Triazolyl-methyl substituted alpha-D-galactopyranoside derivatives

Abstract

The present invention relates to galectin-3 inhibitors of formula (I) and pharma- ceutically acceptable salts thereof, pharmaceutical compositions comprising such compounds, and their medical uses. [Formula 1] TIFF2024509421000112.tif79157

Description

[Technical Field]

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

[0002] Galectins are a family of proteins defined 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). Genome sequencing of humans, mice, and rats has revealed the presence 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, which contain a single carbohydrate-recognition domain (CRD); tandem repeats of proline- and glycine-rich short stretches fused to the CRD; and tandem-repeat-type galectins, which have two distinct CRDs linked in tandem by a linker (Zhong X., Clin Exp Pharmacol Physiol. 2019;46:197-203). Galectins can bind bivalently or multivalently, for example, by cross-linking cell surface glycoconjugates, triggering cell 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 of the galectin family, has a molecular mass 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 is monomeric up to high concentrations (100 μM) but can aggregate with ligands at much lower concentrations, which is promoted by its N-terminal non-CRD region through an oligomerization mechanism that 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 level varies among different organs. Depending on its extracellular or intracellular localization, it can exert diverse biological functions, including immunoregulation, host-pathogen interactions, 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, including myeloid 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), suggesting 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 neoplasia and inflammation (Chiariotti L. et al., Glycoconjugate Journal 2004 19, 441-449; Farhad M. et al., OncoImmunology 2018, 7:6, e1434467).

[0005] Inflammatory / autoimmune diseases such as asthma, rheumatoid arthritis, multiple sclerosis, and diabetes (Liu FT et al., Ann NY 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), cardiovascular diseases such as atherosclerosis, 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 EP. et al., Blood. 2015, 125(11):1813-21), organ fibrosis such as pulmonary fibrosis, liver fibrosis, kidney fibrosis, ocular fibrosis, and skin fibrosis (Mackinnon AC et al., Am. J. Respir. Crit. Care Med. 2012, 185:537-546; Henderson NC et al., PNAS 2006, 103:5060-5065; Henderson NC et al., Am. J. Pathol. 2008, 172:288-298; Chen WS. et al., Investigative Ophthalmology & Visual Science 2017, Vol. 58, 9-20; Taniguchi T. et al., The Journal of Rheumatology 2012, jrheum.110755; Arciniegas E. et al., The American Journal of Dermatopathology 2019;41(3):193-204) and cancer (Farhad M. et al., Oncoimmunology 2018;7(6):e1434467; Vuong L. et al., Cancer Res 2019(79)(7)1480-1492).

[0006] Recently, Gal-3 inhibitors have been shown to have positive effects when used in combination immunotherapy (Galectin Therapeutics, press release, February 7, 2017) and idiopathic pulmonary fibrosis (Galectin Therapeutics, press release, March 10, 2017). WO20180209276, WO2018209255, and WO20190890080 disclose compounds with binding affinity to galectin proteins for the treatment of systemic insulin resistance disorders. Thus, Gal-3 inhibitors, alone or in combination with other treatments, may be useful for the prevention or treatment of diseases or disorders such as acute or chronic heart failure, cancer, chronic and acute kidney disease, idiopathic pulmonary fibrosis, type 2 diabetes, rheumatoid arthritis, psoriasis, scarring, systemic sclerosis, systemic lupus erythematosus, and dry eye.

[0007] Synthetic inhibitors of Gal-3 that have been explored as antifibrotic agents have been described in various publications and patent applications (see, e.g., WO2005 / 113568, WO2005 / 113569, WO2014 / 067986, WO2016 / 120403, US2014 / 0099319, WO2019 / 067702, WO2019 / 075045, and WO2014 / 078655). WO2002 / 057284, WO2005 / 113569, WO2014 / 078655, WO2021 / 028336, WO2021 / 028323, and WO2021 / 028570 disclose beta-configured galectin inhibitors. WO2016 / 120403, WO2020 / 104335, WO2021 / 001528, WO2021 / 038068 and WO2021 / 004940 disclose a broad range of alpha-D-galactoside inhibitors of galectins. Summary of the Invention

[0008] The present invention provides novel compounds of formula (I) that are alpha-configured galectin-3 inhibitors. Accordingly, the compounds of the present invention may be useful in the prevention or treatment of diseases and disorders in which modulation of Gal-3 binding to natural carbohydrate ligands is indicated.

[0009] 1) In a first aspect, the present invention relates to a compound of formula (I):

[0010] [ka] (In the formula, R P2 represents halogen (especially fluoro); R P3 represents halogen (especially fluoro); R P4 represents halogen (especially fluoro, chloro, bromo), methyl or cyano; R 1 teeth, - hydroxy; - C 1-4 -alkoxy (especially methoxy); - -O-CO-C 1-3 - alkyl; - O-CO-NH-R N11 (R N11 is hydrogen or C 1-3 - alkyl;- -O-CH2-C1-fluoroalkyl; - -O-CH2-HET 1 (HET 1 represents a 5-membered heteroaryl (particularly oxazolyl, thiazolyl, or imidazolyl), which 5-membered heteroaryl is independently unsubstituted or substituted by one methyl; or - -O-CH2-CO-R 1X (R 1X teeth, -- -hydroxy; -- C 1-3 -alkoxy (especially methoxy); --morpholin-4-yl; or -- -NR N21 R N22 (R N21 and R N22 each independently represents hydrogen or methyl; or R N21 and R N22together with the nitrogen atom to which they are attached form a 4-6 membered monocyclic heterocycloalkyl selected from azetidin-1-yl, pyrrolidin-1-yl, and piperidin-1-yl, wherein the 4-6 membered heterocycloalkyl is substituted by one hydroxy; represents. ); represents; [In a sub-embodiment, R 1 specifically represents methoxy. A represents [1,2,3]triazole-1,4-diyl (R 2 may be bonded to the 1- or 4-position of the [1,2,3]triazole-1,4-diyl; -R 2 teeth, Branch C 3-6 -alkyl (especially isopropyl or tert-butyl), 3-6 - alkyl is -- substituted by one hydroxy [particularly such groups are 2-hydroxy-1,1 -dimethyl-ethyl or 1-hydroxy-1-methyl-ethyl. -- 1 -CO-OC 1-4 -substituted by alkyl [particularly such a group is 1-methoxy-2-methyl-1-oxopropan-2-yl], or -- substituted by one C1-fluoroalkyl [particularly, such a group is 2,2-difluoro-1,1-dimethyl-ethyl]; Branch C 3-6 -represents alkyl; - or R 2 is a 3- to 8-membered saturated monocyclic or bicyclic group, and the monocyclic or bicyclic group is -- monocyclic C 3-6 cycloalkyl (especially cyclopropyl, cyclobutyl or cyclopentyl), -- 4-6-membered monocyclic heterocycloalkyl having one ring oxygen atom (especially oxetan-3-yl, tetrahydro-2H-pyran-3-yl), --Bridged Bicyclic C 5-8-cycloalkyl (in particular bicyclo[1.1.1]pentan-1-yl, bicyclo[2.2.2]octan-1-yl), -- Fused Bicyclic C 6-8 -cycloalkyl (especially bicyclo[3.1.0]hexan-6-yl), -- Spiro-bicyclic C 6-8 -cycloalkyl (especially spiro[2.3]hexan-5-yl), or 7- or 8-membered spiro-bicyclic heterocycloalkyl having one ring oxygen atom (in particular oxaspiro[3.3]heptan-6-yl); represents a monocyclic or bicyclic group, The monocyclic or bicyclic groups are independently unsubstituted or substituted with 1, 2 or 3 substituents, the substituents being independently hydroxy; C 1-3 - alkyl (especially methyl; or ethyl or isopropyl); C 1-3 -alkoxy (especially methoxy); -C 1-3 -Alkylene-OH (especially hydroxymethyl or 2-hydroxyethyl); C1-fluoroalkyl (especially trifluoromethyl); -NR N1 R N2 (R N1 represents hydrogen, and R N2 is hydrogen or -CO-OC 1-4 alkyl (especially -CO-O-tert.-butyl); and fluoro.

[0011] In a subembodiment, in particular, the monocyclic or bicyclic group is independently -- whether it is unsubstituted; -- substituted by one hydroxy; -- 1 C 1-3 substituted by alkyl (especially methyl; or ethyl or isopropyl); -- 1 C 1-3 -substituted by alkoxy (especially methoxy); -- 1 -C 1-3 -substituted by alkylene-OH (especially hydroxymethyl, 2-hydroxyethyl); -- 1 -C 1-3 -Alkylene-OC 1-3 -substituted by alkyl (especially methoxymethyl); -- substituted by one C1-fluoroalkyl (especially trifluoromethyl); -- 1 piece -NR N1 R N2 (R N1 represents hydrogen, and R N2 is hydrogen or -CO-OC 1-4 -alkyl (especially -CO-O-tert.-butyl); -- substituted by 1 or 2 fluoro; --One substituent is hydroxy and the other is C 1-3 -substituted by two substituents which are alkyl (especially methyl); or -- three substituents, two of which are fluoro (especially attached to the same ring carbon atom); the remaining substituents are C 1-3 -Alkyl (especially methyl) or -C 1-3 -substituted by three substituents, which are -alkylene-OH (especially hydroxymethyl).

[0012] 2) In a second aspect, the present invention provides a method for producing a medicament for a medicament comprising: R P2 represents halogen (especially fluoro); R P3 represents halogen (especially fluoro); R P4 represents halogen (especially fluoro, chloro, bromo), methyl or cyano; R 1 but, - hydroxy; - C 1-4 -alkoxy (especially methoxy); - -O-CO-C 1-3 - alkyl; - O-CO-NH-R N11 (R N11 is hydrogen or C 1-3 - alkyl;- -O-CH2-C1-fluoroalkyl; - -O-CH2-HET 1 (HET 1 represents a 5-membered heteroaryl (particularly oxazolyl, thiazolyl, or imidazolyl), which 5-membered heteroaryl is independently unsubstituted or substituted by one methyl; or - -O-CH2-CO-R 1X (R 1X teeth, -- -hydroxy; -- C 1-3 -alkoxy (especially methoxy); --morpholin-4-yl; or -- -NR N21 R N22 (R N21 and R N22 each independently represents hydrogen or methyl; or R N21 and R N22 together with the nitrogen atom to which they are attached form a 4-6 membered monocyclic heterocycloalkyl selected from azetidin-1-yl, pyrrolidin-1-yl, and piperidin-1-yl, wherein the 4-6 membered heterocycloalkyl is substituted by one hydroxy; represents. ); represents; [In a sub-embodiment, R 1 specifically represents methoxy. A represents [1,2,3]triazole-1,4-diyl (R 2 may be bonded to the 1- or 4-position of the [1,2,3]triazole-1,4-diyl; -R 2 But branch C 3-6 -alkyl (especially isopropyl or tert-butyl), 3-6 - alkyl is -- substituted by one hydroxy [particularly such groups are 2-hydroxy-1,1-dimethyl-ethyl or 1-hydroxy-1-methyl-ethyl], -- 1 -CO-OC 1-4-substituted by alkyl [particularly such a group is 1-methoxy-2-methyl-1-oxopropan-2-yl], or -- substituted by one C1-fluoroalkyl [particularly, such a group is 2,2-difluoro-1,1-dimethyl-ethyl]; Branch C 3-6 -represents alkyl; - or R 2 is a 3- to 8-membered saturated monocyclic or bicyclic group, and the monocyclic or bicyclic group is -- monocyclic C 3-6 cycloalkyl (especially cyclopropyl, cyclobutyl or cyclopentyl), -- 4-6-membered monocyclic heterocycloalkyl having one ring oxygen atom (especially oxetan-3-yl, tetrahydro-2H-pyran-3-yl), --Bridged Bicyclic C 5-8 -cycloalkyl (in particular bicyclo[1.1.1]pentan-1-yl, bicyclo[2.2.2]octan-1-yl), -- Fused Bicyclic C 6-8 -cycloalkyl (especially bicyclo[3.1.0]hexan-6-yl), -- Spiro-bicyclic C 6-8 -cycloalkyl (especially spiro[2.3]hexan-5-yl), or 7- or 8-membered spiro-bicyclic heterocycloalkyl having one ring oxygen atom (in particular oxaspiro[3.3]heptan-6-yl); represents a monocyclic or bicyclic group, The monocyclic or bicyclic groups are independently: -- whether it is unsubstituted; -- substituted by one hydroxy; -- 1 C 1-3 substituted by alkyl (especially methyl; or ethyl or isopropyl); -- 1 C 1-3 -substituted by alkoxy (especially methoxy); -- 1 -C 1-3-substituted by alkylene-OH (especially hydroxymethyl, 2-hydroxyethyl); -- 1 -C 1-3 -Alkylene-OC 1-3 -substituted by alkyl (especially methoxymethyl); -- substituted by one C1-fluoroalkyl (especially trifluoromethyl); -- 1 piece -NR N1 R N2 (R N1 represents hydrogen, and R N2 is hydrogen or -CO-OC 1-4 -alkyl (especially -CO-O-tert.-butyl); -- substituted by 1 or 2 fluoro; --One substituent is hydroxy and the other is C 1-3 -substituted by two substituents which are alkyl (especially methyl); or -- three substituents, two of which are fluoro (especially attached to the same ring carbon atom); the remaining substituents are C 1-3 -Alkyl (especially methyl) or -C 1-3 -substituted by three substituents, which are alkylene-OH (especially hydroxymethyl); It relates to compounds of formula (I) according to embodiment 1).

[0013] In compounds of formula (I), any non-aromatic oxygen or nitrogen atom is preferably separated from another oxygen or nitrogen atom by at least two carbon atoms. In particular, the group R 2 The oxygen atom or nitrogen atom in the part (part of the 3- to 8-membered saturated monocyclic or bicyclic group, or a substituent or part of a substituent of the 3- to 8-membered saturated monocyclic or bicyclic group) is preferably a group R 2and an aromatic nitrogen atom that is part of ring A (for example, when ring A is [1,2,3]triazole-1,4-diyl and R 2 is attached to position 1) by at least two carbon atoms. In particular, a branched C 3-6 - the group R representing alkyl 2 wherein such hydroxy substituent is separated from the ring nitrogen moiety of ring A by at least two carbon atoms; and a group R representing any saturated monocyclic or bicyclic carbocyclic group substituted by one hydroxy. 2 wherein such hydroxy substituent is separated from the ring nitrogen moiety of ring A by at least two carbon atoms; 1-3 - the group R representing any saturated monocyclic or bicyclic carbocyclic group substituted by alkoxy 2 In this case, 1-3 - the oxygen atom of the alkoxy substituent is separated from the ring nitrogen moiety of ring A by at least two carbon atoms; a group R representing any saturated monocyclic or bicyclic heterocycloalkyl group substituted by one hydroxy 2 wherein the hydroxy substituent is separated by at least two carbon atoms from the aromatic ring nitrogen moiety of ring A and the ring oxygen atom moiety of the saturated monocyclic or bicyclic heterocycloalkyl group; 1-3 - the group R representing any saturated monocyclic or bicyclic heterocycloalkyl group substituted by alkoxy 2 In this case, 1-3 The oxygen atom of the -alkoxy substituent will be separated from the aromatic ring nitrogen moiety of Ring A and the ring oxygen atom moiety of such saturated monocyclic or bicyclic heterocycloalkyl group by at least two carbon atoms.

[0014] The compounds of formula (I) have five chiral or asymmetric centers located in the tetrahydropyran moiety and in the absolute configurations set forth in formula (I). In addition, the compounds of formula (I) may have one or more The compounds of formula (I) may contain one or, in some cases, more additional chiral or asymmetric centers, such as an additional asymmetric carbon atom of formula (I). Thus, the compounds of formula (I) may exist as a mixture of stereoisomers or, preferably, as pure stereoisomers. Mixtures of stereoisomers may be separated by methods known to those skilled in the art.

[0015] When a particular compound (or generic structure) is described as being in a particular absolute configuration, e.g., the (R)- or (S)-enantiomer, such description is understood to refer to the respective compound (or generic structure) in enriched, especially essentially pure, enantiomeric form. Similarly, when a particular asymmetric center of a compound is described as being in the (R)- or (S)-configuration, or in a particular relative configuration, such description is understood to refer to the compound in enriched, especially essentially pure form, with respect to each configuration of the asymmetric center. Similarly, when such a chiral or asymmetric center is described as being in the (RS)-configuration, this means that the chiral or asymmetric center in the compound may be present in the (R)-configuration, the (S)-configuration, or any mixture of epimers about that center. When two or more such chiral or asymmetric centers are present in a molecule (in unstated or depicted (RS)-configuration), unless expressly stated otherwise, the order of absolute configurations is not intended to imply any definitive relative configuration for said two or more centers. Explicitly depicted (R)- or (S)-configurations and unstated or depicted (RS)-configurations may coexist in the same molecule and shall be construed in accordance with the above explanations. Similarly, cis- or trans-denotations (or (R * ,R * ) / (R * ,S *The notation 2,3-difluoro-4-(1-((2R,3R,4S,5R,6R)-2-((1-((3R * ,4S * )-3-Fluorotetrahydro-2H-pyran-4-yl)-1H-1,2,3-triazol-4-yl)methyl)-5-hydroxy-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-4-yl)-1H-1,2,3-triazol-4-yl)benzonitrile; 2,3-Difluoro-4-(1-((2R,3R,4S,5R,6R)-2-((1-((3R,4S)-3-fluorotetrahydro-2H-pyran-4-yl)-1H-1,2,3-triazol-4-yl)methyl)-5-hydroxy-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-4-yl)-1H-1,2,3-triazol-4-yl)benzonitrile 2,3-difluoro-4-(1-((2R,3R,4S,5R,6R)-2-((1-((3S,4R)-3-fluorotetrahydro-2H-pyran-4-yl)-1H-1,2,3-triazol-4-yl)methyl)-5-hydroxy-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-4-yl)-1H-1,2,3-triazol-4-yl)benzonitrile, 2,3-difluoro-4-(1-((2R,3R,4S,5R,6R)-2-((1-((3S,4R)-3-fluorotetrahydro-2H-pyran-4-yl)-1H-1,2,3-triazol-4-yl)methyl)-5-hydroxy-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-4-yl)-1H-1,2,3-triazol-4-yl)benzonitrile, or any mixture thereof. Similarly, the compound (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((3R * ,4R *)-4-fluorotetrahydrofuran-3-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol is (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((3R,4R)-4-fluorotetrahydrofuran-3-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol I, (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((3S,4S)-4-fluorotetrahydrofuran-3-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol, or any mixture thereof.

[0016] In this patent application, bonds drawn as dotted lines or interrupted by wavy lines indicate the point of attachment of the depicted group. For example, the group

[0017] [ka] describes the 2,3,4-trifluorophenyl group.

[0018] The term "enriched", when used in connection with stereoisomers, is understood in the context of the present invention to mean that each stereoisomer is present in a ratio of at least 70:30, in particular at least 90:10, relative to the total of each other stereoisomer / each other stereoisomer (i.e. in a purity of at least 70% by weight, in particular at least 90% by weight).

[0019] The term "essentially pure", when used in connection with stereoisomers, is understood in the context of the present invention to mean that each stereoisomer is present in a purity of at least 95% by weight, in particular at least 99% by weight, with respect to each other stereoisomer / total of each other stereoisomer.

[0020] The present invention also provides isotopically labeled, especially 2 H (deuterium)-labeled compounds of formula (I) according to embodiments 1) to 25), which are identical to compounds of formula (I) except that one or more atoms are respectively replaced by atoms having the same atomic number but an atomic mass different from that normally found in nature. Isotopically labeled compounds, especially 2 H (deuterium) labeled compounds of formula (I), (II) and (III) and salts thereof are included within the scope of the present invention. 2 Substitution with H (deuterium) can increase metabolic stability, for example, prolonging in vivo half-life, or reducing the required dose, or reducing inhibition of cytochrome P450 enzymes, for example, improving the safety profile. In one embodiment of the present invention, the compounds of formula (I) are not isotopically labeled, or they are labeled only with one or more deuterium atoms. In a subembodiment, the compounds of formula (I) are not isotopically labeled at all. Isotopically labeled compounds of formula (I) may be prepared similarly to the methods described below, except for using appropriate isotopic species of the appropriate reagents or starting materials.

[0021] When the plural is used for compounds, salts, pharmaceutical compositions, diseases, etc., it is intended to refer to the singular compound, salt, etc. as well.

[0022] Any reference to compounds of formula (I) according to embodiments 1) to 25) will be understood to also refer to salts (especially pharmaceutically acceptable salts) of such compounds, where appropriate.

[0023] The term "pharmaceutically acceptable salt" refers to a salt that retains the desired biological activity of the subject compound and exhibits minimal undesired toxicological 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 subject compound. For reference, see, for example, "Handbook of Pharmaceut ical 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.

[0024] The definitions set forth herein apply uniformly to compounds of formula (I) as defined in any one of embodiments 1) to 20) and apply mutatis mutandis throughout the specification and claims, unless a broader or narrower definition is given by a specific definition. It is to be understood that any definition or preferred definition of a term may independently (and together with) define and replace the respective term in any or all other terms or preferred definitions defined herein.

[0025] In this patent application, compounds are named using IUPAC nomenclature, but may also be named using carbohydrate nomenclature.

[0026] [ka] can be named (2R,3R,4R,5R,6R)-5-hydroxy-6-(hydroxymethyl)-3-methoxy-4-(4-phenyl-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl, or alternatively 1,2,3-tri-deoxy-2-methoxy-3-[4-phenyl-1H-1,2,3-triazol-1-yl]-α-D-galactopyranosid-1-yl, where the absolute configuration of the carbon atom bearing the point of attachment to the rest of the molecule is (2R)-, or alpha. For example, the compound (2R,3R,4S,5R,6R)-6-((4-cyclopentyl-1H-1,2,3-triazol-1-yl)methyl)-2-(hydroxymethyl)-5-methoxy-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol is also understood to be: 1-(1,2,3-tri-deoxy-2-methoxy-3-[4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-α-D-galacto-pyranose)-1-(4-cyclopentyl-1H-triazol-1-yl)-methane.

