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 / 587,354 and US 63 / 665,751 FoRx Therapeutics AG Vossius Ref.: AE3393 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. Similar compounds are disclosed in WO 2024 / 079623. Further reversible WRN inhibitors are disclosed in WO 2024 / 120378. 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 “C0-3 alkylene” indicates that a covalent bond (corresponding to the option “C0 alkylene”) or a C1-3 alkylene is present. Preferred exemplary alkylene groups are methylene (- CH2-), ethylene (e.g., -CH2-CH2- or -CH(-CH3)-), propylene (e.g., -CH2-CH2-CH2-, -CH(-CH2-CH3)-, -CH2- CH(-CH3)-, or -CH(-CH3)-CH2-), or butylene (e.g., -CH2-CH2-CH2-CH2-). Unless defined otherwise, the term “alkylene” preferably refers to C1-4 alkylene (including, in particular, linear C1-4 alkylene), more preferably to methylene or ethylene, and even more preferably to methylene. As used herein, the term “alkenylene” refers to an alkenediyl group, i.e. a divalent unsaturated acyclic hydrocarbon group which may be linear or branched and comprises one or more (e.g., one or two) carbon-to-carbon double bonds while it does not comprise any carbon-to-carbon triple bond. A “C2- 5 alkenylene” denotes an alkenylene group having 2 to 5 carbon atoms. Unless defined otherwise, the term “alkenylene” preferably refers to C2-4 alkenylene (including, in particular, linear C2-4 alkenylene). As used herein, the term “alkynylene” refers to an alkynediyl group, i.e. a divalent unsaturated acyclic hydrocarbon group which may be linear or branched and comprises one or more (e.g., one or two) carbon-to-carbon triple bonds and optionally one or more (e.g., one or two) carbon-to-carbon double bonds. A “C2-5 alkynylene” denotes an alkynylene group having 2 to 5 carbon atoms. Unless defined otherwise, the term “alkynylene” preferably refers to C2-4 alkynylene (including, in particular, linear C2-4 alkynylene). As used herein, the term “carbocyclyl” refers to a hydrocarbon ring group, including monocyclic rings as well as bridged ring, spiro ring and / or fused ring systems (which may be composed, e.g., of two or three rings), wherein said ring group may be saturated, partially unsaturated (i.e., unsaturated but not aromatic) or aromatic. Unless defined otherwise, “carbocyclyl” preferably refers to aryl, cycloalkyl or cycloalkenyl. As used herein, the term “heterocyclyl” refers to a ring group, including monocyclic rings as well as bridged ring, spiro ring and / or fused ring systems (which may be composed, e.g., of two or three rings), wherein said ring group comprises one or more (such as, e.g., one, two, three, or four) ring heteroatoms independently selected from O, S 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 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). “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 two points 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, but having 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 herein above, 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. In one embodiment, haloalkyl may also be a perhaloalkyl. The term “perhaloalkyl” refers to a haloalkyl wherein every -H atom has been substituted with a halo atom. Preferably, said perhaloalkyl is perfluoroalkyl. 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, C2 alkynyl, -N(C1-5 alkyl)(C1-5 alkyl) (such as -N(CH3)(CH(CH3)2)), C2-haloalkyl (such as - CF2CH3) and –(C1-2 haloalkylene)-cycloalkyl (such as -CF2-cyclopropyl), 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, C1-6 haloalkyl, aryl (such as phenyl) or heteroaryl (such as thien-2-yl), preferably with C1-6 alkyl, C1- 6 haloalkyl, or aryl (such as phenyl), more preferably with C1-6 alkyl or C1-6 haloalkyl, such as C1-6 alkyl. 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, such as 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, heterocycloalkyl, 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 heterocycloalkyl, heterocycloalkenyl and C2 alkynyl, wherein said heterocycloalkyl and said heterocycloalkenyl are each optionally substituted with one or more R1, and wherein said C2 alkynyl is optionally substituted with C1-6 alkyl. More preferably, A is heterocycloalkyl, or heterocycloalkenyl wherein said heterocycloalkyl and said heterocycloalkenyl are each optionally substituted with one or more R1. Even more preferably, A is heterocycloalkyl optionally substituted with one or more R1. 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, -NH-(C0-3 alkylene)-carbocyclyl, -NH-(C0-3 alkylene)-heterocyclyl, -N(C1-5 alkyl)-(C0-3 alkylene)-carbocyclyl, -N(C1-5 alkyl)-(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 -NH-(C0-3 alkylene)-carbocyclyl, the carbocyclyl moiety in said -N(C1-5 alkyl)-(C0-3 alkylene)-carbocyclyl, the carbocyclyl moiety in said -(C0-3 alkylene)-carbocyclyl, the heterocyclyl moiety in said -O-(C0-3 alkylene)-heterocyclyl, the heterocyclyl moiety in said -NH-(C0-3 alkylene)-heterocyclyl, the heterocyclyl moiety in said -N(C1-5 alkyl)-(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, 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, -(C0-3alkylene)-NH-O(C1-5alkyl), -(C0-3alkylene)-N(C1-5alkyl)-O(C1-5alkyl), -(C0-3alkylene)-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). 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)-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, -(C0-3alkylene)-(C1-5haloalkyl), -(C0-3alkylene)-O-(C1-5haloalkyl), -(C0-3alkylene)-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), and -(C0-3 alkylene)-SO-(C1-5 alkyl). Even 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)-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), and -(C0-3 alkylene)-O-(C1-5 haloalkyl), 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)-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 R1is 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), C1-5 haloalkyl and halogen, preferably each R1is 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. Even more preferably, each R1is independently selected from -OH and halogen. Particularly suitable A are selected from: , , In one embodiment, A is -CF2-cyclopropyl. In one embodiment, A is -CF2CH3. In one embodiment, A is -N(C1-5 alkyl)(C1-5 alkyl), preferably -N(CH3)(CH(CH3)2. In one embodiment, A is -C C-C6H5. In formula (I), B is selected from arylene and heteroarylene, wherein said arylene and said hereroarylene are each optionally substituted with one or more R2. Preferably, B is arylene, optionally substituted with one or more R2. Particularly preferred arylene in B is phenylene, optionally substituted with one or more R2, in particular 1,4-phenylene optionally substituted with one or more R2. Accordingly, in one embodiment, another embodiment, one particularly preferred embodiment, It is preferred that if B is 1,4-phenylene optionally substituted with one or more R2, for example as recited in the foregoing, B is (further) substituted with -O-(C0-3 alkylene)-carbocyclyl, or -O-(C0-3 alkylene)-heterocyclyl, preferably with -O-carbocyclyl, or -O-heterocyclyl, more preferably with - O-carbocyclyl, in particular -O-phenyl. Preferably, said substitution is at the carbon atom in the ring adjacent to the carbon atom connected to X. In one embodiment, B is heteroarylene, optionally substituted with one or more R2. Particularly preferred are 5 or 6-membered heteroarylene moieties. Accordingly, the heteroarylene may be a 5-membered heteroarylene, optionally substituted with one or more R2. Preferably, said 5-membered heteroarylene may be a heteroarylene comprising at least one N atom in the ring, more preferably at least two N atoms in the ring. Exemplary suitable 5-membered heteroarylenes Alternatively, B may also be a 6-membered heteroarylene, optionally substituted with one or more R2. Preferably, said 6-membered heteroarylene is pyridinylene, preferably a 2,5-pyridinylene, optionally substituted with one or more R2. Suitable examples wherein B is a 2,5-pyridinylene moiety, as disclosed herein, include . The heteroarylene may also be optionally oxidized in the ring. One suitable example of such heteroarylene moiety including an oxo group in the ring wherein the heteroarylene is optionally substituted with one or more R2, and wherein RD1is selected from H and C1-6 alkyl (such as methyl). In one preferred embodiment, the heteroarylene , optionally substituted with one or more R2. As it is to be understood herein, each heteroarylene moiety discussed herein, including each specific example, is optionally substituted with one or more R2. Particularly preferred B being As it is apparent to the skilled person, B is a bivalent moiety and accordingly, as understood herein, preferably the left side of B as shown in the specific structural formulas, is connected to A, and the rights side of B is connected to X. It is preferred that if B is 2,5-pyridinylene, B is substituted with -O-(C0-3 alkylene)-carbocyclyl, or - O-(C0-3 alkylene)-heterocyclyl, preferably with -O-carbocyclyl, or -O-heterocyclyl, more preferably with - O-carbocyclyl, in particular -O-phenyl. Preferably, said substitution is at the carbon atom in the ring adjacent to the carbon atom connected to X. It is further preferred that if B is 2,5-pyrimidinylene, B is substituted with -O-(C0-3 alkylene)-carbocyclyl, or -O-(C0-3 alkylene)-heterocyclyl, preferably with -O-carbocyclyl, or - O-heterocyclyl, more preferably with -O-carbocyclyl, in particular -O-phenyl. Preferably, said substitution is at the carbon atom in the ring adjacent to the carbon atom connected to X, or, in other words, at position 4 in the 2,5-pyrimidinylene. In formula (I), each R2is 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, -(C0-3 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 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(C1-5alkyl), -(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), 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 -CONH-, -CON(C1-6 alkyl)-, -CON(C1-6 haloalkyl)-, -SO2NH-, - SO2N(C1-6 alkyl)-, -SO2N(C1-6 haloalkyl)-, -CH(CF3)NH-, -CH(CF3)N(C1-6 alkyl)-, -CH(CF3)N(C1-6 haloalkyl)-, C2 alkenylene optionally substituted with one or more halogen, C1-6 alkyl or C1-6 haloalkyl (preferably optionally substituted with one or more C1-6 alkyl or C1-6 haloalkyl), cycloalkylene (preferably cyclopropylene) optionally substituted with one or more C1-6 alkyl, -(heterocycloalkylene)-NH-, - (heterocycloalkylene)-N(C1-6 alkyl)-, heterocycloalkylene, heterocycloalkenylene and heteroarylene. Particularly suitable heterocycloalkylene is 3,3-oxetanylene. Particularly suitable cycloalkylene is 1,2- cyclopopylene. Particularly suitable heteroarylene is 1,2,3-triazolyl-1,4-ene. Preferably, X is selected from -CONH-, -CON(C1-6 alkyl)-, -CON(C1-6 haloalkyl)-, -SO2NH-, - SO2N(C1-6 alkyl)-, -SO2N(C1-6 haloalkyl)-, -CH(CF3)NH-, -CH(CF3)N(C1-6 alkyl)-, -CH(CF3)N(C1-6 haloalkyl)-, C2 alkenylene optionally substituted with one or more C1-6 alkyl or C1-6 haloalkyl, cycloalkylene (preferably cyclopropylene) optionally substituted with one or more C1-6 alkyl, -(heterocycloalkylene)-NH- , and -(heterocycloalkylene)-N(C1-6alkyl)- Preferably, X is selected from -CONH-, -CON(C1-6 alkyl)-, -CON(C1-6 haloalkyl)-, -SO2NH-, - SO2N(C1-6 alkyl)-, -SO2N(C1-6 haloalkyl)-, -CH(CF3)NH-, -CH(CF3)N(C1-6 alkyl)-, and -CH(CF3)N(C1-6 haloalkyl)-. More preferably, X is selected from -CONH-, and -CON(C1-6 alkyl)-. Even more preferably, X is - CONH-. It is to be understood that, preferably, the left side of the bivalent formula embodying X, as shown herein, is connected to B, and the right side of said bivalent formula embodying X is connected to Y. Alternatively, X is selected from heterocycloalkylene, heterocycloalkenylene and heteroarylene. Preferably, said heterocycloalkylene is a nitrogen-containing five-membered heterocycloalkylene, said heterocycloalkenylene is a nitrogen-containing five-membered heterocycloalkenylene, and said heteroarylene is a nitrogen-containing five-membered heteroarylene. Particularly suitable heterocycloalkenylene particularly suitable heteroarylene is selected from understood that, preferably, the left side of the bivalent formula embodying X, as shown herein, is connected to B, and the right side of said bivalent formula embodying X is connected to Y. CO(C2 alkenyl), -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, C1-4 haloalkyl, -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(=NH)-(C1-4 alkyl), -SO(=N-(C1-4 alkyl))-(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(=NH)-cycloalkyl, -SO(=N-(C1-4 alkyl))-cycloalkyl, heterocycloalkyl, -SO2-heterocycloalkyl, -SO(=NH)-heterocycloalkyl, -SO(=N-(C1-4 alkyl))- heterocycloalkyl, aryl, -SO2-aryl, -SO(=NH)-aryl, -SO(=N-(C1-4 alkyl))-aryl, heteroaryl, -SO2-heteroaryl, - SO(=NH)-heteroaryl, -SO(=N-(C1-4 alkyl))-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), -SO(=NH)-(C1-4 alkyl), -SO(=N-(C1-4 alkyl))-(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, -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, still more preferably substituted with one or more optional substituents selected from C1-4 alkyl, -CONH-(C1-4 alkyl), and -SO2- (C1-4 alkyl), even more preferably substituted with one or more optional substituents selected from -CONH- alkyl) are each optionally substituted by one or more C1-6 alkyl (such as methyl) or Hal (such as F). Preferably, m is 1. -SO2(C2 alkenyl), -CO(C2 alkenyl), -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, C1-4 haloalkyl, -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(=NH)-(C1-4 alkyl), -SO(=N-(C1-4 alkyl))-(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(=NH)-cycloalkyl, -SO(=N-(C1-4alkyl))- cycloalkyl, heterocycloalkyl, -SO2-heterocycloalkyl, -SO(=NH)-heterocycloalkyl, -SO(=N-(C1-4 alkyl))- heterocycloalkyl, aryl, -SO2-aryl, -SO(=NH)-aryl, -SO(=N-(C1-4 alkyl))-aryl, heteroaryl, -SO2-heteroaryl, - SO(=NH)-heteroaryl, -SO(=N-(C1-4 alkyl))-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), -SO(=NH)-(C1-4 alkyl), -SO(=N-(C1-4 alkyl))-(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, -COO(C1-4 alkyl), - CO(C1-4alkyl), -CONH(C1-4alkyl), -CON(C1-4alkyl)(C1-4alkyl), -SO2(C1-4alkyl), -SO2NH2, -SO2NH(C1-4alkyl), -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, still more preferably substituted with one or more optional substituents selected from C1-4 alkyl, -CONH-(C1-4 alkyl), and -SO2- (C1-4 alkyl), even more preferably substituted with one or more optional substituents selected from -CONH- (C1-4alkyl), and -SO2-(C1-4alkyl), and wherein said , , , and said are each optionally substituted by one or more C1-6 alkyl (such as methyl) or Hal (such as F). Preferably, m is 1. More preferably, Y is selected from: , , -SO2(C2 alkenyl), -CO(C2 alkenyl), -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 C1-4alkyl, C1-4haloalkyl, -COOH, -COO(C1-4alkyl), -CO(C1-4alkyl), -CONH(C1-4alkyl), - 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- (C1-4alkyl), even more preferably substituted with one or more optional substituents selected from -CONH- are each optionally substituted by one or more C1-6 alkyl (such as methyl) or Hal (such as F). Preferably, m is 1. -SO2(C2 alkenyl), -CO(C2 alkenyl), -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, -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 C1-4alkyl, - CONH-(C1-4 alkyl), and -SO2-(C1-4 alkyl), even more preferably substituted with one or more optional substituents selected from -CONH-(C1-4 alkyl), and -SO2-(C1-4 alkyl), and wherein said , said , and said are each optionally substituted by one or more C1-6 alkyl (such as methyl) or Hal (such as F). Preferably, m is 1. Even more preferably, Y is selected from: , , -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, -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), preferably selected from -CONH-(C1-4 alkyl), and -SO2-(C1-4 alkyl), and wherein said , , and said are each optionally substituted by one or more C1-6 alkyl (such as methyl) or Hal (such as F). Preferably, m is 1. Again more preferably, Y is selected from: , , , , , and C1-6 alkyl (such as methyl) or Hal (such as F). Still more preferably, Y is selected from: 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 formula (I) B and X are combined to form a two-ring system according to formula: wherein C is aryl or heteroaryl ring, optionally substituted with one or more R2, Z is selected from C1-2alkylene, -CH=CH-, -N=CH-, -N=C(C1-6alkyl)-, -CH=N-, -C(C1-6alkyl)=N-, -CO-, -SO-, -SO2-, -CONH- , -NHCO-, -CON(C1-6 alkyl)-, -N(C1-6 alkyl)CO-, -NH-, -N(C1-6 alkyl)- and -O-, and A and Y are as defined hereinabove. Preferably, C is benzene ring or pyridine ring, wherein each of these rings is optionally substituted with one or more R2. More preferably C is selected from: wherein each of these rings is optionally substituted with one or more R2. It is to be understood that, preferably, the empty valence on the left side of the molecule is directed to A ring, the empty valence on the upper side of the molecule connects to -CO- moiety of -CONZ-, and the empty valence on the right-lower side of the molecule is connected to -Z- of -CONZ-. Preferably, Z is selected from C1-2 alkylene, -CH=CH-, -N=CH-, -SO2-, and -NHCO-. Alternatively, A and B are as defined hereinabove, and X and Y form a two ring spiro system, defined as: wherein D is a nitrogen-containing heterocycloalkyl or heterocycloalkenyl, m is 1 or 2, and the optionally substituted by one or more C1-6 alkyl (such as methyl) or Hal (such as F). By X and Y forming a two-ring spiro system it is understood that X and Y are replaced with a two ring spiro system, as defined herein. It is to be understood that such compounds are also encompassed by formula (I). Nitrogen containing heterocycloalkyl or heterocycloalkenyl is defined as heterocycloalkyl or heterocycloalkenyl, respectively, including at least one N atom in the ring. Preferably, D is 4, 5 or 6 membered nitrogen-containing heterocycloalkyl or heterocycloalkenyl, preferably connected to B through its nitrogen atom. Accordingly and preferably, D is an N- heterocycloalkyl. Exemplary heterocycloalkyl and heterocycloalkenyl moieties suitable as D are selected from or more C1-6 alkyl (such as methyl) or Hal (such as F). Preferably, the following provisions apply to formula (I): wherein m is 1 or 2, and wherein said optionally substituted by one or more C1-6 alkyl (such as methyl) or Hal (such as F); then: (a1) A is not selected from aryl, heteroaryl, cycloalkyl and cycloakenyl, wherein said aryl, said heteroaryl, said cycloalkyl and said cycloalkenyl are each optionally substituted with one or more R1; and / or (a2) B is not according to formula wherein the left side of the depicted bivalent moiety is connected to A and the rights side of the depicted bivalent moiety is connected to X, wherein RD1is selected from hydrogen and C1-6 alkyl, and wherein the ring is optionally substituted with one or more groups selected from halogen, C1-6 alkyl, C1-6 haloalkyl, -OH, -O-(C1-6 alkyl), -NH-(C1-6 alkyl), -N(C1-6 alkyl)-(C1-6 alkyl) and -CN; and / or (a3) X is not -CONH- wherein the C atom in said -CONH- moiety is connected to B, and the N atom in said -CONH- moiety is connected to Y; (b) if X is -CONH- wherein the C atom in said -CONH- moiety is connected to B, and the N atom in said -CONH- moiety is connected to Y, then: (b1) A is not selected from aryl, heteroaryl, cycloalkyl and cycloakenyl, wherein said aryl, said heteroaryl, said cycloalkyl and said cycloalkenyl are each optionally substituted with one or more R1; and / or (b2) B is not according to formula wherein the left side of the depicted bivalent moiety is connected to A and the rights side of the depicted bivalent moiety is connected to X, wherein RD1is selected from hydrogen and C1-6 alkyl, and wherein the ring is optionally substituted with one or more groups selected from halogen, C1-6 alkyl, C1-6 haloalkyl, -OH, -O-(C1-6 alkyl), -NH-(C1-6 alkyl), -N(C1-6 alkyl)-(C1-6 alkyl) and -CN; and / or (b3) Y is not , wherein m is 1 or 2, and wherein said is optionally substituted by one or more C1-6alkyl (such as methyl) or Hal (such as F); (c) if B is according to formula : , wherein the left side of the depicted bivalent moiety is connected to A and the rights side of the depicted bivalent moiety is connected to X, wherein RD1is selected from hydrogen and C1-6 alkyl, and wherein the ring is optionally substituted with one or more groups selected from halogen, C1-6 alkyl, C1-6 haloalkyl, -OH, -O-( C1-6 alkyl), - NH-(C1-6 alkyl), -N(C1-6 alkyl)-(C1-6 alkyl) and -CN; then (c1) A is not selected from aryl, heteroaryl, cycloalkyl and cycloakenyl, wherein said aryl, said heteroaryl, said cycloalkyl and said cycloalkenyl are each optionally substituted with one or more R1; and / or (c2) X is not -CONH- wherein the C atom in said -CONH- moiety is connected to B, and the N atom in said -CONH- moiety is connected to Y; and / or (c3) Y is not , wherein m is 1 or 2, and wherein said is optionally substituted by one or more C1-6 alkyl (such as methyl) or Hal (such as F). ; (d) if A is selected from aryl, heteroaryl, cycloalkyl and cycloakenyl, wherein said aryl, said heteroaryl, said cycloalkyl and said cycloalkenyl are each optionally substituted with one or more R1, then: (d1) B is not according to formula wherein the left side of the depicted bivalent moiety is connected to A and the rights side of the depicted bivalent moiety is connected to X, wherein RD1is selected from hydrogen and C1-6 alkyl, and wherein the ring is optionally substituted with one or more groups selected from halogen, C1-6 alkyl, C1-6 haloalkyl, -OH, -O-(C1-6 alkyl), -NH-(C1-6 alkyl), -N(C1-6 alkyl)-(C1-6 alkyl) and -CN; and / or (d2) X is not -CONH- wherein the C atom in said -CONH- moiety is connected to B, and the N atom in said -CONH- moiety is connected to Y; and / or (d3) Y is not , wherein m is 1 or 2, and wherein said is optionally substituted by one or more C1-6 alkyl (such as methyl) or Hal (such as F). Alternatively, the following provisions apply to formula (I): (e1) A is not selected from aryl, heteroaryl, cycloalkyl and cycloakenyl, wherein said aryl, said heteroaryl, said cycloalkyl and said cycloalkenyl are each optionally substituted with one or more R1; and / or (e2) B is not according to formula wherein the left side of thedepicted bivalent moiety is connected to A and the rights side of the depicted bivalent moiety is connected to X, wherein RD1is selected from hydrogen and C1-6 alkyl, and wherein the ring is optionally substituted with one or more groups selected from halogen, C1-6 alkyl, C1-6 haloalkyl, -OH, -O-(C1-6 alkyl), -NH-(C1-6 alkyl), -N(C1-6 alkyl)-(C1-6 alkyl) and -CN; and / or (e3) X is not -CONH- wherein the C atom in said -CONH- moiety is connected to B, and the N atom in said -CONH- moiety is connected to Y; and / or (e4) Y is not , wherein m is 1 or 2, and wherein said is optionally substituted by one or more C1-6 alkyl (such as methyl) or Hal (such as F). It is to be understood that at least one of conditions (e1) to (e4) must preferably be fulfilled in the compound of formula (I). Accordingly and preferably, from formula (I) excluded is a compound of formula (I), wherein: A is selected from aryl, heteroaryl, cycloalkyl and cycloakenyl, wherein said aryl, said heteroaryl, said cycloalkyl and said cycloalkenyl are each optionally substituted with one or more R1; B is according to formula wherein the left side of the depicted bivalent moiety is connected to A and the rights side of the depicted bivalent moiety is connected to X, wherein RD1is selected from hydrogen and C1-6 alkyl, and wherein the ring is optionally substituted with one or more groups selected from halogen, C1-6 alkyl, C1-6 haloalkyl, -OH, -O-(C1-6 alkyl), -NH-(C1-6 alkyl), -N(C1-6 alkyl)-(C1-6 alkyl) and -CN; X is -CONH- wherein the C atom in said -CONH- moiety is connected to B, and the N atom in said -CONH- moiety is connected to Y; and Y is not , wherein m is 1 or 2, and wherein said optionally substituted by one or more C1-6 alkyl (such as methyl) or Hal (such as F). In other words, it is preferred that the compound of formula (I) is not a compound wherein: A is selected from aryl, heteroaryl, cycloalkyl and cycloakenyl, wherein said aryl, said heteroaryl, said cycloalkyl and said cycloalkenyl are each optionally substituted with one or more R1; B is according to formula wherein the left side of the depicted bivalent moiety is connected to A and the rights side of the depicted bivalent moiety is connected to X, wherein RD1is selected from hydrogen and C1-6 alkyl, and wherein the ring is optionally substituted with one or more groups selected from halogen, C1-6 alkyl, C1-6 haloalkyl, -OH, -O-(C1-6 alkyl), -NH-(C1-6 alkyl), -N(C1-6 alkyl)-(C1-6 alkyl) and -CN; X is -CONH- wherein the C atom in said -CONH- moiety is connected to B, and the N atom in said -CONH- moiety is connected to Y; and Y is not , wherein m is 1 or 2, and wherein said optionally substituted by one or more C1-6alkyl (such as methyl) or Hal (such as F), or its pharmaceutically acceptable salt. In addition to the provisions recited hereinabove, or alternatively, the following provisions preferably apply to formula (I): (f1) if Y is a moiety 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, Ry2is -H and Ry3is selected from C1-4 alkyl (such as methyl), C3-8 cycloalkyl (such as cyclopropyl), and 5 or 6-membered heterocyclyl, and wherein the bonds drawn as indicate that both Z and E configurations of the double bond are possible, then B is not a moiety according to formula: wherein the left empty valence is connected to A, and the right empty valence is connected to X, wherein: Xv is CRv2or N; Yv is CRv4or N; Zv is CRv5or N; or Yv and Zv taken together form an optionally substituted five- to six-membered heteroaryl, or an optionally substituted five- to six-membered heterocyclyl; with the proviso that Xv, Yv, and Zv are not simultaneously N; Rv is H, -O-(optionally substituted C3-C8 cycloalkyl), -O-(optionally substituted C1-C6 alkyl), -O- (optionally substituted C6-C10 aryl), -O-(optionally substituted five- to six-membered heteroaryl), -O- (optionally substituted five- to six-membered heterocyclyl), or optionally substituted C3-C8 cycloalkyl; or Rvtogether with the carbon atoms to which it is shown attached and Xvform an optionally substituted five- to six-membered heterocyclyl; Rv2is H, optionally substituted C1-C6 alkyl, or halo; Rv4is H, C1-C6 alkyl, cyano, or halo; or Rv4together with the carbon atom to which it is shown attached and Zv form an optionally substituted five- to six-membered heteroaryl; Rv5is H, C1-C6 alkyl, -NR2, or -N(R)-C(=O)-(C1-C6 alkyl); each R independently is H, or optionally substituted C1-C6 alkyl. Said optional substituents of alkyl, alkenyl, cycloalkenyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl groups in Rv, Rv2, Rv4, and Rv5, are selected from the group consisting of halogen, –CN, – NO2, –N3, –SO2H, –SO3H, –OH, –ORaa, –N(Rbb)2, –N(ORcc)Rbb, –SH, –SRaa, –C(=O)Raa, –CO2H, –CHO, – CO2Raa, –OC(=O)Raa, –OCO2Raa, –C(=O)N(Rbb)2, –OC(=O)N(Rbb)2, –NRbbC(=O)Raa, –NRbbCO2Raa, – NRbbC(=O)N(Rbb)2, –C(=NRbb)Raa, –C(=NRbb)ORaa, –OC(=NRbb)Raa, –OC(=NRbb)ORaa, – C(=NRbb)N(Rbb)2, – OC(=NRbb)N(Rbb)2, –NRbbC(=NRbb)N(Rbb)2, –C(=O)NRbbSO2Raa, –NRbbSO2Raa, – SO2N(Rbb)2, –SO2Raa, – S(=O)Raa, –OS(=O)Raa, -B(ORcc)2, C1–10 alkyl, C2–10 alkenyl, C2–10 alkynyl, C3– 14 cycloalkyl, 3– to 14- membered heterocyclyl, C6–14 aryl, and 5– to 14- membered heteroaryl, wherein each alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 Rddgroups, or two geminal hydrogens on a carbon atom are replaced with the group =O; Each instance of Raais, independently, selected from the group consisting of C1–10 alkyl, C1– 10 perhaloalkyl, C2–10 alkenyl, C2–10 alkynyl, C3–14 carbocyclyl, 3– to 14- membered heterocyclyl, C6–14 aryl, and 5– to 14- membered heteroaryl, or two Raagroups are joined to form a 3– to 14- membered heterocyclyl or 5– to 14- membered heteroaryl ring, wherein each alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 Rddgroups; each instance of Rbbis, independently, selected from the group consisting of hydrogen, –OH, – ORaa, –N(Rcc)2, –CN, –C(=O)Raa, –C(=O)N(Rcc)2, –CO2Raa, –SO2Raa, –SO2N(Rcc)2, –SORaa, C1–10 alkyl, C1–10 perhaloalkyl, C2–10 alkenyl, C2–10 alkynyl, C3–14 carbocyclyl, 3– to 14- membered heterocyclyl, C6– 14 aryl, and 5– to 14- membered heteroaryl, or two Rbbgroups are joined to form a 3– to 14- membered heterocyclyl or 5– to 14- membered heteroaryl ring, wherein each alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 Rddgroups; each instance of Rccis, independently, selected from the group consisting of hydrogen, C1– 10 alkyl, C1– 10 perhaloalkyl, C2–10 alkenyl, C2–10 alkynyl, C3–14 carbocyclyl, 3– to 14- membered heterocyclyl, C6–14 aryl, and 5– to 14- membered heteroaryl, or two Rccgroups are joined to form a 3– to 14- membered heterocyclyl or 5– to 14- membered heteroaryl ring, wherein each alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 Rddgroups; and each instance of Rddis, independently, selected from the group consisting of halogen, –CN, – NO2, –N3, –SO2H, –SO3H, –OH, –OC1–6 alkyl, –ON(C1–6 alkyl)2, –N(C1–6 alkyl)2, –N(OC1–6 alkyl)(C1– 6 alkyl), – N(OH)(C1–6 alkyl), –NH(OH), –SH, –SC1–6 alkyl, –C(=O)(C1–6 alkyl), –CO2H, –CO2(C1–6 alkyl), – OC(=O)(C1–6 alkyl), –OCO2(C1–6 alkyl), –C(=O)NH2, –C(=O)N(C1–6 alkyl)2, –OC(=O)NH(C1–6 alkyl), – NHC(=O)(C1–6 alkyl), –N(C1–6 alkyl)C(=O)( C1–6 alkyl), –NHCO2(C1–6 alkyl), –NHC(=O)N(C1–6 alkyl)2, – NHC(=O)NH(C1–6 alkyl), –NHC(=O)NH2, –C(=NH)O(C1–6 alkyl),–OC(=NH)(C1–6 alkyl), –OC(=NH)OC1– 6 alkyl, –C(=NH)N(C1–6 alkyl)2, –C(=NH)NH(C1–6 alkyl), –C(=NH)NH2, –OC(=NH)N(C1–6 alkyl)2, – OC(NH)NH(C1–6 alkyl), –OC(NH)NH2, –NHC(NH)N(C1–6 alkyl)2, –NHC(=NH)NH2, –NHSO2(C1–6 alkyl), – SO2N(C1–6 alkyl)2, –SO2NH(C1–6 alkyl), –SO2NH2,–SO2C1–6 alkyl, -B(OH)2, -B(OC1–6 alkyl)2,C1–6 alkyl, C1– 6 perhaloalkyl, C2–6 alkenyl, C2–6 alkynyl, C3–10 carbocyclyl, C6–10 aryl, 3- to 10- membered heterocyclyl, and 5- to 10- membered heteroaryl; or two geminal Rddsubstituents on a carbon atom may be joined to form =O. (f2) if Y is a moiety 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, Ry2is -H, and Ry3is selected from C1-4 alkyl (such as methyl), C3-8 cycloalkyl (such as cyclopropyl), and 5 or 6-membered heterocyclyl, and wherein the bonds drawn as indicate that both Z and E configurations of the double bond are possible, then B is selected from: a 5-membered heteroarylene, optionally substituted with one or more R2, a 6-membered heteroarylene, oxidised in the ring and optionally substituted with one or more R2, preferably selected from , optionally substituted with one or more R2, and , optionally substituted with one or more R2, wherein RD1is selected from H and C1-6 alkyl (such as methyl), wherein the left empty valence is connected to A, and the right empty valence is connected to X, a 6-membered heteroarylene or phenylene, wherein said heteroarylene and said phenylene are attached to A and X respectively at the opposite positions of the ring (i.e., 1,4 positions), wherein: said heteroarylene and said phenylene are each optionally substituted with at least one group selected from -OH, -COOH, -COO(C1-5 alkyl), -CONH2, -CONH(C1-5 alkyl) and -CON(C1-5 alkyl)(C1-5 alkyl) and / or said heteroarylene and said phenylene are each optionally substituted at a ring position adjacent to the point of attachment of said heteroarylene or said phenylene to X with at least one group selected from halo and -CN, and / or said heteroarylene and said phenylene are each optionally substituted at a ring position adjacent to the point of attachment of said heteroarylene or said phenylene to A with at least one group selected from -NH2, NH(C1-5 alkyl), and -N(C1-5 alkyl)(C1-5 alkyl). Accordingly, in one embodiment, B is a 5-membered heteroarylene, optionally substituted with one or more R2. In one embodiment, B is a 6-membered heteroarylene, oxidised in the ring and optionally substituted with one or more R2, preferably selected from , optionally substituted with one or more optionally substituted with one or more R2, wherein RD1is selected from H and C1-6 alkyl (such as methyl), wherein the left empty valence is connected to A, and the right empty valence is connected to X. In one embodiment, B is a 6-membered heteroarylene or phenylene, wherein said heteroarylene and said phenylene are attached to A and X respectively at the opposite positions of the ring (i.e., 1,4 positions), wherein: said heteroarylene and said phenylene are each optionally substituted with at least one group selected from -OH, -COOH, -COO(C1-5 alkyl), -CONH2, -CONH(C1-5 alkyl) and -CON(C1-5 alkyl)(C1-5 alkyl) and / or said heteroarylene and said phenylene are each optionally substituted at a ring position adjacent to the point of attachment of said heteroarylene or said phenylene to X with at least one group selected from halo and -CN, and / or said heteroarylene and said phenylene are each optionally substituted at a ring position adjacent to the point of attachment of said heteroarylene or said phenylene to A with at least one group selected from -NH2, NH(C1-5 alkyl), and -N(C1-5 alkyl)(C1-5 alkyl). 