2-hydroxycycloalkane-1-carbamoyl derivatives that inhibit galectin-3

Abstract

The present invention is 1 , Ar 2 , L, n and R 1 The present invention relates to compounds of formula (I), as described herein, their preparation, pharmaceutically acceptable salts thereof, and their use as medicaments, pharmaceutical compositions comprising one or more compounds of formula (I), and their use, in particular as galectin-3 inhibitors. [Formula 1] TIFF2023547241000054.tif70163

Description

[Technical Field]

[0001] The present invention relates to compounds of formula (I) that are galectin-3 inhibitors and their use in the prevention or treatment of diseases and disorders involving the binding of galectin-3 to natural ligands. The present invention also relates to related aspects, including methods for producing such compounds, pharmaceutical compositions having one or more compounds of formula (I), and their medical use as galectin-3 inhibitors. Compounds of formula (I) may be used, in particular, as monotherapy or in combination with one or more therapeutic agents. [Background technology]

[0002] Galectins are defined as a family of proteins based on a conserved β-galactoside-binding site found within their characteristic ~130 amino acid (aa) carbohydrate recognition domain (CRD) (Barondes SH et al., Cell). (1994;76, 597-598). Human, mouse, and rat genome sequencing has revealed the existence of at least 16 conserved galectins and galectin-like proteins in a single mammalian genome (Leffler H. et al., Glycoconj.J.2002, 19, 433-440). To date, three galectin subclasses have been identified: prototypical galectins with one carbohydrate recognition domain (CRD); and abnormal tandem repeats of proline- and glycine-rich short stretches fused to the CRD. Galectins include chimeric galectins consisting of repeats, and tandem-repeat-type galectins having two distinct CRDs linked in tandem by a linker (Zhong X., Clin Exp Pharmacol Physiol. 2019;46:197-203). Because galectins can bind in a divalent or polyvalent state, they can, for example, cross-link complex carbohydrates on the cell surface (glycoconjugates) to trigger cellular signaling events. Through this mechanism, galectins regulate a wide range of biological processes (Sundblad V. et al., Histol Histopathol 2011;26:247-265).

[0003] Galectin-3 (Gal-3), the only chimeric form in the galectin family, has a molecular weight of 32-35 kDa and consists of 250 amino acid residues in humans, a highly conserved CRD, and an atypical N-terminal domain (ND). Galectin-3 remains monomeric up to high concentrations (100 μM), but can aggregate with ligands at much lower concentrations. This aggregation is facilitated by its N-terminal non-CRD region via an oligomerization mechanism, but the exact mechanism is not fully understood (Johannes, L. et al., Journal of Cell Science). 2018;131, jcs208884).

[0004] Gal-3 is widely distributed in the body, but its expression levels vary depending on the organ. Depending on its extracellular or intracellular localization, it can exhibit a wide range of biological functions, including immunomodulation, host-pathogen interaction, angiogenesis, cell migration, wound healing, and apoptosis (Sundblad V. et al., Histol Histopathol 2011;26:247-265). Gal-3 is highly expressed in many human tumors and in various cell types such as bone marrow cells, inflammatory cells (macrophages, mast cells, neutrophils, T cells, eosinophils, etc.), fibroblasts, and cardiomyocytes (Zhong X. et al., Clin Exp Pharmacol Physiol. 2019;46:197-203), indicating that Gal-3 is involved in the regulation of inflammatory and fibrotic processes (Henderson NC. et al., Immunological Reviews 2009;230:160-171). Sano H. et al., J Immunol. 2000;165(4):2156-64). Furthermore, the expression level of Gal-3 protein is upregulated in certain pathological conditions such as neoplasms and inflammation (Chiariotti L. et al., Glycoconjugate Journal 2004 19, 441-449; Farhad M. et al., OncoImmunology 2018, 7:6, e1434467).

[0005] Asthma (Gao P. et al., Respir Res. 2013, 14:136; Rao SP et al., Front Med (Lausanne) 2017;4:68), rheumatoid arthritis, multiple sclerosis, diabetes mellitus, psoriasis vulgaris (Lacina L. et al., Folia Biol (Prague) 2006;52(1-2):10-5), atopic dermatitis (Saegusa J. et al., Am J Pathol. 2009, 174(3):922-31), endometriosis (Noel JC et al., Appl Immunohistochem Mol Morphol. 2011 19(3):253-7), or viral encephalitis (Liu FT et al., Ann N There is a great deal of evidence supporting the functional involvement of Gal-3 in the progression of inflammatory / autoimmune diseases, such as Y Acad Sci. 2012;1253:80-91; Henderson NC et al., Immunol Rev. 2009;230(1):160-71; Li P et al., Cell 2016;167:973-984). Recently, Gal-3 has been shown to play a role in the progression of chronic inflammation and organ fibrosis (e.g., liver (Henderson NC et al., PNAS 2006;103:5060-5065; Hsu DK et al., Int J Cancer.1999, 81(4):519-26), kidney (Henderson NC et al., Am.J. Pathol.2008;172:288-298; Dang Z. et al., Transplantation.2012, 93(5):477-84), lung (Mackinnon AC et al., Am.J. Respir. Crit. Care Med 2012, 185:537-546; Nishi Y. et al., Allergol Int.2007, 56(1):57-65), heart (Thandavarayan RA et al., Biochem Pharmacol.2008, 75(9):1797-806;Sharma Gal-3 has attracted attention for its important role in the nervous system (U. et al., Am J Physiol Heart Circ Physiol. 2008;294(3):H1226-32), the nervous system (Burguillos MA et al., Cell Rep. 2015, 10(9):1626-1638), and corneal neovascularization (Chen WS. et al., Investigative Ophthalmology & Visual Science 2017, Vol. 58, 9-20). Furthermore, Gal-3 has been found to be involved in keloid tissue thickening (Arciniegas E. et al., The American Journal of Dermatopathology 2019;41(3):193-204) and systemic sclerosis (SSc), particularly in dermatofibrosis and proliferative vascular disorders observed in such conditions (Taniguchi T. et al., J Rheumatol. 2012, 39(3):539-44). In patients with chronic kidney disease (CKD)-related renal failure, particularly those with diabetes, upregulation of Gal-3 was found. Interestingly, data from this patient population showed a correlation between glomerular Gal-3 upregulation and observed urinary protein excretion (Kikuchi Y. et al., Nephrol Dial Transplant. 2004, 19(3):602-7). In addition, a recent prospective study in 2018 showed that high Gal-3 plasma levels were associated with an increased risk of developing CKD, especially in the hypertensive population (Rebholz CM. et al., Kidney Int. 2018 Jan;93(1):252-259). Gal-3 is associated with atherosclerosis (Nachtigal M. et al., Am J Pathol. 1998;152(5):1199-208), coronary artery disease (Falcone C. et al., Int J Immunopathol Pharmacol 2011, 24(4):905-13), heart failure, and thrombosis (Nachtigal M. et al., Am J Pathol. 1998;152(5):1199-208; Gehlken C. et al., Heart Fail Clin). It is significantly elevated in cardiovascular diseases such as those described in 2018, 14(1):75-92; DeRoo EP. et al., Blood. 2015, 125(11):1813-21 (Zhong X. et al., Clin Exp Pharmacol Physiol. 2019, 46(3):197-203). Blood levels of Gal-3 are elevated in obese and diabetic patients and are associated with an increased risk of microvascular complications (such as heart failure, nephropathy / retinopathy, peripheral artery disease, cerebrovascular events, or myocardial infarction) (Qi-hui-Jin et al., Chin Med J(Engl).2013, 126(11):2109-15). Gal-3 has been shown to promote carcinogenesis, cancer progression and metastasis (Vuong L. et al., Cancer Res 2019(79)(7)1480-1492), function as a pro-tumor factor by acting within the microtumor environment, and suppress immune surveillance (Ruvolo PP. et al., Biochim Biophys Acta.2016 Mar, 1863(3):427-437; Farhad M. et al., Oncoimmunology 2018 Feb 20;7(6):e1434467). Cancers expressing high levels of Gal-3 include those related to the thyroid, central nervous system, tongue, breast, stomach, head and neck squamous epithelial cells, pancreas, bladder, kidney, liver, parathyroid gland, and salivary gland, as well as lymphoma, carcinoma, non-small cell lung cancer, melanoma, and neuroblastoma (Sciacchitano S. et al., Int J Mol Sci 2018 Jan 26, 19(2):379).

[0006] Furthermore, inhibition of Gal-3 is linked to COVID-19 (Caniglia JL et al., Peer It has been suggested that it is beneficial in the treatment of influenza H5N1 (J 2020, 8:e9392) and influenza H5N1 (Chen YJ et al., Am.J. Pathol. 2018, 188(4), 1031-1042), which is thought to be due to its anti-inflammatory effect.

[0007] Recently, Gal-3 inhibitors have been shown to have positive effects when used in combination immunotherapy (Galectin Therapeutics; press release, February 7, 2017), idiopathic pulmonary fibrosis (Galecto Biotech; press release, March 10, 2017), and NASH cirrhosis (December 5, 2017). WO20180209276, WO2018209255, and WO20190890080 disclose compounds with binding affinity to galectin proteins for the treatment of systemic insulin resistance impairment. Therefore, Gal-3 inhibitors, either alone or in combination with other therapies, may be useful in the prevention or treatment of diseases or disorders such as organ fibrosis, cardiovascular diseases and disorders, acute and chronic kidney disease, liver diseases and disorders, interstitial lung diseases and disorders, eye diseases and disorders, proliferative disorders and cancers, inflammatory and autoimmune diseases and disorders, gastrointestinal diseases and disorders, pancreatic diseases and disorders, abnormal angiogenesis-related diseases and disorders, brain-related diseases and disorders, neuropathic pain and peripheral neuropathy, and / or transplant rejection.

[0008] Synthetic inhibitors of Gal-3, which are being explored as antifibrotic agents, have been described in various publications and patent applications (see, for example, WO2005113568, WO2005113569, WO2014067986, WO2016120403, US20140099319, WO2019067702, WO2019075045, WO2014078655, WO2020078807, WO2020078808, and WO2020210308). [Overview of the project]

[0009] The present invention provides a novel compound of formula (I) that is a galectin-3 inhibitor. Accordingly, the compounds of the present invention may be useful in the prevention or treatment of diseases and disorders in which the regulation of Gal-3 binding to natural carbohydrate ligands is required.

[0010] 1) In a first embodiment, the present invention relates to a compound of formula (I):

[0011] [ka] (In the formula, n represents the integer 1 or 2 (in particular, n is 2). Ar 1 teeth, - Aryl (especially phenyl) compounds substituted with 1, 2, 3, 4, or 5 substituents (especially substituted with 1, 2, or 3 substituents), wherein the substituents are independently selected from halogens; methyl; cyano; methoxy; trifluoromethyl; and trifluoromethoxy; [In a secondary embodiment, the aryl is phenyl, substituted with two or three substituents, at least one of which is bonded at the meta or para position of the phenyl; in particular, if a para substituent is present, the para substituent is preferably selected from halogens and methyl; if a meta substituent is present, the meta substituent is preferably a halogen, and the phenyl is such that...] - A 5- or 6-membered heteroaryl, wherein the 5- or 6-membered heteroaryl is independently unsubstituted or substituted with one or two substituents, wherein the substituents are independently selected from halogen, methyl, cyano, and methoxy; or, - A 9 or 10-membered heteroaryl, wherein each of the 9 or 10-membered heteroaryls is independently unsubstituted or substituted by one methyl group; It represents; R 1 teeth, - Hydroxy; - C 1-3 -alkoxy (especially methoxy); - -O-CO-C 1-3 -alkyl; - -O-CH2-CH2-OH; or, - -O-CH2-CO-OH; It represents; L represents a direct bond or methylene (especially a direct bond); Ar 2 teeth, - phenyl, where the phenyl is unsubstituted or substituted by 1, 2 or 3 substituents (especially substituted by 1 or 2 substituents), and the substituents are C 1-6 - alkyl (especially methyl), C 3-6 - cycloalkyl, -CH2-C 3-6 - cycloalkyl, C 1-3 - fluoroalkyl, C 1-3 - fluoroalkoxy, C 1-3 - alkoxy (especially methoxy), halogen and cyano, independently selected phenyl; - 5- or 6-membered heteroaryl, where the 5- or 6-membered heteroaryl is independently unsubstituted or substituted by 1, 2 or 3 substituents, and the substituents are C 1-6 - alkyl, C 3-6 - cycloalkyl, -CH2-C 3-6 - cycloalkyl, C 1-3 - fluoroalkyl, C 1-3 - fluoroalkoxy, C 1-3 - alkoxy, halogen and cyano, independently selected 5- or 6-membered heteroaryl; - 9-membered bicyclic heteroaryl or 10-membered bicyclic heteroaryl, where the 9- or 10-membered bicyclic heteroaryl is independently unsubstituted or substituted by 1 or 2 substituents, and the substituents are independently selected from methyl, methoxy and halogen, 9-membered bicyclic heteroaryl or 10-membered bicyclic heteroaryl; or, - naphthyl; represents.).

[0012] In a sub-aspect, in the compound of formula (I), or, with necessary modifications, in the compound of formula (II) or (III) below, especially, in each formula, the nitrogen that binds the cycloalkane moiety to the rest of the molecule and the hydroxy substituent of the cycloalkane moiety are in a relative trans configuration (i.e., the cycloalkane moiety is relative (R * ,R *)-arranged). ). To avoid doubt, the compounds of formula (I), and, with necessary modifications, the compounds of formula (II) or (III) below, in particular, the compounds of formula (I) shown in aspect 2) below. S ) or a compound of formula (I shown in the following embodiment 3) R ) is a compound of these or any mixture thereof.

[0013] 2) A second aspect of the present invention is the formula (I S Regarding compounds of formula (I) according to embodiment 1):

[0014] [ka] (In the formula, Ar 1 Ar 2 , R 1 L and n are defined as in Embodiment 1).

[0015] 3) Another aspect of the present invention is formula (I R Regarding compounds of formula (I) according to embodiment 1):

[0016] [ka] (In the formula, Ar 1 Ar 2 , R 1 L and n are defined as in Embodiment 1).