[0027] Whenever a substituent is described as optional, it is understood that such substituent may be absent (i.e., the respective residue is unsubstituted with respect to such optional substituent), in which case all valenced sites (e.g., in an aromatic ring, ring carbon atoms and / or ring nitrogen atoms with valences to which such optional substituents may be attached) are replaced by hydrogen, as appropriate. Similarly, when the term "optionally" is used in conjunction with a (ring) heteroatom, it is understood that such substituents may be present in conjunction with a (ring) heteroatom. When used in reference to a group, this term means that each optional heteroatom, etc. is either absent (i.e., the group has no heteroatoms / is carbocyclic / etc.) or that each optional heteroatom, etc. is present as explicitly defined. Unless expressly defined otherwise in each embodiment or claim, groups defined herein are unsubstituted.

[0028] The term "halogen" means fluorine / fluoro (fluoride), chlorine / chloro (chloride), bromine / bromo (bromide) or iodine / iodo (iodide); in particular fluoro, chloro or bromo; especially fluoro. The substituent R P4 In this context, the term especially means fluoro, chloro or bromo.

[0029] The term "alkyl," used alone or in combination, means a straight or branched chain saturated hydrocarbon group having 1 to 6 carbon atoms. x-y The term "-alkyl" (x and y are each integers) refers to an alkyl group as defined above having x to y carbon atoms. For example, C 1-6 -Alkyl groups have 1 to 6 carbon atoms. 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. For the avoidance of any doubt, when a group is written as, for example, propyl or butyl, it is generally meant to mean n-propyl or n-butyl, respectively. The group R 2 Branch C used for 3-6 Examples of -alkyl are the abovementioned branched alkyl groups, especially isopropyl and tert-butyl.

[0030] "-C x-y The term "-alkylene-", used alone or in combination, refers to a bivalently bound alkyl group, as defined above, having x to y carbon atoms. 0-y The term "-alkylene-" refers to either a direct bond or the previously defined -(C 1-y ) alkylene-. Preferably, -C 1-y The points of attachment of the alkylene groups are in the 1,1-diyl or 1,2-diyl or 1,3-diyl configuration. 0-y When an -alkylene group is used in combination with another substituent, the term also applies when that substituent is C 1-y- means that the group is attached to the remainder of the molecule via an alkylene group or that it is directly attached to the remainder of the molecule (i.e., a CO-alkylene group represents a direct bond connecting the group to the remainder of the molecule). Unless explicitly stated otherwise, the alkylene group -C2H4- means -CH2-CH2-. For example, -C 1-3 -Alkylene-OH or -C 1-3 -Alkylene-OC 1-3 -C used in reference to alkyl 1-3 Examples of -alkylene are especially methylene and ethylene (-CH2-CH2-).

[0031] The term "fluoroalkyl," used alone or in combination, refers to an alkyl group, as defined above, having 1 to 3 carbon atoms, in which one or more (and in some cases all) hydrogen atoms have been replaced with fluorine. x-y The term "fluoroalkyl" (x and y are each integers) refers to a fluoroalkyl group as defined above having x to y carbon atoms. For example, C 1-3 A -fluoroalkyl group has 1 to 3 carbon atoms in which 1 to 7 hydrogen atoms have been replaced by fluorine. "C1-fluoroalkyl" refers in particular to trifluoromethyl or difluoromethyl.

[0032] The term "cycloalkyl," used alone or in combination, means a saturated monocyclic or bicyclic (e.g., bridged, fused, or spiro-bicyclic) hydrocarbon ring having 3 to 8 carbon atoms. x-y The term "-cycloalkyl" (x and y are each integers) refers to a cycloalkyl group as defined above having x to y carbon atoms. For example, C 3-6 -Cycloalkyl groups have 3 to 6 carbon atoms. Examples of cycloalkyl groups are cyclopropyl, cyclobutyl, cyclopropyl ... Monocyclic C such as cyclopentyl and cyclohexyl 3-6-cycloalkyl groups (especially cyclopropyl, cyclobutyl and cyclopentyl); bridged bicyclic C groups such as bicyclo[1.1.1]pentan-1-yl or bicyclo[2.2.2]octan-1-yl 5-8 -cycloalkyl groups; spiro-bicyclic C groups such as spiro[2.3]hexan-5-yl 6-8 -cycloalkyl groups; and fused bicyclic C groups such as bicyclo[3.1.0]hexan-6-yl (especially (1R,5S)-bicyclo[3.1.0]hexan-6-yl). 6-8 -cycloalkyl group.

[0033] The term "heterocycloalkyl," whether used alone or in combination, unless a narrower definition is expressly indicated, refers to a saturated cycloalkyl, as defined above, having one or two ring heteroatoms independently selected from nitrogen, sulfur, and oxygen (particularly one oxygen atom; or one sulfur atom, one nitrogen atom, two nitrogen atoms, two oxygen atoms, or one nitrogen atom and one oxygen atom). The term "x-y-membered heterocycloalkyl" refers to such a heterocycloalkyl having a total of x-y ring atoms. Heterocycloalkyl groups are unsubstituted or substituted as expressly defined. Examples of heterocycloalkyl groups are 4- to 6-membered monocyclic heterocycloalkyls having one ring oxygen atom, such as oxetan-3-yl and tetrahydro-2H-pyran-4-yl; and 7- or 8-membered spiro-bicyclic heterocycloalkyls having one ring oxygen atom, such as 2-oxaspiro[3.3]heptan-6-yl.

[0034] The term "alkoxy", used alone or in combination, means an alkyl-O- group, wherein the alkyl group is as previously defined. x-y The term "-alkoxy" (x and y are each integers) means an alkoxy group as defined above having x to y carbon atoms. Preferred is ethoxy and especially methoxy.

[0035] The term "heteroaryl," whether used alone or in combination, unless a broader or narrower definition is explicitly stated, refers to a 5-10 membered monocyclic or bicyclic aromatic ring containing from 1 to 4 heteroatoms, each independently selected from oxygen, nitrogen, and sulfur. Examples of such heteroaryl groups are furanyl, oxazolyl, isoxazolyl, thiophenyl, thiazolyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, indazolyl, benzo[d]imidazolyl, benzo[d]oxazolyl, and indolyl. The above heteroaryl groups are unsubstituted or substituted as explicitly defined. The substituent HET 1 With respect to, examples of 5-membered heteroaryl groups are, inter alia, oxazolyl, thiazolyl and imidazolyl.

[0036] The term "cyano" refers to the group --CN.

[0037] The term "oxo" refers to the group =0, preferably attached to a chain or ring carbon (or sulfur) atom, such as in a carbonyl group -(CO)- (or a sulfonyl group -(SO2)-).

[0038] Whenever the word "between" is used to describe a range of numerical values, the endpoints of the stated range are expressly included in that range. This means, for example, that when a temperature range is stated to be between 40°C and 80°C, the endpoints 40°C and 80°C are included in the range; or, when a variable is defined as an integer between 1 and 4, the variable is meant to be the integer 1, 2, 3, or 4.

[0039] When not used in reference to temperature, the term "about" placed before a numerical value "X" in this application represents a range of 10% of XX to 10% of X+X, preferably a range of 5% of XX to 5% of X+X. In the specific case of temperature, the term "about" placed before a temperature "Y" in this application represents a range of Y-10°C to Y+10°C, preferably a range of Y-5°C to Y+5°C. Furthermore, the term "room temperature" as used herein means a temperature of about 25°C.

[0040] Further aspects of the invention are described below: 3) Another aspect is -R P2 represents fluoro or chloro (especially fluoro); -R P3 represents fluoro or chloro (especially fluoro); -R P4 represents halogen (in particular fluoro, chloro, bromo), methyl or cyano; It relates to compounds according to embodiment 1) or 2).

[0041] 4) Another aspect is -R P2 represents fluoro; -R P3 represents fluoro; -R P4 represents fluoro, chloro, bromo, methyl or cyano; Concerning the compounds according to embodiment 1) or 2) 5) Another aspect is -R P2 represents fluoro or chloro (especially fluoro); -R P3 represents fluoro or chloro (especially fluoro); -R P4 represents halogen (in particular fluoro, chloro, bromo) or methyl; It relates to compounds according to embodiment 1) or 2).

[0042] 6) Another aspect is -RP2 represents fluoro; -R P3 represents fluoro; -R P4 represents fluoro, chloro, bromo or methyl; It relates to compounds according to embodiment 1) or 2).

[0043] 7) Another aspect is R 1 but hydroxy; or C 1-4 -alkoxy (especially methoxy).

[0044] 8) Another aspect is R 1 represents methoxy.

[0045] 9) Another aspect is -R 2 But branch C 3-6 -alkyl, wherein the branched C 3-6 - alkyl is -- substituted by one hydroxy [particularly such groups are 2-hydroxy-1,1-dimethyl-ethyl or 1-hydroxy-1-methyl-ethyl], -- 1 -CO-OC 1-4 -substituted by alkyl [particularly such a group is 1-methoxy-2-methyl-1-oxopropan-2-yl], or -- substituted by one C1-fluoroalkyl [particularly, such a group is 2,2-difluoro-1,1-dimethyl-ethyl]; Branch C 3-6 -represents alkyl; - or R 2 is a 3- to 8-membered saturated monocyclic or bicyclic group, and the monocyclic or bicyclic group is -- monocyclic C 3-6 -cycloalkyl (especially cyclopropyl, cyclobutyl or cyclopropyl) cyclopentyl), wherein the monocyclic C 3-6 -cycloalkyl is --- unsubstituted; --- substituted by one hydroxy; --- 1 C 1-3 substituted by alkyl (especially methyl; or isopropyl); --- 1 piece of -C 1-3 -substituted by alkylene-OH (especially hydroxymethyl); --- 1 piece of -C 1-3 -Alkylene-OC 1-3 -substituted by alkyl (especially methoxymethyl); --- One substituent is hydroxy and the other is C 1-3 -substituted by two substituents which are alkyl (especially methyl); or --- three substituents, two of which are fluoro and the fluoro substituents are both attached to the same ring carbon atom; the remaining substituents are C 1-3 -Alkyl (especially methyl) or -C 1-3 -substituted by three substituents, which are alkylene-OH (especially hydroxymethyl); monocyclic C 3-6 -cycloalkyl; -- 4- to 6-membered monocyclic heterocycloalkyl having one ring oxygen atom (especially oxetan-3-yl, tetrahydro-2H-pyran-3-yl), wherein the 4- to 6-membered monocyclic heterocycloalkyl group is --- substituted by one hydroxy; --- 1 C 1-3 substituted by alkyl (especially methyl; or ethyl); --- 1 piece of -C 1-3 -substituted by alkylene-OH (especially hydroxymethyl, 2-hydroxymethyl); or --- 1 piece of -C 1-3 -Alkylene-OC 1-3 -substituted by alkyl (especially methoxymethyl); 4-6 membered monocyclic heterocycloalkyl; --Bridged Bicyclic C 5-8-cycloalkyl (especially bicyclo[1.1.1]pentan-1-yl, bicyclo[2.2.2]octan-1-yl), 5-8 - the cycloalkyl group is --- unsubstituted; --- substituted by one hydroxy; --- 1 C 1-3 substituted by alkyl (especially methyl; or ethyl or isopropyl); --- 1 C 1-3 -substituted by alkoxy (especially methoxy); --- substituted by one C1-fluoroalkyl (especially trifluoromethyl); --- one -NR N1 R N2 (R N1 represents hydrogen, and R N2 is hydrogen or -CO-OC 1-4 -alkyl (especially -CO-O-tert.-butyl); or --- substituted by one fluoro; Bridged Bicyclic C 5-8 -cycloalkyl; -- Unsubstituted fused bicyclic C 6-8 -cycloalkyl (especially bicyclo[3.1.0]hexan-6-yl); -- Unsubstituted spiro-bicyclic C 6-8 -cycloalkyl (especially spiro[2.3]hexan-5-yl), or unsubstituted 7- or 8-membered spiro-bicyclic heterocycloalkyl having one ring oxygen atom (in particular oxaspiro[3.3]heptan-6-yl); represents a monocyclic or bicyclic group, The compound according to any one of embodiments 1) to 8).

[0046] 10) In another embodiment, A represents [1,2,3]triazole-1,4-diyl and R 2 is attached to the 1-position of the [1,2,3]triazole-1,4-diyl;

[0047] 11) Another embodiment is when A represents [1,2,3]triazole-1,4-diyl and R 2 is attached to the 4-position of the [1,2,3]triazole-1,4-diyl;

[0048] 12) Another aspect is a) Base AR 2 but,

[0049] [ka]

[0050] [ka] A group selected from

[0051] [ka] represents; or b) Base AR 2 but,

[0052] [ka] A group selected from

[0053] [ka] represents; or c) Base AR 2 but,

[0054] [ka]

[0055] [ka] A group selected from

[0056] [ka] represents; With respect to compounds according to any one of embodiments 1) to 8); each of groups a), b) and c) forms a separate sub-embodiment.

[0057] 13) Another aspect is a) Base AR 2 but,

[0058] [ka]

[0059] [ka] A group selected from

[0060] [ka] represents; or b) Base AR 2 but,

[0061] [ka] A group selected from

[0062] [ka] represents; or c) Base AR 2 but,

[0063] [ka]

[0064] [ka] A group selected from

[0065] [ka] represents; With respect to compounds according to any one of embodiments 1) to 8); each of groups a), b) and c) forms a separate sub-embodiment.

[0066] 14) Another aspect is a) Base AR 2 but,

[0067] [ka] A group selected from

[0068] [ka] represents; or b) Base AR 2 but,

[0069] [ka] A group selected from

[0070] [ka] represents; or c) Base AR 2 but,

[0071] [ka]

[0072] [ka] A group selected from

[0073] [ka] represents; With respect to compounds according to any one of embodiments 1) to 8); each of groups a), b) and c) forms a separate sub-embodiment.

[0074] 15) Another aspect is a) Base AR 2 but,

[0075] [ka] A group selected from

[0076] [ka] represents; or b) Base AR 2 but,

[0077] [ka] A group selected from

[0078] [ka] represents; or c) Base AR 2 but,

[0079] [ka]

[0080] [ka] A group selected from

[0081] [ka] represents; With respect to compounds according to any one of embodiments 1) to 8); each of groups a), b) and c) forms a separate sub-embodiment.

[0082] 16) Another aspect is a) Base AR 2 but,

[0083] [ka] A group selected from

[0084] [ka] represents; or b) Base AR 2 but,

[0085] [ka]

[0086] [ka] A group selected from

[0087] [ka] represents; With respect to compounds according to any one of embodiments 1) to 8); groups a) and b) each form a separate sub-embodiment.

[0088] 17) Another aspect is a) Base AR 2 but,

[0089] [ka] A group selected from

[0090] [ka] represents; or b) Base AR 2 but,

[0091] [ka] A group selected from

[0092] [ka] represents; or c) Base AR 2 but,

[0093] [ka]

[0094] [ka] A group selected from

[0095] [ka] represents; With respect to compounds according to any one of embodiments 1) to 8); each of groups a), b) and c) forms a separate sub-embodiment.

[0096] 18) In a further aspect, the invention relates to a compound of formula (I) which is also a compound of formula (II):

[0097] [ka] (In the formula, R P2 represents halogen (especially fluoro); R P3 represents halogen (especially fluoro); R P4 represents halogen (especially fluoro, chloro, bromo), methyl or cyano; Base AR 2 is the base

[0098] [ka] represents; -R 21 and R 21 are independently branched C 3-6 -alkyl (especially isopropyl or tert-butyl), 3-6 - alkyl is -- substituted by one hydroxy [particularly such groups are 2-hydroxy-1,1-dimethyl-ethyl or 1-hydroxy-1-methyl-ethyl], -- 1 -CO-OC 1-4 -alkyl substituted [particularly such groups are 1- methoxy-2-methyl-1-oxopropan-2-yl; or -- substituted by one C1-fluoroalkyl [particularly, such a group is 2,2-difluoro-1,1-dimethyl-ethyl]; Branch C 3-6 -represents alkyl; - or R 21 and R 21 are independently 3-8 membered saturated monocyclic or bicyclic groups, and the monocyclic or bicyclic groups are -- monocyclic C 3-6 cycloalkyl (especially cyclopropyl, cyclobutyl or cyclopentyl), -- 4-6-membered monocyclic heterocycloalkyl having one ring oxygen atom (especially oxetan-3-yl, tetrahydro-2H-pyran-3-yl), --Bridged Bicyclic C 5-8 -cycloalkyl (in particular bicyclo[1.1.1]pentan-1-yl, bicyclo[2.2.2]octan-1-yl), -- Fused Bicyclic C 6-8 -cycloalkyl (especially bicyclo[3.1.0]hexan-6-yl), -- Spiro-bicyclic C 6-8-cycloalkyl (especially spiro[2.3]hexan-5-yl), or 7- or 8-membered spiro-bicyclic heterocycloalkyl having one ring oxygen atom (in particular oxaspiro[3.3]heptan-6-yl); represents a monocyclic or bicyclic group, The monocyclic or bicyclic groups are independently unsubstituted or substituted with 1, 2 or 3 substituents, the substituents being hydroxy; C 1-3 - alkyl (especially methyl; or ethyl or isopropyl); C 1-3 -alkoxy (especially methoxy); -C 1-3 -Alkylene-OH (especially hydroxymethyl or 2-hydroxyethyl); C1-fluoroalkyl (especially trifluoromethyl); -NR N1 R N2 (R N1 represents hydrogen, and R N2 is hydrogen or -CO-OC 1-4 alkyl (especially -CO-O-tert.-butyl); and fluoro.

[0099] In a subembodiment, the monocyclic or bicyclic group is independently: -- whether it is unsubstituted; -- substituted by one hydroxy; -- 1 C 1-3 substituted by alkyl (especially methyl; or ethyl or isopropyl); -- 1 C 1-3 -substituted by alkoxy (especially methoxy); -- 1 -C 1-3 -substituted by alkylene-OH (especially hydroxymethyl, 2-hydroxyethyl); -- 1 -C 1-3 -Alkylene-OC 1-3 -substituted by alkyl (especially methoxymethyl); -- substituted by one C1-fluoroalkyl (especially trifluoromethyl); -- 1 piece -NR N1 R N2(R N1 represents hydrogen, and R N2 is hydrogen or -CO-OC 1-4 -alkyl (especially -CO-O-tert.-butyl); -- substituted by 1 or 2 fluoro; --One substituent is hydroxy and the other is C 1-3 -substituted by two substituents which are alkyl (especially methyl); or -- three substituents, two of which are fluoro (especially attached to the same ring carbon atom); the remaining substituents are C 1-3 -Alkyl (especially methyl) or -C 1-3 -substituted by three substituents, which are -alkylene-OH (especially hydroxymethyl).

[0100] The features disclosed in embodiments 3) to 6) and 9) to 17) are intended to apply mutatis mutandis to compounds of formula (II) according to embodiment 18).

[0101] 19) A further aspect is the base

[0102] [ka] is as defined in embodiment 3); in particular, such groups are:

[0103] [ka] which relates to compounds of formula (II) according to embodiment 18).

[0104] 20) A further embodiment is the group AR 2 is as defined in embodiment 12), 13), 14), 15), 16) or 17).

