(Hetero)aryl-methyl-thio-beta-D-galactopyranoside derivatives

Abstract

The present invention is 1 , Ar 2 , R 1a , R 1b and R 2 The present invention relates to compounds of formula (I), as described herein, their preparation, pharmaceutically acceptable salts thereof, and their use as medicaments, pharmaceutical compositions comprising one or more compounds of formula (I), and their use, in particular as galectin-3 inhibitors. [Formula 1] TIFF2022543666000092.tif62165

Description

[Technical field]

[0001] The present invention relates to compounds of formula (I) that are galectin-3 inhibitors and their use in the prevention or treatment of diseases and disorders involving the binding of galectin-3 to its natural ligands. The invention also relates to related aspects including processes for the preparation of said 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 sequences of human, mouse and rat have revealed the presence of at least 16 conserved galectins and galectin-like proteins in a mammalian genome (Leffler H. et al., Glycoconj. J. 2002,19,433-440). Three galectin subclasses have been identified so far: 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, e.g., crosslinking glycoconjugates on the cell surface to trigger cell signaling events. By 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 from organ to organ. Depending on its extracellular or intracellular localization, it can exhibit a wide variety of biological functions, such as immune regulation, 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, such as 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), indicating that Gal-3 is involved in the control of inflammatory and fibrotic processes (Henderson NC. et al., Immunological Reviews 2009;230:160-171). ;Sano H. et al., J Immunol. 2000;165(4):2156-64). Furthermore, the expression level of Gal-3 protein is upregulated in certain pathological conditions such as neoplasms and inflammation (Chiariotti L. et al., Glycoconjugate Journal 2004 19, 441-449;Farhad M. et al., OncoImmunology 2018, 7:6, e1434467).

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

[0006] In addition, inhibition of Gal-3 has been shown to be effective in preventing COVID-19 (Caniglia JL et al., Peer J 2020, 8:e9392) and influenza H5N1 (Chen YJ et al., Am. J. Pathol. 2018, 188(4), 1031-1042), possibly due to its anti-inflammatory effects.

[0007] Recently, Gal-3 inhibitors have been shown to have positive effects when used in combination immunotherapy (Galectin Therapeutics. Press release, February 7, 2017) and in idiopathic pulmonary fibrosis (Galecto Biotech. Press release, March 10, 2017) and NASH cirrhosis (December 5, 2017). W020180209276, W02018209255 and W020190890080 disclose compounds having binding affinity to galectin proteins for the treatment of systemic insulin resistance disorders. Thus, Gal-3 inhibitors, alone or in combination with other therapies, would be useful in the prevention or treatment of diseases or disorders such as organ fibrosis, cardiovascular diseases and disorders, acute and chronic kidney injury, liver diseases and disorders, interstitial lung diseases and disorders, eye 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, and / or transplant rejection.

[0008] Synthetic inhibitors of Gal-3 that have been explored as antifibrotic agents have been described in various publications and patent applications (see, e.g., W02005113568, W02005113569, W02014067986, W02016120403, US20140099319, W02019067702, W02019075045, W02014078655, W02020078807, and W02020078808).

[0009] Verteramo et al. (J. Am. Chem. Soc. 2019, 141, 5, 2012) disclose a comparative analysis of ligand binding to galectin-3C using two diastereomeric β-D-galactopyranoside ligands. These ligands contain at least the essential substituent, Ar, of the present invention. 2 The same ligand was used by Caldararu et al. (Phys. Chem. Chem. Phys. 2019, 21, 18149) to test whether it was possible to obtain reliable entropies from crystallographic B factors.

[0010] The present invention provides novel compounds of formula (1) that are galectin-3 inhibitors. The compounds of the present invention may therefore be useful in the prevention or treatment of diseases and disorders in which modulation of Gal-3 binding to natural carbohydrate ligands is required. Summary of the Invention

[0011] 1) In a first aspect, the present invention relates to a compound of formula (I):

[0012] [ka] (In the formula, Ar 1 teeth, - aryl (especially phenyl) substituted by 1, 2, 3, 4 or 5 substituents (especially substituted by 1, 2 or 3 substituents), said substituents being independently selected from halogen, methyl, cyano and methoxy; [in particular, at least one of the substituents is attached at the meta or para position of the phenyl; if a para substituent is present, the para substituent is preferably selected from halogen, methyl, cyano and methoxy; if a meta substituent is present, the meta substituent is preferably halogen]; or - 5- or 6-membered heteroaryl (especially pyridinyl), which is independently unsubstituted or substituted by 1 or 2 substituents, said substituents being independently selected from halogen, methyl, cyano and methoxy; represents; Ar 2 teeth, - phenyl or 5- or 6-membered heteroaryl (in particular thiophenyl, thiazolyl, oxazolyl, isoxazolyl, pyridinyl or pyrazinyl; or, in addition, pyrazolyl, triazolyl or pyridazinyl), which phenyl or 5- or 6-membered heteroaryl is independently unsubstituted or substituted by 1, 2 or 3 substituents, which are independently selected from the group consisting of 1-6 -Alkyl, C 3-6 -Cycloalkyl (especially cyclopropyl), C 1-3 -fluoroalkyl (especially trifluoromethyl), C 1-3 -Fluoroalkoxy, halogen, hydroxy-C 1-3 - alkyl (especially 2-hydroxyethyl) or phenyl, phenyl or 5- or 6-membered heteroaryl (especially thiophenyl, thiazolyl, oxazolyl, isoxazolyl, pyridinyl or pyrazinyl; or, in addition, pyrazolyl, triazolyl or pyridazinyl) [especially Ar 2 When represents phenyl, one of the substituents is an Ar 2 and if other substituents are present, the other substituents are attached meta or para to the point of attachment to the remainder of the molecule; or - Naphthyl; represents; - R 1a represents hydrogen; and R 1b teeth, -- -C 2-4 - alkyl (especially ethyl); or -- -C 0-1 -Alkylene-Ar 1b (Ar 1b represents phenyl or 5- or 6-membered heteroaryl, which is independently unsubstituted or substituted by 1 or 2 methyl; represents; - or R 1a and R 1b each represents hydrogen, methyl, ethyl or n-propyl; - or R1a and R 1b together with the carbon atoms to which they are attached, -- C 3-6 -Cycloalkylene (the C 3-6 -cycloalkylene is independently unsubstituted or substituted with 1 or 2 substituents, which are independently methyl or fluoro; tetrahydro-2H-pyran-4,4-diyl, unsubstituted or substituted by 2 or 4 methyl; --tetrahydro-2H-thiopyran-1,1-dioxide-4,4-diyl; or --piperidine-4,4-diyl, pyrrolidine-3,3-diyl or azetidine-3,3-diyl, wherein the piperidine, pyrrolidine or azetidine nitrogens are independently unsubstituted or -C 1-3 -Alkyl, -C 0-2 -Alkylene-C 3-6 -cycloalkyl or -LR N1 ( ----L- is -CO-, -SO2-, * -CO-NH-, * -CO-O- or * -SO2-NH-, --- R N1 -C 1-3 -alkyl or -C 0-2 -Alkylene-C 3-6 -represents cycloalkyl; is replaced by.) (In particular, the piperidine is unsubstituted or substituted by methyl, -CO-methyl, -CO-O-methyl, -CO-NH-cyclopropyl, -SO2-methyl, -SO2-cyclopropyl or -SO2-NH-methyl; the azetidine is substituted by -SO2-methyl, -CO-O-methyl or -CO-NH-cyclopropyl); (In the above groups, the asterisk indicates the bond connecting it to the rest of the molecule); or forming a 3- to 6-membered ring selected from - R 1aand R 1b are attached to the carbon atom of the structure (S 1AB ) spiro-bicyclic ring system

[0013] [ka] (Ring (A) represents a 3- to 6-membered non-aromatic carbocyclic ring, which optionally contains one ring oxygen atom, and which is unsubstituted or substituted with two fluoro; Forming; R 2 is hydroxy or C 1-3 -Alkoxy (especially methoxy).

[0014] The compound of formula (I) has five chiral or asymmetric centers, which are located in the tetrahydropyran moiety and have the absolute configuration described in formula (I).In addition, the compound of formula (I) contains at least one, and possibly more, additional chiral or asymmetric centers, such as one or more additional asymmetric carbon atoms.Therefore, the compound of formula (I) may exist as a mixture of stereoisomers or, preferably, as a pure stereoisomer.The mixture of stereoisomers may be separated by methods known to those skilled in the art.

[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 mean 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 mean said compound in enriched, especially essentially pure form with respect to each configuration of said asymmetric center.

[0016] The term "enriched", when used in connection with stereoisomers, is understood in the context of the present invention to mean that the respective stereoisomer is present in a ratio of at least 70:30, in particular at least 90:10, with respect to the total of each other stereoisomer / each other stereoisomer (i.e. with a purity of at least 70% by weight, in particular at least 90% by weight).

[0017] The term "essentially pure", when used in relation to stereoisomers, is understood in the context of the present invention to mean that each stereoisomer is present in a purity of at least 95 percent by weight, in particular at least 99 percent by weight, with respect to each other stereoisomer / total of each other stereoisomer.

[0018] The present invention also relates to 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, especially 2 H (deuterium) labeled compounds of formula (I) and salts thereof are within the scope of the present invention. 2 Substitution with H (deuterium) can increase metabolic stability, e.g., increase in-vivo half-life, or reduce the required dose, or reduce inhibition of cytochrome P450 enzymes, e.g., improve 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 that appropriate isotopic species of suitable reagents or starting materials are used.

[0019] In this application, bonds drawn as dotted lines indicate the point of attachment of the depicted group. For example, the group

[0020] [ka] is a 3-fluorophenyl group.

[0021] When the plural forms are used with respect to compounds, salts, pharmaceutical compositions, diseases, and the like, these are intended to refer to a singular compound, salt, or the like.

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

[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 Pharmaceutical Salts. Properties, Selection and Use.", P. Heinrich Stahl, Camille G. Wermuth (Eds.), Wiley-VCH, 2008; and "Pharmaceutical Salts and Co-crystals", Johan Wouters and Luc See Quere (Eds.), RSC Publishing, 2012.

[0024] The definitions set forth herein are uniformly applied to the compounds of formula (I) defined in any one of embodiments 1) to 18) and apply mutatis mutandis throughout the specification and claims unless a broader or narrower definition is given by a specific definition. It is understood that a definition or preferred definition of a term may independently (and together) 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 the IUPAC nomenclature system, but may also be named using the carbohydrate nomenclature system. Thus, the group:

[0026] [ka] is (2S,3R,4S,5R,6R)-3,5-dihydroxy-6-(hydroxymethyl) The compound can be named 1,3-di-deoxy-3-[4-phenyl-1H-1,2,3-triazol-1-yl]-β-D-galactopyranoside-1-thiyl, where the absolute configuration of the carbon atom bearing the sulfur atom, which is the point of attachment to the rest of the molecule, is in the (2S)- or beta-configuration. For example, the compound (2S,3R,4S,5R,6R)-2-(((R)-(4-hydroxy-1-methylpyridin-4-yl)(3,5,6-trimethylpyrazin-2-yl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol is understood to also be called: 1,3-di-deoxy-1-((1-methyl-4-hydroxy-piperidin-4-yl)-(3,5,6-trimethylpyrazin-2-yl)methyl-(R)-thio)-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-β-D-galactopyranoside.

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

[0028] The term "halogen" means fluorine, chlorine or bromine, preferably fluorine or chlorine.

[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. Representative 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 doubt, when a group is described as, for example, propyl or butyl, it is meant to be n-propyl or n-butyl, respectively. Methyl is preferred.

[0030] "-C x-yThe 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 a direct bond or to the above-defined -(C 1-y ) alkylene-. Preferably, -C 1-y The attachment points of the -alkylene groups are in a 1,1-diyl or 1,2-diyl or 1,3-diyl configuration. 2-y The attachment points of the -alkylene groups are in a 1,2-diyl or 1,3-diyl configuration. 0-y When the -alkylene group is used in combination with another substituent, the term also applies when the 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., the C0-alkylene group represents a direct bond attaching the substituent to the remainder of the molecule). Unless expressly stated otherwise, the alkylene group -C2H4- means -CH2-CH2-.

[0031] The term "alkenyl", used alone or in combination, means a straight or branched hydrocarbon chain having from 2 to 5 carbon atoms and one carbon-carbon double bond. x-y The term "-alkenyl" (x and y are each integers) refers to an alkenyl group as defined above having x to y carbon atoms. For example, C 2-5 -Alkenyl groups have from 2 to 5 carbon atoms.

[0032] The term "fluoroalkyl", used alone or in combination, means an alkyl group as defined above having one to three carbon atoms in which one or more, and optionally all, hydrogen atoms have been replaced by 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, C1-3 The fluoroalkyl group has 1 to 3 carbon atoms, and 1 to 7 hydrogen atoms are replaced by fluorine. Representative examples of the fluoroalkyl group include trifluoromethyl, 2-fluoroethyl, 2,2-difluoroethyl, and 2,2,2-trifluoroethyl. Preferred are C1-fluoroalkyl groups such as trifluoromethyl.

[0033] The term "fluoroalkoxy", used alone or in combination, means an alkoxy 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 by fluorine. x-y The term "fluoroalkoxy" (x and y are each integers) refers to a fluoroalkoxy group as defined above having x to y carbon atoms. For example, C 1-3 -Fluoroalkoxy groups have 1 to 3 carbon atoms in which 1 to 7 hydrogen atoms have been replaced by fluorine. Representative examples of fluoroalkoxy groups include trifluoromethoxy, difluoromethoxy, 2-fluoroethoxy, 2,2-difluoroethoxy and 2,2,2-trifluoroethoxy.

[0034] The term "cycloalkyl", whether used alone or in combination, specifically refers to a saturated monocyclic, or a fused, bridged or spiro-bicyclic hydrocarbon ring having from 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, cyclopentyl, cyclohexyl and cycloheptyl.

[0035] "-C x-yThe term "-cycloalkylene-", used alone or in combination, refers to a doubly bonded cycloalkyl group as defined above having x to y carbon atoms. Preferably, the attachment points of the doubly bonded cycloalkyl group are in a 1,1-diyl configuration. Examples are cyclopropane-1,1-diyl, cyclobutane-1,1-diyl, cyclopentane-1,1-diyl; and cyclohexane-1,1-diyl, preferably cyclohexane-1,1-diyl. "R 1a and R 1b However, together with the carbon atoms to which they are attached, 3-6 -Cycloalkylene is formed, 3-6 -cycloalkylene is independently unsubstituted or substituted by 1 or 2 substituents", this term in particular means the above groups that are unsubstituted or substituted as explicitly defined; specific examples are cyclobutane-1,1-diyl, cyclopentane-1,1-diyl, cyclohexane-1,1-diyl, 3-methylcyclobutane-1,1-diyl, 2,3-dimethylcyclobutane-1,1-diyl, 3,3-dimethylcyclobutane-1,1-diyl, 3,3-difluorocyclobutane-1,1-diyl or 4,4-difluorocyclohexane-1,1-diyl; in particular 4,4-difluorocyclohexane-1,1-diyl.

[0036] 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. R 2 "C 1-3 When expressing "-alkoxy", this term preferably means methoxy or ethoxy, in particular methoxy.

[0037] The term "heterocyclyl", whether used alone or in combination, unless expressly defined broader or narrower, means a saturated or unsaturated non-aromatic monocyclic hydrocarbon ring having one or two ring heteroatoms independently selected from nitrogen, sulfur and oxygen (particularly one oxygen atom, one sulfur atom, one nitrogen atom, two nitrogen atoms, two oxygen atoms, one nitrogen atom and one oxygen atom). x-y The term "-heterocyclyl" means such a heterocycle having from x to y ring atoms. Heterocyclyl groups are unsubstituted or substituted as explicitly defined.

[0038] The term "aryl", used alone or in combination, means phenyl or naphthyl, preferably phenyl, said aryl groups being unsubstituted or substituted as expressly defined.

[0039] The term "heteroaryl", whether used alone or in combination, unless a broader or narrower definition is expressly indicated, refers to a 5-10 membered monocyclic or bicyclic aromatic ring having from 1 to up to 4 heteroatoms, each of which is independently selected from oxygen, nitrogen and sulfur. Representative examples of such heteroaryl groups are 5-membered heteroaryl groups such as furanyl, oxazolyl, isoxazolyl, oxadiazolyl, thiophenyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, etc.; 6-membered heteroaryl groups such as pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, etc.; and indolyl, isoindolyl, benzofuranyl, isobenzofuranyl, benzothiophenyl, indazolyl, benzimidazolyl, and 8-10 membered bicyclic heteroaryl groups such as benzoxazolyl, benzoisoxazolyl, benzothiazolyl, benzoisothiazolyl, benzotriazolyl, benzoxadiazolyl, benzothiadiazolyl, thienopyridinyl, quinolinyl, isoquinolinyl, naphthyridinyl, cinnolinyl, quinazolinyl, quinoxalinyl, phthalazinyl, pyrrolopyridinyl, pyrazolopyridinyl, pyrazolopyrimidinyl, pyrrolopyrazinyl, imidazopyridinyl, imidazopyridazinyl and imidazothiazolyl. The above heteroaryl groups are unsubstituted or substituted as expressly defined. The group Ar representing "5- or 6-membered heteroaryl" 2 With respect to Ar, this term means in particular thiophenyl, thiazolyl, oxazolyl, isoxazolyl, pyridinyl or pyrazinyl; or, in addition, pyrazolyl, triazolyl, pyridazinyl; especially thiophen-3-yl, thiazol-4-yl, oxazol-4-yl, isoxazol-3-yl, isoxazol-4-yl, pyridin-2-yl, pyridin-3-yl or pyrazin-2-yl; or, in addition, 1H-pyrazol-5-yl, 1H-1,2,3-triazol-5-yl or pyridazin-3-yl. 2 With respect to heteroaryl groups such as Ar, "one substituent is an Ar group to the remainder of the molecule." 2The term "attached ortho to the point of attachment of" means that the substituents are attached in a relative 1,2-configuration.

[0040] Ar 1 When represents "5- or 6-membered heteroaryl", this term refers to the above groups, in particular pyridinyl; especially pyridin-3-yl; said 5- or 6-membered heteroaryl group is unsubstituted or substituted as expressly defined.

[0041] R 1a and R 1b However, together with the carbon atoms to which they are attached, they form the "structure (S 1AB ) Spiro -bicyclic ring system, such a structure (S 1AB ) specifically means 3-oxaspiro[5.5]undecane-9,9-diyl.

[0042] The term "cyano" refers to the group --CN.

[0043] The term "oxo" refers to the group =O, preferably attached to a chain or ring carbon or sulfur atom, such as in a carbonyl group -(CO)- or a sulfonyl group -(SO2)-.

[0044] Whenever the word "between" is used to describe a range of numerical values, it is intended that the endpoints of the stated range are expressly included in that range. This means, for example, that when a temperature range is described as being 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, it means that the variable is the integer 1, 2, 3, or 4.

[0045] When not used in reference to temperature, the term "about" placed before a numerical value "X" in this application refers to between 10% of XX and 10% of X+X, preferably between 5% of XX and 5% of X+X. In the specific case of temperatures, the term "about" placed before a temperature "Y" in this application refers to a temperature between Y-10°C and Y+10°C, preferably between Y-5°C and Y+5°C. Furthermore, the term "room temperature" as used herein refers to a temperature of about 25°C.

[0046] Further aspects of the invention are described below: 2) The second aspect is a compound represented by the formula (I R ) which is also a compound of formula (I) according to embodiment 1):

[0047] [ka] (In the formula, the group Ar 2 The carbon atom to which is bonded is represented by formula (I R ) [i.e., in the absolute (R)-configuration]; R 1a , R 1b , R 2 , Ar 1 and Ar 2 is as defined in embodiment 1.

[0048] 3) In another embodiment, Ar 1 represents phenyl substituted with 1, 2 or 3 substituents independently selected from halogen, methyl, cyano and methoxy; at least one of the substituents is attached at the meta or para position of the phenyl; - if a para-substituent is present, said para-substituent is preferably selected from halogen, methyl, cyano and methoxy; - if there is a meta-substituent, said meta-substituent is preferably a halogen; be; It relates to compounds according to embodiment 1) or 2).

[0049] 4) In another embodiment, Ar 1 represents phenyl substituted by 1, 2 or 3 substituents; one of the substituents is attached at the meta position of the phenyl and the substituent is halogen; the remaining substituents, if present, are halogen (especially fluoro); or - one of the substituents is attached at the para position of the phenyl, and the substituents are independently selected from methyl, cyano, and methoxy; Any remaining substituents, if present, are halogen (especially fluoro); It relates to compounds according to embodiment 1) or 2).

[0050] 5) In another embodiment, Ar 1 The structure:

[0051] [ka] (In the formula, - R m2 represents hydrogen or fluoro; and R p independently represent halogen (especially fluoro or chloro), methyl, cyano or methoxy (especially R p represents fluoro, chloro or methyl; or - R m2 represents hydrogen or fluoro; and R p represents hydrogen. ); It relates to compounds according to embodiment 1) or 2), in which

[0052] 6) In another embodiment, Ar 1 The structure:

[0053] [ka] (In the formula, - R m2 represents halogen (especially fluoro); - R p represents hydrogen, halogen (especially fluoro or chloro), methyl, cyano or methoxy (especially R p represents fluoro, chloro or methyl. It relates to compounds according to embodiment 1) or 2), in which

[0054] 7) In another embodiment, Ar 1 but:

[0055] [ka] relates to compounds according to embodiment 1) or 2).

[0056] In a subembodiment, Ar 1 In particular,

[0057] [ka] Represents. 8) Another embodiment is Ar 2 but, - phenyl, substituted by 1, 2 or 3 substituents (in particular substituted by 1 or 2 substituents); --One substituent is an Ar to the rest of the molecule. 2 is attached at a position ortho to the point of attachment of 1-6 -Alkyl, C 3-6 -Cycloalkyl (especially cyclopropyl), C 1-3 -fluoroalkyl (especially trifluoromethyl), C 1-3 -Fluo Alkoxy, halogen, hydroxy-C 1-3 - alkyl (especially 2-hydroxyethyl) or phenyl; --Other substituents, if present, are not included in the Ar group to the remainder of the molecule. 2 attached at the meta and / or para positions relative to the point of attachment of C 1-6 -Alkyl, C 3-6-Cycloalkyl (especially cyclopropyl), C 1-3 -fluoroalkyl (especially trifluoromethyl) or halogen; Phenyl; Or, - 5- or 6-membered heteroaryl (in particular thiophenyl, thiazolyl, oxazolyl, isoxazolyl, pyridinyl or pyrazinyl; or, in addition, pyrazolyl, triazolyl or pyridazinyl), which 5- or 6-membered heteroaryl is independently substituted by 1, 2 or 3 substituents; --One substituent is an Ar to the rest of the molecule. 2 is attached at a position ortho to the point of attachment of 1-6 -Alkyl (especially methyl), C 3-6 -Cycloalkyl (especially cyclopropyl) or C 1-3 -fluoroalkyl (especially trifluoromethyl) [particularly such ortho substituents are methyl or trifluoromethyl]; --other substituents, if present, are independently: C 1-6 -Alkyl, C 3-6 -Cycloalkyl (especially cyclopropyl), C 1-3 -fluoroalkyl (especially trifluoromethyl) or halogen; 5- or 6-membered heteroaryl (especially thiophenyl, thiazolyl, oxazolyl, isoxazolyl, pyridinyl or pyrazinyl; or, in addition, pyrazolyl, triazolyl or pyridazinyl); represents; relating to a compound according to any one of embodiments 1) to 7).

[0058] 9) In another embodiment, Ar 2 but, - phenyl, substituted by 1 or 2 substituents; --One substituent is an Ar to the rest of the molecule. 2 is attached at a position ortho to the point of attachment of 1-6- alkyl, cyclopropyl, trifluoromethyl, halogen, 2-hydroxyethyl or phenyl; --Other substituents, if present, are not included in the Ar group to the remainder of the molecule. 2 attached at a meta position relative to the point of attachment of 1-3 - alkyl, cyclopropyl, trifluoromethyl or halogen; Phenyl; Or, - thiophenyl, thiazolyl, oxazolyl, isoxazolyl, pyridinyl and pyrazinyl; or, in addition, a 5- or 6-membered heteroaryl selected from pyrazolyl, triazolyl or pyridazinyl (especially isoxazolyl, pyridinyl and pyrazinyl), which 5- or 6-membered heteroaryl is independently substituted by 1, 2 or 3 substituents; --One substituent is an Ar to the rest of the molecule. 2 is attached at a position ortho to the point of attachment of 1-6 - alkyl (especially methyl), cyclopropyl or trifluoromethyl; -- if other substituents are present, such other substituents are independently methyl; 5- or 6-membered heteroaryl; represents; relating to a compound according to any one of embodiments 1) to 7).

[0059] 10) Another embodiment is Ar 2 represents 5- or 6-membered heteroaryl (particularly thiophenyl, thiazolyl, oxazolyl, isoxazolyl, pyridinyl or pyrazinyl; or, in addition, pyrazolyl, triazolyl or pyridazinyl), which 5- or 6-membered heteroaryl is independently unsubstituted or substituted by 1, 2 or 3 substituents, and The substituents of are independently 1-6 -Alkyl, C 3-6 -Cycloalkyl (especially cyclopropyl), C 1-3 -fluoroalkyl (especially trifluoromethyl), C 1-3-fluoroalkoxy or halogen.

[0060] In a subembodiment, the 5- or 6-membered heteroaryl is selected from isoxazolyl, pyridinyl, and pyrazinyl, and the 5- or 6-membered heteroaryl is independently substituted with 1, 2, or 3 substituents; - One substituent is an Ar to the rest of the molecule 2 is attached at a position ortho to the point of attachment of 1-6 - alkyl (especially methyl), cyclopropyl or trifluoromethyl; - if other substituents are present, said other substituents are independently methyl;

[0061] 11) In another embodiment, Ar 2 but:

[0062] [ka]

[0063] [ka] With respect to compounds according to any one of embodiments 1) to 7), each of the above groups A) to D) forms a specific sub-embodiment; further sub-embodiments relate to groups A), B) and / or D).

[0064] 12) In another embodiment, Ar 2 but:

[0065] [ka]

[0066] [ka] With respect to the compounds according to any one of the embodiments 1) to 7), each of the groups A) and B) forms a specific sub-embodiment.

[0067] 13) Another aspect is - R 1a represents hydrogen; and R 1b but, -- -C 2-4 -Alkyl (especially ethyl); phenyl unsubstituted or substituted by one or two methyl; represents; or - or R 1a and R 1b each represents methyl, ethyl or n-propyl; - or R 1a and R 1b together with the carbon atoms to which they are attached. -- C 4-6 - cycloalkylene, which cycloalkyl is independently unsubstituted or substituted by one or two substituents, which are independently methyl or fluoro (in particular cyclobutane-1,1-diyl, cyclopentane-1,1-diyl, cyclohexane-1,1-diyl, 3-methylcyclobutane-1,1-diyl, 2,3-dimethylcyclobutane-1,1-diyl, 3,3-dimethylcyclobutane-1,1-diyl, 3,3-difluorocyclobutane-1,1-diyl or 4,4-difluorocyclohexane-1,1-diyl); -- tetrahydro-2H-pyran-4,4-diyl; 2,2-dimethyltetrahydro-2H-pyran-4,4-diyl or 2,2,6,6-tetramethyltetrahydro-2H-pyran-4,4-diyl; -- tetrahydro-2H-thiopyran-1,1-dioxide-4,4-diyl; -- piperidine-4,4-diyl (the piperidine nitrogen is unsubstituted or is -C 1-3 -Alkyl, -CO-C 1-3 -Alkyl, -CO-OC 1-3 -Alkyl, -CO-NH-Cyclopropyl, -SO2-C 1-3 -alkyl, -SO2-cyclopropyl or -SO2-NH-C 1-3-alkyl (in particular, the piperidine is unsubstituted or substituted by methyl, -CO-methyl, -CO-methoxy, -CO-NH-cyclopropyl, -SO2-methyl, -SO2-cyclopropyl or -SO2-NH-methyl); or -- azetidine-3,3-diyl (the nitrogen of the azetidine is unsubstituted or -SO2-C 1-3 -Alkyl, -CO-OC 1-3 -alkyl or -CO-NH-cyclopropyl; or forming a 3- to 6-membered ring selected from - R 1a and R 1b But together with the carbon atoms to which they are attached, the structure:

[0068] [ka] forming a spiro-bicyclic ring system of; The compound according to any one of the embodiments 1) to 12).

[0069] 14) In another aspect, R 1a represents hydrogen; R 1b but, - -C 2-4 - alkyl (especially ethyl); or - phenyl which is unsubstituted or substituted by one or two methyl; Represents; The compound according to any one of the embodiments 1) to 12).

