 7.21 (d, J = 8.0 Hz, 1H), 5.73-5.60 (m, 1H),4.11 (s, 3H), 4.03-3.96 (m, 1H), 3.77-3.67 (m, 1H), 2.31 (s, 3H), 2.26 (s, 3H), 2.24-2.17 (m, 1H), 2.06-1.92 (m, 2H), 1.79-1.67 (m, 1H), 1.63-1.56 (m, 2H) Preparation of Intermediate 3.4 3-bromo-6-(3,4-dimethylphenyl)-4-methoxy-2-(tetrahydro-2H-pyran-2-yl)-2H-pyrazolo[4,3- c]pyridine To a stirred solution of 6-(3,4-dimethylphenyl)-4-methoxy-2-(tetrahydro-2H-pyran-2-yl)-2H- pyrazolo[4,3-c]pyridine (500 mg, 1.48 mmol) in THF (10 mL) at -78 °C was added LDA / THF (2 M, 1.5 mL, 2.96 mmol) dropwise over 5 min and the mixture was stirred at -78 °C for 1 h. Then, a solution of 1,2- dibromotetrachloroethane (965 mg, 2.96 mmol) in THF (1 mL) was added dropwise over 5 min at -78 °C and the reaction mixture was stirred at -78 °C for 2 h. The resulting mixture was poured into NH4Cl (aq, sat., 20 mL) and extracted with EtOAc (20 mL, 2x). 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 flash silica gel chromatography (ISCO; 20 g SepaFlash. Silica Flash Column, Eluent of 0~30% Ethyl acetate / Petroleum ethergradient @ 50 mL / min) and concentrated under vacuum to give the product 3-bromo-6-(3,4-dimethylphenyl)-4-methoxy-2-(tetrahydro-2H-pyran-2-yl)-2H-pyrazolo[4,3-c]pyridine (500 mg,1.20 mmol, 81.05 % yield) as a white solid LCMS RT 0.844 min (method 2); m / z 416.1 (M +H) + (ESI+).1H NMR (DMSO-d6, ,400 MHz): 7.93(s, 1H), 7.86 (d, J = 7.6 Hz, 1H), 7.69 (s, 1H), 7.22 (d, J = 7.6 Hz, 1H), 5.82-5.75 (m, 1H), 4.13 (s, 3H), 3.97-3.95 (m, 1H), 3.76-3.65 (m, 1H), 2.45-2.36 (m, 1H), 2.30 (s, 3H), 2.26 (s, 3H), 2.11-1.98 (m, 2H), 1.82-1.69 (m, 1H), 1.60-1.59 (m, 2H) Preparation of Intermediate 3.5 3-((6-(3,4-dimethylphenyl)-4-methoxy-2-(tetrahydro-2H-pyran-2-yl)-2H-pyrazolo[4,3- c]pyridin-3-yl)amino)-2,3-dihydrothiophene 1,1-dioxide To a solution of 3-bromo-6-(3,4-dimethylphenyl)-4-methoxy-2-(tetrahydro-2H-pyran-2-yl)-2H-pyrazolo[4,3- c]pyridine (100 mg, 0.240 mmol) and 3-amino-2,3-dihydrothiophene 1,1-dioxide hydrobromide (154 mg, 0.721 mmol) in 1,4-dioxane (5 mL) were added Cs2CO3 (470 mg, 1.44 mmol) and Pd-PEPPSI-IPentCl o-picoline (2- methylpyridine) (61 mg, 0.0721 mmol). The suspension was degassed with N2 (3x) and stirred at 100 °C for 16 h. The resulting mixture was cooled to 20 °C and collected by filtration. The filtrate was diluted with water (40 mL) and extracted with EtOAc (40 mL, 2x). The combined organic layer was washed with brine (40 mL, 2x), dried over anhydrous Na2SO4, filtered and concentrated under vacuum. The residue was purified by preparative TLC (petroleum ether: EtOAc = 1:2) and concentrated under vacuum to give the product 3-((6-(3,4-dimethylphenyl)-4- methoxy-2-(tetrahydro-2H-pyran-2-yl)-2H-pyrazolo[4,3-c]pyridin-3-yl)amino)-2,3-dihydrothiophene 1,1-dioxide (30 mg, 0.0640 mmol, 26.65% yield) as a yellow solid RT 0.695 min (method 2); m / z 469.2 (M+H) + (ESI+).1H NMR (DMSO-d6, ,400 MHz): 7.92 (s, 1H), 7.86 (d, J= 7.6 Hz, 1H), 7.43 (s, 1H), 7.28 (d, J = 7.6 Hz, 1H), 7.21 (d, J = 8.0, 3.2 Hz, 1H) 7.02 (d, J = 8.0, 3.2 Hz, 1H), 6.55-6.50(m, 1H), 5.69-5.63 (m, 1H), 5.47-5.26 (m, 1H), 4.12 (s, 3H), 3.96-3.89 (m, 1H), 3.88-3.82 (m, 1H), 3.82-3.75 (m, 1H), 3.45-3.39 (m, 1H) , 2.28-2.27 (m, 1H), 2.27 (s, 3H), 2.26 (s, 3H), 2.11-1.98 (m, 1H), 1.95-1.90 (m, 1H), 1.75-1.65 (m, 1H), 1.60-1.50 (m, 2H). Preparation of Example 3 6-(3,4-dimethylphenyl)-3-((1,1-dioxido-2,3-dihydrothiophen-3-yl)amino)-1,5-dihydro-4H- To a solution of 3-(5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)-8-((3S,5S)-3,5-dimethylpiperazin-1-yl)-N-(1- methylcyclopropyl)imidazo[1,5-a]pyridine-6-sulfonamide (30 mg, 0.0640 mmol) in DMF (0.5 mL) were added TsOH (55 mg, 0.320 mmol) and LiCl (14 mg, 0.320 mmol). The mixture was stirred at 100 °C for 3 h, then poured into NaHCO3(aq, sat., 5 mL) and extracted with EtOAc (5 mL, 3x). The combined organic layers was washed with brine (5 mL, 2x), dried over anhydrous Na2SO4, filtered and concentrated under vacuum. The residue purified by preparative HPLC (column: Phenomenex luna C18150*25mm* 10µm;mobile phase: A: 0.225% TFA in water, B: MeCN; B%: 13%-43%,10 min) and lyophilized to give the product 6-(3,4-dimethylphenyl)-3-((1,1-dioxido-2,3- dihydrothiophen-3-yl)amino)-1,5-dihydro-4H-pyrazolo[4,3-c]pyridin-4-one trifluoroacetate ( 3.6 mg, 0.00741 mmol, 9.92% yield) as a white solid. LCMS: RT 0.446 min (method 3); m / z 371.1 (M+H)+ (ESI+).; 1H NMR (DMSO-d6, 400 MHz): 12.16(s, 1H), 10.85 (s, 1H), 7.52 (s, 1H), 7.43 (d, J = 7.6 Hz, 1H), 7.21 (d, J = 7.6 Hz, 1H), 7.15 (dd, J = 6.8, 2.4Hz, 1H), 7.02 (dd, J = 6.8, 2.4 Hz, 1H), 6.43 (s, 1H), 6.19-5.93 (br, 1H,, 5.15-5.13 (m, 1H), 3.75-3.65 (m,1H), 3.43-3.37 (m, 1H), 2.30 (s, 3H), 2.26 (s, 3H). Preparation of Intermediate 29.1 3-bromo-6-chloro-4-phenoxy-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-d]pyrimidine To a solution of 3-bromo-4,6-dichloro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-d]pyrimidine (experimental description provided in WO2016 / 116752 & WO2020 / 23323) (1.00 g, 2.51 mmol) in DMF (8 mL) was added K2CO3(1041 mg, 7.53 mmol) and the resulting mixture was cooled to 0° C. Then, a solution of phenol (236 mg, 2.51 mmol) in DMF (2 mL) was added over 20 min. The mixture was stirred at 20 ºC for 2 h, then poured into water (50 mL) and the aqueous layer was extracted with DCM (50 mL, 2x). The combined organic layer was washed with brine (100 mL), dried over anhydrous Na2SO4, filtered and concentrated under vacuum. The residue was purified by flash silica gel chromatography (ISCO; 80 g SepaFlash Silica Flash Column, Eluent of 0~20% Ethyl acetate / Petroleum ether gradient @ 100 mL / min) to give the product 3-bromo-6-chloro-4-phenoxy-1-((2- (trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-d]pyrimidine (488 mg, 1.07 mmol, 42.63% yield) as a white solid.LCMS RT 0.688 min (Method 4); m / z 457.0 (M+H+2)+ (ESI+).1H NMR (DMSO-d6, 400 MHz) 7.62-7.47 (m,2H), 7.45-7.29 (m, 3H), 5.67 (s, 2H), 3.62 (t, J = 8.0 Hz, 2H), 0.87 (t, J = 8.0 Hz, 2H), 0.04(s, 9H)Preparation of Intermediate 29.2 