[0105] 21) Another embodiment relates to compounds of formula (I) according to embodiment 1), which are selected from the following compounds: (2R,3R,4S,5R,6R)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-6-((1-((3R,4R)-4-hydroxytetrahydro-2H-pyran-3-yl)-1H-1,2,3-triazol-4-yl)methyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((1R,2R)-2-hydroxycyclopentyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((1S,2S)-2-hydroxycyclopentyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-6-((1-(1-(hydroxymethyl)cyclopropyl)-1H-1,2,3-triazol-4-yl)methyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-6 -((1-(1-(hydroxymethyl)cyclopentyl)-1H-1,2,3-triazol-4-yl)methyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((1-(3-methyloxetan-3-yl)-1H-1,2,3-triazol-4-yl)methyl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((1-(1-(methoxymethyl)cyclopropyl)-1H-1,2,3-triazol-4-yl)methyl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-6-((1-(4-hydroxybicyclo[2.2.2]octan-1-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-6-((1-(1-hydroxy-2-methylpropan-2-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; Methyl 2-(4-(((2R,3R,4S,5R,6R)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-yl)methyl)-1H-1,2,3-triazol-1-yl)-2-methylpropanoate; (2R,3R,4S,5R,6R)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-6-((1-(1-(hydroxymethyl)cyclobutyl)-1H-1,2,3-triazol-4-yl)methyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-6-((1-(bicyclo[1.1.1]pentan-1-yl)-1H-1,2,3-triazol-4-yl)methyl)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((1-(1-methylcyclobutyl)-1H-1,2,3-triazol-4-yl)methyl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((1-(3-methylbicyclo[1.1.1]pentan-1-yl)-1H-1,2,3-triazol-4-yl)methyl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-6-((1-(3,3-difluoro-1-methylcyclobutyl)-1H-1,2,3-triazol-4-yl)methyl)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-6-((1-(2-oxaspiro[3.3]heptan-6-yl)-1H-1,2,3-triazol-4-yl)methyl)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl) (yl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-6-((1-((1RS,2SR)-2-isopropylcyclopropyl)-1H-1,2,3-triazol-4-yl)methyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-6-((1-(3,3-difluoro-1-(hydroxymethyl)cyclobutyl)-1H-1,2,3-triazol-4-yl)methyl)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((1S,3S)-3-hydroxy-1-methylcyclobutyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-6-((1-((1R,5S)-bicyclo[3.1.0]hexan-6-yl)-1H-1,2,3-triazol-4-yl)methyl)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((1-(3-(methoxymethyl)oxetan-3-yl)-1H-1,2,3-triazol-4-yl)methyl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-6-((1-(3-(2-hydroxyethyl)oxetan-3-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((1-(1-methylcyclopropyl)-1H-1,2,3-triazol-4-yl)methyl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((1-(3-(trifluoromethyl)bicyclo[1.1.1]pentan-1-yl)-1H-1,2,3-triazol-4-yl)methyl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-6-((1-(3-fluorobicyclo[1.1.1]pentan-1-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((1-(spiro[2.3]hexan-5-yl)-1H-1,2,3-triazol-4-yl)methyl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((1r,3R)-3-hydroxy-1-methylcyclobutyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((1-(1-(methoxymethyl)cyclopropyl)-1H-1,2,3-triazol-4-yl)methyl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-(1,1-difluoro-2-methylpropan-2-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-6-((1-(1-(hydroxymethyl)cyclopropyl)-1H-1,2,3-triazol-4-yl)methyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-6-((1-(1-(hydroxymethyl)cyclopentyl)-1H-1,2,3-triazol-4-yl)methyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-6-((1-(1-(hydroxymethyl)cyclobutyl)-1H-1,2,3-triazol-4-yl)methyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-(4-hydroxybicyclo[2.2.2]octan-1-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-(1-hydroxy-2-methylpropan-2-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; Methyl 2-(4-(((2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-yl)methyl)-1H-1,2,3-triazol-1-yl)-2-methylpropanoate; (2R,3R,4S,5R,6R)-6-((1-(bicyclo[1.1.1]pentan-1-yl)-1H-1,2,3-triazol-4-yl)methyl)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((1-(1-methylcyclobutyl)-1H-1,2,3-triazol-4-yl)methyl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-chloro-2,3-difluorophenyl)- nyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((1-(3-methyloxetan-3-yl)-1H-1,2,3-triazol-4-yl)methyl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((1-(3-methylbicyclo[1.1.1]pentan-1-yl)-1H-1,2,3-triazol-4-yl)methyl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((1-(3-methoxybicyclo[1.1.1]pentan-1-yl)-1H-1,2,3-triazol-4-yl)methyl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-(3,3-difluoro-1-methylcyclobutyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-6-((1-(2-oxaspiro[3.3]heptan-6-yl)-1H-1,2,3-triazol-4-yl)methyl)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-6-((1-(2-isopropylcyclopropyl)-1H-1,2,3-triazol-4-yl)methyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-(3,3-difluoro-1-(hydroxymethyl)cyclobutyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((1S,3S)-3-hydroxy-1-methylcyclobutyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-6-((1-((1R,5S)-bicyclo[3.1.0]hexan-6-yl)-1H-1,2,3-triazol-4-yl)methyl)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((1-(3-(methoxymethyl)oxetan-3-yl)-1H-1,2,3-triazol-4-yl)methyl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-(3-(2-hydroxyethyl)oxetan-3-yl)-1H-1,2,3-triazol-4-yl) Methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((1-(1-methylcyclopropyl)-1H-1,2,3-triazol-4-yl)methyl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((1-(3-(trifluoromethyl)bicyclo[1.1.1]pentan-1-yl)-1H-1,2,3-triazol-4-yl)methyl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-(3-fluorobicyclo[1.1.1]pentan-1-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((1-(spiro[2.3]hexan-5-yl)-1H-1,2,3-triazol-4-yl)methyl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((1R,3R)-3-hydroxy-1-methylcyclobutyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-2-(hydroxymethyl)-6-((1-(1-(hydroxymethyl)cyclopentyl)-1H-1,2,3-triazol-4-yl)methyl)-5-methoxy-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-2-(hydroxymethyl)-6-((1-(1-(hydroxymethyl)cyclopropyl)-1H-1,2,3-triazol-4-yl)methyl)-5-methoxy-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-2-(hydroxymethyl)-5-methoxy-6-((1-(1-(methoxymethyl)cyclopropyl)-1H-1,2,3-triazol-4-yl)methyl)-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-6-((1-(bicyclo[1.1.1]pentan-1-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxy-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-2-(hydroxymethyl)-6-((1-(1-(hydroxymethyl)cyclobutyl)-1H-1,2,3-triazol-4-yl)methyl)-5-methoxy-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-6-((1-(3-fluorobicyclo[1.1.1]pentan-1-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxy-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-2-(hydroxymethyl)-5-methoxy-6-((1-(3-(trifluoromethyl)bicyclo[1.1.1]pentan-1-yl)-1H-1,2,3-triazol-4-yl)methyl)-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-6-((1-(3,3-difluoro-1-methylcyclobutyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxy-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-6-((1-(3,3-difluoro-1-(hydroxymethyl)cyclobutyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxy-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-6-((1-(2-oxaspiro[3.3]heptan-6-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxy-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-6-((1-((1R,3R)-3-hydroxy-1-methylcyclobutyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxy-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-6-((1-((1S,3S)-3-hydroxy-1-methylcyclobutyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxy-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-2-(hydroxymethyl)-5-methoxy-6-((1-(3-(methoxymethyl)oxetan-3-yl)-1H-1,2,3-triazol-4-yl)methyl)-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-6-((1-(3-(2-hydroxyethyl)oxetan-3-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxy-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-2-(hydroxymethyl)-5-methoxy-6-((1-(1-methylcyclopropyl)-1H-1,2,3-triazol-4-yl)methyl)-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((1-(3-methyloxetan-3-yl)-1H-1,2,3-triazol-4-yl)methyl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((1-(1-methylcyclobutyl)-1H-1,2,3-triazol-4-yl)methyl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-6-((1-(bicyclo[1.1.1]pentane- (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((1-(1-(methoxymethyl)cyclobutyl)-1H-1,2,3-triazol-4-yl)methyl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-6-((1-(1-(hydroxymethyl)cyclopropyl)-1H-1,2,3-triazol-4-yl)methyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((1S,2S)-2-hydroxycyclopentyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-6-((4-(1-hydroxycyclobutyl)-1H-1,2,3-triazol-1-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-6-((4-cyclopentyl-1H-1,2,3-triazol-1-yl)methyl)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-6-((4-(1-hydroxycyclopentyl)-1H-1,2,3-triazol-1-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-6-((4-(2-hydroxypropan-2-yl)-1H-1,2,3-triazol-1-yl)methyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((4-(3-methyloxetan-3-yl)-1H-1,2,3-triazol-1-yl)methyl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-6-((4-(4-hydroxytetrahydro-2H-pyran-4-yl)-1H-1,2,3-triazol-1-yl)methyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-6-((4-(1-hydroxycyclopropyl)-1H-1,2,3-triazol-1-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-6-((4-(1-(hydroxymethyl)cyclopropyl)-1H-1,2,3-triazol-1-yl)methyl)-5-methoxytetrahydro-2H-pyran-3-ol; tert-Butyl (4-(1-(((2R,3R,4S,5R,6R)-4-(4-( 2,3-Difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-yl)methyl)-1H-1,2,3-triazol-4-yl)bicyclo[2.2.2]octan-1-yl)carbamate; (2R,3R,4S,5R,6R)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-6-((4-(3-ethyloxetan-3-yl)-1H-1,2,3-triazol-1-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-6-((1-(4-aminobicyclo[2.2.2]octan-1-yl)-1H-1,2,3-triazol-4-yl)methyl)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((4-(1-hydroxycyclobutyl)-1H-1,2,3-triazol-1-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((4-cyclopentyl-1H-1,2,3-triazol-1-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((4-(1-hydroxycyclopentyl)-1H-1,2,3-triazol-1-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-6-((4-(2-hydroxypropan-2-yl)-1H-1,2,3-triazol-1-yl)methyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((4-(3-methyloxetan-3-yl)-1H-1,2,3-triazol-1-yl)methyl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-6-((4-(4-hydroxytetrahydro-2H-pyran-4-yl)-1H-1,2,3-triazol-1-yl)methyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((4-(1-hydroxycyclopropyl)-1H-1,2,3-triazol-1-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-6-((4-(1-(hydroxymethyl)cyclopropyl)-1H-1,2,3-triazol-1-yl)methyl)-5-methoxytetrahydro-2H-pyran-3-ol; tert-Butyl (4-(1-(((2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-yl)methyl)-1H-1,2,3-triazol-4-yl)bicyclo[ 2.2.2]octan-1-yl)carbamate; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((4-(3-ethyloxetan-3-yl)-1H-1,2,3-triazol-1-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; and (2R,3R,4S,5R,6R)-6-((1-(4-aminobicyclo[2.2.2]octan-1-yl)-1H-1,2,3-triazol-4-yl)methyl)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol.

[0106] 22) In addition to the compounds described in embodiment 21), further compounds of formula (I) according to embodiment 1) are selected from the following compounds: (2R,3R,4S,5R,6R)-6-((4-(1-hydroxycyclobutyl)-1H-1,2,3-triazol-1-yl)methyl)-2-(hydroxymethyl)-5-methoxy-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-6-((4-cyclopentyl-1H-1,2,3-triazol-1-yl)methyl)-2-(hydroxymethyl)-5-methoxy-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-6-((4-(1-hydroxycyclopentyl)-1H-1,2,3-triazol-1-yl)methyl)-2-(hydroxymethyl)-5-methoxy-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-2-(hydroxymethyl)-6-((4-(2-hydroxypropan-2-yl)-1H-1,2,3-triazol-1-yl)methyl)-5-methoxy-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-2-(hydroxymethyl)-5-methoxy-6-((4-(3-methyloxetan-3-yl)-1H-1,2,3-triazol-1-yl)methyl)-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-2-(hydroxymethyl)-6-((4-(4-hydroxytetrahydro-2H-pyran-4-yl)-1H-1,2,3-triazol-1-yl)methyl)-5-methoxy-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-6-((4-(1-hydroxycyclopropyl)-1H-1,2,3-triazol-1-yl)methyl)-2-(hydroxymethyl)-5-methoxy-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-2-(hydroxymethyl)-6-((4-(1-(hydroxymethyl)cyclopropyl)-1H-1,2,3-triazol-1-yl)methyl)-5-methoxy-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-6-((4-(3-ethyloxetan-3-yl)-1H-1,2,3-triazol-1-yl)methyl)-2-(hydroxymethyl)-5-methoxy-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; tert-butyl (4-(1-(((2R,3R,4S,5R,6R)-5-hydroxy-6-(hydroxymethyl)-3-methoxy-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)methyl)-1H-1,2,3-triazol-4-yl)bicyclo[2.2.2]octan-1-yl)carbamate; and (2R,3R,4S,5R,6R)-6-((1-(4-aminobicyclo[2.2.2]octan-1-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxy-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; and (2R,3R,4S,5R,6R)-6-((4-(bicyclo[1.1.1]pentan-1-yl)-1H-1,2,3-triazol-1-yl)methyl)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((4-(1-methylcyclopropyl)-1H-1,2,3-triazol-1-yl)methyl)tetrahydro-2H-pyran-3-ol; and (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((4-(1-methylcyclobutyl)-1H-1,2,3-triazol-1-yl)methyl)tetrahydro-2H-pyran-3-ol.

[0107] 23) In addition to the compounds described in embodiments 21) and 22), further compounds of formula (I) according to embodiment 1) are selected from the following compounds: (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-(1-(fluoromethyl)cyclobutyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((1-(3-(trifluoromethyl)cyclobutyl)-1H-1,2,3-triazol-4-yl)methyl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((1-(3-methyltetrahydrofuran-3-yl)-1H-1,2,3-triazol-4-yl)methyl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-(1-(difluoromethyl)cyclobutyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-(1-(fluoromethyl)cyclopropyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-2-(hydroxymethyl)-5-methoxy-6-((1-(spiro[2.3]hexan-5-yl)-1H-1,2,3-triazol-4-yl)methyl)-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-2-(hydroxymethyl)-5-methoxy-6-( (1-(3-methylbicyclo[1.1.1]pentan-1-yl)-1H-1,2,3-triazol-4-yl)methyl)-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-2-(hydroxymethyl)-5-methoxy-6-((1-(1-methylcyclobutyl)-1H-1,2,3-triazol-4-yl)methyl)-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-2-(hydroxymethyl)-5-methoxy-6-((1-(spiro[3.3]heptan-1-yl)-1H-1,2,3-triazol-4-yl)methyl)-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-6-((1-(1-(difluoromethyl)cyclopropyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxy-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-(3,3-difluoro-1-methylcyclobutyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((1S,3S)-3-hydroxy-1-methylcyclobutyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-(3-(2-hydroxyethyl)oxetan-3-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((1-(1-methylcyclopropyl)-1H-1,2,3-triazol-4-yl)methyl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((1-(3-(trifluoromethyl)bicyclo[1.1.1]pentan-1-yl)-1H-1,2,3-triazol-4-yl)methyl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((1-(3-methoxybicyclo[1.1.1]pentan-1-yl)-1H-1,2,3-triazol-4-yl)methyl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((3R,4R)-4-fluorotetrahydro-2H-pyran-3-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-(3-(fluoromethyl)oxetan-3-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-(3-(difluoromethyl)oxetan-3-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((1-(3-(trifluoromethyl)oxetan-3-yl)-1H-1,2,3-triazol-4-yl)methyl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((R)-2,2-difluorocyclobutyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((S)-2,2-difluorocyclobutyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((R)-2,2-difluorocyclopentyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((S)-2,2-difluoro (Cyclopentyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol;(2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((3S,4R)-3-fluorotetrahydro-2H-pyran-4-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((3R,4S)-3-fluorotetrahydro-2H-pyran-4-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((1-(4-(trifluoromethyl)tetrahydro-2H-pyran-4-yl)-1H-1,2,3-triazol-4-yl)methyl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((3R,4R)-4-fluorotetrahydrofuran-3-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyra hen-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((3S,4S)-4-fluorotetrahydrofuran-3-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((3R,4S)-4-fluorotetrahydrofuran-3-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((3S,4R)-4-fluorotetrahydrofuran-3-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-(4,4-difluorospiro[2.2]pentan-1-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((1-((R)-3-(trifluoromethyl)tetrahydrofuran-3-yl)-1H-1,2,3-triazol-4-yl)methyl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((1-((S)-3-(trifluoromethyl)tetrahydrofuran-3-yl)-1H-1,2,3-triazol-4-yl)methyl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((R)-3-(difluoromethyl)tetrahydrofuran-3-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((S)-3-(difluoromethyl)tetrahydrofuran-3-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((1R,2S)-2-fluorocyclopentyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((1S,2R)-2-fluorocyclopentyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol ; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((1R,2R)-2-fluorocyclopentyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((1S,2S)-2-fluorocyclopentyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((R)-2,2-difluorocyclohexyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((S)-2,2 -difluorocyclohexyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol;(2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((1S,2R)-2-fluorocyclohexyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((1R,2R)-2-fluorocyclohexyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((1S,2S)-2-fluorocyclohexyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((1R,2S)-2-fluorocyclobutyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((1S,2R)-2-fluorocyclobutyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((1R,2R)-2-fluorocyclobutyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((1S,2S)-2-fluorocyclobutyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((R)-3,3-difluorotetrahydro-2H-pyran-4-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((S)-3,3-difluorotetrahydro-2H-pyran-4-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((R)-4,4-difluorotetrahydrofuran-3-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((S)-4,4-difluorotetrahydrofuran-3-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-2-(hydroxymethyl)-5-methoxy-6-((1-(3-methyloxetan-3-yl)-1H-1,2,3-triazol-4-yl)methyl)-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-6-((1-(1-(fluoromethyl)cyclopropyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxy-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-6-((1-(1-(difluoromethyl)cyclobutyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxy-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-6-((1-(1,1-difluoro-2-methylpropan-2-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxy-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-6-((1-(1-(fluoromethyl)cyclobutyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxy-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-2-(hydroxymethyl)-5-methoxy-6-((1-(1-(trifluoromethyl)cyclobutyl)-1H-1,2,3-triazol-4-yl)methyl)-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-2-(hydroxymethyl)-5-methoxy-6-((1-(3-(trifluoromethyl)oxetan-3-yl)-1H-1,2,3-triazol-4-yl)methyl)-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-6-((1-((3S,4R)-3-fluorotetrahydro (tetrahydro-2H-pyran-4-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxy-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-6-((1-((3R,4S)-3-fluorotetrahydro-2H-pyran-4-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxy-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-(1-(fluoromethyl)cyclopropyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-(3-(fluoromethyl)oxetan-3-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-(3-fluorobicyclo[1.1.1]pentan-1-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((1-(1-(trifluoromethyl)cyclobutyl)-1H-1,2,3-triazol-4-yl)methyl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-(1-(fluoromethyl)cyclobutyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((R)-2,2-difluorocyclopentyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((S)-2,2-difluorocyclopentyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((1-(3-methylbicyclo[1.1.1]pentan-1-yl)-1H-1,2,3-triazol-4-yl)methyl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((1S,2S)-2-fluorocyclopentyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-bromo-2,3-difluorophenyl)- nyl)-1H-1,2,3-triazol-1-yl)-6-((1-((1R,2R)-2-fluorocyclopentyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-(2,2-difluorocyclobutyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((1R,2S)-2-fluorocyclobutyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((1S,2R)- 2-Fluorocyclobutyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol;(2R,3R,4S,5R,6R)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-6-((1-(3-(difluoromethyl)oxetan-3-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-(1-fluoro-2-methylpropan-2-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((1-(1-(trifluoromethyl)cyclopropyl)-1H-1,2,3-triazol-4-yl)methyl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((1-(1-(trifluoromethyl)cyclobutyl)-1H-1,2,3-triazol-4-yl)methyl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((1-(1,1,1-trifluoro-2-methylpropan-2-yl)-1H-1,2,3-triazol-4-yl)methyl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((1-(1-(trifluoromethyl)cyclopentyl)-1H-1,2,3-triazol-4-yl)methyl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R ,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((1-((1R,3R,5S)-3-(trifluoromethyl)bicyclo[3.1.0]hexan-3-yl)-1H-1,2,3-triazol-4-yl)methyl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5 -Methoxy-6-((1-(2-(trifluoromethyl)bicyclo[2.2.1]heptan-2-yl)-1H-1,2,3-triazol-4-yl)methyl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((3R,4R)-3-fluorotetrahydro-2H-pyran-4-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((3S,4S)-3-fluorotetrahydro-2H-pyran-4-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((R)-4,4-difluorotetrahydro-2H-pyran-3-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((S)-4,4-difluorotetrahydro-2H-pyran-3-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-2-(hydroxymethyl)-5-methoxy-6-((1-(3-methoxybicyclo[1.1.1]pentan-1-yl)-1H-1,2,3-triazol-4-yl)methyl)-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-6-((1-(3-(fluoromethyl)oxetan-3-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxy-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-6-((1-(3-(difluoromethyl)oxetan-3-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxy-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-(1,1-difluoro-2-methylpropan-2-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-(1-(difluoromethyl)cyclobutyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-(3-(difluoromethyl)oxetan-3-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((1-(3-(trifluoromethyl)oxetan-3-yl)-1H-1,2,3-triazol-4-yl)methyl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((1-(3-(trifluoromethyl)oxetan-3-yl)-1H-1,2,3-triazol-4-yl)methyl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-(1-(difluoromethyl)cyclopropyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-2-(hydroxymethyl)-5-methoxy-6-((1-(1-(trifluoromethyl)cyclopropyl)-1H-1,2,3-triazol-4-yl)methyl)-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-(1-(difluoromethyl)cyclopropyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((1-(1-(trifluoromethyl)cyclopropyl)-1H-1,2,3-triazol-4-yl)methyl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((1-(tert-pentyl)-1H-1,2,3-triazol-4-yl)methyl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((1-(3-methylpentan-3-yl)-1H-1,2,3-triazol-4-yl)methyl)tetrahydro-2H-pyran-3-ol; 4-(1-((2R,3R,4S,5R,6R)-2-((1-(3-(difluoromethyl)oxetan-3-yl)-1H-1,2,3-triazol-4-yl)methyl)-5-hydroxy-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-4-yl)-1H-1,2,3-triazol-4-yl)-2,3-difluorobenzonitrile; 2,3-difluoro-4-(1-((2R,3R,4S,5R,6R)-3-hydroxy-2-(hydroxymethyl)-5-methoxy-6-((1-(3-(trifluoromethyl)oxetan-3-yl)-1H-1,2,3-triazol-4-yl)methyl)tetrahydro-2H-pyran-4-yl)-1H-1,2,3-triazol-4-yl)benzonitrile; 2,3-difluoro-4-(1-((2R,3R,4S,5R,6R)-3-hydroxy-2-(hydroxymethyl)-5-methoxy-6-((1-(3-methyloxetan-3-yl)-1H-1,2,3-triazol-4-yl)methyl)tetrahydro-2H-pyran-4-yl)-1H-1,2,3-triazol-4-yl)benzonitrile; 4-(1-((2R,3R,4S,5R,6R)-2-((1-(1-(difluoromethyl)cyclobutyl)-1H-1,2,3-triazol-4-yl)methyl)-5-hydroxybenzoate hydroxy-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-4-yl)-1H-1,2,3-triazol-4-yl)-2,3-difluorobenzonitrile; 2,3-difluoro-4-(1-((2R,3R,4S,5R,6R)-2-((1-((3R,4S)-3-fluorotetrahydro-2H-pyran-4-yl)-1H-1,2,3-triazol-4-yl)methyl)-5-hydroxy-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-4-yl)-1H-1,2,3-triazol-4-yl)benzonitrile; 2,3-difluoro-4-(1-((2R,3R,4S,5R,6R)-2-((1-((3S,4R)-3-fluorotetrahydro-2H-pyran-4-yl)-1H-1,2,3-triazol-4-yl)methyl)-5-hydroxy-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-4-yl)-1H-1,2,3-triazol-4-yl)benzonitrile; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((4-(3,3-difluorocyclobutyl)-1H-1,2,3-triazol-1-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((4-(6,6-difluorospiro[3.3]heptan-2-yl)-1H-1,2,3-triazol-1-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((4-(1-(difluoromethyl)cyclopropyl)-1H-1,2,3-triazol-1-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((4-(1-(fluoromethyl)cyclopropyl)-1H-1,2,3-triazol-1-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((4-(1-(trifluoromethyl)cyclopropyl)-1H-1,2,3-triazol-1-yl)methyl)tetrahydro-2H-pyran-3-ol; tert-butyl ((1S,3S)-3-(1-(((2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-yl)methyl)-1H-1,2,3-triazol-4-yl)cyclobutyl)carbamate; (2R,3R,4S,5R,6R)-6-((4-((1S,3S)-3-aminocyclobutyl)-1H-1,2,3-triazol-1-yl)methyl)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-2-(hydroxymethyl)-5-methoxy-6-((4-(1-methylcyclopropyl)-1H-1,2,3-triazol-1-yl)methyl)-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-2-(hydroxymethyl)-5-methoxy-6-((4-(1-methylcyclobutyl)-1H-1,2,3-triazol-1-yl)methyl)-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazo (1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-6-((4-(bicyclo[1.1.1]pentan-1-yl)-1H-1,2,3-triazol-1-yl)methyl)-2-(hydroxymethyl)-5-methoxy-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((4-(1-hydroxycyclobutyl)-1H-1,2,3-triazol-1-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((4-cyclopentyl-1H-1,2,3-triazol-1-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((4-(1-hydroxycyclopentyl)-1H-1,2,3-triazol-1-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-6-((4-(2-hydroxypropan-2-yl)-1H-1,2,3-triazol-1-yl)methyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((4-(3-methyloxetan-3-yl)-1H-1,2,3-triazol-1-yl)methyl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-6-((4-(4-hydroxytetrahydro-2H-pyran-4-yl)-1H-1,2,3-triazol-1-yl)methyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((4-(1-hydroxycyclopropyl)-1H-1,2,3-triazol-1-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-6-((4-(1-(hydroxymethyl)cyclopropyl)-1H-1,2,3-triazol-1-yl)methyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((4-(3-ethyloxetan-3-yl)-1H-1,2,3-triazol-1-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; tert-butyl (4-(1-(((2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-yl)methyl)-1H-1,2,3-triazol-4-yl)bicyclo[2.2.2]octan-1-yl)carbamate; (2R,3R,4S,5R,6R)-6-((4-(4-aminobicyclo[2.2.2]octan-1-yl)-1H-1,2,3-triazol-1-yl)methyl)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazole- 1-yl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((4-(1-methylcyclopropyl)-1H-1,2,3-triazol-1-yl)methyl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((4-(1-methylcyclobutyl)-1H-1,2,3-triazol-1-yl)methyl)tetrahydro-2H-pyran-3-ol; and (2R,3R,4S,5R,6R)-6-((4-(bicyclo[1.1.1]pentan-1-yl)-1H-1,2,3-triazol-1-yl)methyl)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol.