[0070] 15) In another aspect, R 1a and R 1b each represents methyl, ethyl or n-propyl (especially methyl); relates to a compound according to any one of embodiments 1) to 12).

[0071] 16) In another aspect, R 1a and R 1b together with the carbon atoms to which they are attached. - C4-6 - cycloalkylene, which cycloalkyl is independently unsubstituted or substituted by one or two substituents, which are independently methyl or fluoro (in particular cyclobutane-1,1-diyl, cyclopentane-1,1-diyl, cyclohexane-1,1-diyl, 3-methylcyclobutane-1,1-diyl, 2,3-dimethylcyclobutane-1,1-diyl, 3,3-dimethylcyclobutane-1,1-diyl, 3,3-difluorocyclobutane-1,1-diyl or 4,4-difluorocyclohexane-1,1-diyl); tetrahydro-2H-pyran-4,4-diyl, 2,2-dimethyltetrahydro-2H-pyran-4,4-diyl or 2,2,6,6-tetramethyltetrahydro-2H-pyran-4,4-diyl; or piperidine-4,4-diyl, where the piperidine nitrogen is unsubstituted or is -C 1-3 -Alkyl, -CO-C 1-3 -Alkyl, -CO-OC 1-3 -Alkyl, -CO-NH-Cyclopropyl, -SO2-C 1-3 -alkyl, -SO2-cyclopropyl or -SO2-NH-C 1-3 -alkyl (in particular, the piperidine is unsubstituted or substituted with methyl, -CO-methyl, -CO-methoxy, -CO- NH-cyclopropyl, -SO2-methyl, -SO2-cyclopropyl or -SO2-NH-methyl. forming a 4- to 6-membered ring selected from the group consisting of:

[0072] 17) In another aspect, R 2 represents methoxy; relates to compounds according to any one of embodiments 1) to 16).

[0073] 18) In another aspect, R 2 represents hydroxy; relates to compounds according to any one of embodiments 1) to 16).

[0074] 19) The present invention thus relates to compounds of formula (I) as defined in embodiment 1) or such compounds further defined by the features of any one of embodiments 2) to 18) according to their respective subdivisions; pharma- ceutically acceptable salts thereof; and uses of such compounds as further described below. For the avoidance of any doubt, the following embodiments in particular are possible and contemplated with respect to compounds of formula (I) and are specifically disclosed herein as individual forms: 1、2+1、3+1、3+2+1、4+1、4+2+1、5+1、5+2+1、6+1、6+2+1、7+1、7+2+1、8+1、8+2+1、8+3+1、8+3+2+1、8+4+1、8+4+2+1、8+5+1、8+5+2+1、8+6+1、8+6+2+1、8+7+1、8+7+2+1、9+1、9+2+1、9+3+1、9+3+2+1、9+4+1、9+4+2+1、9+5+1、9+5+2+1、9+6+1、9+6+2+1、9+7+1、9+7+2+1、10+1、10+2+1、10+3+1、10+3+2+1、10+4+1、10+4+2+1、10+5+1、10+5+2+1、10+6+1、10+6+2+1、10+7+1、10+7+2+1、11+1、11+2+1、11+3+1、11+3+2+1、11+4+1、11+4+2+1、11+5+1、11+5+2+1、11+6+1、11+6+2+1、11+7+1、11+7+2+1、12+1、12+2+1、12+3+1、12+3+2+1、12+4+1、12+4+2+1、12+5+1、12+5+2+1、12+6+1、12+6+2+1、12+7+1、12+7+2+1、13+1、13+2+1、13+3+1、13+3+2+1、13+4+1、13+4+2+1、13+5+1、13+5+2+1、13+6+1、13+6+2+1、13+7+1、13+7+2+1、13+8+1、13+8+2+1、13+8+3+1、13+8+3+2+1、13+8+4+1、13+8+4+2+1、13+8+5+1、13+8+5+2+1、13+8+6+1、13+8+6+2+1、13+8+7+1、13+8+7+2+1、13+9+1、13+9+2+1、13+9+3+1、13+9+3+2+1、13+9+4+1、13+9+4+2+1、13+9+5+1、13+9+5+2+1、13+9+6+1、13+9+6+2+1、13+9+7+1、13+9+7+2+1、13+10+1、13+10+2+1、13+10+3+1、13+10+3+2+1、13+10+4+1、13+10+4+2+1、13+10+5+1、13+10+5+2+1、13+10+6+1、13+10+6+2+1、13+10+7+1、13+10+7+2+1、13+11+1、13+11+2+1、13+11+3+1、13+11+3+2+1、13+11+4+1、13+11+4+2+1、13+11+5+1、13+11+5+2+1、13+11+6+1、13+11+6+2+1、13+11+7+1、13+11+7+2+1、13+12+1、13+12+2+1、13+12+3+1、13+12+3+2+1、13+12+4+1、13+12+4+2+1、13+12+5+1、13+12+5+2+1、13+12+6+1、13+12+6+2+1、13+12+7+1、13+12+7+2+1、14+1、14+2+1、14+3+1、14+3+2+1、14+4+1、14+4+2+1、14+5+1、14+5+2+1、14+6+1、14+6+2+1、14+7+1、14+7+2+1、14+8+1、14+8+2+1、14+8+3+1、14、 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0+3+2+1, 17+16+10+4+1, 17+16+10+4+2+1, 17+16+10+5+1, 17+16+10+5+2+1, 17+16+10+6+1, 17+16+10+6+2+1, 17+16+10+7+1, 17+16+10+7+2+1, 17+16+11+1, 17+16+11+2+1, 17+16+11+3+1, 17+16+11+3+2+1, 17+16+11+4+1, 17+16+11+4+2+1, 17+16+11+5+1, 17+16+11+5+ 2+1, 17+16+11+6+1, 17+16+11+6+2+1, 17+16+11+7+1, 17+16+11+7+2+1, 17+16+12+1, 17+16+12+2+1, 17+16+12+3+1, 17+16+12+3+2+1, 17+16+12+4+1, 17+16+12+4+2+1, 17+16+12+5+1, 17+16+12+5+2+1, 17+16+12+6+1, 17+16+12+6+2+1, 17+16+12+7+1, 17+16+12+7+2+1.

[0075] In the above list, the numbers refer to the embodiments according to the above numbers, and "+" indicates a dependency from another embodiment. The various embodiments are individually separated by commas. In other words, for example, "13+11+5+1" means embodiment 13) which is dependent on embodiment 11) which is dependent on embodiment 5) which is dependent on embodiment 1), i.e. embodiment "13+11+5+1" corresponds to a compound of formula (I) according to embodiment 1) further limited by all the features of embodiments 5), 11) and 13).

[0076] 20) Another embodiment relates to compounds of formula (I) according to embodiment 1), which are selected from the following compounds: (2S,3R,4S,5R,6R)-2-(((R)-2-hydroxy-2-methyl-1-(o-tolyl)propyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-((1-(2-ethylphenyl)-2-hydroxy-2-methylpropyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-((2-hydroxy-2-methyl-1-(2-propylphenyl)propyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-((2-hydroxy-1-(2-isopropylphenyl)-2-methylpropyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-((1-(2-cyclopropylphenyl)-2-hydroxy-2-methylpropyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-2-hydroxy-1-(2-isobutylphenyl)-2-methylpropyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-1-([1,1'-biphenyl]-2-yl)-2-hydroxy-2-methylpropyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-2-hydroxy-2-methyl-1-(2-(trifluoromethyl)phenyl)propyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-1-(3-fluoro-2-methylphenyl)-2-hydroxy-2-methylpropyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-2-hydroxy-2-methyl-1-(naphthalen-1-yl)propyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-((2-hydroxy-2-methyl-1-(2-methylpyridin-3-yl)propyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-2-hydroxy-2-methyl-1-(3,5,6-trimethylpyrazin-2-yl)propyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-1-(2,5-dimethylthiazol-4-yl)-2-hydroxy-2-methylpropyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-((2-hydroxy-1-(2-(trifluoromethyl)phenyl)butyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(3,3-difluoro-1-hydroxycyclobutyl)(2-(trifluoromethyl)phenyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(1-hydroxycyclopentyl)(o-tolyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(1-hydroxycyclohexyl)(o-tolyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((4-hydroxy-1-methylpyridin-4-yl)(o-tolyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2R,3R,4S,5R,6S)-2-(hydroxymethyl)-6-(((R)-(4-hydroxytetrahydro-2H-pyran-4-yl)(2-(trifluoromethyl)phenyl)methyl)thio)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol;(2S,3R,4S,5R,6R)-2-(((R)-(4-hydroxy-2,2,6,6-tetramethyltetrahydro-2H-pyran-4-yl)(2-(trifluoromethyl)phenyl)methyl)thio)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol )phenyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-((R)-4-hydroxy-2,2-dimethyltetrahydro-2H-pyran-4-yl)(2-(trifluoromethyl)phenyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(3,3-difluoro-1-hydroxycyclobutyl)(3-(trifluoromethyl)pyridin-2-yl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(1-hydroxycyclohexyl)(3-(trifluoromethyl)pyridin-2-yl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(1-hydroxycyclohexyl)(3,5,6-trimethylpyrazin-2-yl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(1-hydroxycyclohexyl)(4-methylisoxazol-3-yl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(4-methylisoxazol-3-yl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol;(2S,3R,4S,5R,6R)-2-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(2-isopropylphenyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(3,5,6-trimethylpyrazin-2-yl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(3-(trifluoromethyl)pyridin-2-yl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(2-chlorophenyl)(4,4-difluoro-1-hydroxycyclohexyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2R,3R,4S,5R,6S)-2-(hydroxymethyl)-6-(((R)-(4-hydroxytetrahydro-2H-pyran-4-yl)(3-(trifluoromethyl)pyridin-2-yl)methyl)thio)-4-(4-(3,4,5-trifluorophenyl) -1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2R,3R,4S,5R,6S)-2-(hydroxymethyl)-6-(((R)-(4-hydroxytetrahydro-2H-pyran-4-yl)(3,5,6-trimethylpyrazin-2-yl)methyl)thio)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(4-hydroxy-1-methylpyridin-4-yl)(2-(trifluoromethyl)phenyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(4-hydroxy-1-methylpyridin-4-yl)(3-(trifluoromethyl)pyridin-2-yl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(4-hydroxy-1-methylpyridin-4-yl)(3,5,6-trimethylpyrazin-2-yl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(1-hydroxycyclopentyl)(3-(trifluoromethyl)pyridin-2-yl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(3-methylpyridin-2-yl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2R,3R,4S,5R,6S)-2-(hydroxymethyl)-6-(((4-hydroxypiperidin-4-yl)(2-(trifluoromethyl)phenyl)methyl)thio)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; 4-((((2S,3R,4S,5R,6R)-3,5-dihydroxy-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)(2-(trifluoromethyl)phenyl)methyl)-4-hydroxy-N-methylpiperidine-1-sulfonamide; (2S,3R,4S,5R,6R)-2-(((R)-(4-hydroxy-1-(methylsulfonyl)piperidin-4-yl)(2-(trifluoromethyl)phenyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; 1-(4-((((2S,3R,4S,5R,6R)-3,5-dihydroxy-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)(2-(trifluoromethyl)phenyl)methyl)-4-hydroxypiperidin-1-yl)ethan-1-one; N-Cyclopropyl-4-((R)-(((2S,3R,4S,5R,6R)-3,5-dihydroxy-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl) (2-(trifluoromethyl)phenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)(2-(trifluoromethyl)phenyl)methyl)-4-hydroxypiperidine-1-carboxamide; Methyl 4-((R)-(((2S,3R,4S,5R,6R)-3,5-dihydroxy-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)(2-(trifluoromethyl)phenyl)methyl)-4-hydroxypiperidine-1-carboxylate; and (2S,3R,4S,5R,6R)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-2-(((R)-2-hydroxy-2-methyl-1-(2-(trifluoromethyl)phenyl)propyl)thio)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,5-diol.

[0077] 21) Another embodiment relates to compounds of formula (I) according to embodiment 1), which are selected from the following compounds: (2S,3R,4S,5R,6R)-2-(((R)-2-hydroxy-1-phenylethyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-1-(2-bromophenyl)-2-hydroxyethyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-2-hydroxy-1-(2-isopropylphenyl)ethyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-2-hydroxy-2-methyl-1-(o-tolyl)propyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-1-(2-ethylphenyl)-2-hydroxy-2-methylpropyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-2-hydroxy-2-methyl-1-(2-propylphenyl)propyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-2-hydroxy-1-(2-isobutylphenyl)-2-methylpropyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-2-hydroxy-2-methyl-1-(2-pentylphenyl)propyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-1-([1,1'-biphenyl]-2-yl)-2-hydroxy-2-methylpropyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl) (yl-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-1-(2-chlorophenyl)-2-hydroxy-2-methylpropyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-2-hydroxy-2-methyl-1-(2-(trifluoromethyl)phenyl)propyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-1-(2,3-dichlorophenyl)-2-hydroxy-2-methylpropyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-1-(3-fluoro-2-methylphenyl)-2-hydroxy-2-methylpropyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-2-hydroxy-2-methyl-1-(naphthalen-1-yl)propyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-2-hydroxy-2-methyl-1-(2-methylpyridin-3-yl)propyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-2-hydroxy-2-methyl-1-(4-methylpyridin-3-yl)propyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-2-hydroxy-2-methyl-1-(3,5,6-trimethylpyrazin-2-yl)propyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-2-hydroxy-2-methyl-1-(4-methylisoxazol-3-yl)propyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-1-(3,5-dimethylisoxazol-4-yl)-2-hydroxy-2-methylpropyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-1-(2,5-dimethylthiazol-4-yl)-2-hydroxy-2-methylpropyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-2-hydroxy-2-methyl-1-(4-methylthiophen-3-yl)propyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-2-ethyl-2-hydroxy-1 -(3-methylisoxazol-4-yl)butyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((1R,2R)-2-hydroxy-1-(2-(trifluoromethyl)phenyl)butyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((1R,2S)-2-hydroxy-1-(2-(trifluoromethyl)phenyl)butyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(3,3-difluoro-1-hydroxycyclobutyl)(2-(trifluoromethyl)phenyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (3R,4R,5R,6R)-2-((R)-2-(1-hydroxycyclobutyl)-2-(o-tolyl)ethyl)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(1-hydroxy-3,3-dimethylcyclobutyl)(o-tolyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((1R)-(1-hydroxy-3-methylcyclobutyl)(o-tolyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((1R)-((2R,3R)-1-hydroxy-2,3-dimethylcyclobutyl)(o-tolyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((1R)-((2R,3S)-1-hydroxy-2,3-dimethylcyclobutyl)(o-tolyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((1R)-((2S,3R)-1-hydroxy-2,3-dimethylcyclobutyl)(o-tolyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((1R)-((2S,3S)-1-hydroxy-2,3-dimethylcyclobutyl)(o-tolyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(1-hydroxycyclopentyl)(o-tolyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(1-hydroxycyclohexyl)(o-tolyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro -2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(4-hydroxy-1-methylpyridin-4-yl)(o-tolyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2R,3R,4S,5R,6S)-2-(hydroxymethyl)-6-(((R)-(4-hydroxytetrahydro-2H-pyran-4-yl)(2-(trifluoromethyl)phenyl)methyl)thio)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol;(2S,3R,4S,5R,6R)-2-(((R)-(4-hydroxy-2,2,6,6-tetramethyltetrahydro-2H-pyran-4-yl)(2-(trifluoromethyl)phenyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-((R)-4-hydroxy-2,2-dimethyltetrahydro-2H-pyran-4-yl)(2-(trifluoromethyl)phenyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-((S)-4-hydroxy-2,2-dimethyltetrahydro-2H-pyran-4-yl)(2-(trifluoromethyl)phenyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(3,3-difluoro-1-hydroxycyclobutyl)(3-(trifluoromethyl)pyridin-2-yl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(1-hydroxycyclohexyl)(3-(trifluoromethyl)pyridin-2-yl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(1-hydroxycyclohexyl)(3,5,6-trimethylpyrazin-2-yl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(1-hydroxycyclohexyl)(4-methylisoxazol-3-yl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(4-methylisoxazol-3-yl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol;(2S,3R,4S,5R,6R)-2-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(2-isopropylphenyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(4,4-difluoro-1-hydro (hydroxycyclohexyl)(3,5,6-trimethylpyrazin-2-yl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(3-(trifluoromethyl)pyridin-2-yl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(2-chlorophenyl)(4,4-difluoro-1-hydroxycyclohexyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2R,3R,4S,5R,6S)-2-(hydroxymethyl)-6-(((R)-(4-hydroxytetrahydro-2H-pyran-4-yl)(3-(trifluoromethyl)pyridin-2-yl)methyl)thio)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2R,3R,4S,5R,6S)-2-(hydroxymethyl)-6-(((R)-(4-hydroxytetrahydro-2H-pyran-4-yl)(3,5,6-trimethylpyrazin-2-yl)methyl)thio)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(4-hydroxy-1-methylpyridin-4-yl)(2-(trifluoromethyl)phenyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(4-hydroxy-1-methylpyridin-4-yl)(3-(trifluoromethyl)pyridin-2-yl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(4-hydroxy-1-methylpyridin-4-yl)(3,5,6-trimethylpyrazin-2-yl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol;(2S,3R,4S,5R,6R)-2-(((R)-(1-hydroxycyclopentyl)(3-(trifluoromethyl)pyridin-2-yl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(3-methylpyridin-2-yl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2R,3R,4S,5R,6S)-2-(hydroxymethyl)-6-(((R)-(4-hydroxypiperidin-4-yl)(2-(trifluoromethyl)phenyl)methyl)thio)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; 4-((R)-(((2S,3R,4S,5R,6R)-3,5-dihydroxy-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2 ,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)(2-(trifluoromethyl)phenyl)methyl)-4-hydroxy-N-methylpiperidine-1-sulfonamide; (2S,3R,4S,5R,6R)-2-(((R)-(4-hydroxy-1-(methylsulfonyl)piperidin-4-yl)(2-(trifluoromethyl)phenyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; 1-(4-((R)-(((2S,3R,4S,5R,6R)-3,5-dihydroxy-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)(2-(trifluoromethyl)phenyl)methyl)-4-hydroxypiperidin-1-yl)ethan-1-one; N-cyclopropyl-4-((R)-(((2S,3R,4S,5R,6R)-3,5-dihydroxy-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)(2-(trifluoromethyl)phenyl)methyl)-4-hydroxypiperidine-1-carboxamide; Methyl 4-((R)-(((2S,3R,4S,5R,6R)-3,5-dihydroxy-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)(2-(trifluoromethyl)phenyl)methyl)-4-hydroxypiperidine-1-carboxylate; (2S,3R,4S,5R,6R)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-2-(((R)-2-hydroxy-2-methyl-1-(2-(trifluoromethyl)phenyl)propyl)thio)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-2-hydroxy-2-methyl-1-(2-(trifluoromethyl)phenyl)propyl)thio)-6-(hydroxymethyl)-4-(4-(naphthalen-2-yl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; and 4-(1-((2S,3R,4S,5R,6R)-3,5-dihydroxy-2-(((R)-2-hydroxy-2-methyl-1-(2-(trifluoromethyl)phenyl)propyl)thio)-6-(hydroxymethyl)tetrahydro-2H-pyran-4-yl)-1H-1,2,3-triazol-4-yl)-2-fluorobenzonitrile.

[0078] 22) In addition to the compounds described in embodiment 20), further compounds according to embodiment 1) are selected from the following compounds: (2R,3R,4S,5R,6S)-2-(hydroxymethyl)-6-(((R)-4-hydroxytetrahydro-2H-pyran-4-yl)(o-tolyl)methyl)thio)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-2-hydroxy-1-(2-isopropylphenyl)-2-methylpropyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-1-(2-cyclopropylphenyl)-2-hydroxy-2-methylpropyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-2-hydroxy-1-(2-(2-hydroxyethyl)phenyl)-2-methylpropyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; and (2S,3R,4S,5R,6R)-2-(((R)-2-hydroxy-2-methyl-1-(2-(trifluoromethyl)pyridin-3-yl)propyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol.

[0079] 23) In addition to the compounds described in embodiment 21), further compounds according to embodiment 1) are selected from the following compounds: (2R,3R,4S,5R,6S)-2-(hydroxymethyl)-6-(((R)-4-hydroxytetrahydro-2H-pyran-4-yl)(o-tolyl)methyl)thio)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-2-hydroxy-1-(2-isopropylphenyl)-2-methylpropyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-1-(2-cyclopropylphenyl)-2-hydroxy-2-methylpropyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-2-hydroxy-1-(2-(2-hydroxyethyl)phenyl)-2-methylpropyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-2-hydroxy-2-methyl-1-(2-(trifluoromethyl)pyridin-3-yl)propyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-1-(2,5-dimethyloxazol-4-yl)-2-hydroxy-2-methylpropyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((1R,2R)-2-hydroxy-2-phenyl-1-(2-(trifluoromethyl)phenyl)ethyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((1R,2S)-2-hydroxy-2-phenyl-1-(2-(trifluoromethyl)phenyl)ethyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((1R,2R)-2-hydroxy-2-(o-tolyl)-1-(2-(trifluoromethyl)phenyl)propyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; and (2S,3R,4S,5R,6R)-2-(((1R,2S)-2-hydroxy-2-(o-tolyl)-1-(2-(trifluoromethyl)phenyl)propyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2 ,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol.

[0080] 24) In addition to the compounds described in embodiments 20) and 22), further compounds according to embodiment 1) are selected from the following compounds: (2S,3R,4S,5R,6R)-2-(((R)-(5-cyclopropyl-3-methylisoxazol-4-yl)(1-hydroxycyclohexyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol;(2S,3R,4S,5R,6R)-2-(((R)-((R)-4-hydroxy-2,2-dimethyltetrahydro-2H-pyran-4-yl)(o-tolyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(2-(trifluoromethyl)phenyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(2-cyclopropylphenyl)(4,4-difluoro-1-hydroxycyclohexyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(3-methylpyrazin-2-yl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(5-cyclopropyl-4-ethylisoxazol-3-yl)(4,4-difluoro-1-hydroxycyclohexyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(5-cyclopropyl-4-isobutylisoxazol-3-yl)(4,4-difluoro-1-hydroxycyclohexyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(3-isopropylpyridin-2-yl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(3-chloropyrazin-2-yl)(4,4-difluoro-1-hydroxycyclohexyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(3-cyclopropylpyridin-2-yl)(4,4-difluoro-1-hydroxycyclohexyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol;(2S,3R,4S,5R,6R)-2-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(4-methylpyridazin-3-yl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2, 3-Triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; 4-((R)-(((2S,3R,4S,5R,6R)-3,5-dihydroxy-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)(4-methylisoxazol-3-yl)methyl)-4-hydroxytetrahydro-2H-thiopyran 1,1-dioxide; 4-((R)-(((2S,3R,4S,5R,6R)-3,5-dihydroxy-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)(3-methylpyridin-2-yl)methyl)-4-hydroxytetrahydro-2H-thiopyran 1,1-dioxide; (2R,3R,4S,5R,6S)-2-(hydroxymethyl)-6-(((R)-(4-hydroxytetrahydro-2H-pyran-4-yl)(3-methylpyridin-2-yl)methyl)thio)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(3-hydroxy-1-(methylsulfonyl)azetidin-3-yl)(2-(trifluoromethyl)phenyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; N-cyclopropyl-3-((((2S,3R,4S,5R,6R)-3,5-dihydroxy-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)(2-(trifluoromethyl)phenyl)methyl)-3-hydroxyazetidine-1-carboxamide; (2R,3R,4S,5R,6S)-6-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(3-methylpyridin-2-yl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol;(2R,3R,4S,5R,6S)-6-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(3-(trifluoromethyl)pyridin-2-yl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-6-(((R)-(1-hydroxycyclohexyl)(3-(trifluoromethyl)pyridin-2-yl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; 2R,3R,4S,5R,6S)-6-(((R)-(3-chloropyridin-2-yl)(4,4-difluoro-1-hydroxycyclohexyl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-6-(((R)-((S)-4-hydroxy-2,2-dimethyltetrahydro-2H-pyran-4-yl)(2-(trifluoromethyl)phenyl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; 4-Hydroxy-4-((R)-(((2S,3R,4S,5R,6R)-5-hydroxy-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran -2-yl)thio)(3-methylpyridin-2-yl)methyl)tetrahydro-2H-thiopyran 1,1-dioxide; (2R,3R,4S,5R,6S)-2-(hydroxymethyl)-6-(((R)-(4-hydroxytetrahydro-2H-pyran-4-yl)(3-methylpyridin-2-yl)methyl)thio)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-6-(((R)-((S)-4-hydroxy-2,2-dimethyltetrahydro-2H-pyran-4-yl)(o-tolyl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-6-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(3-isopropylpyridin-2-yl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-6-(((R)-(3-cyclopropylpyridin-2-yl)(4,4-difluoro-1-hydroxycyclohexyl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-6-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(4-methylpyridazin-3-yl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-6-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(3-methylpyrazin-2-yl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol;(2R,3R,4S,5R,6S)-6-(((R)-(1-hydroxycyclohexyl)(4-methylisoxazol-3-yl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-6-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(4-methylisoxazol-3-yl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-6-(((R)-(2-cyclopropylphenyl)(4,4-difluoro-1-hydroxycyclohexyl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-6-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(1,4-dimethyl-1H-pyrazol-5-yl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-6-(((R)-(4,4-difluoro-1-hydro hydroxycyclohexyl)(1-ethyl-4-methyl-1H-1,2,3-triazol-5-yl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-6-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(5-ethyl-4-methylisoxazol-3-yl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-2-(hydroxymethyl)-6-(((R)-(4-hydroxytetrahydro-2H-pyran-4-yl)(4-methylisoxazol-3-yl)methyl)thio)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; 4-Hydroxy-4-((R)-(((2S,3R,4S,5R,6R)-5-hydroxy-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)(4-methylisoxazol-3-yl)methyl)tetrahydro-2H-thiopyran 1,1-dioxide; (2R,3R,4S,5R,6S)-6-(((R)-(5-cyclopropyl-3-methylisoxazol-4-yl)(1-hydroxycyclohexyl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-6-(((R)-(5-cyclopropyl-4-ethylisoxazol-3-yl)(4,4-difluoro-1-hydroxycyclohexyl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-6-(((R)-(5-cyclopropyl-4-isobutylisoxazol-3-yl)(4,4-difluoro-1-hydroxycyclohexyl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-6-(((R)-(3-chloropyrazin-2-yl)(4,4-difluoro-1-hydroxycyclohexyl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol;(2R,3R,4S,5R,6S)-6-(((R)-(4-chloro-3-methylpyridin-2-yl)(4,4-difluoro-1-hydroxycyclohexyl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-6-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(3-ethylpyridin-2-yl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol;(2R,3R,4S,5R,6S)-6-(((R)-(3,4-dichloropyridin-2-yl)(4,4-difluoro-1-hydroxycyclohexyl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl) )-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-6-(((3,6-dichloropyridin-2-yl)(4,4-difluoro-1-hydroxycyclohexyl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2S,3R,4S,5R,6R)-2-(((R)-((S)-4-hydroxy-2,2-dimethyltetrahydro-2H-pyran-4-yl)(3-methylpyridin-2-yl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2R,3R,4S,5R,6S)-6-(((R)-(5-cyclopropyl-4-methylisoxazol-3-yl)(4,4-difluoro-1-hydroxycyclohexyl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-6-(((4,4-difluoro-1-hydroxycyclohexyl)(4-ethyl-5-propylisoxazol-3-yl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-6-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(3-methyl-4-(trifluoromethyl)pyridin-2-yl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; 2R,3R,4S,5R,6S)-6-(((R)-(3-chloro-6-methylpyridin-2-yl)(4,4-difluoro-1-hydroxycyclohexyl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-6-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(3,5,6-trimethylpyrazin-2-yl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; 9-((((2S,3R,4S,5R,6R)-5-hydroxy-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)(3-methylpyridin-2-yl)methyl)-3-oxaspiro[5.5]undecane-9-ol; (2R,3R,4S,5R,6S)-6-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(3-methylpyridin-2-yl)methyl)thio)-5-ethoxy-2-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol;1-(cyclopropylsulfonyl)-4-((((2S,3R,4S,5R,6R)-5-hydroxy-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)(2-(trifluoromethyl)phenyl)methyl)piperidin-4-ol; 1-(4-hydroxy-4-((((2S,3R,4S,5R,6R)-5-hydroxy-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)(2-(trifluoromethyl)phenyl)methyl)piperidin-1-yl)ethan-1-one; (N-cyclopropyl-4-hydroxy-4-((((2S,3R,4S,5R,6R)-5-hydroxy-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)(2-(trifluoromethyl)phenyl)methyl)piperidine-1-carboxamide; (2R,3R,4S,5R,6S)-6-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(3-methylpyridin-2-yl)methyl)thio)-4-(4-(3,4-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-6-(((4,4-difluoro-1-hydroxycyclohexyl)(3-methylpyridin-2-yl)methyl)thio)-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,6S)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-(((4,4-difluoro-1-hydroxycyclohexyl)(3-methylpyridin-2-yl)methyl)thio)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-6-(((4,4-difluoro-1-hydroxycyclohexyl)(3-methylpyridin-2-yl)methyl)thio)-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,6S)-4-(4-(4-bromo-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-(((4,4-difluoro-1-hydroxycyclohexyl)(3-methylpyridin-2-yl)methyl)thio)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-4-(4-(3,4-dichloro-5-fluorophenyl)-1H-1,2,3-triazol-1-yl)-6-(((4,4-difluoro-1-hydroxycyclohexyl)(3-methylpyridin-2-yl)methyl)thio)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-4-(4-(4-bromo-3-fluorophenyl)-1H-1,2,3-triazol-1-yl)-6-(((4,4-difluoro-1-hydroxycyclohexyl)(3-methylpyridin-2-yl)methyl)thio)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-4-(4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-(((4,4-difluoro-1-hydroxycyclohexyl)(3-methylpyridin-2-yl)methyl)thio)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; and (2R,3R,4S,5R,6S)-6-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(3-methylpyridin-2-yl)methyl)thio)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol.

