Hydroxyheterocycloalkane-carbamoyl derivatives

Abstract

The present invention relates to X, Ar 1 , Ar 2 , L, n, m and R 1 The present invention relates to compounds of formula (I) as described herein, their preparation, pharma- ceutically acceptable salts, 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] TIFF2024506182000060.tif75156

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 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, Gal-3 protein expression levels are 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 development 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 from 2018 showed that high Gal-3 plasma levels were associated with an increased risk of developing incidental CKD, particularly 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) and 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.2018, 14(1):75-92;DeRoo Gal-3 levels are significantly elevated in cardiovascular diseases such as those described in EP. et al., Blood. 2015, 125(11):1813-21 (Zhong X. et al., Clin Exp Pharmacol Physiol. 2019, 46(3):197-203). Serum 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, gastric system, 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).

[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 its natural carbohydrate ligand is required. [Overview of the project]

[0010] 1) In a first embodiment, the present invention relates to a compound of formula (I) or a pharmaceutically acceptable salt thereof (with the absolute configuration as shown in each formula): [Chemical formula]

[0011] (wherein, n and m each independently represent an integer of 1 or 2, and n + m is 2 or 3; X is O or NR 2 ; R 2 is hydrogen, C 1-3 -alkyl (especially methyl or ethyl), -CO-H, -SO2-C 1-3 -alkyl (especially SO2-CH3) or -CO-C 1-3 -alkyl (especially -CO-CH3); Ar 1 is -aryl (especially phenyl), which is substituted by 1, 2, 3, 4 or 5 substituents (especially substituted by 2 or 3 substituents), and the above substituents are halogen; methyl; cyano; methoxy; trifluoromethyl; trifluoromethoxy; and NR N11 R N12 (R N11 represents hydrogen, and R N12 represents hydroxy-C 2-3 -alkyl, or R N11 and R N12 together with the nitrogen atom to which they are attached form a 4- to 6-membered heterocyclyl selected from morpholin-4-yl, azetidin-1-yl, pyrrolidin-1-yl and piperidin-1-yl, and the 4- to 6-membered heterocyclyl is unsubstituted or substituted by one hydroxy. ) independently selected from (especially, the above substituents are independently selected from halogen or methyl. ), aryl (especially phenyl); - a 5- or 6-membered heteroaryl, wherein the 5- or 6-membered heteroaryl is independently unsubstituted or substituted by 1 or 2 substituents, and the above substituents are independently selected from halogen, methyl, cyano and methoxy, a 5- or 6-membered heteroaryl; 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; - -O-CO-C 1-3 -alkyl; - -O-CH2-CH2-OH; or, - -O-CH2-CO-R 1X (R 1X teeth, -- Hydroxy; -- Morpholin-4-yl; or, -NR N21 R N22 (R N21 and R N22 Together with the nitrogen atoms to which they are bound, they form a 4-6 member heterocyclil selected from azetidine-1-yl, pyrrolidine-1-yl, and piperidine-1-yl, and the 4-6 member heterocyclil has one hi It is replaced by Roxy. This represents... It represents; [such substituent R 1 C 1-3 - Represents alkoxy (especially methoxy). L represents direct bonding, methylene, or ethylene (especially direct bonding); Ar 2 teeth, - Phenyl or a 5- or 6-membered heteroaryl (especially phenyl), wherein the phenyl or 5- or 6-membered heteroaryl is independently unsubstituted or substituted with 1, 2, or 3 substituents (especially 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 - Independently selected from alkoxy (especially methoxy), halogen, morpholine-4-yl, amino, ethynyl and cyano (especially C 1-6 -Alkyl (especially methyl), C 1-3 -alkoxy (especially methoxy), halogen (independently selected from cyano), phenyl, or 5- or 6-membered heteroaryl (especially phenyl); - 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...)

[0012] In a secondary embodiment, in the compound of formula (I), or, with necessary modifications, in the compounds of formulas (II), (III), or (IV) below, the nitrogen atom that bonds the heterocycloalkane to the rest of the molecule and the hydroxy substituent of the heterocycloalkane are in a relative trans configuration. To avoid doubt, the compound of formula (I) is particularly as shown in embodiment 3) below. S Compounds of the formula (I shown in the following embodiment 4) R ) is a compound of these or any mixture thereof.

[0013] 2) A second aspect of the present invention relates to a compound of formula (I) according to aspect 1), which is also a compound of formula (II), formula (III), or formula (IV) (the absolute configuration is as shown in each formula):

[0014] [ka]

[0015] (In each of formulas (II), (III), or (IV), base X, Ar 1 Ar 2 , R1 And L are defined independently as in Embodiment 1).

[0016] In the first sub-embodiment, the compound of embodiment 2) is such that X is O; the group Ar 1 Ar 2 , R 1 And L independently represent compounds of formula (II), (III), or (IV), as defined in Embodiment 1).

[0017] In a second sub-embodiment, the compound of embodiment 2) is such that X is NR 2 (R 2 is hydrogen, C 1-3 -Alkyl (especially methyl or ethyl), -CO-H, -SO2-C 1-3 -alkyl (especially SO2-CH3), -CO-C 1-3 - Represents alkyl (especially -CO-CH3). ) and the group Ar 1 Ar 2 , R 1 And L independently represent compounds of formula (II), (III), or (IV), as defined in Embodiment 1).

[0018] 3) A third aspect of the present invention is the formula (I S Regarding the compound of formula (I) according to embodiment 1), which is also a compound of ): (The absolute configuration is as shown in each formula.)

[0019] [ka]

[0020] (In the formula, group X, Ar 1 Ar 2 , R 1 , L, m and n are as defined in Embodiment 1). In a particular embodiment, the formula (I S The compound of formula (II S ), formula (III S ) or formula (IV S It is also a compound of (assuming the absolute configuration is as shown in each formula):

[0021] [ka]

[0022] (Formula (II S ), formula (III S ) or formula (IV S In each of the following, base X, Ar 1 Ar 2 , R 1 And L are defined independently as in Embodiment 1).

[0023] In the first sub-embodiment, the compound of embodiment 3) is such that X is O; the group Ar 1 Ar 2 , R 1 And L are independently defined as in Embodiment 1), equation (II S ), (III S ) or (IV S It means a compound of ).

[0024] In a second sub-embodiment, the compound of embodiment 3) is such that X is NR 2 (R 2 is hydrogen, C 1-3 -Alkyl (especially methyl or ethyl), -CO-H, -SO2-C 1-3 -alkyl (especially SO2-CH3), -CO-C 1-3 - Represents alkyl (especially -CO-CH3). ) and the group Ar 1 Ar 2 , R 1 And L are independently defined as in Embodiment 1), equation (II S ), (III S ) or (IV S It means a compound of ).

[0025] 4) Another aspect of the present invention is formula (I R Regarding the compound of formula (I) according to embodiment 1), which is also a compound of ): (The absolute configuration is as shown in each formula.)

[0026] [ka]

[0027] (wherein the group X, Ar 1 , Ar 2 , R 1 , L, m and n are, independently, as defined in aspect 1).). In certain aspects, the compound of formula (I R ) is also a compound of formula (II R ), formula (III R ) or formula (IV R ) (assuming the absolute configuration is as shown in each formula):

[0028]

Chemical formula

[0029] (In each of formula (II R ), formula (III R ) or formula (IV R ), the groups X, Ar 1 , Ar 2 , R 1 and L are, independently, as defined in aspect 1).).

[0030] ​​​​​​​​​​​​​​​​​​​​​​​​​​​​Ar 2 , R 1 And L are independently defined as in Embodiment 1), equation (II R ), (III R ) or (IV R It means a compound of ).

[0032] 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 heterocycloalkane moiety. In certain embodiments, in the compound of formula (I), or, with necessary modifications, in the compounds of formula (II), (III), or (IV), the nitrogen atom that bonds the heterocycloalkane to the rest of the molecule, as shown in each formula, and the hydroxy substituent of the heterocycloalkane are in a relative trans configuration. To avoid doubt, the compound of formula (I) is particularly as shown in embodiment 3) of formula (I S Compounds of the form shown in aspect 4), formula (I R ) is a compound of these or any mixture thereof.

[0033] 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. Therefore, 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.

[0034] A specific compound (or comprehensive structure) is, for example, an (R)- or (S)-enantiomer. When described as being in a particular absolute configuration, such description is understood to mean each compound (or comprehensive structure) in an enriched, particularly essentially pure, enantiomer form. Similarly, when described as having a particular chiral center of a compound in a (R)- or (S)- configuration, or in a particular 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. Similarly, for example, two chiral centers in a cyclic group may exist in a particular relative configuration.

[0035] 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).

[0036] 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.

[0037] The present invention also relates to isotope-labeled, particularly 2 This also includes compounds of formula (I) according to H (deuterium) labeled embodiments 1) to 18), the isotope-labeled compounds being identical to compounds of formula (I), except that one or more atoms are replaced by atoms having the same atomic number but with atomic weights different from those normally found in nature. 2 H (deuterium) labeled formulas (I), (II), (III), (IV), (I s ), (II s ), (III s ), (IV s ), (I R ), (II R), (III R ), (IV R Compounds of (V) and (V) and their salts are included in the scope of the present invention. Heavier isotopes of hydrogen 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.

[0038] In this patent application, dotted lines represent the bonding points of the described groups. For example, the following groups

[0039] [ka]

[0040] This is a 3-fluorophenyl group.

[0041] When the plural form is used for compounds, salts, pharmaceutical compositions, diseases, etc., the singular compound is used. It is intended to also mean salt, etc.

[0042] Any reference to a compound of formula (I) according to aspects 1) to 18) shall, depending on the context, also be understood to refer to a salt of such compound (especially a pharmaceutically acceptable salt).

[0043] 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.

[0044] The definitions described herein refer to formulas (I), (II), (III), (IV), (I) defined in any one of aspects 1) to 17). s ), (II s ), (III s ), (IV s ), (I R ), (II R ), (III R ), (IV R This applies uniformly to compounds of (A) and (V), and applies throughout this specification and claims with necessary modifications unless a broader or narrower definition is given by a specific definition. Naturally, a definition or preferred definition of a term may independently (and together with) any of the terms defined herein or all of the other terms or each term in a preferred definition.