3-bromo-N-isopropyl-N-methyl-4-phenoxy-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4- d]pyrimidin-6-amine To a solution of 3-bromo-6-chloro-4-phenoxy-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4- d]pyrimidine (500 mg, 1.10 mmol) in DMF (10 mL) was added K2CO3(303 mg, 2.19 mmol) and the solution was stirred at 25 °C for 10 min. Then, N-methylpropan-2-amine (120 mg, 1.65 mmol) was added and the solution was stirred at 25 °C for 1 hr. The mixture was then poured into water (50 mL) and the aqueous layer was extracted with DCM (50 mL, 2x). The combined organic layer was washed with brine (100 mL), dried over anhydrous Na2SO4, filtered and concentrated under vacuum. The residue was purified by flash silica gel chromatography (ISCO; 80 g SepaFlash Silica Flash Column, Eluent of 0 ~ 20% Ethyl acetate / Petroleum ether gradient @ 100 mL / min) to give the product 3-bromo-N-isopropyl-N-methyl-4-phenoxy-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4- d]pyrimidin-6-amine (488 mg, 0.991 mmol, 90.33% yield) as a colorless oil. LCMS RT 0.826 min (Method 4); m / z 494.1 (M+H+2)+ (ESI+); 1H NMR (DMSO-d6, 400 MHz): 7.51 - 7.42(m, 2H), 7.34 - 7.28 (m, 3H), 5.48 (m, 2H), 4.95 - 4.32 (m, 1H), 3.60 (t, J = 8.4 Hz, 2H), 3.00 - 2.59 (m, 3H), 1.15 -0.92 (m, 6H), 0.86 (t, J = 8.4 Hz, 2H), 0.06 (s, 9H)Preparation of Intermediate 29.3 Tert-butyl (E)-(4-(methylsulfonyl)but-3-en-2-yl)carbamate To a mixture of diethyl ((methylsulfonyl)methyl)phosphonate (133 mg, 0.577 mmol) in THF (1 mL) was added K2CO3(199 mg, 1.44 mmol), the mixture was stirred at 20 °C for 10 min, then a solution of tert-butyl (1-oxopropan- 2-yl)carbamate (100 mg, 0.577 mmol) in THF (1.5 mL) was added to above mixture. The reaction was stirred at 60 °C for 12 h. The mixture was poured into water (10 mL). The aqueous phase was extracted with ethyl acetate (10 mL, 2x). The combined organic phase was washed with brine (20 mL), dried with anhydrous Na2SO4, filtered and concentrated in vacuum. The residue was purified by flash silica gel chromatography (ISCO; 20 g SepaFlash Silica Flash Column, Eluent of 0 ~ 70% Ethyl acetate / Petroleum ether gradient @ 80 mL / min) to give the product tert- butyl (E)-(4-(methylsulfonyl)but-3-en-2-yl)carbamate (120 mg, 0.481 mmol, 83.37 % yield) as a white solid. 1H NMR (400 MHz, DMSO-d6): 7.16 (d, J = 7.2 Hz, 1H), 6.70-6.61 (m, 2H), 4.27-4.26 (m, 1H), 2.99 (s, 3H),1.39 (s, 9H), 1.16 (d, J = 7.2 Hz, 3H)Preparation of Intermediate 29.4 (E)-4-(methylsulfonyl)but-3-en-2-amine 2,2,2-trifluoroacetate To a solution of tert-butyl (E)-(4-(methylsulfonyl)but-3-en-2-yl)carbamate (120 mg, 0.481 mmol) in DCM (2 mL) was added TFA (1 mL, 14.3 mmol). The reaction mixture was stirred at 20 °C for 2 hours and concentrated under vacuum. The resulting residue was triturated with MTBE (5 mL) at 20 °C for 20 min, filtered and dried under vacuum to give (E)-4-(methylsulfonyl)but-3-en-2-amine 2,2,2-trifluoroacetate (114 mg, 0.433 mmol, 89.98% yield) as a white solid. .1H NMR (400 MHz, DMSO-d6): 8.41 - 8.19 (m, 3H), 7.00 (d, J = 15.2 Hz, 1H), 6.74 (dd, J = 15.2, 10.4 Hz,1H), 4.16 - 4.05 (m, 1H), 3.05 (s, 3H), 1.33 (d, J = 8 Hz, 3H)Preparation of Intermediate 29.5 (E)-N6-isopropyl-N6-methyl-N3-(4-(methylsulfonyl)but-3-en-2-yl)-4-phenoxy-1-((2- (trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-d]pyrimidine-3,6-diamine To a solution of 3-bromo-N-isopropyl-N-methyl-4-phenoxy-1-((2-(trimethylsilyl)ethoxy)methyl)-1H- pyrazolo[3,4-d]pyrimidin-6-amine (60 mg, 0.122 mmol) and (E)-4-(methylsulfonyl)but-3-en-2-amine 2,2,2- trifluoroacetate (96 mg, 0.365 mmol) in 1,4-Dioxane (1 mL) was added Cs2CO3 (238 mg, 0.731 mmol) and Pd- PEPPSI-IPent Cl o-picoline (51 mg, 0.0609 mmol). The reaction mixture was stirred at 100 °C for 16 h and poured into water (10 mL). The aqueous layer was extracted with ethyl acetate (10 mL, 2x). The combined organic layer was washed with brine (10 mL), dried over anhydrous Na2SO4, filtered and concentrated under vacuum. The residue was purified by preparative TLC ( petroleum ether : ethyl acetate = 5 : 1) to give the product (E)-N6-isopropyl-N6- methyl-N3-(4-(methylsulfonyl)but-3-en-2-yl)-4-phenoxy-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4- d]pyrimidine-3,6-diamine (5.0 mg, 0.00892 mmol, 7.32% yield) as a yellow solid. LCMS RT 0.861 min (Method 5); m / z 561.4 (M+H)+ (ESI+); 1H NMR (CDCl3, 400 MHz) 7.46 - 7.40 (m, 2H),7.27 - 7.22 (m, 3H), 6.97 (dd, J = 15.2, 10.4 Hz, 1H), 6.62 (d, J = 15.2 Hz, 1H), 5.49 - 5.35 (m, 2H), 4.82 - 4.72(m, 1H), 4.44 - 4.35 (m, 1H), 3.63 (t, J = 8.4 Hz, 2H), 2.93 (s, 3H), 2.85 (s, 3H), 1.46 (d, J = 7.2 Hz, 3H), 1.11 -1.01 (m, 6H), 0.96 (t, J = 8.4 Hz , 2H), 0.01 (s, 9H)Preparation of Example 29 (E)-N6-isopropyl-N6-methyl-N3-(4-(methylsulfonyl)but-3-en-2-yl)-4-phenoxy-1H-pyrazolo[3,4- d]pyrimidine-3,6-diamine 2,2,2-trifluoroacetate To a solution of (E)-N6-isopropyl-N6-methyl-N3-(4-(methylsulfonyl)but-3-en-2-yl)-4-phenoxy-1-((2- (trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-d]pyrimidine-3,6-diamine (5.0 mg, 0.00892 mmol) in DCM (1 mL) was added TFA (0.50 mL, 7.16 mmol). The mixture was stirred at 20 °C for 2 h and concentrated under vacuum. The residue was purified by prep-HPLC (column: Welch Ultimate C18150*25mm*5um; mobile phase: A: 0.1% trifluoroacetic acid in water, B: MeCN; B%: 13%-43%, 10min) and lyophilized directly to give the product (E)-N6- isopropyl-N6-methyl-N3-(4-(methylsulfonyl)but-3-en-2-yl)-4-phenoxy-1H-pyrazolo[3,4-d]pyrimidine-3,6-diamine 2,2,2-trifluoroacetate (2.0 mg, 0.00455 mmol, 51.05% yield) as a brown gum. LCMS RT 0.478 min (Method 4); m / z 431.1 (M+H)+ (ESI+) 1H NMR (400 MHz, DMSO-d6) 11.86 - 11.66 (m,1H), 7.48 - 7.42 (m, 2H), 7.32 - 7.25 (m, 3H), 6.87 (dd, J = 15.2, 10.4 Hz, 1H), 6.74 (d, J = 15.2 Hz, 1H), 5.77 (s,1H), 4.59-4.50 (m, 1H), 2.98 (s, 3H), 2.80 (s, 3H), 1.37 (t, J = 8.4 Hz, 3H), 1.04 - 0.94 (m, 6H)The following Table 1 provides an overview on the compounds described in the example section: Table 1 Example No. Structure Name of