[0081] 25) In addition to the compounds described in embodiments 21) and 23), further compounds according to embodiment 1) are The compound is selected from the following compounds: (2S,3R,4S,5R,6R)-2-(((R)-(5-cyclopropyl-3-methylisoxazol-4-yl)(1-hydroxycyclohexyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol;(2S,3R,4S,5R,6R)-2-(((R)-((R)-4-hydroxy-2,2-dimethyltetrahydro-2H-pyran-4-yl)(o-tolyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-((S)-4-hydroxy-2,2-dimethyltetrahydro-2H-pyran-4-yl)(o-tolyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(2-(trifluoromethyl)phenyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(2,3-dichlorophenyl)(4,4-difluoro-1-hydroxycyclohexyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(2-cyclopropylphenyl)(4,4-difluoro-1-hydroxycyclohexyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(3-methylpyrazin-2-yl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(5-cyclopropyl-4-ethylisoxazol-3-yl)(4,4-difluoro-1-hydroxycyclohexyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(5-cyclopropyl-4-isobutylisoxazol-3-yl)(4,4-difluoro-1-hydroxycyclohexyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(3-isopropylpyridin-2-yl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(3-chloropyrazin-2-yl)(4,4-difluoro-1-hydroxycyclohexyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(3-cyclopropylpyridine- 2-yl)(4,4-difluoro-1-hydroxycyclohexyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol;(2S,3R,4S,5R,6R)-2-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(4-methylpyridazin-3-yl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; 4-((R)-(((2S,3R,4S,5R,6R)-3,5-dihydroxy-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)(4-methylisoxazol-3-yl)methyl)-4-hydroxytetrahydro-2H-thiopyran 1,1-dioxide; 4-((R)-(((2S,3R,4S,5R,6R)-3,5-dihydroxy-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)(3-methylpyridin-2-yl)methyl)-4-hydroxytetrahydro-2H-thiopyran 1,1-dioxide; (2R,3R,4S,5R,6S)-2-(hydroxymethyl)-6-(((R)-(4-hydroxytetrahydro-2H-pyran-4-yl)(3-methylpyridin-2-yl)methyl)thio)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(3-hydroxy-1-(methylsulfonyl)azetidin-3-yl)(2-(trifluoromethyl)phenyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; Methyl 3-((R)-(((2S,3R,4S,5R,6R)-3,5-dihydroxy-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)(2-(trifluoromethyl)phenyl)methyl)-3-hydroxyazetidine-1-carboxylate; N-cyclopropyl-3-((R)-(((2S,3R,4S,5R,6R)-3,5-dihydroxy-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)(2-(trifluoromethyl)phenyl)methyl)-3-hydroxyazetidine-1-carboxamide; (2R,3R,4S,5R,6S)-6-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(3-methylpyridin-2-yl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol;(2R,3R,4S,5R,6S)-6-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(3-(trifluoromethyl)pyridin-2-yl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-6-(((R)-(1-hydroxycyclohexyl)(3-(trifluoromethyl)pyridin-2-yl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; 2R,3R,4S,5R,6S)-6-(((R)-(3-chloropyridin-2-yl) (4,4-difluoro-1-hydroxycyclohexyl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-6-(((R)-((R)-4-hydroxy-2,2-dimethyltetrahydro-2H-pyran-4-yl)(2-(trifluoromethyl)phenyl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-6-(((R)-((S)-4-hydroxy-2,2-dimethyltetrahydro-2H-pyran-4-yl)(2-(trifluoromethyl)phenyl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; 4-Hydroxy-4-((R)-(((2S,3R,4S,5R,6R)-5-hydroxy-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)(3-methylpyridin-2-yl)methyl)tetrahydro-2H-thiopyran 1,1-dioxide; (2R,3R,4S,5R,6S)-2-(hydroxymethyl)-6-(((R)-(4-hydroxytetrahydro-2H-pyran-4-yl)(3-methylpyridin-2-yl)methyl)thio)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-6-(((R)-((R)-4-hydroxy-2,2-dimethyltetrahydro-2H-pyran-4-yl)(o-tolyl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-6-(((R)-((S)-4-hydroxy-2,2-dimethyltetrahydro-2H-pyran-4-yl)(o-tolyl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-6-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(3-isopropylpyridin-2-yl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-6-(((R)-(3-cyclopropylpyridin-2-yl)(4,4-difluoro-1-hydroxycyclohexyl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-6-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(4-methylpyridazin-3-yl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-6-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(3-methylpyrazin-2-yl)methyl)thio)-2-(hydro (2R,3R,4S,5R,6S)-6-(((R)-(1-hydroxycyclohexyl)(4-methylisoxazol-3-yl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol;(2R,3R,4S,5R,6S)-6-(((R)-(1-hydroxycyclohexyl)(4-methylisoxazol-3-yl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-6-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(2-isopropylphenyl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-6-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(4-methylisoxazol-3-yl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-6-(((R)-(2-cyclopropylphenyl)(4,4-difluoro-1-hydroxycyclohexyl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-6-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(1,4-dimethyl-1H-pyrazol-5-yl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-6-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(1-ethyl-4-methyl-1H-1,2,3-triazol-5-yl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-6-(((R)-(4-chloro-1-ethyl-1H-pyrazol-5-yl)(4,4-difluoro-1-hydroxycyclohexyl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-6-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(5-ethyl-4-methylisoxazol-3-yl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-2-(hydroxymethyl)-6-(((R)-(4-hydroxytetrahydro-2H-pyran-4-yl)(4-methylisoxazol-3-yl)methyl)thio)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; 4-Hydroxy-4-((R)-(((2S,3R,4S,5R,6R)-5-hydroxy-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)(4-methylisoxazol-3-yl)methyl)tetrahydro-2H-thiopyran 1,1-dioxide; (2R,3R,4S,5R,6S)-6-(((R)-(5-cyclopropyl-3-methyl isoxazol-4-yl)(1-hydroxycyclohexyl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-6-(((R)-(5-cyclopropyl-4-ethylisoxazol-3-yl)(4,4-difluoro-1-hydroxycyclohexyl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-6-(((R)-(5-cyclopropyl-4-isobutylisoxazol-3-yl)(4,4-difluoro-1-hydroxycyclohexyl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-6-(((R)-(3-chloropyrazin-2-yl)(4,4-difluoro-1-hydroxycyclohexyl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol;(2R,3R,4S,5R,6S)-6-(((R)-(4-chloro-3-methylpyridin-2-yl)(4,4-difluoro-1-hydroxycyclohexyl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-6-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(3-ethylpyridin-2-yl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol;(2R,3R,4S,5R,6S)-6-(((R)-(3,4-dichloropyridin-2-yl)(4,4-difluoro-1-hydroxycyclohexyl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2S,3R,4S,5R,6R)-2-(((R)-(3,6-dichloropyridin-2-yl)(4,4-difluoro-1-hydroxycyclohexyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-((R)-4-hydroxy-2,2-dimethyltetrahydro-2H-pyran-4-yl)(3-methylpyridin-2-yl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-((S)-4-hydroxy-2,2-dimethyltetrahydro-2H-pyran-4-yl)(3-methylpyridin-2-yl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2R,3R,4S,5R,6S)-6-(((R)-(5-cyclopropyl-4-methylisoxazol-3-yl)(4,4-difluoro-1-hydroxycyclohexyl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro -2H-pyran-3-ol; (2R,3R,4S,5R,6S)-6-((((R)-4,4-difluoro-1-hydroxycyclohexyl)(4-ethyl-5-propylisoxazol-3-yl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-6-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(3-methyl-4-(trifluoromethyl)pyridin-2-yl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; 2R,3R,4S,5R,6S)-6-(((R)-(3-chloro-6-methylpyridin-2-yl)(4,4-difluoro-1-hydroxycyclohexyl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-6-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(3,5,6-trimethylpyrazin-2-yl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-6-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(3,6-dimethylpyridin-2-yl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; 9-((R)-(((2S,3R,4S,5R,6R)-5-hydroxy-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)(3-methylpyridin-2-yl)methyl)-3-oxaspiro[5.5]undecane-9-ol; (2R,3R,4S,5R,6S)-6-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(3-methylpyridin-2-yl)methyl)thio)-5-ethoxy-2-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; 1-(cyclopropylsulfonyl)-4-((R)-(((2S,3R,4S,5R,6R)-5-hydroxy-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)(2-(trifluoromethyl)phenyl)methyl)piperidin-4-ol; 1-(4-hydroxy-4-((R)-(((2S,3R,4S,5R,6R)-5-hydroxy-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)(2-(trifluoromethyl)phenyl)methyl)piperidin-1-yl)ethan-1-one; N-cyclopropyl-4-hydroxy-4-((R)-(((2S,3R,4S,5R,6R)-5-hydroxy-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)(2-(trifluoromethyl)phenyl)methyl)piperidine-1-carboxamide; (2R,3R,4S,5R,6S)-6-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(3-methylpyridin-2-yl)methyl)thio)-4-(4-(3,4-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-6-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(3-methylpyridin-2-yl)methyl)thio)-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,6S)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(3-methylpyridin-2-yl)methyl)thio)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-6-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(3-methylpyridin-2-yl)methyl)thio)-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,6S)-4-(4-(4-bromo-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(3-methylpyridin-2-yl)methyl)thio)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-4-(4-(3,4-dichloro-5-fluorophenyl)-1H-1,2,3-triazol-1-yl)-6-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(3-methylpyridin-2-yl)methyl)thio)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-4-(4-(4-bromo-3-fluorophenyl)-1H-1,2,3-triazol-1-yl)-6-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(3-methylpyridin-2-yl)methyl)thio)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol;(2R,3R,4S,5R,6S)-4-(4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(3-methylpyridin-2-yl)methyl)thio)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-6-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(3-methylpyridin-2-yl)methyl)thio)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; and (2R,3R,4S,5R,6S)-6-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(3-methylpyridin-2-yl)methyl)thio)-4-(4-(6-fluoro-5-methylpyridin-3-yl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol.

[0082] The compounds of formula (I) according to embodiments 1) to 25) and their pharma- ceutically acceptable salts can be used as medicaments, for example enterally (e.g. in the form of tablets or capsules, in particular orally) or topically (e.g. in the form of tablets or capsules). The composition can be used in the form of a pharmaceutical composition for parenteral administration (including topical application or inhalation).

[0083] The preparation of pharmaceutical compositions can be carried out in a manner well known to any person skilled in the art (see, for example, Remington, The Science and Practice of Pharmacy, 21st Edition (2005), Part 5, "Pharmaceutical Manufacturing" [published by Lippincott Williams & Wilkins]) by combining the above-mentioned compounds of formula (I) or pharma- ceutical acceptable salts thereof, optionally with other therapeutically valuable substances, with suitable non-toxic, inert, therapeutically compatible solid or liquid carrier materials and, if necessary, with conventional pharmaceutical adjuvants, to form a pharmaceutical dosage form.

[0084] The present invention also relates to a method for the prevention or treatment of a disease or disorder described herein, comprising administering to a subject a pharma- ceutically effective amount of a compound of formula (I) according to embodiments 1) to 25). In a subembodiment of the invention, the dosage is comprised between 1 mg and 1000 mg per day.

[0085] 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.Similarly, such compound is also suitable in a method for the prevention or treatment of such disease, comprising administering an effective amount of such compound to a subject (mammal, particularly a human) in need thereof.

[0086] 26) Another embodiment relates to compounds of formula (I) as defined in any one of embodiments 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 involved.

[0087] Such diseases and disorders in which binding of Gal-3 to its natural ligand is implicated are, in particular, diseases and disorders in which inhibition of the physiological activity of Gal-3 is beneficial, e.g., diseases in which the Gal-3 receptor is implicated 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.

[0088] Diseases and disorders in which the binding of galectin-3 to its natural ligands is implicated may be defined as including, in particular: - fibrosis of an organ: -- all forms of fibrotic interstitial lung disease, including in particular idiopathic pulmonary fibrosis (also known as 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 fibrosis, including chronic kidney disease (CKD), renal failure (acute or chronic), tubulointerstitial nephritis and / or chronic nephropathy such as (primary) glomerulonephritis and 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; -- 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; diabetes All forms of heart / cardiac fibrosis, including cardiac fibrosis associated with uremia, hypertension or hypercholesterolemia; --gut 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 fibrosis mediated by fibroblasts; 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) diseases);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 vascular disorders (including Budd-Chiari syndrome, portal vein thrombosis, sinusoidal obstruction syndrome);acute and chronic liver failure (with or without portal hypertension);liver insufficiency; - acute kidney injury and chronic kidney disease (CKD) caused by / associated with heart disease (also called cardiorenal syndrome types 1 and 2), or caused by / associated with hypertension, or caused by / associated with diabetes (also called diabetic nephropathy (DKD) including DKD associated with hypertension), in particular diabetes mellitus type 1 or 2), 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 infections), 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 to 5 CKD as defined by the Kidney Disease Outcomes (KDIGO) Guidelines], especially (particularly) these stages of CKD; and acute and chronic renal failure; - Cardiovascular diseases and disorders (atherosclerosis caused / related to hypertension, hypercholesterolemia, diabetes, inflammation, obesity, elderly / age; peripheral arterial disease caused / related to hypertension, hypercholesterolemia, diabetes, elderly / age; deep vein thrombosis; pulmonary embolism caused / related to obesity or cancer; aortic aneurysm and dissection caused / related to elderly, hypertension, Marfan syndrome, congenital heart defects, inflammatory or infectious disorders; cerebrovascular disease caused / related to hypertension, atrial fibrillation, hypercholesterolemia, diabetes, elderly / age; hypertension, hypercholesterolemia, diabetes, elderly / age or CKD, in particular Kidney Disease Improving Coronary heart disease caused or associated with CKD (stages 1-5 as defined by the Korean Heart Disease Outcomes Global Outcomes (KDIGO) Guidelines); heart failure (HF), specifically defined as including congestive HF, including, inter alia, 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 due to / associated with chronic obstructive pulmonary disease; interstitial pneumonia (including ordinary interstitial pneumonia) associated with collagen vascular disease, or pneumonia); - Cell proliferative disorders and cancer (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); - inflammatory and autoimmune diseases and disorders (including chronic and acute inflammatory and autoimmune diseases and disorders, in particular inflammatory renal / kidney diseases such as sepsis, Q fever, asthma, rheumatoid arthritis, multiple sclerosis, SLE, SSc, polymyositis, plaque psoriasis (including psoriasis caused / associated with NASH), atopic dermatitis, 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 secretions); - 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; - Eye diseases and disorders (including dry eye, age-related macular degeneration (AMD), diabetes-related diseases (diabetic retinopathy), proliferative vitreous retinopathy (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.

[0089] 27) A further embodiment relates to a compound of formula (I) for use 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.

[0090] 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.

[0091] 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).

[0092] 30) 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 or chronic) liver diseases and disorders.

[0093] 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.

[0094] 32) A further embodiment relates to a compound of formula (I) for use according to embodiment 26), wherein the compound is for use in the prevention or treatment of eye diseases and disorders.

[0095] 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.

[0096] 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 and acute inflammatory and autoimmune diseases and disorders.

[0097] 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 gastrointestinal diseases and disorders.

[0098] 36) A further embodiment relates to a compound of formula (I) for use according to embodiment 26), wherein the compound is for use in the prevention or treatment of pancreatic diseases and disorders.

[0099] 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.

[0100] 38) A further embodiment relates to a compound of formula (I) for use according to embodiment 26), wherein the compound is for use in the prevention or treatment of brain-related diseases and disorders.

[0101] 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.

[0102] 40) A further embodiment relates to a compound of formula (I) for use according to embodiment 26), wherein the compound is for use in the treatment of transplant rejection.

[0103] Preparation of Compounds of Formula (I) Compounds of formula (I) can be prepared by well-known literature methods, by the following methods, 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, but 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 groups R, R 1a , R 1b , R 2 , Ar 1 and Ar 2 are as defined for formula (I). Other abbreviations used herein are either explicitly defined or as defined in the experimental section. In some cases, the generic groups R, R 1a , R 1b , R 2 , Ar 1 and Ar 2 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", TW Greene, PG M Huts, Wiley-Interscience, 1999). For this purpose, it is assumed that such protecting groups have been introduced as necessary. In some cases, the final product may be further modified, for example by manipulating the substituents to give new final products. Such manipulations include, but are not limited to, reduction, oxidation, alkylation, acylation, hydrolysis and transition metal catalyzed cross-coupling reactions well known to those skilled in the art. The resulting compounds may be converted into salts, particularly pharma- ceutically acceptable salts, by methods known in the art.

[0104] The compounds of formula (I) of the present invention may be prepared according to the general reaction sequences outlined below: Only a few of the synthetic possibilities which lead to compounds of formula (I) are described.

[0105] [ka] Compounds of formula (I) can be prepared, for example, where R is hydrogen, a suitable protecting group (Pg) or R 1 The compound of Structure 1 is prepared by reacting the compound of Structure 2 in the presence of tetrabutylammonium bromide or tetrabutylammonium hydrogen sulfate and a base such as Na2CO3 under phase transfer catalysis conditions in a solvent such as EA / water (Chem.Comm. 2006, 2379). Alternatively, the compound of Structure 1 can be reacted with the compound of Structure 2 in the presence of NaH in THF or DMF under anhydrous conditions to give the compound of Structure 3. In Structures 1 and 3, the term Pg represents a protecting group such as an acetyl, chloro-acetyl, benzoyl or benzyl group, or 4-chlorobenzyl, which are well known to those skilled in the art. The hydroxy groups at the 4 and 6 positions of Structure 1 can be protected with a cyclic protecting group such as an isopropylidene, benzylidene or bis-tert-butylsilyl group. R represents hydrogen, a suitable protecting group (Pg) or R (as defined in formula (I)). 1 When Pg represents an acyl protecting group, such a protecting group can be cleaved under standard conditions after reaction of the compound of structure 1 with the compound of structure 2, for example with water or alcohol in the presence or absence of an additional solvent such as THF, dioxane, and in the presence of a base such as NaOH, LiOH, etc. When such a protecting group represents a benzyl group, it can be cleaved, for example, with hydrogen in the presence of a catalyst such as Pd / C, PtO, etc. in methanol, ethyl acetate, THF, etc. or mixtures thereof, or with BBr3 in a solvent such as DCM. Pg is a cyclic protecting group such as an isopropylidene, benzylidene or bis-tert-butylsilyl group, and R is hydrogen, a suitable protecting group (Pg) or R (as defined in formula (I)). 1If so, the compound of structure 3 can be deprotected under acidic conditions using acetic acid or aqueous TFA. can.

[0106] [ka] Compounds of structure 1 can be prepared, for example, by reacting compounds of structure 4 with compounds of structure 5 in the presence of CuI and DIPEA in a solvent such as THF or DMF (Click Chemistry in Glycoscience: New Development and Strategies, 1st Edition, 2013, John Wiley & Sons), or the reaction can be carried out in a commercially available continuous-flow reactor (Vapourtec) using a copper coil in a solvent such as THF. Compounds of structure 5 are commercially available or can be prepared by methods known to those skilled in the art (Synthesis 2011, 22, 3604-3611). Compounds of structure 4 can be prepared in three steps from gulo furanose by methods known to those skilled in the art (Carbohydrate Research 1994, 251, 33-67).

[0107] [ka] Compounds of structure 2 can be prepared by reacting compounds of structure 6 with compounds of structure 7 in the presence of a strong base such as LDA or BuLi in a solvent such as THF, diethyl ether, toluene, etc. (EurJOC, 2002, 1690-1695). In structure 6, the term Pg represents a suitable protecting group for nucleophile-stable thiols, such as quinoline or tetrahydropyran. When Pg represents a quinoline group, such a protecting group can be cleaved under standard conditions, for example by mild treatment with sodium cyanoborohydride in acetic acid, following reaction of compounds of structure 6 with compounds of structure 7 (Tet Lett 1999, 40, 1467-1470). When such a protecting group represents a tetrahydropyran group, the protecting group can be cleaved by reaction of a compound of structure 6 with a compound of structure 7 followed by treatment of the silver salt with, for example, AgNO3 in a solvent mixture such as THF / water, followed by NaSH in a solvent mixture such as THF / DCM / water (Tetrahedron 59 2003, 3853-3861), or a combination of boron trifluoride, 2-mercaptoethanol in a solvent such as DCM can be used (Chem Lett 1996, 999-1000).

[0108] Compounds of structure 6 can be prepared from halogen methyl aryl / heteroaryl and thiol protecting groups as described in Ref EurJOC, 2002, 1690-1695. Compounds of structure 7 are commercially available.

[0109] Alternatively, a compound of structure 2 can be prepared by reacting a compound of structure 2 with a 2-hydroxyethyl ether or 2-hydroxyethyl ether in a solvent such as diethyl ether or THF. It can be obtained by reduction with LAH of compound 8. In structure 8, the term Pg represents a suitable protecting group for thiols, carbamodithioate, which can also be removed by treatment with LAH.

[0110] [ka] Compounds of structure 8 are prepared from compounds of structure 9 through the introduction of a thiol-bearing dithiocarbamate group under Mitsunobu conditions in the presence of triphenylphosphine and DEAD in a solvent such as toluene (Macromolecules 2008, 41, 6627-6635). Compounds of structure 9 are commercially available or can be prepared from compounds of structure 10 through an OH insertion reaction in a solvent mixture such as dioxane / water in the presence of HClO4, or this reaction can be carried out solvent-free using silica-supported HClO4 as a catalyst (Green Chem 2018, 20, 4547-4556). Compounds of structure 10 can be prepared from commercially available compounds of structure 11 through a diazo transfer reaction using p-ABSA and DBU in a solvent such as acetonitrile (JOC 2017, 82, 3000-3010).

[0111] [ka] Whenever a compound of formula (I) is obtained in the form of a mixture of stereoisomers, the stereoisomers can be separated, optionally by preparative HPLC, or more often by HPLC on chiral stationary phases such as Daicel ChiralCel OJ-H (5-10 μm) columns, or Daicel ChiralPak IH (5 μm), or AS-H (5 μm) or IB (5 μm) columns. Typical conditions for chiral HPLC are an isocratic mixture of eluent A (CO2) and eluent B (DCM / MeOH, 0.1% Et2NH in EtOH, MeOH, EtOH) at a flow rate of 0.8-160 mL / min.

[0112] Experimental section The following examples illustrate the invention but do not in any way limit its scope.

[0113] All temperatures are given in °C. Commercially available starting materials were used as received without further purification. Unless otherwise noted, reactions were performed under nitrogen atmosphere at rt in a flame-dried round-bottom flask equipped with a magnetic stir bar. Compounds were purified by flash chromatography on silica gel (Kieselgel 60, 60 Å, 35-70 μM) using preparative TLC (TLC plates from Merck, Silica gel 60 F 254 ) or by preparative HPLC / MS or Flashmaster (Büchi or ISCO). The compounds described in this invention are 1 H-NMR (Bruk Brooker Avance II, 400 MHz Ultra Shield™ or Brooker Avance III HD, Ascend 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=sexlet, hept=septet, m=multiplet, br=broad; coupling constants are given in Hz.) and / or LC-MS (retention times t R are given in min; molecular weights obtained from mass spectrometry are given in g / mol.) or chiral HPLC (retention time t R The characteristics are clarified using the conditions described below, using the temperature (indicated as min).

[0114] Abbreviations (used in this section and in the above parts of the specification): ABTS 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid AcOH Acetic acid Ac2O Acetic anhydride AgNO3 Silver nitrate Ag2O Silver oxide aq. aqueous solution Bu (in nBuLi = n-butyl lithium, etc.) CC Silica Column Chromatography Concentrated CSA 10-camphor-sulfonic acid CuI Copper iodide DBU 1,8-Diazabicyclo[5.4.0]undec-7-ene DCM Dichloromethane DEAD Diethyl azodicarboxylate DIPEA N-Ethyldiisopropylamine DMAP 4-Dimethylaminopyridine DMF Dimethylformamide DMSO Dimethyl sulfoxide EA Ethyl acetate E. coli. Escherichia coli EDC HCl N-(3-Dimethylaminopropyl)-N'-ethylcarbodiimide Hydrochloride EtI Ethyl iodide eq (mol) equivalent Et Ethyl EtOH Ethanol Et2O Diethyl ether FC Flash Chromatography h time HATU 1-[Bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate HClO4 perchloric acid Hept Heptane HOBt 1-Hydroxybenzotriazole hydrate HPLC High Performance Liquid Chromatography K2CO3 Potassium Carbonate KMnO4 Potassium Permanganate LAH Lithium Aluminum Hydride LDA Lithium diisopropylamide LC Liquid Chromatography M Molar concentration [mol L -1 ] Me Methyl MeCN Acetonitrile MeI Methyl iodide MeOH Methanol MgSO4 Magnesium Sulfate MS mass spectrometry min. N normality Na2CO3 Sodium Carbonate NaCNBH3 Sodium cyanoborohydride NaHCO3 Sodium bicarbonate NaHMDS Sodium bis-trimethylsilyl-amide or sodium hexamethyldisilazide NaOAc Sodium Acetate NaOMe Sodium methoxide NaOtBu Sodium tert.(tertiary)butoxide NaSH Sodium hydrogen sulfide NBS N-Bromosuccinimide NH4Cl Ammonium chloride OD optical density o / n overnight org.organic p-ABSA p-Acetamidobenzenesulfonyl azide Pd / C Palladium Carbon Pd(Ph3)4 Tetrakis(triphenylphosphine)palladium(0)PPh3 Triphenylphosphine Ph Phenyl PTSA p-Toluenesulfonic acid rt room temperature sat. saturation SBr2 Thionyl bromide TBAB Tetrabutylammonium bromide TBME tert-Butyl methyl ether TBTU O-Benzotriazol-1-yl-N,N,N',N'-tetramethyluronium tetrafluoroborate tBu tert-butyl = tertiary butyl TEA Triethylamine TFA Trifluoroacetic acid THF Tetrahydrofuran TMEDA Tetramethylethylenediamine TMSCl Chlorotrimethylsilane TMSSMe Trimethyl(methylthio)silane TMSOTf Trimethylsilyl trifluoromethanesulfonate t R retention time Ziram Zinc Dimethyldithiocarbamate Qualitative analysis methods used The inhibitory activity values ​​of the compounds are measured in the biological tests described below. Unless expressly stated otherwise, the inhibition data refers to the binding of biotinylated human Gal-3 (hGal-3).

[0115] LC-MS retention times were obtained using the following elution conditions: A) LC-MS(A): Zorbax RRHD SB-Aq, 1.8 μm, 2.1×50 mm column, 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 4.5 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 successive time points):

[0116] [Table 1] B) LC-MS(B): Zorbax RRHD SB-Aq, 1.8 μm, 3.0×50 mm column, 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 1.6 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 successive time points):

[0117] [Table 2] C) LC-MS(C): Waters BEH C18, 2.5 μm, 2.1×50 mm column, 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 related to the time t from the start of the elution are summarized in the table below (a linear gradient is used between two successive time points):

[0118] [Table 3] D) Chiral analytical HPLC (D): ChiralPak IC, 5 μm, 4.6×250 mm column thermostated at 40° C. The two elution solvents are as follows: Solvent A=CO2; Solvent B=DCM / MeOH (1 / 1). The eluent flow rate is 4.0 mL / min for 5 min. Elution: isocratic, 20% solvent B and 80% solvent A. Detection: 230 nm.

[0119] E) Chiral analytical HPLC (E): ChiralPak IH, 5 μm, 4.6×250 mm column thermostated at 40° C. The two elution solvents are as follows: Solvent A=CO2; Solvent B=DCM / MeOH (1 / 1). The eluent flow rate is 4.0 mL / min for 5 min. Elution: isocratic, 15% solvent B and 85% solvent A. Detection: 254 nm.