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 selected In a second specific embodiment of the compound of formula (I), A is selected from heterocycloalkyl and heterocycloalkenyl, wherein said heterocycloalkyl and said heterocycloalkenyl are each optionally substituted with one or more R1. Particularly suitable heterocycloalkyl and heterocycloalkenyl are heterocycloalkyl and heterocycloalkenyl consisting of a single 5 or 6-membered ring (preferably 6-membered), and optionally substituted with one or more R1. Examples of particularly preferred A in this second specific embodiment include . In a third specific embodiment of the compound of formula (I), A is C2 alkynyl, optionally substituted with C1-6 alkyl or C1-6 haloalkyl, such as C1-6 alkyl. Particularly suitable C1-6 alkyl are methyl and isopropyl. Thus, in this third specific embodiment of the compound of formula (I), A is selected from In a fourth specific embodiment of the compound of formula optionally substituted with one or more R2, wherein RD1is selected from H and C1-6 alkyl (such as methyl). Preferably, RD1is H. In this fourth specific embodiment, it is preferred that the heteroarylene moiety bears no further substitutions. Preferably the left side of B as shown in the specific structural formulas, is connected to A, and the rights side of B is connected to X. In a fifth specific embodiment of the compound of formula , optionally substituted with one or more R2. In this fifth specific embodiment, it is preferred that the heteroarylene moiety bears no further substitutions. Alternatively, is optionally substituted with methyl, -OH or F. Particularly preferred B bearing such substitution in this fifth specific embodiment are selected from . Preferably the left side of B as shown in the specific structural formulas, is connected to A, and the rights side of B is connected to X. In a sixth specific embodiment of the compound of formula , optionally substituted with one or more R2. In this sixth specific embodiment, it is preferred that the heteroarylene moiety bears no further substitutions. Preferably the left side of B as shown in the specific structural formulas, is connected to A, and the rights side of B is connected to X. In a seventh specific embodiment of the compound of formula optionally substituted with one or more R2. In this seventh specific embodiment, it is preferred that the heteroarylene moiety bears no further substitutions. Preferably the left side of B as shown in the specific structural formulas, is connected to A, and the rights side of B is connected to X. In an eighth specific embodiment of the compound of formula optionally substituted with one or more R2. In this eighth specific embodiment, it is preferred that the heteroarylene moiety bears no further substitutions. In a ninth specific embodiment of the compound of formula (I), X is -CONH-, wherein the C atom is connected to B and the N atom is connected to Y, C2 alkenylene optionally substituted with one or more C1-6 alkyl or C1-6 haloalkyl, or 1,2-cyclopropylene optionally substituted with one or more C1-6 alkyl. It is to be understood that, preferably, the left side of the bivalent formula embodying X, as shown herein, is connected to B, and the right side of said bivalent formula embodying X is connected to Y. In a tenth specific embodiment of the compound of formula , wherein m is 1 or 2, preferably wherein m is 1. In an eleventh specific embodiment of the compound of formula alkyl) , wherein m is 1 or 2, preferably wherein m is 1. Preferably, in this eleventh alkyl) specific embodiment, . In a twelfth specific embodiment of the compound of formula In a thirteenth specific embodiment of the compound of formula (I), Y is selected from -SO2(C2 alkenyl), -CO-(C2 alkenyl), and -CH2-(C2 alkenyl), wherein said alkenyl is optionally 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), -(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). In a thirteenth specific embodiment of the compound of formula (I), Y is –(C1-2 alkylene)CN. Preferably, Y is -CH2CN or -CH(CH3)CN. In a fourteenth specific embodiment of the compound of formula (I), A and B is as defined for formula (I), and X and Y form a two ring spiro system, defined as: wherein D is a nitrogen-containing heterocycloalkyl or heterocycloalkenyl, m is 1 or 2, and the optionally substituted by one or more C1-6 alkyl (such as methyl) or Hal (such as F). In a fifteenth specific embodiment of the compound of formula (I), A and Y are as defined for formula (I), B and X are combined to form a two-ring system according to formula: wherein C is aryl or heteroaryl ring, optionally substituted with one or more R2, Z is selected from C1-2 alkylene, -CH=CH-, -N=CH-, -CH=N-, -CO-, -SO-, -SO2-, -CONH-, -NHCO-, -CONH(C1-6 alkyl)-, - NH(C1-6 alkyl)CO-, -NH-, -N(C1-6 alkyl)- and -O-, and Y is as defined for formula (I). In a sixteenth specific embodiment of the compound of formula (I), Y is selected from -SO2(C2 alkenyl), -CO(C2 alkenyl), -CH2(C2 alkenyl), and –(C1-2 alkylene)CN, wherein said -CH2- is optionally substituted with C1-4 alkyl, 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), -SO2H, -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(C1-4alkyl)(C1-4alkyl), -(C1-4alkylene)(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 seventeenth specific embodiment of the compound of formula (I), Y is -CH2(C2 alkenyl), wherein said -CH2- is optionally substituted with C1-4 alkyl, 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), -SO2H, -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 seventeenth specific embodiment, Y is a moiety 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, Ry2is selected from -H, -F and -CN (preferably Ry2is -H), and Ry3is selected from H, C1-4 alkyl (such as methyl), C3-8 cycloalkyl (such as cyclopropyl), and 5 or 6-membered heterocyclyl, and wherein the bonds drawn as indicate that both Z and E configurations of the double bond are possible. In this specific embodiment, Y is preferably selected from: In eighteenth 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 (preferably Ry2is H), and wherein the bonds drawn as indicate that both Z and E configurations of the double bond are possible. In a nineteenth specific embodiment of the compound of formula (I), A is a cycloalkenyl. For example, A may be a moiety according to formula: . In a twentieth specific embodiment of the compound of formula (I), A is heteroaryl, optionally substituted with one or more R1. Preferably, in this twentieth specific embodiment, A is selected from In a twenty-first specific embodiment of the compound of formula (I), Y is a moiety 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, Ry2is -F, and Ry3is selected from H, C1-4 alkyl (such as methyl), C3-8 cycloalkyl (such as cyclopropyl), and 5 or 6-membered heterocyclyl, and wherein the bonds drawn as indicate that both Z and E configurations of the double bond are possible. In this twenty-first specific In a twenty-second specific embodiment of the compound of formula (I), Y is a moiety 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 (preferably Ry2is -H), and Ry3is selected from C1-4 alkyl (such as methyl), C3-8 cycloalkyl (such as cyclopropyl), and 5 or 6-membered heterocyclyl, preferably wherein Ry3is C1-4 alkyl, preferably methyl, and wherein the bonds drawn as indicate that both Z and E configurations of the double bond are possible. In this twenty-second second specific embodiment of the compound of formula (I), A is preferably -CF2CH3. In a twenty-third specific embodiment of the compound of formula (I), Y is a moiety 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 (preferably Ry2is -H), and Ry3is selected from C1-4 alkyl (such as methyl), C3-8 cycloalkyl (such as cyclopropyl), and 5 or 6-membered heterocyclyl, preferably wherein Ry3is C1-4 alkyl, preferably methyl, and wherein the bonds drawn as indicate that both Z and E configurations of the double bond are possible. In this twenty-second (such as (selected from twenty third specific embodiment of the compound of formula (I), A is preferably -CF2CH3. In a twenty-fourth specific embodiment of the compound of formula (I), B is 2,5-pyridinylene, optionally substituted with -O-(C0-3 alkylene)-carbocyclyl, or -O-(C0-3 alkylene)-heterocyclyl, preferably with -O-carbocyclyl, or -O-heterocyclyl, more preferably with -O-carbocyclyl, in particular -O-phenyl. Preferably, said substitution is at the carbon atom in the ring adjacent to the carbon atom connected to X. In a twenty-fifth specific embodiment of the compound of formula (I), B is 2,5-pyrimidinylene, optionally substituted with -O-(C0-3 alkylene)-carbocyclyl, or -O-(C0-3 alkylene)-heterocyclyl, preferably with -O-carbocyclyl, or -O-heterocyclyl, more preferably with -O-carbocyclyl, in particular -O-phenyl. Preferably, said substitution is at the carbon atom in the ring adjacent to the carbon atom connected to X, or, in other words, at position 4 in the 2,5-pyrimidinylene. In a twenty-sixth specific embodiment of the compound of formula (I), Y is -CH2(C2 alkenyl), wherein said -CH2- is optionally substituted with C1-4 alkyl, 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, C1-4 haloalkyl, -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(=NH)-(C1-4 alkyl), -SO(=N-(C1-4 alkyl))-(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(=NH)-cycloalkyl, -SO(=N-(C1-4 alkyl))-cycloalkyl, heterocycloalkyl, -SO2-heterocycloalkyl, -SO(=NH)-heterocycloalkyl, -SO(=N-(C1-4 alkyl))- heterocycloalkyl, aryl, -SO2-aryl, -SO(=NH)-aryl, -SO(=N-(C1-4 alkyl))-aryl, heteroaryl, -SO2-heteroaryl, - SO(=NH)-heteroaryl, -SO(=N-(C1-4 alkyl))-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), -SO(=NH)-(C1-4 alkyl), -SO(=N-(C1-4 alkyl))-(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 -SO2(C1-4 alkyl), -SO(=NH)- (C1-4 alkyl), -SO(=N-(C1-4 alkyl))-(C1-4 alkyl), even more preferably substituted with one or more optional substituents selected from -SO(=NH)-(C1-4 alkyl) and -SO(=N-(C1-4 alkyl))-(C1-4 alkyl). Particularly suitable C1-4 alkyl is methyl. In a twenty-seventh specific embodiment of the compound of formula (I), X is selected from heterocycloalkylene, heterocycloalkenylene and heteroarylene, and Y is -CH=CH-SO2-(C1-4 alkyl). Preferably, in this twenty-seventh specific embodiment, said heterocycloalkylene is a nitrogen-containing five-membered heterocycloalkylene, said heterocycloalkenylene is a nitrogen-containing five-membered heterocycloalkenylene, and said heteroarylene is a nitrogen-containing five-membered heteroarylene. Particularly suitable heterocycloalkenylene particularly suitable heteroarylene is selected from understood that, preferably, the left side of the bivalent formula embodying X, as shown herein, is connected to B, and the right side of said bivalent formula embodying X is connected to Y. Further in this twenty-seventh specific embodiment, particularly suitable C1-4 alkyl in Y is methyl. In one particular embodiment, the compound of formula (I) is a compound of formula (Ia): wherein A and B are as defined for formula (I), including any preferred definition and definition in any of the specific embodiments of the compound of formula (I). In one particular embodiment, the compound of formula (I) is a compound of formula (Ib): wherein A and Y are as defined for formula (I), including any preferred definition and definition in any of the specific embodiments of the compound of formula (I). In one particular embodiment, the compound of formula (I) is a compound of formula (Ic): wherein B and Y are as defined for formula (I), including any preferred definition and definition in any of the specific embodiments of the compound of formula (I). Particularly preferred compounds of formula (I) are selected from the following compounds, or their pharmaceutically acceptable salts: , , , , , ,5 , , , , ,5 , , , 5 , , , , 5 , , , , 5 , , , Further preferred compounds of formula (I) are selected from the following compounds or their pharmaceutically suitable salts: 6-(3,4-dimethylphenyl)-N-(1-imino-1-oxido-2,3-dihydro-1H-1l6-thiophen-3-yl)-2-oxo-1,2- dihydropyridine-3-carboxamide; 6-(3,4-dimethylphenyl)-N-((1S or R,3 S)-1-imino-1-oxido-2,3-dihydro-1H-1l6-thiophen-3-yl)-2- oxo-1,2-dihydropyridine-3-carboxamide 6-(3,4-dimethylphenyl)-N-((1R or S,3 S)-1-imino-1-oxido-2,3-dihydro-1H-1l6-thiophen-3-yl)-2- oxo-1,2-dihydropyridine-3-carboxamide; 6-(3,4-dimethylphenyl)-N-((1S or R,3 R)-1-imino-1-oxido-2,3-dihydro-1H-1l6-thiophen-3-yl)-2- oxo-1,2-dihydropyridine-3-carboxamide; 6-(3,4-dimethylphenyl)-N-((1R or S,3 R)-1-imino-1-oxido-2,3-dihydro-1H-1l6-thiophen-3-yl)-2- oxo-1,2-dihydropyridine-3-carboxamide; 6-(3,4-dimethylphenyl)-N-(1-oxido-2,3-dihydrothiophen-3-yl)-2-oxo-1,2-dihydropyridine-3- carboxamide; 5-(3,4-dimethylphenyl)-2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)pyridine 1-oxide; 6-(3,4-dimethylphenyl)-N-(1-(methylimino)-1-oxido-2,3-dihydro-1H-1l6-thiophen-3-yl)-2-oxo-1,2- dihydropyridine-3-carboxamide; 5-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)picolinamide; (R)-5-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)picolinamide; (S)-5-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)picolinamide; N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-2-oxo-6-(piperidin-1-yl)-1,2-dihydropyridine-3- carboxamide; 6-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-2-oxo-1,2-dihydropyridine-3- sulfonamide; N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-2-oxo-6-(prop-1-yn-1-yl)-1,2-dihydropyridine-3- carboxamide; and 6-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-2-thioxo-1,2-dihydropyridine-3- carboxamide. Further suitable compounds of formula (I) are selected from the following compounds, or their pharmaceutically acceptable salts: , , , 5 Further suitable compounds of formula (I) are selected from the following compounds, or their pharmaceutically acceptable salts: , , , , Further suitable compounds of formula (I) are selected from the following compounds, or their pharmaceutically acceptable salts: Further suitable compounds of formula (I) are selected from the following compounds, or their pharmaceutically acceptable salts: In one embodiment, particularly suitable compound of formula is its pharmaceutically acceptable salt. In one embodiment, particularly suitable compound of formula (I) is In one embodiment, particularly suitable compound of formula (I) is In one embodiment, particularly suitable compound of formula (I) is its pharmaceutically acceptable salt. The compound of formula (I) is preferably a compound selected from the following compounds: 6-(3,4-dimethylphenyl)-N-(1-imino-1-oxido-2,3-dihydro-1H-1 6-thiophen-3-yl)-2-oxo-1,2- dihydropyridine-3-carboxamide; 6-(3,4-dimethylphenyl)-N-((1S or R,3S or R)-1-imino-1-oxido-2,3-dihydro-1H-16-thiophen-3-yl)- 2-oxo-1,2-dihydropyridine-3-carboxamide; 6-(3,4-dimethylphenyl)-N-((1R or S,3S or R)-1-imino-1-oxido-2,3-dihydro-1H-1 6-thiophen-3-yl)- 2-oxo-1,2-dihydropyridine-3-carboxamide; 6-(3,4-dimethylphenyl)-N-((1S or R,3R or S)-1-imino-1-oxido-2,3-dihydro-1H-16-thiophen-3-yl)- 2-oxo-1,2-dihydropyridine-3-carboxamide; 6-(3,4-dimethylphenyl)-N-((1R or S,3R or S)-1-imino-1-oxido-2,3-dihydro-1H-16-thiophen-3-yl)- 2-oxo-1,2-dihydropyridine-3-carboxamide; 6-(3,4-dimethylphenyl)-N-(1-oxido-2,3-dihydrothiophen-3-yl)-2-oxo-1,2-dihydropyridine-3- carboxamide; 5-(3,4-dimethylphenyl)-2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)pyridine 1-oxide; 6-(3,4-dimethylphenyl)-N-(1-(methylimino)-1-oxido-2,3-dihydro-1H-16-thiophen-3-yl)-2-oxo-1,2- dihydropyridine-3-carboxamide; 5-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)picolinamide; (R or S)-5-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)picolinamide; (S or R)-5-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)picolinamide; N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-2-oxo-6-(piperidin-1-yl)-1,2-dihydropyridine-3- carboxamide; 6-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-2-oxo-1,2-dihydropyridine-3- sulfonamide; N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-2-oxo-6-(prop-1-yn-1-yl)-1,2-dihydropyridine-3- carboxamide; 6-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-2-thioxo-1,2-dihydropyridine-3- carboxamide; N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-3-fluoro-3',4'-dimethyl-[1,1'-biphenyl]-4-carboxamide; 3-amino-5-(3,4-dimethylphenyl)-2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)pyridine 1- oxide; (R)-3-amino-5-(3,4-dimethylphenyl)-2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)pyridine 1-oxide; 2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)-5-(4-(trifluoromethyl)phenyl)pyridine 1- oxide; 4-amino-5-(3,4-dimethylphenyl)-2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)pyridine 1- oxide; (R)-5-(2-(benzyloxy)phenyl)-2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)pyridine 1-oxide (R)-2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)-5-(5-methylthiophen-3-yl)pyridine 1- oxide; 2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)-5-(spiro[3.3]hept-1-en-2-yl)pyridine 1-oxide; 5-(2-chlorothiophen-3-yl)-2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)pyridine 1-oxide; 3-(4-(6-(3,4-dimethylphenyl)-2-methoxypyridin-3-yl)-1H-1,2,3-triazol-1-yl)-2,3-dihydrothiophene 1,1-dioxide; 3-(4-(6-(3,4-dimethylphenyl)-2-hydroxypyridin-3-yl)-1H-1,2,3-triazol-1-yl)-2,3-dihydrothiophene 1,1-dioxide; (R)-3-(4-(6-(3,4-dimethylphenyl)-2-methoxypyridin-3-yl)-1H-1,2,3-triazol-1-yl)-2,3- dihydrothiophene 1,1-dioxide; (S)-3-(4-(6-(3,4-dimethylphenyl)-2-methoxypyridin-3-yl)-1H-1,2,3-triazol-1-yl)-2,3- dihydrothiophene 1,1-dioxide; (R)-3-(4-(6-(3,4-dimethylphenyl)-2-hydroxypyridin-3-yl)-1H-1,2,3-triazol-1-yl)-2,3- dihydrothiophene 1,1-dioxide hydrochloride; (S)-3-(4-(6-(3,4-dimethylphenyl)-2-hydroxypyridin-3-yl)-1H-1,2,3-triazol-1-yl)-2,3- dihydrothiophene 1,1-dioxide hydrochloride; (S,Z)-5-(3,4-dimethylphenyl)-2-((4-(methylsulfonyl)but-3-en-2-yl)carbamoyl)pyridine 1-oxide; (R)-5-(4,5-dimethylthiophen-2-yl)-2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)pyridine 1- oxide; (R)-2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)-5-(5-(trifluoromethyl)thiophen-2- yl)pyridine 1-oxide; (E)-N-(1-cyclopropyl-3-fluoro-3-(methylsulfonyl)allyl)-2-(cyclopropyldifluoromethyl)-4- phenoxypyrimidine-5-carboxamide ; (Z)-N-(1-cyclopropyl-3-fluoro-3-(methylsulfonyl)allyl)-2-(cyclopropyldifluoromethyl)-4- phenoxypyrimidine-5-carboxamide; (E)-N-(1-cyclopropyl-3-(S-methylsulfonimidoyl)allyl)-2-(1,1-difluoroethyl)-4-phenoxypyrimidine-5- carboxamide; (E)-N-(1-cyclopropyl-3-(N,S-dimethylsulfonimidoyl)allyl)-2-(1,1-difluoroethyl)-4- phenoxypyrimidine-5-carboxamide; N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-6-ethynyl-2-oxo-1,2-dihydropyridine-3-carboxamide; N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-2-oxo-6-(pyrrolidin-1-yl)-1,2-dihydropyridine-3- carboxamide; N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-6-(3-methylbut-1-yn-1-yl)-2-oxo-1,2-dihydropyridine-3- carboxamide; N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-6-(3-methylbut-1-yn-1-yl)-2-oxo-1,2-dihydropyridine-3- carboxamide; (R)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-5-(spiro[3.3]heptan-2-yl)picolinamide; 5-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-1H-1,2,4-triazole-3- carboxamide; (R)-5-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-4H-1,2,4-triazole-3- carboxamide; (R)-2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)-5-(5-methylthiophen-2-yl)pyridine 1- oxide; (R)-5-(cyclohex-1-en-1-yl)-2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)pyridine 1-oxide; (R)-5-cyclohexyl-2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)pyridine 1-oxide; N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-2-oxo-6-(tetrahydro-2H-pyran-3-yl)-1,2- dihydropyridine-3-carboxamide; 6-(3,4-dihydro-2H-pyran-6-yl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-2-oxo-1,2- dihydropyridine-3-carboxamide; N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-2-oxo-6-(tetrahydro-2H-pyran-2-yl)-1,2- dihydropyridine-3-carboxamide; 6-(3,6-dihydro-2H-pyran-4-yl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-2-oxo-1,2- dihydropyridine-3-carboxamide; (R)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-2-oxo-6-(tetrahydro-2H-pyran-4-yl)-1,2- dihydropyridine-3-carboxamide; 6-(5,6-dihydro-2H-pyran-3-yl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-2-oxo-1,2- dihydropyridine-3-carboxamide; (R)-5-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)thiazole-2-carboxamide; (R)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-2-oxo-6-phenyl-2H-pyran-3-carboxamide; 2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)-5-(piperidin-1-yl)pyridine 1-oxide; (R)-5-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-1,3,4-thiadiazole-2- carboxamide; (R)-5-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-1H-imidazole-2- carboxamide; (S)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-1-methyl-2-(p-tolyl)-1H-imidazole-4-carboxamide; (R)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-1-methyl-2-(p-tolyl)-1H-imidazole-4-carboxamide; 2-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-1H-imidazole-4-carboxamide; (R)-5-(4-chlorophenyl)-2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)pyridine 1-oxide; (R)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-2-methoxy-6-(tetrahydro-2H-pyran-4- yl)nicotinamide; 6-(3,4-dimethylphenyl)-N-((3R)-1-oxido-2,3-dihydrothiophen-3-yl)-2-oxo-1,2-dihydropyridine-3- carboxamide; 6-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)nicotinamide; N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-3',4'-dimethyl-[1,1'-biphenyl]-4-carboxamide; (R)-5-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-3-fluorothiophene-2- carboxamide; 2-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)pyrimidine-5-carboxamide; 5-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)pyrimidine-2-carboxamide; 6-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)pyridazine-3-carboxamide; 2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)-5-(spiro[3.3]heptan-2-yl)pyridine 1-oxide; 6-(3,4-dimethylphenyl)-3-(6,6-dioxido-6-thia-2-azaspiro[3.4]oct-7-en-2-yl)pyridin-2(1H)-one; 3-((6-(3,4-dimethylphenyl)-1H-indazol-3-yl)oxy)-2,3-dihydrothiophene 1,1-dioxide; 6-(3,4-dimethylphenyl)-1-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-1,2-dihydro-3H-indazol-3-one; 5-(3,4-dimethylphenyl)-2-(1,1-dioxido-2,3-dihydrothiophen-3-yl)isoindolin-1-one; (R)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-2-oxo-6-(phenylethynyl)-1,2-dihydropyridine-3- carboxamide; 5-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-4-hydroxypicolinamide; 5-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-3-hydroxypicolinamide; 6-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-4-oxo-1,4-dihydropyridine-3- carboxamide; (R)-5-(2,4-dimethylphenyl)-2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)pyridine 1-oxide; (R)-5-(3,4-dichlorophenyl)-2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)pyridine 1-oxide; (R)-5-(3,4-difluorophenyl)-2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)pyridine 1-oxide; (R)-2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)-5-(4-methoxyphenyl)pyridine 1-oxide; 5-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-3-fluoropicolinamide; 5-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-6-fluoropicolinamide; 6-(3,4-dimethylphenyl)-N-(1-methyl-1-oxido-2,3-dihydrophosphol-3-yl)-2-oxo-1,2- dihydropyridine-3-carboxamide; 3-amino-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-3',4'-dimethyl-[1,1'-biphenyl]-4-carboxamide; 5-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-4-methylpicolinamide; 5-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-6-methylpicolinamide; 5-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-3-methylpicolinamide; 2-amino-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-3',4'-dimethyl-[1,1'-biphenyl]-4-carboxamide; (S)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-2-(4-(trifluoromethyl)phenyl)thiazole-4- carboxamide; (R)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-2-(4-(trifluoromethyl)phenyl)thiazole-4- carboxamide; N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-3-hydroxy-3',4'-dimethyl-[1,1'-biphenyl]-4-carboxamide; 3-chloro-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-3',4'-dimethyl-[1,1'-biphenyl]-4-carboxamide; N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-2-fluoro-3',4'-dimethyl-[1,1'-biphenyl]-4-carboxamide; N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-2,3',4'-trimethyl-[1,1'-biphenyl]-4-carboxamide; 2-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-6-oxo-1,6-dihydropyrimidine-5- carboxamide; 5-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-3-oxo-3,4-dihydropyrazine-2- carboxamide; 2-amino-6-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)nicotinamide; (R)-2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)-5-(2,4,6-trifluorophenyl)pyridine 1- oxide; 3-(3,4-dimethylphenyl)-6-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)-2-fluoropyridine 1- oxide; 5-(3,4-dimethylphenyl)-2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)-4-fluoropyridine 1- oxide; 6-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-2-methoxynicotinamide; 5-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-3-methoxypicolinamide; 6-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-1-methyl-4-oxo-1,4- dihydropyridine-3-carboxamide; 3-(3,4-dimethylphenyl)-6-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)-2-methylpyridine 1- oxide; 3-(3,4-dimethylphenyl)-6-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)-2-hydroxypyridine 1- oxide; 5-(3,4-dimethylphenyl)-2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)-4-hydroxypyridine 1- oxide; 5-(3,4-dimethylphenyl)-2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)-3-hydroxypyridine 1- oxide; (R)-5-chloro-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-2-hydroxy-3',4'-dimethyl-[1,1'-biphenyl]-4- carboxamide; (S)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-5-fluoro-2-hydroxy-3',4'-dimethyl-[1,1'-biphenyl]-4- carboxamide; (R)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-5-fluoro-2-hydroxy-3',4'-dimethyl-[1,1'-biphenyl]-4- carboxamide; N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-3-methoxy-3',4'-dimethyl-[1,1'-biphenyl]-4- carboxamide; N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-3-methoxy-3',4'-dimethyl-[1,1'-biphenyl]-4- carboxamide; 2-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-4-methoxypyrimidine-5- carboxamide; 5-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-3-methoxypyrazine-2- carboxamide; 6-(3,4-dimethylphenyl)-N-(1-(methylimino)-1-oxido-2,3-dihydro-1H-16-thiophen-3-yl)-2-oxo-1,2- dihydropyridine-3-carboxamide; (E)-6-(3,4-dimethylphenyl)-3-(5-(2-(methylsulfonyl)vinyl)-1H-imidazol-2-yl)pyridin-2-ol; (R)-5-(4-cyclopropylphenyl)-2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)pyridine 1- oxide; (R)-5-(benzofuran-5-yl)-2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)pyridine 1-oxide; (R)-5-(2,3-dihydrobenzofuran-5-yl)-2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)pyridine 1-oxide; 2-(6-(3,4-dimethylphenyl)-2-methoxypyridin-3-yl)-6-thia-2-azaspiro[3.4]oct-7-ene 6,6-dioxide; 7-(3,4-dimethylphenyl)-3-(1,1-dioxido-2,3-dihydrothiophen-3-yl)quinazolin-4(3H)-one; 2-(3,4-dimethylphenyl)-6-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-7,8-dihydro-1,6-naphthyridin- 5(6H)-one; 6-(3,4-dimethylphenyl)-2-(1,1-dioxido-2,3-dihydrothiophen-3-yl)isoquinolin-1(2H)-one; 6-(3,4-dimethylphenyl)-2-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-3,4-dihydroisoquinolin-1(2H)- one; 7-(3,4-dimethylphenyl)-3-(1,1-dioxido-2,3-dihydrothiophen-3-yl)pyrido[2,3-d]pyrimidin-4(3H)- one; 2-(6-(3,4-dimethylphenyl)-2-hydroxypyridin-3-yl)-7-thia-1,3-diazaspiro[4.4]nona-2,8-diene 7,7- dioxide; (R)-2-(6-(3,4-dimethylphenyl)-2-hydroxypyridin-3-yl)-7-thia-1,3-diazaspiro[4.4]nona-2,8-diene 7,7-dioxide; (S)-2-(6-(3,4-dimethylphenyl)-2-hydroxypyridin-3-yl)-7-thia-1,3-diazaspiro[4.4]nona-2,8-diene 7,7-dioxide; (R,Z)-5-(3,4-dimethylphenyl)-2-((4-(methylsulfonyl)but-3-en-2-yl)carbamoyl)pyridine 1-oxide; (R,E)-5-(3,4-dimethylphenyl)-2-((4-(methylsulfonyl)but-3-en-2-yl)carbamoyl)pyridine 1-oxide; (S,E)-5-(3,4-dimethylphenyl)-2-((4-(methylsulfonyl)but-3-en-2-yl)carbamoyl)pyridine 1-oxide; 7-(5-(4-(trifluoromethyl)phenyl)pyridin-2-yl)-2-thia-7-azaspiro[4.4]non-3-ene 2,2-dioxide; 7-(3,4-dimethylphenyl)-3-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-8-fluoroquinazolin-4(3H)-one; 7-(6-(3,4-dimethylphenyl)-2-methoxypyridin-3-yl)-2-thia-7-azaspiro[4.4]non-3-ene 2,2-dioxide; (S)-4-(3-cyclopropyl-1H-pyrazol-1-yl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-2-methoxy-6- methylbenzamide; (R)-4-(3-cyclopropyl-1H-pyrazol-1-yl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-2-methoxy-6- methylbenzamide; 7-(3,4-dimethylphenyl)-3-(1,1-dioxido-2,3-dihydrothiophen-3-yl)pyrido[2,3-d]pyrimidine- 2,4(1H,3H)-dione; 2-(6-(3,4-dimethylphenyl)-2-methoxypyridin-3-yl)-7-thia-1,3-diazaspiro[4.4]nona-2,8-diene 7,7- dioxide; (R)-2-(6-(3,4-dimethylphenyl)-2-methoxypyridin-3-yl)-7-thia-1,3-diazaspiro[4.4]nona-2,8-diene 7,7-dioxide; (S)-2-(6-(3,4-dimethylphenyl)-2-methoxypyridin-3-yl)-7-thia-1,3-diazaspiro[4.4]nona-2,8-diene 7,7-dioxide; (R)-7-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-1H-benzo[d]imidazole-4- carboxamide; N-(1-(cyanoimino)-1-oxido-2,3-dihydro-1H-16-thiophen-3-yl)-6-(3,4-dimethylphenyl)-2-oxo-1,2- dihydropyridine-3-carboxamide; N-(1-(cyanoimino)-1-oxido-4,5-dihydro-1H-16-thiophen-3-yl)-6-(3,4-dimethylphenyl)-2-oxo-1,2- dihydropyridine-3-carboxamide; 3-(3,4-dimethylphenyl)-6-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)-2-methoxypyridine 1-oxide; 5-(3,4-dimethylphenyl)-2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)-4-methoxypyridine 1-oxide; 5-(3,4-dimethylphenyl)-2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)-3-methoxypyridine 1-oxide; N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-2-oxo-6-(4-(trifluoromethyl)piperidin-1-yl)-1,2- dihydropyridine-3-carboxamide; 2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)-5-(4-(trifluoromethyl)piperidin-1-yl)pyridine 1-oxide; (R)-3-amino-2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)-5-(5-(trifluoromethyl)thiophen- 3-yl)pyridine 1-oxide; (R)-3-amino-2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)-5-(5-(trifluoromethyl)thiophen- 2-yl)pyridine 1-oxide; (R)-3-amino-2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)-5-(4-(trifluoromethyl)thiophen- 2-yl)pyridine 1-oxide; (R)-2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)-5-(3-methyl-4- (trifluoromethyl)phenyl)pyridine 1-oxide; (S,Z)-N-(1-cyclopropyl-3-(methylsulfonyl)allyl)-6-(3,4-dimethylphenyl)-2-oxo-1,2-dihydropyridine- 3-carboxamide; (S,E)-N-(1-cyclopropyl-3-(methylsulfonyl)allyl)-6-(3,4-dimethylphenyl)-2-oxo-1,2-dihydropyridine- 3-carboxamide; (S,Z)-2-((1-cyclopropyl-3-(methylsulfonyl)allyl)carbamoyl)-5-(3,4-dimethylphenyl)pyridine 1- oxide; (S,E)-2-((1-cyclopropyl-3-(methylsulfonyl)allyl)carbamoyl)-5-(3,4-dimethylphenyl)pyridine 1- oxide; (R)-5-(2-chloro-4-(trifluoromethyl)phenyl)-2-((1,1-dioxido-2,3-dihydrothiophen-3- yl)carbamoyl)pyridine 1-oxide; 6-(3,4-dimethylphenyl)-3-(1-((1,1-dioxido-2,3-dihydrothiophen-3-yl)amino)-2,2,2- trifluoroethyl)pyridin-2(1H)-one; 