compound3-((3-(3,4-dimethylphenyl)-1- methoxyisoquinolin-8-yl)amino)-2,3-dihydrothiophene 1 1,1-dioxide 23-(3,4-dimethylphenyl)-8-((1,1-dioxido-2,3-dihydrothiophen-3-yl)amino)isoquinolin-1(2H)-one2a (R or S)-3-(3,4-dimethylphenyl)-8-((1,1-dioxido-2,3-dihydrothiophen-3-yl)amino)isoquinolin-1(2H)-one2b (S or R)-3-(3,4-dimethylphenyl)-8-((1,1-dioxido-2,3-dihydrothiophen-3-yl)amino)isoquinolin-1(2H)-one6-(3,4-dimethylphenyl)-3-((1,1-dioxido-2,3- 3 dihydrothiophen-3-yl)amino)-1,5-dihydro-4H- pyrazolo[4,3-c]pyridin-4-one trifluoroacetate (E)-N6-isopropyl-N6-methyl-N3-(4-(methylsulfonyl)but- 3-en-2-yl)-4-phenoxy-1H-pyrazolo[3,4-d]pyrimidine- 29 3,6-diamine 2,2,2-trifluoroacetate The examples listed in the table below were produced using similar experimental procedures as reported for the example 1 to 3 or 29. Exampl LC / MS & Name of Structure e No. SFC data compound LCMS: RT 0.422 min (method 3); m / z 354.1 3-((6-(3,4-dimethylphenyl)- (M+H)+(ESI+). SFC: RT 1H-pyrrolo[3,2-b]pyridin-3- 4 2.136 min, 2.431 min, yl)amino)-2,3- (Method 2) dihydrothiophene 1,1-dioxide 2,2,2-trifluoroacetate LCMS: RT 0.460 min (method 3); m / z 368.1 3-((6-(3,4-dimethylphenyl)-1- (M+H)+ (ESI+). SFC: methyl-1H-pyrrolo[3,2- 5 RT 1.560 min, 1.746 b]pyridin-3-yl)amino)-2,3- min, (Method 3) dihydrothiophene 1,1-dioxide 2,2,2-trifluoroacetate LCMS: RT 0.740 min 3-((3-(3,4- (method 2); m / z 365.2 dimethylphenyl)quinolin-8- (M+H)+ (ESI+). yl)amino)-2,3- dihydrothiophene 1,1-dioxide LCMS: RT 0.437 min (R)-3-((6-phenyl-1H- (method 3); m / z 327.1 pyrazolo[4,3-b]pyridin-3- (M+H)+ (ESI+). SFC: yl)amino)-2,3- RT 2.173 min, 86.9% dihydrothiophene 1,1-dioxide ee (Method 4) 2,2,2-trifluoroacetate LCMS: RT 0.413 min (method 3); m / z 343.0 (R)-3-((1,1-dioxido-2,3- (M+H)+ (ESI+). SFC: dihydrothiophen-3-yl)amino)- RT 1.959 min, 84.70% 6-phenyl-1H-pyrazolo[4,3- ee (Method 5) b]pyridine 4-oxide 2,2,2- trifluoroacetate LCMS: RT 0.544 min (method 2); m / z 341.1 (R)-3-((1-methyl-6-phenyl-1H- (M+H)+ (ESI+). SFC: pyrazolo[4,3-b]pyridin-3- RT 1.747 min, 85.17% yl)amino)-2,3- ee (Method 6) dihydrothiophene 1,1-dioxide LCMS: RT 0.436min (method 3); m / z 357.1 (R)-3-((1,1-dioxido-2,3- (M+H)+ (ESI+). SFC: dihydrothiophen-3-yl)amino)- RT 2.116 min, 86.45% 1-methyl-6-phenyl-1H- ee (Method 7) pyrazolo[4,3-b]pyridine 4- oxide LCMS: RT 0.482min (method 3); m / z 372.0 6-(3,4-dimethylphenyl)-3- (M+H)+ (ESI+). SFC: ((1,1-dioxido-2,3- RT 2.282, 2.432 min, dihydrothiophen-3- (Method 2) yl)amino)isoxazolo[4,5- c]pyridin-4(5H)-one LCMS: RT 0.453min (R)-3-(3,4-dimethylphenyl)-8- (method 3); m / z 382.1 ((1,1-dioxido-2,3- (M+H)+ (ESI+). SFC: dihydrothiophen-3-yl)amino)- RT 1.811 min, 75.44% 2,6-naphthyridin-1(2H)-one ee (Method 8) LCMS: RT 0.404min (R)-7-(3,4-dimethylphenyl)-4- (method 3); m / z 382.1 ((1,1-dioxido-2,3- (M+H)+ (ESI+). SFC: dihydrothiophen-3-yl)amino)- RT 2.093 min, 87.47% 1,6-naphthyridin-5(6H)-one ee (Method 3) LCMS: RT 0.588min (R)-3-(3,4-dimethylphenyl)-8- (method 3); m / z 399.1 ((1,1-dioxido-2,3- (M+H)+ (ESI+). SFC: dihydrothiophen-3-yl)amino)- RT 2.116 min, 82.40% 7-fluoroisoquinolin-1(2H)-one ee (Method 6) LCMS: RT 0.558min (R)-3-(3,4-dimethylphenyl)-8- (method 3); m / z 399.1 ((1,1-dioxido-2,3- (M+H)+ (ESI+). SFC: dihydrothiophen-3-yl)amino)- RT 2.652 min, 87.12% 6-fluoroisoquinolin-1(2H)-one ee (Method 4) LCMS: RT 0.564min (R)-3-(3,4-dimethylphenyl)-8- (method 3); m / z 399.0 ((1,1-dioxido-2,3- (M+H)+ (ESI+). SFC: dihydrothiophen-3-yl)amino)- RT 1.590 min, 100% ee 5-fluoroisoquinolin-1(2H)-one (Method 3) LCMS: RT 0.560 min (S,E)-3-(3,4-dimethylphenyl)- (method 3); m / z 397.1 8-((4-(methylsulfonyl)but-3- (M+H)+ (ESI+). SFC: en-2-yl)amino)isoquinolin- RT 1.838 min, 94.35% 1(2H)-one ee (Method 5) LCMS: RT 0.741min (R)-3-((7-(3,4- (method 3); m / z 396.2 dimethylphenyl)-5-methoxy- (M+H)+ (ESI+). SFC: 1,6-naphthyridin-4-yl)amino)- RT 2.010 min, 88.59% 2,3-dihydrothiophene 1,1- ee (Method 3) dioxide LCMS: RT 0.635min (R)-3-((3-(3,4- (method 3); m / z 413.3 dimethylphenyl)-7-fluoro-1- (M+H)+ (ESI+). SFC: methoxyisoquinolin-8- RT 1.199 min, 100% ee yl)amino)-2,3- (Method 3) dihydrothiophene 1,1-dioxide LCMS: RT 0.622min (R)-3-((3-(3,4- (method 3); m / z 413.1 dimethylphenyl)-6-fluoro-1- (M+H)+ (ESI+). SFC: methoxyisoquinolin-8- RT 1.306 min, 88.34% yl)amino)-2,3- ee (Method 3) dihydrothiophene 1,1-dioxide LCMS: RT 0.773min (R)-3-((3-(3,4- (method 2); m / z 413.1 dimethylphenyl)-5-fluoro-1- (M+H)+ (ESI+). SFC: methoxyisoquinolin-8- RT 2.288 min, 100% ee yl)amino)-2,3- (Method 4) dihydrothiophene 1,1-dioxide LCMS: RT 0.581min 3-((6-(3,4-dimethylphenyl)-4- (method 3); m / z 386.1 methoxyisoxazolo[4,5- (M+H)+ (ESI+). SFC: c]pyridin-3-yl)amino)-2,3- RT 1.219 min, 1.439 dihydrothiophene 1,1-dioxide min (Method 3) LCMS: RT 0.621min (R)-3-(3,4-dimethylphenyl)-8- (method 3); m / z 395.1 ((1,1-dioxido-2,3- (M+H)+ (ESI+). SFC: dihydrothiophen-3-yl)amino)- RT 1.478 min, 93.98% 2-methylisoquinolin-1(2H)- ee (Method 3) one LCMS: RT 0.648min (S,E)-3-(3,4-dimethylphenyl)- (method 3); m / z 411.1 1-methoxy-N-(4- 26 (M+H)+ (ESI+). SFC: (methylsulfonyl)but-3-en-2- RT 1.881 min, 93.17% yl)isoquinolin-8-amine ee (Method 4) LCMS: RT 0.762min (S,E)-N2-isopropyl-N2- (method 2); m / z 441.2 methyl-N5-(4- 27 (M+H)+ (ESI+). SFC: (methylsulfonyl)but-3-en-2-yl)- RT 1.104 min, 93.30% 4-phenoxyquinazoline-2,5- ee (Method 3) diamine LCMS: RT 0.411min 6-(3,4-dimethylphenyl)-3- (method 3); m / z 387.0 ((1,1-dioxido-2,3- 28 (M+H)+ (ESI+). SFC: dihydrothiophen-3-yl)amino)- RT 1.834 min, 2.294 7-hydroxy-1,5-dihydro-4H- min (Method 9) pyrazolo[4,3-c]pyridin-4-one Biological evaluation of the exemplary compounds Exemplary compounds of formula (I) were 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. WRN Protein Expression and Purification WRN (amino acid 517-1093, L1074F isoform) was purchased from CRELUX GmbH, Planegg, Germany. WRN was produced in a Sf21 expression system, purified, and stored and frozen in 50 mM HEPES / NaOH, 500 mM NaCl, 5% Glycerol and 0.5 mM TCEP, pH 7.5. Forked DNA Preparation The forked DNA was prepared by mixing