[0120] F) Chiral analytical HPLC (F): ChiralPak IH, 5 μm, 4.6×250 mm column thermostated at 40° C. The two elution solvents are as follows: Solvent A=CO2; Solvent B=EtOH. The eluent flow rate is 4.0 mL / min for 5 min. Elution: isocratic, 25% solvent B and 75% solvent A. Detection: 210 nm.

[0121] G) Chiral analytical HPLC (G): Chiralcel OJ-H, 5 μm, 4.6×250 mm column thermostated at 40° C. The two elution solvents are as follows: Solvent A=CO2; Solvent B=MeCN / EtOH (1 / 1). The eluent flow rate is 4.0 mL / min for 3 min. Elution: isocratic, 10% solvent B and 90% solvent A. Detection: 210 nm.

[0122] H) Chiral analytical HPLC (H): ChiralPak IH, 5 μm, 4.6×250 mm column thermostated at 40° C. The two elution solvents are as follows: Solvent A=CO2; Solvent B=DCM / MeOH / DEA (50 / 50 / 0.1). The eluent flow rate is 4.0 mL / min for 5 min. Elution: isocratic, 15% solvent B and 85% solvent A. Detection: 210 nm.

[0123] I) Chiral analytical HPLC (I): The epimers of the epimeric mixture are characterized by chiral analytical HPLC. The conditions vary for each epimeric mixture. Several columns are used, all with the same dimensions: 4.6x250mm, 5m. Elution is performed under isocratic conditions: eluent A is always CO2, eluent B is an organic solvent or a mixture thereof. Run for 2.5-5min.

[0124] The column type, B solvent and elution length are noted for each epimer mixture in the corresponding table.

[0125] J) Chiral analytical HPLC(J): ChiralPak IB, 5 μm, 4.6×250 mm column, thermostated at 40° C. The two elution solvents are as follows: Solvent A=CO2; Solvent B=EtOH. The eluent flow rate is 4.0 mL / min for 5 min. Elution: isocratic, 35% solvent B and 65% solvent A. Detection: 246 nm.

[0126] K) Chiral analytical HPLC (K): ChiralPak IB, 5 μm, 4.6×250 mm column, thermostated at 40° C. The two elution solvents are as follows: Solvent A=CO2; Solvent B=EtOH. The eluent flow rate is 4.0 mL / min for 5 min. Elution: isocratic, 30% solvent B and 70% solvent A. Detection: 210 nm.

[0127] L) Chiral analytical HPLC (L): ChiralPak IB, 5 μm, 4.6×250 mm column, thermostated at 40° C. The two elution solvents are as follows: Solvent A=CO2; Solvent B=MeOH, 01% DEA. The eluent flow rate is 4.0 mL / min over 5 min. Elution: isocratic, 25% solvent B and 75% solvent A. Detection: 210 nm.

[0128] M) Chiral analytical HPLC (M): ChiralPak IB, 5 μm, 4.6×250 mm column thermostated at 40° C. The two elution solvents were as follows: Solvent A=CO2; Solvent B=MeOH, 01% DE A. The eluent flow rate is 4.0 mL / min for 5 min. Elution: isocratic, 30% solvent B and 70% solvent A. Detection: 210 nm.

[0129] N) Chiral analytical HPLC (N): Chiralcel OZ-H, 5 μm, 4.6×250 mm column thermostated at 40° C. The two elution solvents are as follows: Solvent A=CO2; Solvent B=MECN / MEOH, 1:1. The eluent flow rate is 4.0 mL / min over 5 min. Elution: isocratic, 30% solvent B and 70% solvent A. Detection: 247 nm.

[0130] O) Chiral analytical HPLC (O): Chiralcel OZ-H, 5 μm, 4.6×250 mm column thermostated at 40° C. The two elution solvents are as follows: Solvent A=CO2; Solvent B=MECN / MEOH, 1:1. The eluent flow rate is 4.0 mL / min for 5 min. Elution: isocratic, 40% solvent B and 60% solvent A. Detection: 210 nm.

[0131] Non-chiral preparative methods used: Purification by preparative LC-MS is performed using the conditions described below. P) Preparative LC-MS(I): A Waters column (Waters XBridge C18, 10 μm OBD, 30×75 mm) is used. The two elution solvents are: Solvent A=water+0.5% of 25% NH4OH in water; 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 following table (a linear gradient is used between two successive time points):

[0132] [Table 4] Q) Preparative LC-MS(II): A Waters column (Waters XBridge C18, 10 μm OBD, 30x75 mm) 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 eluted mixture related to the time t from the start of the elution are summarized in the following table (a linear gradient is used between two successive time points):

[0133] [Table 5] Chiral preparative HPLC method used: Separation of selected enantiomeric building blocks is achieved by preparative chiral column chromatography using the conditions described below.

[0134] R) Chiral preparative HPLC (I): A ChiralPack IC, 5 μm, 30x250 mm is used. The two elution solvents are as follows: Solvent A = CO2; Solvent B = DCM / MeOH (1 / 1). The flow rate was 160 mL / min. Elution was performed with 80% solvent A and 20% solvent B. Injection V=3 mL, 20 mg / mL DCM / MeOH (1 / 1).

[0135] S) Chiral Preparative HPLC (II): A ChiralPack IH, 5 μm, 30x250 mm is used. The two elution solvents are as follows: Solvent A=CO2; Solvent B=DCM / MeOH (1 / 1). The eluent flow rate was 160 mL / min. Elution is performed with 75% solvent A and 25% solvent B. Injection V=2 mL, 10 mg / mL DCM / MeOH (1 / 1).

[0136] T) Chiral Preparative HPLC (III): A ChiralPack IB, 5 μm, 30x250 mm is used. The two elution solvents are as follows: Solvent A=CO2; Solvent B=EtOH. The eluent flow rate was 160 mL / min. The elution is performed with 60% Solvent A and 40% Solvent B. Injection V=1.0 mL, 21.1 mg / mL EtOH.

[0137] V) Chiral Preparative HPLC (IV): A ChiralPack IB, 5 μm, 30x250 mm is used. The two elution solvents are as follows: Solvent A=CO2; Solvent B=EtOH. The eluent flow rate was 160 mL / min. The elution is performed with 70% Solvent A and 30% Solvent B. Injection V=2.0 mL, 10 mg / mL EtOH.

[0138] W) Chiral preparative HPLC (V): A ChiralPack IB, 5 μm, 30x250 mm is used. The two elution solvents are as follows: Solvent A=CO2; Solvent B=MeOH, 0.1% DEA. The eluent flow rate was 160 mL / min. The elution is performed with 75% Solvent A and 25% Solvent B. Injection V=1.0 mL, 10 mg / mL MeOH.

[0139] X) Chiral Preparative HPLC (VI): A ChiralPack IB, 5 μm, 30x250 mm is used. The two elution solvents are as follows: Solvent A=CO2; Solvent B=MeOH, 0.1% DEA. The eluent flow rate was 160 mL / min. The elution is performed with 70% Solvent A and 30% Solvent B. Injection V=1.0 mL, 7 mg / mL MeOH.

[0140] Y) Chiral Preparative HPLC (VII): ELN012-4912 Chiralcel OZ-H, 5 μm, 30x250 mm is used. The two elution solvents are as follows: Solvent A=CO2; Solvent B=MECN / EtOH, 1:1. The eluent flow rate was 160 mL / min. Elution is performed with 70% Solvent A and 30% Solvent B.

[0141] Z) Chiral preparative HPLC (VIII): ELN370-0120 Chiralcel OZ-H, 5 μm, 30x250 mm is used. The two elution solvents are as follows: Solvent A=CO2; Solvent B=MECN / EtOH, 1:1. The eluent flow rate was 160 mL / min. Elution is performed with 60% Solvent A and 40% Solvent B.

[0142] Preparation of intermediates For the synthesis of the compounds the following intermediates are prepared:

[0143] Intermediate 1 (3R,4S,5R,6R)-6-(acetoxymethyl)-4-azidotetrahydro-2 H-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.

[0144] Intermediate 2 (2R,3R,4S,5R,6R)-2-(Acetoxymethyl)-4-azido-6-bromotetrahydro-2H-pyran-3,5-diyl diacetate (3R,4S,5R,6R)-6-(acetoxymethyl)-4-azidotetrahydro-2H-pyran-2,3,5-triyl triacetate To a solution of intermediate 1 (8.0 g, 21.4 mmol) in DCM (250.0 mL) and EA (25.0 mL) is added titanium(IV) bromide (2.4 g, 64.3 mmol, 3.0 eq). The reaction mixture is stirred at rt for 48 h, quenched with NaOAc (25.0 g, 30.4 mmol, 1.4 eq) and stirred at rt for 1 h. The mixture is partitioned between H2O and DCM, the layers are separated and the aqueous layer is extracted with DCM (3x). The organic layers are combined, dried over Na2SO4, filtered and the solvent is removed in vacuo to give a pale yellow oil. The crude material is purified by Flash Master (Büchi, 120 g column, product added to isolute-dried, Hept / EA 100 / 0 to 8 / 2, Rf(Hept / EA 8 / 2)=0.57, not UV-active, stained with KMnO4) to give the title compound as a colorless oil (11.4 g, 92%). LC-MS(A) t R =0.91min;[M+H] + :394.00. 1H NMR (400MHz, CDCl3) δ:6.73(d, J=3.7Hz, 1H), 5.52(d, J=2.9Hz, 1H), 4.97(dd, J1=3.7Hz, J2=10.5Hz, 1H), 4.44(t, J=6.4Hz, 1H), 4.21(dd, J1=6.0Hz, J 2=11.5Hz, 1H), 4.18(dd, J1=3.3Hz, J2=10.5Hz, 1H), 4.07(dd, J1=7.0Hz, J2=11.5Hz, 1H), 2.20(s, 3H), 2.19(s, 3H), 2.10(s, 3H).

[0145] Intermediate 3 (2R,3R,4S,5R,6R)-2-(Acetoxymethyl)-6-bromo-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diyl diacetate To a solution of intermediate 2 (11.1 g, 28.3 mmol) in THF (306.0 mL) is added 3,4,5-trifluorophenylacetylene (4.55 g, 28.3 mmol, 1.0 eq), CuI (1.6 g, 8.48 mmol, 0.3 eq) and DIPEA (14.5 mL, 84.8 mmol, 3.0 eq). The reaction mixture is stirred at 44 °C for 17 h. The mixture is cooled to rt, diluted with EA and filtered. The organic layer is washed with aq.sat.NH4Cl (2x20 mL), brine, dried over Na2SO4, filtered and the solvent is concentrated under reduced pressure to give a beige solid. The crude material is purified by Flash Master (ISCO, product is added to isolute on column, 220 g column, Hept / EA Purify with 85 / 15 to 50 / 50 EA in Hept, Rf(Hept / EA 1 / 1)=0.52, UV active and stained with KMnO4) to recover intermediate 3 as a white powder (11.1 g, 72%). LC-MS (A) t R =1.04min;[M+H] + :552. 1 H NMR (400MHz, CDCl3) δ:7.82(s, 1H), 7.46(dd, J1=6.5Hz, J2=8.1Hz, 2H), 6.91(d, J=3.8Hz, 1H), 5.84 (dd, J1=3.8Hz, J2=11.3Hz, 1H), 5.64(d, J=1.7Hz), 5.34(dd, J1=3.0Hz, J2=11.4 Hz, 1H), 4.66(t, J=6.4Hz, 1H), 4.26(dd, J1=6.3Hz, J2=11.5Hz, 1H), 4.16(dd, J1=6.5Hz, J2=11.5Hz, 1H), 2.09(s, 6H), 1.98(s, 3H).

[0146] Intermediate 4 (2R,3R,4S,5R,6R)-2-(Acetoxymethyl)-6-bromo-4-(4-(3-fluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diyl diacetate Intermediate 4 (0.51 g) is synthesized from intermediate 2 and 3-trifluorophenylacetylene according to the procedure described for intermediate 3. LC-MS (A) t R =1.03min;[M+H] + :513.82. 1 H NMR (400MHz, CDCl3) δ:7.83(s, 1H), 7.55-7.60(m, 2H), 7.42(dd, J1=7.7Hz, J2=14.0Hz, 1H), 7.07(td, J1=1 .8Hz, J2=8.5Hz), 6.91(d, J=3.7Hz, 1H), 5.84(dd, J1=3.7Hz, J2=11.3Hz, 1H), 5.66(d, J =1.4Hz, 1H), 5.36(dd, J1=2.8Hz, J2=11.3Hz, 1H), 4.67(t, J=6.5Hz, 1H), 4.26(dd, J1= 6.3Hz, J2=11.3Hz, 1H), 4.16(dd, J1=6.8Hz, J2=11.8Hz, 1H), 2.09(s, 6H), 1.98(s, 3H).

[0147] Intermediate 5 Intermediate 5 is prepared by adapting and using procedures from Ref: EurJOC, 2002, 1690-1695 and references cited therein.

[0148] 1-Mercapto-2-methyl-1-(o-tolyl)propan-2-ol 1. 2-((2-methylbenzyl)thio)quinoline DBU (0.27 mL, 1.77 mmol, 1.0 eq) is added to a solution of 2-quinolinethiol (0.30 g, 1.77 mmol) in toluene (6.0 mL) at rt. The reaction mixture is stirred at rt for 30 min, 2-methylbenzyl bromide (0.25 mL, 1.77 mmol, 1.0 eq) is added and stirring is continued for 3 h. The reaction mixture is concentrated under reduced pressure to give a yellow solid which is triturated in Hept. The mother liquor is concentrated in vacuo to give the title compound (0.400 g, 85%). LC-MS (A) t R =1.11min;[M+H] + :266.03.

[0149] 2. 2-Methyl-1-(quinolin-2-ylthio)-1-(o-tolyl)propan-2-ol To a cooled (-78°C) solution of 2-((2-methylbenzyl)thio)quinoline (0.20 g, 0.75 mmol) in THF (8.0 mL) is added n-BuLi (1.6 M in hexanes, 0.71 mL, 1.13 mmol, 1.5 eq) and the reaction mixture is stirred at -78°C for 1 h. Acetone (0.07 mL, 0.90 mmol, 1.2 eq) in THF (4.0 mL) is added and the reaction mixture is allowed to warm to -50°C and stirred at this temperature for 4 h. The reaction mixture is quenched by addition of aq.sat. NH4Cl, extracted with EA, the layers are separated and the aqueous layer is extracted with EA (3x). The organic layers are combined, washed with brine, dried over MgSO4, filtered and the solvent is removed in vacuo to give a yellow oil. The crude material is purified by Flash Master (Büchi, 5 g column, product loaded onto isolute-dried, 10 mL / min, 5 mL fraction Hept / EA 100 / 0 to 8 / 2, Rf(Hept / EA 8 / 2)=0.15) to give 2-methyl-1-phenyl-1-(quinolin-2-ylthio)propan-2-ol as a colorless oil (0.14 g, 57%). LC-MS (A) t R =1.05min;[M+H] + :324.06.

[0150] 3. 1-Mercapto-2-methyl-1-(o-tolyl)propan-2-ol (Intermediate 5) 2-Methyl-1-(quinolin-2-ylthio)-1-(o-tolyl)propan-2-ol (0.13 g, 0.42 mmol) is dissolved in AcOH (9.0 mL) and NaCNBH3 (0.14 g, 2.1 mmol, 5.0 eq) is added. The reaction mixture is stirred at rt for 17 h, quenched with water (6.0 mL), stirred at rt for 1 h, then diluted with DCM. The layers are separated, the aqueous layer is extracted with DCM, the organic layers are combined, washed with brine, dried over MgSO4, and the solvent is removed under vacuum to give the title compound as a yellow oil (0.18 g) which is used without further purification. LC-MS (A) t R =0.85min;[M+H] + :none.

[0151] Intermediate 6R (R)-1-Mercapto-2-methyl-1-(2-(trifluoromethyl)pyridin-3-yl)propan-2-ol 1. 2-Methyl-1-(quinolin-2-ylthio)-1-(2-(trifluoromethyl)pyridin-3-yl)propan-2-ol The title compound is prepared from 3-(bromomethyl)-2-(trifluoromethyl)pyridine and 2-quinolinethiol according to the procedure described for intermediate 5 (steps 1 and 2) as an orange oil (3.8 g). LC-MS (A): R =1.02min;[M+H] + :379.34.

[0152] 2. (R)-2-Methyl-1-(quinolin-2-ylthio)-1-(2-(trifluoromethyl)pyridin-3-yl)propan-2-ol Separation of the epimers of 2-methyl-1-(quinolin-2-ylthio)-1-(2-(trifluoromethyl)pyridin-3-yl)propan-2-ol (3.8 g) by chiral preparative HPLC (I) afforded the title compound (1.87 g) as a yellow oil. Chiral analytical HPLC (D): R =1.45min.

[0153] (R)-1-Mercapto-2-methyl-1-(2-(trifluoromethyl)pyridin-3-yl)propan-2-ol (Intermediate 6R) The title compound is prepared from (R)-2-methyl-1-(quinolin-2-ylthio)-1-(2-(trifluoromethyl)pyridin-3-yl)propan-2-ol following the procedure described for intermediate 5 (step 3) to give a white solid (0.17, 88%). LC-MS (A): R =0.79min;[M+H] + :252.14. 1 H NMR (400MHz, DMSO) δ:8.59(dd, J1=1.3Hz, J2=4.5Hz, 1H), 8.50(d, J=8.0Hz, 1H), 7.70(dd, J1= 4.5Hz, J2=8.2Hz, 1H), 4.13(s, 1H), 3.13(s, 1H), 1.40(s, 3H), 0.97(s, 3H).

[0154] Intermediate 6S (S)-1-Mercapto-2-methyl-1-(2-(trifluoromethyl)pyridin-3-yl)propan-2-ol The title compound, S-epimer, is prepared from 3-(bromomethyl)-2-(trifluoromethyl)pyridine and 2-quinolinethiol following the procedure described for intermediate 6R (S-epimer is obtained in step 2. by chiral separation by chiral preparative HPLC (I)) to give a white solid (0.17 g). LC-MS (A): R =0.79min;[M+H] + :252.15.

[0155] Intermediate 7 4-(Mercapto(3,5,6-trimethylpyrazin-2-yl)methyl)-1-methyl Piperidin-4-ol 1. S-(Tetrahydro-2H-pyran-2-yl)ethanethioate 3,4-Dihydro-2H-pyran (3.2 mL, 34.6 mmol, 1.0 eq) is added slowly to a cooled (0° C.) mixture of thioacetic acid (2.7 g, 34.6 mmol) in HCl (37%, 5.0 mL). After 2 h at rt, the reaction mixture is diluted with Et2O and the organic layer is washed with aq. 10% NaHCO3, dried over MgSO4, filtered and the solvent removed in vacuo to give a beige oil (6.1 g, >99%) which is used without further purification. 1 H NMR (400MHz, CDCl3) δ:1.60-1.82(m, 5H+H2O), 1.96-2.07(m, 1H), 2.38(s, 3H), 3.70-3.76(m, 1H), 3.86-3.93(m, 1H), 5.58-5.80(dd, J=4.3, 3.8Hz, 1H).

[0156] 2. 2,3,5-trimethyl-6-(((tetrahydro-2H-pyran-2-yl)thio)methyl)pyrazine S-(tetrahydro-2H-pyran-2-yl)ethanethioate (3.0 g, 18.7 mmol) is added under stirring to a cooled (0° C.) mixture of KOH (2.3 g, 37.4 mmol, 2.0 eq) in DMSO (28.0 mL) and water (10.0 mL). The reaction mixture is stirred at 0° C. for 15 min and then at rt for 30 min, and finally 2-(bromomethyl)-3,5,6-trimethylpyrazine (4.15 g, 18.7 mmol, 1.0 eq) is added portionwise at 0° C. The reaction mixture is allowed to warm to rt for 17 h, quenched with water and Et2O, the layers are separated, and the aqueous layer is extracted with Et2O (3×). The organic layers are combined, washed with water and brine, dried over MgSO4, filtered, and the solvent is removed under vacuum to give a beige oil. The crude material is purified by Flash Master (ISCO, 80 g column, product loaded into isolute, Hept / EA 100 / 0 to 1 / 1, Rf(Hept / EA 1 / 1)=0.27) to give 2,3,5-trimethyl-6-(((tetrahydro-2H-pyran-2-yl)thio)methyl)pyrazine as a colorless oil (2.9 g, 61%). LC-MS (A):t R =0.76min;[M+H] + : 253.26.

[0157] 3. 1-Methyl-4-(((tetrahydro-2H-pyran-2-yl)thio)(3,5,6-trimethylpyrazin-2-yl)methyl)piperidin-4-ol To a cooled (-78°C) solution of 2,3,5-trimethyl-6-(((tetrahydro-2H-pyran-2-yl)thio)methyl)pyrazine (2.4 g, 9.51 mmol) in THF (25.0 mL) is added n-BuLi (1.6 M in hexanes, 8.9 mL, 14.3 mmol, 1.5 eq). The reaction mixture is stirred at -78°C for 1 h, then a solution of N-methyl-4-piperidone (1.62 mL, 11.4 mmol, 1.2 eq) in THF (25.0 mL) is added at -78°C and stirring is continued at -78°C for 1 h. The reaction mixture is quenched with aq.sat. NH4Cl, extracted with EA, the layers are separated and the aqueous layer is extracted with EA (3x). The organic layers are combined, washed with brine, dried over MgSO4, filtered and the solvent is removed in vacuo to give a yellow oil. The crude material is purified by preparative HPLC / MS (I) to give the title product as a pale yellow oil (2.2 g, 63%). LC-MS (A): R =0.58min;[M+H] + :366.26.

[0158] 4. 4-(Mercapto(3,5,6-trimethylpyrazin-2-yl)methyl)-1-methylpiperidin-4-ol (Intermediate 7) To a solution of 1-methyl-4-(((tetrahydro-2H-pyran-2-yl)thio)(3,5,6-trimethylpyrazin-2-yl)methyl)piperidin-4-ol (1.0 g, 2.74 mmol) in THF (5.0 mL) is added AgNO3 (0.95 g, 5.56 mmol, 2.03 eq) followed by water (5.0 mL) and stirred at rt for 20 min. The reaction mixture is diluted with DCM (100.0 mL) and NaSH (1.53 g, 27.4 mmol). l, 10.0 eq) is added and the mixture is stirred vigorously at rt for 30 min. The resulting black precipitate is removed by filtration and washed with DCM (2x). The filtrate is collected, the layers are separated, the organic layer is washed with aq.sat.NH4Cl, dried over MgSO4, filtered and the solvent is removed in vacuo to give a pale yellow oil (0.98 g). The crude material is purified by Flash Master (ISCO, 12 g gold column, DCM / MeOH 100 / 0 to 8 / 2, Rf(DCM / MeOH 9 / 1)=0.14) to give intermediate 7 as a pale yellow oil (0.56 g, 73%). LC-MS (A):t R =0.51min;[M+H] + :282.27.

[0159] Intermediate 8 (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-(((4-hydroxypiperidin-4-yl)(2-(trifluoromethyl)phenyl)methyl)thio)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diyl diacetate 1. 1,1,1-trichloro-2-methylpropan-2-yl 4-oxopiperidine-1-carboxylate Piperidin-4-one HCl (0.50 g, 3.5 mmol) is dissolved in DCM (25.0 mL) and 2,2,2-trichloro-1,1-dimethylethyl chloroformate (0.87 g, 3.5 mmol, 1.0 eq) is added followed by DIPEA (1.8 mL, 10.5 mmol, 3.0 eq) and the reaction mixture is stirred at rt for 17 h. DIPEA (1.0 mL, 5.8 mmol) is added again and the reaction mixture is stirred for a further 5 h then partitioned between DCM and water. The layers are separated and the aqueous layer is extracted with DCM (3x). The organic layers are combined, dried over MgSO4, filtered and the solvent removed in vacuo to give an orange oil which is purified by preparative HPLC / MS (I) to recover 1,1,1-trichloro-2-methylpropan-2-yl 4-oxopiperidine-1-carboxylate as a white powder (0.434 g, 41%). LC-MS (A): R =0.91min;[M+H] + :301.87.

[0160] 2. 1,1,1-trichloro 4-hydroxy-4-(mercapto(phenyl)methyl)piperidine-1-carboxylate 1,1,1-trichloro 4-hydroxy-4-(mercapto(phenyl)methyl)piperidine-1-carboxylate is prepared from 1-(bromomethyl)-2-(trifluoromethyl)benzene and 1,1,1-trichloro-2-methylpropan-2-yl 4-oxopiperidine-1-carboxylate according to the procedure described for the synthesis of intermediate 5. LC-MS (A): R =1.14min, [M+1 + =493.83.

[0161] 3. (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-(((4-hydroxy-1-(((1,1,1-trichloro-2-methylpropan-2-yl)oxy)carbonyl)piperidin-4-yl)(2-(trifluoromethyl)phenyl)methyl)thio)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diyl diacetate To a solution of intermediate 3 (0.28 g, 0.509 mmol) in EA (8.0 mL), TBAB (0.041 g, 0.13 mmol, 0.25 eq), aq. 1 M Na2CO3 (12.0 mL) and 1,1,1-trichloro 4-Hydroxy-4-(mercapto(phenyl)methyl)piperidine-1-carboxylate (0.25 g, 0.51 mmol, 1.0 eq) is added. The reaction mixture is stirred at rt for 17 h and diluted with EA, then with water and brine. The phases are separated and the aqueous layer is extracted with EA (3x). The organic layers are combined, dried over MgSO4, filtered and the solvent is removed in vacuo to give a yellow oil which is purified by preparative HPLC / MS (I). The title compound is obtained as a beige solid (0.17 g, 34%). LC-MS(A):t R =1.21min;[M+H] + :965.06.

[0162] 4. (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-(((4-hydroxypiperidin-4-yl)(2-(trifluoromethyl)phenyl)methyl)thio)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diyl diacetate (Intermediate 8) To a solution of (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-(((4-hydroxy-1-(((1,1,1-trichloro-2-methylpropan-2-yl)oxy)carbonyl)piperidin-4-yl)(2-(trifluoromethyl)phenyl)methyl)thio)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diyl diacetate (0.17 g, 0.17 mmol) in THF (12.0 mL) and glacial acetic acid (0.3 mL) is added zinc dust (0.114 g, 1.74 mmol, 10.0 eq). The reaction mixture is stirred for 17 h, filtered and diluted with EA and water. The layers are separated, the aqueous layer is extracted with EA, the organic layers are combined, washed with brine, dried over MgSO4, filtered and the solvent is removed in vacuo to give intermediate 8 as a white solid (0.145 g; >99%) which is used without further purification. LC-MS (A): R =0.87min;[M+H] + :761.01.

[0163] Intermediate 8R (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-(((R)-(4-hydroxypiperidin-4-yl)(2-(trifluoromethyl)phenyl)methyl)thio)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diyl diacetate 1. 2-((2-(trifluoromethyl)benzyl)thio)quinoline To a solution of 2-quinolinethiol (1.0 g, 5.9 mmol) in toluene (15.0 mL) is added DBU (0.898 mL, 5.9 mmol). The reaction mixture is stirred at rt for 0.5 h before adding 2-(trifluoromethyl)benzyl bromide (1.44 g, 5.9 mmol, 1.0 eq). The solution is stirred at rt for 17 h and concentrated under reduced pressure to give a solid. Trituration in Hept gives a yellow / orange solid as the title compound (1.24 g, >99%). LC-MS (A):t R= 1.16 min; [M+H] + :320.09.

[0164] 2. 4-((quinolin-2-ylthio)(2-(trifluoromethyl)phenyl)methyl)piperidin-4-ol 2-((2-(trifluoromethyl)benzyl)thio)quinoline (0.90 g, 2.54 mmol) is dissolved in THF (45.0 mL) and cooled to -78°C. n-BuLi (1.6 M in hexanes, 4.75 mL, 7.61 mmol, 3.0 eq) is added and the reaction mixture is stirred at -78°C for 1 h. 1,1,1-trichloro-2-methylpropan-2-yl 4-oxopiperidine-1-carboxylate (described in Intermediate 8, step 1.) (0.84 g, 2.70 mmol, 1.1 eq) in THF (19.0 mL) is added and the reaction mixture is allowed to warm to -70°C. After 2 h at -70°C, the reaction is quenched with aq.sat. NH4Cl, diluted with EA, the layers are separated and the aqueous layer is extracted with EA (3x). The organic layers are combined, washed with brine, dried over MgSO4, filtered and the solvent removed in vacuo to give the title compound as a yellow oil without further purification (1.04 g). LC-MS (A): R =0.81min;[M+H] + :419.11.