7-(3,4-dimethylphenyl)-3-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-8-fluoro-2-hydroxy-2,3- dihydroquinazolin-4(1H)-one; 8-(5-(4-(trifluoromethyl)phenyl)pyridin-2-yl)-2-thia-8-azaspiro[4.5]dec-3-ene 2,2-dioxide; (R)-5-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)quinoline-8-carboxamide; 2-(6-(3,4-dimethylphenyl)-2-methoxypyridin-3-yl)-8-thia-1,3-diazaspiro[4.5]deca-2,6-diene 8,8- dioxide; 3-(6-(3,4-dimethylphenyl)-2-hydroxypyridin-3-yl)-9-thia-2,4-diazaspiro[5.5]undeca-2,7-diene 9,9- dioxide; (R)-5-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)quinazoline-8-carboxamide; 3-(6-(3,4-dimethylphenyl)-2-methoxypyridin-3-yl)-9-thia-2,4-diazaspiro[5.5]undeca-2,7-diene 9,9-dioxide; 3-(4-(6-cyclopentyl-2-phenoxypyridin-3-yl)-1H-1,2,3-triazol-1-yl)-2,3-dihydrothiophene 1,1- dioxide; 2-(2-(cyclopropyldifluoromethyl)-4-phenoxypyrimidin-5-yl)-7-thia-1,3-diazaspiro[4.4]nona-2,8- diene 7,7-dioxide; (E)-2-(cyclopropyldifluoromethyl)-5-(5-(2-(methylsulfonyl)vinyl)-1H-imidazol-2-yl)-4- phenoxypyrimidine; 3-(4-(6-(isopropyl(methyl)amino)-2-phenoxypyridin-3-yl)-1H-1,2,3-triazol-1-yl)-2,3- dihydrothiophene 1,1-dioxide; (R)-5-(2-(benzylamino)phenyl)-2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)pyridine 1- oxide; 2-(6-(3,4-dimethylphenyl)-2-phenoxypyridin-3-yl)-7-thia-1,3-diazaspiro[4.4]nona-2,8-diene 7,7- dioxide; (S)-2-(6-(3,4-dimethylphenyl)-2-phenoxypyridin-3-yl)-7-thia-1,3-diazaspiro[4.4]nona-2,8-diene 7,7-dioxide; (R)-5-(2-(benzyloxy)-3-fluorophenyl)-2-((1,1-dioxido-2,3-dihydrothiophen-3- yl)carbamoyl)pyridine 1-oxide; (R)-5-(2-(benzyloxy)-4-fluorophenyl)-2-((1,1-dioxido-2,3-dihydrothiophen-3- yl)carbamoyl)pyridine 1-oxide; (R)-5-(2-(benzyloxy)-5-fluorophenyl)-2-((1,1-dioxido-2,3-dihydrothiophen-3- yl)carbamoyl)pyridine 1-oxide; (R)-5-(2-(benzyloxy)-6-fluorophenyl)-2-((1,1-dioxido-2,3-dihydrothiophen-3- yl)carbamoyl)pyridine 1-oxide; (R)-5-(2-(benzyloxy)-5-methylphenyl)-2-((1,1-dioxido-2,3-dihydrothiophen-3- yl)carbamoyl)pyridine 1-oxide; (R)-5-(2-(benzyloxy)-3-methylphenyl)-2-((1,1-dioxido-2,3-dihydrothiophen-3- yl)carbamoyl)pyridine 1-oxide; (R)-5-(2-(benzyloxy)-4-methylphenyl)-2-((1,1-dioxido-2,3-dihydrothiophen-3- yl)carbamoyl)pyridine 1-oxide; (R)-5-(2-(benzyloxy)-6-methylphenyl)-2-((1,1-dioxido-2,3-dihydrothiophen-3- yl)carbamoyl)pyridine 1-oxide; (R)-2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)-5-(5-fluoro-2-(pyridin-4- ylmethoxy)phenyl)pyridine 1-oxide; or a pharmaceutically acceptable salt thereof. As further provided herein, particularly preferred is a compound selected from: N-((S,E)-1-cyclopropyl-3-((R)-S-methylsulfonimidoyl)allyl)-2-(1,1-difluoroethyl)-4- phenoxypyrimidine-5-carboxamide, -((S,E)-1-cyclopropyl-3-((S)-S-methylsulfonimidoyl)allyl)-2-(1,1- difluoroethyl)-4-phenoxypyrimidine-5-carboxamide, N-((R,E)-1-cyclopropyl-3-((R)-S- methylsulfonimidoyl)allyl)-2-(1,1-difluoroethyl)-4-phenoxypyrimidine-5-carboxamide, and N-((R,E)-1- cyclopropyl-3-((S)-S-methylsulfonimidoyl)allyl)-2-(1,1-difluoroethyl)-4-phenoxypyrimidine-5-carboxamide, characterized by the highest retention time of these compounds in an SFC experiment according to method 13, or a pharmaceutically acceptable salt thereof. Accordingly, particularly suitable is the compound described as compound 32d, i.e., the compound of formula: as defined in the foregoing. As further provided herein, particularly preferred is a compound selected from: N-((S,E)-1-cyclopropyl-3-((R)-N,S-dimethylsulfonimidoyl)allyl)-2-(1,1-difluoroethyl)-4- phenoxypyrimidine-5-carboxamide, N-((S,E)-1-cyclopropyl-3-((S)-N,S-dimethylsulfonimidoyl)allyl)-2-(1,1- difluoroethyl)-4-phenoxypyrimidine-5-carboxamide, N-((R,E)-1-cyclopropyl-3-((R)-N,S- dimethylsulfonimidoyl)allyl)-2-(1,1-difluoroethyl)-4-phenoxypyrimidine-5-carboxamide, and N-((R,E)-1- cyclopropyl-3-((S)-N,S-dimethylsulfonimidoyl)allyl)-2-(1,1-difluoroethyl)-4-phenoxypyrimidine-5- carboxamide, characterized by the second highest retention time of these compounds in an SFC experiment according to method 14. Accordingly, particularly suitable is a compound described as 33c , i.e., the compound of formula: as defined in the foregoing. Alternatively, particularly preferred is a compound selected from: N-((S,E)-1-cyclopropyl-3-((R)-N,S-dimethylsulfonimidoyl)allyl)-2-(1,1-difluoroethyl)-4- phenoxypyrimidine-5-carboxamide, N-((S,E)-1-cyclopropyl-3-((S)-N,S-dimethylsulfonimidoyl)allyl)-2-(1,1- difluoroethyl)-4-phenoxypyrimidine-5-carboxamide, N-((R,E)-1-cyclopropyl-3-((R)-N,S- dimethylsulfonimidoyl)allyl)-2-(1,1-difluoroethyl)-4-phenoxypyrimidine-5-carboxamide, and N-((R,E)-1- cyclopropyl-3-((S)-N,S-dimethylsulfonimidoyl)allyl)-2-(1,1-difluoroethyl)-4-phenoxypyrimidine-5- carboxamide, characterized by the highest retention time of these compounds in an SFC experiment according to method 14. Accordingly, particularly suitable is a compound described as 33d, i.e., the compound of formula: as defined in the foregoing. For a number of compounds disclosed herein, enantiomeric forms may exist. The present invention further refers to each and every enantiomeric form of such compound individually. 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 replaced by deuterium atoms (i.e.,2H; also referred to as “D”). Accordingly, the invention also embraces compounds of 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 and Radiopharmaceuticals, 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 in deuterium. Accordingly, the presence of naturally occurring hydrogen atoms or1H hydrogen atoms in the compounds of formula (I) is preferred. The present invention also embraces compounds of formula (I), in which one or more atoms are replaced by a positron-emitting isotope of the corresponding atom, such as, e.g.,18F,11C,13N,15O,76Br,77Br,120I and / or124I. Such compounds can be used as tracers, trackers or imaging probes in positron emission tomography (PET). The invention thus includes (i) compounds of formula (I), in which one or more fluorine atoms (or, e.g., all fluorine atoms) are replaced by18F atoms, (ii) compounds of formula (I), in which one or more carbon atoms (or, e.g., all carbon atoms) are replaced by11C atoms, (iii) compounds of formula (I), in which one or more nitrogen atoms (or, e.g., all nitrogen atoms) are replaced by13N atoms, (iv) compounds of formula (I), in which one or more oxygen atoms (or, e.g., all oxygen atoms) are replaced by15O atoms, (v) compounds of formula (I), in which one or more bromine atoms (or, e.g., all bromine atoms) are replaced by76Br atoms, (vi) compounds of formula (I), in which one or more bromine atoms (or, e.g., all bromine atoms) are replaced by77Br atoms, (vii) compounds of formula (I), in which one or more iodine atoms (or, e.g., all iodine atoms) are replaced by120I atoms, and (viii) compounds of formula (I), in which one or more iodine atoms (or, e.g., all iodine atoms) are replaced by124I atoms. In general, it is preferred that none of the atoms in the compounds of formula (I) are replaced by specific isotopes. The present invention further embraces the prodrugs of the compounds of formula (I). As preferably understood herein, the term “prodrug” of the compound of formula (I) refers to a derivative of the compounds of formula (I) that upon administration to a subject becomes metabolized to the said compound of formula (I). Said prodrugs of the compound of formula (I) may include modifications of -OH, -NH2, or -COOH group if present in the compound of formula (I), which preferably can be hydrolyzed to - OH, -NH2, or -COOH groups, respectively, e.g. upon administration to the subject. For example, as known to the skilled person, such prodrugs may preferably include for the compounds of formula (I) which comprise -OH moiety derivatives wherein said -OH moiety is turned into an -ORxmoiety, wherein Rxpreferably comprises a moiety selected from -CO-, -CH2-O-CO, -CH2-O-CO-O-, and -CH(CH3)-O-COO-, more preferably wherein Rx is selected from -CO-Ry, -CH2-O-CO-Ry, -CH2-O-CO-O-Ry, and -CH(CH3)-O- COO-Ry, wherein Ry is preferably carbocyclyl, heterocyclyl, C1-5 alkyl, -NH-(C1-5 alkyl) or -S-(C1-5 alkyl), wherein the said alkyl is optionally substituted with a group selected from halogen, -CN, -OH, C1-5 alkyl, C1-5 haloalkyl, -O(C1-5 alkyl), -O(C1-5 haloalkyl), -SH, -S(C1-5 alkyl), -S(C1-5 haloalkyl), -NH2, -NH(C1-5 alkyl), -NH(C1-5 haloalkyl), -N(C1-5 alkyl)(C1-5 alkyl), -N(C1-5 haloalkyl)(C1-5 alkyl), -CONH2, -CONH(C1-5 alkyl), and -CON(C1-5 alkyl)(C1-5 alkyl), and wherein the said carbocyclyl and heterocyclyl are each optionally substituted with a group selected from halogen, -CN, -OH, C1-5 alkyl, C1-5 haloalkyl, -O(C1-5 alkyl), -O(C1-5haloalkyl), -SH, -S(C1-5alkyl), -S(C1-5haloalkyl), -NH2, -NH(C1-5alkyl), -NH(C1-5haloalkyl), -N(C1-5 alkyl)(C1-5 alkyl), -N(C1-5 haloalkyl)(C1-5 alkyl), -CONH2, -CONH(C1-5 alkyl), and -CON(C1-5 alkyl)(C1-5 alkyl). Furthermore, for example, as known to the skilled person, such prodrugs may preferably include for the compounds of formula (I) which comprise -NH2 moiety derivatives wherein said -NH2 moiety is turned into -NHCOO-Ry moiety, wherein Ry is as defined hereinabove. Furthermore, for examples, as known to the skilled person, such prodrugs may preferably include for the compounds of formula (I) which comprise -COOH moiety derivatives wherein said -COOH group is turned into -COORy moiety, wherein Ry is as defined hereinabove. Further examples of groups that can be derivatized to yield prodrugs are known to the skilled person. Pharmaceutical compositions The compounds provided herein may be administered as compounds per se or may be formulated as 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, dipalmitoyl phosphatidylcholine, 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 lung adenocarcinoma with EGFR mutation E746-A750, or squamous cell carcinoma of the lung), renal cancer (or kidney cancer; e.g., renal carcinoma), gastrointestinal cancer, stomach cancer, colorectal cancer (e.g., colorectal carcinoma), colon cancer, anal cancer, genitourinary cancer, bladder cancer, liver cancer (e.g., hepatocellular carcinoma), pancreatic cancer (e.g., pancreatic adenocarcinoma or pancreatic ductal adenocarcinoma), cervical cancer, endometrial cancer, vaginal cancer, vulvar cancer, ovarian cancer (e.g., ovarian carcinoma), uterine cancer, prostate cancer (e.g., hormone-refractory prostate cancer), testicular cancer, biliary tract cancer, hepatobiliary cancer, neuroblastoma, brain cancer (e.g., glioblastoma), breast cancer (e.g., triple-negative breast cancer, breast cancer having a BRCA1 and / or BRCA2 gene mutation, or breast adenocarcinoma), head and / or neck cancer (e.g., head and neck squamous cell carcinoma), skin cancer, melanoma, Merkel-cell cancer (e.g., Merkel-cell carcinoma), epidermoid cancer, squamous cell cancer (or squamous cell carcinoma; including, e.g., oral squamous cell carcinoma / squamous-cell mouth carcinoma, squamous-cell skin cancer, squamous-cell lung carcinoma, squamous-cell thyroid carcinoma, squamous-cell esophageal carcinoma, or squamous-cell vaginal carcinoma), bone cancer (e.g., osteosarcoma or osteogenic sarcoma), fibrosarcoma, Ewing’s sarcoma, malignant mesothelioma, esophageal cancer, laryngeal cancer, mouth cancer, thymoma, neuroendocrine cancer (e.g., neuroendocrine carcinoma), goblet cell cancer (e.g., goblet cell carcinoid), hematological cancer, leukemia (e.g., acute lymphoblastic leukemia, acute myeloid leukemia, chronic lymphocytic leukemia, or chronic myeloid leukemia), lymphoma (e.g., Hodgkin lymphoma or non-Hodgkin lymphoma, such as, e.g., follicular lymphoma or diffuse large B-cell lymphoma), and multiple myeloma. Moreover, the cancer to be treated (including any one of the aforementioned specific types of cancer) may also be a chemoresistant and / or a metastatic cancer. 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 example linomide, 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). In the first step, compound 3 is prepared via cross-coupling reactions of suitably functionalized building blocks 1 and 2. Formation of a C-C bond between A (1) and B-X (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 or heteroaryl 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 terminal alkyne 1 and an aryl or heteroaryl halide 2 can be achieved employing palladium catalysts as well as copper co-catalysts (Sonogashira coupling, see e.g. I. Kanwal et al, Catalysts 2020, 10(4), 443). Moreover, formation of a C-N can be achieved via the palladium-catalyzed coupling reactions of amines 1 with aryl and heteroaryl halides 2 (Buchwald–Hartwig coupling, see e.g. R. Dorel et al, Angew. Chem. Int. Ed.2019, 58, 17118). In the second step, cross-coupling of A-B-X (3) and Y (4) can be achieved by various methods known of a person skilled in the art of organic synthesis, including e.g. a) coupling of carboxylic acids (3) and amines (4) (amide bond formation; see e.g. E. Massolo et al, Eur. J. Org. Chem.2020, 4641), b) coupling of sulfonyl chlorides (3) and amines (4) (sulfonamide bond formation: see e.g. A. Kolaczek et al, CHEMIK 2014, 68, 620) or c) coupling of amines (3) and halides (4) (amine alkylation: see e.g. R. N. Salvatoreet al, Tetrahedron 2001, 7785). For the synthesis of compounds of formula (I) in which B and X are combined to form a two ring system: similar cross-coupling reactions can be employed. The synthesis of the compounds of formula (I) bearing a spiro moiety: can be achieved utilizing the described cross-coupling reactions, too. Suitable building block containing the spiro motive are either commercial or can be synthesized by various methods known of a person skilled in the art of organic synthesis (see e.g. Spiro Compounds: Synthesis and Applications, ISBN:9781119567646, Editor: R. R. Torres, John Wiley & Sons). Preparative examples General considerations Abbreviations used in the descriptions that follow are: AcOH (acetic acid); aq. (aqueous); Ar (argon); Atm (atmosphere); BH3.THF (boran tetrahydrofuran complex); br (broad,1H NMR signal); Boc2O (di-tert- butyldicarbonate); BuLi (Butyl Lithium), Cataxium APdG3 (mesylate[(di(1-adamantyl)-n-butylphosphine)- 2-(2 -amino-1,1 -biphenyl)]palladium(II)); CDCl3 (deuterated chloroform); cHex (cyclohexane); CMPB (cyanomethylene trimethylphosphorane); Cs2CO3 (cesium carbonate); CuI (copper iodide); CuSO4 (cupric sulfate), DABCO (1,4-diazabicyclo[2.2.2]octane); DAST (diethylaminosulfur trifluoride); DBU (1,8-diazabicyclo(5.4.0)undec-7-ene); DCE (dichloroethane); d (doublet,1H NMR signal); DCM (dichloromethane); DEA (diethylamine); DIBAL-H (diisobutyl aluminium hydride); DIPEA or DIEA (di-iso- propylethylamine); DMA (dimethylacetamide); (DMAP (4- N-N-dimethylaminopyridine), DME (1,2- dimethoxyethane), DMEDA (dimethylethylenediamine ); DMF (N-N-dimethylformamide); DMSO (dimethyl sulfoxide); DPPA (diphenylphosphoride azide); dtbbpy (bis(1,1-dimethylethyl)-2,2 -bipyridine); ee (enantiomeric excess); ES (electrospray); EtOAc or EA (ethyl acetate); EtOH (ethanol); h (hour(s)); FA (formic acid); MgO (magnesium oxide); HATU (1-[bis(dimethylamino)methylene]-1H-1,2,3- triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate); HBr (hydrobromic acid); HFIP ( hexafluoroisopropanol); HI (hydrogen iodide);1H NMR (proton nuclear magnetic resonance spectroscopy); HPLC (high performance liquid chromatography); iPrMgBr (isopropylmagnesium bromide); iPrOH (iso-propanol); K2CO3 (potassium carbonate); K3PO4 (tripotassium phosphate); Ir[dF(CF3)(dtbbpy)PF6 ((4,4'-di-t-butyl-2,2'-bipyridine)bis[3,5-difluoro-2-[5-trifluoromethyl-2-pyridinyl- kN)phenyl-kC]iridium(III) hexafluorophosphate); LiOH (lithium hydroxide); m (multiplet,1H NMR signal); mCPBA (meta-chloroperoxybenzoic acid), MeCN (acetonitrile), MeOH (methanol); MeOK (potassium methanolate); min (minute(s)); MnO2 (manganese (IV) oxide); MS (mass spectrometry); MTBE (methyl tert-butyl ether); NaBH4 (sodium borohydride); NaHCO3 (sodium hydrogenocarbonate); NaI (sodium iodide); NaIO4 (sodium periodate); Na2SO3 (sodium sulfite); Na2S2O3 (sodium thiosulfate); Na2SO4 (sodium sulfate); NCS (N-chlorosuccinimide); NH3(ammonia); NH4Cl (ammonium chloride); NiCl2(nickel dichloride); NIS (N-iodosuccinimide); NMP (N-methylpyrrolidone); NMR (nuclear magnetic resonance); Pd / C (palladium on charcoal); Pd2dba3 (tris(dibenzylideneacetone)dipalladium); Pd(dppf)Cl2 (1,1- bis(diphenylphosphino)ferrocene dichloropalladium); Pd(Ph3)4 (tetrakis(triphenylphosphine) palladium (0)); Pd(Ph3)2Cl2 (bis(triphenylphosphine)palladium(II) dichloride ); PE (petroleum ether); Pd-PEPPSI- IPentCl o-picoline ([1,3-bis[2,6-bis(1-ethylpropyl)phenyl]-4,5-dichloro-imidazol-2-ylidene]-dichloro-(2- methylpyridin-1-ium-1-yl)palladiµm; Pd(OH)2 (palladium hydroxide); Pd(Ph3)4 (palladium- tetrakis(triphenylphosphine)); PhI(OAc)2 ((diacetoxyiodo)benzene)); P(tBu)3 (tri-tert-butylphosphine ); Py (pyridine); q (quartet, 1H NMR signal); quin (quintet, 1H NMR signal); rac (racemic); RT (retention time); s (singlet,1H NMR signal); sat. (saturated); t (triplet,1H NMR signal); SFC (supercritical fluid chromatography); TBAF (tetrabutylammonium fluoride); tert-BuBrettPhos-Pd-G3 ([(2-di-tert- butylphosphino-3,6-dimethoxy-2 ,4 ,6 -triisopropyl-1,1 -biphenyl)-2-(2 -amino-1,1 -biphenyl)]palladium(II) methanesulfonate); tBuXPhos Pd G3 (methanesulfonato(2-di-t-butylphosphino-2',4',6'-tri-i-propyl-1,1'- biphenyl)(2'-amino-1,1'-biphenyl-2-yl)palladium(II)); TBDMSCl or TBSCl (tert-butyldimethylsilyl chloride); tBuOH (tert-butanol); TEA (triethylamine); TFA (trifluoroacetic acid); TFAA (trifluoroacetic anhydride); THF (tetrahydrofuran); TLC (thin layer chromatography); TMSCHN2 (trimethylsilyldiazomethane); TMSCN (trimethylsilyl cyanide); TMSI (trimethylsilyl iodide); TMSOTf (trimethylsilyl trifluoromethanesulfonate); TTMSS (trimethylsilane); TsOH (p-Toluenesulfonic acid); T4P (2,4,6-tributyl- 1,3,5,2,4,6-trioxatriphosphinane 2,4,6-trioxide); UPLC (ultra-high performance liquid chromatography), UV (ultraviolet), wt-% (percent by weight); Xantphos (4,5-bis(diphenylphosphino)-9,9-dimethylxanthene); Xantphos Pd G4 (methanesulfonato[9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene](2'- methylamino-1,1'-biphenyl-2-yl)palladium(II)), Xphos (2-Dicyclohexylphosphin-2 ,4 ,6 - triisopropylbiphenyl). General Procedure: All starting materials and solvents were obtained either from commercial sources 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. Methods for Reversed Phase HPLC conditions for LCMS Analysis of compounds: Method 1: SHIMADZU LCMS-2020 Kinetex EVO C182.1X30mm, 5 m at 50 ; Mobile Phase: A: 0.0375% TFA in water (v / v); B: 0.01875% TFA in MeCN (v / v); flow rate held at 1.5 mL / min; eluted with the mobile phase over 1.55 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 C182.1X30mm, 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 1.55 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 Kinetex EVO C182.1X30mm,5 m at 50 ; Mobile Phase: A: 0.0375% TFA in water (v / v); B: 0.01875% TFA in MeCN (v / v); flow rate held at 2.0 mL / min; eluted with the mobile phase over 0.80 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 4: SHIMADZU LCMS-2020 Kinetex®EVO C182.1X20 mm 2.6 m at 50°C; Mobile Phase: A: 0.0375% TFA in water (v / v); B: 0.01875% TFA in MeCN (v / v); flow rate held at 2.0 mL / min; eluted with the mobile phase over 1.00 min employing UV detection at 220 nm and 254 nm. Gradient information: 0.01-0.60 min, ramped from 95% A-5% B to 5% A-95% B; 0.61-0.78 min, held at 5% A-95% B; 0.78-0.79 min, returned to 95% A-5% B, 0.79-0.80 min, held at 95% A-5% B. Method 5: SHIMADZU LCMS-2020 Kinetex®EVO C182.1X30 mm 5 m at 50°C Mobile Phase: A: 0.0375% TFA in water (v / v); B: 0.01875% TFA in MeCN (v / v); flow rate held at 1.5 mL / min; eluted with the mobile phase over 1.00 min employing UV detection at 220 nm and 254 nm. Gradient information: 0.01-0.80 min, ramped from 95% A-5% B to 5% A-95% B; 0.80-0.95 min, held at 5% A-95% B; 0.95-0.96 min, returned to 95% A-5% B, 0.96-1.00 min, held at 95% A-5% B. Method 6: SHIMADZU LCMS-2020 Kinetex® HALO C183.0X30mm, 5 m at 50 ; Mobile Phase: A: 0.0375% TFA in water (v / v); B: 0.01875% TFA in MeCN (v / v); flow rate held at 1.5 mL / min; eluted with the mobile phase over 1.05 min employing UV detection at 220 nm and 254 nm. Gradient information: 0- 0.80 min, ramped from 50% A-50% B to 0% A-100% B; 0.80-1.05 min, held at 50% A-50% B. Method 7: SHIMADZU LCMS-2020 HALO C183.0X30 mm, 5 m at 50 , Mobile Phase: A: 0.0375% TFA in water (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 8: SHIMADZU LCMS-2020 HALO C183.0X30mm, 5 m at 50 ; Mobile Phase: A: 0.0375% TFA in water (v / v); B: 0.01875% TFA in MeCN (v / v); flow rate held at 1.5 mL / min; eluted with the mobile phase over 0.80 min employing UV detection at 220 nm and 254 nm. Gradient information: 0- 0.45 min, ramped from 95% A-5% B to 5% A-95% B; 0.45-0.70 min, held at 5% A-95% B; 0.70-0.71 min, returned to 95% A-5% B, 0.71-0.80 min, held at 95% A-5% B. Method 9: SHIMADZU LCMS-2020 Kinetex®EVO C182.1X30 mm, 5 m at 40 Mobile Phase: A: water; B: MeCN; 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 10: SHIMADZU LCMS-2020 Waters Xselect HSS T3, 3.5 µm, 4.6*50mm at 40 ; 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 5.20 min employing UV detection at 220 nm and 254 nm. Gradient information: 0-3.50 min, ramped from 95% A-5% B to 5% A-95% B; 3.50-4.80 min, held at 5% A-95% B; 4.80-4.81 min, returned to 95% A-5% B; 4.81-5.20 min, held at 95% A-5% B Method 11: SHIMADZU LCMS-2020 HALO C183.0X30mm,5 m at 50 ; Mobile Phase: A: 0.0375% TFA in water (v / v); B: 0.01875% TFA in MeCN (v / v); flow rate held at 1.5 mL / min; eluted with the mobile phase over 3.00 min employing UV detection at 220 nm and 254 nm. Gradient information: 0- 2.10 min, ramped from 95% A-5% B to 5% A-95% B; 2.10-2.80 min, held at 5% A-95% B; 2.80-2.81 min, returned to 95% A-5% B, 2.81-3.00 min, held at 95% A-5% B. Method 12: SHIMADZU LCMS-2020 HALO C183.0X30 mm, 5 m at 50 , Mobile Phase: A: 0.0375% TFA in water (v / v); B: 0.01875% TFA in Acetonitrile (v / v); flow rate held at 2 mL / min; eluted with the mobile phase over 1.05 min employing UV detection at 220 nm and 254 nm. Gradient information: 0-0.40 min, ramped from 95% A-5% B to 5% A-95% B; 0.40-0.75 min, held at 5% A-95% B; 0.75-0.76 min, returned to 95% A-5% B, 0.76-1.05 min, held at 95% A-5% B. Methods for MS Analysis of compounds: Method 1: SHIMADZU LCMS-2020 Kinetex® EVO C182.1X30 mm, 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 0.40 min employing UV detection at 220 nm. Gradient information: 0-0.40 min, ramped from 10% A-90% B to 10% A-90% B; Methods for SFC analysis of compounds: SFC Method 1: Column: Chiralcel OX-350*4.6 mm I.D., 3 µm; Mobile phase: Phase A for CO2, Phase B for MeOH+ACN with 0.05% DEA additive; Gradient elution: 50% B in CO2, Flow rate: 3 mL / min; Detector: PDA; Column Temp: 35 °C; Back Pressure: 100Bar. SFC Method 2: Column:Chiralpak AD-350*4.6 mm I.D., 3 µm Mobile phase: Phase A for CO2, Phase B for EtOH+ACN with 0.05% DEA additive; Gradient elution: 60% B in CO2 , Flow rate: 3 mL / min; Detector: PDA; Column Temp: 35 °C; Back Pressure: 100Bar. SFC Method 3: Column:Chiralpak IG-350*4.6 mm I.D., 3 m; Mobile phase: Phase A for CO2, and Phase B for MeOH+ACN with 0.05% DEA additive; Gradient elution: 60% B in CO2, Flow rate: 3 mL / min; Detector: PDA; Column Temp: 35 °C; Back Pressure: 100Bar. SFC Method 4: Column:Chiralcel OJ-350*4.6mm I.D.,3 m; Mobile phase: Phase A for CO2,and Phase B for MeOH(0.05% DEA); Gradient elution: MeOH(0.05% DEA) in CO2 from 5% to 40%, Flow rate:3 mL / min; Detector: PDA; Column Temp: 35C; Back Pressure:100Bar. SFC Method 5: Column:Chiralpak IG-350*4.6mm I.D.,3 m; 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:3 mL / min; Detector :PDA; Column Temp: 35C; Back Pressure:100Bar. SFC Method 6: Column: Chiralcel OJ-350*4.6mm I.D.,3 m; 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: 3 mL / min; Detector: PDA; Column Temp: 35C; Back Pressure: 100Bar. SFC Method 7: Column:Chiralcel OJ-350*4.6 mm I.D., 3 m; 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: 3 mL / min;Detector: PDA; Column Temp: 35C; Back Pressure: 100Bar. SFC Method 8: Column: Chiralpak IC-350*4.6mm I.D., 3 m Mobile phase: Phase A for CO2 and Phase B for EtOH(0.05%DEA); Gradient elution: 60% EtOH(0.05%DEA) in CO2 ,Flow rate:3mL / min; Detector:PDA; Column Temp:35C; Back Pressure:100Bar" SFC Method 9: Column: Chiralpak IC-350*4.6mm I.D., 3 m Mobile phase: Phase A for CO2and Phase B for IPA+ACN(0.05%DEA); Gradient elution: IPA+ACN(0.05%DEA) in CO2 from 20% to 60%, Flow rate:3mL / min; Detector:PDA; Column Temp:35C; Back Pressure:100Bar". SFC Method 10: Column: Chiralpak AD-350*4.6mm I.D.,3 m Mobile phase: Phase A for CO2,and Phase B for IPA+ACN(0.05%DEA); Gradient elution: IPA+ACN(0.05%DEA) in CO2 from 20% to 60%, Flow rate:3mL / min; Detector:PDA; Column Temp:35C;Back Pressure:100Bar SFC Method 11: Column: (S,S)Whelk-O150*4.6mm I.D., 3.5 m; 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: 3 mL / min; Detector: PDA; Column Temp: 35 ; Back Pressure: 100 Bar. SFC Method 12: Column: Chiralpak AD-350*4.6mm I.D., 3 m; Mobile phase: Phase A for CO2, and Phase B for MeOH(0.05%DEA); Gradient elution: MeOH (0.05% DEA) in CO2 from 5% to 40%, Flow rate: 3 mL / min; Detector: PDA; Column Temp: 35 ; Back Pressure: 100 Bar. SFC Method 13: Column: Chiralpak AD-350*4.6mm I.D., 3 m 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: 3 mL / min; Detector: PDA; Column Temp: 35 ; Back Pressure: 100 Bar. SFC Method 14: Column: Chiralpak IG-350*4.6 mm I.D., 3 m; Mobile phase: Phase A for CO2, and Phase B for EtOH (0.05% DEA); Gradient elution: EtOH (0.05% DEA) from 20% to 60% in CO2; Flow rate: 3 mL / min; Detector: PDA; Column Temp: 35 ; Back Pressure: 100 Bar. SFC Method 15: Column: Chiralcel OX-350*4.6 mm I.D., 3 µm; Mobile phase: Phase A for CO2, Phase B for MeOH (0.05% DEA), Gradient elution: MeOH (0.05% DEA) from 10% to 60% in CO2, Flow rate: 3 mL / min; Detector: PDA; Column Temp: 35 °C; Back Pressure: 100Bar. SFC Method 16: Column: Chiralcel OD-350*4.6 mm I.D., 3 µm; Mobile phase: Phase A for CO2, Phase B for EtOH (0.05% DEA), Gradient elution: EtOH (0.05% DEA) from 5% to 40% in CO2, Flow rate: 3 mL / min; Detector: PDA; Column Temp: 35 °C; Back Pressure: 100Bar. SFC Method 17: Column: Chiralpak IG-350*4.6 mm I.D., 3 µm; Mobile phase: Phase A for CO2, Phase B for EtOH+ACN (0.05% DEA); Gradient elution: 60% B in CO2, Flow rate: 3 mL / min; Detector: PDA; Column Temp: 35 °C; Back Pressure: 100Bar. SFC Method 18: Column: Chiralpak IG-350*4.6 mm I.D., 3 µm; Mobile phase: Phase A for CO2, Phase B for IPA (0.05% DEA); Gradient elution: 40% B in CO2, Flow rate: 3 mL / min; Detector: PDA; Column Temp: 35 °C; Back Pressure: 100Bar. SFC Method 19: Column: Chiralcel OZ -350*4.6 mm I.D., 3 µm; Mobile phase: Phase A for CO2, Phase B for EtOH+ACN (0.05% DEA); Gradient elution: 60% B in CO2, Flow rate: 3 mL / min; Detector: PDA; Column Temp: 35 °C; Back Pressure: 100Bar. SFC Method 20: Column: Chiralpak AD-350*4.6 mm I.D., 3 µm; Mobile phase: Phase A for CO2, Phase B for IPA (0.05% DEA); Gradient elution: IPA (0.05% DEA) in CO2 from 20% to 60%, Flow rate: 3 mL / min; Detector: PDA; Column Temp: 35 °C; Back Pressure: 100 Bar SFC Method 21: Column:Chiralcel OJ-350*4.6 mm I.D., 3 µm; Mobile phase: Phase A for CO2, Phase B for IPA+ACN (0.05% DEA); Gradient elution: IPA+ACN (0.05% DEA) in CO2 from 5% to 40%, Flow rate: 3 mL / min; Detector: PDA; Column Temp: 35 °C; Back Pressure: 100Bar. SFC Method 22: Column: Chiralpak AD-350*4.6 mm I.D., 3 µm; Mobile phase: Phase A for CO2, Phase B for EtOH (0.05% DEA); Gradient elution: 60% EtOH (0.05% DEA) in CO2, Flow rate: 3 mL / min; Detector: PDA; Column Temp: 35 °C; Back Pressure: 100 Bar. SFC Method 23: Column: Lux 3um Cellulose-250*4.6 mm I.D., 3 µm; Mobile phase: Phase A for CO2, Phase B for MeOH (0.05% DEA); Gradient elution: 60% MeOH (0.05% DEA) in CO2, Flow rate: 3mL / min; Detector: PDA; Column Temp: 35 °C; Back Pressure: 100Bar. SFC Method 24: Column: Chiralpak AD-350*4.6 mm I.D., 3 µm; Mobile phase: Phase A for CO2, Phase B for EtOH (0.05% DEA); Gradient elution: EtOH (0.05% DEA) in CO2 from 5% to 40%, Flow rate: 3 mL / min; Detector: PDA; Column Temp: 35 °C; Back Pressure: 100 Bar. SFC Method 25: Column: Chiralpak AD-350*4.6 mm I.D., 3 µm; Mobile phase: Phase A for CO2, Phase B for EtOH (0.05% DEA); Gradient elution: 40% EtOH (0.05% DEA) in CO2, Flow rate: 3 mL / min; Detector: PDA; Column Temp: 35 °C; Back Pressure: 100 Bar. SFC Method 26: Column: Chiralpak AD-350*4.6 mm I.D., 3 µm; Mobile phase: Phase A for CO2, Phase B for EtOH (0.05% DEA); Gradient elution: EtOH (0.05% DEA) from 20% to 60% in CO2; Flow rate: 3 mL / min; Detector: PDA; Column Temp: 35 °C; Back Pressure: 100 Bar. SFC Method 27: Column: Chiralpak IG-350*4.6 mm I.D., 3 µm; Mobile phase: Phase A for CO2, Phase B for MeOH (0.05% DEA); Gradient elution: 40% MeOH (0.05% DEA) in CO2; Flow rate: 3 mL / min; Detector: PDA; Column Temp: 35 °C; Back Pressure: 100 Bar. SFC Method 28: Column: Chiralpak AD-350*4.6 mm I.D., 3 µm; Mobile phase: Phase A for CO2, Phase B for IPA+ACN (0.05% DEA); Gradient elution: 40% IPA+ACN in CO2, Flow rate: 3mL / min; Detector: PDA; Column Temp: 35 °C; Back Pressure: 100Bar SFC Method 29: Column: Chiralpak ID-350*4.6 mm I.D., 3 µm; Mobile phase: Phase A for CO2, Phase B for IPA+ACN (0.05% DEA); Gradient elution: 60% IPA+ACN (0.05% DEA) in CO2, Flow rate: 3mL / min; Detector: PDA; Column Temp: 35 °C; Back Pressure: 100Bar. SFC Method 30: Column: Chiralpak IC-350*4.6 mm I.D., 3 µm; Mobile phase: Phase A for CO2, Phase B for EtOH (0.05% DEA); Gradient elution: EtOH (0.05% DEA) in CO2 from 10% to 60%, Flow rate: 3mL / min; Detector: PDA; Column Temp: 35 °C; Back Pressure: 100Bar. SFC Method 31: Column: Chiralcel OJ-350*4.6mm I.D., 3 µm; Mobile phase: Phase A for CO2, Phase B for EtOH+ACN (0.05% DEA); Gradient elution: from 20% to 60% of EtOH+ACN (0.05% DEA) in CO2, Flow rate: 3mL / min; Detector: PDA; Column Temp: 35 °C; Back Pressure: 100Bar SFC Method 32: Column: Chiralpak IE-3100*4.6mm I.D., 3 µm; Mobile phase: Phase A for Water with 0.0375%TFA, Phase B for ACN (0.01875% TFA); Gradient elution: 80% B in A; Flow rate: 1mL / min; Detector: PDA; Column Temp: 35 °C; Back Pressure: 100Bar SFC Method 33: Column: Chiralpak IK-350*4.6 mm I.D., 3 µm; Mobile phase: Phase A for CO2, Phase B for IPA+ACN (0.05% DEA); Gradient elution: 50% IPA+ACN (0.05% DEA) in CO2, Flow rate: 3mL / min; Detector: PDA; Column Temp: 35 °C; Back Pressure: 100Bar SFC Method 34: Column: Chiralpak IG-350*4.6 mm I.D., 3 µm; Mobile phase: Phase A for CO2, Phase B for EtOH (0.05% DEA); Gradient elution: EtOH (0.05% DEA) from 20% to 40% in CO2; Flow rate: 3 mL / min; Detector: PDA; Column Temp: 35 °C; Back Pressure: 100 Bar. SFC Method 35: Column: Chiralpak IH-350*4.6 mm I.D., 3 µm; Mobile phase: Phase A for CO2, Phase B for EtOH (0.05% DEA); Gradient elution: EtOH (0.05% DEA) from 5% to 40% in CO2; Flow rate: 3 mL / min; Detector: PDA; Column Temp: 35 °C; Back Pressure: 100 Bar. SFC Method 36: Column: Chiralpak AS-350*4.6 mm I.D., 3 µm; Mobile phase: Phase A for CO2, Phase B for EtOH (0.05% DEA); Gradient elution: EtOH (0.05% DEA) from 5% to 40% in CO2; Flow rate: 3 mL / min; Detector: PDA; Column Temp: 35 °C; Back Pressure: 100 Bar SFC Method 37: Column: Chiralpak IG-350*4.6 mm I.D., 3 µm; Mobile phase: Phase A for CO2, Phase B for MeOH (0.05% DEA); Gradient elution: 60% MeOH (0.05% DEA) in CO2; Flow rate: 3 mL / min; Detector: PDA; Column Temp: 35 °C; Back Pressure: 100 Bar. SFC Method 38: Column: Chiralcel Cellulose-250*4.6 mm I.D., 3 µm; Mobile phase: Phase A for CO2, Phase B for EtOH (0.05% DEA); Gradient elution: EtOH (0.05% DEA) from 20% to 60% in CO2; Flow rate: 3 mL / min; Detector: PDA; Column Temp: 35 °C; Back Pressure: 100 Bar. SFC Method 39: Column: Chiralpak AY-350*4.6mm I.D., 3 µm; Mobile phase: Phase A for CO2, Phase B for EtOH (0.05% DEA); Gradient elution: 40% EtOH (0.05%DEA) in CO2; Flow rate: 3 mL / min; Detector: PDA; Column Temp: 35 °C; Back Pressure: 100 Bar. SFC Method 40: Column: Chiralpak IG-350*4.6 mm I.D., 3 µm; Mobile phase: Phase A for CO2, Phase B for EtOH (0.05% DEA); Gradient elution: EtOH (0.05% DEA) from 5% to 40% in