[0045] In this patent application, compounds are named using IUPAC nomenclature, but they can also be named using carbohydrate nomenclature. Therefore, the base:

[0046] [ka]

[0047] 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, where the bond site to the rest of the molecule is the carbon The absolute configuration of the carbon atom supporting the nyl group is either (2R)- or beta-. For example, the compound (2R,3R,4S,5R,6R)-N-(3-chlorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1-yl)tetrahydro-2H-pyran-2-carboxamide is understood to also be called: 1,3-di-deoxy-2-O-methyl-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1-yl]-N-(3-chlorophenyl)-N-((3S,4R)-4-hydroxy-3-tetrahydrofuranyl)-beta-D-galactopyranose-1-carboxamide.

[0048] 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 (to which such optional substituents may be attached, e.g., ring carbon atoms and / or ring nitrogen atoms with free valence in an aromatic ring) are understood to be substituted with hydrogen as appropriate. Similarly, when the term “optionally” is used with respect to (ring) heteroatoms, it 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.

[0049] The term "halogen" refers to fluorine, chlorine, bromine, or iodine (in particular, fluorine, chlorine, or bromine).

[0050] 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. 1 Or Ar 2 The substituent is "C 1-6 -When referring to alkyl, this term specifically means methyl. 2 is "C 1-6 When "-alkyl" is used to represent "C 1-3 The term "-alkyl" is used in the context of "-SO2-C 1-3 -alkyl or -CO-C 1-3 -alkyl" etc. 2 When used in relation to substituents, this term specifically means methyl.

[0051] 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, C1-3 -Fluoroalkyl groups have 1 to 3 carbon atoms and 1 to 7 hydrogen atoms are replaced by fluorine atoms.

[0052] 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.

[0053] 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.

[0054] 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.

[0055] The term "aryl," whether used alone or in combination, means phenyl or naphthyl, particularly phenyl, where the aryl group is either unsubstituted or substituted as explicitly defined. The substituent Ar represents "aryl." 1 Or Ar 2 In this regard, this term specifically refers to phenyl.

[0056] The term "heteroaryl," whether used alone or in combination, means 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 5-membered heteroaryl groups such as furanyl, oxazolyl, isoxazolyl, oxadiazolyl, thiophenyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, and tetrazolyl; 6-membered heteroaryl groups such as pyridinyl, pyrimidinyl, pyridadinyl, and pyrazinyl; and indolyl, isoindolyl, benzofuranyl, isobenzofuranyl, benzothiophenyl, indazolyl, benzimidazolyl, These are 8- to 10-membered bicyclic heteroaryl groups such as benzoxazolyl, benzoisoxazolyl, benzothiazolyl, benzoisothiazolyl, benzotriazolyl, benzoxadiazolyl, benzothiadiazolyl, thienopyridinyl, quinolinyl, isoquinolinyl, naphthilidinyl, cinolinyl, quinazolinyl, quinoxalinyl, phthalazinyl, pyrrolopyridinyl, pyrazolopyridinyl, pyrazolopyridinyl, pyrazolopyridinyl, pyrrolopyradinyl, imidazopyridadinyl, imidazopyridazolyl, and imidazothiazolyl. The above heteroaryl groups are either unsubstituted or substituted as explicitly defined.

[0057] Substituent Ar represents "5 or 6-membered heteroaryl" 1In this regard, this term specifically refers to thiazolyl (particularly 4-chlorothiazole-2-yl). The substituent Ar represents "a 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 either unsubstituted or substituted as expressly defined.

[0058] The substituent Ar represents a "9 or 10-membered bicyclic heteroaryl." 1 In this regard, this term specifically refers to benzothiazolyl (particularly 2-methylbenzo[d]thiazole-6-yl). The substituent Ar represents a "9-membered bicyclic heteroaryl." 2 In 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.

[0059] The term "cyano" means the base -CN.

[0060] 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.

[0061] Where not used in relation to temperature, the term "about" placed before a number "X" means in this application 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 "about" placed before a temperature "Y" means in this application 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 about 25°C.

[0062] Further aspects of the present invention are described below: 5) Another aspect is, Ar 1 The present invention relates to a compound representing phenyl, wherein the substituents are substituted with 1, 2, 3, 4, or 5 substituents (particularly substituted with 2 or 3 substituents), and the substituents are independently selected from halogens; methyl; cyano; and methoxy; and the present invention relates to a compound according to any of embodiments 1) to 4).

[0063] 6) Another aspect is, Ar 1 The present invention relates to a compound that represents phenyl, wherein the substituents are substituted with two or three substituents, the substituents being independently selected from halogens and methyl groups; this invention relates to a compound according to any of embodiments 1) to 4).

[0064] In a secondary embodiment, at least one of the substituents is bonded to the meta or para position of the phenyl molecule.

[0065] 7) Another aspect is Ar 1 However, phenyl is represented as phenyl substituted with two or three substituents, wherein the substituents are independently selected from halogens, methyl and cyano; At least one of the substituents is bonded at the meta or para position of the phenyl molecule; - In particular, if a substituent is present at the para position, that substituent at the para position is a halogen or a methyl group; - 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 4).

[0066] 8) Another aspect is, Ar 1 However, the term represents phenyl, which is 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 that substituent is particularly halogenated; the other substituent is particularly in the meta position of the other substituent. It is in the para position; or, - 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); This relates to compounds conforming to any of embodiments 1) to 4).

[0067] 9) Another aspect is, Ar 1 but,

[0068] [ka]

[0069] This relates to compounds that conform to any of embodiments 1) to 4).

[0070] In the secondary flight, Ar 1 In particular, represents a group selected from group A) or B):

[0071] [ka]

[0072] Each of the groups A) and B) forms a specific sub-common.

[0073] In another sub-aspect, Ar 1 In particular, represents a group selected from group C), D), or E):

[0074] [ka]

[0075] Each of the groups C), D), and E) forms a specific sub-model.

[0076] 10) Another aspect is R 1 The present invention relates to compounds that represent methoxy; according to any one of embodiments 1) to 9).

[0077] 11) Another aspect relates to a compound in which L represents a direct bond; following any one of aspects 1) to 10).

[0078] 12) 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 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); and conforming to any one of embodiments 1) to 11).

[0079] 13) Another aspect is, Ar 2 However, it is phenyl, substituted with one or two substituents, and the substituents are C 1-4 -Alkyl (especially methyl), 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); and conforming to any one of embodiments 1) to 11).

[0080] 14) 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 C 1-4 -Alkyl (especially methyl), C 1-3 - Independently selected from alkoxy (especially methoxy), halogen, and cyano (especially when the substituent is in the meta position); This relates to a compound representing phenyl; according to any one of embodiments 1) to 11).

[0081] 15) Another aspect is the fragment L-Ar 2 but:

[0082] [ka]

[0083] This relates to a compound that represents; conforms to any one of embodiments 1) to 10).