[0017] The compound of formula (I) has five chiral or chiral centers located at the tetrahydropyran moiety and in the absolute configuration described in formula (I). The compound of formula (I) further has two chiral or chiral centers located at the cycloalkane moiety and in the absolute (S,S)- or absolute (R,R)- configuration, preferably in the absolute (S,S)- configuration. In addition, the compound of formula (I) may contain one, and possibly more, chiral or chiral centers, such as one or two or more further chiral carbon atoms. Thus, the compound of formula (I) may exist as a mixture of stereoisomers, or preferably as a pure stereoisomer. The mixture of stereoisomers may be separated by methods known to those skilled in the art.

[0018] When a particular compound (or comprehensive structure) is described as being in a specific absolute configuration, such as an (R)- or (S)-enantiomer, such description is understood to mean each compound (or comprehensive structure) in an enriched, particularly essentially pure, enantiomer form. Similarly, when a particular chiral center of a compound is described as being in an (R)- or (S)- configuration, or in a specific relative configuration, such description is understood to mean the compound in an enriched, particularly essentially pure form with respect to each configuration of the chiral center. Likewise, two chiral centers in a cyclic group, for example, may exist in a specific relative configuration.

[0019] When the term "enriched" is used in relation to stereoisomers, in the context of this invention, it is understood to mean that each stereoisomer exists in a ratio of at least 70:30, and more particularly at least 90:10, with respect to the other stereoisomers / each other stereoisomer as a whole (i.e., with a purity of at least 70% by weight, and more particularly at least 90% by weight).

[0020] When the term "essentially pure" is used in relation to stereoisomers, in the context of this invention, it is understood to mean that each stereoisomer exists with a purity of at least 95 percent by weight, and in particular at least 99 percent by weight, with respect to the other stereoisomers / the other respective stereoisomers as a whole.

[0021] The present invention also relates to isotope-labeled, particularly 2 This also includes compounds of formula (I) according to the H (deuterium) labeled embodiments 1) to 23), wherein the isotope-labeled compounds have 1 or 2 or more atoms It is identical to the compound of formula (I), except that it is replaced by atoms having the same atomic number but different atomic weights than those normally found in nature. Isotope-labeled, in particular 2 Compounds of formulas (I), (II), and (III) labeled with H (deuterium) and their salts are included in the scope of the present invention. 2 Substitution with H (deuterium) increases metabolic stability, which can lead to, for example, a longer in vivo half-life, a reduction in the required dose, or reduced inhibition of cytochrome P450 enzymes, thus improving the safety profile. In one embodiment of the present invention, the compounds of formula (I) are either unlabeled or labeled only by one or more deuterium atoms. In a secondary embodiment, the compounds of formula (I) are not isotopically labeled at all. Isotopically labeled compounds of formula (I) may be prepared in the same manner as described below, except that appropriate reagents or suitable isotopes of the starting materials are used.

[0022] In this patent application, dotted lines represent the bonding points of the described groups. For example, the following groups

[0023] [ka] This is a 3-fluorophenyl group.

[0024] When the plural form is used for compounds, salts, pharmaceutical compositions, diseases, etc., it is intended to also refer to a single compound, salt, etc.

[0025] Any reference to a compound of formula (I) according to aspects 1) to 23) shall, depending on the context, also be understood to refer to a salt of such a compound (especially a pharmaceutically acceptable salt).

[0026] The term "pharmaceutically acceptable salt" refers to a salt that retains the desired biological activity of the target compound while exhibiting minimal undesirable toxic effects. Such salts include inorganic or organic acid and / or base addition salts, depending on the presence of basic and / or acidic groups in the target compound. For reference, see, for example, "Handbook of Pharmaceutical Salts. Properties, Selection and Use," P. Heinrich Stahl, Camille G. Wermuth (Eds.), Wiley-VCH, 2008; and "Pharmaceutical Salts and Co-crystals," Johan Wouters and Luc. See Quere (Eds.), RSC Publishing, 2012.

[0027] The definitions set forth herein apply uniformly to compounds of formulas (I), (II), and (III) as defined in any one of embodiments 1) to 18), and shall apply throughout this specification and the claims with necessary modifications unless broader or narrower definitions are provided by specific definitions. Naturally, a definition or preferred definition of a term may independently (and together with) define and replace any or all of the terms defined herein or each term in a preferred definition.

[0028] In this patent application, compounds are named using IUPAC nomenclature, but they can also be named using carbohydrate nomenclature. Therefore, the base:

[0029] [ka] It can be named (2R,3R,4S,5R,6R)-3,5-dihydroxy-6-(hydroxymethyl)-4-(4-phenyl-1H-1,2,3-triazole-1-yl)tetrahydro-2H-pyran-2-carbonyl, or 1,3-di-deoxy-3-[4-phenyl-1H-1,2,3-triazole-1-yl]-β-D-galactopyranoside-1-carbonyl, and the absolute configuration of the carbon atom supporting the carbonyl group, which is the bonding site to the rest of the molecule, is in the (2R)- or beta- configuration. For example, the compound (2R,3R,4S,5R,6R)-4-(4-(4-cyano-3-fluorophenyl)-1H-1,2,3-triazole-1-yl)-N-(3-cyano-5-methoxyphenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide is understood to also be called: 1,3-di-deoxy-2-O-methyl-3-[4-(4-cyano-3-fluorophenyl)-1H-1,2,3-triazole-1-yl]-N-(3-cyano-5-methoxyphenyl)-N-((1S,2S)-2-hydroxycyclopentyl)-β-D-galactopyranose-1-carboxamide.

[0030] Whenever a substituent is described as optional, such substituents may not be present (i.e., each residue is unsubstituted with respect to such optional substituents), in which case all sites with free valence (e.g., ring carbon atoms and / or ring nitrogen atoms with free valence in an aromatic ring to which such optional substituents may be attached) are understood to be substituted with hydrogen as appropriate. Similarly, when the term “optionally” is used with respect to (ring) heteroatoms, the term means that each optional heteroatom etc. is either absent (i.e., a group has no heteroatom / is a carbocyclic / etc.) or each optional heteroatom etc. is present as explicitly defined. Unless expressly defined otherwise in each embodiment or claim, the groups as defined herein are unsubstituted.

[0031] The term "halogen" refers to fluorine, chlorine, bromine, or iodine.

[0032] The term "alkyl," whether used alone or in combination, refers to a linear or branched saturated hydrocarbon group having 1 to 6 carbon atoms. x- y The term "alkyl" (where x and y are integers) refers to the previously defined alkyl group having x to y carbon atoms. For example, C 1-6 -Alkyl groups have 1 to 6 carbon atoms. Typical examples of alkyl groups are methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert.-butyl, pentyl, 3-methyl-butyl, 2,2-dimethyl-propyl, and 3,3-dimethyl-butyl. Methyl is preferred. To avoid ambiguity, when a group is described as, for example, propyl or butyl, it means n-propyl or n-butyl, respectively. 2 The substituent is "C 1-6 When referring to "-alkyl," this term specifically means methyl.

[0033] The term "fluoroalkyl," whether used alone or in combination, refers to the previously defined alkyl group having 1 to 3 carbon atoms, in which one or more (and possibly all) hydrogen atoms are replaced by fluorine. x-y The term "-fluoroalkyl" (where x and y are integers) refers to the previously defined fluoroalkyl group having x to y carbon atoms. For example, C 1-3 -Fluoroalkyl groups have 1 to 3 carbon atoms and 1 to 7 hydrogen atoms are replaced by fluorine atoms.

[0034] The term "fluoroalkoxy," whether used alone or in combination, refers to the previously defined alkoxy group having 1 to 3 carbon atoms, in which one or more (and possibly all) hydrogen atoms are replaced by fluorine. x-y The term "-fluoroalkoxy" (where x and y are integers) refers to the previously defined fluoroalkoxy group having x to y carbon atoms. For example, C 1-3 -Fluoroalkoxy groups have 1 to 3 carbon atoms and 1 to 7 hydrogen atoms are replaced by fluorine.

[0035] The term "cycloalkyl," whether used alone or in combination, specifically refers to a saturated monocyclic, condensed, bridged, or spiro-dicyclic hydrocarbon ring having 3 to 8 carbon atoms. x-y The term "cycloalkyl" (where x and y are integers) refers to the previously defined cycloalkyl group having x to y carbon atoms. For example, C 3-6 -Cycloalkyl groups have 3 to 6 carbon atoms. Examples of cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

[0036] The term "alkoxy," whether used alone or in combination, refers to an alkyl-O- group, where alkyl is defined as previously defined. x-y The term "alkoxy" (where x and y are integers) refers to the previously defined alkoxy group having x to y carbon atoms. Preferably, it is ethoxy and especially methoxy. 1 is "C 1-3 -When referring to "alkoxy," this term specifically means methoxy. 2 The substituent is "C 1-3 -When referring to "alkoxy," this term specifically means methoxy.

[0037] The term "aryl," whether used alone or in combination, means phenyl or naphthyl, preferably phenyl, where the aryl group is either unsubstituted or substituted as explicitly defined.

[0038] The term "heteroaryl," whether used alone or in combination, refers to a 5- to 10-membered monocyclic or bicyclic aromatic ring having 1 to 4 heteroatoms, each independently selected from oxygen, nitrogen, and sulfur, unless a broader or narrower definition is explicitly stated. Typical examples of such heteroaryl groups include furanyl, oxazolyl, isoxazolyl, oxadiazolyl, thiophenyl, and thia. Five-membered heteroaryl groups such as zolyl, isothiazolyl, thiadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, and tetrazolyl; six-membered heteroaryl groups such as pyridinyl, pyrimidinyl, pyridadinyl, and pyrazinyl; and indolyl, isoindolyl, benzofuranil, isobenzofuranil, benzothiophenyl, indazolyl, benzimidazolyl, benzoxazolyl, benzoisoxazolyl, and benzothiazolyl These are 8- to 10-membered bicyclic heteroaryl groups such as benzoisothiazolyl, benzotriazolyl, benzoxadiazolyl, benzothiadiazolyl, thienopyridinyl, quinolinyl, isoquinolinyl, naphthilidinyl, cinolinyl, quinazolinyl, quinoxalinyl, phthalazinyl, pyrrolopyridinyl, pyrazolopyridinyl, pyrazolopyridinyl, pyrazolopyridinyl, pyrrolopyradinyl, imidazopyridinyl, imidazopyridadinyl, and imidazothiazolyl. The above heteroaryl groups are unsubstituted or substituted as explicitly defined. Substituents Ar representing "5 or 6-membered heteroaryl" 2 In relation to this, the term means, in particular, furanyl, thiophenyl, pyrrolyl, thiazolyl, isothiazolyl, isoxazolyl, pyrazolyl, imidazolyl, pyridinyl, or pyrimidinyl; the 5 or 6-membered heteroaryl is unsubstituted or substituted as expressly defined. Substituent Ar representing "9-membered bicyclic heteroaryl" 2In relation to this, the term means, in particular, indolyl, benzothiophenyl, benzothiazolyl, or benzimidazolyl, where the 9-membered bicyclic heteroaryl is either unsubstituted or substituted as expressly defined. Substituents Ar representing "10-membered bicyclic heteroaryl" 2 In this regard, the term means, in particular, quinolinyl or quinoxalinyl; the 10-membered bicyclic heteroaryl is either unsubstituted or substituted as expressly defined.

[0039] To avoid ambiguity, whenever a specific position of a substituent on a phenyl or six-membered heteroaryl group is described as being at the para or meta position, that para or meta position should be understood to refer to the bond point of the group to the rest of the molecule.

[0040] The term "cyano" means the base -CN.

[0041] Whenever the word "between" is used to describe a range of numbers, the endpoints of the indicated range are explicitly included within that range. For example, if the temperature range is described as being between 40°C and 80°C, it means that the endpoints, 40°C and 80°C, are included within that range; or if a variable number is defined as an integer between 1 and 4, it means that the variable number is the integer 1, 2, 3, or 4.

[0042] Where not used in relation to temperature, the term "approximately" placed before a number "X" in this application means between 10% of XX and 10% of X+X, preferably between 5% of XX and 5% of X+X. In specific cases of temperature, the term "approximately" placed before a temperature "Y" in this application means between Y-10°C and Y+10°C, preferably between Y-5°C and Y+5°C. Furthermore, as used herein, the term "room temperature" means a temperature of approximately 25°C.

[0043] Further aspects of the present invention are described below: 4) Another aspect is, Ar 1The present invention relates to a compound that represents phenyl, wherein the substituents are substituted with 1, 2, 3, 4, or 5 substituents (particularly substituted with 1, 2, or 3 substituents), and the substituents are independently selected from halogens; methyl; cyano; methoxy; trifluoromethyl; and trifluoromethoxy; and is in accordance with any of embodiments 1) to 3).

[0044] 5) Another aspect is Ar 1 The present invention relates to a compound that is phenyl, substituted with one, two, or three substituents, wherein the substituents are independently selected from halogens, methyl, cyano, and methoxy; and to a compound according to any of embodiments 1) to 3).

[0045] In a secondary embodiment, at least one of the substituents is bonded to the meta or para position of the phenyl molecule.

[0046] 6) Another aspect is, Ar 1 However, phenyl is represented by phenyl substituted with one, two, or three substituents, wherein the substituents are independently selected from halogens, methyl, cyano, and methoxy; At least one of the substituents is bonded at the meta or para position of the phenyl molecule; - In particular, if a substituent at the para position is present, the substituent at the para position is selected from halogen, methyl, cyano, and methoxy; - In particular, if a substituent at the meta position is present, the substituent at the meta position is a halogen;; relating to compounds according to any of embodiments 1) to 3).

[0047] In the sub-application of aspect 6), Ar 1 is a phenyl compound substituted with two or three substituents, wherein the substituents are independently selected from halogens; methyls; and cyanos (in particular, halogens or methyls); - If the phenyl molecule is substituted with two substituents, at least one of the substituents is in the meta position and is particularly a halogen; the other substituent is particularly in the meta or para position of the other substituent; - If the phenyl molecule is substituted with three substituents, the substituents are Ar 1 A 2,3,4 or 3,4,5 substitution pattern is formed at the bond site, and in particular the para substituent is halogen or methyl, and the remaining substituents are independently halogen (especially fluoro); Represents phenyl.

[0048] 7) Another aspect is Ar 1 However, it is phenyl, substituted with one, two, or three substituents; - One of the substituents is bonded at the meta position of the phenyl molecule, and the substituent is a halogen; if any other substituents are present, the remaining substituents are halogens; or, - One of the substituents is bonded at the para position of the phenyl molecule, and the substituent is independently selected from methyl, cyano, and methoxy; if any other substituents are present, the remaining substituents are halogens (particularly fluoro); This relates to compounds representing phenyl; according to any of embodiments 1) to 3).