CO2; Flow rate: 3 mL / min; Detector: PDA; Column Temp: 35 °C; Back Pressure: 100 Bar. SFC Method 41: Column: Chiralpak AS-350*4.6mm I.D., 3 µm; Mobile phase: Phase A for CO2, Phase B for MeOH (0.05% DEA); Gradient elution: MeOH (0.05% DEA) in CO2 from 5% to 40%, Flow rate: 3 mL / min; Detector: PDA; Column Temp: 35 °C; Back Pressure: 100 Bar. SFC Method 42: Column: Lux 3um Cellulose-450*4.6mm I.D, 3 µm; Mobile phase: Phase A for CO2, 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: 35 °C; Back Pressure: 100Bar SFC Method 43: Column: Chiralcel OX-350*4.6 mm I.D., 3 m; 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: 3 mL / min; Detector: PDA; Column Temp: 35 ; Back Pressure: 100Bar. SFC Method 44: Column: Chiralpak IC-350*4.6mm I.D.,3 m Mobile phase: Phase A for CO2 and Phase B for EtOH (0.05%DEA); Gradient elution: EtOH(0.05%DEA) in CO2 from 5% to 40%, Flow rate:3mL / min; Detector: PDA; Column Temp:35 ; Back Pressure:100Bar 1H NMR Spectroscopy: 1H NMR spectra were acquired on a Bruker Avance spectrometer at 400 MHz using residual undeuterated solvent as reference.1H NMR signals are specified with their multiplicity / combined multiplicities as apparent from the spectrµm; possible higher-order effects are not considered. Chemical shifts 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. General procedure 1 (Suzuki coupling): To a solution of the bromide compound (1 eq), the borate ester or borate acid substrate (1 to 2 eq) and Na2CO3 or K2CO3 (2 to 3 eq) in dioxane (20 to 100 mg / mL) and H2O (1 / 10 to 1 / 5 of the dioxane volume) was added Pd(dppf)Cl2 or Pd(PPh3)4 (0.05 to 0.1 eq). The reaction mixture was degassed and purged with N2 (3x), stirred at 80 to 100 °C for 2 to16 h and concentrated under reduced pressure. The resulting residue was purified by preparative-HPLC or phase chromatographic column to give the corresponding product. Alternatively, after stirring at 80 to 100 °C for 2 to 16 h, the reaction mixture was cooled to room temperature, diluted with H2O and extracted with EtOAc or DCM (3x). The combined organic layer was washed with brine, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The resulting residue was purified by preparative-HPLC or phase chromatographic column to give the corresponding product. General procedure 2 (oxidation, via m-CPBA) To a solution of the compound (1.0 eq) in DCM (50 to 100 mg / mL) was added m-CPBA (2.0 to 3.0 eq). The reaction mixture was stirred at 25 °C for 2 to 12 h. The mixture was poured into saturated sodium sulfite aqueous solution. The aqueous layer was extracted with EtOAc or DCM (2x or 3x). The combined organic layer was washed with brine, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The resulting residue was purified by preparative-HPLC or chromatographic column to give the corresponding product. General procedure 3 (Saponification): To the mixture of the ester substrate (1 eq) in MeOH or THF (50 to 100 mg / mL) and H2O (1 / 2 to 1 / 1 of the MeOH or THF volume) was added LiOH or LiOH.H2O (3.0 to 5.0 eq). The mixture was stirred at 20 °C for 1 to 2 h. The pH of the reaction mixture was adjusted to a value ranged between 1 to 6 by addition of an aqueous solution of hydrochloric acid (1N). Work up procedure 1: The resulting precipitate was filtered, collected and dried under reduced pressure to give the desired product. Work up procedure 2: The aqueous layer was extracted with EtOAc or DCM (2x or 3x). The combined organic layer was washed with brine, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure give the desired product. General procedure 4 (amidation): To a solution of the carboxylic acid compound (1.0 eq), the amino compound (1.3 to 2.0 eq), DIEA (3.0 to 4.0 eq,) in DMF or DCM (15 to 70 mg of carboxylic acid compound / mL) was added T4P in EtOAc (1.3 to 2.5 eq, 50% in EtOAc) or HATU (1.3 to 2.5 eq). The mixture was stirred at 25 °C for 1 to 2 h. Work up procedure 1: The resulting mixture was diluted with H2O, followed by extraction with EtOAc (3x). The combined organic layer was washed with brine, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The resulting residue was purified by preparative-HPLC to give the corresponding product. Work up 2: The resulting mixture was directly purified by preparative-HPLC or Reversed-phase flash purification to give the corresponding product. General procedure 5 (Boc cleavage): To a solution of the Boc-protected compound in DCM (0.1 g / mL) was added TFA (1 / 5 to1 / 3 of the DCM volume) at 25 °C. The mixture was stirred at 25 °C for 1 to 2 h and, then, concentrated under reduce pressure. The resulting residue was purified by preparative- HPLC or reversed-phase flash purification to give the corresponding product. Preparation of Intermediate 1.1 S-(2-(((benzyloxy)carbonyl)amino)but-3-yn-1-yl) benzothioate To a solution of triphenylphosphane (44.74 g, 171 mmol) in THF (170 mL) under N2was added diethylazodicarboxylate (25 mL, 171 mmol) at 0 °C and the mixture was stirred at 0 °C for 10 min under N2. Benzyl (1-hydroxybut-3-yn-2-yl)carbamate (17.00 g, 77.5 mmol) in THF (170 mL) was added and the mixture was stirred at 0 °C for 10 min under N2. Benzothioic S-acid (21 mL, 171 mmol) was added and the mixture was stirred at 0 °C for 1 h under N2. The mixture was poured into Na2HCO3 (aq., sat., 150 mL). The aqueous phase was extracted with ethyl acetate (150 mL, 3x). The combined organic layer was washed with brine (150 mL), dried over anhydrous Na2SO4, filtered and the filtrate was concentrated under vacuum. The residue was purified by silica gel column flash chromatography (ISCO®; 400 g SepaFlash®Silica Flash Column, Eluent of 0~12% Ethyl acetate / Petroleum ether gradient, 80 mL / min) to give the product S-(2-(((benzyloxy)carbonyl)amino)but-3-yn-1-yl) benzothioate (39.00 g,115 mmol) as a yellow solid. RT 0.585 min (method 4); m / z 362.0 (M+Na)+(ESI+);1H NMR (CDCl3, 400 MHz): 8.02-7.95 (m, 2H), 7.62-7.57 (m, 1H), 7.49-7.45 (m, 2H), 7.35-7.30 (m, 5H), 5.31 (br, 1H), 5.12 (s, 2H), 4.84-4.74 (m, 1H), 3.49 (s, 2H), 2.37 (s, 1H). Preparation of Intermediate 1.2 Benzyl (2,3-dihydrothiophen-3-yl)carbamate To a solution of S-(2-(((benzyloxy)carbonyl)amino)but-3-yn-1-yl) benzothioate (10.00 g, 29.5 mmol) in methanol (1 L) was added potassium methanolate (4.07 g, 29.5 mmol). The mixture was stirred at 20 °C for 2 h under N2. Water (100 mL) was added and the mixture was stirred at 20 °C for 15 min before NaOH (1M, 60 mL) was added. The mixture was stirred at 20 °C for 0.5 h and a white solid precipitated. After filtration, the precipitate was washed with water (100 mL, 2x) and collected. The precipitate was dried by lyophilization to give the product benzyl (2,3-dihydrothiophen-3-yl)carbamate (8.50 g, 36.1 mmol) as a yellow solid. 1H NMR (DMSO-d6, 400 MHz): 7.71-7.61 (m, 1H), 7.42-7.28 (m, 5H), 6.48 (dd, J = 1.6, 5.6 Hz, 1H), 5.58 (dd, J = 2.4, 5.6 Hz, 1H), 5.02 (s, 2H), 4.97-4.85 (m, 1H), 3.46-3.42 (m, 1H), 3.01-2.93 (m, 1H) Preparation of Intermediate 1.3 Benzyl (1-imino-1-oxido-2,3-dihydro-1H-1 -thiophen-3-yl)carbamate To a solution of benzyl (2,3-dihydrothiophen-3-yl)carbamate (7.50 g, 31.9 mmol) and PhI(OAc)2 (20.53 g, 63.7 mmol) in methanol (150 mL) was added ammonium carbamate (7.47 g, 95.6 mmol) at room temperature. The mixture was stirred at 20 °C for 2 h. The crude was directly purified by preparative normal phase HPLC (column: Welch Ultimate XB-CN 250 mm*100 mm*10 µm; mobile phase: A: Hexane, B: EtOH; B%: 5%-45%, 10 min) and concentrated under vacuum to give benzyl (1-imino-1-oxido-2,3- dihydro-1H-1 -thiophen-3-yl)carbamate (4.80 g,18.0 mmol) as a yellow solid. RT 0.388 min (method 4); m / z 267.0 (M+H)+(ESI+).1H NMR (CDCl3, 400 MHz): 7.42-7.30 (m, 5H), 6.76-6.66 (m, 1H), 6.56-6.45 (m, 1H), 5.96-5.57 (m, 1H), 5.15 (br, 1H), 5.12 (s, 2H), 3.69-3.59 (m, 1H), 3.24-3.17 (m, 1H), 3.01 (br, 1H). Preparation of Intermediate 1.4 3-amino-1-imino-2,3-dihydro-1H-1 -thiophene 1-oxide hydrobromide A solution of benzyl (1-imino-1-oxido-2,3-dihydro-1H-1 -thiophen-3-yl)carbamate (500 mg, 1.88 mmol) in HBr / AcOH (5.79 g, 33% wt / wt, 17.8 mmol) was stirred at 25 °C for 1 h. MTBE (10 mL) was added and a yellow solid precipitated. The suspension was shaken, and then, it was left to stand. The supernatant was removed after static settlement. The lower layer precipitation was used to repeat the work up process 6 times. Then, the lower layer precipitation was directly dried under high reduced pressure at room temperature to give the product 3-amino-1-imino-2,3-dihydro-1H-1 -thiophene 1-oxide hydrobromide (1.10 g, 5.16 mmol, HBr salt) as a yellow solid. 1H NMR (DMSO-d6, 400 MHz): 8.61 (br, 3 H), 7.36-7.69 (m, 1 H), 6.83-7.15 (m, 1 H), 4.82 (m, 1 H), 4.14-4.21 (m, 1 H), 3.42-3.51 (m, 1 H) Preparation of Example 1 6-(3,4-dimethylphenyl)-N-(1-imino-1-oxido-2,3-dihydro-1H-1 -thiophen-3-yl)-2-oxo-1,2- dihydropyridine-3-carboxamide To a solution of 6-(3,4-dimethylphenyl)-2-oxo-1H-pyridine-3-carboxylic acid (60 mg, 0.247 mmol), 1-imino-1-oxo-2,3-dihydrothiophen-3-amine hydrobromide (105 mg, 0.493 mmol, HBr salt) in DMA (18 mL) was added DIEA (0.31 mL, 1.73 mmol) and T4P in EtOAc (355 mg, 50% purity, 0.493 mmol) at 0 °C . The mixture was stirred at 25 °C for 10 mins and then, directly purified by preparative HPLC (column: Unisil 3-100 C18 Ultra 150*50 mm*10 µm; mobile phase: A: 0.225% formic acid in water, B: MeCN; B%: 20%-50%, 10 min). To the resulting solution was added NaHCO3 (aq., sat.) to adjust the pH to 7-8. Then, the solution was extracted with DCM (60 mL, 6x) and washed with pure water (40 mL, 2x). The organic layer was dried over anhydrous Na2SO4, filtered and the filtrate was concentrated at 20 °C to give the product 6-(3,4-dimethylphenyl)-N-(1-imino-1-oxido-2,3-dihydro-1H-1 -thiophen-3-yl)-2-oxo-1,2- dihydropyridine-3-carboxamide (46 mg, 0.129 mmol, 97.72% purity) as a brown solid. RT 0.427 min (method 4); m / z 358.0 (M+H)+(ESI+);1H NMR (CDCl3, 400 MHz): 10.22-10.08 (m, 1H), 10.06-9.99 (m, 1H), 8.12-8.05 (m, 1H), 7.45-7.36 (m, 2H), 7.34-7.29 (m, 1H), 6.80-6.71 (m, 2H), 6.61- 6.55 (m, 1H), 5.63-5.50 (m, 1H), 3.92-3.77 (m, 1H), 3.36-3.22 (m, 1H), 2.36 (s, 6H); SFC Method 2 showed four peaks. Preparation of: Example 2 6-(3,4-dimethylphenyl)-N-((1S or R, 3S)-1-imino-1-oxido-2,3-dihydro-1H-1 -thiophen-3-yl)-2-oxo- 1,2-dihydropyridine-3-carboxamide, Example 3 6-(3,4-dimethylphenyl)-N-((1R or S, 3S)-1-imino-1-oxido-2,3-dihydro-1H-1 -thiophen-3-yl)-2-oxo- 1,2-dihydropyridine-3-carboxamide, Example 4 6-(3,4-dimethylphenyl)-N-((1S or R, 3R)-1-imino-1-oxido-2,3-dihydro-1H-1 -thiophen-3-yl)-2-oxo- 1,2-dihydropyridine-3-carboxamide and Example 5 6-(3,4-dimethylphenyl)-N-((1R or S, 3R)-1-imino-1-oxido-2,3-dihydro-1H-1 -thiophen-3-yl)-2-oxo- 1,2-dihydropyridine-3-carboxamide The 6-(3,4-dimethylphenyl)-N-(1-imino-1-oxido-2,3-dihydro-1H-1 -thiophen-3-yl)-2-oxo-1,2- dihydropyridine-3-carboxamide (80 mg, 0.224 mmol) was purified by preparative SFC (Column: DAICEL CHIRALCEL OX 250 mm*30 mm,10 µm; Mobile phase: A for CO2, B for MeOH+ACN (with 0.1% NH3.H2O additive); Gradient elution: 60% B in CO2,10 min) to give two product solutions. The solution containing peak 1 was concentrated under vacuum (30 °C) until a remaining volume of ~20 mL. The resulting solution was diluted with pure water (20 mL) and extracted with DCM (40 mL, 2x). The combined organic layer was washed with pure water (20 mL, 2x), dried over anhydrous Na2SO4, filtered and the filtrate was concentrated under vacuum to give peak A (SFC Method 1, RT: 1.156 min). The solution containing peak 2 was concentrated under vacuum (30 °C) until a remaining volume of ~20 mL. The resulting solution was diluted with pure water (20 mL) and extracted with DCM (40 mL, 2x). The combined organic layers were washed with pure water (20 mL, 2x), dried over anhydrous Na2SO4, filtered, and the filtrate was concentrated under vacuum to give peak B (SFC Method 1, RT: 1.606 min). Peak A (SFC Method 1, :1.156 min) (20 mg, 0.0560 mmol) was further purified by preparative SFC (Column: DAICEL CHIRALCEL OJ 250 mm*30 mm, 10 µm; Mobile phase: Mobile phase: A for CO2, B for i-PrOH (with 0.1% NH3.H2O additive); B%: 25%-25%,10 min) to afford 2 solutions which were concentrated separately under vacuum (30 °C) to give: - Example 2 (SFC Method 2, RT: 1.208 min), which was further purified by preparative HPLC (column: Welch Xtimate C18150*25 mm*5 µm; mobile phase: A: 0.225% formic acid in water; B%: 18%-48%,10 min) and lyophilized to give the product 6-(3,4-dimethylphenyl)-N-((1S or R,3R)-1-imino-1-oxido-2,3-dihydro-1H-16-thiophen-3-yl)-2-oxo-1,2-dihydropyridine-3- carboxamide (1.16 mg, 0.00321 mmol, 99.04% purity, 83.23%ee) as an off-white solid. RT 0.447 min (method 2); m / z 358.2 (M+H)+(ESI+);1H NMR (CDCl3, 400 MHz): 10.51-10.30 (m, 1H), 10.06 (d, J = 7.6 Hz, 1H), 8.57 (d, J = 7.6 Hz, 1H), 7.45-7.36 (m, 2H), 7.40-7.32 (m, 1H), 6.77-6.70 (m, 2H), 6.64-6.55 (m, 1H), 5.64-5.48 (m, 1H), 3.80 (dd, J = 7.6, 13.6 Hz, 1H), 3.39- 3.29 (m, 1H), 2.96 (br, 1H), 2.36 (s, 6H). - Example 3 (SFC Method 2, RT: 1.457 min), which was further purified by preparative HPLC (column: Welch Xtimate C18150*25 mm*5 µm; mobile phase: A: 0.225% formic acid in water; B%: 18%-48%,10 min) and lyophilized to give the product 6-(3,4-dimethylphenyl)-N-((1R or S,3S)-1-imino-1-oxido-2,3-dihydro-1H-16-thiophen-3-yl)-2-oxo-1,2-dihydropyridine-3- carboxamide (1.66 mg, 0.0044 mmol, 94.7% purity, 93.06%ee) as an off-white solid. RT 0.437 min (method 2); m / z 358.2 (M+H)+(ESI+);1H NMR (CDCl3, 400 MHz): 10.40-10.15 (m, 1H), 10.10-10.00 (m, 1H), 8.58 (d, J = 7.6 Hz, 1H), 7.44-7.37 (m, 2H), 7.40-7.32 (m, 1H), 6.80-6.70 (m, 2H), 6.63-6.55 (m, 1H), 5.65-5.50 (m, 1H), 3.86 (dd, J = 7.6, 13.6 Hz, 1H), 3.27 (dd, J = 5.2, 13.6 Hz, 1H), , 2.36 (s, 6H). Peak B (SFC Method 1, RT: 1.606 min) (35 mg, 0.0979 mmol) was further purified by preparative SFC (Column:DAICEL CHIRALPAK IG 250 mm*30 mm,10 µm; Mobile phase: A for CO2, B for MeOH+ACN (with 0.1% NH3.H2O additive); Gradient elution: B%: 75%-75%,10 min). The pH of the two resulting solutions were adjusted to 7 with formic acid and concentrated separately under vacuum (30 °C) until a volume of ~ 20 mL was left. Then, to the two solutions was added DCM (40 mL) and pure water (20 mL). The organic layer was washed with pure water (20 mL, 2x), dried over anhydrous Na2SO4, filtered and the filtrate was concentrated separately under vacuum to give : - Example 4 (SFC Method 2, RT: 1.611 min) 6-(3,4-dimethylphenyl)-N-((1S or R,3R)-1-imino- 1-oxido-2,3-dihydro-1H-66-thiophen-3-yl)-2-oxo-1,2-dihydropyridine-3-carboxamide (6.6 mg, 0.0173 mmol, 93.93% purity, 100% ee) as a brown solid. (We proceed arbitrarily with the attribution of the stereochemistry). RT 0.433 min (method 2); m / z 358.1 (M+H)+(ESI+);; 1H NMR (CDCl3, 400 MHz): 10.23-9.92 (m, 2H), 8.57 (d, J = 7.6 Hz, 1H), 7.42-7.36 (m, 2H), 7.33-7.29 (m, 1H), 6.79-6.70 (m, 2H), 6.61 (dd, J = 2.8, 6.4 Hz, 1H), 5.63-5.50 (m, 1H), 3.81 (dd, J = 7.6, 13.6 Hz, 1H), 3.36-3.30 (m, 1H), 2.94 (br, 1H), 2.36 (s, 6H). - Example 5 (SFC Method 2, RT: 1.834 min) 6-(3,4-dimethylphenyl)-N-((1R or S,3R)-1-imino-1- oxido-2,3-dihydro-1H-16-thiophen-3-yl)-2-oxo-1,2-dihydropyridine-3-carboxamide (1.9 mg, 0.00487 mmol, 94.13% purity, 100%ee) as a brown solid. RT 0.436 min (method 2); m / z 358.1 (M+H)+(ESI+);;1H NMR (CDCl3, 400 MHz): 10.23-9.90 (m, 2H), 8.60-8.56 (m, 1H), 7.43-7.37 (m, 2H), 7.33-7.30 (m, 1H), 6.79-6.71 (m, 2H), 6.60 (dd, J = 2.8, 6.4 Hz, 1H), 5.65-5.55 (m, 1H), 3.86 (dd, J = 7.6,13.6 Hz, 1H), 3.3-3.24 (m, 1H), 3.06-2.81 (m, 1H), 2.36 (s, 6H) Preparation of Example 6 6-(3,4-dimethylphenyl)-N-(1-oxido-2,3-dihydrothiophen-3-yl)-2-oxo-1,2-dihydropyridine-3- carboxamide To tert-butyl nitrite (30 mg, 0.294 mmol) was added a solution of 6-(3,4-dimethylphenyl)-N-(1-imino- 1-oxido-2,3-dihydro-1H-16-thiophen-3-yl)-2-oxo-1,2-dihydropyridine-3-carboxamide (30 mg, 0.0839 mmol) in chloroform (1.0 mL) at 25 °C. The mixture was stirred at 25 °C for 2 h and then, directly purified by preparative HPLC (column: Waters xbridge 150*25 mm 10 µm; mobile phase: A: 10 mmol / L NH4HCO3 in water, B: MeCN; B%: 18%-55%, 10 min). The resulting fraction was lyophilized to give the product 6- (3,4-dimethylphenyl)-N-(1-oxido-2,3-dihydrothiophen-3-yl)-2-oxo-1,2-dihydropyridine-3-carboxamide (6.0 mg,0.0166 mmol, 97.86% purity) as an off-white gum. RT 0.596 min (method 2); m / z 343.1 (M+H)+(ESI+);1H NMR (CDCl3, 400 MHz): 10.60-10.21 (m, 1H), 10.13-9.70 (m, 1H), 8.63-8.50 (m, 1H), 7.44-7.37 (m, 2H), 7.30 (d, J = 7.6 Hz, 1H), 6.84-6.58 (m, 3H), 5.93-5.42 (m, 1H), 4.25-3.28 (m, 1H), 3.23-2.76 (m, 1H), 2.37 (s, 6H); SFC (Column:Chiralpak IG-3 50*4.6mm I.D., 3µm; Mobile phase: Phase A for CO2, Phase B for EtOH+ACN (with 0.05% DEA additive); Gradient elution: 60% B in CO2, Flow rate: 3mL / min) showed four peaks. Preparation of Intermediate 7.1 5-(3,4-dimethylphenyl)picolinic acid To a solution of 5-bromopyridine-2-carboxylic acid (500 mg, 2.48 mmol) in 1,4-dioxane (10 mL) and water (2 mL) was added 2-(3,4-dimethylphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (445 mg, 2.97 mmol), Na2CO3 (525 mg, 4.95 mmol) and Pd(dppf)Cl2 (181 mg, 0.248 mmol). The reaction mixture was degassed and purged with N2 (3x) and stirred at 100 °C for 16 h. The reaction mixture was filtered and the cake was washed with MeOH (5 mL, 3x). The filtrate was acidified with HCl (aq., 1N) until pH=1 and the mixture was concentrated under reduced pressure. The residue was purified by preparative HPLC (column: Phenomenex luna C18150*40 mm* 15 µm; mobile phase: A: 0.225% formic acid in water, B: MeCN; B%: 28%-58%, 15 min) and lyophilized to give the product 5-(3,4-dimethylphenyl)pyridine-2- carboxylic acid (240 mg, 0.444 mmol, 17.92 % yield) as a grey solid. RT 0.471 min (method 4); m / z 228.1 (M+H)+(ESI+); Preparation of Intermediate 7.2 2-carboxy-5-(3,4-dimethylphenyl)pyridine 1-oxide To a solution of 5-(3,4-dimethylphenyl)pyridine-2-carboxylic acid (80 mg, 0.352 mmol) in MeCN (4 mL) was added urea-H2O2 (70 mg, 0.739 mmol) at 0 °C. TFAA (0.098 mL, 0.704 mmol) was added dropwise and the mixture was stirred at 25 °C for 3 h. The mixture was poured into Na2SO3 (aq., sat., 6 mL) and extracted with DCM (10 mL, 3x). The combined organic layers were washed with brine (10 mL, 3x), dried over anhydrous Na2SO4, filtered and the filtrate was concentrated under vacuum. 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%: 40%-70%, 10 min) and lyophilized to give the product 5-(3,4- dimethylphenyl)-1-oxido-pyridin-1-ium-2-carboxylic acid (25 mg,0.103 mmol, 29.19 % yield) as a white solid. RT 0.507 min (method 4); m / z 244.1 (M+H)+(ESI+);1H NMR (CDCl3, 400 MHz) 8.57 (d, J = 1.2 Hz, 1H), 8.45 (d, J = 8.4 Hz, 1H), 7.86 (dd, J = 1.6, 8.4 Hz, 1H), 7.39-7.27 (m, 3H), 2.39-2.35 (m, 6H). Preparation of Example 7 5-(3,4-dimethylphenyl)-2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)pyridine 1-oxide To a solution of 5-(3,4-dimethylphenyl)-1-oxido-pyridin-1-ium-2-carboxylic acid (12 mg, 0.0493 mmol), DIEA (0.044 mL, 0.247 mmol) and 1,1-dioxo-2,3-dihydrothiophen-3-amine hydrochloride (11 mg, 0.0641 mmol, HCl salt) in DMF (2 mL) was added T4P in EtOAc (46 mg, 50% purity, 0.0641 mmol) at 0°C. The reaction mixture was stirred at 20°C for 2 h. The mixture was poured into water (5 mL) and extracted with EtOAc (5 mL, 3x). The combined organic layer was 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%: 38%- 68%, 10 min) and lyophilized to give the product 5-(3,4-dimethylphenyl)-2-((1,1-dioxido-2,3- dihydrothiophen-3-yl)carbamoyl)pyridine 1-oxide (8.9 mg, 0.0248 mmol, 50.34 % yield) as an off-white solid. RT 0.486 min (method 4); m / z 359.1 (M+H)+(ESI+);1H NMR (DMSO-d6, 400 MHz) 11.61 (d, J = 7.6 Hz, 1H), 8.81 (d, J = 1.6 Hz, 1H), 8.24 (d, J = 8.4 Hz, 1H), 7.95 (dd, J = 1.6, 8.4 Hz, 1H), 7.66 (s, 1H), 7.59-7.56 (m, 1H), 7.32-7.28 (m, 2H), 7.04-7.00 (m, 1H), 5.45-5.35 (m, 1H), 3.78-3.74 (m, 1H), 3.40-3.36 (m, 1H), 2.30 (s, 3H), 2.28 (s, 3H); Preparation of Example 7a &7b (R or S)-5-(3,4-dimethylphenyl)-2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)pyridine 1- oxide and (S or R)-5-(3,4-dimethylphenyl)-2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)pyridine 1- oxide The compound 5-(3,4-dimethylphenyl)-2-((1,1-dioxido-2,3-dihydrothiophen-3- yl)carbamoyl)pyridine 1-oxide (30 mg, 0.0837 mmol) was purified by preparative SFC (Column: DAICEL CHIRALCEL OJ 250 mm*30 mm,10 µm; Mobile phase: A for CO2, B for MeOH+ACN (neutral; Gradient elution: 40% B in CO2, 2.56 min) to give two product solutions. The solution containing Example 7a was concentrated under vacuum (40 °C) to give (R or S)-5-(3,4-dimethylphenyl)-2-((1,1-dioxido-2,3- dihydrothiophen-3-yl)carbamoyl)pyridine 1-oxide (10 mg, 0.0289 mmol, 34.53 % yield, ee.100 % based on SFC method 4) as off-white solid. The solution containing Example 7b was concentrated under vacuum (40 °C) to give (S or R)-5-(3,4-dimethylphenyl)-2-((1,1-dioxido-2,3-dihydrothiophen-3- yl)carbamoyl)pyridine 1-oxide (9.5 mg, 0.0263 mmol, 31.48 % yield, ee.99.57 % based on SFC method 4) as off-white solid. Example 7a: LCMS: RT 0.489 min (method 7); m / z 359.1 (M+H)+(ESI+); SFC: RT: 1.880 min, 100% ee (Method 4);1H NMR (CDCl3, 400 MHz): 11.95 (d, J = 7.2 Hz, 1H), 8.49 (d, J = 1.6 Hz, 1H), 8.39 (d, J = 8.4 Hz, 1H), 7.68 (dd, J = 1.6, 8.4 Hz, 1H), 7.40-7.26 (m, 3H), 6.86-6.78 (m, 2H), 5.60-5.53 (m, 1H), 3.81 (dd, J = 8.0, 13.6 Hz, 1H), 3.28 (dd, J = 4.8, 13.6 Hz, 1H), 2.36 (s, 3H), 2.35 (s, 3H) Example 7b: LCMS RT 0.488 min (method 7); m / z 359.1 (M+H)+(ESI+); SFC: RT: 2.121 min, 99.57% ee (Method 4);1H NMR (CDCl3, 400 MHz): 11.95 (d, J = 7.6 Hz, 1H), 8.49 (d, J = 1.6 Hz, 1H), 8.39 (d, J = 8.4 Hz, 1H), 7.68 (dd, J = 1.6, 8.4 Hz, 1H), 7.40-7.26 (m, 3H), 6.86-6.78 (m, 2H), 5.60-5.53 (m, 1H), 3.81 (dd, J = 8.0, 13.6 Hz, 1H), 3.28 (dd, J = 4.8, 13.6 Hz, 1H), 2.36 (s, 3H), 2.35(s, 3H) Preparation of Intermediate 8.1 Benzyl (1-(methylimino)-1-oxido-2,3-dihydro-1H-16-thiophen-3-yl)carbamate To the mixture of benzyl (1-imino-1-oxido-2,3-dihydro-1H-16-thiophen-3-yl)carbamate (200 mg, 0.751 mmol) in DCM (4mL) was added trimethyloxonium tetrafluoroborate (133 mg, 0.901 mmol). The mixture was stirred at 20 °C for 2 h and then, concentrated under vacuum. The resulting residue was purified by preparative HPLC (column: Unisil 3-100 C18 Ultra 150*50 mm*10 m; mobile phase: A: 1 mM aqueous solution of NH4HCO3, B: MeCN; B%: 15%-45%, 9 min) and the resulting fraction was extracted with DCM (30 mL, 3x). The combined organic layer was washed with brine (50 mL), dried over Na2SO4, filtered and concentrated in vacuo to give benzyl (1-(methylimino)-1-oxido-2,3-dihydro-1H-16-thiophen- 3-yl)carbamate (24 mg, 0.0856 mmol, 11.40 % yield) as a yellow oil. RT 0.577 min (method 2); m / z 281.1 (M+H)+(ESI+);1H NMR (400 MHz, DMSO-d6) 7.88-8.04 (m, 1 H), 7.30-7.39 (m, 5 H), 7.07-7.16 (m, 1 H), 6.5-6.69 (m, 1 H), 5.05 (s, 2 H), 4.78-4.94 (m, 1 H), 3.50- 3.80 (m, 1 H), 2.90-3.08 (m, 1 H) Preparation of Intermediate 8.2 3-amino-1-(methylimino)-2,3-dihydro-1H-16-thiophene 1-oxide hydrobromide A solution of benzyl (1-(methylimino)-1-oxido-2,3-dihydro-1H-16-thiophen-3-yl)carbamate (1.00 eq, 23 mg, 0.0820 mmol) in HBr / AcOH (253 mg, 33% wt / wt, 0.779 mmol) was stirred at 25 °C for 1 h. MTBE (10 mL) was added to precipitate a solid and the supernatant was removed after static settlement. This process was repeated six times to give a residue. The resulting residue was dried under vacuum to give 3-amino-1-(methylimino)-2,3-dihydro-1H-16-thiophene 1-oxide hydrobromide (18 mg, 0.0793 mmol, 96.60 % yield, HBr salt) as a yellow oil. Preparation of Example 8 6-(3,4-dimethylphenyl)-N-(1-(methylimino)-1-oxido-2,3-dihydro-1H-16-thiophen-3-yl)-2-oxo-1,2- To a solution of 6-(3,4-dimethylphenyl)-2-oxo-1,2-dihydropyridine-3-carboxylic acid (10 mg, 0.0411 mmol) and 3-amino-1-(methylimino)-2,3-dihydro-1H-16-thiophene 1-oxide (19 mg, 0.0822 mmol, HBr salt) in DMA (0.30 mL) was added DIEA (51 µL, 0.288 mmol) and T4P in EtOAc (59 mg, 50% purity, 0.0822 mmol) at 0 °C. The mixture was stirred at 25 °C for 1 h. The reaction mixture was poured into water (5 mL) and extracted with DCM (5 mL, 3x). The combined organic layer was dried over anhydrous Na2SO4, filtered and the filtrate was concentrated under reduced pressure. The residue was purified by preparative normal phase HPLC (column: Welch Ultimate XB-CN 250 mm*100 mm*10 µm; mobile phase: A: Hexane, B: EtOH; B%: 15%-55%, 15 min) and concentrated under vacuum to give a crude product, which was further purified by preparative HPLC (column: Unisil 3-100 C18 Ultra 150*25 mm*10 µm; mobile phase: A: 10 mM aqueous solution of NH4HCO3, B: MeCN; B%: 20%-50%, 9 min) and lyophilized directly to give the product 6-(3,4-dimethylphenyl)-N-(1-(methylimino)-1-oxido-2,3-dihydro-1H-16- thiophen-3-yl)-2-oxo-1,2-dihydropyridine-3-carboxamide (1.0 mg, 0.00269 mmol, 6.55 % yield) as a white solid. RT 0.428 min (method 2); m / z 372.2 (M+H)+(ESI+);1H NMR (CDCl3, 400 MHz): 10.00-10.24 (m, 1 H), 9.71-9.99 (m, 1 H), 8.53-8.61 (m, 1 H), 7.36-7.44 (m, 2 H), 7.29-7.34 (m, 1 H), 6.64-6.90 (m, 3 H), 5.54-5.68 (m, 1 H), 3.67-3.77 (m, 1 H), 3.24-3.42 (m, 1 H), 2.88-2.95 (m, 3 H), 2.36 (s, 6 H). Preparation of Intermediate 9.1 5-(3,4-dimethylphenyl)picolinic acid To a solution of 5-bromopicolinic acid (500 mg, 2.48 mmol) in 1,4-dioxane (10 mL) and water (2 mL) was added (3,4-dimethylphenyl)boronic acid (445 mg, 2.97 mmol), Na2CO3 (525 mg, 4.95 mmol) and Pd(dppf)Cl2 (181 mg, 0.248 mmol). The reaction mixture was degassed and purged with N2 (3x) before it was stirred at 100°C for 2 h and then filtered. The cake was washed with MeOH (5 mL, 3x) and the filtrate was acidified with 1 M HCl until pH = 1. The resulting solution was concentrated under reduced pressure. The residue was purified by reversed-phase flash (ISCO®; 20 g Flash column Welch Ultimate XB_C18 20-40 µm; 120 A; Mobile phase: A: 0.1% formic acid in water, B: MeCN; B%: 5%-95%, 50 mL / min) and lyophilized to give the product 5-(3,4-dimethylphenyl)picolinic acid (120 mg, 0.296 mmol, 11.95 % yield) as a gray solid. RT 0.453 min (method 5); m / z 228.1 (M+H)+(ESI+);1H NMR (DMSO-d6, 400 MHz): 8.99 (d, J = 2.0 Hz, 1H), 8.23 (dd, J = 8.0, 2.0 Hz, 1H), 8.09 (d, J = 8.0 Hz, 1H), 7.61 (s, 1H), 7.49 (d, J = 7.6 Hz, 1H), 7.29 (d, J = 7.6 Hz, 1H), 2.31 (s, 3H), 2.28 (s, 3H). Preparation of Example 9 5-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)picolinamide To a solution of 5-(3,4-dimethylphenyl)picolinic acid (80 mg, 0.352 mmol), DIEA (0.31 mL, 1.76 mmol) and 3-amino-2,3-dihydrothiophene 1,1-dioxide (78 mg, 0.458 mmol, HCl salt) in DMF (2 mL) was added T4P in EtOAc (329 mg, 50% purity, 0.458 mmol). The reaction mixture was stirred at 20oC for 2 h before it was poured into water (5 mL) and extracted with EtOAc (5 mL, 3x). The combined organic layer was dried over anhydrous Na2SO4, filtered and the filtrate was 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%: 43%-73%, 10 min) and lyophilized directly to give the product 5-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)picolinamide (28 mg,0.0801 mmol, 22.77 % yield) as an off-white solid. RT 0.519 min (method 5); m / z 343.1 (M+H)+(ESI+)1H NMR (DMSO-d6, 400 MHz): 9.41 (d, J = 8.0 Hz, 1H), 8.93 (d, J = 2.0 Hz, 1H), 8.26 (dd, J = 8.0, 2.0 Hz, 1H), 8.09 (d, J = 8.0 Hz, 1H), 7.60 (s, 1H), 7.53 (d, J = 8.0 Hz, 1H), 7.29 (d, J = 8.0 Hz, 1H), 7.22 (dd, J = 6.4, 2.4 Hz, 1H), 6.94 (dd, J = 6.4, 2.4 Hz, 1H), 5.54-5.26 (m, 1H), 3.76 (dd, J = 13.6, 6.0 Hz, 1H), 3.44 (dd, J = 13.6, 6.0 Hz, 1H), 2.32 (s, 3H), 2.28 (s, 3H); Preparation of Example 10 (R or S)-5-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3- yl)picolinamide and Example 11 (S or R)-5-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3- yl)picolinamide 5-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)picolinamide (28 mg, 0.0818 mmol) was separated by SFC (column: DAICEL CHIRALPAK IG 250 mm*30 mm, 10 µm; mobile phase: CO2-MeOH / ACN; B%: 75%-75%,12 min) and concentrated separately to give: - Example 10 (SFC Method 3, Rt 1.093 min) (R or S)-5-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3- dihydrothiophen-3-yl)picolinamide (13 mg, 0.0376 mmol, 45.94 % yield, 98.56% purity, 100% ee) as an brown solid. RT 0.516min (method 5); m / z 343.1 (M+H)+(ESI+);1H NMR (DMSO-d6, 400 MHz): 9.41 (d, J = 8.0 Hz, 1H), 8.93 (d, J = 2.0 Hz, 1H), 8.26 (dd, J = 8.0, 2.0 Hz, 1H), 8.09 (d, J = 8.0 Hz, 1H), 7.60 (s, 1H), 7.53 (d, J = 8.0 Hz, 1H), 7.29 (d, J = 8.0 Hz, 1H), 7.22 (dd, J = 6.4, 2.4 Hz, 1H), 6.94 (dd, J = 6.4, 2.4 Hz, 1H), 5.54-5.26 (m, 1H), 3.76 (dd, J = 13.6, 6.0 Hz, 1H), 3.44 (dd, J = 13.6, 6.0 Hz, 1H), 2.32 (s, 3H), 2.28 (s, 3H); - Example 11 (SFC Method 3, Rt 3.075 min) (S or R)-5-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3- dihydrothiophen-3-yl)picolinamide (14 mg, 0.0394 mmol, 48.17 % yield, 98.03% purity, 100% ee) as an off-white solid. RT 0.516min (method 5); m / z 343.1 (M+H)+(ESI+);1H NMR (DMSO-d6, 400 MHz): 9.41 (d, J = 8.0 Hz, 1H), 8.93 (d, J = 2.0 Hz, 1H), 8.26 (dd, J = 8.0, 2.0 Hz, 1H), 8.09 (d, J = 8.0 Hz, 1H), 7.60 (s, 1H), 7.53 (d, J = 8.0 Hz, 1H), 7.29 (d, J = 8.0 Hz, 1H), 7.22 (dd, J = 6.4, 2.4 Hz, 1H), 6.94 (dd, J = 6.4, 2.4 Hz, 1H), 5.54-5.26 (m, 1H), 3.76 (dd, J = 13.2, 6.0 Hz, 1H), 3.44 (dd, J = 13.2, 6.0 Hz, 1H), 2.32 (s, 3H), 2.28 (s, 3H); Preparation of Intermediate 12.1 Methyl 2-methoxy-6-(piperidin-1-yl)nicotinate To a solution of methyl 6-bromo-2-methoxynicotinate (500 mg, 2.03 mmol) in DMF (5 mL) was added piperidine hydrochloride (494 mg, 4.06 mmol, HCl salt) and DIEA (1.8 mL, 10.2 mmol). The mixture was stirred at 100 °C for 2 h. The resulting mixture was poured into water (10 mL) and extracted with ethyl acetate (10 mL, 2x). The combined organic layer was washed with brine (5 ml, 3x), dried over anhydrous Na2SO4, filtered and the filtrate was concentrated under vacuum to give the product methyl 2-methoxy-6- (piperidin-1-yl)nicotinate (600 mg, crude) as a yellow oil. RT 0.565 min (method 5); m / z 251.0 (M+H)+(ESI+);1H NMR (CDCl3, 400 MHz): 8.01 (d, J = 8.8 Hz, 1 H), 6.14 (d, J = 8.8 Hz, 1 H), 3.96 (s, 3 H), 3.81 (s, 3 H), 3.57-3.67 (m, 4 H), 1.55-1.72 (m, 6 H). Preparation of Intermediate 12.2 Methyl 2-oxo-6-(piperidin-1-yl)-1,2-dihydropyridine-3-carboxylate A solution of ethyl 2-methoxy-6-(piperidin-1-yl)nicotinate (300 mg, 1.20 mmol) and sodium iodide (719 mg, 4.79 mmol) in MeCN (3 mL) was cooled to 0°C and TMSI ( 0.68 mL, 4.79 mmol) was added. The mixture was stirred at 0 °C for 20 min and then for 16h at 25 °C. The resulting mixture was poured into water (10 mL) and extracted with ethyl acetate (10 mL, 2x). The combined organic layer was washed with brine (5 ml, 3x), dried over anhydrous Na2SO4, filtered and the filtrate was concentrated under vacuum to give the crude product methyl 2-oxo-6-(piperidin-1-yl)-1,2-dihydropyridine-3-carboxylate (300 mg, crude), which was used directly in the next step without further purification. RT 0.484 min (method 5); m / z 259.0 (M+Na)+(ESI+) Preparation of Intermediate 12.3 2-oxo-6-(piperidin-1-yl)-1,2-dihydropyridine-3-carboxylic acid To a solution of methyl 2-oxo-6-(piperidin-1-yl)-1,2-dihydropyridine-3-carboxylate (150 mg, 0.635 mmol) in methanol (1.5 mL) and water (0.30 mL) was added LiOH.H2O (76 mg, 3.17 mmol). The mixture was stirred at 50 °C for 16 h. Then pH was adjusted to 3 with HCl (aq., 1N). The reaction mixture was diluted with water (5 mL) and extracted with EtOAc (5 mL, 3x). The combined organic layer was washed with brine (5 mL, 2x), dried over anhydrous Na2SO4, filtered, and the filtrate was concentrated under vacuum to give the product 2-oxo-6-(piperidin-1-yl)-1,2-dihydropyridine-3-carboxylic acid (150 mg, crude) as a brown solid which was used in the next step without further purification. 