[0084] 16) 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 15) 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): 2+1、3+1、4+1、5+1、5+2+1、5+3+1、5+4+1、6+1、6+2+1、6+3+1、6+4+1、7+1、7+2+1、7+3+1、7+4+1、8+1、8+2+1、8+3+1、8+4+1、9+1、9+2+1、9+3+1、9+4+1、10+1、10+2+1、10+3+1、10+4+1、10+5+1、10+5+2+1、10+5+3+1、10+5+4+1、10+6+1、10+6+2+1、10+6+3+1、10+6+4+1、10+7+1、10+7+2+1、10+7+3+1、10+7+4+1、10+8+1、10+8+2+1、10+8+3+1、10+8+4+1、10+9+1、10+9+2+1、10+9+3+1、10+9+4+1、11+1、11+2+1、11+3+1、11+4+1、11+5+1、11+5+2+1、11+5+3+1、11+5+4+1、11+6+1、11+6+2+1、11+6+3+1、11+6+4+1、11+7+1、11+7+2+1、11+7+3+1、11+7+4+1、11+8+1、11+8+2+1、11+8+3+1、11+8+4+1、11+9+1、11+9+2+1、11+9+3+1、11+9+4+1、11+10+1、11+10+2+1、11+10+3+1、11+10+4+1、11+10+5+1、11+10+5+2+1、11+10+5+3+1、11+10+5+4+1、11+10+6+1、11+10+6+2+1、11+10+6+3+1、11+10+6+4+1、11+10+7+1、11+10+7+2+1、11+10+7+3+1、11+10+7+4+1、11+10+8+1、11+10+8+2+1、11+10+8+3+1、11+10+8+4+1、11+10+9+1、11+10+9+2+1、11+10+9+3+1、11+10+9+4+1、12+1、12+2+1、12+3+1、12+4+1、12+5+1、12+5+2+1、12+5+3+1、12+5+4+1、12+6+1、12+6+2+1、12+6+3+1、12+6+4+1、12+7+1、12+7+2+1、12+7+3+1、12+7+4+1、12+8+1、12+8+2+1、12+8+3+1、12+8+4+1、12+9+1、12+9+2+1、12+9+3+1、12+9+4+1、12+10+1、12+10+2+1、12+10+3+1、12+10+4+1、12+10+5+1、12+10+5+2+1、12+10+5+3+1、12+10+5+4+1、12+10+6+1、12+10+6+2+1、12+10+6+3+1、12+10+6+4+1、12+10+7+1、12+10+7+2+1、12+10+7+3+1、12+10+7+4+1、12+10+8+1、12+10+8+2+1、12+10+8+3+1、12+10+8+4+1、12+10+9+1、12+10+9+2+1、12+10+9+3+1、12+10+9+4+1、12+11+1、12+11+2+1、12+11+3+1、12+11+4+1、12+11+5+1、12+11+5+2+1、12+11+5+3+1、12+11+5+4+1、12+11+6+1、12+11+6+2+1、12+11+6+3+1、12+11+6+4+1、12+11+7+1、12+11+7+2+1、12+11+7+3+1、12+11+7+4+1、12+11+8+1、12+11+8+2+1、12+11+8+3+1、12+11+8+4+1、12+11+9+1、12+11+9+2+1、12+11+9+3+1、12+11+9+4+1、12+11+10+1、12+11+10+2+1、12+11+10+3+1、12+11+10+4+1、12+11+10+5+1、12+11+10+5+2+1、12+11+10+5+3+1、12+11+10+5+4+1、12+11+10+6+1、12+11、 +10+6+2+1、12+11+10+6+3+1、12+11+10+6+4+1、12+11+10+7+1、12+11+10+7+2+1、12+11+10+7+3+1、12+11+10+7+4+1、12+11+10+8+1、12+11+10+8+2+1、12+11+10+8+3+1、12+11+10+8+4+1、12+11+10+9+1、12+11+10+9+2+1、12+11+10+9+3+1、12+11+10+9+4+1、 13+1、13+2+1、13+3+1、13+4+1、13+5+1、13+5+2+1、13+5+3+1、13+5+4+1、13+6+1、13+6+2+1、13+6+3+1、13+6+4+1、13+7+1、13+7+2+1、13+7+3+1、13+7+4+1、13+8+1、13+8+2+1、13+8+3+1、13+8+4+1、13+9+1、13+9+2+1、13+9+3+1、13+9+4+1、13+10+1、13+10+2+1、13+10+3+1、13+10+4+1、13+10+5+1、13+10+5+2+1、13+10+5+3+1、13+10+5+4+1、13+10+6+1、13+10+6+2+1、13+10+6+3+1、13+10+6+4+1、13+10+7+1、13+10+7+2+1、13+10+7+3+1、13+10+7+4+1、13+10+8+1、13+10+8+2+1、13+10+8+3+1、13+10+8+4+1、13+10+9+1、13+10+9+2+1、13+10+9+3+1、13+10+9+4+1、13+11+1、13+11+2+1、13+11+3+1、13+11+4+1、13+11+5+1、13+11+5+2+1、13+11+5+3+1、13+11+5+4+1、13+11+6+1、13+11+6+2+1、13+11+6+3+1、13+11+6+4+1、13+11+7+1、13+11+7+2+1、13+11+7+3+1、13+11+7+4+1、13+11+8+1、13+11+8+2+1、13+11+8+3+1、13+11+8+4+1、13+11+9+1、13+11+9+2+1、13+11+9+3+1、13+11+9+4+1、13+11+10+1、13+11+10+2+1、13+11+10+3+1、13+11+10+4+1、13+11+10+5+1、13+11+10+5+2+1、13+11+10+5+3+1、13+11+10+5+4+1、13+11+10+6+1、13+11+10+6+2+1、13+11+10+6+3+1、13+11+10+6+4+1、13+11+10+7+1、13+11+10+7+2+1、13+11+10+7+3+1、13+11+10+7+4+1、13+11+10+8+1、13+11+10+8+2+1、13+11+10+8+3+1、13+11+10+8+4+1、13+11+10+9+1、13+11+10+9+2+1、13+11+10+9+3+1、13+11+10+9+4+1、14+1、14+2+1、14+3+1、14+4+1、14+5+1、14+5+2+1、14+5+3+1、14+5+4+1、14+6+1、14+6+2+1、14+6+3+1、14+6+4+1、14+7+1、14+7+2+1、14+7+3+1、14+7+4+1、14+8+1、14+8+2+1、14+8+3+1、14+8+4+1、14+9+1、14+9+2+1、14+9+3+1、14+9+4+1、14+10+1、14+10+2+1、14+10+3+1、14+10+4+1、14+10+5+1、14+10+5+2+1、14+10+5+3+1、14+10+5+4+1、14+10+6+1、14+10+6+2+1、14+10+6+3+1、14+10+6+4+1、14+10+7+1、14+10+7+2+1、14+10+7+3+1、14+10+7+4+1、14+10+8+1、14+10+8+2+1、14+10+8+3+1、14+10+8+4+1、14+10+9+1、14+10+9+2+1、14+10+9+3+1、14+10+9+4+1、14+11+1、14+11+2+1、14+11+3+1、14+11+4+1、14+11+5+1、14+11+5+2+1、14+11+5+3+1、14+11+5+4+1、14+11+6+1、14+11+6+2+1、14+11+6+3+1、14+11+6+4+1、14+11+7+1、14+11+7+2+1、14+11+7+3+1、14+11+7+4+1、14+11+8+1、14+11+8+2+1、14+11+8+3+1、14+11+8+4+1、14、 +11+9+1、14+11+9+2+1、14+11+9+3+1、14+11+9+4+1、14+11+10+1、14+11+10+2+1、14+11+10+3+1、14+11+10+4+1、14+11+10+5+1、14+11+10+5+2+1、14+11+10+5+3+1、14+11+10+5+4+1、14+11+10+6+1、14+11+10+6+2+1、14+11+10+6+3+1、14+11+10+6+4+1、14+11+10+7+1、14+11+10+7+2+1、14+11+10+7+3+1、14+11+10+7+4+1、14+11+10+8+1、14+11+10+8+2+1、14+11+10+8+3+1、14+11+10+8+4+1、14+11+10+9+1、14+11+10+9+2+1、14+11+10+9+3+1、14+11+10+9+4+1、 15+1、15+2+1、15+3+1、15+4+1、15+5+1、15+5+2+1、15+5+3+1、15+5+4+1、15+6+1、15+6+2+1、15+6+3+1、15+6+4+1、15+7+1、15+7+2+1、15+7+3+1、15+7+4+1、15+8+1、15+8+2+1、15+8+3+1、15+8+4+1、15+9+1、15+9+2+1、15+9+3+1、15+9+4+1、15+10+1、15+10+2+1、15+10+3+1、15+10+4+1、15+10+5+1、15+10+5+2+1、15+10+5+3+1、15+10+5+4+1、15+10+6+1、15+10+6+2+1、15+10+6+3+1、15+10+6+4+1、15+10+7+1、15+10+7+2+1、15+10+7+3+1、15+10+7+4+1、15+10+8+1、15+10+8+2+1、15+10+8+3+1、15+10+8+4+1、15+10+9+1、15+10+9+2+1、15+10+9+3+1、15+10+9+4+1。

[0085] 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).

[0086] 17) 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 (V) (with absolute configurations as shown in each formula):

[0087] [ka]

[0088] (In the formula, X is O or NR 2 Represents; R 2 is hydrogen, C 1-3 -Alkyl (especially methyl or ethyl) (Lu), -CO-H, -SO2-C 1-3 -alkyl (especially SO2-CH3) or -CO-C 1-3 - Represents alkyl (especially -CO-CH3); Ar 1 is phenyl, substituted with 1, 2, 3, 4, or 5 substituents (especially substituted with 2 or 3 substituents), wherein the substituents are independently selected from halogens; methyl; cyano; and methoxy (especially independently selected from halogens and methyl), and represents phenyl; [BaseAr 1 This specifically refers to a base described in either embodiment 9) or its sub-embodiments. R 1 teeth, - Hydroxy; - C 1-3 -alkoxy; - -O-CO-C 1-3 -alkyl; - -O-CH2-CH2-OH; or, - -O-CH2-CO-OH; It represents; [such substituent R 1 C 1-3 - Represents alkoxy (especially methoxy). L represents a direct bond or methylene (especially a direct bond); Ar 2 teeth, - Phenyl, wherein the phenyl is unsubstituted or substituted with one, two, or three substituents (in particular, substituted with one or two substituents), the substituents being independently selected from methyl, methoxy, halogen, and cyano; This represents... The features disclosed in aspects 2) to 16) are intended to be applied to compounds of formula (V) according to aspect 17) with necessary modifications.