[0049] 8) Another aspect is, Ar 1 but,

[0050] [ka] This relates to compounds that conform to any of embodiments 1) to 3).

[0051] In a sub-application of aspect 8), Ar 1 In particular, represents a group selected from group A) or B) below:

[0052] [ka] 9) Another aspect is R 1 The present invention relates to compounds that represent methoxy; according to any one of embodiments 1) to 8).

[0053] 10) Another aspect relates to a compound in which L represents a direct bond; following any one of aspects 1) to 9).

[0054] 11) Another aspect is, Ar 2 However, the phenyl is either unsubstituted or substituted with 1, 2, or 3 substituents (in particular, substituted with 1 or 2 substituents), and the substituents are C 1-6 -Alkyl (especially methyl), C 3-6 -Cycloalkyl, -CH2-C 3-6 -Cycloalkyl, C 1-3 -Fluoroalkyl, C 1-3 -Fluoroalkoxy, C 1-3 The present invention relates to compounds representing phenyl, independently selected from alkoxy (especially methoxy), halogen, and cyano (in particular, having at least one substituent in the meta position); according to any one of embodiments 1) to 10).

[0055] 12) Another aspect is, Ar 2 However, it is phenyl, which is substituted with one or two substituents, and the substituents are C 1-4 -Alkyl (especially methyl), C 1-3 -Fluoroalkyl, C 1-3 - Independently selected from alkoxy (especially methoxy), halogen and cyano (in particular, the substituent is C 1-4 -Alkyl (especially methyl), C 1-3 The present invention relates to compounds that represent phenyl (in particular, an alkoxy (especially methoxy), a halogen, and a cyano, independently selected from these) (especially, at least one of the substituents is in the meta position); and compounds that conform to any one of embodiments 1) to 10).

[0056] 13) Another aspect is, Ar 2 However, it is phenyl, - Substituted by one substituent, where the substituent is C 1-4 -Alkyl (especially methyl), C 1-3 - Selected from alkoxy (especially methoxy), halogen, and cyano (especially, the substituent is in the meta position); or, - Substituted by two substituents, where the substituents are C1-4 -Alkyl (especially methyl), C 1-3 - Independently selected from alkoxy (especially methoxy), halogen, and cyano substituents (in particular, both substituents being in the meta position); This relates to a compound representing phenyl; according to any one of embodiments 1) to 10).

[0057] 14) Another aspect is the fragment L-Ar 2 but:

[0058] [ka] This relates to a compound that conforms to any one of embodiments 1) to 9).

[0059] 15) Accordingly, the present invention relates to compounds of formula (I) as defined in aspect 1), or such compounds further limited by any one feature of aspects 2) to 14) according to their respective dependencies; pharmaceutically acceptable salts thereof; and the use of such compounds as further described below. To avoid any doubt, the following aspects are possible, intended, and specifically disclosed as individual forms with respect to compounds of formula (I): 1、2+1、3+1、4+1、4+2+1、4+3+1、5+1、5+2+1、5+3+1、6+1、6+2+1、6+3+1、7+1、7+2+1、7+3+1、8+1、8+2+1、8+3+1、9+1、9+2+1、9+3+1、9+4+1、9+4+2+1、9+4+3+1、9+5+1、9+5+2+1、9+5+3+1、9+6+1、9+6+2+1、9+6+3+1、9+7+1、9+7+2+1、9+7+3+1、9+8+1、9+8+2+1、9+8+3+1、10+1、10+2+1、10+3+1、10+4+1、10+4+2+1、10+4+3+1、10+5+1、10+5+2+1、10+5+3+1、10+6+1、10+6+2+1、10+6+3+1、10+7+1、10+7+2+1、10+7+3+1、10+8+1、10+8+2+1、10+8+3+1、10+9+1、10+9+2+1、10+9+3+1、10+9+4+1、10+9+4+2+1、10+9+4+3+1、10+9+5+1、10+9+5+2+1、10+9+5+3+1、10+9+6+1、10+9+6+2+1、10+9+6+3+1、10+9+7+1、10+9+7+2+1、10+9+7+3+1、10+9+8+1、10+9+8+2+1、10+9+8+3+1、11+1、11+2+1、11+3+1、11+4+1、11+4+2+1、11+4+3+1、11+5+1、11+5+2+1、11+5+3+1、11+6+1、11+6+2+1、11+6+3+1、11+7+1、11+7+2+1、11+7+3+1、11+8+1、11+8+2+1、11+8+3+1、11+9+1、11+9+2+1、11+9+3+1、11+9+4+1、11+9+4+2+1、11+9+4+3+1、11+9+5+1、11+9+5+2+1、11+9+5+3+1、11+9+6+1、11+9+6+2+1、11+9+6+3 +1、11+9+7+1、11+9+7+2+1、11+9+7+3+1、11+9+8+1、11+9+8+2+1、11+9+8+3+1、11+10+1、11+10+2+1、11+10+3+1、11+10+4+1、11+10+4+2+1、11+10+4+3+1、11+10+5+1、11+10+5+2+1、11+10+5+3+1、11+10+6+1、11+10+6+2+1、11+10+6+3+1、11+10+7+1、11+10+7+2+1、11+10+7+3+1、11+10+8+1、11+10+8+2+1、11+10+8+3+1、11+10+9+1、11+10+9+2+1、11+10+9+3+1、11+10+9+4+1、11+10+9+4+2+1、11+10+9+4+3+1、11+10+9+5+1、11+10+9+5+2+1、11+10+9+5+3+1、11+10+9+6+1、11+10+9+6+2+1、11+10+9+6+3+1、11+10+9+7+1、11+10+9+7+2+1、11+10+9+7+3+1、11+10+9+8+1、11+10+9+8+2+1、11+10+9+8+3+1、 12+1、12+2+1、12+3+1、12+4+1、12+4+2+1、12+4+3+1、12+5+1、12+5+2+1、12+5+3+1、12+6+1、12+6+2+1、12+6+3+1、12+7+1、12+7+2+1、12+7+3+1、12+8+1、12+8+2+1、12+8+3+1、12+9+1、12+9+2+1、12+9+3+1、12+9+4+1、12+9+4+2+1、12+9+4+3+1、12+9+5+1、12+9+5+2+1、12+9+5+3+1、12+9+6+1、12+9+6+2+1、12+9+6+3+1、12+9+7+1、12+9+7+2+1、12+9+7+3+1、12+9+8+1、12+9+8+2+1、12+9+8+3+1、12+10+1、12+10+2+1、12+10+3+1、12+10+4+1、12+10+4+2+1、12+10+4+3+1、12+10+5+1、12+10+5+2+1、12+10+5+3+1、12+10+6+1、12+10+6+2+1、12+10+6+3+1、12+10+7+1、12+10+7+2+1、12+10+7+3+1、12+10+8+1、12+10+8+2+1、12+10+8+3+1、12+10+9+1、12+10+9+2+1、12+10+9+3+1、12+10+9+4+1、12+10+9+4+2+1、12+10+9+4+3+1、12+10+9+5+1、12+10+9+5+2+1、12+10+9+5+3+1、12+10+9+6+1、12+10+9+6+2+1、12+10+9+6+3+1、12+10+9+7+1、12+10+9+7+2+1、12+10+9+7+3+1、12+10+9+8+1、12+10+9+8+2+1、12+10+9+8+3+1、13+1、13+2+1、13+3+1、13+4+1、13+4+2+1、13+4+3+1、13+5+1、13+5+2+1、13+5+3+1、13+6+1、13+6+2+1、13+6+3+1、13+7+1、13+7+2+1、13+7+3+1、13+8+1、13+8+2+1、13+8+3+1、13+9+1、13+9+2+1、13+9+3+1、13+9+4+1、13+9+4+2+1、13+9+4+3+1、13+9+5+1、13+9+5+2+1、13+9+5+3+1、13+9+6+1、13+9+6+2+1、13+9+6+3+1、13+9+7+1、13+9+7+2+1、13+9+7+3+1、13+9+8+1、13+9+8+2+1、13+9+8+3+1、13+10+1、13+10+2+1、13+10+3+1、13+10+4+1、13+10+4+2+1、13+10+4+3+1、13+10+5+1、13+10+5+2+1、13+10+5+3+1、13+10+6+1、13+10+6+2+1、13+10+6+3+1、13+10+7+1、13+10+7+2+1、13+10+7+3+1、13+10+8+1、13+10+8+2+1、13+10+8+3+1、13+10+9+1、13+10+9+2+1、13+10+9+3+1、13+10+9+4+1、13+10+9+4+2+1、13+10+9+4+3+1、13+10+9+5+1、13+10+9+5+2+1、13+10+9+5+3+1、13+10+9+6+1、13+10+9+6+2+1、13+10+9+6+3+1、13+10+9+7+1、13+10+9+7+2+1、13+10+9+7+3+1、13+10+9+、 8+1、13+10+9+8+2+1、13+10+9+8+3+1、14+1、14+2+1、14+3+1、14+4+1、14+4+2+1、14+4+3+1、14+5+1、14+5+2+1、14+5+3+1、14+6+1、14+6+2+1、14+6+3+1、14+7+1、14+7+2+1、14+7+3+1、14+8+1、14+8+2+1、14+8+3+1、14+9+1、14+9+2+1、14+9+3+1、14+9+4+1、14+9+4+2+1、14+9+4+3+1、14+9+5+1、14+9+5+2+1、14+9+5+3+1、14+9+6+1、14+9+6+2+1、14+9+6+3+1、14+9+7+1、14+9+7+2+1、14+9+7+3+1、14+9+8+1、14+9+8+2+1、14+9+8+3+1。

[0060] In the list above, the numbers represent the corresponding aspects, and the "+" indicates a dependency relationship from other aspects. The various aspects are separated individually by commas. In other words, for example, "11+9+4+1" means aspect 11) which is dependent on aspect 9) which is dependent on aspect 4) which is dependent on aspect 1), that is, aspect "11+9+4+1" corresponds to a compound of formula (I) that follows aspect 1) which is further limited by all the features of aspects 4), 9), and 11).

[0061] 16) A further aspect of the present invention relates to a compound of formula (I) according to embodiment 1), which is also a compound of formula (II):

[0062] [ka] (In the formula, Ar 1 teeth, - Aryl (especially phenyl) compounds substituted with 1, 2, 3, 4, or 5 substituents (especially substituted with 1, 2, or 3 substituents), wherein the substituents are independently selected from halogens; methyl; cyano; methoxy; trifluoromethyl; and trifluoromethoxy; [In a secondary embodiment, the aryl is a phenyl molecule substituted with two or three substituents, at least one of which is bonded at the meta or para position of the phenyl molecule; in particular, if a para substituent is present, the para substituent is preferably a halogen or a methyl substituent; if a meta substituent is present, the meta substituent is preferably a halogen substituent, and the molecule is a phenyl molecule.] - A 5- or 6-membered heteroaryl, wherein the 5- or 6-membered heteroaryl is independently unsubstituted or substituted with one or two substituents, wherein the substituents are independently selected from halogen, methyl, cyano, and methoxy; or, - A 9 or 10-membered heteroaryl, wherein each of the 9 or 10-membered heteroaryls is independently unsubstituted or substituted by one methyl group; It represents; R 1 represents - hydroxy; - C 1-3 - alkoxy (especially methoxy); - -O-CO-C 1-3 - alkyl; - -O-CH2-CH2-OH; or, - -O-CH2-CO-OH; represents; L represents a direct bond or methylene (especially a direct bond); Ar 2 represents - phenyl, where the phenyl is unsubstituted or substituted by 1, 2 or 3 substituents (especially substituted by 1 or 2 substituents), and the substituents are independently selected from C 1-6 - alkyl (especially methyl), C 3-6 - cycloalkyl, -CH2-C 3-6 - cycloalkyl, C 1-3 - fluoroalkyl, C 1-3 - fluoroalkoxy, C 1-3 - alkoxy (especially methoxy), halogen and cyano, phenyl [In a sub-aspect, at least one of the substituents is in the meta position.]; - a 5- or 6-membered heteroaryl, where the 5- or 6-membered heteroaryl is independently unsubstituted or substituted by 1, 2 or 3 substituents, and the substituents are independently selected from C 1-6 - alkyl, C 3-6 - cycloalkyl, -CH2-C 3-6 - cycloalkyl, C 1-3 - fluoroalkyl, C 1-3 - fluoroalkoxy, C 1-3 - alkoxy, halogen and cyano, a 5- or 6-membered heteroaryl; - A 9-membered bicyclic heteroaryl or a 10-membered bicyclic heteroaryl, wherein the 9- or 10-membered bicyclic heteroaryl is independently unsubstituted or substituted by 1 or 2 substituents, and the substituents are independently selected from methyl, methoxy and halogen; or a 9-membered bicyclic heteroaryl or a 10-membered bicyclic heteroaryl; or, - naphthyl; represents.); It is intended that the features disclosed in embodiments 2) to 15) be applied to the compounds of formula (II) according to embodiment 16) with the necessary modifications.