[0108] 24) In addition to the compounds described in embodiments 21), 22) and 23), further compounds of formula (I) according to embodiment 1) are selected from the following compounds: (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((2R,3R)-2,3-dimethyltetrahydrofuran-3-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((2S,3R)-2,3-dimethyltetrahydrofuran-3-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-(4,4-difluoro-1-(trifluoromethyl)cyclohexyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-(2,2-difluoro-1-(fluoromethyl)cyclopropyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((1S,3S)-3-fluoro-1-methylcyclobutyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((1R,3R)-3-fluoro-1-methylcyclobutyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-6-((1-(3,3-bis(trifluoromethyl)cyclobutyl)-1H-1,2,3-triazol-4-yl)methyl)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazole-1- yl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((1R,3R)-3-fluorocyclobutyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((1S,3S)-3-fluorocyclobutyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; and (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((4-(3,3-difluoro-1-hydroxycyclobutyl)-1H-1,2,3-triazol-1-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol.

[0109] 25) In addition to the compounds described in embodiments 21), 22), 23) and 24), further compounds of formula (I) according to embodiment 1) are selected from the following compounds: (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-(3-(fluoromethyl)oxetan-3-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-(3-(difluoromethyl)oxetan-3-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((1-(3-(trifluoromethyl)oxetan-3-yl)-1H-1,2,3-triazol-4-yl)methyl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((3R,4S)-3-fluorotetrahydro-2H-pyran-4-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((3R,4R)-4-fluorotetrahydrofuran-3-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((3S,4S)-4-fluorotetrahydrofuran-3-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-chloro-2,3-difluorophenyl)- nyl)-1H-1,2,3-triazol-1-yl)-6-((1-((R)-3,3-difluorotetrahydro-2H-pyran-4-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((S)-3,3-difluorotetrahydro-2H-pyran-4-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((R)-4,4-difluorotetrahydrofuran-3-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((S)-4,4-difluorotetrahydrofuran-3-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-6-((1-((3S,4R)-3-fluorotetrahydro-2H-pyran-4-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxy-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-6-((1-((3R,4S)-3-fluorotetrahydro-2H-pyran-4-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxy-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((3R,4R)-3-fluorotetrahydro-2H-pyran-4-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((3S,4S)-3-fluorotetrahydro-2H-pyran-4-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-(3-(difluoromethyl)oxetan-3-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((1-(3-(trifluoromethyl)oxetan-3-yl)-1H-1,2,3-triazol-4-yl)methyl)tetrahydro-2H-pyran-3-ol; 2,3-Difluoro-4-(1-((2R,3R,4S,5R,6R)-2-((1-( (3R,4S)-3-fluorotetrahydro-2H-pyran-4-yl)-1H-1,2,3-triazol-4-yl)methyl)-5-hydroxy-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-4-yl)-1H-1,2,3-triazol-4-yl)benzonitrile; and 2,3-Difluoro-4-(1-((2R,3R,4S,5R,6R)-2-((1-((3S,4R)-3-fluorotetrahydro-2H-pyran-4-yl)-1H-1,2,3-triazol-4-yl)methyl)-5-hydroxy-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-4-yl)-1H-1,2,3-triazol-4-yl)benzonitrile.

[0110] I) Further disclosed is a compound of formula (III):

[0111] [ka] (In the formula, R P2 represents halogen (especially fluoro); R P3 represents halogen (especially fluoro); R P4 represents halogen (especially fluoro, chloro, bromo), methyl or cyano; A represents [1,2,3]triazole-1,4-diyl (R 2 may be bonded to the 1- or 4-position of the [1,2,3]triazole-1,4-diyl; -R 2 teeth, 6- or 7-membered bridged bicyclic heterocycloalkyl having one ring oxygen atom (in particular 2-oxabicyclo[2.1.1]hexan-4-yl or 2-oxabicyclo[3.1.1]heptan-5-yl); wherein the 6- or 7-membered bridged bicyclic heterocycloalkyl having one ring oxygen atom is independently unsubstituted or substituted with 1, 2, or 3 substituents, the substituents being hydroxy; 1-3- alkyl (especially methyl; or ethyl or isopropyl); C 1-3 -alkoxy (especially methoxy); -C 1-3 -Alkylene-OH (especially hydroxymethyl or 2-hydroxyethyl); C1-fluoroalkyl (especially trifluoromethyl); -NR N1 R N2 (R N1 represents hydrogen, and R N2 is hydrogen or -CO-OC 1-4 alkyl (especially -CO-O-tert.-butyl); and fluoro.

[0112] II) A further disclosure is provided in which A represents [1.2.3]triazole-1,4-diyl; R 2 is attached to the 4-position of the [1,2,3]triazole-1,4-diyl.

[0113] III) Further disclosures are available at R 2 but, - 6- or 7-membered bridged bicyclic heterocycloalkyl having one ring oxygen atom (in particular 2-oxabicyclo[2.1.1]hexan-4-yl or 2-oxabicyclo[3.1.1]heptan-5-yl), in which the 6- or 7-membered bridged bicyclic heterocycloalkyl having one ring oxygen atom is unsubstituted or contains one C 1-3 -6- or 7-membered bridged bicyclic heterocycloalkyl substituted by alkyl (especially methyl); The present invention relates to compounds of formula (III) according to disclosure I) or II), which represent

[0114] IV) Further disclosed are compounds of formula (III) according to disclosure I), selected from the following compounds: (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((1-(1-methyl-2-oxabicyclo[3.1.1]heptan-5-yl)-1H-1,2,3-triazol-4-yl)methyl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((1-(1-methyl-2-oxabicyclo[2.1.1]hexan-4-yl)-1H-1,2,3-triazol-4-yl)methyl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-6-((1-(2-oxabicyclo[2.1.1]hexan-4-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxy-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((1-(1-methyl-2-oxabicyclo[2.1.1]hexan-4-yl)-1H-1,2,3-triazol-4-yl)methyl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-6-((1-(2-oxabicyclo[2.1.1]hexan-4-yl)-1H-1,2,3-triazol-4-yl)methyl)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-2-(hydroxymethyl)-5-methoxy-6-((1-(1-methyl-2-oxabicyclo[2.1.1]hexan-4-yl)-1H-1,2,3-triazol-4-yl)methyl)-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((1-(1-methyl-2-oxabicyclo[3.1.1]heptan-5-yl)-1H-1,2,3-triazol-4-yl)methyl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-2-(hydroxymethyl)-5-methoxy-6-((1-(1-methyl-2-oxabicyclo[3.1.1]heptan-5-yl)-1H- 1,2,3-triazol-4-yl)methyl)-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; and (2R,3R,4S,5R,6R)-6-((1-(2-oxabicyclo[2.1.1]hexan-4-yl)-1H-1,2,3-triazol-4-yl)methyl)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol.

[0115] Pharmaceutical compositions can be produced in a manner well known to anyone 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 compounds of formula (I) or pharmaceutically acceptable salts thereof, optionally with other therapeutically valuable substances, with suitable non-toxic, inert, therapeutically compatible solid or liquid carrier materials and, if necessary, conventional pharmaceutical adjuvants, to form a pharmaceutical dosage form.

[0116] 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 25).

[0117] For the avoidance of any doubt, where a compound is described as being useful for the prevention or treatment of a disease, such compound is also suitable for use in the manufacture of a medicament for the prevention or treatment of that disease, as well as in a method for the prevention or treatment of such disease, which comprises administering an effective amount of such compound to a subject (mammal, particularly a human) in need thereof.

[0118] 26) Another aspect relates to compounds of formula (I) as defined in any one of aspects 1) to 25) useful for the prevention or treatment of diseases and disorders in which the binding of galectin-3 to its natural ligand is implicated.

[0119] Such diseases and disorders in which the binding of galectin-3 to its natural ligands is implicated are, in particular, diseases and disorders in which inhibition of the physiological activity of Gal-3 is beneficial, such as diseases in which the Gal-3 receptor is involved and which are implicated in the etiology or pathology of the disease or which are otherwise implicated in at least one symptom of the disease.

[0120] Diseases and disorders in which the binding of galectin-3 to its natural ligands is involved may be defined as including, inter alia: - fibrosis of an organ, characterized in that: all forms of fibrosing interstitial lung disease, including, in particular, idiopathic pulmonary fibrosis (also called cryptogenic fibrosing alveolitis); pulmonary fibrosis secondary to systemic inflammatory diseases such as rheumatoid arthritis, scleroderma (systemic sclerosis, SSc), lupus (systemic lupus erythematosus, SLE), polymyositis, or mixed connective tissue disease (MCTD); pulmonary fibrosis secondary to sarcoidosis; iatrogenic pulmonary fibrosis, including radiation-induced fibrosis; silicosis-induced pulmonary fibrosis; asbestos-induced pulmonary fibrosis; and pleural fibrosis; Renal / kidney diseases, including chronic kidney disease (CKD), (acute or chronic) renal failure, tubulointerstitial nephritis, and / or (primary) glomerulonephritis or glomerulonephritis secondary to systemic inflammatory diseases such as SLE and SSc, diabetes, focal segmental glomerulosclerosis, IgA nephropathy, hypertension, renal transplantation, and renal fibrosis due to / associated with Alport syndrome y) fibrosis; --All forms of liver / hepatic fibrosis (whether or not associated with portal hypertension), including cirrhosis, alcohol-induced liver fibrosis, non-alcoholic steatohepatitis, bile duct injury, primary biliary cirrhosis (also known as primary biliary cholangitis), infectious or virally induced liver 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, including gastrointestinal fibrosis secondary to SSc and radiation-induced gastrointestinal fibrosis; -- Skin fibrosis, including SSc and skin scarring; --Head and neck fibrosis, including radiation-induced head and neck fibrosis; -- ocular / corneal fibrosis, including scarring (e.g., sequelae of laser-assisted in situ keratomileusis or trabeculectomy); -- Hypertrophic scars and keloids, including burn-induced or surgical hypertrophic scars and keloids; --fibrotic sequelae of organ transplants (including corneal transplants); -- and other fibrotic diseases, including endometriosis, spinal fibrosis, myelofibrosis, perivascular and arterial 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; - Liver diseases and disorders (acute or chronic) (acute and chronic viral hepatitis; cirrhosis due to / associated with arthritis and vasculitis; metabolic liver diseases due to / associated with arthritis, myocarditis, diabetes or neurological conditions; cholestatic diseases due to / associated with hyperlipidemia, inflammatory bowel disease (IBD) or ulcerative colitis) liver tumors; autoimmune hepatitis and cirrhosis caused by / associated with celiac disease, autoimmune hemolytic anemia, IBD, autoimmune thyroiditis, ulcerative colitis, diabetes, glomerulonephritis, pericarditis, autoimmune thyroiditis, hyperthyroidism, polymyositis, Sjögren's syndrome, panniculitis, alveolitis or alcoholic steatosis; cirrhosis associated with dementia; cirrhosis associated with peripheral neuropathy; cirrhosis caused by / associated with oral or esophageal cancer; non-alcoholic fatty liver disease (particularly non-alcoholic steatohepatitis) caused by / associated with obesity, metabolic syndrome or type 2 diabetes; hepatic vasculopathy (including Budd-Chiari syndrome, portal vein thrombosis, sinusoidal obstruction syndrome); acute and chronic liver failure (whether or not associated with portal hypertension); hepatic dysfunction; - acute kidney injury and chronic kidney disease (CKD) caused by / associated with heart disease (also known as cardiorenal syndrome types 1 and 2), or caused by / associated with hypertension, or caused by / associated with diabetes (also known as diabetic nephropathy (DKD) including DKD associated with hypertension), where such diabetes is particularly type 1 or 2 diabetes, or caused by / associated with inflammatory diseases and disorders (such as glomerulonephritis and glomerulonephritis secondary to systemic inflammatory diseases such as SLE or SSc, tubulointerstitial nephritis, vasculitis, sepsis, urinary tract infection), or caused by / associated with polycystic kidney disease, or caused by / associated with obstructive nephropathy (including stones, benign prostatic hyperplasia, prostate cancer, retroperitoneal pelvic tumors), or caused by / associated with neurogenic bladder disease-related symptoms) [in particular, the Kidney Disease Improving Global Stages 1-5 CKD as defined by the KDIGO Guidelines for Clinical Outcomes], especially (particularly these stages) CKD; and acute and chronic renal failure; - Cardiovascular diseases and disorders (hypertension, hypercholesterolemia, diabetes, inflammation, obesity, elderly / age-related atherosclerosis; hypertension, hypercholesterolemia, diabetes, elderly / age-related peripheral arterial disease; deep vein thrombosis; obesity or Pulmonary embolism caused by / related to cancer; aortic aneurysm and dissection caused by / related to aging, hypertension, Marfan syndrome, congenital heart defects, inflammatory or infectious disorders; cerebrovascular disease caused by / related to hypertension, atrial fibrillation, hypercholesterolemia, diabetes, aging; hypertension, hypercholesterolemia, diabetes, aging, or CKD (especially Kidney Disease Improving Coronary heart disease caused by / associated with CKD (stages 1-5 as defined by the Kingsley International Global Outcomes (KDIGO) Guidelines); rheumatic heart disease caused by / associated with bacterial infection; cardiac and vascular tumors; cardiomyopathies and arrhythmias; valvular heart disease (including cardiac valve calcification and degenerative aortic stenosis); inflammatory heart disease caused by / associated with infection, carditis, glomerulonephritis, and cancer; heart failure (HF) defined as including congestive HF, particularly 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 disease; interstitial lung disease caused by / associated with chronic obstructive pulmonary disease; interstitial pneumonia (including ordinary interstitial pneumonia) or pneumonia associated with collagen vascular disease); - cell proliferative disorders and cancers (including solid tumors, solid tumor metastases, carcinomas, sarcomas, myeloma (and multiple myeloma), leukemia, lymphoma, mixed cancers, angiofibroma, Kaposi's sarcoma, chronic lymphocytic leukemia (CLL), spinal tumors and invasive metastases of cancer cells; in particular, said cell proliferative disorders and cancers are cancers of the thyroid, central nervous system, tongue, breast, digestive system, head and neck squamous cell, pancreas, bladder, kidney, liver, parathyroid or salivary gland; or lymphoma, carcinoma, non-small cell lung cancer, melanoma or neuroblastoma); - inflammatory and autoimmune diseases and disorders (including chronic and acute inflammatory and autoimmune diseases and disorders, in particular sepsis, Q fever, asthma, rheumatoid arthritis, multiple sclerosis (MS), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), polymyositis, plaque psoriasis (including psoriasis caused by / associated with NASH), atopic dermatitis, inflammatory renal / kidney diseases such as nephropathy (including diabetic nephropathy, glomerulonephritis, tubulointerstitial nephritis), inflammatory cardiac / 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 vasculopathy, diabetic nephropathy, diabetic retinopathy, diabetic peripheral neuropathy or skin-related diseases; viral encephalitis; and COVID-19 and its sequelae); - Digestive diseases and disorders (including irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), gastritis and abnormal pancreatic secretion); - Pancreatic diseases and disorders (including, for example, pancreatitis associated with cystic fibrosis); - Diseases and disorders associated with abnormal angiogenesis (including arterial occlusive disease); - Brain-related diseases and disorders (including stroke and cerebral hemorrhage); - Neuropathic pain and peripheral neuropathy; - Ocular diseases and disorders (including dry eye (xerophthalmia), age-related macular degeneration (AMD), diabetes-related diseases (diabetic retinopathy), proliferative vitreoretinopathy (PVR), cicatricial pemphigoid and glaucoma (including ocular scarring after glaucoma filtration surgery and glaucoma associated with elevated intraocular pressure) and corneal angiogenesis / neovascularization); and - Transplant rejection (including rejection of transplanted organs such as kidney, liver, heart, lung, pancreas, cornea and skin; graft-versus-host disease resulting from hematopoietic stem cell transplantation; chronic allograft rejection and chronic allograft vasculopathy); and sequelae of such transplant rejection.

[0121] 27) A further embodiment is according to embodiment 26), wherein the compound is 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 skin fibrosis; and gastrointestinal fibrosis, head and neck fibrosis, hypertrophic scars and keloids; and fibrotic sequelae of organ transplantation. The present invention relates to a compound of formula (I) for use in

[0122] 28) A further embodiment relates to compounds of formula (I) for use according to embodiment 26), wherein the compounds are for use in the prevention or treatment of cardiovascular diseases and disorders.

[0123] 29) A further embodiment relates to compounds of formula (I) for use according to embodiment 26), wherein the compounds are for use in the prevention or treatment of acute kidney injury and chronic kidney disease (CKD).

[0124] 30) A further embodiment relates to compounds of formula (I) for use according to embodiment 26), in which the compounds are for use in the prevention or treatment of (acute or chronic) liver diseases and disorders.

[0125] 31) A further embodiment relates to compounds of formula (I) for use according to embodiment 26), wherein the compounds are for use in the prevention or treatment of interstitial lung diseases and disorders.

[0126] 32) A further embodiment relates to compounds of formula (I) for use according to embodiment 26), wherein the compounds are for use in the prevention or treatment of eye diseases and disorders.

[0127] 33) A further embodiment relates to compounds of formula (I) for use according to embodiment 26), wherein the compounds are for use in the prevention or treatment of cell proliferative disorders and cancer.

[0128] In particular, such cell proliferative disorders and cancers are cancers of the thyroid, central nervous system, tongue, breast, digestive system, head and neck squamous cell, pancreas, bladder, kidney, liver, parathyroid or salivary gland; or lymphoma, carcinoma, non-small cell lung cancer, melanoma or neuroblastoma.

[0129] 34) A further embodiment relates to compounds of formula (I) for use according to embodiment 26), wherein the compounds are for use in the prevention or treatment of chronic or acute inflammatory and autoimmune diseases and disorders.

[0130] 35) A further embodiment relates to compounds of formula (I) for use according to embodiment 26), wherein the compounds are for use in the prevention or treatment of digestive diseases and disorders.

[0131] 36) A further embodiment relates to compounds of formula (I) for use according to embodiment 26), wherein the compounds are for use in the prevention or treatment of pancreatic diseases and disorders.

[0132] 37) A further embodiment relates to compounds of formula (I) for use according to embodiment 26), wherein the compounds are for use in the prevention or treatment of diseases and disorders associated with abnormal angiogenesis.

[0133] 38) A further embodiment relates to compounds of formula (I) for use according to embodiment 26), wherein the compounds are for use in the prevention or treatment of brain-related diseases and disorders.

[0134] 39) A further embodiment relates to compounds of formula (I) for use according to embodiment 26), wherein the compounds are for use in the prevention or treatment of neuropathic pain and peripheral neuropathy.

[0135] 40) A further embodiment is wherein the compound is for use in the treatment of transplant rejection. 26) relates to a compound of formula (I) for use according to embodiment 26), wherein

[0136] For the avoidance of any doubt, where a compound is described as being useful for the prevention or treatment of a disease, such compound is also suitable for use in the manufacture of a medicament for the prevention or treatment of that disease, as well as in a method for the prevention or treatment of such disease, which comprises administering an effective amount of such compound to a subject (mammal, particularly a human) in need thereof.