[0089] 18) 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-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-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-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-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-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-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-dichlorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-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-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-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-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-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-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-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-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-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-cyano-5-methoxyphenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-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-cyano-5-methylphenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-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-cyano-5-fluorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-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)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3,5-dichlorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-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-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-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-methylphenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-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-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-3-methoxytetrahydro-2H-pyran-2- Carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dibromophenyl)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-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-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-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-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-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-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-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-(3,5-dichlorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-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-(3,5-dibromophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-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-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-4-(4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-3-methoxytetrahydro-2H-pyran -2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-4-(4-(3,4-dichlorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dibromophenyl)-4-(4-(3,4-dichlorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-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-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-4-(4-(3,4-dichlorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chlorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-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-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-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-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-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-dichlorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-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-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-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-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1-yl)tetrahydro-2H-pyran-2-carb Xamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-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-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-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-cyano-5-methoxyphenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-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-cyano-5-methylphenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-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-cyano-5-fluorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-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)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3,5-dichlorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-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-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-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-methylphenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-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-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dibromophenyl)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-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-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-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-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-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-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-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-(3,5-dichlorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-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-(3,5-dibromophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-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-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-4-(4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-4-(4-(3,4-dichlorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-3-methoxytetrahydro-2H-pyran-2-carboxamide ; (2R,3R,4S,5R,6R)-N-(3,5-dibromophenyl)-4-(4-(3,4-dichlorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-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-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-4-(4-(3,4-dichlorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4S)-4-hydroxypyrrolidine-3-yl)-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-6-(hydroxymethyl)-N-((3S,4S)-4-hydroxypyrrolidine-3-yl)-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-6-(hydroxymethyl)-N-((3S,4S)-4-hydroxypyrrolidine-3-yl)-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)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-N-(3,5-dichlorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4S)-4-hydroxypyrrolidine-3-yl)-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-6-(hydroxymethyl)-N-((3S,4S)-4-hydroxypyrrolidine-3-yl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4S)-4-hydroxypyrrolidine-3-yl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-4-(4-(3,4-dichlorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4S)-4-hydroxypyrrolidine-3-yl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4R)-4-hydroxypyrrolidine-3-yl)-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-6-(hydroxymethyl)-N-((3R,4R)-4-hydroxypyrrolidine-3-yl)-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-6-(hydroxymethyl)-N-((3R,4R)-4-hydroxypyrrolidine-3-yl)-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)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4R)-4-hydroxypyrrolidine-3-yl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4S)-4-hydroxypyrrolidine-3-yl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4R)-4-hydroxypyrrolidine-3-yl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-((3S,4S)-1-acetyl-4-hydroxypyrrolidine-3-yl)-N-(3,5-dichlorophenyl)-5-hydroxy-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-((3S,4S)-1-acetyl-4-hydroxypyrrolidine-3-yl)-N-(3-bromo-5-methylphenyl)-5-hydroxy-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-((3S,4S)-1-acetyl-4-hydroxypyrrolidine-3-yl)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazole-1-yl)-N-(3,5-dichlorophenyl)-5-hydroxy-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-((3S,4S)-1-acetyl-4-hydroxypyrrolidine-3-yl)-N-(3,5-dibromophenyl)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-((3S,4S)-1-acetyl-4-hydroxypyrrolidine-3-yl)-N-(3-bromo-5-methylphenyl)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-((3S,4S)-1-acetyl-4-hydroxypyrrolidine-3-yl)-N-(3-bromo-5-methylphenyl)-4-(4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-((3R,4R)-1-acetyl-4-hydroxypyrrolidine-3-yl)-N-(3,5-dichlorophenyl)-5-hydroxy-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-((3R,4R)-1-acetyl-4-hydroxypyrrolidine-3-yl)-N-(3-bromo-5-cyanophenyl)-5-hydroxy-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-((3R,4R)-1-acetyl-4-hydroxypyrrolidine-3-yl)-N-(3-bromo-5-methylphenyl)-5-hydroxy-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-((3R,4R)-1-acetyl-4-hydroxypyrrolidine-3-yl)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazole-1-yl)-N-(3,5-dichlorophenyl)-5-hydroxy-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-((3R,4R)-1-acetyl-4-hydroxypyrrolidine-3-yl)-N-(3,5-dibromophenyl)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-((3R,4R)-1-acetyl-4-hydroxypyrrolidine-3-yl)-N-(3-bromo-5-methylphenyl)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-((3R,4R)-1-acetyl-4-hydroxypyrrolidine-3-yl)-N-(3-bromo-5-methylphenyl)-4-(4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-((3S,4S)-1-acetyl-4-hydroxypyrrolidine-3-yl)-N-(3,5-dibromophenyl)-5-hydroxy-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-((3R,4R)-1-acetyl-4-hydroxypyrrolidine-3-yl)-N-(3,5-dibromophenyl)-5-hydroxy-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-((3S,4S)-1-acetyl-4-hydroxypyrrolidine-3-yl)-N-(3,5-dichlorophenyl)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-((3R,4R)-1-acetyl-4-hydroxypyrrolidine-3-yl)-N-(3,5-dichlorophenyl)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-((3S,4S)-1-acetyl-4-hydroxypyrrolidine-3-yl)-4-(4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazole-1-yl)-N-(3,5-dichlorophenyl)-5-hydroxy-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-((3R,4R)-1-acetyl-4-hydroxypyrrolidine-3-yl)-4-(4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazole-1-yl)-N-(3,5-dichlorophenyl)-5-hydroxy-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-((3S,4S)-1-acetyl-4-hydroxypyrrolidine-3-yl)-4-(4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazole-1-yl)-N-(3,5-dibromophenyl)-5-hydroxy-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-((3R,4R)-1-acetyl-4-hydroxypyrrolidine-3-yl)-4-(4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazole-1-yl)-N-(3,5-dibromophenyl)-5-hydroxy-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-((3S,4S)-1-acetyl-4-hydroxypyrrolidine-3-yl)-N-(3,5-dichlorophenyl)-4-(4-(3,4-dichlorophenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-((3R,4R)-1-acetyl-4-hydroxypyrrolidine-3-yl)-N-(3,5-dichlorophenyl)-4-(4-(3,4-dichlorophenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-N-((3S,4S)-1-formyl-4-hydroxypyrrolidine-3-yl)-5-hydroxy-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)-N-((3S,4S)-1-formyl-4-hydroxypyrrolidine-3-yl)-5-hydroxy-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)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazole-1-yl)-N-(3,5-dichlorophenyl)-N-((3S,4S)-1-formyl-4-hydroxypyrrolidine-3-yl)-5-hydroxy-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazole-1-yl)-N-((3S,4S)-1-formyl-4-hydroxypyrrolidine-3-yl)-5-hydroxy-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-N-((3R,4R)-1-formyl-4-hydroxypyrrolidine-3-yl)-5-hydroxy-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)-N-((3R,4R)-1-formyl-4-hydroxypyrrolidine-3-yl)-5-hydroxy-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)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazole-1-yl)-N-((3R,4R)-1-formyl-4-hydroxypyrrolidine-3-yl)-5-hydroxy-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-5-hydroxy-N-((3S,4S)-4-hydroxy-1-methylpyrrolidine-3-yl)-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)-N-((3S,4S)-1-ethyl-4-hydroxypyrrolidine-3-yl)-5-hydroxy-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-((3S,4S)-4-hydroxy-1-(methylsulfonyl)pyrrolidine-3-yl)-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-6-(hydroxymethyl)-N-((3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl)-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-6-(hydroxymethyl)-N-((3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl)-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-6-(hydroxymethyl)-N-((3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl)-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-6-(hydroxymethyl)-N-((3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl)-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-6-(hydroxymethyl)-N-((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)-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-6-(hydroxymethyl)-N-((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)-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-6-(hydroxymethyl)-N-((3S,4S)-4-hydroxytetrahydro-2H-pyran-3-yl)-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-6-(hydroxymethyl)-N-((3S,4S)-4-hydroxytetrahydro-2H-pyran-3-yl)-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-6-(hydroxymethyl)-N-((3R,4R)-4-hydroxytetrahydro-2H-pyran-3-yl)-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-6-(hydroxymethyl)-N-((3R,4R)-4-hydroxytetrahydro-2H-pyran-3-yl)-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-6-(hydroxymethyl)-N-((3S,4S)-3-hydroxypiperidine-4-yl)-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-6-(hydroxymethyl)-N-((3S,4S)-3-hydroxypiperidine-4-yl)-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-6-(hydroxymethyl)-N-((3S,4S)-3-hydroxypiperidine-4-yl)-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-6-(hydroxymethyl)-N-((3R,4R)-3-hydroxypiperidine-4-yl)-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-6-(hydroxymethyl)-N-((3S,4S)-4-hydroxypiperidine-3-yl)-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-6-(hydroxymethyl)-N-((3S,4S)-4-hydroxypiperidine-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1-yl)tetrahydro-2H-pyran-2-carboxamide; and (2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4R)-4-hydroxypiperidine-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1-yl)tetrahydro-2H-pyran-2-carboxamide.

[0090] Compounds of formula (I) according to embodiments 1) to 18) 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).

[0091] 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.

[0092] 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 18). In a secondary embodiment of the present invention, the dose is between 1 mg and 1000 mg per day.

[0093] To avoid any doubt, if a compound is described as useful for the prevention or treatment of a certain disease, then such a compound is also described as useful for the prevention or treatment of that disease. Such compounds are suitable for use in the manufacture of pharmaceuticals. Similarly, such compounds are also suitable in methods for the prevention or treatment of such diseases, which involve administering an effective amount of such compound to a subject (mammal, especially human) that requires it.

[0094] 19) Another embodiment relates to a compound of formula (I) as defined in any one of embodiments 1) to 18) 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.

[0095] 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.

[0096] Diseases or 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 or 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) Diseases; liver tumors; celiac disease, autoimmune hemolytic anemia, IBD, autoimmune thyroiditis, ulcerative colitis, diabetes mellitus, glomerulonephritis, pericarditis, autoimmune thyroiditis, hyperthyroidism, polymyositis, Sjögren's syndrome, pancreatitis, alveolitis, or alcoholic steatohepatitis; cirrhosis associated with dementia; cirrhosis associated with peripheral neuropathy; cirrhosis associated with oral or esophageal cancer; non-alcoholic fatty liver disease (especially non-alcoholic steatohepatitis) 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); 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; in particular, such cellular proliferative disorders and cancers include cancers of the thyroid, central nervous system, tongue, breast, digestive system, head and neck squamous epithelial cells, pancreas, bladder, kidney, liver, parathyroid gland, or salivary gland; or lymphoma; carcinoma, non-small cell lung cancer, melanoma, or neuroblastoma). - Inflammatory and autoimmune diseases and disorders (chronic and acute inflammatory and autoimmune diseases and disorders (especially sepsis, Q fever, asthma, rheumatoid arthritis, multiple sclerosis, SLE, SSc, polymyositis) This includes inflammation, 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.

[0097] 20) Further embodiments relate to compounds of formula (I) for use in accordance with embodiment 19), 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.

[0098] 21) Further embodiments relate to compounds of formula (I) for use in accordance with embodiment 19), wherein the compound is for use in the prevention or treatment of cardiovascular diseases and disorders.

[0099] 22) Further embodiments relate to compounds of formula (I) for use in accordance with embodiment 19), wherein the compound is for use in the prevention or treatment of acute kidney injury and chronic kidney disease (CKD).

[0100] 23) Further embodiments relate to compounds of formula (I) for use in accordance with embodiment 19), wherein the compound is for use in the prevention or treatment of (acute or chronic) liver diseases and disorders.

[0101] 24) Further embodiments relate to compounds of formula (I) for use in accordance with embodiment 19), wherein the compound is for use in the prevention or treatment of interstitial lung disease and impairment.

[0102] 25) Further embodiments relate to compounds of formula (I) for use in accordance with embodiment 19), wherein the compound is for use in the prevention or treatment of eye diseases and disorders.

[0103] 26) Further embodiments relate to compounds of formula (I) for use in accordance with embodiment 19), wherein the compound is for use in the prevention or treatment of cell proliferation disorders and cancer.

[0104] In particular, such cell proliferative disorders and cancers include cancers of the thyroid, central nervous system, tongue, breast, digestive system, head and neck squamous epithelial cells, pancreas, bladder, kidney, liver, parathyroid or salivary gland; or lymphoma; carcinoma, non-small cell lung cancer, melanoma or neuroblastoma.

[0105] 27) Further embodiments relate to compounds of formula (I) for use in accordance with embodiment 19), wherein the compound is intended for use in the prevention or treatment of chronic or acute inflammatory and autoimmune diseases and disorders.

[0106] 28) Further embodiments relate to compounds of formula (I) for use in accordance with embodiment 19), wherein the compound is for use in the prevention or treatment of gastrointestinal diseases and disorders.

[0107] 29) A further aspect relates to a compound of formula (I) for use according to aspect 19), wherein the compound is for use in the prevention or treatment of pancreatic diseases and disorders.

[0108] 30) A further aspect relates to a compound of formula (I) for use according to aspect 19), wherein the compound is for use in the prevention or treatment of diseases and disorders associated with abnormal angiogenesis.

[0109] 31) A further aspect relates to a compound of formula (I) for use according to aspect 19), wherein the compound is for use in the prevention or treatment of brain-related diseases and disorders.

[0110] 32) A further aspect relates to a compound of formula (I) for use according to aspect 19), wherein the compound is for use in the prevention or treatment of neuropathic pain and peripheral neuropathy.

[0111] 33) A further aspect relates to a compound of formula (I) for use according to aspect 19), wherein the compound is for use in the treatment of transplant rejection.