1H NMR (DMSO-d6, 400 MHz): 13.50-14.75 (m, 1 H), 11.49-12.13 (m, 1 H), 7.91 (d, J = 8.8 Hz, 1 H), 6.10 (d, J = 8.4 Hz, 1 H), 3.54-3.58 (m, 4 H), 1.59-1.66 (m, 2 H), 1.55 (d, J = 4.4 Hz, 4 H). Preparation of Example 12 N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-2-oxo-6-(piperidin-1-yl)-1,2-dihydropyridine-3- carboxamide To a solution of 2-oxo-6-(piperidin-1-yl)-1,2-dihydropyridine-3-carboxylic acid (50 mg, 0.225 mmol) in DMF (0.50 mL) was added 1,1-dioxo-2,3-dihydrothiophen-3-amine hydrochloride (46 mg, 0.270 mmol, HCl salt), DIEA (0.12 mL, 0.675 mmol) and T4P in EtOAc (211 mg, 50% purity, 0.292 mmol). The mixture was stirred at 20 °C for 2 h and purified by preparative HPLC (column: Phenomenex luna C18150*25 mm*10 µm; Mobile phase: A: 0.225% formic acid in water, B: MeCN; B%: 15%-45%; 10 min). The product solution was lyophilized to give the product N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-2-oxo-6-(piperidin-1- yl)-1,2-dihydropyridine-3-carboxamide (1.8 mg, 0.00534 mmol, 2.37 % yield) as a white solid. RT 0.401 min (method 1); m / z 338.1 (M+H)+(ESI+);1H NMR (DMSO-d6, 400 MHz) 11.24 (s, 1 H), 9.69-9.92 (m, 1 H), 8.00 (d, J = 8.8 Hz, 1 H), 7.20 (m, 1 H), 6.93 (m, 1 H), 5.77-6.00 (m, 1 H), 5.21-5.40 (m, 1 H), 3.64-3.75 (m, 1 H), 3.46-3.53 (m, 4 H), 3.13-3.18 (m, 1 H), 1.58-1.64 (m, 2 H), 1.51-1.57 (m, 4 H) Preparation of Intermediate 13.1 3-chloro-6-(3,4-dimethylphenyl)-2-methoxypyridine To a solution of 6-bromo-3-chloro-2-methoxypyridine (1.00 g, 4.49 mmol) and 2-(3,4- dimethylphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1.04 g, 4.50 mmol) in 1,4-dioxane (9 mL) and water (1.5 mL) was added Na2CO3 (953 mg, 8.99 mmol)) and Pd(dppf)Cl2 (367 mg, 0.449 mmol). The reaction mixture was stirred at 80 °C for 2 h under N2 atmosphere. The resulting mixture was filtered and the filtrate was purified by flash silica gel chromatography (ISCO®; 20 g SepaFlash®Silica Flash Column, Mobile phase: A: Petroleum ether, B: Ethyl acetate; B%: 0% to 0%; 50 mL / min) to give the product 3- chloro-6-(3,4-dimethylphenyl)-2-methoxypyridine (920 mg, 2.97 mmol, 66.10 % yield) as a white solid. RT 0.754 min (method 5); m / z 248.0 (M+H)+(ESI+);1H NMR (CDCl3, 400 MHz): 7.9-8.0 (m, 1H), 7.35-7.44 (m, 3H), 7.16 (d, 1H, J = 7.6 Hz), 3.88 (s, 3H), 2.27 (s, 3H), 2.25 (s, 3H). Preparation of Intermediate 13.2 3-(benzylthio)-6-(3,4-dimethylphenyl)-2-methoxypyridine To a solution of 3-chloro-6-(3,4-dimethylphenyl)-2-methoxypyridine (500 mg, 2.02 mmol) in 1,4- dioxane (8 mL) was added Cs2CO3 (837 mg, 6.06 mmol) and BrettPhos-Pd-G4 (186 mg, 0.202 mmol). The reaction mixture was degassed and purged with N2 (3x). Phenylmethanethiol (376 mg, 3.03 mmol) was added and the reaction mixture was stirred at 90 °C for 2 h under N2 atmosphere. The mixture was filtered and the filtrate was purified by flash chromatography (ISCO®; 12 g SepaFlash®Silica Flash Column, Mobile phase: A: Petroleum ether, B: Ethyl acetate; B%: 5% to 5%; 50 mL / min) to give the product (3-(benzylthio)-6-(3,4-dimethylphenyl)-2-methoxypyridine (180 mg,0.447 mmol, 22.15 % yield) as a white solid. RT 0.772 min (method 5); m / z 336.2 (M+H)+(ESI+);1H NMR (CDCl3, 400 MHz): 7.79 (s, 1H), 7.71- 7.81 (m, 1H), 7.46 (d, 1H, J = 7.8 Hz), 7.31-7.34 (m, 4H), 7.22-7.24 (m, 3H), 4.14 (s, 3H), 4.13 (s, 2H), 2.35 (s, 3H), 2.33 (s, 3H) Preparation of Intermediate 13.3 3-(benzylthio)-6-(3,4-dimethylphenyl)pyridin-2(1H)-one To a solution of 3-(benzylthio)-6-(3,4-dimethylphenyl)-2-methoxypyridine (149 mg, 0.444 mmol) in MeCN (2 mL) was added sodium iodide (333 mg, 2.22 mmol) and TMSI (445 mg, 2.22 mmol) at 0 °C. The mixture was stirred at 25 °C for 2 h. The mixture was filtered and the filtrate was purified by reversed phase flash (ISCO®; 40 g SepaFlash® column: Spherical C1820-45 µm, 100 A, mobile phase: A: 0.225% formic acid in water, B: MeCN; B%: 80%-95%, 50 mL / min). The resulting solution was lyophilized to give the product 3-(benzylthio)-6-(3,4-dimethylphenyl)pyridin-2(1H)-one (100 mg, 0.280 mmol, 62.99 % yield) as a black solid. 1H NMR (CDCl3, 400 MHz): 10.07 (br, 1H), 7.30-7.38 (m, 6H), 7.30-7.23 (m, 3H), 6.38 (d, 1H, J = 7.2 Hz), 4.18 (s, 2H), 2.33 (s, 3H), 2.31 (s, 3H) Preparation of Intermediate 13.4 6-(3,4-dimethylphenyl)-2-hydroxy-pyridine-3-sulfonyl chloride To a solution of 3-(benzylthio)-6-(3,4-dimethylphenyl)pyridin-2(1H)-one (35 mg, 0.109 mmol) in acetic acid (1 mL) was added 1-chloropyrrolidine-2,5-dione (58 mg, 0.436 mmol) and H2O (0.3 mL) at 0 °C .The mixture was stirred at 0 °C for 18 mins before it was filtered and concentrated to give the crude product 6-(3,4-dimethylphenyl)-2-hydroxy-pyridine-3-sulfonyl chloride (20 mg,0.0672 mmol, 61.69 % yield) as a colorless oil. RT 0.577min (method 5); m / z 298.0 (M+H)+(ESI+); Preparation of Example 13 6-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-2-oxo-1,2-dihydropyridine-3- sulfonamide To a solution of 6-(3,4-dimethylphenyl)-2-oxo-1,2-dihydropyridine-3-sulfonyl chloride (20 mg, 0.0672 mmol) in THF (0.50 mL) and water (0.10 mL) was added NaHCO3 (5.6 mg, 0.0672 mmol) and 3-amino- 2,3-dihydrothiophene 1,1-dioxide hydrochloride (9.1 mg, 0.0536 mmol, HCl salt) at 0 °C. The mixture was stirred at 0 °C for 6 min and then filtered. The filtrate was purified by preparative HPLC (Column Phenomenex luna C18150*25 mm* 10 µm; Mobile phase: A: 0.225% formic acid in water, B: MeCN; B%: 29%-59%; 10 min). The resulting solution was lyophilized to give the product 6-(3,4-dimethylphenyl)-N- (1,1-dioxido-2,3-dihydrothiophen-3-yl)-2-oxo-1,2-dihydropyridine-3-sulfonamide (6.3 mg, 96.70% purity, 0.0161 mmol, 23.93 % yield) as a white solid. RT 0.498 min (method 5); m / z 395.1 (M+H)+(ESI+);1H NMR (DMSO-d6, 400 MHz): 8.06 (d, J = 7.6 Hz, 1H), 7.63 (s, 1H), 7.55 (d, J = 7.6 Hz, 1H ), 7.29 (d, 1H, J = 8.0 Hz), 7.16 (dd, J = 2.4, 6.8 Hz,1H), 6.71-6.74 (m, 2H), 4.99-5.02 (m, 1H), 3.66 (dd, J = 8.0, 13.6 Hz, 1H), 3.06 (dd, J = 5.2, 13.6 Hz, 1H), 2.29 (s, 6H) Preparation of Intermediate 14.1 2-oxo-6-(prop-1-yn-1-yl)-1,2-dihydropyridine-3-carboxylic acid To a solution of 6-bromo-2-oxo-1,2-dihydropyridine-3-carboxylic acid (60 mg, 0.275 mmol) in MeCN (1.5 mL) was added CuI (21 mg, 0.110 mmol), Pd(PPh3)4 (32 mg, 0.0275 mmol) and TEA (0.11 mL, 0.826 mmol). The reaction mixture was degassed and purged with N2 (3x) before prop-1-yne (0.83 mL, 0.826 mmol) was added at 20°C. The reaction mixture was stirred at 60 °C for 16 h under N2 atmosphere and then filtered. The pH of the filtrate was adjusted with HCl (aq., 6N) to around 4-5. The resulting solution was purified by preparative HPLC (column: Phenomenex luna C18150*25 mm* 10 µm; mobile phase: A: 0.225% formic acid in water, B: MeCN; B%: 8%-38%, 10 min) and lyophilized directly to give the product 2-oxo-6-(prop-1-yn-1-yl)-1,2-dihydropyridine-3-carboxylic acid (30 mg, 0.169 mmol, 61.53 % yield) as a white solid. RT 0.351 min (method 5); m / z 199.9 (M+Na)+(ESI+);1H NMR (400MHz, DMSO-d6): 14.60 (br, 1H), 13.66 (br, 1H), 8.27 (d, J = 7.6 Hz, 1H), 6.75 (d, J =7.6 Hz, 1H), 2.18 (s, 3H). Preparation of Example 14 N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-2-oxo-6-(prop-1-yn-1-yl)-1,2-dihydropyridine-3- carboxamide To a solution of 2-oxo-6-(prop-1-yn-1-yl)-1,2-dihydropyridine-3-carboxylic acid (10 mg, 0.0564 mmol) in DMF (1mL) was added at 0°C 3-amino-2,3-dihydrothiophene 1,1-dioxide hydrochloride (12 mg, 0.0734 mmol, HCl salt), DIEA (0.050 mL, 0.282 mmol) followed by T4P in EtOAc (47 mg, 50% purity, 0.0734 mmol). The mixture was then stirred at 20 °C for 2 h and directly purified by prep-HPLC (column: Phenomenex luna C18150*25 mm* 10 µm; mobile phase: A: 0.225% formic acid in water, B: MeCN; B%: 10%-40%, 10min). The resulting impure product was further purified by preparative HPLC (column: Waters Xbridge 150*25 mm* 5 µm; mobile phase: A: 0.05% Ammonia in water, B: MeCN; B%: 30%-60%, 10 min) and lyophilized directly to give the product N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-2-oxo-6- (prop-1-yn-1-yl)-1,2-dihydropyridine-3-carboxamide (0.66 mg, 0.00219 mmol, 3.88 % yield, 97.68% purity) as a grey solid . RT 0.391 min (method 1); m / z 293.2 (M+H)+(ESI+);1H NMR (DMSO-d6, 400 MHz): 12.93 (br, 1H), 10.16 (br, 1H), 8.21 (d, J = 7.6 Hz, 1H), 7.24 (dd, J = 6.8, 2.0 Hz, 1H), 6.95 (dd, J = 6.8, 2.0 Hz, 1H), 6.57 (d, J = 7.6 Hz, 1H), 5.32 (s, 1H), 3.73-3.67 (m ,1H), 3.25-3.21 (m ,1H), 2.13 (s, 3H). Preparation of Intermediate 15.1 Methyl 2-chloro-6-(3,4-dimethylphenyl)nicotinate To a solution of methyl 6-bromo-2-chloronicotinate (1.0 g, 3.99 mmol) in 1,4-dioxane (10 mL) and water (2 mL) was added (3,4-dimethylphenyl)boronic acid (659 mg, 4.39 mmol), Na2CO3 (846 mg, 7.98 mmol) and Pd(dppf)Cl2 (163 mg, 0.200 mmol). The mixture was stirred at 80 °C for 2 h under N2. The reaction mixture was poured into water (20 mL) and extracted with ethyl acetate (20 mL, 2x). The combined organic layer was washed with brine (20 mL), dried over anhydrous Na2SO4, filtered and the filtrate was concentrated. The residue was purified by preparative normal phase HPLC (Welch Ultimate XB-CN 250*70*10 µm, mobile phase: A: Hexane, B: EtOH; B%: 0%-1%, 15 min) to give methyl 2-chloro- 6-(3,4-dimethylphenyl)nicotinate (950 mg, 3.45 mmol, 86.30 % yield) as a yellow solid. RT 0.617 min (method 5); m / z 276.1 (M+H)+(ESI+);1H NMR (DMSO-d6, 400MHz): 8.30 (d, J = 8.0 Hz, 1H), 8.08 (d, J = 8.0 Hz, 1H), 7.92 (s, 1H), 7.85 (dd, J = 8.0, 1.6 Hz, 1H), 7.30 (d, J = 8.0 Hz, 1H), 3.89 (s, 3H), 2.32 (s, 3H), 2.29 (s, 3H) Preparation of Intermediate 15.2 Methyl 6-(3,4-dimethylphenyl)-2-((3-((2-ethylhexyl)oxy)-3-oxopropyl)thio)nicotinate To a solution of methyl 2-chloro-6-(3,4-dimethylphenyl)nicotinate (950 mg, 3.45 mmol) and 2- ethylhexyl 3-mercaptopropanoate (1505 mg, 6.89 mmol) in 1,4-dioxane (12 mL) was added DIEA (1.8 mL, 10.3 mmol), Xantphos (399 mg, 0.689 mmol) and Pd2(dba)3 (316 mg, 0.345 mmol). The reaction mixture was degassed and purged with N2 (3x) before it was stirred at 90 °C for 16 h. The mixture was filtered and the filtrate was purified by preparative normal phase HPLC (Welch Ultimate XB-CN 250*70*10 µm, mobile phase: A: Hexane, B: EtOH; B%: 0%-0%, 15 min) to give the product methyl 6-(3,4- dimethylphenyl)-2-((3-((2-ethylhexyl)oxy)-3-oxopropyl)thio)nicotinate (1.3 g, 2.84 mmol, 82.45 % yield) as a yellow oil RT 0.805 min (method 5); m / z 458.2 (M+H)+(ESI+);1H NMR (CDCl3, 400 MHz ): 8.25 (d, J = 8.0 Hz, 1H), 7.88 (s, 1H), 7.84 (dd, J = 8.0, 1.6 Hz, 1H), 7.51 (d, J = 8.0 Hz, 1H), 7.25 (d, J = 8.0 Hz, 1H), 4.06-4.02 (m, 2H), 3.94 (s, 3H), 3.57 (t, J = 7.6 Hz, 2H), 2.88 (t, J = 7.6 Hz, 2H), 2.35 (d, J = 10.4 Hz, 6H), 1.59-1.55 (m, 2H), 1.42-1.28 (m, 6H), 0.91-0.84 (m, 7H). Preparation of Intermediate 15.3 Methyl 6-(3,4-dimethylphenyl)-2-thioxo-1,2-dihydropyridine-3-carboxylate A solution of methyl 6-(3,4-dimethylphenyl)-2-((3-((2-ethylhexyl)oxy)-3-oxopropyl)thio)nicotinate (300 mg, 0.656 mmol) in THF (3 mL) was cooled to -60 °C. A solution of t-BuOK in THF (0.74 mL, 6.56 mmol, 1M) was added dropwise and the solution was stirred at -60 °C for 2 h. The resulting solution was quenched with water (5 mL), the pH was adjusted to 3 with HCl (aq., 1N) and the mixture was extracted with ethyl acetate (5 mL, 2x). The combined organic layer was washed with brine (5 mL), dried over anhydrous Na2SO4, filtered and the filtrate was concentrated under vacuum to give methyl 6-(3,4- dimethylphenyl)-2-thioxo-1,2-dihydropyridine-3-carboxylate (100 mg, 0.366 mmol, 55.81% yield) as a yellow solid. RT 0.530min (method 5); m / z 274.1 (M+H)+(ESI+);1H NMR (CDCl3, 400 MHz): 8.18 (d, J = 8.0 Hz, 1H), 7.74 (s, 1H), 7.67 (d, J = 8.0 Hz, 1H), 7.35 (d, J = 8.0 Hz, 1H), 7.25 (d, J = 8.0 Hz, 1H), 3.96 (s, 3H), 2.36 (s, 3H), 2.34 (s, 3H) Preparation of Intermediate 15.4 6-(3,4-dimethylphenyl)-2-thioxo-1,2-dihydropyridine-3-carboxylic acid To a solution of methyl 6-(3,4-dimethylphenyl)-2-thioxo-1,2-dihydropyridine-3-carboxylate (100 mg, 0.366 mmol) in methanol (0.50 mL), THF (0.50 mL) and water (0.50 mL) was added LiOH.H2O (77 mg, 1.83 mmol) and the mixture was stirred at 20 °C for 12 h. The pH of the mixture was adjusted to 3 with 1M HCl. The resulting solid was filtered and dried under vacuum to give the product 6-(3,4- dimethylphenyl)-2-thioxo-1,2-dihydropyridine-3-carboxylic acid (65 mg, 0.251 mmol, 68.52 % yield) as a yellow solid. RT 0.493 min (method 1); m / z 260.0 (M+H)+(ESI+);1H NMR (400 MHz, DMSO-d6): 14.85 (br, 1H), 14.40 (br, 1H), 8.54 (d, J = 8.0 Hz, 1H), 7.67 (s, 1H), 7.58 (d, J = 7.6 Hz, 1H), 7.30-7.35 (m, 2H), 2.31 (s, 6H) Preparation of Example 15 6-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-2-thioxo-1,2-dihydropyridine-3- carboxamide To a solution of 6-(3,4-dimethylphenyl)-2-thioxo-1,2-dihydropyridine-3-carboxylic acid (20 mg, 0.0771 mmol) in DMF (1 mL) was added HATU (26 mg, 0.100 mmol) and DIEA (0.041 mL, 0.231 mmol) at 0 °C. The mixture was stirred at 0 °C for 6 min under N2.3-amino-2,3-dihydrothiophene 1,1-dioxide hydrochloride (17 mg, 0.100 mmol, HCl salt) was added and the mixture was stirred at 0 °C for 1 h under N2. The resulting mixture was diluted with water (2 mL) and EtOAc (2 mL) leading to formation of a precipitate. After filtration, the solid was collected, dissolved in DMSO, purified by preparative HPLC (column: Welch Ultimate C18150*25 mm*10 µm; mobile phase: A: 10 mM aqueous solution of NH4HCO3, B: MeCN; B%: 24%-54%, 9 min) and lyophilized to give the product 6-(3,4-dimethylphenyl)-N-(1,1-dioxido- 2,3-dihydrothiophen-3-yl)-2-thioxo-1,2-dihydropyridine-3-carboxamide (6.0 mg, 0.0158 mmol, 20.48 % yield, 98.56% purity ) as a yellow solid. RT 0.460 min (method 4); m / z 375.1 (M+H)+(ESI+); 1H NMR (CDCl3, 400 MHz): 11.48 (d, J = 0.64 Hz, 1H), 10.81 (br, 1H), 8.76 (d, J = 8.0 Hz, 1H), 7.45-7.40 (m, 2H), 7.37-7.33 (m, 1H), 7.14 (d, J = 8.0 Hz, 1H), 6.88-6.80 (m, 2H), 5.58-5.50 (m, 1H), 3.84- 3.78 (m, 1H), 3.34-3.26 (m, 1H), 2.38 (s, 6H). Preparation of Intermediate 16.1 Methyl 3-fluoro-3',4'-dimethyl-[1,1'-biphenyl]-4-carboxylate To a solution of methyl 4-bromo-2-fluorobenzoate (1000 mg, 4.29 mmol) in 1,4-dioxane (10 mL) and water (2 mL) was added (3,4-dimethylphenyl)boronic acid (708 mg, 4.72 mmol), K2CO3 (1186 mg, 8.58 mmol) and Pd(dppf)Cl2 (157 mg, 0.215 mmol). The mixture was stirred at 80 °C for 2 h under N2. The resulting mixture was concentrated under reduced pressure. The residue was purified by flash silica gel chromatography (ISCO; 20 g SepaFlash Silica Flash Column, Eluent of 0~20% Ethyl acetate / Petroleum ether gradient, 60 mL / min) to give the product methyl 3-fluoro-3',4'-dimethyl-[1,1'-biphenyl]-4-carboxylate (1.00 g, 3.76 mmol, 87.51 % yield) as a white solid. RT 0.634 min (method 1); m / z 259.1 (M+H)+(ESI+);1H NMR (CDCl3, 400 MHz): 7.99 (t, J = 8.0 Hz, 1H), 7.4-7.35 (m, 4H), 7.24 (d, J = 7.6 Hz, 1H), 3.96 (s, 3H), 2.35-2.33 (m, 6H) Preparation of Intermediate 16.2 3-fluoro-3',4'-dimethyl-[1,1'-biphenyl]-4-carboxylic acid To a solution of methyl 3-fluoro-3',4'-dimethyl-[1,1'-biphenyl]-4-carboxylate (100 mg, 0.387 mmol) in THF (0.50 mL) and water (0.50 mL) was added LiOH.H2O (81 mg, 1.94 mmol) at 25 °C. The mixture was stirred at 25 °C for 1 h. Methanol (0.50 mL) was added and the reaction mixture was stirred at 25 °C for 1 h. The resulting mixture was concentrated under reduced pressure. The residue was diluted with water (0.5 m L) and then, HCl (aq., 1N) was added to the mixture until pH = 3~4. The aqueous layer was extracted with ethyl acetate (5 mL, 3x). The combined organic layer was dried over anhydrous Na2SO4, filtered and the filtrate was concentrated under reduced pressure to give the product 3-fluoro-3',4'- dimethyl-[1,1'-biphenyl]-4-carboxylic acid (90 mg, 0.361 mmol, 93.27 % yield) as a white solid. RT 0.553 min (method 1); m / z 244.9 (M+H)+(ESI+); Preparation of Example 16 N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-3-fluoro-3',4'-dimethyl-[1,1'-biphenyl]-4-carboxamide To a solution of 3-fluoro-3',4'-dimethyl-[1,1'-biphenyl]-4-carboxylic acid (20 mg, 0.0819 mmol), DIEA (3.00 eq, 0.044 mL, 0.246 mmol), 3-amino-2,3-dihydrothiophene 1,1-dioxide hydrochloride (18 mg, 0.106 mmol) in DMF (1.5 mL) was added T4P in EtOAc (77 mg, 50% purity, 0.106 mmol) at 0 ºC. The mixture was stirred at 20 ºC for 2 h. The reaction mixture was purified by preparative HPLC (column: Phenomenex Synergi C18150*25 mm*10 µm; mobile phase: A: 0.225% formic acid in water, B: MeCN; B%: 45%-75%, 15 min) and lyophilized to give the product N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-3-fluoro-3',4'- dimethyl-[1,1'-biphenyl]-4-carboxamide (20 mg, 0.0543 mmol, 66.26 % yield) as a white solid. RT 360.1 min (method 1); m / z 360.1 (M+H)+(ESI+);1H NMR (DMSO-d6, 400 MHz): 8.98 (d, J = 7.6 Hz, 1H), 7.74-7.67 (m, 1H), 7.65-7.58 (m, 2H), 7.56 (s, 1H), 7.51-7.46 (m, 1H), 7.29-7.20 (m, 2H), 6.92 (dd, J = 2.5, 6.7 Hz, 1H), 5.38-5.34 (m, 1H), 3.82 (dd, J = 8.1, 13.7 Hz, 1H), 3.23 (dd, J = 5.4, 13.7 Hz, 1H), 2.30 (s, 3H), 2.26 (s, 3H). Preparation of Intermediate 17.1 Methyl 3-amino-5-(3,4-dimethylphenyl)picolinate To a solution of methyl 3-amino-5-bromopicolinate (1 g, 4.33 mmol) in dioxane (10 mL) and water (2 mL) was added (3,4-dimethylphenyl)boronic acid (714 mg, 4.76 mmol) K2CO3 (1196 mg, 8.66 mmol) and Pd(dppf)Cl2 (158 mg, 0.216 mmol). The mixture was degassed with N2 three times and then, stirred at 80 °C for 2 h. The resulting reaction mixture was filtered and the filtrate was concentrated under vacuum. The residue was diluted with water (20 mL) and then, extracted with ethyl acetate (20 mL, 3x). The combined organic phase was washed with brine (20 mL, 2x) and dried over anhydrous Na2SO4, filtered and concentrated under vacuum. The residue was purified by flash silica gel chromatography (ISCO; 12 g SepaFlash Silica Flash Column, Eluent of 0~36% Ethyl acetate / Petroleum ether, gradient 60 mL / min) and concentrated under vacuum to give the product methyl 3-amino-5-(3,4- dimethylphenyl)picolinate (800 mg, 3.09 mmol, 71.40 % yield) as a red solid. RT 0.446 min (method 1); m / z 257.1 (M+H)+(ESI+).1H NMR (DMSO-d6, 400 MHz): 8.14 (s, 1H), 7.45 (s, 1H), 7.41 (s, 1H), 7.39 (d, J = 8.0 Hz, 1H), 7.26 (d, J = 8.0 Hz, 1H), 6.72 (s, 2H), 3.82 (s, 3H), 2.29 (s, 3H), 2.26 (s, 3H) Preparation of Intermediate 17.2 Methyl 3-(bis-(tert-butoxycarbonyl)amino)-5-(3,4-dimethylphenyl)picolinate To a solution of methyl 3-amino-5-(3,4-dimethylphenyl)picolinate (400 mg, 1.56 mmol) and (Boc)2O (1362 mg, 6.24 mmol) in DCM (4 mL) was added DIEA (0.83 mL, 4.68 mmol) and DMAP (19 mg, 0.156 mmol) at 0 °C. The mixture was stirred at °C for 12 h and then, concentrated under reduced pressure. The residue was purified by flash silica gel chromatography (ISCO; 12 g SepaFlash Silica Flash Column, Eluent of 0~16% Ethyl acetate / Petroleum ether, gradient 60 mL / min) and concentrated under vacuum to give the product methyl 3-(bis-(tert-butoxycarbonyl)amino)-5-(3,4-dimethylphenyl)picolinate (400 mg, 0.850 mmol, 54.46 % yield) as a yellow solid. RT 0.626 min (method 1); m / z 457.2 (M+H)+(ESI+).1H NMR (DMSO-d6, 400 MHz): 8.98 (s, 1H), 8.24 (s, 1H), 7.68 (s, 1H), 7.59 (d, J = 8.0 Hz, 1H), 7.29 (d, J = 8.0 Hz, 1H), 3.84 (s, 3H), 2.31 (s, 3H), 2.28 (s, 3H), 1.34 (s, 18H) Preparation of Intermediate 17.3 3-(bis-(tert-butoxycarbonyl)amino)-5-(3,4-dimethylphenyl)-2-(methoxycarbonyl)pyridine 1-oxide To a solution of methyl 3-(di-(tert-butoxycarbonyl)amino)-5-(3,4-dimethylphenyl)picolinate (400 mg, 0.876 mmol) in DCM (5 mL) was added m-CPBA (454 mg, 2.24 mmol, 85% purity) at 0°C. The reaction mixture was stirred at 25 °C for 12 h, then quenched by addition of 80 mL of saturated Na2SO3 aqueous solution and extracted with EtOAc (60 mL; 3x). The combined organic layer was washed with brine (60 mL; 3x), separated, dried over anhydrous Na2SO4, filtered and concentrated under vacuum. The residue was purified by flash silica gel chromatography (ISCO; 12 g SepaFlash Silica Flash Column, Eluent of 0~36% Ethyl acetate / Petroleum ether, gradient 60 mL / min) and concentrated under vacuum to give the product 3-(bis-(tert-butoxycarbonyl)amino)-5-(3,4-dimethylphenyl)-2-(methoxycarbonyl)pyridine 1-oxide (220 mg, 0.466 mmol, 53.14 % yield) as colorless oil. RT 0.581 min (method 1); m / z 473.2 (M+H)+(ESI+);1H NMR (DMSO-d6, 400 MHz): 8.78 (s, 1H), 8.02 (s, 1H), 7.65 (s, 1H), 7.55 (d, J = 8.0 Hz, 1H), 7.27 (d, J = 8.0 Hz, 1H), 3.85 (s, 3H), 2.29 (s, 3H), 2.27 (s, 3H), 1.37 (s, 18H) Preparation of Intermediate 17.4 3-((tert-butoxycarbonyl)amino)-2-carboxy-5-(3,4-dimethylphenyl)pyridine 1-oxide To a solution of 3-(bis-(tert-butoxycarbonyl)amino)-5-(3,4-dimethylphenyl)-2- (methoxycarbonyl)pyridine 1-oxide (220 mg, 0.466 mmol) in THF (1 mL), water (1 mL) and methanol (1 mL) was added LiOH·H2O (98 mg, 2.33 mmol) at 25 °C. The mixture was stirred at 25 °C for 12 h and then, concentrated under reduced pressure. The residue was diluted with water (2 mL). Then, the pH was adjusted to pH 3~4 by adding HCl (aq., 1N) . The resulting suspension was filtered and the filter cake was washed with MeCN (3 mL). The solid was collected and dried under reduced pressure to give the product 3-((tert-butoxycarbonyl)amino)-2-carboxy-5-(3,4-dimethylphenyl)pyridine 1-oxide (160 mg, 0.420 mmol, 90.14 % yield) as a white solid. RT 0.634 min (method 1); m / z 359.1 (M +H)+(ESI+).1H NMR (DMSO-d6, 400 MHz): 11.46 (br s, 1H), 8.95 (s, 1H), 8.84 (s, 1H), 7.59 (s, 1H), 7.51 (d, J = 7.6 Hz, 1H), 7.32 (d, J = 7.6 Hz, 1H), 2.31 (s, 3H), 2.29 (s, 3H), 1.52 (s, 9H) Preparation of Intermediate 17.5 3-((tert-butoxycarbonyl)amino)-5-(3,4-dimethylphenyl)-2-((1,1-dioxido-2,3-dihydrothiophen-3- yl)carbamoyl)pyridine 1-oxide To a solution of 3-((tert-butoxycarbonyl)amino)-2-carboxy-5-(3,4-dimethylphenyl)pyridine 1-oxide (40 mg, 0.112 mmol) in DMF (0.5 mL) was added 3-amino-2,3-dihydrothiophene 1,1-dioxide hydrogen bromide (31 mg, 0.145 mmol) DIEA (0.060 mL, 0.335 mmol) and HATU (55 mg, 0.145 mmol) at 25 °C. The mixture was stirred at 25 °C for 2 h, then diluted with water (5 mL) and extracted with ethyl acetate (5 mL, 3x). The combined organic layer was washed with brine (5 mL, 2x), dried over anhydrous Na2SO4, filtered and concentrated under vacuum. The residue was purified by reversed-phase flash (ISCO; 20 g Flash Column Welch Ultimate XB_C1820-40 m; 120 A, mobile phase: A: 0.1% formic acid in water, B: MeCN; B%: 0%-60%, 40mL / min) and lyophilized directly to give the product 3-((tert- butoxycarbonyl)amino)-5-(3,4-dimethylphenyl)-2-((1,1-dioxido-2,3-dihydrothiophen-3- yl)carbamoyl)pyridine 1-oxide (40 mg, 0.0667 mmol, 59.79 % yield) as a yellow solid. RT 0.607 min (method 1); m / z 474.1 (M+H)+(ESI+). Preparation of Example 17 3-amino-5-(3,4-dimethylphenyl)-2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl) pyridine 1- oxide A solution of 3-((tert-butoxycarbonyl)amino)-5-(3,4-dimethylphenyl)-2-((1,1-dioxido-2,3- dihydrothiophen-3-yl)carbamoyl)pyridine 1-oxide (20 mg, 0.0422 mmol) in TFA (0.1 mL) and DCM (0.5 mL) was stirred at 25 °C for 2 h. The resulting mixture was concentrated under reduced pressure. The resulting residue was purified by preparative HPLC (column: Phenomenex Synergi C18150*25 mm*10 µm; mobile phase: A: 0.225% formic acid in water, B: MeCN; B%: 32%-62%, 9 min) and lyophilized directly to give the product 3-amino-5-(3,4-dimethylphenyl)-2-((1,1-dioxido-2,3-dihydrothiophen-3- yl)carbamoyl)pyridine 1-oxide (6.5 mg, 0.0169 mmol, 46.03 % yield) as an off-white solid. RT 0.475 min (LCMS: method 1); m / z 374.3 (M+H)+(ESI+); RT 2.149, 2.621 min (SFC: Method 4);1H NMR (DMSO-d6, 400 MHz):12.13 (d, J = 7.2 Hz, 1H), 8.03 (d, J = 1.6 Hz, 1H), 7.51-7.48 (m, 3H), 7.40 (dd, J = 1.6, 8.0 Hz, 1H), 7.29-7.24 (m, 2H), 7.20 (d, J = 1.6 Hz, 1H), 7.00 (dd, J = 1.6, 8.0 Hz, 1H), 5.38- 5.30 (m, 1H), 3.74 (dd, J = 7.2, 13.6 Hz, 1H), 3.29 (J = 4.8, 13.6 Hz, 1H), 2.29 (s, 3H), 2.27 (s, 3H) Preparation of Intermediate 18.1 (R)-3-((tert-butoxycarbonyl)amino)-5-(3,4-dimethylphenyl)-2-((1,1-dioxido-2,3-dihydrothiophen-3- yl)carbamoyl)pyridine 1-oxide To a solution of 3-((tert-butoxycarbonyl)amino)-2-carboxy-5-(3,4-dimethylphenyl)pyridine 1-oxide (260 mg, 0.725 mmol) DIEA (0.65 mL, 3.63 mmol) and (R)-3-amino-2,3-dihydrothiophene 1,1-dioxide hydrogen bromide (202 mg, 0.943 mmol, 91.5% ee) in DMF (6 mL) was added T4P in EtOAc (1567 mg, 2.18 mmol, wt%: 50%).The mixture was stirred at 30 °C for 12 h, then diluted with water (20 mL) and extracted with ethyl acetate (20 mL, 3x). The combined organic layer was washed with brine (20 mL, 2x), dried over anhydrous Na2SO4, filtered and concentrated under vacuum. The residue was purified by flash silica gel chromatography (ISCO; 12 g SepaFlash Silica Flash Column, Eluent of 0~20% Ethyl acetate / Petroleum ether; gradient, 60 mL / min) and concentrated under vacuum to give the product (R)-3- ((tert-butoxycarbonyl)amino)-5-(3,4-dimethylphenyl)-2-((1,1-dioxido-2,3-dihydrothiophen-3- yl)carbamoyl)pyridine 1-oxide (130 mg, 0.187 mmol, 25.73% yield) as a yellow solid. RT 0.604 min (method 1); m / z 474.1 (M+H)+(ESI+). Preparation of Example 18 (R)-3-amino-5-(3,4-dimethylphenyl)-2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)pyridine 1-oxide A solution of (R)-3-((tert-butoxycarbonyl)amino)-5-(3,4-dimethylphenyl)-2-((1,1-dioxido-2,3- dihydrothiophen-3-yl)carbamoyl)pyridine 1-oxide (107 mg, 0.227 mmol) in TFA (0.3 mL) and DCM (0.9 mL) was stirred at 25 °C for 1 h. The resulting mixture was concentrated under reduced pressure. The residue was purified by reversed-phase flash (ISCO®; 40 g Flash Column Welch Ultimate XB_C1820-40 m; 120 A, mobile phase: A: 0.1% TFA in water, B: MeCN; B%: 0%-40%, 40mL / min) and lyophilized directly to give the product (R)-3-amino-5-(3,4-dimethylphenyl)-2-((1,1-dioxido-2,3-dihydrothiophen-3- yl)carbamoyl)pyridine 1-oxide (47 mg, 0.125 mmol, 55.14 % yield, ee%: 90.78% based on SFC) as a yellow solid. RT 0.469 min (LCMS: method 1); m / z 374.3 (M+H)+(ESI+); RT 2.588 min, ee%: 90.78% (SFC: Method 4);1H NMR (DMSO-d6, 400 MHz): 12.12 (d, J = 7.6 Hz, 1H), 8.03 (d, J = 1.6 Hz, 1H), 7.60-7.50 (m, 3H), 7.40 (dd, J = 1.2, 7.2 Hz, 1H), 7.30-7.24 (m, 2H), 7.20 (d, J = 1.6 Hz, 1H), 7.00 (dd, J = 1.2, 7.2 Hz, 1H), 5.38-5.30 (m, 1H), 3.74 (dd, J = 7.6, 13.6 Hz, 1H), 3.30 (dd, J = 4.4, 13.6 Hz, 1H), 2.29 (s, 3H), 2.27 (s, 3H) Examples listed in the table below were prepared according to the corresponding general procedures and starting from the corresponding intermediates or examples. Cpd Structure Yield Procedures LC / MS and SFC1H NMR number (%) information 1H NMR (DMSO-d6, 400 MHz):11.55 (d, J = 8.0 Hz, Procedure1, LCMS: RT 0.484 min 1H), 8.95 (s, Procedure 3, ((Method 1), m / z 399.0 ++1H), 8.30 (d, 19 50.43 Procedure 2, (M+H) (ESI); J = 8.4 Hz, then SFC: RT 1.549 min, 1H), 8.07 (d, Procedure 4 2.068 min (Method 5) J = 8.0 Hz, 2H), 8.02 (d, J = 8.4 Hz, 1H), 7.90 (d, J = 8.0 Hz, 2H), 7.31 (dd, J = 1.6, 6.8Hz, 1H), 7.02 (dd, J = 1.6, 6.8 Hz, 1H), 5.41- 5.40 (m, 1H), 3.77 (dd, J = 8.0, 13.6 Hz, 1H), 3.39 (dd, J = 4.0, 13.6 Hz, 1H) 1H NMR (CDCl3 , 400 MHz): 11.36 (s, 1H), 8.04 (br s, 1H), 7.70 (br s, 1H), 7.33 Procedure 1, LCMS: RT 0.427 min (d, J = 7.2 Hz, Procedure 2, (Method 1), m / z 374.1 1H), 7.20(s, Procedure 3, (M+H)+(ESI+); 45.35 1H), 7.15 (d, Procedure 4, SFC: Two peaks, RT J = 7.2 Hz, then 1.764 min, 2.076 min 1H), 6.84 (br Procedure 5 (Method 5) s, 2H), 5.46 (s, 1H) , 3.82- 3.77 (m, 1H), 3.35-3.32 (m, 1H), 2.36 (s, 3H), 2.35 (s, 3H)1H NMR (CDCl3, 400 MHz): 12.00 (d, J = 6.4 Hz, 1H), 8.53 (d, J = 1.6 Hz, 1H), 8.35 (d, J = 8.4 Hz, 1H), 7.73 (dd, LCMS: RT 0.507 min J = 1.6, 8.4 Procedure 1, (Method 1), m / z 437.0 Hz, 1H), Procedure 2, (M+H)+(ESI+); 7.47-7.42 (m, 42.35 Procedure 3 SFC: RT 2.462 min, 1H), 7.39- then ee%: 90.75% (Method 7.31 (m, 6H), Procedure 4 6) 7.15-7.09 (m, 2H), 6.90- 6.84 (m, 2H), 5.58-5.53 (m, 1H), 5.16 (s, 2H), 3.81 (dd, J = 6.4, 13.6 Hz, 1H), 3.28 (dd, J = 4.8, 13.6 Hz, 1H). 1H NMR (DMSO-d6, LCMS:RT 0. 503 min 400 MHz): Procedure 1 (method 1), m / z 351.1 11.52 (d, J = then (M+H)+(ESI+); 7.6 Hz, 1H), 5.87 Procedure 4 SFC: RT 1.950 min, 8.78 (s, 1H), ee%=87.32% (Method 8.21 (d, J = 5) 8.4 Hz, 1H), 8.10 (s, 1H), 7.90 (d, J = 8.4 Hz, 1H), 7.40 (s, 1H), 7.20 (dd, J = 2.8, 6.8 Hz, 1H), 6.98 (dd, J = 2.8, 6.8 Hz, 1H), 5.47-5.37 (m, 1H), 3.79- 3.73 (dd, J = 7.6, 13.6 Hz, 1H), 3.28 (dd, J = 4.4, 13.6 Hz, 1H), 2.50 (s, 3H) 1H NMR (DMSO-d6, 400 MHz):11.55 (d, J = 8.0 Hz, 1H), 8.46 (s, 1H), 8.17 (d, LCMS: RT 0.499 min J = 8.4 Hz, (Method 1), m / z 347.2 Procedure 1 1H), 7.58 (d, (M+H)+(ESI+); 56.13 then 8.4 Hz, 1H), SFC: Two peaks, RT Procedure 4 7.28 (dd, J = 0.970 min, 2.048 min 3.2, 6.8 Hz, (Method 5) 1H), 7.00 (dd, J = 3.2, 6.8 Hz, 1H), 6– 96 (s, 1H), 5.39 - 5.33 (m, 1H), 3.74 (dd, J = 8.0, 13.6 Hz, 1H), 3.36 (dd, J = 4.4, 13.6 Hz, 1H), 2–78 (s, 2H), 2.21 - 2– 12 (m, 4H), 1.96 - 1.80 (m, 2H) 1H NMR (DMSO-d6, 400 MHz): 11.49 (d, J = 8.0 Hz, 1H), 8.72 (d, J = 1.2 Hz, 1H), 8.28 (d, J = 8.4 Hz, 1H), 7.89 (dd, J = 1.2, 8.4 Hz, Procedure 1, LCMS: RT 0.442 min ocedure 2 (Meth 1H), 7.68 (d, Pr od 1), m / z 370.9 (M+H)+(ESI+) J = 5.6 Hz, 29.74 Procedure 3 SFC: Two peaks, RT 1H), 7.42 (d, and then 2.056 min 2.257 min J = 5.6 Hz, Procedure 4 (Method 7) 1H), 7.30 (dd, J = 2.8, 6.8 Hz, 1H), 7.01 (dd, J = 2.8, 6.8 Hz, 1H), 5.46-5.35 (m, 1H), 3.76 (dd, J = 8.0, 13.6 Hz, 1H), 3.38 (dd, J = 4.0, 13.6 Hz, 1H) Preparation of Intermediate 25.1 3-chloro-6-(3,4-dimethylphenyl)-2-methoxypyridine To a solution of 6-bromo-3-chloro-2-methoxypyridine (1.5 g, 6.74 mmol) in 1,4-Dioxane (15 mL) and water (3 mL) were added (3,4-dimethylphenyl)boronic acid (1213 mg, 8.09 mmol), K2CO3 (1864 mg, 13.5 mmol) and Pd(dppf)Cl2·DCM (275 mg, 0.337 mmol). The mixture was degassed with N2 (3x) and, then stirred at 80 °C for 12 h. The resulting reaction mixture was filtered and the cake was washed with EtOAc (50 mL). The combined filtrate was concentrated to give a residue which was purified by flash silica gel chromatography (ISCO®; 20 g SepaFlash® Silica Flash Column, Eluent of 0~10% Ethyl acetate / Petroleum ether gradient, 20 mL / min) to give the product 3-chloro-6-(3,4-dimethylphenyl)-2- methoxy-pyridine (1.80 g, 5.96 mmol, 88.42 % yield) as a yellow solid. RT 0.645 min (method 1); m / z 247.9 (M+H)+(ESI+);1H NMR (CDCl3, 400 MHz): 7.77 (s, 1H), 7.76 - 7.72 (, J = 8.0 Hz, 1H), 7.64 (d, J = 8.0 Hz, 1H), 7.28 (d, J = 8.0 Hz, 1H), 7.24 - 7.18 (J = 8.0 Hz, 1H), 4.13 (s, 3H), 2.35 (s, 3H), 2.31 (s, 3H) Preparation of Intermediate 25.2 6-(3,4-dimethylphenyl)-2-methoxy-3-((triisopropylsilyl)ethynyl)pyridine To a mixture of 3-chloro-6-(3,4-dimethylphenyl)-2-methoxy-pyridine (300 mg, 1.21 mmol), ethynyl(triisopropyl)silane (663 mg, 3.63 mmol), Cs2CO3 (1184 mg, 3.63 mmol), X-phos (173 mg, 0.363 mmol) in MeCN (7.5 mL) was added Pd2(dba)3 (111 mg, 0.121 mmol). The reaction mixture was degassed with N2 (3X), then stirred at 80 °C for 12 h, poured into water (50 mL) and extracted with EtOAc (50 mL, 3x). The combined organic layer was washed with brine (20 mL), dried over anhydrous Na2SO4,filtered concentrated under vacuum. The residue was purified by flash silica gel chromatography (ISCO®; 20 g SepaFlash® Silica Flash Column, Eluent of 0~10% Ethyl acetate / Petroleum ether gradient, 20 mL / min) and concentrated under vacuum to give the product 6-(3, 4-dimethylphenyl)-2-methoxy-3- ((triisopropylsilyl) ethynyl)pyridine (340 mg, 0.864 mmol, 71.32 % yield) as a yellow solid. RT 0.793 min (method 6); m / z 394.4 (M +H)+(ESI+);1H NMR (CDCl3, 400 MHz): 7.81 (s, 1H), 7.77 (d, J = 7.8 Hz, 1H), 7.70 (d, J = 7.8 Hz, 1H), 7.28 (d, J = 8.0 Hz, 1H), 7.21 (d, J = 8.0 Hz, 1H), 4.08 (s, 3H), 2.34 (s, 3H), 2.31 (s, 3H), 1.21-1.26 (m, 3H), 1.15 (s, 18H). Preparation of Intermediate 25.3 6-(3,4-dimethylphenyl)-3-ethynyl-2-methoxypyridine To a solution of 6-(3,4-dimethylphenyl)-2-methoxy-3-((triisopropylsilyl)ethynyl)pyridine (340 mg, 0.864 mmol) in THF (3.5 mL) was added TBAF (271 mg, 1.04 mmol). The reaction mixture was stirred at 20°C for 4 h, then poured into water (50 mL) and extracted with EtOAc (20 mL; 3x). The combined organic layer was washed with brine (20 mL), dried over anhydrous Na2SO4, filtered and concentrated under vacuum. The residue was purified by preparative-TLC (UV, Rf=0.4, eluent: Ethyl acetate: Petroleum ether (1:5)) and concentrated under vacuum to give the product 6-(3,4-dimethylphenyl)-3-ethynyl-2-methoxy- pyridine (200 mg, 0.820 mmol, 94.94 % yield) as a yellow oil. RT 0.405 min (method 6); m / z 237.9 (M+H)+(ESI+);1H NMR (CDCl3, 400 MHz): 7.81 (s, 1H), 7.80 - 7.73 (m, 2H), 7.31 (d, J = 7.8 Hz, 1H), 7.22 (d, J = 7.8 Hz, 1H), 4.14 (s, 3H), 3.39 (s, 1H), 2.35 (s, 3H), 2.32 (s, 3H) Preparation of Example 25 3-(4-(6-(3,4-dimethylphenyl)-2-methoxypyridin-3-yl)-1H-1,2,3-triazol-1-yl)-2,3-dihydrothiophene 1,1-dioxide To solution of 3-azido-2,3-dihydrothiophene 1,1-dioxide (20 mg, 0.126 mmol), 6-(3,4- dimethylphenyl)-3-ethynyl-2-methoxypyridine (20 mg, 0.0843 mmol), CuSO4·5H2O (4.2 mg, 0.0169 mmol) in tert-butanol (0.5 mL) and water (0.5 mL) was added (+)-Sodium