[0063] 17) Another aspect of the present invention relates to a compound of formula (II S ) according to embodiment 16):

[0064]

Chemical formula

[0065] 18) Another aspect of the present invention relates to a compound of formula (III), also a compound of formula (II) according to embodiment 16):

[0066]

Chemical formula

[0067] 19) Another embodiment relates to a compound of formula (I) according to embodiment 1), selected from the following compounds: (2R,3R,4S,5R,6R)-N-(3-chlorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chloro-5-methylphenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chloro-5-cyanophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-N-(3-iodophenyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dibromophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-4-(4-(3,4-difluoro-5-methoxyphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxami Do; (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(3,4-difluoro-5-methoxyphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dibromophenyl)-4-(4-(3,4-difluoro-5-methoxyphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-4-(4-(3,4-difluoro-5-methoxyphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chloro-5-cyanophenyl)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-chloro-5-cyanophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-chloro-5-cyanophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-bromo-5-cyanophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carbocyanyl Samido; (2R,3R,4S,5R,6R)-4-(4-(3-chloro-4,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-chloro-5-cyanophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(3-chloro-4,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chloro-5-cyanophenyl)-4-(4-(3,4-dichlorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(3,4-dichlorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(3-chloro-5-fluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(3-bromo-5-fluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-chloro-5-cyanophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(3-bromo-5-fluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(3-bromo-5-fluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-cyano-5-fluorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(3-bromo-5-fluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-cyano-5-methylphenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(3-bromo-5-fluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-cyano-5-methoxyphenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-4-(4-( 2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chloro-5-cyanophenyl)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3,5-dichlorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-chloro-5-cyanophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-bromo-5-cyanophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-cyano-5-fluorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(3-fluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-cyano-5-methylphenyl)-4-(4-(3-fluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-chloro-5-cyanophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-( 4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chloro-5-cyanophenyl)-4-(4-(3-fluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(3-fluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chloro-5-cyanophenyl)-4-(4-(4-cyano-3-fluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(4-cyano-3-fluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-cyano-3-fluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-cyano-5-methylphenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-cyano-3-fluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-cyano-5-methoxyphenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(3,4-dichloro-5-fluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chloro-5-cyanophenyl)-4-(4-(4-chlorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-bromophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-chloro-5-cyanophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chlorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-5-hydrox C-N-((1S,2S)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chloro-5-methylphenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chloro-5-cyanophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1-yl)tetrahydro-2H-pyran-2-carboxamide Mido; (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-5-hydroxy-N-((1S,2S)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-N-(3-iodophenyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dibromophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-4-(4-(3,4-difluoro-5-methoxyphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dibromophenyl)-4-(4-(3,4-difluoro-5-methoxyphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-4-(4-(3,4-difluoro-5-methoxyphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-chloro-5-cyanophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-bromo-5-cyanophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-cyano-5-fluorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(3-chloro-4,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-chloro-5-cyanophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(3-chloro-4,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chloro-5-cyanophenyl)-4-(4-(3,4-dichlorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(3,4-dichlorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(3-chloro-5-fluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(3-bromo-5-fluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-cyano-5-methylphenyl) (L)-5-hydroxy-N-((1S,2S)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(3-bromo-5-fluorophenyl)-1H-1,2,3-triazole-1-yl)-N-(3-cyano-5-methoxyphenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide ; (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-chloro-5-cyanophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-bromo-5-cyanophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-cyano-5-fluorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; and (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(4-cyano-3-fluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide.

[0068] 20) In addition to the compounds described in Embodiment 19), further compounds of formula (I) according to Embodiment 1) are selected from the following compounds: (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-5-hydroxy-N-((1R,2R)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-N-(3-iodophenyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dibromophenyl)-4-(4-(3,4-difluoro-5-methoxyphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chloro-5-cyanophenyl)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-chloro-5-cyanophenyl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-chloro-5-cyanophenyl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(3-chloro-4,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-chloro-5-cyanophenyl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chloro-5-cyanophenyl)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-chloro-5-cyanophenyl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-cyano-5-fluorophenyl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(3-fluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-cyano-5-methylphenyl)-4-(4-(3-fluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-chloro-5-cyanophenyl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chloro-5-methylphenyl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclobutyl)-6-(hydro (Xymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-5-hydroxy-N-((1R,2R)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-N-(3-iodophenyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromophenyl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-4-(4-(3,4-difluoro-5-methoxyphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dibromophenyl)-4-(4-(3,4-difluoro-5-methoxyphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide;(2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazole- 1-yl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-chloro-5-cyanophenyl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(3-chloro-4,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-chloro-5-cyanophenyl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(3-chloro-4,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-chloro-5-cyanophenyl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-bromo-5-cyanophenyl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; and (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-cyano-5-fluorophenyl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide.

[0069] 21) In addition to the compounds described in aspects 19) and 20), further compounds of formula (I) according to aspect 1) are selected from the following compounds: (2R,3R,4S,5R,6R)-N-(3-chloro-5-cyanophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; and (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide.

[0070] 22) In addition to the compounds described in aspects 19), 20), and 21), further compounds of formula (I) according to aspect 1) are selected from the following compounds: (2R,3R,4S,5R,6R)-2-((3,5-dichlorophenyl)((1S,2S)-2-hydroxycyclopentyl)carbamoyl)-5-hydroxy-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-yl acetate; (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-3,5-dihydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-2-((3-chloro-5-cyanophenyl)((1S,2S)-2-hydroxycyclopentyl)carbamoyl)-5-hydroxy-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-yl acetate; (2R,3R,4S,5R,6R)-N-(3-chloro-5-cyanophenyl)-3,5-dihydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-2-((3,5-dichlorophenyl)((1S,2S)-2-hydroxycyclopentyl)carbamoyl)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-3-yl acetate; (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-3,5-dihydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-2-((3-chloro-5-cyanophenyl)((1S,2S)-2-hydroxycyclopentyl)carbamoyl)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-3-yl acetate; (2R,3R,4S,5R,6R)-N-(3-chloro-5-cyanophenyl)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-3,5-dihydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-((3,5-dichlorophenyl)((1S,2S)-2-hydroxycyclopentyl)carbamoyl)-5-hydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-3-yl Acetate; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3,5-dichlorophenyl)-3,5-dihydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-3,5-difluorophen Nyl)-1H-1,2,3-triazol-1-yl)-2-((3-chloro-5-cyanophenyl)((1S,2S)-2-hydroxycyclopentyl)carbamoyl)-5-hydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-3-yl acetate; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-chloro-5-cyanophenyl)-3,5-dihydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chloro-5-cyanophenyl)-4-(4-(3,4-dichloro-5-fluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-2-((3,5-dichlorophenyl)((1S,2S)-2-hydroxycyclobutyl)carbamoyl)-5-hydroxy-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-yl acetate; (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-3,5-dihydroxy-N-((1S,2S)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-2-((3-chloro-5-cyanophenyl)((1S,2S)-2-hydroxycyclobutyl)carbamoyl)-5-hydroxy-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-yl acetate; (2R,3R,4S,5R,6R)-N-(3-chloro-5-cyanophenyl)-3,5-dihydroxy-N-((1S,2S)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-chloro-5-cyanophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3,5-dichlorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chloro-5-cyanophenyl)-4-(4-(3,4-dichloro-5-fluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; and (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(3,4-dichloro-5-fluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide.

[0071] 23) In addition to the compounds described in aspects 19), 20), 21), and 22), aspect 1) Further compounds of formula (I) following the following formula are selected from the following compounds: (2R,3R,4S,5R,6R)-N-(3-bromophenyl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dibromophenyl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-4-(4-(3,4-difluoro-5-methoxyphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chloro-5-cyanophenyl)-4-(4-(3,4-dichlorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(3-bromo-5-fluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-chloro-5-cyanophenyl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(3-bromo-5-fluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(3-bromo-5-fluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-cyano-5-fluorophenyl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(3-bromo-5-fluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-cyano-5-methylphenyl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(3-bromo-5-fluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-cyano-5-methoxyphenyl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclopentyl)-6 -(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chloro-5-cyanophenyl)-4-(4-(3-fluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(3-fluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chloro-5-cyanophenyl)-4-(4-(4-cyano-3-fluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(4-cyano-3-fluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-cyano-3-fluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-cyano-5-methylphenyl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-cyano-3-fluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-cyano-5-methoxyphenyl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chloro-5-cyanophenyl)-4-(4-(3,4-dichloro-5-fluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chloro-5-cyanophenyl)-4-(4-(4-chlorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-bromophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-chloro-5-cyanophenyl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chlorophenyl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chloro-5-cyanophenyl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1, 2,3-Triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-2-((3-chloro-5-cyanophenyl)((1R,2R)-2-hydroxycyclobutyl)carbamoyl)-5-hydroxy-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-yl acetate; (2R,3R,4S,5R,6R)-N-(3-chloro-5-cyanophenyl)-3,5-dihydroxy-N-((1R,2R)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dibromophenyl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-4-(4-(3,4-difluoro-5-methoxyphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-chloro-5-cyanophenyl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-bromo-5-cyanophenyl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-cyano-5-fluorophenyl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chloro-5-cyanophenyl)-4-(4-(3,4-dichlorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(3,4-dichlorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(3-chloro-5-fluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide;(2R,3R,4S,5R,6R)-4-( 4-(3-bromo-5-fluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3-cyano-5-methylphenyl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide;(2R,3R,4S,5R,6R)-4-(4-(3-bromo-5-fluorophenyl) -1H-1,2,3-triazol-1-yl)-N-(3-cyano-5-methoxyphenyl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3,5-dichlorophenyl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide;(2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(4-cyano-3-fluorophenyl)-1H-1,2,3-triazol-1-yl) -5-Hydroxy-N-((1R,2R)-2-Hydroxycyclobutyl)-6-(Hydroxymethyl)-3-Methoxytetrahydro-2H-Pyran-2-Carboxamide; (2R,3R,4S,5R,6R)-N-(3-Chloro-5-Cyanophenyl)-4-(4-(3,4-Dichloro-5-Fluorophenyl)-1H-1,2,3-Triazole-1-yl)-5-Hydroxy-N-((1R,2R)-2-Hydroxycyclobutyl)-6-(Hydroxymethyl)-3-Hydroxytetrahydro-2H-Pyran-2-Carboxamide; and (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(3,4-dichloro-5-fluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide.

[0072] Compounds of formula (I) according to embodiments 1) to 23) and pharmaceutically acceptable salts thereof can be used as pharmaceuticals, for example, in the form of pharmaceutical compositions for enteral administration (e.g., in the form of tablets or capsules, particularly orally) or parenteral administration (including topical application or inhalation).

[0073] The manufacture of the pharmaceutical composition may be carried out by methods well known to any person skilled in the art (see, for example, Remington, The Science and Practice of Pharmacy, 21st Edition (2005), Part 5, “Pharmaceutical Manufacturing” [published by Lippincott Williams & Wilkins]), by combining the compound of formula (I) described above or a pharmaceutically acceptable salt thereof, optionally with other therapeutically beneficial substances, with a suitable non-toxic, inert, therapeutically compatible solid or liquid carrier material and, if necessary, a conventional pharmaceutical adjuvant, to form a pharmaceutical dosage.

[0074] The present invention also relates to a method for preventing or treating a disease or disorder described herein, comprising administering to a subject a pharmaceutically effective amount of a compound of formula (I) according to embodiments 1) to 23). In a secondary embodiment of the present invention, the dose is between 1 mg and 1000 mg per day.

[0075] To avoid any doubt, where a compound is described as useful for the prevention or treatment of a disease, such a compound is also suitable for use in the manufacture of a medicine for the prevention or treatment of such disease. Similarly, such a compound is also suitable in a method for the prevention or treatment of such disease, which involves administering an effective amount of such compound to a subject (mammal, especially human) that needs it.

[0076] 24) Another embodiment relates to a compound of formula (I) as defined in any one of embodiments 1) to 23) that is useful for the prevention or treatment of diseases and disorders in which the binding of galectin-3 to a native ligand is involved.

[0077] Such diseases and disorders involving the binding of Gal-3 to its natural ligand are, in particular, diseases and disorders in which inhibition of the physiological activity of Gal-3 is beneficial, for example, diseases in which the Gal-3 receptor is involved, is related to the pathogenesis or pathology of the disease, or is otherwise related to at least one symptom of the disease.