[0112] Furthermore, any suitability and (sub)aspects shown for the compound of formula (I) also apply to the compounds of formula (II), (III), (IV), (I s ), (II s ), (III s ), (IV s ), (I R ), (II R ), (III R ), (IV R ), and (V) with the necessary modifications (regardless of whether it is about the compound itself, its salts, compositions having the compound or its salts, or the use of the compound or its salts, etc.).

[0113] <00009​​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, integers n and m and the inclusive group, R 1 , L, Ar 1 Ar 2 n and m 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 2 n and m 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," TWGreene, PGMWuts, Wiley-Interscience, 1999). For this purpose, such a protecting group is It is assumed that these are introduced as necessary. In some cases, the final product may be further modified, for example, by manipulating substituents to obtain new final products. Such manipulations 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.

[0114] 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.

[0115] 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 of structure 1 is produced by coupling it with the compound of 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 can be used together with pyridine as the base. 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 1 This corresponds to the compound of structure 3. Next, the compound of formula (I) is deprotected to obtain the compound of formula (I).

[0116] [ka]

[0117] 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.

[0118] [ka]

[0119] 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 can be obtained, for example, by reacting the compound of structure 5 with the compound of structure 6 in a solvent such as THF or DMF in the presence of CuI and DIPEA (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 prepared 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).

[0120] 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 amines of 3,6-dioxabicyclo[3.1.0]hexane, tert-butyl 6-oxa-3-azabicyclo[3.1.0]hexane-3-carboxylate, 1-(6-oxa-3-azabicyclo[3.1.0]hexane-3-yl)ethane-1-one, 3,7-dioxabicyclo[4.1.0]heptane, or tert-butyl 7-oxa-3-azabicyclo[4.1.0]heptane-3-carboxylate.

[0121] In coupling with the compound of structure 1, the compound of structure 2 is used as a racemate or a separated enantiomer. The diastereomer of structure 3 or formula I (after deprotection) is separated using an achiral or chiral stationary phase, using techniques well known to those skilled in the art, such as chiral preparative HPLC. Commonly used achiral or chiral stationary phases for chiral preparative HPLC include, for example, Waters XBridge C18, 10 μm OBD, 30 x 75 mm, or Daicel Chiralcel OZ-H (5 μm) column, Daicel ChiralCel OJ-H (5-10 μm) column, ChiralPak IC (5 μm) column, ChiralPak ID (5 μm) column, and ChiralPak These are IG (5 μm) column, ChiralPak IH (5 μm) column, ChiralPak IE (5 μm) column, ChiralPak AS-H (5 μm), AD-H (5 μm) or IB (5 μm) column.

[0122] Typical conditions for chiral HPLC involve elution at flow rates of 0.8–160 mL / min. This is a gradient-free mixture of solution A (CO2) and eluate B (DCM / MeOH, MeCN / MeOH, MeCN / EtOH, 0.1% Et2NH in EtOH, MeOH, EtOH, iPrOH). 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. If the diastereomers are not separated, IC 50 The values ​​are measured for a mixture of diastereomers.

[0123] Experiment section The following examples illustrate the present invention, but are not intended to limit its scope in any way.

[0124] Temperatures are all shown in °C. Commercially available starting materials were used as received without further purification. Unless otherwise stated, all reactions were carried out under a nitrogen or argon atmosphere. Compounds were purified by flash chromatography on silica gel (Biotage, Redisep), preparative TLC (TLC plates from Merck, Silica gel 60 F 254 ), or by preparative HPLC. The compounds described in the present invention were 1 characterized by 1H-NMR (Bruker Neo, 400 MHz Ultra Shield™ or Bruker Avance III HD, Ascend 500 MHz); chemical shifts are shown in ppm relative to the solvent used; multiplicities: s = singlet, d = doublet, t = triplet, q = quartet, quint = quintet, hex = sextet, hept = heptet, m = multiplet, br = broad; coupling constants are shown in Hz.) and / or LC-MS (retention time t R is shown in min; molecular weights obtained from mass spectrometry are shown in g / mol.) using the conditions described below.

[0125] Qualitative analysis methods used The LC-MS retention times were obtained using the following elution conditions: A) LC-MS (A): Zorbax RRHD SB-Aq, 1.8 μm, 2.1 x 50 mm column temperature-controlled at 40 °C. The two elution solvents were as follows: Solvent A = water + 0.04% TFA; Solvent B = MeCN. The flow rate of the eluent was 0.8 mL / min, and the characteristics of the ratio of the elution mixture related to the time t from the start of elution are summarized in the following table (a linear gradient is used between two consecutive time points):

[0126] [Table 1]

[0127] Purification by preparative LC-MS was carried out using the conditions described below.

[0128] 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):

[0129] [Table 2]

[0130] 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):

[0131] [Table 3]

[0132] Abbreviations (as used herein): ABTS 2,2'-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) Acetyl acetate, etc. 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. N normality NaOH (Sodium Hydroxide) OD optical density o / n overnight org.organic Pg protecting group Ph Phenyl PTSA (p-toluenesulfonic acid) rt room temperature sat. saturation TBME tert-butylmethyl ether TBS tert-butyldimethylsilyl tBu tert-butyl = tertiary butyl TEA (Triethylamine) Tf Trifluoromethanesulfonate TFA (Trifluoroacetic Acid) THF (Tetrahydrofuran) TMS (trimethylsilyl) T3P Propylphosphonic Acid Anhydride t R retention time

[0133] A. Production of precursors and intermediates Production of intermediates for structure 1 The following precursors were prepared for the synthesis of the compound:

[0134] [ka]

[0135] 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 Ref:Carbohydrate Research 1994, 251, 33-67 and references cited herein.

[0136] 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.

[0137] 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) 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 Intermediate 2 is dissolved in DMF (80 mL), and 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) are added under N2. The yellow mixture is stirred at rt for 1 hour. Exothermic reaction occurs. The yellow solution is slowly poured into water (800 mL) and stirred for 10 minutes. The beige precipitate is filtered, and the filtrate is discarded. The beige solid is washed with MeOH, then dissolved in EA (300 mL), and stirred for 10 minutes. The fine Cu residue is filtered, the filtrate is washed with NH4Cl solution (half-saturated) and brine, dried over MgSO4, and concentrated. The residue is pulverized with MeOH (ca 100 mL), filtered, and dried under hv to obtain the desired intermediate 3a as a beige solid.

[0138] 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):t R =0.97min;[M+H] + =497.21 Intermediate 3 is further functionalized as shown in the scheme below.

[0139] [ka]

[0140] 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) 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 newly prepared by dissolving 95-98% H2SO4 (0.136 ml) in 2.5 ml of MeOH. Stir the mixture over the weekend at rt. K2 Add CO3 (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 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 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 Acids 2-6 are synthesized in the same way as acid 1, using the corresponding acetylene for cycloaddition via intermediate 2.

[0141] [Table 4]

[0142] Production of intermediate for structure 2

[0143] [ka]

[0144] Intermediate 7: 4-((3-chlorophenyl)amino)tetrahydrofuran-3-ol Step 1: Add InCl3 (71 mg, 0.32 mmol) to a solution of 3,6-dioxabicyclo[3.1.0]hexane (400 mg, 4.55 mmol) and 3-chloroaniline (639 mg, 5.01 mmol) in toluene (4 ml), and stir the reaction mixture at 85°C for 3 days. Add water and EA at rt and stir the mixture at rt for 30 min. 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 prep.LC-MS MS(II) to obtain the title intermediate 7 as a yellow oil. LCMS(A):t R =0.72min;[M+H] + =214.06 Amine 1: 4-((tert-butyldimethylsilyl)oxy)-N-(3-chlorophenyl)tetrahydrofuran-3-amine Step 2: Add tert-butyldimethylsilyl trifluoromethanesulfonate (447 mg, 1.69 mmol) to a solution of intermediate 7 (250 mg, 1.41 mmol) and 2,6-lutidine (333 mg, 3.1 mmol) in DCM (10 ml) at 0°C, and stir the mixture at 0°C for 1 hour. Add water and quench the mixture with saturated NH4Cl aqueous solution. Extract twice using DCM. Wash the organic layer with brine. Combine the organic layers, dry over MgSO4, filter, and concentrate. Purify the crude product using FC CombiFlash (24g RediSep column, 0-30% EA in heptane within 10 min) to obtain amine 1 as a colorless oil. LCMS(A):t R =1.21min;[M+H] + =328.05 The amines 2-11 below are produced in two steps, similar to amine 1, by coupling the corresponding aniline with 3,6-dioxabicyclo[3.1.0]hexane.

[0145] [Table 5]

[0146] Amines 12 and 13 below are prepared in two steps, similar to amine 1, by coupling the corresponding aniline with tert-butyl 6-oxa-3-azabicyclo[3.1.0]hexane-3-carboxylate. After separating the enantiomers by chiral chromatography, they are silylated and used for amide coupling.

[0147] [ka]

[0148] [Table 6]

[0149] The amines 14-17 below are produced in two steps, similar to amine 1, by coupling with the corresponding aniline 1-(6-oxa-3-azabicyclo[3.1.0]hexane-3-yl)ethane-1-one. The enantiomer of 16 is separated by chiral chromatography, silylated, and used in amide coupling, while amines 14, 15, and 17 are used in amide coupling as racemates.

[0150] [ka]

[0151] [Table 7]

[0152] The amines 18-21 below are produced in two steps, similar to amine 1, by coupling the corresponding aniline with 3,7-dioxabicyclo[4.1.0]heptane. In these cases, the resulting amino alcohols are separated by chiral chromatography, silylated, and then used for amide coupling.

[0153] [ka]

[0154] [Table 8]

[0155] The amines 22-25 below are produced in two steps, similar to amine 1, by coupling the corresponding aniline tert-butyl 7-oxa-3-azabicyclo[4.1.0]heptane-3-carboxylate. In these cases, the resulting amino alcohols are separated by chiral chromatography, silylated, and then used for amide coupling.

[0156] [ka]

[0157] [Table 9]

[0158] Manufacturing of Example B

[0159] [ka]

[0160] Example 1: (2R,3R,4S,5R,6R)-N-(3-chlorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1-yl)tetrahydro-2H-pyran-2-carboxamide Step 1: (4aR,6R,7R,8R,8aR)-N-((3S,4R)-4-((tert-butyldimethylsilyl)oxy)tetrahydrofuran-3-yl)-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 mixture of Acid 1 (50 mg; 0.113 mmol) and Amine 1 (39 mg; 0.118 mmol) in DCM (4 ml), phosphorus oxychloride (V) (1 M solution in pyridine, 0.14 mL, 0.135 mmol) was added at rt, and the mixture was stirred at rt for 24 hours. Water was added, and 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 purified by prep.LC-MS(I) to obtain intermediate 8 (as a mixture of diastereomers). LCMS(A):t R = 1.29 / 1.30 min; [M+H] + = 753.10.