[0137] Furthermore, any preferences and (sub)embodiments given for compounds of formula (I) (whether for said compounds themselves, their salts, compositions comprising said compounds or their salts or the use of said compounds or their salts, etc.) apply mutatis mutandis to compounds of formula (II).

[0138] Preparation of Compounds of Formula (I) Compounds of formula (I) can be prepared by well-known literature methods, by the methods described below, by the methods described in the experimental section below, or by analogous methods. Optimum reaction conditions will vary with the specific reactants or solvents used; such conditions can be determined by one skilled in the art by routine optimization procedures. In some cases, the reaction schemes below and / or the order of carrying out the reaction steps may be modified to facilitate the reaction or to avoid unwanted reaction products. In the general reaction sequences outlined below, the generic group, R 1 , R 2 , A and Ar 1 is as defined for formula (I). Other abbreviations used herein are either explicitly defined or as defined in the experimental section. In some cases, the generic group, R 1 , R 2 , A and Ar 1 may not be compatible with the preparation illustrated in the scheme below and would require the use of a protecting group (Pg). The use of protecting groups is well known in the art (see, for example, "Protective Groups in Organic Synthesis," T.W. Greene, P.G.M. Buts, Wiley-Interscience, 1999). For this purpose, it is assumed that such protecting groups have been introduced as necessary. Optionally, 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 into salts, in particular pharmaceutically acceptable salts, by methods known per se.

[0139] The compounds of formula (I) of the present invention can be prepared according to the general reaction sequences outlined below: Only a few of the synthetic possibilities leading to compounds of formula (I) are described.

[0140] [ka] Compounds of formula (I) can be prepared by reacting R with R as defined in formula (I), where R is hydrogen; a suitable protecting group such as acetyl, trimethylsilyl, TBDMS, or the like; 1 The compound is prepared by deprotecting a compound of structure 1, which represents:

[0141] Compounds of structure 1 in which A represents a 1,4-disubstituted 1,2,3-triazole (structure 2a or structure 2b) can be prepared by copper-catalyzed 1,3-dipolar cycloaddition of alkynes of structure 3 or 6 with azides of structure 4 or 5 (Click Chemistry in Glycoscience: New Development and Strategies, 1st Edition, 2013, John Wiley & Sons, 2017 / 007689A1) according to a batch procedure; alternatively, the reaction can be carried out in a commercially available continuous-flow reactor (Vapourtec) using a copper coil in a solvent such as THF, as shown below.

[0142] [ka] Azides of structure 4 are commercially available or can be prepared according to methods known to those skilled in the art (Org. Biomol. Chem. 2014, 12, 4397-4406; Nature 2019, 574, 86-89; Org. Lett., 2007, 9, 3797-3800).

[0143] Experimental section The following examples illustrate the present invention but do not in any way limit its scope.

[0144] All temperatures are given in °C. Commercially available starting materials were used as received without further purification. Unless otherwise noted, all reactions were carried out under a nitrogen or argon atmosphere. Compounds were purified by flash chromatography on silica gel (Combiflash, ISCO) or by preparative TLC (Merck TLC plates, Silica gel 60 F 254 ) or by preparative HPLC. The compounds described in this invention are 1 H-NMR spectrum (Bruker Avance II, 400 MHz U Recorded on a Ultra Shield™ or Bruker Avance III HD, Descend 500 MHz; chemical shifts are given in ppm relative to the solvent used; multiplicities: s = singlet, d = doublet, t = triplet, q = quartet, quint = quintet, hex = sextet, hept = septet, m = multiplet, br = broad; coupling constants are given in Hz.) and / or LC-MS (retention times t R The molecular weights obtained from mass spectrometry are given in g / mol) using the conditions described below, and / or by chiral analytical HPLC (retention time t R is indicated by min.) to clarify the characteristics.

[0145] Qualitative analysis methods used LC-MS retention times are obtained using the following elution conditions: A) LC-MS(A): A Zorbax RRHD SB-Aq, 1.8 μm, 2.1×50 mm column was thermostated at 40° C. The two elution solvents were as follows: Solvent A = water + 0.04% TFA; Solvent B = acetonitrile. The eluent flow rate was 0.8 mL / min and the characteristics of the proportion of the elution mixture in relation to the time t from the start of elution are summarized in the table below (a linear gradient was used between two consecutive time points):

[0146] [Table 1] B) LC-MS(B): Waters BEH C18, 1.8 μm, 1.2×50 mm column, thermostated at 40° C. The two elution solvents were as follows: Solvent A = water + 13 mM NH4OH; Solvent B = acetonitrile. The eluent flow rate was 0.8 mL / min and the characteristics of the proportion of the elution mixture in relation to the time t from the start of the elution are summarized in the table below (a linear gradient is used between two consecutive time points):

[0147] [Table 2] Purification by preparative LC-MS is carried out using the conditions described below.

[0148] C) Preparative LC-MS(I): A Waters column (Waters XBridge C18, 10 μm OBD, 30×75 mm) is used. The two elution solvents are as follows: Solvent A = water + 0.5% of 25% aqueous NH4OH; Solvent B = acetonitrile. The eluent flow rate is 75 mL / min and the characteristics of the proportion of the eluted mixture related to the time t from the start of the elution are summarized in the table below (a linear gradient is used between two consecutive time points):

[0149] [Table 3] D) Preparative LC-MS(II): A Waters column (Zorbax SB-AQ, 30x75 mm, 5 μm) is used. The two elution solvents are as follows: solvent A = water + HCOOH 0.5%; solvent B = acetonitrile. The eluent flow rate is 75 mL / min and the characteristics of the proportion of the elution mixture related to the time t from the start of the elution are summarized in the table below (a linear gradient is used between two consecutive time points):

[0150] [Table 4] Chiral preparative HPLC method used: E) Chiral Preparative HPLC (I): A ChiralPack IC, 5 μm, 30 × 250 mm, was used, and the column was thermostated at 40 °C. The two elution solvents were as follows: solvent A = CO2; solvent B = (MeCN / EtOH) = (1 / 1). The eluent flow rate was 160 mL / min. Elution was performed isocratically with 60% solvent A and 40% solvent B. Injection V = 1.0 mL, 10 mg / mL EtOH.

[0151] F) Chiral Preparative HPLC (II): Chiralcel OJ-H, 5 μm, 30 × 250 mm, column thermostated at 40 °C. Two elution solvents are as follows: solvent A = CO2; solvent B = (MeCN / EtOH) = (1 / 1). The flow rate of the eluent is 160 mL / min. Elution is carried out isocratically with 80% solvent A and 20% solvent B. Injection volume = 1.0 mL, 10 mg / mL. EtOH.

[0152] G) Chiral Preparative HPLC (III): A ChiralPack IB, 5 μm, 30 × 250 mm column was used, thermostated at 40 °C. The two elution solvents were as follows: solvent A = CO2; solvent B = EtOH. The eluent flow rate was 160 mL / min. Elution was performed isocratically with 75% solvent A and 25% solvent B. Injection V = 2.0 mL, 10 mg / mL EtOH.

[0153] H) Chiral Preparative HPLC (IV): Chiralcel OJ-H, 5 μm, 30 × 250 mm, column thermostated at 40 °C. The two elution solvents are as follows: solvent A = CO2; solvent B = EtOH. The eluent flow rate is 160 mL / min. Elution is performed isocratically with 80% solvent A and 20% solvent B. Injection V = 1.5 mL, 10 mg / mL EtOH.

[0154] I) Chiral analytical HPLC (I): The diastereomers of the diastereomeric mixture are characterized by chiral analytical HPLC. Conditions vary for each diastereomeric mixture. Several columns are used, all of the same size: 4.6 x 250 mm, 5 μm. Unless otherwise specified, elution is performed isocratically; unless otherwise specified, eluent A is usually CO2, and eluent B is an organic solvent or mixture thereof. Runs last 2.5-5 min.

[0155] The column type, B solvent, solvent A when necessary, and elution length are also given for each diastereomer in the corresponding table below.

[0156] Abbreviations (as used herein): Ac2O acetic anhydride AcOH acetic acid ADMP 2-Azido-1,3-dimethylimidazolinium hexafluorophosphate aq. aqueous solution BB Building Blocks BF3OEt2 Boron trifluoride diethyl ether BOC tert-butoxycarbonyl Bu (nBuLi = n-butyllithium, etc.) butyl CC silica column chromatography Concentrated DCM dichloromethane dil. Dilution DIPEA N-Ethyldiisopropylamine DMAP 4-dimethylaminopyridine DMF Dimethylformamide DMSO dimethyl sulfoxide EA Ethyl acetate eq (mol) equivalent Et Ethyl EtOH ethanol Et2O diethyl ether FC flash chromatography h time Hept Heptane HPLC High Performance Liquid Chromatography M Molar concentration [mol L -1 ] Me methyl MeCN acetonitrile MeOH Methanol MS mass spectrometry min. N normality K2[OsO2(OH)4] Potassium osmate(VI) dihydrate NaIO4 Sodium Metaperiodate NaOAc Sodium Acetate NaOMe Sodium methoxide o / n overnight org.organic Pg protecting group Ph Phenyl PTSA p-toluenesulfonic acid rt room temperature sat. saturation TBME tert-butyl methyl ether tBu tert-butyl = tertiary butyl Tf Trifluoromethanesulfonyl Tf2O Trifluoromethanesulfonic anhydride TFA trifluoroacetic acid THF tetrahydrofuran TMEDA Tetramethylethylenediamine TMSCl Chlorotrimethylsilane TMSOTf Trimethylsilyl trifluoromethanesulfonate T3P Propylphosphonic Anhydride t R retention time

[0157] A. Preparation of precursors and intermediates

[0158] [ka] 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-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-ol according to the literature procedure from Ref: Carbohydrate Research 1994, 251, 33-67 and references cited therein.

[0159] Intermediate 2: (2R,3R,4R,5R,6R)-2-(acetoxymethyl)-6-allyl-4-azidotetrahydro-2H-pyran-3,5-diyl diacetate To a cooled (0 °C) solution of intermediate 1 (10 g, 26.8 mmol) in MeCN (100 mL) was added allyltrimethylsilane 98% (13 mL, 80.4 mmol, 3 eq) and, dropwise, TMSOTf (99%, 2.45 mL, 13.4 mmol, 0.5 eq). After the addition was complete, the ice bath was removed and the mixture was stirred at rt for 72 h. The mixture was then poured into saturated aqueous NaHCO3 and extracted with TBME. The phases were separated, and the combined organic phases were washed with brine, dried over MgSO4, and concentrated in vacuo. The crude product was purified by filtration over SiO2 (10% TBME in DCM) to afford the title intermediate (as a 9:1 mixture of alpha / beta isomers) as a colorless oil, which was used in the next step without further purification.

[0160] Main isomer: 1H NMR (500MHz, DMSO-d6) δ:5.70-5.78( m, 1H), 5.31(dd, J1=1.6Hz, J2=3.4Hz, 1H), 5.06-5.14(m, 2H), 5.00(dd, J 1 =5.6Hz, J 2 =10.5H, 1H), 4.39(dd, J 1 =3.4Hz, J 2=10.6Hz, 1H), 4.15(quint, J=4.7Hz, 1H), 3.91-4.09(m, 3H), 2.56-2.65(m, 1H), 2.22-2.28(m, 1H), 2.11(s, 3H), 2.09(s, 3H), 1.99(s, 3H) Intermediate 3: (2R,3R,4R,5R,6R)-2-(acetoxymethyl)-6-allyl-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diyl diacetate To a warmed (60 °C) solution of intermediate 2 (18.75 g, 52.8 mmol) in DMF (120 mL) is added copper(I) iodide (0.5 g, 2.64 mmol, 0.05 eq), DIPEA (27.1 mL, 158 mmol, 3.0 eq), and 1-chloro-4-ethynyl-2,3-difluorobenzene (9.6 g, 55.4 mmol, 1.05 eq). Stirring is continued at 60 °C for 2 h and then at rt for 15 h. The mixture is diluted with EA, the phases are separated, and the organic phase is washed with saturated aqueous NH4Cl, water, and saturated aqueous NaCl, dried over MgSO4, and concentrated in vacuo. Purification by Combiflash (330 g cartridge, eluted with 0 to 50% EA in Hept.) gives the desired product as a beige solid (26.1 g, 94%, 12% β-anomer). LCMS(A):t R = 1.04 min; [M+H] + =528.08.

[0161] [ka] Intermediate 4: (2R,3R,4R,5R,6R)-2-allyl-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,5-diol To a solution of intermediate 3 (26.0 g, 49.3 mmol) in MeOH (150 mL) is added K2CO3 (0.68 g, 4.93 mmol, 0.1 eq). The reaction mixture is stirred at rt for 1 h and acidified to pH = 5 with Amber Chromatography (Dowex, 50WX2 Hydrogen Foam), then filtered and concentrated under vacuum. The crude compound is triturated from TDBME and filtered to give the desired product as a beige solid (15.22 g, 77%, as a 9:1 mixture of alpha / beta isomers). LCMS (A): t R =0.74 min; [M+H] + =401.75.

[0162] 1 H NMR (500MHz, DMSO-d6) δ:8.41(d, J=2.8Hz, 1H), 7.98(m, 1H), 7.57(m, 1H), 5.82-5.92(m, 1H), 5.34(m, 1H), 5.1(m, 1H), 5.1 7(d, J=16.0Hz, 1H), 5.06(d, J=10.3Hz, 1H), 4.97(d, J=11.8Hz, 1H), 4.57(dd, J 1 =5.8Hz, J 2 =11.0Hz, 1H), 3.98-4.04(m, 1H), 3.95(s, 1H), 3.78(t, J=6.3, 1H), 3.38-3.52(m, 2H), 2.66-2.78(m, 1H), 2.3-2.4(m, 1H).

[0163] Intermediate 5: (4aR,6R,7R,8R,8aR)-6-Allyl-8-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2,2-dimethylhexahydropyrano[3,2-d][1,3]dioxin-7-ol. A solution of intermediate 4 (15.22 g, 36.6 mmol) in THF / acetone (100 mL / 20 mL) is treated with 2,2-dimethoxypropane (16.1 mL, 128 mmol, 3.5 eq) and PTSA monohydrate (0.355 g, 1.83 mmol, 0.05 eq), and the solution is stirred at 50° C. for 4 h. The mixture is diluted with EA, the layers are separated, and the organic layer is washed with saturated aqueous NaHCO3, water, and brine, dried over MgSO4, filtered, and concentrated under reduced pressure to give the crude title intermediate as a beige foam (as a 9:1 mixture of alpha / beta isomers). LCMS (A):t R =0.93 min; [M+H] + =442.15.

[0164] 1 H NMR (500 MHz, DMSO-d6) δ:8.3(d, J=3.0Hz, 1H), 7.96(m, 1H), 7.57(m, 1H), 5.86(m, 1H), 5.41(d, J=5.5Hz, 1H), 5.06-5.18(m, 3H), 4.49(m, 1H), 4.33(d, J=2.5Hz, 1H) , 4.09-4.12(m, 1H), 3.98-4.06(m, 1H), 3.68(s, 1H), 3.63(d, J=12.8Hz , 1H), 2.65-2.74(m, 1H), 2.33-2.43(m, 1H), 1.32(s, 3H), 1.20(m, 3H).

[0165] Intermediate 6: (4aR,5aR,8aR,9R,9aR)-9-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2,2-dimethyloctahydrofuro[2',3':5,6]pyrano[3,2-d][1,3]dioxin-7-ol To a solution of intermediate 5 (17.72 g, 40.1 mmol, 1 eq) in 1,4-dioxane (216 mL) and water (20 mL) were added 2,6-lutidine (14.2 mL, 120 mmol, 3 eq) and NaIO (25.7 g, 120 mmol, 3 eq), followed by K[OsO(OH)] (0.074 g, 0.20 mmol, 0.005 eq). The suspension was vigorously stirred at rt for 15 h, diluted with EA (100 mL), filtered, and the precipitate was washed with EA (50 mL). The combined filtrate was washed with water (50 mL), aq. 1 N HCl, brine, dried over NaSO, filtered, and concentrated in vacuo to recover the crude title compound (as a 9:1 mixture of alpha / beta isomers). LCMS(A):tR=0.91min;[M+H]+=444.06.

[0166] Intermediate 7: (4aR,6R,7R,8R,8aR)-8-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2,2-dimethyl-6-(prop-2-yn-1-yl)hexahydropyrano[3,2-d][1,3]dioxin-7-ol To a cooled (-3 °C) solution of intermediate 6 (17.8 g, 40.1 mmol) in MeOH (242 mL) and MeCN (81 mL) was added dimethyl (1-diazo-2-oxopropyl)phosphonate (10.61 g, 54.1 mmol, 1.35 eq) and K2CO3 (11.1 g, 80.2 mmol, 2 eq). The mixture was heated to -5 °C (cryostat). The mixture is stirred for 15 h, then dimethyl (1-diazo-2-oxopropyl)phosphonate (1.57 g, 8 mmol, 0.2 eq) is added again. The solution is stirred for an additional 4 h while slowly warming to rt, then partitioned between DCM and saturated aqueous NH4Cl. The layers are separated and the aqueous layer is extracted once more with DCM. The combined organic layers are dried over Na2SO4, filtered, and concentrated under reduced pressure to recover the crude product. Purification by Combiflash (220 g cartridge, elution gradient from 20 to 100% EA in heptane) affords the title compound (11.78 g, 67%, as a 9:1 mixture of alpha / beta isomers). LCMS (A): tR=0.94 min; [M+H] + =440.39.

[0167] 1 H NMR (400MHz, DMSO) δ:8.30(d, J=3.5Hz, 1H), 7.9-7.97(m, 1H), 7.55-7.59(m, 1H), 5.54(d, J=5.4Hz, 1H), 5.12(dd, J 1 =11.3Hz, J 2 =3.2Hz, 1H), 4.47-4.52(m, 1H), 4.30(d, J=3.0Hz, 1H), 4.22-4.17(m, 1H), 4.05-4.08(m, 1H) ), 3.75-3.65(m, 2H), 2.89-2.97(m, 1H), 2.80(s, 1H), 2.54(m, 1H) 1.31(s, 3H), 1.22(s, 3H).

[0168] Intermediate 8: 4-(4-chloro-2,3-difluorophenyl)-1-((4aR,6R,7R,8R,8aR)-7-methoxy-2,2-dimethyl-6-(prop-2-yn-1-yl)hexahydropyrano[3,2-d][1,3]dioxin-8-yl)-1H-1,2,3-triazole To a cooled (0 °C) solution of intermediate 7 (11.78 g, 26.8 mmol) in DMF (130 mL) is added MeI (2.19 mL, 34.8 mmol, 1.3 eq), followed by NaH (55%, 0.1287 g, 29.5 mmol, 1.1 eq). The solution is stirred at 0 °C for 1 h, partitioned between saturated aqueous NH4Cl and EA, and the phases are separated. The organic layer is washed with water and brine, dried over MgSO4, filtered, and concentrated under reduced pressure to give the crude product. Purification by Combiflash (product bound to Isolute, 80 g column, elution gradient 20 to 60% EA in heptane) affords the title product (as a 9:1 mixture of alpha / beta isomers) as a white powder (10.57 g, 87%). LCMS (A): tR = 1.03 min; [M+H] + =453.78.

[0169] 1 H NMR (400MHz, DMSO) δ:8.43(d, J=3.3Hz, 1H), 7.91-7.95(m, 1H), 7.56(m, 1H), 5.25(dd, J 1 =11.4Hz, J 2 =3.3Hz, 1H), 4.55(m, 1H), 4.35-4.27(m, 2H), 4.07(dd, J 1 =13.0Hz, J 2 =2.0Hz, 1H), 3.70(t, J=5.6Hz, 2H), 3.18(s, 3H), 2.89-2.98(m, 1H), 2.85(t, J =2.5Hz, 1H), 2.55-2.67(m, 1H), 2.41-2.48(m, 1H), 1.32(s, 3H), 1.22(s, 3H).

[0170] Intermediate 9a: 4-(2,3-difluoro-4-methyl-phenyl)-1-((4aR,6R,7R,8R,8aR)-7-methoxy-2,2-dimethyl-6-(prop-2-yn-1-yl)hexahydropyrano[3,2-d][1,3]dioxin-8-yl)-1H-1,2,3-triazole This intermediate is prepared from intermediate 2 and 1-ethynyl-2,3-difluoro-4-methylbenzene as essentially pure alpha isomer in analogy to intermediate 8. LCMS (A): R =0.97 min; [M+H] + =434.02. 1 H NMR (400MHz, DMSO) δ:8.34(s, 1H), 7.79(t, J=7.5Hz, 1H), 7.23(t, J=7.5Hz, 1H), 5.23(d, J=12.5Hz, 1H), 4.55(m , 1H), 4.29-4.33(m, 2H), 4.07(d, J=13.0Hz, 1H), 3.70(m, 2H), 3.17(s, 3H), 2.91-3.01(m, 1H) ), 2.85(t, J=2.6Hz, 1H), 2.44(m, 2H), 1.33(s, 3H), 1.23(s, 3H).

[0171] Intermediate 10a: 4-(2,3,4-trifluorophenyl)-1-((4aR,6R,7R,8R,8aR)-7-methoxy-2,2-dimethyl-6-(prop-2-yn-1-yl)hexahydropyrano[3,2-d][1,3]dioxin-8-yl)-1H-1,2,3-triazole This intermediate is prepared from intermediate 2 and 1-ethynyl-2,3,4-trifluorobenzene as an essentially pure alpha isomer in analogy to intermediate 8. LCMS (A): R = 1.01 min; [M+H] + =453.85. 1 H NMR (500MHz, DMSO) δ:8.39(d, J=3.4Hz, 1H), 7.76-8.02(m, 1H), 7.43-7.49(m, 1H), 5.24(dd, J1=11. 4Hz, J2=3.4Hz, 1H), 4.55(m, 1H), 4.27-4.36(m, 2H), 4.07(dd, J1=13.1Hz, J2=2. 4Hz, 1H), 3.69-3.73(m, 2H), 3.18(s, 3H), 2.94(ddd, J1=2.6Hz, J2=10.7Hz, J3=1 7.5Hz, 1H), 2.84(t, J=2.6Hz, 1H), 2.78-2.87(m, 2H), 1.33(s, 3H), 1.22(s, 3H).