the two DNA strands in a 1:1.8 ratio of OLIGOB-FLU (FAM(fluorescein)-GAACGA ACA CAT CGG GTA CGT TTT TTT TTT TTT TTT TTT TTT TTT TTT TT) (SEQ ID NO.: 1) to OLIGOA-BHQ1 (TTT TTT TTT TTT TTT TTT TTT TTT TTT TTT CGT ACC CGA TGT GTT CGT TC-BHQ1) (SEQ ID NO.: 2) in DNA-annealing buffer (10 mM Tris / HCl pH 7.5, 50 mM NaCl & 1 mM EDTA, pH 8.0). The mixture is heated to 95 °C and cooled down to 35 °C at a rate of 5°C per minute in a Roche LightCycler® 96 System. In vitro WRN Helicase assay A continuous, fluorescence-based helicase assay was set up to measure ATP-coupled unwinding of a forked DNA substrate by WRN (517-1093, L1074F isoform). Fluorescently labelled forked DNA was used as a DNA substrate, the DNA sequences were described by Sommers et al. 2019 (doi: 10.1371 / journal.pone.0210525), with different fluorescent dyes. WRN mediated separation of the forked DNA leads to an increase in fluorescence. ssDNA complementary to the quenching strand, oligo-block (GAA CGA ACA CAT CGG GTA CG) (SEQ ID NO.: 3), is included in 10-fold excess to prevent reannealing of the forked DNA. Labelled DNA was purchased from IDT (Integrated DNA Technologies, Inc.) and ssDNA oligo-block from Microsynth AG. Reaction A typical reaction consists of 30 µL of 1 nM WRN in 25 mM Tris / HCl pH 7.5, 100 mM NaCl, 1 mM DTT, 0.01 % TWEEN-20, 0.025 mg / mL BSA, 0.1 mM forked DNA substrate, 1 mM Oligo-BLOCK and 0.5 mM Mg-ATP in a 384 well black plate (Thermo Scientific). To assess inhibition, IC50s were determined by pre-incubating compounds (10 mM DMSO stock solutions) with WRN in a 12-point custom dilution series to a final DMSO concentration of 1 %. DMSO only controls were included to represent no inhibition (high control) Compounds and WRN were pre-incubated for 2 or 6 hours at room temperature, before the addition of forked DNA, ssDNA oligo-block, and Mg-ATP to initiate the reaction. Fluorescence (Ex: 485 nm, Em: 535 nm, gain 66, 5 flashes per measurement) was measured on a Tecan Spark plate reader for 45 minutes, in 60 seconds intervals at 27.5°C. All points were measured in triplicate. Data Analysis Data analysis was performed using dotmatics (www.dotmatics.com). Enzymatic activity was assessed by the rates of DNA unwinding, measured by the rate of increase in fluorescence. The initial slopes were normalized to % activity, as follows: percentage of activity (Normalized) = (Sample Value / High Control Value (Average of DMSO only wells)) * 100%. The resulting dose response was fitted with the following equation: Y=Bottom + (Top-Bottom) / (1+(IC50 / X)^HillSlope), where X values are concentrations and Y is the response (decreasing as X increases). The curve fitting was performed using the least squares regression method. Reported values are the mean of at least 2 independent replicates. The Absorbance IC50 value of compounds of Formula (I) in Examples 1 to 29 are provided in Table 2 below. In case there is a blank cell in the Table, this means that no data have been generated. Cellular Viability Assay The colon carcinoma cell lines HCT116 and SW48 (both microsatellite instability- high and WRN- inhibition sensitive cell lines) and SW620 (microsatellite stable and WRN-inhibition insensitive cell line) were obtained from ATCC. HCT116 were cultured in growth medium composed of McCoy's 5A (Modified) Medium (ThermoFisher Scientific Cat# 16600082), 1x Penicillin-Streptomycin (ThermoFisher Scientific Cat# 15140163), and 10% fetal bovine serum (ThermoFisher Scientific Cat#A5256801). SW48 and SW620 were cultured in growth medium composed of Leibovitz's L-15 Medium (ThermoFisher Scientific Cat#11415056), 1x Penicillin-Streptomycin and 10% fetal bovine serum. HCT116, SW48 and SW620 were plated at 1500 cells / well, 2000 cells / well and 2000 cells / well, respectively, in 96-well black plates with clear flat bottom (Huberlab #.655983), in a volume of 200 µL per well. The outer wells of the plate were filled with DPBS (ThermoFisher Scientific Cat#14190250) to compensate evaporation mediated effects in the plate periphery. After 24 hours, the compounds were dispensed with the Tecan digital dispenser (D300e), starting at 20 µM for a 8-point dose curve at 1:4 dilution, in duplicates. The final concentration of DMSO was normalized to the highest compound concentration and a maximum of 0.1%.. After 4d of incubation, 145 µl of the growth medium were removed and 50 µL of Cell Titer-Glo (Promega Cat#G9243) were added per well. Plates were shaken for 2 minutes and after an incubation of 10 minutes, luminescence was read using a plate reader (Tecan Spark). For data analysis, the assay background signal which was determined in wells that contained medium only was subtracted from all the data points. Averaged values of the samples were normalized to DMSO treated control samples. The fitting of the logistic curve were performed using the following equation: Y=Bottom + (Top-Bottom) / (1+(IC50 / X)^HillSlope), where X values are concentrations and Y is the response (decreasing as X increases). The curve fitting was performed using the least squares regression method. The IC50 value of compounds of Formula (I) in Examples 1 to 29 are provided in Table 2 below. In case there is a blank cell in the Table, this means that no data have been generated. Table 2 Example number IC50 in M determined in WRN helicase assay described under In vitro WRN Helicase assayfollowing 2 hours incubation IC50 in M determined in WRN helicase assay described under In vitro WRN Helicase assay following6 hours incubation IC50 in M determined in SW48 assay described under Cellular viability assayIC50 in M determined in HCT116 assay described under Cellular viability assayIC50 in M determined in SW620 assay described under Cellular viability assay1 10002 0.726 (63%0.239 (70% inhibition at inhibition at 100µM) 100µM) 2a 17.12b 0.365 0.1483 0.300 0.0924 32.1 6.1553 8.266 >15.85 150 6.361 6.7716 2007 4.05 1.98 0.744 0.3019 12510 39 21.711 0.093 0.047 1.673 8.141 >2012 0.02 0.013 2.351 2.696 5.03113 0.223 1.583 0.915 0.54714 0.34 0.17515 0.5865 0.23916 2.418 10019 18.520 4.321 100022 100023 1.6 1.524 10026 100027 1000 4.071 5.52928 1.7529 1.3 0.714 1.010 >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 shaken in an orbital shaker for 24 hr at room temperature .5. 