[0161] Step 2: (2R,3R,4S,5R,6R)-N-(3-chlorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1-yl)tetrahydro-2H-pyran-2-carboxamide To a solution of intermediate 8 (a mixture of diastereomers) (74 mg, 0.98 mmol) in dioxane (1 ml) and water (0.5 ml), TFA (0.60 ml, 7.8 mmol) was added at 0°C, and the reaction mixture was stirred in rt for 21 hours. The solvent was evaporated, MeCN was added, and the mixture was basicized with 25% NH4OH aqueous solution (until pH 11). The product was purified by prep.LCMS(II) to obtain the final compound as a mixture of diastereomers, which was separated by chiral column chromatography to obtain Examples 1 and 30.

[0162] Example 1: 1 H NMR (500MHz, DMSO) δ:9.00(s, 1H), 7.88(dd, J1=9.0Hz, J2=6.8Hz, 2H), 7.57(m, 1H), 7.49-7.52(m, 1H), 7.46(s, 1H), 7 .35-7.39(m, 1H), 5.39(d, J=4.9Hz, 1H), 5.33(d, J=6.0Hz, 1H), 4.83(d, J=9.2Hz, 1H), 4.63-4.72( m, 2H), 4.39(dd, J1=9.1Hz, J2=10.6Hz, 1H), 4.24(m, 1H), 4.03(dd, J1=7.1Hz, J2=9.5Hz, 1H), 3.76 (m, 1H), 3.64(m, 2H), 3.50(d, J=9.0Hz, 1H), 3.38-3.46(m, 3H), 3.17(t, J=6.4Hz, 1H), 3.07(s, 3H).

[0163] LC-MS(A):t R =0.85min;[M+H] + =599.05

[0164] [ka]

[0165] Example 59: (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4S)-4-hydroxypyrrolidine-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1-yl)tetrahydro-2H-pyran-2-carboxamide Step 1: Add phosphorus oxychloride (V) (1 M solution in pyridine, 1.22 ml, 1.22 mmol) to a mixture of tert-butyl (3S,4S)-3-((tert-butyldimethylsilyl)oxy)-4-((4aR,6R,7R,8R,8aR)-N-(3,5-dichlorophenyl)-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)pyrrolidine-1-carboxylate acid 1 (450 mg; 1.01 mmol) and amine 12 (554 mg, 1.07 mmol) in DCM (35 ml) at rt, and stir the mixture at rt for 24 hours. Add water, quench the mixture with saturated NH4Cl aqueous solution, and extract twice with DCM. Wash the organic layers with brine. Combine the organic layers, dry over MgSO4, filter, and concentrate. Crude The substance was purified by ISCO (24g RediSep column, 0-80% EA in heptane within 15 min) to obtain intermediate 9 as a yellow foam. LCMS(A):t R =1.37min;[M+H] + = 886.09.

[0166] The product may contain tert-butyldimethylsilyl (3S,4S)-3-((tert-butyldimethylsilyl)oxy)-4-((4aR,6R,7R,8R,8aR)-N-(3,5-dichlorophenyl)-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)pyrrolidine-1-carboxylate. LCMS(A):t R=1.42min;[M+H] + =944.10 Step 2: (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4S)-4-hydroxypyrrolidine-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1-yl)tetrahydro-2H-pyran-2-carboxamide To a solution of intermediate 9 (486 mg, 0.51 mmol) in dioxane (10 ml) and water (5 ml), add TFA (1.97 ml, 25.7 mmol) at 0°C and stir the reaction mixture in rt for 2 weeks [add further TFA (0.5 ml) after 3 days and 1 week]. Add EA and basicize the mixture with 25% NH4OH aqueous solution (until pH 9), and extract twice with EA. Wash the organic layer with brine. Combine the organic layers, dry over MgSO4, filter, and concentrate. Purify the crude product by ISCO (12 g RediSep column, 0-30% 7N NH3 / MeOH in DCM) and prep.LC-MS (II) to obtain the final product as a colorless solid. LCMS(A):t R =0.71min;[M+H] + =631.96 Example 59: 1H NMR (500MHz, DMSO) δ:9.01(s, 1H), 7.89(dd, J1=9.0Hz, J2=6.8Hz, 2H), 7.76(t, J=1.8Hz, 1H), 7.48(s, 2H), 5.34(d, J=6.0Hz, 1H), 5.11( d, J=5.1Hz, 1H), 4.92(dd, J1=10.7Hz, J2=2.9Hz, 1H), 4.70(m, 1H), 4.40(dd, J1=9.0Hz, J2=10.7Hz, 1H), 4.33(m, 1H), 4.01(m, 1H), 3.79(dd, J1=6.0Hz, J2=2.8Hz, 1H), 3.59(d, J=9.0Hz, 1H), 3.40-3.56(m, 2H), 3.31(m, 2H), 3.16(dd, J1= 8.3Hz, J2=11.3Hz, 1H), 3.00-3.07(m, 3H), 2.87(dd, J1=6.6Hz, J2=11.2Hz, 1H), 2.80(dd, J1=7.4Hz, J2=11.4Hz, 1H).

[0167] [ka]

[0168] Example 72: (2R,3R,4S,5R,6R)-N-((3S,4S)-1-acetyl-4-hydroxypyrrolidine-3-yl)-N-(3-bromo-5-methylphenyl)-5-hydroxy-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1-yl)tetrahydro-2H-pyran-2-carboxamide This product is prepared from acid 1 and amine 15 in two steps, similar to Example 1. The diastereomers are separated by chiral chromatography to obtain Examples 72 and 79. LCMS(A):t R =0.84min;[M+H] + =697.91 Example 72: 100℃: 1H NMR (400MHz, DMSO) δ:8.82(m, 1H), 7.77-7.83(m, 2H), 7.49-7.51(m, 1H), 7.31-7.42(m, 1H), 7.17-7.28(m , 1H), 5.17-5.29(m, 1H), 4.96-5.02(m, 1H), 4.64-4.82(m, 2H), 4.42-4.49(m, 1H), 4.3 3-4.42(m, 1H), 4.13-4.29(m, 1H), 3.84-3.93(m, 1H+0.5H), 3.70-3.75(m, 0.5H), 3.33 -3.65(m, 5H), 3.16-3.33(m, 1H), 3.09(s, 3H), 2.97(m, 1H), 2.39(s, 3H), 1.83(s, 3H).

[0169] This N-acetyl analog can also be produced in a two-step procedure—peracetylation and O-deacetylation of the corresponding NH product as shown in Example 71.

[0170] Example 71: (2R,3R,4S,5R,6R)-N-((3S,4S)-1-acetyl-4-hydroxypyrrolidine-3-yl)-N-(3,5-dichlorophenyl)-5-hydroxy-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1-yl)tetrahydro-2H-pyran-2-carboxamide Step 1: (2R,3R,4R,5R,6R)-6-(((3S,4S)-4-acetoxy-1-acetylpyrrolidine-3-yl)(3,5-dichlorophenyl)carbamoyl)-2-(acetoxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1-yl)tetrahydro-2H-pyran-3-yl acetate To a solution of compound 59 (23 mg, 0.0364 mmol) in DCM (1.5 ml), triethylamine (0.050 ml, 0.364 mmol), acetic anhydride (0.017 ml, 0.182 mmol), and DMAP (6.7 mg, 0.054 mmol) are added at rt, and the mixture is stirred at rt for 15 min. 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. Intermediate 11 is used in the next step without purification. LCMS(A):t R =1.07min;[M+H] + =800.03 Step 2: (2R,3R,4S,5R,6R)-N-((3S,4S)-1-acetyl-4-hydroxypyrrolidine-3-yl)-N-(3,5-dichlorophenyl)-5-hydroxy-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1-yl)tetrahydro-2H-pyran-2-carboxamide To a solution of intermediate 11 (27 mg, 0.0337 mmol) in MeOH (1.5 ml), a solution of NaOMe in MeOH (1.26 ml; prepared by dissolving 0.25 mg of NaOMe in 1 ml of MeOH) is added at rt, and the mixture is stirred for 3 hours. The mixture is quenched with saturated NH4Cl aqueous solution and extracted twice with ethyl acetate. The organic layers are washed with brine. The organic layers are dried over MgSO4, filtered, and concentrated. The crude product is purified by prep.LC-MS(II) to obtain the final product as a colorless solid. LCMS(A):t R =0.85min;[M+H] + = 673.86.

[0171] [ka]

[0172] Example 90: (2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-N-((3S,4S)-1-formyl-4-hydroxypyrrolidine-3-yl)-5-hydroxy-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1-yl)tetrahydro-2H-pyran-2-carboxamide To a solution of Example 61 (35 mg, 0.053 mmol) in ethyl formate (0.44 ml, 5.33 mmol), triethylamine (0.008 ml, 0.053 mmol) is added, and the reaction mixture is stirred at 50°C for 4 hours in a sealed tube. The solvent is evaporated, and the mixture is purified by prep.LC-MS(II) to obtain the final product as a colorless solid. LCMS(A):t R =0.84min;[M+H] + =683.83 Example 90: 100℃ 1 H NMR (400MHz, DMSO) δ:8.82(s, 1H), 8.00(brs, 1H), 7.78-7.82(m, 2H), 7.50(s, 1H), 7.37(m, 1H), 7. 23(s, 1H), 5.22-5.37(m, 1H), 4.97-5.03(m, 1H), 4.74-4.79(m, 1H), 4.59-4.65( m, 1H), 4.45(m, 1H), 4.34-4.41(m, 1H), 4.18-4.28(m, 1H), 3.50-4.0(m, 6H), 3. 34-3.49(m, 1H), 3.19-3.32(m, 1H), 3.09(s, 3H), 3.01-3.05(m, 1H), 2.39(s, 3H)

[0173] [ka]

[0174] Example 99: (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1-yl)tetrahydro-2H-pyran-2-carboxamide This product is prepared from acid 1 and amine 18 in two steps, similar to Example 1. LCMS(A):t R =0.93min;[M+H] + =646.97 Example 99: 1 H NMR (500MHz, DMSO) δ:9.00(s, 1H), 7.89(dd, J1=6.8Hz, J2=9.1Hz, 2H), 7.78(t, J=1.9Hz, 1H), 7.55(s, 1H), 7.38( s, 1H), 5.33 (d, J=6.0Hz, 1H), 5.10 (d, J=5.7Hz, 1H), 4.90 (dd, J1=10.8Hz, J2=2.9Hz, 1H), 4.68 (t, J=5.6Hz, 1H), 4.31-4.41(m, 2H), 3.76-3.81(m, 4H), 3.55(d, J=9.0Hz, 1H), 3.45(t, J=6.1 Hz, 2H), 3.31-3.36(m, 1H), 3.28(t, J=6.7Hz, 1H), 3.21(m, 1H), 3.07(s, 3H), 1.71-1.84(m, 2H)

[0175] [ka]

[0176] Example 105: (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4S)-4-hydroxytetrahydro-2H-pyran-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1-yl)tetrahydro-2H-pyran-2-carboxamide This product is prepared from acid 1 and amine 20 in two steps, similar to Example 1. LCMS(A):t R =0.93min;[M+H] + = 647.00.