[0165] 3. 1,1,1-trichloro-2-methylpropan-2-yl 4-hydroxy-4-((quinolin-2-ylthio)(2-(trifluoromethyl)phenyl)methyl)piperidine Lysine-1-carboxylate 4-((Quinolin-2-ylthio)(2-(trifluoromethyl)phenyl)methyl)piperidin-4-ol (1.04 g, 2.49 mmol) is dissolved in DCM (25.0 mL) and 2,2,2-trichloro-1,1-dimethylethyl chloroformate (0.61 g, 2.49 mmol, 1.0 eq) and DIPEA (1.28 mL, 7.46 mmol, 3.0 eq) are added. The reaction mixture is stirred at rt for 4 h, then partitioned between DCM and water, the layers are separated and the aqueous layer is extracted with DCM (3x). The organic layers are combined, dried over MgSO4, filtered and the solvent is removed in vacuo to give an orange oil. The crude is purified by preparative HPLC / MS (I) to recover the title compound as a white solid (0.82 g, 53%). LC-MS (A):t R =1.24min;[M+H] + :621.13.

[0166] 4. 1,1,1-trichloro-2-methylpropan-2-yl (R)-4-hydroxy-4-((quinolin-2-ylthio)(2-(trifluoromethyl)phenyl)methyl)piperidine-1-carboxylate Chiral separation of 1,1,1-trichloro-2-methylpropan-2-yl 4-hydroxy-4-((quinolin-2-ylthio)(2-(trifluoromethyl)phenyl)methyl)piperidine-1-carboxylate (1.54 g) by chiral preparative HPLC (II) gave the title compound (0.71 g). Chiral analytical HPLC (E):t R =1.81min.

[0167] 5. 1,1,1-trichloro-2-methylpropan-2-yl (R)-4-hydroxy-4-(mercapto(2-(trifluoromethyl)phenyl)methyl)piperidine-1-carboxylate To a solution of 1,1,1-trichloro-2-methylpropan-2-yl (R)-4-hydroxy-4-((quinolin-2-ylthio)(2-(trifluoromethyl)phenyl)methyl)piperidine-1-carboxylate (0.71 g, 1.14 mmol) in acetic acid (50.0 mL) is added NaCNBH3 (0.38 g, 5.71 mmol, 5.0 eq). The reaction mixture is stirred at rt for 72 h, quenched with water (9.0 mL) and stirred for 1 h. DCM is added, the layers are separated, the aqueous layer is extracted with DCM, the organic layers are combined, washed with brine, dried over MgSO4 and the solvent is removed in vacuo to give a yellow oil. The crude material is purified by preparative HPLC / MS (II) to give the title compound as a colourless oil (0.28 g, 49%). LC-MS (A):t R = 1.15 min; [M+H] + : 494.01. Chiral analytical HPLC (F): t R =1.947min.

[0168] 6. (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-(((R)-(4-hydroxy-1-(((1,1,1-trichloro-2-methylpropan-2-yl)oxy)carbonyl)piperidin-4-yl)(2-(trifluoromethyl)phenyl)methyl)thio)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diyl diacetate To a solution of intermediate 3 (0.31 g, 0.563 mmol, 1.0 eq) in EA (36.0 mL) was added TBAB (0.045 g, 0.141 mmol, 0.25 eq), aq. 1M Na2CO3 (6.0 mL) and 1,1,1-trichloro-2-methylpropan-2-yl (R)-4-Hydroxy-4-(mercapto(2-(trifluoromethyl)phenyl)methyl)piperidine-1-carboxylate (0.28 g, 0.563 mmol) is added. The reaction mixture is stirred at rt for 17 h and diluted with EA, then with water and brine. The phases are separated and the aqueous layer is extracted with EA (3x). The organic layers are combined, dried over MgSO4, filtered and the solvent is removed in vacuo to give a yellow oil. The crude is purified by preparative HPLC / MS (I) to give the title compound as a beige solid (0.059 g, 39%). LC-M S(A):t R = 1.23 min; [M+H] + : 965.28. Chiral analytical HPLC (G): t R =1.59min.

[0169] 7. (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-(((S)-(4-hydroxypiperidin-4-yl)(2-(trifluoromethyl)phenyl)methyl)thio)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diyl diacetate (intermediate 8R) To a solution of (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-(((R)-(4-hydroxy-1-(((1,1,1-trichloro-2-methylpropan-2-yl)oxy)carbonyl)piperidin-4-yl)(2-(trifluoromethyl)phenyl)methyl)thio)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diyl diacetate (0.25 g, 0.26 mmol) in THF (18.0 mL) and glacial acetic acid (0.75 mL) is added zinc dust (0.17 mg, 2.6 mmol, 10.0 eq). The reaction mixture is stirred at rt for 17 h, filtered and partitioned between EA and water. The layers are separated, the aqueous layer is extracted with EA, the organic layers are combined, washed with brine, dried over MgSO4, filtered and the solvent is removed in vacuo to give a white solid. The crude is purified by preparative HPLC / MS (I) to give the title compound as a white powder (0.13 g, 68%). LC-MS (A):tR =0.87min;[M+H] + : 761.13. Chiral analytical HPLC (H): t R =2.0 min. 1 H NMR (400MHz, MeOD) δ:8.41(s, 1H), 8.16(d, J=8.0Hz, 1H), 7.76(d, J=7.9Hz, 1H), 7.69(t, J=7.6Hz, 1H), 7.60(dd, J1=6.7Hz, J 2=8.6Hz, 2H), 7.53(t, J=7.7Hz, 1H), 5.78(t, J=10.4Hz, 1H), 5.54(d, J=3.0Hz, 1H), 5.33(dd, J1=3.2Hz, J2 =10.8Hz, 1H), 4.57(s, 1H), 4.52(d, J=9.9Hz, 1H), 4.25-4.08(m, 3H), 3.33(m), 3.29-3.06(m, 3H), 2.68(dd , J1=1.8Hz, J2=14.7Hz, 1H), 2.10(s, 3H), 2.07(s, 3H), 1.92-1.77(m, 2H), 1.75(s, 3H), 1.35-1.09(m, 2H).

[0170] Intermediate 8S (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-(((S)-(4-hydroxypiperidin-4-yl)(2-(trifluoromethyl)phenyl)methyl)thio)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diyl diacetate (Intermediate 8S) The title compound, S-epimer, is prepared from 2-(trifluoromethyl)benzyl bromide and 2-quinolinethiol following the procedure described for intermediate 8R (the S-epimer is obtained by chiral separation in step 4.) to give a white solid (0.18 g). LC-MS (A): R =0.87min;[M+H] + : 761.01. Chiral analytical HPLC (H): t R =2.91min.

[0171] Intermediate 8A (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-(((3-hydroxyazetidin-3-yl)(2-(trifluoromethyl)phenyl)methyl)thio)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diyl diacetate Intermediate 8A is prepared by the reaction of 2-((2-(trifluoromethyl)benzyl)thio)quinoline and 1,1,1-trichloro-2-methylpropan-2-yl 3-oxoazetidine-1-carboxamide. Prepared from the carboxylate analogously to intermediate 8 to give a light yellow solid (0.11 g). LC-MS (A) tR =0.84min, [M+H] + =733.18.

[0172] Intermediate 9 (2R,3R,4S,5R,6S)-2-(Acetoxymethyl)-4-azido-6-((2-hydroxy-2-methyl-1-(2-(trifluoromethyl)phenyl)propyl)thio)tetrahydro-2H-pyran-3,5-diyl diacetate 1. 1-Mercapto-2-methyl-1-(2-(trifluoromethyl)phenyl)propan-2-ol 1-Mercapto-2-methyl-1-(2-(trifluoromethyl)phenyl)propan-2-ol is synthesized from 1-(bromomethyl)-2-(trifluoromethyl)benzene and acetone according to the procedure described for the synthesis of 1-mercapto-2-methyl-1-phenylpropan-2-ol (intermediate 5). LC-MS (A) t R =0.93min, [M+H] + = no mass spectrometry. 1 H NMR (400MHz, CDCl3) δ:8.04(d, J=8.0Hz, 1H), 7.64(d, J=8.3Hz, 1H), 7.55(t, J=7.8Hz, 1H), 7.37(t, J=7 .8Hz, 1H), 4.37(d, J=7.3Hz, 1H), 2.06(d, J=6.8Hz, 1H), 1.48(s, 3H), 1.12(s, 3H).

[0173] 2. (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-4-azido-6-((2-hydroxy-2-methyl-1-(2-(trifluoromethyl)phenyl)propyl)thio)tetrahydro-2H-pyran-3,5-diyl diacetate (Intermediate 9) To a solution of intermediate 2 (0.71 g, 1.8 mmol) in EA (30.0 mL) is added TBAB (0.14 g, 0.45 mmol, 0.25 eq), aq. 1M Na2CO3 (15.0 mL) and 1-mercapto-2-methyl-1-(2-(trifluoromethyl)phenyl)propan-2-ol (0.45 g, 1.8 mmol, 1.0 eq). The reaction mixture is stirred at rt for 72 h and then diluted with EA, followed by water and brine. The phases are separated and the aqueous layer is extracted with EA (3x). The organic layers are combined, dried over MgSO4, filtered and the solvent removed in vacuo to give an orange foam. The crude is purified by Flash Master (Büchi, product loaded into isolute, 20 g column, 15 mL / min, 15 mL fractions, Hept / EA 100 / 0 to 7 / 3, Rf(Hept / EA 7 / 3)=0.17, stained with KMnO4) to give the title compound as a colorless oil (0.67 g, 66%). LC-MS (A):t R =1.02min;[M+H] + :564.18.

[0174] Intermediate 10 ((2R,3R,4S,5R,6R)-3-acetoxy-6-bromo-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)methyl acetate 1. (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-4-azido-6-(methylthio)tetrahydro-2H-pyran-3,5-diyl diacetate To a solution of intermediate 1 (14.50 g, 38.8 mmol) in DCM (300.0 mL) at rt, TMS-SMe (15.0 mL, 103.00 mmol, 2.6 eq) and molecular sieves (30.0 g, 4 Å) are added followed by TMS-OTf (6.5 mL, 35.3 mmol, 0.9 eq). The reaction mixture is stirred at rt for 15 h and then quenched with aq.sat.Na2CO3. The resulting solution is stirred for 1 h and then diluted with DCM and then with water. The phases are separated and the aqueous phase is extracted with DCM (2x). The organic layers are combined, dried over Na2SO4, filtered and the solvent is removed under vacuum to give an oil. The crude product is Flash purified by HPLC. Master (ISCO, product added to isolute, 220g column, Hept / EA 100 / 0 to 60 / 40) to give the title compound as a colourless oil (13.5 g, 96%). LC-MS (A): R =0.85min;[M+H] + :314.16.

[0175] 2. (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-(methylthio)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diyl diacetate To a solution of (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-4-azido-6-(methylthio)tetrahydro-2H-pyran-3,5-diyl diacetate (14.02 g, 38.8 mmol) in DMF (200.0 mL) is added 3,4,5-trifluorophenylacetylene (6.24 g, 38.8 mmol, 1.0 eq), CuI (2.22 g, 11.6 mmol, 0.3 eq) and DIPEA (19.9 mL, 116.0 mmol, 3.0 eq). The reaction mixture is stirred at 45 °C for 1 h, cooled to rt, diluted with EA and filtered. The organic layer is washed with aq.sat.NH4Cl, then brine, dried over Na2SO4, filtered and the solvent removed in vacuo to give the title compound as a beige solid (21.24 g, >99%) which is used without further purification. LC-MS (A):t R =0.98min;[M+H] + :517.81.

[0176] 3. (2R,3R,4S,5R,6S)-2-(hydroxymethyl)-6-(methylthio)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol NaOMe (3.05 g, 56.5 mmol, 1.5 eq) is added at rt to a suspension of (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-(methylthio)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diyl diacetate (21.24 g, 37.7 mmol) in MeOH (400.0 mL) and stirring is continued at rt for 48 h. The reaction mixture is neutralized (until pH=6-7) by adding DOWEX 50WX2, filtered, the solvent is removed under vacuum and the crude product is recovered, which is dissolved in EA. The organic layer is washed with water, dried over Na2SO4, filtered and the solvent is removed under vacuum to give a light brown solid (17.12 g, >99%) which is used without further purification. LC-MS(A):t R =0.65min;[M+H] + :392.12.

[0177] 4. (4aR,6S,7R,8R,8aR)-2,2-dimethyl-6-(methylthio)-8-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)hexahydropyrano[3,2-d][1,3]dioxin-7-ol 2,2-Dimethoxypropane (14.1 mL, 115.0 mmol, 3.0 eq) and CSA (4.38 g, 18.9 mmol, 0.5 eq) are added to a solution of (2R,3R,4S,5R,6S)-2-(hydroxymethyl)-6-(methylthio)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol (14.76 g, 37.7 mmol) in DMF (200.0 mL). The reaction mixture is heated at 50° C. for 1 h, cooled to rt and quenched with EA and brine. The phases are separated and the aqueous layer is extracted with EA (3×). The organic layers are combined, dried over Na2SO4, filtered and the solvent removed in vacuo to give the crude material which is purified on a Flash Master (ISCO, product loaded onto isolute, 120 g column, Hept / EA 95 / 5 to 55 / 45) to give the title compound as a beige solid (9.85 g, 61%). LC-MS (A):t R =0.91min;[M+H] + :432.14.

[0178] 5. 1-((4aR,6S,7R,8S,8aR)-7-Methoxy-2,2-dimethyl-6-(methylthio)hexahydropyrano[3,2-d][1,3]dioxine-8- To a solution of (4aR,6S,7R,8R,8aR)-2,2-dimethyl-6-(methylthio)-8-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)hexahydropyrano[3,2-d][1,3]dioxin-7-ol (9.85 g, 22.8 mmol) in DMF (200.0 mL) is added molecular sieves (4 Å) followed by Ag2O (26.46 g, 114.00 mmol, 5.0 eq). The reaction mixture is stirred at rt for 15 min, then MeI (7.34 mL, 114.0 mmol, 5.0 eq) is added and stirring is continued at rt for 15 h. The mixture is filtered, diluted with EA then water, the phases are separated and the aqueous layer is extracted with EA (2x). The organic layers are combined, dried over Na2SO4, filtered and the solvent is removed in vacuo to give a beige solid which is purified by Flash Master (ISCO, product loaded into isolute, 120 g column, Hept / EA 90 / 10 to 30 / 70 Rf(Hept / EA 1 / 1)=0.52, UV active). The title compound is obtained as a white powder (6.18 g, 61%). LC-MS (A):t R =0.99min;[M+H] + :446.21.

[0179] 6. (2R,3R,4S,5R,6S)-2-(hydroxymethyl)-5-methoxy-6-(methylthio)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol To a solution of 1-((4aR,6S,7R,8S,8aR)-7-methoxy-2,2-dimethyl-6-(methylthio)hexahydropyrano[3,2-d][1,3]dioxin-8-yl)-4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazole (1.55 g, 2.96 mmol, 1.0 eq) in THF (35.0 mL) is added a mixture of AcOH / water (1:1, 100.0 mL) and the solution is stirred at 65 °C for 15 h. The reaction mixture is diluted with EA, then aq.sat.NaHCO3. The layers are separated and the aqueous phase is extracted with EA (2x). The organic layers are combined, dried over Na2SO4, filtered and the solvent is removed in vacuo to recover the title compound as a beige solid (1.63 g, >99%) which is used without further purification. LC-MS(A):t R =0.80min;[M+H] + :405.96.

[0180] 7. ((2R,3R,4S,5R,6S)-3-acetoxy-5-methoxy-6-(methylthio)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)methyl acetate To a cooled (0° C.) solution of (2R,3R,4S,5R,6S)-2-(hydroxymethyl)-5-methoxy-6-(methylthio)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol (5.64 g, 13.9 mmol, 1.0 eq) in pyridine (99.0 mL) is added AcO (8.0 mL, 83.4 mmol, 6.0 eq). The reaction mixture is stirred at rt for 2 h and then concentrated under reduced pressure. The resulting residue is partitioned between EA and water, the phases are separated, the organic layer is washed with water, dried over Na2SO4, filtered and the solvent is removed in vacuo to give a beige solid. Purification by Flash master (ISCO, product loaded into isolute, 1200 g column, Hept / EA 95 / 5 to 30 / 70) gave the title compound as a white solid (5.66 g, 83%). LC-MS (A):t R =1.00min;[M+H] +:490.07.

[0181] 8. ((2R,3R,4S,5R,6RS)-3-acetoxy-6-bromo-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)methyl acetate (Intermediate 10) NBS (4.00 g, 22.4 mmol, 2.0 eq) was dissolved in 100 mL of 10 ... Add 5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)methyl acetate (5.66 g, 11.2 mmol) to a solution in DCM (165.0 mL). The reaction mixture is stirred at rt for 15 h, quenched with water and diluted with DCM. Separate the layers and extract the aqueous layer with DCM (2x). Combine the organic layers, wash with brine, dry over Na2SO4, filter and remove the solvent in vacuo to give the crude. Purification by Flash Master (ISCO, product loaded into isolute, 80 g column, Hept / EA 100 / 0 to 30 / 70) gave intermediate 10 as a beige solid (1.72 g, 29%). LC-MS (A):t R =1.01min;[M+H] + :524.02. 1 H NMR (500 MHz, CDCl3) δ:7.82(s, 1H), 7.45(dd, J1=7.3Hz, J2=7.3Hz, 2H), 6.87(d, J=3.6Hz, 1H), 5. 60(d, J=2.3Hz, 1H), 5.01(dd, J1=10.7Hz, J2=2.9Hz, 1H), 4.63(t, J=6.6Hz, 1 H), 4.48(dd, J1=10.7Hz, J2=3.6Hz, 1H), 4.24(dd, J1=11.3Hz, J2=6.4Hz, 1H) , 4.18(dd, J1=11.3Hz, J2=6.4Hz, 1H), 3.39(s, 3H), 2.10(s, 3H), 2.08(s, 3H).

[0182] Intermediate 11 ((2R,3R,4S,5R,6R)-3-acetoxy-6-bromo-5-ethoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)methyl acetate Intermediate 11 is prepared from intermediate 1 in the same manner as intermediate 10. In step 5, EtI is added to the reaction mixture to give intermediate 11 as a white powder. LC-MS (A): R =1.03min;[M+H] + :538.15.

[0183] Intermediate 12 ((2R,3R,4S,5R,6S)-3-acetoxy-6-(((4-hydroxypiperidin-4-yl)(2-(trifluoromethyl)phenyl)methyl)thio)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)methyl acetate Intermediate 12 is prepared from (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-(((4-hydroxy-1-(((1,1,1-trichloro-2-methylpropan-2-yl)oxy)carbonyl)piperidin-4-yl)(2-(trifluoromethyl)phenyl)methyl)thio)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diyl diacetate (Intermediate 8, step 3.).

[0184] 1. 2,2,2-Trichloroethyl 4-hydroxy-4-((((4aR,6S,7R,8S,8aR)-7-methoxy-2,2-dimethyl-8-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)hexahydropyrano[3,2-d][1,3]dioxin-6-yl)thio)(2-(trifluoromethyl)phenyl)methyl)piperidine-1-carboxylate 2,2,2-Trichloroethyl 4-hydroxy-4-((((4aR,6S,7R,8S,8aR)-7-methoxy-2,2-dimethyl-8-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)hexahydropyrano[3,2-d][1,3]dioxin-6-yl)thio)(2-(trifluoromethyl)phenyl)methyl)piperidine-1-carboxylate is obtained as a white powder in three steps starting from intermediate 8, step 3., following the procedure described for intermediate 10, steps 3-5. LC-MS (A) t R =1.25min, [M+H] + =891.07.

[0185] 2. ((2R,3R,4S,5R,6S)-3-acetoxy-6-(((4-hydroxypiperidin-4-yl)(2-(trifluoromethyl)phenyl)methyl)thio)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)methyl acetate (Intermediate 12) 1. To a solution of 2,2,2-trichloroethyl 4-hydroxy-4-((((4aR,6S,7R,8S,8aR)-7-methoxy-2,2-dimethyl-8-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)hexahydropyrano[3,2-d][1,3]dioxin-6-yl)thio)(2-(trifluoromethyl)phenyl)methyl)piperidine-1-carboxylate (0.16 g, 0.18 mmol) in THF (10.0 mL) and AcOH (0.15 mL) is added zinc (0.12 g, 1.85 mmol, 10.0 eq). The reaction mixture is stirred at rt for 15 h, filtered and partitioned between EA and water. The layers were separated, the aqueous layer was extracted with EA, and the organic layers were combined, washed with brine, dried over MgSO4, filtered, and the solvent removed in vacuo to give the title compound as a white solid (0.053 g, >99%) without further purification. LC-MS (A) t R =0.85min, [M+H] + =688.95.

[0186] Preparation of the Reference Example Reference Example 1 (2R,3R,4S,5R,6S)-2-(hydroxymethyl)-6-((2-methoxy-1-phenylethyl)thio)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol (2.30.100.OMe) 1. (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-((2-methoxy-1-phenylethyl)thio)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diyl diacetate To a solution of intermediate 3 (0.088 g, 0.15 mmol) in EA (1.65 mL) is added TBAB (0.012 g, 0.037 mmol, 0.25 eq), aq. 1M Na2CO3 (0.8 mL) and 2-methoxy-1-phenylethane-1-thiol (0.038 g, 0.225 mmol, 1.5 eq). The reaction mixture is stirred at rt for 17 and diluted with EA, then with water and brine. The phases are separated and the aqueous layer is extracted with EA (3x). The organic layers are combined, dried over MgSO4, filtered and the solvent is removed under vacuum. The crude material is purified by preparative HPLC / MS (II) to give the title compound as a white solid (0.019 g, 20%). LC-MS (A):t R =1.12min;[M+H] + :638.03.

[0187] 2. (2R,3R,4S,5R,6S)-2-(hydroxymethyl)-6-((2-methoxy-1-phenylethyl)thio)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol (2.30.100.OMe) (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-((2-methoxy-1-phenylethyl)thio)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diyl diacetate (0.019 g, 0.029 mmol) is dissolved in MeOH (1.4 mL) and NaOMe (0.003 g, 0.0588 mmol, 2.0 eq) is added. The reaction mixture is stirred at rt for 17 h. The mixture is neutralized with HCl 1N, concentrated under vacuum and purified by preparative HPLC / MS (I) to give the title compound as a white solid (0.01, 67%). LC-MS (A):t R =0.85min;[M+H] + :512.26.

[0188] The following examples are described for Reference Example 1 using thiol and intermediate 3 as starting materials. The LC-MS and Gal-3 inhibition data are shown in Table 1 below. The LC-MS conditions used were LC-MS(A).

[0189] [Table 6] Preparation of Compounds of Structure 1 and Examples Thereof Example 2.30.100R. (2S,3R,4S,5R,6R)-2-(((R)-2-hydroxy-1-phenylethyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol 1. Ethyl (R)-2-((dimethylcarbamothioyl)thio)-2-phenylacetate To a solution of ethyl S-mandelate (1.0 g, 5.55 mmol) in toluene (50.0 mL) is added PPh3 (2.9 g, 11.1 mmol, 2.0 eq) and Ziram (1.2 g, 3.9 mmol, 0.7 eq). The suspension is cooled to 2-4 °C, DEAD (40% in toluene, 5.05 mL, 11.1 mmol, 2.0 eq) is added dropwise and the reaction mixture is stirred at rt for 17 h. The solvent is removed under vacuum and the crude product is directly purified by silica gel column chromatography eluting with (Hept / EA 4 / 1) to give ethyl (R)-2-((dimethylcarbamothioyl)thio)-2-phenylacetate as an oil (1.3 g, 81%). LC-MS (B):t R =1.04min;[M+H] + :284.21.

[0190] 2. (R)-2-Mercapto-2-phenylethan-1-ol To a cooled solution (0°) of ethyl (R)-2-((dimethylcarbamothioyl)thio)-2-phenylacetate (1.27 g, 4.48 mmol) in Et2O (50.0 mL) is added LAH (2 M in THF, 4.5 mL, 8.96 mmol, 2.0 eq). The cooling bath is removed, the reaction mixture is allowed to warm to rt and heated to reflux for 1 h. The suspension is cooled to rt, carefully quenched with water and Et2O and the pH is adjusted to 4 by adding aq. 2M HCl. The phases are separated, the aqueous phase is extracted with Et2O (2x), the organic layers are combined, dried over MgSO4, filtered and the solvent is removed under vacuum. The crude is purified by preparative HPLC / MS (II) to give (R)-2-mercapto-2-phenylethan-1-ol as an oil (0.4 g, 57%). LC-MS(B):t R =072min;[M+H] + :Not observed. 1 H NMR (400MHz, CDCl3) δ:7.38(m, 4H), 7.30-7.33(m, 1H), 4.13(q, J=7.3Hz, 1H), 3.96 (dd, J1=6.5Hz, J2=11.3Hz, 1H), 3.84(dd, J1=7.5Hz, J2=11.0Hz, 1H), 2.03(s, 1H), 2.00(d, J=7.5Hz, 1H).

[0191] 3. (2S,3R,4S,5R,6R)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(((R)-2-hydroxy-1-phenylethyl)thio)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,5-diol (2.30.100R.) To a solution of intermediate 3 (0.8 g, 1.46 mmol) in EA (32.0 mL) is added TBAB (0.117 g, 0.364 mmol, 0.25 eq) and aq. 1M Na2CO3 (16.0 mL). The reaction mixture is stirred at rt for 16 h, diluted with EA, the layers are separated and the aqueous layer is extracted with EA. The organic layers are combined, dried over MgSO4 and the solvent is removed under vacuum. Purification by preparative HPLC / MS (I) afforded the desired acetyl-protected thioglycoside as an oil (0.085 g, 9%). LC-MS (B):t R =1.03min;[M+H] + :623.95.

[0192] The above thioglycoside is dissolved in a 0.02M solution of NaOMe in MeOH and stirred at rt for 2 h. The solvent is removed in vacuo and the residue is purified by preparative HPLC / MS (I) to give the title compound (0.0041 g, 6%) as a solid. LC-MS (B): R =0.77min;[M+H] + :498.17.

[0193] Example 1.30.101. (2S,3R,4S,5R,6R)-2-((1-(2-bromophenyl)-2-hydroxyethyl)thio)-4-(4-(3-fluorophenyl)-1H-1,2,3-triazol-1-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,5-diol 1. Ethyl 2-(2-bromophenyl)-2-diazoacetate Ethyl-(2-bromophenyl)acetate (1.0 g, 4.11 mmol) and p-ABSA (1.28 g, 5.35 mmol, 1.3 eq) are dissolved in MeCN (20.0 mL) and the solution is cooled to 0 °C. DBU (0.77 mL, 5.35 mmol, 1.45 eq) is added and stirring is continued at 0 °C. After 20 min the cooling bath is removed and the reaction mixture is stirred at rt for 15 h. The mixture is diluted with DCM, the organic phase is washed with water, dried over MgSO4, filtered and the solvent is removed under vacuum. The residue is purified by silica gel column chromatography eluting with (Hept / EA 4 / 1) to give ethyl 2-(2-bromophenyl)-2-diazoacetate (1.0 g, 90%) as an oil. LC-MS (C):t R =1.09min;[M+H] + : No mass spectrometry.

[0194] 2. Ethyl-2-(2-bromophenyl)-2-hydroxyacetate Ethyl 2-(2-bromophenyl)-2-diazoacetate (1.0 g, 3.72 mmol) is added to 0.5 M HClO4 in dioxane / water 6 / 4. After 2 h at rt, the reaction mixture is poured into water and extracted with DCM (2x), the organic layers are combined, dried over MgSO4, filtered and the solvent is removed under vacuum. The residue is purified by preparative HPLC / MS (II) to give ethyl-2-(2-bromophenyl)-2-hydroxyacetate as an oil (0.69 g, 72%). LC-MS (C):t R =0.80min;[M+H] + :258.90.

[0195] 3. (2S,3R,4S,5R,6R)-2-((1-(2-bromophenyl)-2-hydroxyethyl)thio)-4-(4-(3-fluorophenyl)-1H-1,2,3-triazol-1-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,5-diol (1.30.101.) The last three steps are carried out according to the procedure described for Example 1.30.100R to give the title compound (1.30.101.) as a solid (0.065 g). LC-MS (C): R =0.74min;[M+H] + :539.92.

[0196] Example 2.30.105. (2S,3R,4S,5R,6R)-2-((2-hydroxy-1-(2-isopropylphenyl)ethyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol 1. Methyl 2-(2-bromophenyl)-2-hydroxyacetate The title compound is prepared from methyl-(2-bromophenyl)acetate following the procedure (Steps 1 and 2) described in Example 1.30.101. LC-MS (C): R =0.71min;[M+H] + :244.86.