L-ascorbate (8.3 mg, 0.0421 mmol). The reaction mixture was stirred at 70°C for 2 h, then filtered and the filtrate was concentrated. The crude product was purified by reversed-phase flash (ISCO®; 20 g Flash Column Welch Ultimate XB_C1820-40 m; 120 A, mobile phase: A: 0.1% formic acid in water, B: MeCN; B%: 40%-60%, 10 mL / min) and lyophilized directly to give the product 3-(4-(6-(3,4-dimethylphenyl)-2-methoxypyridin-3-yl)-1H-1,2,3- triazol-1-yl)-2,3-dihydrothiophene 1,1-dioxide (0.93 mg, 0.00235 mmol, 1.86 % yield) as an off-white solid. LCMS: RT 0.553 min (method 1); m / z 397.0 (M+H)+(ESI+); SFC: RT 1.866 min, 2.230 min (Method 8);1H NMR (CDCl3, 400 MHz): 8.60 (d, J = 8.0 Hz, 1H), 8.19 (s, 1H), 7.86 (s, 1H), 7.83 (d, J = 8.0 Hz, 1H), 7.49 (d, J = 8.0 Hz, 1H), 7.23 (d, J = 8.0 Hz, 1H), 7.08 (d, J = 6.7 Hz, 1H), 6.93 (d, J = 6.7 Hz, 1H), 6.26 - 6.17 (m, 1H), 4.19 (s, 3H), 3.99-3.93 (m, 1H), 3.57-3.52 (m, 1H), 2.36 (s, 3H), 2.33 (s, 3H). Preparation of Example 26 3-(4-(6-(3,4-dimethylphenyl)-2-hydroxypyridin-3-yl)-1H-1,2,3-triazol-1-yl)-2,3-dihydrothiophene 1,1-dioxide A solution of 3-(4-(6-(3,4-dimethylphenyl)-2-methoxypyridin-3-yl)-1H-1,2,3-triazol-1-yl)-2,3- dihydrothiophene 1,1-dioxide (16 mg, 0.0404 mmol) in HCl (aq, 12 mol / L., 0.5 mL) was stirred at 100°C for 1 h. The resulting suspension was filtered,was washed with water (10 mL) and EtOH (10 mL), collected and dried under vacuum to give the product 3-(4-(6-(3,4-dimethylphenyl)-2-hydroxypyridin-3-yl)-1H-1,2,3- triazol-1-yl)-2,3-dihydrothiophene 1,1-dioxide (4.6 mg, 0.0119 mmol, HCl salt, 29.54 % yield) as a yellow solid. LCMS: RT 0.692 min (method 4); m / z 383.0 (M+H)+(ESI+); SFC: RT 1.247 min, 1.594 min (Method 8);1H NMR (DMSO-d6, 400 MHz): 12.15 (br, 1H), 8.68 (s, 1H), 8.35 (d, J = 7.5 Hz, 1H), 7.61 (s, 1H), 7.60 - 7.50 (m, 2H), 7.33 - 7.19 (m, 2H), 6.75 (d, J = 7.5 Hz, 1H), 6.50 - 6.38 (m, 1H), 4.06 (dd, J = 8.6, 14.3 Hz, 1H), 3.63 (dd, J = 4.1, 14.3 Hz, 1H), 2.29 (s, 3H), 2.28 (s, 3H). Preparation of Example 25a&25b (R or S)-3-(4-(6-(3,4-dimethylphenyl)-2-methoxypyridin-3-yl)-1H-1,2,3-triazol-1-yl)-2,3- dihydrothiophene 1,1-dioxide and (S or R)-3-(4-(6-(3,4-dimethylphenyl)-2-methoxypyridin-3-yl)-1H- 1,2,3-triazol-1-yl)-2,3-dihydrothiophene 1,1-dioxide 3-(4-(6-(3,4-dimethylphenyl)-2-methoxypyridin-3-yl)-1H-1,2,3-triazol-1-yl)-2,3-dihydrothiophene 1,1-dioxide (85 mg, 0.210 mmol) was separated by preparative SFC (column: Daicel Chiralpak IC 250x30mm I.D., 10 m particle size; Mobile Phase: A: Supercritical CO2, B: EtOH (NEU): 60% Phase B in Supercritical CO2, Gradient information:10 min, Flow Rate: 120 g / min) and lyophilized to give (R or S)- 3-(4-(6-(3,4-dimethylphenyl)-2-methoxypyridin-3-yl)-1H-1,2,3-triazol-1-yl)-2,3-dihydrothiophene 1,1- dioxide (30 mg, 0.0757 mmol, 36.0 % yield, ee%: 98.33% based on SFC method 8) as a light yellow solid and (S or R)-3-(4-(6-(3,4-dimethylphenyl)-2-methoxypyridin-3-yl)-1H-1,2,3-triazol-1-yl)-2,3- dihydrothiophene 1,1-dioxide (30 mg, 0.0757 mmol, 36.0 % yield, ee%: 100% based on SFC method 8) as a light yellow solid. Example 25a: LCMS: RT 0.562 min (method 1); m / z 397.1 (M+H)+(ESI+); SFC: RT 1.853 min, ee%: 98.33% (Method 8);1H NMR (CDCl3, 400 MHz): 8.61 (d, J = 8.0 Hz, 1H), 8.19 (s, 1H), 7.87 (s, 1H), 7.83 (d, J = 8.0 Hz, 1H), 7.50 (d, J = 8.0 Hz, 1H), 7.23 (d, J = 8.0 Hz, 1H), 7.08 (d, J = 6.6 Hz, 1H), 6.93 (d, J = 6.6 Hz, 1H), 6.26 - 6.16 (m, 1H), 4.20 (s, 3H), 3.99-3.93 (m, 1H), 3.57-3.52 (m, 1H), 2.36 (s, 3H), 2.33 (s, 3H). Example 25b: LCMS: RT 0.563 min (method 1); m / z 397.1 (M+H)+(ESI+); SFC: RT 2.225 min, ee%: 100% (SFC: Method 8);1H NMR (CDCl3, 400 MHz): 8.61 (d, J = 8.0 Hz, 1H), 8.19 (s, 1H), 7.87 (s, 1H), 7.83 (d, J = 8.0 Hz, 1H), 7.50 (d, J = 8.0 Hz, 1H), 7.23 (d, J = 8.0 Hz, 1H), 7.08 (d, J = 6.6 Hz, 1H), 6.93 (d, J =6.6 Hz, 1H), 6.25 - 6.18 (m, 1H), 4.20 (s, 3H), 3.99-3.93 (m, 1H), 3.57-3.52 (m, 1H), 2.36 (s, 3H), 2.33 (s, 3H). Preparation of Example 26a (R or S)-3-(4-(6-(3,4-dimethylphenyl)-2-hydroxypyridin-3-yl)-1H-1,2,3-triazol-1-yl)-2,3- dihydrothiophene 1,1-dioxide hydrochloride A solution of (R or S)-3-(4-(6-(3,4-dimethylphenyl)-2-methoxypyridin-3-yl)-1H-1,2,3-triazol-1-yl)-2,3- dihydrothiophene 1,1-dioxide (15 mg, 0.0378 mmol) in conc. HCl (0.20 mL) was stirred at 100°C for 1 h. The reaction mixture was then filtered and the filter cake was washed with water (10 mL) and MeCN (10 mL). The cake was collected and dried under vacuum to give the product (R or S)-3-(4-(6-(3,4- dimethylphenyl)-2-hydroxypyridin-3-yl)-1H-1,2,3-triazol-1-yl)-2,3-dihydrothiophene 1,1-dioxide hydrochloride (7.1 mg, 0.0169 mmol, 44.61 % yield, ee%: 100% based on SFC method 8, HCl salt) as a yellow solid. LCMS: RT 0.475 min (method 1); m / z 383.0 (M+H)+(ESI+); SFC: RT 1.564 min, ee%: 100% (Method 8);1H NMR (DMSO-d6, 400 MHz): 12.80 (br s, 1H), 8.69 (s, 1H), 8.36 (d, J = 7.4 Hz, 1H), 7.63 (s, 1H), 7.60 - 7.49 (m, 2H), 7.32 - 7.17 (m, 2H), 6.76 (d, J = 7.4 Hz, 1H), 6.44-6.40 (m, 1H), 4.10-4.04 (m, 1H), 3.66-3.61 (m, 1H), 2.29 (s, 3H), 2.28 (s, 3H). Preparation of Example 26b (S or R)-3-(4-(6-(3,4-dimethylphenyl)-2-hydroxypyridin-3-yl)-1H-1,2,3-triazol-1-yl)-2,3- dihydrothiophene 1,1-dioxide hydrochloride A solution of (S or R)-3-(4-(6-(3,4-dimethylphenyl)-2-methoxypyridin-3-yl)-1H-1,2,3-triazol-1-yl)-2,3- dihydrothiophene 1,1-dioxide (15 mg, 0.0378 mmol) in conc. HCl (0.20 mL) was stirred at 100°C for 1 h. The reaction mixture was then filtered and the filter cake was washed with water (10 mL) and EtOH (10 mL). The cake was collected and dried under vacuum to give the product (S or R)-3-(4-(6-(3,4- dimethylphenyl)-2-hydroxypyridin-3-yl)-1H-1,2,3-triazol-1-yl)-2,3-dihydrothiophene 1,1-dioxide hydrochloride (11 mg, 0.0252 mmol, 66.63 % yield, ee%: 100% based on SFC method 8, HCl salt) as a light yellow solid. LCMS: RT 0.466 min (method 1); m / z 383.1 (M+H)+(ESI+); SFC: RT 1.222 min, ee%: 100% (Method 8);1H NMR (DMSO-d6, 400 MHz): 12.15 (s, 1H), 8.68 (s, 1H), 8.35 (d, J = 7.4 Hz, 1H), 7.62 (s, 1H), 7.59 - 7.50 (m, 2H), 7.31 - 7.19 (m, 2H), 6.75 (d, J = 7.4 Hz, 1H), 6.47 - 6.37 (m, 1H), 4.09-4.03 (mm, 1H), 3.65-3.61 (m, 1H), 2.29 (s, 3H), 2.28 (s, 3H). Preparation of Intermediate 27.1 Bis(2,2,2-trifluoroethyl) ((methylsulfonyl)methyl)phosphonate At 0°C, to a solution of bis(2,2,2-trifluoroethyl) ((methylthio)methyl)phosphonate (2000 mg, 6.53 mmol) in DCM (20 mL) was added m-CPBA (3979 mg, 19.6 mmol, 85% purity). The mixture was stirred at 25°C for 1.5 h, then, poured into water (50 mL) and extracted with DCM (30 mL, 2x). The combined organic layer was washed with brine (80 mL, 2x), dried with anhydrous Na2SO4, filtered, concentrated under vacuum. The residue was purified by flash silica gel chromatography (ISCO; 40 g SepaFlash Silica Flash Column, Eluent of 0~30% Ethyl acetate / Petroleum ether gradient, 80mL / min) to give the product bis(2,2,2-trifluoroethyl) ((methylsulfonyl)methyl)phosphonate (1800 mg, 5.32 mmol, 81.48 % yield) as a white solid. 1H NMR (DMSO-d6, ,400 MHz) : 4.80 - 4.69 (m, 4H), 4.63 (s, 2H), 3.18 (s, 1H) Preparation of Intermediate 27.2 tert-butyl (S)-(4-(methylsulfonyl)but-3-en-2-yl)carbamate To a solution of bis(2,2,2-trifluoroethyl) ((methylsulfonyl)methyl)phosphonate (300 mg, 0.887 mmol) in THF (3 mL) was added K2CO3 (368 mg, 2.66 mmol) and tert-butyl (S)-(1-oxopropan-2- yl)carbamate (154 mg, 0.887 mmol). The mixture was stirred at 20 °C for 2 h then poured into water (20 mL) and extracted with EtOAc (30 mL, 2x). The combined organic layer was washed with brine (30 mL, 2x), dried over anhydrous Na2SO4, filtered, and concentrated under vacuum to give product tert-butyl (S)- (4-(methylsulfonyl)but-3-en-2-yl)carbamate (140 mg,0.519 mmol, 58.55 % yield) as coloress oil. RT 0.430 min (method 1); m / z 194.0 (M –tBu+H)+(ESI+).1H NMR (DMSO-d6, ,400 MHz): 6.86 (dd, J = 4.8, 15.2 Hz, 0.4H), 6.47 (d, J =15.2 Hz, 0.4H), 6.25 (d, J =11.2 Hz, 0.6 H), 6.19 (d, J =2.0, 11.2 Hz, 0.6 H), , 5.15-5.00 (m, 1H), 2.95 (s, 1.8H), 1.63-1.58 (m, 1.2H), 1.62-1.49 (m, 9H), 1.33-1.31 (m, 3 H). Preparation of Intermediate 27.3 (S)-4-(methylsulfonyl)but-3-en-2-amine To a solution of tert-butyl (S)-(4-(methylsulfonyl)but-3-en-2-yl)carbamate (125 mg, 0.464 mmol) in MeCN (2 mL) was added TsOH (96 mg, 0.557 mmol).The mixture was stirred at 50°C for 1 h and concentrated under vacuum to give the crude product (S)-4-(methylsulfonyl)but-3-en-2-amine (80 mg, 0.249 mmol, 53.66 % yield TsOH salt) as transparent oil. The crude product was used directly in the next step. Alternative preparation of Intermediate 7.2 2-carboxy-5-(3,4-dimethylphenyl)pyridine 1-oxide To a solution of (3,4-dimethylphenyl)boronic acid (1000 mg, 6.67 mmol) and 5-bromo-2- (methoxycarbonyl)pyridine 1-oxide (1.20 eq, 1856 mg, 8.00 mmol) in 1,4-Dioxane (20 mL)and Water (2 mL) was added K2CO3 (2027 mg, 14.7 mmol)and Pd(dppf)Cl2 (544 mg, 0.667 mmol). The mixture was degassed with N2 (3x), stirred at 80°C for 1 h, then poured into water (20 mL) and extracted with EtOAc (60 mL, 2x). The combined organic layer was washed with brine (60 mL, 2x), dried over anhydrous Na2SO4, filtered and concentrated under vacuum. The residue was purified by flash silica gel chromatography (ISCO; 40 g SepaFlash Silica Flash Column, Eluent of 0~10% Methyl alcohol / dichloromethane, 80mL / min) to give the product 2-carboxy-5-(3,4-dimethylphenyl)pyridine 1-oxide (1100 mg,3.62 mmol, 54.26 % yield) as a white solid. RT 0.497 min (method 1); m / z 244.1 (M+H)+(ESI+).1H NMR (DMSO-d6, ,400 MHz) : 9.11 (s, 1H), 8.30 (d, J = 8.2 Hz, 1H), 8.23 (d, J = 8.2 Hz, 1H)7.71 (s, 1H), 7.62 (d, J = 7.6 Hz, 1H), 7.31 (d, J = 7.6 Hz, 1H), 2.31 (s, 3H), 2.28 (s, 3H) Preparation of Example 27 (S,Z)-5-(3,4-dimethylphenyl)-2-((4-(methylsulfonyl)but-3-en-2-yl)carbamoyl)pyridine 1-oxide At 0°C, to a solution of 2-carboxy-5-(3,4-dimethylphenyl)pyridine 1-oxide (50 mg, 0.164 mmol) DIEA (0.088 mL, 0.493 mmol) and (S)-4-(methylsulfonyl)but-3-en-2-amine (80 mg, 0.249 mmol) in DMF (2 mL) was added T4P (77 mg, 0.214 mmol in EtOAc, wt%: 50%) .The reaction was stirred at 20 °C for 2 h, then poured into water (10 mL)and extracted with EtOAc (30 mL, 2x). The combined organic layer was washed with brine (30 mL, 2x), dried over anhydrous Na2SO4, filtered, and t concentrated under vacuum. The residue was purified by preparative-HPLC ( column: Phenomenex luna C18150*25mm* 10 m; mobile phase: A: 0.225% FA in water, B: MeCN; B%: 13%-43%,10 min) and lyophilized to give an impure product (~ 20 mg) which was purified by preparative-TLC(petroleum ether ethyl acetate=0:1,Rf=0.5) and further purified by preparative-HPLC (column: Phenomenex luna C18150*25mm* 10 m;mobile phase: A: 0.225% TFA in water, B: MeCN; B%: 13%-43%,10min) to afford, after lyophilization, the product (S,Z)-5-(3,4-dimethylphenyl)-2-((4-(methylsulfonyl)but-3-en-2-yl)carbamoyl)pyridine 1-oxide (2.5 mg, 0.00674 mmol, 4.10 % yield) as a white solid. LCMS: RT 0.497 min (method 1); m / z 375.1 (M+H)+(ESI+); SFC: RT 1.652 min, 87.52% ee (method 9);1H NMR (MeOD, 400 MHz) : 11.47 (d, J = 6.4 Hz, 1H,), 8.66 (s, 1H), 8.33 (d, J = 8.4 Hz, 1H), 7.91 (d, J = 8.4 Hz, 1H), 7.52 (s, 1H), 7.46 (d, J =8.0 Hz, 1H), 7.30 (d, J = 8.0 Hz, 1H), 6.47 (d, J = 10.8 Hz, 1H), 6.42 (dd, J = 6.4, 10.8 Hz, 1H), 5.74 - 5.62 (m, 1H), 3.23 (s, 3H), 2.36 (s, 3H), 2.34 (s, 3H), 1.47 (d, J = 6.8 Hz, 3H) Preparation of Intermediate 28.1 2-(4,5-dimethylthiophen-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane To a solution of 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (292 mg, 1.57 mmol) and 5- bromo-2,3-dimethylthiophene (200 mg, 1.05 mmol) in THF (10 mL) was added n-BuLi (0.63 mL, 1.57 mmol, 2.5 M) at -70°C under N2. The mixture was stirred at -70°C for 1 h., thenpoured into NH4Cl (aq, sat., 5 ml) and extracted with EtOAc (5 ml; 3x). The combined organic layer was dried over anhydrous Na2SO4, filtered and concentrated to give the product 2-(4,5-dimethylthiophen-2-yl)-4,4,5,5-tetramethyl- 1,3,2-dioxaborolane (250 mg,1.05 mmol, crude) as a yellow oil which was directly used in the next step without further purification. 1H NMR (DMSO-d6, 400 MHz): 7.25 (s, 1H), 2.33 (s, 3H), 2.10 (s, 3H), 1.25 (s, 12H) Preparation of Intermediate 28.2 2-carboxy-5-(4,5-dimethylthiophen-2-yl)pyridine 1-oxide A mixture of 5-bromo-2-(methoxycarbonyl)pyridine 1-oxide (200 mg, 0.862 mmol), 2-(4,5- dimethylthiophen-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (246 mg, 1.03 mmol), K2CO3 (357 mg, 2.59 mmol) and Pd(PPh3)4 (100 mg, 0.0862 mmol) in 1,4-dioxane (2 mL) and water (0.2 mL) was stirred at 80°C under N2 atmosphere for 12 h. The resulting mixture was filtered and the filtrate was concentrated under vacuum. The residue was purified by reversed-phase flash chromatography (ISCO; 80 g Flash Column Welch Ultimate XB_C1820-40 m; 120 A, mobile phase: A: 0.1% HCl in water, B: MeCN, B%: 0%-40%, 80 mL / min) and lyophilized directly to give the product 2-carboxy-5-(4,5-dimethylthiophen-2- yl)pyridine 1-oxide (45 mg,0.0415 mmol, 4.82 % yield) as a yellow solid. LCMS: RT 0.510 min (method 1); m / z 250.0 (M+H)+(ESI+); 1H NMR (DMSO-d6, 400 MHz): 9.04 (s, 1H), 8.22 (d, J = 8.4 Hz, 1H), 8.01 (d, J = 8.4 Hz, 1H), 7.73 (s, 1H), 2.39 (s, 3H), 2.15 (s, 3H) Preparation of Example 28 (R)-5-(4,5-dimethylthiophen-2-yl)-2-((1,1-dioxido-2,3-dihydrothiophen-3- yl)carbamoyl)pyridine 1-oxide To a solution of 2-carboxy-5-(4,5-dimethylthiophen-2-yl)pyridine 1-oxide (30 mg, 0.120 mmol) and (R)-3-amino-2,3-dihydrothiophene 1,1-dioxide (26 mg, 0.120 mmol) in DMSO (1 mL) was added DIEA (0.064 mL, 0.361 mmol) and T4P (130 mg, 0.181 mmol in EtOAc, wt%: 50%). The mixture was stirred at 20°C for 1 h, then filtered and the filtrate was collected. The filtrate was 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 Na2SO4 and concentrated under reduced pressure. The residue was dissolved in 2mL MeCN, the solution was purified by preparative HPLC (column: Waters Xbridge 150*25 mm* 5 µm; mobile phase: A: 10 mM aqueous solution of NH4HCO3, B: MeCN; B%: 30%-60%, 25 mL / min, 9 min) and the resulting product solution was lyophilized directly to give the product (R)-5-(4,5-dimethylthiophen-2-yl)-2-((1,1- dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)pyridine 1-oxide (8.5 mg, 0.0225 mmol, 18.70 % yield) as a white solid. LCMS: RT 0.466 min (method 1); m / z 365.1 (M+H)+(ESI+). SFC: RT 1.761 min; 90.14% ee (method 9).1H NMR (DMSO-d6, 400 MHz): 11.49 (d, J = 7.6 Hz, 1H), 8.72 (s, 1H), 8.17 (d, J = 8.4 Hz, 1H), 7.72 (d, J = 8.4 Hz, 1H), 7.64 (s, 1H), 7.31 - 7.26 (m, 1H), 7.03 - 6.98 (m, 1H), 5.43 - 5.32 (m, 1H), 3.79 - 3.70 (m, 1H), 3.39 - 3.34 (m, 1H), 2.37 (s, 3H), 2.13 (s, 3H); Preparation of Intermediate 29.1 2-carboxy-5-(5-(trifluoromethyl)thiophen-2-yl)pyridine 1-oxide A mixture of 5-bromo-2-(methoxycarbonyl)pyridine 1-oxide (200 mg, 0.862 mmol), (5- (trifluoromethyl)thiophen-2-yl)boronic acid (186 mg, 0.948 mmol), K2CO3 (357 mg, 2.59 mmol) and Pd(PPh3)4 (100 mg, 0.0862 mmol) in 1,4-dioxane (2 mL) and water (0.2 mL) was stirred at 80°C under N2 atmosphere for 12 h. The resulting mixture was filtered and the filtrated was concentrated under vacuum. The residue was purified by reversed-phase flash chromatography (ISCO; 40 g Flash Column Welch Ultimate XB_C1820-40 m; 120 A, mobile phase: A: 0.1% HCl in water, B: MeCN; B%: 0%-20%, 80 mL / min) and lyophilized directly to give the product 2-carboxy-5-(5-(trifluoromethyl)thiophen-2-yl)pyridine 1-oxide (40 mg,0.135 mmol, 15.67 % yield) as an off-white solid. LCMS: RT 0.511 min (method 1); m / z 289.9 (M+H)+(ESI+); 1H NMR (DMSO-d6, 400 MHz): 8.54 (s, 1H), 7.81 - 7.71 (m, 2H), 7.51 (d, J = 8.0 Hz, 1H), 7.19 (d, J = 8.0 Hz, 1H) Preparation of Example 29 (R)-2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)-5-(5-(trifluoromethyl)thiophen-2- yl)pyridine 1-oxide At 0°C, to a solution of 2-carboxy-5-(5-(trifluoromethyl)thiophen-2-yl)pyridine 1-oxide (35 mg, 0.121 mmol) and (R)-3-amino-2,3-dihydrothiophene 1,1-dioxide hydrobromide (26 mg, 0.121 mmol) in DMF (0.2 mL) was added DIEA (0.065 mL, 0.363 mmol) and T4P (131 mg, 0.182 mmol in EtOAc, wt%: 50%).The mixture was stirred at 0°C for 1 h, then poured into water (5 mL) and extracted with ethyl acetate (5 mL; 2x). The combined organic layer was washed with brine (5 mL), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The residue was dissolved in 2mL MeCN, the solution was purified by preparative HPLC (column: Waters Xbridge 150*25 mm* 5 µm; mobile phase: A: 10 mM aqueous solution of NH4HCO3, B: MeCN; B%: 32%-62%, 25 mL / min, 9 min) and the resulting product solution was lyophilized directly to give the product (R)-2-((1,1-dioxido-2,3-dihydrothiophen-3- yl)carbamoyl)-5-(5-(trifluoromethyl)thiophen-2-yl)pyridine 1-oxide (4.2 mg, 0.0103 mmol, 8.48 % yield) as a white solid. LCMS: RT 0.557 min (method 2); m / z 405.1 (M+H)+(ESI+). SFC: RT 1.656 min; 92.37% ee.(method 10).1H NMR (DMSO-d6, 400 MHz): 11.41 (d, J = 7.6 Hz, 1H), 9.04 (s, 1H), 8.25 (d, J = 8.0 Hz, 1H), 7.98 (d, J = 2.0 Hz, 1H), 7.94 (d, J = 8.0 Hz, 1H), 7.90 - 7.84 (J = 2.0 Hz, 1H), 7.30 - 7.20 (m, 1H), 7.02 - 7.01 (m, 1H), 5.45 - 5.34 (m, 1H), 3.82 - 3.71 (m, 1H), 3.42 - 3.35 (m, 1H) Preparation of Intermediate 30.1 5-bromo-2-chloro-4-phenoxypyrimidine To a solution of 5-bromo-2,4-dichloropyrimidine (40.00 g, 176 mmol) and K2CO3 (60.65 g, 439 mmol) in DMF (400 mL) was added phenol (16.52 g, 176 mmol). The mixture was stirred at 100 °C for 12 h. The resulting reaction mixture was diluted with water (1 L) and then extracted with ethyl acetate (600 mL, 3x). The combined organic layer was washed with brine (1 L, 2x), separated, dried over anhydrous Na2SO4, filtered and concentrated under vacuum. The residue was purified by flash silica gel chromatography (ISCO; 330 g SepaFlash Silica Flash Column, Eluent of 0 to ~6% Ethyl acetate / Petroleum ether gradient @ 100 mL / min) and concentrated under vacuum to give the product 5-bromo-2-chloro-4- phenoxypyrimidine (35.00 g, 123 mmol, 69.83 % yield) as a white solid. RT 0.553 min (LCMS: method 7); m / z 286.9 (M+H+2)+(ESI+).1H NMR (DMSO-d6, 400 MHz): 8.90 (s, 1H), 7.53-7.47 (m, 2H), 7.37-7.33 (m, 1H), 7.32-7.28 (m, 2H) Preparation of Intermediate 30.2 5-bromo-2-iodo-4-phenoxypyrimidine To a solution of 5-bromo-2-chloro-4-phenoxypyrimidine (20.00 g, 70.0 mmol) in DCE (200 mL) at 0 °C was added HI (aq., 19 mL, 210 mmol, 11 mol / L) and NaI (23.10 g, 154 mmol). The mixture was heated to 80 °C, stirred for 12 h, cooled to room temperature, poured into NaHCO3 (aq., sat., 300 mL) and then, extracted with ethyl acetate (400 mL, 3x). The combined organic layer was washed with brine (500 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 to ~10% Ethyl acetate / Petroleum ether gradient @ 100mL / min) and concentrated under vacuum to give the product 5- bromo-2-iodo-4-phenoxypyrimidine (23.00 g, 61.0 mmol, 87.10 % yield) as a yellow solid. RT 0.566 min (LCMS: method 7); m / z 378.7 (M+H+2)+(ESI+);1H NMR (DMSO-d6, 400 MHz): 8.68 (s, 1H), 7.54-7.45 (m, 2H), 7.37-7.31 (m, 1H), 7.31-7.24 (m, 2H) Preparation of Intermediate 30.3 (5-bromo-4-phenoxypyrimidin-2-yl)(cyclopropyl)methanone To a solution of 5-bromo-2-iodo-4-phenoxypyrimidine (12.5 g, 33.2 mmol) in THF (130 mL) was added iPrMgCl in THF (17 mL, 33.2 mmol) at -10 °C under N2 atmosphere. The mixture was stirred at - 10 °C for 1 h. Then, N-methoxy-N-methylcyclopropanecarboxamide (4.71 g, 36.5 mmol) was added and the mixture was stirred at 20 °C for 12 h under N2atmosphere. The resulting reaction mixture was poured into NH4Cl (aq., sat., 100 mL) and extracted with ethyl acetate (50 ml, 3x). The combined organic layer was washed with brine (50 mL, 2x), dried over anhydrous Na2SO4 and concentrated under vacuum to give a residue, which was purified by flash silica gel chromatography (ISCO; 80 g SepaFlash Silica Flash Column, Eluent of 0 to ~7% Ethyl acetate / Petroleum ether gradient @ 60 mL / min) and concentrated under vacuum to give an impure product as a yellow solid which was further triturated in Petroleum ether (5 mL) at 25 °C for 30 min. The precipitate was filtered and dried under reduce pressure to give the product (5- bromo-4-phenoxypyrimidin-2-yl)(cyclopropyl)methanone (3.1 g, 9.71 mmol, 29.29 % yield) as a white solid. RT 0.553 min (LCMS: method 7; m / z 320.9 (M+H+2)+(ESI+);1H NMR (DMSO-d6, 400 MHz): 9.15 (s, 1H), 7.55-7.44 (m, 2H), 7.38-7.27 (m, 3H), 3.10-2.81 (m, 1H), 1.10-1.03 (m, 2H), 1.02-0.90 (m, 2H) Preparation of Intermediate 30.4 5-bromo-2-(cyclopropyldifluoromethyl)-4-phenoxypyrimidine A solution of (5-bromo-4-phenoxypyrimidin-2-yl)(cyclopropyl)methanone (3100 mg, 9.71 mmol) in DAST (32 mL, 9.71 mmol) was stirred at 30 °C for 48 h. The resulting mixture was cooled to room temperature, slowly poured into Na2SO3 (aq., sat., 50 mL) and extracted with ethyl acetate (50 ml, 3x). The combined organic layer was washed with brine (50 mL, 2x), dried over anhydrous Na2SO4 and concentrated under vacuum to give a residue, which was purified by flash silica gel chromatography (ISCO; 40 g SepaFlash Silica Flash Column, Eluent of 0 to ~5% Ethyl acetate / Petroleum ether gradient @ 60 mL / min) and concentrated under vacuum to give the product 5-bromo-2-(cyclopropyldifluoromethyl)- 4-phenoxypyrimidine (2600 mg, 7.62 mmol, 78.46 % yield) as a white solid. RT 0.613 min (LCMS: method 8); m / z 342.8 (M+H+2)+(ESI+);1H NMR (DMSO-d6, 400 MHz): 9.08 (s, 1H), 7.53-7.45 (m, 2H), 7.36-7.26 (m, 3H), 1.68-1.47 (m, 1H), 0.64-0.49 (m, 4H);19F NMR (DMSO-d6, 400 MHz): -102.75 (s, 2F) Preparation of Intermediate 30.5 Methyl 2-(cyclopropyldifluoromethyl)-4-phenoxypyrimidine-5-carboxylate To a solution of 5-bromo-2-(cyclopropyldifluoromethyl)-4-phenoxypyrimidine (200 mg, 0.586 mmol) in methanol (4 mL) were added Pd(dppf)Cl2 (48 mg, 0.0586 mmol) and TEA (0.16 mL, 1.17 mmol). Then, the mixture was degassed with argon ( 3x) and stirred under CO atmosphere (50 psi) at 80 °C for 12 h. The resulting reaction mixture was 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 to ~15% Ethyl acetate / Petroleum ether gradient @ 60 mL / min) and concentrated under vacuum to give the product methyl 2-(cyclopropyldifluoromethyl)-4-phenoxypyrimidine-5-carboxylate (140 mg, 0.437 mmol, 74.56 % yield) as a white solid. RT 0.571 min (method 8); m / z 321.0 (M +H)+(ESI+).1H NMR (DMSO-d6, 400 MHz): 9.22 (s, 1H), 7.51-7.45 (m, 2H), 7.34-7.30 (m, 1H), 7.27-7.25 (m, 2H), 3.92 (s, 3H), 1.65-1.53 (m, 1H), 0.61-0.52 (m, 4H).19F NMR (DMSO-d6, 400 MHz): -103.76 (s, 2F) Preparation of Intermediate 30.6 2-(cyclopropyldifluoromethyl)-4-phenoxypyrimidine-5-carboxylic acid To a solution of methyl 2-(cyclopropyldifluoromethyl)-4-phenoxypyrimidine-5-carboxylate (110 mg, 0.343 mmol) in water (2 mL) and THF (2 mL) was added LiOH·H2O ( 72 mg, 1.72 mmol) at 0 °C. The mixture was stirred at 0 °C for 1 h and concentrated under reduced pressure. The residue was diluted with water (2 mL), the pH was adjusted to 3-4 by adding HCl (aq., 1N) and aqueous layer was extracted with ethyl acetate (5 mL; 3x). The combined organic layer was washed with brine (3 mL), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to give the product 2- (cyclopropyldifluoromethyl)-4-phenoxypyrimidine-5-carboxylic acid (100 mg, 0.327 mmol, 95.07 % yield) as white solid. RT 0.503 min (method 8); m / z 307.0 (M+H)+(ESI+).1H NMR (DMSO-d6, 400 MHz): 9.16 (s, 1H), 7.49-7.45 (m, 2H), 7.33-7.31 (m, 1H), 7.26-7.24 (m, 2H), 1.64-1.53 (m, 1H), 0.61-0.51 (m, 4H).19F NMR (DMSO-d6, 400 MHz): -103.67(s, 2F) Preparation of Intermediate 30.7 Tert-butyl (S,E)-(1-cyclopropyl-3-fluoro-3-(methylsulfonyl)allyl)carbamate and preparation of To a solution of tert-butyl (S)-(1-cyclopropyl-2-oxoethyl)carbamate (40 mg, 0.201 mmol) in THF (1 mL) were added diethyl (fluoro(methylsulfonyl)methyl)phosphonate (50 mg, 0.201 mmol) and K2CO3 (69 mg, 0.502 mmol). The reaction mixture was stirred at 80 °C for 3 h, then cooled to room temperature and filtered. The filtrate was purified by preparative-TLC (petroleum ether / ethyl acetate : 3 / 1) to give the product tert-butyl (S,Z)-(1-cyclopropyl-3-fluoro-3-(methylsulfonyl)allyl)carbamate (15 mg, 0.0511 mmol, 25.47 % yield) as a light yellow oil and the product tert-butyl (S,E)-(1-cyclopropyl-3-fluoro-3- (methylsulfonyl)allyl)carbamate (10 mg, 0.0341 mmol, 16.98 % yield) as a light yellow oil. Intermediate 30.7: RT 0.494 min (LCMS: method 7; m / z 316.0 (M+Na)+(ESI+);1H NMR (CDCl3, 400 MHz): 6.08 (dd, J = 8.8, 32.8 Hz, 1H), 4.91-4.70 (m, 1H), 3.99-3.76 (m, 1H), 3.05 (s, 3H), 1.45 (s, 9H), 1.05-0.94 (m, 1H), 0.66-0.55 (m, 2H), 0.47-0.33 (m, 2H).19F NMR (CDCl3, 400 MHz): -126.43 (s, 1F) Intermediate 30.8:1H NMR (CDCl3, 400 MHz): 8.81 (dd, J = 10.4, 21.2 Hz, 1H), 4.95-4.65 (m, 1H), 4.43-4.28 (m, 1H), 3.23 (s, 3H), 1.43 (s, 9H), 0.99 - 0.88 (m, 1H), 0.58 - 0.42 (m, 4H).19F NMR (CDCl3, 400 MHz): -116.26 (s, 1F) Preparation of Intermediate 30.9 (S,E)-1-cyclopropyl-3-fluoro-3-(methylsulfonyl)prop-2-en-1-amine A solution of tert-butyl (S,E)-(1-cyclopropyl-3-fluoro-3-(methylsulfonyl)allyl)carbamate (12 mg, 0.0409 mmol) in HCl in ethyl acetate (0.5 mL, 2M) was stirred at 25 °C for 1 h. The resulting mixture was concentrated under reduced pressure to give crude product (S,E)-1-cyclopropyl-3-fluoro-3- (methylsulfonyl)prop-2-en-1-amine hydrochloride (12 mg, HCl salt, crude) as a yellow solid. The crude was used directly in the next step. Preparation of Example 30 (E)-N-(1-cyclopropyl-3-fluoro-3-(methylsulfonyl)allyl)-2-(cyclopropyldifluoromethyl)-4- phenoxypyrimidine-5-carboxamide To a solution of 2-(cyclopropyldifluoromethyl)-4-phenoxypyrimidine-5-carboxylic acid (5.0 mg, 0.0163 mmol), DIEA (17 uL, 0.0980 mmol) and (S,E)-1-cyclopropyl-3-fluoro-3-(methylsulfonyl)prop-2-en- 1-amine hydrochloride (5.2 mg, 0.0180 mmol, HCl salt) in DMF (1 mL) was added T4P in ethyl acetate (15 mg, 0.0212 mmol, purity: 50%). The mixture was stirred at 0 °C for 2 h and then filtered. The filtrate was purified by preparative HPLC (column: Waters xbridge 150*25mm 10 m; mobile phase: A: 10 mmol / L NH4HCO3 in water, B: MeCN; B%: 43%-73%, 10 min, @ 28 mL / min) and lyophilized directly to give the product (E)-N-(1-cyclopropyl-3-fluoro-3-(methylsulfonyl)allyl)-2-(cyclopropyldifluoromethyl)-4- phenoxypyrimidine-5-carboxamide (3.4 mg, 0.00700 mmol, 42.87 % yield) as a white solid. It is noted that in the process of preparation of Example 30, racemization of the stereogenic centre took place. It has been noted only at the final stage of the synthesis. However, it cannot be excluded that it took place already at an earlier stage, such as preparation of Intermediate 30.7. Thus, it cannot be excluded that intermediates 30.7, 30.8 and 30.9 are in fact not chiral. RT 0.687 min (LCMS: method 2; m / z 482.2 (M+H)+(ESI+); RT 1.032 min (SFC: Method 6 showed 2 peaks, 15.83 ee%) ;1H NMR (CDCl3, 400 MHz): 9.48 (s, 1H), 7.89 (d, J = 6.8 Hz, 1H), 7.55-7.46 (m, 2H), 7.41-7.34 (m, 1H), 7.25-7.19 (m, 2H), 6.22 (dd, J= 8.8, 32.4 Hz, 1H), 4.49-4.37 (m, 1H), 3.08 (s, 3H), 1.55-1.47 (m, 1H), 1.24-1.13 (m, 1H), 0.75-0.65 (m, 4H), 0.58-0.45 (m, 4H) Preparation of Intermediate 31.1 (S,Z)-1-cyclopropyl-3-fluoro-3-(methylsulfonyl)prop-2-en-1-amine A solution of tert-butyl (S,Z)-(1-cyclopropyl-3-fluoro-3-(methylsulfonyl)allyl)carbamate (15 mg, 0.0511 mmol) in HCl in ethyl acetate (0.50 mL, 2 M) was stirred at 25 °C for 2 h. The mixture was concentrated to give crude product (S,Z)-1-cyclopropyl-3-fluoro-3-(methylsulfonyl)prop-2-en-1-amine (13 mg, HCl salt, crude) as a yellow solid. The crude was used directly in the next step. Preparation of Example 31 (Z)-N-(1-cyclopropyl-3-fluoro-3-(methylsulfonyl)allyl)-2-(cyclopropyldifluoromethyl)-4- phenoxypyrimidine-5-carboxamide To a solution of (S,Z)-1-cyclopropyl-3-fluoro-3-(methylsulfonyl)prop-2-en-1-amine hydrochloride (8.2 mg, 0.0359 mmol, HCl salt) in DMF (0.5 mL) was added 2-(cyclopropyldifluoromethyl)-4- phenoxypyrimidine-5-carboxylic acid (10 mg, 0.0327 mmol), DIEA (0.035 mL, 0.196 mmol) and then T4P in ethyl acetate ( 32 mg, 0.0424 mmol) at 0 °C. The mixture was stirred at 0 °C for 1 h and, then filtered. The filtrate was collected and purified by preparative HPLC (column: Waters xbridge 150*25 mm 10 m; mobile phase: A: 10 mmol / L NH4HCO3 in water, B: MeCN; B%: 45%-75%, 10 min, @ 28 mL / min) and lyophilized directly to give an impure solid which was further purified by preparative TLC (Ethyl acetate / Petroleum ether =3 / 1) three times. After removal of the purification organic solvent, the residue was dissolved in MeCN (2mL) and water (80 mL) and the resulting solution was lyophilized to give (Z)-N- (1-cyclopropyl-3-fluoro-3-(methylsulfonyl)allyl)-2-(cyclopropyldifluoromethyl)-4-phenoxypyrimidine-5- carboxamide (2.12 mg, 0.00440 mmol, 13.49 % yield) as a white solid. It is noted that in the process of preparation of Example 31, racemization of the stereogenic centre took place. It has been noted only at the final stage of the synthesis. However, it cannot be excluded that it took place already at an earlier stage (see above). RT 0.704 min (LCMS: method 2; m / z 482.2 (M+H)+(ESI+); RT 1.775 min (SFC: Method 11 showed 2 peaks, 1.79 ee%) ;1H NMR (CDCl3, 400 MHz): 9.44 (s, 1H), 7.88 (d, J = 5.6 Hz, 1H), 7.57- 7.47 (m, 2H), 7.42-7.34 (m, 1H), 7.26-7.22 (m, 2H), 5.95 (dd, J = 10.4, 20.4 Hz, 1H), 4.88-4.72 (m, 1H), 3.32 (s, 3H), 1.55-1.45 (m, 1H), 1.19-1.08 (m, 1H), 0.73-0.68 (m, 2H), 0.68-0.60 (m, 3H), 0.58-0.48 (m, 3H) Preparation of Intermediate 32.1 Diethyl ((methylsulfinyl)methyl)phosphonate To a solution of diethyl ((methylthio)methyl)phosphonate (2000 mg, 10.1 mmol) in MeCN (20 mL) was added dropwise a solution of NaIO4 (4337 mg, 20.2 mmol) in Water (16 mL) at 0 °C. The reaction mixture was stirred at 0 °C for 3 h, then diluted with water(20 mL) and extracted with ethyl acetate (30 mL;3x). The combined organic layer was washed with aq. Solution of Na2SO3 (sat., 30 mL), dried over Na2SO4, filtered and concentrated. The residue was purified by column chromatography (ISCO; 12 g SepaFlash Silica Flash Column, Eluent DCM / MeOH gradient from 100 / 0 to ~90 / ~10 @ 60 mL / min) to give the product diethyl ((methylsulfinyl)methyl)phosphonate (870 mg, 4.06 mmol, 40.25 % yield) as colorless oil. MS: (method 1); m / z 215.1 (M+H)+(ESI+).1H NMR (CDCl3, 400 MHz): 4.26-4.14 (m, 4H), 3.42-3.19 (m, 2H), 2.86 (s, 3H), 1.37 (t, J = 7.2 Hz, 6H) Preparation of Intermediate 32.2 Tert-butyl (((diethoxyphosphoryl)methyl)(methyl)(oxo)- 6-sulfaneylidene)carbamate To a solution of diethyl ((methylsulfinyl)methyl)phosphonate (840 mg, 3.92 mmol) in DCM (15 mL) was added tert-butyl carbamate (919 mg, 7.84 mmol), rhodium(II) acetate dimer powder (52 mg, 0.118 mmol) and MgO (627 mg, 15.7 mmol). The mixture was stirred at 20 °C under N2 for 20 min and PhI(OAc)2 (1895 mg, 5.88 mmol) was added. The mixture was stirred at 50 °C for 3 h under N2, then cooled to room temperature and filtered. The filtrate was purified by column chromatography (ISCO; 12 g SepaFlash Silica Flash Column, Eluent Petroleum ether / Ethyl acetate gradient from 60 / 40 to 0 / 100 @ 40 mL / min) to give the product tert-butyl (((diethoxyphosphoryl)methyl)(methyl)(oxo)- 6-sulfaneylidene)carbamate (1000 mg, 3.04 mmol, 77.43 % yield) as yellow oil. MS: (method 1); m / z 230.2(M+H-Boc)+(ESI+);1H NMR (CDCl3, 400 MHz): 4.36 (t, J = 15.6 Hz, 1H), 4.31-4.19 (m, 4H), 3.95 (t, J = 15.6 Hz, 1H), 3.41 (s, 3H), 1.50 (s, 9H), 1.38 (t, J = 7.2 Hz, 6H) Preparation of Intermediate 32.3 Tert- To a solution of tert-butyl (((diethoxyphosphoryl)methyl)(methyl)(oxo)- 6-sulfaneylidene)carbamate (400 mg, 1.21 mmol) in THF (8 mL) was added tert-butyl (S)-(1-cyclopropyl-2-oxoethyl)carbamate (290 mg, 1.46 mmol) and K2CO3 (420 mg, 3.04 mmol). The reaction mixture was stirred at 80 °C for 1 h, then cooled to room temperature, diluted with water (20 mL) and extracted with ethyl acetate (30 mL;3x). The combined organic layer was washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified by column chromatography (ISCO; 12 g SepaFlash Silica Flash Column, Eluent Petroleum ether / Ethylacetate / gradient from 90 / 10 to 70 / 30 @ 100 mL / min) to give the product Tert-butyl (E)-(3-(N- (tert-butoxycarbonyl)-S-methylsulfonimidoyl)-1-cyclopropylallyl)carbamate (130 mg, 0.347 mmol, 28.58 % yield) as yellow oil. It is noted that the starting material has likely racemized in the course of the reaction, as the product appears to be a mixture of four stereoisomers (as indi...