[0172] Intermediate 11a: 4-(4-bromo-2,3-difluorophenyl)-1-((4aR,6R,7R,8R,8aR)-7-methoxy-2,2-dimethyl-6-(prop-2-yn-1-yl)hexahydropyrano[3,2-d][1,3]dioxin-8-yl)-1H-1,2,3-triazole This intermediate is prepared from intermediate 2 and 1-bromo-4-ethynyl-2,3-difluorobenzene as an essentially pure alpha isomer in analogy to intermediate 8. LCMS (A): R = 1.03 min; [M+H] + =497.89. 1 H NMR (500 MHz, DMSO) δ:8.43(d, J=3.3Hz, 1H), 7.88(m, 1H), 7.66(m, 1H), 5.25(dd, J1=11.4Hz, J 2=3.4Hz, 1H), 4.55(m, 1H), 4.29-4.34(m, 2H), 4.07(dd, J1=13.1Hz, J2=2. 2Hz, 1H), 3.70(m, 2H), 3.18(s, 3H), 2.94(ddd, J1=17.6Hz, J2=10.8Hz, J3= 2.5Hz, 1H), 2.84(t, J=2.6Hz, 1H), 2.47(m, 2H), 1.33(s, 3H), 1.22(s, 3H).

[0173] [ka] Intermediate 12: (2R,3R,4R,5R,6R)-2-(acetoxymethyl)-6-(propa-1,2-dien-1-yl)-4-(214-triaza-1,2-dien-1-yl)tetrahydro-2H-pyran-3,5-diyl diacetate To a cooled (3 °C) solution of intermediate 1 (19.0 g, 50.9 mmol) in MeCN (120 mL) was added dropwise trimethyl(propargyl)silane (23.76 mL, 127 mmol, 2.5 eq), followed by BF3OEt2 (18.8 mL, 153 mmol, 3 eq) and trimethylsilyl trifluoromethanesulfonate (18.6 mL, 102 mmol, 2.0 eq). The mixture was stirred at 0 °C for 1.5 h and at rt for 1 h, then partitioned between TBME and saturated aqueous NaHCO3. The phases were separated, and the organic phase was washed with brine, dried over MgSO4, filtered, and the solvent was removed in vacuo. The crude product was purified by FC (10% TBME in DCM) to give the desired allene intermediate as a yellowish oil, which was further transformed directly (TLC: EA / Hept = 2:1).

[0174] Intermediate 13: (2R,3R,4R,5R,6R)-2-(acetoxymethyl)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-(propa-1,2-dien-1-yl)tetrahydro-2H-pyran-3,5-diyl diacetate The title compound is prepared analogously to intermediate 3 starting from intermediate 12 (as a 98 / 2 mixture of alpha / beta isomers). LCMS (A): t R = 1.05 min; [M+H] + =526.10.

[0175] 1 H NMR (500MHz, DMSO-d6) δ:8.68(d, J=3.4Hz, 1H), 7.93(m, 1H), 7.56(m, 1H), 5.86(dd, J1=5.8Hz, J2=11.9, 1H), 5.72(q , J=6.7Hz, 1H), 5.67(dd, J1=3.1Hz, J2=11.9, 1H), 5.44(dd, J1=1.2Hz, J2=3.1, 1H), 5.06(dd, J 1 =0.6Hz, J 2 =2.6Hz, 1H), 5.06(dd, J 1 =0.8Hz, J 2 =2.9Hz, J 3=6.7Hz, 2H), 5.01-4.97(m, 1H), 4.46(t, J=6.3Hz, 1H), 4.01-3.97(m, 2H), 2.01-1.99(m, 6H), 1.87(s, 3H).

[0176] Intermediate 14: 4-(4-chloro-2,3-difluorophenyl)-1-((4aR,6 R,7R,8R,8aR)-7-Methoxy-2,2-dimethyl-6-(propa-1,2-dien-1-yl)hexahydropyrano[3,2-d][1,3]dioxin-8-yl)-1H-1,2,3-triazole The title intermediate is prepared as a 98 / 2 mixture of alpha / beta isomers following the procedure for Intermediates 4, 5 and 8, starting from Intermediate 13. LCMS(A): R = 1.06 min; [M+H] + =454.12.

[0177] 1 H NMR (500 MHz, DMSO-d6) δ:8.44(d, J=3.4Hz, 1H), 7.91-7.96(m, 1H), 7.59-7.54(m, 1H), 5.73(q, J=7 .0Hz, 1H), 5.19(dd, J1=3.9Hz, J2=11.4Hz), 4.95-5.05(m, 3H), 4.34-4.38( m, 2H), 4.03-4.06(m, 1H), 3.82(m, 1H), 3.73(dd, J1=1.5Hz, J2=12.8Hz, 1H) , 3.69(dd, J1=1.7Hz, J2=13Hz, 1H), 3.19(s, 3H), 1.32(s, 3H), 1.22(s, 3H).

[0178] Intermediate 15a: ((4aR,6R,7R,8R,8aR)-8-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-7-methoxy-2,2-dimethylhexahydropyrano[3,2-d][1,3]dioxin-6-yl)methanol Intermediate 14 (11.4 g, 25.1 mmol) was dissolved in DCM / MeOH (4:1, 500 mL) and cooled to -70 °C. Ozone was bubbled through the solution until the KI solution in the scrubber turned brown (~2 h). Excess O was purged by bubbling N through the solution for 10 min. NaBH (0.95 g, 25.1 mmol, 1 eq) was added at -78 °C, the dry ice bath was removed, and the mixture was allowed to warm to rt within 1 h. The mixture was then carefully quenched with water (25 mL), and the layers were separated. The organic layer was extracted once more with DCM, and the combined organic layers were washed with water, dried over MgSO, filtered, and concentrated under reduced pressure. The crude solid is purified by FC using CombiFlash (SiO2 column; elution gradient 0 to 50% EA in Hept) to give the title intermediate as a white solid as essentially pure alpha isomer. LCMS (A): R =0.87 min; [M+H] + =446.12.

[0179] 1 H NMR (500MHz, DMSO-d6) δ:8.44(d, J=3.4Hz 1H), 7.91-7.96(m, 1H), 7.59-7.54(m, 1H), 5.34(dd, J1=3.5Hz, J2=11.0Hz, 1H), 4 .81(t, J=5.5Hz, 1H), 4.36(dd, J1=1.1Hz, J2=3.5Hz, 1H), 4.32-4.37(m, 2H), 3.97 -4.05(m, 2H), 3.91(d, J=0.9Hz, 1H), 3.73(dd, J1=1.5Hz, J2=12.8Hz, 1H), 3.64(d dd, J1=2.3Hz, J2=5.6Hz, J3=12.2Hz, 1H), 3.19(s, 3H), 1.32(s, 3H), 1.22(s, 3H).

[0180] Intermediate 16a: ((4aR,6R,7R,8R,8aR)-8-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-7-methoxy-2,2-dimethylhexahydropyrano[3,2-d][1,3]dioxin-6-yl)methyl trifluoromethanesulfonate Intermediate 15a (5.0 g, 0.011 mmol) is dissolved in DCM (50 mL), pyridine (1.81 mL, 0.024 mmol, 2.0 eq) is added, and the reaction mixture is cooled to 0 °C. TfO (1 M solution in DCM, 14.0 mL, 0.014 mmol, 1.2 eq) is added dropwise at 0 °C, and stirring is continued at 0 °C for 1 h. The mixture is diluted with DCM and washed with aq. 10% citric acid and water. The layers are separated, and the organic layer is dried over MgSO and concentrated under reduced pressure. The crude form is used directly without further purification. LCMS (A) :t R = 1.13 min; [M+H] + =577.76.

[0181] Intermediate 17a: 1-((4aR,6R,7R,8R,8aR)-6-(azidomethyl)-7-methoxy-2,2-dimethylhexahydropyrano[3,2-d][1,3]dioxin-8-yl)-4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazole To a solution of intermediate 16a (7.6 g, 13.2 mmol) in dry DMF (120 mL) is added sodium azide (0.942 g, 14.5 mmol, 1.2 eq) and the reaction mixture is heated at 70 °C for 1 h. The mixture is then cooled to rt, diluted with EA and water, and the layers are separated. The aqueous layer is extracted once with EA (2x). The combined organic layers are washed with water (2x), brine, dried over MgSO4, filtered, and concentrated under reduced pressure. The crude brown oil is purified by FC using CombiFlash (SiO2 column; elution gradient: 0 to 10% MeOH in DCM) to give the desired intermediate as a white foam. A second purification of the impure fractions using CombiFlash (SiO2 column; elution gradient: 0 to 20% EA in Hept) gives a second batch of the desired product, giving the desired intermediate as a white foam (4.89 g, 79%). LCMS (A): t R = 1.05 min; [M+H] + =471.13.

[0182] 1H NMR (500Mz, DMSO) δ:8.45(d, J=3.2Hz, 1H), 7.94(m, 1H), 7.57(m, 1H), 5.24(dd, J 1 =11.6Hz, J 2 =3.4Hz, 1H), 4.65(m, 1H), 4.39(dd, J 1 =6.1Hz, J 2 =11.4Hz, 1H), 4.35(dd, J 1 =1.2Hz, J 2 =3.4Hz, 1H), 4.2(dd, J 1 =10.5Hz, J 2 =13.7Hz, 1H), 4.1(dd, J 1 =13.0Hz, J 2 =2.1Hz, 1H), 3.83(s, 1H), 3.7(dd, J 1 =12.8Hz, J 2 =1.8Hz, 1H), 3.26(dd, J 1 =13.7Hz, J 2 =3.4Hz, 1H), 1.34(s, 3H), 1.25(s, 6H).

[0183] Intermediate 18a: 1-((4aR,6R,7R,8R,8aR)-6-(azidomethyl)-7-methoxy-2,2-dimethylhexahydropyrano[3,2-d][1,3]dioxin-8-yl)-4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazole The title compound is prepared analogously to intermediate 17a starting from intermediate 12 and 1-ethynyl-2,3-difluoro-4-methylbenzene. LCMS (A): t R = 1.03 min; [M+H] + =451.22. 1 H NMR (500Mz, DMSO) δ:8.37(d, J=3.4Hz, 1H), 7.77-7.80(m, 1H), 7.57(m, 1H), 5.22(dd, J 1 =3.5Hz, J 2 =11.6Hz, 1H), 4.63-4.68(m, 1H), 4.7(dd, J 1 =6.1Hz, J 2=11.7Hz, 1H), 4.35(m, 1H), 4.2(dd, J 1 =10.7Hz, J 2 =13.7Hz, 1H), 4.0.9(dd, J 1 = 2Hz, J 2 =13Hz, 1H), 3.83(s, 1H), 3.69(dd, J 1 =1.4Hz, J 2 =13.0Hz, 1H), 3.26(dd, J 1 =3.4Hz, J 2 =13.7Hz, 1H), 1.34(s, 3H), 1.25(s, 6H).

[0184] Intermediate 19a: 1-((4aR,6R,7R,8R,8aR)-6-(azidomethyl)-7-methoxy-2,2-dimethylhexahydropyrano[3,2-d][1,3]dioxin-8-yl)-4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazole The title compound is prepared analogously to intermediate 17a starting from intermediate 12 and 1-ethynyl-2,3,4-trifluorobenzene. LCMS (A): t R = 1.0 min; [M+H] + =455.18.

[0185] Intermediate 20a: 1-((4aR,6R,7R,8R,8aR)-6-(azidomethyl)-7-methoxy-2,2-dimethylhexahydropyrano[3,2-d][1,3]dioxin-8-yl)-4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazole The title compound is prepared analogously to intermediate 17a starting from intermediate 12 and 1-bromo-4-ethynyl-2,3-difluorobenzene. LCMS (A): t R = 1.04 min; [M+H] + =515.12.

[0186] B. Preparation of Examples Example 3.1.7. (2R,3R,4S,5R,6R)-2-(hydroxymethyl)-5-methoxy-6-((1-(1-(methoxymethyl)cyclopropyl)-1H-1,2,3-triazol-4-yl)methyl)-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol 1. 4-(((4aR,6R,7R,8R,8aR)-7-methoxy-2,2-dimethyl-8-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)hexahydropyrano[3,2-d][1,3]dioxin-6-yl)methyl)-1-(1-(methoxymethyl)cyclopropyl)-1H-1,2,3-triazole To a solution of 1-(methoxymethyl)cyclopropan-1-amine hydrochloride (0.189 g, 1.37 mmol, 4.0 eq) and TEA (0.335 mL, 2.40 mmol, 7.0 eq) in MeCN (2.5 mL) is added dropwise a solution of ADMP (0.535 g, 1.78 mmol, 5.2 eq) in MeCN (2.5 mL) at rt. Immediately after the addition was complete, the mixture was stirred at 30 °C for 40 min, then cooled to rt, and Intermediate 10 (0.15 g, 0.343 mmol, 1.0 eq) was added, followed by a solution of (+)-L-sodium ascorbate (0.007 g, 0.0343 mmol, 0.1 eq), CuI (0.007 g, 0.0343 mmol, 0.1 eq), and trans-N,N'-dimethylcyclohexane-1,2-diamine (0.00836 mL, 0.0514 mmol, 0.15 eq) in DMSO / HO (5 / 1, 2.0 mL). The reaction mixture was stirred at 50 °C for 20 h, cooled to rt, partitioned between EA and water, and the layers were separated. The aqueous layer was extracted with EA, and the combined organic layers were dried over MgSO, filtered, and the solvent removed in vacuo to give a yellow oil. The crude material is purified by preparative HPLC / MS (I) to recover the title compound as a yellow oil (0.120 g, 62%). LCMS (A): R =0.94 min; [M+H] + =565.22.

[0187] 1H NMR (400MHz, DMSO) δ:8.43(d, 2.5Hz, 1H), 7.98(s, 1H), 7.85-7.97(m, 1H), 7.37-7.56(m, 1H), 5.32(dd, J 1 =2.8Hz, J 2 =12.8Hz, 1H), 4.54-4.65(m, 1H), 4.35-4.4(m, 2H), 4.03(d, J=12.8, 1H), 3..85(s, 1H), 3. 69(m, 2H), 3.62(d, J=12.8Hz, 1H), 3.27-3.32(m, 1H), 3.25(s, 3H), 3.20(s, 3H), 2.88(dd, J 1 =1.8Hz, J 2 =15Hz, 1H), 1.32-1.38(m, 5H), 1.27(s, 3H), 1.18(m, 2H).

[0188] 2. (2R,3R,4S,5R,6R)-2-(hydroxymethyl)-5-methoxy-6-((1-(1-(methoxymethyl)cyclopropyl)-1H-1,2,3-triazol-4-yl)methyl)-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol (Example 3.1.7.) To a solution of Example 3.1.7., Step 1. (0.120 g, 0.213 mmol, 1.0 eq) in THF (4.0 mL) is added glacial AcOH (8.0 mL) and HO (8.0 mL). The reaction mixture is stirred at 55 °C for 20 h, cooled to rt, and the solvent is removed in vacuo to give a slightly yellow oil, which is directly purified by preparative HPLC / MS (I) to give the title compound as a white solid (0.045 g, 40%). LCMS (A): R =0.77 min; [M+H] + =525.16.

[0189] 1 H NMR (400MHz, MeOD) δ:8.47(d, J=3.0Hz, 1H), 8.12(s, 1H), 7.88-7.97(m, 1H), 7.25-7.35(m, 1H), 5.17(dd, J 1 =1.5Hz, J 2=11.5Hz, 1H), 4.6-4.7(m, 1H), 4.5(dd, J 1 =6.0Hz, J 2 =11.5Hz, 1H), 4.15(s, 1H), 4.06(t, J=5.8Hz, 1H), 3.63-3.80(m, 4H), 3.42(m, 1H), 3.35(s, 3H), 3.34(s, 3H), 3.10(dd, J 1 =3.0Hz, J 2 =15.5Hz, 1H), 1.42(m, 2H), 1.26(m, 2H).

[0190] The following examples are prepared starting from any of Intermediates 8, 9a, 10a, or 11a and the corresponding amine according to the procedure described for Example 3.1.7. The LC-MS data are listed in Table 1 below. The LC-MS conditions are LC-MS(A).

[0191] [Table 5]

[0192] [Table 6]

[0193] [Table 7]

[0194] [Table 8]

[0195] [Table 9]

[0196] [Table 10]

[0197] [Table 11]

[0198] [Table 12]

[0199] [Table 13]

[0200] [Table 14]

[0201] [Table 15]

[0202] Example 2.1.65.A (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((3R,4R)-4-fluorotetrahydro-2H-pyran-3-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol 1. 4-(4-chloro-2,3-difluorophenyl)-1-((4aR,6R,7R,8R,8aR)-6-((1-((3R,4R)-4-fluorotetrahydro-2H-pyran-3-yl)-1H-1,2,3-triazol-4-yl)methyl)-7-methoxy-2,2-dimethylhexahydropyrano[3,2-d][1,3]dioxin-8- (yl)-1H-1,2,3-triazole To a solution of (3R,4R)-4-fluorooxan-3-amine hydrochloride (0.034 g, 0.22 mmol, 2.0 eq) and DBU (0.049 mL, 0.33 mmol, 3.0 eq) in MeCN (2.5 mL) was added ADMP (0.066 g, 0.22 mmol, 2.0 eq), and the reaction mixture was stirred at rt for 17 h. This solution was then added to a suspension of Intermediate 8 (50 mg, 0.11 mmol, 1.0 eq), copper (35 mg, 0.551 mmol, 5.0 eq), AcOH (0.12 mL, 2.2 mmol, 20 eq), and saturated aqueous CuSO (0.203 mL, 1.1 mmol, 10 eq) in THF (2.0 mL) and stirred at rt for 1.0 h. Copper (0.035 g, 0.551 mmol, 5.0 eq) is added again and the reaction mixture is stirred at rt for 17 h. The reaction mixture is filtered, the filtrate is extracted with EA and the phases are separated. The organic phase is washed with saturated aqueous NaCl, dried over MgSO4, filtered and the solvent is removed in vacuo to recover the crude product as an oil. Purification by preparative HPLC (I) gives the desired product as a white solid (0.012 g, 19%). LCMS (A): t R =0.99 min; [M+H] + =599.05.

[0203] 2. (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((3R,4R)-4-fluorotetrahydro-2H-pyran-3-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol (Example 2.1.65.A) To a solution of Example 2.1.65.A, Step 1. (0.012 g, 0.021 mmol, 1.0 eq) in dioxane (1.0 mL) is added water (0.5 mL) followed by TFA (0.023 mL, 0.417 mmol, 20 eq), which is stirred at rt for 17 h. The reaction mixture is quenched with 25% NH4OH (pH = 10) and directly purified by preparative HPLC (I) to recover the desired product as a white solid (0.008 g, 66%). LCMS (A): R=0.82 min; [M+H] + =559.

[0204] 1 H NMR (400MHz, MeOD) δ:8.51(d, J=3.0Hz, 1H), 8.19(s, 1H), 7.95(t, J=7.8Hz, 1H), 7.44(t, J=8.5Hz, 1H), 5. 1-5.30(m, 2H), 4.62-4.79(m, 2H), 4.51(dd, J1=6.0Hz, J2=11.5Hz), 4.18-4.27(m, 1H) , 4.16(s), 4.04-4.13(m, 2H), 3.78-3.88(m, 1H), 3.6-3.75(m, 3H), 3.41(dd, J1=12.0H) z, J2=16.0Hz), 3.14(dd, J1=3.3Hz, J2=16.5Hz), 2.25-2.35(m, 1H), 1.95-2.05(m, 1H).

[0205] The following examples are prepared analogously to the procedure described for Example 2.1.65.A., starting from intermediates 8, 9a, 10a, or 11a and the corresponding amines. Step 2 is carried out using TFA as described, or AcOH as described for Example 3.1.7. Step 2. Selected examples are synthesized using chiral amines to produce mixtures of diastereomers, which are separated by chiral preparative HPLC.

[0206] The LC-MS data are listed in Table 2 below. The LC-MS conditions are LC-MS (A). The chiral analytical HPLC (I) (conditions and retention times) of the diastereomers of selected examples are also listed.

[0207] [Table 16]

[0208] [Table 17]

[0209] [Table 18]

[0210] [Table 19]

[0211] [Table 20]

[0212] [Table 21]

[0213] [Table 22]

[0214] [Table 23]

[0215] [Table 24]

[0216] [Table 25]

[0217] [Table 26]

[0218] Example 2.1.45. (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-(1-fluoro-2-methylpropan-2-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol 1. 4-(4-chloro-2,3-difluorophenyl)-1-((4aR,6R,7R,8R,8aR)-6-((1-(1-fluoro-2-methylpropan-2-yl)-1H-1,2,3-triazol-4-yl)methyl)-7-methoxy-2,2-dimethylhexahydropyrano[3,2-d][1,3]dioxin-8-yl)-1H-1,2,3-triazole To a solution of 1-fluoro-2-methylpropan-2-amine hydrochloride (0.1 g, 0.745 mmol) in MeOH (1.0 mL) was added KCO (0.210 g, 1.49 mmol, 2.0 eq), copper(II) sulfate pentahydrate (0.02 g, 0.074 mmol, 0.1 eq), and 1H-imidazole-1-sulfonyl azide hydrochloride (0.2 g, 0.893 mmol, 1.2 eq), and the reaction mixture was stirred at rt for 17 h. A solution of intermediate 8 (0.2 g, 0.44 mmol, 1.0 eq) and copper(I) thiophene-2-carboxylate (0.025 g, 0.132 mmol, 0.3 eq) in THF (6.0 mL) was added to the mixture, and the mixture was stirred at 50 °C for 4 days. The reaction mixture is quenched with saturated aqueous NH4Cl (10.0 mL) and water and diluted with EA (10.0 mL). The aqueous phase is extracted once more with EA (10.0 mL), the phases are separated, the organic phases are combined and dried on a phase separator, the solvent is removed under vacuum and the crude product is recovered as a brown oil. Purification by preparative HPLC (I) gives the desired product as a white foam (0.038 g, 15%). LCMS (A): t R = 1.01 min; [M+H] + =571.09.