[0197] 2. Methyl 2-acetoxy-2-(2-bromophenyl)acetate Methyl 2-(2-bromophenyl)-2-hydroxyacetate (2.46 g, 10.0 mmol) is dissolved in pyridine (20.0 mL). Acetic anhydride (1.42 mL, 15.1 mmol, 1.5 eq) is added and the reaction mixture is stirred at rt for 72 h. The solvent is removed in vacuo to give the title compound (2.99, >99%) without further purification. LC-MS (C):t R =0.93min;[M+H] + :288.82.

[0198] 3. Methyl 2-acetoxy-2-(2-(prop-1-en-2-yl)phenyl)acetate Methyl 2-acetoxy-2-(2-bromophenyl)acetate (1.50 g, 5.22 mmol) and isopropenylboronic acid pinacol ester (1.55 mL, 7.84 mmol, 1.5 eq) are dissolved in dioxane (50.0 mL) and water (12.0 mL). K2CO3 and Pd(Ph3)4 are added and the reaction mixture is heated at 100 °C for 17 h. The mixture is cooled to rt, diluted with EA, the layers are separated, the organic layer is washed with water, dried over MgSO4, filtered and the solvent is removed under vacuum. The residue is purified by silica gel column chromatography eluting with (Hept / EA 4 / 1) to give methyl 2-acetoxy-2-(2-(prop-1-en-2-yl)phenyl)acetate (0.96 g, 74%). LC-MS (C) t R = 1.0 min; [M+H] + :248.99.

[0199] 4. Methyl 2-acetoxy-2-(2-isopropylphenyl)acetate Methyl 2-acetoxy-2-(2-(prop-1-en-2-yl)phenyl)acetate (0.96 g, 3.87 mmol) is dissolved in THF. Palladium on carbon is added, followed by MeOH, and the reaction mixture is subjected to hydrogenation at 5 bar for 72 h. The suspension is filtered (glass microfiber) and the solvent is removed under vacuum to give the title compound (0.93, 96%) without further purification. LC-MS (C) t R =1.03min;[M+H] + :250.08.

[0200] 5. Methyl 2-hydroxy-2-(2-isopropylphenyl)acetate Methyl 2-acetoxy-2-(2-isopropylphenyl)acetate is dissolved in 0.02M NaOMe in MeOH (20.0 mL) and stirred at rt for 1 h. The reaction mixture is poured into water and extracted with EA (2x). The organic layers are combined, dried over MgSO4, filtered and the solvent removed in vacuo to give the title compound (0.71 g, 92%) without further purification. LC-MS (C) t R =0.83min;[M+H] + : No mass spectrometry.

[0201] 6. Methyl 2-bromo-2-(2-isopropylphenyl)acetate Methyl 2-hydroxy-2-(2-isopropylphenyl)acetate (0.715g To a solution of 2-bromo-2-(2-isopropylphenyl)-1,3-dihydro-1,4-trimethyl-1,5-triphenyl-2,4-dihydro-1,5-trimethyl-1,5-triphenyl-2,5-trimethyl-1,6-dihydro-1,7-triphenyl-2,6-dihydro-1,7-trimethyl-1,5-triphenyl-2,7-dihydro-1,5-trimethyl-1,6-dihydro-1,7-trimethyl-1,5-triphenyl-2,5-dihydro-1,5-trimethyl-1,6-dihydro-1,7 ... R =0.63min;[M+H] + :270.04.

[0202] 7. Methyl 2-(acetylthio)-2-(2-isopropylphenyl)acetate To a solution of methyl 2-bromo-2-(2-isopropylphenyl)acetate (0.49 g, 1.81 mmol) in acetone (10.0 mL) potassium thioacetate (0.41 g, 3.61 mmol, 2.0 eq) is added and the reaction mixture is stirred at rt for 1 h. The mixture is filtered, diluted with EA and washed with water and brine. The organic layer is dried over MgSO4, filtered and the solvent removed in vacuo to give the title compound (0.63 g, >99%) without further purification. LC-MS (C) t R =1.10min;[M+H] + :267.01.

[0203] 8. 2-Mercapto-2-phenylethan-1-ol Methyl 2-(acetylthio)-2-(2-isopropylphenyl)acetate (0.4 g, 1.5 mmol) is dissolved in THF (10.0 mL) and the solution is cooled to 0° C. LAH (1.5 mL of a 2 M solution in THF, 3.0 mmol, 2.0 eq) is added dropwise. After the addition of LAH is complete, the cooling bath is removed immediately and the reaction is allowed to reach rt and stirred at rt for 1 h. The mixture is quenched with aq. 1 M HCl and extracted with EA (2×). The organic layers are combined, dried over MgSO4, filtered, the solvent is removed in vacuo and the crude is purified by preparative HPLC / MS (II) to give the title compound (0.174, 59%). LC-MS (C) t R =0.92min;[M+H] + : No mass spectrometry.

[0204] 9. (2S,3R,4S,5R,6R)-2-((2-hydroxy-1-(2-isopropylphenyl)ethyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol (2.30.105.) A 1M aqueous solution of K2CO3 (5.0 mL) is added at rt to a solution of (intermediate 3) (0.20 g, 0.36 mmol) in EA (10.0 mL). The reaction mixture is stirred at rt for 52 h, diluted with EA and washed with water. The organic layer is dried over MgSO4, filtered, the solvent is removed in vacuo and the crude is purified by preparative HPLC / MS (I) to give the thioglycoside. LC-MS (A):t R = 1.13 min; [M+H] + :666.00.

[0205] The above thioglycoside is dissolved in a 0.01M NaOMe solution in MeOH and stirred at rt for 40 min. The solvent is removed in vacuo and the residue is purified by preparative HPLC / MS (I) to give the title compound (0.023 g, 12%). LC-MS (B): R =0.89min;[M+H] + :540.01.

[0206] The LC-MS and Gal-3 inhibition data for Examples 2.30.100R. through 2.30.105. are set forth below in Table 2. The LC-MS conditions used were LC-MS(C).

[0207] [Table 7] Example 2.31.102. (2S,3R,4S,5R,6R)-2-((2-hydroxy-2-methyl-1-(o-tolyl)propyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol 1. (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-((2-hydroxy-2-methyl-1-(o-tolyl)propyl)thio)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diyl diacetate To a solution of intermediate 3 (0.15 g, 0.27 mmol) in EA (3.0 mL) is added TBAB (0.022 g, 0.068 mmol, 0.25 eq), aq. 1M Na2CO3 (2.0 mL) and intermediate 5 (0.161 g, 0.41 mmol, 1.5 eq). The reaction mixture is stirred at rt for 72 h and diluted with EA, then with water and brine. The phases are separated and the aqueous layer is extracted with EA (3x). The organic layers are combined, dried over MgSO4, filtered and the solvent is removed in vacuo to give a yellow oil. The crude material is purified by preparative HPLC / MS (I) to give a colourless oil (0.066 g, 36%) as the title compound. LC-MS (A) t R =1.08min;[M+H] + :666.03.

[0208] 2. ((2S,3R,4S,5R,6R)-2-((2-hydroxy-2-methyl-1-(o-tolyl)propyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol (2.31.102.) (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-((2-hydroxy-2-methyl-1-(o-tolyl)propyl)thio)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diyl diacetate (0.066 g, 0.10 mmol) is dissolved in MeOH (2.0 mL) and NaOMe (0.5 M in MeOH, 0.60 mL, 0.29 mmol, 3.0 eq) is added. The reaction mixture is stirred at rt for 17 h, the solvent is removed under vacuum and the residue is dissolved in MeCN and then purified by preparative HPLC / MS (I) to give the title compound as a white solid (0.024 g, 44%). LC-MS (A) t R =0.86min;[M+H] + :540.04.

[0209] Example 2.31.102R. (2S,3R,4S,5R,6R)-2-(((R)-2-hydroxy-2-methyl-1-(o-tolyl)propyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol Separation of the epimers of Example 2.31.102. (0.02 g) by chiral preparative HPLC (III) afforded the title compound (0.09 g) as a white solid. R =1.8min.

[0210] Example 2.31.102S. (2S,3R,4S,5R,6R)-2-(((S)-2-hydroxy-2-methyl-1-(o-tolyl)propyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol Separation of the epimers of Example 2.31.102. (0.02 g) by chiral preparative HPLC (III) afforded the title compound (0.05 g) as a white solid. R =1.23min.

[0211] Example 2.31.118R. (2S,3R,4S,5R,6R)-2-(((R)-2-hydroxy-2-methyl-1-(2-(trifluoromethyl)pyridin-3-yl)propyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol The title compound is prepared from Intermediate 3 and Intermediate 6R according to the procedure (Steps 1 and 2) described for Example 2.31.102. as a white solid (0.145 g). LC-MS (A) t R =0.79min;[M+H] + :595.05.

[0212] Example 2.31.118S. (2S,3R,4S,5R,6R)-2-(((S)-2-hydroxy-2-methyl-1-(2-(trifluoromethyl)pyridin-3-yl)propyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol The title compound is prepared from Intermediate 3 and Intermediate 6S according to the procedure (Steps 1 and 2) described for Example 2.31.102. as a white solid (0.135 g). LC-MS (A) t R =0.8min;[M+H] + :595.21.

[0213] The following examples are prepared starting from o-substituted benzyl bromides, the corresponding dimethyl or diethyl ketones and intermediate 3 following the procedure described for example 2.31.102. The LC-MS and Gal-3 inhibition data are listed in Table 3 below. The LC-MS conditions used were LC-MS(A). Chiral analytical HPLC(I) (conditions and retention times) and inhibition data for epimers R and S of selected examples are also listed.

[0214] [Table 8]

[0215] [Table 9]

[0216] [Table 10]

[0217] [Table 11]

[0218] [Table 12]

[0219] [Table 13]

[0220] [Table 14]

[0221] [Table 15]

[0222] [Table 16] * The epimers can be obtained from chiral separation of the corresponding thioquinoline intermediates, similar to the procedures described for Example 2.31.118R. and Example 2.31.118S.

[0223] The following examples are prepared starting from 1-(bromomethyl)-2-(trifluoromethyl)benzene, the corresponding aldehyde and intermediate 3 following the procedure described for 2.31.102. The LC-MS and Gal-3 inhibition data are listed below in Table 4. The LC-MS conditions used were LC-MS(A).

[0224] [Table 17] Example 2.33.112. (2S,3R,4S,5R,6R)-2-(((3,3-difluoro-1-hydroxycyclobutyl)(2-(trifluoromethyl)phenyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol 1. 2-((2-(trifluoromethyl)benzyl)thio)quinoline DBU (1.8 mL, 11.8 mmol, 1.0 eq) is added to a solution of 2-quinolinethiol (2.0 g, 11.8 mmol, 1.0 eq) in toluene (40.0 mL) at rt. The reaction mixture is stirred at rt for 30 min. 2-(Trifluoromethyl)benzyl bromide (2.8 g, 11.8 mmol) is added and the solution is stirred at rt for 48 h. The reaction mixture is concentrated under reduced pressure to give a yellow solid. Trituration with Hept gives a solid which is removed by filtration and the remaining Hept is concentrated under vacuum to give an orange solid as 2-((2-(trifluoromethyl)benzyl)thio)quinoline (3.61 g, 96%). LC-MS (A) t R = 1.16 min; [M+H] + :320.08.

[0225] 2. 3,3-Difluoro-1-((quinolin-2-ylthio)(2-(trifluoromethyl)phenyl)methyl)cyclobutan-1-ol To a cooled (-78°C) solution of 2-((2-(trifluoromethyl)benzyl)thio)quinoline (1.0 g, 3.1 mmol) in THF (30.0 mL) at -78°C, n-BuLi (1.6 M in hexanes, 4.7 mmol, 1.5 eq) is added and the reaction mixture is stirred at -78°C for 60 min. 3,3-difluoro-cyclobutanone (0.41 g, 3.7 mmol, 1.2 eq) in THF (15.0 mL) is added and the reaction mixture is warmed to -50°C for 2 h, then cooled to -78°C and n-BuLi (1.6 M in hexanes, 3.0 mL, 4.68 mmol, 1.5 eq) is added again followed by 3,3-difluoro-cyclobutanone (0.41 g, 3.76 mmol, 1.2 eq). The reaction mixture is allowed to warm to rt for 17 h, quenched with aq.sat.NH4Cl, extracted with EA, the layers are separated and the aqueous layer is extracted with EA (3x). The organic layers are combined, washed with brine, dried over MgSO4, filtered and the solvent is removed in vacuo to give a brown oil. The crude is purified by preparative HPLC-MS (I) to give a brown solid as the title compound (0.23 g, 18%). LC-MS (A):t R =1.12min;[M+H] + :426.1.

[0226] 3. 3,3-Difluoro-1-(mercapto(2-(trifluoromethyl)phenyl) )Methyl)cyclobutan-1-ol To a solution of 3,3-difluoro-1-((quinolin-2-ylthio)(2-(trifluoromethyl)phenyl)methyl)cyclobutan-1-ol (0.24 g, 0.55 mmol, 1.0 eq) in glacial acetic acid (10.0 mL) is added sodium cyanoborohydride (0.22 g, 3.33 mmol, 6.0 eq) and stirring is continued at rt for 17 h. The reaction mixture is quenched by addition of water (5.0 mL), stirring is continued at rt for 1 h, diluted with DCM, the layers are separated and the aqueous layer is extracted with DCM. The organic layers are combined, washed with brine, dried over MgSO4 and the solvent is removed in vacuo to give a yellow oil. The crude material is purified by Flash Master (Büchi, product is added to isolute and dried, 10 g column, 15 mL / min, 10 mL fractions, Hept / EA 100 / 0 to 1 / 1, Rf(Hept / EA 1 / 1)=0.38) to give 3,3-difluoro-1-(mercapto(2-(trifluoromethyl)phenyl)methyl)cyclobutan-1-ol as a yellow oil (0.13 g, 77%). LC-MS (A):t R =0.97min;[M+H] + :Not observed.

[0227] 4. (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-(((3,3-difluoro-1-hydroxycyclobutyl)(2-(trifluoromethyl)phenyl)methyl)thio)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diyl diacetate To a solution of intermediate 3 (0.20 g, 0.36 mmol) in EA (6.0 mL) is added 3,3-difluoro-1-(mercapto(2-(trifluoromethyl)phenyl)methyl)cyclobutan-1-ol (0.13 g, 0.43 mmol, 1.2 eq) and TBAB (0.03 g, 0.09 mmol, 0.25 eq) followed by aq 1M Na2CO3 (3.0 mL). The reaction mixture is stirred at rt for 72 h then diluted with EA, followed by water and brine. The phases are separated and the aqueous layer is extracted with EA (3x). The organic layers are combined, dried over MgSO4, filtered and the solvent removed in vacuo to give a brown oil which is purified by preparative HPLC / MS (I) to give the title compound as a beige oil (0.27 g, 96%). LC-MS (A):t R =1.12min;[M+H] + :768.19.

[0228] 5. (2S,3R,4S,5R,6R)-2-(((3,3-difluoro-1-hydroxycyclobutyl)(2-(trifluoromethyl)phenyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol (2.33.112.) (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-(((3,3-difluoro-1-hydroxycyclobutyl)(2-(trifluoromethyl)phenyl)methyl)thio)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diyl diacetate (0.27 g, 0.35 mmol, 1.0 eq) is dissolved in MeOH (4.0 mL) and K2CO3 (0.09 g, 0.07 mmol, 0.2 eq) is added at rt. The reaction mixture is stirred at rt for 48 h, then diluted with MeCN, then with water, and the mixture is directly purified by preparative HPLC / MS (I) to give the title compound as a white solid (0.12 g, 52%). LC-MS (A):t R =0.94min;[M+H] + :642.04.

[0229] Example 2.33.112R. (2S,3R,4S,5R,6R)-2-(((R)-(3,3-difluoro-1-hydroxycyclobutyl)(2-(trifluoromethyl)phenyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2 ,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol [1,3-di-deoxy-1-((3,3-difluoro-1-hydroxy-cyclobutan-1-yl)-(2-(trifluoromethyl)phenyl)methyl-(R)-thio)-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-β-D-galactopyranoside] Separation of the epimers of Example 2.33.112. (0.116 g) by chiral preparative HPLC (IV) afforded the title compound (0.038 g) as a white solid. R =1.7min.

[0230] Example 2.33.112S. (2S,3R,4S,5R,6R)-2-(((S)-(3,3-difluoro-1-hydroxycyclobutyl)(2-(trifluoromethyl)phenyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol Separation of the epimers of Example 2.33.112. (0.116 g) by chiral preparative HPLC (IV) afforded the title compound (0.041 g) as a white solid. R =1.25min.

[0231] The following examples are prepared starting from o-substituted benzyl bromides, the corresponding cyclic ketones and intermediate 3 following the procedure described for example 2.33.112. LC-MS and Gal-3 inhibition data are listed in Table 5 below. The LC-MS conditions used were LC-MS(A). Chiral analytical HPLC (conditions and retention times) and inhibition data for epimers R and S of selected examples are also listed.

[0232] [Table 18]

[0233] [Table 19]

[0234] [Table 20]

[0235] [Table 21]

[0236]

Table 22

[0237]

Table 23

[0238]

Table 24

[0239]

Table 25

[0240]

Table 26

[0241]

Table 27

[0242]

Table 28

[0243]

Table 29

[0244]

Table 30

[0245]

Table 31

[0246] Example 2.40.119. (2S,3R,4S,5R,6R)-2-(((4-hydroxy-1-methylpiperidin-4-yl)(3,5,6-trimethylpyrazin-2-yl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol [1,3-di-deoxy-1-((1-methyl-4-hydroxy-piperidin-4-yl)-(3,5,6-trimethylpyrazin-2-yl)methyl-thio)-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-β-D-galactopyranoside] Example 2.40.119 is synthesized from intermediate 3 and intermediate 5. 1. (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-(((4-hydroxy-1-methylpiperidin-4-yl)(3,5,6-trimethylpyrazin-2-yl)methyl)thio)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diyl diacetate To a solution of intermediate 3 (0.80 g, 1.45 mmol) in EA (20.0 mL) is added intermediate 5 (0.480 g, 1.71 mmol, 1.17 eq), TBAB (0.12 g, 0.36 mmol, 0.25 eq) and aq. 1M Na2CO3 (10.0 mL) at rt. The reaction mixture is stirred at rt for 48 h and diluted with EA, then water, then brine. The phases are separated and the aqueous layer is extracted with EA (3x). The organic layers are combined, dried over MgSO4, filtered and the solvent is removed in vacuo to give a beige solid which is purified by preparative HPLC / MS (I) to give the title compound as a white solid (0.33 g, 30%). LC-MS (A):t R =0.82min;[M+H] + :751.27.

[0247] 2. (2S,3R,4S,5R,6R)-2-(((4-hydroxy-1-methylpiperidin-4-yl)(3,5,6-trimethylpyrazin-2-yl)methyl)thio)- 6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol (2.40.119.) K2CO3 (0.012 g, 0.09 mmol, 0.2 eq) is added to a solution of (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-(((4-hydroxy-1-methylpiperidin-4-yl)(3,5,6-trimethylpyrazin-2-yl)methyl)thio)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diyl diacetate (0.33 g, 0.44 mmol) in MeOH (3.0 mL) at rt. The reaction mixture is stirred at rt for 1 h, quenched by addition of MeCN and water, and the mixture is directly purified by preparative HPLC / MS (I) to give the title compound as a white solid (0.21 g, 75%). LC-MS (A):t R =0.63min;[M+H] + :625.06. 1 H NMR (400MHz, MeOD) δ:8.53(s, 1H), 7.65(dd, J1=7.6Hz, J2=7.6Hz, 2H), 4.79(dd, J1=2.8Hz, J2=10.7Hz, 1H), 4.55(s , 1H), 4.47(d, J=9.4Hz, 1H), 4.24(t, J=10.0Hz, 1H), 4.11(d, J=2.6Hz, 1H), 3.68(m, 3H), 2.71(d, J=11.5Hz, 1H), 2.64(s, 3H), 2.57-2.61(m, 1H), 2.53(s, 6H), 2.38-2.46(m, 2H), 2.30(s, 3H), 2.2 5(bd, J=13.8Hz, 1H), 1.85-1.94(m, 1H), 1.71-1.81(m, 1H), 1.45(dd, J1=1.5Hz, J2=13.7Hz, 1H).

[0248] Example 2.40.119R. (2S,3R,4S,5R,6R)-2-(((R)-(4-hydroxy-1-methylpiperidin-4-yl)(3,5,6-trimethylpyrazin-2-yl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol [1,3-di-deoxy-1-((1-methyl-4-hydroxy-piperidin-4-yl)-(3,5,6-trimethylpyrazin-2-yl)methyl-(R)-thio)-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-β-D-galactopyranoside] Separation of the epimers of Example 2.40.119. (0.017 g) by chiral preparative HPLC (V) afforded the title compound (0.006 g) as a white solid. R =1.7min.

[0249] Example 2.40.119S. (2S,3R,4S,5R,6R)-2-(((S)-(4-hydroxy-1-methylpiperidin-4-yl)(3,5,6-trimethylpyrazin-2-yl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol [1,3-di-deoxy-1-((1-methyl-4-hydroxy-piperidin-4-yl)-(3,5,6-trimethylpyrazin-2-yl)methyl-(S)-thio)-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-β-D-galactopyranoside] Separation of the epimers of Example 2.40.119. (0.017 g) by chiral preparative HPLC (V) afforded the title compound (0.006 g) as a white solid. R =2.4min.

[0250] The following examples are prepared starting from o-substituted bromomethyl heteroaryl, the corresponding cyclic ketone and intermediate 3 according to the procedures described for example 2.40.119. LC-MS and Gal-3 inhibition data are listed in Table 6 below. The LC-MS conditions used were LC-MS(A). Chiral analytical HPLC(I) (conditions and retention times) and inhibition data for the epimers R and S of selected examples are also listed.

[0251] [Table 32]

[0252] [Table 33]

[0253] [Table 34]

[0254] [Table 35]

[0255] [Table 36]

[0256] [Table 37]

[0257] [Table 38] Example 2.45.112. (2R,3R,4S,5R,6S)-2-(hydroxymethyl)-6-(((4-hydroxypiperidin-4-yl)(2-(trifluoromethyl)phenyl)methyl)thio)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol Intermediate 8 (0.023 g, 0.03 mmol) is dissolved in MeOH (1.0 mL) and K2CO3 (0.004 g, 0.03 mmol, 1.0 eq) is added. The reaction mixture is stirred at rt for 17 h. The crude material is directly purified by preparative HPLC / MS (I) to give the title product as a white solid (0.003 g, 17%). LC-MS (A):t R =0.69min;[M+H] + :635.3.

[0258] Example 2.46.112. (2S,3R,4S,5R,6R)-2-(((4-hydroxy-1-(methylsulfonyl)piperidin-4-yl)(2-(trifluoromethyl)phenyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol 1. (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-(((4-hydroxy-1-(N-methylsulfamoyl)piperidin-4-yl)(2-(trifluoromethyl)phenyl)methyl)thio)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diyl diacetate Methylsulfamoyl chloride (0.007, 0.06 mmol, 1.0 eq) and DIPEA (0.03 mL, 0.17 mmol, 3.0 eq) are added to a solution of intermediate 8 (0.044 g, 0.06 mmol) in DCM (2.0 mL) at rt. The reaction mixture is stirred at rt for 48 h, partitioned between DCM and water, the layers are separated and the aqueous layer is extracted with DCM (3x). The organic layers are combined, dried over MgSO4, filtered and the solvent is removed in vacuo to give a colourless oil. The crude material is purified by preparative HPLC / MS (I) to give the title compound as a white solid (0.007 g, 14%). LC-MS (A):t R =1.05mi n;[M+H] + :853.98.

[0259] 2. 4-((((2S,3R,4S,5R,6R)-3,5-dihydroxy-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)(2-(trifluoromethyl)phenyl)methyl)-4-hydroxy-N-methylpiperidine-1-sulfonamide (2.46.112.) To a solution of (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-(((4-hydroxy-1-(N-methylsulfamoyl)piperidin-4-yl)(2-(trifluoromethyl)phenyl)methyl)thio)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diyl diacetate (0.007 g, 0.008 mmol) in MeOH (1.0 mL) is added K2CO3 (0.002 g, 0.0002 mmol, 0.2 eq) at rt. The reaction mixture is stirred at rt for 17 h, diluted with MeCN and then with water and the mixture is directly purified by preparative HPLC / MS (I). The title compound is obtained as a white solid (0.003 g, 52%). LC-MS (A):t R =0.86min;[M+H] + :727.94.

[0260] Example 2.47.112. (2S,3R,4S,5R,6R)-2-(((4-hydroxy-1-(methylsulfonyl)piperidin-4-yl)(2-(trifluoromethyl)phenyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol Example 2.47.112. is synthesized similarly to Example 2.46.112. from intermediate 8 and methanesulfonyl chloride. LC-MS (A): R =0.86min;[M+H] + :712.9.

[0261] Example 2.47.112R. (2S,3R,4S,5R,6R)-2-(((R)-(4-hydroxy-1-(methylsulfonyl)piperidin-4-yl)(2-(trifluoromethyl)phenyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol [1,3-di-deoxy-1-((1-methylsulfonyl-4-hydroxy-piperidin-4-yl)-(2-(trifluoromethyl)phenyl)methyl-(R)-thio)-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-β-D-galactopyranoside] Example 2.47.112R is synthesized from intermediate 8R and methanesulfonyl chloride in a similar manner to Example 2.47.112. LC-MS (A): R =0.86min;[M+H] +:713.19. 1 H NMR (400MHz, MeOD) δ:8.49(s, 1H), 8.17(d, J=7.9Hz, 1H), 7.70(d, J=7.9Hz, 1H), 7.64(m, 3H), 7.46(t, J=7.7Hz, 1H), 4.71(dd, J1=3.0Hz, J 2=10.5Hz, 1H), 4.62(s, 1H), 4.37(d, J=9.5Hz, 1H), 4.21(t, J=10.3Hz, 1H), 4.16(d, J=2.8Hz, 1H), 3.78-3.80(m, 2H), 3. 67(t, J=6.3Hz, 1H), 3.58-3.64(m, 1H), 3.42-3.47(m, 1H), 3.05(td, J1=2.5Hz, J2=12.5Hz, 1H), 2.94(td, J1=2.3Hz, J2 =12.0Hz, 1H), 2.83(s, 3H), 2.54(dd, J1=2.5Hz, J2=14.1Hz, 1H), 1.2(dd, J1=2.4Hz, J2=13.7Hz, 1H), 1.64-1.79(m, 2H). HPL for chiral analysis C(L):t R =1.7min.

[0262] Example 2.48.112. 1 -(4-((((2S,3R,4S,5R,6R)-3,5-dihydroxy-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)(2-(trifluoromethyl)phenyl)methyl)-4-hydroxypiperidin-1-yl)ethan-1-one Example 2.48.112. is obtained as a by-product in the preparation of Example 2.47.112. LC-MS (A): t R =0.84min;[M+H] + :676.96.

[0263] Example 2.49.112R. N-Cyclopropyl-4-((R)-(((2S,3R,4S,5R,6R)-3,5-dihydroxy-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)(2-(trifluoromethyl)phenyl)methyl)-4-hydroxypiperidine-1-carboxamide Example 2.49.112R is prepared from intermediate 8R and isocyanatocyclopropane as a white powder in analogy to Example 2.46.112. LC-MS (A): R =0.89min;[M+H] + :693.23. LC-MS(A):t R =0.84min;[M+H] + : 718.0. Chiral analytical HPLC (G): t R =1.84min. 1H NMR (400MHz, MeOD) δ:8.49(s, 1H), 8.18(d, J=8.0Hz, 1H), 7.70-7.59(m, 4H), 7.44(t, J=7.7Hz, 1H), 4.70(dd, J1=10.5Hz, J2=3.0Hz, 1H), 4. 58(s, 1H), 4.34(d, J=9.5Hz, 1H), 4.2(t, J=10.0Hz, 1H), 4.15(d, J=2.8Hz, 1H), 3.92-3.85(m, 1H), 3.78-3.75(m, 1H), 3.7 4-3.68(m, 1H), 3.65(t, J=3.65Hz, 1H), 3.08(td, J1=13.5Hz, J2=3.0Hz, 1H), 2.96(td, J1=13.5Hz, J2=3.0Hz, 1H), 2.53( m, 1H), 2.38(dd, J1=13.6Hz, J2=2.2Hz, 1H), 1.55(m, 2H), 1.06(dd, J1=13.6Hz, J2=2.1Hz, 1H), 0.65(m, 2H), 0.44(m, 2H).