[0078] Diseases and disorders involving the binding of galectin-3 to its native ligand may be defined to include, in particular, the following: - Fibrosis of the organs: -- All forms of fibrotic interstitial lung disease, particularly idiopathic pulmonary fibrosis (also known as cryptogenic fibrosing alveolitis); pulmonary fibrosis as a secondary disease of systemic inflammatory diseases such as rheumatoid arthritis, scleroderma (systemic scleroderma, SSc), lupus (systemic lupus erythematosus; SLE), polymyositis, or mixed connective tissue disease (MCTD); pulmonary fibrosis as a secondary disease of sarcoidosis; iatrogenic pulmonary fibrosis, including radiation-induced fibrosis; silicosis-induced pulmonary fibrosis; asbestos-induced pulmonary fibrosis; and pleural fibrosis; and all forms of lung / pulmonary fibrosis. -- Chronic nephropathy including chronic kidney disease (CKD), (acute or chronic) renal failure, tubulointerstitial nephritis, and / or (primary) glomerulonephritis and glomerulonephritis as a secondary disease of systemic inflammatory diseases such as SLE and SSc; diabetes mellitus, focal segmental glomerulosclerosis, IgA nephropathy, hypertension, kidney transplantation, and renal fibrosis, including renal fibrosis resulting from / associated with Alport syndrome; -- All forms of liver / hepatic fibrosis (associated with or unassociated with portal hypertension), including cirrhosis, alcohol-induced hepatic fibrosis, non-alcoholic steatohepatitis, bile duct injury, primary biliary cirrhosis (also known as primary biliary cholangitis), infection- or virus-induced hepatic fibrosis (e.g., chronic HCV infection), and autoimmune hepatitis; -- Cardiovascular disease, heart failure, Fabry disease, CKD; all forms of heart / cardiac fibrosis, including cardiac fibrosis associated with diabetes, hypertension, or hypercholesterolemia; -- Gastrointestinal fibrosis (gut fibrosis), including gastrointestinal fibrosis and radiation-induced gastrointestinal fibrosis, which are secondary diseases of SSc; -- Dermatofibrosis, including SSc and skin scarring; -- Head and neck fibrosis, including radiation-induced head and neck fibrosis; -- Ocular / corneal fibrosis including scarring (e.g., complications of laser-assisted in situ keratomileusis or trabeculectomy); -- Hypertrophic scars and keloids, including burn-induced or surgical hypertrophic scars and keloids; -- Fibrosis complications following organ transplantation (including corneal transplantation); -- and other fibrotic diseases including endometriosis, spinal fibrosis, myelofibrosis, perivascular and aterial fibrosis; as well as scar tissue formation, Peyronie's disease, abdominal or intestinal adhesions, bladder fibrosis, nasal fibrosis, and fibroblast-mediated fibrosis; Fibrosis of organs including; - (Acute or chronic) liver diseases and disorders (acute and chronic viral hepatitis; cirrhosis resulting from / associated with arthritis and vasculitis; metabolic liver diseases resulting from / associated with arthritis, myocarditis, diabetes, or neurological symptoms; cholestatic diseases resulting from / associated with hyperlipidemia, inflammatory bowel disease (IBD), or ulcerative colitis; liver tumors; celiac disease, autoimmune hemolytic anemia, IBD, autoimmune thyroiditis, ulcerative colitis, diabetes, glomerulonephritis, pericarditis, autoimmune thyroiditis, hyperthyroidism, polymyositis, Sjögren's syndrome, pancreatitis, alveolitis, or alcoholic steatohepatitis; cirrhosis associated with dementia; cirrhosis associated with peripheral neuropathy; oral cavity or esophagus) This includes cirrhosis caused by / associated with cancer; non-alcoholic fatty liver disease (especially non-alcoholic steatohepatitis) caused by / associated with obesity, metabolic syndrome, or type 2 diabetes; hepatic vascular disorders (including Budd-Chiari syndrome, portal vein thrombosis, and sinusoidal obstruction syndrome); acute and chronic liver failure (associated with or unassociated with portal hypertension); and liver dysfunction. - Acute kidney injury and chronic kidney disease (CKD) caused by / associated with heart disease (also known as cardiorenal syndrome type 1 and type 2), or caused by / associated with hypertension, or caused by / associated with diabetes (also known as diabetic nephropathy (DKD), including hypertension-associated DKD, where such diabetes is particularly type 1 or 2 diabetes), or caused by / associated with inflammatory diseases and disorders (such as glomerulonephritis and systemic inflammatory diseases like SLE or SSc, tubulointerstitial nephritis, vasculitis, sepsis, glomerulonephritis as a secondary disease of urinary tract infections), or caused by / associated with polycystic kidney disease, or caused by / associated with obstructive nephropathy (including kidney stones, benign prostatic hyperplasia, prostate cancer, retroperitoneal pelvic tumor), or caused by / associated with neurogenic bladder disease-related symptoms) [especially Kidney Disease Improving Global]. CKD of stages 1-5 as defined in the Outcomes (KDIGO) Guidelines, particularly CKD of these stages; and acute and chronic renal failure; - Cardiovascular diseases and disorders (atherosclerosis caused by / associated with hypertension, hypercholesterolemia, diabetes, inflammation, obesity, and aging; peripheral artery disease caused by / associated with hypertension, hypercholesterolemia, diabetes, and aging; deep vein thrombosis; pulmonary embolism caused by / associated with obesity or cancer; aortic aneurysms and dissections caused by / associated with aging, hypertension, Marfan syndrome, congenital heart defects, inflammatory or infectious disorders; cerebrovascular diseases caused by / associated with hypertension, atrial fibrillation, hypercholesterolemia, diabetes, and aging; hypertension, hypercholesterolemia, diabetes, aging, or CKD (especially Kidney Disease Improving) Coronary heart disease caused by / associated with stage 1-5 CKD as defined in the Global Outcomes (KDIGO) Guidelines; rheumatic heart disease caused by / associated with bacterial infections; cardiac and vascular tumors; cardiomyopathy and arrhythmias; valvular heart disease (including cardiac valve calcification and degenerative aortic stenosis); inflammatory heart disease caused by / associated with infections, carditis, glomerulonephritis, and cancer; and heart failure (HF), defined in particular as including congestive HF, especially systolic HF / HF with reduced ejection fraction (HFrEF) and diastolic HF / HF with preserved ejection fraction (HFpEF). - Interstitial lung diseases and disorders (including smoking-related interstitial lung diseases; interstitial lung diseases caused by / associated with chronic obstructive pulmonary disease; interstitial pneumonia associated with collagen vascular disease (including ordinary interstitial pneumonia), or pneumonia). - Cellular proliferative disorders and cancers (including solid tumors, solid tumor metastases, carcinomas, sarcomas, myelomas (and multiple myelomas), leukemias, lymphomas, mixed-type carcinomas, angiofibromas, Kaposi's sarcomas, chronic lymphocytic leukemia (CLL), spinal cord tumors, and invasive metastases of cancer cells). - Inflammatory and autoimmune diseases and disorders (including chronic and acute inflammatory and autoimmune diseases and disorders, particularly sepsis, Q fever, asthma, rheumatoid arthritis, multiple sclerosis, SLE, SSc, polymyositis, psoriasis vulgaris (including psoriasis caused by / associated with NASH), atopic dermatitis, inflammatory kidney diseases (renal / kidney diseases) such as nephropathy (including diabetic nephropathy, glomerulonephritis, and tubulointerstitial nephritis), inflammatory heart diseases, inflammatory lung / lung-related diseases; inflammatory liver / liver-related diseases; diabetes (type 1 or type 2) and diabetes-related diseases such as diabetic vascular disorders, diabetic nephropathy, diabetic retinopathy, diabetic peripheral neuropathy, or skin-related diseases; viral encephalitis; and COVID-19 and its complications). - Digestive disorders and conditions (including irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), gastritis, and abnormal pancreatic juice secretion); - Pancreatic diseases and disorders (including, for example, pancreatitis associated with cystic fibrosis); - Diseases and disorders related to abnormal angiogenesis (including arterial occlusion); - Brain-related diseases and disorders (including stroke and cerebral hemorrhage); - Neuropathic pain and peripheral neuropathy; - Eye diseases and disorders (including dry eye (xerophthalmos), age-related macular degeneration (AMD), diabetes-related diseases (diabetic retinopathy), proliferative vitreoretinopathy (PVR), scarring pemphigoid and glaucoma (including ocular scarring after glaucoma filtration surgery and glaucoma associated with increased intraocular pressure), and corneal angiogenesis / neovascularization); and - Transplant rejection (including rejection of transplanted organs such as kidneys, livers, hearts, lungs, pancreas, corneas, and skin; graft-versus-host disease resulting from hematopoietic stem cell transplantation; chronic allograft rejection and chronic allograft vasculopathy); and complications of such transplant rejection.

[0079] 25) Further embodiments relate to compounds of formula (I) for use in accordance with embodiment 24), for use in the prevention or treatment of organ fibrosis, including liver / hepatic fibrosis, renal / kidney fibrosis, lung / pulmonary fibrosis, heart / cardiac fibrosis, ocular / corneal fibrosis and cutaneous fibrosis; as well as gastrointestinal fibrosis, head and neck fibrosis, hypertrophic scars and keloids; and fibrotic complications of organ transplants.

[0080] 26) Further embodiments relate to compounds of formula (I) for use in accordance with embodiment 24), wherein the compound is for use in the prevention or treatment of cardiovascular diseases and disorders.

[0081] 27) Further embodiments relate to a compound of formula (I) for use in accordance with embodiment 24), wherein the compound is for use in the prevention or treatment of acute kidney injury and chronic kidney disease (CKD).

[0082] 28) Further embodiments relate to compounds of formula (I) for use in accordance with embodiment 24), wherein the compound is for use in the prevention or treatment of (acute or chronic) liver diseases and disorders.

[0083] 29) Further embodiments relate to compounds of formula (I) for use in accordance with embodiment 24), wherein the compound is for use in the prevention or treatment of interstitial lung disease and disorders.

[0084] 30) Further embodiments relate to compounds of formula (I) for use in accordance with embodiment 24), wherein the compound is for use in the prevention or treatment of eye diseases and disorders.

[0085] 31) Further embodiments relate to compounds of formula (I) for use in accordance with embodiment 24), wherein the compound is for use in the prevention or treatment of cell proliferation disorders and cancer.

[0086] 32) Further embodiments relate to compounds of formula (I) for use in accordance with embodiment 24), wherein the compound is for use in the prevention or treatment of chronic or acute inflammatory and autoimmune diseases and disorders.

[0087] 33) Further embodiments relate to compounds of formula (I) for use in accordance with embodiment 24), wherein the compound is for use in the prevention or treatment of gastrointestinal diseases and disorders.

[0088] 34) Further embodiments relate to compounds of formula (I) for use in accordance with embodiment 24), wherein the compound is for use in the prevention or treatment of pancreatic diseases and disorders.

[0089] 35) Further embodiments relate to compounds of formula (I) for use in accordance with embodiment 24), wherein the compound is for use in the prevention or treatment of abnormal angiogenesis-related diseases and disorders.

[0090] 36) Further embodiments relate to compounds of formula (I) for use in accordance with embodiment 24), wherein the compound is for use in the prevention or treatment of brain-related diseases and disorders.

[0091] 37) Further embodiments relate to a compound of formula (I) for use in accordance with embodiment 24), wherein the compound is for use in the prevention or treatment of neuropathic pain and peripheral neuropathy.

[0092] 38) Further embodiments relate to a compound of formula (I) for use according to embodiment 24), wherein the compound is for use in the treatment of transplant rejection.

[0093] Furthermore, any suitability and (sub)aspects shown for the compound of formula (I) (whether relating to the compound itself, its salts, compositions containing the compound or its salts, or the use of the compound or its salts, etc.) are applicable to the compounds of formula (II) and (III) with necessary modifications.

[0094] Preparation of the compound of formula (I) Compounds of formula (I) can be prepared by well-known literature methods, by the methods described below, by the methods described in the experimental section below, or by similar methods. The optimal reaction conditions vary depending on the specific reactants or solvents used, but such conditions can be determined by routine optimization procedures by those skilled in the art. In some cases, the reaction scheme and / or the order of the reaction steps described below may be modified to facilitate the reaction or to avoid undesirable byproducts. In the general reaction sequence outlined below, integer n and the inclusive group, R 1 , L, Ar 1 Ar 2 and n are as defined for formula (I). Other abbreviations used herein are either explicitly defined or as defined in the Experimental section. In some cases, the comprehensive group, R 1 , L, Ar 1 Ar 2and n may not be compatible with the preparation method illustrated in the scheme below, and the use of a protecting group (Pg) will be necessary. The use of protecting groups is well known in the art (see, for example, "Protective Groups in Organic Synthesis," TW Greene, PGMWuts, Wiley-Interscience, 1999). For this purpose, we assume that such protecting groups have been introduced as needed. In some cases, the final product may be further modified, for example, by manipulating substituents to obtain new final products. Such operations include, but are not limited to, reduction, oxidation, alkylation, acylation, hydrolysis, and transition metal-catalyzed cross-coupling reactions, which are well known to those skilled in the art. The resulting compounds may be converted to salts, in particular pharmaceutically acceptable salts, by methods known in themselves.

[0095] The compound of formula (I) of the present invention can be prepared according to the general reaction sequence outlined below. Only a few of the possible syntheses yielding the compound of formula (I) are described.

[0096] Compounds of formula (I) are those in which R is hydrogen, a suitable protecting group (Pg), or (as defined in formula (I)) R 1 The compound with structure 1 is produced by coupling it with the compound with structure 2 to obtain structure 3. The coupling reaction is carried out in the presence of a base such as TEA or DIPEA, in a suitable solvent such as DCM or DMF or a mixture thereof, and under standard peptide coupling conditions such as DCC, HOBT or T3P. Alternatively, POCl3 is coupled with a base. It can be used with pyridine as follows. In structures 2 and 3, Pg is a suitable protecting group such as acetyl, trimethylsilyl (TMS), tert-butyldimethylsilyl (TBS), or benzyl, which are well known to those skilled in the art. The hydroxyl groups at positions 4 and 6 of structure 1 can be protected with a cyclic protecting group such as isopropylidene, benzylidene, or bis-tert-butylsilyl group. R is a suitable protecting group (Pg), or the group OR is (as defined in formula (I)) R 1This corresponds to the compound of structure 3. Next, the compound of formula (I) is deprotected to obtain the compound of formula (I).

[0097] [ka] If Pg represents an acyl protecting group, such a protecting group can be cleaved with water or alcohol under standard conditions, for example, in or without additional solvents such as THF or dioxane, and in the presence of bases such as K2CO3, NaOH, or LiOH. If such a protecting group represents a benzyl group, it can be cleaved with hydrogen in methanol, EA, THF, or mixtures thereof, in the presence of catalysts such as Pd / C or PtO2, or with BBr3 in a solvent such as DCM. If such a protecting group is TMS or TBS, it is cleaved using fluoride ions such as HF in TBAF or pyridine. Alternatively, silyl protecting groups are removed under mild acidic conditions such as aqueous AcOH at temperatures between rt and reflux. If Pg is a cyclic protecting group such as isopropylidene, benzylidene, or bis-tert-butylsilylene, cleavage can be carried out under acidic conditions using aqueous AcOH or TFA.

[0098] [ka] The compound of structure 1 is produced by hydrolyzing the nitrile functional group in structure 4 to a carboxylic acid under aqueous acidic (conc. HCl) or basic (NaOH) conditions at a temperature between 20 and 100°C, and then appropriately protecting or modifying the free hydroxyl group. Alternatively, structure 4 is produced in the presence of CuI and DIPEA in a solvent such as THF or DMF, for example. The compound of structure 5 can be obtained by reacting the compound of structure 6 with the compound of structure 6 (Click Chemistry in Glycoscience: New Development and Strategies, 1st edition, 2013, John Wiley & Sons), or the reaction can be carried out in a solvent such as THF using a copper coil in a commercially available continuous-flow reactor (Vapourtec). The compound of structure 6 is commercially available or can be produced according to methods known to those skilled in the art (Synthesis 2011, 22, 3604-3611). The compound of structure 5 can be produced from the corresponding gulo furanose derivative by methods well known to those skilled in the art (Carbohydrate Research 1994, 251, 33-67; Bioorg.Med.Chem. 2002, 10, 1911-2013).

[0099] The compound of structure 2 is obtained by protecting the compound of structure 7 with a suitable silyl protecting group under standard conditions. The compound of structure 7 is obtained by the reaction of cyclopentene oxide or cyclobutyl oxide with an amine. This reaction, when carried out with a racemic trans-amino alcohol or a suitable catalyst such as those reported in Org. Lett. 2014, 16, 2798-2801, produces enantiomer-enriched derivatives.

[0100] In coupling with the compound of structure 1, the compound of structure 2 is used in a racemic mixture. The diastereomers of structure 3 or formula I (after deprotection) are separated using techniques well known to those skilled in the art, such as chiral preparative HPLC, with achiral or chiral stationary phases such as Waters XBridge C18, 10 μm OBD, 30 x 75 mm, or Daicel ChiralCel OJ-H (5-10 μm) column, ChiralPak IH (5 μm) column, ChiralPak IE (5 μm) column, ChiralPak IC (5 μm) column, ChiralPak (5 μm) column, AS-H (5 μm), or IB (5 μm) column. Typical conditions for chiral HPLC are a gradient-free mixture of eluent A (CO2) and eluent B (DCM / MeOH, MeCN / MeOH, MeCN / EtOH, 0.1% Et2NH in EtOH, MeOH, EtOH, iPrOH) at a flow rate of 0.8–160 mL / min. In some cases, the pure form of the compound of structure 2 is used as an enantiomer in amide coupling with the compound of structure 1, giving pure enantiomers of the compounds of structure 3 and formula I, respectively.