200 L of each solubility solution were transferred 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, 2hours; 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 Assay1. 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.006161.3 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, labeled 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 uL) 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 M) was added into the 'incubation' plates(T60 and NCF60) containing microsomes and mixed 3 times thoroughly. For the 'Incubation' NCF60 plate, 50 uL 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 AnalysisConcentrations 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 following equation: CLint(mic) = 0.693 / T1 / 2 / mg microsome protein per mL CLint(liver) = CLint(mic) × mg microsomal protein / g liver weight × g liver weight / kg body weight According to the well-stirred model, hepatic intrinsic clearance and hepatic clearance can be calculated by the following formula. CL(liver) = (CLint(liver) × fu × Qh) / (CLint(liver) × fu + Qh) The default value of fu (the fraction unbound in blood) is assumed as 1. The parameters in equations are listed in following table. Liver Weight Hepatic Blood Flow (Qh) Microsomal Protein (g / kg Body Weight)[1-2](mL / min / kg)[1-2](mg / g liver weight) Mouse 88 90.0Rat 40 55.2Dog 32 30.945 Monkey 30 43.6Human 20 20.7When the %Remaining value at the maximal incubation time, which was 60 min in this study, was higher than 75%, it is considered to be within the acceptable experimental variation, i.e., CV =25%. Therefore, a corresponding T1 / 2 value of >145 min is reported. Consequently, the correspondingCLint(mic)value is reported as <9.6 L / min / mg protein.6. References[1] Brian Davies and Tim Morris, Physiological Parameters in Laboratory Animals and Human. Pharmaceutical Research, Vol.10 No.7, 1993 [2] Journal of Pharmacology and Experimental Therapeutics, 1997, 283(1): 46-58 Hepatocyte Metabolic Stability1. Materials1.1 Hepatocyte Animal or human hepatocytes were purchased from BioreclamationIVT or RILD.1.2 Control compounds: 7-Ethoxycoumarin and 7-Hydroxycoumarin2. Preparation of Working SolutionStock Solution: 10 mM test compound and 30 mM control compound in DMSO. Working solution: 100 µM test compound or 300 µM control compounds in 100% acetonitrile (Concentration of organic solvent: 1% (v / v) DMSO and 99% (v / v) acetonitrile)3. Assay ProcedureCryopreserved hepatocytes were thawed, isolated, and suspended in Williams’ Medium E, then diluted with pre-incubated Williams’ Medium E to a final concentration of 0.510×106 cells / mL.One hundred and ninety-eight (198) L of cells suspension (0.510×106 cells / mL) were added intoappropriate wells. The incubation plate was pre-incubated in a 37.0 C incubator for about 10minutes. Then 2 L of test compound and positive controls were added into plate except for theblank plate. Incubate all plates at 37.0°C in a 95.0% humidified incubator at 5.0% CO2 to start the reactions with constant shaking. For the T0 plate, a corresponding quenching plate was prepared by adding 125 µL / well of acetonitrile containing 200 ng / mL tolbutamide and 200 ng / mL labetalol as internal standards (stop solution), and 25 µL / well of the incubation sample were transferred to this plate after shaking for 1 minute to ensure homogeneity. At each time-point, the corresponding plate was removed from the incubator, and 25 µL / well of the corresponding sample was transferred to its corresponding quenching plate containing 125 µL / well of stop solution. Medium control (MC) plates (T0-MC and T90-MC) were prepared by adding everything except for Williams’ Medium E at the corresponding time-points. The plates were then sealed and shaken for 10 minutes prior to centrifugation at 4000 rpm and 4°C for 20 minutes. 80 µL / well of the resulting supernatant were diluted with 240 µL / well of pure water and sealed and shaken for 10 minutes prior to LC-MS / MS analysis.4. Bioanalytical AnalysisConcentrations of test compounds and positive controls, 7-Ethoxycoumarin and 7- Hydroxycoumarin 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 following equation: CLint (hep) = k / million cells per mL CLint (liver) = CLint (hep) × liver weight (g / kg body weight) × hepatocellularity According to the well-stirred model, hepatic intrinsic clearance and hepatic clearance can be calculated by the following formula. CL(liver) = (CLint(liver) × fu× Qh) / (CLint(liver) × fu+ Qh) The default value of fu (the fraction unbound in blood) is assumed as 1. The parameters in equations are listed in following table. Liver Weight (g / kg BodyLiver Blo Hepatocellularity Speciesod Flow Weight) [2-3](Qh) (mL / min / kg)[2-3] Mouse 88 90.0 135×106Rat 40 55.2 117×106Dog 32 30.9 215×106Monkey 30 43.6 120×106Human 20 20.7 139×106When the %Remaining value at the maximal incubation time, which was 90 min in this study, was higher than 75%, it is considered to be within the acceptable experimental variation, i.e., CV =25%. Therefore, a corresponding T1 / 2 value of >216.8 min is reported. Consequently, the corresponding CLint(hep) (µL / min / 106 cells) is reported as <7.5.6. References[1] Anna-Karin Sohlenius-Sternbeck. Determination of the hepatocellularity number for human, dog, rabbit, rat and mouse livers from protein concentration measurements. Toxicology in Vitro, Vol.20 No.8, 2006 [2] Brian Davies and Tim Morris, Physiological Parameters in Laboratory Animals and Human. Pharmaceutical Research, Vol.10 No.7, 1993 [3] Obach R S, Baxter J G, Liston T E, et al. The prediction of human pharmacokinetic parameters from preclinical and in vitro metabolism data [J]. Journal of Pharmacology and Experimental Therapeutics, 1997, 283(1): 46