[0264] Example 2.50.112R. Methyl 4-((R)-(((2S,3R,4S,5R,6R)-3,5-dihydroxy-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)(2-(trifluoromethyl)phenyl)methyl)-4-hydroxypiperidine-1-carboxylate Example 2.50.112. is prepared from intermediate 8R and methyl chloroformate as a white powder in analogy to Example 2.46.112. LC-MS (A): R =0.89min;[M+H] + :693.23. 1 H NMR (400MHz, MeOD) δ:8.49(s, 1H), 8.18(d, J=8.0Hz, 1H), 7.69(d, J=8.0Hz, 1H), 7.62-7.66(m, 3H), 7.46(t, J=7.7Hz , 1H), 4.70(dd, J1=3.0Hz, J2=10.5Hz, 1H), 4.58(s, 1H), 4.34(d, J=9.5Hz, 1H), 4.20(t, J=10.1Hz , 1H), 4.15 (d, J=2.8Hz, 1H), 4.01 (bd, J=13.3Hz, 1H), 3.85 (bd, J=13.8Hz, 1H), 3.75-3.80 (m, 2H) , 3.69(s, 3H), 3.65(t, J=6.3Hz, 1H), 2.92-3.23(m, 2H), 2.43(d, J=13.8Hz, 1H), 1.47-1.62(m, 2H) ), 1.08(d, J=14.0Hz, 1H).

[0265] The following examples are prepared similarly to the above procedures starting from intermediate 8, intermediate 8R or intermediate 8A. The LC-MS and Gal-3 inhibition data are listed in Table 7 below. The LC-MS conditions used were LC-MS(A). Chiral analytical HPLC(I) (conditions and retention times) and inhibition data of epimers R and S of selected examples are also listed.

[0266] [Table 39]

[0267] [Table 40]

[0268] [Table 41] * The epimers are obtained from intermediate 8R and intermediate 8S.

[0269] Example 3.31.112. (2S,3R,4S,5R,6R)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-2-((2-hydroxy-2-methyl-1-(2-(trifluoromethyl)phenyl)propyl)thio)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,5-diol 1. (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-4-(4-(3 ,5-Difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-6-((2-hydroxy-2-methyl-1-(2-(trifluoromethyl)phenyl)propyl)thio)tetrahydro-2H-pyran-3,5-diyl diacetate The synthesis of the triazole is carried out in a commercial continuous flow reactor (Vapourtec) using a copper coil (internal volume 10.0 mL) and a back pressure regulator (6.0 bar). Intermediate 9 (0.062 g, 0.11 mmol) is dissolved in THF (2.0 mL) and then 5-ethynyl-1,3-difluoro-2-methylbenzene (4.41 mg, 0.11 mmol, 1 eq) and DIPEA (0.056 mL, 0.33 mmol, 3.0 eq) are added. The mixture is pumped through the coil, which is kept at a temperature of 90° C., at a flow rate of 0.4 mL / min. The reactor outlet is collected and concentrated under reduced pressure on a GeneVac EZ-2 Elite (40° C., 0 mbar, overnight) to give the crude product, which is purified by preparative HPLC / MS (I) to give the title compound (0.033 g, 42%). LC-MS (A):t R = 1.1 min; [M+H] + :716.16.

[0270] 2. (2S,3R,4S,5R,6R)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-2-(((R)-2-hydroxy-2-methyl-1-(2-(trifluoromethyl)phenyl)propyl)thio)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,5-diol (3.31.112.) (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-6-((2-hydroxy-2-methyl-1-(2-(trifluoromethyl)phenyl)propyl)thio)tetrahydro-2H-pyran-3,5-diyl diacetate (0.033 g, 0.0461 mmol) is dissolved in MeOH (2.0 mL) and K2CO3 (0.001 g, 0.009 mmol, 0.2 eq) is added at rt. The reaction mixture is stirred at rt for 2 h, quenched with MeCN and then water, and the mixture is directly purified by preparative HPLC / MS (I) to give a white solid (0.022 g, 82%) as the title compound. LC-MS (A):t R =0.9min;[M+H] + :590.24.

[0271] Example 3.31.112R. (2S,3R,4S,5R,6R)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-2-(((R)-2-hydroxy-2-methyl-1-(2-(trifluoromethyl)phenyl)propyl)thio)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,5-diol Separation of the epimer Example 3.31.112. (0.022 g) by chiral preparative HPLC (VI) followed by preparative HPLC / MS (I) afforded the title compound (0.006 g) as a white solid. Chiral analytical HPLC (M): R =1.67min. 1 H NMR (400MHz, MeOD) δ:8.45(s, 1H), 8.20(d, J=8.0Hz, 1H), 7.68(d, J=7.9Hz, 1H), 7.62(t, J=7.5Hz, 1H), 7.39-7.46(m, 3H), 4.7-4.66(m, 2H) ), 4.18-4.27(m, 2H), 4.15(d, J=2.8Hz, 1H), 3.77(m, 2H), 3.63(t, J=6.4Hz, 1H), 2.22(s, 3H), 1.52(s, 3H), 1.09(s, 3H).

[0272] Example 3.31.112S. (2S,3R,4S,5R,6R)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-2-(((S)-2-hydroxy-2-methyl-1-(2-(trifluoromethyl)phenyl)propyl)thio)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,5-diol Chiral preparative HPLC (VI) followed by epimer separation by preparative HPLC / MS (I) Separation of Example 3.31.112. (0.022 g) gave the title compound (0.004 g) as a white solid. Chiral analytical HPLC (M): R =1.34min.

[0273] The following examples are prepared analogously to Example 3.31.112 starting from intermediate 9 and the corresponding alkyne. LC-MS and Gal-3 inhibition data are listed in Table 8 below. The LC-MS conditions used were LC-MS(A). Chiral analytical HPLC(I) (conditions and retention times) and inhibition data for epimers R and S of selected examples are also listed.

[0274] [Table 42] Example 2.44.126R.I. (2R,3R,4S,5R,6S)-6-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(3-methylpyridin-2-yl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol [1,3-di-deoxy-1-((4,4-difluoro-1-hydroxy-cyclohexyl)-(3-(-methyl)pyridin-2-yl)methyl-(R)-thio)-2-O-methyl-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-bD-galactopyranoside] Example 2.44.126R.I. is synthesized from Example 2.44.126R. as follows. 1. (4aR,6S,7R,8R,8aR)-6-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(3-methylpyridin-2-yl)methyl)thio)-2,2-dimethyl-8-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)hexahydropyrano[3,2-d][1,3]dioxin-7-ol A mixture of Example 2.44.126R. (0.26 g, 0.43 mmol), 2,2-dimethoxypropane (0.3 mL, 2.35 mmol, 5.5 eq), acetone (0.7 mL) and CSA (0.05 g, 0.21 mmol, 0.5 eq) in THF (4.0 mL) is heated at 60° C. for 6 h, then at rt for 15 h and again at 60° C. for 6 h. The reaction mixture is partitioned between EA and aq.sat.NaHCO3, the layers are separated and the aqueous layer is extracted with EA (3×). The organic layers are combined, washed with brine, dried over MgSO4, filtered and the solvent removed under vacuum to give the title compound as a white solid (0.28 g, >99%) which is used without further purification. LC-MS (A):t R =0.88min;[M+H] + :657.92.

[0275] 2. 4,4-difluoro-1-((R)-(((4aR,6S,7R,8S,8aR)-7-methoxy-2,2-dimethyl-8-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)hexahydropyrano[3,2-d][1,3]dioxin-6-yl)thio)(3-methylpyridin-2-yl)methyl)cyclohexan-1-ol To a stirred solution of (4aR,6S,7R,8R,8aR)-6-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(3-methylpyridin-2-yl)methyl)thio)-2,2-dimethyl-8-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)hexahydropyrano[3,2-d][1,3]dioxin-7-ol (0.26 g, 0.4 mmol) in DMF (3.0 mL) is added MeI (0.05 mL, 0.8 mmol, 2.0 eq) followed after 5 min by CsCO3 (0.14 g, 0.4 mmol, 1.1 eq). The reaction mixture is stirred at rt for 48 h, partitioned between water and EA, the layers are separated and the aqueous layer is extracted with EA (3x). The combined organic layers are washed with brine, dried over MgSO4, filtered and the solvent removed in vacuo to give a yellow oil. Purification by preparative HPLC / MS (I) afforded the title compound as a white solid (0.20 g, 74%). LC-MS (A): R =0.95min;[M+H] + :671.1.

[0276] 3. (2R,3R,4S,5R,6S)-6-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(3-methylpyridin-2-yl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol (2.44.126R.I.) To a mixture of 4,4-difluoro-1-((R)-(((4aR,6S,7R,8S,8aR)-7-methoxy-2,2-dimethyl-8-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)hexahydropyrano[3,2-d][1,3]dioxin-6-yl)thio)(3-methylpyridin-2-yl)methyl)cyclohexan-1-ol (0.20 g, 0.3 mmol) in water (2.0 mL) is added AcOH (2.0 mL) and the resulting solution is stirred at 60° C. for 8 h and then at rt for 24 h. The reaction mixture is cooled to 0° C. and quenched with (HO / MeCN=1 / 1) (1.0 mL) and aq. NH4OH is added (until pH 5-6). The resulting solution is purified by preparative HPLC / MS (I) to give the title compound as a white solid (0.14 g, 76%). LC-MS (A): R =0.79min;[M+H] + :631.1. 1 H NMR (400MHz, MeOD) δ:8.63(s, 1H), 8.42(d, J=4.0Hz, 1H), 7.63-7.70(m, 3H), 7.26(dd, J1=4.8Hz , J2=7.8Hz, 1H), 4.85(dd, J1=2.9Hz, J2=10.5Hz, 1H), 4.65(s, 1H), 4.47(d, J=9.5Hz, 1H), 4.06(d, J=2.9Hz, 1H), 3.95( t, J=9.9Hz, 1H), 3.88-3.64(m, 7H), 3.15(s, 3H), 2.48(s, 3H), 2.24(m, 1H), 1.85(m, 1H), 1.72(m, 1H), 1.25-1.20(m, 1H).

[0277] The following 2-OMe-Gal inhibitors are prepared as single epimers or mixtures of epimers from the corresponding 2-OH-Gal inhibitors according to the procedure described for Example 2.44.126R.I. The LC-MS, Gal-3 inhibition data are listed in Table 9 below. The LC-MS conditions used were LC-MS(A). Chiral analytical HPLC(I) (conditions and retention times) and inhibition data for epimers R and S of selected examples are also listed.

[0278] [Table 43]

[0279] [Table 44]

[0280] [Table 45] Example 2.39.120 R.I. (2R,3R,4S,5R,6S)-6-(((R)-(1-hydroxycyclohexyl)(4-methylisoxazol-3-yl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol (2.39.120R.I.). Example 2.39.120R.I. is synthesized from Example 2.39.120R. as follows.

[0281] 1. (4aR,6S,7R,8R,8aR)-6-(((R)-(1-hydroxycyclohexyl)(4-methylisoxazol-3-yl)methyl)thio)-2,2-dimethyl-8-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)hexahydropyrano[3,2-d][1,3]dioxin-7-ol Example 2.39. Mixture of 120R. (0.14 g, 0.24 mmol), 2,2-dimethoxypropane (0.16 mL, 1.3 mmol, 5.5 eq), acetone (0.5 mL) and CSA (0.03 g, 0.12 mmol, 0.5 eq) in THF (1.5 mL). The mixture is heated at 50° C. for 2 h. The reaction mixture is partitioned between EA and sat. aq. NaHCO3, the layers are separated and the aqueous layer is extracted with EA (3×). The organic layers are combined, washed with brine, dried over MgSO4, filtered and the solvent is removed in vacuo to give a colorless oil which is purified by preparative HPLC / MS (I) to give the title compound as a white solid (0.11 g, 76%). LC-MS (A):t R =1.03min;[M+H] + :611.22.

[0282] 2. 1-((R)-(((4aR,6S,7R,8S,8aR)-7-Methoxy-2,2-dimethyl-8-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)hexahydropyrano[3,2-d][1,3]dioxin-6-yl)thio)(4-methylisoxazol-3-yl)methyl)cyclohexan-1-ol To a stirred solution of (4aR,6S,7R,8R,8aR)-6-(((R)-(1-hydroxycyclohexyl)(4-methylisoxazol-3-yl)methyl)thio)-2,2-dimethyl-8-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)hexahydropyrano[3,2-d][1,3]dioxin-7-ol (0.11 g, 0.18 mmol) in THF (2.0 mL) was added MeI (0.02 mL, 0.4 mmol, 2.0 eq) and then after 5 min NaH (0.01 g, 0.2 mmol, 1.1 eq) and stirring was continued for 2 h at rt. The reaction mixture was partitioned between water and EA, the layers were separated and the aqueous layer was extracted with EA (3x). The combined organic layers are washed with brine, dried over MgSO4, filtered and the solvent removed in vacuo to give a brown oil. Purification by preparative HPLC / MS (I) affords the title compound as a white solid (0.07 g, 63%). LC-MS (A): R =1,10min;[M+H] + :625.25.

[0283] 3. (2R,3R,4S,5R,6S)-6-(((R)-(1-hydroxycyclohexyl)(4-methylisoxazol-3-yl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol (2.39.120R.I.) To a mixture of 1-((R)-(((4aR,6S,7R,8S,8aR)-7-methoxy-2,2-dimethyl-8-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)hexahydropyrano[3,2-d][1,3]dioxin-6-yl)thio)(4-methylisoxazol-3-yl)methyl)cyclohexan-1-ol (0.07 g, 0.11 mmol) in water (2.0 mL) is added AcOH (2.0 mL). The solution is stirred at 55 °C for 2.5 h, cooled (0°), quenched with (HO / MeCN 1 / 1, 1.0 mL) and aq. NH4OH is added at 0 °C (until pH 5-6). The resulting solution is purified by preparative HPLC / MS (I) to afford the title compound as a white solid (0.05 g, 68%). 1 H NMR (400MHz, MeOD) δ:8.63(s, 1H), 8.39(s, 1H), 7.62-7.74(m, 2H), 4.84(dd, J=2.9Hz, J=10.5Hz, 1H), 4.52(s, 1H), 4.32(d, J=9.5Hz, 1H), 4.09(d, J=2.8Hz, 1H), 4. 01(t, J=10.0Hz, 1H), 3.83-3.68(m, 2H), 3.64(t, J=6.3Hz, 1H), 3.23(s, 3H), 2.21(s, 3H), 1.87-2.03(m, 1H), 1.5-1.8(m, 8H), 1.28-1.38(m, 1H). LC-MS(A):t R =0.94min;[M+H] + :585.23.

[0284] Example 2.39.120S.I. (2R,3R,4S,5R,6S)-6-(((S)-(1-hydroxycyclohexyl)(4-methylisoxazol-3-yl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2, 3-Triazol-1-yl)tetrahydro-2H-pyran-3-ol (2.39.120S.I.). Example 2.39.120S.I. is synthesized from Example 2.39.120S. similarly to Example 2.39.120R.I. as a white solid. LC-MS (A): R =0.95min;[M+H] + :585.2.

[0285] The following 2-OMe-Gal inhibitors are prepared from the corresponding 2-OMe-Gal inhibitors following the procedure described for Example 2.39.120R.I. The LC-MS and Gal-3 inhibition data are listed in Table 10 below. The LC-MS conditions used were LC-MS(A). Chiral analytical HPLC(I) (conditions and retention times) and inhibition data for epimers R and S of selected examples are also listed.

[0286] [Table 46]

[0287] [Table 47]

[0288] [Table 48]

[0289] [Table 49]

[0290] [Table 50] Example 2.44.141.I. (2R,3R,4S,5R,6S)-6-(((4-chloro-3-methylpyridin-2-yl)(4,4-difluoro-1-hydroxycyclohexyl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol Example 2.44.141.I. is prepared from 1-((4-chloro-3-methylpyridin-2-yl)(mercapto)methyl)-4,4-difluorocyclohexan-1-ol (prepared similarly to intermediate 7) and intermediate 10 as a beige solid, similarly to example 2.40.119. LC-MS (A):t R =0.98min;[M+H] + :665.16.

[0291] Example 2.44.141R.I. (2R,3R,4S,5R,6S)-6-(((R)-(4-chloro-3-methylpyridin-2-yl)(4,4-difluoro-1-hydroxycyclohexyl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol Separation of the epimers of Example 2.44.141.I. (0.026 g) by chiral preparative HPLC (VII) afforded the title compound (0.010 g) as a white solid. R = 1.9 min. LC-MS (A): t R =0.98min;[M+H] + :665.1.

[0292] Example 2.44.141S.I. (2R,3R,4S,5R,6S)-6-(((S)-(4-chloro-3-methylpyridin-2-yl)(4,4-difluoro-1-hydroxycyclohexyl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol Separation of the epimers of Example 2.44.141.I. (0.026 g) by chiral preparative HPLC (VII) afforded the title compound (0.008 g) as a white solid. R = 2.98 min. LC-MS (A): t R =0.97min;[M+H] + :665.11.

[0293] The following examples are prepared analogously to Example 2.44.141.I. from intermediate 10 and the corresponding mercaptoalcohol (prepared analogously to intermediate 7). LC-MS and Gal-3 inhibition data are listed in Table 11 below. LC-MS conditions used were LC-MS(A). Chiral analytical HPLC(I) (conditions and retention times) and inhibition data for epimers R and S of selected examples are also listed.

[0294] [Table 51]

[0295] [Table 52]

[0296] [Table 53]

[0297] [Table 54]

[0298] [Table 55]

[0299] [Table 56]

[0300] [Table 57] Example 2.44.126.II. (2R,3R,4S,5R,6S)-6-(((4,4-difluoro-1-hydroxycyclohexyl)(3-methylpyridin-2-yl)methyl)thio)-5-ethoxy-2- (Hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol Example 2.44.126.II. is prepared from 1-((4-chloro-3-methylpyridin-2-yl)(mercapto)methyl)-4,4-difluorocyclohexan-1-ol (prepared analogously to intermediate 7) and intermediate 11 as a beige solid according to the procedure described for example 2.40.119. LC-MS (A):t R =0.81min;[M+H] + :645.42.

[0301] The LC-MS and Gal-3 inhibition data for Example 2.44.126.II. is set forth below in Table 14. The LC-MS conditions used were LC-MS(A).

[0302] [Table 58] Example 2.51.112.I. 1-(Cyclopropylsulfonyl)-4-((((2S,3R,4S,5R,6R)-5-hydroxy-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)(2-(trifluoromethyl)phenyl)methyl)piperidin-4-ol 1. 1-(Cyclopropylsulfonyl)-4-((((4aR,6S,7R,8S,8aR)-7-methoxy-2,2-dimethyl-8-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)hexahydropyrano[3,2-d][1,3]dioxin-6-yl)thio)(2-(trifluoromethyl)phenyl)methyl)piperidin-4-ol To a solution of intermediate 12 (0.06 g, 0.087 mmol) in DCM (3.0 mL) at rt, cyclopropylsulfonyl chloride (0.01 mL, 0.105 mmol, 1.2 eq) and DIPEA (33.9 μL, 0.26 mmol, 3.0 eq) are added. The reaction mixture is stirred at rt for 15 h, partitioned between DCM and water, the layers are separated and the aqueous layer is purified by distillation with DC Extract with M (3x). The organic layers are combined, dried over MgSO4, filtered and the solvent removed in vacuo to give a brown oil which is purified by prep HPLC / MS (I) to give the title compound (0.011 g, 16%) as a white solid. LC-MS (A): R =1.11min;[M+H] + :793.22.

[0303] 2. 1-(Cyclopropylsulfonyl)-4-((((2S,3R,4S,5R,6R)-5-hydroxy-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)(2-(trifluoromethyl)phenyl)methyl)piperidin-4-ol (2.51.112.I.) To a mixture of 1-(cyclopropylsulfonyl)-4-((((4aR,6S,7R,8S,8aR)-7-methoxy-2,2-dimethyl-8-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)hexahydropyrano[3,2-d][1,3]dioxin-6-yl)thio)(2-(trifluoromethyl)phenyl)methyl)piperidin-4-ol (0.011 g, 0.014 mmol) in water, AcOH (0.5 mL) is added and the solution is stirred at 60° C. for 2 h and then at rt for 15 h. With cooling (0° C.), a 1 / 1 mixture of water / MeCN (1.0 mL) and NH4OH (until pH 5-6) are added and the solution is purified by prep HPLC / MS (I) to give a white solid (0.006 g). LC-MS (A):t R =0.98min;[M+H] + :753.11.

[0304] Example 2.48.112.I. 1-(4-hydroxy-4-((((2S,3R,4S,5R,6R)-5-hydroxy-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)(2-(trifluoromethyl)phenyl)methyl)piperidin-1-yl)ethan-1-one Example 2.48.112.I. is obtained as a by-product of the synthesis of Example 2.51.112.I., step 1., and is deprotected as in step 2. of the same example to give a white solid. LC-MS (A): R =0.92min;[M+H] + :691.12.

[0305] Example 2.49.112.I. (N-cyclopropyl-4-hydroxy-4-((((2S,3R,4S,5R,6R)-5-hydroxy-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)(2-(trifluoromethyl)phenyl)methyl)piperidine-1-carboxamide Example 2.49.112.I. is obtained from intermediate 12 and isocyanatocyclopropane as in Example 2.51.112.I. as a white solid. LC-MS (A): t R =0.91min;[M+H] + :732.2.

[0306] The LC-MS and Gal-3 inhibition data for Examples 2.51.112.I. through 2.49.112.I. are set forth below in Table 13. The LC-MS conditions used were LC-MS(A).

[0307] [Table 59] Example 16.44.126.I. (2R,3R,4S,5R,6S)-6-(((4,4-difluoro-1-hydroxycyclohexyl)(3-methylpyridin-2-yl)methyl)thio)-4-(4-(3,4-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol 1. 4,4-Difluoro-1-(mercapto(3-methylpyridin-2-yl)methyl)cyclohexan-1-ol 4,4-Difluoro-1-(mercapto(3-methylpyridin-2-yl)methyl)cyclohexan-1-ol is prepared as a yellow oil from S-(tetrahydro-2H-pyran-2-yl)ethanethioate, 2-(bromomethyl)-3-methylpyridine and 4,4-difluorocyclohexan-1-one, similar to intermediate 7. LC-MS (A):t R =0.62min;[M+H] + :273.91.

[0308] 2. (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-4-azido-6-(((4,4-difluoro-1-hydroxycyclohexyl)(3-methylpyridin-2-yl)methyl)thio)tetrahydro-2H-pyran-3,5-diyl diacetate (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-4-azido-6-(((4,4-difluoro-1-hydroxycyclohexyl)(3-methylpyridin-2-yl)methyl)thio)tetrahydro-2H-pyran-3,5-diyl diacetate is prepared as a white powder from 4,4-difluoro-1-(mercapto(3-methylpyridin-2-yl)methyl)cyclohexan-1-ol and intermediate 2, similar to intermediate 9. LC-MS (A):t R =0.81min;[M+H] + :587.20.

[0309] 3. (2S,3R,4S,5R,6R)-4-Azido-2-(((4,4-difluoro-1-hydroxycyclohexyl)(3-methylpyridin-2-yl)methyl)thio)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,5-diol To a suspension of (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-4-azido-6-(((4,4-difluoro-1-hydroxycyclohexyl)(3-methylpyridin-2-yl)methyl)thio)tetrahydro-2H-pyran-3,5-diyl diacetate (1.04 g, 1.77 mmol) in MeOH (21.0 mL) at rt is added NaOMe (0.14 g, 2.66 mmol, 1.5 eq). The mixture is stirred at rt for 15 h, neutralized with DOWEX 50WX2, filtered and the solvent removed in vacuo to give the title compound as an orange oil (0.87 g, >99%) which was further purified. LC-MS(A):t R =0.48min;[M+H] + :461.12.

[0310] 4. (4aR,6S,7R,8R,8aR)-8-Azido-6-(((4,4-difluoro-1-hydroxycyclohexyl)(3-methylpyridin-2-yl)methyl)thio)-2,2-dimethylhexahydropyrano[3,2-d][1,3]dioxin-7-ol A solution of (2S,3R,4S,5R,6R)-4-azido-2-(((4,4-difluoro-1-hydroxycyclohexyl)(3-methylpyridin-2-yl)methyl)thio)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,5-diol (0.75 g, 1.62 mmol) in THF (11.5 mL) and acetone (11.5 mL) is treated with 2,2-dimethoxypropane (2.03 mL, 16.2 mmol, 10.0 eq) and p-TsOH HO (0.04 g, 0.18 mmol, 0.1 eq) and stirred at 50 °C for 9 h. The reaction mixture is concentrated under reduced pressure, diluted with EA, washed with aq.sat.NaHCO3, dried over MgSO4, filtered and the solvent removed in vacuo to give a white solid (0.72 g, 89%) which is used without further purification. LC-MS (A): R =0.65-0.68min;[M+H] + :501.16.

[0311] 5. 1-((((4aR,6S,7R,8S,8aR)-8-azido-7-methoxy-2,2-dimethylhexahydropyrano[3,2-d][1,3]dioxin-6-yl)thio)(3-methylpyridin-2-yl)methyl)-4,4-difluorocyclohexan-1-ol To a solution of (4aR,6S,7R,8R,8aR)-8-azido-6-(((4,4-difluoro-1-hydroxycyclohexyl)(3-methylpyridin-2-yl)methyl)thio)-2,2-dimethylhexahydropyrano[3,2-d][1,3]dioxin-7-ol (0.57 g, 1.14 mmol) in DMF (12.0 mL) at rt is added MeI (0.43 mL, 6.87 mmol, 6.0 eq). After 5 min CsCO3 (1.23 g, 3.78 mmol, 3.3 eq) is added and the reaction mixture is stirred at rt for 15 h then partitioned between water and EA. The layers are separated and the aqueous layer is extracted with EA (3x). The organic layers are combined, washed with brine, dried over MgSO4, filtered and the solvent removed in vacuo to give a brown oil which is purified by combi flash (ISCO system, product added to isolute-dried, 12 g column, Hept / EA 100 / 0 to 20 / 80, Rf(Hept / EA 1 / 1)=0.33 and 0.42) to give the title compound as a yellow oil (0.59 g, >99%). LC-MS(A):t R =0.76-0.78min;[M+H] + :515.18.

[0312] 6. 1-((((4aR,6S,7R,8S,8aR)-8-(4-(3,4-difluorophenyl)-1H-1,2,3-triazol-1-yl)-7-methoxy-2,2-dimethylhexahydropyrano[3,2-d][1,3]dioxin-6-yl)thio)(3-methylpyridin-2-yl)methyl)-4,4-difluorocyclohexan-1-ol To a solution of 1-((((4aR,6S,7R,8S,8aR)-8-azido-7-methoxy-2,2-dimethylhexahydropyrano[3,2-d][1,3]dioxin-6-yl)thio)(3-methylpyridin-2-yl)methyl)-4,4-difluorocyclohexan-1-ol (0.058 g, 0.11 mmol) in DMF (1.0 mL) at rt is added 4-ethynyl-1,2-difluorobenzene (0.0202 mL, 0.16 mmol, 1.5 eq), CuI (0.07 g, 0.01 mmol, 0.1 eq)) and DIPEA (0.05 mL, 0.32 mmol, 3.0 eq). The reaction mixture is stirred at rt for 3 h and diluted with EA. The organic layer is washed with aq.sat.NH4Cl, brine, dried over MgSO4, filtered and the solvent concentrated in vacuo to give a beige solid. Purify by preparative HPLC / MS (I) to give the title compound as a white solid (0.05 g, 77%). LC-MS (A): R =0.92min;[M+H] + :653.21.

[0313] 7. (2R,3R,4S,5R,6S)-6-(((4,4-difluoro-1-hydroxycyclohexyl)(3-methylpyridin-2-yl)methyl)thio)-4-(4-(3,4-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol (16.44.126.I.) To a mixture of 1-((((4aR,6S,7R,8S,8aR)-8-(4-(3,4-difluorophenyl)-1H-1,2,3-triazol-1-yl)-7-methoxy-2,2-dimethylhexahydropyrano[3,2-d][1,3]dioxin-6-yl)thio)(3-methylpyridin-2-yl)methyl)-4,4-difluorocyclohexan-1-ol (0.05 g, 0.08 mmol) in water (2.0 mL) is added AcOH (2.0 mL) and the solution is heated at 80° C. for 15 h. The reaction mixture is cooled (0°), quenched with (HO / MeCN 1 / 1, 1.0 mL) and aq. NH4OH is added at 0° C. (until pH 5-6). The resulting solution is purified by preparative HPLC / MS (I) to give the title compound as a white solid (0.03 g, 64%). LC-MS (A):t R =0.75min;[M+H] + :613.36.

[0314] Example 16.44.126R.I. (2R,3R,4S,5R,6S)-6-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(3-methylpyridin-2-yl)methyl)thio)-4-(4-(3,4-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol Separation of the epimers of Example 16.44.126.I. (0.032 g) by chiral preparative HPLC (VIII) afforded the title compound (0.009 g) as a white solid. R = 1.4 min. LC-MS (A): t R =0.75min;[M+H] + :613.13.