[0101] Experiment section The following examples illustrate the present invention, but are not intended to limit its scope in any way.

[0102] All temperatures are indicated in °C. Commercially available starting materials were used in their obtained state without further purification. Unless otherwise stated, all reactions were carried out under a nitrogen or argon atmosphere. Compounds were separated by preparative TLC (Merck TLC plates, Silica gel) by flash chromatography on silica gel (Biotage, Redisep). 60 F 254 The compounds described in this invention were purified by ) or by preparative HPLC. 1¹H-NMR (Bruker Neo, 400MHz Ultra Shield™ or Bruker Avance III HD, Ascend 500MHz); chemical shifts are expressed in ppm relative to the solvent used; multiplicity: s=singlet, d=doublet, t=triplet, q=quadruplet, quint=quintlet, hex=hexatlet, hept=septuplet, m=multitlet, br=broad; coupling constants are expressed in Hz.) and / or LC-MS (retention time t R The values ​​are shown in min; the molecular weight obtained from mass spectrometry is shown in g / mol.) The characteristics are clarified using the conditions described below.

[0103] Qualitative analysis methods used LC-MS retention times were obtained using the following elution conditions: A) LC-MS(A): A Zorbax RRHD SB-Aq, 1.8□m, 2.1x50mm column was temperature-controlled at 40°C. Two elution solvents were used: Solvent A = Water + 0.04% TFA; Solvent B = MeCN. The elution flow rate was 0.8 mL / min. The characteristics of the proportion of the eluted mixture relative to time t from the start of elution are summarized in the table below (a linear gradient is used between two consecutive time points):

[0104] [Table 1] Purification by preparative LC-MS was performed under the conditions described below.

[0105] B) Preparative LC-MS(I): A Zorbax column (Zorbax Dr. Maisch, 5 μm, 30 x 75 mm) was used. The two elution solvents were as follows: Solvent A = water + 0.5% formic acid aqueous solution; Solvent B = MeCN. The elution flow rate was 75 mL / min. The characteristics of the proportion of the eluted mixture relative to time t from the start of elution are summarized in the table below (a linear gradient is used between two consecutive time points):

[0106] [Table 2] C) Preparative LC-MS(II): A Waters column (Waters XBridge C18, 10 μm OBD, 30 x 75 mm) was used. The two elution solvents were as follows: Solvent A = water + 0.5% 25% NH4OH aqueous solution; Solvent B = MeCN. The elution flow rate was 75 mL / min, and the characteristics of the proportion of the eluted mixture as a function of time t from the start of elution are summarized in the table below (a linear gradient is used between two consecutive time points):

[0107] [Table 3] Abbreviations (as used herein): ABTS 2,2'-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) Acetyl Acetic acid (ACOH) aq. aqueous solution Bu (nBuLi = n-butyllithium, etc.) Ca approx. CC Silica Column Chromatography I will use this. Concentrated DCM Dichloromethane DIPEA N-ethyldiisopropylamine DMF Dimethylformamide DMSO (Dimethyl Sulfoxide) EA ethyl acetate eq (molar) equivalent Et ethyl EtOH Ethanol Et2O Diethyl ether Example FC Flash Chromatography h time HOBt 1-Hydroxybenzotriazole hydrate HPLC (High-Performance Liquid Chromatography) hv high vacuum LC (Reset Chromatography) M molar concentration [mol L -1 Me methyl MeCN acetonitrile MeOH methanol MS mass spectrometry min. minute N normality OD optical density o / n overnight org. organic Pg protecting group Ph phenyl PTSA p-toluenesulfonic acid rt room temperature sat. saturated TBME tert-butyl methyl ether TBS tert-butyldimethylsilyl tBu tert-butyl = tertiary butyl TEA triethylamine Tf trifluoromethanesulfonate TFA trifluoroacetic acid THF tetrahydrofuran TMS trimethylsilyl T3P propylphosphonic anhydride [[ID=5|0]]t R [[ID=|52]]Retention time

[0108] A Production of Precursors and Intermediates Production of the Intermediate of Structure 1 The following precursors were produced for the synthesis of the compound:

[0109]

Chemical Structure

[0110] Intermediate 1: (3R,4S,5R,6R)-6-(acetoxymethyl)-4-azidotetrahydro-2H-pyran-2,3,5-triyl triacetate ​(3R,4S,5R,6R)-6-(acetoxymethyl)-4-azidotetrahydro-2H-pyran-2,3,5-triyl triacetate is synthesized from (3aR,5S,6S,6aR)-5-((R)-2,2-dimethyl-1,3-dioxolan-4-yl)-2,2-dimethyltetrahydroflo[2,3-d][1,3]dioxol-6-ol according to literature-based methods from Carbohydrate Research 1994, 251, 33-67 and references cited herein.

[0111] Intermediate 2: (2R,3R,4R,5R,6S)-2-(acetoxymethyl)-6-cyano-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diyl diacetate Dissolve intermediate 1 (10000 mg, 26.5 mmol, 1 eq) in nitromethane (4 vol.) (40 mL), and gradually add 98% trimethylsilyl cyanide (10.2 mL, 79.6 mmol, 3 eq) and boron trifluoride diethyl etherate (3.93 mL, 31.8 mmol, 1.2 eq) over 30 min. Maintain the temperature below 35°C in a water bath. Stir the mixture in rt for 2 hours. Fractionate the mixture between water (400 mL), saturated bicarbonate aqueous solution (100 mL), and TBME (300 mL). Extract the aqueous phase again with TBME (200 mL), wash the organic phase twice with water / brine (ca. 5:1) and brine, and dry over MgSO4. Evaporate the TBME in a Rotavap at 20°C. The crude intermediate is purified by filtration with SiO2 (150 mL cartridge, 3 / 4 filled, DCM / TBME 10:1). The intermediate is used immediately in the next step.

[0112] 1 H NMR (500MHz, DMSO) δ:5.47(dd, J 1 =0.7Hz, J 2 =3.2Hz, 1H), 5.17(t, J=10.3Hz, 1H), 5.04(d, J=10.1Hz, 1H), 4.22(dd, J 1 =3.2Hz, J 2=10.4Hz, 1H), 4.15(ddd, J 1 =0.8Hz, J 2 =4.5Hz, J 3 =7.2Hz, 1H), 4.03-4.08(m, 1H), 3.97(dd, J 1 =7.4Hz, J 2 =11.7Hz, 1H), 2.18(s, 3H), 2.15(m, 3H), 2.04(s, 3H)

[0113] Intermediate 3: (2R,3R,4R,5R,6S)-2-(acetoxymethyl)-6-cyano-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diyl diacetate Dissolve intermediate 2 in DMF (80 mL), and add 5-ethynyl-1,2,3-trifluorobenzene (312 mg, 21.2 mmol, 0.8 eq), DIPEA (13.6 mL, 79.6 mmol, 3 eq), and CuI (505 mg, 2.65 mmol, 0.1 eq) under N2. Stir the yellow mixture at rt for 1 hour. Exothermic reaction occurs. Slowly dissolve the yellow solution. Pour into water (800 mL) and stir for 10 minutes. Filter the beige precipitate and discard the filtrate. Wash the beige solid with MeOH, then dissolve in EA (300 mL) and stir for 10 minutes. Filter the fine Cu residue, wash the filtrate with NH4Cl solution (semi-saturated) and brine, dry over MgSO4 and concentrate. Grind the residue with MeOH (ca 100 mL), filter, and dry under high heat to obtain the desired intermediate 3a as a beige solid.

[0114] 1 H NMR (500MHz, DMSO-d6) δ:8.85(s, 1H), 7.81-7.85(m, 2H), 5.91(m, 1H), 5.64(dd, J1=3.1Hz, J2=11.0Hz, 1H), 5.51(dd, J1=0.7Hz, J2=3 .0Hz, 1H), 5.24(d, J=9.9Hz, 1H), 4.43-4.46(m, 1H), 4.03-4.12(m, 2H), 2.10(s, 3H), 2.04(m, 3H), 1.94(m, 3H). LCMS(A):tR =0.97min;[M+H] + =497.21

[0115] Intermediate 3 is further functionalized as shown in the scheme below.

[0116] [ka]

[0117] Intermediate 4: (2R,3R,4S,5R,6R)-3,5-dihydroxy-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxylic acid Intermediate 3 (2800 mg, 5.64 mmol, 1 eq) is suspended in 25% HCl (20.6 mL, 169 mmol, 30 eq) and heated under reflux for 1.5 hours. The solution is poured onto an MCI® gel column (ca 100 mL gel) containing water. The column is eluted with water until it reaches a neutral pH (5 fractions, 40 mL). The compound is then eluted with H2O / MeCN (3:1). A 40 mL fraction is taken. The fraction containing the product is first concentrated under vacuum to remove MeCN, and then freeze-dried to obtain the title compound as a colorless solid. LCMS(A):t R =0.59min;[M+H]+=390.22 1 H NMR (500MHz, DMSO-d6) δ:12.88-12.90(br, 1H), 8.79(s, 1H), 7.86(dd, J 1 =6.8Hz, J 2 =9.1Hz, 2H), 5.43-5.46(m, 1H), 5.30(d, J=6.2Hz, 1H), 4.84(dd, J 1 =3.0Hz, J 2 =10.8Hz, 1H), 4.72(d, J=0.5Hz, 1H), 4.36(t, J=10.0Hz, 1H), 3.94(dd, J 1 =3.0Hz, J 2=6.0Hz, 1H), 3.85(d, J=9.4Hz, 1H), 3.71(t, J=6.5Hz, 1H), 3.48-3.55(m, 2H)

[0118] Intermediate 5: Methyl (4aR,6R,7R,8R,8aR)-7-hydroxy-2,2-dimethyl-8-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)hexahydropyrano[3,2-d][1,3]dioxin-6-carboxylate Step 1: Methyl (2R,3R,4S,5R,6R)-3,5-dihydroxy-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxylate To the suspension of intermediate 4 (14.2 g, 0.036 mol) in MeOH (60 ml) and THF (40 ml), add 1 M H2SO4 (1.82 ml, 0.00182 mol) in MeOH, which was freshly prepared by dissolving 95-98% H2SO4 (0.136 ml) in 2.5 ml of MeOH. Stir the mixture at rt for 72 hours. Add K2CO3 (0.25 g, 0.0018 mol), filter the mixture, and evaporate the solvent under vacuum. Purify the crude intermediate by filtration over SiO2 (EA / MeOH 9:1). Use the crude product—a colorless solid—in the next step without purification. LCMS(A):t R =0.85min;[M+H]+=403.87 Step 2: Methyl (4aR,6R,7R,8R,8aR)-7-hydroxy-2,2-dimethyl-8-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1-yl)hexa-hydropyrano[3,2-d][1,3]dioxin-6-carboxylate To a mixture of the crude product from step 1 (15.5 g, 0.038 mmol) and 2,2-dimethoxypropane (7.22 ml, 0.058 mmol) in THF (400 ml), PTSA (0.165 g, 0.001 mol) is added at rt. The reaction mixture is stirred at 75°C for 1.5 hours, during which time ca. 150 ml of solvent is removed from the mixture by distillation. The mixture is cooled to rt and fractionated between saturated NaHCO3 aqueous solution and EA. The aqueous layer is extracted again with EA. The organic layers are combined, washed with water and brine, dried over MgSO4, filtered, and evaporated under vacuum. The crude product—a yellowish solid—is used in the next step without purification. LCMS(A):t R =0.88min;[M+H]+=444.01

[0119] Intermediate 6: Methyl (4aR,6R,7R,8R,8aR)-7-methoxy-2,2-dimethyl-8-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1-yl)hexahydropyrano[3,2-d][1,3]dioxin-6-carboxylate To a solution of intermediate 5 (16.5 g, 0.037 mol) in DMF (180 ml), iodomethane (2.57 ml, 0.041 mol) and then NaH (60% dispersion in mineral oil, 1.57 g, 0.041 mol) are added at 0°C. The mixture is warmed to rt and stirred at rt for 4 hours. The mixture is cooled to 0°C, carefully quenched by adding water, and extracted twice with EA. The organic layers are washed together with water and brine, dried over MgSO4, filtered, and evaporated under vacuum. The crude product is purified by column chromatography (6 cm x 24 cm SiO2 column; gradient: heptane / EA 2:1 to heptane / EA 1:1) to obtain the desired product as a yellowish solid. LCMS(A):t R =0.98min;[M+H]+=458.03

[0120] Intermediate 7 (Acid 1): (4aR,6R,7R,8R,8aR)-7-methoxy-2,2-dimethyl-8-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1-yl)hexahydropyrano[3,2-d][1,3]dioxin-6-carboxylic acid The mixture of intermediate 6 (12.8 g, 0.028 mol) in THF / MeOH / H2O (3.2:1, 90 ml) and LiOH / H2O (1.77 g, 0.042 mmol) was stirred at rt for 2 hours. The mixture was diluted with water (100 ml) and the THF / MeOH was evaporated. Further water (100 ml) and citric acid (10% aqueous solution) were added to adjust the pH to 3. The suspension was filtered, the solid was washed with water, and the crude product—a colorless solid—was dried under hv. LCMS(A):t R =0.87min;[M+H]+=444.03

[0121] Intermediate 8 (Acid 21): (4aR,6R,7R,8S,8aR)-7-acetoxy-2,2-dimethyl-8-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1-yl)hexahydropyrano[3,2-d][1,3]dioxin-6-carboxylic acid The solution of intermediate 5 (0.779 g, 1.76 mmol) in THF / MeOH / H2O (3:2:1, 18 ml) and LiOH (64 mg, 2.64 mmol) is stirred at rt for 2 hours. The mixture is carefully diluted with aq. HCl (0.1 N, 100 ml) to pH 4. The mixture is extracted with EA, dried over MgSO4, filtered, and the solvent is evaporated. The crude product—a colorless solid—is dried under hv and used in the next step without purification. LCMS(A):t R =0.80min;[M+H]+=430.07 A solution of the acid from the previous step (0.420 g, 0.978 mol), Ac2O (0.19 ml, 1.96 mmol), and TEA (0.54 ml, 3.91 mmol) in DCM (20 ml) is stirred at rt for 4 days. The mixture is quenched with NH4Cl solution (saturated aqueous solution), water, and citric acid solution (5% aqueous solution), and extracted twice with DCM. The combined organic layers are dried over MgSO4, filtered, and evaporated under vacuum. The crude product - a beige solid - is dried under hv and used in the next step without purification. LCMS(A): t R = 0.88 min; [M + H]+ = 471.91 Acids 2 - 23 were synthesized in the same manner as Intermediate 7 (Acid 1) or Intermediate 8 (Acid 21) using the corresponding acetylene for the addition cyclization with Intermediate 2.