[0177] Example 105: 1 H NMR (500MHz, DMSO) δ:9.00(s, 1H), 7.89(dd, J1=6.8Hz, J2=9.1Hz, 2H), 7.76(m, 1H), 7.59(s, 1H), 7.31-7.39(m, 1H), 5.32(d, J=6.0Hz, 1H), 5.04( d, J=5.8Hz, 1H), 4.89(dd, J1=10.8Hz, J2=2.9Hz, 1H), 4.68(t, J=5.6Hz, 1H), 4.39(dd, J1=10.7Hz, J2=9.0Hz, 1H), 4.23(td, J1 =10.4Hz, J2=4.4Hz, 1H), 3.85(dd, J1=4.7Hz, J2=11.0Hz, 1H), 3.74-3.79(m, 2H), 3.53(d, J=9.0Hz, 1H), 3.45(t, J=6.0Hz, 2H) , 3.32-3.36(m, 1H), 3.25-3.30(m, 2H), 3.20(td, J1=1.4Hz, J2=12.1Hz, 1H), 3.07(s, 3H), 1.84-1.87(m, 1H), 1.42-1.61(m, 1H)

[0178] [ka]

[0179] Example 109: (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4S)-3-hydroxypiperidine-4-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1-yl)tetrahydro-2H-pyran-2-carboxamide This product is prepared from acid 1 and amine 22 in two steps, similar to Example 1. LCMS(A):t R =0.71min;[M+H] +=645.90 Example 109: 1 H NMR (500MHz, DMSO) δ:9.00(s, 1H), 7.89(dd, J1=9.1Hz, J2=6.8Hz, 2H), 7.77(t, J=1.9Hz, 1H), 7.57(s, 1H), 7.27-7.34(m, 1H), 5.33(d, J=6. 0Hz, 1H), 4.88(dd, J1=2.9Hz, J2=10.8Hz, 1H), 4.85(d, J=5.4Hz, 1H), 4.68(t, J=5.4Hz, 1H), 4.38(dd, J1=10.7Hz, J2=9.0 Hz, 1H), 4.24-4.33(m, 1H), 3.79(dd, J1=6.1Hz, J2=3.0Hz, 1H), 3.52-3.55(m, 1H), 3.45(m, 2H), 3.23-3.28(m, 1H), 3.06( s, 3H), 2.87-3.03(m, 2H), 2.78-2.87(m, 1H), 2.37-2.43(m, 1H), 2.22-2.27(m, 1H), 1.67-1.81(m, 1H), 1.31-1.54(m, 1H) Example 113: (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4S)-4-hydroxypiperidine-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1-yl)tetrahydro-2H-pyran-2-carboxamide This product is prepared from acid 1 and amine 24 in two steps, similar to Example 1. LCMS(A):t R =0.70min;[M+H] + =645.90 Example 113: 1H NMR (500MHz, DMSO) δ:9.00(s, 1H), 7.89(dd, J1=6.8Hz, J2=9.1Hz, 2H), 7.75(t, J=1.9Hz, 1H), 7.58(s, 1H), 7.31-7.35(m, 1H), 5.33(d, J=6.0Hz, 1H), 4.88 (dd, J1=2.9Hz, J2=10.8Hz, 1H), 4.85(d, J=5.6Hz, 1H), 4.69(t, J=5.5Hz, 1H), 4.39(dd, J1=10.7Hz, J2=9.0Hz, 1H), 4.11-4.19(m, 1H), 3.79(dd, J1=6.0Hz, J2=3.0Hz, 1H), 3.52(d, J=8.9Hz, 1H), 3.45(t, J=6.0Hz, 2H), 3.26(t, J=6.6Hz, 1H), 3.10-3.21(m, 1H), 3.07(s, 3H) ), 2.96-2.99(m, 1H), 2.78(dd, J1=10.9Hz, J2=1.3Hz, 1H), 2.43-2.49(m, 1H), 2.20-2.30(m, 1H), 1.80-1.83(m, 1H), 1.32-1.39(m, 1H) The compounds listed below are prepared from the corresponding acids and amines in the same manner as in Example 1, or as described in Reference Examples 59, 71, 72, 90, 99, 105, 109, or 113.

[0180] [Table 10]

[0181] [Table 11]

[0182] [Table 12]

[0183] [Table 13]

[0184] [Table 14]

[0185] [Table 15]

[0186] [Table 16]

[0187] [Table 17]

[0188] [Table 18]

[0189] [Table 19]

[0190] [Table 20]

[0191] [Table 21]

[0192] [Table 22]

[0193] [Table 23]

[0194] II. Biological Tests Inhibitory activity of the compound (IC 50 ) evaluation 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 Sci 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.

[0195] In summary, the compound is serially diluted in DMSO (test diluent). Biotin-labeled hGal-3 or hGal-1 is added to 22.8 μL / well of assay buffer in an ASF-coated 384-well plate (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.

[0196] 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 min and IC50. 50 Value Calculate.

[0197] 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.

[0198] [Table 24]

[0199] [Table 25]

[0200] The compounds of the present invention may be further characterized using conventional assay methods well known in the art with respect to their general pharmacokinetic and pharmacological properties; for example, with respect to their bioavailability in different species (such as rats or dogs) (including aspects such as solubility, permeability, metabolic stability, and absorption); or with respect to their pharmacosafety and / or toxicological properties, for example, cytochrome P450 enzyme inhibition and time-dependent inhibition, pregnane X receptor (PXR) activation, glutathione binding, or phototoxic behavior.

Claims

1. Compounds of formula (I) or pharmaceutically acceptable salts thereof: 【Chemistry 1】 (In the formula, n and m each independently represent the integers 1 or 2, and n + m is 2 or 3; X is O or NR ２ Represents; R ２ is hydrogen, C １－３ -alkyl, -CO-H, -SO ２ -C １－３ -Alkyl or -CO-C １－３ - Represents alkyl; Ar １ teeth, - aryl, substituted by 1, 2, 3, 4 or 5 substituents, said substituents being halogen; methyl; cyano; methoxy; trifluoromethyl; trifluoromethoxy; and NR Ｎ１１ R Ｎ１２ (R Ｎ１１ represents hydrogen, and R Ｎ１２ represents hydroxy-C ２－３ -alkyl, or R Ｎ１１ and R Ｎ１２ together with the nitrogen atom to which they are attached, are morpholin-4-yl, azetidin-1-yl, pyrrolidin-1-yl and piperi An aryl, independently selected from (which forms a 4- to 6-membered heterocycline selected from din-1-yl, wherein the 4- to 6-membered heterocycline is either unsubstituted or substituted with one hydroxyl group); - 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-R １Ｘ (R １Ｘ は、 -- Hydroxyl; -- Morpholine-4-yl; Or, -- NR Ｎ２１ R Ｎ２２ (R Ｎ２１ and R Ｎ２２ These, together with the nitrogen atoms to which they are bound, form a 4- to 6-membered heterocycline selected from azetidine-1-yl, pyrrolidine-1-yl, and piperidine-1-yl, and the 4- to 6-membered heterocycline is substituted with one hydroxyl group. (This represents...) It represents; L represents a direct bond, methylene, or ethylene; Ar ２ teeth, - Phenyl or a 5- or 6-membered heteroaryl, wherein the phenyl or 5- or 6-membered heteroaryl is independently unsubstituted or substituted with 1, 2, or 3 substituents; 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 - Phenyl or 5- or 6-membered heteroaryl compounds independently selected from alkoxy, halogen, morpholine-4-yl, amino, ethynyl, and cyano; - 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 a compound of formula (I) as described in claim 1 or a pharmaceutically acceptable salt thereof: 【Chemistry 2】 (In the formula, n, m, X, Ar1, R1, L, and Ar2 are the same as defined in claim 1.)

3. Ar １ The compound according to claim 1 or 2 or a pharmaceutically acceptable salt thereof, wherein the phenyl is substituted with two or three substituents, the substituents being independently selected from halogens, methyl and cyano; at least one of the substituents is bonded at the meta or para position of the phenyl.

4. Ar １ However, based on the following formula, 【Transformation 3】 Represents; the compound according to claim 1 or 2 or a pharmaceutically acceptable salt thereof.

5. R １ is a methoxy compound; the compound according to any one of claims 1 to 4 or a pharmaceutically acceptable salt thereof.

6. L represents a direct bond; the compound according to any one of claims 1 to 5 or a pharmaceutically acceptable salt thereof.

7. Ar ２ However, it is phenyl, substituted with one or two substituents, and the substituents are C １－４ - Alkyl, C １－３ - Representing phenyl, independently selected from alkoxy, halogen, and cyano; the compound according to any one of claims 1 to 6 or a pharmaceutically acceptable salt thereof.

8. Fragment L-Ar ２ However, based on the following formula, 【Chemistry 4】 Represents; the compound according to any one of claims 1 to 5 or a pharmaceutically acceptable salt thereof.