[0315] Example 16.44.126S.I. (2R,3R,4S,5R,6S)-6-(((S)-(4,4-difluoro-1-hydroxycyclohexyl)(3-methylpyridin-2-yl)methyl)thio)-4-(4-(3,4-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol Separation of the epimers of Example 16.44.126.I. (0.032 g) by chiral preparative HPLC (VIII) afforded the title compound (0.008 g) as a white solid. R = 2.0 min. LC-MS(A):t R =0.75min;[M+H] + :613.13.

[0316] The following examples are prepared analogously to Example 16.44.126.I., steps 6-7., starting from 1-((((4aR,6S,7R,8S,8aR)-8-azido-7-methoxy-2,2-dimethylhexahydropyrano[3,2-d][1,3]dioxin-6-yl)thio)(3-methylpyridin-2-yl)methyl)-4,4-difluorocyclohexan-1-ol, Example 16.44.126.I., step 5., and the corresponding alkyne. LC-MS and Gal-3 inhibition data are listed in Table 14 below. LC-MS conditions used were LC-MS(A). Chiral analytical HPLC(I) (conditions and retention times) and inhibition data for epimers R and S of selected examples are also listed.

[0317] [Table 60]

[0318] [Table 61]

[0319] [Table 62] Galectin-1 inhibition data is set forth below in Table 15. Inhibition data for epimers R and S of selected examples are also provided.

[0320] [Table 63]

[0321] [Table 64] Biological testing Inhibitory activity of the compound (IC 50 ) Evaluation The inhibitory activity of the compounds is determined in a competitive binding assay, a spectrophotometric assay that measures the binding of biotin-labeled human Gal-3 (hGal-3) or human Gal-1 (hGal-1), respectively, to the glycoprotein asialofetuin (ASF) adsorbed on microplates (Proc Natl Acad Seis USA. 2013 Mar 26;110(13):5052-7).

[0322] Briefly, compounds are serially diluted in DMSO (Test Diluent). Add 22.8 μL / well of biotinylated hGal-3 or hGal-1 in assay buffer (i.e., 300-1000 ng / ml biotinylated hGal-3 or hGal-1) to an ASF-coated 384-well plate, add 1.2 μL of compound test diluent and mix.

[0323] The plates are incubated for 3 hours at 4° C., then washed with cold assay buffer (3×50 μl), incubated with 25 μl / well of streptavidin-peroxidase solution (diluted to 80 ng / ml in assay buffer) for 1 hour at 4° C., then further washed with assay buffer (3×50 μl). Finally, 25 μl / well of A Add BTS substrate. After 30-45 min, record OD (410 nm) and IC 50 Calculate the value.

[0324] 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 average values.

Claims

1. A compound of formula (I) or a pharma- ceutically acceptable salt thereof: 【Chemistry 1】 (In the formula, Ar １ teeth, aryl selected from phenyl and naphthyl substituted by 1, 2, 3, 4 or 5 substituents, said substituents being independently selected from halogen, methyl, cyano and methoxy; represents; Ar ２ teeth, - phenyl or 5- or 6-membered heteroaryl, which phenyl or 5- or 6-membered heteroaryl is independently unsubstituted or substituted by 1, 2 or 3 substituents, said substituents being independently selected from the group consisting of: １－６ -Alkyl, C ３－６ -Cycloalkyl, C １－３ -fluoroalkyl, C １－３ -fluoroalkoxy, halogen, hydroxy-C １－３ - alkyl or phenyl, phenyl or 5- or 6-membered heteroaryl; Or, - naphthyl; represents; - R １ａ represents hydrogen; and R １ｂ teeth, -- -C ２－４ - alkyl; Or, -- -C ０－１ -Alkylene-Ar １ｂ (Ar １ｂ represents phenyl or a 5- or 6-membered heteroaryl, which is independently unsubstituted or substituted by 1 or 2 methyl; represents; - or R １ａ and R １ｂ each represents hydrogen, methyl, ethyl, or n-propyl; - or R １ａ and R １ｂ together with the carbon atoms to which they are attached, -- C ３－６ -Cycloalkylene (the C ３－６ -cycloalkylene is independently unsubstituted or substituted with 1 or 2 substituents, said substituents being independently methyl or fluoro; -- tetrahydro-2H-pyran-4,4-diyl, unsubstituted or substituted by 2 or 4 methyl; -- tetrahydro-2H-thiopyran-1,1-dioxide-4,4-diyl; or piperidine-4,4-diyl, pyrrolidine-3,3-diyl, or azetidine-3,3-diyl, wherein the piperidine, pyrrolidine, or azetidine nitrogens are independently unsubstituted or are each independently selected from the group consisting of -C １－３ -alkyl, -C ０－２ -Alkylene-C ３－６ -cycloalkyl or -L-R Ｎ１ ( --- -L- is -CO-, -SO ２ --, ＊ —CO—NH—, ＊ -CO-O- or ＊ -SO ２ represents —NH—, --- R Ｎ１ is -C １－３ -Alkyl or -C ０－２ -Alkylene-C ３－６ -represents cycloalkyl; ) is replaced by; (In the above groups, the asterisk indicates the bond attaching to the remainder of the molecule); or forming a 3- to 6-membered ring selected from Or, - R １ａ and R １ｂ are, together with the carbon atoms to which they are attached, the structure (S １ＡＢ ) spiro-bicyclic ring system 【Chemistry 2】 wherein ring (A) represents a 3- to 6-membered non-aromatic carbocyclic ring which optionally contains one ring oxygen atom, and which is unsubstituted or substituted by two fluoro; Forming R ２ is hydroxy or C １－３ - represents alkoxy.

2. Formula (I Ｒ 2. A compound of formula (I) as defined in claim 1, which is also a compound of the formula: 【Chemistry 3】 (wherein the group Ar ２ The carbon atom to which is attached is represented by formula (I Ｒ ) has the absolute configuration shown in

3. Ar １ represents phenyl substituted with 1, 2 or 3 substituents independently selected from halogen, methyl, cyano and methoxy; at least one of the substituents is attached at the meta or para position of the phenyl; the para-substituent, if present, is selected from halogen, methyl, cyano and methoxy; - if a meta substituent is present, said meta substituent is halogen; 3. The compound according to claim 1 or 2, or a pharma- ceutically acceptable salt thereof.

4. Ar １ The structure is: 【Chemistry 4】 (In the formula, - R ｍ２ represents a halogen; - R ｐ represents hydrogen, halogen, methyl, cyano or methoxy; 3. The compound according to claim 1 or 2, or a pharma- ceutically acceptable salt thereof, wherein R represents a phenyl group;

5. Ar ２ but, - phenyl, substituted by 1, 2 or 3 substituents; --One substituent is an Ar to the rest of the molecule ２ is attached at the ortho position to the point of attachment of １－６ -Alkyl, C ３－６ -Cycloalkyl, C １－３ -fluoroalkyl, C １－３ -fluoroalkoxy, halogen, hydroxy-C １－３ - alkyl or phenyl; --Other substituents, if present, are not included in the attachment of Ar to the remainder of the molecule. ２ attached at the meta and / or para positions relative to the point of attachment of C １－６ -Alkyl, C ３－６ -Cycloalkyl, C １－３ -fluoroalkyl or halogen; phenyl; or - 5- or 6-membered heteroaryl, each of which is independently , substituted by 1, 2 or 3 substituents; --One substituent is an Ar to the rest of the molecule ２ is attached at the ortho position to the point of attachment of １－６ -Alkyl, C ３－６ -Cycloalkyl or C １－３ -fluoroalkyl; --other substituents, if present, are independently selected from the group consisting of: C １－６ -Alkyl, C ３－６ -Cycloalkyl, C １－３ -fluoroalkyl or halogen; 5- or 6-membered heteroaryl; Represents; The compound according to any one of claims 1 to 4, or a pharma- ceutically acceptable salt thereof.

6. Ar ２ but, 【Chemistry 5】 【Chemistry 6】 The compound according to any one of claims 1 to 4, or a pharma- ceutically acceptable salt thereof.

7. - R １ａ represents hydrogen; and R １ｂ but, -- -C ２－４ - alkyl; --phenyl unsubstituted or substituted by one or two methyls; represents; - or R １ａ and R １ｂ each represents methyl, ethyl or n-propyl; - or R １ａ and R １ｂ together with the carbon atoms to which they are attached. -- C ４－６ -Cycloalkylene (C ４－６ -cycloalkylene is independently unsubstituted or substituted with 1 or 2 substituents, said substituents being independently methyl or fluoro; -- tetrahydro-2H-pyran-4,4-diyl; 2,2-dimethyltetrahydro-2H-pyran-4,4-diyl or 2,2,6,6-tetramethyltetrahydro-2H-pyran-4,4-diyl; -- tetrahydro-2H-thiopyran-1,1-dioxide-4,4-diyl; -- piperidine-4,4-diyl (the piperidine nitrogen is unsubstituted or is -C １－３ -Alkyl, -CO-C １－３ -Alkyl, -CO-O-C １－３ -Alkyl, -CO-NH-cyclopropyl, -SO ２ -C １－３ -Alkyl, -SO ２ -Cyclopropyl or -SO ２ -NH-C １－３ -substituted by alkyl; or --azetidine-3,3-diyl (the azetidine nitrogen is unsubstituted or substituted with --SO ２ -C １－３ -Alkyl, -CO-O-C １－３ -alkyl or -CO-NH-cyclopropyl; or forming a 3- to 6-membered ring selected from Or, - R １ａ and R １ｂ along with the carbon atoms to which they are attached: 【Chemistry 7】 forming a spiro-bicyclic ring system of the formula: The compound according to any one of claims 1 to 6, or a pharma- ceutically acceptable salt thereof.

8. R ２ A compound according to any one of claims 1 to 7, or a pharma- ceutically acceptable salt thereof, wherein: represents methoxy.

9. The compound is (2S,3R,4S,5R,6R)-2-(((R)-2-hydroxy-1-phenylethyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-1-(2-bromophenyl)-2-hydroxyethyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-2-hydroxy-1-(2-isopropylphenyl)ethyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-2-hydroxy-2-methyl-1-(o-tolyl)propyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-1-(2-ethylphenyl)-2-hydroxy-2-methylpropyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-2-hydroxy-2-methyl-1-(2-propylphenyl)propyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-2-hydroxy-1-(2-isobutylphenyl)-2-methylpropyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-2-hydroxy-2-methyl-1-(2-pentylphenyl)propyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-1-([1,1'-biphenyl]-2-yl)-2-hydroxy-2-methylpropyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-1-(2-chlorophenyl)-2-hydroxy-2-methylpropyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-2-hydroxy-2-methyl-1-(2-(trifluoromethyl)phenyl)propyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-1-(2,3-dichlorophenyl)-2-hydroxy-2-methylpropyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-1-(3-fluoro-2-methylphenyl)-2-hydroxy-2-methylpropyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-2-hydroxy-2-methyl-1-(naphthalen-1-yl)propyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-2-hydroxy-2-methyl-1-(2-methylpyridin-3-yl)propyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-2-hydroxy-2-methyl-1-(4-methylpyridin-3-yl)propyl)thio)-6-(hydroxymethyl)-4 -(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-2-hydroxy-2-methyl-1-(3,5,6-trimethylpyrazin-2-yl)propyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-2-hydroxy-2-methyl-1-(4-methylisoxazol-3-yl)propyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-1-(3,5-dimethylisoxazol-4-yl)-2-hydroxy-2-methylpropyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-1-(2,5-dimethylthiazol-4-yl)-2-hydroxy-2-methylpropyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-2-hydroxy-2-methyl-1-(4-methylthiophen-3-yl)propyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-2-ethyl-2-hydroxy-1-(3-methylisoxazol-4-yl)butyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((1R,2R)-2-hydroxy-1-(2-(trifluoromethyl)phenyl)butyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((1R,2S)-2-hydroxy-1-(2-(trifluoromethyl)phenyl)butyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(3,3-difluoro-1-hydroxycyclobutyl)(2-(trifluoromethyl)phenyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (3R,4R,5R,6R)-2-((R)-2-(1-hydroxycyclobutyl)-2-(o-tolyl)ethyl)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(1-hydroxy-3,3-dimethylcyclobutyl)(o-tolyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((1R)-(1-hydroxy-3-methylcyclobutyl)(o-tolyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((1R)-((2R,3R)-1-hydroxy-2,3-dimethylcyclobutyl)(o-tolyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((1R)-((2R,3S)-1-hydroxy-2,3-dimethylcyclobutyl)(o-tolyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((1R)-((2S,3R)-1-hydroxy-2,3-dimethylcyclobutyl)(o-tolyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((1R)-((2S,3S)-1-hydroxy-2,3-dimethylcyclobutyl)(o-tolyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(1-hydroxycyclopentyl)(o-tolyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(1-hydroxycyclohexyl)(o-tolyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(4-hydroxy-1-methylpyridin-4-yl)(o-tolyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2R,3R,4S,5R,6S)-2-(hydroxymethyl)-6-(((R)-(4-hydroxytetrahydro-2H-pyran-4-yl)(2-(trifluoromethyl)phenyl)methyl)thio)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(4-hydroxy-2,2,6,6-tetramethyltetrahydro-2H-pyran-4-yl)(2-(trifluoromethyl)phenyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-((R)-4-hydroxy-2,2-dimethyltetrahydro-2H-pyran-4-yl)(2-(trifluoromethyl)phenyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-((S)-4-hydroxy-2,2-dimethyltetrahydro-2H-pyran-4-yl)(2-(trifluoromethyl)phenyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(3,3-difluoro-1-hydroxycyclobutyl)(3-(trifluoromethyl)pyridin-2-yl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1 H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(1-hydroxycyclohexyl)(3-(trifluoromethyl)pyridin-2-yl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(1-hydroxycyclohexyl)(3,5,6-trimethylpyrazin-2-yl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(1-hydroxycyclohexyl)(4-methylisoxazol-3-yl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(4-methylisoxazol-3-yl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(2-isopropylphenyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(3,5,6-trimethylpyrazin-2-yl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(3-(trifluoromethyl)pyridin-2-yl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(2-chlorophenyl)(4,4-difluoro-1-hydroxycyclohexyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2R,3R,4S,5R,6S)-2-(hydroxymethyl)-6-(((R)-(4-hydroxytetrahydro-2H-pyran-4-yl)(3-(trifluoromethyl)pyridin-2-yl)methyl)thio)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2R,3R,4S,5R,6S)-2-(hydroxymethyl)-6-(((R)-(4-hydroxytetrahydro-2H-pyran-4-yl)(3,5,6-trimethylpyrazin-2-yl)methyl)thio)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(4-hydroxy-1-methylpyridin-4-yl)(2-(trifluoromethyl)phenyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(4-hydroxy-1-methylpyridin-4-yl)(3-(trifluoromethyl)pyridin-2-yl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(4-hydroxy-1-methylpyridin-4-yl)(3,5,6-trimethylpyrazin-2-yl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(1-hydroxycyclopentyl)(3-(trifluoromethyl)pyridin-2-yl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(3-methylpyridin-2-yl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2R,3R,4S,5R,6S)-2-(hydroxymethyl)-6-(((R)-(4-hydroxypiperidin-4-yl)(2-(trifluoromethyl)phenyl)methyl)thio)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; 4-((R)-(((2S,3R,4S,5R,6R)-3,5-dihydroxy-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)(2-(trifluoromethyl)phenyl)methyl)-4-hydroxy-N-methylpiperidine-1-sulfonamide; (2S,3R,4S,5R,6R)-2-(((R)-(4-hydroxy-1-(methylsulfonyl)piperidin-4-yl)(2-(trifluoromethyl)phenyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; 1-(4-((R)-(((2S,3R,4S,5R,6R)-3,5-dihydroxy-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)(2-(trifluoromethyl)phenyl)methyl)-4-hydroxypiperidin-1-yl)ethan-1-one; N-cyclopropyl-4-((R)-(((2S,3R,4S,5R,6R)-3,5-dihydroxy-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)(2-(trifluoromethyl)phenyl)methyl)-4-hydroxypiperidine-1-carboxamide; Methyl 4-((R)-(((2S,3R,4S,5R,6R)-3,5-dihydroxy-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)(2-(trifluoromethyl)phenyl)methyl)-4-hydroxypiperidine-1-carboxylate; (2S,3R,4S,5R,6R)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-2-(((R)-2-hydroxy-2-methyl-1-(2-(trifluoromethyl)phenyl)propyl)thio)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-2-hydroxy-2-methyl-1-(2-(trifluoromethyl)phenyl)propyl)thio)-6-(hydroxymethyl)-4-(4-(naphthalen-2-yl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; 4-(1-((2S,3R,4S,5R,6R)-3,5-dihydroxy-2-(((R)-2-hydroxy-2-methyl-1-(2-(trifluoromethyl)phenyl)propyl)thio)-6-(hydroxymethyl)tetrahydro-2H-pyran-4-yl)-1H-1,2,3-triazol-4-yl)-2-fluorobenzonitrile; (2R,3R,4S,5R,6S)-2-(hydroxymethyl)-6-(((R)-4-hydroxytetrahydro-2H-pyran-4-yl)(o-tolyl)methyl)thio)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-2-hydroxy-1-(2-isopropylphenyl)-2-methylpropyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-1-(2-cyclopropylphenyl)-2-hydroxy-2-methylpropyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-2-hydroxy-1-(2-(2-hydroxyethyl)phenyl)-2-methylpropyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-2-hydroxy-2-methyl-1-(2-(trifluoromethyl)pyridin-3-yl)propyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-1-(2,5-dimethyloxazol-4-yl)-2-hydroxy-2-methylpropyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((1R,2R)-2-hydroxy-2-phenyl-1-(2-(trifluoromethyl)phenyl)ethyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((1R,2S)-2-hydroxy-2-phenyl-1-(2-(trifluoromethyl)phenyl)ethyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((1R,2R)-2-hydroxy-2-(o-tolyl)-1-(2-(trifluoromethyl)phenyl)propyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((1R,2S)-2-hydroxy-2-(o-tolyl)-1-(2-(trifluoromethyl)phenyl)propyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(5-cyclopropyl-3-methylisoxazol-4-yl)(1-hydroxycyclohexyl)methyl)thio)-6 -(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-((R)-4-hydroxy-2,2-dimethyltetrahydro-2H-pyran-4-yl)(o-tolyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-((S)-4-hydroxy-2,2-dimethyltetrahydro-2H-pyran-4-yl)(o-tolyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(2-(trifluoromethyl)phenyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(2,3-dichlorophenyl)(4,4-difluoro-1-hydroxycyclohexyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(2-cyclopropylphenyl)(4,4-difluoro-1-hydroxycyclohexyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(3-methylpyrazin-2-yl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(5-cyclopropyl-4-ethylisoxazol-3-yl)(4,4-difluoro-1-hydroxycyclohexyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(5-cyclopropyl-4-isobutylisoxazol-3-yl)(4,4-difluoro-1-hydroxycyclohexyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(3-isopropylpyridin-2-yl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(3-chloropyrazin-2-yl)(4,4-difluoro-1-hydroxycyclohexyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(3-cyclopropylpyridin-2-yl)(4,4-difluoro-1-hydroxycyclohexyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(4-methylpyridazin-3-yl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; 4-((R)-(((2S,3R,4S,5R,6R)-3,5-dihydroxy-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)(4-methylisoxazol-3-yl)methyl)-4-hydroxytetrahydro-2H-thiopyran 1,1-dioxide; 4-((R)-(((2S,3R,4S,5R,6R)-3,5-dihydroxy-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)(3-methylpyridin-2-yl)methyl)-4-hydroxytetrahydro-2H-thiopyran 1,1-dioxide; (2R,3R,4S,5R,6S)-2-(hydroxymethyl)-6-(((R)-(4-hydroxytetrahydro-2H-pyran-4-yl)(3-methylpyridin-2-yl)methyl)thio)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-(3-hydroxy-1-(methylsulfonyl)azetidin-3-yl)(2-(trifluoromethyl)phenyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; Methyl 3-((R)-(((2S,3R,4S,5R,6R)-3,5-dihydroxy-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)(2-(trifluoromethyl)phenyl)methyl)-3-hydroxyazetidine-1-carboxylate; N-cyclopropyl-3-((R)-(((2S,3R,4S,5R,6R)-3,5-dihydroxy-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)(2-(trifluoromethyl)phenyl)methyl)-3-hydroxyazetidine-1-carboxamide; (2R,3R,4S,5R,6S)-6-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(3-methylpyridin-2-yl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-6-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(3-(trifluoromethyl)pyridin-2-yl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-6-(((R)-(1-hydroxycyclohexyl)(3-(trifluoromethyl)pyridin-2-yl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; 2R,3R,4S,5R,6S)-6-(((R)-(3-chloropyridin-2-yl)(4,4-difluoro-1-hydroxycyclohexyl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-6-(((R)-((R)-4-hydroxy-2,2-dimethyltetrahydro-2H-pyran-4-yl)(2-(trifluoromethyl)phenyl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-6-(((R)-((S)-4-hydroxy-2,2-dimethyltetrahydro-2H-pyran-4-yl)(2-(trifluoromethyl)phenyl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; 4-hydroxy-4-((R)-(((2S,3R,4S,5R,6R)-5-hydroxy-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)(3-methylpyridin-2-yl)methyl)tetrahydro-2H-thiopyran 1,1-dioxide; (2R,3R,4S,5R,6S)-2-(hydroxymethyl)-6-(((R)-(4-hydroxytetrahydro-2H-pyran-4-yl)(3-methylpyridin-2-yl)methyl)thio)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-6-(((R)-((R)-4-hydroxy-2,2-dimethyltetrahydro-2H-pyran-4-yl)(o-tolyl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-6-(((R)-((S)-4-hydroxy-2,2-dimethyltetrahydro-2H-pyran-4-yl)(o-tolyl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-6-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(3-isopropylpyridin-2-yl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-6-(((R)-(3-cyclopropylpyridin-2-yl)(4,4-difluoro-1-hydroxycyclohexyl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-6-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(4-methylpyridazin-3-yl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-6-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(3-methylpyrazin-2-yl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-6-(((R)-(1-hydroxycyclohexyl ) (4-methylisoxazol-3-yl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-6-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(2-isopropylphenyl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-6-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(4-methylisoxazol-3-yl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-6-(((R)-(2-cyclopropylphenyl)(4,4-difluoro-1-hydroxycyclohexyl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-6-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(1,4-dimethyl-1H-pyrazol-5-yl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-6-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(1-ethyl-4-methyl-1H-1,2,3-triazol-5-yl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-6-(((R)-(4-chloro-1-ethyl-1H-pyrazol-5-yl)(4,4-difluoro-1-hydroxycyclohexyl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-6-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(5-ethyl-4-methylisoxazol-3-yl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-2-(hydroxymethyl)-6-(((R)-(4-hydroxytetrahydro-2H-pyran-4-yl)(4-methylisoxazol-3-yl)methyl)thio)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; 4-hydroxy-4-((R)-(((2S,3R,4S,5R,6R)-5-hydroxy-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)(4-methylisoxazol-3-yl)methyl)tetrahydro-2H-thiopyran 1,1-dioxide; (2R,3R,4S,5R,6S)-6-(((R)-(5-cyclopropyl-3-methylisoxazol-4-yl)(1-hydroxycyclohexyl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3- Oar; (2R,3R,4S,5R,6S)-6-(((R)-(5-cyclopropyl-4-ethylisoxazol-3-yl)(4,4-difluoro-1-hydroxycyclohexyl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-6-(((R)-(5-cyclopropyl-4-isobutylisoxazol-3-yl)(4,4-difluoro-1-hydroxycyclohexyl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-6-(((R)-(3-chloropyrazin-2-yl)(4,4-difluoro-1-hydroxycyclohexyl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-6-(((R)-(4-chloro-3-methylpyridin-2-yl)(4,4-difluoro-1-hydroxycyclohexyl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-6-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(3-ethylpyridin-2-yl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-6-(((R)-(3,4-dichloropyridin-2-yl)(4,4-difluoro-1-hydroxycyclohexyl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2S,3R,4S,5R,6R)-2-(((R)-(3,6-dichloropyridin-2-yl)(4,4-difluoro-1-hydroxycyclohexyl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-((R)-4-hydroxy-2,2-dimethyltetrahydro-2H-pyran-4-yl)(3-methylpyridin-2-yl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2S,3R,4S,5R,6R)-2-(((R)-((S)-4-hydroxy-2,2-dimethyltetrahydro-2H-pyran-4-yl)(3-methylpyridin-2-yl)methyl)thio)-6-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,5-diol; (2R,3R,4S,5R,6S)-6-(((R)-(5-cyclopropyl-4-methylisoxazol-3-yl)(4,4-difluoro-1-hydroxycyclohexyl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-6-((((R)-4,4-difluoro-1-hydroxycyclohexyl)(4-ethyl-5-propylisoxazol-3-yl)methyl (3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-6-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(3-methyl-4-(trifluoromethyl)pyridin-2-yl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; 2R,3R,4S,5R,6S)-6-(((R)-(3-chloro-6-methylpyridin-2-yl)(4,4-difluoro-1-hydroxycyclohexyl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-6-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(3,5,6-trimethylpyrazin-2-yl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-6-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(3,6-dimethylpyridin-2-yl)methyl)thio)-2-(hydroxymethyl)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; 9-((R)-(((2S,3R,4S,5R,6R)-5-hydroxy-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)(3-methylpyridin-2-yl)methyl)-3-oxaspiro[5.5]undecan-9-ol; (2R,3R,4S,5R,6S)-6-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(3-methylpyridin-2-yl)methyl)thio)-5-ethoxy-2-(hydroxymethyl)-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3-ol; 1-(cyclopropylsulfonyl)-4-((R)-(((2S,3R,4S,5R,6R)-5-hydroxy-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)(2-(trifluoromethyl)phenyl)methyl)piperidin-4-ol; 1-(4-hydroxy-4-((R)-(((2S,3R,4S,5R,6R)-5-hydroxy-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)(2-(trifluoromethyl)phenyl)methyl)piperidin-1-yl)ethan-1-one; N-cyclopropyl-4-hydroxy-4-((R)-(((2S,3R,4S,5R,6R)-5-hydroxy-6-(hydroxymethyl)-3-methoxy-4-(4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-2-yl)thio)(2-(trifluoromethyl)phenyl)methyl)piperidine-1-carboxamide; (2R,3R,4S,5R,6S)-6-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(3-methylpyridin-2-yl)methyl)thio)-4-(4-(3,4-difluorophenyl)-1H-1,2,3-triazol-1-yl)-2- (Hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-6-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(3-methylpyridin-2-yl)methyl)thio)-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,6S)-4-(4-(4-chloro-2,3-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(3-methylpyridin-2-yl)methyl)thio)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-6-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(3-methylpyridin-2-yl)methyl)thio)-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,6S)-4-(4-(4-bromo-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(3-methylpyridin-2-yl)methyl)thio)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-4-(4-(3,4-dichloro-5-fluorophenyl)-1H-1,2,3-triazol-1-yl)-6-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(3-methylpyridin-2-yl)methyl)thio)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-4-(4-(4-bromo-3-fluorophenyl)-1H-1,2,3-triazol-1-yl)-6-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(3-methylpyridin-2-yl)methyl)thio)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-4-(4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl)-6-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(3-methylpyridin-2-yl)methyl)thio)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; (2R,3R,4S,5R,6S)-6-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(3-methylpyridin-2-yl)methyl)thio)-4-(4-(3,5-difluoro-4-methylphenyl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; Or, (2R,3R,4S,5R,6S)-6-(((R)-(4,4-difluoro-1-hydroxycyclohexyl)(3-methylpyridin-2-yl)methyl)thio)-4-(4-(6-fluoro-5-methylpyridin-3-yl)-1H-1,2,3-triazol-1-yl)-2-(hydroxymethyl)-5-methoxytetrahydro-2H-pyran-3-ol; 2. The compound of claim 1, wherein:

10. A pharmaceutical composition comprising a compound according to any one of claims 1 to 9, or a pharma- ceutically acceptable salt thereof; and a pharma- ceutically acceptable carrier.

11. A compound according to any one of claims 1 to 9 or a pharmaceutical composition thereof for use as a medicament. Acceptable salts.

12. A medicament for the prevention or treatment of organ fibrosis; liver diseases and disorders; cardiovascular 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; acute kidney injury and chronic kidney disease; interstitial lung diseases and disorders; or transplant rejection, comprising as an active ingredient a compound according to any one of claims 1 to 9 or a pharma-ceutically acceptable salt thereof.

13. Use of a compound according to any one of claims 1 to 9, or a pharma- ceutically acceptable salt thereof, in the manufacture of a medicament for the prevention or treatment of organ fibrosis; liver diseases and disorders; cardiovascular 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; acute kidney injury and chronic kidney disease; interstitial lung diseases and disorders; or transplant rejection.

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