[0122]

Table 4

[0123]

Table 5

[0124]

Chem.

[0125] Intermediate 9: rac-(1S,2S)-2-((3-chlorophenyl)amino)cyclopentan-1-ol<XXX00989>6-oxabicyclo[3.1.0]hexane (400 mg, 4.76 mmol) and 3- To a solution of chloroaniline (667 mg, 5.23 mmol) in toluene (3 ml), add InCl3 (74 mg, 0.33 mmol) and stir the reaction mixture at 85°C for 40 hours. Add water and EA at rt and stir the mixture at rt for 30 minutes. Separate the aqueous phase and extract with EA. Combine the organic layers, dry over MgSO4, filter, and evaporate under vacuum. Purify the crude product by FC CombiFlash (12 g RediSep column, 0-100% EA in heptane within 10 min) to obtain the title intermediate 8 as a yellow oil. LCMS(A):t R =0.80min;[M+H]+=212.13

[0126] Intermediate 10 (Amine 1): rac-N-((1S,2S)-2-((tert-butyldimethylsilyl)oxy)cyclopentyl)-3-chloroaniline To a solution of intermediate 9 (200 mg, 0.94 mmol) and 2,6-lutidine (223 mg, 2.1 mmol) in DCM (3 ml), tert-butyldimethylsilyl trifluoromethanesulfonate (300 mg, 1.13 mmol) is added at 0°C, and the mixture is stirred at 0°C for 30 min. Water is added, the mixture is quenched with saturated NH4Cl aqueous solution, and extracted twice with DCM. The organic layers are washed with brine. The combined organic layers are dried over MgSO4, filtered, and concentrated. The crude product is purified by FC CombiFlash (40 g RediSep column, 0-100% EA in heptane within 10 min) to obtain intermediate 9 as a colorless oil. LCMS(A):t R =1.28min;[M+H]+=326.11 The following amines 2 to 24 are produced in two steps, similar to intermediate 9 (amine 1), by coupling the corresponding aniline with 6-oxabicyclo[3.1.0]hexane or 5-oxabicyclo[2.1.0]pentane, respectively.

[0127] [Table 6]

[0128] [Table 7] Manufacturing of Example B

[0129] [ka]

[0130] Example 1.1.1: (2R,3R,4S,5R,6R)-N-(3-chlorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide Step 1: (4aR,6R,7R,8R,8aR)-N-((1S,2S)-2-((tert-butyldimethylsilyl)oxy)cyclopentyl)-N-(3-chlorophenyl)-7-methoxy-2,2-dimethyl-8-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1-yl)hexahydropyrano[3,2-d][1,3]dioxin-6-carboxamide To a solution of Acid 1 (40 mg; 90 mmol) and Amine 1 (31 mg, 95 mmol) in DCM (4 mL), phosphorus oxychloride (V) (1 M solution in pyridine, 0.11 mL, 0.108 mmol) was added at rt, and the mixture was stirred at rt for 24 hours. Water was added, the mixture was quenched with saturated NH4Cl aqueous solution, and extracted twice with DCM. The organic layers were washed with brine. The combined organic layers were dried over MgSO4, filtered, and concentrated. The crude product was adsorbed onto an isolute and purified by FC CombiFlash (4 g RediSep column, 0-40% EA in heptane within 12 min) to obtain intermediate 11 (as a mixture of diastereomers). LCMS(A):t R =1.36 / 1.37min;[M+H]+=751.25 Step 2: (2R,3R,4S,5R,6R)-N-(3-chlorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxy To a solution of methyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1-yl)tetrahydro-2H-pyran-2-carboxamide intermediate 11 (mixture of diastereomers) (56 mg, 0.75 mmol) in dioxane (1 ml) and water (0.5 ml), TFA (0.46 ml, 6.0 mmol) was added at 0°C, and the reaction mixture was stirred in rt for 21 hours. The mixture was basicized with 25% NH4OH aqueous solution (to pH 11), filtered, and the product was purified by prep LCMS(I) to obtain the final compound as a mixture of diastereomers, which was then separated by chiral column chromatography.

[0131] Example 1.1.1: 1 H NMR (500MHz, DMSO) δ:8.99(s, 1H), 7.89(dd, J1=6.8Hz, J2=9.0Hz, 2H), 7.11-7.61(m, 4H), 5.32(d, J=6.0H) z, 1H), 4.90(d, J=5.4Hz, 1H), 4.73-4.85(m, 1H), 4.69(t, J=5.7Hz, 1H), 4.43-4.53(m, 1H), 4.39(dd, J1=9.1Hz, J2=10.7Hz, 1H), 3.65-3.85(m, 2H), 3.39-3.53(m, 3H), 3.21( t, J=6.3Hz, 1H), 3.07(m, 3H), 1.85-1.97(m, 1H), 1.69-1.80(m, 1H), 1.37-1.68(m, 4H). LC-MS(A):t R =0.94min;[M+H]+=597.08

[0132] Examples 1A.1.2 and 1H.1.2 were prepared from acid 21 in the same manner as in Example 1.1.1, as shown in the scheme below:

[0133] [ka] The following compounds are prepared from the corresponding acids and amines in the same manner as in Example 1.1.1, Example 1A.1.2, or Example 1H.1.2.

[0134] Table 8

[0135] Table 9

[0136] Table 10

[0137] Table 11

[0138] Table 12

[0139] Table 13

[0140] Table 14

[0141] Table 15

[0142] Table 16

[0143] Table 17

[0144] Table 18

[0145] [Table 19]

[0146] [Table 20]

[0147] [Table 21]

[0148] [Table 22]

[0149] [Table 23]

[0150] [Table 24]

[0151] [Table 25]

[0152] [Table 26]

[0153] [Table 27]

[0154] [Table 28] NMR of the selected example: Example 1.1.2: 1 1H NMR (500 MHz, C6D6) δ: 8.10 (s, 1H), 7.67 (s, 1H), 7.41 - 7.44 (m, 2H), 7.14 (s, 1H), 6.81 - 6.90 (m, 1H), 4.85 (m, 2H), 4.69 (dd, J1 = 9.3 Hz, J2 = 10.3 Hz, 1H), 4.31 (dd, J1 = 10.6 Hz, J2 = 2.4 Hz, 1H), 3.90 - 3.92 (m, 1H), 3.71 - 3.79 (m, 4H), 3.56 - 3.65 (m, 1H), 3.44 (d, J = 9.0 Hz, 1H), 3.07 (s, 3H), 2.37 (s, 1H), 1.56 - 1.74 (m, 2H), 1.26 - 1.48 (m, 2H), 0.98 - 1.16 (m, 1H), 0.79 - 0.93 (m, 1H)

[0155] Example 1.1.2R: 1 1H NMR (500 MHz, C6D6) δ: 7.92 (s, 1H), 7.41 (dd, J1 = 7.2 Hz, J2 = 8.4 Hz, 2H), 7.21 (d, J = 1.2 Hz, 2H), 7.10 (t, J = 1.8 Hz, 1H), 4.60 (m, 1H), 4.40 - 4.43 (m, 1H), 4.37 (dt, J1 = 7.8 Hz, J2 = 10.2 Hz, 1H), 4.25 (dd, J1 = 2.5 Hz, J2 = 10.6 Hz, 1H), 3.98 (dd, J1 = 4.1 Hz, J2 = 6.4 Hz, 1H), 3.63 - 3.66 (m, 2H), 3.56 (m, 1H), 3.47 (d, J = 9.0 Hz, 1H), 3.04 (s, 3H), 2.96 (d, J = 2.4 Hz, 1H), 2.80 - 2.93 (m, 1H), 2.40 (t, J = 3.9 Hz, 1H), 1.52 - 1.68 (m, 1H), 1.36 - 1.46 (m, 3H), 1.15 - 1.22 (m, 1H), 1.03 - 1.13 (m, 1H)

[0156] Example 1.1.4: 11H NMR (500 MHz, DMSO) δ: 9.01 (s, 1H), 8.19 (s, 1H), 7.89 (dd, J1 = 6.8 Hz, J2 = 8.9 Hz, 2H), 7.76 - 7.87 (m, 2H), 5.34 (d, J = 6.0 Hz, 1H), 4.99 (d, J = 5.5 Hz, 1H), 4.89 (dd, J1 = 10.8 Hz, J2 = 2.9 Hz, 1H), 4 .68 - 4.72 (m, 1H), 4.36 - 4.42 (m, 2H), 3.73 - 3.77 (m, 1H), 3.62 - 3.73 (m, 1H), 3.55 (m, 1H), 3.41 - 3.46 (m, 2H), 3.23 - 3.25 (m, 1H), 3.06 (m, 3H), 1.89 - 2.00 (m, 1H), 1.73 - 1.79 (m, 1H), 1.40 - 1.64 (m, 4H)

[0157] Example 1.1.5R: 1 1H NMR (500 MHz, DMSO) δ: 9.00 (s, 1H), 8.30 - 8.32 (m, 1H), 7.85 - 7.91 (m, 4H), 5.32 (d, J = 6.0 Hz, 1H), 5.03 (d, J = 5.8 Hz, 1H), 4.90 (dd, J1 = 2.9 Hz, J2 = 10.8 Hz, 1H), 4.67 (s, 1H), 4.50 - 4.52 (m, 1H), 4.38 (dd, J1 = 9.0 Hz, J2 = 10.7 Hz, 1H), 3.75 (m, 1H), 3.63 - 3.67 (m, 1H), 3.54 - 3.57 (m, 1H), 3.39 - 3.46 (m, 2H), 3.21 (m, 1H), 3.07 (s, 3H), 1.90 (m, 1H), 1.73 - 1.78 (m, 1H), 1.59 - 1.65 (m, 1H), 1.36 - 1.47 (m, 3H)

[0158] Example 2.1.1: 1H NMR (500MHz, DMSO) δ:9.01(s,1H),7.89(dd,J1=6.8Hz,J2=9.0Hz,2H),7.54-7.59(m,2H),7.05-7.41(m,2H) ,5.36-5.42(m,1H),5.30-5.34(m,1H),4.81-4.83(m,1H),4.70(m,2H),4.38(dd,J1=10.6 Hz, J2=9.1Hz, 1H), 3.74-3.81(m, 1H), 3.52-3.62(m, 1H), 3.50(m, 1H), 3.41-3.48(m, 2H) ,3.17-3.22(m,1H),3.05(s,3H),1.81-1.87(m,2H),1.40-1.43(m,1H),1.12-1.32(m,1H)

[0159] Example 2.1.2: 1 H NMR (500MHz, C6D6) δ:7.97(s,1H),7.40(dd,J1=6.7Hz,J2=8.1Hz,2H),7.40(m,1H),7.06(t,J=1.7Hz,1 H), 6.50-6.73 (m, 1H), 4.59 (m, 1H), 4.24-4.39 (m, 4H), 3.85 (q, J=7.8Hz, 1H), 3.56-3 .65(m, 3H), 3.39-3.47(m, 1H), 2.96(s, 3H), 2.73-2.82(m, 1H), 2.42(t, J=4.0Hz, 1H ), 1.69(q, J=9.2Hz, 1H), 1.46-1.53(m, 1H), 1.25(q, J=9.2Hz, 1H), 0.57-0.65(m, 1H)

[0160] Example 2.1.2R: 11H NMR (500 MHz, C6D6) δ: 7.94 (s, 1H), 7.39 - 7.42 (m, 2H), 7.05 (s, 1H), 6.98 (s, 2H), 4.56 (t, J = 9.5 Hz, 1H), 4.40 - 4.47 (m, 1H), 4.27 - 4.29 (m, 1H), 3.99 - 4.16 (m, 2H), 3.88 - 3.98 (m, 1H), 3.57 - 3.63 (m, 2H), 3.49 - 3.53 (m, 2H), 2.98 (s, 3H), 2.60 - 2.88 (m, 1H), 2.32 (d, J = 3.6 Hz, 1H), 1.76 (q, J = 9.0 Hz, 1H), 1.45 (t, J = 9.6 Hz, 1H), 1.19 - 1.25 (m, 1H), 0.67 - 0.76 (m, 1H)

[0161] Example 2.1.3: 1 1H NMR (500 MHz, DMSO) δ: 9.01 (s, 1H), 7.89 (dd, J1 = 6.8 Hz, J2 = 9.0 Hz, 2H), 7.40 (s, 1H), 6.96 - 7 .30 (m, 2H), 5.36 (d, J = 6.0 Hz, 1H), 5.33 (d, J = 6.0 Hz, 1H), 4.84 (dd, J1 = 10.8 Hz, J2 = 2.5 Hz, 1H), 4.60 - 4.78 (m, 2H), 4.39 (dd, J1 = 9.1 Hz, J2 = 10.7 Hz, 1H), 3.77 - 3.77 (m, J = 1.3 Hz, 1H), 3.57 - 3.65 (m, 1H), 3.37 - 3.55 (m, 3H), 3.20 (t, J = 6.2 Hz, 1H), 3.04 (m, 3H), 2.39 (s, 3H), 1.85 (m, 2H), 1.35 - 1.45 (m, 1H), 1.18 - 1.31 (m, 1H)

[0162] II. Biological Tests Evaluation of the inhibitory activity (IC 50 ) of the compound The inhibitory activity of the compound is determined in a competitive binding test. This spectrophotometric analysis measures the binding of the glycoprotein asialofetuin (ASF) to microplates adsorbed with biotin-labeled human Gal-3 (hGal-3) or human Gal-1 (hGal-1), respectively (Proc Natl Acad Sei USA. 2013 Mar 26;110(13):5052-7). Alternatively, and preferably, a human Gal-1 version in which all six cysteine ​​groups are replaced with serine may be used.

[0163] In summary, the compound is serially diluted in DMSO (test diluent). Biotin-labeled hGal-3 or hGal-1 is added to an ASF-coated 384-well plate in 22.8 μL / well of assay buffer (i.e., 300-1000 ng / ml of biotin-labeled hGal-3 or hGal-1), and then 1.2 μL of the compound test diluent is added and mixed.