Claims

New PCT international application based on US 63 / 587,354 and US 63 / 665,751 FoRx Therapeutics AG Vossius Ref.: AE3393 PCT BS Claims 1. A compound of formulaor a pharmaceutically acceptable salt thereof, wherein: A is selected from aryl, heteroaryl, heterocycloalkyl, heterocycloalkenyl, cycloalkyl, cycloalkenyl, C2 alkynyl, -N(C1-5 alkyl)(C1-5 alkyl) (such as -N(CH3)(CH(CH3)2)), C2-haloalkyl (such as -CF2CH3) and –(C1-2 haloalkylene)-cycloalkyl (such as -CF2-cyclopropyl), 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, C1-6 haloalkyl, aryl (such as phenyl) or heteroaryl (such as thien-2-yl), preferably with C1-6 alkyl, C1-6 haloalkyl, or aryl (such as phenyl), more preferably with C1-6 alkyl or C1-6 haloalkyl, such as C1-6 alkyl; B is selected from arylene and heteroarylene, wherein said arylene and said hereroarylene are each optionally substituted with one or more R2; X is selected from -CONH-, -CON(C1-6 alkyl)-, -CON(C1-6 haloalkyl)-, -SO2NH-, -SO2N(C1-6 alkyl)- , -SO2N(C1-6 haloalkyl)-, -CH(CF3)NH-, -CH(CF3)N(C1-6 alkyl)-, -CH(CF3)N(C1-6 haloalkyl)-, C2 alkenylene optionally substituted with one or more halogen, C1-6 alkyl or C1-6 haloalkyl, cycloalkylene optionally substituted with one or more C1-6 alkyl, -(heterocycloalkylene)-NH-, - (heterocycloalkylene)-N(C1-6 alkyl)-, heterocycloalkylene, heterocycloalkenylene and heteroarylene;alkenyl), -CO(C2 alkenyl), -CH2(C2 alkenyl), and -(C1-2 alkylene)CN, wherein m is 1 or 2, whereinsaid -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, C1-4 haloalkyl, -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(=NH)-(C1-4 alkyl), -SO(=N-(C1-4 alkyl))-(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(=NH)-cycloalkyl, -SO(=N-(C1-4 alkyl))-cycloalkyl, heterocycloalkyl, -SO2- heterocycloalkyl, -SO(=NH)-heterocycloalkyl, -SO(=N-(C1-4 alkyl))-heterocycloalkyl, aryl, -SO2- aryl, -SO(=NH)-aryl, -SO(=N-(C1-4 alkyl))-aryl, heteroaryl, -SO2-heteroaryl, -SO(=NH)-heteroaryl, -SO(=N-(C1-4 alkyl))-heteroaryl,-Hal, -CN and -CF3, and wherein said, , ,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, -(C0-3 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), -(C0-3alkylene)-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, -NH-(C0-3 alkylene)-carbocyclyl, -NH-(C0-3 alkylene)-heterocyclyl, -N(C1-5 alkyl)-(C0-3 alkylene)-carbocyclyl, -N(C1-5 alkyl)-(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 -NH-(C0-3 alkylene)-carbocyclyl, the carbocyclyl moiety in said -N(C1-5 alkyl)-(C0-3 alkylene)-carbocyclyl, the carbocyclyl moiety in said -(C0-3 alkylene)-carbocyclyl, the heterocyclyl moiety in said -O-(C0-3 alkylene)-heterocyclyl, the heterocyclyl moiety in said -NH-(C0-3 alkylene)-heterocyclyl, the heterocyclyl moiety in said - N(C1-5 alkyl)-(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); 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(C1-5alkyl), -(C0-3alkylene)-N(C1-5alkyl)(C1-5alkyl), -(C0-3alkylene)-NH-OH, -(C0-3alkylene)-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), -(C0-3alkylene)-SO2-NH2, -(C0-3alkylene)-SO2-NH(C1-5alkyl), -(C0-3alkylene)-SO2-N(C1-5alkyl)(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 thecarbocyclyl 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); or wherein A and Y are as defined hereinabove and B and X are combined to form a two-ring system according to formula:wherein C is aryl or heteroaryl ring, optionally substituted with one or more R2, Z is selected from C1-2 alkylene, -CH=CH-, -N=CH-, -N=C(C1-6 alkyl)-, -CH=N-, -C(C1-6 alkyl)=N-, -CO-, -SO-, -SO2- , -CONH-, -NHCO-, -CON(C1-6 alkyl)-, -N(C1-6 alkyl)CO-, -NH-, -N(C1-6 alkyl)- and -O-; or wherein A and B are as defined hereinabove, and X and Y form a two ring spiro system according to formula:wherein D is a nitrogen-containing heterocycloalkyl or heterocycloalkenyl, m is 1 or 2, and theoptionally substituted by one or more C1-6 alkyl or Hal.