[0219] 2. (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-(1-fluoro-2-methylpropan-2-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol (Example 2.1.45.) To a solution of Example 2.1.45., Step 1. (0.035 g, 0.061 mmol, 1.0 eq) in dioxane (1.0 mL) was added water (0.5 mL) and the reaction mixture was cooled to 0° C. (ice bath). TFA (0.38 mL, 4.9 mmol, 80 eq) is added dropwise and the solution is stirred at rt for 20 h. The reaction mixture is quenched with 25% NH4OH (pH = 10) and directly purified by preparative HPLC (I) to recover the desired product as a white solid (0.026 g, 88%). LCMS (A): R =0.84 min; [M+H] + =531.02.

[0220] 1 H NMR (500 MHz, DMSO) δ:8.57(d, J=3.2Hz, 1H), 8.22(s, 1H), 7.95-7.98(m, 1H), 7.55-7.9(m, 1H) , 5.32(d, J=6.8Hz, 1H), 5.21(dd, J1=2.9Hz, J2=11.0Hz), 4.85(t, J=5.5Hz, 1H), 4.68(d, J=47.1Hz, 2H), 4.44-4.49(m, 2H), 3.93-4.0(m, 2H), 3.47-3.5 3(m, 2H), 3.38-3.333(m, 1H), 3.22(s, 3H), 2.87-2.91(m, 1H), 1.62(s, 6H).

[0221] The following examples are prepared starting from intermediate 8 and the corresponding amine according to the procedure described for Example 2.1.45. The LC-MS data are listed in Table 3 below. The LC-MS conditions are LC-MS(A).

[0222] [Table 27]

[0223] Example 2.1.54. (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((1-(1-(trifluoromethyl)cyclopropyl)-1H-1,2,3-triazol-4-yl)methyl)tetrahydro-2H-pyran-3-ol 1. 4-(4-chloro-2,3-difluorophenyl)-1-((4aR,6R,7R,8R,8aR)-7-methoxy-2,2-dimethyl-6-((1-(1-(trifluoromethyl)cyclopropyl)-1H-1,2,3-triazol-4-yl)methyl) (3,2-d)[1,3]dioxin-8-yl)-1H-1,2,3-triazole To a suspension of 1H-imidazole-1-sulfonyl azide hydrochloride (0.16 g, 0.71 mmol, 1.2 eq) in MeOH (2.0 mL) was added KCO (0.210 g, 1.2 mmol, 2.0 eq) and copper(II) sulfate pentahydrate (0.015 g, 0.059 mmol, 0.1 eq), followed by 1-(trifluoromethyl)cyclopropan-1-amine hydrochloride (0.1 g, 0.59 mmol) and stirred at rt for 17 h. This suspension is added to a solution of Intermediate 8 (0.12 g, 0.44 mmol, 1.0 eq) in THF (3.0 mL) along with copper(I) (0.085 g, 1.32 mmol, 5.0 eq), AcOH (0.61 mL, 10.6 mmol, 40 eq), and saturated aqueous CuSO (0.54 mL) and stirred at rt for 1.5 h. The reaction mixture is quenched with saturated aqueous NH Cl (10.0 mL) and water, diluted with EA (10.0 mL), and the aqueous phase is extracted once more with EA (10.0 mL). The combined organic phases are extracted with saturated aqueous NaHCO (10 mL), saturated aqueous NaCl (10 mL), dried over MgSO, filtered, and the solvent is removed in vacuo to recover the crude product as an oil. Purification by preparative HPLC (I) affords the title product as a white solid (0.134 g, 82%). LCMS (A): R = 1.05 min; [M+H] + =604.83.

[0224] 2. (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((1-(1-(trifluoromethyl)cyclopropyl)-1H-1,2,3-triazol-4-yl)methyl)tetrahydro-2H-pyran-3-ol (Example 2.1.54.) To a solution of Example 2.1.54, Step 1 (0.128 g, 0.212 mmol, 1.0 eq) in dioxane (3.0 mL) is added water (1.5 mL) and the reaction mixture is cooled to 0 °C (ice bath). TFA (0.33 mL, 4.24 mmol, 20 eq) is added dropwise and the solution is stirred at rt for 20 h. The reaction mixture is quenched with 25% NH4OH (pH = 10) and directly purified by preparative HPLC (I) to recover the title product as a white solid (0.098 g, 82%). LCMS (A): t R =0.0.9min;[M+H] + =564.91.

[0225] 1 H NMR (500MHz, DMSO) δ:8.57(d, J=3.2Hz, 1H), 8.32(s, 1H), 7.96(m, 1H), 7.57(m, 1H), 5.33(d, J=6 .8Hz, 1H), 5.21(dd, J1=11.3Hz, J2=3.0Hz, 1H), 4.77(t, J=5.6Hz, 1H), 4.45-4 .53(m, 2H), 3.94(m, 2H), 3.48(t, J=5.7Hz, 2H), 3.39(dd, J1=15.7Hz, J2=11.5 Hz, 1H), 3.22(s, 3H), 2.91(dd, J1=3.2Hz, J2=15.7Hz, 1H), 1.63-1.83(m, 4H).

[0226] The following examples are prepared analogously to the procedure described for Example 2.1.54, starting from intermediates 8, 9a, 10a, or 11a and the corresponding amines. Step 2 is carried out using TFA as described, or AcOH as described for Example 3.1.7, Step 2. Selected examples are synthesized using chiral amines to produce mixtures of diastereomers, which are separated by chiral preparative HPLC.

[0227] The LC-MS data are listed in Table 4 below. The LC-MS conditions are LC-MS (A). The chiral analytical HPLC (I) (conditions and retention times) of the diastereomers of selected examples are also listed.

[0228] [Table 28]

[0229] [Table 29]

[0230] [Table 30]

[0231] [Table 31]

[0232] Example 2.1.51. (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-(1-(difluoromethyl)cyclopropyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol 1. 4-(4-chloro-2,3-difluorophenyl)-1-((4aR,6R,7R,8R,8aR)-6-((1-(1-(difluoromethyl)cyclopropyl)-1H-1,2,3-triazol-4-yl)methyl)-7-methoxy-2,2-dimethylhexahydropyrano[3,2-d][1,3]dioxin-8-yl)-1H-1,2,3-triazole To a solution of intermediate 8 (0.1 g, 0.22 mmol, 1.0 eq) in DMF (2.0 mL) was added 1-azido-1-(difluoromethyl)cyclopropane (14.5% in TBME, 0.22 g, 0.242 mmol, 1.1 eq), copper(I) iodide (0.0042 g, 0.022 mmol, 0.1 eq), and DIPEA (0.115 mL, 0.661 mmol, 3.0 eq), and the reaction mixture was stirred at 50 °C for 3 h. The mixture was partitioned between EA and water / NH4Cl, and the layers were separated. The aqueous layer was extracted with EA (1x), and the combined organic layers were washed with saturated aqueous NH4Cl, water, and brine, dried over MgSO4, filtered, and the solvent was reduced under pressure to recover the crude product. Purification by preparative HPLC / MS (I) gives the desired product as a beige solid (0.1 g, 77%). LCMS (A): R = 1.01 min; [M+H] + =587.07.

[0233] 2. (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-(1-di (Fluoromethyl)cyclopropyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol (Example 2.1.51.) To a solution of Example 2.1.51, Step 1 (99 mg, 0.169 mmol, 1 eq) in water (4.0 mL) is added acetic acid (4.0 mL) and the solution is stirred at 55° C. for 48 h. The solvent is removed in vacuo and the crude material is purified by preparative HPLC / MS (I) to give the title compound as a white solid (0.045 g, 49%). LC-MS (A): R =0.84 min; [M+H] + :547.01.

[0234] 1H NMR (400MHz, MeOD) δ:8.50(d, J=3.5Hz, 1H), 8.2(s, 1H), 7.85(m, 1H), 7.45(m, 1H), 6.02(t, J=55Hz , 1H), 5.18(dd, J1=3.0Hz, J2=11.5Hz, 1Hz), 4.64-4.7(m, 1H), 4.50(dd, J1=6.0 Hz, J2=11.5Hz, 1H), 4.15(d, J=2.3Hz, 1H), 4.06(t, J=6.3Hz, 1H), 3.65-3.75(m , 2H), 3.41(dd, J1=11.3Hz, J2=15.8Hz, 1H), 3.1-3.17(m, 1H), 1.54-1.6(m, 4H).

[0235] The following examples are prepared starting from intermediates 8, 10a, or 11a and the corresponding azides according to the procedure described for Example 2.1.51. Step 2 is carried out using AcOH as described, or using TFA as described for Example 2.1.54., Step 2. The LC-MS data are listed in Table 5 below. The LC-MS conditions are LC-MS(A).

[0236] [Table 32]

[0237] Example 2.1.49. (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((1-(tert-pentyl)-1H-1,2,3-triazol-4-yl)methyl)tetrahydro-2H-pyran-3-ol 1. 4-(4-chloro-2,3-difluorophenyl)-1-((4aR,6R,7R,8R,8aR)-7-methoxy-2,2-dimethyl-6-((1-(tert-pentyl)-1H-1,2,3-triazol-4-yl)methyl)hexahydropyrano[3,2-d][1,3]dioxin-8-yl)-1H-1,2,3-triazole Triazole synthesis was carried out in a commercially available continuous-flow reactor (Vapourtec) using PFA (internal volume 2.0 mL), a copper coil (internal volume 10.0 mL), and a backpressure regulator (7.0 bar). tert-Amilamine (0.0315 mL, 0.264 mmol, 1.2 eq, 0.12 M in DMSO) and diethylamine (0.165 mL, 1.59 mmol, 7.2 eq) were dissolved in DMSO (1.96 mL). 2-Azido-1,3-dimethylimidazolinium hexafluorophosphate (95.2 mg, 0.317 mmol, 1.44 eq, 0.15 M in DMSO) was dissolved in DMSO (2.15 mL). The two solutions were pumped through the PFA coil at a flow rate of 0.063 mL / min at T = 50 °C. Maintaining a temperature of 145 °C, the reactor outlet is pumped directly into the copper coil at a flow rate of 0.125 mL / min with a solution of intermediate 8 (0.1 g, 0.22 mmol, 1 eq, 0.05 M in DMSO / water), sodium (+)-L-ascorbate (4.41 mg, 0.022 mmol, 0.1 eq), and trans-N,N'-dimethylcyclohexane-1,2-diamine (0.00537 mL, 0.033 mmol, 0.15 eq) in DMSO / water (5 / 1) (4.3 mL). The reactor outlet is collected and diluted with EA (20 mL) and saturated aqueous NH4Cl (20 mL). The layers are separated, and the organic layer is washed with saturated aqueous NH4Cl (20 mL) and brine (20 mL). The layers are separated, and the remaining aqueous layer is extracted once more with EA (20 mL). The combined organic layers are dried over MgSO4, filtered and concentrated in vacuo to recover the crude product which is purified by preparative HPLC (I) to give a white foam as the title compound (0.058 g). LC-MS (A): R = 1.05 min; [M+H] + :567.05. 2. (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((1-(tert-pentyl)-1H-1,2,3-triazol-4-yl)methyl)tetrahydro-2H-pyran-3-ol (Example 2.1.49.) The title compound is prepared from Example 2.1.49, Step 1. in TFA as a colorless glass (0.014, 25%) analogously to Example 2.1.51, Step 2. LCMS (A): t R =0.88min;[M+H] + =527.01.

[0238] The following examples are prepared starting from intermediate 8 and the corresponding amine according to the procedure described for Example 2.1.49. The LC-MS data are listed in Table 6 below. The LC-MS conditions are LC-MS(A).

[0239] [Table 33]

[0240] Example 5.1.53. 4-(1-((2R,3R,4S,5R,6R)-2-((1-(3-(difluoromethyl)oxetan-3-yl)-1H-1,2,3-triazol-4-yl)methyl)-5-hydroxy-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-4-yl)-1H-1,2,3-triazol-4-yl)-2,3-difluorobenzonitrile 1. 4-(4-bromo-2,3-difluorophenyl)-1-((4aR,6R,7R,8R,8aR)-6-((1-(3-(difluoromethyl)oxetan-3-yl)-1H-1,2,3-triazol-4-yl)methyl)-7-methoxy-2,2-dimethylhexahydropyrano[3,2-d][1,3]dioxin-8-yl)-1H-1,2,3-triazole The title compound is prepared from intermediate 11a and 3-(difluoromethyl)oxetan-3-amine as a light green glass (0.21, 65%) analogously to Example 2.1.51, Step 1. LCMS (A): R =0.99 min; [M+H] + =647.09.

[0241] 2. 4-(1-((4aR,6R,7R,8R,8aR)-6-((1-(3-(difluoromethyl)oxetan-3-yl)-1H-1,2,3-triazol-4-yl)methyl)-7-methoxy-2,2-dimethylhexahydropyrano[3,2-d][1,3]dioxin-8-yl)-1H-1,2,3-triazol-4-yl)-2,3-difluorobenzonitrile To a mixture of Example 5.1.53. Step 1. (0.15 g, 0.232 mmol, 1.0 eq) and copper(I) cyanide (0.042 g, 0.463 mmol, 2.0 eq) in DMF (3.0 mL) is added copper(I) iodide (0.0004 g, 0.0232 mmol, 0.1 eq) and the resulting yellow solution is stirred at 120 °C for 72 h. The reaction mixture is cooled to rt and quenched with EA and water. The phases are separated and the organic phase is washed with brine, dried over MgSO4, filtered and concentrated under reduced pressure. The crude material is purified by ISCO to recover (0.112 g, 81%) of the desired product as a colorless solid. LCMS (A): t R =0.94 min; [M+H] + =593.99.

[0242] 3. 4-(1-((2R,3R,4S,5R,6R)-2-((1-(3-(difluoromethyl)oxetan-3-yl)-1H-1,2,3-triazol-4-yl)methyl)-5-hydroxy-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-4-yl)-1H-1,2,3-triazol-4-yl)-2,3-difluorobenzonitrile (Example 5.1.53) The title compound is prepared analogously to Example 2.1.51, Step 2, from Example 5.1.53, Step 2, in TFA as a colorless glass (0.087, 65%). LCMS (A): R =0.77 min; [M+H] + =554.16.

[0243] 1H NMR (500MHz, MeOD) δ:8.63(d, J=3.5Hz, 1H), 8.26(s, 1H), 8.16(m, 1H), 7.70(m, 1H), 6.57(t, J=54.5Hz), 5.19-5.24(m, 3H), 5.15(dd, J 1= 2.3Hz, J 2= 7.7Hz, 2H), 4.70(m, 1H), 4.53(dd, J 1= 5.9Hz, J 2= 11.5Hz, 2H, 1H), 4.15(d, J=2.4Hz, 1H), 4.07-4.10(m, 1H), 3.67-3.76(m, 2H), 3.46(dd, J1=15.8Hz, J2=11.9Hz, 1H), 3.15-3.19(m, 1H).

[0244] The following examples are prepared starting from intermediate 11a and the corresponding amine according to the procedure described for Example 5.1.53. Step 3 is carried out using TFA as described, or using AcOH as reported for Example 3.1.7. Step 2. The LC-MS data are listed in Table 7 below. The LC-MS conditions are LC-MS(A).

[0245] [Table 34]

[0246] Example 1.2.34. (2R,3R,4S,5R,6R)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-6-((4-(2-hydroxypropan-2-yl)-1H-1,2,3-triazol-1-yl)methyl)-5-methoxytetrahydro-2H-pyran-3-ol 1. 2-(1-(((4aR,6R,7R,8R,8aR)-8-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-7-methoxy-2,2-dimethylhexahydropyrano[3,2-d][1,3]dioxin-6-yl)methyl)-1H-1,2,3-triazol-4-yl)propan-2-ol 2-Methylbut-3-yn-2-ol (0.017 g, 0.2 mmol, 1 eq) and Intermediate 18a (90.1 mg, 0.2 mmol) was dissolved in DMF (2 mL) and copper(I) iodide (3.89 mg, 0.02 mmol, 0.1 eq) and DIPEA (0.10 mL, 0.6 mmol, 3.0 eq) were added. The mixture was stirred at rt for 15 h, then filtered and purified directly by prep HPLC / MS (I) to recover the desired compound (0.094 g, 88%). LCMS (A): R =0.86 min; [M+H] + =535.23.

[0247] 2. (2R,3R,4S,5R,6R)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-6-((4-(2-hydroxypropan-2-yl)-1H-1,2,3-triazol-1-yl)methyl)-5-methoxytetrahydro-2H-pyran-3-ol (Example 1.2.34.) Example 1.2.34. To a solution of step 1 (0.094, 0.18 mmol) in THF (6.0 mL) is added a mixture of AcOH / water (1 / 1, 10 mL) and the solution is stirred at 65° C. for 24 h. The reaction mixture is partitioned between EA and saturated aqueous NaHCO3. The layers are separated, the aqueous phase is extracted with EA (2×15 mL), the organic phases are combined, dried over Na2SO4, filtered and concentrated in vacuo. The crude is purified by prep HPLC / MS (I) to recover the desired product (0.072 g, 83%). LCMS (A): t R =0.73 min; [M+H] + =495.20.

[0248] 1 H NMR (400MHz, MeOD) δ:8.47(d, J=3.3Hz, 1H), 8.06(s, 1H), 7.78(m, 1H), 7.15(t, J=7.3Hz, 1H), 5.21(dd, J 1 =2.8Hz, J 2 =11.5Hz, 1H), 5.09(dd, J 1 =11.5Hz, J 2 =15.1Hz, 1H), 4.85-4.75(m, 2H), 4.59(dd, J 1 =6.5Hz, J 2 =11.5Hz, 1H), 4.25-4.21(m, 2H), 3.71(m, 2H), 3.37(s, 3H), 2.36(s, 3H), 1.63(s, 6H).

[0249] The following examples are prepared starting from either intermediate 17a or 18a and the corresponding alkyne according to the procedure described for Example 1.2.34. The LC-MS data are listed in Table 8 below. The LC-MS conditions are LC-MS(A).

[0250] [Table 35]

[0251] [Table 36]

[0252] [Table 37]

[0253] The following examples are / can be prepared starting from either intermediate 18a, 19a or 20a and the corresponding alkyne according to the procedure described for Example 1.2.34. The LC-MS data are listed in Table 9 below. The LC-MS conditions are LC-MS(A).

[0254] [Table 38]

[0255] [Table 39]

[0256] [Table 40]

[0257] [Table 41]

[0258] [Table 42]

[0259] II. Biological Testing Inhibitory activity of the compound (IC 50 ) evaluation The inhibitory activity of the compounds is determined in a competitive binding assay. This spectrophotometric assay measures the binding of biotin-labeled human Gal-3 (hGal-3) or human Gal-1 (hGal-1), respectively, to the glycoprotein asialofetuin (ASF) adsorbed to microplates (Proc Natl Acad Sci USA. 2013 Mar 26;110(13):5052-7). Alternatively, and preferably, a version of human Gal-1 in which all six cysteines are replaced by serine may be used.

[0260] Briefly, compounds are serially diluted in DMSO (test diluent). To an ASF-coated 384-well plate, 22.8 μL / well of biotin-labeled hGal-3 or hGal-1 (i.e., 300-1000 ng / mL biotin-labeled hGal-3 or hGal-1) in assay buffer is added, followed by 1.2 μL of compound test diluent and mixing.

[0261] The plate is incubated at 4°C for 3 hours, then washed with cold assay buffer (3 x 50 μL), and incubated with 25 μL / well of streptavidin-peroxidase solution (diluted to 80 ng / mL in assay buffer) for 1 hour at 4°C, followed by further washing with assay buffer (3 x 50 μL). Finally, 25 μL / well of ABTS substrate is added. After 30-45 minutes, the OD (410 nm) is recorded and the IC is calculated. 50 Calculate the value.

[0262] Calculated IC 50 Values ​​may vary with each day's assay run. This type of variation is known to those skilled in the art. IC values ​​obtained from several measurements 50 Values ​​are reported as geometric means.

[0263] [Table 43]

[0264] [Table 44]

[0265] [Table 45]

[0266] [Table 46]

[0267] The compounds of the invention can be assayed for their potency / selectivity in competitive binding assays, for example, using Gal-1, Gal-2, Gal-4N, Gal-4C, Gal-8N, Gal-8C, Gal-9N, Gal-9C, Gal-10 as probes; for their ability using impedance-based cellular assays, which measure inhibition of Gal-3-induced cell morphological changes; for their ability to inhibit hepatic stellate cell activation or inhibit T-cell apoptosis; for their ability in thermal shift assays, which measure the ability of a compound to inhibit thermal denaturation of purified Gal-3 or intracellular Gal-3 (including that in blood and organs); for their ability to inhibit the recruitment of intracellular Gal-3 to sites of organelle damage (Stegmayr et al., 2019; doi.org / 10.1038 / s41598-019-38497-8); or ... assay (Biacore), or an isothermal calorimetric assay that measures the binding enthalpy, binding entropy, binding affinity, on-rate, and off-rate of Gal-3-compound interactions. These proteins may be further characterized with respect to their thermodynamic and kinetic interaction profiles with Gal-3 using interferometry (ITC).