[0164] Incubate the plate at 4°C for 3 hours, then wash with cold assay buffer (3 x 50 μl), incubate with 25 μL / well of streptavidin-peroxidase solution (diluted to 80 ng / ml with assay buffer) at 4°C for 1 hour, then wash again with assay buffer (3 x 50 μl). Finally, add 25 μL / well of ABTS substrate. Record OD (410 nm) after 30-45 mins and IC50. 50 Calculate the value.

[0165] The calculated IC 50 The values ​​may vary depending on the assay procedure each day. This type of variation is known to those skilled in the art. IC obtained from several measurements. 50 The values ​​are listed as averages.

[0166] [Table 29]

[0167] [Table 30]

[0168] Table 31

[0169] Table 32

Claims

1. Compounds of formula (I) or pharmaceutically acceptable salts thereof: 【Chemistry 1】 (In the formula, n represents the integer 1 or 2; Ar １ teeth, - An aryl molecule substituted with 1, 2, 3, 4, or 5 substituents, wherein the substituents are independently selected from halogens; methyl; cyano; methoxy; trifluoromethyl; and trifluoromethoxy; - A 5- or 6-membered heteroaryl, wherein the 5- or 6-membered heteroaryl is independently unsubstituted or substituted with one or two substituents, wherein the substituents are independently selected from halogen, methyl, cyano, and methoxy; or, - A 9 or 10-membered heteroaryl, wherein each of the 9 or 10-membered heteroaryls is independently unsubstituted or substituted by one methyl group; It represents; R １ teeth, - Hydroxyl; - C １－３ - Alkoxy; - -O-CO-C １－３ - Alkyl; - -O-CH ２ -CH ２ -OH; or, - -O-CH ２ -CO-OH; It represents; L represents a direct bond or methylene; Ar ２ teeth, - phenyl, wherein the phenyl is unsubstituted or substituted by 1, 2 or 3 substituents, and the substituents are selected independently from C １－６ - alkyl, C ３－６ - cycloalkyl, -CH ２ - C ３－６ - cycloalkyl, C １－３ - fluoroalkyl, C １－３ - fluoroalkoxy, C １－３ - alkoxy, halogen and cyano; phenyl - A 5- or 6-membered heteroaryl, wherein the 5- or 6-membered heteroaryl is independently unsubstituted or substituted with 1, 2, or 3 substituents, and the substituents are C １－６ - Alkyl, C ３－６ -Cycloalkyl, -CH ２ -C ３－６ - Cycloalkyl, C １－３ - Fluoroalkyl, C １－３ - Fluoroalkoxy, C １－３ - Five or six-membered heteroaryl compounds independently selected from alkoxy, halogen, and cyano compounds; - A 9-membered bicyclic heteroaryl or a 10-membered bicyclic heteroaryl, wherein the 9 or 10-membered bicyclic heteroaryl is independently unsubstituted or substituted with one or two substituents, the substituents being independently selected from methyl, methoxy, and halogen; or, - Naphthyl; (This represents...)

2. Equation (I Ｓ ) is also a compound of formula (I) as described in claim 1 or a pharmaceutically acceptable salt thereof. 【Chemistry 2】

3. Ar １ The compound according to claim 1 or 2 or a pharmaceutically acceptable salt thereof, wherein the substituent is phenyl, substituted with 1, 2, 3, 4 or 5 substituents, the substituents being independently selected from halogen; methyl; cyano; methoxy; trifluoromethyl; and trifluoromethoxy; and the compound according to claim 1 or 2 or a pharmaceutically acceptable salt thereof.

4. Ar １ The compound according to claim 1 or 2 or a pharmaceutically acceptable salt thereof.

5. Ar １ However, phenyl is represented by phenyl substituted with one, two, or three substituents, wherein the substituents are independently selected from halogens, methyl, cyano, and methoxy; At least one of the substituents is bonded at the meta or para position of the phenyl; - In particular, if a para substituent is present, the para substituent is selected from halogen, methyl, cyano, and methoxy; - In particular, if a substituent at the meta position is present, the substituent at the meta position is a halogen; the compound according to claim 1 or 2 or a pharmaceutically acceptable salt thereof.

6. R １ is a methoxy compound; the compound according to any one of claims 1 to 5 or a pharmaceutically acceptable salt thereof.

7. L represents a direct bond; the compound according to any one of claims 1 to 6 or a pharmaceutically acceptable salt thereof.

8. Ar ２ However, the phenyl is either unsubstituted or substituted with one, two, or three substituents, and the substituents are C １－６ - Alkyl, C ３－６ -Cycloalkyl, -CH ２ -C ３－６ - Cycloalkyl, C １－３ - Fluoroalkyl, C １－３ - Fluoroalkoxy, C １－３ - Representing phenyl, independently selected from alkoxy, halogen, and cyano; the compound according to any one of claims 1 to 7 or a pharmaceutically acceptable salt thereof.

9. Ar ２ However, it is phenyl, - Substituted by one substituent, the substituent is C １－４ - Alkyl, C １－３ - Selected from alkoxy, halogen, and cyano, with the substituent at the meta position; or, - Substituted by two substituents, the substituents are C １－４ - Alkyl, C １－３ - A compound independently selected from alkoxy, halogen, and cyano, wherein both substituents are in the meta position; representing phenyl; or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 7.

10. The compound in question, (2R,3R,4S,5R,6R)-N-(3-chlorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chloro-5-methylphenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1 ,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chloro-5-cyanophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-N-(3-iodophenyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dibromophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(3,5-difluorophenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-4-(4-(3,4-difluoro-5-methoxyphenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(3,4-difluoro-5-methoxyphenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dibromophenyl)-4-(4-(3,4-difluoro-5-methoxyphenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-4-(4-(3,4-difluoro-5-methoxyphenyl)-1H-1,2,3-triazole -1-yl)5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chloro-5-cyanophenyl)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazole-1-yl)-N-(3-chloro-5-cyanophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-3,5-difluorophenyl)-1H-1,2,3-triazole-1-yl)-N-(3-chloro-5-cyanophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-3,5-difluorophenyl)-1H-1,2,3-triazole-1-yl)-N-(3-bromo-5-cyanophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(3-chloro-4,5-difluorophenyl)-1H-1,2,3-triazole-1-yl)-N-(3-chloro-5-cyanophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(3-chloro-4,5-difluorophenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chloro-5-cyanophenyl)-4-(4-(3,4-dichlorophenyl)-1H-1,2,3-triazole-1-yl)-5 -Hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(3,4-dichlorophenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(3-chloro-5-fluorophenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(3-bromo-5-fluorophenyl)-1H-1,2,3-triazole-1-yl)-N-(3-chloro-5-cyanophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(3-bromo-5-fluorophenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(3-bromo-5-fluorophenyl)-1H-1,2,3-triazole-1-yl)-N-(3-cyano-5-fluorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(3-bromo-5-fluorophenyl)-1H-1,2,3-triazole-1-yl)-N-(3-cyano-5-methylphenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(3-bromo-5-fluorophenyl)-1H-1,2,3-triazole-1-yl)-N-(3-cyano-5-methoxyphenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chloro-5-cyanophenyl)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carbbox Thamid; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazole-1-yl)-N-(3,5-dichlorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazole-1-yl)-N-(3-chloro-5-cyanophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazole-1-yl)-N-(3-bromo-5-cyanophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazole-1-yl)-N-(3-cyano-5-fluorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(3-fluoro-4-methylphenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-cyano-5-methylphenyl)-4-(4-(3-fluoro-4-methylphenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazole-1-yl)-N-(3-chloro-5-cyanophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chloro-5-cyanophenyl)-4-(4-(3-fluorophenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(3-fluorophenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R, 3R, 4S, 5R, 6R)-N-(3-chloro-5-cyanophenyl)-4-( 4-(4-cyano-3-fluorophenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(4-cyano-3-fluorophenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-cyano-3-fluorophenyl)-1H-1,2,3-triazole-1-yl)-N-(3-cyano-5-methylphenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-cyano-3-fluorophenyl)-1H-1,2,3-triazole-1-yl)-N-(3-cyano-5-methoxyphenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(3,4-dichloro-5-fluorophenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chloro-5-cyanophenyl)-4-(4-(4-chlorophenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-bromophenyl)-1H-1,2,3-triazole-1-yl)-N-(3-chloro-5-cyanophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chlorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chloro-5-methylphenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chloro-5-cyanophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclobutyl)-6-(hydroxymethyl (Tyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-5-hydroxy-N-((1S,2S)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-N-(3-iodophenyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dibromophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-4-(4-(3,4-difluoro-5-methoxyphenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dibromophenyl)-4-(4-(3,4-difluoro-5-methoxyphenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-4-(4-(3,4-difluoro-5-methoxyphenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-3,5-difluorophenyl)-1H-1,2,3-triazole-1-yl)-N-(3-chloro-5-cyanophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-3,5-difluorophenyl)-1H-1,2,3-triazole-1-yl)-N-(3-bromo-5-cyanophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclobutyl)- 6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-3,5-difluorophenyl)-1H-1,2,3-triazole-1-yl)-N-(3-cyano-5-fluorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(3-chloro-4,5-difluorophenyl)-1H-1,2,3-triazole-1-yl)-N-(3-chloro-5-cyanophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(3-chloro-4,5-difluorophenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chloro-5-cyanophenyl)-4-(4-(3,4-dichlorophenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(3,4-dichlorophenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(3-chloro-5-fluorophenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(3-bromo-5-fluorophenyl)-1H-1,2,3-triazole-1-yl)-N-(3-cyano-5-methylphenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(3-bromo-5-fluorophenyl)-1H-1,2,3-triazole-1-yl)-N-(3-cyano-5-methoxyphenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazole-1-yl)-N-(3-chloro-5-cyanophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclobutyl)- 6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazole-1-yl)-N-(3-bromo-5-cyanophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazole-1-yl)-N-(3-cyano-5-fluorophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(4-cyano-3-fluorophenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-5-hydroxy-N-((1R,2R)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-N-(3-iodophenyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dibromophenyl)-4-(4-(3,4-difluoro-5-methoxyphenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chloro-5-cyanophenyl)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazole-1-yl)-N-(3-chloro-5-cyanophenyl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-3,5-difluorophenyl)-1H-1,2,3-triazole-1-yl)-N-(3-chloro-5-cyanophenyl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R, 3R, 4S, 5R, 6R)-4-(4-(3-chloro-4,5-difluorophen (Nyl)-1H-1,2,3-triazole-1-yl)-N-(3-chloro-5-cyanophenyl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chloro-5-cyanophenyl)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazole-1-yl)-N-(3-chloro-5-cyanophenyl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazole-1-yl)-N-(3-cyano-5-fluorophenyl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(3-fluoro-4-methylphenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-cyano-5-methylphenyl)-4-(4-(3-fluoro-4-methylphenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazole-1-yl)-N-(3-chloro-5-cyanophenyl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chloro-5-methylphenyl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclobutyl)-6-(hydroxymethylphenyl) (Tyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-5-hydroxy-N-((1R,2R)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-N-(3-iodophenyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromophenyl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-4-(4-(3,4-difluoro-5-methoxyphenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dibromophenyl)-4-(4-(3,4-difluoro-5-methoxyphenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-3,5-difluorophenyl)-1H-1,2,3-triazole-1-yl)-N-(3-chloro-5-cyanophenyl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(3-chloro-4,5-difluorophenyl)-1H-1,2,3-triazole-1-yl)-N-(3-chloro-5-cyanophenyl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(3-chloro-4,5-difluorophenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclobutyl)- 6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazole-1-yl)-N-(3-chloro-5-cyanophenyl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazole-1-yl)-N-(3-bromo-5-cyanophenyl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazole-1-yl)-N-(3-cyano-5-fluorophenyl)-5-hydroxy-N-((1R,2R)-2-hydroxycyclobutyl)-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chloro-5-cyanophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazole-1-yl)tetrahydro-2H-pyran-2-carboxamide; or (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-5-hydroxy-N-((1S,2S)-2-hydroxycyclopentyl)-6-(hydroxymethyl)-3-methoxy-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazole-1-yl)tetrahydro-2H-pyran-2-carboxamide; The compound according to claim 1 or a pharmaceutically acceptable salt thereof.

11. A pharmaceutical composition comprising a compound according to any one of claims 1 to 10 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

12. A compound according to any one of claims 1 to 10 or a pharmaceutically acceptable salt thereof, for use as a pharmaceutical.

13. An active ingredient comprising a compound described in any one of claims 1 to 10 or a pharmaceutically acceptable salt thereof, for organ fibrosis; liver diseases and disorders; cardiovascular diseases and disorders; proliferative disorders and cancers; inflammatory and autoimmune diseases and disorders; digestive diseases and disorders; pancreatic diseases and disorders; abnormal angiogenesis-related diseases and disorders; brain-related diseases and disorders; neuropathic pain and peripheral neuropathy; eye diseases and disorders; acute kidney injury and chronic kidney disease; interstitial lung diseases and disorders; or a prophylactic agent for transplant rejection.

14. A therapeutic agent for organ fibrosis; liver diseases and disorders; cardiovascular diseases and disorders; proliferative disorders and cancers; inflammatory and autoimmune diseases and disorders; digestive diseases and disorders; pancreatic diseases and disorders; angiogenesis-related diseases and disorders; brain-related diseases and disorders; neuropathic pain and peripheral neuropathy; eye diseases and disorders; acute kidney injury and chronic kidney disease; interstitial lung diseases and disorders; or transplant rejection, comprising as an active ingredient a compound described in any one of claims 1 to 10 or a pharmaceutically acceptable salt thereof.

15. Use of the compound or a pharmaceutically acceptable salt thereof described in any one of claims 1 to 10 in the manufacture of a pharmaceutical product for the prevention or treatment of organ fibrosis; liver diseases and disorders; cardiovascular diseases and disorders; proliferative disorders and cancers; inflammatory and autoimmune diseases and disorders; digestive diseases and disorders; pancreatic diseases and disorders; abnormal angiogenesis-related diseases and disorders; brain-related diseases and disorders; neuropathic pain and peripheral neuropathy; eye diseases and disorders; acute kidney injury and chronic kidney disease; interstitial lung diseases and disorders; or transplant rejection.

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