Claims

New PCT Patent Application based on US 63 / 614,186 and US 63 / 574,703 FoRx Therapeutics AG Vossius Ref.: AG4386 PCT BS Claims1. A compound of formulaor a pharmaceutically acceptable salt thereof, wherein: A is selected from aryl, heteroaryl, heterocycloalkyl, heterocycloalkenyl, cycloalkyl, cycloalkenyl, -N(C1-5 alkyl)(C1-5 alkyl), C2-haloalkyl and –(C1-2 haloalkylene)-cycloalkyl, and C2 alkynyl, wherein said aryl, said heteroaryl, said heterocycloalkyl, said heterocycloalkenyl, said cycloalkyl and said cycloalkenyl are each optionally substituted with one or more R1, and wherein said C2 alkynyl is optionally substituted with C1-6 alkyl or C1-6 haloalkyl; B is selected from bicyclic arylene and bicyclic heteroarylene, wherein said arylene and said hereroarylene are each optionally substituted with one or more R2; X is selected from -NH-, and -NRN-, wherein RNis selected from C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, -(C0-8 alkylene)-(C1-2 haloalkyl), -(C0-8 alkylene)-heteroaryl, -(C0-8 alkylene)-aryl, -(C0-8 alkylene)-heterocycloalkyl, -(C0-8 alkylene)-heterocycloalkenyl, -(C0-8 alkylene)-cycloalkyl and - (C0-8 alkylene)-cycloalkenyl, wherein said alkyl, said alkenyl, said alkynyl and said alkylene are each optionally substituted with one or more optional substituents selected from -OH, -O(C1-5 alkyl), -SH, -NH2, -NH(C1-5 alkyl), and halogen, and wherein one or two -CH2– groups in said alkyl, said alkenyl, said alkynyl and said alkylene may independently of each other be replaced with a group selected from -O-, -S-, -NH-, -N(C1-5 alkyl)-, -CO-, -CO-NH-, -CO-N(C1-5 alkyl)-, -NH-CO-, - N(C1-5 alkyl)-CO-, C3-6 cycloalkylene and 4-6 membered heterocycloalkylene, wherein said heteroaryl, said aryl, said heterocycloalkyl, said heterocycloalkenyl, said cycloalkyl and said cycloalkenyl are each optionally substituted with one or more groups selected from R3;m is 1 or 2, wherein said -CH2- is optionally substituted with C1-4 alkyl, C1-4 haloalkyl, C3-8 cycloalkyl or 5 or 6-membered heterocyclyl, and wherein said alkenyl is optionally substituted with one or more optional substituents selected from C1-4 alkyl, -COOH, -COO(C1-4 alkyl), -CO(C1-4 alkyl), -CONH(C1-4 alkyl), -CON(C1-4 alkyl)(C1-4 alkyl), -SO3H, -SO2(C1-4 alkyl), -SO(=NRNN)-(C1-4 alkyl), -SO2NH2, -SO2NH(C1-4 alkyl), -SO2N(C1-4 alkyl)(C1-4 alkyl), -(C1-4 alkylene)N(C1-4 alkyl)(C1- 4 alkyl), -(C1-4 alkylene)(N-heterocycloalkyl), cycloalkyl, -SO2-cycloalkyl, SO(=NRNN)-cycloalkyl, heterocycloalkyl, -SO2-heterocycloalkyl, SO(=NRNN)-heterocycloalkyl, aryl, -SO2-aryl, - SO(=NRNN)-aryl, heteroaryl, -SO2-heteroaryl, -SO(=NRNN)-heteroaryl, -SO(=N-(C1-4 alkyl))- heteroaryl, -Hal, -CN and -CF3, wherein RNNis selected from H, C1-4 alkyl, cycloalkyl and aryl (preferably wherein RNNis selected from H and C1-4 alkyl), preferably substituted with one or more optional substituents selected from C1-4 alkyl, -COO(C1-4 alkyl), -CO(C1-4 alkyl), -CONH(C1-4 alkyl), -CON(C1-4 alkyl)(C1-4 alkyl), -SO2(C1-4 alkyl), -SO2NH2, -SO2NH(C1-4 alkyl), -SO2N(C1-4 alkyl)(C1-4 alkyl), -(C1-4 alkylene)N(C1-4 alkyl)(C1-4 alkyl), -(C1-4 alkylene)(N-heterocycloalkyl), cycloalkyl, heterocycloalkyl, aryl, heteroaryl, -Hal, -CN and -CF3, more preferably substituted with one or more optional substituents selected from C1-4 alkyl, -CONH-(C1-4 alkyl), and -SO2-(C1-4 alkyl),are each optionally substituted by one or more C1-6 alkyl or Hal; each R1is independently selected from C1-5 alkyl, C2-5 alkenyl, C2-5 alkynyl, -(C0-3 alkylene)-OH, -(C0-3 alkylene)-O(C1-5 alkyl), -(C0-3 alkylene)-O(C1-5 alkylene)-OH, -(C0-3 alkylene)-O(C1-5 alkylene)-O(C1-5 alkyl), -(C0-3 alkylene)-SH, -(C0-3 alkylene)-S(C1-5 alkyl), -(C0-3 alkylene)-S(C1-5 alkylene)-SH, -(C0-3 alkylene)-S(C1-5 alkylene)-S(C1-5 alkyl), -(C0-3 alkylene)-NH2, -(C0-3alkylene)-NH(C1-5alkyl), -(C0-3alkylene)-N(C1-5alkyl)(C1-5alkyl), -(C0-3alkylene)-NH-OH, -(C0-3 alkylene)-N(C1-5 alkyl)-OH, -(C0-3 alkylene)-NH-O(C1-5 alkyl), -(C0-3 alkylene)-N(C1-5 alkyl)-O(C1-5 alkyl), -(C0-3 alkylene)-halogen, -(C0-3 alkylene)-(C1-5 haloalkyl), -(C0-3 alkylene)-O-(C1-5 haloalkyl), -(C0-3 alkylene)-CN, -(C0-3 alkylene)-NO2, -(C0-3 alkylene)-CHO, -(C0-3 alkylene)-CO-(C1-5 alkyl), -(C0-3 alkylene)-COOH, -(C0-3 alkylene)-CO-O-(C1-5 alkyl), -(C0-3 alkylene)-O-CO-(C1-5 alkyl), -(C0-3 alkylene)-CO-NH2, -(C0-3 alkylene)-CO-NH(C1-5 alkyl), -(C0-3 alkylene)-CO-N(C1-5 alkyl)(C1-5 alkyl), -(C0-3 alkylene)-NH-CO-(C1-5 alkyl), -(C0-3 alkylene)-N(C1-5 alkyl)-CO-(C1-5 alkyl), -(C0-3 alkylene)-NH-CO-O-(C1-5 alkyl), -(C0-3 alkylene)-N(C1-5 alkyl)-CO-O-(C1-5 alkyl), -(C0-3 alkylene)-O-CO-NH-(C1-5 alkyl), -(C0-3 alkylene)-O-CO-N(C1-5 alkyl)-(C1-5 alkyl), -(C0-3 alkylene)-SO2-NH2, -(C0-3 alkylene)-SO2-NH(C1-5 alkyl), -(C0-3 alkylene)-SO2-N(C1-5 alkyl)(C1-5 alkyl), -(C0-3 alkylene)-NH-SO2-(C1-5 alkyl), -(C0-3 alkylene)-N(C1-5 alkyl)-SO2-(C1-5 alkyl), -(C0-3 alkylene)-SO2-(C1-5 alkyl), -(C0-3 alkylene)-SO-(C1-5 alkyl), -(C0-3 alkylene)-Si(C1-5 alkyl)(C1-5 alkyl)(C1-5 alkyl), -(C0-3 alkylene)-SF5, -O-(C0-3 alkylene)-carbocyclyl, -O-(C0-3 alkylene)-heterocyclyl, -(C0-3 alkylene)-carbocyclyl, and -(C0-3 alkylene)-heterocyclyl, wherein the carbocyclyl moiety in said -O-(C0-3 alkylene)-carbocyclyl, the