9. The compound in question, (2R,3R,4S,5R,6R)-N-(3-chlorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-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-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-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-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-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-dichlorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-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-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-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-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrof Ran-3-yl)-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-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-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-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-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-cyano-5-methoxyphenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-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-cyano-5-methylphenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-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-cyano-5-fluorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-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)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazole-1-yl)-N-(3,5-dichlorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-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-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-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-methylphenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-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-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dibromophenyl)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazole-1-i (L)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-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-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-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-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-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-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-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-(3,5-dichlorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-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-(3,5-dibromophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-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-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-4-(4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-4-(4-(3,4-dichlorophenyl)-1H-1,2,3-triazole-1-yl)-5-Hyd Roxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dibromophenyl)-4-(4-(3,4-dichlorophenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-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-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-4-(4-(3,4-dichlorophenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4R)-4-hydroxytetrahydrofuran-3-yl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-chlorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-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-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-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-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-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-dichlorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-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-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-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-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-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-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetraphenyl) (Drofuran-3-yl)-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-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-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-cyano-5-methoxyphenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-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-cyano-5-methylphenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-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-cyano-5-fluorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-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)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazole-1-yl)-N-(3,5-dichlorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-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-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-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-methylphenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-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-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dibromophenyl)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-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-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-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-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-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-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-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-(3,5-dichlorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-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-(3,5-dibromophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-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-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-4-(4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-4-(4-(3,4-dichlorophenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dibromophenyl)-4-(4-(3,4-dichlorophenyl)-1H-1,2,3-triazole-1-yl)-5-Hyd Roxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-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-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-4-(4-(3,4-dichlorophenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-4-hydroxytetrahydrofuran-3-yl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4S)-4-hydroxypyrrolidine-3-yl)-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-6-(hydroxymethyl)-N-((3S,4S)-4-hydroxypyrrolidine-3-yl)-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-6-(hydroxymethyl)-N-((3S,4S)-4-hydroxypyrrolidine-3-yl)-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)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazole-1-yl)-N-(3,5-dichlorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4S)-4-hydroxypyrrolidine-3-yl)-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-6-(hydroxymethyl)-N-((3S,4S)-4-hydroxypyrrolidine-3-yl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4S)-4-hydroxypyrrolidine-3-yl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-4-(4-(3,4-dichlorophenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4S)-4-hydroxypyrrolidine-3-yl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4R)-4-hydroxypyrrolidine-3-yl)-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-6-(hydroxymethyl)-N-((3R,4R)-4-hydroxypyrrolidine-3-yl)-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-6-(hydroxymethyl)-N-((3R,4R)-4-hydroxypyrrolidine-3-yl)-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)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4R)-4-hydroxypyrrolidine-3-yl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4S)-4-hydroxypyrrolidine-3-yl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4R)-4-hydroxypyrrolidine-3-yl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-((3S,4S)-1-acetyl-4-hydroxypyrrolidine-3-yl)-N-(3,5-dichlorophenyl)-5-hydroxy-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-((3S,4S)-1-acetyl-4-hydroxypyrrolidine-3-yl)-N-(3-bromo-5-methylphenyl)-5-hydroxy-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-((3S,4S)-1-acetyl-4-hydroxypyrrolidine-3-yl)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazole-1-yl)-N-(3,5-dichlorophenyl)-5-hydroxy-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-((3S,4S)-1-acetyl-4-hydroxypyrrolidine-3-yl)-N-(3,5-dibromophenyl)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-((3S,4S)-1-acetyl-4-hydroxypyrrolidine-3-yl)-N-(3-bromo-5-methylphenyl)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazole-1-yl (Lu)-5-hydroxy-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-((3S,4S)-1-acetyl-4-hydroxypyrrolidine-3-yl)-N-(3-bromo-5-methylphenyl)-4-(4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-((3R,4R)-1-acetyl-4-hydroxypyrrolidine-3-yl)-N-(3,5-dichlorophenyl)-5-hydroxy-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-((3R,4R)-1-acetyl-4-hydroxypyrrolidine-3-yl)-N-(3-bromo-5-cyanophenyl)-5-hydroxy-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-((3R,4R)-1-acetyl-4-hydroxypyrrolidine-3-yl)-N-(3-bromo-5-methylphenyl)-5-hydroxy-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-((3R,4R)-1-acetyl-4-hydroxypyrrolidine-3-yl)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazole-1-yl)-N-(3,5-dichlorophenyl)-5-hydroxy-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-((3R,4R)-1-acetyl-4-hydroxypyrrolidine-3-yl)-N-(3,5-dibromophenyl)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-((3R,4R)-1-acetyl-4-hydroxypyrrolidine-3-yl)-N-(3-bromo-5-methylphenyl)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-((3R,4R)-1-acetyl-4-hydroxypyrrolidine-3-yl)-N-(3-bromo-5-methylphenyl)-4-(4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-((3S,4S)-1-acetyl-4-hydroxypyrrolidine-3-yl)-N-(3,5-dibromophenyl)-5-hydroxy-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-((3R,4R)-1-acetyl-4-hydroxypyrrolidine-3-yl)-N-(3,5-dibromophenyl)-5-hydroxy-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl (Lu)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-((3S,4S)-1-acetyl-4-hydroxypyrrolidine-3-yl)-N-(3,5-dichlorophenyl)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-((3R,4R)-1-acetyl-4-hydroxypyrrolidine-3-yl)-N-(3,5-dichlorophenyl)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-((3S,4S)-1-acetyl-4-hydroxypyrrolidine-3-yl)-4-(4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazole-1-yl)-N-(3,5-dichlorophenyl)-5-hydroxy-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-((3R,4R)-1-acetyl-4-hydroxypyrrolidine-3-yl)-4-(4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazole-1-yl)-N-(3,5-dichlorophenyl)-5-hydroxy-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-((3S,4S)-1-acetyl-4-hydroxypyrrolidine-3-yl)-4-(4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazole-1-yl)-N-(3,5-dibromophenyl)-5-hydroxy-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-((3R,4R)-1-acetyl-4-hydroxypyrrolidine-3-yl)-4-(4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazole-1-yl)-N-(3,5-dibromophenyl)-5-hydroxy-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-((3S,4S)-1-acetyl-4-hydroxypyrrolidine-3-yl)-N-(3,5-dichlorophenyl)-4-(4-(3,4-dichlorophenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-((3R,4R)-1-acetyl-4-hydroxypyrrolidine-3-yl)-N-(3,5-dichlorophenyl)-4-(4-(3,4-dichlorophenyl)-1H-1,2,3-triazole-1-yl)-5-hydroxy-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-N-((3S,4S)-1-formyl-4-hydroxypyrrolidine-3-yl)-5-hydroxy-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)-N-((3S,4S)-1-formyl-4-hydroxypyrrolidine-3-yl)-5-hydroxy-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluoro Phenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazole-1-yl)-N-(3,5-dichlorophenyl)-N-((3S,4S)-1-formyl-4-hydroxypyrrolidine-3-yl)-5-hydroxy-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazole-1-yl)-N-((3S,4S)-1-formyl-4-hydroxypyrrolidine-3-yl)-5-hydroxy-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-N-((3R,4R)-1-formyl-4-hydroxypyrrolidine-3-yl)-5-hydroxy-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)-N-((3R,4R)-1-formyl-4-hydroxypyrrolidine-3-yl)-5-hydroxy-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)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazole-1-yl)-N-((3R,4R)-1-formyl-4-hydroxypyrrolidine-3-yl)-5-hydroxy-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-5-hydroxy-N-((3S,4S)-4-hydroxy-1-methylpyrrolidine-3-yl)-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)-N-((3S,4S)-1-ethyl-4-hydroxypyrrolidine-3-yl)-5-hydroxy-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-((3S,4S)-4-hydroxy-1-(methylsulfonyl)pyrrolidine-3-yl)-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-6-(hydroxymethyl)-N-((3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl)-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-6-(hydroxymethyl)-N-((3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl)-3-methoxy-4-(4-(3,4,5-trifluor (Lofenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-cyanophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl)-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-6-(hydroxymethyl)-N-((3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl)-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-6-(hydroxymethyl)-N-((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)-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-6-(hydroxymethyl)-N-((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)-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-6-(hydroxymethyl)-N-((3S,4S)-4-hydroxytetrahydro-2H-pyran-3-yl)-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-6-(hydroxymethyl)-N-((3S,4S)-4-hydroxytetrahydro-2H-pyran-3-yl)-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-6-(hydroxymethyl)-N-((3R,4R)-4-hydroxytetrahydro-2H-pyran-3-yl)-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-6-(hydroxymethyl)-N-((3R,4R)-4-hydroxytetrahydro-2H-pyran-3-yl)-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-6-(hydroxymethyl)-N-((3S,4S)-3-hydroxypiperidine-4-yl)-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-6-(hydroxymethyl)-N-((3S,4S)-3-hydroxypiperidine-4-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1 H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-carboxamide; (2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4S)-3-hydroxypiperidine-4-yl)-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-6-(hydroxymethyl)-N-((3R,4R)-3-hydroxypiperidine-4-yl)-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-6-(hydroxymethyl)-N-((3S,4S)-4-hydroxypiperidine-3-yl)-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-6-(hydroxymethyl)-N-((3S,4S)-4-hydroxypiperidine-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1-yl)tetrahydro-2H-pyran-2-carboxamide; Or, (2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3R,4R)-4-hydroxypiperidine-3-yl)-3-methoxy-4-(4-(3,4,5-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.

10. The compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein the compound is (2R,3R,4S,5R,6R)-N-(3-bromo-5-methylphenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4S)-4-hydroxypiperidine-3-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1-yl)tetrahydro-2H-pyran-2-carboxamide.

11. The compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein the compound is (2R,3R,4S,5R,6R)-N-(3,5-dichlorophenyl)-5-hydroxy-6-(hydroxymethyl)-N-((3S,4S)-3-hydroxypiperidine-4-yl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole-1-yl)tetrahydro-2H-pyran-2-carboxamide.

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

13. A compound according to any one of claims 1 to 11 or a pharmaceutically acceptable salt thereof, for use as a pharmaceutical.

14. The active ingredient comprises a compound described in any one of claims 1 to 11 or a pharmaceutically acceptable salt thereof, for organ fibrosis; liver disease and disorders; acute kidney injury and chronic kidney disease; cardiovascular disease and disorders; interstitial lung disease and disorders; proliferative disorders and cancer; inflammatory and autoimmune diseases and Medicines for the prevention or treatment of 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; or transplant rejection.

15. Use of a compound or a pharmaceutically acceptable salt thereof described in any one of claims 1 to 11 in the manufacture of a pharmaceutical product for the prevention or treatment of organ fibrosis; liver diseases and disorders; acute kidney injury and chronic kidney disease; cardiovascular diseases and disorders; interstitial lung diseases and disorders; proliferative disorders and cancer; 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; or transplant rejection.

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