2. The compound of claim 1, wherein the compound is a compound of formula(I)or a pharmaceutically acceptable salt thereof, wherein: 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; B is selected from arylene and heteroarylene, wherein said arylene and said hereroarylene are each optionally substituted with one or more R2; X is selected from -CONH-, -CON(C1-6 alkyl)-, -CON(C1-6 haloalkyl)-, -SO2NH-, -SO2N(C1-6 alkyl)- , -SO2N(C1-6 haloalkyl)-, -CH(CF3)NH-, -CH(CF3)N(C1-6 alkyl)-, -CH(CF3)N(C1-6 haloalkyl)-, C2 alkenylene optionally substituted with one or more C1-6 alkyl or C1-6 haloalkyl, cycloalkylene optionally substituted with one or more C1-6 alkyl, -(heterocycloalkylene)-NH-, and - (heterocycloalkylene)-N(C1-6 alkyl)-;CO(C2 alkenyl), -CH2(C2 alkenyl), and -(C1-2 alkylene)CN, wherein m is 1 or 2 and wherein said alkenyl is optionally 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, -are each optionally substituted by one or more C1-6 alkyl (such as methyl) or Hal (such as F);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-(C0-3alkylene)-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 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(C1-5alkylene)-SH, -(C0-3alkylene)-S(C1-5alkylene)-S(C1-5alkyl), -(C0-3alkylene)-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, -(C0-3alkylene)-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-(C1-5 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); or wherein A and Y are as defined hereinabove and B and X are combined to form a two-ring system according to formula:wherein C is aryl or heteroaryl ring, optionally substituted with one or more R2, Z is selected from C1-2 alkylene, -CH=CH-, -N=CH-, -N=C(C1-6 alkyl)-, -CH=N-, -C(C1-6 alkyl)=N-, -CO-, -SO-, -SO2- , -CONH-, -NHCO-, -CON(C1-6 alkyl)-, -N(C1-6 alkyl)CO-, -NH-, -N(C1-6 alkyl)- and -O-; or wherein A and B are as defined hereinabove, and X and Y form a two ring spiro system according to formula:wherein D is a nitrogen-containing heterocycloalkyl or heterocycloalkenyl, m is 1 or 2, and theoptionally substituted by one or more C1-6 alkyl or Hal.

3. The compound of claim 1 or 2, wherein 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; B is selected from arylene and heteroarylene, wherein said arylene and said hereroarylene are each optionally substituted with one or more R2; X is selected from -CONH-, -CON(C1-6alkyl)-, -CON(C1-6haloalkyl)-, -SO2NH-, -SO2N(C1-6alkyl)- , -SO2N(C1-6 haloalkyl)-, -CH(CF3)NH-, -CH(CF3)N(C1-6 alkyl)-, -CH(CF3)N(C1-6 haloalkyl)-, C2 alkenylene optionally substituted with one or more C1-6 alkyl or C1-6 haloalkyl, cycloalkylene optionally substituted with one or more C1-6 alkyl, -(heterocycloalkylene)-NH-, and - (heterocycloalkylene)-N(C1-6 alkyl)-; ,- CO(C2 alkenyl), -CH2(C2 alkenyl), and -(C1-2 alkylene)CN, wherein m is 1 or 2 and wherein said alkenyl is optionally 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, and wherein said, said, said, , , and saidare 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(C1-5alkylene)-O(C1-5alkyl), -(C0-3alkylene)-SH, -(C0-3alkylene)-S(C1-5alkyl), -(C0-3alkylene)-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); and 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, -(C0-3alkylene)-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 C1-4alkyl, halogen, -CN, -NO2, -OH, -O-(C1-4alkyl), -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).

4. The compound of any one of claims 1 to 3, wherein the following provisions apply to formula (I): (e1) A is not selected from aryl, heteroaryl, cycloalkyl and cycloakenyl, wherein said aryl, said heteroaryl, said cycloalkyl and said cycloalkenyl are each optionally substituted with one or more R1; and / or (e2) B is not according to formulawherein the left side of the depicted bivalent moiety is connected to A and the rights side of the depicted bivalentmoiety is connected to X, wherein RD1is selected from hydrogen and C1-6 alkyl, and wherein the ring is optionally substituted with one or more groups selected from halogen, C1-6 alkyl, C1-6 haloalkyl, -OH, -O-(C1-6 alkyl), -NH-(C1-6 alkyl), -N(C1-6 alkyl)-(C1-6 alkyl) and -CN; and / or (e3) X is not -CONH- wherein the C atom in said -CONH- moiety is connected to B, and the N atom in said -CONH- moiety is connected to Y; and / or (e4) Y is not, wherein m is 1 or 2, and wherein saidis optionally substituted by one or more C1-6 alkyl (such as methyl) or Hal (such as F).

5. The compound of any one of claims 1 to 4, wherein A is selected from heterocycloalkyl, heterocycloalkenyl and C2 alkynyl, wherein said heterocycloalkyl and said heterocycloalkenyl are each optionally substituted with one or more R1, and wherein said C2 alkynyl is optionally substituted with C1-6alkyl.

6. The compound of claim 5, wherein A are selected from:,.

7. The compound of any one of claims 1 to 6, wherein B is arylene, optionally substituted with one or more R2.

8. The compound of claim 7, wherein, optionally substituted with one or more R2.

9. The compound of any one of claims 1 to 8, wherein X is -CONH-.

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

11. The compound of any one of claims 1 to 10, wherein, wherein m is 1 or 2, wherein saidoptionally substituted by one or more C1-6 alkyl or Hal.

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

13. The compound of claim 1, selected from 6-(3,4-dimethylphenyl)-N-(1-imino-1-oxido-2,3-dihydro-1H-1l6-thiophen-3-yl)-2-oxo-1,2- dihydropyridine-3-carboxamide; 6-(3,4-dimethylphenyl)-N-((1S or R,3 S)-1-imino-1-oxido-2,3-dihydro-1H-1l6-thiophen-3-yl)-2- oxo-1,2-dihydropyridine-3-carboxamide6-(3,4-dimethylphenyl)-N-((1R or S,3 S)-1-imino-1-oxido-2,3-dihydro-1H-1l6-thiophen-3-yl)-2- oxo-1,2-dihydropyridine-3-carboxamide; 6-(3,4-dimethylphenyl)-N-((1S or R,3 R)-1-imino-1-oxido-2,3-dihydro-1H-1l6-thiophen-3-yl)-2- oxo-1,2-dihydropyridine-3-carboxamide; 6-(3,4-dimethylphenyl)-N-((1R or S,3 R)-1-imino-1-oxido-2,3-dihydro-1H-1l6-thiophen-3-yl)-2- oxo-1,2-dihydropyridine-3-carboxamide; 6-(3,4-dimethylphenyl)-N-(1-oxido-2,3-dihydrothiophen-3-yl)-2-oxo-1,2-dihydropyridine-3- carboxamide; 5-(3,4-dimethylphenyl)-2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)pyridine 1-oxide; 6-(3,4-dimethylphenyl)-N-(1-(methylimino)-1-oxido-2,3-dihydro-1H-1l6-thiophen-3-yl)-2-oxo-1,2- dihydropyridine-3-carboxamide; 5-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)picolinamide; (R)-5-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)picolinamide; (S)-5-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)picolinamide; N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-2-oxo-6-(piperidin-1-yl)-1,2-dihydropyridine-3- carboxamide; 6-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-2-oxo-1,2-dihydropyridine-3- sulfonamide; N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-2-oxo-6-(prop-1-yn-1-yl)-1,2-dihydropyridine-3- carboxamide; and 6-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-2-thioxo-1,2-dihydropyridine-3- carboxamide, or its pharmaceutically acceptable salt.

14. The compound of claim 1, selected from: 6-(3,4-dimethylphenyl)-N-(1-imino-1-oxido-2,3-dihydro-1H-1 6-thiophen-3-yl)-2-oxo-1,2- dihydropyridine-3-carboxamide; 6-(3,4-dimethylphenyl)-N-((1S or R,3S or R)-1-imino-1-oxido-2,3-dihydro-1H-16-thiophen-3-yl)- 2-oxo-1,2-dihydropyridine-3-carboxamide; 6-(3,4-dimethylphenyl)-N-((1R or S,3S or R)-1-imino-1-oxido-2,3-dihydro-1H-1 6-thiophen-3-yl)- 2-oxo-1,2-dihydropyridine-3-carboxamide; 6-(3,4-dimethylphenyl)-N-((1S or R,3R or S)-1-imino-1-oxido-2,3-dihydro-1H-16-thiophen-3-yl)- 2-oxo-1,2-dihydropyridine-3-carboxamide; 6-(3,4-dimethylphenyl)-N-((1R or S,3R or S)-1-imino-1-oxido-2,3-dihydro-1H-16-thiophen-3-yl)-2-oxo-1,2-dihydropyridine-3-carboxamide; 6-(3,4-dimethylphenyl)-N-(1-oxido-2,3-dihydrothiophen-3-yl)-2-oxo-1,2-dihydropyridine-3- carboxamide; 5-(3,4-dimethylphenyl)-2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)pyridine 1-oxide; 6-(3,4-dimethylphenyl)-N-(1-(methylimino)-1-oxido-2,3-dihydro-1H-16-thiophen-3-yl)-2-oxo-1,2- dihydropyridine-3-carboxamide; 5-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)picolinamide; (R or S)-5-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)picolinamide; (S or R)-5-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)picolinamide; N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-2-oxo-6-(piperidin-1-yl)-1,2-dihydropyridine-3- carboxamide; 6-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-2-oxo-1,2-dihydropyridine-3- sulfonamide; N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-2-oxo-6-(prop-1-yn-1-yl)-1,2-dihydropyridine-3- carboxamide; 6-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-2-thioxo-1,2-dihydropyridine-3- carboxamide; N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-3-fluoro-3',4'-dimethyl-[1,1'-biphenyl]-4-carboxamide; 3-amino-5-(3,4-dimethylphenyl)-2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)pyridine 1- oxide; (R)-3-amino-5-(3,4-dimethylphenyl)-2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)pyridine 1-oxide; 2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)-5-(4-(trifluoromethyl)phenyl)pyridine 1- oxide; 4-amino-5-(3,4-dimethylphenyl)-2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)pyridine 1- oxide; (R)-5-(2-(benzyloxy)phenyl)-2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)pyridine 1-oxide (R)-2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)-5-(5-methylthiophen-3-yl)pyridine 1- oxide; 2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)-5-(spiro[3.3]hept-1-en-2-yl)pyridine 1-oxide; 5-(2-chlorothiophen-3-yl)-2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)pyridine 1-oxide; 3-(4-(6-(3,4-dimethylphenyl)-2-methoxypyridin-3-yl)-1H-1,2,3-triazol-1-yl)-2,3-dihydrothiophene 1,1-dioxide; 3-(4-(6-(3,4-dimethylphenyl)-2-hydroxypyridin-3-yl)-1H-1,2,3-triazol-1-yl)-2,3-dihydrothiophene1,1-dioxide; (R)-3-(4-(6-(3,4-dimethylphenyl)-2-methoxypyridin-3-yl)-1H-1,2,3-triazol-1-yl)-2,3- dihydrothiophene 1,1-dioxide; (S)-3-(4-(6-(3,4-dimethylphenyl)-2-methoxypyridin-3-yl)-1H-1,2,3-triazol-1-yl)-2,3- dihydrothiophene 1,1-dioxide; (R)-3-(4-(6-(3,4-dimethylphenyl)-2-hydroxypyridin-3-yl)-1H-1,2,3-triazol-1-yl)-2,3- dihydrothiophene 1,1-dioxide hydrochloride; (S)-3-(4-(6-(3,4-dimethylphenyl)-2-hydroxypyridin-3-yl)-1H-1,2,3-triazol-1-yl)-2,3- dihydrothiophene 1,1-dioxide hydrochloride; (S,Z)-5-(3,4-dimethylphenyl)-2-((4-(methylsulfonyl)but-3-en-2-yl)carbamoyl)pyridine 1-oxide; (R)-5-(4,5-dimethylthiophen-2-yl)-2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)pyridine 1- oxide; (R)-2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)-5-(5-(trifluoromethyl)thiophen-2- yl)pyridine 1-oxide; (E)-N-(1-cyclopropyl-3-fluoro-3-(methylsulfonyl)allyl)-2-(cyclopropyldifluoromethyl)-4- phenoxypyrimidine-5-carboxamide ; (Z)-N-(1-cyclopropyl-3-fluoro-3-(methylsulfonyl)allyl)-2-(cyclopropyldifluoromethyl)-4- phenoxypyrimidine-5-carboxamide; (E)-N-(1-cyclopropyl-3-(S-methylsulfonimidoyl)allyl)-2-(1,1-difluoroethyl)-4-phenoxypyrimidine-5- carboxamide; (E)-N-(1-cyclopropyl-3-(N,S-dimethylsulfonimidoyl)allyl)-2-(1,1-difluoroethyl)-4- phenoxypyrimidine-5-carboxamide; N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-6-ethynyl-2-oxo-1,2-dihydropyridine-3-carboxamide; N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-2-oxo-6-(pyrrolidin-1-yl)-1,2-dihydropyridine-3- carboxamide; N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-6-(3-methylbut-1-yn-1-yl)-2-oxo-1,2-dihydropyridine-3- carboxamide; N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-6-(3-methylbut-1-yn-1-yl)-2-oxo-1,2-dihydropyridine-3- carboxamide; (R)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-5-(spiro[3.3]heptan-2-yl)picolinamide; 5-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-1H-1,2,4-triazole-3- carboxamide; (R)-5-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-4H-1,2,4-triazole-3- carboxamide;(R)-2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)-5-(5-methylthiophen-2-yl)pyridine 1- oxide; (R)-5-(cyclohex-1-en-1-yl)-2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)pyridine 1-oxide; (R)-5-cyclohexyl-2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)pyridine 1-oxide; N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-2-oxo-6-(tetrahydro-2H-pyran-3-yl)-1,2- dihydropyridine-3-carboxamide; 6-(3,4-dihydro-2H-pyran-6-yl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-2-oxo-1,2- dihydropyridine-3-carboxamide; N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-2-oxo-6-(tetrahydro-2H-pyran-2-yl)-1,2- dihydropyridine-3-carboxamide; 6-(3,6-dihydro-2H-pyran-4-yl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-2-oxo-1,2- dihydropyridine-3-carboxamide; (R)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-2-oxo-6-(tetrahydro-2H-pyran-4-yl)-1,2- dihydropyridine-3-carboxamide; 6-(5,6-dihydro-2H-pyran-3-yl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-2-oxo-1,2- dihydropyridine-3-carboxamide; (R)-5-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)thiazole-2-carboxamide; (R)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-2-oxo-6-phenyl-2H-pyran-3-carboxamide; 2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)-5-(piperidin-1-yl)pyridine 1-oxide; (R)-5-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-1,3,4-thiadiazole-2- carboxamide; (R)-5-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-1H-imidazole-2- carboxamide; (S)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-1-methyl-2-(p-tolyl)-1H-imidazole-4-carboxamide; (R)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-1-methyl-2-(p-tolyl)-1H-imidazole-4-carboxamide; 2-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-1H-imidazole-4-carboxamide; (R)-5-(4-chlorophenyl)-2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)pyridine 1-oxide; (R)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-2-methoxy-6-(tetrahydro-2H-pyran-4- yl)nicotinamide; 6-(3,4-dimethylphenyl)-N-((3R)-1-oxido-2,3-dihydrothiophen-3-yl)-2-oxo-1,2-dihydropyridine-3- carboxamide; 6-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)nicotinamide; N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-3',4'-dimethyl-[1,1'-biphenyl]-4-carboxamide; (R)-5-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-3-fluorothiophene-2-carboxamide; 2-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)pyrimidine-5-carboxamide; 5-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)pyrimidine-2-carboxamide; 6-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)pyridazine-3-carboxamide; 2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)-5-(spiro[3.3]heptan-2-yl)pyridine 1-oxide; 6-(3,4-dimethylphenyl)-3-(6,6-dioxido-6-thia-2-azaspiro[3.4]oct-7-en-2-yl)pyridin-2(1H)-one; 3-((6-(3,4-dimethylphenyl)-1H-indazol-3-yl)oxy)-2,3-dihydrothiophene 1,1-dioxide; 6-(3,4-dimethylphenyl)-1-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-1,2-dihydro-3H-indazol-3-one; 5-(3,4-dimethylphenyl)-2-(1,1-dioxido-2,3-dihydrothiophen-3-yl)isoindolin-1-one; (R)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-2-oxo-6-(phenylethynyl)-1,2-dihydropyridine-3- carboxamide; 5-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-4-hydroxypicolinamide; 5-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-3-hydroxypicolinamide; 6-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-4-oxo-1,4-dihydropyridine-3- carboxamide; (R)-5-(2,4-dimethylphenyl)-2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)pyridine 1-oxide; (R)-5-(3,4-dichlorophenyl)-2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)pyridine 1-oxide; (R)-5-(3,4-difluorophenyl)-2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)pyridine 1-oxide; (R)-2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)-5-(4-methoxyphenyl)pyridine 1-oxide; 5-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-3-fluoropicolinamide; 5-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-6-fluoropicolinamide; 6-(3,4-dimethylphenyl)-N-(1-methyl-1-oxido-2,3-dihydrophosphol-3-yl)-2-oxo-1,2- dihydropyridine-3-carboxamide; 3-amino-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-3',4'-dimethyl-[1,1'-biphenyl]-4-carboxamide; 5-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-4-methylpicolinamide; 5-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-6-methylpicolinamide; 5-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-3-methylpicolinamide; 2-amino-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-3',4'-dimethyl-[1,1'-biphenyl]-4-carboxamide; (S)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-2-(4-(trifluoromethyl)phenyl)thiazole-4- carboxamide; (R)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-2-(4-(trifluoromethyl)phenyl)thiazole-4- carboxamide; N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-3-hydroxy-3',4'-dimethyl-[1,1'-biphenyl]-4-carboxamide; 3-chloro-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-3',4'-dimethyl-[1,1'-biphenyl]-4-carboxamide;N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-2-fluoro-3',4'-dimethyl-[1,1'-biphenyl]-4-carboxamide; N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-2,3',4'-trimethyl-[1,1'-biphenyl]-4-carboxamide; 2-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-6-oxo-1,6-dihydropyrimidine-5- carboxamide; 5-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-3-oxo-3,4-dihydropyrazine-2- carboxamide; 2-amino-6-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)nicotinamide; (R)-2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)-5-(2,4,6-trifluorophenyl)pyridine 1- oxide; 3-(3,4-dimethylphenyl)-6-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)-2-fluoropyridine 1- oxide; 5-(3,4-dimethylphenyl)-2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)-4-fluoropyridine 1- oxide; 6-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-2-methoxynicotinamide; 5-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-3-methoxypicolinamide; 6-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-1-methyl-4-oxo-1,4- dihydropyridine-3-carboxamide; 3-(3,4-dimethylphenyl)-6-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)-2-methylpyridine 1- oxide; 3-(3,4-dimethylphenyl)-6-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)-2-hydroxypyridine 1- oxide; 5-(3,4-dimethylphenyl)-2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)-4-hydroxypyridine 1- oxide; 5-(3,4-dimethylphenyl)-2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)-3-hydroxypyridine 1- oxide; (R)-5-chloro-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-2-hydroxy-3',4'-dimethyl-[1,1'-biphenyl]-4- carboxamide; (S)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-5-fluoro-2-hydroxy-3',4'-dimethyl-[1,1'-biphenyl]-4- carboxamide; (R)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-5-fluoro-2-hydroxy-3',4'-dimethyl-[1,1'-biphenyl]-4- carboxamide; N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-3-methoxy-3',4'-dimethyl-[1,1'-biphenyl]-4- carboxamide; N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-3-methoxy-3',4'-dimethyl-[1,1'-biphenyl]-4-carboxamide; 2-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-4-methoxypyrimidine-5- carboxamide; 5-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-3-methoxypyrazine-2- carboxamide; 6-(3,4-dimethylphenyl)-N-(1-(methylimino)-1-oxido-2,3-dihydro-1H-16-thiophen-3-yl)-2-oxo-1,2- dihydropyridine-3-carboxamide; (E)-6-(3,4-dimethylphenyl)-3-(5-(2-(methylsulfonyl)vinyl)-1H-imidazol-2-yl)pyridin-2-ol; (R)-5-(4-cyclopropylphenyl)-2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)pyridine 1- oxide; (R)-5-(benzofuran-5-yl)-2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)pyridine 1-oxide; (R)-5-(2,3-dihydrobenzofuran-5-yl)-2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)pyridine 1-oxide; 2-(6-(3,4-dimethylphenyl)-2-methoxypyridin-3-yl)-6-thia-2-azaspiro[3.4]oct-7-ene 6,6-dioxide; 7-(3,4-dimethylphenyl)-3-(1,1-dioxido-2,3-dihydrothiophen-3-yl)quinazolin-4(3H)-one; 2-(3,4-dimethylphenyl)-6-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-7,8-dihydro-1,6-naphthyridin- 5(6H)-one; 6-(3,4-dimethylphenyl)-2-(1,1-dioxido-2,3-dihydrothiophen-3-yl)isoquinolin-1(2H)-one; 6-(3,4-dimethylphenyl)-2-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-3,4-dihydroisoquinolin-1(2H)- one; 7-(3,4-dimethylphenyl)-3-(1,1-dioxido-2,3-dihydrothiophen-3-yl)pyrido[2,3-d]pyrimidin-4(3H)- one; 2-(6-(3,4-dimethylphenyl)-2-hydroxypyridin-3-yl)-7-thia-1,3-diazaspiro[4.4]nona-2,8-diene 7,7- dioxide; (R)-2-(6-(3,4-dimethylphenyl)-2-hydroxypyridin-3-yl)-7-thia-1,3-diazaspiro[4.4]nona-2,8-diene 7,7-dioxide; (S)-2-(6-(3,4-dimethylphenyl)-2-hydroxypyridin-3-yl)-7-thia-1,3-diazaspiro[4.4]nona-2,8-diene 7,7-dioxide; (R,Z)-5-(3,4-dimethylphenyl)-2-((4-(methylsulfonyl)but-3-en-2-yl)carbamoyl)pyridine 1-oxide; (R,E)-5-(3,4-dimethylphenyl)-2-((4-(methylsulfonyl)but-3-en-2-yl)carbamoyl)pyridine 1-oxide; (S,E)-5-(3,4-dimethylphenyl)-2-((4-(methylsulfonyl)but-3-en-2-yl)carbamoyl)pyridine 1-oxide; 7-(5-(4-(trifluoromethyl)phenyl)pyridin-2-yl)-2-thia-7-azaspiro[4.4]non-3-ene 2,2-dioxide; 7-(3,4-dimethylphenyl)-3-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-8-fluoroquinazolin-4(3H)-one; 7-(6-(3,4-dimethylphenyl)-2-methoxypyridin-3-yl)-2-thia-7-azaspiro[4.4]non-3-ene 2,2-dioxide;(S)-4-(3-cyclopropyl-1H-pyrazol-1-yl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-2-methoxy-6- methylbenzamide; (R)-4-(3-cyclopropyl-1H-pyrazol-1-yl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-2-methoxy-6- methylbenzamide; 7-(3,4-dimethylphenyl)-3-(1,1-dioxido-2,3-dihydrothiophen-3-yl)pyrido[2,3-d]pyrimidine- 2,4(1H,3H)-dione; 2-(6-(3,4-dimethylphenyl)-2-methoxypyridin-3-yl)-7-thia-1,3-diazaspiro[4.4]nona-2,8-diene 7,7- dioxide; (R)-2-(6-(3,4-dimethylphenyl)-2-methoxypyridin-3-yl)-7-thia-1,3-diazaspiro[4.4]nona-2,8-diene 7,7-dioxide; (S)-2-(6-(3,4-dimethylphenyl)-2-methoxypyridin-3-yl)-7-thia-1,3-diazaspiro[4.4]nona-2,8-diene 7,7-dioxide; (R)-7-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-1H-benzo[d]imidazole-4- carboxamide; N-(1-(cyanoimino)-1-oxido-2,3-dihydro-1H-16-thiophen-3-yl)-6-(3,4-dimethylphenyl)-2-oxo-1,2- dihydropyridine-3-carboxamide; N-(1-(cyanoimino)-1-oxido-4,5-dihydro-1H-16-thiophen-3-yl)-6-(3,4-dimethylphenyl)-2-oxo-1,2- dihydropyridine-3-carboxamide; 3-(3,4-dimethylphenyl)-6-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)-2-methoxypyridine 1-oxide; 5-(3,4-dimethylphenyl)-2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)-4-methoxypyridine 1-oxide; 5-(3,4-dimethylphenyl)-2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)-3-methoxypyridine 1-oxide; N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-2-oxo-6-(4-(trifluoromethyl)piperidin-1-yl)-1,2- dihydropyridine-3-carboxamide; 2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)-5-(4-(trifluoromethyl)piperidin-1-yl)pyridine 1-oxide; (R)-3-amino-2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)-5-(5-(trifluoromethyl)thiophen- 3-yl)pyridine 1-oxide; (R)-3-amino-2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)-5-(5-(trifluoromethyl)thiophen- 2-yl)pyridine 1-oxide; (R)-3-amino-2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)-5-(4-(trifluoromethyl)thiophen- 2-yl)pyridine 1-oxide;(R)-2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)-5-(3-methyl-4- (trifluoromethyl)phenyl)pyridine 1-oxide; (S,Z)-N-(1-cyclopropyl-3-(methylsulfonyl)allyl)-6-(3,4-dimethylphenyl)-2-oxo-1,2-dihydropyridine- 3-carboxamide; (S,E)-N-(1-cyclopropyl-3-(methylsulfonyl)allyl)-6-(3,4-dimethylphenyl)-2-oxo-1,2-dihydropyridine- 3-carboxamide; (S,Z)-2-((1-cyclopropyl-3-(methylsulfonyl)allyl)carbamoyl)-5-(3,4-dimethylphenyl)pyridine 1- oxide; (S,E)-2-((1-cyclopropyl-3-(methylsulfonyl)allyl)carbamoyl)-5-(3,4-dimethylphenyl)pyridine 1- oxide; (R)-5-(2-chloro-4-(trifluoromethyl)phenyl)-2-((1,1-dioxido-2,3-dihydrothiophen-3- yl)carbamoyl)pyridine 1-oxide; 6-(3,4-dimethylphenyl)-3-(1-((1,1-dioxido-2,3-dihydrothiophen-3-yl)amino)-2,2,2- trifluoroethyl)pyridin-2(1H)-one; 7-(3,4-dimethylphenyl)-3-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-8-fluoro-2-hydroxy-2,3- dihydroquinazolin-4(1H)-one; 8-(5-(4-(trifluoromethyl)phenyl)pyridin-2-yl)-2-thia-8-azaspiro[4.5]dec-3-ene 2,2-dioxide; (R)-5-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)quinoline-8-carboxamide; 2-(6-(3,4-dimethylphenyl)-2-methoxypyridin-3-yl)-8-thia-1,3-diazaspiro[4.5]deca-2,6-diene 8,8- dioxide; 3-(6-(3,4-dimethylphenyl)-2-hydroxypyridin-3-yl)-9-thia-2,4-diazaspiro[5.5]undeca-2,7-diene 9,9- dioxide; (R)-5-(3,4-dimethylphenyl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)quinazoline-8-carboxamide; 3-(6-(3,4-dimethylphenyl)-2-methoxypyridin-3-yl)-9-thia-2,4-diazaspiro[5.5]undeca-2,7-diene 9,9-dioxide; 3-(4-(6-cyclopentyl-2-phenoxypyridin-3-yl)-1H-1,2,3-triazol-1-yl)-2,3-dihydrothiophene 1,1- dioxide; 2-(2-(cyclopropyldifluoromethyl)-4-phenoxypyrimidin-5-yl)-7-thia-1,3-diazaspiro[4.4]nona-2,8- diene 7,7-dioxide; (E)-2-(cyclopropyldifluoromethyl)-5-(5-(2-(methylsulfonyl)vinyl)-1H-imidazol-2-yl)-4- phenoxypyrimidine; 3-(4-(6-(isopropyl(methyl)amino)-2-phenoxypyridin-3-yl)-1H-1,2,3-triazol-1-yl)-2,3- dihydrothiophene 1,1-dioxide; (R)-5-(2-(benzylamino)phenyl)-2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)pyridine 1-oxide; 2-(6-(3,4-dimethylphenyl)-2-phenoxypyridin-3-yl)-7-thia-1,3-diazaspiro[4.4]nona-2,8-diene 7,7- dioxide; (S)-2-(6-(3,4-dimethylphenyl)-2-phenoxypyridin-3-yl)-7-thia-1,3-diazaspiro[4.4]nona-2,8-diene 7,7-dioxide; (R)-5-(2-(benzyloxy)-3-fluorophenyl)-2-((1,1-dioxido-2,3-dihydrothiophen-3- yl)carbamoyl)pyridine 1-oxide; (R)-5-(2-(benzyloxy)-4-fluorophenyl)-2-((1,1-dioxido-2,3-dihydrothiophen-3- yl)carbamoyl)pyridine 1-oxide; (R)-5-(2-(benzyloxy)-5-fluorophenyl)-2-((1,1-dioxido-2,3-dihydrothiophen-3- yl)carbamoyl)pyridine 1-oxide; (R)-5-(2-(benzyloxy)-6-fluorophenyl)-2-((1,1-dioxido-2,3-dihydrothiophen-3- yl)carbamoyl)pyridine 1-oxide; (R)-5-(2-(benzyloxy)-5-methylphenyl)-2-((1,1-dioxido-2,3-dihydrothiophen-3- yl)carbamoyl)pyridine 1-oxide; (R)-5-(2-(benzyloxy)-3-methylphenyl)-2-((1,1-dioxido-2,3-dihydrothiophen-3- yl)carbamoyl)pyridine 1-oxide; (R)-5-(2-(benzyloxy)-4-methylphenyl)-2-((1,1-dioxido-2,3-dihydrothiophen-3- yl)carbamoyl)pyridine 1-oxide; (R)-5-(2-(benzyloxy)-6-methylphenyl)-2-((1,1-dioxido-2,3-dihydrothiophen-3- yl)carbamoyl)pyridine 1-oxide; (R)-2-((1,1-dioxido-2,3-dihydrothiophen-3-yl)carbamoyl)-5-(5-fluoro-2-(pyridin-4- ylmethoxy)phenyl)pyridine 1-oxide; or a pharmaceutically acceptable salt thereof.

15. The compound of claim 1, wherein A and B are as defined in any one of claims 1 to 12, wherein X is -CONH-, wherein X is connected to B through its carbon atom, and wherein Y is a moiety according to formula:or a moiety according to formula:wherein Ry1is selected from H, C1-4 alkyl, C3-8 cycloalkyl, and 5 or 6-membered heterocyclyl, Ry2is selected from -H, -F and -CN, and Ry3is selected from C1-4 alkyl, C3-8 cycloalkyl, and 5 or 6- membered heterocyclyl, and wherein the bonds drawn as indicate that both Z and E configurations of the double bond are possible.

16. The compound of claim 15, selected from.

17. A pharmaceutical composition comprising the compound of any one of claims 1 to 16, and a pharmaceutically acceptable excipient.

18. The compound of any one of claims 1 to 16 or the pharmaceutical composition of claim 17 for use as a medicament.

19. The compound of any one of claims 1 to 16 or the pharmaceutical composition of claim 17 for use in the treatment of cancer.

20. The compound for use or the pharmaceutical composition for use of claim 19, wherein the cancer is treatable by inhibition of WRN and / or the cancer is characterized by MSI-H and / or dMMR.

21. Use of the compound of any one of claims 1 to 16 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.

22. A method for treating a cancer in a subject in need thereof, the method comprising the step of administering to the subject the therapeutically effective amount of the compound of any one of claims 1 to 16, preferably wherein the cancer is treatable by inhibition of WRN and / or the cancer is characterized by MSI-H and / or dMMR.

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