[0268] The compounds of the present invention may be evaluated for their general pharmacokinetic and pharmacological properties using conventional assays well known in the art; for example, for their drug safety and / or toxicological properties using conventional assays well known in the art, such as cytochrome P450 enzyme inhibition and time-dependent inhibition, pregnane X receptor (PXR) activation, glutathione binding, or for their ability to bind to different proteins using, for example, a plasma protein binding assay, or their ability to enter blood cells using, for example, a blood to plasma distribution coefficient assay; for example, for their ability to enter blood cells using, for example, a (human) liver microsome assay or a fresh (human) hepatocyte assay. They may be further characterized for their in vitro metabolic stability; or for their penetration ability, e.g., using Caco-2 (human colon carcinoma cell line) or MDCK (Madin-Darby canine kidney cell line) cell assays; or for their ability to cross the blood-brain barrier, e.g., using a human P-glycoprotein 1 (MDR1) substrate assay; or for their bioavailability in different species (such as rats or dogs).

[0269] Compounds of the invention may be further characterized for their cardiovascular safety behavior using, for example, a human induced pluripotent stem cell (iPSC)-derived cardiomyocyte assay, or for their effects on the Kv11.1 channel, a potassium ion channel encoded by the human ether-a-go-go-related gene (hERG channel), using, for example, patch clamp measurements of the effect on hERG K+ current in a Chinese Hamster Ovary (CHO) cell assay.

[0270] Compounds of the invention may be further characterized for their effect on cell viability using the commercially available CellTiter-Glo luminescent assay, which quantifies cellular ATP as a marker of metabolically active cells. Compounds may be further evaluated for their cytotoxic effects using fluorescent marker dyes that label and quantify live from dead cells.

Claims

1. A compound of formula (I) or a pharmaceutically acceptable salt thereof: 【Chemistry 1】 (In the formula, R Ｐ２ represents a halogen; R Ｐ３ represents a halogen; R Ｐ４ represents halogen, methyl or cyano; R １ teeth, - hydroxy; - C １－４ -alkoxy; - -O-CO-C １－３ - alkyl; -O-CO-NH-R Ｎ１１ (R Ｎ１１ is hydrogen or C １－３ - represents alkyl; - -O-CH ２ -C １ -fluoroalkyl; - -O-CH ２ -HET １ (H.E.T. １ represents a 5-membered heteroaryl, The heteroaryl is independently unsubstituted or substituted with one methyl; or - -O-CH ２ -CO-R １Ｘ (R １Ｘ は、 -- -hydroxy; -- C １－３ -alkoxy; --morpholin-4-yl; Or, -- --NR Ｎ２１ R Ｎ２２ (R Ｎ２１ and R Ｎ２２ each independently represents hydrogen or methyl; or R Ｎ２１ and R Ｎ２２ together with the nitrogen atom to which they are attached form a 4-6 membered monocyclic heterocycloalkyl selected from azetidin-1-yl, pyrrolidin-1-yl and piperidin-1-yl, said 4-6 membered heterocycloalkyl being substituted by one hydroxy; represents.) represents; A represents [1,2,3]triazole-1,4-diyl; -R ２ is branch C ３－６ - alkyl, wherein the branched C ３－６ - alkyl is --substituted by one hydroxy, -- 1 -CO-O-C １－４ -substituted by alkyl, or -- 1 C １ - substituted by fluoroalkyl; Branch C ３－６ - represents alkyl; - or R ２ is a 3-8 membered saturated monocyclic or bicyclic group, wherein the monocyclic or bicyclic group is -- Monocyclic C ３－６ -cycloalkyl, -- 4-6 membered monocyclic heterocycloalkyl having one ring oxygen atom, --Bridged bicyclic C ５－８ -cycloalkyl, -- Fused bicyclic C ６－８ -cycloalkyl, --spiro-bicyclic C ６－８ -cycloalkyl, or -- 7- or 8-membered spiro-bicyclic heterocycloalkyl having one ring oxygen atom; represents a monocyclic or bicyclic group, The monocyclic or bicyclic groups are independently -- unsubstituted; -- substituted by one hydroxy; -- 1 C １－３ substituted with alkyl; -- 1 C １－３ -substituted by alkoxy; -- 1 -C １－３ -substituted by alkylene-OH; -- 1 -C １－３ -Alkylene-O-C １－３ -substituted by alkyl; -- 1 C １ -substituted by fluoroalkyl; -- 1 -NR Ｎ１ R Ｎ２ (R Ｎ１ represents hydrogen, R Ｎ２ is hydrogen or —CO—O—C １－４ -represents alkyl; -- substituted by 1 or 2 fluoro; --One substituent is hydroxy and the other is C １－３ -substituted by two substituents which are alkyl; or --3 substituents, two of which are fluoro; the remaining substituents are C １－３ -alkyl or -C １－３ -alkylene-OH.

2. -R Ｐ２ represents fluoro or chloro; -R Ｐ３ represents fluoro or chloro; -R Ｐ４ represents halogen, methyl or cyano; 2. The compound of claim 1 or a pharmaceutically acceptable salt thereof.

3. -R Ｐ２ represents fluoro; -R Ｐ３ represents fluoro; -R Ｐ４ represents fluoro, chloro, bromo or methyl; 2. The compound of claim 1 or a pharmaceutically acceptable salt thereof.

4. R １ The compound according to any one of claims 1 to 3, or a pharmaceutically acceptable salt thereof, wherein: represents methoxy.

5. A represents [1,2,3]triazole-1,4-diyl; R ２ is bonded to the 1-position of the [1,2,3]triazole-1,4-diyl; or a pharmaceutically acceptable salt thereof.

6. A represents [1,2,3]triazole-1,4-diyl; R ２ is bonded to the 4-position of the [1,2,3]triazole-1,4-diyl; or a pharmaceutically acceptable salt thereof.

7. d) Group AR ２ but, 【Chemistry 2】 【Transformation 3】 A group selected from 【Chemistry 4】 or e) Group AR ２ but, 【Transformation 5】 A group selected from 【Transformation 6】 or f) Group AR ２ but, 【Transformation 7】 【Transformation 8】 A group selected from 【Chemistry 9】 The compound according to any one of claims 1 to 4, or a pharmaceutically acceptable salt thereof, which represents:

8. The compound is (2R,3R,4S,5R,6R)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-6-((1-((3R,4R)-4-hydroxytetrahydro-2H-pyran-3-yl)-1H-1,2,3-triazol-4-yl)methyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((1R,2R)-2-hydroxycyclopentyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((1S,2S)-2-hydroxycyclopentyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-6-((1-(1-(hydroxymethyl)cyclopropyl)-1H-1,2,3-triazol-4-yl)methyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-6-((1-(1-(hydroxymethyl)cyclopentyl)-1H-1,2,3-triazol-4-yl)methyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((1-(3-methyloxetan-3-yl)-1H-1,2,3-triazol-4-yl)methyl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((1-(1-(methoxymethyl)cyclopropyl)-1H-1,2,3-triazol-4-yl)methyl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-6-((1-(4-hydroxybicyclo[2.2.2]octan-1-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-6-((1-(1-hydroxy-2-methylpropan-2-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol Lu; Methyl 2-(4-(((2R,3R,4S,5R,6R)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-yl)methyl)-1H-1,2,3-triazol-1-yl)-2-methylpropanoate; (2R,3R,4S,5R,6R)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-6-((1-(1-(hydroxymethyl)cyclobutyl)-1H-1,2,3-triazol-4-yl)methyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-6-((1-(bicyclo[1.1.1]pentan-1-yl)-1H-1,2,3-triazol-4-yl)methyl)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((1-(1-methylcyclobutyl)-1H-1,2,3-triazol-4-yl)methyl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((1-(3-methylbicyclo[1.1.1]pentan-1-yl)-1H-1,2,3-triazol-4-yl)methyl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-6-((1-(3,3-difluoro-1-methylcyclobutyl)-1H-1,2,3-triazol-4-yl)methyl)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-6-((1-(2-oxaspiro[3.3]heptan-6-yl)-1H-1,2,3-triazol-4-yl)methyl)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-6-((1-((1RS,2SR)-2-isopropylcyclopropyl)-1H-1,2,3-triazol-4-yl)methyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-6-((1-(3,3-difluoro-1-(hydroxymethyl)cyclobutyl)-1H-1,2,3-triazol-4-yl)methyl)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((1S,3S)-3-hydroxy-1-methylcyclobutyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-6-((1-((1R,5S)-bicyclo[3.1.0]hexan-6-yl)-1H-1,2,3-triazol-4-yl)methyl)- 4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((1-(3-(methoxymethyl)oxetan-3-yl)-1H-1,2,3-triazol-4-yl)methyl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-6-((1-(3-(2-hydroxyethyl)oxetan-3-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((1-(1-methylcyclopropyl)-1H-1,2,3-triazol-4-yl)methyl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((1-(3-(trifluoromethyl)bicyclo[1.1.1]pentan-1-yl)-1H-1,2,3-triazol-4-yl)methyl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-6-((1-(3-fluorobicyclo[1.1.1]pentan-1-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((1-(spiro[2.3]hexan-5-yl)-1H-1,2,3-triazol-4-yl)methyl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((1R,3R)-3-hydroxy-1-methylcyclobutyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((1-(1-(methoxymethyl)cyclopropyl)-1H-1,2,3-triazol-4-yl)methyl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-(1,1-difluoro-2-methylpropan-2-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-6-((1-(1-(hydroxymethyl)cyclopropyl)-1H-1,2,3-triazol-4-yl)methyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl) (1-(1-(hydroxymethyl)cyclopentyl)-1H-1,2,3-triazol-4-yl)methyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-6-((1-(1-(hydroxymethyl)cyclobutyl)-1H-1,2,3-triazol-4-yl)methyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-(4-hydroxybicyclo[2.2.2]octan-1-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-(1-hydroxy-2-methylpropan-2-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; Methyl 2-(4-(((2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-yl)methyl)-1H-1,2,3-triazol-1-yl)-2-methylpropanoate; (2R,3R,4S,5R,6R)-6-((1-(bicyclo[1.1.1]pentan-1-yl)-1H-1,2,3-triazol-4-yl)methyl)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((1-(1-methylcyclobutyl)-1H-1,2,3-triazol-4-yl)methyl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((1-(3-methyloxetan-3-yl)-1H-1,2,3-triazol-4-yl)methyl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((1-(3-methylbicyclo[1.1.1]pentan-1-yl)-1H-1,2,3-triazol-4-yl)methyl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((1-(3-methoxybicyclo[1.1.1]pentan-1-yl)-1H-1,2,3-triazol-4-yl)methyl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-(3,3-difluoro-1-methylcyclobutyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-6-((1-(2-oxaspiro[3.3]hepta) (4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-6-((1-(2-isopropylcyclopropyl)-1H-1,2,3-triazol-4-yl)methyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-(3,3-difluoro-1-(hydroxymethyl)cyclobutyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((1S,3S)-3-hydroxy-1-methylcyclobutyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-6-((1-((1R,5S)-bicyclo[3.1.0]hexan-6-yl)-1H-1,2,3-triazol-4-yl)methyl)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((1-(3-(methoxymethyl)oxetan-3-yl)-1H-1,2,3-triazol-4-yl)methyl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-(3-(2-hydroxyethyl)oxetan-3-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((1-(1-methylcyclopropyl)-1H-1,2,3-triazol-4-yl)methyl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((1-(3-(trifluoromethyl)bicyclo[1.1.1]pentan-1-yl)-1H-1,2,3-triazol-4-yl)methyl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-(3-fluorobicyclo[1.1.1]pentan-1-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((1-(spiro[2.3]hexan-5-yl)-1H-1,2,3 -triazol-4-yl)methyl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((1R,3R)-3-hydroxy-1-methylcyclobutyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-2-(hydroxymethyl)-6-((1-(1-(hydroxymethyl)cyclopentyl)-1H-1,2,3-triazol-4-yl)methyl)-5-methoxy-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-2-(hydroxymethyl)-6-((1-(1-(hydroxymethyl)cyclopropyl)-1H-1,2,3-triazol-4-yl)methyl)-5-methoxy-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-2-(hydroxymethyl)-5-methoxy-6-((1-(1-(methoxymethyl)cyclopropyl)-1H-1,2,3-triazol-4-yl)methyl)-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-6-((1-(bicyclo[1.1.1]pentan-1-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxy-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-2-(hydroxymethyl)-6-((1-(1-(hydroxymethyl)cyclobutyl)-1H-1,2,3-triazol-4-yl)methyl)-5-methoxy-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-6-((1-(3-fluorobicyclo[1.1.1]pentan-1-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxy-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-2-(hydroxymethyl)-5-methoxy-6-((1-(3-(trifluoromethyl)bicyclo[1.1.1]pentan-1-yl)-1H-1,2,3-triazol-4-yl)methyl)-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-6-((1-(3,3-difluoro-1-methylcyclobutyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxy-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-6-((1-(3,3-difluoro-1-(hydroxymethyl)cyclobutyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxy-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-6-((1-(2-oxaspiro[3.3]heptan-6-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxy-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-6-((1-((1R,3R)-3-hydroxy- 1-methylcyclobutyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxy-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-6-((1-((1S,3S)-3-hydroxy-1-methylcyclobutyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxy-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-2-(hydroxymethyl)-5-methoxy-6-((1-(3-(methoxymethyl)oxetan-3-yl)-1H-1,2,3-triazol-4-yl)methyl)-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-6-((1-(3-(2-hydroxyethyl)oxetan-3-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxy-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-2-(hydroxymethyl)-5-methoxy-6-((1-(1-methylcyclopropyl)-1H-1,2,3-triazol-4-yl)methyl)-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((1-(3-methyloxetan-3-yl)-1H-1,2,3-triazol-4-yl)methyl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((1-(1-methylcyclobutyl)-1H-1,2,3-triazol-4-yl)methyl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-6-((1-(bicyclo[1.1.1]pentan-1-yl)-1H-1,2,3-triazol-4-yl)methyl)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((1-(1-(methoxymethyl)cyclobutyl)-1H-1,2,3-triazol-4-yl)methyl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-6-((1-(1-(hydroxymethyl)cyclopropyl)-1H-1,2,3-triazol-4-yl)methyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((1S,2S)-2-hydroxycyclopentyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-6-((4-(1-hydroxycyclobutyl)-1H-1,2,3-triazol-1-yl)methyl)-2-(hydro (xymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-6-((4-cyclopentyl-1H-1,2,3-triazol-1-yl)methyl)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-6-((4-(1-hydroxycyclopentyl)-1H-1,2,3-triazol-1-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-6-((4-(2-hydroxypropan-2-yl)-1H-1,2,3-triazol-1-yl)methyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((4-(3-methyloxetan-3-yl)-1H-1,2,3-triazol-1-yl)methyl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-6-((4-(4-hydroxytetrahydro-2H-pyran-4-yl)-1H-1,2,3-triazol-1-yl)methyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-6-((4-(1-hydroxycyclopropyl)-1H-1,2,3-triazol-1-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-6-((4-(1-(hydroxymethyl)cyclopropyl)-1H-1,2,3-triazol-1-yl)methyl)-5-methoxytetrahydro-2H-pyran-3-ol; tert-butyl (4-(1-(((2R,3R,4S,5R,6R)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-yl)methyl)-1H-1,2,3-triazol-4-yl)bicyclo[2.2.2]octan-1-yl)carbamate; (2R,3R,4S,5R,6R)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-6-((4-(3-ethyloxetan-3-yl)-1H-1,2,3-triazol-1-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-6-((1-(4-aminobicyclo[2.2.2]octan-1-yl)-1H-1,2,3-triazol-4-yl)methyl)-4-(4-(2,3-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((4-(1-hydroxycyclobutyl)-1H-1,2,3-triazol-1-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((4-cyclopentyl- 1H-1,2,3-triazol-1-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((4-(1-hydroxycyclopentyl)-1H-1,2,3-triazol-1-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-6-((4-(2-hydroxypropan-2-yl)-1H-1,2,3-triazol-1-yl)methyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((4-(3-methyloxetan-3-yl)-1H-1,2,3-triazol-1-yl)methyl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-6-((4-(4-hydroxytetrahydro-2H-pyran-4-yl)-1H-1,2,3-triazol-1-yl)methyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((4-(1-hydroxycyclopropyl)-1H-1,2,3-triazol-1-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-6-((4-(1-(hydroxymethyl)cyclopropyl)-1H-1,2,3-triazol-1-yl)methyl)-5-methoxytetrahydro-2H-pyran-3-ol; tert-butyl (4-(1-(((2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-5-hydroxy-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-2-yl)methyl)-1H-1,2,3-triazol-4-yl)bicyclo[2.2.2]octan-1-yl)carbamate; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((4-(3-ethyloxetan-3-yl)-1H-1,2,3-triazol-1-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-6-((1-(4-aminobicyclo[2.2.2]octan-1-yl)-1H-1,2,3-triazol-4-yl)methyl)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-6-((4-(1-hydroxycyclobutyl)-1H-1,2,3-triazol-1-yl)methyl)-2-(hydroxymethyl)-5-methoxy-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-6-((4-cyclopentyl-1H-1,2,3-triazol-1-yl)methyl)-2-(hydroxymethyl)-5-methoxy-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-6-((4-(1-hydroxycyclopentyl)- 1H-1,2,3-triazol-1-yl)methyl)-2-(hydroxymethyl)-5-methoxy-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-2-(hydroxymethyl)-6-((4-(2-hydroxypropan-2-yl)-1H-1,2,3-triazol-1-yl)methyl)-5-methoxy-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-2-(hydroxymethyl)-5-methoxy-6-((4-(3-methyloxetan-3-yl)-1H-1,2,3-triazol-1-yl)methyl)-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-2-(hydroxymethyl)-6-((4-(4-hydroxytetrahydro-2H-pyran-4-yl)-1H-1,2,3-triazol-1-yl)methyl)-5-methoxy-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-6-((4-(1-hydroxycyclopropyl)-1H-1,2,3-triazol-1-yl)methyl)-2-(hydroxymethyl)-5-methoxy-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-2-(hydroxymethyl)-6-((4-(1-(hydroxymethyl)cyclopropyl)-1H-1,2,3-triazol-1-yl)methyl)-5-methoxy-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-6-((4-(3-ethyloxetan-3-yl)-1H-1,2,3-triazol-1-yl)methyl)-2-(hydroxymethyl)-5-methoxy-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; tert-butyl (4-(1-(((2R,3R,4S,5R,6R)-5-hydroxy-6-(hydroxymethyl)-3-methoxy-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)methyl)-1H-1,2,3-triazol-4-yl)bicyclo[2.2.2]octan-1-yl)carbamate; (2R,3R,4S,5R,6R)-6-((1-(4-aminobicyclo[2.2.2]octan-1-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxy-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-6-((4-(bicyclo[1.1.1]pentan-1-yl)-1H-1,2,3-triazol-1-yl)methyl)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((4-(1-methylcyclopropyl)-1H-1,2,3-triazol-1-yl)methyl)tetrahydro-2H-pyran-3-ol; Or, (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((4-(1-methylcyclobutyl)-1H-1,2,3-triazol-1-yl)methyl)tetrahydro-2H-pyran-3-ol; 2. The compound of claim 1, wherein:

9. The compound is (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-(3-(fluoromethyl)oxetan-3-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-(3-(difluoromethyl)oxetan-3-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((1-(3-(trifluoromethyl)oxetan-3-yl)-1H-1,2,3-triazol-4-yl)methyl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((3R,4S)-3-fluorotetrahydro-2H-pyran-4-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((3R,4R)-4-fluorotetrahydrofuran-3-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((3S,4S)-4-fluorotetrahydrofuran-3-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((R)-3,3-difluorotetrahydro-2H-pyran-4-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((S)-3,3-difluorotetrahydro-2H-pyran-4-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((R)-4,4-difluorotetrahydrofuran-3-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((S)-4,4 -difluorotetrahydrofuran-3-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-6-((1-((3S,4R)-3-fluorotetrahydro-2H-pyran-4-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxy-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-6-((1-((3R,4S)-3-fluorotetrahydro-2H-pyran-4-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxy-4-(4-(2,3,4-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((3R,4R)-3-fluorotetrahydro-2H-pyran-4-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-((3S,4S)-3-fluorotetrahydro-2H-pyran-4-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-((1-(3-(difluoromethyl)oxetan-3-yl)-1H-1,2,3-triazol-4-yl)methyl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6R)-4-(4-(4-bromo-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxy-6-((1-(3-(trifluoromethyl)oxetan-3-yl)-1H-1,2,3-triazol-4-yl)methyl)tetrahydro-2H-pyran-3-ol; 2,3-difluoro-4-(1-((2R,3R,4S,5R,6R)-2-((1-((3R,4S)-3-fluorotetrahydro-2H-pyran-4-yl)-1H-1,2,3-triazol-4-yl)methyl)-5-hydroxy-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-4-yl)-1H-1,2,3-triazol-4-yl)benzonitrile; Or, 2,3-difluoro-4-(1-((2R,3R,4S,5R,6R)-2-((1-((3S,4R)-3-fluorotetrahydro-2H-pyran-4-yl)-1H-1,2,3-triazol-4-yl)methyl)-5-hydroxy-6-(hydroxymethyl)-3-methoxytetrahydro-2H-pyran-4-yl)-1H-1,2,3-triazol-4-yl)benzonitrile; 2. The compound of claim 1, wherein:

10. A pharmaceutical composition comprising the compound according to any one of claims 1 to 9 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

11. A compound according to any one of claims 1 to 9 or a pharmaceutically acceptable salt thereof for use as a pharmaceutical.

12. A pharmaceutical 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; cell 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, comprising as an active ingredient a compound according to any one of claims 1 to 9 or a pharmaceutically acceptable salt thereof.

13. Use of a compound according to any one of claims 1 to 9 or a pharmaceutically acceptable salt thereof in the manufacture of a medicament 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; cell proliferative disorders and cancer; 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 neuropathies; eye diseases and disorders; or transplant rejection.

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