carbocyclyl moiety in said -(C0-3 alkylene)-carbocyclyl, the heterocyclyl moiety in said -O-(C0-3 alkylene)-heterocyclyl and the heterocyclyl moiety in said -(C0-3 alkylene)-heterocyclyl are each optionally substituted with one or more groups independently selected from C1-4 alkyl, halogen, -CN, -NO2, -OH, -O-(C1-4 alkyl), -SH, -S-(C1-4 alkyl), -NH2, -NH(C1-4 alkyl), -N(C1-4 alkyl)(C1-4 alkyl), -COOH, -COO(C1-4 alkyl), - CONH2, -CONH(C1-4 alkyl), -CON(C1-4 alkyl)(C1-4 alkyl), -NHCO(C1-4 alkyl) and -N(C1-4 alkyl)- CO(C1-4alkyl); each R2is independently selected from C1-5 alkyl, C2-5 alkenyl, C2-5 alkynyl, -(C0-3 alkylene)-OH, -(C0-3 alkylene)-O(C1-5 alkyl), -(C0-3 alkylene)-O(C1-5 alkylene)-OH, -(C0-3 alkylene)-O(C1-5 alkylene)-O(C1-5 alkyl), -(C0-3 alkylene)-SH, -(C0-3 alkylene)-S(C1-5 alkyl), -(C0-3 alkylene)-S(C1-5 alkylene)-SH, -(C0-3 alkylene)-S(C1-5 alkylene)-S(C1-5 alkyl), -(C0-3 alkylene)-NH2, -(C0-3 alkylene)-NH(C1-5 alkyl), -(C0-3 alkylene)-N(C1-5 alkyl)(C1-5 alkyl), -(C0-3 alkylene)-NH-OH, -(C0-3 alkylene)-N(C1-5 alkyl)-OH, -(C0-3 alkylene)-NH-O(C1-5 alkyl), -(C0-3 alkylene)-N(C1-5 alkyl)-O(C1-5 alkyl), -(C0-3 alkylene)-halogen, -(C0-3 alkylene)-(C1-5 haloalkyl), -(C0-3 alkylene)-O-(C1-5 haloalkyl), -(C0-3 alkylene)-CN, -(C0-3 alkylene)-NO2, -(C0-3 alkylene)-CHO, -(C0-3alkylene)-CO-(C1-5alkyl), -(C0-3alkylene)-COOH, -(C0-3alkylene)-CO-O-(C1-5 alkyl), -(C0-3 alkylene)-O-CO-(C1-5 alkyl), -(C0-3 alkylene)-CO-NH2, -(C0-3 alkylene)-CO-NH(C1-5 alkyl), -(C0-3 alkylene)-CO-N(C1-5 alkyl)(C1-5 alkyl), -(C0-3 alkylene)-NH-CO-(C1-5 alkyl), -(C0-3 alkylene)-N(C1-5 alkyl)-CO-(C1-5 alkyl), -(C0-3 alkylene)-NH-CO-O-(C1-5 alkyl), -(C0-3 alkylene)-N(C1-5 alkyl)-CO-O-(C1-5 alkyl), -(C0-3alkylene)-O-CO-NH-(C1-5 alkyl), -(C0-3 alkylene)-O-CO-N(C1-5 alkyl)-(C1-5 alkyl), -(C0-3 alkylene)-SO2-NH2, -(C0-3 alkylene)-SO2-NH(C1-5 alkyl), -(C0-3 alkylene)-SO2-N(C1-5 alkyl)(C1-5 alkyl), -(C0-3 alkylene)-NH-SO2-(C1-5 alkyl), -(C0-3 alkylene)-N(C1-5 alkyl)-SO2-(C1-5 alkyl), -(C0-3 alkylene)-SO2-(C1-5 alkyl), -(C0-3 alkylene)-SO-(C1-5 alkyl), -(C0-3 alkylene)-Si(C1-5 alkyl)(C1-5 alkyl)(C1-5 alkyl), -(C0-3 alkylene)-SF5, -O-(C0-3 alkylene)-carbocyclyl, -O-(C0-3 alkylene)-heterocyclyl -(C0-3 alkylene)-carbocyclyl, and -(C0-3 alkylene)-heterocyclyl, wherein the carbocyclyl moiety in said -O-(C0-3 alkylene)-carbocyclyl, the carbocyclyl moiety in said -(C0-3 alkylene)-carbocyclyl, the heterocyclyl moiety in said -O-(C0-3 alkylene)-heterocyclyl and the heterocyclyl moiety in said -(C0-3 alkylene)-heterocyclyl are each optionally substituted with one or more groups independently selected from C1-4 alkyl, halogen, -CN, -NO2, -OH, -O-(C1-4 alkyl), -SH, -S-(C1-4 alkyl), -NH2, -NH(C1-4 alkyl), -N(C1-4 alkyl)(C1-4 alkyl), -COOH, -COO(C1-4 alkyl), - CONH2, -CONH(C1-4 alkyl), -CON(C1-4 alkyl)(C1-4 alkyl), -NHCO(C1-4 alkyl) and -N(C1-4 alkyl)- CO(C1-4 alkyl); and each R3is independently selected from C1-5 alkyl, C2-5 alkenyl, C2-5 alkynyl, -(C0-3 alkylene)-OH, -(C0-3 alkylene)-O(C1-5 alkyl), -(C0-3 alkylene)-O(C1-5 alkylene)-OH, -(C0-3 alkylene)-O(C1-5 alkylene)-O(C1-5 alkyl), -(C0-3 alkylene)-SH, -(C0-3 alkylene)-S(C1-5 alkyl), -(C0-3 alkylene)-S(C1-5 alkylene)-SH, -(C0-3 alkylene)-S(C1-5 alkylene)-S(C1-5 alkyl), -(C0-3 alkylene)-NH2, -(C0-3 alkylene)-NH(C1-5 alkyl), -(C0-3 alkylene)-N(C1-5 alkyl)(C1-5 alkyl), -(C0-3 alkylene)-NH-OH, -(C0-3 alkylene)-N(C1-5 alkyl)-OH, -(C0-3 alkylene)-NH-O(C1-5 alkyl), -(C0-3 alkylene)-N(C1-5 alkyl)-O(C1-5 alkyl), -(C0-3 alkylene)-halogen, -(C0-3 alkylene)-(C1-5 haloalkyl), -(C0-3alkylene)-O-(C1-5haloalkyl), -(C0-3alkylene)-CN, -(C0-3alkylene)-NO2, -(C0-3alkylene)-CHO, -(C0-3 alkylene)-CO-(C1-5 alkyl), -(C0-3 alkylene)-COOH, -(C0-3 alkylene)-CO-O-(C1-5 alkyl), -(C0-3 alkylene)-O-CO-(C1-5 alkyl), -(C0-3 alkylene)-CO-NH2, -(C0-3 alkylene)-CO-NH(C1-5 alkyl), -(C0-3 alkylene)-CO-N(C1-5 alkyl)(C1-5 alkyl), -(C0-3 alkylene)-NH-CO-(C1-5 alkyl), -(C0-3 alkylene)-N(C1-5 alkyl)-CO-(C1-5 alkyl), -(C0-3 alkylene)-NH-CO-O-(C1-5 alkyl), -(C0-3 alkylene)-N(C1-5 alkyl)-CO-O-(C1-5 alkyl), -(C0-3 alkylene)-O-CO-NH-(C1-5 alkyl), -(C0-3 alkylene)-O-CO-N(C1-5 alkyl)-(C1-5 alkyl), -(C0-3 alkylene)-SO2-NH2, -(C0-3 alkylene)-SO2-NH(C1-5 alkyl), -(C0-3 alkylene)-SO2-N(C1-5 alkyl)(C1-5 alkyl), -(C0-3 alkylene)-NH-SO2-(C1-5 alkyl), -(C0-3 alkylene)-N(C1-5 alkyl)-SO2-(C1-5 alkyl), -(C0-3 alkylene)-SO2-(C1-5alkyl), -(C0-3alkylene)-SO-(C1-5alkyl), -(C0-3alkylene)-Si(C1-5alkyl)(C1-5alkyl)(C1-5 alkyl), -(C0-3 alkylene)-SF5, -O-(C0-3 alkylene)-carbocyclyl, -O-(C0-3 alkylene)-heterocyclyl -(C0-3 alkylene)-carbocyclyl, and -(C0-3 alkylene)-heterocyclyl, wherein the carbocyclyl moiety in said -O-(C0-3 alkylene)-carbocyclyl, the carbocyclyl moiety in said -(C0-3 alkylene)-carbocyclyl, the heterocyclyl moiety in said -O-(C0-3 alkylene)-heterocyclyl and theheterocyclyl moiety in said -(C0-3 alkylene)-heterocyclyl are each optionally substituted with one or more groups independently selected from C1-4 alkyl, halogen, -CN, -NO2, -OH, -O-(C1-4 alkyl), -SH, -S-(C1-4 alkyl), -NH2, -NH(C1-4 alkyl), -N(C1-4 alkyl)(C1-4 alkyl), -COOH, -COO(C1-4 alkyl), - CONH2, -CONH(C1-4 alkyl), -CON(C1-4 alkyl)(C1-4 alkyl), -NHCO(C1-4 alkyl) and -N(C1-4 alkyl)- CO(C1-4 alkyl).

2. The compound of claim 1, wherein A is selected from aryl, heteroaryl and cycloalkyl, wherein saidaryl, said heteroaryl and said cycloalkyl are each optionally substituted with one or more R1.

3. The compound of claim 2, wherein A is selected from:, ,4. The compound of any one of claims 1 to 3, wherein B is bicyclic heteroarylene, optionallysubstituted with one or more R2.

5. The compound of claim 4, wherein B is according to formula:, and is optionally substituted with one or more R2, whereinselected from -NH-CO-, -CH=N-, -CR=N-, -CH=NO-, -N=CH-, and -N=CR-, wherein R is selected from C1-5 alkyl, C2-5 alkenyl, C2-5 alkynyl, -O(C1-5 alkyl), -S(C1-5 alkyl), -CN, NH2, -NH(C1-5 alkyl) , -N(C1-5 alkyl)(C1-5 alkyl) and Hal; Z3 is selected from -CH=CH-, -NH-, -N(C1-5 alkyl)-, -O- and -S-; Z4 is CH or N; wherein the left empty valence of B is connected to A, and the right empty valence of B is connected to X.

6. The compound of any one of claims 1 to 5, wherein B is selected from:, , ,, which are each optionally substituted with one or more R2, wherein theleft empty valence of B is connected to A, and the right empty valence of B is connected to X.

7. The compound of any one of claims 1 to 5, wherein B is selected from,left empty valence of B is connected to A, and the right empty valence of B is connected to X.

8. The compound of any one of claims 1 to 7, wherein X is -NH-.

9. The compound of any one of claims 1 to 8, wherein Y is selected from:,wherein m is 1 or 2, wherein saidoptionally substituted by one or more C1-6 alkyl or Hal.

10. The compound of any one of claims 1 to 9, whereinwherein saidoptionally substituted by one or more C1-6 alkyl or Hal.

11. The compound of claim 9 or 10, wherein m is 1.

12. The compound of any one of claims 1 to 8, Y is a moiety according to formula:wherein Ry1is selected from H, C1-4 alkyl, C1-4 haloalkyl, C3-8 cycloalkyl, and 5 or 6-membered heterocyclyl, Ry2is selected from -H, -F and -CN, and Ry3is selected from H, C1-4 alkyl, C3-8 cycloalkyl, and 5 or 6-membered heterocyclyl, and wherein the bonds drawn as indicatethat both Z and E configurations of the double bond are possible.

13. The compound of claim 1, selected from 3-((3-(3,4-dimethylphenyl)-1-methoxyisoquinolin-8-yl)amino)-2,3-dihydrothiophene 1,1-dioxide; and 3-(3,4-dimethylphenyl)-8-((1,1-dioxido-2,3-dihydrothiophen-3-yl)amino)isoquinolin-1(2H)-one or its pharmaceutically acceptable salt.

14. The compound of claim 1, wherein the compound is a compound selected from: 3-((3-(3,4-dimethylphenyl)-1-methoxyisoquinolin-8-yl)amino)-2,3-dihydrothiophene 1,1-dioxide; 3-(3,4-dimethylphenyl)-8-((1,1-dioxido-2,3-dihydrothiophen-3-yl)amino)isoquinolin-1(2H)-one; 6-(3,4-dimethylphenyl)-3-((1,1-dioxido-2,3-dihydrothiophen-3-yl)amino)-1,5-dihydro-4H- pyrazolo[4,3-c]pyridin-4-one trifluoroacetate; (E)-N6-isopropyl-N6-methyl-N3-(4-(methylsulfonyl)but-3-en-2-yl)-4-phenoxy-1H-pyrazolo[3,4- d]pyrimidine-3,6-diamine 2,2,2-trifluoroacetate; 3-((6-(3,4-dimethylphenyl)-1H-pyrrolo[3,2-b]100yridine-3-yl)amino)-2,3-dihydrothiophene 1,1- dioxide; 3-((6-(3,4-dimethylphenyl)-1-methyl-1H-pyrrolo[3,2-b]pyridin-3-yl)amino)-2,3-dihydrothiophene 1,1-dioxide; 3-((3-(3,4-dimethylphenyl)quinolin-8-yl)amino)-2,3-dihydrothiophene 1,1-dioxide; (R)-3-((6-phenyl-1H-pyrazolo[4,3-b]pyridin-3-yl)amino)-2,3-dihydrothiophene 1,1-dioxide 2,2,2- trifluoroacetate; (R)-3-((1,1-dioxido-2,3-dihydrothiophen-3-yl)amino)-6-phenyl-1H-pyrazolo[4,3-b]pyridine 4-oxide; (R)-3-((1-methyl-6-phenyl-1H-pyrazolo[4,3-b]pyridin-3-yl)amino)-2,3-dihydrothiophene 1,1- dioxide; (R)-3-((1,1-dioxido-2,3-dihydrothiophen-3-yl)amino)-1-methyl-6-phenyl-1H-pyrazolo[4,3- b]pyridine 4-oxide; 6-(3,4-dimethylphenyl)-3-((1,1-dioxido-2,3-dihydrothiophen-3-yl)amino)isoxazolo[4,5-c]pyridin- 4(5H)-one; (R)-3-(3,4-dimethylphenyl)-8-((1,1-dioxido-2,3-dihydrothiophen-3-yl)amino)-2,6-naphthyridin- 1(2H)-one; (R)-7-(3,4-dimethylphenyl)-4-((1,1-dioxido-2,3-dihydrothiophen-3-yl)amino)-1,6-naphthyridin- 5(6H)-one; (R)-3-(3,4-dimethylphenyl)-8-((1,1-dioxido-2,3-dihydrothiophen-3-yl)amino)-7-fluoroisoquinolin- 1(2H)-one; (R)-3-(3,4-dimethylphenyl)-8-((1,1-dioxido-2,3-dihydrothiophen-3-yl)amino)-6-fluoroisoquinolin- 1(2H)-one; (R)-3-(3,4-dimethylphenyl)-8-((1,1-dioxido-2,3-dihydrothiophen-3-yl)amino)-5-fluoroisoquinolin- 1(2H)-one; (S,E)-3-(3,4-dimethylphenyl)-8-((4-(methylsulfonyl)but-3-en-2-yl)amino)isoquinolin-1(2H)-one; (R)-3-((7-(3,4-dimethylphenyl)-5-methoxy-1,6-naphthyridin-4-yl)amino)-2,3-dihydrothiophene 1,1-dioxide; (R)-3-((3-(3,4-dimethylphenyl)-7-fluoro-1-methoxyisoquinolin-8-yl)amino)-2,3-dihydrothiophene 1,1-dioxide; (R)-3-((3-(3,4-dimethylphenyl)-6-fluoro-1-methoxyisoquinolin-8-yl)amino)-2,3-dihydrothiophene 1,1-dioxide; (R)-3-((3-(3,4-dimethylphenyl)-5-fluoro-1-methoxyisoquinolin-8-yl)amino)-2,3-dihydrothiophene 1,1-dioxide; 3-((6-(3,4-dimethylphenyl)-4-methoxyisoxazolo[4,5-c]pyridin-3-yl)amino)-2,3-dihydrothiophene 1,1-dioxide; (R)-3-(3,4-dimethylphenyl)-8-((1,1-dioxido-2,3-dihydrothiophen-3-yl)amino)-2-methylisoquinolin- 1(2H)-one; (S,E)-3-(3,4-dimethylphenyl)-1-methoxy-N-(4-(methylsulfonyl)but-3-en-2-yl)isoquinolin-8-amine; (S,E)-N2-isopropyl-N2-methyl-N5-(4-(methylsulfonyl)but-3-en-2-yl)-4-phenoxyquinazoline-2,5- diamine; and6-(3,4-dimethylphenyl)-3-((1,1-dioxido-2,3-dihydrothiophen-3-yl)amino)-7-hydroxy-1,5-dihydro- 4H-pyrazolo[4,3-c]pyridin-4-one, or a pharmaceutically acceptable salt thereof.

15. A pharmaceutical composition comprising the compound of any one of claims 1 to 14, and a pharmaceutically acceptable excipient.

16. The compound of any one of claims 1 to 14 or the pharmaceutical composition of claim 15 for use as a medicament.

17. The compound of any one of claims 1 to 14 or the pharmaceutical composition of claim 15 for use in the treatment of cancer.

18. The compound for use or the pharmaceutical composition for use of claim 17, wherein the cancer is treatable by inhibition of WRN and / or the cancer is characterized by MSI-H and / or dMMR.

19. Use of the compound of any one of claims 1 to 14 in the manufacture of a medicament for treating cancer, preferably wherein the cancer is treatable by inhibition of WRN and / or the cancer is characterized by MSI-H and / or dMMR.

20. A method for treating a cancer in a subject in need thereof, the method comprising the step ofadministering to the subject the therapeutically effective amount of the compound of any one of claims1 to 14, preferably wherein the cancer is treatable by inhibition of WRN and / or the cancer ischaracterized by MSI-H and / or dMMR.

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